OBJECTIVE To explore the effect and potential mechanism of the compatibility of Astragali Radix-Puerariae Lobatae Radix on ferroptosis of liver cells in type 2 diabetes mellitus （T2DM） insulin resistance （IR） rats. METHODS Sixty male SD rats were randomly divided into control group （12 rats） and modeling group （48 rats）. The modeling group was fed with a high- fat diet for 4 consecutive weeks and then given a one-time tail vein injection of 1% streptozotocin to establish T2DM IR model. The model rats were randomly divided into model group， the compatibility of Astragali Radix-Puerariae Lobatae Radix group [QG group， 4.05 g/（kg·d）， intragastric administration]， ferroptosis inhibitor ferrostatin-1 group [Fer-1 group， 5 mg/kg by intraperitoneal injection， once every other day]， the compatibility of Astragali Radix-Puerariae Lobatae Radix+ferroptosis inducer erastin group [QG+erastin group， 4.05 g/（kg·d） by intragastric administration+erastin 10 mg/（kg·d）， intraperitoneal injection]. After 4 weeks of intervention， serum fasting blood glucose （FBG） and fasting insulin （FINS） were measured in each group of rats， and homeostasis model assessment of insulin resistance （HOMA-IR） and the natural logarithm of insulin action index（IAI） were calculated； the serum levels of total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， aspartate transaminase （AST） and alanine transaminase （ALT）， Fe2+ and Fe content， glutathione （GSH）， malondialdehyde （MDA） and superoxide dismutase （SOD） levels， NADP+/NADPH ratio and reactive oxygen species （ROS） were determined. The pathological morphology of its liver tissue was observed； the protein expressions of glutathione peroxidase 4 （GPX4）， ferritin heavy chain 1 （FTH1）， long-chain acyl-CoA synthetase 3 （ACSL3）， ACSL4， ferritin mitochondrial （FTMT）， and cystine/glutamate anti-porter （xCT） in the liver tissue of rats were detected. RESULTS Compared with control group， the liver cells in the model group of rats showed disordered arrangement， swelling， deepened nuclear staining， and more infiltration of inflammatory cells， as well as a large number of hepatocyte vacuoles and steatosis； FBG （after medication）， the levels of TC， TG， LDL-C， AST， ALT， FINS， MDA and ROS， HOMA-IR， Fe2+ and Fe content， NADP+/NADPH ratio and protein expression of ACSL4 were significantly increased or up-regulated， while the levels of HDL-C， GSH and SOD， IAI， protein expressions of GPX4， FTH1， ACSL3， FTMT and xCT were significantly reduced or down-regulated （P＜0.01）. Compared with the model group， both QG group and Fer-1 group showed varying degrees of improvement in pathological damage of liver tissue and the levels of the above indicators， the differences in the changes of most indicators were statistically significant （P＜0.01 or P＜0.05）. Compared with QG group， the improvement of the above indexes of QG+erastin group had been reversed significantly （P＜0.01）. CONCLUSIONS The compatibility decoction of Astragali Radix-Puerariae Lobatae Radix can reduce the level of FBG in T2DM IR rats， and alleviate IR degree， ion overload and pathological damage of liver tissue. The above effects are related to the inhibition of ferroptosis.

Objective To investigate the preventive effects of lidocaine administered through different routes on cardiovascular stress responses during anesthesia tracheal intubation. Methods Total 120 patients scheduled for elective surgery under general anesthesia were randomly divided into three groups: intravenous injection group （group IV）, throat spray group （group LJ）, and control group （group CT）, with 40 patients in each. Group IV received 50 mg of lidocaine via intravenous injection 1 minute before tracheal intubation. Group LJ received 50 mg of lidocaine sprayed into the pharyngeal cavity, glottis, and subglottic area. Group CT did not receive any treatment, and the remaining procedures were performed following the routine general anesthesia induction protocol. Heart rate （HR）, systolic blood pressure （SBP）, diastolic blood pressure （DBP）, and mean arterial pressure （MAP） were recorded at four time points: T₀ （before tracheal intubation）, T₁ （immediately after tracheal intubation）, T₂ （3 minutes after intubation）, and T₃ （5 minutes after intubation）. Statistical analysis of the data was performed using SPSS 22.0. Results There were no significant differences in HR at various time points within the group LJ. The changes in HR in the group IV and group CT were different statistically from those in the throat spray group. The blood pressure of patients in all three groups increased to varying degrees immediately after tracheal intubation, with the group CT showing particularly significant changes that differed significantly from both the group IV and the group LJ. The group LJ rapidly returned to levels close to those before intubation. Conclusion The preventive effects of lidocaine on stress responses during tracheal intubation were different depending on the route of administration. The inhibitory preventive effect of the throat spray method was superior to that of intravenous lidocaine, especially in preventing changes in heart rate.

ObjectiveThis study aims to explore the mechanism and targets of Shenfu Injection in regulating glycolysis to intervene in myocardial fibrosis in chronic heart failure based on the hypoxia-inducible factor-1α （HIF-1α）/ 6-phosphofructo-2-kinase/fructose-2，6-bisphosphatase 3 （PFKFB3） signaling pathway. MethodsA rat model of chronic heart failure was established by subcutaneous injection of isoproterenol （ISO）. After successful modeling， the rats were randomly divided into the Sham group， Model group， Shenfu injection （SFI， 6 mL·kg^-1） group， and inhibitor （3PO， 35 mg·kg^-1） group， according to a random number table， and they were treated for 15 days. Cardiac function was evaluated by echocardiography， and serum N-terminal pro-brain natriuretic peptide （NT-proBNP） levels were detected by enzyme-linked immunosorbent assay （ELISA）. Fasting body weight and heart weight were measured， and the heart index （HI） was calculated. Pathological changes in myocardial tissue were observed by hematoxylin-eosin （HE） and Masson staining， and the fibrosis rate was calculated. Biochemical assays were used to determine serum levels of glucose （GLU）， lactic acid （LA）， and pyruvic acid （PA）. Western blot was used to analyze the expression of proteins related to the HIF-1α/PFKFB3 signaling pathway （HIF-1α and PFKFB3）， glycolysis-related proteins （HK1， HK2， PKM2， and LDHA）， and fibrosis-related proteins ［transforming growth factor （TGF）-β₁， α-smooth muscle actin （α-SMA）， and Collagen type Ⅰ α1 （ColⅠA1）］. Real-time PCR was used to detect the mRNA expression of HIF-1α and PFKFB3 in myocardial tissue. ResultsCompared with the Sham group， the Model group showed significantly decreased left ventricular ejection fraction （LVEF）， left ventricular shortening fraction （LVFS）， interventricular septal thickness （IVSd）， and interventricular septal strain （IVSs） （P<0.05）， while left ventricular internal dimension at end-diastole （LVDd） and end-systole （LVIDs） were increased （P<0.05）. Serum NT-proBNP levels were significantly increased （P<0.01）， and body weight was decreased. Heart weight was increased， and the HIT index was increased （P<0.05）. Myocardial tissue exhibited inflammatory cell infiltration and collagen fiber deposition， and the fibrosis rate was significantly increased （P<0.05）. Serum GLU was decreased （P<0.05）， while LA and PA levels were increased （P<0.05）. Protein expressions of HIF-1α， PFKFB3， HK1， HK2， PKM2， LDHA， TGF-β₁， α-SMA， and ColⅠA1， as well as the mRNA expression of HIF-1α and PFKFB3 were increased （P<0.05）. Compared with the Model group， both the SFI group and 3PO groups showed significant improvements in LVEF， LVFS， IVSd， and IVSs （P<0.05） and decreases in LVDd， LVIDs， and NT-proBNP levels （P<0.05）. Body weight was significantly increased. Heart weight was significantly decreased， and the HIT index was significantly decreased （P<0.05）. Inflammatory cell infiltration， collagen fiber deposition， and the fibrosis rate were significantly decreased （P<0.05）. Serum GLU levels were significantly increased （P<0.05）， while LA and PA levels were decreased （P<0.05）. Expressions of glycolysis-related proteins， fibrosis-related proteins， and HIF-1α/PFKFB3 pathway-related proteins and mRNAs were significantly suppressed （P<0.05）. ConclusionSFI improves cardiac function in chronic heart failure by downregulating the expression of HIF-1α/PFKFB3 signaling pathway-related proteins， regulating glycolysis， and inhibiting myocardial fibrosis.

Epimedium sagittatum is a perennial herb of Berberidaceae. Its leaves have a long history of medicinal use in China. This plant is widely used as a Chinese traditional medicine，with the main functions of tonifying kidney Yang，strengthening bones and muscles，and dispelling wind and dampness. It can be used for treating kidney Yang deficiency，impotence，spermatorrhea，flaccidity of bones and muscles，rheumatic arthralgia，numbness，and spasms. The chemical constituents of this plant include flavonoids，polysaccharides，lignans，and alkaloids. Flavonoids are the main active ingredients. These compounds show a wide range of biological activities，including cartilage repair，anti-aging，anti-fatigue，cough-relieving，blood glucose-lowering，and anti-tumor effects. Modern pharmacological research has shown that E. sagittatum has definite pharmacological effects on the reproductive system，respiratory system，nervous system，cardiovascular system，skeletal system，etc. It has remarkable effects of helping pregnancy，resisting osteoporosis，controlling diabetes，improving immunity，and inhibiting tumor. Under the background of advocating one health and Chinese medicine，E. sagittatum is widely used in health care products，serving as the main raw material of various products. It has great market potential and is a Chinese medicinal herb with great clinical application and research value. This paper reviews the main chemical constituents and pharmacological effects of E. sagittatum based on domestic and foreign reports， providing a theoretical basis for further study on E. sagittatum and its safe clinical application.

Epimedium sagittatum is a perennial herb of Berberidaceae. Its leaves have a long history of medicinal use in China. This plant is widely used as a Chinese traditional medicine，with the main functions of tonifying kidney Yang，strengthening bones and muscles，and dispelling wind and dampness. It can be used for treating kidney Yang deficiency，impotence，spermatorrhea，flaccidity of bones and muscles，rheumatic arthralgia，numbness，and spasms. The chemical constituents of this plant include flavonoids，polysaccharides，lignans，and alkaloids. Flavonoids are the main active ingredients. These compounds show a wide range of biological activities，including cartilage repair，anti-aging，anti-fatigue，cough-relieving，blood glucose-lowering，and anti-tumor effects. Modern pharmacological research has shown that E. sagittatum has definite pharmacological effects on the reproductive system，respiratory system，nervous system，cardiovascular system，skeletal system，etc. It has remarkable effects of helping pregnancy，resisting osteoporosis，controlling diabetes，improving immunity，and inhibiting tumor. Under the background of advocating one health and Chinese medicine，E. sagittatum is widely used in health care products，serving as the main raw material of various products. It has great market potential and is a Chinese medicinal herb with great clinical application and research value. This paper reviews the main chemical constituents and pharmacological effects of E. sagittatum based on domestic and foreign reports， providing a theoretical basis for further study on E. sagittatum and its safe clinical application.

Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APC^min/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.

OBJECTIVE To explore the effects of ADRB1 Arg389Gly polymorphisms on the efficacy of bisoprolol， thus providing some information for individualized drug therapy. METHODS A systematic search was conducted in PubMed， Embase， Cochrane Library， CBM， CNKI， and Wanfang Data to retrieve and find out all relevant literature about bisoprolol and ADRB1 Arg389Gly polymorphism from the inception to May 2023. The retrieved literature was screened and selected according to the inclusive and exclusive criteria， thereafter quality assessment was conducted. RevMan 5.4 software was utilized to perform the meta- analysis for the outcome index. RESULTS Overall 7 literature with 1 339 cases were included. Among them， 4 studies provided the changes in systolic blood pressure （SBP）， diastolic blood pressure （DBP） （ΔSBP and ΔDBP）； 4 involving the change （ΔLVEF） of left ventricular ejection fraction （LVEF）. Results of the study showed that there was no statistical significance in the improvement of blood pressure between wild-type group （AA） and mutation group （AG+GG） of ADRB1 Arg389Gly treated with bisoprolol {ΔSBP [SMD＝0.17，95%CI （－0.97，1.31）， P＝0.77]， ΔDBP [SMD＝－0.01，95%CI （－0.65，0.62）， P＝0.97]}； there was no statistical significance in the improvement of ΔLVEF [SMD＝－0.61， 95%CI （－2.74，1.53）， P＝0.58] between 2 groups. CONCLUSIONS ADRB1 Arg389Gly gene polymorphism has no significant influence on the improvement of SBP， DBP， and LVEF in cardiovascular patients who use bisoprolol.

China is a country with a high incidence of esophageal cancer.The pathological type is mainly squamous cell carcinoma.Squamous intraepithelial neoplasia is the most recognized precancerous lesion of esopha-geal squamous cell carcinoma,and its monitoring and intervention is an effective method to reduce the incidence of esophageal squamous cell carcinoma and improve the quality of life of patients.Understanding the etiology,clinical features,diagnosis and treatment of esophageal squamous cell carcinoma plays a crucial role in the prevention and early diagnosis and treatment of esophageal squamous cell carcinoma.At present,the clinical research related to esophageal squamous intraepithelial neoplasia is still insufficient,and there are some differences in clinical treat-ment.This review summarizes the risk factors,clinical features,diagnosis,prognosis and treatment of esophageal squamous intraepithelial neoplasia,hoping to provide ideas for the clinical management of esophageal squamous intraepithelial neoplasia.

BACKGROUND:The threaded conical implant has a good ability to control micro movements and is conducive to immediate loading.However,the effects of double-threaded conical cylindrical implants and conical cylindrical implants on stress distribution and initial stability of implant-bone interface after immediate loading have not been reported. OBJECTIVE:To investigate the impact of double-threaded conical cylindrical implants and conical cylindrical implants on the biological distribution of the implant and the surrounding bone interface during immediate loading in the mandibular molar region. METHODS:(1)Three-dimensional finite element analysis:Conical beam CT scans of the mandible and first molar of a volunteer were used to develop a basal model of the mandible.The double-threaded conical cylindrical implants and conical cylindrical implants were assembled with the mandibular models,and an immediate-load(or delayed implantation)implant model(a total of four models)for the first mandibular molar was established.Loads in four directions(100 N):axial,lingual and buccal 45°,mesial and distal,and buccal and lingual,were applied to the central fossa of each model's crown.Three-dimensional finite element method was used to analyze the implant displacement and the stress distribution at the implant-bone interface.(2)In vitro experiment:With the assistance of the oral implant robot,the double-threaded conical cylindrical implants and conical cylindrical implants were implanted on the same artificial bone pieces,separately,and the immediate load model of immediate implant implantation(or delayed implantation)was established in vitro(a total of four groups of models).Osstell resonance frequency analyzer and SmartPeg sensor were used to measure the implant stability coefficient in four vertical directions:front,rear,left,and right measurements,evaluate the initial stability,and verify the finite element analysis results. RESULTS AND CONCLUSION:(1)The displacement difference between double-threaded conical cylindrical implants and conical cylindrical implants was small when the immediate loading of delayed implantation was applied,but the maximum stress value of conical cylindrical implant-bone interface was greater than that of double-threaded conical cylindrical implant-bone interface.When the immediate loading of immediate implantation was applied,the maximum stress value and the maximum displacement of bone around the implant appeared when the load was applied in mesiodistal direction.The stress value of the conical cylindrical implant reached 298.84 MPa and the maximum displacement was 0.31 mm,both of which were larger than that of the double-threaded conical cylindrical implant.(2)The results of in vitro experiments showed that the stability coefficient of the double-threaded conical cylindrical implant was greater than that of the conical cylindrical implant.(3)Compared with the conical cylindrical implant,the double-threaded conical cylindrical implant has higher initial stability under immediate loading,suggesting that the use of double-threaded conical cylindrical implant should be given priority in clinical immediate loading.

Objective To analyze the role of the key items list in the quality control of running medical records by com-paring the improvements of the quality of medical records,and to explore more effective ways of quality management of medical records.Methods Based on the goal setting theory and influencing factors of goal incentive utility,a list of key items for medi-cal record quality management was formulated,which was implemented in a children's hospital in Tianjin since April 2023.A to-tal of 4 823 operating medical records were collected from June 2022 to September 2023,and the defect rates of quality control items were compared by using statistical methods.Results After the implementation of the key items list,the average score of operating medical records was improved,and the defect rate decreased from 13.63％to 7.94％.Moreover,the defect rates of admission records,first-trip records,senior physician rounds records,consultation records,and surgical records decreased from 4.25％,3.07％,8.26％,and 10.56％to 1.61％,1.56％,4.41％,and 5.06％.Conclusion The implementation of key i-tems list management can effectively improve the quality of running medical records,reduce the defects of medical records,and improve the effects of medical record management.