BACKGROUND: Peripheral helper T (T PH ) cells are uniquely positioned within pathologically inflamed non-lymphoid tissues to stimulate B-cell responses and antibody production. However, the phenotype, function, and clinical relevance of T PH cells in hepatocellular carcinoma (HCC) are currently unknown. METHODS: Blood, tumor, and peritumoral liver tissue samples from 39 HCC patients (Sep 2016-Aug 2017) and 101 HCC patients (Sep 2011-Dec 2012) at the Third Affiliated Hospital of Sun Yat-sen University were used. Flow cytometry was used to quantify the expression, phenotype, and function of T PH cells. Log-rank tests were performed to evaluate disease-free survival and overall survival in samples from 39 patients and 101 patients with HCC. T PH cells, CD19 + B cells, and T follicular helper (T FH ) cells were cultured separately in vitro or isolated from C57/B6L mice in vivo for functional assays. RESULTS: T PH cells highly infiltrated tumor tissues, which was correlated with tumor size, early recurrence, and shorter survival time. The tumor-infiltrated T PH cells showed a unique ICOS hi CXCL13 + IL-21 - MAF + BCL-6 - phenotype and triggered naïve B-cell differentiation into regulatory B cells. Triggering programmed cell death protein 1 (PD-1) induced the production of C-X-C motif chemokine ligand 13 (CXCL13) by T PH cells, which then suppressed tumor-specific immunity and promoted disease progression. CONCLUSION Our study reveals a novel regulatory mechanism of T PH cell-regulatory B-cell-mediated immunosuppression and provides an important perspective for determining the balance between the differentiation of protumorigenic T PH cells and that of antitumorigenic T FH cells in the HCC microenvironment.
Carcinoma, Hepatocellular/metabolism* ; Liver Neoplasms/metabolism* ; Humans ; T-Lymphocytes, Helper-Inducer/metabolism* ; Animals ; Mice ; Male ; Female ; Mice, Inbred C57BL ; Middle Aged ; B-Lymphocytes, Regulatory/metabolism* ; Flow Cytometry ; Interleukin-21 ; Aged ; Chemokine CXCL13/metabolism*

Objective:To comparatively the efficacy of the combined external fixator and the Ilizarov in the treatment of open tibia-fibula fractures and their influence on postoperative infection.Methods:A total of 215 patients with open tibio-fibula fractures diagnosed and treated at Tianjin Medical University General Hospital Airport Site from January 2021 to January 2024 were retrospectively selected as the research subjects. They were divided into the observation group (110 cases, using the combined external frame) and the control group (105 cases, using theIlizarov) according to the types of external fixators adopted. The clinical efficacy, bone healing condition, X-ray callus score, and serological indicators, including the bone morphogenetic protein (BMP-2), vascular endothelial growth factor (VEGF), osteocalcin (OC), C-reactive protein (CRP) in the two groups were compared. The America Orthopedic Foot & Ankle Society(AOFAS) score, Hospital for Special Surgery (HSS) score, and Health Survey Scale (SF-36) score were applied to evaluate the recovery of patients, and the postoperative infection conditions in the two groups were compared.Results:At 12 months after the operation, the excellent and good rate of clinical efficacy in the observation group was higher than that in the control group:90.00%(99/110) vs. 80.00%(84/105), there was statistical difference ( χ2 = 4.24, P<0.05). The complete weight-bearing time, swelling elimination time, bone healing time and postoperative hospital stay in the observation group were shorter than those in the control group:(144.73 ± 15.48) d vs. (152.12 ± 15.55) d, (11.25 ± 1.34) d vs. (13.18 ± 1.37) d, (123.01 ± 12.53) d vs. (136.38 ± 13.45) d, (30.15 ± 3.24) d vs. (31.47 ± 3.48) d, there were statistical differences ( P<0.01). The X-ray callus scores in the observation group at 1 week and 1, 3 and 6 months after the operation were higher than those in the control group: (1.37 ± 0.15) scores vs. (1.28 ± 0.14) scores, (7.65 ± 0.83) scores vs. (5.64 ± 0.75) scores,(12.34 ± 1.25) scores vs. (10.78 ± 1.16) scores,(14.52 ± 1.56) scores vs.(12.11 ± 1.35) scores, there were statistical differences ( P<0.01). Six months after the operation, the levels of BMP-2, VEGF and OC in the observation group were higher than those in the control group: (84.23 ± 8.51) ng/L vs. (76.79 ± 7.82) ng/L, (17.26 ± 1.83) ng/L vs. (15.34 ± 1.67) ng/L, (18.34 ± 1.92) μg/L vs. (6.48 ± 1.75) μg/L; while CRP was lower than that in the control group: (6.49 ± 0.76) mg/L vs. (7.13 ± 0.78) mg/L; there were statistical differences ( P<0.01). The scores of AOFAS, HSS and SF-36 in the observation group at 6 months after the operation were higher than those in the control group: (76.34 ± 7.85) scores vs. (70.11 ± 7.49) scores,(70.12 ± 7.63) scores vs. (67.77 ± 6.68) scores, (93.57 ± 10.34) scores vs. (85.73 ± 8.65) scores, there were statistical differences ( P<0.01 or <0.05). The patients were followed up for 12 months after the operation. There was no statistical difference in the incidence of complications between the two groups ( P>0.05). Conclusions:Compared with the Ilizarov, the combined external fixator has a better therapeutic effect in the treatment of open tibia-fibula fractures. It can promote the healing of bone wounds, improve joint function and quality of life, and has good safety.

Objective To explore the value of CT-enhanced portal venous phase radiomics combined with machine learning algo-rithms in assessing microvascular invasion(MVI)in hepatocellular carcinoma(HCC).Methods A retrospective analysis was con-ducted on imaging and clinical data of 132 HCC patients.The patients were randomly divided into training set and test set at a 7︰3 ratio.Independent influencing factors for predicting MVI status in HCC patients were identified through univariate and multivariate logistic regression analyses.Radiomics features were selected using the least absolute shrinkage and selection operator(LASSO)algorithm,and a Radiomics score(Radscore)was calculated to construct the final combined model.Four machine learning algorithms including-logistic regression(LR),naive Bayes(NB),support vector machine(SVM),and K-nearest neighbor(KNN)were applied to evaluate the model.The performance of each machine model was assessed using the receiver operating characteristic(ROC)curves and the area under the curve(AUC).Results Univariate and multivariate logistic regression analyses revealed that venous phase CT values were independentinfluencing factors,and six radiomics features were ultimately selected.After the Radscore was calculated,a combined model was constructed using Radscore and venous phase CT values.Machine learning algorithms showed that the combined model achieved the following AUC in the training set:0.895[95%confidence interval(CI)0.821-0.965]for LR,0.892(95%CI 0.831-0.963)for NB,0.644(95%CI 0.532-0.765)for SVM,and 0.855(95%CI 0.783-0.947)for KNN.In the test set,the respective AUC were 0.845(95%CI 0.712-0.961),0.840(95%CI 0.723-0.964),0.492(95%CI 0.311-0.687),and 0.716(95%CI 0.566-0.871).Conclusion Radiomics based on CT-enhanced portal venous phase combined with machine learning algorithms demonstrates high efficiency in preoperative evaluation of MVI in HCC,with the LR model showing the best performance.

Objective To provide a comprehensive review of the modeling method of the empty bottle stimulation(EBS)anxiety model,including commonly used experimental animal strains and genders,animal grouping,modeling procedures,modeling duration,primary behavioral evaluation method,and the underlying pathological mechanisms.This aims to offer a reference for the application of the EBS anxiety model in anxiety disorder research.Methods Searches were conducted in databases such as CNKI and PubMed to collect all literature related to the EBS anxiety model,which were then systematically summarized and organized.Results(1)Male adult SD or Wistar rats are predominantly used as experimental animals;(2)The optimal modeling period is 2 weeks;(3)Behavioral evaluations primarily utilize the open field test,elevated plus maze test,and light-dark box test;(4)Pathological mechanisms involve abnormal neurotransmitter metabolism in brain regions such as the hippocampus,prefrontal cortex,and amygdala.Conclusions The EBS anxiety model exhibits an anxiety-like behavioral phenotype and associated neurobiological mechanisms,validating its utility as an animal model for the study of anxiety disorders.However,further exploration and refinement are required for its standardized construction protocol and the understanding of its mechanistic underpinnings.

Objective:To dry fresh Ginseng Radix et Rhizoma using different drying conditions; To investigate the effects of different drying conditions on the drying characteristics and medicinal quality of Ginseng Radix et Rhizoma.Methods:With moisture, powder color, extract, total polysaccharide and ginsenoside contents of Rg 1, Re, Rf, Rb 1, Rc, Rb 2 and Rd as indexes, the drying characteristics of Ginseng Radix et Rhizoma were studied based on Weibull function model, and the quality of Ginseng Radix et Rhizoma after drying was evaluated by entropy weight-TOPSIS model. Results:The drying method for Ginseng Radix et Rhizoma from its origin can be achieved by controlling the relative humidity of the drying medium to 50%, drying at 70 ℃ for 24 h, and then reducing the drying temperature to 60 ℃ until the moisture content was below 12.0%. This method could achieve high drying efficiency and produce high-quality Ginseng Radix et Rhizoma.Conclusions:The drying process of Ginseng Radix et Rhizoma is a falling rate process controlled by internal moisture diffusion. The drying rate of fresh Ginseng Radix et Rhizoma is affected by temperature and humidity. There is a certain correlation between the color of powder and the content of moisture, alcohol-soluble extractives and ginsenosides.

Objective:To analyze the clinical efficacy and safety of carglumic acid in the treatment of neonatal hyperammonemia caused by organic acidemia.Methods:A case summary was made.Six cases of neonatal hyperammonemia caused by organic acidemia treated at the Neonatal Intensive Care Unit of Henan Children′s Hospital from March to September in 2024 were included.They received comprehensive ammonia-lowering treatment in combination with oral carglumic acid dispersible tablets.The clinical data of the children were collected and analyzed retrospectively.Changes in blood ammonia levels, blood gas parameters, and complete blood count before and after treatment with carglumic acid were analyzed using the Wilcoxon test.The incidence of adverse reactions and clinical regression during the treatment with carglumic acid was observed.Results:There were 2 females and 4 males in the 6 patients included.Four children suffered from isolated methylmalonic acidemia caused by MUT gene mutations, and the other 2 had propionic acidemia.The clinical manifestations were poor breastfeeding in 6 cases, vomiting in 2 cases, poor response in 6 cases, weight loss in 6 cases, and convulsions in 3 cases.Acute metabolic decompensation abnormalities were presented in all children, such as metabolic acidosis, hyperammonemia, leukopenia and thrombocytopenia.The first dose of carglumic acid was 62-255 mg/kg, the second dose was 75-172 mg/kg.The blood ammonia level decreased from 411.7 (339.7, 623.8) μmol/L before treatment to 108.1 (35.5, 229.1) μmol/L after 48 hours of treatment, showing a statistically significant reduction ( Z=2.20, P<0.05).Three cases with a blood ammonia level higher than 400 μmol/L, it was effectively reduced after treatment with carglumic acid.Two cases did not undergo hemodialysis or peritoneal dialysis.One case underwent hemodialysis but died after withdrawing the treatment.After administration of carglumic acid, metabolic acidosis was corrected in all children, and 2 patients ultimately died after discontinuing the treatment.No causal relationship was identified between adverse events and carglumic acid treatment.The examinations at discharge and during the follow-up period (2-7 months) showed that most laboratory abnormalities (including leukopenia, anemia, thrombocytopenia, hyperlactatemia, hyponatremia, hyperkalemia, elevated myocardial enzymes, and hyperbilirubinemia) returned to normal. Conclusions:Carglumic acid can effectively reduce neonatal hyperammonemia caused by organic academia, improve metabolic disorders, and reduce the need for blood purification or peritoneal dialysis, with good safety.

Objective To explore the value of CT-enhanced portal venous phase radiomics combined with machine learning algo-rithms in assessing microvascular invasion(MVI)in hepatocellular carcinoma(HCC).Methods A retrospective analysis was con-ducted on imaging and clinical data of 132 HCC patients.The patients were randomly divided into training set and test set at a 7︰3 ratio.Independent influencing factors for predicting MVI status in HCC patients were identified through univariate and multivariate logistic regression analyses.Radiomics features were selected using the least absolute shrinkage and selection operator(LASSO)algorithm,and a Radiomics score(Radscore)was calculated to construct the final combined model.Four machine learning algorithms including-logistic regression(LR),naive Bayes(NB),support vector machine(SVM),and K-nearest neighbor(KNN)were applied to evaluate the model.The performance of each machine model was assessed using the receiver operating characteristic(ROC)curves and the area under the curve(AUC).Results Univariate and multivariate logistic regression analyses revealed that venous phase CT values were independentinfluencing factors,and six radiomics features were ultimately selected.After the Radscore was calculated,a combined model was constructed using Radscore and venous phase CT values.Machine learning algorithms showed that the combined model achieved the following AUC in the training set:0.895[95%confidence interval(CI)0.821-0.965]for LR,0.892(95%CI 0.831-0.963)for NB,0.644(95%CI 0.532-0.765)for SVM,and 0.855(95%CI 0.783-0.947)for KNN.In the test set,the respective AUC were 0.845(95%CI 0.712-0.961),0.840(95%CI 0.723-0.964),0.492(95%CI 0.311-0.687),and 0.716(95%CI 0.566-0.871).Conclusion Radiomics based on CT-enhanced portal venous phase combined with machine learning algorithms demonstrates high efficiency in preoperative evaluation of MVI in HCC,with the LR model showing the best performance.

Objective To provide a comprehensive review of the modeling method of the empty bottle stimulation(EBS)anxiety model,including commonly used experimental animal strains and genders,animal grouping,modeling procedures,modeling duration,primary behavioral evaluation method,and the underlying pathological mechanisms.This aims to offer a reference for the application of the EBS anxiety model in anxiety disorder research.Methods Searches were conducted in databases such as CNKI and PubMed to collect all literature related to the EBS anxiety model,which were then systematically summarized and organized.Results(1)Male adult SD or Wistar rats are predominantly used as experimental animals;(2)The optimal modeling period is 2 weeks;(3)Behavioral evaluations primarily utilize the open field test,elevated plus maze test,and light-dark box test;(4)Pathological mechanisms involve abnormal neurotransmitter metabolism in brain regions such as the hippocampus,prefrontal cortex,and amygdala.Conclusions The EBS anxiety model exhibits an anxiety-like behavioral phenotype and associated neurobiological mechanisms,validating its utility as an animal model for the study of anxiety disorders.However,further exploration and refinement are required for its standardized construction protocol and the understanding of its mechanistic underpinnings.

Objective:To analyze the clinical efficacy and safety of carglumic acid in the treatment of neonatal hyperammonemia caused by organic acidemia.Methods:A case summary was made.Six cases of neonatal hyperammonemia caused by organic acidemia treated at the Neonatal Intensive Care Unit of Henan Children′s Hospital from March to September in 2024 were included.They received comprehensive ammonia-lowering treatment in combination with oral carglumic acid dispersible tablets.The clinical data of the children were collected and analyzed retrospectively.Changes in blood ammonia levels, blood gas parameters, and complete blood count before and after treatment with carglumic acid were analyzed using the Wilcoxon test.The incidence of adverse reactions and clinical regression during the treatment with carglumic acid was observed.Results:There were 2 females and 4 males in the 6 patients included.Four children suffered from isolated methylmalonic acidemia caused by MUT gene mutations, and the other 2 had propionic acidemia.The clinical manifestations were poor breastfeeding in 6 cases, vomiting in 2 cases, poor response in 6 cases, weight loss in 6 cases, and convulsions in 3 cases.Acute metabolic decompensation abnormalities were presented in all children, such as metabolic acidosis, hyperammonemia, leukopenia and thrombocytopenia.The first dose of carglumic acid was 62-255 mg/kg, the second dose was 75-172 mg/kg.The blood ammonia level decreased from 411.7 (339.7, 623.8) μmol/L before treatment to 108.1 (35.5, 229.1) μmol/L after 48 hours of treatment, showing a statistically significant reduction ( Z=2.20, P<0.05).Three cases with a blood ammonia level higher than 400 μmol/L, it was effectively reduced after treatment with carglumic acid.Two cases did not undergo hemodialysis or peritoneal dialysis.One case underwent hemodialysis but died after withdrawing the treatment.After administration of carglumic acid, metabolic acidosis was corrected in all children, and 2 patients ultimately died after discontinuing the treatment.No causal relationship was identified between adverse events and carglumic acid treatment.The examinations at discharge and during the follow-up period (2-7 months) showed that most laboratory abnormalities (including leukopenia, anemia, thrombocytopenia, hyperlactatemia, hyponatremia, hyperkalemia, elevated myocardial enzymes, and hyperbilirubinemia) returned to normal. Conclusions:Carglumic acid can effectively reduce neonatal hyperammonemia caused by organic academia, improve metabolic disorders, and reduce the need for blood purification or peritoneal dialysis, with good safety.

Objective:To comparatively the efficacy of the combined external fixator and the Ilizarov in the treatment of open tibia-fibula fractures and their influence on postoperative infection.Methods:A total of 215 patients with open tibio-fibula fractures diagnosed and treated at Tianjin Medical University General Hospital Airport Site from January 2021 to January 2024 were retrospectively selected as the research subjects. They were divided into the observation group (110 cases, using the combined external frame) and the control group (105 cases, using theIlizarov) according to the types of external fixators adopted. The clinical efficacy, bone healing condition, X-ray callus score, and serological indicators, including the bone morphogenetic protein (BMP-2), vascular endothelial growth factor (VEGF), osteocalcin (OC), C-reactive protein (CRP) in the two groups were compared. The America Orthopedic Foot & Ankle Society(AOFAS) score, Hospital for Special Surgery (HSS) score, and Health Survey Scale (SF-36) score were applied to evaluate the recovery of patients, and the postoperative infection conditions in the two groups were compared.Results:At 12 months after the operation, the excellent and good rate of clinical efficacy in the observation group was higher than that in the control group:90.00%(99/110) vs. 80.00%(84/105), there was statistical difference ( χ2 = 4.24, P<0.05). The complete weight-bearing time, swelling elimination time, bone healing time and postoperative hospital stay in the observation group were shorter than those in the control group:(144.73 ± 15.48) d vs. (152.12 ± 15.55) d, (11.25 ± 1.34) d vs. (13.18 ± 1.37) d, (123.01 ± 12.53) d vs. (136.38 ± 13.45) d, (30.15 ± 3.24) d vs. (31.47 ± 3.48) d, there were statistical differences ( P<0.01). The X-ray callus scores in the observation group at 1 week and 1, 3 and 6 months after the operation were higher than those in the control group: (1.37 ± 0.15) scores vs. (1.28 ± 0.14) scores, (7.65 ± 0.83) scores vs. (5.64 ± 0.75) scores,(12.34 ± 1.25) scores vs. (10.78 ± 1.16) scores,(14.52 ± 1.56) scores vs.(12.11 ± 1.35) scores, there were statistical differences ( P<0.01). Six months after the operation, the levels of BMP-2, VEGF and OC in the observation group were higher than those in the control group: (84.23 ± 8.51) ng/L vs. (76.79 ± 7.82) ng/L, (17.26 ± 1.83) ng/L vs. (15.34 ± 1.67) ng/L, (18.34 ± 1.92) μg/L vs. (6.48 ± 1.75) μg/L; while CRP was lower than that in the control group: (6.49 ± 0.76) mg/L vs. (7.13 ± 0.78) mg/L; there were statistical differences ( P<0.01). The scores of AOFAS, HSS and SF-36 in the observation group at 6 months after the operation were higher than those in the control group: (76.34 ± 7.85) scores vs. (70.11 ± 7.49) scores,(70.12 ± 7.63) scores vs. (67.77 ± 6.68) scores, (93.57 ± 10.34) scores vs. (85.73 ± 8.65) scores, there were statistical differences ( P<0.01 or <0.05). The patients were followed up for 12 months after the operation. There was no statistical difference in the incidence of complications between the two groups ( P>0.05). Conclusions:Compared with the Ilizarov, the combined external fixator has a better therapeutic effect in the treatment of open tibia-fibula fractures. It can promote the healing of bone wounds, improve joint function and quality of life, and has good safety.