As one of the most common malignant tumors， digestive system tumors exhibit an increase in the incidence and mortality year by year. Its pathogenesis is complex， making it difficult to carry out early prevention. Autophagy is a process in which cells use lysosomes to degrade their organelles and macromolecules to maintain cellular homeostasis under the regulation of autophagy-related genes. Cellular autophagy has a dual regulatory effect on the tumor microenvironment， which always affects the occurrence and development of digestive system tumors. Therefore， the effect and mechanism of action of cellular autophagy on digestive system tumors have become a hot topic in tumor therapy in recent years. Meanwhile， the remarkable research results of targeted autophagy drugs indicate that cellular autophagy may become an important target for anti-digestive system tumors. Traditional Chinese medicine （TCM） has been widely used in the comprehensive treatment of digestive system tumors with good efficacy. A variety of active ingredients in TCM， such as flavonoids， glycosides， terpenoids， quinones， and alkaloids， can increase the expression of autophagy-associated proteins microtubule-associated protein 1 light chain 3 （LC3）Ⅱ/Ⅰ， autophagy-related gene （ATG）5， ATG7， inhibit the expression of autophagy-related protein p62 ， and induce autophagy in digestive system tumor cells， thereby exerting the anti-digestive system tumor effect. By summarizing the research results in recent years on the modulation of cell autophagy by active ingredients in TCM to fight against digestive system tumors， this paper analyzed the relevant signaling pathways， regulatory factors， and functional characteristics of cell autophagy modulation， so as to elucidate the mechanism by which active ingredients of TCM induce autophagy and to provide ideas and references for clinical application.

As one of the most common malignant tumors， digestive system tumors exhibit an increase in the incidence and mortality year by year. Its pathogenesis is complex， making it difficult to carry out early prevention. Autophagy is a process in which cells use lysosomes to degrade their organelles and macromolecules to maintain cellular homeostasis under the regulation of autophagy-related genes. Cellular autophagy has a dual regulatory effect on the tumor microenvironment， which always affects the occurrence and development of digestive system tumors. Therefore， the effect and mechanism of action of cellular autophagy on digestive system tumors have become a hot topic in tumor therapy in recent years. Meanwhile， the remarkable research results of targeted autophagy drugs indicate that cellular autophagy may become an important target for anti-digestive system tumors. Traditional Chinese medicine （TCM） has been widely used in the comprehensive treatment of digestive system tumors with good efficacy. A variety of active ingredients in TCM， such as flavonoids， glycosides， terpenoids， quinones， and alkaloids， can increase the expression of autophagy-associated proteins microtubule-associated protein 1 light chain 3 （LC3）Ⅱ/Ⅰ， autophagy-related gene （ATG）5， ATG7， inhibit the expression of autophagy-related protein p62 ， and induce autophagy in digestive system tumor cells， thereby exerting the anti-digestive system tumor effect. By summarizing the research results in recent years on the modulation of cell autophagy by active ingredients in TCM to fight against digestive system tumors， this paper analyzed the relevant signaling pathways， regulatory factors， and functional characteristics of cell autophagy modulation， so as to elucidate the mechanism by which active ingredients of TCM induce autophagy and to provide ideas and references for clinical application.

OBJECTIVE:Postoperative recurrence is a common complication of percutaneous endoscopic lumbar discectomy for lumbar disc herniation,which can significantly increase the risk of reoperation.A well-performing risk prediction model can help identify high-risk groups early and prevent postoperative recurrence.This study systematically evaluated the risk prediction model for postoperative recurrence after percutaneous endoscopic lumbar discectomy to provide a reference for surgical decision-making.METHODS:The PubMed,Embase,Web of Science,CNKI,WanFang Data,VIP,and CBM were electronically searched to collect studies on the recurrence risk prediction models after percutaneous endoscopic lumbar discectomy from inception to July 1,2024.Two reviewers independently screened the literature and extracted data.The models' risk of bias,applicability,and report quality were assessed using prediction model risk of bias assessment tool(PROBAST)and Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis(TRIPOD)tools,respectively.Meta-analysis of postoperative recurrence rate of percutaneous endoscopic lumbar discectomy and related predictors was performed using Revman 5.4 software.RESULTS:(1)A total of 15 studies were included,all of which were retrospective studies,including 24 models for predicting the risk of recurrence after percutaneous endoscopic lumbar discectomy.(2)The PROBAST evaluation results indicated that all 15 studies exhibited a high risk of bias.Regarding applicability,two studies demonstrated a low risk,while 13 presented a high risk.(3)Regarding the TRIPOD reporting quality,the overall quality across the 15 studies was low.The primary reasons for this low compliance included the failure to report blinding,a lack of explanation for the sample size calculation method,lack of detailed description of missing data processing methods,and lack of information such as introduction to the model used.(4)Furthermore,the area under the receiver operating characteristic curve for the model ranged from 0.684 to 0.972,with the number of potential predictor variables varying from 15 to 28.(5)The results of meta-analysis showed that the postoperative recurrence rate of lumbar disc herniation patients treated with percutaneous endoscopic lumbar discectomy was 12％(95％CI=9.0％-15.0％),Modic changes(OR=6.72,95％CI=3.90-11.59),body mass index(OR=1.28,95％CI=1.10-1.49),work intensity(OR=3.22,95％CI=1.85-5.59),age(OR=2.28,95％CI=1.50-3.48),and smoking history(OR=2.65,95％CI=1.75-4.00)were independent influencing factors for postoperative recurrence of percutaneous endoscopic lumbar discectomy(all P＜0.05).CONCLUSION:The overall predictive performance of the recurrence risk prediction models after percutaneous endoscopic lumbar discectomy is satisfactory;however,the model exhibits a high overall risk of bias and applicability,coupled with low reporting quality.Additionally,there is a lack of prospective research and external validation.Future,risk prediction models should consider factors such as Modic changes,body mass index,work intensity,age,and smoking history as potential predictors.

OBJECTIVE:Postoperative recurrence is a common complication of percutaneous endoscopic lumbar discectomy for lumbar disc herniation,which can significantly increase the risk of reoperation.A well-performing risk prediction model can help identify high-risk groups early and prevent postoperative recurrence.This study systematically evaluated the risk prediction model for postoperative recurrence after percutaneous endoscopic lumbar discectomy to provide a reference for surgical decision-making.METHODS:The PubMed,Embase,Web of Science,CNKI,WanFang Data,VIP,and CBM were electronically searched to collect studies on the recurrence risk prediction models after percutaneous endoscopic lumbar discectomy from inception to July 1,2024.Two reviewers independently screened the literature and extracted data.The models' risk of bias,applicability,and report quality were assessed using prediction model risk of bias assessment tool(PROBAST)and Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis(TRIPOD)tools,respectively.Meta-analysis of postoperative recurrence rate of percutaneous endoscopic lumbar discectomy and related predictors was performed using Revman 5.4 software.RESULTS:(1)A total of 15 studies were included,all of which were retrospective studies,including 24 models for predicting the risk of recurrence after percutaneous endoscopic lumbar discectomy.(2)The PROBAST evaluation results indicated that all 15 studies exhibited a high risk of bias.Regarding applicability,two studies demonstrated a low risk,while 13 presented a high risk.(3)Regarding the TRIPOD reporting quality,the overall quality across the 15 studies was low.The primary reasons for this low compliance included the failure to report blinding,a lack of explanation for the sample size calculation method,lack of detailed description of missing data processing methods,and lack of information such as introduction to the model used.(4)Furthermore,the area under the receiver operating characteristic curve for the model ranged from 0.684 to 0.972,with the number of potential predictor variables varying from 15 to 28.(5)The results of meta-analysis showed that the postoperative recurrence rate of lumbar disc herniation patients treated with percutaneous endoscopic lumbar discectomy was 12％(95％CI=9.0％-15.0％),Modic changes(OR=6.72,95％CI=3.90-11.59),body mass index(OR=1.28,95％CI=1.10-1.49),work intensity(OR=3.22,95％CI=1.85-5.59),age(OR=2.28,95％CI=1.50-3.48),and smoking history(OR=2.65,95％CI=1.75-4.00)were independent influencing factors for postoperative recurrence of percutaneous endoscopic lumbar discectomy(all P＜0.05).CONCLUSION:The overall predictive performance of the recurrence risk prediction models after percutaneous endoscopic lumbar discectomy is satisfactory;however,the model exhibits a high overall risk of bias and applicability,coupled with low reporting quality.Additionally,there is a lack of prospective research and external validation.Future,risk prediction models should consider factors such as Modic changes,body mass index,work intensity,age,and smoking history as potential predictors.

ObjectiveTo investigate the association between endothelin receptor type A gene （EDNRA） and congenital bilateral absence of the vas deferens （CBAVD）. MethodsThis case-control study consisted of 124 subjects with CBAVD and 100 fertile controls.Two single nucleotide polymorphisms （SNPs： rs5335 and rs1801708） in the EDNRA gene were genotyped via PCR， PCR-RFLP analysis， and direct sequencing. ResultsNo significant differences existed between EDNRA polymorphisms and CBAVD phenotype （rs1801708： P=0.220 2， 0.163 2； rs5335： P=0.805 8， 0.818 6）. However， the rs1801708-rs5335 haplotype AG was notably associated with an increased risk of CBAVD （P=0.008 6， OR=2.178， 95% CI： 1.207-3.929）. A significantly protective effect of rs1801708-rs5335 haplotype GG on CBAVD （P=0.038 5， OR= 0.671， 95% CI： 0.460-0.980） was observed. After Bonferroni correction， the result for haplotype A-G remained significant （P =0.008 6<0.012 5）， while haplotype G-G was not significant. ConclusionThe rs1801708-rs5335 AG haplotype of EDNRA is a potential risk factor for CBAVD development in Han Chinese.

BACKGROUND: Severe stroke has high rates of mortality and morbidity. This study aimed to investigate the clinical course, causes of worsening, and outcomes of severe ischemic stroke. METHODS: This prospective, multicenter cohort study enrolled adult patients admitted ≤30 days after ischemic stroke from nine hospitals in China between September 2017 and December 2019. Severe stroke was defined as a score of ≥15 on the National Institutes of Health Stroke Scale (NIHSS). Clinical worsening was defined as an increase of 4 in the NIHSS score from baseline. Unfavorable functional outcome was defined as a modified Rankin scale score ≥3 at 3 months and 1 year after stroke onset, respectively. We performed Logistic regression to explore baseline features and reperfusion therapies associated with clinical worsening and functional outcomes. RESULTS: Among 4201 patients enrolled, 854 patients (20.33%) had severe stroke on admission. Of 3347 patients without severe stroke on admission, 142 (4.24%) patients developed severe stroke in hospital. Of 854 patients with severe stroke on admission, 33.95% (290/854) experienced clinical worsening (median time from stroke onset: 43 h, Q1-Q3: 20-88 h), with brain edema (54.83% [159/290]) as the leading cause; 24.59% (210/854) of these patients died by 30 days, and 81.47% (677/831) and 78.44% (633/807) had unfavorable functional outcomes at 3 months and 1 year respectively. Reperfusion reduced the risk of worsening (adjusted odds ratio [OR]: 0.24, 95% confidence interval [CI]: 0.12-0.49, P  <0.01), 30-day death (adjusted OR: 0.22, 95% CI: 0.11-0.41, P  <0.01), and unfavorable functional outcomes at 3 months (adjusted OR: 0.24, 95% CI: 0.08-0.68, P <0.01) and 1 year (adjusted OR: 0.17, 95% CI: 0.06-0.50, P  <0.01). CONCLUSIONS: Approximately one-fifth of patients with ischemic stroke had severe neurological deficits on admission. Clinical worsening mainly occurred in the first 3 to 4 days after stroke onset, with brain edema as the leading cause of worsening. Reperfusion reduced the risk of clinical worsening and improved functional outcomes. REGISTRATION ClinicalTrials.gov , NCT03222024.
Humans ; Male ; Female ; Prospective Studies ; Ischemic Stroke/mortality* ; Aged ; Middle Aged ; Aged, 80 and over ; Stroke ; Brain Ischemia

OBJECTIVE: To compare the efficacy of the fourth-generation minimally invasive technique-minimally invasive extra-articular metaphyseal distal transverse osteotomy (META) and Chevron osteotomy in treatment of hallux valgus. METHODS: A total of 80 patients with hallux valgus, who underwent single-foot surgery between July 2023 and January 2025 and met the inclusion criteria, were included in the study. Among them, 40 patients were treated with META and 40 with Chevron osteotomy. There was no significant difference in baseline data between the two groups ( P>0.05), including gender, age, height, weight, body mass index, disease duration, lesion site, hallux valgus deformity degree, as well as preoperative scores of each item (pain, function, alignment, total score) in the American Orthopaedic Foot and Ankle Society Hallux Metatarsophalangeal-Interphalangeal Joint Scale (AOFAS-Hallux-MTP-IP), scores of each item (pain, walking/standing, social interaction, total score) in the Manchester-Oxford Foot Questionnaire (MOXFQ), hallux valgus angle (HVA), intermetatarsal angle (IMA), distal metatarsal articular angle (DMAA), sesamoid position, and the 1st metatarsal head morphology. The postoperative AOFAS-Hallux-MTP-IP scores, MOXFQ scores, as well as HVA, IMA, DMAA, the 1st metatarsal head morphology, and sesamoid position measured based on weight-bearing foot X-ray films were compared between the two groups; the occurrence of postoperative complications was recorded. RESULTS: All patients in both groups were followed up 6-18 months, and there was no significant difference in the follow-up time between the two groups ( P>0.05). At last follow-up, the scores of all items in AOFAS-Hallux-MTP-IP in both groups were higher than those before operation, and the scores of all items in MOXFQ were lower than those before operation, with significant differences ( P<0.05); there was no significant difference in the change values of all items in MOXFQ between the two groups ( P>0.05). The change value in AOFAS function score in the META group was significantly higher than that in the Chevron osteotomy group ( P<0.05), while there was no significant difference in the change value of AOFAS pain score, alignment score, and total score between the two groups ( P>0.05). After operation, 1 case (2.5%) of superficial incision infection and 2 cases (5.0%) of numbness around the incision occurred in the Chevron osteotomy group, while only 2 cases (5.0%) of numbness around the incision occurred in the META group. Imaging reexamination showed that HVA, IMA, and DMAA in both groups were signifncatly smaller than those before operation ( P<0.05), and there was no significant difference in the change values of the above angles between the two groups ( P>0.05). The 1st metatarsal head morphology and sesamoid position in the META group were better than those in the Chevron osteotomy group after operation, with significant differences ( P<0.05). CONCLUSION Both META and Chevron osteotomy can correct hallux valgus deformity, improve foot function, and relieve pain, but META has more advantages in correcting metatarsal rotation and reducing dislocated sesamoids.
Humans ; Hallux Valgus/diagnostic imaging* ; Osteotomy/methods* ; Minimally Invasive Surgical Procedures/methods* ; Male ; Female ; Middle Aged ; Treatment Outcome ; Adult ; Metatarsophalangeal Joint/surgery* ; Aged ; Retrospective Studies

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

The deficiency in immunogenicity and the presence of immunosuppression within the tumor microenvironment significantly hindered the efficacy of immunotherapy. Consequently, a nanoformulation containing metal sulfide of FeS and GSDMD plasmid (NP_FeS/GD) had been developed to effectively augment antitumor immune responses through dual activation of immunogenic PANoptosis and ferroptosis, as well as reprogramming immunosuppressive effects via H₂S amplification. The bioactive NP_FeS/GD exhibited controlled release of GSDMD plasmid, H₂S, and Fe²⁺ in response to the tumor microenvironment. Fe²⁺, H₂S, and the expression of GSDMD protein could effectively elicit highly immunogenic PANoptosis and ferroptosis. Furthermore, releasing H₂S could mitigate the overexpression of indoleamine 2,3-dioxygenase1 (IDO1) induced by immunogenic PANoptotic and ferroptotic cell death and disrupt the activity of IDO1. Consequently, NP_FeS/GD effectively triggered the antitumor innate and adaptive immune responses through induction of PANoptotic and ferroptotic cell death and reshaped the tumor immunosuppressive microenvironment to enhance antitumor immunotherapy for metastasis inhibition. This study unveiled the significant potential of immunogenic PANoptosis and ferroptosis in H₂S gas therapy for enhancing tumor immunotherapy, offering novel insights and ideas for the rational design of nanomedicine to enhance tumor immunogenicity while reprogramming the tumor immunosuppressive microenvironment.

Objective:Assessing the therapeutic efficacy of methotrexate(MTX)-modified magnetic nanoparticles in thermo-chemotherapy for rat breast cancer and its impact on immune function.Methods:Female Wistar rats were subcutaneously inoculated with breast cancer Walker-256 cells to establish a transplantation tumor model,and injected with polyethyleneimine(PEI)-modified Fe3O4 magnetic nanoparticles(47T group,42T group and multiple 42T group)or MTX-modified Fe3O4 magnetic nanoparticles(47TC group,42TC group and multiple 42TC group)for thermotherapy under the magnetic field at different temperatures(47℃and 42℃).The rats injected with MTX-modified magnetic fluid only(MFC group)and the tumor-bearing rats without any treatment(blank control group),with irradiation treatment in an alternating magnetic field only for 30 minutes(M group),with injection of PEI-modified magnetic fluid only(MF group),with treatment of MTX-mono drug(MTX group)and not inoculated with tumor cells(normal group)were used as control groups.X-ray radiography was used to display the distribution of magnetic fluid in the tumor tissue 24 hours,2 weeks and 2 months after intra-tumor injection.After 24 hours of treatment,three rats were selected from each of the 47T and 47TC groups,and the effect of magnetic fluid on tumor cells was observed under an electron microscope after execution.After 14 days of treatment,the tumor volume of rats was measured and statistically analyzed.At the same time,4 rats were selected from each of the 47TC,47T,42TC,42T,MFC,MTX,blank control and normal groups,and the levels of IL-2,IFN-γ and IL-4 in peripheral blood were detected by ELISA method.The remaining rats were observed for long-term survival.Results:The magnetic nanoparticles were evenly distributed in the center of the tumor but unevenly distributed at the tumor's edge;they primarily localize amomg tumor cells and can penertrate into tumor cells.Tumor growth was inhibited in rats in the 47TC,47T,multiple 42TC and multiple 42T groups(all P<0.05),and the survival rates of the rats were high.As compared with the blank control group,the levels of IL-2 and IFN-γ were increased while the IL-4 level was decreased in the 47TC and 47T groups(all P<0.05).Conclusion:Thermo-chemotherapy at 47℃for 30 minutes and multiple sessions at 42℃for 60 minutes can partially inhibit tumor growth and prolong rat survival.This effect maybe related to the thermo-chemotherapy at 47℃for 30 minutes which can activate the body's immune function.