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.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective:To investigate the role of hypoxia-induced angiopoietin-like protein 4 (ANGPTL4) expression in experimental choroidal neovascularization (CNV).Methods:Twenty-seven SPF male C57BL/6J mice aged 6-8 weeks were selected.Eighteen of the mice were used to establish a laser-induced CNV model.On the 7th day after laser photocoagulation, success of the modeling was verified using optical coherence tomography angiography (OCTA) and fundus fluorescein angiography (FFA). The retinal pigment epithelium (RPE)-choroid-sclera complex was extracted for protein analysis before modeling and on the 3rd and 7th days after modeling.The relative expression levels of ANGPTL4 and vascular endothelial growth factor (VEGF) at different time points were detected by Western blot.Additionally, frozen sections of mouse eyeballs on day 7 after modeling were prepared and the expression and cellular localization of ANGPTL4 were observed by immunofluorescence.RF/6A cells, derived from monkey choroidal retinal endothelial cells, were treated with 200 μmol/L cobalt chloride (CoCl 2) in the culture medium for 0, 3, 6, and 12 hours.RF/6A cells were also divided into a normal control group, a hypoxia group, and a hypoxia+ si-ANGPTL4 group, and cells were transfected with a plasmid containing si-ANGPTL4 sequence.The relative expression levels of ANGPTL4 and VEGF proteins in each group were detected by Western blot, and the differences in tube formation among the groups were observed by tube formation assay.A total of 27 male C57BL/6J mice were randomly divided into CNV group, CNV+ si-NC group, and CNV+ si-ANGPTL4 group, with 9 mice in each group.In the CNV+ si-NC and CNV+ si-ANGPTL4 groups, si-NC and si-ANGPTL4 were respectively injected into the vitreous cavity after the CNV model was established.Fluorescence leakage in mice was observed by FFA, and the length, thickness and area of CNV was observed using OCTA and immunofluorescence staining of choroidal flat mounts.The relative expression levels of ANGPTL4 and VEGF proteins in each group were detected by Western blot.All animal experiments were conducted in accordance with ARVO Statement on the Use of Animals in Ophthalmic and Vision Research.The experimental protocol was approved by the Affiliated Hospital of Nantong University (No.S20220822-902). Results:Before modeling and on the 3rd and 7th days after modeling, the relative expression levels of ANGPTL4 protein were 1.00±0.00, 1.58±0.05, and 1.90±0.04, respectively, and the relative expression levels of VEGF protein were 1.00±0.00, 1.31±0.05, and 1.84±0.04, respectively, with statistically significant overall differences ( F=528.934, 390.424, both P<0.05). Among them, on the 3rd and 7th days after modeling, the relative expression levels of ANGPTL4 and VEGF proteins were significantly higher in CNV group than in the control group (all P<0.05). The tissues of each layer of the retina were clear in the control group, while neovascularization could be seen growing under the retinal neuroepithelial layer in the CNV group.Compared with the control group, ANGPTL4 expression was significantly increased and colocalized with vascular endothelial cells in the CNV group.After CoCl 2 treatment of RF/6A cells for 3, 6, and 12 hours, the relative expression levels of ANGPTL4 and VEGF proteins were higher than at 0 hour, with statistically significant differences (all P<0.05). Compared with the control group, the relative ANGPTL4 protein expression was increased in the hypoxia group and significantly decreased in the hypoxia+ si-ANGPTL4 group, showing statistically significant differences (both P<0.05). The number of tube formations in the control group, hypoxia group, and hypoxia+ si-ANGPTL4 group were 12.67±1.53, 19.64±1.56, and 17.01±1.04, respectively, with a statistically significant overall difference ( F=33.091, P<0.01). The number of tube formations increased in the hypoxia group and hypoxia+ si-ANGPTL4 group compared with the control group, and the number of tube formations decreased in the hypoxia+ si-ANGPTL4 group compared with the hypoxia group, with statistically significant differences (all P<0.05). Relative expression levels of ANGPTL4 and VEGF proteins were significantly lower in the CNV+ si-ANGPTL4 group than those in the CNV group (both P<0.05). The CNV area was significantly lower in the CNV+ si-ANGPTL4 group than in the CNV group and CNV+ si-NC group (both P<0.05). Conclusions:Hypoxia-induced ANGPTL4 promotes experimental CNV formation in vivo and in vitro.Inhibiting ANGPTL4 can reduce CNV formation and leakage.

Aim To investigate the effects of breast cancer-related depression model on microglial activa-tion and neuronal function via the NLRP3-COX-2 sig-naling pathway.Methods In the cell experiment,BV2 and HT22 cells were co-cultured to observe the polarization of BV2 cells and the injury of HT22 cells.In the animal experiment,behavioral experiments were used to evaluate the depressive behaviors of mice.HE staining and tumor weight were used to evaluate the changes of axillary tumors.ELISA was used to detect the contents of CA153,CA125,CEA,as well as the changes in the contents of 5-HT,DA and others in the serum and hippocampus.RT-qPCR and immunohisto-chemistry were used to detect the mRNA and protein expression of IL-1 β,IL-18 and other indicators,re-spectively.Immunofluorescence was used to detect CD1 1b and Iba-1.Nissl staining and transmission elec-tron microscopy were used to observe the hippocampal neurons.Results The results of cell experiments showed that compared with the model group,the pro-tein contents and mRNA expression levels of NLRP3,COX-2,and IL-1 β in the NLRP3 knockdown group were all decreased.The results of animal experiments showed that compared with the model group,the be-havioral performance of the experimental group was im-proved,and the mRNA and protein expression levels of IL-1 β,IL-18,and NLRP3 were decreased.Conclu-sion BCRD may mediate the polarization of microglia and the injury of hippocampal neurons through the NL-RP3-COX-2 signaling pathway.

Objective To explore the relationship between insulin resistance and idiopathic central precocious puberty(ICPP)in girls and the diagnostic value of insulin resistance.Methods Clinical data of 245 girls aged 4 to 7.5 years with low luteinizing hormone(LH)levels(0.2-0.83 IU/L),normal body weight(body mass index standard deviation score between-2 and+2),and early breast development who visited the Department of Pediatric Endocrinology,Henan Provincial Maternal and Child Health Hospital from January 2022 to March 2025 were retrospectively analyzed.According to the Expert Consensus on the Diagnosis and Treatment of Central Precocious Puberty(2022),patients were assigned to an ICPP group(n=123)or a control group(n=122).Correlations between the homeostasis model assessment of insulin resistance(HOMA-IR)and selected indices were assessed.Multivariable logistic regression was used to evaluate the association between HOMA-IR and ICPP,and the diagnostic performance of various indices for ICPP was evaluated.Results HOMA-IR was higher in the ICPP group than in the control group(P<0.001)and was positively correlated with LH peak(rs=0.467,P<0.05)and the LH peak/FSH peak ratio(rs=0.444,P<0.05).The multivariable logistic regression model including age,BMI,and basal LH showed that HOMA-IR was closely associated with ICPP(OR=2.756,95%CI:1.940-3.913).Receiver operating characteristic curve analysis showed that the areas under the curve for basal LH,HOMA-IR,and their combination in diagnosing ICPP were 0.735,0.735,and 0.805,respectively(P<0.05),and the combined model had a greater area under the curve than either basal LH or HOMA-IR alone(both P<0.05).Conclusions HOMA-IR is closely associated with ICPP in girls with low LH and normal body weight,and combining HOMA-IR with basal LH improves early identification and diagnostic efficiency in this population.

Objective:To investigate the effects of Japan tallow(JT)on liver injury and gut microbiota regulation in type 2 diabetes mellitus(T2DM)mice,thereby providing a theoretical basis for developing therapeutic edible oils for diabetes treatment.Methods:T2DM animal model was established through a combined approach of nutritional intervention and chemical induction.Experimental animals were first fed a high-fat diet(HFD)for 6 weeks,followed by intraperitoneal injection of freshly prepared streptozotocin(STZ).After successful model establishment,the mice were divided into five groups(n=6 per group):control group without any intervention;T2DM group;HFD reversion to standard chow group;metformin group;and JT intervention group,which received respective treatments for 4 weeks.At the endpoint,fresh fecal samples were collected from all groups,and the gut microbiota composition was analyzed using 16s rDNA high-throughput sequencing.Liver histopathological changes were examined using histological methods.Results:Compared with the normal control(ND),T2DM mice showed significantly increased fasting blood glucose(FBG)levels,with evident hepatocyte lipid accumulation,steatosis,inflammatory cell infiltration,and widespread vacuolar and fatty degeneration.After Japan tallow(JT)intervention,FBG levels decreased significantly,liver color approximated normal appearance,and pathological morphology improved noticeably.16s rDNA sequencing analysis demonstrated that JT treatment could effectively regulate the intestinal microbiota structure in T2DM mice.Increased microbial α-diversity indices(Chao1,observed_species,Faith_pd,Simpson);At the phylum level,increased Verrucomicrobia abundance while decreased Proteobacteria were detected;At the family level,elevated Bifidobacteriaceae and reduced Porphyromonadaceae were seen;At the genus level,Bifidobacterium was promoted and Akkermansia proliferat while Escherichia and Klebsiella were downregulated.Conclusions:Japan tallow exhibits significant effects in alleviating liver tissue damage and regulating intestinal microbiota disorders in T2DM mice,our study indicated new theoretical basis for the research and development of potential strategy for diabetes.

Objective:To explore the predictive value of serum interleukin-6(IL-6)combined with Montreal Cognitive Assessment(MoCA)score and CHANGE risk score for post-stroke cognitive impairment(PSCI),and to provide a basis for early identification and intervention of high-risk patients.Methods:The general data of 200 patients with acute stroke who were admitted to our hospital from October 2022 to September 2024 were retrospectively analyzed,they were divided into PSCI group(49 cases)and non PSCI group(151 cases)based on whether PSCI occurred 3 months after acute stroke.The general data of two groups were compared,multiple logistic regression was used to analyze the influencing factors of PSCI,and receiver operating characteristic(ROC)curves were used to evaluate predictive efficiency of serum IL-6,MoCA score and CHANGE risk score for of PSCI.Results:There was a statistically significant difference in age and education level between the two groups(P＜0.05).The serum IL-6 level and CHANGE risk score in the PSCI group were higher than those in the non PSCI group,while the MoCA score was lower than that in the non PSCI group(P＜0.05).Multivariate logistic regression showed that elevated IL-6 levels(OR=1.851,P=0.001)and elevated CHANGE risk scores(OR=1.076,P=0.016)were independent risk factors of the occurrence of PSCI,while elevated in MoCA score(OR=0.806,P=0.001)was a protective factor(P＜0.05).IL-6 levels,MoCA scores and CHANGE risk scores have high predictive efficiency for the occurrence of PSCI,the area under the curve(AUC)for predicting occurrence of PSCI by the three alone were 0.783,0.825 and 0.857 respectively,the AUC for the combined detection of the three indicators was 0.912,significantly higher than that of each indicator detected separately.Conclusion:Elevated serum IL-6,decreased MoCA score and increased CHANGE risk score are risk factors for PSCI,the combined detection model of the three has the highest predictive efficiency for occurrence of PSCI and can provide scientific basis for early clinical intervention.

Objective To investigate the early postoperative efficacy between Kahook dual blade(KDB)internal tra-beculectomy and internal gonioscopy-assisted transluminal trabeculotomy(GATT)in the treatment of primary open-angle glaucoma(POAG).Methods A total of 120 patients(120 eyes)with POAG were included and divided according to dif-ferent surgical treatment methods.Among them,62 patients(62 eyes)undergoing internal trabeculectomy by KDB were di-vided into Group A,and 58 patients(58 eyes)undergoing GATT were divided into Group B.Relevant data of patients in the two groups were collected,and the efficacy of the two surgical methods was compared.Results The intraocular pres-sure in both groups decreased 1 day,1 week,and 1 month after surgery compared with preoperative levels(all P＜0.05).However,there was no significant difference in the intraocular pressure measured at the above time points between the two groups(all P＞0.05).The type of drugs for reducing the intraocular pressure in both groups decreased significantly 1 day,1 week,and 1 month after surgery compared with preoperative levels(all P＜0.05).However,there was no significant difference in the type of drugs for reducing the intraocular pressure at the above time points between the two groups(all P＞0.05).There was no statistically significant difference in the total incidence of complications between Group A(45.16％)and Group B(39.66％)(P＞0.05).Specifically,the main complications in Group A included anterior chamber hemorrhage and intraocular pressure rebound,while those in Group B included anterior chamber hemorrhage and ciliary detachment.Conclusion Both KDB internal trabeculectomy and GATT can effectively reduce the intraocular pressure in patients with POAG and reduce the use of postoperative intraocular pressure-lowering drugs.There was no significant difference in surgical complications between the two surgical methods.The selection of surgical procedures in clinical prac-tice can be determined based on patients' wishes and actual situation.

This study was aimed at tracing the molecular typing and drug resistance characteristics of a suspected food poi-soning event caused by Clostridium perfringens in a district of Wuhan City.The FilmArray detection system and multiple fluo-rescence quantitative PCR methods were used to rapidly screen for pathogens in samples from the poisoning event.According to the initial screening results,bacteria were isolated,cultured,and identified by mass spectrometry.Fluorescence PCR was used to detect six virulence genes of the isolated Clostridium perfringens strains.On the basis of whole genome sequencing results,we conducted virulence genes,resistance genes,and whole genome single nucleotide polymorphism genetic evolution(wgSNPs)analyses.Antibiotic sensitivity testing was conducted with the agar dilution method.A total of ten strains of Clos-tridium perfringens were isolated,including eight strains from seven anal swab samples,one strain from fecal samples,and one strain from food samples.Food with suspected contamination had a Clostridium perfringens count of 7.8×106 CFU/g.The PLC(a)toxin gene was detected in all ten gas producing capsule isolation strains,but no other 5 tox-in genes such as CPE were detected,thus confirming that all were type A bacteria producing capsule Clostridium.All strains were 100％resistant to clindamycin and almost completely sensitive to antibiotics such as vancomycin,cefoxitin,and meropenem.Ten strains of Clos-tridium perfringens carried resistance genes such as tetB(P),tetA(P),and mprF,followed by ermQ(70％),ant(6)-Ⅰb(10％),and LnuP(10％).Genetic evolution analysis of wgSNPs indicated that the four outbreak strains clustered together and belonged to an independent subbranch with the suspected food sourcestrains,thus indicating close genetic relationships.In con-clusion,this food poisoning incident might have been be caused by hand torn chickens contaminated with Clostridium perfrin-gens,and the molecular types of the strains revealed high genetic diversity.No multiple drug resistance was observed,but all strains were resistant to clindamycin,an aspect requiring further clinical attention.