Diabetes is a very complex endocrine disease whose common feature is the increase in blood glucose concentration. Persistent hyperglycemia can lead to blindness, kidney and heart disease, neurodegeneration, and many other serious complications that have a significant impact on human health and quality of life. The number of people with diabetes is increasing yearly. The global diabetes prevalence in 20-79 year olds in 2021 was estimated to be 10.5% (536.6 million), and it will rise to 12.2% (783.2 million) in 2045. The main modes of intervention for diabetes include medication, dietary management, and exercise conditioning. Medication is the mainstay of treatment. Marketed diabetes drugs such as metformin and insulin, as well as GLP-1 receptor agonists, are effective in controlling blood sugar levels to some extent, but the preventive and therapeutic effects are still unsatisfactory. Peptide drugs have many advantages such as low toxicity, high target specificity, and good biocompatibility, which opens up new avenues for the treatment of diabetes and other diseases. Currently, insulin and its analogs are by far the main life-saving drugs in clinical diabetes treatment, enabling effective control of blood glucose levels, but the risk of hypoglycemia is relatively high and treatment is limited by the route of delivery. New and oral anti-diabetic drugs have always been a market demand and research hotspot. Inhibitor cystine knot (ICK) peptides are a class of multifunctional cyclic peptides. In structure, they contain three conserved disulfide bonds (C3-C20, C7-C22, and C15-C32) form a compact “knot” structure, which can resist degradation of digestive protease. Recent studies have shown that ICK peptides derived from legume, such as PA1b, Aglycin, Vglycin, Iglycin, Dglycin, and aM₁, exhibit excellent regulatory activities on glucose and lipid metabolism at the cellular and animal levels. Mechanistically, ICK peptides promote glucose utilization by muscle and liver through activation of IR/AKT signaling pathway, which also improves insulin resistance. They can repair the damaged pancrease through activation of PI3K/AKT/Erk signaling pathway, thus lowering blood glucose. The biostability and hypoglycemic efficacy of the ICK peptides meet the requirements for commercialization of oral drugs, and in theory, they can be developed into natural oral anti-diabetes peptide drugs. In this review, the structural properties, activity and mechanism of ICK pattern peptides in regulating glucose and lipid metabolism were summaried, which provided a reference for the development of new oral peptides for diabetes.

This article discussed the evolution of the traditional preparation process of Pinelliae Rhizoma Fermentata.The production methods for Pinelliae Rhizoma Fermentata in Song Dynasty include cake-making of Pinelliae Rhizoma together with ginger juice and fermentation after cake-making,and the former method of cake-making was the mainstream.The process technology in Jin and Yuan Dynasties inherited from that in Song Dynasty,and the application of Pinelliae Rhizoma Fermentata had certain limitations.The medical practitioners of Ming Dynasty elucidated the mechanism of processing of Pinelliae Rhizoma Fermentata,and proposed the view of"sliced Pinelliae Rhizoma being potent while fermented Pinelliae Rhizoma being mild".In the Ming Dynasty,LI Shi-Zhen defined the cake-making process and fermentation process for Pinelliae Rhizoma,and HAN Mao's Han Shi Yi Tong(Han's Clear View of Medicine)contained five prescriptions for the processing of Pinelliae Rhizoma Fermentata,which had the epoch-making signficance in the expansion of prescriptions for the processing of Pinelliae Rhizoma Fermentata.In the Qing Dynasty,HAN Fei-Xia's ten methods for making Pinelliae Rhizoma Fermentata were summarized on the basis of the methods recorded in Han Shi Yi Tong,and at that time,the processing of Pinelliae Rhizoma Fermentata and the preparation of Massa Medicata Fermentata interacted with each other.After the founding of the People's Republic of China,the local experience in the preparation of Pinelliae Rhizoma Fermentata was deeply influenced by the methods in the Qing Dynasty,and the local preparation technical standards gradually became the same.Moreover,this article also explored the issues of the importance of"Pinelliae Rhizoma"and"ingredients for fermentation",the pre-treatment of Pinelliae Rhizoma,the distinction between cake-making process and fermentation process for Pinelliae Rhizoma,the amount of flour added as well as the timing of adding,the addition of Massa Medicata Fermentata powder,the role of Alum in Pinelliae Rhizoma Fermentata and so on.

Objective:To investigate the current situation of the use of transjugular intrahepatic portosystemic shunt (TIPS) for portal hypertension, which should aid the development of TIPS in China.Methods:The China Portal Hypertension Alliance (CHESS) initiated this study that comprehensively investigated the basic situation of TIPS for portal hypertension in China through network research. The survey included the following: the number of surgical cases, main indications, the development of Early-TIPS, TIPS for portal vein cavernous transformation, collateral circulation embolization, intraoperative portal pressure gradient measurement, commonly used stent types, conventional anticoagulation and time, postoperative follow-up, obstacles, and the application of domestic instruments.Results:According to the survey, a total of 13 527 TIPS operations were carried out in 545 hospitals participating in the survey in 2021, and 94.1% of the hospital had the habit of routine follow-up after TIPS. Most hospitals believed that the main indications of TIPS were the control of acute bleeding (42.6%) and the prevention of rebleeding (40.7%). 48.1% of the teams carried out early or priority TIPS, 53.0% of the teams carried out TIPS for the cavernous transformation of the portal vein, and 81.0% chose routine embolization of collateral circulation during operation. Most of them used coils and biological glue as embolic materials, and 78.5% of the team routinely performed intraoperative portal pressure gradient measurements. In selecting TIPS stents, 57.1% of the hospitals woulel choose Viator-specific stents, 57.2% woulel choose conventional anticoagulation after TIPS, and the duration of anticoagulation was between 3-6 months (55.4%). The limitation of TIPS surgery was mainly due to cost (72.3%) and insufficient understanding of doctors in related departments (77.4%). Most teams accepted the domestic instruments used in TIPS (92.7%).Conclusions:This survey shows that TIPS treatment is an essential part of treating portal hypertension in China. The total number of TIPS cases is far from that of patients with portal hypertension. In the future, it is still necessary to popularize TIPS technology and further standardize surgical indications, routine operations, and instrument application.

Objective:To analyze the status of anemia at the beginning of dialysis in maintenance hemodialysis (MHD) adult patients, and to explore the relationship between early dialysis anemia and early survival and long-term survival.Methods:It was a retrospective cohort study. The baseline demographic and clinical data of newly admitted MHD patients from January 1, 2013 to December 31, 2020 were retrospectively analyzed. According to the hemoglobin (Hb) level at the beginning of dialysis, the patients were divided into high Hb group (Hb≥110 g/L), middle Hb group (80 g/L≤Hb<110 g/L) and low Hb group (Hb<80 g/L). The baseline data among the three groups were compared, and the changing trend of Hb level in MHD patients during the 8 years was analyzed. The follow-up ended at peritoneal dialysis, kidney transplantation, death or on December 31, 2021. All-cause death event within 6 months after the initiation of dialysis was defined as early death, while all-cause death event more than 6 months after the initiation of dialysis was defined as long-term death. Kaplan-Meier survival curve was used to analyze the survival rate, and log-rank test was used to compare the survival rates among the three groups. Multivariate Cox regression analysis model was used to analyze the association between anemia (Hb<110 g/L) at the beginning of dialysis and both early and long-term mortality.Results:A total of 36 216 MHD patients were included in this study, with age of (61.3±15.5) years old and 22 163 males (61.20%). The Hb at the beginning of dialysis was (89.33±20.89) g/L. The compliance rate of Hb (≥110 g/L) was 16.43% (5 952/36 216). There were 12 232 patients (33.78%), 18 032 patients (49.79%), and 5 952 patients (16.43%) in low Hb group, middle Hb group, and high Hb group, respectively. There were statistically significant differences in gender distribution, age, serum creatinine, blood phosphorus, blood calcium, C-reactive protein, intact parathyroid hormone, blood leukocytes, platelets, serum albumin, triglyceride, total cholesterol, and proportions of chronic glomerulonephritis, diabetic nephropathy, diabetes mellitus, cardiovascular and cerebrovascular diseases, tumors, emporary catheter, long-term catheter and autologous arteriovenous fistula among the three groups (all P<0.05). During the 8-year period, the Hb level had an increased trend steadily each year, and Hb was (88.48±22.07) g/L, (88.52±21.43) g/L, (87.86±21.29) g/L, (88.93±20.69) g/L, (88.87±20.69) g/L, (90.03±20.47) g/L, (90.74±20.31) g/L and (90.31±20.54) g/L year by year. There were 2 176 early deaths (6.01%), and 6 557 long-term deaths (18.10%) by the end of follow-up. Kaplan-Meier survival curve showed that early survival rate of low Hb group was significantly lower than those of high Hb group (log-rank test, χ2=57.115, P<0.001) and middle Hb group (log-rank test, χ2=49.918, P<0.001), and long-term survival rates of low Hb group (log-rank test, χ2=107.097, P<0.001) and middle Hb group (log-rank test, χ2=47.430, P<0.001) were significantly lower than that of high Hb group. Multivariate Cox regression analysis showed that Hb<80 g/L at the beginning of dialysis was an independent influencing factor of early death (Hb ≥110 g/L as a reference, HR=1.307, 95% CI 1.096-1.559), and 80 g/L≤Hb<110 g/L and Hb<80 g/L at the beginning of dialysis were the independent influencing factors of long-term death (Hb≥110 g/L as a reference, HR=1.108, 95% CI 1.021-1.203; HR=1.228, 95% CI 1.127-1.339, respectively) in MHD patients. Conclusions:The compliance rate of Hb at the beginning of dialysis in MHD patients is low. Hb <80 g/L at the beginning of dialysis is an independent risk factor of early death, and Hb <110 g/L at the beginning of dialysis is an independent risk factor of long-term death in MHD patients.

Objective To evaluate the pharmacokinetics characteristics of single-dose of Etripamil nasal spray 70 mg in healthy adult Chinese subjects.Methods This was a single-center,randomized,double-blind,placebo-controlled study.Twelve healthy adult Chinese subjects were randomized to receive single-dose of Etripamil nasal spray 70 mg(n=10)or placebo nasal spray(n=2).Blood and urine samples were collected prior and post dose.Etripamil in plasma and urine were analyzed by liquid chromatography-tandem mass spectrometry.The pharmacokinetic parameters were calculated by WinNonlin non-compartmental model.Results Following the single-dose of Etripamil nasal spray 70 mg in healthy adult Chinese subjects,the peak concentration of Etripamil in plasma was quickly attained,with a Cmax of(66.76±56.61)ng·mL-1 and a median(range)tmax of 4.00(3.00-5.00)min.The plasma concentrations of Etripamil had fallen approximately 65％from peak value at 25 min after dosing,and close to 80％within 50 min.The AUC0-last and AUC0-∞ were(3 104.16±2 654.46)and(4 048.77±2 682.38)ng·min·mL-1,respectively.The urine excretion percentage of Etripamil during 24 h was(0.01±0.01)％.Among the 12 subjects who were treated with Etripamil or placebo,10 subjects reported a total of 29 treatment-emergent adverse events(TEAEs).All of the TEAEs were mild in severity.The most common TEAEs were rhinorrhoea and lacrimation increased.Conclusion Etripamil was quickly absorbed after intranasal administration,followed by rapid distribution and elimination(not primarily excreted by renal);Etripamil 70 mg was safe and well tolerated by the healthy Chinese adult subjects.

Objective To investigate the role of caspase-1-medicated canonical pyroptosis pathway in chlorogenic acid(CGA)treatment of acute kidney injury(AKI)in mice.Method Twenty-four C57Bl/6J mice were randomized into sham-operated group,cecal ligation and puncture(CLP)group,CLP+dexamethasone group(CLP+DXM group),and CLP+CGA group(n=6)and subjected to either sham operation(laparotomy only)or CLP.After modeling the mice received intravenous infusion of 10 mg/kg normal saline(in sham and CLP groups),1 μg/kg dexamethasone or 15 mg/kg of chlorogenic acid for 6 h delivered using an intravenous pump.Eight hours after the infusion,renal morphology and histology,renal cell apoptosis,and the renal function parameters such as urea nitrogen(BUN),creatinine(Scr),and kidney injury molecule 1(KIM-1)were compared among the 4 groups;the 7-day survival rates of the mice were recorded,and the expressions of NLRP3 inflammasomes and key proteins of the caspase-1 pathway in the renal tissue were detected.Results CGA treatment significantly improved the 7-day survival rate,reduced renal pathologies of the septic mice(P<0.05),and lowered the levels of BUN,Scr,KIM-1,NLRP3 inflammasome and expressions of key proteins of the caspase-1 pathway.Conclusion CGA alleviates AKI in mice with CLP-induced sepsis by inhibiting NLRP3 inflammasomes and the caspase-1 signaling pathway.

Objective To construct a 3D printed PLLA/β-tricalcium(PLLA/β-TCP)bone tissue engineering scaffold surface porous structure through simple treatment with NaOH solution,increase the roughness and hydrophilicity of the scaffold,and promote cell adhesion on the scaffold surface.Methods The PLLA/β-TCP mesh scaffold was prepared by 3D printing melt deposition molding technology,and the scaffold was roughed by NaOH etching.The effects of NaOH concentration and time on the scaffold were observed according to the microstructure,energy spectrum,contact angle,mechanics,and cell adhesion of the scaffold.Results The PLLA/β-TCP composite scaffold constructed by melt deposition technology had a pre-set porous structure,and the pores were interconnected.After NaOH etching,a porous structure with both macroscopic and microscopic pores was formed.The increase in any of the NaOH concentration and time parameters would lead to the increase of pore diameter and surface roughness.When the NaOH treatment parameter was 0.1 mol/L(9 h),it could significantly reduce the water contact angle on the surface of the scaffold,and had no significant effect on the compressive strength of the scaffold.In vitro cell testing showed that the surface porous composite scaffold etched with NaOH had more advantages in the adhesion and proliferation of BMSCs.Conclusion Using NaOH to process 3D printing of PLLA/β-TCP bone tissue engineering scaffolds can effectively improve the surface morphology of the scaffold,and optimize its hydrophilicity and cell adhesion.

Objective To solve the problem of insufficient hydrophilicity on the surface of polycaprolactone(PCL)/β-TCP bone tissue engineering scaffolds,NaOH etching method was used to improve the surface microstructure of 3D printed PCL/β-TCP scaffolds,further affecting their hydrophilicity and cell response.Methods PCL/β-TCP mesh scaffolds were prepared using 3D printing melt deposition molding technology,and the surface roughness of the scaffolds was modified by NaOH etching.The effects of two reaction parameters,NaOH concentration and time,on the microstructure,spectral elements,contact angle,compressive strength,and cell adhesion of the scaffolds before and after modification were observed.Results After NaOH etching,the surface microporous structure of the mesh scaffold was successfully prepared.With the increase of either NaOH concentration or time,the surface micropores of the scaffold increased while the contact angle of the material surface decreased.However,the compression strength of the etched scaffold treated with NaOH for 1 mol/L(24 h)or 10 mol/L(6 h)was not statistically significant compared to the untreated group(P＞0.05).The number of cells on the etched scaffold increased,with a larger spreading area of individual cells,making it more advantageous in the adhesion and proliferation of BMSCs.Conclusion The use of NaOH etching to improve the hydrophilicity of 3D printed PCL/β-TCP bone tissue engineering scaffolds is a low-cost and effective strategy which can effectively improve the wettability and cell adhesion of the scaffolds.

Three-dimensional ordered porous carbon materials exhibit potential application prospects as excellent drug supports in drug delivery systems due to their high specific surface area, tunable pore structure, and excellent biocompatibility. In this study, three-dimensional ordered porous carbon materials were prepared using Acanthopanax senticosus herbal residues as raw material and KOH as activating agent through a one-step pyrolysis method. The prepared carbon-based material was systematically characterized by powder X-ray diffraction, scanning electron microscopy, N₂ adsorption-desorption and Fourier-transform infrared spectroscopy. The results show that the three-dimensional ordered porous carbon materials prepared with KOH as the activator via pyrolysis possess abundant functional groups, high porosity, and high specific surface area, with a specific surface area of 1 471.6 m²·g^-1. The three-dimensional ordered porous carbon materials prepared at 800 ℃ exhibits a high drug loading capacity (78.0%) and drug release rate (86.8%) for 5-fluorouracil. Three-dimensional orderly porous carbon materials show significant application advantages in drug construction, and their high specific surface area and adjustable pore size structure significantly improve the drug load rate and drug release rate, providing a solid foundation for the development of efficient and accurate drug delivery system.

Objective:To explore the role of mechanical hemodynamic support (MHS) in mapping and catheter ablation of patients with hemodynamically unstable ventricular tachycardia (VT), report single-center experience in a cohort of consecutive patients receiving VT ablation during MHS therapy, and provide evidence-based medical evidence for clinical practice.Methods:This was a retrospective cohort study. Patients with hemodynamically unstable VT who underwent catheter ablation with MHS at Beijing Anzhen Hospital, Capital Medical University between August 2021 and December 2023 were included. Patients were divided into rescue group and preventive group according to the purpose of treatment. Their demographic data, periprocedural details, and clinical outcomes were collected and analyzed.Results:A total of 15 patients with hemodynamically unstable VT were included (8 patients in the rescue group and 7 patients in the preventive group). The acute procedure was successful in all patients. One patient in the rescue group had surgical left ventricular assist device (LVAD) implantation, remaining 14 patients received extracorporeal membrane oxygenation (ECMO) for circulation support. ECMO decannulation was performed in 12 patients due to clinical and hemodynamic stability, of which 6 patients were decannulation immediately after surgery and the remaining patients were decannulation at 2.0 (2.5) d after surgery. Two patients in the rescue group died during the index admission due to refractory heart failure and cerebral hemorrhage. During a median follow-up of 30 d (1 d to 12 months), one patient with LVAD had one episode of ventricular fibrillation at 6 months after discharge, and no further episodes of ventricular fibrillation and/or VT occurred after treatment with antiarrhythmic drugs. No malignant ventricular arrhythmia occurred in the remaining 12 patients who were followed up.Conclusions:MHS contributes to the successful completion of mapping and catheter ablation in patients with hemodynamically unstable VT, providing desirable hemodynamic status for emergency and elective conditions.