1.Research Progress of Traditional Chinese Medicine Intervention in Nrf2/HO-1 Signaling Pathway for Acute Pancreatitis: A Review
Wanling XIN ; Ning WANG ; Cenyi LIANG ; Yue ZU ; Sijia LI ; Minchao FENG ; Guozhong CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(5):265-271
Acute pancreatitis (AP) is a common clinical acute abdominal disease, which is characterized by acute onset, rapid development, severe disease, many complications, and high mortality rate. It can progress to severe AP (SAP) if not treated promptly in the early stage. The pathogenesis of AP is complex and involves multiple cellular and molecular levels. It is now clear that oxidative stress and reactive oxygen species (ROS) production are involved in the physiopathological process of AP, which is associated with a low quantity and activity of antioxidant enzymes in pancreatic cells. Nuclear factor E2-related factor 2 (Nrf2) serves as the ''golden key'' to maintain redox homeostasis in tissue cells and constitutes an important signaling pathway for antioxidant response and inflammation in vivo by collaborating with downstream antioxidant enzymes such as heme oxygenase-1 (HO-1). Traditional Chinese medicine has unique efficacy in treating diseases due to its multi-component, multi-target, multi-drug delivery, and multi-formulation characteristics. Based on the concept of synergy between traditional Chinese and Western medicine, traditional Chinese medicine is becoming a new craze in the treatment of AP. The level of oxidative stress and Nrf2/HO-1 signaling pathway in AP pancreatic tissue are in a dynamic change process, and the intervention of traditional Chinese medicine can clean ROS production, affect the inflammatory pathway, and reduce oxidative stress damage, so as to protect against pancreatic injury. This suggests that this pathway plays an important role in AP. This article reviews the recent literature on the regulation of the Nrf2/HO-1 signaling pathway by traditional Chinese medicine for AP and summarizes that the monomers of traditional Chinese medicine targeting this pathway are mainly heat-clearing and detoxifying, blood-activating and blood-stasis-removing, and Qi benefiting and middle warming, and the compounds of traditional Chinese medicine include Yinchenhao Decoction and QingYi Ⅱ, so as to provide a new direction for the prevention and treatment of AP and further drug development.
2.Protective effect of Qingjie Huagong decoction on pancreatic tissue of mice with severe acute pancreatitis by regulating the NOD-like receptor protein 3/Toll-like receptor 4/nuclear factor-kappa B signaling pathway
Minchao FENG ; Baijun QIN ; Fang LUO ; Kai LI ; Ning WANG ; Guozhong CHEN ; Xiping TANG
Journal of Clinical Hepatology 2024;40(2):343-350
ObjectiveTo investigate the therapeutic effect of Qingjie Huagong decoction (QJHGD) on a mouse model of severe acute pancreatitis (SAP) and the mechanism of action of QJHGD against inflammatory response. MethodsA total of 36 male C57BL/6J mice were randomly divided into blank group, model group, Western medicine group (ulinastatin), and low-, middle-, and high-dose QJHGD groups, with 6 mice in each group. All mice except those in the blank group were given 5% sodium taurocholate by retrograde pancreaticobiliary injection to establish a model of SAP. After modeling, the mice in the low-, middle-, and high-dose groups were given QJHGD (1, 2, and 4 g/kg, respectively) by gavage, and those in the Western medicine group were given intraperitoneal injection of ulinastatin (5×104 U/kg), for 7 days in total. HE staining was used to observe the histopathological changes of the pancreas; ELISA was used to measure the levels of α-amylase, lipase, interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-18 (IL-18), and tumor necrosis factor-α (TNF-α) in mice; RT-qPCR was used to measure the mRNA expression levels of NOD-like receptor protein3 (NLRP3), Toll-like receptor 4 (TLR4), and nuclear factor-kappa B (NF-κB) in pancreatic tissue; immunohistochemistry was used to measure the positive expression rates of NLRP3, TLR4, and NF-κB in pancreatic tissue; Western blot was used to measure the protein expression levels of NLRP3, TLR4, NF-κB, IL-1β, and IL-6. An analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the blank group, the model group had diffuse destruction of pancreatic tissue structure, focal dilatation of pancreatic lobular septum, pancreatic acinar atrophy, and massive inflammatory cell infiltration, as well as significant increases in the content of α-amylase, lipase, IL-1β, IL-6, IL-8, IL-18, and TNF-α (all P<0.05), the mRNA expression levels and positive expression rates of NLRP3, TLR4, and NF-κB (all P<0.05), and the protein expression levels of NLRP3, TLR4, NF-κB, IL-1β, and IL-6 (all P<0.05). Compared with the model group, the low-, middle-, and high-dose QJHGD groups and the Western medicine group had slightly tighter and more intact structure of pancreatic tissue, ordered arrangement of pancreatic acinar cells, a small amount of inflammatory cell infiltration, and hemorrhagic foci of pancreatic lobules, as well as significant reductions in the content of α-amylase, lipase, IL-1β, IL-6, IL-8, IL-18, and TNF-α (all P<0.05), the mRNA expression levels and positive expression rates of NLRP3, TLR4, and NF-κB (all P<0.05), and the protein expression levels of NLRP3, TLR4, NF-κB, IL-1β, and IL-6 (all P<0.05). ConclusionQJHGD may exert a protective effect on the pancreatic tissue of SAP mice by inhibiting the activation of NLRP3/TLR4/NF-κB signaling pathway-related proteins, reducing the release of inflammatory mediators, and preventing the enhancement of inflammatory cascade response.
3.Efficacy evaluation of extending or switching to tenofovir amibufenamide in patients with chronic hepatitis B: a phase Ⅲ randomized controlled study
Zhihong LIU ; Qinglong JIN ; Yuexin ZHANG ; Guozhong GONG ; Guicheng WU ; Lvfeng YAO ; Xiaofeng WEN ; Zhiliang GAO ; Yan HUANG ; Daokun YANG ; Enqiang CHEN ; Qing MAO ; Shide LIN ; Jia SHANG ; Huanyu GONG ; Lihua ZHONG ; Huafa YIN ; Fengmei WANG ; Peng HU ; Xiaoqing ZHANG ; Qunjie GAO ; Chaonan JIN ; Chuan LI ; Junqi NIU ; Jinlin HOU
Chinese Journal of Hepatology 2024;32(10):883-892
Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the efficacy of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects who were previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extended or switched TMF treatment for 48 weeks. Efficacy was evaluated based on virological, serological, biological parameters, and fibrosis staging. Statistical analysis was performed using the McNemar test, t-test, or Log-Rank test according to the data. Results:593 subjects from the initial TMF group and 287 subjects from the TDF group were included at week 144, with the proportions of HBV DNA<20 IU/ml at week 144 being 86.2% and 83.3%, respectively, and 78.1% and 73.8% in patients with baseline HBV DNA levels ≥8 log10 IU/ml. Resistance to tenofovir was not detected in both groups. For HBeAg loss and seroconversion rates, both groups showed a further increase from week 96 to 144 and the 3-year cumulative rates of HBeAg loss were about 35% in each group. However, HBsAg levels were less affected during 96 to 144 weeks. For patients switched from TDF to TMF, a substantial further increase in the alanine aminotransferase (ALT) normalization rate was observed (11.4%), along with improved FIB-4 scores.Conclusion:After 144 weeks of TMF treatment, CHB patients achieved high rates of virological, serological, and biochemical responses, as well as improved liver fibrosis outcomes. Also, switching to TMF resulted in significant benefits in ALT normalization rates (NCT03903796).
4.Safety profile of tenofovir amibufenamide therapy extension or switching in patients with chronic hepatitis B: a phase Ⅲ multicenter, randomized controlled trial
Zhihong LIU ; Qinglong JIN ; Yuexin ZHANG ; Guozhong GONG ; Guicheng WU ; Lvfeng YAO ; Xiaofeng WEN ; Zhiliang GAO ; Yan HUANG ; Daokun YANG ; Enqiang CHEN ; Qing MAO ; Shide LIN ; Jia SHANG ; Huanyu GONG ; Lihua ZHONG ; Huafa YIN ; Fengmei WANG ; Peng HU ; Xiaoqing ZHANG ; Qunjie GAO ; Peng XIA ; Chuan LI ; Junqi NIU ; Jinlin HOU
Chinese Journal of Hepatology 2024;32(10):893-903
Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the safety profile of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects that previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extending or switching TMF treatment for 48 weeks. Safety profiles of kidney, bone, metabolism, body weight, and others were evaluated.Results:666 subjects from the initial TMF group and 336 subjects from TDF group with at least one dose of assigned treatment were included at week 144. The overall safety profile was favorable in each group and generally similar between extended or switched TMF treatments from week 96 to 144. In subjects switching from TDF to TMF, the non-indexed estimated glomerular filtration rate (by non-indexed CKD-EPI formula) and creatinine clearance (by Cockcroft-Gault formula) were both increased, which were (2.31±8.33) ml/min and (4.24±13.94) ml/min, respectively. These changes were also higher than those in subjects with extending TMF treatment [(0.91±8.06) ml/min and (1.30±13.94) ml/min]. Meanwhile, switching to TMF also led to an increase of the bone mineral density (BMD) by 0.75% in hip and 1.41% in spine. On the other side, a slight change in TC/HDL ratio by 0.16 (IQR: 0.00, 0.43) and an increase in body mass index (BMI) by (0.54±0.98) kg/m 2 were oberved with patients switched to TMF, which were significantly higher than that in TMF group. Conclusion:CHB patients receiving 144 weeks of TMF treatment showed favorable safety profile. After switching to TMF, the bone and renal safety was significantly improved in TDF group, though experienceing change in metabolic parameters and weight gain (NCT03903796).
5.Application of ultrasound diaphragmatic function assessment in guiding mechanical evacuation of patients with mechanical ventilation
Lei ZHANG ; Guozhong CHEN ; Huaying WANG ; Wanjun YU
Chinese Journal of Emergency Medicine 2023;32(2):241-246
Objective:To explore the application value of ultrasound diaphragmatic function assessment in weaning from invasive mechanical ventilation in patients with respiratory failure.Method:Fifty-three patients with acute respiratory failure who underwent mechanical ventilation and weaning in People’s Hospital Affiliated to Ningbo University from January 2020 to February 2022 were selected for research. After weaning conditions, T-tube was used for spontaneous breathing test (SBT). At SBT-30 min, beside ultrasound was used to collect the right diaphragm movement (DE) and diaphragm thickness, and the shallow rapid breathing index (RSBI), diaphragm shallow rapid breathing index (D-RSBI) and diaphragm thickness change rate (DTF) were calculated. According to the outcome of weaning, the patients were divided into the successfully weaned group and unsuccessfully weaned group. All patients’ clinical data were collected, and the relationship between ultrasound parameters and clinical indexes was compared between the two groups The efficiency of each index for predicting the success rate of weaning was analyzed with the receiver operating characteristic (ROC) curve.Results:Fifty-three patients were enrolled in this study, including 36 patients in the successfully weaned group and 17 patients in the unsuccessfully weaned group. DE and DTF in the successfully weaned group were higher than those in the unsuccessfully weaned group (all P<0.05), RSBI and D-RSBI in the successfully weaned group were significantly lower than those in the unsuccessfully weaned group (all P<0.05). ROC curve analysis showed that when the cut-off value of DE, DTF, RSBI and D-RSBI were >1.21 cm, >27.5%, <48.68 times/(min·L) and <1.31 times/(min·mm), the sensitivity of predicting the success of weaning was 69.0%, 97.2%, 83.0% and 83.0% respectively, and the specificity was 59.0%, 47.1%, 94.1% and 94.3%, respectively. Conclusions:The evaluation of ultrasound diaphragmatic function can effectively guide the clinical mechanical ventilation patients to withdraw the machine, and improve the accuracy of predicting the success rate of weaning. Therefore, t ultrasound diaphragmatic function assessment has a high application value in guiding the mechanical evacuation of patients with mechanical ventilation, and can be widely applied in clinical practice.
6.Application of incision subcutaneous porous catheter combined with ropivacaine analgesia in enhanced recovery after laparoscopic gastrointestinal surgery
Qizhi LIU ; Lisi WAN ; Guozhong CHEN ; Cheng LI ; Junyi CHEN ; Hanrong LIU ; Zhuo CHEN ; Dehua ZHOU ; Jing CHEN ; Xiaohuang TU
Chinese Journal of Postgraduates of Medicine 2023;46(3):271-275
Objective:To investigate the feasibility and effectiveness of incision subcutaneous porous catheter combined with ropivacaine analgesia in enhanced recovery after laparoscopic gastrointestinal surgery.Methods:The clinical data of 140 patients underwent gastrointestinal surgery from August 2021 to April 2022 in Shanghai Fourth People′s Hospital, School of Medicine, Tongji University were retrospectively analyzed. Among them, 70 patients were given routine postoperative analgesia (control group), and 70 patients were given incision subcutaneous porous catheter combined with ropivacaine analgesia on the basis of routine postoperative analgesia (observation group). The visual analogue score (VAS) 4, 24, 32, 48, 56 and 72 h after operation was evaluated; and the complications of subcutaneous catheterization, incision infection, postoperative nausea vomiting, neurological symptoms, time to extubation, patient satisfaction degree, recovery time of intestinal function and hospital stay were recorded.Results:The VAS 4, 24, 32, 48, 56 and 72 h after operation in observation group was significantly lower than that in control group: 1.000 (- 0.250, 2.250) scores vs. 1.000 (- 1.000, 3.000) scores, 2.000 (1.000, 3.000) scores vs. 4.000 (2.000, 6.000) scores, 1.000 (0.000, 2.000) scores vs. 3.000 (1.000, 5.000) scores, 2.000 (1.000, 3.000) scores vs. 3.000 (1.750, 4.250) scores, (1.100 ± 0.934) scores vs. (2.085 ± 0.943) scores and (0.985 ± 0.842) scores vs. (1.814 ± 0.921) scores, and there was statistical difference ( P<0.05 or <0.01). The recovery time of intestinal function and hospital stay in observation group were significantly shorter than that that in control group: (1.743 ± 0.557) d vs. (2.200 ± 0.714) d and (8.043 ± 1.160) d vs. (8.757 ± 1.221) d, and there were statistical difference ( P<0.01); there were no statistical differences in the rate of incision infection, incidence of postoperative nausea vomiting, time to extubation and patient dissatisfaction rate between two groups ( P>0.05); there were no the complications of subcutaneous catheterization and neurological symptoms in two groups. Conclusions:The incision subcutaneous porous catheter combined with ropivacaine analgesia after laparoscopic gastrointestinal surgery is a safe, effective and feasible method. Multimodal analgesia under enhanced recovery after surgery can increase the postoperative recovery after gastrointestinal operations and shorten the postoperative hospital stay.
7.Practice and discussion of cultural integration in multi-campus hospitals
Xu FANG ; Xiaoxian TONG ; Dan CHEN ; Ziying XU ; Xiaoyue ZHANG ; Qing LU ; Fuhui QIU ; Guozhong CHEN
Chinese Journal of Hospital Administration 2023;39(3):175-178
The multi-campus mode is an important way to give full play to the advantages of public hospitals and promote the expansion of high-quality medical resources and balanced regional layout. The authors summarized the practical experience of the Second Affiliated Hospital Zhejiang University School of Medicine in promoting multi-campus cultural integration, including vertical dimensional initiatives including raising cultural construction to a strategic level, improving the working mechanism of cultural construction, and building a distinctive cultural identity system; horizontal dimensional initiatives including creating equal status and intergroup cooperation conducive to cultural integration, building a variety of forms of the main cultural communication platform, and building a unified and diverse cross-campus communication bridge. Through cultural integration, the internal cohesion of the hospital was enhanced and the influence of the hospital brand was improved. The authors suggested that cultural integration should always be based on the principle of " seeking common ground while preserving minor differences" , focusing on the construction of systems and standards, and focusing on the construction of communication platforms.
8.The rule of Traditional Chinese Medicine compounds for acute pancreatitis analyzed based on the National Patent Database
Caixing XIE ; Guozhong CHEN ; Xiaoxia CHEN ; Rihui ZHENG ; Xin YANG ; Yifeng LIANG
International Journal of Traditional Chinese Medicine 2022;44(7):796-800
Objective:Based on the Ancient and Modern Medical Record Cloud Platform, we aimed to analyze the rules of TCM compound patents for the treatment of acute pancreatitis.Methods:Compound patents for acute pancreatitis were retrieved from the National Patent Database. After the steps of data screening, data entry, and data specification, a database of compound patents treated for acute pancreatitis was established. The frequency analysis, attribute analysis, association analysis, cluster analysis, and complex network analysis were performed by using the Ancient and modern medical record cloud platform.Results:A total of 87 compound patents were obtained, comprising 213 herbs, of which the core drugs were Rhei radix et rhizoma, Bupleuri radix, Aurantii fructus immaturus, Glycyrrhizae radix et rhizoma, Magnoliae officinalis cortex, Corydalis rhizoma, Scutellariae radix, Aucklandiae radix, Natrii sulfas, Coptidis rhizoma. The drugs were mainly warm, cold and slightly cold, and the drugs taste mostly bitter and spicy, and the drugs mainly belonged to the spleen meridian and liver meridian. The cluster analysis results contained 5 categories. The associations of drugs included Bupleuri radix - Rhei radix et rhizoma, Aurantii fructus immaturus - Rhei radix et rhizoma, Magnoliae officinalis cortex - Rhei radix et rhizoma, for which complex network analysis yielded a core composition of Rhei radix et rhizoma, Bupleuri radix, Glycyrrhizae radix et rhizoma, Natrii sulfas, Aurantii fructus immaturus, Corydalis rhizoma, Scutellariae radix, Magnoliae officinalis cortex. Conclusion:The eliminating stasis by purging for acute pancreatitis is dominated by Rhei radix et rhizoma, channeling Fu Qi method is based on Aurantii fructus immaturus and Bupleuri radix, and eliminating stasis by purging combined with channeling Fu Qi methods can be used with Magnoliae officinalis cortex, Natrii sulfas, etc.
9.Study on the molecular mechanism of Qifang Weitong granules in treating gastric cancer based on network pharmacology
Xiaoxia CHEN ; Guozhong CHEN ; Yifeng LIANG ; Caixing XIE ; Xin YANG ; Rihui ZHENG
International Journal of Traditional Chinese Medicine 2022;44(8):925-930
Objective:To analyze the potential mechanism of Qifang Weitong granules in the treatment of gastric cancer based on network pharmacology and molecular docking method.Methods:TCMSP, TCMID, and Swiss Target Prediction databases were used to screen out the chemical components and related targets of Qifang Weitong Granules. GeneCards and OMIM databases were used to screen out the gastric cancer targets to obtain common targets of this disease and Qifang Weitong Granules and upload them to STRING database to form a PPI network, and obtain the key targets and analyze the correlation between the key targets and gastric cancer in Oncomine tumor database. In addition, the regulatory network of gastric cancer and Qifang Weitong Granules was constructed by using Cytoscape software, and the CluoGO plug-in and R language of Cytoscape software were used to perform GO and KEGG enrichment analysis on the key targets. The possibility of the binding between the molecules of this medicine and targeted molecules is verified by molecular docking.Results:There were 168 medicinal chemical components obtained in Qifang Weitong Granules, 2 803 gastric cancer targets, and 49 common targets. In the regulatory network of gastric cancer and Qifang Weitong Granules, β-sitosterol, formononet, stigmasterol have higher values of chemical composition. The key targets in the PPI network are MAPK8, FOS, AR, etc. The GO enrichment analysis focused on the positive regulation of mitochondrial outer membrane permeability in the apoptosis signaling pathway, while the KEGG enrichment analysis is significantly enriched in apoptosis access. The result of molecular docking showed good binding and stable conformation.Conclusion:Qifang Weitong Granules can induce the expression of genes and proteins related to gastric cancer, show its effect by affecting the level of hormones, cell apoptosis and other biological processes, and activating the apoptosis signal pathway.
10.Different Anesthesia and Sedation Depths of BIS-guided Closed-loop Target-controlled Infusion on Perioperative Th1/Th2 Balance in Elderly Patients Undergoing Laparoscopic Radical Gastrectomy
Huayong JIANG ; Weilong LAO ; Guozhong ZHOU ; Qiliang SONG ; Zongming JIANG ; Weisheng YU ; Zhonghua CHEN
Cancer Research on Prevention and Treatment 2022;49(5):444-447
Objective To investigate the effect of BIS-guided closed-loop target-controlled infusion on perioperative Th1/Th2 balance in elderly patients undergoing laparoscopic radical gastrectomy under different anesthesia and sedation depths. Methods We applied random number table method to divide 73 elderly patients undergoing elective laparoscopic radical gastrectomy into BIS closed-loop target-controlled infusion group with BIS value of 55(group H,

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