The connotation of "treat heat with cold" and "disperse fire constraint" differs， and under the guidance of these two principles， there are variations in the selection of acupoints， choice of needles， and manipulation techniques in clinical acupuncture. "Treat heat with cold" is used to clear and drain heat pathogens， while "disperse fire constraint" focuses on diffusing and dissipating fire from constraint. When both fire constraint and internal heat coexist， treatment should combine both "dispersing the fire" and "cooling the heat". In clinical acupuncture， for clearing heat and draining heat pathogens， acupoints on Governor vessel （督脉） and Yangming （阳明经） channel are commonly selected， with Jing-well points， Ying-spring points and He-sea points. To diffuse and dissipate fire constraint， acupoints on the Taiyang （太阳） and Shaoyang （少阳） channels are usually chosen， with Jing-river points and Ashi points as the primary options. In terms of needle choice， for heat syndrome， filiform needles， three-edged needles， and cupping are often used for clearing heat and resolving toxins； for fire constraint syndrome， moxibustion and fire needles are employed to expel fire from the body. Regarding manipulation techniques， draining method can be used in both conditions， with heat syndrome requiring shallow needling and quick removal， while fire constraint syndrome requiring deeper and longer retention of needles， having an emphasis on hand pressure coordination and smooth qi flow. In clinical practice， it is essential to distinguish the presence of "constraint" and the depth of the disease location to appropriately combine "dispersing fire" and "cooling heat".

ObjectiveTo investigate the clinical features of tumor-induced acute pancreatitis （TIAP）， to construct and validate a predictive model for TIAP， and to provide help for early identification in clinical practice. MethodsA retrospective analysis was performed for the clinical data of 3 051 patients with acute pancreatitis （AP） who were admitted to The First Affiliated Hospital of Xinjiang Medical University from January 2020 to January 2026， among whom there were 72 patients with TIAP. To reduce class imbalance， 216 patients with non-tumor-related AP （2 979 patients） were randomly selected as conventional group using sex-stratified sampling， resulting in a cohort of 288 patients， and this cohort was randomly divided into a training set with 201 patients and a test set with 87 patients at a ratio of 7∶3. The two groups were compared in terms of general information and laboratory markers. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between two groups. Recursive feature elimination and least absolute shrinkage and selection operator regression were used for screening of characteristic variables， and five machine learning models were constructed， i.e.， logistic regression model， random forest model， support vector machine model， extreme gradient boosting model， and light gradient boosting machine model. The receiver operating characteristic curve and the precision-recall curve were used to assess model performance； the calibration curve was used to assess goodness of fit； decision curve analysis was used to evaluate clinical applicability and practicality； Shapley additive explanations were used to assess model interpretability. ResultsIn the training set of 201 patients， there were 52 patients （25.9%） in the TIAP group， and in the test set of 87 patients， there were 20 patients （23.0%） in the TIAP group. Compared with the conventional group， the TIAP group had a significantly higher proportion of patients with pancreatic duct dilatation （χ²=79.474， P<0.05）， a significantly higher age （Z=-5.838， P<0.05）， and significantly lower levels of white blood cell count （Z=5.630， P<0.05）， amylase （Z=2.606， P<0.05）， hemoglobin （Z=5.038， P<0.05）， and neutrophil percentage （Z=5.269， P<0.05）， as well as a lower level of direct bilirubin （Z=0.936， P>0.05）. The five machine learning models constructed based on these seven variables had a certain predictive ability， among which the logistic regression model had the best performance in the test set， with an area under the curve of 0.893 （95% confidence interval： 0.821 — 0.953）， an average precision of 0.654 in the precision-recall curve， good calibration， and good clinical benefits based on the decision curve analysis. ConclusionThe predictive model for TIAP based on pancreatic duct dilatation， age， white blood cell count， amylase， hemoglobin， neutrophil percentage， and direct bilirubin shows good predictive performance and can provide important guidance for the early diagnosis of TIAP.

It is believed that the head and facial orifices are connected with the brain's spirit and the spirits of the five organs. Their functions， including vision， hearing， smell， taste， and speech， are manifestations of the activity of the spirit. Furthermore， head and facial orifice disorders are interrelated with spirit disorders， forming a cause-and-effect relationship. Acupuncture has a regulatory effect on the spirit. Based on this， acupuncture for regulating the spirit in treating head and facial orifice disorders is proposed. This includes regulating the brain's spirit to treat functional disorders， regulating the heart's spirit to clarify the functions of governing substances， regulating the organ's spirit to benefit the orifices and enhance the communication of the spirit， and regulating the liver's spirit to promote the flow of Qi （气） and relieve stagnation， thereby providing a framework for acupuncture to treat head and facial orifice disorders.

Objective:To investigate the effect of nuclear receptor subfamily 2 group F member 2(NR2F2)on the biological behaviors of human ovarian cancer SKOV3 cells,and to clarify its molecular mechauism and provide the new idea for treatment of ovarian cancer.Methods:Gene Expression Profiling Interactive Analysis(GEPIA)Database analyse the expression level of NR2F2 gene in ovarian tissue,and analyse its correlation with clinical prognosis of ovarian cancer patients.The human ovarian cancer SKOV3 cells were divided into control group and NR2F2 over-expression(NR2F2 OE)group,which were transfected with mCherry control virus and NR2F2 OE over-expression virus,respectively,when the cell deusity reached 70％,and the stable transfection SKOV3 cell lines were screened with puromycin(puro)48h lafter.Real-time fluorescence quantitative PCR(RT-qPCR)and Western blotting methods were used to detect the transfection efficiencies of the cells;RT-qPCR method was used to detect the expression levels of NR2F2 and sex-determining region Y-box 2(SOX2)mRNA in the cells in two groups;Western blotting method was used to detect the expression levels of NR2F2,ATP-binding cassette superfamily G member 2(ABCG2),and programmed cell death 1-ligand 1(PD-L1)protcins in the cells in two groups.CCK-8 assay was used to detect the proliferation activities of the cells in two groups;Wound assay was used to detect the migration rates of the cells in two groups;Transwell chamber assay was used to detect the number of transmembrane cells;Spheroidization assay was used to detect the numbers of spheroids in the cells;peripheral blood mononuclear cells(PBMCs)-mediated tumor cell killing assay was used to detect the relative densities of surviving tumor cells;CCK-8 assay was used to detect the half maximal inhibitory concentration(IC50)of paclitaxel(PTX)and carboplatin(CBP).Results:Compared with normal ovarian tissue,the expression level of NR2F2 gene in ovarian tumor tissue was decreased(P＜0.05),and decreased with the improvement of clinical pathological grading of ovarian tumor.The patients with higher expression level of NR2F2 gene had better clincal prognosis.The SKOV3 cells with NR2F2 over-expresson were successfully constructed,and the expression levels of NR2F2 mRNA and protein in the cells in NR2F2 OE group were increased compared with control group(P＜0.001).The CCK-8 assay results showed that compared with control group,the proliferation activities of the cells in NR2F2 OE group were decreased at different time points(1,2,3,and 4 d)(P＜0.05 or P＜0.01).The cell wound assay results showed that compared with control group,the migration rate of the cells in NR2F2 OE group was decreased(P＜0.001).The Transwell assay results showed that compared with control group,the number of transmembrane cells in NR2F2 OE group was decreased(P＜0.01).Compared with control group,the number of the spheroids in NR2F2 OE group was decreased(P＜0.05),and the expression levels of SOX2 mRNA(P＜0.01)and protein(P＜0.001)were increased.Compared with control group,the relative density of surviving tumor cells in NR2F2 OE group was decreased,but the difference was not significant(P＜0.05),and the expression level of PD-L1 protein was decreased(P＜0.05).Compared with control group,the proliferation activities of cells in NR2F2 OE group were decreased(P＜0.05),and the drug sensitivities of the cells to PTX and CBP were enhanced(P＜0.05);the IC50 of PTX was significantly reduced,while the IC50of CBP could not be calculated due to excessively high drug concentration;the expression level of ABCG2 protein was decreased(P＜0.05).Conclusion:The over-expression of NR2F2 may inhibit the proliferation,migration,and invasion of the human ovarian cancer SKOV3 cells,decrease the expression levels of SOX2,PD-L1 and ABCG2 proteins,suppress the stemness and immune evasion ability of the SKOV3 cells,and enhance the sensitivities of the SKOV3 cells to PTX and CBP.

Objective:To discuss the effect of long non-coding RNA(lncRNA)LINC00973 on the migration,invasion,and distant metastasis of epithelial ovarian cancer,and to clarify its molecular mechanism.Methods:The human ovarian cancer SKOV3 and OVCAR3 cells were divided into EF1a-FH empty vector control group(control group),LINC00973 overexpression group(LINC00973 OE group),U6-shRNA empty vector control group(SHV group),and LINC00973 knockdown group(LINC00973 KD group),and were transfected with lentivirus containing nonsense sequence(pLent-EF1a-FH-CMV-copGFP-P2A-Puro),LINC00973 overexpression,nonsense sequence(pLent-U6-shRNA-CMV-copGFP-P2A-Puro)and LINC00973 shRNA,respectively,followed by puromycin screening to obtain stably transfected SKOV3 and OVCAR3 cells.Real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the mRNA expression levels of target genes in the cells in various groups;wound healing assay was used to detect the migration rate of the cells in various groups;Transwell chamber assay was used to detect the number of transmembrane cells in various groups;The mice were divided into control group(WT group),LINC00973 OE group,and LINC00973 KD group,with 4 mice in each group.SKOV3 wild-type cells,LINC00973 OE cells,and LINC00973 KD cells were intraperitoneally injected into the mice in various groups,respectively,to establish the epithelial ovarian cancer intraperitoneal implantation and metastasis model;HE staining was used to observe the morphology of the colon and liver tissues of the mice in various groups;RNA-secquencing(RNA-seq)was used to analyze the differentially expressed genes between SHV and LINC00973 KD groups in the SKOV3 cell line;RT-qPCR method was used to detect the mRNA expression levels of LINC00973 in the normal ovarian epithelial cells IOSE-80 and epithelial ovarian cancer cells SKOV3,A2780 and OVCAR3,the mRNA expression levels of LINC00973,Vimentin,Snail family transcriptional repressor 1(Snail),Twist family basic helix-loop-helix transcription factor 1(Twist),zinc finger E-box binding homeobox 1(ZEB1),zinc finger E-box binding homeobox 2(ZEB2),CXCL8 and matrix metalloproteinase(MMP)16 in the cells in various groups,and the mRNA expression levels of LINC00973,Vimentin and Twist in liver and colon tissues of the mice in various groups.Results:Compared with normal ovarian epithelial cells IOSE-80,the expression level of LINC00973 mRNA in the epithelial ovarian cancer cells SKOV3,OVCAR3 and A2780 was significantly increased(P<0.01),with the highest expression level of LINC00973 in SKOV3 and OVCAR3 cells,which were therefore selected for subsequent experiments.In SKOV3 and OVCAR3 cells,compared with control group,the expression level of LINC00973 mRNA in the cells in LINC00973 OE group was increased(P<0.01);compared with SHV group,the expression level of LINC00973 mRNA in the cells in LINC00973 KD group was decreased(P<0.05 or P<0.01),indicating successful construction of LINC00973 overexpression and knockdown cell lines.In SKOV3 cells,compared with control group,the mRNA expression levels of Vimentin and Twist in LINC00973 OE group were increased(P<0.05 or P<0.01),while no significant difference was observed in Snail mRNA expression level(P>0.05);compared with SHV group,the mRNA expression levels of Vimentin,Snail and Twist in LINC00973 KD group were decreased(P<0.01).In OVCAR3 cells,compared with control group,the mRNA expression levels of Vimentin,Snail and Twist in LINC00973 OE group were increased(P<0.01);compared with SHV group,the expression levels of Vimentin,Snail,and mRNA Twist in LINC00973 KD group were decreased(P<0.01).The wound healing assay results showed that compared with control group,the wound healing rates of the SKOV3 and OVCAR3 cells in LINC00973 OE group were significantly increased(P<0.01);compared with SHV group,the wound healing rates of the cells in LINC00973 KD group were significantly decreased(P<0.01).The Transwell chamber assay results showed that compared with control group,the numbers of transmembrane cells of the SKOV3 and OVCAR3 cells in LINC00973 OE group were significantly increased(P<0.01);compared with SHV group,the numbers of transmembrane cells in LINC00973 KD group were significantly decreased(P<0.01).Compared with WT group,the number of peritoneal nodules in LINC00973 OE group was increased,with rough liver surface and multiple nodules formed on mesentery and colon surface,and the expression levels of LINC00973,Vimentin,and Twist mRNA in colon tissue were increased(P<0.01);compared with WT group,no nodules were formed in the peritoneal cavity of LINC00973 KD group,with smooth liver surface,no nodules in liver tissue,and decreased expression levels of LINC00973,Vimentin,and Twist mRNA,and no nodules were observed on mesentery and colon surface.The HE staining results showed that compared with WT group,the multiple lesions were observed in liver and colon tissues in LINC00973 OE group,manifested as uneven cell size,irregular shape,unclear cell boundaries,increased nuclear division,and uneven red staining in cytoplasm,while in LINC00973 KD group,the cells in liver and colon tissues were arranged neatly with regular shape,and uniform distribution of nuclei and cytoplasm.The RNA-seq results showed that compared with SHV group,no key signaling pathways related to tumor metastasis were enriched in LINC00973 KD group,and the transcription levels of metastasis-related genes CXCL8,MMP16,ZEB1,and ZEB2 were decreased.The RT-qPCR results showed that compared with control group,the expression levels of ZEB1,ZEB2,CXCL8,and MMP16 mRNA in the cells in LINC00973 OE group were significantly increased(P<0.01);compared with SHV group,the expression levels of ZEB1,ZEB2,CXCL8,and MMP16 mRNA in the cells in LINC00973 KD group were significantly decreased(P<0.01).Conclusion:LINC00973 can up-regulate the expression of metastasis-related factors Vimentin,Snail,Twist,ZEB1,ZEB2,CXCL8,and MMP16,and promote the migration,invasion,and distant metastasis of epithelial ovarian cancer.

Danggui Buxue decoction(DBD)is a classic prescription with immunomodulatory and hematopoietic effects.Previous studies have shown the DBD has potential to be used as an oral im-mune booster.However,its immunomodulatory effects and mechanism of action have not been thoroughly studied,especially the protective mechanism of immunomodulatory regulation in the state of immunosuppressive is still unclear.The aim of this study was to explore the protective mechanism of DBD in the immunosuppressive state using network pharmacology combined with animal experiments verification.The active components,core targets and signaling pathways of DBD in treating immunosuppression were obtained using network pharmacology tools.On this ba-sis,the active components of DBD were identified using HPLC-MS,and in vivo studies were con-ducted at the same time.The key active components of DBD obtained using network pharmacology included quercetin,kaempferol and formononetin.The core targets included TP53,RELA,TNF,AKT1,and IL-6.KEGG pathway enrichment analysis showed that phosphoinositide 3-kinase(PI3K)-protein kinase B(AKT)may play an important role in the treatment of immunosuppres-sive diseases using DBD.Molecular docking confirmed that each core target had good binding activ-ity with its corresponding compounds.Animal experiments showed that after DBD intervention,the mRNA gene and protein expression of RELA,TNF,and IL-6 in the serum was significantly down-regulated.The mRNA expression of PI3K and AKT in the ileum and PI3K protein expression were also downregulated.In conclusion,DBD exerts its role in treating immunosuppressive diseases by regulating the PI3K-AKT signaling pathway.

Objective:To explore the dual mediating effects of health belief and depression among health knowledge, social support, and health behaviors based on the capacity, opportunity, motivation-behavior (COM-B) model, and analyze the influencing factors of health behaviors in patients with ischemic stroke.Methods:This multi-center cluster sampling research recruited ischemic stroke patients ( n=1 696) who were hospitalized in neurology departments of five tertiary hospitals in Henan Province from October 2023 to October 2024. A cross-sectional investigation was conducted using the general information questionnaire, social support rating scale (SSRS), stroke prevention knowledge questionnaire(SPKQ), short form health belief model scale(SF-HBMS), health promoting lifestyle profile-Ⅱ (HPLP-Ⅱ), and patient health questionnaire-9(PHQ-9) to ultimately reveal the pathways and effect sizes among variables. Partial correlation analysis and multiple linear stepwise regression analysis were conducted to examine the relationships among social support, health knowledge, health belief, health behaviors, and depression in stroke patients by SPSS 26.0 software. Structural equation modeling was constructed using AMOS 28.0 software, and the mediating effect was tested using the Bootstrap method. Results:The scores of social support, health knowledge, health belief, and health behaviors among ischemic stroke patients were (37.46±9.94), (26.56±6.84), (75.62±12.62) and (130.79±26.27), respectively. The score of depression was 5.00 (2.00, 8.00). Health behaviors were positively correlated with health knowledge, social support, and health belief( r=0.333, 0.246, 0.267, all P<0.05), while negatively correlated with depression ( r=-0.146, P<0.05). Multiple linear stepwise regression analysis showed that health knowledge, social support, health belief, and depression were all influencing factors of health behaviors in ischemic stroke patients (all P<0.05). Health belief (effect value=0.068, 95% CI=0.048-0.093) and depression (effect value=0.009, 95% CI=0.003-0.018) both played partial mediating roles between health knowledge and health behaviors, accounting for 17.3%(0.077/0.446) of the total effect. Meanwhile, health belief (effect value=0.045, 95% CI=0.029-0.063) and depression (effect value=0.016, 95% CI=0.008-0.027) both played partial mediating roles between social support and health behaviors, accounting for 26.5%(0.061/0.230) of the total effect. Conclusion:Health knowledge and social support can not only directly influence health behaviors but also indirectly affect them through health belief and depression in patients with ischemic stroke.

Objective:To screen broadly neutralizing antibodies in human immunodeficiency virus-1（HIV-1）chronically infected individuals and characterize their molecular features and to provide new strategies for rational vaccine development and antibody-based therapeutics.Methods:A total of 34 treatment-na?ve individuals with chronic HIV-1 infection were enrolled. Plasma antibody binding levels were measured against two HIV-1 envelope proteins. Single antigen-specific memory B cells were sorted from high-binding samples，and antibody variable region genes were amplified by PCR for paired expression. The monoclonal antibodies were evaluated for neutralizing activity using pseudovirus assays，and their structural features were analyzed by integrating AlphaFold 3 prediction with Discovery Studio molecular docking.Results:Plasma samples showed strong binding to DU422-GP140 and BG505-GP140. Eight monoclonal antibodies were isolated from two donors. Among them，antibodies 0919-A4，0919-A9 and 0808-A2 could cross-react with GP140 from HIV-1 subtypes AE，BC and B. The monoclonal antibody 0919-A9 demonstrated potent neutralizing activity against SF162（Tier 1）and CH181（Tier 2）pseudoviruses，with somatic hypermutation rates of 13.27%（heavy chain）and 15.58%（light chain）. Structural modeling revealed its specific targeting of the V1V2 region on GP120.Conclusion:The isolated antibody 0919-A9 effectively neutralizes Tier 2 pseudoviruses. Its high somatic mutation frequency and V1V2-targeting property underlie its neutralizing activity，providing both a promising candidate and mechanistic insights for HIV vaccine development and antibody-based therapeutic strategies.

Objective:To explore the dual mediating effects of health belief and depression among health knowledge, social support, and health behaviors based on the capacity, opportunity, motivation-behavior (COM-B) model, and analyze the influencing factors of health behaviors in patients with ischemic stroke.Methods:This multi-center cluster sampling research recruited ischemic stroke patients ( n=1 696) who were hospitalized in neurology departments of five tertiary hospitals in Henan Province from October 2023 to October 2024. A cross-sectional investigation was conducted using the general information questionnaire, social support rating scale (SSRS), stroke prevention knowledge questionnaire(SPKQ), short form health belief model scale(SF-HBMS), health promoting lifestyle profile-Ⅱ (HPLP-Ⅱ), and patient health questionnaire-9(PHQ-9) to ultimately reveal the pathways and effect sizes among variables. Partial correlation analysis and multiple linear stepwise regression analysis were conducted to examine the relationships among social support, health knowledge, health belief, health behaviors, and depression in stroke patients by SPSS 26.0 software. Structural equation modeling was constructed using AMOS 28.0 software, and the mediating effect was tested using the Bootstrap method. Results:The scores of social support, health knowledge, health belief, and health behaviors among ischemic stroke patients were (37.46±9.94), (26.56±6.84), (75.62±12.62) and (130.79±26.27), respectively. The score of depression was 5.00 (2.00, 8.00). Health behaviors were positively correlated with health knowledge, social support, and health belief( r=0.333, 0.246, 0.267, all P<0.05), while negatively correlated with depression ( r=-0.146, P<0.05). Multiple linear stepwise regression analysis showed that health knowledge, social support, health belief, and depression were all influencing factors of health behaviors in ischemic stroke patients (all P<0.05). Health belief (effect value=0.068, 95% CI=0.048-0.093) and depression (effect value=0.009, 95% CI=0.003-0.018) both played partial mediating roles between health knowledge and health behaviors, accounting for 17.3%(0.077/0.446) of the total effect. Meanwhile, health belief (effect value=0.045, 95% CI=0.029-0.063) and depression (effect value=0.016, 95% CI=0.008-0.027) both played partial mediating roles between social support and health behaviors, accounting for 26.5%(0.061/0.230) of the total effect. Conclusion:Health knowledge and social support can not only directly influence health behaviors but also indirectly affect them through health belief and depression in patients with ischemic stroke.

Background and Purpose:Previous studies have investigated the prognostic significance of skeletal muscle and adipose tissue composition and distribution in colorectal cancer patients,yet most have not differentiated between rectal and colon cancer patient cohorts.This study aimed to explore the relationship between body composition and long-term prognosis,and to develop a postoperative predictive model.Methods:Clinical data of rectal cancer patients who underwent surgical treatment at Qingdao University Affiliated Hospital from January 2018 to December 2021 were retrospectively collected.Inclusion criteria:①Age＞18 years;② Preoperative colonoscopy and pathological diagnosis of colorectal cancer;③ Complete surgical resection;④Abdominal computed tomography(CT)scan 1 month before surgery.Exclusion criteria:① Clinical data is missing;② Multiple metastases of tumors;③ Tumor T stage 0 or carcinoma in situ;④ Severe artifacts lead to poor quality CT imaging,making it difficult to distinguish between fat and muscle;⑤ Inability to obtain follow-up results.This study has been approved by the Medical Ethics Committee of the Affiliated Hospital of Qingdao University(approval number:QYFYWZLL30313),and informed consent has been waived in the ethical approval process.The skeletal muscle index(SMI)and subcutaneous adipose tissue index(SATI)were calculated by dividing the areas of skeletal muscle and subcutaneous fat observed on CT scans by the square of the patient's height.Univariate and multivariate COX regression analyses were conducted to identify risk factors influencing recurrence-free survival(RFS)and overall survival(OS)in rectal cancer patients.Based on the results of the multivariate analysis,a nomogram prediction model was developed,its predictive power and accuracy were assessed using the receiver operating characteristic(ROC)curve,calibration plots and decision curve analysis(DCA),and internal validation was conducted.Results:A total of 696 patients were included in this study,with 96(13.8%)patients experiencing postoperative recurrence and 89(12.8%)patients dying.Multivariate COX regression analysis showed that SMI,SATI,tumor T stage and N stage were independent factors affecting the postoperative RFS and OS of patients.Nomogram prediction models for RFS and OS in rectal cancer patients were constructed based on the above independent predictors.The area under ROC curve(AUC)for 3-,4-and 5-year RFS was 0.862,0.846 and 0.824,respectively;the AUC for 3-,4-and 5-year OS was 0.886,0.898 and 0.875,respectively.The models were evaluated using calibration curves and decision curves,and internal validation was performed,which showed that the prediction accuracy of the models was good.Conclusion:CT body composition is an independent predictor of RFS and OS in rectal cancer patients,and the nomogram model developed based on these factors demonstrates good predictive value for patient prognosis.