OBJECTIVE: To investigate the effects of Danmu Extract Syrup (DMS) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice and explore the mechanism. METHODS: Seventy-two male Balb/C mice were randomly divided into 6 groups according to a random number table (n=12), including control (normal saline), LPS (5 mg/kg), LPS+DMS 2.5 mL/kg, LPS+DMS 5 mL/kg, LPS+DMS 10 mL/kg, and LPS+Dexamethasone (DXM, 5 mg/kg) groups. After pretreatment with DMS and DXM, the ALI mice model was induced by LPS, and the bronchoalveolar lavage fluid (BALF) were collected to determine protein concentration, cell counts and inflammatory cytokines. The lung tissues of mice were stained with hematoxylin-eosin, and the wet/dry weight ratio (W/D) of lung tissue was calculated. The levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1 β in BALF of mice were detected by enzyme linked immunosorbent assay. The expression levels of Claudin-5, vascular endothelial (VE)-cadherin, vascular endothelial growth factor (VEGF), phospho-protein kinase B (p-Akt) and Akt were detected by Western blot analysis. RESULTS: DMS pre-treatment significantly ameliorated lung histopathological changes. Compared with the LPS group, the W/D ratio and protein contents in BALF were obviously reduced after DMS pretreatment (P<0.05 or P<0.01). The number of cells in BALF and myeloperoxidase (MPO) activity decreased significantly after DMS pretreatment (P<0.05 or P<0.01). DMS pre-treatment decreased the levels of TNF-α, IL-6 and IL-1 β (P<0.01). Meanwhile, DMS activated the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway and reversed the expressions of Claudin-5, VE-cadherin and VEGF (P<0.01). CONCLUSIONS DMS attenuated LPS-induced ALI in mice through repairing endothelial barrier. It might be a potential therapeutic drug for LPS-induced lung injury.
Mice ; Male ; Animals ; Proto-Oncogene Proteins c-akt/metabolism* ; Lipopolysaccharides ; Phosphatidylinositol 3-Kinases/metabolism* ; Interleukin-1beta/metabolism* ; Vascular Endothelial Growth Factor A/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Claudin-5/metabolism* ; Acute Lung Injury/chemically induced* ; Lung/pathology* ; Interleukin-6/metabolism* ; Drugs, Chinese Herbal

Objective To analyze the clinical risk factors for chronic complications in patients with type 2 diabetes and their correlation with bone mineral density and 1,25-dihydroxyvitamin D3. Methods A total of 163 patients with type 2 diabetes mellitus were selected as research subjects and were divided into complication group and non-complication group according to the presence or absence of chronic complications. The independent related factors for chronic complications in patients with type 2 diabetes mellitus were analyzed. Spearman rank correlation analysis was used to evaluate the correlation between bone mineral density, 1,25-dihydroxyvitamin D3 and chronic complications. Results Among the 326 patients with type 2 diabetes mellitus, 202 developed chronic complications (61.96%), including 71 cases of cardiovascular disease, 59 cases of neuropathy, 33 cases of renal lesion, and 28 cases of retinopathy. There were statistically significant differences in the duration of diabetes mellitus, fasting blood glucose, systolic blood pressure, glycosylated hemoglobin, triglyceride, low density lipoprotein cholesterol, serum creatinine, bone mineral density, and 1,25-dihydroxyvitamin D3 between the complication group and the non-complication group (P<0.05). Logistic multivariate regression analysis showed that the duration of diabetes mellitus, systolic blood pressure, glycosylated hemoglobin, ow density lipoprotein cholesterol, serum creatinine, bone mineral density, and 1,25-dihydroxyvitamin D3 were all independent related factors for the occurrence of chronic complications in patients with type 2 diabetes mellitus (P<0.05). Spearman correlation analysis showed that bone mineral density and 1,25-dihydroxyvitamin D3 were negatively correlated with chronic complications (P<0.05). Conclusion Bone mineral density and 1,25-dihydroxyvitamin D3 in patients with type 2 diabetes mellitus are closely related to chronic complications.

Objective To investigate the expressions of 12 cytokines(IL-1β,IL-2,IL-4,IL-5,IL-6,IL-8,IL-10,IL-12p70,IL-17,IFN-α,IFN-γ,TNF-α)and procalcitonin in patients with infective endocarditis(IE).Methods Ten IE patients admitted to our hospital from December 2021 to December 2022 were included into the IE group,10 patients with non-infectious and non-rheumatic valvular diseases who were admitted to our hospital at the same period were randomly selected as the control group,and blood sampling of all patients were conducted at admission.The expressions of 12 cytokines and blood routine indexes were detected by flow cytometry,and the level of procalcitonin was detected by ELISA.The correlations among the expression levels of cytokines in IE patients were analyzed by Pearson method and the correlations of IL-8 level and white blood cell count with procalcitonin in IE patients were analyzed by Spearman method.Results Compared with the control group,the levels of cytokines of IL-1β,IL-2,IL-6,IL-10,TNF-α,IFN-α,IFN-γ and IL-12p70 in the IE group were significantly increased(P<0.05),the white blood cell count,neutrophil percentage and procalcitonin were significantly increased(P<0.05).There was no significant difference in the percentage of monocytes between the two groups(P>0.05).IFN-α of IE patients was positively correlated with IL-2,TNF-α,IL-1β and IL-12p70,IL-2 was positively correlated with TNF-α and IL-1β,IL-12p70 was positively correlated with IFN-γ,and procalcitonin was significantly positively correlated with IL-8 and white blood cell count,with statistically significant differences(P<0.05).Conclusion The levels of IL-1β,IL-2,IL-6,IL-10,TNF-α,IFN-α,IFN-γ,IL-12p70 and procalcitonin in IE patients are significantly higher than those in the normal population,and the detections of these indicators are of guiding significance for the early diagnosis of IE and the evaluation of the severity of the disease.

Objective To establish an early prediction model for the diagnosis of severe acute pancreatitis based on the improved machine learning models,and to analyze its clinical value.Methods A case-control study was conducted on 352 patients with acute pancreatitis admitted to the Gastroenterology and Hepatobiliary Surgery Departments of the Army Medical Center of PLA and Emergency and Critical Care Medicine Department of No.945 Hospital of Joint Logistics Support Force of PLA from January 2014 to August 2023.According to the severity of the disease,the patients were divided into the severe group(n=88)and the non-severe group(n=264).The RUSBoost model and improved Archimead optimization algorithm was used to analyze 39 routine laboratory biochemical indicators within 48 h after admission to construct an early diagnosis and prediction model for severe acute pancreatitis.The task of feature screening and hyperparameter optimization was completed simultaneously.The ReliefF algorithm feature importance rank and multivariate logistic analysis were used to analyze the value of the selected features.Results In the training set,the area under curve(AUC)of the improved machine learning model was 0.922.In the testing set,the AUC of the improved machine learning model reached 0.888.The 4 key features of predicting severe acute pancreatitis based on the improved Archimedes optimization algorithm were C-reactive protein,blood chlorine,blood magnesium and fibrinogen level,which were consistent with the results of ReliefF algorithm feature importance ranking and multivariate logistic analysis.Conclusion The application of improved machine learning model analyzing the laboratory examination results can help to early predict the occurrence of severe acute pancreatitis.

Zhuye Shigaotang is one of the 100 classic prescriptions published by the National Administration of Traditional Chinese Medicine. This study used the traceability method and bibliometrics method to analyze the main applicable syndromes， efficacy and meanings， modern disease spectrum， and other aspects of Zhuye Shigaotang， so as to further promote the research and development of this prescription. The results showed that Zhuye Shigaotang originated from the Treatise on Febrile Diseases， and its ingredients included Lophatheri Herba， Gypsum Fibrosum， Pinelliae Rhizoma， Ophiopogonis Radix， Ginseng Radix et Rhizoma， Glycyrrhizae Radix et Rhizoma， and Oryza sativa. The main applicable syndromes of Zhuye Shigaotang recorded in ancient books included heatstroke， cough and asthma， sores， sweat syndrome， hiccup， insomnia， malaria， headache， blood syndrome， nasosinusitis， laryngitis， etc.， involving diseases of internal medicine， surgery， gynecology， and pediatrics. Its pathogenesis was "incomplete residual heat， both Qi and Yin injuries， and stomach-Qi disharmony". The research found that Zhuye Shigaotang could also be used to treat acne， measles， and cholera， and it was especially suitable for the treatment at the later stage of epidemic diseases. Lophatheri Herba and Gypsum Fibrosum in the prescription could clear away heat and relieve vexation. Ginseng Radix et Rhizoma，Ophiopogonis Radix， Ginseng Radix et Rhizoma， and Oryza sativa could promote body fluid production and invigorate Qi. Pinelliae Rhizoma could harmonize the stomach and stop vomiting. The prescription had stable compatibility and had the effects of clearing away heat， relieving vexation， invigorating Qi， promoting body fluid production， and harmonizing the stomach. Zhuye Shigaotang was widely applied in modern clinical practices， with high application frequency in the digestive system， pediatric-related diseases， respiratory system， infectious diseases， circulatory system， and neuropsychiatric system. The specific symptoms included recurrent aphtha， hiccup， infantile pneumonia， infantile summer fever， unexplained fever， upper respiratory tract infection， epidemic hemorrhagic fever， and late measles.

ObjectiveIn kinesin-3, the neck coil correlates with the following segments to form an extended neck that contains a characteristic hinge diverse from a proline in KIF13B to a long flexible linker in KIF1A. The function of this neck hinge for controlling processive movement, however, remains unclear. MethodsWe made a series of modifications to the neck hinges of KIF13B and KIF1A and tested their movement using a single-molecule motility assay. ResultsIn KIF13B, the insertion of flexible residues before or after the proline differentially impacts the processivity or velocity, while the removal of this proline increases the both. In KIF1A, the deletion of entire flexible neck hinge merely enhances the processivity. The engineering of these hinge-truncated necks of kinesin-3 into kinesin-1 similarly boosts the processive movement of kinesin-1. ConclusionThe neck hinge in kinesin-3 controls its processive movement and proper modifications tune the motor motility, which provides a novel strategy to reshape the processive movement of kinesin motors.

Nitazoxanide is an FDA-approved antiprotozoal drug. Our previous study found that oral administration of nitazoxanide inhibited Western diet (WD)-induced hepatic steatosis in ApoE^-/- mice. However, the specific mechanism remains to be elucidated. In the present study, we performed an untargeted metabolomics approach to reveal the effect of nitazoxanide on the liver metabolic profiles in WD-fed ApoE^-/- mice, and carried out the cellular experiments to elucidate the underlying mechanisms. UPLC-MS-based untargeted metabolomics analysis was used to investigate the effect of nitazoxanide on global metabolite changes in liver tissues. The differential metabolites were screened for enrichment analysis and pathway analysis. Hepatocytes were treated with tizoxanide, the metabolite of nitazoxanide, to investigate the underlying mechanism based on the findings in metabolomics study. The improvement of liver lipid metabolism disorders by nitazoxanide treatment in WD-fed ApoE^-/- mice was mainly through regulating glycerophospholipid metabolism, D-glutamine and glutamate metabolism, glutathione metabolism, and arginine biosynthesis metabolism. Tizoxanide, the active metabolite of nitazoxanide, increased glutathione (GSH) contents and glutamate-cysteine ligase catalytic subunit (Gcl-c) and glutathione reductase (Gsr) mRNA expressions in HepG2 cells. Tizoxanide increased cystathionine β-synthase (CBS) and phosphatidylethanolamine N-methyltransferase (PEMT) protein levels, inhibited lipid accumulation in hepatocytes induced by free fatty acid (FFA). Tizoxanide increased S-adenosyl-L-homocysteine hydrolase (SAHH) protein levels in HepG2 cells and mouse primary liver cells stimulated with free fatty acid (FFA). Tizoxanide increased N-acetyl glutamate synthase (Nags) and carbamoylphosphate synthetase 1 (Cps1) mRNA expressions in HepG2 cells. In conclusion, nitazoxanide improves WD-induced hepatic steatosis in ApoE^-/- mice and the underlying mechanisms include increasing CBS expression, GSH content, PEMT protein expression, Nags and Cps1 mRNA expression in hepatocytes.

Aim To explore the improvement effect of Bazi Bushen capsule on thymic degeneration in SAMP6 mice and the possible mechanism.Methods Twenty 12 week old male SAMP6 mice were randomly divided into the model group(SAMP6)and the Bazi Busheng capsule treatment group(SAMP6+BZBS).Ten SAMR1 mice were assigned to a homologous control group(SAMR1).The SAMP6+BZBS group was oral-ly administered Bazi Bushen capsule suspension(2.8 g·kg-1)daily,while the other two groups were orally administered an equal amount of distilled water.After nine weeks of administration,the morphology of the thymus in each group was observed and the thymus in-dex was calculated;HE staining was used to observe the structural changes of thymus tissue;SA-β-gal stai-ning was used to detect thymic aging;flow cytometry was used to detect the proportion of thymic CD3+T cells in each group;Western blot was used to detect the levels of p16,Bax,Bcl-2,and cleaved caspase-3 proteins in thymus;immunofluorescence was applied to detect the proportion of cortical thymic epithelial cells in each group;ELISA was employed to detect IL-7 lev-els in thymus.Results Compared with the SAMP6 group,the thymic index of the SAMP6+BZBS group significantly increased(P＜0.05);the disordered thy-mic structure was significantly improved;the positive proportion of SA-β-gal staining significantly decreased(P＜0.01);the proportion of CD3+T cells apparently increased(P＜0.05);the level of p16 protein signifi-cantly decreased(P＜0.05);the level of Bcl-2 pro-tein significantly increased(P＜0.05),while the lev-el of cleaved caspase-3 protein markedly decreased(P＜0.05);the proportion of cortical thymic epithelial cells evidently increased;the level of IL-7 significantly increased(P＜0.01).Conclusions Bazi Bushen capsule can delay thymic degeneration,inhibit cell ap-optosis in thymus and promote thymic cell development in SAMP6 mice,which may be related to increasing the proportion of cortical thymic epithelial cells and promoting IL-7 secretion.

Aim To study the mechanism of action of licorice in alleviating cisplatin liver injury.Methods Forty-eight SD rats were randomly divided into a blank group,a model group,a positive control group and lico-rice administration groups(450,900 and 1 800 mg·kg-1).After 5 days of prophylactic administration,8 mg·kg-1 of cisplatin was injected intraperitoneally in-to the model,positive control,and licorice administra-tion groups to establish an acute liver injury model.LC-MS/MS untargeted metabolomics was used to ana-lyze the differential metabolites and metabolic pathways of licorice to alleviate cisplatin acute liver injury.Re-sults PLS-DA score plots showed significant separa-tion of metabolomics samples.The analysis yielded 119 differential metabolites associated with cisplatin liver injury,of which 31 differential metabolites were signifi-cantly regressed after licorice intervention and were mainly involved in D-arginine and D-ornithine metabo-lism;parathyroid hormone synthesis,secretion,and ac-tion;tyrosine metabolism;biosynthesis of phenylala-nine,tyrosine,and tryptophan;β-alanine metabolism;and amino acid and nucleotide sugar metabolism.Con-clusions Metabolomics analysis indicates that licorice can alter the metabolic profile of cisplatin-induced he-patic injury rats,and its mechanism of action may be related to its improvement of the levels of differential metabolites and its involvement in the regulation of a-mino acid metabolism and other related pathways.

Objective:To systematically evaluate the effectiveness of Kunxian capsule related regimens for patients with lupus nephritis(LN)in order to provide a reference basis for treatment strategies for LN patients.Methods:The computer searched the rele-vant studies of Kunxian capsule in PubMed,Web of Science,Cochrane Library,CBM,CNKI,Wanfang and VIP databases on the treatment of LN,the limited time for the establishment of the database is April 6,2022,and used R 4.0.2 software and Revman 5.3 software for Meta-analysis.Results:Four RCTs with 1 cohort study including 310 patients were finally included.The results of the Me-ta-analysis showed that:In terms of 24 h urinary protein and SLEDAI score,Glucocorticoid+Cyclophosphamide+Kunxian capsule achieved the best result after treatment;in terms of Scr,IgE,and IgG,the levels of each index were significantly lower in Glucocorti-coid+Cyclophosphamide+Kunxian capsules than in Glucocorticoid+Cyclophosphamide(P<0.05).Conclusion:The 5 regimens may work best as Glucocorticoids+Cyclophosphamide+Kunxian capsules in terms of clinical efficacy in treating LN patients.Because of the quality and quantity limitations of the included studies,more high-quality studies are needed for validation.