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.

Nonobstructive azoospermia (NOA), one of the most severe types of male infertility, etiology often remains unclear in most cases. Therefore, this study aimed to detect four biallelic detrimental variants (0.5%) in the minichromosome maintenance domain containing 2 ( MCMDC2 ) genes in 768 NOA patients by whole-exome sequencing (WES). Hematoxylin and eosin (H&E) demonstrated that MCMDC2 deleterious variants caused meiotic arrest in three patients (c.1360G>T, c.1956G>T, and c.685C>T) and hypospermatogenesis in one patient (c.94G>T), as further confirmed through immunofluorescence (IF) staining. The single-cell RNA sequencing data indicated that MCMDC2 was substantially expressed during spermatogenesis. The variants were confirmed as deleterious and responsible for patient infertility through bioinformatics and in vitro experimental analyses. The results revealed four MCMDC2 variants related to NOA, which contributes to the current perception of the function of MCMDC2 in male fertility and presents new perspectives on the genetic etiology of NOA.
Humans ; Male ; Azoospermia/genetics* ; Meiosis/genetics* ; Spermatogenesis/genetics* ; Adult ; Exome Sequencing ; Microtubule-Associated Proteins/genetics* ; Alleles ; Infertility, Male/genetics*

In the progression of end-stage liver disease,the incidence of sleep disorders in patients with liver cirrhosis is high.Currently,western medicine treatment has obvious liver and kidney damage and adverse reactions after discontinuation,which affects the therapeutic effect.Cirrhosis and sleep disorders can be separately attributed to the category of"abdominal mass"and"insomnia"in traditional Chinese medicine.The"abdominal mass"is caused by the disorder of liver and spleen qi movement,as well as the obstruction of phlegm-dampness and blood stasis.In the development of"abdominal mass",the liver failed in ensuring free movement of qi,the spleen failed in transportation and transformation,liver yin and liver blood became insufficiency and the imbalance of yin and yang in the zang-fu organs became imbalanced,and then the ethereal soul depart from the housing,which leads to"insomnia"as an outward manifestation.Professor ZHOU Xiao-Zhou focuses on the concept of qi and blood,and points out that the pathogenesis of sleep disorder in cirrhosis is characterized by liver stagnation and spleen deficiency.He proposed that the treatment principle is to regulate the liver and spleen simultaneously,as well as to nourish the heart and calm the mind.Professor ZHOU has developed Ganyinghua Anshen Formula for treating sleep disorders in cirrhosis,which is derived from the modification of Xiangsha Liujunzi Decoction,and is composed of 14 Chinese medicines of vinegar-prepared Cyperi Rhizoma,Amomi Fructus,Coicis Semen,Dioscoreae Rhizoma,bran-fried Atractylodis Macrocephalae Rhizoma,Galli Gigerii Endothelium Corneum,Gardeniae Fructus,Codonopsis Radix,Salviae Miltiorrhizae Radix et Rhizoma,Citri Reticulatae Pericarpium,Sclerotium Poriae Pararadicis,Longan Arillus,Albiziae Cortex,and Glycyrrhizae Radix et Rhizoma Praeparata cum Melle.The formula has achieved remarkable clinical effect.The clinical experience of Professor ZHOU Xiao-Zhou for treating sleep disorders in cirrhosis through regulating the liver and spleen simultaneously will provide a reference for its clinical treatment with traditional Chinese medicine.

Objective: To analyze the trends of the age of menarche among Chinese Han girls aged 9 to 18 years from 2010 to 2019. Methods: Data were extracted from the Chinese National Surveys on Students' Constitution and Health in 2010, 2014 and 2019. A total of 253 037 Han girls aged 9 to 18 years with complete data on menarche were selected in this study. They were asked one-on-one about their menstrual status, age and residence information. The median age of menarche was estimated by probability regression. U tests were used to compare the difference in median age at menarche in different years. Results: The median age at menarche (95%CI) among Chinese Han girls was 12.47 (12.09-12.83) years in 2010, 12.17 (11.95-12.38) years in 2014 and 12.05 (10.82-13.08) years in 2019, respectively. Compared with that in 2010, the median age at menarche in 2019 decreased by 0.42 years (U=-77.27, P<0.001). The annual average changes were-0.076 years from 2010 to 2014 (U=-57.19, P<0.001) and-0.023 years from 2014 to 2019 (U=-21.41, P<0.001), respectively. The average annual changes in urban areas in the periods of 2010 to 2014 and 2014 to 2019 were-0.071 years and 0.006 years, respectively, while those in rural areas were-0.082 years and-0.053 years, respectively. The average annual changes in the regions of north, northeast, east, south central, southwest and northwest were-0.064, -0.099, -0.091, -0.080, -0.096 and-0.041 years in the period of 2010 to 2014 and 0.001, -0.040, -0.002, -0.005, -0.043 and-0.081 years in the period of 2014 to 2019. Conclusion: The age of menarche among Chinese Han girls aged 9 to 18 years shows an advanced trend from 2010 to 2019, and the trends in urban and rural areas and different regions have different characteristics.

Objective: To analyze the long-term trend of the age of spermarche among Chinese Han boys aged 11 to 18 from 2010 to 2019 and its association with nutritional status. Methods: The data from Chinese National Surveys on Students' Constitution and Health in 2010, 2014 and 2019 were used. The age, residence and spermarche of the participants were collected by questionnaire, and their height and weight were measured. A total of 184 633 Han boys aged 11‒18 years with complete data on spermarche, height, and weight were included in this study. The probability regression method was used to calculate the median age (95%CI) at spermarche in different areas, and the trend of age at spermarche in different groups was compared. The multivariate logistic regression model was used to analyze the association between nutritional status and spermarche of Chinese Han boys aged 11‒18 years. Results: The median age of spermarche (95%CI) was 13.85 (13.45-14.22) years old among Chinese Han boys aged 11‒18 years in 2019, with 0.18 years earlier than that in 2010. The median age at spermarche in urban and rural boys was 13.89 and 13.81 years, respectively. Compared with that in 2010, the age at spermarche in urban and rural boys was 0.08 and 0.27 years earlier, respectively. After adjusting for age, province and urban/rural areas, compared with normal weight, spermarche was negatively associated with wasting and positively associated with overweight and obesity, with OR (95%CI) about 0.73 (0.67-0.80), 1.09 (1.02-1.17) and 1.09 (1.01-1.18), respectively. Conclusion: The age of spermarche generally shows an advanced trend among Chinese Han boys and is associated with nutritional status.

Objective: To analyze the trend of the detection rate of myopia among Chinese Han children and adolescents aged 7-18 years from 2010 to 2019. Methods: Data from the Chinese National Survey on Students' Constitution and Health in 2010, 2014 and 2019 were used, and about 213 833, 212 742 and 209 942 Han students aged 7-18 years were included in this study. The χ² test was used to compare the differences in the prevalence of myopia among the subgroups in the survey year, and logistic regression was used to compare the differences in the prevalence of myopia between different years. A curve-fitting method was used to obtain the growth rate of myopia among Han Chinese students from 2010 to 2019, and the differences in the change of myopia between different age groups were analyzed. Results: In 2019, the overall detection rate of myopia among Chinese Han children and adolescents aged 7-18 was 60.1%. The detection rate of urban students (62.7%) was higher than that of rural students (57.4%) and the detection rate of girls (63.5%) was higher than that of boys (56.7%). In 2019, the regional disparities were large in the detection rate of myopia in various provinces, with the lowest in Guizhou (49.6%) and the highest in Zhejiang (71.3%). The detection rate of myopia showed an upward trend from 2010 to 2019, from 55.5% in 2010 to 57.1% in 2014, and finally to 60.1% in 2019. The gap in the detection rate of myopia between urban and rural children and adolescents gradually shrank. The average annual growth rate of myopia detection rate from 2014 to 2019 was 0.6 percentage points per year, higher than that from 2010 to 2014 about 0.4 percentage points per year. The peak age of the growth rate of myopia detection rate decreased from 12 years in 2010 to 10 years in 2014, and finally to 7 years in 2019. Conclusions: The detection rate of myopia among Chinese Han children and adolescents is still at a high level, and the peak age of the growth rate of myopia detection rate continues to advance.

Objective: To analyze the perceived exercise benefits and barriers and their association with physical activity time in Chinese Han children and adolescents aged 9-18 years. Methods: Data were extracted from the 2019 Chinese National Survey on Students' Constitution and Health and a total of 163 656 children and adolescents aged 9-18 years in Han ethnic group were included in the analysis. Mann-Whitney U test and Kruskal-Wallis test were used to compare the perceived exercise benefits score, perceived exercise barriers score and perceived exercise benefits to barriers ratio in the children and adolescents with different demographic characteristics and physical activity time. The differences in physical activity time in subgroups were compared with χ² tests. log-binomial regression model was used to evaluate the association between physical activity time and perceived exercise benefits and barriers. Results: The M (Q₁,Q₃) of the perceived exercise benefits score, perceived exercise barriers score, and perceived exercise benefits to barriers ratio in the children and adolescents were 4.11 (3.78, 4.78), 2.70 (2.10, 3.20) and 1.55 (1.22, 2.07), respectively. Children and adolescents living in urban area, boys, those at younger age and those with physical activity time ≥1 hour had higher perceived exercise benefits score and perceived exercise benefits to barriers ratio, but lower perceived exercise barriers score (all P<0.001). The prevalence of physical activity time ≥1 hour was 41.4% in the children and adolescents. In the log-binomial model with two variables of perceived exercise benefits score and perceived exercise barriers score, for each 1-point increase in the perceived exercise benefits, the possibility of physical activity time ≥1 hour increased by 11% (OR=1.11, 95%CI: 1.10-1.12), and for each 1-point increase in the perceived exercise barriers, the possibility of physical activity time ≥1 hour decreased by 15% (OR=0.85, 95%CI: 0.84-0.85). In the log-binomial model with variable of perceived exercise benefits to barriers ratio, for each 1-point increase in the perceived exercise benefits to barriers ratio, the possibility of physical activity time ≥1 hour increased by 12% (OR=1.12, 95%CI: 1.11-1.12). Conclusion: The perceived exercise benefits and barriers are significantly associated with physical activity time in children and adolescents in China.
Adolescent ; Child ; Humans ; Male ; Asian People ; China ; Ethnicity ; Exercise ; Students ; Female

Objective:To explore the feasibility of smart phone real-time picture exchange-assisted telecytopathology for rapid on-site evaluation (tele-ROSE), and the role of tele-ROSE in improving the diagnostic efficiency of endoscopic physicians.Methods:Data of patients who underwent endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) from April 2020 to May 2021 in Qilu Hospital of Shandong University were retrospectively collected. Patients who didn't receive ROSE from April 2020 to October 2020 were enrolled in the non-ROSE group, and those who underwent ROSE from November 2020 to May 2021 were enrolled in the ROSE group, of which endosonographers used WeChat on the smartphone to send ROSE images to cytopathologists from November 2020 to March 2021 were the mobile phone group, and those whose ROSE results independently diagnosed by trained endosonographers from April 2021 to May 2021 were the self-ROSE group. Basic information, ROSE results, postoperative pathology and follow-up were compared, and the diagnostic effectiveness of tele-ROSE was analyzed.Results:A total of 188 cases were included, of which 179 cases (95.2%) were solid pancreatic lesions and 9 (4.8%) were enterocoelia lesions. There was no significant difference in the puncture time among the non-ROSE, mobile phone and self-ROSE groups [3 (3, 4) VS 3 (3, 4) VS 3 (2, 4), H=1.320, P=0.517]. With the final diagnosis as the golden standard, the sensitivity, the specificity, the accuracy, the positive predictive value, the negative predictive value and Kappa value of the non-ROSE group were 80.6% (58/72), 89.5% (17/19), 82.4% (75/91), 96.7% (58/60), 54.8% (17/31), and 0.6 respectively. The corresponding indices in the ROSE group were 97.4% (74/76), 100.0% (21/21), 97.9% (95/97), 100.0% (74/74), 91.3% (21/23), and 0.9 respectively, those of the mobile phone group were 95.2% (40/42), 100.0% (10/10), 96.2% (50/52), 100.0% (40/40), 83.3% (10/12), and 0.9 respcetively, and those of the self-ROSE group were 100.0% (34/34), 100.0% (11/11), 100.0% (45/45), 100.0% (34/34), 100.0% (11/11), and 1.0 respectively. The sensitivity ( P=0.002), the accuracy ( P=0.001) and the negative predictive value ( P=0.009) of the ROSE group were significantly higher than those of the non-ROSE group, and there was no significant difference in other diagnostic efficacy indices ( P>0.05). There was no significant difference between the mobile phone group and the self-ROSE group in diagnostic efficacy ( P>0.05). Conclusion:Instant smartphone-assisted tele-ROSE through WeChat can well meet the needs of pathologists and endoscopic physicians. After the application of tele-ROSE training, the diagnostic accuracy of endoscopic physicians is equivalent to that of cytopathologist, which helps to obtain more sufficient specimens under endoscopy and improve the diagnostic accuracy of EUS-FNA.

{L-End}Objective To analyze the local muscle response under continuous ergonomic workload by simulating manual lifting, and to screen the sensitive metabolic biomarkers during fatigue process. {L-End}Methods A total of 13 healthy male volunteers were selected as the study subjects using simple random sampling method. Study subjects underwent repetitive simulated manual lifting for four periods (T1 to T4), each lasting 12 minutes. The degree of work-related fatigue in the forearm, upper arm, shoulder, back, and leg muscles, and the whole body was accessed using Borg 6-20 Rating of Perceived Exertion (RPE) Scale. The venous blood samples were collected from elbow between each two periods to detect the levels of eight metabolic biomarkers: ammonia, lactate, creatine kinase, lactate dehydrogenase (LDH), C-terminal telopeptide of type Ⅰ collagen (CTX-Ⅰ), C-terminal telopeptide of type Ⅱ collagen (CTX-Ⅱ), cartilage oligomeric matrix protein (COMP), and calcium ions. {L-End}Results The RPE scores of the study subjects for the muscles of five body parts and the whole body increased with the increasing lifting periods (all P<0.01). Fatigue was observed in all target muscles, with overall body fatigue occurring in the T2 period. The levels of ammonia, lactate, creatine kinase, LDH, COMP, and calcium ions in the serum of study subjects were higher in the T1 to T4 periods than in the T0 period (all P<0.05). The serum CTX-Ⅰ level was higher in the T1 and T3 periods than that in the T0 period (all P<0.05) , and the serum CTX-Ⅱ level was higher in the T1, T2 and T4 periods than that in the T0 period (all P<0.05). The level of these eight serum metabolic biomarkers fluctuated during the T1 to T4 periods. The serum creatine kinase level increased with the period of lifting (all P<0.05). The serum lactate level was higher in the T3 period than those in the T1 and T2 periods (all P<0.05). The serum LDH and calcium ion levels were higher in the T2 to T4 periods than that in the T1 period (all P<0.05). The serum COMP level was higher in the T2 and T3 periods than that in the T1 period (all P<0.05). Except for CTX-Ⅰ, the levels of other seven metabolic markers in serum were higher in individuals after fatigue than before fatigue (all P<0.05). {L-End}Conclusion Serum metabolic biomarkers such as ammonia, lactate, creatine kinase, calcium ions, LDH, CTX-Ⅱ, and COMP exhibit significant changes before and after fatigue. These metabolic biomarkers could be used as sensitive biomarkers for evaluating muscle fatigue during repetitive works.

OBJECTIVES: To investigate the prevalence rate of non-alcoholic fatty liver disease (NAFLD) in overweight/obese children who visit a hospital, and to explore the influencing factors of NAFLD, in order to provide a basis for the prevention of NAFLD in overweight/obese children. METHODS: Overweight/obese children who visited Hunan Children's Hospital from June 2019 to September 2021 were recruited. The prevalence rate of NAFLD was examined. Logistic regression analysis was used to explore the factors influencing the development of NAFLD [non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH)]. Receiver operating characteristic curve analysis was used to evaluate the predictive value of the influencing factors for NAFL and NASH. RESULTS: A total of 844 overweight/obese children aged 6-17 years were enrolled. The prevalence rate of NAFLD in overweight/obese children was 38.2% (322/844), among which the prevalence rates of NAFL and NASH were 28.8% (243/844) and 9.4% (79/844), respectively. Multivariate logistic regression analysis showed that the increase of waist-to-hip ratio (WHR) and low high-density lipoprotein cholesterol (HDL-C) were associated with the development of NAFL and NASH (P<0.05). The receiver operating characteristic curve analysis showed that the combined measurement of WHR and HDL-C had a predictive value for NAFL (area under the curve: 0.653, 95%CI: 0.613-0.694), and for NASH (area under the curve: 0.771, 95%CI: 0.723-0.819). CONCLUSIONS The prevalence rate of NAFLD in overweight/obese children who visit a hospital is high. WHR and HDL-C are associated with the development of NAFLD and the combined measurement of WHR and HDL-C has a certain value for predicating the development of NAFLD.
Child ; Humans ; Cholesterol, HDL ; Cross-Sectional Studies ; Non-alcoholic Fatty Liver Disease/complications* ; Overweight/complications* ; Pediatric Obesity/epidemiology* ; Prevalence ; Adolescent