ObjectiveTo investigate the mechanism by which Gegen Qinliantang（GQT） improves skeletal muscle insulin resistance. MethodsThe db/m mice were used as the normal group， while db/db mice were assigned to a model group， low-dose （3.12 g·kg^-1）， medium-dose （6.24 g·kg^-1）， and high-dose （12.48 g·kg^-1） GQT groups， and a Western medicine group （semaglutide， 0.045 mg·kg^-1），n=6 in each group. All groups received corresponding interventions. Intraperitoneal glucose tolerance test （IPGTT）， intraperitoneal insulin tolerance test （IPITT）， and hematoxylin-eosin （HE） staining were used to evaluate insulin resistance and therapeutic efficacy. Serum lipid levels were measured using an automatic biochemical analyzer， and apoptosis in skeletal muscle was assessed via TUNEL assay. Transcriptome sequencing combined with gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） analyses was performed to identify differentially expressed genes （DEGs）. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to validate gene expression. Molecular docking was applied to evaluate the binding patterns between active components of GQT and key regulatory genes to elucidate pharmacological mechanisms. ResultsCompared with the model group， the medium-dose and high-dose GQT groups showed significantly reduced fasting blood glucose （FBG） levels （P<0.01）. Triglycerides （TG）， total cholesterol （TC）， and low-density lipoprotein cholesterol （LDL-C） were markedly decreased （P<0.01）， while high-density lipoprotein cholesterol （HDL-C） was significantly increased （P<0.01）. IPGTT， IPITT， and HE staining demonstrated that GQT enhanced insulin sensitivity and restored skeletal muscle morphology. GQT also alleviated apoptosis in skeletal muscle tissue. Transcriptome analysis revealed that GQT primarily affected biological processes such as oxidative phosphorylation， metabolic pathways， cellular processes， and protein binding. Real-time PCR results showed that CBR2， CDK6， F830016B08Rik， IL-1β， Rab27b， and COLEC12 were key regulatory genes. Molecular docking demonstrated that CBR2， IL-1β， Rab27b， and COLEC12 formed stable binding with the main active components of GQT. The therapeutic effects of high- and medium-dose GQT were comparable to those of the semaglutide group. ConclusionGQT improves skeletal muscle insulin resistance， potentially by regulating apoptosis as part of its underlying biological mechanism.

Objective:To investigate the predictive value of Pitt bacteremia score (PBS) on 28-day mortality of patients with extensively drug-resistant Klebsiella pneumoniae (XDR-KP) bloodstream infection.Methods:A retrospective cohort study was conducted to analyze the clinical characteristics of patients with XDR-KP bloodstream infection admitted to the Emergency Intensive Care Unit of Nanjing Drum Tower Hospital from January, 2018, to December, 2021. The patients were divided into the survival and non-survival groups according to the 28-day survival. Multivariate logistic regression analysis was performed to determine the risk factors of 28-day mortality of the patients. Receiver operating curve (ROC) curve was drawn to analyze the predictive value of PBS in 28-day mortality of patients with XDR-KP bloodstream infection. The correlations between PBS, and acute physiology and chronic health evaluation II (APACHE II) and sequential organ failure (SOFA) assessment were performed using Pearson correlation coefficient. The optimal cut-off value of PBS score was used as the boundary point to group the differences between APACHE II and SOFA scores in different groups. Kaplan-Meier method was used to analyze the prognosis of patients with XDR-KP bloodstream infection.Results:A total of 118 patients (82 males and 36 females) with XDR-KP bloodstream infection, aged (65.98±15.16) years, were included in this study. The 28-day mortality was 61.02%. The PBS was significant higher in the non-survival group than in the survival group [(5.68±1.86) vs. (2.48±1.02), P=0.011]. Multivariate logistic regression analysis showed that PBS ( OR=4.940, 95% CI: 2.720-8.968, P=0.008), APACHE II score ( OR=1.630, 95% CI: 1.361-1.952, P=0.010) and SOFA score ( OR=1.879, 95% CI: 1.451-2.422, P=0.009) were independently risk factors of 28-day mortality of patients with XDR-KP bloodstream infection. The area under the ROC curve of the PBS predicting 28-day mortality was 0.970 (95% CI: 0.945-0.995, P<0.001), and the optimal cut-of value was 3.5. In addition, PBS was significantly associated with APACHE II score ( r=0.916, P<0.001) and SOFA score ( r=0.829, P<0.001). Moreover, Kaplan-Meier analysis showed that the 28-day survival rate of patients with PBS <3.5 was significantly higher than that of patients with PBS >3.5 ( P=0.001). Conclusions:PBS is a significant, independent predictor of 28-day mortality in patients with XDR-KP bloodstream infection.

Objective To observe the expression of tumor necrosis factor-α(TNF-α)in acute lung injury caused by paraquat(PQ)in rats,and investigate the mechanism of the rhubarb in respect of pmteetive effects.Method PQ intragastrically poisoning at the dose of 50 mg/kg made a model of the acute lung injury in Sprague-Dawley(SD)rats.Totally 144 adult healthy SD rats(72 female,72male)were randomly divided into control group (group A,n=24),poisoned group(group B,n=48),rhubarb treated group(group C,n=48)and the shaln poisoning group(group D,n=24).Rats of group B and group C were poisoned intmgastrically with PQ(50 mg/kg).and rats of group C and group D were intervened intragastrieally with 300 mg/(kg·d)of rhubarb in 15 min-utes.The white blood cells and total cells in bronchoalveolar lavage fluid(BALF)were counted by using a blood cell counting plate and the protein content of BALF was measured by using the way of Lowry in order to calculate the neutmphiks pereentage and lung permeability index.A small portion of left lung was stained with HE to observe the pathological changes and the expression oftumor necrosis factor-α in the rest of the left lung was observed with immunohistochemistry.The data were handled by the analysis of variance and NK method using SPSS 14.0.Re-suits Compared with group A,the lungs of rats mainly showed congestion,edema and leukocytes infiltration in group B,and fibrosis was found onlyt in a few rats.And the rate neutrophils percentage,protein content and lung permeability index in BALF increased(P＜0.01).The expression of TNF-α were obviously inereased at 12 hours after PQ poisoning,and immtmohistochemistry score (IHS)was higher,and peaked at 24 hours later(P＜0.05),then remained on a high level for a while and sluggishly declined.Compared with group B,the changes of above mentioned were alleviated obviously,and the expression of TNF-α delayed with the less magnitude of increasing an an obvious tendency of less expression.Compared with group B,delayed,lower increasing extent,obviously re-ducing tendency in group C with statistical difference in IHS(P＜0.05).Conclusions Rhubarb ameliorates a-cute lung injury caused by PQ poisoning in rats by means of inhibiting the expression of TNF-α in turn to alleviate inflammatory reaction.

Objective To investigate the effects of melatonin (MT) on rats with acute paraquat (PQ) poisoning. Method Fifty-four Sprague-Dawley (SD) rats were randomly divided into three groups (each group 18 rats) and given the following treatment: intragastric injection of PQ at 50 mg/kg (PQ); intragastric injection of paraquat followed by intraperitoneal injection of MT at 10mg/kg once a day (MT); intragastric injection of normal saline (Control). Serum assays for malondialdehyde (MDA) levels and superoxide dismutase (SOD) and glu tathione peroxidase (GSH-Px) activities were determined on the 1st, 3rd and 7th day post treatment. Clinical manifestations of poisoning and pathological changes in the lungs were also observed. Results Serum MDA levels were significantly increased (P ＜ 0.01), and SOD and GSH-Px activities significantly decreased (P ＜ 0.05) in the PQ group compared to the control group. Serum MDA levels were significantly decreased, and serum SOD and GSH-Px activities increased in MT group compared to the PQ group (P ＜ 0.05). Clinical manifestations of intoxication and pathological lung changes were also ameliorated in poisoned rats treated with MT. Condutions Administration of MT alleviates clinical manifestations of acute paraquat poisoning in rats by Limiting the damage from lipid peroxidation.