Peptide-based therapies have attracted considerable interest in the treatment of cancer, diabetes, bacterial infections, and neurodegenerative diseases due to their promising therapeutic properties and enhanced safety profiles. This review provides a comprehensive overview of the major trends in peptide drug discovery and development, emphasizing preclinical strategies aimed at improving peptide stability, specificity, and pharmacokinetic properties. It assesses the current applications and challenges of peptide-based drugs in these diseases, illustrating the pharmaceutical areas where peptide-based drugs demonstrate significant potential. Furthermore, this review analyzes the obstacles that must be overcome in the future, aiming to provide valuable insights and references for the continued advancement of peptide-based drugs.
Humans ; Peptides/pharmacology* ; Animals ; Neoplasms/drug therapy* ; Drug Discovery ; Neurodegenerative Diseases/drug therapy* ; Diabetes Mellitus/drug therapy*

Objective:To study anti-tumor effect of Dunhuang medical prescription Dabupi Decoction on gastric cancer-bearing mice and effect of Dabupi Decoction combined with oxaliplatin on inflammatory immunity of gastric cancer-bearing mice based on IL-17/NF-κB signaling pathway.Methods:Mouse model of MFC gastric cancer subcutaneously bearing tumor was established and ran-domly divided into model group,oxaliplatin group,high,medium and low doses of Dabupi Decoction combined with oxaliplatin groups[21.58,10.79,5.40 g/(kg·d)],with 10 mice in each group,male and female cage rearing.Administration began after 8 days of inoculation and continued for 14 days;next day after the last administration,eyeball blood was taken,mice were killed,tumor tissues were taken and weighed,and tumor inhibition rate was calculated.ELISA was used to detect contents of IL-17 and IL-6 in mice serum,immunohistochemistry(IHC),RT-qPCR and Western blot were used to detect IL-17,IL-6,NF-κB and p-NF-κB mRNA and protein expressions in mice tumor tissues,respectively.Results:Tumor inhibition rates of oxaliplatin group,high,medium and low doses of Dabupi decoction combined with oxaliplatin groups were 33.02%,52.92%,46.33%and 39.52%,respectively,and tumor quality of each treatment group was significantly lower than that of model group(P<0.01).High,medium and low doses of Dabupi Decoction combined with oxaliplatin groups were higher than that of oxaliplatin group.Compared with model group,contents of IL-17 and IL-6 in serum and expressions of IL-17,IL-6,NF-κB p65 and pNF-κB p65 mRNA and protein in tumor tissues in each treatment group were significantly reduced(P<0.01,P<0.05).Compared with oxaliplatin group,levels of IL-17 and IL-6 in serum and expres-sions of IL-17,IL-6,NF-κB p65 and pNF-κB p65 mRNA and protein in tumor tissues in high and medium doses of Dabupi Decoction combined with oxaliplatin groups were significantly reduced(P<0.01,P<0.05).Conclusion:Dunhuang medical prescription Dabupi Decoction has a certain anti-tumor effect on MFC gastric cancer-bearing mice,which can regulate inflammatory immunity and inhibit occurrence and development of gastric cancer by inhibiting IL-17/NF-κB signaling pathway.

Objective:To investigate whether end-tidal carbon dioxide (etCO 2) is associated with acute kidney injury (AKI) after liver transplantation. Methods:Clinical data of 83 patients undergoing classic allogeneic liver transplantation were retrospectively collected. Patients were divided into AKI group and non AKI group based on changes in serum creatinine levels within 48 hours after surgery, and differences in baseline data, intraoperative etCO 2 decrease rate [ΔetCO 2(%)], and postoperative creatinine values were analyzed between the groups. Results:The incidence of AKI within 48 hours after liver transplantation in 83 patients was 56.6%(47/83). The proportion of male patients in the AKI group was higher ( P=0.003), and the ΔetCO 2(%) in the anhepatic phase of AKI group patients was higher than that of non AKI patients [(0.26±0.08)% vs (0.22±0.07)%, P=0.024]. There was no statistically significant difference in ΔetCO 2(%) between the two groups during pre liver, inferior vena cava (IVC) occlusion, and new liver phase (all P>0.05). On the 7th day after surgery, the creatinine value in the AKI group was significantly higher than that in the non AKI group [68.7(55.4, 92.6)]μmol/L vs 52.7(44.1, 69.3)μmol/L, P<0.001], at a 3-month follow-up, creatinine levels in 43 patients (91.5%) in the AKI group returned to normal. Conclusions:The decrease in ΔetCO 2(%) during the anhepatic phase of liver transplantation reflects to some extent the severe fluctuations in circulation during the operation, which may be related to the occurrence of AKI within 48 hours after surgery.

Background/Aims: To evaluate the causal correlation between complement components and non-viral liver diseases and their potential use as druggable targets. Methods: We conducted Mendelian randomization (MR) to assess the causal role of circulating complements in the risk of non-viral liver diseases. A complement-centric protein interaction network was constructed to explore biological functions and identify potential therapeutic options. Results: In the MR analysis, genetically predicted levels of complement C1q C chain (C1QC) were positively associated with the risk of autoimmune hepatitis (odds ratio 1.125, 95% confidence interval 1.018–1.244), while complement factor H-related protein 5 (CFHR5) was positively associated with the risk of primary sclerosing cholangitis (PSC;1.193, 1.048– 1.357). On the other hand, CFHR1 (0.621, 0.497–0.776) and CFHR2 (0.824, 0.703–0.965) were inversely associated with the risk of alcohol-related cirrhosis. There were also significant inverse associations between C8 gamma chain (C8G) and PSC (0.832, 0.707–0.979), as well as the risk of metabolic dysfunction-associated steatotic liver disease (1.167, 1.036–1.314). Additionally, C1S (0.111, 0.018–0.672), C7 (1.631, 1.190–2.236), and CFHR2 (1.279, 1.059–1.546) were significantly associated with the risk of hepatocellular carcinoma. Proteins from the complement regulatory networks and various liver diseaserelated proteins share common biological processes. Furthermore, potential therapeutic drugs for various liver diseases were identified through drug repurposing based on the complement regulatory network. Conclusions Our study suggests that certain complement components, including C1S, C1QC, CFHR1, CFHR2, CFHR5, C7, and C8G, might play a role in non-viral liver diseases and could be potential targets for drug development.

Objective:To explore the effects of the deep inspiration breath-hold (DIBH) technique on cardiac dosimetry in internal mammary node irradiation with intensity-modulated radiation therapy (IMN-IMRT) for postoperative left breast cancer.Methods:Totally 23 left breast cancer patients in the First Affiliated Hospital of Bengbu Medical College from Octorber 2021 to July 2022 receiving postoperative IMN-IMRT were enrolled in this study. The changes in dosimetric parameters for their heart and left anterior descending coronary artery (LAD) in the DIBH mode were observed, and the potential factors affecting DIBH effects were analyzed.Results:Compared with the free breath (FB) mode, the DIBH mode manifested a heart volume decrease by 18% ( t = 10.47, P < 0.001), a left lung volume increase by 42% ( t = -14.55, P < 0.001), and significantly reduced dosimetric parameters ( Dmean, Dmax, V5- V30) for the heart and LAD, exhibiting statistically significant differences ( t=-13.38 to -3.30, P<0.05). As indicated by the Pearson correlation analysis, the relative ratio of cardiac dose reduction was positively correlated with that of left lung expansion ( r = 0.82, P < 0.001) and negatively correlated with the patient′age ( r = -0.56, P = 0.005). Conclusions:DIBH can effectively reduce the heart and LAD radiation doses in IMN-IMRT for postoperative left breast cancer and that the patient's age, and the DIBH effects might be affected by the vital capacity.

Objective:To predicate whether China can achieve the United Nations Sustainable Development Goals (SDGs) 3.4.1 to reduce the age-standardized mortality rate of four major non-communicable diseases (NCDs) in residents aged 30-70 years by 2030 based on the trend of the mortality from 1990 to 2019.Methods:We collected the mortality data on cardiovascular diseases, cancers, chronic respiratory diseases, and diabetes by age, gender and year in China from the Global Disease Burden Study 2019 (GBD2019). The age-period-cohort (APC) Bayesian model was applied for modeling the age-standardized mortality rate of four major NCDs in China during 2020-2030 according to the trend of the mortality during 1990-2019, and comparing the predicted value in 2030 with the observed value in 2015 to evaluate the possibility of achieving SDGs 3.4.1.Results:The age-standardized mortality rate of the four major NCDs in China showed a downward trend during 1990-2019. It is predicted that the number of death of the four NCDs in Chinese residents aged 30-70 years would increase from 2.96 million in 2020 to 3.19 million in 2030, while the age-standardized mortality rate would decrease from 308.49/100 000 in 2020 to 277.80/100 000 in 2030. The age-standardized mortality rate in 2030 would only decrease by 15.94% (18.73% for males and 14.31% for females) compared with 330.46/100 000 in 2015, with a 25.09% decrease for cardiovascular diseases, 4.76% for cancers, 37.21% for chronic respiratory diseases, and unchanged for diabetes.Conclusion:Although the age-standardized mortality rate of four major NCDs declined from 1990 to 2019 in China, it is difficult to achieve the SDGs of a 1/3 mortality rate reduction by 2030 according to the current declining trend, suggesting more active and effective efforts for NCD prevention and control are needed.

Abstract Ischemic stroke is characterized by high morbidity, disability and mortality. At present, there is a lack of effective treatment for ischemic stroke, so it is of great significance to reduce the incidence risk of ischemic stroke. Studies show that vitamin C can prevent atherosclerosis, thus reduce the incidence risk of ischemic stroke. However, this point is controversial due to the differences of study population, inconsistent evaluation methods of vitamin C content and the influence of various confounding factors. This paper reviews the related animal experiments, clinical trials and cohort studies, in order to provide reference for subsequent studies on reducing the incidence risk of ischemic stroke.

Objective:To analyze the clinical and pathological features and gene mutations of pancreatic acinar cell carcinoma (PACC).Methods:Clinical data of 34 patients with PACC admitted to the Department of Pancreatic Surgery of the First Affiliated Hospital of Naval Medical University from December 2009 to July 2018 were retrospectively analyzed to summarize its clinical characteristics, and the expressions of α1-ACT, CaM5.2, Syn and CgA in pancreatic tumor tissues were detected by immunohistochemistry. Next-generation gene sequencing technology was used to detect gene mutations in tumor specimens.Results:Among the 34 PACC patients, 23(68%) were males and 11(32%) were females; the age ranged from 25 to 75 years, with an average age of 54 years. The first symptom was abdominal pain or distension in 21 cases (62%), skin or scleral yellow staining in 4 cases(12%), and 9 cases(26%) were found in routine physical examination. BMI was 17.6-34.0 kg/m 2, of which 3 cases (9%) were <18.5 kg/m 2, 23 cases (68%) were 18.5-24.0 kg/m 2, and 8 cases (23%) were >24.0 kg/m 2. Preoperative examination showed elevated CA19-9 in 7 cases (20.6%), elevated CEA in 3 cases (8.8%), and elevated AFP in 7 cases (20.6%). Blood amylase was 16-247 U/L, with an average of 80 U/L. Enhanced CT showed that the lesion was irregular in shape, showing inhomogeneity and slightly low density, with areas of cystic degeneration and necrosis. The tumor was located in the head of the pancreas in 14 cases (41%), the body and tail of the pancreas in 19 cases (56%), and the neck of the pancreas in 1 case (3%). The largest tumor diameter was 1.5-15.5 cm, with an average of 5.4 cm. Postoperative pathologic stage I was confirmed in 4 cases (12%), stage Ⅱ in 14 cases (41%), stage Ⅲ in 14 cases (41%) and stage Ⅳ in 2 cases (6%). Immunohistochemical results showed that both α1-ACT and CaM5.2 were positively expressed (100%). Syn was positive in 8 cases (23.5%) and CgA was positive in 6 cases (17.6%). Ki-67 index was from 9% to 70%, with an average of 41%. Gene sequencing of pancreatic tumor tissue from 6 patients showed BRCA2 mutation in 2 patients (7155C>G), K-ras mutation in 1 patient (35G>T), RET mutation in 1 patient (200G>A), and LKB1 mutation (234G>T) in 1 patient, and one double mutation of K-ras and RET (35G>A, 1 798C>T). 30 patients were followed up, and the median survival was 38.3 months. Conclusions:PACC was a rare pancreatic tumor with no specific clinical manifestations. The positive expression rates of α1-ACT and CAM5.2 in tumor tissues were 100%. BRCA2, K-ras, RET and LKB1 were common gene mutations.

Objective:To explore the safety and clinical efficacy of orthotopic liver transplantation after treatment with gelatin sponge microparticles by transcatheter arterial chemoembolization (GSMs-TACE) for hepatocellular carcinoma with type II/III portal vein tumor thrombus.Methods:For this retrospective study, patients with hepatocellular carcinoma with portal vein tumor thrombosis undergoing GSMs-TACE before liver transplantation from January 2018 to June 2018. The clinical efficacy and safety were evaluated by alpha feto-protein (AFP), imaging changes, postoperative complications and survival time.Results:The median follow-up period was 24 months. The average number of GSMs-TACE was 1.5. No postoperative complications such as biliary fistula, abdominal hemorrhage, liver and kidney failure, arterial stenosis and biliary stricture occurred. After GSMs-TACE, there were varying degrees of tumor necrosis or thrombus, AFP decreased (n=5) and PIVKAII declined (n=7). The 1-year survival rate was 100% and the 1-year disease-free survival rate 71.4%. For two cases of lung metastasis, the recurrent time was 4 and 10 months respectively.Conclusions:GSMs-TACE plus liver transplantation offer good safety and clinical efficacy for hepatocellular carcinoma patients with portal vein cancer thrombus.