Objective To investigate the expression changes of heat shock protein beta-1 （HSPB1） during myocardial injury and its regulatory role in the maturation process of transforming growth factor-β1 （TGF-β1）. Methods Publicly accessible cardiac single-cell transcriptomic datasets， an isoproterenol （ISO）-induced mouse myocardial injury model， and H9c2 cell experiments were integrated to evaluate the expression changes of HSPB1. The overexpression of HSPB1 and the Cys137 mutation were employed to assess their impacts on pro-TGF-β1， mature TGF-β1， and the Smad signaling pathway. Molecular docking and bidirectional co-immunoprecipitation （Co-IP） assays were carried out to analyze the interaction between HSPB1 and pro-TGF-β1. Results Public cardiac single-cell transcriptomic data have demonstrated that HSPB1 is expressed in multiple cardiac cell populations， with relatively higher expression levels in cardiomyocytes. In comparison with the control group， ISO treatment led to a reduction in the left ventricular ejection fraction （LVEF） in mice from （95.20 ± 2.82）% to （82.28 ± 3.05）% and （63.18 ± 4.20）%， as well as a decrease in the left ventricular fractional shortening （LVFS） from （69.45 ± 8.32）% to （48.66 ± 3.16）% and （38.32 ± 2.23）% （all P < 0.001）. This was accompanied by aggravated myocardial fibrosis and cardiomyocyte hypertrophy. Immunohistochemistry and Western blot analyses indicated that HSPB1 expression was significantly up-regulated in myocardial tissue after 14 days of ISO treatment （P = 0.000 4 and P < 0.000 1， respectively）. H9c2 cell experiments revealed that， under ISO stimulation， overexpression of wild-type HSPB1 （HSPB1-WT） increased pro-TGF-β1 levels， while reducing the mature TGF-β1/pro-TGF-β1 ratio， partially decreasing mature TGF-β1 levels， and lowering p-Smad2/3 levels （vs. ISO group， P = 0.037 5， 0.049 9， and 0.002 1， respectively）. These effects were markedly attenuated in the Cys137 mutant， with related indicators significantly elevated compared with the HSPB1-WT group （P = 0.000 1， 0.001 8， and 0.000 6， respectively）. Molecular docking analysis suggested a potential interaction interface between HSPB1 and pro-TGF-β1. Bidirectional Co-IP further confirmed the interaction between the two proteins， whereas the Cys137 mutation weakened their binding signal. Conclusions HSPB1 may interact with pro-TGF-β1 via its redox-sensitive residue Cys137 and participate in restricting its excessive maturation process， thus modulating the TGF-β1/Smad signaling activity. This study offers a novel molecular perspective for comprehending the fine-tuned regulation of myocardial fibrosis-related signaling pathways.

Objective To explore the molecular mechanism by which F-box/leucine-rich repeat protein 4 （FBXL4） inhibits oxidative stress and apoptosis， and prevents cerebral ischemia-reperfusion injury （CIRI） induced by cardiopulmonary resuscitation （CPR） after cardiac arrest （CA） through regulating dynamin-related protein 1 （Drp1）-mediated mitochondrial dynamics. Methods A total of 48 male SD rats were randomly divided into 4 groups， with 6 rats in each group （n = 6）： Control group， Control + FBXL4 overexpression （OE-FBXL4） group， CA/CPR group， and CA/CPR + OE-FBXL4 group. Survival analysis was also conducted， with 6 cases in each group. The rats were sacrificed at 24 h after the return of spontaneous circulation （ROSC） for sampling. The neurological deficit score （NDS） and the 7-day survival rate were detected. The expressions of FBXL4 and Drp1 mRNA and proteins were determined by RT-qPCR and Western blot. The expressions of mitochondrial dynamics proteins were measured by Western blot. The interaction between FBXL4 and Drp1 was verified by the co-immunoprecipitation method. The pathology of brain tissues was examined by HE staining and Nissl staining. The ultrastructure of mitochondria was observed using a transmission electron microscope. The levels of malondialdehyde （MDA）， superoxide dismutase （SOD）， glutathione （GSH）， and catalase （CAT） were measured by a biochemical method to evaluate the oxidative stress level. The expressions of apoptosis-related proteins ［B cell lymphoma-2 associated X protein （Bax）， B cell lymphoma-2 （Bcl-2）， cysteine aspartase peptidases （Caspase）-3/8］ were measured by Western blot. Results （1） When compared to the Control group， the Neurological Deficit Score （NDS） in the CA/CPR group was significantly lower （P < 0.01）， and the 7-day survival rate was also reduced. In the brain tissues， the expressions of FBXL4 mRNA and protein were significantly down-regulated （all P < 0.01）， while the expressions of Drp1， Fis1， and MFF were significantly up-regulated （all P < 0.01）， and the expressions of OPA1， MFN1， and MFN2 were significantly down-regulated （all P < 0.01）. HE and Nissl staining results indicated that in the cortex and the CA1 and CA3 regions of the hippocampus， neurons were arranged in a disordered manner， with cell body atrophy， dissolution of Nissl bodies， and a decreased number of surviving neurons. Transmission electron microscopy （TEM） revealed mitochondrial swelling， vacuolization， cristae fracture， and fragmentation. The content of MDA was increased （P < 0.01）， whereas the activities of SOD， GSH， and CAT were decreased （all P < 0.01）. The Bax/Bcl-2 ratio was elevated （P < 0.01）， and the expressions of Caspase-3 and Caspase-8 were increased （both P < 0.01）. （2） In comparison with the CA/CPR group， the Neurological Deficit Score （NDS） was significantly elevated in the CA/CPR + OE-FBXL4 group （P < 0.01）， and the 7-day survival rate was also significantly increased. The expression of the FBXL4 protein was at a high level. The levels of Drp1， Fis1， and MFF proteins decreased （all P < 0.01）， while the levels of OPA1， MFN1， and MFN2 proteins increased （all P < 0.01）. HE and Nissl staining indicated an improvement in neuronal morphology， a reduction in the number of degenerated and necrotic cells， and an increase in the number of survived neurons. Transmission electron microscopy （TEM） revealed the recovery of the mitochondrial pipe-network structure and a clear and complete cristae structure. The content of MDA decreased （P < 0.01）， and the activities of SOD， GSH， and catalase （CAT） increased （all P < 0.01）. The Bax/Bcl-2 ratio decreased （P < 0.01）， and the expressions of Caspase-3 and Caspase-8 decreased （both P < 0.01）. （3） A Co-IP experiment confirmed a protein-protein interaction between FBXL4 and Drp1. The formation amount of the FBXL4-Drp1 complex in the Control + OE-FBXL4 group was significantly higher than that in the Control group （P < 0.01）. The formation amount of the FBXL4-Drp1 complex decreased in the CA/CPR group， and the binding amount was significantly restored in the CA/CPR + OE-FBXL4 group. Conclusions FBXL4 serves as a crucial protective regulator against brain injury following CA/CPR. The overexpression of FBXL4 can restore mitochondrial dynamic balance by targeting Drp1， thus suppressing oxidative stress and neuronal apoptosis. Moreover， the further up-regulation of the Nrf2/HO-1 pathways may be synergistically involved in the antioxidant protection provided by FBXL4.

Objective To investigate the predictive value of remnant cholesterol （RC） for intracoronary thin-cap fibroatheroma （TCFA） in patients with acute coronary syndrome （ACS） and analyze its relationship with plaque vulnerability features. Methods A total of 186 patients who were hospitalized for chest pain or suspected myocardial ischemia and underwent coronary angiography at Heze Hospital Affiliated to Shandong First Medical University from January 2024 to December 2025 were retrospectively enrolled. These patients were divided into an ACS group （n = 117） and a non-ACS group （n = 69） based on clinical and angiographic findings. All ACS patients underwent optical coherence tomography （OCT） and were further classified into a TCFA group （n = 49） and a non-TCFA group （n = 68）. Clinical data and lipid profiles were compared among the groups. Multivariable logistic regression was employed to identify independent factors for intracoronary TCFA， ROC curve analysis was used to evaluate the predictive value of RC， and Spearman rank correlation was utilized to assess the associations between RC and OCT-derived plaque features. Results Total cholesterol （TC）， low-density lipoprotein cholesterol （LDL-C）， remnant cholesterol （RC）， and high-density lipoprotein cholesterol （HDL-C） exhibited significant differences between the ACS and non-ACS groups （P < 0.05）. Among ACS patients， the TCFA group significantly differed from the non-TCFA group in terms of the proportions of patients with a history of smoking and diabetes mellitus， as well as the levels of TC， LDL-C， and RC （P < 0.05）. Multivariable analysis revealed that diabetes， smoking， elevated LDL-C， and elevated RC （odds ratio ［OR］ = 2.917， 95% confidence interval ［CI］： 1.407 - 6.048） were independent risk factors for intracoronary TCFA （P < 0.05）. Receiver operating characteristic （ROC） curve analysis demonstrated that the area under the curve （AUC） of RC for predicting intracoronary TCFA was 0.702 （95%CI： 0.600 ? 0.803）， with an optimal cutoff value of 0.975 mmol/L， a sensitivity of 0.653， and a specificity of 0.794. Spearman rank correlation analysis indicated that RC was positively correlated with the maximum lipid arc and macrophage infiltration （r_s = 0.438 and 0.248， respectively； P < 0.05）， and negatively correlated with the thinnest fibrous cap thickness and minimum lumen area （MLA） （r_s = -0.369 and -0.342， respectively； P < 0.05）. Conclusions Elevated RC is an independent factor associated with intracoronary TCFA in patients with ACS and possesses a certain predictive value for TCFA. It is also correlated with features of plaque vulnerability， such as a thinner fibrous cap， a larger lipid arc， a smaller MLA， and increased macrophage infiltration. RC can serve as a reference for the risk stratification of high-risk coronary plaques in patients with ACS.

Objective To compare the short-term neurological prognosis and rebleeding risk among patients with supratentorial hypertensive intracerebral hemorrhage （HICH） who were treated with neuroendoscopic hematoma evacuation （neuroendoscopy group）， soft-channel puncture drainage with urokinase infusion （puncture group）， and craniotomy for hematoma evacuation （craniotomy group）. Methods A total of 384 patients with supratentorial HICH who were admitted to the Department of Neurosurgery， Huai'an First People's Hospital Affiliated to Nanjing Medical University between January 2021 and December 2025 were retrospectively enrolled. These patients were assigned to the craniotomy group （n = 121）， neuroendoscopy group （n = 107）， and puncture group （n = 156） based on the surgical modality. The inclusion criteria were a hematoma volume ranging from 30 to 80 mL and an admission Glasgow coma scale （GCS） score between 5 and 12. Three-category propensity score overlap weighting （PS-OW） was employed to balance the baseline characteristics across the groups. The primary outcome was a poor short-term prognosis， which was defined as a modified Rankin scale （mRS） score of 4 or higher at the time of discharge. Secondary outcomes included the rebleeding rate， the GCS score at discharge， the length of hospital stay， and the total hospitalization cost. Results After weighting， the baseline covariates were well-balanced among the three groups （all absolute standardized mean differences < 0.1）. The weighted event rate of poor prognosis in the craniotomy group was 22.8%， which was higher than the 11.0% in the neuroendoscopy group and the 11.5% in the puncture group. When compared with the neuroendoscopy group， the craniotomy group exhibited a significantly higher risk of poor prognosis （odds ratio ［OR］=2.389， 95%CI： 1.029 - 5.545， P = 0.043）. A similar trend was noted when comparing the craniotomy group with the puncture group （OR = 2.280， 95%CI： 0.982 - 5.290， P = 0.055）. No statistically significant difference in the rebleeding rate was detected among the three groups. The craniotomy group had the longest hospital stay and the highest total cost， whereas the puncture group had the lowest. The neuroendoscopy group presented a slightly better GCS score at discharge than the craniotomy group. Conclusions In the overlapping population eligible for all three surgical modalities， craniotomy was associated with a poorer short-term neurological prognosis and a greater medical burden compared with minimally invasive approaches. Meanwhile， no clinically significant difference in rebleeding risk was observed among the three procedures.

Objective To explore the independent factors associated with early acute kidney injury （AKI） in patients with traumatic brain injury （TBI）， construct and validate a nomogram prediction model， and compare its discriminative efficacy with that of random forest and XGBoost models. Methods Clinical data of TBI patients admitted to the Affiliated Hospital of Xuzhou Medical University from January 2023 to December 2025 were retrospectively collected. The patients were then divided into the AKI group and the non-AKI group according to whether AKI occurred within 48 hours after admission. Univariate and multivariate logistic regression analyses were employed to identify the independent factors associated with early AKI. Subsequently， a nomogram was constructed based on the multivariate model. In addition， random forest and XGBoost models were developed， and the discriminative efficacy of these three models was compared through 5-fold cross-validation. Results A total of 368 patients with TBI were included， among whom 54 （14.7%） developed AKI. Multivariate logistic regression analysis demonstrated that age， blood transfusion， mechanical ventilation， systemic infection， and coagulation dysfunction score were independently associated with early AKI， whereas the Glasgow Coma Scale （GCS） score served as a protective factor （all P < 0.05）. The nomogram presented excellent calibration， with a mean absolute error of 0.034. Decision curve analysis suggested potential clinical benefits across low-to-moderate threshold probabilities. The 5-fold cross-validation area under the curve （AUC） values were 0.862 for the logistic model， 0.870 for the random forest model， and 0.852 for the XGBoost model. According to DeLong tests， there were no statistically significant differences among the three models. SHAP analysis disclosed the relative contribution and importance ranking of each variable. Conclusions The logistic nomogram model， which is based on age， GCS score， blood transfusion， mechanical ventilation， systemic infection， and coagulation dysfunction score， demonstrated excellent discrimination， calibration， and significant potential clinical reference value. It can offer a reliable reference for the early identification of AKI risk and the individualized management of TBI patients in neurosurgical practice. Considering that this was a single-center retrospective study with internal validation， the model still needs to be further validated in multicenter prospective cohorts.

Objective To investigate the effect of NEDD4L on the proliferation and apoptosis of acute myeloid leukemia （AML） cells and its underlying mechanism via the regulation of the Wnt/β-catenin pathway. Methods Stable NEDD4L-overexpressing and NEDD4L-knockdown Kasumi-1 and U937 cell lines were successfully established via lentiviral transduction technology. The efficiency of NEDD4L overexpression and knockdown was rigorously verified by RT-qPCR and Western blot. Cell proliferation was accurately assessed using the CCK-8 assay， and apoptosis was precisely detected through flow cytometry. The expression levels of the apoptosis-related proteins BAX and Bcl2， along with the key proteins of the Wnt/β-catenin pathway （β-catenin， c-Myc， and cyclin D1）， were measured by Western blot. Results Results from RT-qPCR and Western blot assays demonstrated that NEDD4L was successfully overexpressed and knocked down in Kasumi-1 and U937 cell lines （P < 0.05）. CCK-8 assay results indicated that overexpression of NEDD4L significantly inhibited the proliferative capacity of Kasumi-1 and U937 cells （P < 0.05）. Flow cytometry results showed that overexpression of NEDD4L significantly increased the apoptosis rate in Kasumi-1 and U937 cells. Western blot analysis results revealed that overexpression of NEDD4L upregulated the pro-apoptotic protein BAX and downregulated the anti-apoptotic protein Bcl2 （P < 0.05）. Mechanistic studies results showed that overexpression of NEDD4L decreased the expression of β-catenin， c-Myc， and cyclin D1， whereas knockdown of NEDD4L upregulated these proteins. Furthermore， the Wnt/β-catenin pathway agonist SKL2001 partially reversed the pathway inhibition induced by overexpression of NEDD4L （P < 0.05）. Conclusion NEDD4L inhibits the proliferation of AML cells and induces the apoptosis of AML cells by suppressing the activity of the Wnt/β-catenin pathway， which suggests that NEDD4L may serve as a potential therapeutic target for AML.

Objective To investigate the effects of trigonelline （Trig） on the regulation of the sphingosine kinase 1 （SPHK1）/sphingosine-1-phosphate （S1P）/sphingosine-1-phosphate receptor 3 （S1PR3） pathway and its impact on the proliferation and tumorigenicity of endometrial cancer （EC） cells. Methods Ishikawa cells were divided into the following groups： The blank group， groups treated with different concentrations of Trig （low-Trig and high-Trig groups）， the SPHK1 group， the high-Trig + empty vector group， and the high-Trig + SPHK1 group. Cell proliferation was detected by colony formation assay and CCK-8 assay. The expression level of SPHK1 mRNA was measured by qRT-PCR. Western blot analysis was performed to detect the expression of antigen ki67， Myc proto-oncogene （c-Myc）proteins and proteins related to the SPHK1/S1P/S1PR3 pathway. A nude mouse xenograft tumor model was established. The tumors were excised and weighed. Western blotting was used to measure the expressions of ki67， c-Myc， and proteins related to the SPHK1/S1P/S1PR3 pathway in the xenograft tumor tissues. Hematoxylin and eosin （HE） staining and immunohistochemistry were used to detect the pathological changes of the xenograft tumor tissues and the expressions of ki67 and c-Myc， respectively. Results Compared with the blank group， the clone number， optical density （OD）， expression levels of ki67， c-Myc， SPHK1 mRNA and protein， as well as the levels of S1P and S1PR3 were lower in both the Trig-low group and the Trig-high group， while these parameters were higher in the SPHK1 group （P < 0.05）. Compared with the Trig-high + empty group， the clone number， OD， expression levels of ki67， c-Myc， SPHK1 mRNA and protein， and the levels of S1P and S1PR3 were higher in the Trig-high + SPHK1 group （P < 0.05）. Compared with the SPHK1 group， the clone number， OD， expression levels of ki67， c-Myc， SPHK1 mRNA and protein， and the levels of S1P and S1PR3 were lower in the Trig-high + SPHK1 group （P < 0.05）. In vivo experiments demonstrated that different doses of Trig could reduce the increase in the weight of transplanted tumors and inhibit the expression of proliferation-related proteins and proteins related to the SPHK1/S1P/S1PR3 pathway （P < 0.05）. Conclusions Trig effectively inhibits the proliferation of EC cells and suppresses tumor growth. The underlying mechanism is closely associated with the inhibition of the SPHK1/S1P/S1PR3 pathway.

Objective To investigate the association between the methylation levels of plasma cyclin E1 （CCNE1）， iroquois homeobox protein 2 （IRX2）， and xenotropic and polytropic retrovirus receptor 1 （XPR1） genes， and the clinicopathological features and prognosis in patients with endometrial cancer （EC）. Methods A total of 120 patients with EC who underwent surgical treatment at the hospital between June 2018 and December 2022 （study group） were selected and divided into the survival group （88 cases） and the death group （32 cases） based on the patients' prognosis. Another 100 healthy volunteers of matching age were recruited as the control group. The methylation levels of plasma CCNE1， IRX2， and XPR1 genes were detected using methylation-specific real-time quantitative polymerase chain reaction. The relationship between the methylation levels of plasma CCNE1， IRX2， and XPR1 and the prognosis of EC patients was analyzed by the Kaplan-Meier method. The Cox risk regression model was employed to analyze the prognostic factors of EC patients. Receiver operating characteristic （ROC） curves were utilized to evaluate the predictive value of plasma CCNE1， IRX2， and XPR1 methylation for poor prognosis in patients with endometrial cancer. Results Compared with the control group， the methylation levels of plasma CCNE1 and XPR1 in the study group were lower， whereas the methylation level of IRX2 was higher （P < 0.05）. In patients with FIGO stage Ⅲ + Ⅳ， poorly differentiated histological grade， myometrial infiltration depth ≥ 1/2 myometrium， and lymph node metastasis， the methylation levels of CCNE1 and XPR1 were low， while the methylation level of IRX2 was high （P < 0.05）. A total of 120 EC patients were followed up for 5 - 36 months， with a median follow-up time of 21 months. Among them， 32 patients died， and the 3-year overall survival rate was 73.33% （88/120）. The 3-year overall survival rate of patients with low expression of plasma CCNE1 and XPR1 methylations was lower than that of the high-expression groups （χ² = 4.729， 6.136； P = 0.030， 0.013）， and the 3-year overall survival rate of patients with high expression of plasma IRX2 methylation was lower than that of the low-expression groups （χ² = 6.569； P = 0.010）. Compared with the survival group， the methylation levels of CCNE1 and XPR1 in the death group were lower， and the methylation level of IRX2 was higher （P < 0.05）. Hypermethylation of IRX2 was a risk factor for poor prognosis in patients with EC， while hypermethylation of CCNE1 and hypermethylation of XPR1 were protective factors （P < 0.05）. The AUC values for plasma CCNE1， IRX2， and XPR1 methylation as individual predictors of poor prognosis in EC patients were 0.827， 0.820， and 0.816， respectively； The AUC for the combined prediction was 0.941， indicating superior predictive performance （Z = 3.427， 2.610， 3.068； P = 0.001， 0.009， 0.002）. Conclusions Reduced levels of CCNE1 and XPR1 methylation， along with elevated levels of IRX2 methylation， in the plasma of endometrial cancer patients are closely associated with clinical and pathological characteristics as well as poor prognosis. The combination of these three markers holds high predictive value for poor prognosis in endometrial cancer patients.

Objective This study aims to analyze the burden of liver cancer due to hepatitis B（LCHB）at the global， regional and national levels， and predict the trend of the disease burden up to 2040. Methods The number of cases， age-standardized incidence rate（ASIR），number of deaths， age-standardized mortality rate（ASMR）， disability-adjusted life years（DALYs）， and age-standardized disability-adjusted life years rate（ASDR）of LCHB in the global geographical population from 1990 to 2021 were collected from the 2021 Global Burden of Disease（GBD）database，stratified by Sociodemographic index（SDI）， sex， and age group. Global， regional and national LCHB burden from 1990 to 2021 were analyzed. Estimated annual percentage change（EAPC）was used to assess the trend of LCHB burden， and the Bayesian age-period-cohort（BAPC） model was used to project the burden to 2040. Results From 1990 to 2021， the global ASIR，ASMR and ASDR of LCHB generally showed a downward trend. At the regional level， Australasia， Southern Latin America， and high-income North America showed the most significant growth trends in ASIR； At the national level，there were significant differences among countries， China，India and South Korea ranked as the top three countries in terms of the number of incident cases， deaths， and DALYs in 2021. The burden of disease in males was significantly higher than that in females， and both of them increased first and then decreased with age， with the burden mainly affecting the elderly. The highest ASIR， ASMR and ASDR were found in middle SDI regions. It is expected that by 2040， ASIR， ASMR and ASDR of liver cancer due to hepatitis B in the overall， male and female population will continue to decline. Conclusions Although ASIR， ASMR and ASDR have been decreasing year by year， due to factors such as population aging， the absolute number of LCHB cases is still on the rise， and the burden is concentrated in middle and low SDI regions， among men and the elderly. China has significantly reduced the burden of LCHB by promoting the universal vaccination of newborn hepatitis B vaccines， and its prevention and control experience holds significant reference value. In the future， it is necessary to promote precise prevention and control at different levels， by gender and age， and integrate vaccination， screening and treatment to continuously reduce the global burden of LCHB.

Objective To explore the effects of quadratus lumborum block combined with oxycodone on the perioperative stress response， serum substance P （SP）， and prostaglandin E2 （PGE2） in patients undergoing laparoscopic transabdominal radical resection of rectal cancer. Methods A prospective， non-randomized controlled design was employed. From January 2023 to June 2025， a total of 150 patients who underwent laparoscopic transabdominal radical resection of rectal cancer in the hospital were recruited. Group allocation was determined based on the anesthesiologist's decision and the patient's preference. There were 77 cases in the control group ［quadratus lumborum block （20 mL of 0.375% ropivacaine） after tracheal intubation + fentanyl analgesia during the perioperative period］ and 73 cases in the study group ［quadratus lumborum block combined with oxycodone anesthesia （intravenous injection of 0.1 mg/kg oxycodone during anesthesia induction and 0.05 mg/kg oxycodone 30 min before the end of surgery）］. The changes in mean arterial pressure （MAP） and heart rate （HR） at different time points ［before surgery （T0）， before intubation （T1）， immediately after pneumoperitoneum （T2）， immediately after intestinal anastomosis （T3）， at the end of surgery （T4）］ were compared between the two groups. The perioperative indexes （operation time， intraoperative blood loss， first time out of bed， exhaust time， frequency of analgesic pump presses within 48 h after surgery） were recorded. The levels of stress indexes ［cortisol （Cor）， norepinephrine （NE）， C-reactive protein （CRP）， tumor necrosis factor-α （TNF-α）］， serum SP and PGE2 were compared before surgery and 1 day after surgery， and adverse reactions were recorded. Results Compared with T0， both mean arterial pressure （MAP） and heart rate （HR） increased at T1 and T2 in both groups. The increasing trend of MAP and HR in the study group was lower than that in the control group （P < 0.05）. At T3， the HR in the study group was lower than that in the control group （P < 0.05）. There was no significant difference in the operation time or intraoperative blood loss between the two groups （P > 0.05）. However， the postoperative first leaving-bed time， exhaust time， and the frequency of analgesic pump presses within 48 hours after surgery in the study group were shorter or lower than those in the control group （P < 0.05）. One day after surgery， the levels of cortisol （Cor）， norepinephrine （NE）， C-reactive protein （CRP）， tumor necrosis factor-α （TNF-α）， substance P （SP）， and prostaglandin E2 （PGE2） increased in both groups， but these levels were lower in the study group than in the control group （P < 0.05）. There was no significant difference in the incidence of postoperative adverse reactions between the two groups （P > 0.05）. Conclusion Quadratus lumbarum block combined with oxycodone can stabilize the peri-operative stress response， mitigate the increasing trend of serum SP and PGE2 levels in patients undergoing laparoscopic transabdominal radical resection of rectal cancer， which is beneficial for the early postoperative recovery of patients with rectal cancer.

Objective To investigate whether piR-13663072 inhibits homocysteine （Hcy）-induced apoptosis in mouse podocyte cell line-5 （MPC-5） by regulating the Bcl-2/Bax-Caspase-3 signaling pathway. Methods A hyperhomocysteinemia （HHcy）-induced kidney injury model was established using Cbs^+/- mice， and RNA sequencing （RNA-seq） was employed to screen for differentially expressed piRNAs in kidney tissues. An in vitro podocyte injury model was created by treating MPC-5 cells with Hcy （80 μmol/L）. The expression of piR-13663072 was verified by quantitative real-time PCR （qRT-PCR）， and its species conservation was analyzed. An overexpression cell model was constructed through the transfection of cells with a piR-13663072 mimic. A silenced cell model was constructed via the transfection of cells with a piR-13663072 inhibitor. The expression levels of apoptosis-related proteins （Bax， Caspase-3， and Bcl-2） were detected via Western blot. The number of apoptotic cells was assessed by propidium iodide （PI） staining， and cytoskeletal morphology was observed using phalloidin staining. Results Hcy intervention notably induced apoptosis in MPC-5 cells （as evidenced by the elevated expressions of the pro-apoptotic proteins Bax and Caspase-3， and the reduced expression of the anti-apoptotic protein Bcl-2）， accompanied by cytoskeletal disruption. RNA-seq and qRT-PCR validation demonstrated that piR-13663072 was significantly downregulated in both the kidneys of mice with HHcy-induced injury and Hcy-treated MPC-5 cells. Moreover， this piRNA exhibits moderate conservation among mammals. Following transfection with the piR-13663072 mimic， the expression level of piR-13663072 was significantly elevated. Overexpression of piR-13663072 suppressed the expressions of Bax and Caspase-3， promoted the expression of Bcl-2， effectively decreased the number of Hcy-induced PI-positive cells， and alleviated cytoskeletal damage. Conversely， transfection with the piR-13663072 inhibitor markedly decreased the level of piR-13663072， upregulated the expressions of Bax and Caspase-3， inhibited the expression of Bcl-2， further increased the number of Hcy-induced PI-positive cells， and exacerbated cytoskeletal damage. Conclusions The expression of piR-13663072 is down-regulated in Hcy-induced podocyte injury. Overexpression of piR-13663072 can effectively inhibit podocyte apoptosis and attenuate cytoskeletal damage through the regulation of the Bcl-2/Bax-Caspase-3 signaling pathway， thus exerting a protective effect on podocytes. In contrast， silencing of piR-13663072 aggravates the aforementioned injuries. Therefore， this molecule shows promise as a potential biomarker and therapeutic target for HHcy-induced kidney injury.

Objective To investigate whether the local application of parathyroid hormone （PTH） can activate the protein kinase A （PKA）/transient receptor potential vanilloid 4 （TRPV4） pathway to synergistically accelerate orthodontic tooth movement in rats and to explore its mechanism of action. Methods Forty-eight male Sprague-Dawley （SD） rats were randomly divided into four groups： a blank control group， a pure orthodontic tooth movement （OTM） group， a pure PTH administration group （PTH group）， and a combined orthodontic tooth movement and PTH administration group （OTM + PTH group）. A left maxillary first molar orthodontic movement model was established in the rats. A constant traction force of 0.6 N was applied， and the corresponding drugs were injected locally every other day. On the 10th day after model establishment， the tooth movement distance， the bone density on the pressure side， the periodontal histopathological changes， and the expression levels of PKA， TRPV4， and the ratio of receptor activator of nuclear factor-κB ligand （RANKL） to osteoprotegerin （OPG） were measured. RAW264.7 cells were cultured in vitro and induced to differentiate into osteoclasts with 50 ng/mL RANKL. Subsequently， PTH and PKA/TRPV4 pathway agonists or inhibitors were added， and the expression of relevant molecules was detected. Results Compared with the OTM group， the tooth movement distance in the OTM + PTH group was significantly greater. The bone density on the pressure side decreased， the number of osteoclasts increased， and the levels of PKA， TRPV4， and the RANKL/OPG ratio were significantly upregulated （P < 0.05）. In vitro experiments demonstrated that PKA or TRPV4 agonists could enhance the osteoclast-differentiation-promoting effect of PTH， whereas inhibitors could significantly impede this effect. Conclusions Local PTH treatment activates the PKA/TRPV4 signaling pathway， increases the RANKL/OPG ratio， and acts synergistically with orthodontic forces to promote osteoclast differentiation and activation. This enhances the efficiency of alveolar bone remodeling and consequently accelerates orthodontic tooth movement. This study offers a new theoretical foundation for optimizing clinical orthodontic treatment protocols.

Objective To investigate the value of cervical sagittal parameters and the degree of prevertebral soft tissue swelling in predicting dysphagia following Anterior Cervical Spine Surgery （ACSS）. Methods Clinical data of 262 patients with cervical spondylosis who were scheduled to undergo ACSS at the hospital from January 2021 to December 2023 were retrospectively collected. All patients were closely monitored for 48 hours post-operatively and then assigned to either a dysphagia group （n = 127） or a non-dysphagia group （n = 135） based on the development of dysphagia within 48 hours. The clinical data， cervical sagittal parameters， and the degree of prevertebral soft tissue swelling were compared between the two groups. Multivariable logistic regression analysis was employed to identify the factors associated with dysphagia after ACSS. Receiver Operating Characteristic （ROC） curves were plotted to assess the predictive value of each factor for post-ACSS dysphagia， and a nomogram model was constructed. Results Multivariable logistic regression analysis demonstrated that TIS， TIA， and NT were independent protective factors against dysphagia following ACSS. In contrast， C2-7 SVA and the degree of prevertebral soft tissue swelling were identified as independent risk factors （P < 0.05）. The combined prediction utilizing TIS， C2-7 SVA， TIA， NT， and the degree of prevertebral soft tissue swelling exhibited a higher predictive value compared to any individual parameter （Z_TIS-combined = 5.848， Z_{C2-7 SVA-combined} = 5.384， Z_TIA-combined = 6.708， Z_NT-combined = 5.848， Z_{degree of prevertebral soft tissue swelling-combined} = 6.643， P < 0.05）. The nomogram indicated that the predictive performance of the model was in line with the observed outcomes. The area under the ROC curve （AUC） was 0.84 （0.75 - 0.92） for the training set and 0.83 （0.74 - 0.92） for the validation set， suggesting good predictive performance. Moreover， the model showed a high net benefit across probability thresholds ranging from 50% to 90%. Conclusion Cervical sagittal parameters， when combined with the degree of prevertebral soft tissue swelling， demonstrated good predictive performance for postoperative dysphagia after ACSS and may offer a theoretical basis for the clinical screening of high-risk individuals.

Objective To explore the expressions of NOD-like receptor thermal protein domain associated protein 3 （NLRP3）， cysteinyl aspartate specific proteinase-1 （caspase-1）， and interleukin-17 （IL-17） in the pathological tissues of granulomatous mastitis （GM）， and to analyze their clinical significance. Methods Between January 2021 and December 2025， pathological tissues were obtained from 60 patients diagnosed with granulomatous mastitis （GM） at Hunan Provincial People's Hospital， while normal breast tissues were collected from 60 patients with benign breast lesions at the same hospital. These samples were respectively designated as the GM group and the control group. The expression levels of NLRP3， caspase-1， and IL-17 in the two groups were detected by means of the immunohistochemical streptavidin-peroxidase （SP） method. Based on the detection results of the above three indicators， the samples were classified into a positive group and a negative group. The clinicopathological characteristics of the patients were recorded， and the differences between the positive and negative groups （NLRP3， caspase-1， IL-17） were compared using the χ² test. The differences in NLRP3， caspase-1， and IL-17 among GM patients at different disease activity stages were analyzed. A P-value less than 0.05 indicated that the difference was statistically significant. Results The positive expression rates of NLRP3， caspase-1， and IL-17 in the GM group were significantly higher compared to those in the control group （P < 0.05）. In different clinical stages of GM， the positive expression rates of NLRP3， caspase-1， and IL-17 in the abscess stage and the ulcerative stage were significantly higher than those in the lump stage （P < 0.05）. Additionally， the positive expression rates in the ulcerative stage were slightly higher than those in the abscess stage， yet there was no significant difference among different groups （P > 0.05）. The positive expression rates of NLRP3， caspase-1， and IL-17 in patients with a maximum tumor diameter of ≥ 5 cm were significantly higher than those in patients with a maximum tumor diameter of < 5 cm （P < 0.05）. Conclusions The expressions of NLRP3， caspase-1， and IL-17 are up-regulated in GM tissues. All three of these molecules are associated with the clinical staging of GM and lesion size. NLRP3， caspase-1， and IL-17 may be involved in the inflammation and progression of GM.

Objective To retrospectively analyze the disease spectrum， diagnostic proportion， and mutational profile of pediatric rare diseases at the First Affiliated Hospital of Henan Medical University， and to characterize their genetic features. Methods Between April 2017 and December 2024， 514 children suspected of having rare diseases and admitted to the Department of Pediatrics were enrolled. Diagnostic evaluation included serum matrix metalloproteinase-7 （MMP-7） testing， tandem mass spectrometry （MS/MS）， and high-throughput sequencing （HTS）. The disease spectrum， diagnostic yield， and genetic variation profiles of confirmed cases were systematically analyzed. Results During the study period， 70 362 children were hospitalized at the center， of whom 314 were definitively diagnosed with rare diseases， corresponding to a proportion of approximately 45/10 000 admissions. The ten most frequently diagnosed conditions accounted for 43.6% of all cases and included muscular dystrophy， retinopathy of prematurity， primary immunodeficiencies， Alport syndrome， methylmalonic acidemia， biliary atresia， mitochondrial encephalomyopathy， Wilson disease， ornithine transcarbamylase deficiency， and spinal muscular atrophy. In the top three most prevalent diseases （each comprising > 10 cases）， genetic analysis identified 125 distinct variants and 4 large genomic deletions across 30 genes. Additionally， nine cases exhibited digenic inheritance. Conclusions Neurological， metabolic-endocrine， primary immunodeficiency， and urinary system disorders constitute the predominant categories of pediatric rare diseases in this cohort. These findings highlight the necessity of strengthening early screening and standardized differential diagnosis to enhance clinical management. Notably， five cases representing disease phenotypes or genetic variants not previously reported in China were identified.

Objective To compare the overall efficacy of procalcitonin （PCT）-guided antimicrobial therapy with that of conventional antimicrobial therapy in patients with sepsis， and to analyze the interaction and differential benefits of the PCT-guided strategy among subgroups with different clinical characteristics， thereby providing real-world evidence for individualized clinical application. Methods A total of 515 patients with sepsis who were admitted to Sun Yat-sen Memorial Hospital of Sun Yat-sen University from January 2021 to June 2024 were included in this retrospective cohort study. According to the actual monitoring and treatment strategies implemented in clinical practice， the patients were divided into a PCT-guided group （n = 245） and a conventional treatment group （n = 270）. The baseline characteristics， such as age， sex， and underlying diseases， were well-balanced between the two groups. In the PCT-guided group， the PCT levels were dynamically monitored every 24 - 48 hours for at least three times. The core antibiotic discontinuation threshold was defined as a ≥ 80% decline in the peak PCT level or two consecutive PCT values < 0.5 ng/mL， and the antimicrobial therapy was adjusted accordingly in combination with the clinical assessment. In contrast， the conventional treatment group received antibiotic adjustments based on traditional indicators and clinical experience. Subsequently， the overall core efficacy and safety outcomes were compared between the two groups. Subgroup analyses were carried out based on age， Sequential Organ Failure Assessment （SOFA） score， and the presence of diabetes mellitus. A regression model-based interaction term test was employed to examine the interaction effects of each clinical characteristic with the PCT-guided strategy. Results The PCT-guided group exhibited a significantly shorter duration of antibiotic use ［408.01 （228.06， 887.00） h vs. 579.01 （288.99， 1 290.77） h， P = 0.001］ when compared with the conventional group. The PCT level at the time of antibiotic discontinuation ［0.31 （0.09， 1.41） ng/mL vs. 0.97 （0.22， 6.04） ng/mL， P < 0.001］， antibiotic costs ［6 790.44 （2 393.00， 21 712.71） yuan vs. 12 231.96 （3 396.04， 27 211.60） yuan， P = 0.004］， and the 28-day mortality rate （16.7% vs. 28.1%， P = 0.003） were also notably lower in the PCT-guided group. No significant differences were detected between the two groups in terms of the average daily antibiotic cost or the incidence of kidney dysfunction （all P > 0.05）. Subgroup and interaction analyses indicated that there was a significant interaction between age and the PCT-guided strategy regarding antibiotic duration （P for interaction = 0.039）， and between diabetes status and the PCT-guided strategy regarding the length of hospital stay （P for interaction = 0.003）； no significant interaction was identified between the SOFA score and the PCT-guided strategy （all P for interaction > 0.05）. Conclusions Dynamic monitoring of PCT can assist in shortening the duration of antibiotic therapy， reducing medical costs， and enhancing short-term prognosis. This benefit is more pronounced in patients aged less than 65 years and without diabetes. Elderly patients and those with diabetes should undergo comprehensive clinical evaluation.

Objective To evaluate and compare the anesthetic efficacy and safety profiles of three ultrasound-guided nerve block regimens for clavicle fracture surgery： C5 nerve root block （C5-NRB） combined with cervical nerve pathway block （CNPB）， C5 nerve root block paired with superficial cervical plexus block （SCPB）， and interscalene brachial plexus block （ISBPB） combined with SCPB. Methods By using a random number table， 90 patients scheduled for clavicle fracture surgery （ASA Ⅰ-Ⅱ） were randomly allocated to three groups （30 patients per group）： the C5C group （C5-NRB combined with CNPB）， the C5S group （C5-NRB paired with SCPB）， and the IS group （ISBPB coupled with SCPB）. All nerve blocks were performed under ultrasound guidance with 0.4% ropivacaine. In the C5C group， 5 mL of the anesthetic was injected at the C5 nerve root， followed by 10 mL within the cervical nerve pathway. The C5S group underwent a C5 nerve root block plus a superficial cervical plexus block （10 mL）. In contrast， the IS group received 10 mL each for the interscalene brachial plexus block and the superficial cervical plexus block. After the nerve block was completed， the cutaneous sensory level over the clavicular surgical field was verified using the pinprick technique， and the pain intensity was documented simultaneously. Both the onset time of the sensory block and the intraoperative requirements of sufentanil were recorded. The Modified Bromage Score （MBS） was used to assess the motor function of the affected-side upper limb at the end of surgery and at 6 and 12 hours postoperatively. Diaphragmatic excursion alterations during deep breathing and changes in blood pressure were monitored during the operation. The occurrence of adverse events， including local anesthetic toxicity， stellate ganglion block， recurrent laryngeal nerve involvement， ipsilateral phrenic nerve paralysis， and puncture pain， was systematically recorded throughout the perioperative period. Results The onset of block in the C5C group was significantly faster than that in the C5S and IS groups （P < 0.05）. The intraoperative sufentanil requirements in the C5C group were significantly lower compared to those in the C5S group （P < 0.05）， but there was no statistically significant difference compared to the IS group. Regarding the preservation of motor function， significantly higher MBS scores were recorded at 6 and 12 hours after surgery in the C5C and C5S groups than in the IS group （P < 0.05）. Moreover， the incidence of phrenic nerve block was markedly reduced in both the C5C and C5S groups compared with the IS group （P < 0.05）. Conclusions The combination of ultrasound-guided C5 nerve root block and cervical nerve pathway block offers a regional anesthetic approach with a rapid onset， analgesic effectiveness， and motor sparing for clavicle fracture surgery. Moreover， it significantly reduces the risk of phrenic nerve block. This technique exhibits superior clinical efficacy and safety.

Objective To compare the mid-term clinical efficacy and the impact on foot pressure distribution of two techniques for deepening the bony fibular groove-sub-cortical drilling and pressurization technique and bone flap flipping and window opening technique-in the treatment of chronic fibular tendon dissociation （CPTS）， and to provide a biomechanical basis for clinical surgical selection. Methods A retrospective cohort study design was employed. A total of 52 patients with CPTS who underwent surgical treatment at Hongdu Central Hospital in Nanchang City between January 2022 and December 2024 were included in the study. Based on the surgical methods， the patients were divided into the modified group （sub-cortical drilling and pressurization technique combined with fibular upper support band reconstruction， n = 26） and the conventional group （bone flap flipping and window opening technique combined with fibular upper support band reconstruction， n = 26）. The average postoperative follow-up period was 18.4 months. The American Orthopedic Foot and Ankle Society （AOFAS） ankle-hindfoot scores and pain visual analogue scale （VAS） scores of the two groups at 12 months after surgery were compared. Additionally， the peak pressure （PP）， pressure-time integral （PTI）， and symmetry index （SI） of each area of both feet during the gait cycle were analyzed using the Sennoscan 120 foot pressure force plate system. Results Twelve months after surgery， the AOFAS and VAS scores of both groups were significantly improved compared with those before surgery （P < 0.05）. However， there was no statistically significant difference between the groups （P > 0.05）. Foot pressure analysis indicated that， during the gait progression phase， the SI-PP of the affected side in the fourth and fifth metatarsal regions of the modified group was significantly better than that of the conventional group （P < 0.05）. The SI-PTI of the affected side in the hindfoot region of the conventional group was significantly higher than that of the modified group （P < 0.05）， which suggests the presence of compensatory gait with prolonged load time on the hindfoot and insufficient external column thrust. The coronal plane swing amplitude of the pressure center （CoP） of the modified group was closer to that of the healthy side. Conclusions The two surgical methods exhibit comparable efficacy in relieving pain and enhancing ankle joint function. Nevertheless， the sub-cortical drilling and pressurization technique can more effectively restore the load characteristics of the lateral column of the foot during the gait progression phase and mitigate compensatory gait， thereby presenting biomechanical advantages in facilitating the recovery of natural gait.

Septic acute kidney injury （SAKI）， a common and severe complication among sepsis patients， is characterized by a complex pathogenesis， a high morbidity rate， and a high mortality rate. In recent years， the role of metabolic reprogramming in the onset and development of diseases has drawn growing attention. As a crucial part of metabolic reprogramming， glycolytic metabolic reprogramming plays a significant role in the development and advancement of SAKI. This article reviews the research progress regarding the concept of glycolytic metabolic reprogramming， the mechanisms behind glycolytic metabolic reprogramming in SAKI， its regulatory impacts on SAKI， and SAKI treatment strategies based on glycolytic metabolic reprogramming. The purpose of this review is to thoroughly explore the pathogenesis of SAKI and offer potential targets for its clinical treatment.

Polycystic ovary syndrome （PCOS） is a common endocrine and metabolic disorder affecting women of reproductive age， with hyperandrogenism （HA） being one of its core pathological features. This review systematically summarizes the pathogenesis of PCOS with hyperandrogenism （PCOS-HA）， including classical pathways such as dysregulation of the hypothalamic-pituitary-ovarian/adrenal axis， obesity-driven insulin resistance （IR）， and genetic and epigenetic regulation. Importantly， we incorporate emerging factors such as gut microbiota dysbiosis and the imbalance of the traditional Chinese medicine （TCM） "kidney-tiankui-chongren-uterus axis"， while also integrating molecular mechanisms at the membrane and granulosa cell levels， as well as novel cell death pathways like ferroptosis and pyroptosis.In terms of treatment， the review outlines multiple strategies， including direct androgen suppression， improvement of insulin resistance， neuroendocrine and hypothalamic-pituitary-ovarian （HPO） axis modulation， and regulation of gut microbiota. These approaches cover conventional pharmacotherapy， TCM herbal formulas， acupuncture， lifestyle interventions， and emerging therapeutic targets.The key highlights of this article include incorporating gut microbiota dysbiosis and novel cell death mechanisms （ferroptosis and pyroptosis） into the pathogenic framework of PCOS-HA alongside established theories， thereby constructing a multidimensional model spanning from molecular and cellular levels to whole-body systems， and bridging modern and traditional medicine； clearly delineating emerging therapeutic strategies—particularly those targeting gut microbiota and novel cell death pathways—in the treatment section， thus providing forward-looking theoretical guidance for the precise diagnosis and management of PCOS-HA.