Cow’s milk protein allergy （CMPA） is an abnormal immune response triggered by cow′s milk proteins. Clinically， CMPA can be categorized into immediate-onset IgE-mediated， delayed-onset non-IgE-mediated， or mixed forms. Although several expert consensus statements on CMPA have been published in China， they often fail to clearly differentiate between IgE-mediated and non-IgE-mediated subtypes. Non-IgE-mediated CMPA is more prevalent in infants； however， due to the absence of specific clinical manifestations and standardized diagnostic approaches， its diagnosis and management remain significant clinical challenges. To facilitate the standardized diagnosis and management of non-IgE-mediated CMPA in infants， a multidisciplinary panel of experts convened by the Allergy Prevention and Control Professional Committee of the Chinese Preventive Medicine Association has developed the “Guidelines for Diagnosis and Nutritional Intervention of Mild to Moderate Non-IgE-Mediated Cow′s Milk Protein Allergy in Chinese Infants.” This article presents and interprets the key recommendations of the guideline， focusing on clinical features， diagnostic procedures， nutritional management， and complementary feeding strategies for infants with mild to moderate non-IgE-mediated CMPA.

Alzheimer's disease （AD） is a neurodegenerative disorder characterized by β-amyloid （Aβ） deposition and hyperphosphorylation of the Tau protein. Oxidative stress plays a pivotal role throughout its pathological progression. Recent studies have demonstrated that DNA methylation， a key epigenetic regulatory mechanism， interacts with oxidative stress to form a core network underlying AD pathogenesis. This review summarizes the molecular mechanisms through which aberrant DNA methylation in AD exacerbates oxidative damage by impairing antioxidant defenses， inducing mitochondrial dysfunction， and activating inflammatory pathways. Moreover， it examines the bidirectional interplay between oxidative stress and DNA methylation imbalance in AD： Oxidative stress depletes methyl donors， causes oxidative DNA lesions， and impairs the activity of epigenetic regulatory enzymes. The study aims to identify potential molecular diagnostic markers for early-stage AD and to provide novel insights and a theoretical basis for developing combined therapeutic strategies targeting both redox imbalance and epigenetic dysregulation.

Generalized anxiety disorder （GAD） is a highly prevalent psychiatric condition that imposes a substantial burden on individuals and society. Although various treatments are available， their efficacy remains inconsistent and often limited. In recent years， the rapid advancement of non-invasive brain stimulation （NIBS） technologies has opened new avenues for individualized and precise interventions in GAD， demonstrating promising clinical potential. This article provides a systematic review of the clinical applications and progress of NIBS techniques-including repetitive transcranial magnetic stimulation （rTMS）， transcranial direct current stimulation （tDCS）， transcutaneous auricular vagus nerve stimulation （taVNS）， and cranial electrotherapy stimulation （CES）in the treatment of GAD. Furthermore， it examines the underlying mechanisms through which these techniques modulate key brain regions， neurotransmitter systems， inflammatory responses， and neuroendocrine processes， aiming to establish a theoretical foundation for future clinical research and practice.

Objective Mechanism study of electroacupuncture on improving motor coordination in Parkinson′s disease mice model based on silent mating type information regulation 2 homolog 3/forkhead box protein O3/superoxide dismutase 2（SIRT3/FOXO3/SOD2） pathway. Methods A total of 66 C57BL/6 mice were divided into a control group （Ctrl， n = 15） and a model-establishment group （n = 51） using a random number table. The PD mouse model with impaired coordination was established by intraperitoneal injection of 1-methyl-4-phenyl-1，2，3，6-tetrahydropyridine （MPTP）. Forty-eight successfully MPTP-induced PD model mice were equally divided into four groups using a random number table： the model group （MPTP， n = 12）， the EA group （EA， n = 12）， the inhibitor group （3-TYP， n = 12）， and the inhibitor + EA group （3-TYP + EA， n = 12）.The Ctrl group was given an equal volume of normal saline. The MPTP group received intraperitoneal injection of MPTP （30 mg/kg） once a day for 7 consecutive days to establish the PD animal model.The EA group was given EA stimulation at the "Fengfu" （GV16） and "Taichong" （LR3） acupoints 2 hours after MPTP injection， once a day for 14 consecutive days.The 3-TYP group was given intraperitoneal injection of 3-TYP （10 mg/kg） 2 hours before MPTP injection. The 3-TYP + EA group received EA stimulation at the "Fengfu" （GV16） and "Taichong" （LR3） acupoints 2 hours after MPTP injection on the basis of the treatment for the 3-TYP group， once a day for 14 consecutive days. In addition， other mice not receiving EA were restrained for 15 minutes. The pole test and hanging test were used to evaluate the motor coordination of mice. Immunohistochemistry was employed to detect the expression of tyrosine hydroxylase （TH） in the midbrain substantia nigra of mice. Western blot was used to measure the protein levels of the SIRT3/FOXO3/SOD2 pathway in the midbrain substantia nigra. Flow cytometry was applied to detect changes in mitochondrial membrane potential （MMP） and reactive oxygen species （ROS） levels in the midbrain substantia nigra of mice. Results Compared with the Ctrl group， the MPTP group showed a significantly prolonged total time in the pole test （P < 0.01）， a significantly decreased score in the hanging test （P < 0.01）， a significantly reduced average optical density of TH in the midbrain substantia nigra （P < 0.01）， a significant down-regulation of SIRT3， FOXO3， and SOD2 contents in the midbrain substantia nigra （P < 0.01）， a significant decrease in MMP （P < 0.01）， and a significant increase in ROS levels （P < 0.01）.Compared with the MPTP group， the EA group exhibited a significantly shortened total time in the pole test （P < 0.01）， a significantly increased score in the hanging test （P < 0.01）， an increased average optical density of TH in the midbrain substantia nigra （P < 0.01）， a significant up-regulation of SIRT3 and SOD2 expressions （P < 0.01）， an increased FOXO3 content （P < 0.05）， a significant increase in MMP （P < 0.01）， and a significant decrease in ROS levels in the midbrain substantia nigra （P < 0.01）.There were no significant differences in all the above indicators between the 3-TYP group and the MPTP group （P > 0.05）. Compared with the EA group， the 3-TYP group had a prolonged total time in the pole test （P < 0.01）， a significantly decreased score in the hanging test （P < 0.01）， a reduced average optical density of TH in the midbrain substantia nigra （P < 0.01）， a significant down-regulation of SIRT3 and SOD2 expressions （P < 0.01）， a decreased FOXO3 content （P < 0.05）， a significant decrease in MMP （P < 0.01）， and a significant increase in ROS levels （P < 0.01）.Compared with the 3-TYP group， the 3-TYP + EA group had increased protein expressions of SIRT3 （P < 0.05）， while there were no significant differences in the other above-mentioned indicators （P > 0.05）. Conclusions EA can activate the SIRT3/FOXO3/SOD2 signaling pathway， inhibit the excessive accumulation of ROS， and alleviate mitochondrial oxidative stress， thereby protecting TH in the midbrain substantia nigra and improving motor coordination in PD model mice. However， EA cannot completely reverse the effect of the SIRT3 inhibitor.

Objective To investigate the clinical characteristics of depressive disorders in adolescents with non-suicidal self-injury （NSSI） behaviors and to analyze the impact mechanism of childhood trauma on NSSI through a psychological resilience-depression dual-pathway model. Methods A case-control study was conducted involving 99 participants aged 12 ~ 18 years， comprising 51 individuals with depression and NSSI （KD group）， 24 healthy controls （NOR1 group）， and 24 patients with depression but without NSSI （NOR2 group）. The Childhood Trauma Questionnaire （CTQ）， Resilience Scale for Chinese Adolescents （RSCA）， and the 24-item Hamilton Depression Rating Scale （HAMD-24） were administered to assess childhood trauma， psychological resilience， and depressive symptom severity， respectively. Structural equation modeling was used to examine the mediating role of psychological resilience and the moderating effect of depression severity in the relationship between childhood trauma and NSSI. Results In the KD group， 84.3% of participants reported experiencing childhood trauma， with emotional neglect （64.7%） and physical neglect （50.1%） being the most prevalent types. Emotional neglect （r = 0.582， P < 0.001） and physical abuse （r = 0.464， P = 0.002） were significantly associated with NSSI behaviors. Mediation analysis indicated that psychological resilience partially mediated the relationship between childhood trauma and NSSI， such that trauma exposure indirectly increased NSSI risk through reduced psychological resilience， with this indirect effect accounting for 45.7% （95% CI： 15.3% ~ 48.1%， P < 0.01）. Moderation analysis further revealed that the effect of trauma on NSSI was more pronounced among individuals with high levels of depression （HAMD-24 ≥ 20）， where the association was statistically significant （β = 0.603， P < 0.01）. Conclusions This study reveals that childhood trauma， particularly emotional neglect and abuse， is highly prevalent （> 84%） among adolescents exhibiting depressive symptoms and NSSI. A moderated mediation model was constructed and validated， demonstrating that childhood trauma not only directly predicts NSSI but also exerts an indirect effect through diminished psychological resilience， with depressive symptoms serving as a dual moderator in both the direct and indirect pathways. These findings offer a multi-targeted foundation for clinical interventions， highlighting the importance of systematic trauma screening， the promotion of psychological resilience， and the active management of depressive symptoms.

Objective To analyze the influence of perioperative sleep disorders on anesthesia recovery and postoperative pain in patients undergoing laparoscopic gynecological surgery under general anesthesia. Methods A total of 160 patients who underwent laparoscopic gynecological surgery at the hospital from March 2024 to March 2025 were retrospectively selected as research subjects. According to the preoperative Pittsburgh Sleep Quality Index （PSQI）， they were divided into the non-sleep-disorder （NSD） group （PSQI ≤ 5 points， n = 80） and the sleep-disorder （SD） group （PSQI > 5 points， n = 80）.The following aspects were compared between the two groups： anesthesia recovery indicators ［recovery time， modified Aldrete score， orientation recovery time， adverse reactions during the recovery period， total dosage of remifentanil， total dosage of propofol， minimum alveolar concentration （MAC） value of sevoflurane， time from drug discontinuation to extubation， intraoperative mean arterial pressure （MAP）， intraoperative heart rate （HR）， and rescue analgesia utilization rate］； pain indicators ［Visual Analogue Scale （VAS） score， opioid dosage， and number of patient-controlled analgesia （PCA） presses］. Moreover， multivariate linear regression， decision tree modeling， and mediation effect analysis were employed to explore the relationships among sleep quality， anesthesia recovery， and postoperative pain. Results The recovery time and orientation recovery time in the NSD group were shorter than those in the SD group （P < 0.05）， and the modified Aldrete score was higher （P < 0.05）. The total propofol dosage， intraoperative HR， and rescue analgesia utilization rate in the SD group were higher than those in the NSD group （P < 0.05）. The incidence of adverse reactions， VAS scores at various postoperative time points， opioid dosage， and number of PCA presses in the NSD group were all lower than those in the SD group （P < 0.05）. Multivariate regression analysis indicated that for every 1-point increase in PSQI， recovery time was prolonged by 0.63 minutes， orientation recovery time was delayed by 0.55 minutes， the modified Aldrete score decreased by 0.05 points， postoperative VAS score increased by 0.20 ~ 0.22 points， opioid dosage increased by 0.87 mg， and the number of PCA presses increased by 0.98 （P < 0.05）. The extended model demonstrated that after incorporating intraoperative factors， the predictive performance for recovery time （R² = 0.456） and postoperative pain （R² = 0.524） was significantly enhanced. Time from drug discontinuation to extubation， remifentanil dosage， and bispectral index （BIS） value were key predictive factors for recovery time； sevoflurane MAC value and MAP fluctuations made significant contributions to postoperative pain prediction. PSQI score maintained an independent predictive role in both models （β = 0.421/0.312）. Decision tree analysis confirmed that PSQI was the core factor for predicting anesthesia recovery and postoperative pain （importance： 51%）. Recovery time in patients with PSQI < 5.5 was significantly shorter than in those with PSQI ≥ 5.5 （18.68 minutes vs. 23.29 minutes）. The pain prediction model incorporating anesthesia recovery indicators exhibited better performance than the model without such indicators （R² = 0.391 vs. 0.336）.Mediation effect analysis revealed that the modified Aldrete score exerted a mild mediating effect between PSQI and postoperative pain （mediation proportion： 5.98%）. The direct effect of PSQI on pain accounted for 93.8% of the total effect， suggesting that sleep disorders mainly affect postoperative pain through other mechanisms. Conclusions Sleep disorders affect postoperative pain experience by prolonging anesthesia recovery time and reducing the modified Aldrete score. The direct effect is dominant， indicating that clinical practice should focus on sleep quality assessment and intervention to improve postoperative pain management.

Objective To evaluate the clinical efficacy of modified Suanzaoren decoction combined with auricular point pressing with beans in the treatment of insomnia during pregnancy， thereby providing a reference for clinical practice. Methods A total of 120 pregnant patients with insomnia were randomly assigned to either the control group （n = 60） or the treatment group （n = 60）. The control group received modified Suanzaoren decoction， whereas the treatment group received additional auricular point pressing with beans based on the same herbal treatment. The treatment duration was 4 weeks. Outcomes including clinical efficacy， TCM syndrome scores， sleep monitoring parameters （total sleep time， wake-up time， and awakening frequency）， PSQI scores， serum FPG levels， and neurotransmitter levels （DA， GABA， 5-HT， and NE） were assessed before and after intervention， along with the incidence of adverse reactions. Results The total effective rate in the treatment group was significantly higher than that in the control group （P < 0.05）. Following treatment， TCM syndrome scores， awakening time， awakening frequency， PSQI score， serum FPG， and NE levels were significantly reduced in both groups （P < 0.05）， while sleep duration and serum levels of DA， GABA， and 5-HT were significantly increased （P < 0.05）. These improvements were more pronounced in the treatment group （P < 0.05）. No significant difference was observed in the incidence of adverse reactions between the two groups （P > 0.05）. Conclusion The modified Suanzaoren decoction combined with auricular point pressing using beans demonstrates definite therapeutic efficacy in pregnant patients with insomnia， effectively alleviating sleep-related symptoms， reducing serum FPG levels， and modulating neurotransmitter release， thereby indicating considerable clinical application value.

Objective To investigate the role of junction plakoglobin （JUP） in high-grade serous ovarian cancer （HGSOC） and its influence on SET domain bifurcated 1 （SETDB1）. Methods Human HGSOC cell lines with stable JUP overexpression or knockdown were established. The impact of JUP on cell proliferation， invasion， and migration was evaluated in vitro using colony formation， Transwell invasion， and wound healing assays. A subcutaneous xenograft model in nude mice was generated to dynamically monitor tumor growth and peritoneal nodule development， thereby elucidating the role of JUP in tumoral proliferation and metastasis. Co-immunoprecipitation （Co-IP） assays were performed to identify downstream molecules regulated by JUP. RT-qPCR， Western blotting， and histone methyltransferase activity assays were utilized to validate the influence of JUP on SETDB1 expression and enzymatic activity. Furthermore， rescue experiments were conducted to assess whether reconstitution of SETDB1 could reverse the malignant phenotypes induced by JUP knockdown in HGSOC cells. Results JUP was significantly overexpressed in high-grade serous ovarian cancer （HGSOC） tissues （P < 0.000 1）， and patients with elevated JUP expression exhibited a poorer prognosis （P < 0.05）. In vitro experiments demonstrated that JUP overexpression enhanced tumor cell proliferation， invasion， and migration， whereas JUP knockdown suppressed these malignant phenotypes （P < 0.01）. In vivo studies further confirmed that JUP promoted tumor growth and peritoneal metastasis. Mechanistic analyses revealed that JUP directly interacts with SETDB1 and enhances its methyltransferase activity； notably， the oncogenic effects induced by JUP overexpression were reversed upon SETDB1 knockdown （P < 0.05）. Conclusion JUP promotes the malignant progression of HGSOC by directly binding to and modulating the enzymatic activity of SETDB1， highlighting its potential as a therapeutic target for HGSOC.

Objective To establish an efficient method for the isolation， culture， and purification of rat bone marrow mesenchymal stem cells （BMSCs）， while simultaneously investigating the biological characteristics of these cells. Methods The 3 ~ 4 weeks old male SD rats were sacrificed via cervical dislocation， followed by the sterile dissection of both femurs and tibiae. BMSCs from rats were separated and cultivated employing two techniques： the traditional marrow flush-out method and the optimized whole marrow adhesion method. When cell confluence reached 80%， the cells were digested for subculture and purified. Cellular morphology was observed under an inverted microscope； Colony formation and the colony-forming rate of BMSCs were assessed following Giemsa staining； Flow cytometric analysis was performed to identify specific surface markers （CD29 and CD45）； Cell proliferation capacity was measured using the CCK-8 assay， and growth curves from day 1 to day 8 after passaging were plotted； To assess osteogenic differentiation capability， BMSCs were directed toward the osteoblast lineage， and the differentiation efficacy was analyzed in the two groups through ALP staining with quantitative analysis and Alizarin Red staining followed by quantification； Additionally， adipogenic differentiation was induced in BMSCs， and the lipid accumulation capacity of the two groups was detected via Oil Red O staining and subsequent quantitative measurement. Results Compared to the control group， SD rat BMSCs isolated and purified in vitro using the modified and optimized whole bone marrow adherence method exhibited superior morphology， higher purity， and enhanced proliferation capacity. Furthermore， regarding cellular biological properties， BMSCs from the modified group showed a slight enhancement in osteogenic differentiation potential and a mild reduction in adipogenic differentiation capacity compared to those from the control group. Conclusion BMSCs derived from SD rats using the optimized whole marrow adhesion technique demonstrate superior morphological characteristics， enhanced proliferation ability， and optimal differentiation capability， thus qualifying as viable progenitor cells for tissue engineering purposes.

Objective To investigate the impact of a personalized positive end-expiratory pressure （PEEP） strategy， guided by bedside chest CT morphological features， on the outcomes and prognosis of patients with moderate to severe acute respiratory distress syndrome （ARDS）. Methods A prospective clinical controlled study was conducted， involving 92 patients with moderate to severe ARDS admitted to the intensive care unit of Changsha First Hospital between January 2023 and January 2025. Patients were randomly assigned to one of two groups using stratified randomization. The control group （n = 49） received ventilation according to the ARDSnet low PEEP strategy， while the experimental group （n = 43） was managed with a personalized PEEP strategy based on CT morphological characteristics-low PEEP for focal ARDS and high PEEP for diffuse ARDS. The primary outcome measure was 28-day all-cause mortality， while secondary outcomes included duration of mechanical ventilation， length of ICU stay， and indices of respiratory mechanics. Results There was no statistically significant difference in the 28-day mortality rate between the two groups （P > 0.05）. Compared with the control group， the experimental group showed significant improvements in lung compliance and oxygenation index （PaO₂/FiO?） in patients with moderate to severe ARDS， along with significant reductions in plateau pressure， inhaled oxygen concentration （FiO?）， and PEEP levels （all P < 0.05）. Additionally， the duration of mechanical ventilation was significantly shorter in the experimental group （P < 0.05）. However， there was no statistically significant difference in the length of ICU stay between the two groups （P > 0.05）. Conclusion A PEEP strategy guided by chest CT morphology does not significantly reduce mortality in patients with moderate to severe ARDS； however， it effectively improves respiratory mechanics and oxygenation， shortens mechanical ventilation duration， and provides valuable insights for ventilation management in these patients.

Objective To investigate the application of catheter-directed thrombolysis combined with various endovascular interventions in improving arteriosclerotic indices in patients with lower limb arteriosclerosis obliterans. Methods A total of 125 patients with lower limb arteriosclerosis obliterans admitted to the hospital between December 2021 and December 2024 were randomly assigned， using a random number table method， into a control group （n = 63， with 3 lost to follow-up， resulting in 60 evaluable cases） and an observation group （n = 62， with 2 lost to follow-up， resulting in 60 evaluable cases）. The control group received endovascular interventional therapy alone， whereas the observation group underwent catheter-directed thrombolysis prior to the same endovascular intervention. Both groups were followed up for 6 months post-intervention. Outcomes assessed included clinical efficacy at 6 months after treatment， Walking Impairment Questionnaire （WIQ） scores， Berg Balance Scale （BBS） scores， Visual Analogue Scale （VAS） scores， Rutherford classification， hemodynamic indices， arteriosclerosis index， nerve conduction velocity in the lower limbs， serological markers （measured before treatment and 6 months post-treatment）， and incidence of complications during follow-up. These outcomes were compared between the two groups. Results Six months after treatment， the total clinical effective rate in the observation group （93.33%） was significantly higher than that in the control group （78.33%） （P < 0.05）. Compared with pre-treatment levels， both groups showed improvements in walking distance， walking speed， and stair-climbing ability， with greater gains observed in the observation group （P < 0.05）. The Berg Balance Scale （BBS） scores increased in both groups， with a more pronounced improvement in the observation group （P < 0.05）. Additionally， the proportion of patients with Visual Analog Scale （VAS） scores and Rutherford classification exceeding grade 3 decreased， with a lower proportion in the observation group （P < 0.05）. The arterial lumen diameter increased in both groups， while blood flow volume and peak velocity improved more significantly in the observation group， along with a greater increase in ankle-brachial index （ABI） （P < 0.05）. Carotid intima-media thickness （IMT） decreased in both groups， with a greater reduction in the observation group； pulse wave velocity （PWV） slowed， and both motor and sensory nerve conduction velocities increased， with more favorable changes in the observation group （P < 0.05）. Serum levels of vascular endothelial growth factor （VEGF） increased in both groups， particularly in the observation group， while levels of endothelin-1 （ET-1）， high-sensitivity C-reactive protein （hs-CRP）， and tumor necrosis factor-α （TNF-α） decreased， with more marked reductions in the observation group （P < 0.05）. During the follow-up period， the overall complication rate in the observation group （3.33%） was significantly lower than that in the control group （15.00%） （P < 0.05）. Conclusions Endovascular interventional therapy following catheter-directed thrombolysis can stabilize hemodynamic parameters in patients with lower limb arteriosclerosis obliterans， modulate atherosclerotic markers， accelerate lower limb nerve conduction velocity， improve vascular endothelial function， reduce systemic inflammatory factor levels， enhance walking capacity and motor function， alleviate patient pain， and mitigate the degree of lower limb arterial ischemia. This combined approach demonstrates significant therapeutic efficacy and reduces the incidence of complications.

Objective To evaluate the impact of combining immunotherapy with hypofractionated radiotherapy or stereotactic body radiotherapy （SBRT） on survival outcomes in patients with lung metastases， and to analyze the efficacy and safety of this combined treatment approach. Methods Clinical data from 56 patients （104 lesions） with various pathological types of lung metastases who received hypofractionated radiotherapy or SBRT at The First Affiliated Hospital of Guangzhou Medical University between January 2021 and January 2023 were retrospectively analyzed. According to treatment strategy， patients were categorized into two groups： The combination group （hypofractionated radiotherapy or SBRT followed by immunotherapy， n = 24） and the non-combination group （hypofractionated radiotherapy or SBRT without immunotherapy， n = 32）. The primary endpoint was overall survival （OS）， while secondary endpoints included progression-free survival （PFS）， local control rate （LCR）， and safety. Survival outcomes were evaluated using the Kaplan-Meier method and Cox proportional hazards regression models. Additionally， the prognostic impact of concurrent extrapulmonary metastases under different treatment strategies was assessed. Results The primary tumors in the included patients were predominantly lung cancer （35/56， 62.5%）， followed by digestive system cancers （8/56， 14.3%） and head and neck cancers （6/56， 10.7%）. As of the data cutoff date for analysis （July 31， 2025）， the combination group demonstrated higher 2-year and 3-year overall survival （OS） rates compared to the non-combination group， indicating a trend toward improved survival； however， the difference did not reach statistical significance （2-year OS： 83.3% vs. 65.6%； 3-year OS： 59.8% vs. 55.8%； P = 0.337）. In exploratory analyses， patients in the non-combination group with concurrent extrapulmonary metastases had significantly worse survival outcomes than those with pulmonary-only metastases， with a median OS of 16 months versus not reached （HR = 3.343， 95% CI： 1.005 ~ 11.120， P = 0.049） and a median progression-free survival （PFS） of 8 months versus 26 months （HR = 3.136， 95% CI： 1.042 ~ 9.437， P = 0.042）. In contrast， in the combination group， the presence of extrapulmonary metastases did not significantly affect OS （HR = 1.099， 95% CI： 0.268 ~ 4.496， P = 0.891） or PFS （HR = 1.525， 95% CI： 0.558 ~ 4.167， P = 0.460）. The 2-year and 3-year LCRs were numerically higher in the combination group compared to the non-combination group （2-year： 95% vs. 91.2%； 3-year： 91.9% vs. 79.7%， P = 0.089）. Treatment was well tolerated， with a ≥ grade 2 acute radiation pneumonitis （ARP） incidence of 15.4%， and no grade 4 or higher ARP events were observed. Conclusions The combination of immunotherapy with hypofractionated radiotherapy or SBRT demonstrates a promising trend toward improved survival in patients with lung metastases. Notably， for patients who also have extrapulmonary metastases， this combined approach may yield survival outcomes comparable to those observed in patients with lung-limited disease alone. These findings offer valuable insights into optimizing treatment strategies for advanced-stage lung metastases.

Objective To identify risk factors for multidrug-resistant organism （MDRO） infections in patients with perianal abscesses and develop a nomogram-based predictive model to guide individualized clinical management.. Methods A total of 757 patients with perianal abscesses admitted to the Nanjing Hospital of Traditional Chinese Medicine between January 2022 and December 2023 were included in this study. Clinical data were systematically collected， and potential risk factors were identified through univariate and multivariate logistic regression analyses. Patients were randomly assigned to a training set （n = 530， 70%） or a validation set （n = 227， 30%） to develop and validate the nomogram prediction model. Results Among the 757 patients， 137 （18.1%） had MDRO infections， while 620 （81.9%） had non-MDRO infections. A total of 927 pathogenic strains were isolated， of which 298 （32.15%） were classified as MDROs. The predominant MDROs included Escherichia coli （149 strains， 50.00%）， extended-spectrum β-lactamase （ESBL）-producing organisms （68 strains， 22.82%）， and Streptococcus intermedius （27 strains， 9.06%）. Both univariate and multivariate logistic regression analyses revealed that a history of alcohol consumption， hypertension， and diabetes was significantly associated with MDRO infections （P < 0.05）. The nomogram model exhibited good discriminative ability， and the calibration curve demonstrated strong agreement between predicted probabilities and observed outcomes. Conclusions MDRO infections are commonly observed in patients with perianal abscess and are primarily attributed to Gram-negative bacteria. By incorporating key clinical indicators?such as a history of alcohol use， hypertension， and diabetes?the nomogram model developed in this study demonstrates strong predictive accuracy for identifying the risk of multidrug-resistant organism infection in these patients. This robust model can serve as a reliable quantitative tool to guide antimicrobial therapy and support clinical decision-making.

Objective To investigate the role of plasma aldosterone （ALD） in the development of left ventricular hypertrophy （LVH） in women with essential hypertension （EH）， and to develop a predictive model incorporating ALD and clinical parameters to improve early detection and risk stratification of LVH. Methods A total of 200 female patients with EH were enrolled and classified into the LVH group （n = 104） and the NLVH group （n = 96）. Clinical characteristics， laboratory parameters， ALD levels， and ambulatory blood pressure monitoring （ABPM） data were systematically collected. Spearman′s rank correlation coefficient was used to evaluate the association between ALD levels and left ventricular mass index （LVMI）. Multivariate logistic regression analyses were conducted to identify independent predictors of LVH， with three models constructed： Model 1 included ALD alone； Model 2 adjusted for ALD， diabetes， 24-hour systolic blood pressure （24hSBP）， nighttime SBP （nSBP）， blood pressure load （BPL）， and nighttime blood pressure decline （NBD）； Model 3 further incorporated ALD， diabetes， blood glucose （BG）， NT-proBNP， 24hSBP， 24-hour diastolic blood pressure （24hDBP）， and arterial stiffness index （ASI）. The discriminative performance of each model was assessed using receiver operating characteristic （ROC） curve analysis， with internal validation performed to ensure robustness. Results Compared with the NLVH group， the LVH group exhibited a higher prevalence of diabetes and significantly elevated levels of BG， NT-proBNP，24hSBP， 24hDBP， and ALD， along with a smaller NBD （all P < 0.05）. Spearman′s rank correlation analysis revealed a statistically significant positive correlation between ALD and LVMI （r = 0.478， P < 0.001）. In multivariate logistic regression analysis， ALD remained an independent predictor of LVH （OR = 1.014， P = 0.002）， after adjusting for other significant variables including diabetes， BG， NT-proBNP， 24hSBP， 24hDBP， and ASI. The combined predictive model （Model 3） demonstrated the highest discriminative ability （AUC = 0.852； Hosmer?Lemeshow test P > 0.05）， surpassing models based on single predictors. Internal bootstrap validation confirmed excellent calibration and robustness of the model′s predictive performance. Conclusions Elevated plasma aldosterone concentration is an independent risk factor for LVH in women with essential hypertension. A multimodal predictive model that integrates aldosterone levels， clinical parameters， and dynamic blood pressure measurements can substantially enhance the accuracy of LVH prediction， offering a reliable approach for individualized management and early intervention in female patients with hypertension.

Objective To investigate the effect of ozone autohemotherapy on serum lipoprotein（a） ［Lp（a）］，sleep quality，and heart rate variability in postmenopausal patients with hypercholesterolemia. Methods This study is a prospective cohort study. A total of 100 postmenopausal female patients diagnosed with hypercholesterolemia during health check-ups at the South Lake Campus of Wuhan Wuchang Hospital between August 2024 and May 2025 were selected. They were randomly divided into a control group and a treatment group，with 50 patients in each group. Two patients dropped out of the control group，and four patients dropped out of the treatment group. The control group received atorvastatin calcium tablets，while the treatment group received ozone autohemotherapy in addition to the treatment in the control group. The treatment lasted for 10 days per cycle，and both groups were treated and observed for one month. The levels of Lp（a），total cholesterol （CHO），high-density lipoprotein cholesterol （HDL-C），low-density lipoprotein cholesterol （LDL-C），triglycerides （TG），uric acid （UA），homocysteine （Hcy），and fasting plasma glucose （FPG），as well as Pittsburgh Sleep Quality Index （PSQI） scores and heart rate variability were compared before and after treatment between the two groups. Correlation analysis was conducted to evaluate the relationship between Lp（a），PSQI scores，and heart rate variability after treatment in both groups，along with the incidence of adverse reactions. Results After treatment，the serum Lp（a），CHO，and LDL-C levels in the treatment group were significantly lower than before treatment （P < 0.01 or 0.05），but no statistically significant difference was found between the two groups （P > 0.05）. The PSQI scores in both groups were significantly reduced compared to before treatment，with the treatment group showing a more significant decrease than the control group （P < 0.05）. In the treatment group，standard deviation of the averages of 5-minute RR interval （SDANN）， standard deviation of RR interval （SDNN）， and the root mean square of the difference between adjacent RR interval （rMSSD） were significantly higher compared to both before treatment and the control group at the same time，with statistical significance （P < 0.01 or 0.05）. After treatment， there was no correlation between Lp（a） levels and SDANN， SDNN， or rMSSD. PSQI scores were negatively correlated with SDANN， SDNN， and rMSSD （P < 0.01）. Conclusions Ozone autohemotherapy has a regulatory effect on lipid metabolism and autonomic nervous function in postmenopausal women. The improvement in autonomic nervous function may be associated with the enhancement of sleep quality.

Objective To investigate the impact of deltoid ligament reconstruction using suture anchors on multidimensional motor function in patients with ankle fractures combined with ligament injuries. Methods A retrospective cohort study included 210 patients undergoing open reduction and internal fixation （ORIF） for ankle fractures with confirmed DL injuries between March 2023 and March 2024. Based on intraoperative management of the DL， patients were allocated to a reconstruction group （received suture anchor-based DL reconstruction， n = 110； 4 lost to follow-up） or a control group （ORIF alone without DL reconstruction， n = 100； 2 lost to follow-up）. Outcomes assessed preoperatively and at 3， 6， and 12 months postoperatively included： 6DOF ankle motion parameters （internal/external rotation， dorsiflexion/plantarflexion， inversion/eversion， superior/inferior translation， medial/lateral translation， anterior/posterior translation）， American Orthopaedic Foot & Ankle Society （AOFAS） scores， visual analogue scale （VAS） pain scores， and radiographic parameters （medial clear space， talar tilt angle）. Clinical efficacy at 12 months and postoperative complication rates were also compared. Results The reconstruction group demonstrated significantly longer operative times， greater intraoperative blood loss， and longer hospital stays compared to the control group （all P < 0.001）. At 12-month follow-up， the excellent and good rate （based on AOFAS） was significantly higher in the reconstruction group （93.40% vs. 81.63%， P < 0.05）. While all parameters improved significantly over time in both groups， the reconstruction group exhibited significantly greater improvements in all 6DOF motion parameters， higher AOFAS scores， and lower VAS scores at all postoperative time points （all P < 0.001）. Radiographically， the reconstruction group achieved significantly better restoration of the medial clear space and talar tilt angle at all postoperative assessments （all P < 0.001）. Postoperative complication rates did not differ significantly between the groups （P > 0.05）. Conclusion For patients with ankle fractures combined with deltoid ligament injuries， suture anchor-based anatomical reconstruction of the deltoid ligament effectively restores multidirectional ankle kinematics， improves functional outcomes as measured by the AOFAS score， alleviates pain， and facilitates radiographic reduction， without increasing the risk of postoperative complications， thereby representing a safe and effective treatment strategy.

Objective To develop and validate an interpretable machine learning model based on bedside lung and diaphragm ultrasound for preoperative prediction of pulmonary dysfunction in patients undergoing gastrointestinal tumor surgery. Methods In this prospective study， data from 424 patients （June 2021?December 2023） were used for model development， with external validation conducted on an independent cohort of 101 patients （January 2024-December 2024）. Clinical variables， PFTs results， and ultrasound parameters （LUS score， diaphragmatic excursion， and thickening fraction） were collected. Three feature selection methods-Least Absolute Shrinkage and Selection Operator （LASSO）， Support Vector Machine Recursive Feature Elimination （SVM-RFE）， eXtreme Gradient Boosting Recursive Feature Elimination （XGBoost-RFE）- were employed to identify key predictors. Five machine learning algorithms were trained and evaluated using 5-fold cross-validation. The optimal model was assessed based on the area under the receiver operating characteristic curve （AUC）， accuracy， sensitivity， specificity， calibration， and decision curve analysis. SHapley Additive exPlanations （SHAP） analysis was applied to enhance model interpretability. Results The prevalence of preoperative pulmonary dysfunction was 36.8%. Three key predictors were consistently identified： diaphragmatic excursion during deep breathing ［D-DE （4.26 cm vs. 5.05 cm， P < 0.001）］， LUS score ［LUSs （4 vs. 1， P < 0.001）］， and diaphragmatic thickening fraction during deep breathing ［D-DTF （39.83% vs. 71.80%， P < 0.001）］. The Support Vector Machine （SVM） model demonstrated superior generalizability， achieving an AUC of 0.867 on the internal test set （accuracy of 80.0%， sensitivity of 81.8%， specificity of 79.4%）. External validation confirmed its robust performance， with an AUC of 0.934 （95% CI： 0.881 ~ 0.987） and an accuracy of 88.0%. SHAP analysis revealed D-DTF as the most influential protective factor. Conclusion An interpretable SVM model integrating D-DE， LUSs， and D-DTF accurately predicts preoperative pulmonary dysfunction in patients with gastrointestinal tumors， offering a non-invasive， bedside-compatible new approach for preoperative risk assessment.

Objective To analyze alterations in pelvic floor structure among patients with pelvic floor dysfunction （PFD） using perineal real-time three-dimensional ultrasound and to investigate the associations with serum levels of relaxin， connective tissue growth factor （CTGF）， and soluble microfibril-associated protein 4 （sMFAP4）. Methods The clinical data of 102 puerperae diagnosed with PFD at 42 ~ 60 days postpartum between August 2022 and July 2025 were retrospectively reviewed （PFD group）. Based on the severity of pelvic organ prolapse， the patients were further classified into a mild （Stage Ⅰ） subgroup （n = 43） and a moderate （Stage Ⅱ） subgroup （n = 59）. Additionally， 32 puerperae without PFD who underwent routine postpartum examinations during the same period were enrolled as the control group. Fasting peripheral cubital venous blood samples were collected on the day of examination to measure serum levels of relaxin， CTGF， and sMFAP4， and perineal real-time three-dimensional ultrasound was performed to evaluate pelvic floor structural parameters. The differences in these ultrasound parameters and serum biomarker levels were compared across the three groups. Pearson correlation analysis was employed to assess the association between perineal real-time three-dimensional ultrasound parameters and serum levels of relaxin， CTGF， and sMFAP4 in the PFD group. To account for potential confounding factors， multivariate linear regression analysis was subsequently performed to further examine these associations. Results There were no significant differences in ultrasound-based pelvic floor parameters， such as levator hiatus area at rest， among the three groups （P > 0.05）. However， the levator hiatus area during maximal Valsalva maneuver， as well as serum levels of relaxin and CTGF， were significantly higher in the PFD grade Ⅱ subgroup compared to both the PFD grade Ⅰ subgroup and the control group （P < 0.05）. Moreover， these parameters were also elevated in the PFD grade Ⅰ subgroup relative to the control group （P < 0.05）. Serum sMFAP4 levels were significantly lower in the PFD Ⅱ subgroup compared to both the PFD I subgroup and the control group （P < 0.05）， and were also lower in the PFD I subgroup than in the control group （P < 0.05）. Pearson correlation analysis showed that in the PFD group， the levator hiatus area during maximum Valsalva maneuver was significantly positively correlated with serum relaxin and CTGF levels （r = 0.655， r = 0.721， P < 0.05）， and significantly negatively correlated with serum sMFAP4 （r = -0.493， P < 0.05）. Multivariate linear regression analysis revealed that， after adjusting for potential confounding factors?including age， gestational age at delivery， time from postpartum to examination， body mass index， parity （primipara vs. multipara）， and neonatal birth weight—the levator hiatus area during maximal Valsalva maneuver remained significantly positively associated with serum relaxin （β = 0.312， 95%CI： 0.070 ~ 0.596， P < 0.05） and CTGF （β = 0.972， 95% CI： 0.571 ~ 1.682， P < 0.05）， and significantly negatively correlated with sMFAP4 （β = -0.352， 95% CI： -0.614 ~ -0.102， P < 0.05）. Conclusion Perineal real-time three-dimensional ultrasound imaging of puerperal women with PFD revealed a significantly increased area of the levator hiatus during maximal Valsalva maneuver， which was correlated with serum levels of relaxin， CTGF， and sMFAP4， offering potential insights for clinical management strategies.

Objective To investigate the potential causal relationship between 35 blood and urine markers and bone mineral density （BMD） at different skeletal sites using a two-sample Mendelian randomization design. Methods Genetic instruments （single-nucleotide polymorphisms， SNPs） associated with the 35 biomarkers were selected from the UK Biobank （UKB）. GWAS aggregate data for bone mineral density were obtained from the Osteoporosis Genetic Factors Consortium （GEFOS）. The inverse-variance weighted （IVW） method served as the primary analysis， supplemented by the weighted median， simple median， and MR-Egger methods. Sensitivity analyses， including tests for pleiotropy and heterogeneity， were performed to ensure robustness. Furthermore， the significant findings were validated in independent European GWAS datasets. Results IVW results showed that apolipoprotein B was negatively associated with heel BMD （OR = 0.98， 95%CI： 0.97 ~ 1.00， P = 0.027）. There may be a causal relationship between blood phosphorus and bone mineral density of femoral neck （OR = 1.09，95%CI： 1.03 ~ 1.15， P = 0.003）； Elevated blood calcium levels were potentially causally linked to reduced BMD in the skull （OR = 0.90， 95% CI： 0.85 ~ 0.95， P = 1.75 × 10??） and lumbar spine （OR = 0.92， 95% CI： 0.86 ~ 0.98， P = 0.007）. We also found blood urea nitrogen， glomerular filtration rate， apolipoprotein B， triglycerides， and total protein also have potential correlations with bone mineral density， and the P-values are all less than 0.05. MR-Egger regression suggests that the above causal association is not affected by horizontal pleiotropy， and weighted median method and simple median method can obtain results similar to IVW. All these biomarker-BMD associations were replicated in the validation cohort. Conclusions This large-scale two-sample MR study systematically identifies potential causal effects of specific biomarkers on site-specific BMD. The findings suggest that higher apolipoprotein B may reduce heel BMD， elevated blood phosphorus might help maintain femoral neck BMD， and increased blood calcium could be associated with lower BMD in the skull and lumbar spine.

Objective To systematically evaluate the causal relationships between oral microbiota， circulating metabolites， and biliary tract cancer （BTC） using Mendelian randomization （MR） and mediation analysis， and to elucidate the mediatory role of metabolites. Methods Using two-sample bidirectional Mendelian randomization and mediation analysis， we analyzed data from the China National GeneBank Life Data Platform and the BioBank Japan. Primary causal inference was based on inverse variance weighting （IVW）， supplemented by Bayesian weighted MR， linkage disequilibrium score regression， reverse MR， and sensitivity analyses. Results Thirteen salivary microbial taxa （e.g.， Prevotella seregens mgs 811， P = 0.013， OR = 2.387） and nineteen tongue dorsum microbial taxa （e.g.， Eikenella corrodens mgs 3538， P = 0.015， OR = 2.635） demonstrated significant associations with BTC risk. Concurrently， direct bilirubin （OR = 1.768） and lead （OR = 2.448） were identified as risk factors， whereas manganese （OR = 0.509） and citrulline （OR = 0.440） were protective factors. Mediation analysis revealed that three blood metabolites indirectly mediated the effects of five bacterial taxa on BTC， with a maximum mediation proportion reaching 10.3%. Conclusion This study demonstrates causal associations among oral microbiota， circulating metabolites， and BTC， thereby providing a theoretical foundation for precision prevention and treatment strategies rooted in the microbiota-metabolite axis.

Objective To evaluate the clinical efficacy of combining herbal fumigation （Xiaoqinglong Decoction） and sharp hook needle therapy on the basis of mometasone furoate nasal spray in treating allergic rhinitis with lung?qi deficiency and cold syndrome. Methods A randomized controlled trial was conducted. A total of 144 patients with allergic rhinitis of lung?qi deficiency and cold syndrome， treated at the Beibei Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Chinese Medicine from January to July 2025， were enrolled. Patients were divided into： Control group （mometasone furoate nasal spray）， Fumigation group （mometasone furoate nasal spray + herbal fumigation）， Hook needle group （mometasone furoate nasal spray + sharp hook needle）， and Combination group （mometasone furoate nasal spray + herbal fumigation + sharp hook needle）. Mometasone furoate nasal spray was administered twice daily， 2 sprays per nostril each time， for 14 days. Herbal fumigation was applied for 6 days， followed by a 2-day break， then another 6 days， totaling 14 days. Sharp hook needle therapy was performed once on the day of enrollment and again on day 8， totaling 2 sessions. The corresponding procedures in the other three groups followed the same schedule as the Combination group. Serum levels of interleukin-4 （IL-4）， interleukin-5 （IL-5）， interleukin-13 （IL-13）， immunoglobulin E （IgE）， thymic stromal lymphopoietin （TSLP）， and interferon-gamma （IFN-γ） were measured by enzyme-linked immunosorbent assay （ELISA） before and after treatment. The distribution degree of eosinophils （EOS） in nasal secretions and subjective symptom scores were also assessed. Results After treatment， serum levels of IL-4， IL-5， IL-13， IgE， TSLP， EOS distribution scores， and subjective symptom scores decreased significantly in all four groups compared to before treatment （P < 0.05）. The Combination group showed significantly greater reductions in serum inflammatory factor levels， TNNSS， and VAS scores compared to the other three groups （P < 0.01）， and greater reductions in EOS distribution scores， TNSS， and RQLQ scores compared to the Control group （P < 0.05）. Serum IFN-γ levels increased after treatment in the Combination， Fumigation， and Hook needle groups （P < 0.05）， while no statistically significant change in IFN-γ was observed in the Control group before and after treatment （P > 0.05）. Conclusion The combination of herbal fumigation （Xiaoqinglong Decoction） and sharp hook needle therapy on the basis of mometasone furoate nasal spray is safe and effective in regulating inflammatory cytokine levels and alleviating subjective symptoms in patients with allergic rhinitis of lung?qi deficiency and cold syndrome.

The rapid evolution of modern lifestyles has led to increasing public demand for proactive health interventions and the effective management of major chronic diseases. Traditional health management approaches have demonstrated limitations in addressing diverse and complex health needs， whereas digital therapeutics powered by multimodal large language models present transformative opportunities for advancing intervention strategies in chronic disease care. By integrating big data， artificial intelligence， and other cutting-edge information technologies， digital therapeutics deliver personalized， remote， and data-driven solutions that enhance the prevention， monitoring， and management of major chronic conditions. These innovations not only improve clinical outcomes but also optimize the allocation of healthcare resources and elevate patients′ quality of life. Multimodal large language models， acting as "digital health assistants，" enable intelligent integration of text and visual data to support medical image interpretation， real-time health monitoring， and conversational clinical decision-making for both clinicians and patients. This paper aims to investigate the integration of multimodal large language models into digital therapeutics for proactive health management， examining their applications， current domestic and international research advancements， existing challenges， and future development trends， thereby offering theoretical insights and practical guidance for the advancement of proactive healthcare systems.