1.Study on The Anti-aging Effects of Longevity-enriched Metabolite Dimethylglycine
Jie HU ; Gong-Yu PU ; Jun-Lin LI ; Ju CAO ; Zhi-Xin LIN ; Wei-Wei AN ; Xue-Meng LI ; Jing AN
Progress in Biochemistry and Biophysics 2026;53(4):1048-1061
ObjectiveThe exacerbating trend of global population aging poses profound socioeconomic and public health challenges, making the comprehensive elucidation of biological aging mechanisms and the discovery of effective anti-aging interventions an urgent priority in the life sciences. Based on our previous serum metabolomics findings that dimethylglycine, an intermediate metabolite of amino acid metabolism naturally present in the human body, was significantly enriched in the serum of longevity families, this study aimed to systematically investigate the anti-aging effects of dimethylglycine both in living organisms and in controlled laboratory environments, and to preliminarily elucidate its underlying molecular mechanisms. While existing literature indicates that dimethylglycine possesses antioxidant and immunomodulatory properties, its direct anti-aging efficacy and the specific molecular pathways through which it operates remain largely unexplored. MethodsTo comprehensively evaluate the anti-aging properties of dimethylglycine, we utilized replicative senescent human embryonic lung fibroblasts, specifically the WI-38 cell line, as an experimental model in a controlled laboratory environment. Cell viability and safety were thoroughly assessed using Cell Counting Kit-8 and lactate dehydrogenase release assays across various concentrations of dimethylglycine. The impact of dimethylglycine on cellular senescence phenotypes, oxidative stress, and proliferative capacity was evaluated via senescence-associated beta-galactosidase staining, reactive oxygen species fluorescence detection, and 5-ethynyl-2'-deoxyuridine incorporation assays. Furthermore, the molecular alterations of senescence-associated secretory phenotype factors and core senescence signaling pathways were quantified using quantitative reverse transcription polymerase chain reaction for the messenger RNA levels of interleukin-6, interleukin-8, p21, and matrix metalloproteinase-1, and enzyme-linked immunosorbent assay for the measurement of p16 and p21 protein expression levels. For the living organism model, the wild-type nematode Caenorhabditis elegans was used to evaluate systemic physiological effects. We conducted a comprehensive lifespan analysis at 20°C, heat stress resistance survival assays at 35℃, senescence-associated beta-galactosidase staining, lipofuscin accumulation tracking, intracellular reactive oxygen species measurement, and Oil Red O staining to ascertain systemic lipid accumulation. Additionally, network pharmacology bioinformatics tools, including PharmMapper and STRING databases, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were utilized to predict target pathways, alongside highly detailed molecular docking simulations utilizing SwissDock and Protein-Ligand Interaction Profiler to examine interactions with the cytochrome P450 family 2 subfamily C member 9 protein. ResultsThe experimental outcomes robustly demonstrate the potent anti-aging capabilities of dimethylglycine. At the cellular level, toxicity analyses firmly confirmed that dimethylglycine is highly safe; continuous treatment with 50 mol/L and 70 mol/L of dimethylglycine for 5 d did not induce any cellular membrane damage or cytotoxicity, but rather actively promoted cellular proliferation. Utilizing the optimal standardized concentration of 50 mol/L, dimethylglycine treatment significantly ameliorated senescent phenotypic markers in human embryonic lung fibroblasts, which was evidenced by a drastic and highly significant reduction in the senescence-associated beta-galactosidase positive cell percentage (P<0.000 1) and intracellular reactive oxygen species levels (P<0.000 1), alongside a marked increase in the 5-ethynyl-2'-deoxyuridine-positive proliferation rate (P=0.003 5). On a molecular expression scale, dimethylglycine significantly downregulated the messenger RNA expression of multiple core senescence-associated secretory phenotype inflammatory factors, including interleukin-6, interleukin-8, p21, and matrix metalloproteinase-1. Concurrently, it effectively suppressed the protein expression of critical cell cycle arrest markers, diminishing p16 protein levels by 57.3% (P=0.000 4) and p21 protein levels by 27.2% (P=0.000 7). In the nematode Caenorhabditis elegans animal model, dimethylglycine significantly extended the mean lifespan from 20.402 d to an impressive 23.066 d (P<0.000 1) and notably enhanced overall survival rates under severe heat stress environmental conditions (P=0.017). Furthermore, systemic dimethylglycine intervention significantly mitigated age-related physiological decline by decreasing bodily lipofuscin accumulation (P<0.000 1), significantly reducing senescence-associated beta-galactosidase activity, lowering systemic reactive oxygen species fluorescence (P=0.008), and effectively alleviating overall fat accumulation (P<0.000 1). Mechanistically, extensive network pharmacology and Kyoto Encyclopedia of Genes and Genomes analyses strongly revealed that the potential targets of dimethylglycine are significantly enriched in fundamental drug metabolism and oxidative stress response pathways. Precision molecular docking simulations conclusively demonstrated that dimethylglycine forms highly stable structural interactions with the cytochrome P450 family 2 subfamily C member 9 protein, specifically highlighting the definitive formation of 5 stable hydrogen bonds involving serine 365, leucine 366, and serine 429 residues, as well as two critical salt bridge formations with arginine 97 and histidine 368 residues. It is additionally predicted to interact favorably with glutathione S-transferase family proteins. ConclusionDimethylglycine exhibits a profoundly significant and multifaceted anti-aging activity at both the cellular and entire living animal levels. By powerfully alleviating oxidative stress, heavily suppressing the core p16 and p21-dependent cellular senescence signaling pathways, and substantially mitigating the detrimental senescence-associated secretory phenotype, dimethylglycine effectively delays fundamental cellular senescence processes and drastically extends whole-organism lifespan. The biological mechanisms driving these robust protective effects are highly likely closely associated with its direct stable interactions with crucial metabolic and detoxifying enzyme systems, such as cytochrome P450 family 2 subfamily C member 9 and glutathione S-transferase family proteins, thereby systemically improving metabolic dysregulation and restoring critical redox homeostasis. This comprehensive study provides highly solid experimental evidence supporting dimethylglycine as a highly potent and safe potential anti-aging intervention agent, while simultaneously offering a clear molecular mechanistic explanation for the previously documented high abundance of dimethylglycine observed within exceptionally long-lived human populations.
2.Prognostic analysis and application value of adjuvant chemotherapy after radical resection for stage Ⅰ gastric cancer
Jie CHEN ; Xiaogang QU ; Keshu HU ; Mingde ZANG ; Hongda PAN ; Jun LU ; Xiaowen LIU ; Yanong WANG ; Fenglin LIU
Chinese Journal of Digestive Surgery 2025;24(8):1033-1043
Objective:To explore the prognosis after radical resection for stage Ⅰ gastric cancer and the application value of adjuvant chemotherapy.Methods:The retrospective cohort study was conducted. The clinicopathological data of 3 353 patients with stage Ⅰ gastric cancer who were admitted to Fudan University Shanghai Cancer Center from January 2000 to December 2022 were collected. There were 2 369 males and 984 females, aged 60(range, 21-91) years. All patients underwent radical R 0 resection. Observation indicators: (1) clinicopathological characteristics of patients; (2) influencing factors for postoperative prognosis of patients; (3) prognostic analysis of patients; (4) construction and validation of a predictive model for the efficacy of postoperative adjuvant chemotherapy. Comparison of count data between groups was conducted using the chi-square test. Univariate and multivariate analyses were performed using the Cox proportional hazards regression model. The Kaplan-Meier method was used to calculate survival rates and draw survival curves, and the Log-rank test was used for survival analysis. Based on the multivariate analysis result, a nomogram prediction model was constructed to predict survival benefit. Results:(1) Clinicopatho-logical characteristics of patients. The highly, moderately, and poorly differentiated tumors were observed in 16, 234, 396 cases of 646 patients aged <50 years and 279, 1 617, 811 cases of 2 707 pati-ents aged ≥50 years, respectively, showing a significant difference in degree of tumor differentiation between them ( P<0.05). For 297 patients in stage T1N1M0, cases aged <50 years and ≥50 years were 71 and 226, cases of males and females were 184 and 113, cases with negative and positive vascular invasion were 37 and 260, cases with negative and positive nerve invasion were 275 and 22, cases without and with postoperative adjuvant chemotherapy were 222 and 75, respectively. The above indicators for 678 patients in stage T2N0M0 105, 573, 533, 145, 517, 161, 526, 152, 563, 115, respectively. There were significant differences in the above indicators between the two groups ( P<0.05). (2) Influencing factors for postoperative prognosis of patients. Results of multivariate analysis showed that age ≥50 years, stage T2, moderately differentiated tumor, the number of lymph nodes dissected <16, positive vascular invasion, carcinoembryonic antigen (CEA) ≥5 μg/L, and CA19-9 ≥37 U/mL were independent risk factors for disease-free survival (DFS) after surgery for stage Ⅰ gastric cancer ( hazard ratio=4.600, 1.555, 1.835, 1.362, 1.451, 1.571, 2.134, 95% confidence interval as 2.806-7.541, 1.205-2.006, 1.016-3.314, 1.059-1.753, 1.057-1.993, 1.100-2.243, 1.257-3.625, P<0.05). Age ≥50 years, stage T2, the number of lymph nodes dissected <16, positive vascular invasion, CEA ≥5 μg/L, and CA19-9 ≥37 U/mL were independent risk factors for overall survival (OS) after surgery for stage Ⅰ gastric cancer ( hazard ratio=5.208, 1.597, 1.373, 1.520, 1.464, 2.356, 95% confidence interval as 3.028-8.955, 1.231-2.072, 1.060-1.777, 1.099-2.104, 1.004-2.134, 1.385-4.009, P<0.05). Postoperative adjuvant chemotherapy was an independent protective factor for both DFS and OS after surgery for stage I gastric cancer ( hazard ratio=0.361 0.297, 95% confidence interval as 0.177-0.736, 0.131-0.674, P<0.05). (3) Prognostic analysis of patients. According to the results of multi-variate analysis, among 3 353 patients, there were significant differences in 5-year DFS rate and 10-year OS rate between patients aged <50 years and ≥50 years ( P<0.05). There were significant differences in 5-year DFS rate and 10-year OS rate among patients in TNM stage ⅠA and ⅠB ( P<0.05). There were significant differences in 5-year DFS rate and 10-year OS rate among patients in stage T1N0M0, T1N1M0, T2N0M0 ( P<0.05). There were significant differences in 5-year DFS rate and 10-year OS rate among patients with the highly, moderately, and poorly differentiated tumors ( P<0.05). There were significant differences in 5-year DFS rate and 10-year OS rate among patients with the number of lymph lodes dissected <16 and ≥16 ( P<0.05). There were significant differences in 5-year DFS rate and 10-year OS rate between patients with negative and positive vascular invasion ( P<0.05). There were significant differences in 5-year DFS rate and 10-year OS rate between patients with and without postoperative adjuvant chemotherapy ( P<0.05), among patients in stage T1N0M0, T1N1M0, T2N0M0 who received no postoperative adjuvant chemotherapy ( P<0.05). For patients in stage T1N1M0, there was no significant difference in 5-year DFS rate and 10-year OS rate between patients with and without postoperative adjuvant chemotherapy ( P>0.05).Results of stratified analysis showed that for patients aged ≥ 50 years, there were significant differences in 5-year DFS rate and 10-year OS rate between patients with and without postoperative adjuvant chemotherapy ( P<0.05). For patients in stage T2N0M0, there were significant differences in 5-year DFS rate and 10-year OS rate between patients with and without postoperative adjuvant chemotherapy ( P<0.05). For patients with positive vascular invasion, there were significant differences in 5-year DFS rate and 10-year OS rate between patients with and without postoperative adjuvant chemotherapy ( P<0.05). (4) Construction and validation of a predictive model for the efficacy of adjuvant chemotherapy. A nomogram predictive model was constructed based on the multivariate analysis results of OS and used for calculating net benefits and distribution. Among the 3 096 patients without postoperative adjuvant chemotherapy, 1 009 cases had a predicted net benefit of >5%-10%, and 250 patients had a predicted net benefit >10%. The predicted survival analysis further verified that the predicted benefit of adjuvant chemotherapy was consistent with the prognosis of patients. Conclusions:Patients with age ≥50 years, stage T2 tumors, moderately differentiated tumor, the number of lymph nodes dissected <16, positive vascular invasion have worse survival prognosis postoperative. Postoperative adjuvant chemotherapy provides better prognosis in high-risk patients. Patients in stage T1N1M0 have lower recurrence and survival risks, of whom with 1 metastatic lymph node is more suitable for follow-up rather than postoperative adjuvant chemotherapy.
3.Application of wide awake local anesthesia no tourniquet technique in locking of metacarpophalangeal joint with extension lag surgery
Guo-tao YANG ; Hua-jie MAO ; Zhi-jun CHEN ; Xu ZHANG ; Huan HU ; Qi-ting JIANG
Journal of Regional Anatomy and Operative Surgery 2025;34(9):836-839
Objective To explore the application value of wide awake local anesthesia no tourniquet(WALANT)technique in outpatient surgery for locking of metacarpophalangeal joint with extension lag.Methods The clinical data of 6 patients with locking of meta-carpophalangeal joint with extension lag in Danyang People's Hospital from January 2019 to October 2023 were retrospectively analyzed.The patients were received outpatient surgery under the WALLANT technique for release,and lidocaine mixed solution containing 1∶100 000 epinephrine was injected into the proximal midpoint of the volar projection of the metacarpophalangeal joint.The joint was exposed with a volar or dorsal finger web incision to determine the unrestricted structure,and the collateral ligament and paralateral collateral ligament with high tension were cut off.The intraoperative blood loss,postoperative incision healing and complications were recorded.Visual analogue scale(VAS)was used to evaluate the intraoperative pain,and the range of motion of metacarpophalangeal joint and total active movement(TAM)of finger joint were observed during postoperative follow-up.Results The incision of patients were healed successfully in the first phase after surgery,without wound necrosis.The anesthesia effects of patients were all satisfied and the operation was successfully completed.The VAS score was less than 3 points and there was only a small amount of bleeding during the operation.The recovery of joint flexion and extension movements could be observed during the operation,and the TAM score after the operation was 20 points.No significant change was found on the range of motion of metacarpophalangeal joint or TAM of finger joint between the injured finger and the corresponding healthy finger(P>0.05).Conclusion WALANT technique for locking of metacarpophalangeal joint with extension lag surgery has good anesthesia effect,less bleeding in the incision,and clear vision of the surgery.It can avoid vascular and nerve injuries,observe the recovery of joint activities during the operation and relieve pain of patients,which is conducive to outpatient surgery and saving medical and social resources at the same time.
4.Advances in regulation of dysregulated bone remodeling by immune cells within rheumatoid arthritis synovial microenvironment
Jun-jie HE ; Zhong-liu YAO ; Ming-yue HU ; Hong HUANG ; Xiong CAI
Chinese Pharmacological Bulletin 2025;41(10):1801-1807
Rheumatoid arthritis(RA)is characterized by bidi-rectional bone remodeling imbalance,clinically termed the "high resorption-low formation" paradox,stemming not only from osteoclast hyperactivation but also critically involving pro-found suppression of osteoblast differentiation and function.No-tably,this suppression cannot be fully attributed to osteoclast hyperactivity;synovium-resident immune cells exert a pivotal regulatory influence through distinct mechanisms.This review systematically examines how synovial immune cells orchestrate bone remodeling in RA through both paracrine cytokine networks and direct cell-cell communication with bone lineage cells,thereby perturbing physiological homeostasis and driving patho-logical progression.These mechanistic revelations yield innova-tive perspectives on RA pathogenesis,positioning immune-medi-ated osteoimmune dysregulation as a promising therapeutic fron-tier for targeted intervention.
5.Analysis of risk factors for adverse events in painless gastroenteroscopy and construction of a nomogram model
Jie LI ; Jun HU ; Tingting CHEN ; Junwu LIU ; Hongping HE
China Journal of Endoscopy 2025;31(3):37-45
Objective To investigate the risk factors of adverse events in elderly patients with painless gastroenteroscopy,and construct a nomogram model for predicting the risk of adverse events.Methods 302 patients who underwent painless gastroenteroscopy from September 2023 to March 2024 were retrospectively enrolled and randomly divided into training set(211 cases)and validation set(91 cases)according to the 7∶3 ratio.The training set was divided into adverse event group(64 cases)and non-adverse event group(147 cases)according to whether adverse events occurred.Multivariate Logistic regression analysis was used to screen the risk factors for adverse events in elderly painless gastroenteroscopy patients,R 3.4.3 software was used to construct a nomogram model,and the validation set was used for external verification.The nomogram model discrimination was evaluated by drawing the receiver operator characteristic curve(ROC curve),and the calibration curve was drawn to evaluate the calibration degree of the nomogram model.Results Univariate analysis showed that,the comparison of overweight or obesity,smoking,hypertension,coronary heart disease,education level,pre examination sleep time,and exercise habits between the adverse event group and the non-adverse event group were statistically significant(P<0.05);Multivariate Logistic regression analysis showed that overweight or obesity(OR=4.821,95%CI:1.052~11.651),smoking(OR=1.056,95%CI:1.313~3.109),hypertension(OR=1.356,95%CI:1.175~2.677),and coronary heart disease(OR=1.385,95%CI:1.168~2.765)were risk factors for adverse events during painless gastroenteroscopy in elderly patients(P<0.05);The areas under the ROC curves for the training and validation sets were 0.921 and 0.795,respectively.The sensitivity was 90.62%(95%CI:0.846~0.965)and 82.14%(95%CI:0.689~0.856),and the specificity was 74.83%(95%CI:1.056~2.939)and 76.19%(95%CI:1.245~4.161),indicating that the nomogram model had good discriminability;The Hosmer-Lemeshow goodness of fit test results showed that the nomogram model had a good fit(P>0.05),and the calibration curves of the training and validation sets both showed that the nomogram model had a good consistency between the actual and predicting incidence of adverse events(P>0.05).Conclusion Overweight or obesity,hypertension,cornary heart disease and smoking are independently correlated with adverse events in painless gastroenteroscopy,and the nomogram model constructed based on the above factors to predict the risk of adverse events in painless gastroenteroscopy has good predictive efficacy.
6.The Correlation between MMR and PD-L1 Protein Expression and Clinical Pathological Characteristics in Colorectal Cancer Tissues
Xian-jie MENG ; Li XIAO ; Hai-jun ZHANG ; Jian-ming HU ; Li WEI
Progress in Modern Biomedicine 2025;25(19):3056-3061,3113
Objective:To explore and analyze the correlation between the expression of mismatch repair(MMR)protein and programmed death ligand 1(PD-L1)in colorectal cancer(CRC)tissue and clinical pathological characteristics.Methods:The study period were from July 2021 to December 2024,200 cases of colorectal cancer patients treated in our hospital were selected as the research subjects.Collected all patient lesion tissue samples(lesion group)and adjacent tissue samples(located ≥5 cm from the tumor edge,adjacent group),and used the immunohistochemistry(IHC)method to detect the expression of Mismatch repair(MMR)(MLH1,MSH2,MSH6,and PMS2)protein and PD-L1 protein.Investigated the clinical and pathological characteristics of patients and conducted correlation analysis.Results:The positive rates of dMMR and pMMR protein expression in the lesion group were 39.00%and 70.00%,respectively,while those in the adjacent cancer group were 11.00%and 89.00%,respectively.There were significant difference compared between the lesion group and the adjacent cancer group(P<0.05).The positive rate of PD-L1 protein expression in the lesion group were 25.00%,while that in the adjacent cancer group were 80.00%.The expression of PD-L1 protein in the lesion group were significantly lower than that in the adjacent cancer group(P<0.05).There were significant differences in the positive rates of MMR and PD-L1 protein expression among patients with different histological differentiation,clinical stages,and lymph node metastasis(P<0.05),while there were no significant differences in the positive rates of MMR and PD-L1 protein expression among patients of different genders,ages,and disease sites(P>0.05).Spearman analysis showed there were correlation between the expression of MMR and PD-L1 proteins in colorectal cancer tissues and clinical pathological features such as histological differentiation,clinical staging,and lymph node metastasis(P<0.05).Conclusion:Low expression of MMR and PD-L1 proteins are commonly observed in colorectal cancer tissues.The expression of MMR and PD-L1 proteins in colorectal cancer tissues are correlated with clinical pathological features such as histological differentiation,clinical staging,and lymph node metastasis.
7.The Correlation between MMR and PD-L1 Protein Expression and Clinical Pathological Characteristics in Colorectal Cancer Tissues
Xian-jie MENG ; Li XIAO ; Hai-jun ZHANG ; Jian-ming HU ; Li WEI
Progress in Modern Biomedicine 2025;25(19):3056-3061,3113
Objective:To explore and analyze the correlation between the expression of mismatch repair(MMR)protein and programmed death ligand 1(PD-L1)in colorectal cancer(CRC)tissue and clinical pathological characteristics.Methods:The study period were from July 2021 to December 2024,200 cases of colorectal cancer patients treated in our hospital were selected as the research subjects.Collected all patient lesion tissue samples(lesion group)and adjacent tissue samples(located ≥5 cm from the tumor edge,adjacent group),and used the immunohistochemistry(IHC)method to detect the expression of Mismatch repair(MMR)(MLH1,MSH2,MSH6,and PMS2)protein and PD-L1 protein.Investigated the clinical and pathological characteristics of patients and conducted correlation analysis.Results:The positive rates of dMMR and pMMR protein expression in the lesion group were 39.00%and 70.00%,respectively,while those in the adjacent cancer group were 11.00%and 89.00%,respectively.There were significant difference compared between the lesion group and the adjacent cancer group(P<0.05).The positive rate of PD-L1 protein expression in the lesion group were 25.00%,while that in the adjacent cancer group were 80.00%.The expression of PD-L1 protein in the lesion group were significantly lower than that in the adjacent cancer group(P<0.05).There were significant differences in the positive rates of MMR and PD-L1 protein expression among patients with different histological differentiation,clinical stages,and lymph node metastasis(P<0.05),while there were no significant differences in the positive rates of MMR and PD-L1 protein expression among patients of different genders,ages,and disease sites(P>0.05).Spearman analysis showed there were correlation between the expression of MMR and PD-L1 proteins in colorectal cancer tissues and clinical pathological features such as histological differentiation,clinical staging,and lymph node metastasis(P<0.05).Conclusion:Low expression of MMR and PD-L1 proteins are commonly observed in colorectal cancer tissues.The expression of MMR and PD-L1 proteins in colorectal cancer tissues are correlated with clinical pathological features such as histological differentiation,clinical staging,and lymph node metastasis.
8.Prognostic analysis and application value of adjuvant chemotherapy after radical resection for stage Ⅰ gastric cancer
Jie CHEN ; Xiaogang QU ; Keshu HU ; Mingde ZANG ; Hongda PAN ; Jun LU ; Xiaowen LIU ; Yanong WANG ; Fenglin LIU
Chinese Journal of Digestive Surgery 2025;24(8):1033-1043
Objective:To explore the prognosis after radical resection for stage Ⅰ gastric cancer and the application value of adjuvant chemotherapy.Methods:The retrospective cohort study was conducted. The clinicopathological data of 3 353 patients with stage Ⅰ gastric cancer who were admitted to Fudan University Shanghai Cancer Center from January 2000 to December 2022 were collected. There were 2 369 males and 984 females, aged 60(range, 21-91) years. All patients underwent radical R 0 resection. Observation indicators: (1) clinicopathological characteristics of patients; (2) influencing factors for postoperative prognosis of patients; (3) prognostic analysis of patients; (4) construction and validation of a predictive model for the efficacy of postoperative adjuvant chemotherapy. Comparison of count data between groups was conducted using the chi-square test. Univariate and multivariate analyses were performed using the Cox proportional hazards regression model. The Kaplan-Meier method was used to calculate survival rates and draw survival curves, and the Log-rank test was used for survival analysis. Based on the multivariate analysis result, a nomogram prediction model was constructed to predict survival benefit. Results:(1) Clinicopatho-logical characteristics of patients. The highly, moderately, and poorly differentiated tumors were observed in 16, 234, 396 cases of 646 patients aged <50 years and 279, 1 617, 811 cases of 2 707 pati-ents aged ≥50 years, respectively, showing a significant difference in degree of tumor differentiation between them ( P<0.05). For 297 patients in stage T1N1M0, cases aged <50 years and ≥50 years were 71 and 226, cases of males and females were 184 and 113, cases with negative and positive vascular invasion were 37 and 260, cases with negative and positive nerve invasion were 275 and 22, cases without and with postoperative adjuvant chemotherapy were 222 and 75, respectively. The above indicators for 678 patients in stage T2N0M0 105, 573, 533, 145, 517, 161, 526, 152, 563, 115, respectively. There were significant differences in the above indicators between the two groups ( P<0.05). (2) Influencing factors for postoperative prognosis of patients. Results of multivariate analysis showed that age ≥50 years, stage T2, moderately differentiated tumor, the number of lymph nodes dissected <16, positive vascular invasion, carcinoembryonic antigen (CEA) ≥5 μg/L, and CA19-9 ≥37 U/mL were independent risk factors for disease-free survival (DFS) after surgery for stage Ⅰ gastric cancer ( hazard ratio=4.600, 1.555, 1.835, 1.362, 1.451, 1.571, 2.134, 95% confidence interval as 2.806-7.541, 1.205-2.006, 1.016-3.314, 1.059-1.753, 1.057-1.993, 1.100-2.243, 1.257-3.625, P<0.05). Age ≥50 years, stage T2, the number of lymph nodes dissected <16, positive vascular invasion, CEA ≥5 μg/L, and CA19-9 ≥37 U/mL were independent risk factors for overall survival (OS) after surgery for stage Ⅰ gastric cancer ( hazard ratio=5.208, 1.597, 1.373, 1.520, 1.464, 2.356, 95% confidence interval as 3.028-8.955, 1.231-2.072, 1.060-1.777, 1.099-2.104, 1.004-2.134, 1.385-4.009, P<0.05). Postoperative adjuvant chemotherapy was an independent protective factor for both DFS and OS after surgery for stage I gastric cancer ( hazard ratio=0.361 0.297, 95% confidence interval as 0.177-0.736, 0.131-0.674, P<0.05). (3) Prognostic analysis of patients. According to the results of multi-variate analysis, among 3 353 patients, there were significant differences in 5-year DFS rate and 10-year OS rate between patients aged <50 years and ≥50 years ( P<0.05). There were significant differences in 5-year DFS rate and 10-year OS rate among patients in TNM stage ⅠA and ⅠB ( P<0.05). There were significant differences in 5-year DFS rate and 10-year OS rate among patients in stage T1N0M0, T1N1M0, T2N0M0 ( P<0.05). There were significant differences in 5-year DFS rate and 10-year OS rate among patients with the highly, moderately, and poorly differentiated tumors ( P<0.05). There were significant differences in 5-year DFS rate and 10-year OS rate among patients with the number of lymph lodes dissected <16 and ≥16 ( P<0.05). There were significant differences in 5-year DFS rate and 10-year OS rate between patients with negative and positive vascular invasion ( P<0.05). There were significant differences in 5-year DFS rate and 10-year OS rate between patients with and without postoperative adjuvant chemotherapy ( P<0.05), among patients in stage T1N0M0, T1N1M0, T2N0M0 who received no postoperative adjuvant chemotherapy ( P<0.05). For patients in stage T1N1M0, there was no significant difference in 5-year DFS rate and 10-year OS rate between patients with and without postoperative adjuvant chemotherapy ( P>0.05).Results of stratified analysis showed that for patients aged ≥ 50 years, there were significant differences in 5-year DFS rate and 10-year OS rate between patients with and without postoperative adjuvant chemotherapy ( P<0.05). For patients in stage T2N0M0, there were significant differences in 5-year DFS rate and 10-year OS rate between patients with and without postoperative adjuvant chemotherapy ( P<0.05). For patients with positive vascular invasion, there were significant differences in 5-year DFS rate and 10-year OS rate between patients with and without postoperative adjuvant chemotherapy ( P<0.05). (4) Construction and validation of a predictive model for the efficacy of adjuvant chemotherapy. A nomogram predictive model was constructed based on the multivariate analysis results of OS and used for calculating net benefits and distribution. Among the 3 096 patients without postoperative adjuvant chemotherapy, 1 009 cases had a predicted net benefit of >5%-10%, and 250 patients had a predicted net benefit >10%. The predicted survival analysis further verified that the predicted benefit of adjuvant chemotherapy was consistent with the prognosis of patients. Conclusions:Patients with age ≥50 years, stage T2 tumors, moderately differentiated tumor, the number of lymph nodes dissected <16, positive vascular invasion have worse survival prognosis postoperative. Postoperative adjuvant chemotherapy provides better prognosis in high-risk patients. Patients in stage T1N1M0 have lower recurrence and survival risks, of whom with 1 metastatic lymph node is more suitable for follow-up rather than postoperative adjuvant chemotherapy.
9.Application of wide awake local anesthesia no tourniquet technique in locking of metacarpophalangeal joint with extension lag surgery
Guo-tao YANG ; Hua-jie MAO ; Zhi-jun CHEN ; Xu ZHANG ; Huan HU ; Qi-ting JIANG
Journal of Regional Anatomy and Operative Surgery 2025;34(9):836-839
Objective To explore the application value of wide awake local anesthesia no tourniquet(WALANT)technique in outpatient surgery for locking of metacarpophalangeal joint with extension lag.Methods The clinical data of 6 patients with locking of meta-carpophalangeal joint with extension lag in Danyang People's Hospital from January 2019 to October 2023 were retrospectively analyzed.The patients were received outpatient surgery under the WALLANT technique for release,and lidocaine mixed solution containing 1∶100 000 epinephrine was injected into the proximal midpoint of the volar projection of the metacarpophalangeal joint.The joint was exposed with a volar or dorsal finger web incision to determine the unrestricted structure,and the collateral ligament and paralateral collateral ligament with high tension were cut off.The intraoperative blood loss,postoperative incision healing and complications were recorded.Visual analogue scale(VAS)was used to evaluate the intraoperative pain,and the range of motion of metacarpophalangeal joint and total active movement(TAM)of finger joint were observed during postoperative follow-up.Results The incision of patients were healed successfully in the first phase after surgery,without wound necrosis.The anesthesia effects of patients were all satisfied and the operation was successfully completed.The VAS score was less than 3 points and there was only a small amount of bleeding during the operation.The recovery of joint flexion and extension movements could be observed during the operation,and the TAM score after the operation was 20 points.No significant change was found on the range of motion of metacarpophalangeal joint or TAM of finger joint between the injured finger and the corresponding healthy finger(P>0.05).Conclusion WALANT technique for locking of metacarpophalangeal joint with extension lag surgery has good anesthesia effect,less bleeding in the incision,and clear vision of the surgery.It can avoid vascular and nerve injuries,observe the recovery of joint activities during the operation and relieve pain of patients,which is conducive to outpatient surgery and saving medical and social resources at the same time.
10.Advances in regulation of dysregulated bone remodeling by immune cells within rheumatoid arthritis synovial microenvironment
Jun-jie HE ; Zhong-liu YAO ; Ming-yue HU ; Hong HUANG ; Xiong CAI
Chinese Pharmacological Bulletin 2025;41(10):1801-1807
Rheumatoid arthritis(RA)is characterized by bidi-rectional bone remodeling imbalance,clinically termed the "high resorption-low formation" paradox,stemming not only from osteoclast hyperactivation but also critically involving pro-found suppression of osteoblast differentiation and function.No-tably,this suppression cannot be fully attributed to osteoclast hyperactivity;synovium-resident immune cells exert a pivotal regulatory influence through distinct mechanisms.This review systematically examines how synovial immune cells orchestrate bone remodeling in RA through both paracrine cytokine networks and direct cell-cell communication with bone lineage cells,thereby perturbing physiological homeostasis and driving patho-logical progression.These mechanistic revelations yield innova-tive perspectives on RA pathogenesis,positioning immune-medi-ated osteoimmune dysregulation as a promising therapeutic fron-tier for targeted intervention.

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