ObjectiveThe essence of syndrome manifestation recognition in traditional Chinese medicine (TCM) is to infer the body’s latent pathogenesis state from clinical observational information, rather than to perform simple label matching. However, previous studies have largely modeled this task as syndrome pattern classification within a fixed label space, which does not adequately reflect the cognition process of TCM syndrome differentiation centered on pathogenesis reasoning, and is also insufficient to capture the openness, semantic variability, and cross-disease reusability of syndrome manifestation expression. This study aimed to investigate whether introducing pathogenesis reasoning chain-of-thought (PR-CoT) supervision into large language models (LLMs) could improve the quality and cognitive consistency of syndrome manifestation recognition and support cross-disease transfer. MethodsSyndrome manifestation recognition was formulated as a conditional generation task under the framework of clinical observational information (X)→pathogenesis structure (Z)→syndrome pattern output (Y), where Z serves as an explicit intermediate structural variable linking the clinical evidence and syndrome judgment. Within this framework, a PR-CoT-supervised dataset for syndrome manifestation recognition was constructed based on medical case records of spleen-stomach disorders. After preprocessing, information extraction, manual proofreading, and data cleaning, the dataset comprised 4 800 training cases, 400 development cases, and 400 test cases. Each sample was annotated with a structured PR-CoT consisting of three progressive levels: clinical information summarization, comprehensive pathogenesis analysis, and syndrome pattern output. Supervised fine-tuning was conducted on open-source LLMs, with an end-to-end model serving as the baseline. Qwen3-32B was used as the primary experimental model, and Qwen3-14B as the scale comparison model. A progressive multidimensional evaluation framework was further established, comprising a structural parsing level, a semantic similarity level, and an expert blind review level. At the structural parsing level, syndrome pattern expressions were decomposed into structural elements and evaluated using Precision, Recall, F1 score, and Jaccard similarity. At the semantic similarity level, independent LLMs scored the theoretical proximity between predicted and reference syndrome patterns. At the expert blind review level, three TCM experts independently evaluated model outputs on two dimensions: syndrome differentiation consistency and terminology standardization of syndrome patterns. In addition, zero-shot cross-disease transfer evaluation was conducted on gynecological and heart-system disorder test sets. ResultsAt the structural parsing level, PR-CoT supervision did not lead to a stable improvement in the element-wise overlap of syndrome pattern structural components. Compared with the corresponding baselines, neither Qwen3-32B nor Qwen3-14B showed consistent advantages in structural matching metrics after the introduction of PR-CoT supervision. In contrast, at the semantic similarity level, PR-CoT supervision produced stable positive gains across different model scales and evaluation systems. The average semantic score of Qwen3-32B increased from 6.425 8 in the baseline model to 6.585 0 after PR-CoT supervision, and that of Qwen3-14B increased from 5.870 0 to 5.964 2. At the expert blind review level, the overall score of Qwen3-32B (PR-CoT) was 7.026 0±0.107 7, higher than 6.416 3±0.288 9 for its baseline. In zero-shot cross-disease testing, the PR-CoT model still showed advantages in semantic evaluation and expert evaluation on both gynecological and heart-system disorder test sets, indicating a certain degree of transferability. ConclusionThe benefits of PR-CoT supervision are mainly reflected in TCM semantic consistency and clinical plausibility, rather than in improved hard matching of structural elements. These findings support understanding syndrome manifestation recognition as a process of generating and expressing latent pathogenesis structures, rather than as a classification task within a traditional fixed label space. By introducing pathogenesis reasoning as an explicit intermediate structure into the modeling process and combining it with a progressive multidimensional evaluation framework, this study provides a methodological pathway for intelligent TCM syndrome differentiation that integrates theoretical alignment, interpretability, and multi-level evaluation.

ObjectiveThe essence of syndrome manifestation recognition in traditional Chinese medicine (TCM) is to infer the body’s latent pathogenesis state from clinical observational information, rather than to perform simple label matching. However, previous studies have largely modeled this task as syndrome pattern classification within a fixed label space, which does not adequately reflect the cognition process of TCM syndrome differentiation centered on pathogenesis reasoning, and is also insufficient to capture the openness, semantic variability, and cross-disease reusability of syndrome manifestation expression. This study aimed to investigate whether introducing pathogenesis reasoning chain-of-thought (PR-CoT) supervision into large language models (LLMs) could improve the quality and cognitive consistency of syndrome manifestation recognition and support cross-disease transfer. MethodsSyndrome manifestation recognition was formulated as a conditional generation task under the framework of clinical observational information (X)→pathogenesis structure (Z)→syndrome pattern output (Y), where Z serves as an explicit intermediate structural variable linking the clinical evidence and syndrome judgment. Within this framework, a PR-CoT-supervised dataset for syndrome manifestation recognition was constructed based on medical case records of spleen-stomach disorders. After preprocessing, information extraction, manual proofreading, and data cleaning, the dataset comprised 4 800 training cases, 400 development cases, and 400 test cases. Each sample was annotated with a structured PR-CoT consisting of three progressive levels: clinical information summarization, comprehensive pathogenesis analysis, and syndrome pattern output. Supervised fine-tuning was conducted on open-source LLMs, with an end-to-end model serving as the baseline. Qwen3-32B was used as the primary experimental model, and Qwen3-14B as the scale comparison model. A progressive multidimensional evaluation framework was further established, comprising a structural parsing level, a semantic similarity level, and an expert blind review level. At the structural parsing level, syndrome pattern expressions were decomposed into structural elements and evaluated using Precision, Recall, F1 score, and Jaccard similarity. At the semantic similarity level, independent LLMs scored the theoretical proximity between predicted and reference syndrome patterns. At the expert blind review level, three TCM experts independently evaluated model outputs on two dimensions: syndrome differentiation consistency and terminology standardization of syndrome patterns. In addition, zero-shot cross-disease transfer evaluation was conducted on gynecological and heart-system disorder test sets. ResultsAt the structural parsing level, PR-CoT supervision did not lead to a stable improvement in the element-wise overlap of syndrome pattern structural components. Compared with the corresponding baselines, neither Qwen3-32B nor Qwen3-14B showed consistent advantages in structural matching metrics after the introduction of PR-CoT supervision. In contrast, at the semantic similarity level, PR-CoT supervision produced stable positive gains across different model scales and evaluation systems. The average semantic score of Qwen3-32B increased from 6.425 8 in the baseline model to 6.585 0 after PR-CoT supervision, and that of Qwen3-14B increased from 5.870 0 to 5.964 2. At the expert blind review level, the overall score of Qwen3-32B (PR-CoT) was 7.026 0±0.107 7, higher than 6.416 3±0.288 9 for its baseline. In zero-shot cross-disease testing, the PR-CoT model still showed advantages in semantic evaluation and expert evaluation on both gynecological and heart-system disorder test sets, indicating a certain degree of transferability. ConclusionThe benefits of PR-CoT supervision are mainly reflected in TCM semantic consistency and clinical plausibility, rather than in improved hard matching of structural elements. These findings support understanding syndrome manifestation recognition as a process of generating and expressing latent pathogenesis structures, rather than as a classification task within a traditional fixed label space. By introducing pathogenesis reasoning as an explicit intermediate structure into the modeling process and combining it with a progressive multidimensional evaluation framework, this study provides a methodological pathway for intelligent TCM syndrome differentiation that integrates theoretical alignment, interpretability, and multi-level evaluation.

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.

Objective:To explore the relationship between the expression of peripheral blood interleukin-17 (IL)-17 and IL-8 and the short-term prognosis of sepsis patients.Methods:The data of 158 patients with sepsis admitted to Huzhou Central Hospital from January 2020 to January 2024 were retrospectively collected. The patient′s data were carefully reviewed, and the results of the study were recorded, including the severity of the patient′s condition (138 cases of sepsis, 20 cases of septic shock), baseline data, and short-term prognosis (28-day mortality). The levels of procalcitonin (PCT), peripheral blood IL-17, IL-8, and other laboratory indicators were compared between patients with different severity and different prognosis. COX regression model analysis and interaction test were used to verify the relationship between peripheral blood IL-17, IL-8 levels, and short-term prognosis in patients with sepsis. The receiver operating characteristic (ROC) curve was drawn and the decision curve was constructed to analyze the predictive value of peripheral blood IL-17 and IL-8 levels on the short-term prognosis of patients with sepsis.Results:The levels of IL-17 and IL-8 in the peripheral blood of patients with different severity of sepsis at admission were higher in the septic shock group than those in the sepsis group: (82.48 ± 13.54) μg/L vs. (62.84 ± 12.09) μg/L, (41.80 ± 5.46) ng/L vs. (34.22 ± 6.77) ng/L,( P<0.05). The acute physiology and chronic health evaluation (APACHE) Ⅱ score, PCT, IL-17, and IL-8 levels at admission in the death group were higher than those in the survival group, and the proportion of patients with septic shock was higher than that in the survival group: (12.09 ± 2.06) points vs. (10.81 ± 2.36) points, (2.23 ± 1.18) μg/L vs. (1.78 ± 0.69) μg/L, (79.24 ± 13.72) μg/L vs. (61.37 ± 11.15) μg/L, (42.43 ± 5.07) ng/L vs. (33.09 ± 6.14) ng/L, 51.43%(18/35) vs. 1.63%(2/123), P<0.05. COX regression analysis showed that the short-term prognosis of patients with sepsis was related to the abnormal expression of IL-17 and IL-8 in peripheral blood. The high expression of both may be a risk factor for the short-term prognosis of patients with sepsis ( P<0.05). The levels of IL-17 and IL-8 in peripheral blood had a positive interaction on the short-term prognosis of patients with sepsis. The risk of death when both were highly expressed was 97.500 times that when both were lowly expressed and the synergistic effect was 9.362 times higher than the sum of the effects produced by the two alone (synergy index = 9.362). ROC curve was drawn to obtain the area under the curve (AUC). The AUC of peripheral blood IL-17, IL-8 alone and combined to predict the short-term prognosis risk of sepsis patients were 0.839, 0.889 and 0.960, respectively, which had ideal predictive value, and the combined predictive value was higher than that of the two alone ( Z = 3.85, 2.66, P<0.05). The decision curve was drawn. When the threshold was 0.1-1.0, the net return rate of the combined prediction model of IL-17 and IL-8 in peripheral blood to predict the short-term prognosis risk of sepsis patients was better than that of IL-17 and IL-8 alone, and the maximum net return rate was 0.222. Conclusions:The more severe the condition of sepsis patients, the higher the expression of IL-17 and IL-8 in peripheral blood, which may suggest that patients have a high risk of short-term death. Early combined detection of IL-17 and IL-8 levels in the peripheral blood of sepsis patients can predict their short-term prognostic risk.

Objective:This study aims to investigate the feasibility and safety of implanting leadless pacemakers in the low septum and its impact on cardiac electrical synchronization.Methods:A total of 36 patients who received leadless pacemaker implantation at Fuwai Central China Cardiovascular Hospital from January 2021 to August 2023 were included in this study.According to implantation sites of leadless pacemakers,patients were divided into mid-septal group(n=16)and low-septal group(n=20).The clinical characteristics and cardiac electrical synchronization were compared between the two groups.Results:There were 21 male patients,mean age was(68±13)years old.There was no statistical difference in the type of brady-arrhythmia between the two groups(P=0.73).There were 61 implant attempts in these 36 patients,and there was no significant difference in the number of attempts,procedure time,and pacemaker parameters between the two groups,but the average procedure time tended to be shorter in the low-septal group([84±37]minutes vs.[105±35]minutes,P=0.09).In terms of electrical synchronization,there was no statistical difference in QRS duration between the low-septal group and the mid-septal group([162.0±21.1]ms vs.[174.0±14.8]ms,P=0.20).There were no vascular puncture complications,cardiac perforation,or pericardial tamponade during the procedure.There were no complications and readmissions related to the leadless pacemaker during follow-up period.Conclusions:Our results show that the implantation of a leadless pacemaker in the low ventricular septum is safe and effective,has a similar impact on cardiac electrical synchronization as mid-septal pacing.

Objective To investigate the bidirectional causal relationship between circulating amino acid levels and the risk of myasthenia gravis(MG)using Mendelian randomization(MR).Methods A two-sample Mendelian randomization a-nalysis was conducted using publicly available genome-wide association study(GWAS)genetic data,with validation from GWAS data from different sources to assess the robustness of the results.Five models were used for the two-sample bidirectional MR anal-ysis,and odds ratios(OR)were calculated to evaluate the causal relationship between the levels of nine circulating amino acids and MG risk.Sensitivity analyses,heterogeneity tests,and pleiotropy tests were performed to assess the robustness of the results.The causal effect estimated by the inverse variance weighted(IVW)method was the primary result,and the IVW-estimated causal effects were further validated using data from different GWAS sources to assess robustness.Results Genetically predicted high-er circulating glutamine levels were significantly associated with a lower risk of MG[OR(95％CI)=0.696(0.524,0.926),P=0.012 7,IVW model].Validation analyses using GWAS data from various sources also demonstrated a significant negative associa-tion between genetically predicted higher circulating glutamine levels and MG risk[OR(95％CI)=0.321(0.178,0.581),P=1.67x10-1,IVW model].Moreover,genetically predicted higher MG risk was associated with lower levels of circulating glutamine and alanine(β=-0.178±0.009,P=0.049;β=-0.013±0.007,P=0.048,IVW model,respectively).Conclusion Genetic evidence reveals a potential bidirectional causal relationship between circulating amino acid levels and MG risk.Further studies are required to elucidate the mechanisms underlying this relationship.

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.

Objective To explore the change of nucleoplasm distribution of glucocorticoid receptor alpha(GRα)in peripheral blood of children with primary nephrotic syndrome(PNS)during the course of the disease,aiming at evaluating the correlation between nuclear transport abnormality and different GC responses.Methods A total of 45 children with PNS were enrolled as subjects in this prospective study,and divided into steroid-sensitive nephrotic syndrome(SSNS,n=36)and steroid-resistant nephrotic syndrome(SRNS,n=9)groups,according to their response to GC.The SSNS group was further subclassified into non-frequently relapsing nephrotic syndrome(NFRNS,n=21)and frequently relapsing nephrotic syndrome(FRNS,n=15)based on relapse frequency during 12-month follow-up.Peripheral blood samples were collected before GC treatment,6-week and 6-month after GC treatment.GRα nuclear localization was detected by immunofluorescence assay,and their correlations with clinical-laboratory indicators were analyzed.Results Before the GC treatment,the average fluorescence intensity showed no significantly difference among different groups(P＞0.05),the GRαin the three groups were localized mainly in cytoplasm,and the nucleocytoplasmic ratio showed no significantly difference among the three groups(P＞0.05).6-week after the GC treatment,the average fluorescence intensity showed no significantly difference among the three groups(P＞0.05),the GRα in SSNS group were localized mainly in nucleus,while those in SRNS group were localized mainly in cytoplasm.Furthermore,nucleocytoplasmic ratio in NFRNS group and SRNS group demonstrated significant differences,while those in NFRNS group and FRNS group showed no significant difference(P＞0.05).6-month after the GC treatment,the average fluorescence intensity in NFRNS group and FRNS group showed no significant difference(P＞0.05),GRα in the two groups were localized mainly in nucleus,and their nucleocytoplasmic ratio had significantly differences(P＜0.05).The GRα nucleocytoplasmic ratio in children with PNS was negatively correlated with 24-hour urine protein(24 h-UTP),TNF-α,while positively correlated with serum albumin(Alb).Conclusion There are differences in nuclear transport ability among PNS children of SRNS,NFRNS and FRNS groups,and these differences are correlated with the differency of GC responses.

Objective:To establish the minimum number of negative lymph nodes (nLN) required for patients undergoing gastrectomy.Methods:This was a retrospective cohort study with inclusion criteria as follows: (1) radical gastrectomy; (2) histologically confirmed adenocarcinoma; (3) complete tumor staging information; and (4) known number of lymph nodes harvested. The exclusion criteria were: (1) other concurrent malignant tumors; (2) metastatic or recurrent gastric cancer; (3) initial surgery performed at another hospital; (4) preoperative neoadjuvant therapy; (5) distant metastasis; and (6) incomplete clinical data or follow-up information. Based on the above criteria, a total of 11 167 patients with gastric adenocarcinoma who underwent radical subtotal gastrectomy (RSG) or radical total gastrectomy (RTG) in the Department of Gastric Surgery, Fudan University Shanghai Cancer Center between January 1, 2000, and December 31, 2022, were included in the study. Among them, there were 7 596 cases in the RSG group and 3 571 cases in the RTG group. Restricted cubic spline (RCS) analysis was used to determine the ideal threshold for nLN for RSG and RTG patients. Survival analysis was conducted using Kaplan-Meier (KM) curves and log-rank tests, and propensity score matching (PSM) was utilized to balance parameters between two groups. Furthermore, subgroup analysis was conducted for RSG patients based on tumor location (upper, middle and lower) to determine the minimum number of nLN in each subgroup.Results:For patients who underwent RSG, the mean number of nLN was 21.9, with a median of 21. RCS analysis showed that more than 21 nLN was associated with better survival. Moreover, both pre- and post-PSM analysis confirmed that patients with nLN ≥21 had better survival benefits compared to those with nLN <21 (overall survival [OS]: P<0.001 before PSM, P=0.013 after PSM; disease-free survival [DFS]: P<0.001 before PSM, P=0.013 after PSM). For patients who underwent RTG, the mean number of nLN was 23.5, with a median of 22. Here RCS analysis indicated that more than 22 nLN was associated with better postoperative survival in RTG patients, and both pre- and post-PSM analysis confirmed that patients with nLN ≥22 had better survival benefits compared to those with nLN<22 (OS: P<0.001 both before and after PSM; DFS: P<0.001 both before and after PSM). Subgroup analysis showed that for RSG patients with tumor located in the upper part, having ≥17 nLN (OS: both P<0.001), and for RSG patients with tumor located in the middle and lower part, having ≥22 nLN (OS: both P<0.001), were associated with better prognoses. Conclusions:For patients who receive RSG, the minimal number of nLN is ideally ≥21 (upper ≥17, middle and lower ≥22). Similarly, for patients who receive RTG, the minimum number of nLN ideally is 22.

Objective To construct a risk score model for basement membrane-related genes(BMRGs)in triple-negative breast cancer(TNBC).Methods The TNBC risk score model based on BMRGs was established in the cancer genome atlas(TCGA)cohort by the LASSO-COX regression machine learning method,and verified in the Yau-2010 cohort and the molecular taxonomy of breast cancer international consortium(METABRIC)cohort.A nomogram containing BMRG risk score and clinical factors was constructed to predict the survival prognosis of TNBC patients.Based on the functional annotations of gene ontology(GO)and the Kyoto encyclopedia of genes and genomes,KEGG and Gene Set Enrichment Analysis(GSEA)were used to explore differences in protein functional enrichment in risk subgroups.The Immuno-Oncology Biological Research(IOBR)package was used to explore differences in immune infiltration based on risk subgroups.The Mutation Annotation Format Tools(Maltools)package was used to explore genomic changes.Finally,based on the cancer therapeutics response portal(CTRP)and the cancer single-cell expression map(CSEP)to explore differences in drug sensitivity and single-cell expression status in risk score subgroups.Results Six BMRGS-constructed risk subgroups were identified by Kaplan-Meier(KM)survival analysis and LASSO-COX regression analysis and were closely related to the prognosis of TNBC patients(all P<0.001).Among them,SDC1 and ADAM9 were poor prognostic factors,HAPLN1,FREM1,FBLN5 and ITGB4 were protective prognostic factors.The combination of BMRGs risk score and TNM tumor stage has excellent predictive ability for the prognosis of TNBC patients.Protein function analysis showed that the up-regulated genes in the high-risk group were enriched in the pathways and biological functions of neuroactive ligand-receptor interactions,synthesis of various biological complexes,and participation in immune defense responses.Compared with the high-risk group,the infiltration degree of mast cells and cytotoxic lymphocytes was higher in the low-risk group.The genetic map revealed that the most frequently mutated genes in the high-low-risk subgroups were not identical Drug sensitivity analysis showed that patients in the high-risk group had higher sensitivity to bortezomib,fluvastatin,and ouabain(all P<0.05).Patients in the low-risk group had higher sensitivity to nintedanib,BRD-A86708339,and vandetanib(all P<0.05).Single-cell analysis showed that the above six genes were highly expressed in TNBC tumor cells.Conclusion The risk score based on BMRGs was constructed and validated to provide effective biological indicators for predicting the survival and prognosis of TNBC patients.