Traditional treatment for type 1 diabetes mellitus （T1DM） primarily involves insulin replacement， yet some patients encounter issues such as significant blood glucose fluctuations， high risk of hypoglycemia， and weight gain. In recent years， the adjuvant therapeutic role of non-insulin hypoglycemic drugs in T1DM has gradually gained attention. This article reviews the mechanisms of action and clinical research progress of five types of non-insulin hypoglycemic drugs in the treatment of T1DM： amylin analogues （pramlintide）， biguanides （metformin）， sodium-glucose co-transporter 2 inhibitor， dipeptidyl peptidase-4 inhibitor， and glucagon-like peptide-1 receptor agonist. It is found that these drugs can enhance clinical benefits for T1DM patients by improving insulin sensitivity， delaying gastric emptying， promoting urinary glucose excretion， and regulating incretin levels， thereby reducing glycated hemoglobin levels， decreasing insulin dosage， and managing body weight. Simultaneously， these drugs also present limitations such as low patient compliance due to complex dosing regimens， increased risk of diabetic ketoacidosis， and heterogeneity in glycemic control. Future research could focus on developing individualized treatment strategies， combining pharmacogenomics with novel biomarkers to precisely identify subpopulations of patients who may benefit， and delving into the potential value of these drugs in delaying diabetic vascular complications and improving patients’ quality of life.

Objective To establish an HPLC method to determine the concentration of inositol nicotinate（IN） in rat skin, and study the pharmacokinetic characteristics of IN after transdermal administration of heparin sodium inositol nicotinate cream in rats. Methods HPLC method was used to establish a simple and rapid analytical method for the determination of IN concentration in the skin of rats at different time points after administration. The established method was used to study the pharmacokinetics of IN after transdermal administration of heparin sodium inositol nicotinate cream in rats, and the pharmacokinetic parameters were fitted with DAS software. Results The linearity of the analytical method was good in the concentration range of 0.25-20 μg/ml, the quantitative limit was 0.25 μg/ml, and the average recovery rate was 96.18%. The pharmacokinetic parameters of IN after transdermal administration of heparin sodium inositol nicotinate cream in rats were as follows: t_1/2 was （4.555±2.054） h, T_max was （6±0）h, C_max was （16.929±2.153）mg/L, AUC_0−t was （150.665±16.568） mg·h /L ,AUC_0−∞ was （161.074±23.917） mg·h /L, MRT_（0−t） was （9.044±0.618）h, MRT_{（0−∞）} was （10.444±1.91） h, CLz/F was （0.19±0.03） L/（h·kg）, and Vz/F was （1.19±0.437） L/（h·kg）. Conclusion IN could quickly penetrate the skin and accumulate in the skin for a long time, which was beneficial to the pharmacological action of drugs on the lesion site for a long time. The method is simple, rapid, specific and reproducible, which could be successfully applied to the pharmacokinetic study of IN after transdermal administration in rats.

Objective To establish the fingerprint of Jianggui granules, and evaluate it by chemometrics. Methods The fingerprint of Jianggui granules was established by HPLC. Similarity evaluation system of chromatographic fingerprint of TCM （2012 edition） was used to evaluate the similarity evaluation. Then, the quality of the drug was assessed by cluster analysis （CA）, principal components analysis （PCA） and partial least squares discriminant analysis （PLS-DA）. Results The characteristic fingerprint of Jianggui granules was established and 18 common peaks were verified. Five chromatographic peaks were identified，i.e. Puerarin, glycyrrhizin, cinnamic acid, cinnamaldehyde and ammonium glycyrrhizinate. The similarities of samples were >0.9. Results of CA showed that 14 batches of samples could be classified into two categories：S1 and S4 were grouped into one category；others were grouped into the other category. The results of PCA showed that the cumulative contribution rate of the first two principal components was 96.61%. The results of OPLS-DA showed that the eleven peaks with VIP value >1 were puerarin （peak 8）, glycyrrhizin （peak 14）, cinnamaldehyde （peak 17） and ammonium glycyrrhizinate （peak 18）. Conclusion HPLC fingerprint of Jianggui granules was established. The established method was accurate and reliable，which could be used in quality evaluation of Jianggui granules.

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.

Objective:To explore the mechanism of acupuncture combined with sand therapy on bone biomechanics and immune function in rabbits with knee osteoarthritis based on G protein coupled signal.Methods:Totally 35 rabbits were randomly divided into normal group, model group, sand therapy group, acupuncture and moxibustion group and combined group, with 7 rabbits in each group. Except for the normal group, all other groups were prepared with knee osteoarthritis models. After 12 h modeling, rabbits in the sand therapy group and the combined group were treated with sand therapy. Rabbits in the acupuncture and moxibustion group and the combined group received acupuncture stimulation intervention therapy. Rabbits in normal group and model group only moved freely. The levels of IgG, IgM and IgA in serum and IL-1β and TNF-α were detected by ELISA method. The biomechanical properties of femur were measured by American Instron universal material experimental machine. The pathological changes of rabbits in each group were observed by HE staining. Protein expression levels of Gαs, cAMP and Gi in rabbit cartilage tissues were detected by Western blot.Results:Compared with model group, the levels of IgG, IgM and IgA increased ( P<0.05)l the levels of IL-1β and TNF-α decreased ( P<0.05); the maximum load, breaking load, structural stiffness and capacity absorption of rabbits in sand therapy group, acupuncture group and combined group increased ( P<0.05); the expressions of Gαs and cAMP protein increased ( P<0.05), while the expression of Gi protein decreased ( P<0.05). Conclusion:Acupuncture combined with sand therapy in the treatment of knee osteoarthritis can effectively improve the bone strength of osteoarthritis, reduce the inflammatory response, balance the expression of G protein and improve the imbalance of immunoglobulin.

Objective:To investigate the effects of external application of Compound Dahuang Powder combined with acupuncture on the synovial ultrastructure, pathological angiogenesis, and Ras/Raf signaling pathway in rheumatoid arthritis rats.Methods:Totally 100 SPF grade SD rats were selected and divided into normal group, model group, acupuncture group, external application group, and combination group according to random number table method, with 20 rats in each group. Except for the normal group, Freund's complete adjuvant was injected into the bilateral plantars to establish a rheumatoid arthritis model. One week after modeling, the acupuncture group received acupuncture at "Yinlingquan (SP9)" and "Sanyinjiao (SP6)" for 30 minutes, with continuous intervention for 6 days and 7 days as one course of treatment, for a total of 3 courses of intervention. The external application group of rats applied compound Dahuang Powder on the right hind foot and ankle joint, 10 g/time, twice a day, for 7 days as one course of treatment, with a total of 3 intervention courses; the combination group received a combined intervention of acupuncture and external application of compound Dahuang Powder. No intervention was performed in the normal group and model group. The levels of TNF-α and IL-1β in serum of rats in each group were detected using enzyme-linked immunosorbent assay. Transmission electron microscopy was used to observe the ultrastructure of synovial cells. HE staining was used to observe the morphology of synovial tissue. Immunohistochemistry was used to detect vascular endothelial growth factor (VEGF) and its receptor VEGFR2 in synovial tissue. Western blot and RT qPCR were used to detect Ras/Raf protein and mRNA in synovial tissue, respectively.Results:Compared with model group, the levels of TNF-α and IL-1β in serum of rats in acupuncture group and external application group decreased ( P<0.05), the expressions of VEGF and VEGFR2 decreased ( P<0.05), and the expressions of Ras and Raf protein and mRNA in acupuncture group and external application group decreased ( P<0.05). Compared with acupuncture group and external application group, the levels of TNF-α and IL-1β in serum of rats in the combination group decreased ( P<0.05), the expressions of VEGF and VEGFR2 decreased ( P<0.05), and the expressions of Ras and Raf protein and mRNA in the combination group decreased ( P<0.05). The results of synovial cell ultrastructure showed that the nuclear membrane of synovial cells in normal group was good, and the nuclear membrane in model group was seriously damaged. The acupuncture group and external application group had different degrees of improvement, and the combination group had the most significant improvement. HE staining results showed that the joint synovial tissue of the normal group was normal, the joint synovial tissue of the model group had a large amount of inflammatory infiltration, the joint synovial injury of the acupuncture group and the external application group was slightly improved, and the pathological injury of the combined group was significantly reduced. Conclusion:The combination of external application of compound Dahuang Powder and acupuncture can regulate angiogenesis related factors, regulate the Ras/Raf signaling pathway, and improve the ultrastructure of synovial cells in rheumatoid arthritis model rats.

Objective:To investigate the management of patients with intravenous misplacement of nephrostomy tube following percutaneous renal surgery.Methods:The data of 6 patients with intravenous misplacement of nephrostomy tube during percutaneous nephrolithotomy (PCNL) treated in the two hospitals of Chenzhou from January 2006 to December 2020 were retrospectively analyzed. The median age was 41.0(38.5, 53.0) years old. There were 4 males and 2 females. Three patients had undergone contralateral upper urinary tract operation. One patient had undergone ipsilateral upper urinary tract operation. Two patients had not undergone upper urinary tract operation. Two of the 6 patients had a solitary kidney. Two patients were diagnosed with staghorn calculi (combined with mild hydronephrosis in 1 patient, moderate hydronephrosis in 1 patient). Four patients were diagnosed with ureteral calculus (combined with mild hydronephrosis in 2 patients, moderate hydronephrosis in 1 patient, severe hydronephrosis in 1 patient). In all 6 patients, the tract was dilated with fascial dilators. Immediately after dilator removal, brisk venous bleeding was noted. A nephrostomy tube was inserted promptly through the sheath to tamponade the tract and was immediately closed. Five cases were diagnosed by CT after operation, and 1 case was early diagnosed by intraoperative injection of contrast medium through nephrostomy tube. The nephrostomy tube was misplaced in 5 patients with left upper urinary tract calculi, and in 1 patient with right upper urinary tract calculi. The tip of nephrostomy tube was located in ipsilateral renal vein in 3 patients with left upper urinary tract calculus, inferior vena cava in 2 patients with left upper urinary tract calculus, and contralateral renal vein in 1 patient with right upper urinary tract calculus. No venous thrombosis of renal vein or inferior vena cava was founded in the 6 patients. All 6 patients were managed with strict bed rest, intravenous antibiotics, and one-step or two-step tube withdrawal under close monitoring. One step method referred to total removal of nephrostomy tube under ultrasonic monitoring. Two step method referred to retracting the end of nephrostomy tube into the renal sinus under CT monitoring in the first step, then the nephrostomy tube was completely removed under ultrasound monitoring.Results:All 6 patients were successfully managed with strict bed rest, intravenous antibiotics, and one-step or two-step tube withdrawal under close monitoring. The tube was withdrew by one-step method in 1 patient, by two-step method in 5 patients. The original operations were performed successfully under close observation in 4 patients during the same hospitalization and in 1 patient during the next hospitalization. Other type of operation in 1 patient was performed during the next hospitalization. The all 6 patients were discharged uneventfully. The stone was cleared.Conclusions:Intravenous misplacement of a nephrostomy tube is mainly diagnosed by CT. The nephrostomy tube should be sealed immediately after diagnosis. The intravenously misplaced nephrostomy tube can be successfully removed by one-step or two-step withdrawing under close monitoring. Upper urinary tract stones can be successfully treated at the same time or by stages.

Objective To construct and validate a predictive model for the risk of deep vein thrombosis(DVT)after lower extremity orthopedic surgery.Methods Clinical records of hospital-ized patients who underwent lower extremity orthopedic surgery in Wuxi Traditional Chinese Medicine Hospital from January 2017 to October 2019 were collected.The univariate and multivariate analysis with the backward stepwise method were applied to screen variables and build a nomogram prediction model,and the performance of the nomogram was evaluated with respect to its discriminant capabili-ty,calibration ability,and clinical utility.Results A total of 5 773 hospitalized patients with ortho-pedic surgery of lower extremity were included in the study,with the incidence of DVT of 0.9％.Through single factor and multi-factor stepwise regression analysis,5 variables were selected from 31 variables to construct the prediction model,including age,mean corpuscular hemoglobin concentra-tion(MCHC),D-dimer,platelet distribution width(PDW),and thrombin time(TT).The receiver operating characteristic(ROC)curve showed that areas under the ROC curve in the training and vali-dation cohort were 0.859 and 0.857,respectively.The model had good calibration ability and clini-cal practicability.Conclusion The DVT risk prediction model constructed in this study has good dif-ferentiation ability,calibration ability and clinical practicability,which is helpful for doctors to classi-fy DVT patients after lower extremity orthopedic surgery and formulate early treatment plan.

Objective To construct and validate a predictive model for the risk of deep vein thrombosis(DVT)after lower extremity orthopedic surgery.Methods Clinical records of hospital-ized patients who underwent lower extremity orthopedic surgery in Wuxi Traditional Chinese Medicine Hospital from January 2017 to October 2019 were collected.The univariate and multivariate analysis with the backward stepwise method were applied to screen variables and build a nomogram prediction model,and the performance of the nomogram was evaluated with respect to its discriminant capabili-ty,calibration ability,and clinical utility.Results A total of 5 773 hospitalized patients with ortho-pedic surgery of lower extremity were included in the study,with the incidence of DVT of 0.9％.Through single factor and multi-factor stepwise regression analysis,5 variables were selected from 31 variables to construct the prediction model,including age,mean corpuscular hemoglobin concentra-tion(MCHC),D-dimer,platelet distribution width(PDW),and thrombin time(TT).The receiver operating characteristic(ROC)curve showed that areas under the ROC curve in the training and vali-dation cohort were 0.859 and 0.857,respectively.The model had good calibration ability and clini-cal practicability.Conclusion The DVT risk prediction model constructed in this study has good dif-ferentiation ability,calibration ability and clinical practicability,which is helpful for doctors to classi-fy DVT patients after lower extremity orthopedic surgery and formulate early treatment plan.

Background: Xylazole (Xyl) is a veterinary anesthetic that is structurally and functionally similar to xylazine. However, the effects of Xyl in vitro remain unknown. Objectives: This study aimed to investigate the anesthetic mechanism of Xyl using fetal rat nerve cells treated with Xyl. Methods: Fetal rat nerve cells cultured for seven days were treated with 10, 20, 30, and 40 μg/ mL Xyl for 0, 5, 10, 15, 20, 25, 30, 45, 60, 90, and 120 min. Variations of amino acid neurotransmitters (AANTs), Nitric oxide-Cyclic GMP (NO-cGMP) signaling pathway, and ATPase were evaluated. Results: Xyl decreased the levels of cGMP and NO in nerve cells. Furthermore, Xyl affected the AANT content and Na+ -K+ -ATPase and Ca2+ -Mg2+ -ATPase activity in nerve cells. These findings suggested that Xyl inhibited the NO-cGMP signaling pathway in nerve cells in vitro. Conclusions This study provided new evidence that the anesthetic and analgesic effects of Xyl are related to the inhibition of the NO-cGMP signaling pathway.