Immune checkpoint inhibitors （ICIs） have become a cornerstone in the treatment of driver-gene-negative and EGFR-TKI-resistant advanced non-small cell lung cancer （NSCLC）. With the accelerating aging of the global population， the proportion of elderly patients diagnosed with advanced NSCLC continues to increase， posing unique clinical challenges for ICI therapy. These challenges stem from age-related reductions in organ reserve， higher comorbidity burdens， and a higher prevalence of frailty in this population. However， most pivotal phase Ⅲ clinical trials only enrolled patients with a median age of 61 ⁃ 65 years old， leading to substantial underrepresentation of elderly individuals， particularly those aged ≥ 75 years old. The Chinese Expert Consensus on Immune Checkpoint Inhibitor Therapy for Elderly Patients with Advanced Non-Small Cell Lung Cancer （2025 Edition） is the first standardized clinical guidance specifically developed for ICI treatment in elderly Chinese patients with NSCLC. This article systematically interprets the core content of this consensus， highlighting that comprehensive geriatric assessment （CGA） serves as the cornerstone for guiding immunotherapy decision-making for elderly patients with lung cancer， and recommends combining the G8 screening tool with ASCO-recommended multidimensional assessment instruments. The consensus proposes an age-stratified treatment algorithm for the first time： for patients aged 65 ⁃ 74 years old， immunotherapy combined with platinum-based doublet chemotherapy is the preferred first-line regimen； for patients aged ≥ 75 years old， treatment decisions should be individualized based on PD-L1 expression levels and tolerance status. Specifically， ICI monotherapy is recommended for patients with high PD-L1 expression （≥ 50%）， while ICIs combined with or without single-agent chemotherapy can be considered for patients with low PD-L1 expression. The consensus also provides in-depth discussion on the pattern of immune-related adverse events （irAEs） and corresponding management strategies in elderly patients， and delineates future research directions including the development of localized geriatric assessment tools and prospective clinical trials specifically targeting older adults. The publication of this consensus fills an important gap in the standardization of ICI therapy for elderly patients with lung cancer in China， and has important guiding value for improving the homogeneity of clinical practice. Nevertheless， its recommendations still require further validation and refinement in real-world studies and prospective clinical trials.

In 2026， the Society for Immunotherapy of Cancer released the Clinical Practice Guideline on Immunotherapy for Renal Cell Carcinoma （version 3.0）， which provides updated recommendations covering postoperative adjuvant therapy， first-line combination therapy， post-immunotherapy progression management， non-clear-cell renal cell carcinoma subtypes， and management for special populations. Compared with the 2019 SITC consensus statement on immunotherapy for advanced renal cell carcinoma （RCC）， this updated guideline expands the scope of recommendations from advanced disease to full-spectrum disease course management. Based on the disease-free survival and overall survival benefits validated by the KEYNOTE-564 trial， adjuvant pembrolizumab has become a core treatment option for postoperative patients at high recurrence risk. For metastatic clear-cell RCC， dual immunotherapy regimens and immunotherapy in combination with tyrosine kinase inhibitors are both established as recommended first-line strategies. Following disease progression on immunotherapy， routine sequential anti-programmed cell death protein 1/programmed death ligand 1 therapy is no longer recommended， and subsequent-line treatment places greater emphasis on alternative tyrosine kinase inhibitors and novel agents targeting mechanisms such as hypoxia-inducible factor-2α inhibition. Although clinical evidence for non-clear-cell RCC has expanded， enrollment in clinical trials remains the preferred approach when clinically feasible. From the perspective of clinical pharmacy， this article interprets key updates to this guideline， with a focus on changes to drug recommendations and their supporting evidence. It further compares these recommendations with domestic drug approval status， reimbursement policies， drug accessibility， and the renal cell carcinoma management guideline released by the Chinese Society of Clinical Oncology. This article also discusses core pharmaceutical considerations including indication verification， toxicity attribution， identification and management of immune-related adverse events， management of tyrosine kinase inhibitor-associated toxicities， treatment duration monitoring， patient education， and pharmacoeconomic evaluation， so as to provide a reference for clinical pharmacists engaged in individualized immunotherapy decision-making and medication safety management for patients with renal cell carcinoma.

Chronic pain is a complex disorder sustained by multilevel mechanisms， including peripheral sensitization， central sensitization， neuroinflammation， synaptic plasticity， and epigenetic regulation. Current analgesic strategies remain constrained by substantial interindividual efficacy heterogeneity， inadequate long-term safety profiles， and the absence of disease-modifying effects. Traditional investigations into pain signal transduction have historically focused primarily on protein kinases； however， the association between sustained kinase activation and pain chronification is critically governed by the dynamic antagonism and homeostatic balance between kinases and phosphatases. Protein phosphatase 2A （PP2A）， a serine/threonine protein phosphatase highly expressed in the central nervous system， counteracts protein kinase-mediated signal amplification via dephosphorylation and regulates key signaling molecules including N-methyl-D-aspartate receptors （NMDAR）， α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptors （AMPAR）， Ca²⁺/calmodulin-dependent protein kinase Ⅱ （CaMK Ⅱ）， protein kinase A （PKA）， protein kinase C （PKC）， extracellular signal-regulated kinase （ERK）， cAMP response element-binding protein （CREB）， and histone deacetylases （HDAC）. Its substrate specificity is tightly modulated by subunit composition， post-translational modifications， endogenous inhibitory proteins， and exogenous regulators. Current， research targeting endogenous negative regulators of PP2A-including protein phosphatase methylesterase 1 （PME-1）， SE translocation protein （SET）， and Cancerous Inhibitor of Protein Phosphatase 2A （CIP2A） along with advances in the development of small-molecule PP2A activators， covalent modulators， and holoenzyme- and substrate-specific interventions， has yielded novel insights into the mechanisms underlying chronic pain. Collectively， these advances indicate that the development of chronic pain interventions is transitioning from non-specific global activation or inhibition toward holoenzyme-selective and substrate-selective targeting. This review focuses on the regulatory role of PP2A in synaptic plasticity and central sensitization， summarizing its molecular mechanisms， inactivation pathways， and therapeutic potential during chronic pain progression. Additionally， we discuss the translational barriers and future prospects of diverse PP2A-targeted pharmacological strategies， with the aim of providing a novel perspective for the development of targeted interventions for chronic pain.

Objective To evaluate the clinical value of mixed reality technology in facilitating the precise resection of gliomas located within language-eloquent brain regions. Methods A total of 50 patients with gliomas located in language-eloquent areas who were admitted to the Second Hospital of Hebei Medical University between March 2024 and April 2026 were prospectively enrolled. Patients were assigned to either the observation group （n = 25） or the control group （n = 25） according to whether mixed reality technology was used for preoperative doctor-patient communication and surgical assistance. Clinical indicators， the quality of preoperative doctor-patient communication， arcuate fasciculus preservation， and postoperative functional outcomes were compared between the two groups. Results Compared with the control group， the observation group exhibited significantly smaller differences in arcuate fasciculus fiber tract counts and volume-corrected fiber tract count differences ［（254.36 ± 81.74） vs. （527.52 ± 171.23）； 5.21 （3.85， 11.20） vs. 13.30 （11.22， 24.08）］. In addition， intraoperative blood loss and volume-corrected blood loss were significantly lower in the observation group ［437.00 （349.00， 795.50） mL vs. 762.00 （511.00， 967.00） mL； 10.32 （9.15， 20.96） mL/cm³ vs. 20.62 （13.86， 31.20） mL/cm³］. The observation group also achieved significantly higher postoperative Aphasia Quotient （AQ） scores and Karnofsky Performance Status （KPS） scores than the control group ［（81.75 ± 10.15） vs. （72.05 ± 10.32）； 90 （80， 100） vs. 80 （75， 90）］. Furthermore， the Patient-Doctor Relationship Questionnaire-13 （PDRQ-13） scores were significantly higher in the observation group than in the control group ［（56.24 ± 3.70） vs. （43.44 ± 4.81）］. All of these differences were statistically significant （all P < 0.05）. No significant differences were observed between the two groups in volume-corrected operative time， extent of tumor resection， or postoperative length of hospital stay （all P > 0.05）. Conclusions Mixed reality technology may facilitate preservation of the arcuate fasciculus， reduce intraoperative blood loss during resection of gliomas in language-eloquent areas， and improve postoperative language function and overall functional status. In addition， it may enhance the quality of preoperative doctor–patient communication.

HIV-associated neurocognitive disorder （HAND） is a prevalent chronic neurological complication among people living with human immunodeficiency virus （HIV）， clinically characterized by cognitive impairment that significantly reduces patients' quality of life and compromises antiretroviral treatment adherence. In recent decades， accumulating evidence has confirmed that microglia are core mediators of neuroinflammation and neuronal injury in the pathogenesis of HAND. Concurrently， research on the regulatory role of gut microbiota in central nervous system homeostasis via the gut-brain axis has attracted growing scholarly attention. This systematic review elaborates on the mechanisms by which gut microbiota modulate the metabolism and functional polarization of microglia by mediating gut-brain crosstalk， thereby influencing the onset and progression of HAND. It also summarizes existing HAND intervention strategies from the gut-brain axis perspective， aiming to provide novel insights for the mechanistic investigation and clinical prevention and treatment of HAND.

Objective This study aims to project the global burden of oral diseases through 2041， so as to fill this critical research gap. Methods We extracted data on the incidence， prevalence， and years lived with disability （YLDs） of oral diseases covering the period 1990—2021 from the Global Burden of Disease （GBD） database. Joinpoint regression analysis was performed to identify statistically significant temporal trends in oral disease burden， and a Bayesian age-period-cohort （BAPC） model was applied to project the future global oral disease burden for 2022—2041， adjusting for demographic covariates including population aging. Results From 1990 to 2021， the global age-standardized incidence， prevalence， and years lived with disability （YLD） rates for oral diseases remained relatively stable， despite substantial absolute increases in total case counts： incidence increased by 36%， prevalence by 52%， and YLDs by 81%. Joinpoint regression analysis revealed significant heterogeneity in trends across disease subtypes： the age-standardized incidence of permanent tooth caries followed a sustained upward trajectory， while that of deciduous tooth caries declined overall. Periodontal disease showed a gradual decreasing trend accompanied by stage-specific fluctuations， and edentulism reversed to an upward trend after 2015. Sex-stratified analyses showed broadly consistent trends between sexes； however， age-standardized incidence rates increased moderately in males， while remaining stable with a slight decrease in females. Further stratification by region and sociodemographic index （SDI） identified pronounced disparities： the African region experienced the largest absolute increase in incident cases （+113.6%）， and China observed a marked increase in age-standardized incidence （estimated annual percentage change ［EAPC］， +0.71%）， while Pakistan， Nigeria， and India exhibited downward trends. In addition， high-SDI regions recorded the fastest growth in YLD rates. BAPC projections predict a significant further increase in the above indicators by 2041， particularly for age-standardized incidence， which is projected to rise from 48，600 to 60 700 per 100 000 population， with older adults bearing a disproportionate burden of disease. Conclusions Our joinpoint regression analysis detected minimal historical improvement in global oral disease prevalence and incidence trends， indicating that currently deployed oral health strategies are insufficient to reverse the current disease burden trajectory. Projections from the BAPC model further demonstrate that without intensified population-level preventive measures and strengthened primary oral healthcare systems， the global burden of oral diseases will see a substantial increase by 2030， posing a major barrier to achieving the World Health Organization （WHO）’s 2030 global oral health targets.

Objective This study aims to investigate the value of computed tomography perfusion-based machine learning models for predicting 90-day functional outcomes in patients with acute cerebral infarction receiving conservative treatment. Methods This study performed a retrospective analysis of 192 consecutive patients with acute cerebral infarction who received conservative treatment. Functional outcomes were assessed via the modified Rankin Scale （mRS） at the 3-month follow-up， and patients were stratified into two groups： the good outcome group （mRS score ≤ 2） and the poor outcome group （mRS score > 2）. All patients were randomly divided into a training set （n = 134） and a validation set （n = 58） at a 7∶3 ratio. Univariate and multivariate logistic regression analyses were conducted to screen for independent clinical influencing factors， which were then used to construct the clinical prediction model. Radiomic features were extracted from baseline CT perfusion images for feature selection. Based on the selected radiomic features， four machine learning models-including logistic regression， support vector machine， random forest， and light gradient boosting machine-were developed and compared to identify the optimal radiomics prediction model. A combined prediction model was then established by integrating the selected independent clinical risk factors and optimized radiomic features. The predictive performance of all constructed models was systematically evaluated and compared using receiver operating characteristic （ROC） curves， calibration curves， decision curve analysis （DCA）， and the DeLong test. Results Age， body mass index （BMI）， the National Institutes of Health Stroke Scale （NIHSS） score， perfusion parameters， and the stratified Tmax thresholds including Tmax > 4 s， Tmax > 6 s， Tmax > 8 s， and Tmax > 10 s were identified as independent prognostic factors. Among the four constructed machine learning models， the random forest model achieved the optimal predictive performance， with areas under the receiver operating characteristic curve （AUC） of 0.828 in the training set and 0.826 in the validation set. The integrated prediction model， which combined clinical features and radiomic features， further improved predictive performance， yielding AUCs of 0.888 and 0.864 in the training and validation sets， respectively. Model validation confirmed that the combined model exhibited satisfactory calibration （Hosmer-Lemeshow test， P = 0.340） and favorable clinical utility. DCA demonstrated that the model provided a substantial net clinical benefit across a wide range of threshold probabilities. The DeLong test indicated that the predictive performance of the combined model was significantly superior to that of the single-modality clinical model and single-modality radiomics model in both the training and validation sets （P < 0.05）. Conclusions The integrated machine learning model constructed by incorporating clinical risk factors and radiomic features extracted from CT perfusion imaging exhibits favorable predictive performance for 90-day clinical outcomes in patients with acute cerebral infarction receiving conservative management. This model lays a solid foundation for early clinical risk stratification and personalized clinical decision-making.

Objective This study aims to investigate the regulatory effect of miR-let-7f on oxygen-glucose deprivation-induced inflammatory responses in microglia and its underlying molecular mechanism. Methods The murine microglial cell line BV2 was cultured to establish an oxygen-glucose deprivation/reoxygenation （OGD/R） cell model. miR-let-7f mimics and inhibitors were designed and synthesized. Quantitative real-time PCR （qPCR） and enzyme-linked immunosorbent assay （ELISA） were employed to quantify the expression levels of miR-let-7f， high mobility group AT-hook 2 （HMGA2）， and inflammatory cytokines across all treatment groups. Cellular immunofluorescence staining was conducted to visualize the subcellular localization and activation status of microglia. Results Transfection with miR-let-7f mimics and inhibitor significantly upregulated and downregulated miR-let-7f expression in BV2 cells， respectively （P < 0.000 1）. OGD/R treatment increased the expression of the pro-inflammatory protein HMGA2 and the inflammatory cytokines tumor necrosis factor-alpha （TNF-α） and interleukin-1 beta （IL-1β） （P < 0.05）， accompanied by increased nuclear translocation of NF-κB p65. Treatment with miR-let-7f mimics significantly reduced HMGA2 and inflammatory cytokine levels （P < 0.05） and decreased NF-κB p65 nuclear translocation. Following the addition of the miR-let-7f inhibitor， these inhibitory effects were significantly attenuated （P < 0.05）. Conclusions miR-let-7f exerts anti-inflammatory effects in BV2 microglia under OGD/R conditions. This bioactivity may be mediated via the regulation of HMGA2 expression and subsequent suppression of the NF-κB signaling pathway. The present study provides robust experimental evidence for the intervention of neuroinflammation secondary to cerebral ischemia and hypoxia.

Objective To develop a combined predictive model incorporating the Venous Excess Ultrasound （VExUS） score and clinical risk indicators for acute kidney injury （AKI） in patients with acute heart failure （AHF） admitted to the cardiac care unit （CCU）， and to evaluate the incremental predictive value of the VExUS score. Methods This study included 122 AHF patients hospitalized in the CCU between January 2022 and January 2025. The VExUS score， incorporating Doppler hemodynamic assessments of the maximum inferior vena cava diameter， hepatic vein， portal vein， and renal vein， was evaluated within 24 hours of admission. Patients were categorized into an AKI group （n = 40） and a non-AKI group （n = 82） based on the KDIGO guidelines. A combined predictive model was developed using logistic regression. Model discrimination was evaluated and compared using receiver operating characteristic （ROC） curves and the DeLong test. The net reclassification improvement （NRI） and integrated discrimination improvement （IDI） were calculated to assess the incremental predictive value of the VExUS score. Internal validation was performed using a bootstrapping approach， and calibration curves were plotted to evaluate model calibration. Results Among the 122 patients， the proportion of individuals with a VExUS score ≥ 2 was significantly higher in the AKI group （score of 2： 23%； score of 3： 43%） compared to the non-AKI group （11% and 12%， respectively） （P < 0.001）. Multivariate logistic regression analysis revealed that a VExUS score of 2 （OR = 6.44， 95% CI： 1.71 - 24.22， P = 0.006） and a VExUS score of 3 （OR = 7.81， 95% CI： 2.25 - 27.10， P < 0.001） were independent predictors of AKI occurrence. The area under the curve （AUC） for the VExUS score alone in predicting AKI was 0.749. When integrated with a baseline clinical model （including a history of CKD， APACHE Ⅱ score， etc.）， the AUC further improved to 0.821， demonstrating superior predictive performance compared to the clinical model alone （P < 0.001）. Compared with the VExUS model alone， the combined model yielded a continuous NRI of 0.690 （P < 0.001） and an IDI of 0.063 （P = 0.021）. Bootstrap internal validation demonstrated good calibration for the combined model. Conclusion A combined predictive model incorporating the VExUS score and clinical risk factors accurately predicts AKI risk in patients with AHF， outperforming the standalone VExUS score. The VExUS score offers incremental predictive insights beyond traditional clinical risk assessment， helping inform volume management and renal protection strategies in this population.

Objective This study aims to develop machine learning-based prediction models for postoperative delirium （POD） in elderly patients undergoing spinal surgery， and to compare the predictive performance of different algorithms. Methods This retrospective study enrolled 809 elderly patients who underwent spinal surgery at our hospital between January 2018 and May 2025. All patients were randomly divided into a training set and a validation set at an 8：2 ratio. Least absolute shrinkage and selection operator （LASSO） regression analysis was applied to identify potential predictive factors for POD， the synthetic minority oversampling technique （SMOTE） algorithm was adopted to resolve the class imbalance issue， and nine machine learning models were subsequently constructed. Receiver operating characteristic （ROC） curves were generated to assess the predictive performance of the established models in the validation set. SHapley Additive exPlanations （SHAP） analysis was utilized to interpret the best-performing model and rank the importance of each feature variable. Results Statistically significant differences （P < 0.05） were observed between the study groups in age， prevalence of diabetes， prevalence of cerebrovascular disease， drinking history， albumin level， intraoperative hypotension， intraoperative blood loss， duration of surgery， duration of anesthesia， and intraoperative sevoflurane dosage. LASSO regression analysis identified age， diabetes， albumin level， intraoperative hypotension， intraoperative sevoflurane dosage， and duration of surgery as independent predictive factors for POD in elderly patients undergoing spinal surgery. Among the nine tested machine learning models， the Light Gradient Boosting Machine model achieved the optimal predictive performance， with an area under the receiver operating characteristic curve （AUC） of 0.928. Feature importance ranking indicated that albumin made the greatest contribution to POD prediction. Conclusion The prediction model for postoperative delirium in elderly patients undergoing spinal surgery based on Light Gradient Boosting Machine demonstrates good predictive performance and can provide a reference for the early identification of high-risk patients and the formulation of perioperative intervention strategies.

Perioperative patient safety relies on real-time， accurate， and individualized bedside monitoring. Traditional single-parameter surveillance is limited in simultaneously evaluating anesthetic drug effects， organ perfusion， and internal homeostasis. This narrative review systematically summarizes key technological advances in bedside anesthesia monitoring from 2023 to 2025， structured into three core dimensions： innovative basic vital sign monitoring， organ-targeted precision monitoring and internal environment homeostasis assessment. We highlight breakthroughs including end-tidal propofol detection， extended minimum alveolar concentration （eMAC） multimodal depth of anesthesia monitoring， point-of-care ultrasound-integrated hemodynamic assessment， and wearable noninvasive respiratory and metabolic monitoring. Clinical performance， validation evidence grades， advantages， and limitations of each technology are critically compared to address the weakness of previous reviews that only enumerate devices without systematic evidence integration. Current shared bottlenecks include insufficient technical operation standardization， limited high-quality multicenter RCT evidence， unbalanced cost-utility of equipment purchase and maintenance， and large variability in clinical interpretation of monitoring indexes. Future development paths center on multimodal physiological data fusion， explainable artificial intelligence-driven early warning， lightweight wireless wearable monitoring devices， and full closed-loop continuous monitoring covering preoperation-intraoperation-PACU-ward phases. This review provides an evidence-based framework for precision anesthesia practice and perioperative adverse event risk reduction.

Objective To compare the short-term clinical efficacy and safety of multi-arm single-port robotic systems versus multi-port robotic-assisted systems in the treatment of choledochal cysts in children， and to provide reference for clinical practice. Methods A retrospective analysis was conducted on the clinical data of 47 children who underwent robot-assisted laparoscopic cyst excision with Roux-en-Y hepaticojejunostomy at the Affiliated Hospital of Zunyi Medical University， from January 2023 to October 2025. The patients were divided into a single-port group （n = 19） and a multi-port group （n = 28） according to the surgical approach. Perioperative indicators， postoperative pain scores， incision satisfaction， and complications were compared between the two groups. Results No statistically significant differences were observed in baseline characteristics， including sex， age at surgery， body weight， maximum cyst diameter， or incidence of preoperative positive symptoms between the two groups （P > 0.05）. The single-port group showed significantly better outcomes than the multi-port group in terms of time to oral intake ［（2.6 ± 0.5） vs. （3.2 ± 0.6） days］， drainage tube retention time ［（2.3 ± 0.7） vs. （4.7 ± 1.0） days］， postoperative pain score ［（1.6 ± 0.5） vs. （2.2 ± 0.8） points］， and incision aesthetic satisfaction score ［（9.4 ± 0.5） vs. （8.5 ± 0.6） points］ （P < 0.05）. There were no significant differences between the two groups in operative time， intraoperative blood loss， postoperative hospital stay， or complication rate （P > 0.05）. No patient required conversion to open laparotomy. In the multi-port group， two patients developed internal herniation through a transverse mesocolonic defect at 2 and 4 weeks postoperatively， respectively. Both underwent repeat laparoscopic exploration， which revealed no intestinal necrosis； the jejunal loops were reduced to the infra-colonic compartment and the mesenteric defect was sutured closed. Both recovered uneventfully. No serious complications such as bile leakage， pancreatic fistula， intra-abdominal hemorrhage， wound infection， or anastomotic stricture occurred in either group. All patients had normal findings at the 3-month follow-up. Conclusions Both single‑port and multi-port robotic-assisted systems are safe and effective for treating pediatric choledochal cysts. The single-port approach offers advantages in earlier postoperative feeding recovery， better pain control， and superior cosmetic outcomes. However， its long-term efficacy needs to be validated by medium- and long-term follow-up studies.

Objective To compare the clinical efficacy of micro-screw anchorage and traditional anchorage in the orthodontic treatment of adult skeletal Class Ⅲ malocclusion. Methods A total of 86 adult patients with skeletal Class Ⅲ malocclusion admitted to our hospital were prospectively included. The case collection period was from June 2019 to June 2024. The patients were divided into two groups according to the random number table method： the study group （n = 43） and the control group （n = 43）. The control group received traditional extracoronal arch anchorage treatment， while the study group received micro-screw anchorage treatment. Compare the sella-nasion-A point （SNA）， sella-nasion-B point （SNB）， A point-nasion-B point （ANB）， probing depth （PD）， plaque index （PLI）， occlusal function indicators， and the occurrence of complications between the two groups. Results After treatment， there was no statistically significant difference in the SNA， ANB， and SNB angles between the two groups compared with those before treatment （P > 0.05）； there was also no statistically significant difference in each index between the two groups （P > 0.05）. After treatment， the PD and PLI values in the control group significantly increased compared to those before treatment （P < 0.05）； although the various indicators in the study group slightly rose， there was no statistically significant difference compared to those before treatment （P > 0.05）. The PD results of the two groups after treatment were comparable （P > 0.05）， and the PLI of the study group was lower than that of the control group （P < 0.05）. After treatment， the contact area of occlusion in both groups increased， and the occlusion time and the asymmetry index of bite force decreased. Moreover， the improvement in each indicator in the study group was more significant （P < 0.05）. During the treatment period， the total incidence rates of complications in the study group and the control group were comparable （P > 0.05）. Conclusions In the orthodontic treatment of adult skeletal Class Ⅲ malocclusion， the effect of micro-implant anchorage in improving the sagittal relationship of the jawbone is comparable to that of traditional extracoronal arch anchorage， without increasing the risk of complications. However， in terms of maintaining periodontal health and optimizing occlusal function， micro-implant anchorage demonstrates significant advantages.

Objective This study aims to investigate the clinical characteristics， associated risk factors， and pathogen profiles of cryptogenic and non-cryptogenic pyogenic liver abscess （PLA）， and to evaluate the diagnostic performance of metagenomic next-generation sequencing （mNGS） for pathogen identification in PLA. Methods A retrospective analysis was performed on 167 patients diagnosed with pyogenic liver abscess admitted to our hospital between January 2020 and December 2025. Patients were stratified into the cryptogenic group （n = 105） and the non-cryptogenic group （n = 62） based on whether a definitive infectious source was identified. Baseline characteristics， laboratory results， and imaging features were compared between the two groups. Among 41 patients who underwent both examinations， we further evaluated the diagnostic performance of mNGS versus conventional bacterial culture. Results A total of 167 patients diagnosed with PLA were enrolled in this study. Compared with the non-cryptogenic group， patients in the cryptogenic group had a higher prevalence of diabetes mellitus， a higher neutrophil percentage， and elevated procalcitonin levels （all P < 0.05）. In contrast， biliary diseases， intra-abdominal malignancies， and multiple hepatic lesions were significantly more prevalent in the non-cryptogenic group （all P < 0.05）. Multivariate logistic regression analysis identified fever （OR = 3.778， 95%CI： 1.688 ⁃8.456）， diabetes mellitus （OR = 2.212， 95%CI： 1.043 ⁃ 4.691）， and elevated hemoglobin level （OR = 1.019， 95%CI： 1.002 ⁃ 1.036） as independent risk factors for cryptogenic PLA. Klebsiella pneumoniae was the most common predominant pathogen isolated in this cohort. Among the 41 patients who received both mNGS testing and conventional pathogen culture， mNGS achieved a significantly higher positive detection rate than conventional culture ［95.12% （39/41） vs. 73.17% （30/41）， P = 0.022］. Additionally， mNGS had a shorter turnaround time and superior detection performance for anaerobic bacteria and uncommon pathogens. Conclusions Cryptogenic and non-cryptogenic pyogenic liver abscesses demonstrate distinct clinical heterogeneity in underlying etiologies， clinical manifestations， inflammatory profiles， and lesion distribution. Etiology-based classification can facilitate early risk stratification and individualized clinical management. For patients with complicated pyogenic liver abscesses or unclear infectious sources， mNGS acts as a valuable adjunct to conventional microbiological testing， enabling accurate pathogen identification and targeted optimization of antimicrobial therapy.

Objective To evaluate the clinical efficacy of endoscopic ultrasound combined with multi-band mucosectomy for the treatment of small gastric elevated lesions， to identify the risk factors for full-thickness resection （EFR） during the procedure， and to construct a risk prediction model. Methods Clinical data of 303 patients with a total of 336 small gastric elevated lesions who underwent endoscopic ultrasound examination and multi-band mucosectomy at our hospital from August 2015 to August 2025 were retrospectively analyzed. The clinical characteristics， endoscopic findings， endoscopic ultrasound features， intraoperative and postoperative complications， postoperative pathology， and follow-up outcomes were reviewed. Patients were divided into a non-full-thickness resection group （n = 155） and a full-thickness resection group （n = 181） based on whether perforation occurred during the procedure. Clinical data， endoscopic and endoscopic ultrasound features， postoperative pathology， and complications were compared between the two groups. Univariate and multivariate analyses were performed to identify risk factors for intraoperative full-thickness resection. A nomogram prediction model was constructed using R software， and its predictive performance was evaluated. Results Postoperative pathology revealed leiomyoma in 163 lesions （48.5%） and gastrointestinal stromal tumor （GIST） in 158 lesions （47.0%）. The majority of lesions were located in the gastric fundus （64.9%）. The median operative time was 14.00 （10.00， 20.00） minutes， with a mean of 16.05 minutes. The median number of hemoclips used for wound closure was 4.0 （4.0， 5.0）. Postoperative bleeding occurred in 5 cases， all of which were successfully managed by repeat endoscopy or conservative medical treatment. Postoperative abdominal pain occurred in 25 cases and fever in 24 cases， all of which resolved after medical treatment. No recurrence or metastasis was observed during follow-up. Multivariate logistic regression analysis showed that gastric fundus lesions （OR = 7.464， 95%CI： 4.219 - 13.204）， age （OR = 1.042， 95%CI： 1.012 - 1.072）， number of ligation bands （OR = 12.257， 95%CI： 3.406 - 44.110）， origin from the muscularis propria （OR = 9.763， 95%CI：1.112 - 85.716）， endoscopic ultrasound calcification （OR = 3.260， 95%CI： 1.257 - 8.455）， and extraluminal growth pattern （OR = 4.524， 95%CI： 1.179 - 17.365） were independent risk factors for intraoperative full-thickness resection. The nomogram model demonstrated good discriminative ability with an AUC of 0.805 （95%CI： 0.759 - 0.851）， a specificity of 74.8%， a sensitivity of 71.3%， a optimal cut-off value of 0.603， and a Youden index of 0.461， indicating good predictive accuracy. Conclusions Endoscopic ultrasound combined with multi-band mucosectomy is safe and effective for the resection of small gastric elevated lesions. Advanced age， lesions located in the gastric fundus， an increased number of ligation bands， origin from the muscularis propria， extraluminal growth pattern， and EUS revealed calcification are risk factors for full-thickness resection during the procedure. Preoperative assessment should focus on these risk factors， and adequate preparation of hemostatic devices such as hemoclips should be made for intraoperative precaution.

Objective To investigate the expression and nuclear translocation of Yin Yang 1 （YY1） in an inflammatory model of human fallopian tube epithelial cells， as well as its regulatory role in fibrosis and epithelial-mesenchymal transition. Methods Human fallopian tube epithelial cells were cultured in vitro， and an inflammatory cell model was established via lipopolysaccharide （LPS） stimulation. Enzyme-linked immunosorbent assay （ELISA） was applied to detect the levels of inflammatory cytokines in cell culture supernatant to identify the optimal stimulation conditions. Real-time quantitative PCR （RT-qPCR） was performed to quantify YY1 mRNA expression， and Western blot analysis was conducted to evaluate YY1 protein nuclear translocation. YY1 expression was knocked down via transfection with human YY1-targeted siRNA interference plasmids， and cells were divided into four groups： the Control group， the LPS group， the LPS + si-NC group， and the LPS + si-YY1 group. Immunofluorescence staining was performed to detect the expression levels of α-SMA and YY1. RT-qPCR and Western blot were used to assess the expression changes of fibrosis markers including α-smooth muscle actin （α-SMA） and collagen type I alpha chain （Collagen Ⅰα）， as well as epithelial-mesenchymal transition markers N-cadherin and E-cadherin. Results Based on the levels of the inflammatory cytokine IL-1β in the cell supernatant， the optimal LPS concentration and treatment duration were determined as 200 ng/mL and 24 h， respectively， which were applied in all subsequent experiments. Compared with the control group， the levels of IL-6， IL-8， IFN-γ， and IL-1β were significantly increased in the LPS group （P < 0.05）， confirming the successful establishment of the inflammatory cell model. After LPS stimulation， YY1 mRNA levels were significantly upregulated （P < 0.05）， and YY1 protein expression was increased in the nucleus， indicating nuclear translocation of YY1. Immunofluorescence staining showed that the nuclear fluorescence intensity of YY1 was enhanced and α-SMA expression was upregulated in the LPS group， while YY1 knockdown significantly inhibited these changes. Results from RT-qPCR and Western blot consistently showed that， compared with the control group， the LPS group had increased expression of α-SMA， Collagen Ⅰα， and N-cadherin， accompanied by decreased expression of E-cadherin （P < 0.05）. Compared with the LPS group， the LPS+si-YY1 group exhibited a significant reversal of the expression trends of these fibrosis and epithelial-mesenchymal transition markers （P < 0.05）. Conclusion LPS induces the upregulation of YY1 and promotes its nuclear translocation in human fallopian tube epithelial cells. Knockdown of YY1 suppresses fibrosis and EMT in fallopian tube epithelial cells， ultimately ameliorating tubal inflammatory infertility.

Objective To investigate whether long non-coding RNA growth arrest-specific 5 （LncRNA GAS5， GAS5） regulates hyperoxia-induced apoptosis of type Ⅱ alveolar epithelial cells via the microRNA-21-5p （miR-21-5p）/PTEN axis. Methods A hyperoxia-induced acute lung injury （HALI） cell model was established using the murine lung epithelial-12 （MLE-12） mouse type II alveolar epithelial cell line in the logarithmic growth phase， and cells were allocated into four experimental groups： The normoxic control （Control） group， the hyperoxic HALI （HALI） group， the hyperoxia + GAS5 silencing （siGAS5） group， and the hyperoxia + GAS5 silencing + miR-21 silencing （siGAS5 + shmiR-21） group. The following assays were performed in this study： a dual-luciferase reporter gene assay was conducted to verify the direct interaction between GAS5 and miR-21； cell viability was measured via the Cell Counting Kit-8 （CCK-8） assay； the transcript levels of GAS5 and miR-21 were quantified by reverse transcription polymerase chain reaction （RT-PCR）； the levels of superoxide dismutase （SOD） and malondialdehyde （MDA） were determined using commercially available detection kits； reactive oxygen species （ROS） accumulation and mitochondrial membrane potential were observed via immunofluorescence microscopy； the secretion levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6） and interleukin-1β （IL-1β） were measured by enzyme-linked immunosorbent assay （ELISA）； cell apoptosis rate was analyzed via flow cytometry； and the protein expression levels of PTEN， AKT， p-AKT， Cleaved-caspase-3， Bcl-2 and Bax were detected via western blotting. Results GAS5 directly targets and regulates the expression of microRNA-21 （miR-21）. Relative to the control group， the HALI group exhibited significantly decreased cell viability， alongside increased levels of GAS5， MDA， ROS， inflammatory mediators including TNF-α， IL-6， and IL-1β， and an elevated apoptosis rate. Furthermore， the HALI group showed significantly upregulated expression of PTEN， Cleaved caspase-3， and Bax proteins （all P < 0.05）， along with decreased miR-21 expression， reduced SOD activity， lower mitochondrial membrane potential， and significantly downregulated expression of p-AKT and Bcl-2 proteins （all P < 0.05）. Compared with the HALI group， the siGAS5 group had restored cell viability， decreased levels of GAS5， MDA， ROS， inflammatory mediators （TNF-α， IL-6， IL-1β）， and reduced apoptosis rate. The siGAS5 group also showed significantly downregulated expression of PTEN， Cleaved caspase-3， and Bax proteins （all P < 0.05）， along with increased miR-21 expression， elevated SOD activity， higher mitochondrial membrane potential， and significantly upregulated expression of p-AKT and Bcl-2 proteins （all P < 0.05）. Finally， co-silencing of miR-21 largely reversed the cytoprotective effect of GAS5 silencing in MLE-12 cells. Conclusion Silencing of GAS5 attenuates hyperoxia-induced apoptosis in type II alveolar epithelial cells， and this protective effect is potentially mediated via the miR-21/PTEN axis.

Objective This study aims to investigate the correlations between SCN10A， glutathione S‑transferase P‑1 （GSTP1）， and methylenetetrahydrofolate reductase （MTHFR） gene polymorphisms and oxaliplatin‑induced peripheral neurotoxicity （OIPN） among colorectal cancer patients treated with oxaliplatin‑based chemotherapy. Methods The clinical data of 160 patients with colorectal cancer who received oxaliplatin-based chemotherapy at Wuhan No.1 Hospital between January 2023 and January 2025 were retrospectively analyzed. Genotypes of the SCN10A （rs12632942）， GSTP1 rs1695 （Ile105Val）， and MTHFR rs1801133 （C677T） loci were detected via polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP）. Associations between the genotypes of these loci， patients' clinicopathological characteristics， OIPN grading， and OIPN risk were further investigated. Results Among the 160 enrolled patients， the overall incidence of OIPN was 77.5% （124/160）， and the incidence of severe neurotoxicity （grade ≥ 3） was 23.1% （37/160）. Comparisons of pathophysiological characteristics across different genotype groups at the SCN10A rs12632942， GSTP1 rs1695， and MTHFR rs1801133 loci revealed no statistically significant between-group differences （all P > 0.05）. At the SCN10A rs12632942 locus， patients with the CT or TT genotype had a significantly higher incidence of chronic OIPN than patients with the CC genotype （P < 0.05）， and the CT or TT genotype was identified as an independent risk factor for chronic OIPN （P < 0.05）. At the GSTP1 rs1695 locus， patients with the AG or GG genotype had a significantly higher incidence of acute OIPN than patients with the AA genotype （P < 0.05）. Multivariate regression analysis confirmed that the AG or GG genotype is an independent risk factor for acute OIPN （P < 0.05）. No statistically significant differences in the incidence of either acute or chronic OIPN were observed across different genotype groups at the MTHFR rs1801133 locus （all P > 0.05）. Conclusions SCN10A rs12632942 and GSTP1 rs1695 polymorphisms are potential genetic risk factors for chronic and acute OIPN in patients with colorectal cancer， respectively. No significant correlation was observed between MTHFR rs1801133 and the occurrence of OIPN.

Therapeutic testicular sperm retrieval and clinical application are essential for achieving biological parenthood in patients with azoospermia and severe male infertility. In recent years， significant progress has been made in the optimization of retrieval techniques， expansion of clinical indications， and exploration of regenerative medicine strategies. Focusing on the core theme of "from targeted sperm retrieval to spermatogenic function reconstruction"， this article systematically reviews the evolution of therapeutic testicular sperm retrieval techniques from blind biopsy and targeted localization to functional spermatogenesis reconstruction， and summarizes the research progress in assisted reproduction and fertility preservation， analyzes the current challenges， and discusses future directions. This review aims to provide reference for clinical standardized diagnosis and treatment as well as translational research of basic science.

Objective To evaluate the interaction between adherence to the Mediterranean diet （MD） and pre-pregnancy BMI， as well as the modifying effect of physical activity during pregnancy， on the risk of pregnancy complications. Methods A total of 568 pregnant women were randomly selected from Urumqi Maternal and Child Health Hospital and Urumqi Youai Hospital between January 2025 and January 2026. Dietary intake during pregnancy was assessed using a 14-point Mediterranean Diet Adherence Score （MEDAS）. Logistic regression models were used to analyze the independent effects and interactions of MD adherence with pre-pregnancy BMI， as well as the modifying role of exercise during pregnancy， on pregnancy complications. Results The average age of the subjects was （30.39 ± 4.046） years， and 192 cases of pregnancy complications occurred. Among them，83（14.61%） had gestational diabetes（GDM）， 63（11.09%） had gestational hypertension（HDP），28（4.93%） had anemia，26（4.58%） had too much or too little amniotic fluid， 20 （3.52%） had thyroid abnormalities， and 10（1.76%） had placental abnormalities. Logistic regression showed that after adjusting for confounding factors， highly adherence MD was a protective factor for overall disease during pregnancy （OR = 0.912， 95%CI： 0.838 - 0.991， P = 0.030）， HDP（OR = 0.770， 95%CI： 0.675 - 0.879， P < 0.001）， and GDM （OR = 0.882， 95%CI： 0.789 - 0.985， P = 0.027）. Stratified display suggests that this protective effect is more significant in the exercise pregnant population. Pre pregnancy overweight and obesity are risk factors for HDP （OR = 3.256，95%CI： 1.683 - 6.299， P < 0.001； OR = 12.095， 95% CI： 5.288 - 27.663， P < 0.001） and GDM （OR = 2.499， 95%CI： 1.409 - 4.430， P = 0.002； OR = 9.035， 95%CI： 4.097 - 19.923， P < 0.001）， with a more significant increase in risk in the non exercise group. Interaction analysis showed a significant interaction between pre pregnancy BMI and MD compliance， with overweight （total disease OR = 0.773， P = 0.022）；HDP OR = 0.707，P = 0.040）、Obese pregnant women （total disease OR = 0.500， P = 0.006）；HDP OR = 0.457，P = 0.009；GDM OR = 0.565， P = 0.017） MD has a stronger protective effect. After exercise stratification， the combination of high compliance MD diet with exercise during pregnancy is a protective factor for HDP in pre pregnancy overweight population （OR = 0.484， 95%CI： 0.264 - 0.887， P < 0.05）. Conclusion Improving adherence to the Mediterranean diet， maintaining a normal pre-pregnancy BMI， and engaging in regular physical activity during pregnancy can effectively reduce the risk of pregnancy complications such as HDP and GDM.

Objective This study aims to analyze the catch-up growth trajectory patterns of premature infants aged 0 - 18 months in the middle and late stages， and further explore the influencing factors of the observed growth trajectories. Methods A single-center retrospective cohort study was conducted on 201 mid-to-late preterm infants （32 - 36 weeks of gestation） admitted to hospital between January 2021 and September 2024. Birth characteristics and longitudinal follow-up data were collected， and periodic anthropometric measurements were performed in accordance with the Recommendations for Physical Growth Evaluation of Chinese Children. The weight-for-height Z-score （WHZ） was calculated based on the Growth Standards for Children Under 7 Years of Age （WS/T 423） issued by the National Health Commission of the People's Republic of China to assess participants' growth status. WHZ was adopted as the longitudinal observation indicator， and corrected age （0， 6， 12， and 18 months） was set as the time variable. The group-based trajectory model was constructed using StataMP 16 software to characterize the growth trajectories of mid-to-late preterm infants during the catch-up growth period from 0 to 18 months corrected age. Infants were categorized into three trajectory groups： slow catch-up， appropriate catch-up， and accelerated catch-up. Univariate analysis and multiple logistic regression analysis were performed to identify influencing factors associated with the distinct growth trajectories. Results Among the 201 included cases， 121 were boys （60.20%） and 80 were girls （39.80%）. The average birth weight was （2.5 ± 0.5） kg， and the average birth height （length） was （46.0 ± 3.4） cm. Using the group-based trajectory modeling， three distinct growth trajectory patterns were identified： the slow catch-up group （n = 22）， the appropriate catch-up group （n = 131）， and the rapid catch-up group （n = 48）. The birth weight of the rapid catch-up group was significantly higher than that of both the slow catch-up group and the appropriate catch-up group. The age at initiation of enteral feeding in the appropriate catch-up group was later than that in the slow catch-up group and the rapid catch-up group. The age at achievement of full enteral feeding in the slow catch-up group was later than that in the appropriate catch-up group. The proportion of exclusive breastfeeding within 6 months was lower in both the slow catch-up group and the rapid catch-up group than in the appropriate catch-up group. The incidence of extrauterine growth restriction （EUGR） was significantly higher in the slow catch-up group than in the appropriate catch-up group， and the difference was statistically significant （P < 0.05）. Results from multiple logistic regression analysis showed that exclusive breastfeeding within 6 months of age is a protective factor for slow postnatal catch-up growth in preterm infants during the mid-to-late period， while birth weight， age at achievement of full enteral feeding， and EUGR are risk factors. For rapid mid-to-late catch-up growth in preterm infants， exclusive breastfeeding within 6 months of age is a protective factor， and birth weight is a risk factor. Conclusions The group-based trajectory model identifies heterogeneous catch-up growth trajectory patterns of preterm infants during the mid-to-late postnatal period after adjusting for gestational age for the 0-18-month age range. The slow versus fast catch-up trajectory is significantly associated with birth weight， enteral nutrition， breastfeeding， and EUGR. It is therefore necessary to account for these influencing factors and implement targeted clinical regulation to facilitate the transition of preterm infants in the mid-to-late postnatal period to an optimal catch-up growth pattern.

Objective To compare the effects of sequential culture media and single-step culture media on early embryonic development in IVF/ICSI procedures， and to assess the differences between different single-step culture medium formulations. Methods This study conducted a retrospective analysis of 259 patients who obtained ≥10 retrieved oocytes per cycle between June and December 2025， with a total of 3，578 mature oocytes included. A sibling oocyte study design was adopted to compare early embryo development indicators and Day 3 blastomere fusion between the sequential culture medium group and the single-step culture medium group， where the latter was further divided into 6 subgroups： OS-1 to OS-6. Results No statistically significant differences were observed between the two groups in the 2PN cleavage rate， Day 3 good-quality embryo rate， blastocyst formation rate， usable blastocyst rate， or clinical pregnancy rate （all P > 0.05）. Compared with the sequential culture group， the single-step culture group exhibited a lower high-quality blastocyst rate （31.36% vs. 39.80%， P < 0.001） and a higher Day 3 cell fusion rate （6.69% vs. 3.55%， P < 0.001）. Multivariate regression analysis demonstrated that single-step culture medium was independently associated with decreased odds of obtaining high-quality blastocysts （OR = 0.700， 95%CI： 0.571-0.859， P < 0.001）. Subgroup analysis yielded the following results： the OS-1 subgroup presented a reduced Day 3 usable embryo rate （P = 0.003）； the OS-3 and OS-4 subgroups showed decreased high-quality blastocyst rates （P = 0.004， P = 0.037 respectively）； the OS-5 subgroup had a lower Day 3 good-quality embryo rate （P = 0.045）. No statistically significant differences were detected between groups in the OS-2 and OS-6 subgroups（P > 0.05）. Conclusions Single-step culture media generally yield comparable early embryonic development outcomes to sequential culture media. However， certain single-step formulations exhibit slightly lower rates of high-quality blastocyst formation alongside higher rates of Day 3 embryonic cell fusion， indicating that individualized medium selection is required in clinical practice.

Objective To investigate the anti-inflammatory efficacy and the underlying molecular mechanisms of Thymosin α1 （Tα1） in a mouse model of necrotizing enterocolitis （NEC）. Methods Thirty 5-day-old specific pathogen-free （SPF） C57BL/6J mice were randomly divided into five groups： normal control group （GC）， necrotizing enterocolitis （NEC） model group， Tα1 treatment group （TF）， N-acetylcysteine （NAC） treatment group， and combined Tα1 and NAC treatment group （TF+NAC）. The NEC model was established via formula feeding combined with hypoxia stimulation and lipopolysaccharide （LPS） challenge. Starting from the fourth day of modeling， mice in each treatment group received daily intraperitoneal injections for 5 consecutive days. Intestinal injury was assessed via abdominal X-ray examination， hematoxylin-eosin （HE） staining， and fluorescein isothiocyanate-dextran 70kDa （FD70） intestinal permeability assay. The levels of pro-inflammatory cytokines including interleukin-6 （IL-6）， interleukin-17A （IL-17A） and tumor necrosis factor-α （TNF-α） were measured by enzyme-linked immunosorbent assay （ELISA）. The ratio of regulatory T cells （Treg） to T helper 17 cells （Th17） was analyzed by flow cytometry， and the expression levels of TLR4/MyD88/TRAF6/TRIF signaling pathway proteins were detected by Western blot. Results Compared with the GC group， the NEC group exhibited significant growth retardation， intestinal distension， pneumatosis intestinalis， and mucosal barrier damage， accompanied by increased pro-inflammatory cytokine concentrations， an imbalanced Treg/Th17 ratio， and upregulated expression of TLR4 signaling proteins （P < 0.05）. In contrast， the treatment groups showed attenuated intestinal injury， decreased pro-inflammatory cytokine concentrations， restored Treg/Th17 homeostasis， and downregulated expression of TLR4 signaling proteins （P < 0.05）. Notably， the combined treatment of TF and NAC exerted superior efficacy in alleviating inflammatory storms and correcting immune dysregulation （P < 0.05）. Conclusion Tα1 alleviates intestinal injury in NEC mouse models via inhibiting the TLR4 signaling pathway and correcting Treg/Th17 immune imbalance. Furthermore， the synergistic effect of Tα1 and cysteine offers a promising immunomodulatory strategy for the clinical management of NEC.