1.Study on the Mechanism of Hepatotoxicity Induced by Rhubarb Based on Network Pharmacology and Experimental Verification
Hongxin WANG ; Shiyu ZHANG ; Yang JIN ; Taotao CAO ; Qin QIN ; Wen LIU
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(1):167-178
		                        		
		                        			
		                        			Objective The potential mechanism of hepatotoxicity induced by rhubarb was preliminarily explored by network pharmacology and verified by cell experiments.Methods Based on network pharmacology,component collection and target prediction are carried out through multiple databases.PPI network construction,GO enrichment analysis and KEGG pathway analysis were combined with software to systematically predict the mechanism of hepatotoxicity induced by rhubarb.The pathway information predicted by network pharmacology was verified by primary hepatocyte experiments and Western blot experiments.Results The results of network pharmacology showed that RH was the main component of hepatotoxicity induced by rhubarb.Seventeen core targets of hepatotoxicity induced by rhubarb were obtained.KEGG results suggested that DNA damage and apoptosis were one of the key mechanisms of hepatotoxicity induced by rhubarb.The results of primary hepatocytes and Western blot showed that RH could inhibit the viability of primary hepatocytes in a time-dose dependent manner.ABT and SFP can significantly reduce the toxicity of RH on primary liver cells in mice,and RFP can increase the toxicity of RH to mouse primary liver cells.Upregulation of γ-H2AX and PARP-1 protein in primary liver cells of mice after treatment with different concentrations of RH.Conclusion RH in rhubarb can significantly inhibit the viability of mouse primary hepatocytes,and its toxicity to mouse primary hepatocytes is mainly caused by the metabolic activation of RH by CYP 2C9.RH can activate PARP-1 protein,phosphorylate H2AX,induce DNA damage and apoptosis in mouse primary hepatocytes.
		                        		
		                        		
		                        		
		                        	
2.Comparison of robotic natural orifice specimen extraction surgery and robotic-assisted surgery for radical resection of rectal cancer: a propensity score matching study
Shanping YE ; Hongxin YU ; Huiyu HU ; Dongning LIU ; Can WU ; Ruixiang ZOU ; Penghui HE ; Taiyuan LI
Chinese Journal of Gastrointestinal Surgery 2024;27(8):833-839
		                        		
		                        			
		                        			Objective:To compare the surgical outcomes of robotic natural orifice specimen extraction surgery (NOSES) and robotic-assisted radical resection for rectal cancer.Methods:A retrospective analysis using propensity score matching (PSM) was conducted on 547 patients who had undergone radical resection of rectal cancer at the First Affiliated Hospital of Nanchang University from June 2018 to March 2024. The study cohort comprised 157 patients in the robotic NOSES group and 390 in the robotic-assisted group. PSM was used in a 1:1 manner to match relevant general clinical preoperative data of the study patients (age, sex, body mass index, preoperative comorbidities, abnormal preoperative carcinoembryonic antigen (>6.5 μg/L) and carbohydrate antigen 19-9 levels (>27 kU/L), preoperative American Society of Anesthesiologists score, tumor diameter, tumor distance from the anal margin, and TNM stage), with a clamp value of 0.05. After performing PSM to match the general clinical data of the two groups of patients, 77 patients in each of the robotic NOSES and robotic-assisted groups were included in the analysis. We found no statistically significant difference in preoperative general clinical data between the robot NOSES and robot-assisted groups ( P>0.05). We compared the surgical outcomes, postoperative recovery, postoperative pathological data, and incidence of complications between the robotic NOSES and robot-assisted groups. Results:Compared with the robot-assisted groups. the robot NOSES group had a significantly shorter time to first postoperative passage of flatus (48 [38, 50] hours vs. 56 [50, 60] hours, Z=-7.513, P<0.001), time to taking a liquid diet (60 [54,63] hours vs. 66 [62, 72] hours, Z=-6.303, P<0.001), lower pain scores (3 [3, 4] vs. 4 [4, 5], Z=-5.237, P<0.001), and lower incision infection rates (0 vs. 5 [6.5%], χ 2=5.237, P=0.028) within 24 hours after surgery ( P<0.05). However, there were no significant differences in surgical time, intraoperative blood loss, postoperative hospital stay, postoperative anastomotic complications, or incidence of other complications between the two groups (all P>0.05). Conclusion:Robotic NOSES surgery is a safe and feasible procedure for resecting rectal cancer and postoperative recovery is faster after robotic NOSES than after standard robot-assisted surgery.
		                        		
		                        		
		                        		
		                        	
3.Exploring the Comorbidity Mechanisms of Coronary Heart Disease and Depression Based on "Constraint Causing Disease" and "Disease Causing Constraint" Theories
Huiying HAN ; Zhaihua LIU ; Huamin ZHANG ; Hongxin CAO
Journal of Traditional Chinese Medicine 2024;65(8):858-861
		                        		
		                        			
		                        			This study explored the comorbidity mechanisms of coronary heart disease and depression from the perspectives of "constraint causing disease" and "disease causing constraint", for which "constraint" is the link, and the key lies in the stagnation of qi. The heart storing manifestations in traditional Chinese medicine (TCM) encompasses most physiological processes of the circulatory system, the mental nervous system, and some functions of the endocrine system, and cardiovascular diseases and psychological disorders are closely related to it. In TCM, it is proposed that the stagnation of heart yang leading to "yang deficiency" is the pathogenesis of chest tightness, and emotional disturbance leading to the stagnation of yang qi aggravates the chest tightness, reflecting the process of "disease causing constraint". As the disease progresses, the appearance of phlegm and stasis further worsens the condition, reflecting the process of "constraint causing disease". Based on modern medical understanding, the abnormal accumulation of lipids, platelets, oxidative products, cytokines, and other substances constitute a form of "constraint", which is also the material basis for the comorbidity of coronary heart disease and depression. These substances promote neuronal damage or apoptosis in the emotional and cognitive regions, inducing the onset of depression, reflecting the process of "disease causing constraint". Meanwhile, adverse emotions lead to sympathetic nerve excitement, resulting in the production of catecholamines, promoting platelet aggregation, elevating levels of inflammatory markers, and increasing the risk of coronary heart disease, reflecting the process of "disease causing constraint". 
		                        		
		                        		
		                        		
		                        	
4.Research progress on toxicokinetics and toxicology of chlorfenapyr
Hongxin ZHANG ; Zejun MA ; Yu GONG ; Na MENG ; Hao XIAO ; Liang LIU ; Baopu LYU ; Hengbo GAO ; Yingping TIAN
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care 2024;31(3):380-384
		                        		
		                        			
		                        			Chlorfenapyr,an emerging synthetic pesticide,has been linked to a growing number of poisoning incidents,attributed to heightened human exposure as its application becomes more widespread.However,the toxicokinetics and toxicology of chlorfenapyr remain incompletely understood.Research since the 1990s,including animal experiments,has illuminated the absorption,distribution,excretion,and metabolism of chlorfenapyr.Toxicological investigations have revealed that the primary toxicity of chlorfenapyr is the uncoupling of oxidative phosphorylation.Chlorfenapyr exposure in humans and other animals can lead to various toxic effects,including neurotoxicity,cardiotoxicity,skeletal muscle toxicity,genotoxicity,reproductive and developmental toxicity,renal toxicity,splenic toxicity,and hematotoxicity.This article presents a comprehensive review of the toxicokinetics and toxicology of chlorfenapyr,integrating data from animal experiments,human cell line studies,clinical reports,and human autopsy.Its objective is to raise clinical awareness regarding chlorfenapyr poisoning and offer valuable references for its treatment and management.
		                        		
		                        		
		                        		
		                        	
5.A Survey on the Mental Health Status of Social Workers Under Long-term Stress of COVID-19 and the Exploration of Associated Factors: A Case Study of Chaoyang District, Beijing
Han ZHANG ; Yuan GAO ; Wanxin MA ; Hongxin LIU ; Fanrui MENG ; Danping ZHANG ; Chunyu LIU ; Lu LIU ; Ying XING
Medical Journal of Peking Union Medical College Hospital 2024;15(4):845-854
		                        		
		                        			
		                        			 To study the prevalence of depression, anxiety, and insomnia among social workers during the prolonged battle against the COVID-19 pandemic and explore the associated risk factors. Using a stratified cluster sampling method, we selected all social workers in the five streets of Chaoyang District, Beijing(Jiuxianqiao, Wangjing, Taiyanggong, Shibalidian, Sunhe) from November 2021 to March 2022 as the study population(social worker group), and the frontline medical staffs(medical professional group) of the same age range of the corresponding community hospitals of the same five streets, and the community residents(resident group) as the control population. The ratio of the social worker group, medical professional group, and resident group was 1∶1∶1. The Sojump platform was used to send electronic questionnaires to the wechat groups of social workers, healthcare workers, and community residents to carry out the survey. The screen positive rates for anxiety, depression, and sleep disorders were compared among the 3 groups. Multifactorial Logistic regression and decision tree were used to analyze the influencing factors of anxiety, depression, and sleep disorders among social workers. A total of 954 questionnaires were collected, of which 62 were disqualified and excluded. Finally, 892 valid questionnaires(93.5%) were included for data analysis. Among them, there were 372 questionnaires(41.7%) from the social worker group, 262(29.4%) from the medical professional group, and 258(28.9%) from the resident group. The prevalences of anxiety, depression, and sleep disorders among social workers group were found to be 15.3%, 22.0%, and 48.1%, respectively, which were significantly higher than those in the medical professional group(7.6%, 10.3%, and 30.5%) and the resident group(7.0%, 8.5%, and 29.5%), all  Social workers exhibited significant levels of anxiety, depression, and sleep disorders during the long-term pandemic prevention, with CPSS being the most significant influencing factor.
		                        		
		                        	
6.Comparison of robotic natural orifice specimen extraction surgery and robotic-assisted surgery for radical resection of rectal cancer: a propensity score matching study
Shanping YE ; Hongxin YU ; Huiyu HU ; Dongning LIU ; Can WU ; Ruixiang ZOU ; Penghui HE ; Taiyuan LI
Chinese Journal of Gastrointestinal Surgery 2024;27(8):833-839
		                        		
		                        			
		                        			Objective:To compare the surgical outcomes of robotic natural orifice specimen extraction surgery (NOSES) and robotic-assisted radical resection for rectal cancer.Methods:A retrospective analysis using propensity score matching (PSM) was conducted on 547 patients who had undergone radical resection of rectal cancer at the First Affiliated Hospital of Nanchang University from June 2018 to March 2024. The study cohort comprised 157 patients in the robotic NOSES group and 390 in the robotic-assisted group. PSM was used in a 1:1 manner to match relevant general clinical preoperative data of the study patients (age, sex, body mass index, preoperative comorbidities, abnormal preoperative carcinoembryonic antigen (>6.5 μg/L) and carbohydrate antigen 19-9 levels (>27 kU/L), preoperative American Society of Anesthesiologists score, tumor diameter, tumor distance from the anal margin, and TNM stage), with a clamp value of 0.05. After performing PSM to match the general clinical data of the two groups of patients, 77 patients in each of the robotic NOSES and robotic-assisted groups were included in the analysis. We found no statistically significant difference in preoperative general clinical data between the robot NOSES and robot-assisted groups ( P>0.05). We compared the surgical outcomes, postoperative recovery, postoperative pathological data, and incidence of complications between the robotic NOSES and robot-assisted groups. Results:Compared with the robot-assisted groups. the robot NOSES group had a significantly shorter time to first postoperative passage of flatus (48 [38, 50] hours vs. 56 [50, 60] hours, Z=-7.513, P<0.001), time to taking a liquid diet (60 [54,63] hours vs. 66 [62, 72] hours, Z=-6.303, P<0.001), lower pain scores (3 [3, 4] vs. 4 [4, 5], Z=-5.237, P<0.001), and lower incision infection rates (0 vs. 5 [6.5%], χ 2=5.237, P=0.028) within 24 hours after surgery ( P<0.05). However, there were no significant differences in surgical time, intraoperative blood loss, postoperative hospital stay, postoperative anastomotic complications, or incidence of other complications between the two groups (all P>0.05). Conclusion:Robotic NOSES surgery is a safe and feasible procedure for resecting rectal cancer and postoperative recovery is faster after robotic NOSES than after standard robot-assisted surgery.
		                        		
		                        		
		                        		
		                        	
7.Characteristic Analysis of "Imprinting Template" for Pungent Herbs Based on Molecular Connectivity Index and Matching Frequency Total Statistical Moment
Xuebing QIAN ; Liangqi ZHANG ; Yin XIAO ; Hongxin LIU ; Yuanqing SHEN ; Meifeng XIAO ; Fuyuan HE
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(9):218-224
		                        		
		                        			
		                        			ObjectiveTo analyze the fingerprint of six pungent herbs based on the molecular connectivity index(MCI)and the matching frequency total statistical moment method, and to study the division and integration of the "imprinting template" of their volatile components, so as to find the common "imprinting template" characteristics of the pungent herbs. MethodThe volatile components of six pungent herbs were extracted by steam distillation, and their fingerprints were established by gas chromatography-mass spectrometry(GC-MS) with a programmed temperature increase(80 ℃ for 5 min, 5 ℃·min-1 to 200 ℃ for 5 min, 2 ℃·min-1 to 230 ℃ for 10 min), a splitting ratio of 20∶1, an electron bombardment ion source(EI) and the detection range of m/z 35-650, and the average MCI and total statistical moment parameters of the fingerprints were calculated. Then the matching frequency method was used to classify, integrate and confirm the chromatographic peaks of the fingerprints of six pungent herbs. ResultThe average zero order, first-order and second-order MCI values of the volatile components of Pogostemonis Herba, Artemisiae Argyi Folium, Atractylodis Rhizoma, Asari Radix et Rhizoma, Magnoliae Flos and Schizonepetae Herba were 9.02, 5.28 and 5.05, respectively. The average values of peak number, total zero-order moment, total first-order moment and total second-order moment were 60, 169×107, 22.49 min and 36.82 min2, respectively. The 20 integrated imprinting templates were obtained by the matching frequency method for the six pungent herbs, among which three were common imprinting templates with the retention times of (25.97±0.21),(26.90±0.20),(31.64±1.24) min, respectively, and the representative components were valencene,β-elemene, caryophyllin, etc. ConclusionMCI combined the matching frequency total statistical moment can divide and integrate the characteristics of imprinting templates of six pungent herbs, and find their common chromatographic imprinting characteristics, which can provide a reference for the determination of effective substances of pungent herbs. 
		                        		
		                        		
		                        		
		                        	
8.Effects of Shaoyao gancao decoction on intestinal flora in rats with acute lung injury
Ganchun ZHANG ; Wen LIU ; Xinli SONG ; Xingde LIU ; Wanfen SHU ; Qin QIN ; Hongxin WANG
China Pharmacy 2023;34(17):2063-2068
		                        		
		                        			
		                        			OBJECTIVE To study the improvement effects of Shaoyao gancao decoction (SGD) on acute lung injury (ALI) in rats and its effects on the intestinal flora. METHODS Sixty SD rats were randomly divided into normal group (CON group, normal saline), model group (MOD group, normal saline), positive control group (DEX group, 5 mg/kg dexamethasone), SGD low-dose, medium-dose and high-dose groups (SGD-L, SGD-M, SGD-H groups, 5.8, 11.6, 23.2 g/kg, calculated by crude drug), with 10 rats in each group. Each group was given relevant medicine 10 mL/kg intragastrically, for 7 consecutive days. Thirty minutes after the last administration, CON group was given constant volume of normal saline via airway infusion, and other groups were given lipopolysaccharide (5 mg/kg) via airway infusion to induce ALI model. After 12 hours of modeling, the lung tissue wet/dry weight ratio was calculated, and the contents of interleukin 1β (IL-1β), IL-6 and tumor necrosis factor α(TNF-α) in rat bronchial alveolar lavage fluid (BALF) were all detected; the pathological changes of lung tissue were observed after hematoxylin-eosin staining. The intestinal flora of rat feces was analyzed by 16S rRNA sequencing technology, and the correlation of differential bacteria genera with inflammatory factors was also analyzed. RESULTS Compared with MOD group, the infiltration of inflammatory cells in the lung tissue of rats in each SGD dose group was decreased, and the thickening of alveolar septum and pulmonary edema improved; lung tissue wet/dry weight ratio, the levels of IL-1β, IL-6 and TNF-α in BALF significantly decreased (P<0.05 or P<0.01). SGD (low dose) could improve the intestinal flora disorder in ALI rats, restore the diversity and richness of intestinal flora, regulate the structure of flora, reduce the abundance of Lactobacillus, Streptococcus and Escherichia-Shigella, and increase the abundance of Firmicutes, Lachnospira, Ruminococcus, Clostridia,Dubosiella and Akkermansia. Through correlation analysis, it was found that the relative abundance of Lactobacillus, Streptococcus and Escherichia-Shigella was positively related to the levels of inflammatory factor IL-1β, IL-6 and TNF-α (P<0.05 or P<0.01). The relative abundance of Lachnospira, Dubosiella, Firmicutes was significantly negatively correlated with the levels of inflammatory factors mentioned above (P<0.05 or P<0.01). CONCLUSIONS SGD may improve ALI by reducing lung tissue injury and inflammatory response and regulating flora structure in rats.
		                        		
		                        		
		                        		
		                        	
9.Risk factors and prediction model of perioperative esophagogastric anastomotic leakage after esophageal cancer surgery
Hongxin NIE ; Sihao YANG ; Honggang LIU ; Gaoping CAI ; Dong CHAO ; Hui MENG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2023;30(04):586-592
		                        		
		                        			
		                        			Objective    To analyze the risk factors for esophagogastric anastomotic leakage (EGAL) after esophageal cancer surgery, and to establish a risk prediction model for early prevention and treatment. Methods    Clinical data of patients undergoing esophagectomy in our hospital from January 2013 to October 2020 were retrospectively analyzed. The independent risk factors for postoperative EGAL were analyzed by univariate and multivariate logistic regression analyses, and a clinical nomogram prediction model was established. According to whether EGAL occurred after operation, the patients were divided into an anastomotic fistula group and a non-anastomotic fistula group. Results    A total of 303 patiens were enrolled, including 267 males and 36 females with a mean age of 62.30±7.36 years. The incidence rate of postoperative EGAL was 15.2% (46/303). The multivariate logistic regression analysis showed that high blood pressure, chronic bronchitis, peptic ulcer, operation way, the number of lymph node dissected, anastomotic way, the number of intraoperative chest drainage tube, tumor location, no-supplementing albumin in the first three days after operation, postoperative pulmonary infection, postoperative use of bronchoscope were the independent risk factors for EGAL after esophageal cancer surgery (P<0.05). A prognostic nomogram model was established based on these factors with the area under the receiver operating characteristic curve of 0.954 (95%CI 0.924-0.975), indicating a high predictive  value. Conclusion    The clinical prediction model based on 11 perioperative risk factors in the study has a good evaluation efficacy and can promote the early detection, diagnosis and treatment of EGAL.
		                        		
		                        		
		                        		
		                        	
10.Analysis of Mechanism of Qinggan Jianpi Huoxue Prescription in Treatment of Hepatic Fibrosis Rats by Regulating M1/M2 Macrophages
Fuzhen PAN ; Hongxin CAO ; Yongsheng ZHANG ; Xiaqiu WU ; Weifang ZHENG ; Ding LIU
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(21):94-102
		                        		
		                        			
		                        			ObjectiveTo observe the effect of Qinggan Jianpi Huoxue prescription(QGJPHXP) on the polarization of M1/M2 macrophages in rats with hepatic fibrosis induced by carbon tetrachloride(CCl4). MethodA rat hepatic fibrosis model was established by intraperitoneal injection of 40% CCl4-olive oil suspension twice a week at the dosage of 2.0 mL·kg-1 for 8 weeks. After the model was successfully established, these rats were randomly divided into the model group, QGJPHXP group(32.084 g·kg-1) and Biejiajian pills(BJJP) group(0.925 5 g·kg-1), with 12 rats in each group. The blank group was injected intraperitoneally with the same amount of olive oil. The rats in the administration groups were given the corresponding solution according to the dose, and the blank and model groups were given the same dose of purified water, once a day. After 4 weeks of continuous administration, the liver tissues of rats were taken and stained with hematoxylin-eosin(HE) and Masson to observe the pathological changes. The serums were collected to detect the alanine aminotransferase(ALT) and aspartate aminotransferase(AST) levels. Interleukin(IL)-6, IL-12, IL-10, IL-1β, transforming growth factor-β1(TGF-β1) and tumor necrosis factor-α(TNF-α) levels in liver tissues were measured by enzyme-linked immunosorbent assay(ELISA). The expression levels of CD86 and CD206 were detected by immunohistochemistry(IHC). Western blot and real-time fluorescence quantitative polymerase chain reaction(Real-time PCR) were used to detect the protein and mRNA expression levels of inducible nitric oxide synthase(iNOS), arginase-1(Arg-1), phosphorylated p38 mitogen-activated protein kinase(p-p38 MAPK), nuclear transcription factor-κB p65(NF-κB p65) in liver tissues of rats. ResultCompared with the blank group, the hepatic cell plate was irregularly arranged, and local inflammatory cell infiltration and fibrous hyperplasia were observed, while the serum levels of ALT and AST were significantly increased in the model group(P<0.01), and IL-1β, IL-6, IL-12, TGF-β1, TNF-α, CD86, CD206, iNOS, p-p38 MAPK,p38 MAPK and NF-κB p65 levels in liver tissues were obviously increased(P<0.05, P<0.01), while the levels of IL-10 and Arg-1 were obviously decreased(P<0.05, P<0.01). Compared with the model group, QGJPHXP group reduced the degree of liver cell fibrosis,and serum levels of ALT and AST(P<0.01), and IL-1β, IL-6, IL-12, TGF-β1, TNF-α, CD86, iNOS, p-p38 MAPK, p38 MAPK, and NF-κB p65 levels in liver tissues were obviously decreased(P<0.05, P<0.01), the levels of IL-10, CD206 and Arg-1 were obviously increased in the QGJPHXP group(P<0.05, P<0.01). ConclusionQGJPHXP has ability to inhibit the activation of pro-inflammatory M1 macrophages, induce the secretion of anti-inflammatory cytokines by M2 macrophages, reduce the release of pro-fibrogenic cytokines, and promote the macrophage polarization of M1 to M2 in liver for tissue repair, thereby serving as an anti-inflammatory and anti-hepatic fibrosis drug. 
		                        		
		                        		
		                        		
		                        	
            
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