Objective To explore the effects and mechanisms of Sanzi Sijun Formula(SSF)in non-alcoholic fatty liver disease(NAFLD)through network pharmacology,molecular docking and molecular dynamics simulation;To carry out experimental validation in vivo and in vitro.Methods The active components and target genes of SSF were screened using TCMSP,TCMIP and TCMIO databases.NAFLD-related targets were screened using the GeneCards database,and the intersection targets were obtained to construct a protein-protein interaction network and screen for core targets.The intersection targets were imported into the DAVID database for GO and KEGG enrichment analysis.Molecular docking was performed using AutoDock Vina software between the key active components of SSF and core targets,and molecular dynamics simulations were conducted using Gromacs 2022 for 100 ns.C57BL/6J mice NAFLD model was established by diet induction.SSF was administered by gavage for 8 weeks.Liver histopathological changes and the levels of non-esterified fatty acids(NEFA)were detected.In vitro NAFLD model was established by inducing AML12 cells with palmitic acid(PA)for 24 hours.SSF-containing serum was added to incubate simultaneously.The lipid accumulation and cell viability were detected.The core targets of SSF intervention in the in vitro and in vivo NAFLD models were verified by RT-qPCR and Western blot.Results Network pharmacological analysis identified 75 active components in SSF and revealed 179 shared targets between these components and NAFLD.Ten main active components including arachidonate,12-senecioyl-2E,8E,10E-atractylodin,cerebrosterol,glycyrrhizol B and sinapic acid,etc.as well as 8 core targets were identified.GO enrichment analysis of targets mainly involved protein phosphorylation,inflammatory response,and apoptosis,while the KEGG enrichment analysis mainly included AGE-RAGE,TNF,AMPK,PPAR and NF-κB signaling pathways.Molecular docking demonstrated that the major active components of SSF exhibited favorable binding affinity and stability with the core targets.Molecular dynamics simulation confirmed the stability of the complex of glyasperin B with AKT1,SIRT1,STAT3,PPARG,and TNF.SSF alleviated the pathological damage of liver tissues in mice NAFLD model,reduced NAS score and NEFA levels in liver tissues(P<0.05).Additionally,SSF reversed lipid accumulation and decreased cell viability of PA-induced AML12 cells(P<0.01).Further in vivo and in vitro experiments demonstrated that SSF significantly reversed the elevated mRNA levels of TNF-α,IL-6,IL-1β and PPARγ and protein expression of STAT3(P<0.05,P<0.01)in NAFLD models,up-regulated the protein levels of SIRT1 and p-Akt/Akt(P<0.05,P<0.01).Conclusion SSF can improve NAFLD of both in vitro and in vivo models.The regulation of multiple targets,such as AKT,SIRT1,STAT3 and PPARG,by its multiple active components,and adjustment of multiple approaches,such as lipid metabolism disorder,inflammatory responses,are involved in the potential underlying mechanisms.

Objective To explore the mechanism of Bufei Jiedu Granules in the treatment of methicillin-resistant Staphylococcus aureus(MRSA)chronic infection using network pharmacology;To verify it through animal experiments.Methods Active components and potential targets in Bufei Jiedu Granules were screened through the TCMSP database,and genes related to MRSA infection were retrieved through GeneCards,OMIM,DisGeNET,TTD,DrugBank and PharmGKB databases.The STRING database was employed to construct a protein-protein interaction network on common targets,and GO and KEGG pathway enrichment analysis were conducted to identify key signaling pathways for Bufei Jiedu Granules treatment of MRSA infection.The effects of Bufei Jiedu Granules on bacterial load and pathological changes in the lung,liver and kidney of MRSA chronic infection mice models were evaluated through WT and T/B immune cell deficient Rag2-/-mouse animal experiments.The mRNA expressions of inflammatory factors(IFN-γ,IL-10)and immune checkpoints(PD1,TIM3)were detected.Results Totally 54 active components related to Bufei Jiedu Granules were selected,and 50 potential targets related to MRSA infection were identified.118 signaling pathways significantly associated with MRSA infection were identified through GO and KEGG pathway enrichment analysis,in which the JAK-STAT signaling pathway,Th17 cell differentiation,and PD-L1 expression and PD-1 checkpoint pathway were closely related to cell activation and T cell differentiation.Animal experimental results indicated that Bufei Jiedu Granules could effectively reduce the bacterial load in organs and ameliorate the pathological damage in the chronic MRSA infection mouse model,increase the mRNA expression of IFN-γ in the lung tissue,and decrease the mRNA expressions of IL-10,PD1 and TIM3.Conclusion Bufei Jiedu Granules has the characteristics of multi-component and multi-target in the treatment of MRSA infection,and may be involved in adaptive immune activation to effectively treat chronic MRSA infection.

Objective To explore the effects and mechanisms of Sanzi Sijun Formula(SSF)in non-alcoholic fatty liver disease(NAFLD)through network pharmacology,molecular docking and molecular dynamics simulation;To carry out experimental validation in vivo and in vitro.Methods The active components and target genes of SSF were screened using TCMSP,TCMIP and TCMIO databases.NAFLD-related targets were screened using the GeneCards database,and the intersection targets were obtained to construct a protein-protein interaction network and screen for core targets.The intersection targets were imported into the DAVID database for GO and KEGG enrichment analysis.Molecular docking was performed using AutoDock Vina software between the key active components of SSF and core targets,and molecular dynamics simulations were conducted using Gromacs 2022 for 100 ns.C57BL/6J mice NAFLD model was established by diet induction.SSF was administered by gavage for 8 weeks.Liver histopathological changes and the levels of non-esterified fatty acids(NEFA)were detected.In vitro NAFLD model was established by inducing AML12 cells with palmitic acid(PA)for 24 hours.SSF-containing serum was added to incubate simultaneously.The lipid accumulation and cell viability were detected.The core targets of SSF intervention in the in vitro and in vivo NAFLD models were verified by RT-qPCR and Western blot.Results Network pharmacological analysis identified 75 active components in SSF and revealed 179 shared targets between these components and NAFLD.Ten main active components including arachidonate,12-senecioyl-2E,8E,10E-atractylodin,cerebrosterol,glycyrrhizol B and sinapic acid,etc.as well as 8 core targets were identified.GO enrichment analysis of targets mainly involved protein phosphorylation,inflammatory response,and apoptosis,while the KEGG enrichment analysis mainly included AGE-RAGE,TNF,AMPK,PPAR and NF-κB signaling pathways.Molecular docking demonstrated that the major active components of SSF exhibited favorable binding affinity and stability with the core targets.Molecular dynamics simulation confirmed the stability of the complex of glyasperin B with AKT1,SIRT1,STAT3,PPARG,and TNF.SSF alleviated the pathological damage of liver tissues in mice NAFLD model,reduced NAS score and NEFA levels in liver tissues(P<0.05).Additionally,SSF reversed lipid accumulation and decreased cell viability of PA-induced AML12 cells(P<0.01).Further in vivo and in vitro experiments demonstrated that SSF significantly reversed the elevated mRNA levels of TNF-α,IL-6,IL-1β and PPARγ and protein expression of STAT3(P<0.05,P<0.01)in NAFLD models,up-regulated the protein levels of SIRT1 and p-Akt/Akt(P<0.05,P<0.01).Conclusion SSF can improve NAFLD of both in vitro and in vivo models.The regulation of multiple targets,such as AKT,SIRT1,STAT3 and PPARG,by its multiple active components,and adjustment of multiple approaches,such as lipid metabolism disorder,inflammatory responses,are involved in the potential underlying mechanisms.

Objective To explore the mechanism of Bufei Jiedu Granules in the treatment of methicillin-resistant Staphylococcus aureus(MRSA)chronic infection using network pharmacology;To verify it through animal experiments.Methods Active components and potential targets in Bufei Jiedu Granules were screened through the TCMSP database,and genes related to MRSA infection were retrieved through GeneCards,OMIM,DisGeNET,TTD,DrugBank and PharmGKB databases.The STRING database was employed to construct a protein-protein interaction network on common targets,and GO and KEGG pathway enrichment analysis were conducted to identify key signaling pathways for Bufei Jiedu Granules treatment of MRSA infection.The effects of Bufei Jiedu Granules on bacterial load and pathological changes in the lung,liver and kidney of MRSA chronic infection mice models were evaluated through WT and T/B immune cell deficient Rag2-/-mouse animal experiments.The mRNA expressions of inflammatory factors(IFN-γ,IL-10)and immune checkpoints(PD1,TIM3)were detected.Results Totally 54 active components related to Bufei Jiedu Granules were selected,and 50 potential targets related to MRSA infection were identified.118 signaling pathways significantly associated with MRSA infection were identified through GO and KEGG pathway enrichment analysis,in which the JAK-STAT signaling pathway,Th17 cell differentiation,and PD-L1 expression and PD-1 checkpoint pathway were closely related to cell activation and T cell differentiation.Animal experimental results indicated that Bufei Jiedu Granules could effectively reduce the bacterial load in organs and ameliorate the pathological damage in the chronic MRSA infection mouse model,increase the mRNA expression of IFN-γ in the lung tissue,and decrease the mRNA expressions of IL-10,PD1 and TIM3.Conclusion Bufei Jiedu Granules has the characteristics of multi-component and multi-target in the treatment of MRSA infection,and may be involved in adaptive immune activation to effectively treat chronic MRSA infection.

Metastasis is an important factor for the high recurrence and mortality rates of hepatocellular carcinoma (HCC), and epithelial-mesenchymal transition (EMT) is an important mechanism of HCC metastasis. EMT is regulated by the transcription factors such as Snail, Twist, and ZEB which are mediated by a variety of signaling pathways including TGF-β, Wnt/β-catenin, and Notch. Inhibition of EMT-related molecules and signal pathways in HCC is considered as an important approach to inhibit the invasion and metastasis of HCC. Recent studies have shown that a variety of compound traditional Chinese medicine (TCM) formula or their effective constituents can inhibit the invasion and metastasis of HCC by arresting or reversing EMT in HCC. This article reviews the role and mechanism of EMT and recent studies on TCM drugs and their derived natural compounds in inhibiting the invasion and metastasis of HCC by regulating cell EMT, so as to provide a scientific basis for the TCM prevention and treatment of HCC metastasis and new ideas for HCC treatment.

Objective:To investigate the long-term efficacy and safety of alternating double balloon occlusion combined with intra-aneurysm injection of human fibrin binder in the endovascular repair of ruptured abdominal aortic aneurysm (rAAA).Methods:The clinical data of 28 patients with rAAA admitted to Department of Vascular Surgery, the Fourth Affiliated Hospital of Guangxi Medical University from January 2015 to December 2019 were retrospectively analyzed. There were 23 males and 5 females, aged (62±5) years (range: 46 to 88 years).The maximum diameter of the tumors was (65.2±10.5) mm (range: 47.3 to 100.5 mm), all of which were subrenal rAAA. The intraoperative EVAR for abdominal aortic aneurysm was successfully performed under the emergency green channel procedure, and this surgery was assisted used the double balloon occlusion technique in aorta of inferior renal and superior renalcombined with intraoperative human fibrin binder injection technique. Observation indexes included: patients with preoperative preparation, operation time, hospitalization days, surgical treatment success rate and the incidence of postoperative complications, and aortic stent form during the follow-up period, the incidence of leakage, branch stents patency rate and infection rates.Results:The preoperative preparation time of 28 patients was (45.5±8.5) minutes (range:20 to 100 minutes). The operation time was (100.0±15.5) minutes (range:85 to 210 minutes), the ICU stay time was (7±2) days(range:1 to 17 days). The length of hospitalization was (13.5±2.5) days(range:5 to 43 days). The success rate of surgical treatment was 92.9% (26/28). Two patients died, 1 case died of postoperative multifocal lacunar cerebral infarction and massive gastrointestinal hemorrhage, and another elderly patient (84 years old) died of massive abdominal fluid due to preoperative abdominal aortic aneurysm rupture, postoperative complicated with significant abdominal compartment syndrome, and secondary multiple organ failure. Balloon occlusion of the upper renal aorta took (13±2)minutes (range:12 to 30 minutes). The intraoperative injection of fibrin adhesive was (14±2) ml(range:6 to 28 ml) in 22 cases. The incidence of major postoperative complications was 57.1% (16/28). Among the 26 patients who survived the surgery, 69.2% (18/26) completed the 3-year follow-up, and the follow-up time was (30±3) months(range:13 to 36 months). During the follow-up, the aortic stent was in good shape without obvious displacement. The incidence of leakage within 6 months after the operation was 10.7% (3/28), and there was no internal leakage in the patients who were followed up for 36 months after the operation. The patency rate of renal artery and iliac artery branch stents was 16/18. The incidence of stent infection was 7.7% (2/26), 1 case occurred at 1 month and another case at 6 months, respectively. All patients recovered after prolonged intensive anti-infection therapy.Conclusions:Under the standard emergency treatment process, the double balloon alternating occlusion technique combined with the intra-aneurysm injection of human fibrin adhesive technique can assist the successful completion of the endovascular repair of rAAA, effectively improve the success rate of treatment for patients, and reduce the incidence of postoperative leakage and serious complications. The mid-term and long-term results of EVAR for rAAA are good, safe and reliable.

Objective:To investigate the long-term efficacy and safety of alternating double balloon occlusion combined with intra-aneurysm injection of human fibrin binder in the endovascular repair of ruptured abdominal aortic aneurysm (rAAA).Methods:The clinical data of 28 patients with rAAA admitted to Department of Vascular Surgery, the Fourth Affiliated Hospital of Guangxi Medical University from January 2015 to December 2019 were retrospectively analyzed. There were 23 males and 5 females, aged (62±5) years (range: 46 to 88 years).The maximum diameter of the tumors was (65.2±10.5) mm (range: 47.3 to 100.5 mm), all of which were subrenal rAAA. The intraoperative EVAR for abdominal aortic aneurysm was successfully performed under the emergency green channel procedure, and this surgery was assisted used the double balloon occlusion technique in aorta of inferior renal and superior renalcombined with intraoperative human fibrin binder injection technique. Observation indexes included: patients with preoperative preparation, operation time, hospitalization days, surgical treatment success rate and the incidence of postoperative complications, and aortic stent form during the follow-up period, the incidence of leakage, branch stents patency rate and infection rates.Results:The preoperative preparation time of 28 patients was (45.5±8.5) minutes (range:20 to 100 minutes). The operation time was (100.0±15.5) minutes (range:85 to 210 minutes), the ICU stay time was (7±2) days(range:1 to 17 days). The length of hospitalization was (13.5±2.5) days(range:5 to 43 days). The success rate of surgical treatment was 92.9% (26/28). Two patients died, 1 case died of postoperative multifocal lacunar cerebral infarction and massive gastrointestinal hemorrhage, and another elderly patient (84 years old) died of massive abdominal fluid due to preoperative abdominal aortic aneurysm rupture, postoperative complicated with significant abdominal compartment syndrome, and secondary multiple organ failure. Balloon occlusion of the upper renal aorta took (13±2)minutes (range:12 to 30 minutes). The intraoperative injection of fibrin adhesive was (14±2) ml(range:6 to 28 ml) in 22 cases. The incidence of major postoperative complications was 57.1% (16/28). Among the 26 patients who survived the surgery, 69.2% (18/26) completed the 3-year follow-up, and the follow-up time was (30±3) months(range:13 to 36 months). During the follow-up, the aortic stent was in good shape without obvious displacement. The incidence of leakage within 6 months after the operation was 10.7% (3/28), and there was no internal leakage in the patients who were followed up for 36 months after the operation. The patency rate of renal artery and iliac artery branch stents was 16/18. The incidence of stent infection was 7.7% (2/26), 1 case occurred at 1 month and another case at 6 months, respectively. All patients recovered after prolonged intensive anti-infection therapy.Conclusions:Under the standard emergency treatment process, the double balloon alternating occlusion technique combined with the intra-aneurysm injection of human fibrin adhesive technique can assist the successful completion of the endovascular repair of rAAA, effectively improve the success rate of treatment for patients, and reduce the incidence of postoperative leakage and serious complications. The mid-term and long-term results of EVAR for rAAA are good, safe and reliable.

Objective:To systematically analyze the clinical features of severe fever with thrombocytopenia syndrome (SFTS) and to provide evidence for the prevention and treatment of SFTS.Methods:Relevant studies of SFTS from six databases, including China National Knowledge Infrastructure, Wanfang Database, Chongqing VIP, PubMed, Cochrane Library and Embase from January 2009 to May 2019 were systematically searched and identified. The literatures were screened and the data of patients′ epidemiology, clinical manifestations, laboratory examinations and prognosis were obtained. Revman 5.2 software was used for meta analysis.Results:Sixty-eight Chinese literatures and fourteen English literatures encompassing 6 780 patients with SFTS were included in the final analysis. Of these patients, 845 cases (12.46%) died. SFTS mostly occurred in mountainous and hilly areas, and farmers (3 637 cases) were the usual victims. The onset season was mostly in summer and the peak was from May to August each year. There were 1 434 patients had a clear history of tick bites, and 21 cases were human-to-human transmitted.There were 6 071 cases (89.54%) presented with fever, 5 407 cases (79.75%) presented with fatigue, 3 140 cases (46.31%) presented with muscle soreness, and 2 300 cases (33.92%) presented with chills.Using random effects model for meta analysis, the levels of creatine kinase (CK) (mean difference ( MD)=500.40, 95% confidence interval ( CI) 380.51-620.28, P<0.01) and lactic acid dehydrogenase (LDH)( MD=442.81, 95% CI 152.85-732.78, P=0.003) in severe patients were both higher than those in mild patients, and the difference were both statistically significant. The risk of death increased in patients aged>60 years( MD=8.19, 95% CI 4.03-12.36, P<0.01). The levels of CK( MD=530.92, 95% CI 29.27-1 032.56, P=0.040), LDH( MD=609.28, 95% CI 80.25-1 138.31, P=0.020), urea nitrogen ( MD=4.67, 95% CI 3.05-6.30, P<0.01) and creatinine ( MD=43.05, 95% CI 23.49-62.62, P<0.01) of patients in the death group were all higher than those in the survival group. The differences were all statistically significant. Conclusions:During the course of SFTS, the patients may show impaired blood system, heart, liver and kidney functions with high mortality. Clinicians should timely monitor the changes of blood routine, myocardial enzyme spectrum, liver and kidney functions and other indicators, so as to find cardiovascular and other system complications as early as possible. Timely treatment could not only reduce liver, heart and other organ injuries, but also reduce mortality.

Objective: To analyze the prevalence of severe fever with thrombocytopenia syndrome virus(SFTSV)infection in Zhoushan island of Zhejiang province and the duration of serum positive IgG antibody in patients infected with SFTSV. Methods: One thousand one hundred and twenty-two healthy people from Zhoushan island of Zhejiang province were recruited for cross-sectional study in August 2019, including 641 from non-epidemic areas and 481 from epidemic areas. The serum SFTSV-IgG antibody was detected by enzyme-linked immunosorbent assay (ELISA), and the positive rates of SFTSV-IgG antibody were compared between people from the epidemic areas and non epidemic areas. Meanwhile, the antibody titer of SFTSV-IgG in 19 patients confirmed between July 2011 and June 2018 was detected by indirect ELISA. SPSS 17.0 software was used to analyze data. Results: The positive rate of SFTSV-IgG antibody was 1.5% (7/481) in the epidemic area, which was higher than that in the non-epidemic area (0/641) (χ²=7.187, P<0.01). The positive rates of SFTSV-IgG antibody in 2019 were lower than those in the epidemic area (11.7%) and non-epidemic area (2.5%) in 2013 (χ²=22.556 and 10.352, both P<0.01). The serum SFTSV-IgG antibody of 18 patients with previous infection was still positive, and the longest one lasted for 8 years. Conclusions There is a SFTSV latent infection in population from epidemic area of Zhoushan island. The SFTSV-IgG antibody can last for a long time in patients with SFTS and it may have certain protective effect.

By means of joint research of new advanced technology project,joint development and application of appropriate health technology project,comprehensive prevention and control of chronic diseases between municipal hospitals and community clinics project and research supporting platform project,Shanghai Hospital Development Center has effectively improved the clinical science and technology innovation capability, promoted the development of medical disciplines and talents and improved the discipline influence of such hospitals.