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.

Objective:To systematically evaluate the effect of cognitive behavioral therapy (CBT) in elderly patients with depression.Methods:The randomized controlled trials on the effect of CBT in elderly patients with depression, published until December 15, 2022, were searched in PubMed, CINHAL, Cochrane Library, China Biology Medicine, China National Knowledge Infrastructure, WanFang Data, and VIP. Two researchers independently screened the literature, extracted data, and used the revised Cochrane risk of bias tool for randomized trials (ROB 2.0) to evaluate the quality of the included studies. Statistical analysis was conducted using Stata 16.0, and the quality of evidence was rated using Appraisal of Guidelines for Research and Evaluation (GRADE) predictor software.Results:A total of 11 randomized controlled trials were included, with a total of 833 elderly patients with depression. Randomized effect models were used to analyze outcome indicators such as depression, anxiety, and quality of life by combining effect quantities. Meta-analysis and GRADE evidence quality showed that compared to the control group, medium quality evidence showed that CBT could relieve depression in elderly depression patients with a statistical difference [ SMD=-1.58, 95% CI (-2.16, -0.99), P<0.05]. Low quality evidence suggested that CBT could alleviate anxiety in elderly depression patients also with a statistical difference [ SMD=-2.25, 95% CI (-4.04, -0.47), P<0.05]. Very low quality evidence indicated that CBT did not significantly improve the quality of life in elderly depression patients compared to conventional or pharmacological treatment [ SMD=-0.09, 95% CI (-2.07, 1.88), P>0.05] . Conclusions:Existing evidence suggests that CBT can alleviate depression and anxiety in elderly depression patients, but its improvement in quality of life is not yet significant. Treatment feedback and forms of CBT may become a research focus in recent years on intervention for elderly depression patients.

Objective:To analyze the occurrence of concomitant gene mutations in cytogenetically normal acute myeloid leukemia(CN-AML)patients with CEBPA mutation and its impact on the clinical characteristics and prognosis of the patients.Methods:151 newly diagnosed patients with CN-AML in the Second Hospital of Shanxi Medical University from June 2013 to June 2020 were analyzed retrospectively.34 common genetic mutations associated with hematologic malignancies were detected by next-generation sequencing technology.The occurrence of concomitant gene mutations in patients with CEBPA positive and negative groups was compared,and the correlation between concomitant mutations in different functional groups and the clinical characteristics and prognosis of CN-AML patients with CEBPA mutation was analyzed.Results:In 151 patients with CN-AML,55(36.42％)were positive for CEBPA mutation(including 36 cases of CEBPAdm and 19 cases of CEBPAsm),of which 41(74.55％)had co-mutations with other genes.The main mutated genes were GATA2(25.45％,14/55),TET2(21.82％,12/55),FLT3(20.00％,11/55),NRAS(12.73％,7/55)and WT1(9.09％,9/55),etc.Some cases had two or more concomitant gene mutations.Grouping the mutant genes according to their functions showed that CEBPA+group had lower mutation rates of histone methylation(P=0.002)and chromatin modification genes(P=0.002,P=0.033),and higher mutation rates of transcription factors(P=0.037)than CEBPA-group.In 55 patients with CEBPA+CN-AML,the platelet count at diagnosis in signaling pathway gene mutation-positive group was lower than that in the mutation-negative group(P=0.005),the proportion of bone marrow blasts in transcription factor mutation-positive group was higher than that in the mutation-negative group(P=0.003),and the onset age in DNA methylation gene mutation-positive group and chromatin modifier mutation-positive group was older than that in the mutation-negative group,respectively(P=0.002,P=0.008).DFS of CEBPA+CN-AML patients in signaling pathway gene mutation group was shorter than that in signaling pathway gene mutation-negative group(median DFS:12 months vs not reached)(P=0.034).Compared with DNA methylation gene mutation-negative group,CEBPA+CN-AML patients with DNA methylation gene mutation had lower CR rate(P=0.025)significantly shorter OS and DFS(median OS:20 months vs not reached,P=0.006;median DFS:15 months vs not reached,P=0.049).OS in patients with histone methylation gene mutation was significantly shorter than that in the histone methylation gene mutation-negative group(median OS:12 months vs 40 months)(P=0.008).Multivariate analysis of prognostic factors showed that the proportion of bone marrow blasts(P=0.046),concomitant DNA methylation gene mutation(P=0.006)and histone methylation gene mutation(P=0.036)were independent risk factors affecting the prognosis.Conclusion:CN-AML patients with CEBPA mutation have specific concomitant gene profile,and the concomitant mutations of different functional genes have a certain impact on the clinical characteristics and prognosis of the patients.

OBJECTIVE: To observe the effects of electroacupuncture at "Siguan" points on behavior, colonic 5-hydroxytryptamine (5-HT) and fecal short-chain fatty acids (SCFAs) in rats with post-stroke depression (PSD), and explore the effect mechanism of electroacupuncture at Siguan points on PSD. METHODS: Fifty SD rats were randomly divided into a sham-operation group, a stroke group, a PSD group, a drug group and an electroacupuncture group, with 10 rats in each one. The stroke model was established by middle cerebral artery occlusion (MCAO) method in the stroke group; except for the sham-operation group, the rats in the other groups were intervened with MCAO combined with solitary and chronic unpredictable mild stress (CUMS) to establish PSD model. In the electroacupuncture group, electroacupuncture was delivered at "Hegu" (LI 4) and "Taichong" (LR 3), with disperse-dense wave, 2 Hz/10 Hz in frequency, for 30 min in each intervention, once daily, for consecutive 21 days. Simultaneously, distilled water (0.01 L•kg^-1•d^-1) was administrated intragastrically. Fluoxetine solution (2.33 mg•kg^-1•d^-1) was given by gavage , once a day and for 21 days in the drug group. The same procedure of fixation and gavage with distilled water were adopted in the sham-operation group, the stroke group and the PSD group. Separately, before stroke modeling, after PSD modeling and after 21-day intervention, the consumption of sugar water and the scores of horizontal movement and vertical movement in open-field test were observed. After 21-day intervention, the content of colonic 5-HT was detected by immunohistochemical method, and that of fecal SCFAs was determined by gas chromatography mass spectrometry. RESULTS: After PSD modeling, compared with the stroke group, the sugar water consumption, the horizontal movement scores and vertical movement scores of the open-field test were all reduced in the PSD group, the drug group and the electroacupuncture group (P<0.05). After 21-day intervention, the sugar water consumption and the scores of horizontal movement and vertical movement of the open-field test were increased in the drug group and the electroacupuncture group (P<0.05) when compared with the PSD group; and the horizontal movement score in the electroacupuncture group was lower than that of the drug group (P<0.05). Compared with the sham-operation group, the contents of total fecal SCFAs and acetic acid were lower in the stroke group (P<0.05), and the contents of colonic 5-HT and total fecal SCFAs, acetic acid, propionic acid and butyric acid were reduced in the PSD group (P<0.05). In comparison with the PSD group, the contents of colonic 5-HT and total fecal SCFAs, acetic acid and propionic acid were increased in the drug group and the electroacupuncture group (P<0.05); and the content of colonic 5-HT in the electroacupuncture group was lower than that of the drug group (P<0.05). The level of colonic 5-HT was positively correlated with the contents of total fecal SCFAs and propionic acid (r=0.424, P=0.005; r=0.427, P=0.004). CONCLUSION Electroacupuncture at "Siguan" points can relieve the depression-like behavior of PSD rats, and its underlying mechanism may be related to the regulation of fecal SCFAs, which affects the release of colonic 5-HT.
Animals ; Rats ; Rats, Sprague-Dawley ; Propionates ; Serotonin ; Depression/therapy* ; Electroacupuncture ; Fatty Acids, Volatile ; Stroke/complications* ; Acetic Acid ; Butyric Acid ; Water

BACKGROUND: Human umbilical cord mesenchymal stem cells (hUCMSCs) have emerged as promising therapy for immune and inflammatory diseases. However, how to maintain the activity and unique properties during cold storage and transportation is one of the key factors affecting the therapeutic efficiency of hUCMSCs. Schisandrin B (SchB) has many functions in cell protection as a natural medicine. In this study, we investigated the protective effects of SchB on the hypothermic preservation of hUCMSCs. METHODS: hUCMSCs were isolated from Wharton’s jelly. Subsequently, hUCMSCs were exposed to cold storage (4 °C) and 24-h re-warming. After that, cells viability, surface markers, immunomodulatory effects, reactive oxygen species (ROS), mitochondrial integrity, apoptosis-related and antioxidant proteins expression level were evaluated. RESULTS: SchB significantly alleviated the cells injury and maintained unique properties such as differentiation potential, level of surface markers and immunomodulatory effects of hUCMSCs. The protective effects of SchB on hUCMSCs after hypothermic storage seemed associated with its inhibition of apoptosis and the anti-oxidative stress effect mediated by nuclear factor erythroid 2–related factor 2 signaling. CONCLUSION These results demonstrate SchB could be used as an agent for hypothermic preservation of hUCMSCs.

ObjectiveTo explore the clinical application of molecular classification in endometrial cancers with the next generation sequencing （NGS）. MethodsTotally 112 cases of endometrial carcinoma diagnosed by pathology in The Sun Yat-sen University Cancer Center were collected. All of them were tested by hybridized-capture second-generation sequencing based on 1，021 gene panel. The molecular variation spectrum of each subtype and its relationship between the clinicopathological features were analyzed. ResultsThe cases were distributed as follows： 8 （7.1%） POLE mutation， 34 （30.4%） mismatch repair deficient， 26 （23.2%） TP53 mutation， 44 （39.3%） non-specific molecular profile. The median tumor mutation burden was respectively 252.0， 38.4， 5.8 and 5.4 Muts/Mb. There were no significantly differences among four subtypes in clinicopathological features such as age， histological grade， lymph node metastasis and clinical stage. PTEN （75.5%）， PIK3CA （66.7%）， ARID1A （55.9%）， TP53 （40.2%）， NF1 （29.4%） were the most common mutations in endometrial cancers. ConclusionsThe utilization of NGS in endometrial cancers can simultaneously identify molecular subgroups， screen Lynch syndrome and obtain molecular variation spectrum， which can provide guidance for immunotherapy and targeted therapy， contribute to further accumulation and exploration of molecular genetic characteristics.

The mixing process is a critical link in the formation of oral solid preparations of traditional Chinese medicine. This paper took the extract powder of Guizhi Fuling Capsules and Paeonol powder as research objects. The angle of repose, loose packing density, and particle size of the two powders were measured to calibrate discrete element simulation parameters for the mixing process. The discrete element method was used to calibrate the simulated solid density of Paeonol powder and extract powder of Guizhi Fuling Capsules based on the Hertz-Mindlin with JKR V2 contact model and particle scaling. The Plackett-Burman experimental design was used to screen out the critical contact parameters that had a significant effect on the simulation of the angle of repose. The regression model between the critical contact parameters and the simulated angle of repose was established by the Box-Behnken experimental design, and the critical contact parameters of each powder were optimized based on the regression model. The best combination of critical contact parameters of the extract powder of Guizhi Fuling Capsules was found to be 0.51 for particle-particle static friction coefficient, 0.31 for particle-particle rolling friction coefficient, and 0.64 for particle-stainless steel static friction coefficient. For Paeonol powder, the best combination of critical contact parameters was 0.4 for particle-particle static friction coefficient and 0.19 for particle-particle rolling friction coefficient. The best combination of contact parameters between Paeonol powder and extract powder of Guizhi Fuling Capsules was 0.27 for collision recovery coefficient, 0.49 for static friction coefficient, and 0.38 for rolling friction coefficient. The verification results show that the relative error between the simulated value and the measured value of the angle of repose of the two single powders is less than 1%, while the relative error between the simulated value and the measured value of the angle of repose of the mixed powder with a mass ratio of 1∶1 is less than 4%. These research results provide reliable physical property simulation data for the mixed simulation experiment of extract powder of Guizhi Fuling Capsules and Paeonol powder.
Wolfiporia ; Calibration ; Powders ; Medicine, Chinese Traditional ; Capsules

Parvalbumin interneurons belong to the major types of GABAergic interneurons. Although the distribution and pathological alterations of parvalbumin interneuron somata have been widely studied, the distribution and vulnerability of the neurites and fibers extending from parvalbumin interneurons have not been detailly interrogated. Through the Cre recombinase-reporter system, we visualized parvalbumin-positive fibers and thoroughly investigated their spatial distribution in the mouse brain. We found that parvalbumin fibers are widely distributed in the brain with specific morphological characteristics in different regions, among which the cortex and thalamus exhibited the most intense parvalbumin signals. In regions such as the striatum and optic tract, even long-range thick parvalbumin projections were detected. Furthermore, in mouse models of temporal lobe epilepsy and Parkinson's disease, parvalbumin fibers suffered both massive and subtle morphological alterations. Our study provides an overview of parvalbumin fibers in the brain and emphasizes the potential pathological implications of parvalbumin fiber alterations.
Mice ; Animals ; Epilepsy, Temporal Lobe/pathology* ; Parvalbumins/metabolism* ; Parkinson Disease/pathology* ; Neurons/metabolism* ; Interneurons/physiology* ; Disease Models, Animal ; Brain/pathology*

Objective:By analyzing visually field of standardized residency training from 2008 to 2018, and exploring the field research hotspots and the frontier trend, to provide direction and reference for the field of standardized residency training in our country.Methods:Using CiteSpace visualized analysis software as a research tool, a statistical analysis was conducted on 1 120 pieces of literature in the field of standardized residency training retrieved from the core database of Web of Science.Results:The research strength of standardized residency training was mainly concentrated in the United States, with a total output of 697 papers, accounting for 62.23% of the total number of articles published in the past decade. High yield author Gillespie C published 8 papers, and highly cited author Aggarwal R's paper was cited 54 times. Acad Med, a highly cited journal, was cited the most frequently, with 470 citations in past 10 years. High frequency key words were "resident", "education", "performance", etc. Mutators included "system", "older adult", "operating room", and so on.Conclusion:The research hotspots in the field of standardized residency training in recent ten years include the teaching of residents, the assessment of clinical ability of residents, the standardized patients, etc. Frontier trends focus on resident self-assessment system, surgical training, resident professional core competences, etc.