This study aims to investigate the mechanism of Qingrun Decoction in alleviating hepatic insulin resistance in type 2 diabetes mellitus(T2DM) rats through the reprogramming of amino acid metabolism. A T2DM rat model was established by inducing insulin resistance through a high-fat diet combined with intraperitoneal injection of streptozotocin. The model rats were randomly divided into five groups: model group, high-, medium-, and low-dose Qingrun Decoction groups, and metformin group. A normal control group was also established. The rats in the normal and model groups received 10 mL·kg~(-1) distilled water daily by gavage. The metformin group received 150 mg·kg~(-1) metformin suspension by gavage, and the Qingrun Decoction groups received 11.2, 5.6, and 2.8 g·kg~(-1) Qingrun Decoction by gavage for 8 weeks. Blood lipid levels were measured in different groups of rats. Pathological damage in rat liver tissue was assessed by hematoxylin-eosin(HE) staining and oil red O staining. Transcriptome sequencing and untargeted metabolomics were performed on rat liver and serum samples, integrated with bioinformatics analyses. Key metabolites(branched-chain amino acids, BCAAs), amino acid transporters, amino acid metabolites, critical enzymes for amino acid metabolism, resistin, adiponectin(ADPN), and mammalian target of rapamycin(mTOR) pathway-related molecules were quantified using quantitative real-time polymerase chain reaction(qRT-PCR), Western blot, and enzyme-linked immunosorbent assay(ELISA). The results showed that compared with the normal group, the model group had significantly increased serum levels of total cholesterol(TC), triglycerides(TG), low-density lipoprotein cholesterol(LDL-C), and resistin and significantly decreased ADPN levels. Hepatocytes in the model group exhibited loose arrangement, significant lipid accumulation, fatty degeneration, and pronounced inflammatory cell infiltration. In liver tissue, the mRNA transcriptional levels of solute carrier family 7 member 2(Slc7a2), solute carrier family 38 member 2(Slc38a2), solute carrier family 38 member 4(Slc38a4), and arginase(ARG) were significantly downregulated, while the mRNA transcriptional levels of solute carrier family 1 member 4(Slc1a4), solute carrier family 16 member 1(Slc16a1), and methionine adenosyltransferase(MAT) were upregulated. Furthermore, the mRNA transcription and protein expression levels of branched-chain α-keto acid dehydrogenase E1α(BCKDHA) and DEP domain-containing mTOR-interacting protein(DEPTOR) were downregulated, while mRNA transcription and protein expression levels of mTOR, as well as ribosomal protein S6 kinase 1(S6K1), were upregulated. The levels of BCAAs and S-adenosyl-L-methionine(SAM) were elevated. The serum level of 6-hydroxymelatonin was significantly reduced, while imidazole-4-one-5-propionic acid and N-(5-phospho-D-ribosyl)anthranilic acid levels were significantly increased. Compared with the model group, Qingrun Decoction significantly reduced blood lipid and resistin levels while increasing ADPN levels. Hepatocytes had improved morphology with reduced inflammatory cells, and fatty degeneration and lipid deposition were alleviated. Differentially expressed genes and differential metabolites were mainly enriched in amino acid metabolic pathways. The expression levels of Slc7a2, Slc38a2, Slc38a4, and ARG in the liver tissue were significantly upregulated, while Slc1a4, Slc16a1, and MAT expression levels were significantly downregulated. BCKDHA and DEPTOR expression levels were upregulated, while mTOR and S6K1 expression levels were downregulated. Additionally, the levels of BCAAs and SAM were significantly decreased. The serum level of 6-hydroxymelatonin was increased, while those of imidazole-4-one-5-propionic acid and N-(5-phospho-D-ribosyl)anthranilic acid were decreased. In summary, Qingrun Decoction may improve amino acid metabolism reprogramming, inhibit mTOR pathway activation, alleviate insulin resistance in the liver, and mitigate pathological damage of liver tissue in T2DM rats by downregulating hepatic BCAAs and SAM and regulating key enzymes involved in amino acid metabolism, such as BCKDHA, ARG, and MAT, as well as amino acid metabolites and transporters.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Insulin Resistance ; Diabetes Mellitus, Type 2/genetics* ; Male ; Liver/drug effects* ; Amino Acids/metabolism* ; Rats, Sprague-Dawley ; Humans ; Metabolic Reprogramming

The medicinal materials of Bawei Chenxiang Pills(BCPs) were extracted via three methods: reflux extraction by water, reflux extraction by 70% ethanol, and extraction by pure water following reflux extraction by 70% ethanol, yielding three extracts of ST, CT, and CST. The efficacy of ST(760 mg·kg~(-1)), CT(620 mg·kg~(-1)), and CST(1 040 mg·kg~(-1)) were evaluated by acute myocardial ischemia(AMI) and p-chlorophenylalanine(PCPA)-induced insomnia in mice, respectively. Western blot was further utilized to investigate their hypnosis mechanisms. The main chemical components of different extracts were identified by the UPLC-Q-Exactive-MS technique. The results showed that CT and CST significantly increased the ejection fraction(EF) and fractional shortening(FS) of myocardial infarction mice, reduced left ventricular internal dimension at end-diastole(LVIDd) and left ventricular internal dimension at end-systole(LVIDs). In contrast, ST did not exhibit significant effects on these parameters. In the insomnia model, CT significantly reduced sleep latency and prolonged sleep duration, whereas ST only prolonged sleep duration without shortening sleep latency. CST showed no significant effects on either sleep latency or sleep duration. Additionally, both CT and ST upregulated glutamic acid decarboxylase 67(GAD67) protein expression in brain tissue. A total of 15 main chemical components were identified from CT, including 2-(2-phenylethyl) chromone and 6-methoxy-2-(2-phenylethyl) chromone. Six chemical components including chebulidic acid were identified from ST. The results suggested that chromones and terpenes were potential anti-myocardial ischemia drugs of BCPs, and tannin and phenolic acids were potential hypnosis drugs. This study enriches the pharmacological and chemical research of BCPs, providing a basis and reference for their secondary development, quality standard improvement, and clinical application.
Animals ; Drugs, Chinese Herbal/isolation & purification* ; Mice ; Male ; Sleep Initiation and Maintenance Disorders/physiopathology* ; Humans ; Myocardial Infarction/drug therapy* ; Myocardial Ischemia/drug therapy*

Background Self-perceived burden,anxiety and depression are among the most important factors affecting quality of life.At present,there is a lack of understanding on the research status and influencing factors of self-perceived burden in liver transplant recipients.Previous studies have shown that self-perceived burden,anxiety,depression and quality of life are correlated in pairs,but the effecting path among the three are not yet clear.Objective To explore the correlation of self-perceived burden and anxiety/depression with quality of life in liver transplant recipients,so as to provide guidance for psychological nursing intervention in clinical patients.Methods A total of 200 patients liver transplant recipients were enrolled from the liver transplantation inpatient and outpatient clinics of Jiangsu Province Hospital and Qinhuai Medical Area,General Hosptial of Eastern Theater Command of People's Liberation Army of China from March 2022 to February 2023.Patients were evaluated using Self-perceived Burden Scale(SPBS),Hospital Anxiety and Depression Scale(HADS)and the Chinese version of Post Liver Transplant Quality of Life Questionnaire(pLTQ).Spearman correlation analysis was used to examine the correlation among the scales.A structural equation model using Mplus 8.3 was utilized to testify the relationship among self-perceived burden,anxiety/depression and quality of life in liver transplant recipients.Bootstrap method was used to test the effecting pathway.Results There were statistically significant differences in SPBS scores of liver transplant recipients with different levels of education and fannual family income(H=9.656,18.796,P<0.05).There were statistically significant differences in HADS scores of liver transplant recipients with different numbers of somatic symptoms(H=9.859,P<0.05).There were statistically significant differences in the Chinese version of pLTQ scores of liver transplant recipients with different levels of education,postoperative survival time and numbers of somatic symptoms(H=6.892,8.023,16.099,P<0.05).The total and each dimension scores in SPBS of liver transplant recipients were positively correlated with the total score and anxiety/depression dimension scores in HADS(r=0.464～0.586,0.460～0.593,0.286～0.408,0.464～0.583,P<0.01)and negatively correlated with the total score and each dimension scores in the Chinese version of pLTQ(r=-0.572～-0.416,-0.599～-0.441,-0.365～-0.213,-0.559～-0.428,P<0.01).Structural equation model denoted that self-perceived burden negatively affected quality of life(β=-0.186,P<0.01).Anxiety/depression also negatively affected quality of life(β=-0.679,P<0.01).The self-perceived burden indirectly affected the quality of life of liver transplant recipients through anxiety and depression,with an effect value of-0.429,accounting for 69.76％of the total effect.Conclusion The quality of life in liver transplant recipients may be related to their self-perceived burden and anxiety/depression.Self-perceived burden may affect the quality of life of liver transplant patients through anxiety and depression.

Deficiencies in the clearance of peripheral amyloid β (Aβ) play a crucial role in the progression of Alzheimer's disease (AD). Previous studies have shown that the ability of blood monocytes to phagocytose Aβ is decreased in AD. However, the exact mechanism of Aβ clearance dysfunction in AD monocytes remains unclear. In the present study, we found that blood monocytes in AD mice exhibited decreases in energy metabolism, which was accompanied by cellular senescence, a senescence-associated secretory phenotype, and dysfunctional phagocytosis of Aβ. Improving energy metabolism rejuvenated monocytes and enhanced their ability to phagocytose Aβ in vivo and in vitro. Moreover, enhancing blood monocyte Aβ phagocytosis by improving energy metabolism alleviated brain Aβ deposition and neuroinflammation and eventually improved cognitive function in AD mice. This study reveals a new mechanism of impaired Aβ phagocytosis in monocytes and provides evidence that restoring their energy metabolism may be a novel therapeutic strategy for AD.
Animals ; Mice ; Alzheimer Disease ; Amyloid beta-Peptides ; Monocytes ; Cognition ; Energy Metabolism ; Phagocytosis

Objective:To explore the current status of surgery for portal hypertension to grasp current status and future development of surgery in China.Methods:This study is jointly sponsored by China Hepatobiliary & Pancreatic Specialist Alliance & Portal Hypertension Alliance in China (CHESS).Comprehensive surveying is conducted for basic domestic situations of surgery for portal hypertension, including case load, surgical approaches, management of postoperative complications, primary effects, existing confusion and obstacles, liver transplantation(LT), laparoscopic procedures and transjugular intrahepatic portosystemic shunt(TIPS), etc.Results:A total of 8 512 cases of portal hypertension surgery are performed at 378 hospitals nationwide in 2021.Splenectomy plus devascularization predominated(53.0%)and laparoscopy accounted for 76.1%.Primary goal is preventing rebleeding(67.0%) and 72.8% of hospitals used preventive anticoagulants after conventional surgery.And 80.7% of teams believe that the formation of postoperative portal vein thrombosis is a surgical dilemma and 65.3% of hospitals practiced both laparoscopy and TIPS.The major reasons for patients with portal hypertension not receiving LT are due to a lack of qualifications for LT(69.3%)and economic factors(69.0%).Conclusions:Surgery is an integral part of management of portal hypertension in China.However, it is imperative to further standardize the grasp of surgical indications, the handling of surgical operation and the management of postoperative complications.Moreover, prospective, multi-center randomized controlled clinical studies should be performed.

Objective:The evidence-based and Delphi methods were used to construct the exercise program for hospitalized patients with diabetes foot to provide guidance for clinical practice.Methods:Evidence on exercise management of diabetic foot patients was systematically searched from BMJ Best Practice, UpToDate, Registered Nurses′ Association of Ontario and other domestic and foreign databases and professional association websites. The retrieval period was from the establishment of the database to April 2021. The quality of the included literature was independently evaluated, and the evidence of the literature meeting the quality standards was extracted and summarized to form the first draft of exercise program for inpatients with diabetic foot. After two rounds of Delphi expert letter consultation, the program items were revised, and the final draft of the exercise program for inpatients with diabetic foot suitable for clinical practice was formed.Results:The effective recovery rate of the two rounds of expert correspondence questionnaire both were15/15. The expert authority coefficient was 0.865 and 0.895 respectively. And the Kendall coordination coefficient was 0.232 and 0.291 (both P<0.01). An exercise program for inpatients with diabetic foot had been formed, including 5 modules(exercise evaluation, exercise prescription, exercise monitoring, post-exercise evaluation and exercise management), 12 items and 40 operational items. Conclusions:The exercise program for inpatients with diabetic foot constructed in this study is scientific and clinically applicable, which provide scientific guidance for clinical medical staff to carry out exercise practice.

Objective : To screen differentially expressed miRNAs and explore its effect and mechanism on cell mi- gration in lung adenocarcinoma (LUAD) ． Methods : Differentially expressed miRNAs in LUAD tissues and normal lung tissues were screened by miRNA microarrays，and then bioinformatics analysis was used to predict their poten- tial biological functions and signaling pathways．The cancer genome atlas (TCGA) analysis and quantitative real- time PCR (qRT-PCR) verified the expression level of hsa-let-7e-5p in LUAD tissues and cell lines．The effect of hsa-let-7e-5p cell migration in LUAD was examined by would healing experiment．After screening the underlying target genes by bioinformatics analysis ，the targeting relationship between hsa-let-7e-5p and DTX2，NME6， C8orf58，GATM and DHX57 were verified by qRT-PCR. Results : The miRNA microarray results showed that 347 miRNAs were down-regulated while 229 miRNAs were up-regulated in lung adenocarcinoma tissues．Compared with normal lung tissue and cells，the expression level of hsa-let-7e-5p was significantly down-regulated．Besides，over- expression of hsa-let-7e-5p inhibitedLUAD cell migration． Conclusion Non-coding RNA hsa-let-7e-5p is down- regulated in LUAD and inhibits the migration of lung adenocarcinoma cells．DTX2，NME6，C8orf58，GATM and DHX57 are the potential target genes of hsa-let-7e-5p.

The present study investigated the therapeutic effect and mechanism of Di'ao Xinxuekang(DXXK) on non-alcoholic steatohepatitis(NASH) in mice. Sixty-five C57 BL/6 J mice were randomly divided into a normal group and an experimental group for model induction with the high-fat diet for 16 weeks. Then the mice in the experimental group were randomly divided into a model group, an atorvastatin group(4 mg·kg~(-1)·d~(-1)), and high-(200 mg·kg~(-1)·d~(-1)), medium-(60 mg·kg~(-1)·d~(-1)), and low-dose(20 mg·kg~(-1)·d~(-1)) DXXK groups, with 10 mice in each group. Drugs were administered by gavage for eight weeks. Serum lipid, liver lipid, serum alanine aminotransferase(ALT), aspartate aminotransferase(AST), malondialdehyde(MDA), superoxide dismutase(SOD), and glutathione reductase(GSH-Px) were determined. Interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α) were measured by enzyme-linked immunosorbent assay(ELISA). The liver index was calculated. The liver pathological change and lipid accumulation were observed by HE and oil red O staining. The liver ultrastructure was observed by the transmission electron microscope. The mRNA and protein expression of nuclear factor-erythroid 2 related factor 2(Nrf2) and heme oxygenase-1(HO-1) was detected by real-time fluorescence-based quantitative PCR and Western blot, respectively. The results showed that compared with the normal group, the model group displayed serum lipid and liver lipid metabolism disorders, elevated transaminase, lipid deposition, steatosis, and inflammation, suggesting that the NASH model in mice was properly induced. Compared with the model group, the DXXK groups showed decreased serum lipid, liver lipid, ALT, AST, MDA, IL-1β, and TNF-α, increased SOD and GSH-Px, alleviated hepatic steatosis, ballooning, and inflammation, and up-regulated Nrf2 and HO-1 gene and protein expression. In conclusion, DXXK can significantly alleviate NASH in mice, which is related to the inhibition of oxidative stress and inflammatory damage by up-regulating the Nrf2/HO-1 signaling pathway.
Animals ; Drugs, Chinese Herbal ; Inflammation/metabolism* ; Lipids ; Liver ; Mice ; NF-E2-Related Factor 2/metabolism* ; Non-alcoholic Fatty Liver Disease/metabolism* ; Oxidative Stress ; Signal Transduction ; Superoxide Dismutase/metabolism* ; Tumor Necrosis Factor-alpha/metabolism*

Nonalcoholic fatty liver disease （NAFLD） is a metabolic stress-induced liver injury characterized by excessive lipid accumulation in hepatocytes， which is closely related to insulin resistance and genetic susceptibility. It falls into the category of "liver lump" in traditional Chinese medicine （TCM）. NAFLD affects about 25% of the population worldwide and has become a major burden of the world health care system. However， its exact pathogenesis remains unclear. Conducting the basic research on NAFLD is of great clinical significance and social value. As an important tool for NAFLD research， animal model plays a particularly important role in clarifying the pathophysiological mechanism of NAFLD. In recent years， the modeling methods for NAFLD in China and abroad have been constantly updated， and in particular， certain progress has been made in the duplication of TCM syndrome models. By consulting and sorting out the relevant literature published in recent years in China and abroad， the author summarized the replication methods of NAFLD animal models. This paper reviewed the advantages and disadvantages of models established via dietary induction （high-fat feed， high-fat and high-fructose feed， high-fat and high-cholesterol feed， and methionine choline-deficient feed）， models with genetic defects ［leptin-deficiency （Lep^ob/Lep^ob）， autosomal recessive diabetes gene homozygous deficiency （ob/ob）， Alms1 gene （foz/foz） mutation， and FATZO mice］ and exposure to special diets， and models for TCM syndromes （liver depression and spleen deficiency syndrome， phlegm-dampness syndrome， blood stasis syndrome， combined phlegm and stasis syndrome， and qi stagnation and blood stasis syndrome）， in order to provide reference for the preparation of more scientific， reasonable， economical， and convenient animal models of NAFLD， thus laying a foundation for in-depth study of the pathogenesis， prevention， and treatment of NAFLD.

Objective:To analyze the negative effect of prolonged postoperative ileus on postoperative recovery in patients underwent open alimentary tract surgery.Methods:This study was a retrospective cohort study. The subjects of the study were patients who underwent open gastrointestinal surgery at the General Surgery Department of Beijing Friendship Hospital, Capital Medical University from October 2016 to November 2018. According to the PPOI diagnostic criteria proposed by the University of Auckland, the included patients were classified as PPOI Group ( n=14) and non-PPOI group ( n=112). The postoperative complications, postoperative hospital stay and medical expenses during hospitalization were selected as the study endpoint indicators. T-test or Fisher′s exact test were performed to compare the differences between the two groups, and linear regression analysis was used to explore the independent effects of PPOI on hospital stay and medical expenses. Results:The incidence of PPOI in this study cohort was 11.1%. The total postoperative complications occurred more frequent in PPOI group (64.29% vs 38.39%, P=0.08). The average postoperative hospital stay of patients in the PPOI group was longer than that in non-PPOI group [(21.21±14.83) d vs (13.98±14.21) d, P=0.070]. Adjusting for various possible confounding factors, the PPOI regression coefficient beta (95% CI) that affects the length of hospital stay was [-0.43 (-7.16, 6.3), P=0.90]. The average medical cost of patients in the PPOI group was more than that in non-PPOI group [(104 389.64±52 427.66)元比(79 111.41±50 832.29)元, P=0.070]. Adjusting for various possible confounding factors, the PPOI regression coefficient beta (95% CI) that affects medical expenditure was [-134.12 (-21656.85, 21388.62), P=0.99]. Conclusions:Prolonged postoperative ileus leads to delayed postoperative recovery, which is related to increased postoperative complications, hospital stay duration and medical cost. But it needs further confirmation from large sample data.