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.

BACKGROUND:Currently,there have been studies on the regulatory mechanism of lncRNA\miRNA\mRNA co-expression network on the occurrence and development of osteoarthritis.Our research group has screened qualified NONHSAT248596.1 and miR-146a-5p through the database in the previous stage,but the corresponding in vivo experiments to verify the above regulatory mechanisms are still lacking. OBJECTIVE:To explore the role of NONHSAT248596.1 in regulating competitive endogenous RNA of miR-146a-5p in cartilage degeneration mediated by stromal cell derived factor type 1/chemokine receptor 4 axis in vivo. METHODS:The models of osteoarthritis were established in 36 New Zealand rabbits by injecting stromal cell derived factor 1 solution into the knee joint of the right hind limb.According to the random number table method,they were divided into four groups.lncRNA group,miRNA group,ceRNA group and control group were injected with lentivirus vector overexpressing NONHSAT248596.1,lentivirus vector overexpressing miR-146a-5p,lentivirus vector overexpressing miR-146a-5p+NONHSAT248596.1 and empty lentivirus vector into the molded knee joint,respectively.At 4,8 and 12 weeks of modeling,cartilage tissues and subchondral bone tissues of the knee joint were taken for relevant detection. RESULTS AND CONCLUSION:Hematoxylin-eosin staining and safranin fast green staining showed different degrees of degeneration in the four groups.At 4 weeks,the cartilage tissue of the lncRNA group showed swelling of chondrocytes,loss of cell polarity,destruction of extracellular matrix,surface erosion,fracture formation and partial or full layer loss of cartilage tissue.The degree of cartilage injury was gradually aggravated with time.The progression of articular cartilage inflammation in the miRNA group was the slowest among the four groups.qRT-PCR showed that at the same time point,mRNA expression levels of NONHSAT248596.1,chemokine receptor 4,matrix metalloproteinase 3,matrix metalloproteinase 9 and matrix metalloproteinase 13 in cartilage tissue of the lncRNA group were higher than those of the other three groups(P＜0.05).The mRNA expression levels of miR-146a-5p,aggrecan and type Ⅱ collagen were lower than those of the other three groups(P＜0.05).The mRNA expression levels of NONHSAT248596.1,chemokine receptor 4,matrix metalloproteinase 3,matrix metalloproteinase 9 and matrix metalloproteinase 13 in the miRNA group were lower than those in the ceRNA group and control group at 8 and 12 weeks after the model construction(P＜0.05).The mRNA expressions of miR-146a-5p,aggrecan and type Ⅱ collagen were higher than those of the ceRNA group and control group(P＜0.05).Western blot assay showed that at the same time point,the expression levels of aggrecan and type Ⅱ collagen in cartilage tissue of the lncRNA group were always lower than those of the other three groups(P＜0.05).The expression levels of aggrecan and type Ⅱ collagen in cartilage tissue of the miRNA group at 8 and 12 weeks after modeling were higher than those of the ceRNA group and control group(P＜0.05).The results showed that miR-146a-5p,as the target of NONHSAT248596.1,could be inhibited by the effect of its ceRNA.After acting on miR-146a-5p,NONHSAT248596.1 regulates the stromal cell derived factor type 1/chemokine receptor 4 axis to affect the expression of matrix metalloprotein,type Ⅱ collagen,and aggrecan in osteoarthritis chondrocytes,resulting in the degradation of extracellular matrix and the loss of proteoglycan.

Dyslipidemia is closely related to the development and progression of atherosclerosis. However, current clinical practice often relies on fasting lipid levels for the assessment of dyslipidemia, with little attention given to postprandial lipid levels, thereby overlooking the cardiometabolic disease risk associated with postprandial dyslipidemia. As an indispensable component of lipid management, postprandial lipids are not routinely measured in clinical practice due to the lack of standardized protocols about test meals and blood collection program. The paper titled " Optimization of oral fat tolerance test" published in this issue proposed a standardized protocol for postprandial lipid measurement. More studies are needed to accumulate evidence about the health benefits of possible interventions and to provide a reliable scientific basis for the early identification of dyslipidemic population as well as for the prevention and treatment of cardiovascular diseases.

Human physiological indicators have become an important standard for assessing health in modern society.Traditional detection methods often require a separate laboratory,complex operation process and long detection time,so it is urgent to develop portable,fast and accurate on-site detection technologies for bioanalysis.Point-of-care testing(POCT),which differs from traditional laboratory testing,can realize the rapid in situ detection of biomarkers without the complicated analytical process of the laboratory.Smartphones,which are an essential tool in our daily life,not only have independent operating systems and built-in storage functions,but also have high-definition cameras,which have great application potential in POCT visualization.The combination of various biosensing technologies and smartphones has developed into a new direction in the field of POCT.This review mainly introduced the research progress of smartphone-based visual biosensors in POCT in recent years,including colorimetric sensors,fluorescence sensors,chemiluminescence sensors and electrochemiluminescence sensors.Finally,the problems faced by smart-phone-based visual biosensors in the application of POCT were summarized,and their future development was prospected.

Objective To investigate the effects of palmatine on migration,invasion and epithelial mesenchymal transformation(EMT)in human oral cancer KB cells.Methods KB cells were divided into control group and palmatine-L,-M,-H groups,cultured with 0,4,8 and 16 μmol·L-1 palmatine.After incubation for 48 h,scratch assay was used to detect migration;Traswell assay was used to detect invasion;matrix metalloproteinase 2(MMP-2),MMP-9 and fibronectin(FN)contents were detected by enzyme-linked immunosorbent assay;the expression of Vimentin,N-cadherin and E-cadherin mRNA were detected by real-time quantitative polymerase chain reaction;the expression of Vimentin,N-cadherin,E-cadherin,Wnt3 and β-catenin protein were detected by Western blot.Results Cell mobility in control group and palmatine-L,-M,-H groups were(69.27±8.62)％,(52.94±4.49)％,(45.22±5.05)％and(37.63±4.88)％;the number of transmembrane cells were 197.33±20.26,125.33±12.01,97.00±9.17 and 62.67±7.51;the content of MMP-2 were(2.93±0.21),(1.49±0.13),(1.16±0.15)and(0.95±0.09)ng·mL-1;the content of MMP-9 were(3.51±0.36),(2.37±0.23),(2.06±0.35)and(1.72±0.16)ng·mL-1;the content of FN were(41.28±4.02),(24.03±3.17),(20.67±2.63)and(13.82±2.19)ng·mL-1;the above indexes in palmatine-L,-M,-H groups were compared with the control group,and the differences were statistically significant(P＜0.05,P＜0.01).The mRNA and protein expressions of Vimentin,N-cadherin and E-cadherin,and the expressions of Wnt3 and β-catenin protein in palmatine-L,-M,-H groups were statistically significant compared with those in control group(P＜0.05,P＜0.01).Conclusion Palmatine can inhibit the migration,invasion and EMT of human oral cancer KB cells,and its mechanism is related to the regulation of Wnt/β-catenin signaling pathway.

Urine nontargeted metabolomics technology was developed for investigating the effect and mechanism of improving learning and memory ability in APP/PS1 mice of Psoralea corylifolia. All animal experiments were approved by the Animal Ethics Committee of Heilongjiang University of Chinese Medicine (Approval No.: 2020092502). Sixteen APP/PS1 mice were randomly divided into the model group and Psoralea corylifolia group (0.5 g·kg^-1), and eight male C57BL/6J mice of the same background were selected as control group, step-through test and novel object recognition were used as evaluation indexes. Changes in urine endogenous metabolites of mice from eachgroup were determined by ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS), and differential metabolites were screened, and metabolic pathway enrichment analysis was performed. The results of pharmacodynamic investigation showed that Psoralea corylifolia can reduce the dark incubation period and number of errors in APP/PS1 mice (P < 0.01) and improve the new object recognition index of APP/PS1 mice (P < 0.01). Metabolomics analysis identified 15 differential metabolites, and 9 differential metabolites were significantly call back by Psoralea corylifolia. Metabolic pathway analysis showed that histidine metabolism, citric acid cycle, taurine and hypotaurine metabolism and glucose metabolism were the main metabolic pathways of Psoralea corylifolia in improving learning and memory ability. These studies suggest that Psoralea corylifolia improves the learning and memory ability of APP/PS1 mice, and its mechanism may be related to improving mitochondrial dysfunction, reducing peripheral histamine level, regulating energy metabolism disorders and antioxidant levels.

Objective To explore the accuracy and influencing factors of contrast-enhanced spectral mammography(CESM)and MRI in the dimension measurement of breast lesions.Methods A retrospective analysis was performed on 104 patients with breast lesions who underwent CESM and MRI examinations within one week.The pathological size was used as the gold standard to com-pare the accuracy of the two measurement methods.Logistic regression analysis was used to compare the influencing factors of the measurement accuracy of CESM and MRI.Results The measured values of CESM,MRI and pathology were 1.70 cm(1.20-2.70 cm),1.65 cm(1.20-2.28 cm),1.75 cm(1.00-2.50 cm),respectively,and there were no statistically significant differences between the two measurement methods and the pathological results(P＞0.05).Bland-Altman plot analysis showed that 95.2％(99/104)of the differences in CESM fell within the consistency interval,and 93.3％(97/104)of the differences in MRI fell within the consistency interval.Logistic regression analysis showed that the independent risk factors affecting the accuracy of CESM and MRI measurement were lesion size and enhancement type.Conclusion Both CESM and MRI show good accuracy.As a potential alternative to MRI technology,CESM can be used for imaging evaluation of breast lesion size.

Objective:To evaluate the efficacy and safety of unilateral adrenalectomy for treating primary bilateral macronodular adrenal hyperplasia (PBMAH) of different clinical types.Methods:The clinical and biochemical data of 54 patients with PBMAH who underwent unilateral adrenalectomy from May 2008 to March 2023 were retrospectively collected. Preoperative CT images of all patients showed enlarged bilateral adrenal glands with multiple nodules of " fused masses". Mean preoperative blood cortisol concentration at 8am was (21.5±7.7)μg/dl, urinary free cortisol concentration was (442.6±300.4)μg/24h, and mean 8am ACTH concentration was (6.4±2.3)pg/ml. Postoperative symptoms, BMI, blood pressure, mass diameter, cortisol and ACTH concentration were recorded and analyzed.Results:Compared with ordinary laparoscopic surgery, robot-assisted surgery showed shorter operation time [(115.4±22.1)min vs.(95.0±19.8)min, P=0.045]; less blood loss [(118.2±57.0)ml vs. (125.6±45.3)ml, P=0.441] and shorter hospitalization time [(5.2±0.9)day vs. (6.4±1.2)day, P=0.279]. Compared with laparoscopic surgery, open surgery showed longer operation time [(134 34.5) min vs. (104.3±20.1) min, P=0.035]; more blood loss [(305.5±85.2) ml vs. (122.5±44.3) ml, P=0.012] and longer hospitalization time[(10.4±3.2)day vs. (5.7±1.0) day, P=0.020]. The average follow-up time was (23.7±11.7) months. Sixteen cases biochemically relapsed, and the average relapse-free time was (25.4±13.4) month. Mean postoperative systolic blood pressure was (131.1±16.8)mmHg ( P=0.001) while diastolic blood pressure decreased to (82.2±11.1)mmHg ( P=0.002). Postsurgical average blood cortisol concentration decreased to (10.2±4.0)μg/dl ( P<0.01), while urine cortisol concentration decreased to (106.6±43.4)μg/24h( P<0.01). Average ACTH concentration increased to (12.6±4.1)pg/ml( P=0.005). Recurrent patients had higher preoperative blood and urine cortisol concentration(24.7±8.2)μg/dl( P=0.046), (522.8±234.2)μg/24h( P=0.028), and all of them underwent contralateral adrenalectomy. Conclusions:Unilateral adrenalectomy is safe and effective for treatment of PBMAH while part of patients biochemically relapsed. Subclinical patients were observed no recurrent cases after surgery. Recurrent patients have higher preoperative blood and urine cortisol levels and should undertake contralateral adrenalectomy and supplement corticosteroids for whole life.

Objective Toobserve the clinical efficacy of arthroscopic superior fulcrum reconstruction versus superior capsule reconstruction in the treatment of irreparable massive rotator cuff tears,in order to provide more therapeutic choices.Methods A total of 28 patients with irreparable massive rotator cuff tears,who had been admitted to the Department of Orthopedics,the Third Affiliated Hospital of Anhui Medical University from September 2021 to July 2023 were selected,14 of whom underwent arthroscopic superior fulcrum reconstruction(superior fulcrum reconstruction group)and 14 underwent arthroscopic superior capsule reconstruction(superior capsule reconstruction group).The observation indexes were operative time,intraoperative blood loss,shoulder joint active range of motion,the university of California at Los Angeles shoulder rating scale(UCLA),American Shoulder and Elbow Surgeons' score(ASES),the shoulder score of Constant-Murley(CMS)and Visual Analogue Scale(VAS).Results All patients had a successful surgery and a postoperative follow-up was at least 12 months.The postoperative shoulder joint active range of motion,UCLA,ASES and CMS between the two groups,which were statistically significant(P＜0.05),superior fulcrum reconstruction group was better than superior capsule reconstruction group.There was no significant difference in postoperative VAS,operative time or intraoperative blood loss between the two groups(P＞0.05).Conclusions Arthroscopic superior fulcrum reconstruction outper-forms superior capsule reconstruction in the treatment of irreparable massive rotator cuff tears.

Neonatal necrotizing enterocolitis(NEC)is the most common inflammatory intestinal disease in preterm infants,with a high incidence and mortality rate.The etiology and mechanisms of NEC are not yet fully understood,and multiple factors contribute to its occurrence and development.Recent studies have found that anemia is a risk factor for NEC in neonates,but the specific pathogenic mechanism remains unclear.This article reviews recent research on the relationship between anemia and NEC,providing a reference for further understanding the impact of anemia on intestinal injury and its association with NEC.