OBJECTIVE To construct an intelligent pharmaceutical Q&A platform for precision medication with low “artificial intelligence （AI） hallucination”， aiming to enhance the accuracy， consistency， and traceability of medication consultations. METHODS Medication package inserts were batch-processed and converted into structured data through Python programming to build a local pharmaceutical knowledge base. The retrieval and question-answering processes were designed based on large language models， and system integration and localized deployment were completed on Dify platform. By designing typical clinical medication questions and comparing the output of the intelligent pharmaceutical Q&A platform with the online version of DeepSeek across dimensions such as peak time retrieval， half-life， and dosage adjustment reasoning for patients with renal impairment， the accuracy and reliability of its retrieval and reasoning results were evaluated. RESULTS The intelligent pharmaceutical Q&A platform， constructed based on local drug package inserts， achieved 100% accuracy in retrieval and reasoning for peak time， half-life， and dosage adjustment schemes. In comparison， the online version of DeepSeek demonstrated accuracies of 30%（6/20）， 50%（10/20）， and 38%（23/60） across these three dimensions， respectively. CONCLUSIONS The constructed intelligent pharmaceutical Q&A platform is capable of accurately retrieving and extracting information from the local knowledge base based on clinical inquiries， thereby avoiding the occurrence of AI hallucinations and providing reliable medication decision support for healthcare professionals.

Objective To observe the clinical efficacy of Tongyuan acupuncture in the treatment of acute gouty arthritis.Methods A total of 126 cases of patients with definitive diagnosis of acute gouty arthritis admitted to the wards and outpatient clinics of Guangzhou Nansha District Hospital of Traditional Chinese Medicine from November 2023 to June 2024 were selected as the study subjects.The patients were randomly divided into observation group and control group according to the random number table method,with 63 cases in each group.The control group was given health training and conventional treatment,while the observation group was given Tongyuan acupuncture on the basis of treatment in the control group.Patients in both groups were treated for 14 consecutive days.After two weeks of treatment,the clinical efficacy of the two groups was evaluated.The changes in the clinical symptom scores,the Visual Analogue Scale(VAS)scores of pain,the levels of musculoskeletal ultrasonography(synovial proliferation,blood flow signals,and joint fluid)before and after the treatment were observed in patients of both groups.The changes of blood uric acid(UA),erythrocyte sedimentation rate(ESR),C-reactive protein(CRP),tumor necrosis factor α(TNF-α),and interleukin 1(IL-1)before and after treatment were compared between the two groups.Results(1)The total effective rate was 95.24%(60/63)in the observation group and 84.13%(53/63)in the control group.The efficacy of the observation group was superior to that of the control group,the difference being statistically significant(P<0.05).(2)After treatment,the clinical symptom scores and VAS scores of the patients in the two groups were improved significantly(P<0.05),and the improvement in the observation group was significantly superior to that in the control group,the difference being statistically significant(P<0.05).(3)After treatment,the serum UA,ESR,and CRP levels of patients in the two groups were improved significantly(P<0.05),and the improvement in the observation group was significantly superior to that in the control group,the difference being statistically significant(P<0.05).(4)After treatment,the TNF-α and IL-1 levels of patients in the two groups were improved significantly(P<0.05),and the improvement in the observation group was significantly superior to that in the control group,the difference being statistically significant(P<0.05).(5)After treatment,the musculoskeletal ultrasound indicators of the two groups of patients were improved significantly(P<0.05),and the improvement in the observation group was significantly superior to that in the control group,the difference being statistically significant(P<0.05).Conclusion Tongyuan acupuncture in the treatment of acute gouty arthritis can significantly improve the clinical symptoms of patients,reduce the level of patients'blood UA and inflammatory factor.

Objective To identify the independent predictors of programmed death-1 (PD-1) inhibitor-related endocrine adverse events and construct a clinically usable risk prediction model. Methods A total of 302 patients with solid tumors treated with PD-1 inhibitors were retrospectively enrolled. According to the presence or absence of endocrine immune-related adverse events (irAEs), the patients were divided into case group and control group. The clinical and laboratory indexes were compared between the two groups. Multivariable logistic regression was used to confirm independent predictors of endocrine irAEs. The nomogram was constructed, while the receiver operating characteristic (ROC) curve was used to test the prediction performance of the model. Results The overall incidence of endocrine irAEs was 21.9% (66/302), and the incidence of hypothyroidism was 19.5% (59/302). The age, PD-1 inhibitors, free thyroxine, thyroid peroxidase antibody (TPOAb), thyroglobulin, amylase, lymphocyte subset CD3 expression were statistically different between the two groups (P＜0.05). Multivariable logistic regression showed that higher expression of lymphocyte subset CD3 was a protective factor to prevent endocrine irAEs occurrence (P＝0.004), while age＜60 years, higher TPOAb and use of pembrolizumab were independent risk factors of endocrine irAEs (P＜0.05). The nomogram model thus constructed, and when the threshold probability of the model exceeded 0.1, its net benefit was higher. ROC curve showed that the AUC of the model to predict endocrine irAEs was 0.760. The prediction result of the model was highly consistent with the actual result. Conclusions The age, type of PD-1 inhibitor, baseline TPOAb level, and baseline CD3 expression can independently predict endocrine irAEs occurrence or not. The nomogram model based on this model has good predictive efficiency, which can provide reference for early identification of high-risk patients and immunotherapy management.

BACKGROUND: The transcription factor POU2F1 regulates the expression levels of microRNAs in neoplasia. However, the miR-29b1/a cluster modulated by POU2F1 in gastric cancer (GC) remains unknown. METHODS: Gene expression in GC cells was evaluated using reverse-transcription polymerase chain reaction (PCR), western blotting, immunohistochemistry, and RNA in situ hybridization. Co-immunoprecipitation was performed to evaluate protein interactions. Transwell migration and invasion assays were performed to investigate the biological behavior of GC cells. MiR-29b1/a cluster promoter analysis and luciferase activity assay for the 3'-UTR study were performed in GC cells. In vivo tumor metastasis was evaluated in nude mice. RESULTS: POU2F1 is overexpressed in GC cell lines and binds to the miR-29b1/a cluster promoter. POU2F1 is upregulated, whereas mature miR-29b-3p and miR-29a-3p are downregulated in GC tissues. POU2F1 promotes GC metastasis by inhibiting miR-29b-3p or miR-29a-3p expression in vitro and in vivo . Furthermore, PIK3R1 and/or PIK3R3 are direct targets of miR-29b-3p and/or miR-29a-3p , and the ectopic expression of PIK3R1 or PIK3R3 reverses the suppressive effect of mature miR-29b-3p and/or miR-29a-3p on GC cell metastasis and invasion. Additionally, the interaction of PIK3R1 with PIK3R3 promotes migration and invasion, and miR-29b-3p , miR-29a-3p , PIK3R1 , and PIK3R3 regulate migration and invasion via the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway in GC cells. In addition, POU2F1 , PIK3R1 , and PIK3R3 expression levels negatively correlated with miR-29b-3p and miR-29a-3p expression levels in GC tissue samples. CONCLUSIONS The POU2F1 - miR-29b-3p / miR-29a-3p-PIK3R1 / PIK3R1 signaling axis regulates tumor progression and may be a promising therapeutic target for GC.
MicroRNAs/metabolism* ; Humans ; Stomach Neoplasms/pathology* ; Cell Line, Tumor ; Cell Movement/physiology* ; Phosphatidylinositol 3-Kinases/metabolism* ; Animals ; Mice ; Octamer Transcription Factor-1/metabolism* ; Mice, Nude ; Class Ia Phosphatidylinositol 3-Kinase/metabolism* ; Neoplasm Invasiveness ; Gene Expression Regulation, Neoplastic/genetics* ; Male ; Immunohistochemistry ; Female

Purpose To investigate the clinicopathological features,differential diagnosis and prognosis of atypical fibroxanthoma(AFX).Methods Pathological features of 15 cases of AFX and 3 cases of pleomorphic dermal sarcoma(PDS)misdiagnosed as AFX were retrospectively analyzed by hematoxylin and eosin staining and immunohistochemical EnVision staining technology.Clinical information was collected and analyzed,and the relevant literatures were re-viewed.Results The age of the 15 patients with AFX ranged from 18 to 78 years,with an average age of 57 years.4 cases occurred in the head and neck,and 11 cases occurred in the trunk and limbs.3 patients with PDS misdiagnosed as AFX were aged from 56 to 60 years,with an average age of 58 years.The tumors were located in the trunk and limbs.Microscopically,15 cases of AFX and 3 cases of PDS misdiagnosed as AFX were composed of proliferative pleo-morphic and atypical spindle cells interspersed with a varying number of multinucleated cells.15 cases of AFX tumors were superficial and located in the dermis.In 3 cases of PDS misdiagnosed as AFX,1 case was located in subcutane-ous adipose tissue,1 case had superficial subcutaneous extension,and the third case had positive basal margin.Immu-nohistochemically,the immunophenotypes of the two groups were consistent.CD10 was expressed in all cases,CD68 was positive in most cases,SMA was expressed in a few cases,desmin was focal expressed in a very few cases,and S-100,SOX10,CD34,HMB-45,Melan A,STAT6 and CK(AE1/AE3)were not expressed in all cases.Ki67 prolifera-tion index ranged from 2％to 30％.15 patients with AFX were followed up from 12 to 108 months.One patient had tumor recurrence 1 year and 3 years after operation due to positive basal margin.Most of the other patients underwent extended resection after diagnosis and were in good condition without tumor recurrence and metastasis.3 cases of PDS misdiagnosed as AFX were followed up for 31 to 78 months.One patient had lung metastasis after 2 years,one patient recurred 4 times after operation,and the other patient died after 4 times of recurrence.Conclusion AFX is a rare dis-ease with similar pathological characteristics and immunophenotype to PDS.AFX can be diagnosed only when the tumor is small and completely confined to the dermis.When the maximum diameter of the tumor is more than 3 cm,or the presence of any form of subcutaneous extension requires a high level of vigilance for PDS.Careful differentiation and correct classification of AFX and PDS are very important for the treatment and prognosis of the disease.

AIM:To investigate the mechanism by which interleukin-13(IL-13)influences vascular smooth muscle cell(VSMC)phenotypic transformation and subsequently contributes to vascular intimal hyperplasia in rats.METHODS:A total of 32 male SD rats,aged 5～7 weeks and weighing 330～360 g,were randomly divided into 4 groups(n=8 per group):normal(Nor)group,normal treatment(Nor+IL-13 neutralizing antibody,Nor+IL-13Nab)group,inju-ry(Inj)group,and injruy treatment(Inj+IL-13Nab)group.A 2F balloon catheter was used to induce mechanical injury in the left common carotid artery of SD rats to establish a vascular intimal hyperplasia model.Hematoxylin-eosin staining was performed to observe vascular structural changes.Enzyme-linked immunosorbent assay(ELISA)kits were used to measure IL-13 and transforming growth factor-β1(TGF-β1)levels.Human aortic smooth muscle cells(HA-SMCs)were cultured in vitro.Flow cytometry was conducted to assess peripheral blood CD4+IL-13+T cell content.Real-time quantita-tive PCR(RT-qPCR)was employed to evaluate gene expression levels of α-smooth muscle actin,osteopontin,calponin,collagen type Ⅰ/Ⅲ,proliferating cell nuclear antigen and Ki-67 antigen.Transwell and scratch wound assays were per-formed to assess cell migration.RESULTS:Compared with the model group,administration of IL-13Nab significantly in-hibited vascular intimal hyperplasia induced by mechanical vascular injury by antagonizing high plasma IL-13 levels(P<0.01).Immunofluorescence and mRNA analysis showed that neutralizing high plasma IL-13 suppressed collagen accumu-lation(P<0.01)and VSMC phenotypic transformation(P<0.01)in the injured vessels but did not inhibit peripheral blood CD4+IL-13+T cell activation.Incubation of HA-SMCs with recombinant human IL-13(rhIL-13)promoted cell pro-liferation and migration(P<0.01)as well as phenotypic transformation(P<0.01).Additional evidence suggested that rhIL-13-induced HA-SMC phenotypic transformation was associated with the regulation of TGF-β1 secretion by HA-SMCs.CONCLUSION:Interleukin-13 promotes vascular intimal hyperplasia by regulating VSMC phenotypic transformation through TGF-β1 secretion in rat models.

Purpose To investigate the clinicopathological features,differential diagnosis and prognosis of atypical fibroxanthoma(AFX).Methods Pathological features of 15 cases of AFX and 3 cases of pleomorphic dermal sarcoma(PDS)misdiagnosed as AFX were retrospectively analyzed by hematoxylin and eosin staining and immunohistochemical EnVision staining technology.Clinical information was collected and analyzed,and the relevant literatures were re-viewed.Results The age of the 15 patients with AFX ranged from 18 to 78 years,with an average age of 57 years.4 cases occurred in the head and neck,and 11 cases occurred in the trunk and limbs.3 patients with PDS misdiagnosed as AFX were aged from 56 to 60 years,with an average age of 58 years.The tumors were located in the trunk and limbs.Microscopically,15 cases of AFX and 3 cases of PDS misdiagnosed as AFX were composed of proliferative pleo-morphic and atypical spindle cells interspersed with a varying number of multinucleated cells.15 cases of AFX tumors were superficial and located in the dermis.In 3 cases of PDS misdiagnosed as AFX,1 case was located in subcutane-ous adipose tissue,1 case had superficial subcutaneous extension,and the third case had positive basal margin.Immu-nohistochemically,the immunophenotypes of the two groups were consistent.CD10 was expressed in all cases,CD68 was positive in most cases,SMA was expressed in a few cases,desmin was focal expressed in a very few cases,and S-100,SOX10,CD34,HMB-45,Melan A,STAT6 and CK(AE1/AE3)were not expressed in all cases.Ki67 prolifera-tion index ranged from 2％to 30％.15 patients with AFX were followed up from 12 to 108 months.One patient had tumor recurrence 1 year and 3 years after operation due to positive basal margin.Most of the other patients underwent extended resection after diagnosis and were in good condition without tumor recurrence and metastasis.3 cases of PDS misdiagnosed as AFX were followed up for 31 to 78 months.One patient had lung metastasis after 2 years,one patient recurred 4 times after operation,and the other patient died after 4 times of recurrence.Conclusion AFX is a rare dis-ease with similar pathological characteristics and immunophenotype to PDS.AFX can be diagnosed only when the tumor is small and completely confined to the dermis.When the maximum diameter of the tumor is more than 3 cm,or the presence of any form of subcutaneous extension requires a high level of vigilance for PDS.Careful differentiation and correct classification of AFX and PDS are very important for the treatment and prognosis of the disease.

AIM:To investigate the mechanism by which interleukin-13(IL-13)influences vascular smooth muscle cell(VSMC)phenotypic transformation and subsequently contributes to vascular intimal hyperplasia in rats.METHODS:A total of 32 male SD rats,aged 5～7 weeks and weighing 330～360 g,were randomly divided into 4 groups(n=8 per group):normal(Nor)group,normal treatment(Nor+IL-13 neutralizing antibody,Nor+IL-13Nab)group,inju-ry(Inj)group,and injruy treatment(Inj+IL-13Nab)group.A 2F balloon catheter was used to induce mechanical injury in the left common carotid artery of SD rats to establish a vascular intimal hyperplasia model.Hematoxylin-eosin staining was performed to observe vascular structural changes.Enzyme-linked immunosorbent assay(ELISA)kits were used to measure IL-13 and transforming growth factor-β1(TGF-β1)levels.Human aortic smooth muscle cells(HA-SMCs)were cultured in vitro.Flow cytometry was conducted to assess peripheral blood CD4+IL-13+T cell content.Real-time quantita-tive PCR(RT-qPCR)was employed to evaluate gene expression levels of α-smooth muscle actin,osteopontin,calponin,collagen type Ⅰ/Ⅲ,proliferating cell nuclear antigen and Ki-67 antigen.Transwell and scratch wound assays were per-formed to assess cell migration.RESULTS:Compared with the model group,administration of IL-13Nab significantly in-hibited vascular intimal hyperplasia induced by mechanical vascular injury by antagonizing high plasma IL-13 levels(P<0.01).Immunofluorescence and mRNA analysis showed that neutralizing high plasma IL-13 suppressed collagen accumu-lation(P<0.01)and VSMC phenotypic transformation(P<0.01)in the injured vessels but did not inhibit peripheral blood CD4+IL-13+T cell activation.Incubation of HA-SMCs with recombinant human IL-13(rhIL-13)promoted cell pro-liferation and migration(P<0.01)as well as phenotypic transformation(P<0.01).Additional evidence suggested that rhIL-13-induced HA-SMC phenotypic transformation was associated with the regulation of TGF-β1 secretion by HA-SMCs.CONCLUSION:Interleukin-13 promotes vascular intimal hyperplasia by regulating VSMC phenotypic transformation through TGF-β1 secretion in rat models.

OBJECTIVES: This study examined the associations between adverse childhood experiences (ACEs) and diabetes within a social-ecological framework, incorporating personal and environmental unfavorable conditions during childhood from family, school, and community contexts. METHODS: Data were obtained from the China Health and Retirement Longitudinal Study (2014 life history survey and 2015 survey), including 9,179 participants aged ≥45 years. ACEs were collected through self-report questionnaires, and participants were categorized based on the number of distinct ACEs experienced (0, 1, 2, 3, or ≥4 ACEs). Diabetes was defined by biomarkers, self-reported diagnosis, and treatment status. Logistic regression was conducted to explore the associations between ACEs and diabetes. Subgroup analyses were conducted by gender, age, and obesity status. RESULTS: Compared with participants without ACEs, those exposed to any ACE (odds ratio [OR], 1.19; 95% confidence interval [CI], 1.01 to 1.40), 3 ACEs (OR, 1.32; 95% CI, 1.07 to 1.62) and ≥4 ACEs (OR, 1.29; 95% CI, 1.07 to 1.56) had an increased risk of diabetes. For each additional ACE, the risk of diabetes increased by about 5%. Regarding the source of ACEs, those originating from the family (OR, 1.23; 95% CI, 1.08 to 1.41) were associated with diabetes. In terms of specific ACE types, family members with substance abuse (OR, 1.23; 95% CI, 1.01 to 1.52), emotional abuse (OR, 1.28; 95% CI, 1.12 to 1.46), and poor parental relationship (OR, 1.25; 95% CI, 1.09 to 1.43) were associated with diabetes. CONCLUSIONS ACEs, particularly those originating from the family, were associated with diabetes. Interventions aimed at preventing and mitigating ACEs are essential for the early prevention of diabetes.

Objective:To study the mechanistic role of myeloid-specific Notch1 knockout inhibiting STING signaling to regulate hepatocyte lipophagy.Methods:A mouse model of nonalcoholic steatohepatitis (NASH) was established using a high-fat diet (HFD) and mouse bone marrow-derived macrophages (BMMs). Primary hepatocytes were isolated to construct a co-culture system. Twelve Notch1 FL/FL mice were randomly divided into two groups: the Notch1 FL/FL + normal diet (NCD) and the Notch1 FL/FL + HFD group. Further, 12 Notch1 M-KO mice were randomly divided into two groups: Notch1 M-KO + NCD, and Notch1 M-KO + HFD group.Serum alanine aminotransferase (sALT), total cholesterol (TC) and triglyceride (TG) were collected from mice serum samples. Liver tissue samples were collected for H&E staining, immunofluorescence (IF), Western blot and qRT-PCR. Tumor necrosis factor (TNF)-α was detected in the supernatant by enzyme-linked immunosorbent assay (ELISA). The comparison of inter group data was conducted using a t-test. Results:The mouse NASH model, mouse BMMs co-culture system, and primary hepatocytes were successfully constructed. Compared with the Notch1 FL/FL + HFD group, the Notch1 M-KO + HFD group showed a significant increase in serum ALT [(250.02 ± 58.21) U/L vs (370.70 ± 54.57) U/L, t = 3.705, P = 0.004], TG [(29.90 ± 3.54) mg/g vs (43.83 ± 8.56) mg/g, t = 3.685, P = 0.004], and TC [(33.70 ± 8.43) mg/g vs (90.53 ± 12.53) mg/g, t = 9.917, P < 0.001]. HE staining of liver tissue showed remarkable balloon-like alterations in liver cells, while IF staining demonstrated increased macrophage infiltration ( t = 7.346, P < 0.001). Compared with the hepatocyte group co-cultured with Notch1 FL/FL BMMs, the BODIPY probe showed a significant increase in lipid droplet (LDs) deposition in liver cells in the Notch1 M-KO group ( t = 3.835, P < 0.001). The co-localization of lysosomal associated membrane protein 1 (LAMP1), LDs ( t = 7.103, P < 0.001), microtubule-associated protein light chain 3 (LC3) -II/LC3-I ( t = 5.0, P = 0.007), and autophagy associated gene 12 (Atg12) ( t = 28.36, P < 0.001) had decreased expression, while P-62 had increased expression ( t = 3.253, P = 0.03), indicating a decrease in autophagic flow. Additionally, LC3 and LDs colocalization decreased ( t = 5.24, P = 0.0003), indicating reduced lipophagy. Compared with the Notch1 FL/FL group, the Notch1 M-KO BMMS mouse group showed an increase in the expression of p-STING ( t = 5.318, P = 0.006), p-TANK1 binding kinase 1 (TKB1) ( t = 6.467, P = 0.002), p-interferon regulatory factor 3 (IRF3) ( t = 14.61, P < 0.001), and p-P65 ( t = 12.7, P = 0.002) protein, accompanied by mRNA expression of the inflammatory mediators interferon (IFN)-β ( t = 7.978, P < 0.001), TNFα ( t = 8.496, P = 0.001), interleukin-1 β (IL-1 β) ( t = 4.7, P < 0.001), and CXCL-10 ( t = 4.428, P = 0.001). The STING gene was knocked out in the BMMs Notch1 M-KO mice using CRISPR/Cas9. Compared with the CRISPR-Control group, the expression of P-TKB1 ( t = 2.909, P = 0.044), p-IRF3 ( t = 10.96, P < 0.001), p-IRF3 ( t = 10.96, P < 0.001), and p-P65 ( t = 7.091, P = 0.002) proteins was lower in the STING-KO BMMs group. The release of TNF-α in the supernatant was decreased (732.3 ± 129.35 pg/ml vs. 398.17 ± 47.15 pg/ml, t = 4.204, P = 0.014). However, in hepatocytes co-cultured with STING-KO BMMs, LC3-II/LC3-I ( t = 7.546, P = 0.001) increased, p-62 ( t = 10.96, P < 0.001) expression decreased, autophagic flow increased, and the colocalization of LC3 and LDs increased, lipophagy increased, and LDs deposition decreased. Conclusion:Myeloid-specific Notch1 knockout can activate macrophages STING signaling, increase the expression of inflammatory mediator genes, inhibit the occurrence of autophagy flow and lipophagy in hepatocyte cells, and aggravate LDs deposition and NASH progression.