BACKGROUND:Rheumatoid arthritis is a complex autoimmune disease characterized by joint swelling,pain,and progressive damage.The basic pathological changes include synovitis and pannus formation,with T lymphocyte infiltration being the key to its pathogenesis.In recent years,the application of traditional Chinese medicine(TCM)monomers in the treatment of rheumatoid arthritis has attracted increasing attention.They have shown long-lasting effcacy and fewer side effects by regulating the T helper cell 17(Th17)/regulatory T cells(Treg)balance in the treatment of rheumatoid arthritis.OBJECTIVE:To discuss the mechanisms by which TCM monomers regulate the Th17/Treg balance to treat rheumatoid arthritis,based on the latest basic research,providing a solid theoretical basis for future applications of TCM in the treatment of rheumatoid arthritis.METHODS:Using keywords such as"rheumatoid arthritis,Th17/Treg,traditional Chinese medicine,Chinese herbal monomer,"and their Chinese equivalents,literature searches were conducted in PubMed,Web of Science,Embase,Cochrane,VIP,CBM,CNKI,and WanFang databases for relevant studies from their inception to August 2024.Inclusion and exclusion criteria were established,and the articles were screened by reading the titles,abstracts,and full texts.Finally,57 relevant articles were included.RESULTS AND CONCLUSION:(1)TCM monomers have immunoregulatory effects in the treatment of rheumatoid arthritis.They exert therapeutic effects by maintaining the Th17/Treg balance through the regulation of transcription factors,cytokines,signaling pathways,and miRNAs.(2)There may be synergistic effects among some TCM monomers,but the specific mechanisms and enhancement effects in regulating the Th17/Treg balance require further exploration.(3)Regulating the Th17/Treg balance using TCM monomers may become a key clinical therapy for the treatment of rheumatoid arthritis.

BACKGROUND:Rheumatoid arthritis is a complex autoimmune disease characterized by joint swelling,pain,and progressive damage.The basic pathological changes include synovitis and pannus formation,with T lymphocyte infiltration being the key to its pathogenesis.In recent years,the application of traditional Chinese medicine(TCM)monomers in the treatment of rheumatoid arthritis has attracted increasing attention.They have shown long-lasting effcacy and fewer side effects by regulating the T helper cell 17(Th17)/regulatory T cells(Treg)balance in the treatment of rheumatoid arthritis.OBJECTIVE:To discuss the mechanisms by which TCM monomers regulate the Th17/Treg balance to treat rheumatoid arthritis,based on the latest basic research,providing a solid theoretical basis for future applications of TCM in the treatment of rheumatoid arthritis.METHODS:Using keywords such as"rheumatoid arthritis,Th17/Treg,traditional Chinese medicine,Chinese herbal monomer,"and their Chinese equivalents,literature searches were conducted in PubMed,Web of Science,Embase,Cochrane,VIP,CBM,CNKI,and WanFang databases for relevant studies from their inception to August 2024.Inclusion and exclusion criteria were established,and the articles were screened by reading the titles,abstracts,and full texts.Finally,57 relevant articles were included.RESULTS AND CONCLUSION:(1)TCM monomers have immunoregulatory effects in the treatment of rheumatoid arthritis.They exert therapeutic effects by maintaining the Th17/Treg balance through the regulation of transcription factors,cytokines,signaling pathways,and miRNAs.(2)There may be synergistic effects among some TCM monomers,but the specific mechanisms and enhancement effects in regulating the Th17/Treg balance require further exploration.(3)Regulating the Th17/Treg balance using TCM monomers may become a key clinical therapy for the treatment of rheumatoid arthritis.

Objective:To explore the independent risk factors of acute respiratory distress syndrome (ARDS) in patients with sepsis, establish an early warning model, and verify the predictive value of the model based on synthetic minority oversampling technique (SMOTE) algorithm.Methods:A retrospective case-control study was conducted. 566 patients with sepsis who were admitted to Jinan People's Hospital from October 2016 to October 2022 were enrolled. General information, underlying diseases, infection sites, initial cause, severity scores, blood and arterial blood gas analysis indicators at admission, treatment measures, complications, and prognosis indicators of patients were collected. The patients were grouped according to whether ARDS occurred during hospitalization, and the clinical data between the two groups were observed and compared. Univariate and binary multivariate Logistic regression analysis were used to select the independent risk factors of ARDS during hospitalization in septic patients, and regression equation was established to construct the early warning model. Simultaneously, the dataset was improved using the SMOTE algorithm to build an enhanced warning model. Receiver operator characteristic curve (ROC curve) was drawn to validate the prediction efficiency of the model.Results:566 patients with sepsis were included in the final analysis, of which 163 developed ARDS during hospitalization and 403 did not. Univariate analysis showed that there were statistically significant differences in age, body mass index (BMI), malignant tumor, blood transfusion history, pancreas and peripancreatic infection, gastrointestinal tract infection, pulmonary infection as the initial etiology, acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score, sequential organ failure assessment (SOFA) score, albumin (Alb), blood urea nitrogen (BUN), mechanical ventilation therapy, septic shock and length of intensive care unit (ICU) stay between the two groups. Binary multivariate Logistic regression analysis showed that age [odds ratio ( OR) = 3.449, 95% confidence interval (95% CI) was 2.197-5.414, P = 0.000], pulmonary infection as the initial etiology ( OR = 2.309, 95% CI was 1.427-3.737, P = 0.001), pancreas and peripancreatic infection ( OR = 1.937, 95% CI was 1.236-3.035, P = 0.004), septic shock ( OR = 3.381, 95% CI was 1.890-6.047, P = 0.000), SOFA score ( OR = 9.311, 95% CI was 5.831-14.867, P = 0.000) were independent influencing factors of ARDS during hospitalization in septic patients. An early warning model was established based on the above risk factors: P1 = -4.558+1.238×age+0.837×pulmonary infection as the initial etiology+0.661×pancreas and peripancreatic infection+1.218×septic shock+2.231×SOFA score. ROC curve analysis showed that the area under the ROC curve (AUC) of the model for ARDS during hospitalization in septic patients was 0.882 (95% CI was 0.851-0.914) with sensitivity of 79.8% and specificity of 83.4%. The dataset was improved based on the SMOTE algorithm, and the early warning model was rebuilt: P2 = -3.279+1.288×age+0.763×pulmonary infection as the initial etiology+0.635×pancreas and peripancreatic infection+1.068×septic shock+2.201×SOFA score. ROC curve analysis showed that the AUC of the model for ARDS during hospitalization in septic patients was 0.890 (95% CI was 0.867-0.913) with sensitivity of 85.3% and specificity of 79.1%. This result further confirmed that the early warning model constructed by the independent risk factors mentioned above had high predictive performance. Conclusions:Risk factors for the occurrence of ARDS during hospitalization in patients with sepsis include age, pulmonary infection as the initial etiology, pancreatic and peripancreatic infection, septic shock, and SOFA score. Clinically, the probability of ARDS in patients with sepsis can be assessed based on the warning model established using these risk factors, allowing for early intervention and improvement of prognosis.

Objective To analyze the risk factors of pulmonary infection in elderly patients with heart fail-ure with reduced left ventricular ejection fraction heart failure,and establish a risk predicting model of pulmonary infection in those patients by decision tree CART algorithm.Methods 320 elderly patients with heart failure with reduced left ventricular ejection fraction admitted from January 2020 to December 2022 were retrospectively selected as study objects,and were divided into an infection group and a non-infection group according to whether the patients were complicated with pulmonary infection.Logistic regression model and decision tree CART model were used to construct a prediction model of heart failure with reduced left ventricular ejection fraction complicated with pulmonary infection,and 5-fold cross-validation method was used for internal verification.The prediction effi-ciency of the models was compared.Results In the 320 patients,the incidence of pulmonary infection was 30.94％.The data on age,smoking history,diabetes mellitus,cardiac function grades,COPD,invasive procedures,length of hospital stay were compared between the infection and non-infection groups(P＜0.05).logistic regression analysis showed that age of ≥ 75 years smoking history,complications with diabetes or/and COPD,cardiac function gradeⅢ/Ⅳ,invasive procedures,and hospital stay of ≥ 14 days were independent risk factors for pulmonary infection in the patients(P＜0.05).Probability forecasting model P=1/[1+e(-3368+0.763*X1+0.814*X2+0.652*X3+1.05*X4+0.865*X5+1.027*X6+0.652*X7)],with an overall accurate rate of prediction of 80.9％.The Omnibus test showed P＜0.001.The accuracy of predic-tion was 73.6％after the cross-validation of 5 fold.The decision tree model showed that invasive procedures were the most important influencing factors for pulmonary infection in elderly patients with heart failure with reduced left ventricular ejection fraction,with an information gain of 0.280.The ROC showed that the AUC value of logistic regression model was slightly higher than that of the decision tree(Z=2.850,P=0.004),and the prediction efficiency of both models was medium.Conclusions Age,smoking history,complications with diabetes mellitus or/and COPD,cardiac function grades,invasive procedures,and length of hospital stay are all influencing factors for pulmonary infection in elderly patients with heart failure with reduced left ventricular ejection fraction.The deci-sion tree model constructed in this study has a better efficiency for risk prediction,and it can provide reference for early clinical screening and intervention of heart failure with reduced left ventricular ejection fraction.

Objective To analyze the risk factors of pulmonary infection in elderly patients with heart fail-ure with reduced left ventricular ejection fraction heart failure,and establish a risk predicting model of pulmonary infection in those patients by decision tree CART algorithm.Methods 320 elderly patients with heart failure with reduced left ventricular ejection fraction admitted from January 2020 to December 2022 were retrospectively selected as study objects,and were divided into an infection group and a non-infection group according to whether the patients were complicated with pulmonary infection.Logistic regression model and decision tree CART model were used to construct a prediction model of heart failure with reduced left ventricular ejection fraction complicated with pulmonary infection,and 5-fold cross-validation method was used for internal verification.The prediction effi-ciency of the models was compared.Results In the 320 patients,the incidence of pulmonary infection was 30.94％.The data on age,smoking history,diabetes mellitus,cardiac function grades,COPD,invasive procedures,length of hospital stay were compared between the infection and non-infection groups(P＜0.05).logistic regression analysis showed that age of ≥ 75 years smoking history,complications with diabetes or/and COPD,cardiac function gradeⅢ/Ⅳ,invasive procedures,and hospital stay of ≥ 14 days were independent risk factors for pulmonary infection in the patients(P＜0.05).Probability forecasting model P=1/[1+e(-3368+0.763*X1+0.814*X2+0.652*X3+1.05*X4+0.865*X5+1.027*X6+0.652*X7)],with an overall accurate rate of prediction of 80.9％.The Omnibus test showed P＜0.001.The accuracy of predic-tion was 73.6％after the cross-validation of 5 fold.The decision tree model showed that invasive procedures were the most important influencing factors for pulmonary infection in elderly patients with heart failure with reduced left ventricular ejection fraction,with an information gain of 0.280.The ROC showed that the AUC value of logistic regression model was slightly higher than that of the decision tree(Z=2.850,P=0.004),and the prediction efficiency of both models was medium.Conclusions Age,smoking history,complications with diabetes mellitus or/and COPD,cardiac function grades,invasive procedures,and length of hospital stay are all influencing factors for pulmonary infection in elderly patients with heart failure with reduced left ventricular ejection fraction.The deci-sion tree model constructed in this study has a better efficiency for risk prediction,and it can provide reference for early clinical screening and intervention of heart failure with reduced left ventricular ejection fraction.

Objective To explore the effect and mechanism of penehyclidine hydrochloride (PHCD) on vascular endothelial injury in septic rats. Methods Fifty male SD rats were randomly divided into control group, lipopolysaccharide (LPS) induced sepsis group (model group), low dose PHCD (0.3 mg/kg) group, medium dose PHCD (1.0 mg/kg) group and high dose PHCD (3.0 mg/kg) groups, ten mice for each group. Normal saline was injected into the tail vein of the control group, and 10 mg/kg lipopolysaccharide (LPS) was injected into the tail vein of the rats in other groups to prepare the sepsis rat models. After the models were successfully established, low, medium and high doses (0.3, 1.0, 3.0 mg/kg) of PHCD solution were injected into the tail vein of the rats of corresponding groups. Wet/dry mass ratio (W/D) of lung tissue of rats in each group was measured, and ELISA was used to assay interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), IL-6 content and rat plasma angiopoietin 2 (Ang2) content in bronchoalveolar lavage fluid (BALF). HE staining was used to observe the pathological changes of lung tissues. Immunohistochemical staining was used to observe the expression of Ang2 in the right lung tissues. Western blot analysis was performed to detect Ang2 and vascular endothelial cadherin (VE-cadherin) protein in lung tissues. Results Compared with the control group, the W/D ratio of the lung tissues of rats in the model group and the contents of IL-1β, IL-6 and TNF-α in BALF were significantly increased; the lung tissues showed obvious pathological damage, with up-regulation of Ang2 expression and down-regulation of VE-Cadherin expression. Compared with the model group, the W/D ratio of the lung tissues of rats in three PHCD treatment groups and the contents of IL-1β, IL-6 and TNF-α in BALF were significantly reduced; the pathological damage of lung tissue was significantly reduced, with down-regulation of Ang2 expression and up-regulation of VE-cadherin expression. Conclusion PHCD can reduce LPS-induced lung inflammation in rats with sepsis by regulating the Ang2/VE-Cadherin pathway, thereby improving vascular endothelial injury.
Rats ; Mice ; Animals ; Male ; Lipopolysaccharides/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Angiopoietin-2/pharmacology* ; Interleukin-6/metabolism* ; Rats, Sprague-Dawley ; Lung ; Acute Lung Injury/metabolism* ; Sepsis/metabolism*

【Objective】 To analyze the influence of β-lactam antibiotics on RBC aging and clearance by detecting various indicators of aging and clearance on RBCs, as well as the differences in phagocytosis for erythrocytes before and after drugs treated in vitro. 【Methods】 RBCs were treated by β-lactam antibiotics, including Penicillin, Cefepime, Cefoperazone and Ceftazidime, and the changing of phosphatidylserine (PS) and clearance related CD markers, including CD35, CD47, CD55 and CD59 on the surface of the RBCs, were detected by flow cytometry at 0h and 24h after drugs treatment. The proportion of acanthocytes by microscope also at 0h and 24h after drugs treatment was calculated. The phagocytosis of drug-treated RBC was detected by monocyte monolayer assay (MMA). Untreated RBCs were incubated in PBS by the same condition as a negative control.The influence of β-lactam antibiotics on RBC aging and clearance by all the results above was studied. 【Results】 Compare to the untreated RBCs, the drug treated RBCs showed a higher PS level on the cell surface. The results showed by percentage as following(0 h vs 24 h): Penicillin 9.42% vs 93.30%, Cefepime 3.88% vs 57.27%, Cefoperazone 4.71% vs 75.75% and Ceftazidime 3.05% vs 43.19%. The acanthocytes ratio was as following(0 h vs 24 h): Penicillin 7.33% vs 86%, Cefepime 2.67% vs 52.67%, Cefoperazone 3.33% vs 67.67% and Ceftazidime 3.33% vs 90.67%. On the opposite, the clearance related CD markers, showed an obviously lower level after drugs treated(0 h vs 24 h): CD35: Penicillin 7.36% vs 11.87%, Cefepime 0.14% vs 28.51%, Cefoperazone 11.85% vs 21.55% and Ceftazidime 7.63% vs 8.73%; CD47: Penicillin 1.22% vs 9.13%, Cefepime 1.80% vs 0.86%, Cefoperazone 0.08% vs 6.85% and Ceftazidime 1.54% vs 5.50%; CD55: Penicillin 14.46% vs 44.31%, Cefepime 17.27% vs 38.41%, Cefoperazone 19.28% vs 33.28% and Ceftazidime 14.62% vs 34.13%; CD59: Penicillin 4.71% vs 20.56%, Cefepime 4.03% vs 7.60%, Cefoperazone 5.91% vs 22.38% and Ceftazidime 5.93% vs 30.89%. Drug-treated RBCs attached more to monocytes than untreated RBCs. 【Conclusion】 The β-lactam antibiotics could induce the changing of PS and the clearance of related CD markers on surface of RBCs. They also could lead acanthocytes and make the RBCs more susceptible to phagocytosis by monocytes. The β-lactam antibiotics could promote the RBCs aging and clearance, which might deteriorate the DIIHA.

【Objective】 To establish human hybridoma cell lines, secreting monoclonal antibody against antigens of Rh blood system, from a donor with rare D--phenotype. 【Methods】 Peripheral blood B lymphocytes of an O type female donor, lacking C/c/E/e antigens on her erythrocyte, were transformed with Epstein-Barr virus (EBVs). EBVs were harvested from the cultural supernatant of B95-8 cells. The transformed lymphoblastoid cell line (LCL) secreting antibodies to C antigens were picked up and then hybridized with the myeloma SHM-D33 using electric fusion technique. Hybridoma cells were selected by HATD-Ouabain(HOTD)(Hypoxantine, Aminopterin, Thymidine, 2-Deoxycytide, and Ouabain)culture medium, microplate antibody screening and limited dilution subcloning. The monoclonal antibody was assayed by serological test and was confirmed by flow cytometry (FCM). 【Results】 From the cultural supernatant of D--peripheral blood transformed B lymphocytes, 3A6-C6, which agglutinated with R1R1(DCe/DCe)O-type RBCs but not with R2R2(DcE/DcE)O-type RBCs, was screened and preliminarily identified as anti-C. We established a hybridoma cell line secreting anti-C immunoglobulin M from B cells of D--individual successfully after hybridization with SHM-D33 myeloma cells. 【Conclusion】 The study had laid the groundwork for future research and development of human monoclonal antibodies against Rh antigens of RBC in future for diagnosis and screening purpose.

Purpose: miR-205 is a tumor suppressor and plays an important role in tumor invasiveness. However, the role of miR-205 in human gastric cancer (GC) epithelial-mesenchymal transition (EMT) remains unclear. The aim of this study was to investigate the molecular mechanism of miR-205 in the regulation of EMT in GC invasion. Materials and Methods: Quantitative polymerase chain reaction (qPCR) was used to detect the expression of miR-205 in GC. Further, the correlation between the pathological parameters and prognosis of GC was statistically analyzed. A transwell model was used to evaluate the effect of miR-205-3p on the invasion and migration of GC cells. qPCR, western blotting, and luciferase assay were performed to analyze the relationship and target effects between miR-205-3p and the expression of zinc finger electron box binding homologous box 1 (ZEB1) and 2 (ZEB2). Results: We found that the levels of miR-205-3p were significantly lower (P<0.05) in GC tissues than in matched normal tissues. Additionally, the expression of miR-205-3p was related to the tumor invasion depth, lymph node metastasis, lymph node invasion, and tumor, node, metastasis stage. Patients with lower miR-205-3p expression levels in the tumors had a poorer prognosis. The in vitro assays indicated that miR-205-3p could affect the invasion ability and EMT of GC cells by targeting the expression of both ZEB1 and ZEB2. Conclusions miR-205-3p promotes GC progression and affects the prognosis of patients by targeting both ZEB1 and ZEB2 to directly influence EMT.

Objective To explore the feasibility of robot-assisted laparoscopic inferior vena cava (IVC) thrombectomy in treating renal tumor with Mayo level Ⅲ-Ⅳ inferior vena cava thrombus.Methods From November 2014 to January 2017,5 cases of renal tumor with Mayo level Ⅲ-Ⅳ inferior vena cava tumor thrombus were treated with robot-assisted surgery.There were 4 males and 1 female with the median age of 59 years (range 54-71 years).Four cases had the renal tumor on the right side and one on the left side.The mean tumor size was 6.8 cm (range 5-9 cm) with 3 cases of T3b and 2 cases of T3c.There were 4 cases of level Ⅲ and 1 case of level Ⅳ inferior vena cava thrombus with the median length of 9 cm (range 7-11 cm).The surgical procedure for Mayo level Ⅲ inferior vena cava thrombus included mobilization of both left and right robes of liver,subsequently controlling the suprahepatic infradiaphramatic IVC and first porta hepatis simultaneously.The surgical procedure for Mayo level Ⅳ inferior vena cava thrombus included cardiopulmonary bypass by multi-disciplinary cooperation among urologists,hepatobiliary and cardiovascular surgeons.The procedures included live mobilization,control of the superior vena cava and first porta hepatis and remove thrombus in the atrium and IVC respectively.Results All operations were completed successfully.The median operative time was 440 min (320-630 min).The blood recovery device was used and the intraoperative estimated blood loss was 2 500 ml (500-6 000 ml) and all cases required intraoperative blood transfusion.The median time of intraoperative occlusion of IVC was 35 min (25-50 min).All patients were transferred to the intensive care unit for median of 4 days (2-8 days) after surgery.The median time to remove the postoperative drainage tube was 9 days (7-12 days).Postoperative pathological diagnosis revealed 5 cases of clear cell carcinoma.Postoperative renal dysfunction occurred in 3 patients and liver dysfunction occurred in 2 patients who improved after medical therapy.During median 19.6 months (12-48 months) of follow-up,1 patient died and 1 patient progressed.Conclusions Despite the high risk of surgery,robot-assisted laparoscopic IVC thrombectomy for renal tumor with Mayo level Ⅲ-Ⅳ thrombus is feasible for experienced surgeons in selected patients.However,the oncological outcomes need further investigation.