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.

The gut microbiota regulates intestinal nutrient absorption, participates in modulating host glucolipid metabolism, and contributes to ameliorating glucolipid metabolism disorder. Dysbiosis of the gut microbiota can compromise the integrity of the intestinal mucosal barrier, induce inflammatory responses, and exacerbate insulin resistance and abnormal lipid metabolism in the host. Dangua Humai Oral Liquid, a hospital-developed formulation for regulating glucolipid metabolism, has been granted a national invention patent and demonstrates significant clinical efficacy. This study aimed to investigate the effects of Dangua Humai Oral Liquid on gut microbiota and the intestinal mucosal barrier in a mouse model with glucolipid metabolism disorder. A glucolipid metabolism disorder model was established by feeding mice a high-glucose and high-fat diet. The mice were divided into a normal group, a model group, and a treatment group, with eight mice in each group. The treatment group received a daily gavage of Dangua Humai Oral Liquid(20 g·kg~(-1)), while the normal group and model group were given an equivalent volume of sterile water. After 15 weeks of intervention, glucolipid metabolism, intestinal mucosal barrier function, and inflammatory responses were evaluated. Metagenomics and untargeted metabolomics were employed to analyze changes in gut microbiota and associated metabolic pathways. Significant differences were observed between the indicators of the normal group and the model group. Compared with the model group, the treatment group exhibited marked improvements in glucolipid metabolism disorder, alleviated pathological damage in the liver and small intestine tissue, elevated expression of recombinant claudin 1(CLDN1), occluding(OCLN), and zonula occludens 1(ZO-1) in the small intestine tissue, and reduced serum levels of inflammatory factors lipopolysaccharides(LPS), lipopolysaccharide-binding protein(LBP), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α). At the phylum level, the relative abundance of Bacteroidota decreased, while that of Firmicutes increased. Lipid-related metabolic pathways were significantly altered. In conclusion, based on the successful establishment of the mouse model of glucolipid metabolism disorder, this study confirmed that Dangua Humai Oral Liquid effectively modulates gut microbiota and mucosal barrier function, reduces serum inflammatory factor levels, and regulates lipid-related metabolic pathways, thereby ameliorating glucolipid metabolism disorder.
Animals ; Gastrointestinal Microbiome/drug effects* ; Mice ; Intestinal Mucosa/microbiology* ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Mice, Inbred C57BL ; Humans ; Glycolipids/metabolism* ; Lipid Metabolism/drug effects* ; Administration, Oral ; Disease Models, Animal

OBJECTIVE: To observe the clinical symptoms and MRI outcomes of patients with ruptured lumbar disc herniation(LDH) through a multicenter randomized controlled study, and to evaluate the clinical efficacy and safety of Yiqi Huoxue formula() in the treatment of this disease. METHODS: A total of 160 outpatients and inpatients with ruptured LDH admitted to 4 medical centers from January 2023 to June 2023 were selected and randomly divided into the Yiqi Huoxue formula group and the control group, with 80 patients in each group. In the Yiqi Huoxue formula group, there were 43 males and 37 females, with an age of (41.03±9.56) years and a disease duration of (10.45±25.37) days, and the patients were treated with Yiqi Huoxue formula. In the control group, there were 34 males and 46 females, with an age of (42.14±8.73) years and a disease duration of (11.31±21.14) days;during the acute phase, patients in this group could take celecoxib capsules orally, and methylcobalamin orally at the same time. The Japanese Orthopaedic Association (JOA) score, Oswestry disability index (ODI), changes in the volume of herniated disc tissue on MRI, herniation rate, and absorption rate were recorded at the time of enrollment and during follow-ups at the 3rd, 6th, and 12th month after treatment. RESULTS: A total of 156 patients completed the clinical follow-up, and 4 patients withdrew midway. The clinical symptoms of all patients who completed the study were relieved to varying degrees, and reabsorption of herniated disc tissue was observed in all patients in the Yiqi Huoxue formula group after treatment. For the JOA score:in the Yiqi Huoxue formula group, it was (10.73±2.76) points before treatment and (24.65±2.19) points at the 12th month after treatment;in the control group, it was (11.01±1.20) points before treatment and (17.07±3.26) points at the 12th month after treatment. For the ODI score:in the Yiqi Huoxue formula group, it was (26.21±3.55) points before treatment and (5.65±2.19) points at the 12th month after treatment;in the control group, it was (27.92±2.51) points before treatment and (9.09±2.15) points at the 12th month after treatment. At the 12th month after treatment, the JOA and ODI scores of both groups were better than those before treatment, and the scores of the Yiqi Huoxue formula group were better than those of the control group, with statistically significant differences (P<0.05). In terms of the herniated disc volume and herniation rate on MRI, the Yiqi Huoxue formula group was superior to the control group, with statistically significant differences(P<0.05). Reabsorption occurred in 56.96%(45/79) of patients in the Yiqi Huoxue formula group, which was significantly higher than the 37.66%(29/77) in the control group. CONCLUSION After treatment with Yiqi Huoxue formula, patients with ruptured LDH show significant improvement in clinical symptoms and a marked reduction in the volume of herniated discs. During the follow-up period, no obvious adverse drug reactions are observed in patients, and no recurrence of symptoms is found at the last follow-up, indicating that the formula has safe and reliable efficacy.
Humans ; Male ; Female ; Intervertebral Disc Displacement/drug therapy* ; Adult ; Drugs, Chinese Herbal/adverse effects* ; Middle Aged ; Lumbar Vertebrae

Case 1: A 19-day-old male infant presented with poor feeding and decreased activity for 2 weeks, worsening with poor responsiveness for 3 days. At 5 days old, he developed poor feeding and poor responsiveness, was hospitalized, and was found to have elevated blood ammonia and thrombocytopenia. Whole-genome genetic analysis revealed a pathogenic homozygous mutation in the PCCA gene, NM-000282.4: c.1834-1835del (p.Arg612AspfsTer44), leading to a diagnosis of propionic acidemia. Case 2: A 4-day-old male infant presented with poor responsiveness and feeding difficulties since birth, with elevated blood ammonia for 1 day. He showed weak sucking and deteriorating responsiveness, with blood ammonia >200 µmol/L. Genetic testing identified two heterozygous mutations in the MMUT gene: NM_000255.4: c.1677-1G>A and NM_000255.4: ex.5del, confirming methylmalonic acidemia. Case 3: A 20-day-old male infant presented with poor feeding for 15 days and skin petechiae for 8 days. He developed feeding difficulties at 5 days old and lower limb petechiae at 12 days old, with blood ammonia measured at 551.6 µmol/L. Genetic analysis found two heterozygous mutations in the PCCA gene: NM_000282.4: c.1118T>A (p.Met373Lys) and NM_000282.4: ex.16-18del, confirming propionic acidemia. In the first two cases, continuous hemodiafiltration was performed for 30 hours and 20 hours, respectively, before administering carglumic acid. In the third case, carglumic acid was administered orally without continuous hemodiafiltration, resulting in a decrease in blood ammonia from 551.6 µmol/L to 72.0 µmol/L within 6 hours, with a reduction rate of approximately 20-25 µmol/(kg·h), similar to the first two cases. Carglumic acid was effective in all three cases, suggesting it may help optimize future treatment protocols for organic acidemia.
Humans ; Male ; Infant, Newborn ; Propionic Acidemia/drug therapy* ; Amino Acid Metabolism, Inborn Errors/genetics* ; Mutation ; Methylmalonyl-CoA Decarboxylase/genetics* ; Citrates/administration & dosage* ; Carbon-Carbon Ligases/genetics* ; Glutamates

OBJECTIVE: To explore the application of targeted mRNA sequencing in fusion gene diagnosis of hematologic diseases. METHODS: Bone marrow or peripheral blood samples of 105 patients with abnormally elevated eosinophil proportions and 291 acute leukemia patients from January 2015 to June 2023 in the First Affiliated Hospital of Soochow University were analyzed and gene structural variants were detected by targeted mRNA sequencing. RESULTS: Among 105 patients with abnormally elevated eosinophil proportions, 6 cases were detected with gene structural variants, among which fusion gene testing results in 5 cases could serve as diagnostic indicators for myeloid neoplasms with eosinophilia. In addition, a IL3∷ETV6 fusion gene was detected in one patient with chronic eosinophilic leukemia, not otherwise specified. Among 119 patients with acute myeloid leukemia (AML), 38 cases were detected structural variants by targeted mRNA sequencing, accounting for 31.9%, which was significantly higher than 20.2% (24/119) detected by multiple quantitative PCR (P < 0.05). We also found one patient with AML had both NUP98∷PRRX2 and KCTD5∷JAK2 fusion genes. A total of 104 patients were detected structural variants by targeted mRNA sequencing in 172 cases with acute B-lymphoblastic leukemia who were tested negative by multiple quantitative PCR, with a detection rate of 60.5% (102/172). CONCLUSION Targeted mRNA sequencing can effectively detect fusion gene and has potential clinical application value in diagnosis and classificatation in hematologic diseases.
Humans ; Hematologic Diseases/diagnosis* ; RNA, Messenger/genetics* ; Oncogene Proteins, Fusion/genetics* ; Sequence Analysis, RNA ; Leukemia, Myeloid, Acute/diagnosis*

BACKGROUND: Cardiovascular disease (CVD) is the predominant cause of mortality in China. However, the mechanisms linking sarcopenia to CVD remain poorly understood, particularly in normal-weight populations. Individuals with the absence of overweight or obesity may tend to experience missed opportunities for timely intervention. This study aimed to investigate the longitudinal association between sarcopenia and incidence of new-onset CVD in a normal-weight population, and to examine the mediating effect of functional limitation in this relationship. METHODS: We conducted a closed-cohort analysis using a nationwide sample of 4,147 middle-aged and older adults with normal weight in China. We performed Cox proportional hazards regression analysis to explore the associations of baseline sarcopenia with incident CVD. The difference method was applied to estimate the mediation proportion of functional limitation in this association. RESULTS: Over a mean follow-up period of 7.62 years, CVD occurred in 835 participants. In the multivariable-adjusted Cox model, individuals with sarcopenia exhibited a significantly higher likelihood of developing incident CVD compared to those without sarcopenia (adjusted hazard ratio [aHR] = 1.45, 95% confidence interval [CI]: 1.21-1.73, P < 0.001). Similar associations were observed for the incidence of heart disease and stroke. Functional limitation accounted for approximately 15.0% of the total effect of sarcopenia on incident CVD (P < 0.001). CONCLUSIONS Sarcopenia exerts both direct and indirect effects on incident CVD among middle-aged and older adults who are normal weight, with functional limitation serving as a significant mediator. Interventions targeting both sarcopenia and functional limitation may offer a promising strategy for enhancing cardiovascular health in this population.
Humans ; Sarcopenia/complications* ; China/epidemiology* ; Male ; Female ; Middle Aged ; Cardiovascular Diseases/etiology* ; Aged ; Incidence ; Cohort Studies ; Proportional Hazards Models ; Risk Factors ; Aged, 80 and over ; Longitudinal Studies

OBJECTIVES: To determine the pharmacological impact of hesperidin, the main component of Citri Reticulatae Pericarpium, on depressive behavior and elucidate the mechanism by which hesperidin treats depression, focusing on the gut-brain axis. METHODS: Fifty-four Sprague Dawley male rats were randomly allocated to 6 groups using a random number table, including control, model, hesperidin, probiotics, fluoxetine, and Citri Reticulatae Pericarpium groups. Except for the control group, rats in the remaining 5 groups were challenged with chronic unpredictable mild stress (CUMS) for 21 days and housed in single cages. The sucrose preference test (SPT), immobility time in the forced swim test (FST), and number in the open field test (OFT) were performed to measure the behavioral changes in the rats. Enzyme-linked immunosorbent assay was used to determine the levels of 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor (BDNF) in brain tissue, and the histopathology was performed to evaluate the changes of colon tissue, together with sequencing of the V3-V4 regions of 16S rRNA gene on feces to explore the changes of intestinal flora in the rats. RESULTS: Compared to the control group, the rats in the model group showed notable reductions in body weight, SPF, and number in OFT (P<0.01). Hesperidin was found to ameliorate depression induced by CUMS, as seen by improvements in body weight, SPT, immobility time in FST, and number in OFT (P<0.05 or P<0.01). Regarding neurotransmitters, it was found that at a dose of 50 mg/kg hesperidin treatment upregulated the levels of 5-HT and BDNF in depressed rats (P<0.05). Compared to the control group, the colon tissue of the model group exhibited greater inflammatory cell infiltration, with markedly reduced numbers of goblet cells and crypts and were significantly improved following treatment with hesperidin. Simultaneously, the administration of hesperidin demonstrated a positive impact on the gut microbiome of rats treated with CUMS, such as Shannon index increased and Simpson index decreased (P<0.01), while the abundance of Pseudomonadota and Bacteroidota increased in the hesperidin-treated group (P<0.05). CONCLUSION The mechanism responsible for the beneficial effects of hesperidin on depressive behavior in rats may be related to inhibition of the expressions of BDNF and 5-HT and preservation of the gut microbiota.
Animals ; Hesperidin/therapeutic use* ; Rats, Sprague-Dawley ; Depression/drug therapy* ; Male ; Stress, Psychological/drug therapy* ; Brain/metabolism* ; Brain-Derived Neurotrophic Factor/metabolism* ; Serotonin/metabolism* ; Gastrointestinal Microbiome/drug effects* ; Behavior, Animal/drug effects* ; Rats ; Brain-Gut Axis/drug effects* ; Chronic Disease ; Colon/drug effects*

Objective To explore the efficacy of using a single branch stent-graft to treat primary intramural hematoma located at the distal arch or descending aorta in Stanford A type aortic intramural hematoma. Methods From July 2020 to November 2022, 10 patients with primary intramural hematoma of Stanford A type aortic intramural hematoma were treated with endovascular repair using a single branch stent-graft in the Department of Cardiovascular Surgery at The University of Hong Kong-Shenzhen Hospital. There were 9 males and 1 female, aged from 32 to 66 years, with a mean age of (47.0±10.4) years. All patients had intramural hematoma involving the ascending aorta and aortic arch, diagnosed as type A intramural hematoma, with the tear located in the descending aorta. Among them, 6 patients were complicated by ulceration of the descending aorta with intramural hematoma, and 4 patients had changes of the descending aortic dissection. All patients underwent endovascular stent repair, with 8 patients undergoing emergency surgery (≤14 days) and 2 patients undergoing subacute surgery (15 days to 3 months). Results There were no neurological complications, paraplegia, stent fracture or displacement, or limb or visceral ischemia during the perioperative period in all patients. One patient had continuous chest pain after surgery, and the stent had a new tear at the proximal end, requiring ascending aorta and partial arch replacement. As of the latest follow-up, all patients had obvious absorption or complete absorption of the intramural hematoma in the ascending aorta and aortic arch compared with before the operation. Conclusion Single branch stent-graft treatment of retrograde ascending aortic intramural hematoma is safe and effective, with good short-term results.

Objective To analyze the lung function condition and the prevalence of pulmonary ventilation disorders in the occupational population of Wuhan, and to explore their influencing factors. Methods Physical examination data from the Wuhan Prevention and Treatment Center for Occupational Diseases were used in this study, and finally 9499 people were selected as the study subjects. The linear regression model and logistic regression model were used to analyze the influencing factors of pulmonary ventilation function and pulmonary dysfunction. The restricted cubic spline was used to explore the nonlinear relationship. Results The prevalence of pulmonary ventilation disorders was 1.7%, and the lung function indexes FVC, FEV1, and FEV1/FVC were significantly lower in the population aged >27 years than in the population aged <27 years (P<0.001). The lung function indexes FVC and FEV1 were significantly lower in females than in males (P<0.001). The lung function indexes FVC and FEV1 were significantly lower in underweight occupational groups than in normal-weight groups (P<0.001), and FVC and FEV1 were significantly lower in dust-exposed occupational groups than in groups without dust exposure(P<0.05). Restricted cubic spline plots showed a nonlinear relationship between age and lung function indexes FVC and FEV1 (P_nonlinear< 0.05). Age and BMI were the risk factors for pulmonary ventilation disorders. Conclusion Age, gender, BMI, and dust exposure are risk factors for decreased FVC and FEV1. Age is the risk factor for decreased FEV1/FVC. Age and BMI are the risk factors for pulmonary ventilation disorders.