Objective: To investigate the mechanism of Yishen Tongluo Formula in ameliorating renal pyroptosis in diabetic nephropathy mice by regulating the toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor-κB (NF-κB) signaling pathway. Methods: Sixty C57BL/6 male mice were randomly divided into control (10 mice) and intervention groups (50 mice) using random number table method. The diabetes nephropathy model was established by intraperitoneally injecting streptozotocin(50 mg/kg). After modeling, the intervention group was further divided into model, semaglutide (40 μg/kg), and high-, medium-, and low-dose Yishen Tongluo Formula groups (15.6, 7.8, and 3.9 g/kg, respectively) using random number table method. The high-, medium-, and low-dose Yishen Tongluo Formula groups were administered corresponding doses of medication by gavage, the semaglutide group received a subcutaneous injection of semaglutide injection, and the control group and model groups were administered distilled water by gavage for 12 consecutive weeks. Random blood glucose levels of mice in each group were monitored, and the 24-h urinary protein content was measured using biochemical method every 4 weeks; after treatment, the serum creatinine and urea nitrogen levels were measured using biochemical method. The weight of the kidneys was measured, and the renal index was calculated. Hematoxylin and eosin, periodic acid-Schiff, periodic Schiff-methenamine, and Masson staining were used to observe the pathological changes in renal tissue. An enzyme-linked immunosorbent assay was used to detect urinary β2-microglobulin (β2-MG), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) levels. Western blotting and real-time fluorescence PCR were used to detect the relative protein and mRNA expression levels of nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3), Caspase-1, gasdermin D (GSDMD), interleukin-1β (IL-1β), and interleukin-18 (IL-18) in renal tissue. Immunohistochemistry was used to detect the proportion of protein staining area of the TLR4, MyD88, and NF-κB in renal tissue. Results: Compared with the control group, the random blood glucose, 24-h urinary protein, serum creatinine, urea nitrogen, and renal index of the model group increased, and the urine β2-MG, NGAL, and KIM-1 levels increased. The relative protein and mRNA expression levels of NLRP3, Caspase-1, GSDMD, IL-1β, and IL-18 in renal tissue increased, and the proportion of TLR4, MyD88, and NF-κB protein positive staining areas increased (P<0.05). Pathological changes such as glomerular hypertrophy were observed in the renal tissue of the model group. Compared with the model group, the Yishen Tongluo Formula high-dose group showed a decrease in random blood glucose after 12 weeks of treatment (P<0.05). The Yishen Tongluo Formula high- and medium-dose groups showed a decrease in 24-h urinary protein, creatinine, urea nitrogen, and renal index, as well as decreased β2-MG, NGAL, and KIM-1 levels. NLRP3, Caspase-1, GSDMD, IL-1 β, and IL-18 relative protein and mRNA expression levels were also reduced, and the proportion of TLR4, MyD88, and NF-κB protein positive staining areas was reduced (P<0.05). Pathological damage to renal tissue was ameliorated. Conclusion Yishen Tongluo Formula may exert protective renal effects by inhibiting renal pyroptosis and alleviating tubular interstitial injury in diabetic nephropathy mice by regulating the TLR4/MyD88/NF-κB signaling pathway.

ObjectiveTo investigate the effect and mechanism of Yishen Tongluo prescription in protecting mice from oxidative stress injury in diabetic kidney disease （DKD） via the nuclear factor erythroid 2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1）/NAD（P）H quinone oxidoreductase 1 （NQO1） signaling pathway. MethodsSpecific pathogen-free （SPF） male C57BL/6 mice were assigned into a control group （n=10） and a modeling group （n=50）. The DKD model was established by intraperitoneal injection of streptozotocin. The mice in the modeling group were randomized into a model group， a semaglutide （40 μg·kg^-1） group， and high-， medium-， and low-dose （18.2， 9.1， 4.55 g·kg^-1， respectively） Yishen Tongluo prescription groups， with 10 mice in each group. The treatment lasted for 12 weeks. Blood glucose and 24-h urine protein levels were measured， and the kidney index （KI） was calculated. Serum levels of creatinine （SCr）， blood urea nitrogen （BUN）， alanine aminotransferase （ALT）， and aspartate aminotransferase （AST） were assessed. The pathological changes in the renal tissue were evaluated by hematoxylin-eosin， periodic acid-Schiff， periodic acid-silver methenamine， and Masson’s trichrome staining. Enzyme-linked immunosorbent assay kits were used to measure the levels of β2-microglobulin （β2-MG）， neutrophil gelatinase-associated lipocalin （NGAL）， kidney injury molecule-1 （KIM-1）， liver fatty acid-binding protein （L-FABP）， nitric oxide synthase （NOS）， glutathione （GSH）， total antioxidant capacity （T-AOC）， and 8-hydroxy-2'-deoxyguanosine （8-OHdG）. Immunohistochemical staining was performed to examine the expression of Kelch-like ECH-associated protein 1 （Keap1） and malondialdehyde （MDA）. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR） and Western blot were employed to determine the mRNA and protein levels， respectively， of factors in the Nrf2/HO-1/NQO1 signaling pathway. ResultsCompared with the control group， the DKD model group showed rises in blood glucose， 24-h urine protein， KI， SCr， BUN， and ALT levels， along with glomerular hypertrophy， renal tubular dilation， thickened basement membrane， mesangial expansion， and collagen deposition. Additionally， the model group showed elevated levels of β2-MG， NGAL， KIM-1， L-FABP， NOS， and 8-OHdG， lowered levels of GSH and T-AOC， up-regulated expression of MDA and Keap1， and down-regulated expression of Nrf2， HO-1， NQO1， and glutamate-cysteine ligase catalytic subunit （GCLC） （P<0.05）. Compared with the model group， the semaglutide group and the medium- and high-dose Yishen Tongluo prescription groups showed reductions in blood glucose， 24-h urine protein， KI， SCr， BUN， and ALT levels， along with alleviated pathological injuries in the renal tissue. In addition， the three groups showed lowered levels of β2-MG， NGAL， KIM-1， L-FABP， NOS， and 8-OHdG， elevated levels of GSH and T-AOC， down-regulated expression of MDA and Keap1， and up-regulated expression of Nrf2， HO-1， NQO1， and GCLC （P<0.05）. ConclusionYishen Tongluo prescription exerts renoprotective effects in the mouse model of DKD by modulating the Nrf2/HO-1/NQO1 signaling pathway， mitigating oxidative stress， and reducing renal tubular injuries.

Purpose: This study aimed to evaluate changes in ultrafast pulse wave velocity (ufPWV) in individuals with arterial stiffness and subclinical atherosclerosis (subAS), and to provide cutoff values. Methods: This retrospective study recruited 231 participants, including 67 patients with subAS. The pulse wave velocity was measured at the beginning and end of systole (PWV-BS and PWVES, respectively) using ultrafast ultrasonography to assess arterial stiffness. The right and left common carotid arteries were measured separately, and laboratory metabolic parameters were also collected. Participants were balanced between groups using propensity score matching (PSM) at a 1:1 ratio, adjusting for age, sex, and waist-to-hip ratio as potential confounders. Cutoff values of ufPWV for monitoring subAS were determined via receiver operating characteristic (ROC) curve analysis. Results: PWV-ES, unlike PWV-BS, was higher in the subAS subgroup than in the subAS-free group after PSM (all P<0.05). For each 1 m/s increase in left, right, and bilateral mean PWV-ES, the risk of subAS increased by 23% (95% confidence interval [CI], 1.04 to 1.46), 26% (95% CI, 1.07 to 1.52), and 38% (95% CI, 1.12 to 1.72), respectively. According to ROC analyses, predictive potential was found for left PWV-ES (cutoff value=7.910 m/s, P=0.002), right PWV-ES (cutoff value=6.615 m/s, P=0.003), and bilateral mean PWV-ES (cutoff value=7.415 m/s, P<0.001), but not for PWV-BS (all P>0.05). Conclusion PWV-ES measured using ultrafast ultrasonography was significantly higher in individuals with subAS than in those without. Specific PWV-ES cutoff values showed potential for predicting an increased risk of subAS.

Objective To explore the efficacy of semaglutide in the treatment of type 2 diabetes mellitus(T2DM)com-bined with non-alcoholic fatty liver disease(NAFLD)and its effect on oxidative stress and inflammatory factors.Methods Totally 80 patients with T2DM accompanied by NAFLD admitted to the First Affiliated Hospital of Xinxiang Medical University from July 2021 to December 2022 were selected and randomly assigned to the observation group and the control group,with 40 patients in each group.Patients in the control group were treated with pioglitazone metformin and dapagliflozin,while patients in the observation group were treated with pioglitazone metformin,dapagliflozin,and semaglutide.The levels of glycated hemoglobin(HbA1c),fasting blood glucose(FBG),2-hour postprandial blood glucose(2hPG),body mass,body mass index(BMI),waist circumference,alanine aminotransferase(ALT),aspartate aminotransferase(AST),gamma-glutamyl transferase(GGT),controlled attenuation parameter(CAP),liver stiffness measurement(LSM),malondialdehyde(MDA),glutathione peroxidase(GSH-PX),lipid peroxide(LPO),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and interleukin-10(IL-10)before and after the treatment were compared.Results After 24 weeks of treatment,the overall response rate(ORR)in the observation group and control group was 92.5％(37/40)and 72.5％(29/40),respectively;and the ORR in the observation group was significantly higher than that in the control group(x2=5.541,P＜0.05).Before treatment,there was no statistically significant difference in the body mass,BMI,waist circumference,HbA1c,FBG,2hPG,ALT,AST,GGT,CAP,LSM,MDA,GSH-PX,LPO,TNF-α,IL-6,and IL-10 of patients between the 2 groups(P＞0.05);after 24 weeks of treatment,the body mass,BMI,waist circumference,HbA1c,FBG,2hPG,ALT,AST,GGT,CAP,LSM,MDA,LPO,TNF-α,IL-6,and IL-10 were significantly lower than before treatment,while GSH-PX was significantly higher than before treatment(P＜0.05);after 24 weeks of treatment,the body mass,BMI,waist circumference,HbA1c,FBG,2hPG,ALT,AST,GGT,CAP,LSM,MDA,LPO,TNF-α,IL-6,and IL-10 of patients in the observation group were significantly lower than those in the control group,and GSH-PX was significantly higher than that in the control group(P＜0.05).The incidence of adverse reactions in the observation group and the control group during the treatment period was 17.5％(7/40)and 12.5％(5/40),respectively;and the difference in the incidence of adverse reactions between the two groups was not statistically significant(P＞0.05).Conclusion Semaglutide significantly downregulates the levels of FBG,2hPG and HbA1c in patients with T2DM combined with NAFLD and reduces the body mass,waist circumference,liver enzyme level,hepatic fat content,hepatic fibrosis,oxidative stress,and inflammatory indicators.

Objective To develope a clinical decision support system(CDSS)on insulin titration and validate its effectiveness and safety.Methods Eighty patients with type 2 diabetes mellitus treated at the Department of Endocrinology of the First Affiliated Hospital of Xinxiang Medical University from January 2021 to July 2023,who had difficulty in achieving glycemic control on the basis of lifestyle interventions and oral hypoglycemic drug treatments,were selected for the study.The patients were divided into the observation group and the control group using a random number table,with 40 cases in each group.Patients in both groups received oral metformin extended-release tablets,subcutaneous insulin degludec before bedtime,and subcutaneous aspartate insulin injection before three meals for glycemic control.Patients in the observation group were given insulin titration using the CDSS,and patients in the control group were given insulin titration using the conventional method.The retrospective continuous glucose monitoring system was used to monitor time in range(TIR)for glucose,mean amplitude of glycemic excursion(MAGE),mean blood glucose(MBG),standard deviation of blood glucose(SDBG),and the coefficient of variation(CV)of blood glucose.Fasting blood glucose(FBG),2-hour postprandial glucose(2hPG),length of hospitalization,time to achieve standard blood glucose control,and incidence of hypoglycemia of patients were recorded before and after treatment in the two groups.Results There was no significant difference in FBG and 2hPG of patients between the two groups before treat-ment(P＞0.05).The FBG and 2hPG levels of patients in the two groups were significantly lower than those before treatment(P＜0.05).The FBG and 2hPG levels of patients in the observation group were significantly lower than those in the control group after treatment(P＜0.05).TIR of patients in the observation group was significantly higher than that in the control group,while MAGE,MBG,SDBG,and CV were significantly lower than those in the control group after treatment(P＜0.05).The length of hospitalization was 9.0(7.3,10.0)days and 11.0(8.3,12.0)days of patients in the observation group and control group,respectively;and the length of hospitalization of patients in the control group was significantly longer than that in the observation group(Z=-2.408,P＜0.05).The time required to achieve glycemic control was 6.5(5.0,8.8)days and 7.5(6.0,10.0)days of patients in the observation group and control group,respectively;and the time required to achieve glycemic control of patients in the control group was significantly longer than that in the observation group(Z=-2.019,P＜0.05).The incidence of hypoglycemia of patients in the observation group and control group was 20.0％(8/40),12.5％(5/40),respectively;there was no significant difference in the incidence of hypoglycemia between the observation group and the control group(x2=0.827,P＞0.05).Conclusion Compared with the conventional titration of insulin,the application of CDSS can provide decision support during the implementation of a basal-meal insulin regimen,which can lead to more effective glycemic control,improved glucose TIR,reduced glycemic fluctuations,shorter time required for patients to achieve glycemic control,and shorter hospital stays without increasing the risk of hypoglycemia.

Purpose: This study aimed to evaluate changes in ultrafast pulse wave velocity (ufPWV) in individuals with arterial stiffness and subclinical atherosclerosis (subAS), and to provide cutoff values. Methods: This retrospective study recruited 231 participants, including 67 patients with subAS. The pulse wave velocity was measured at the beginning and end of systole (PWV-BS and PWVES, respectively) using ultrafast ultrasonography to assess arterial stiffness. The right and left common carotid arteries were measured separately, and laboratory metabolic parameters were also collected. Participants were balanced between groups using propensity score matching (PSM) at a 1:1 ratio, adjusting for age, sex, and waist-to-hip ratio as potential confounders. Cutoff values of ufPWV for monitoring subAS were determined via receiver operating characteristic (ROC) curve analysis. Results: PWV-ES, unlike PWV-BS, was higher in the subAS subgroup than in the subAS-free group after PSM (all P<0.05). For each 1 m/s increase in left, right, and bilateral mean PWV-ES, the risk of subAS increased by 23% (95% confidence interval [CI], 1.04 to 1.46), 26% (95% CI, 1.07 to 1.52), and 38% (95% CI, 1.12 to 1.72), respectively. According to ROC analyses, predictive potential was found for left PWV-ES (cutoff value=7.910 m/s, P=0.002), right PWV-ES (cutoff value=6.615 m/s, P=0.003), and bilateral mean PWV-ES (cutoff value=7.415 m/s, P<0.001), but not for PWV-BS (all P>0.05). Conclusion PWV-ES measured using ultrafast ultrasonography was significantly higher in individuals with subAS than in those without. Specific PWV-ES cutoff values showed potential for predicting an increased risk of subAS.

Purpose: This study aimed to evaluate changes in ultrafast pulse wave velocity (ufPWV) in individuals with arterial stiffness and subclinical atherosclerosis (subAS), and to provide cutoff values. Methods: This retrospective study recruited 231 participants, including 67 patients with subAS. The pulse wave velocity was measured at the beginning and end of systole (PWV-BS and PWVES, respectively) using ultrafast ultrasonography to assess arterial stiffness. The right and left common carotid arteries were measured separately, and laboratory metabolic parameters were also collected. Participants were balanced between groups using propensity score matching (PSM) at a 1:1 ratio, adjusting for age, sex, and waist-to-hip ratio as potential confounders. Cutoff values of ufPWV for monitoring subAS were determined via receiver operating characteristic (ROC) curve analysis. Results: PWV-ES, unlike PWV-BS, was higher in the subAS subgroup than in the subAS-free group after PSM (all P<0.05). For each 1 m/s increase in left, right, and bilateral mean PWV-ES, the risk of subAS increased by 23% (95% confidence interval [CI], 1.04 to 1.46), 26% (95% CI, 1.07 to 1.52), and 38% (95% CI, 1.12 to 1.72), respectively. According to ROC analyses, predictive potential was found for left PWV-ES (cutoff value=7.910 m/s, P=0.002), right PWV-ES (cutoff value=6.615 m/s, P=0.003), and bilateral mean PWV-ES (cutoff value=7.415 m/s, P<0.001), but not for PWV-BS (all P>0.05). Conclusion PWV-ES measured using ultrafast ultrasonography was significantly higher in individuals with subAS than in those without. Specific PWV-ES cutoff values showed potential for predicting an increased risk of subAS.

Cirrhotic portal hypertension (CPH) is a manifestation of decompensated liver cirrhosis, with ascites, portal collateral circulation formation, hypersplenism and splenomegaly as the typical clinical symptoms. In recent years, the incidence of CPH has been increasing year by year, and the treatment of CPH has gradually become a hot issue in medical research. In order to further explore the diagnosis and treatment scheme of CPH. We briefly describe the pathophysiological mechanism and diagnosis of CPH, and the current situation of CPH treatment and the new progress of internal and external treatment were reviewed.

Oral diseases concern almost every individual and are a serious health risk to the popula-tion.The restorative treatment of tooth and jaw defects is an important means to achieve oral function and support the appearance of the contour.Based on the principle of"learning from the nature",Deng Xu-liang's group of Peking University School and Hospital of Stomatology has proposed a new concept of"microstructural biomimetic design and tissue adaptation of tooth/jaw materials"to address the worldwide problems of difficulty in treating dentine hypersensitivity,poor prognosis of restoration of tooth defects,and vertical bone augmentation of alveolar bone after tooth loss.The group has broken through the bottle-neck of multi-stage biomimetic technology from the design of microscopic features to the enhancement of macroscopic effects,and invented key technologies such as crystalline/amorphous multi-level assembly,ion-transportation blocking,and multi-physical properties of the micro-environment reconstruction,etc.The group also pioneered the cationic-hydrogel desensitizer,digital stump and core integrated restora-tions,and developed new crown and bridge restorative materials,gradient functionalisation guided tissue regeneration membrane,and electrically responsive alveolar bone augmentation restorative membranes,etc.These products have established new clinical strategies for tooth/jaw defect repair and achieved inno-vative results.In conclusion,the research results of our group have strongly supported the theoretical im-provement of stomatology,developed the technical system of oral hard tissue restoration,innovated the clinical treatment strategy,and led the progress of the stomatology industry.

BACKGROUND:Diabetic osteoporosis is gaining public attention.However,few studies have reported the effect of a high-glucose environment on the osteogenic differentiation of human umbilical cord mesenchymal stem cells and the corresponding therapeutic strategies. OBJECTIVE:To investigate whether vitamin D3 can restore the osteogenic differentiation potential of human umbilical cord mesenchymal stem cells in a high-glucose environment. METHODS:The viability of human umbilical cord mesenchymal stem cells was detected by CCK-8 assay to screen the appropriate vitamin D3 intervention concentration.Under the high-glucose environment,RT-qPCR,western blot assay,immunofluorescence,JC-1 mitochondrial membrane potential,alizarin red staining,and β-galactosidase staining were used to evaluate the osteogenic differentiation potential,intracellular reactive oxygen species accumulation,mitochondrial membrane potential alteration,and cell senescence of human umbilical cord mesenchymal stem cells after vitamin D3 intervention.The underlying mechanism was also discussed. RESULTS AND CONCLUSION:(1)Vitamin D3 significantly promoted the proliferation of human umbilical cord mesenchymal stem cells in the range of 0.1 μmol/L to 1 mmol/L.(2)High-glucose environment down-regulated the mRNA and protein level expressions of osteogenic-related genes α1-I collagen,alkaline phosphatase,Runt-associated transcription factor 2,and osteocalcin in human umbilical cord mesenchymal stem cells,which induced oxidative stress and cellular senescence.(3)Vitamin D3 at an intervention concentration of 10 μmol/L significantly restored the osteogenic phenotype of human umbilical cord mesenchymal stem cells under high-glucose conditions and attenuated intracellular oxidative stress and cellular senescence by activating the Nrf2/HO-1 signaling pathway.(4)These findings suggested that the osteogenic differentiation ability of human umbilical cord mesenchymal stem cells was reduced in the high-glucose environment,and vitamin D3 could partially improve their osteogenic differentiation ability and reduce cell damage.