Cyclin-dependent kinases (CDKs) are proline-induced serine/threonine kinases that are primarily involved in the regulation of cell cycle, gene transcription, and cell differentiation. In general, CDKs are activated by binding to specific regulatory subunits of cell cycle proteins and are regulated by phosphorylation of specific T-loops by CDK activated kinases. In the CDKs family, cyclin-dependent kinase 5 (CDK5) is a specialized member whose activity is triggered only by interaction with p35 and p39, which do not have the same sequence as the cell cycle proteins, and this may be one reason why CDK5 is distinguished from other CDK members by its structural and functional differences. In addition, unlike most CDK members that require phosphorylation at specific sites to function, CDK5 does not require such phosphorylation, and it can be activated simply by binding to p35 and p39. More notably, inhibitors that are commonly used to inhibit the activity of other CDK members have almost zero effect on CDK5. In contrast, CDK5, as a unique CDK family member, plays an important role in the development of numerous diseases. In metabolic diseases, elevated CDK5 expression leads to decreased insulin secretion, increased foam cell formation and triggers decreased bone mass in the body, thus accelerating metabolic diseases, and the role of CDK5 in bone biology is gradually gaining attention, and the role of CDK5 in bone metabolic diseases may become a hotspot for research in the future; in neurodegenerative diseases, hyperphosphorylation of Tau protein is an important hallmark of Alzheimer’s disease development, and changes in CDK5 expression are associated with Tau protein phosphorylation and nerve death, indicating that CDK5 is highly related to the development of the nervous system; in tumor diseases, the role of CDK5 in the proliferation, differentiation and migration and invasion of tumor cells marks the development of tumorigenesis, but different researchers hold different views, and further studies are needed in the follow-up. Therefore, the study of its mechanism of action in diseases can help to reveal the pathogenesis and pathological process of diseases. Appropriate exercise not only helps in the prevention of diseases, but also plays a positive role in the treatment of diseases. Exercise-induced mechanical stress can improve bone microstructure and increase bone mass in osteoporosis patients. In addition, exercise can effectively inhibit neuronal apoptosis and improve mitochondrial dysfunction, more importantly, appropriate exercise can inhibit the proliferation of cancer cells to a certain extent. It can be seen that exercise occupies a pivotal position in the prevention and treatment of pathologic diseases. It has been shown that exercise can reduce the expression of CDK5 and affect the pathological process of neurological diseases. Currently, there is a dearth of research on the specific mechanisms of CDK5’s role in improving disease outcomes through exercise. In order to understand its effects more comprehensively, subsequent studies need to employ diverse exercise modalities, targeting patients with various types of diseases or corresponding animal models for in-depth exploration. This article focuses on the pathological functions of CDK5 and its relationship with exercise, with a view to providing new insights into the prevention and treatment of disease by CDK5.

Objective: To explore the prevalence and related factors of overweight, obesity and hypertension comorbidities among children and adolescents in Ningxia, so as to provide a scientific basis for effective early health intervention in children and adolescents. Methods: From September 2021 to June 2022, a total of 4 577 students aged 9-16 were selected from Jinfeng District of Yinchuan City, Shapotou District of Zhongwei City, Yanchi County of Wuzhong City and Pingluo County of Shizuishan City in Ningxia by multi stage cluster random sampling method for questionnaire survey and physical measurement. The influencing factors of overweight, obesity and hypertension comorbidities in children and adolescents were investigated by Chi square test and multivariate unconditioned Logistic regression analysis with weighted complex sampling design. Results: The prevalence of overweight and obesity among primary and secondary school students in Ningxia was 22.87%, the prevalence of hypertension was 1.30%, and the comorbity rate of overweight, obesity and hypertension was 1.07%. Multivariate Logistic regression analysis showed that students aged 13-16 ( OR =15.66,95% CI =3.84-63.96, P <0.05) were more likely to suffer from overweight, obesity and hypertension than students aged 9-12. The students of insufficient sleep duration ( OR =5.47, 95% CI =1.73-17.33, P <0.05) had higher levels of overweight, obesity and hypertension comorbidities than those of adequate sleep duration. Students who had breakfast 1 to 7 times a week ( OR =0.08, 95% CI =0.02-0.37) had lower incidence than those who had breakfast once a week ( P <0.05). Conclusions Age, sleep time and breakfast frequency are all related factors of overweight, obesity and hypertension co morbidity among primary and secondary school students in Ningxia. Close attention should be paid to students aged 9-12 years with insufficient sleep time and fasting in the morning, and carry out scientific education and prevention and control interventions should be carried out.

Osteosarcopenia (OS) is a multifactorial, multiaetiologic degenerative metabolic syndrome in which sarcopenia coexists with osteoporosis, and its influences are related to aging-induced mechanics, genetics, inflammatory factors, endocrine disorders, and irregular lifestyles. With the accelerated aging process in our country, osteosarcopenia has become a public health problem that cannot be ignored, with a higher risk of falls, fractures, impaired mobility and death. In recent years, scholars at home and abroad have conducted a lot of research on osteosarcopenia, but their pathogenesis is still unclear. Understanding the signaling pathways associated with osteosarcopenia is of great significance for further research on the pathogenesis of these disorders and for finding new targets for treatment. Studies have shown that activation of the PI3K/Akt signaling pathway promotes osteoblast differentiation as well as skeletal muscle regeneration, indicating that inhibition of thePI3K/Akt signaling pathway is closely related to the development of osteosarcopenia. Muscle factor-mechanical stress interactions can maintain osteoblast viability by activating the Wnt/β-catenin signaling pathway, suggesting that Wnt signaling is important in muscle and bone crosstalk. The Notch signaling pathway also plays an important role in improving bone and muscle mass and function, but different researchers hold different views, which need to be further validated and refined in subsequent studies. Exercise, as an existing non-pharmacological treatment with strong and sustained effects on physical function and muscle strength, also significantly increases bone density in osteoporosis patients, which may be mainly due to the fact that exercise induces changes in the form and function of bones, in the form of muscular pulling and indirectly improves the bone mass, and changes in the bone strength can also change the number, shape as well as the function of the muscles. At the same time, the mechanism of different exercise modalities focuses on different aspects, and there are differences in exercise time, exercise intensity, and therapeutic effects in the implementation of interventions. Aerobic exercise can improve the quality of skeletal muscle and increase the expression of osteogenesis-related genes by stimulating mitochondrial biosynthesis, as well as improve the quality and strength of bones and muscles through the Wnt/β- catenin and PI3K/Akt signaling pathways, effectively preventing and controlling the occurrence of musculoskeletal disorders. High-intensity resistance exercise has a significant effect on improving the quality of muscles and bone mineral density, but older people with osteosarcopenia suffer from a decline in muscle quality and strength, and a decline in bone mineral density, which makes them very susceptible to fracture, so they should select the intensity of the training in a gradual and orderly manner, from small to large. What kind of exercise intensity and exercise modalities are most effective in improving the occurrence and development of osteosarcopenia needs to be further investigated. Therefore, this paper mainly reviews the epidemiology of osteosarcopenia, diagnostic criteria, the related signaling pathways (PI3K/Akt pathway, Wnt/β-catenin pathway, Notch pathway, NF-κB pathway) that jointly regulate the metabolic process of myocytes and skeletal cells, as well as the interventional effects of different exercise modes on osteosarcopenia, with the aim of providing theoretical bases for the clinical treatment of osteosarcopenia, as well as enhancing the preventive capacity of the disease in old age.

Osteoporosis leads to an imbalance in bone remodelling, where bone resorption is greater than bone formation and osteoclast degradation increases, resulting in severe bone loss. Autophagy is a lysosomal degradation pathway that regulates the proliferation, differentiation, and apoptosis of various bone cells (including osteoblasts, osteoclasts, and osteoclasts), and is deeply involved in the bone remodelling process. In recent years, the role of autophagy in the progression of osteoporosis and related bone metabolic diseases has received more and more attention, and it has become a research hotspot in this field. Summarising the existing studies, it is found that senile osteoporosis is the result of a combination of factors. On the one hand, it is the imbalance of bone remodelling and the increase of bone resorption/bone formation ratio with ageing, which causes progressive bone loss. On the other hand, aging leads to a general decrease in the level of autophagy, a decrease in the activity of osteoblasts and osteoclasts, and an inhibition of osteogenic differentiation. The lack of oestrogen leads to the immune system being in a low activation state, and the antioxidant capacity is weakened and inflammatory response is increased, inducing autophagy-related proteins to participate in the transmission of inflammatory signals, excessive accumulation of reactive oxygen species (ROS) in the skeleton, and negatively regulating bone formation. In addition, with aging and the occurrence of related diseases, glucocorticoid treatments also mediate autophagy in bone tissue cells, contributing to the decline in bone strength. Exercise, as an effective means of combating osteoporosis, improves bone biomechanical properties and increases bone density. It has been found that exercise induces oxidative stress, energy imbalance, protein defolding and increased intracellular calcium ions in the organism, which in turn activates autophagy. In bone, exercise of different intensities activates messengers such as ROS, PI3K, and AMP. These messengers signal downstream cascades, which in turn induce autophagy to restore dynamic homeostasis in vivo. During exercise, increased production of AMP, PI3K, and ROS activate their downstream effectors, AMPK, Akt, and p38MAPK, respectively, and these molecules in turn lead to activation of the autophagy pathway. Activation of AMPK inhibits mTOR activity and phosphorylates ULK1 at different sites, inducing autophagy. AMPK and p38 up-regulate per-PGC-1α activity and activate transcription factors in the nucleus, resulting in increased autophagy and lysosomal genes. Together, they activate FoxOs, whose transcriptional activity controls cellular processes including autophagy and can act on autophagy key proteins, while FoxOs proteins are expressed in osteoblasts. Exercise also regulates the expression of mTORC1, FoxO1, and PGC-1 through the PI3K/Akt signalling pathway, which ultimately plays a role in the differentiation and proliferation of osteoblasts and regulates bone metabolism. In addition, BMPs signaling pathway and long chain non-coding RNAs also play a role in the proliferation and differentiation of osteoblasts and autophagy process under exercise stimulation. Therefore, exercise may become a new molecular regulatory mechanism to improve osteoporosis through the bone autophagy pathway, but the specific mechanism needs to be further investigated. How exercise affects bone autophagy and thus prevents and treats bone-related diseases will become a future research hotspot in the fields of biology, sports medicine and sports science, and it is believed that future studies will further reveal its mechanism and provide new theoretical basis and ideas.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

OBJECTIVE: To explore the expression level of exosome derived miR-181b-5p in different disease stages of children with acute lymphoblastic leukemia and its relationship with clinical characteristics. METHODS: Bone marrow plasma samples of 86 children with ALL were collected. Exosomes were extracted by exosome extraction kit, and RNA in exosomes was extracted by TRIzol method. The levels of miR-181b-5p in the blood plasma exosomes of the patients in the newly diagnosed group, relapse group, remission group and control group were detected by qRT- PCR. The difference of miR-181b-5p expression level in each group was compared and analyzed, and the relationship between miR-181b-5p expression level and clinical characteristics was analyzed. RESULTS: The expression level of exosomal miR-181b-5p in the newly diagnosed group and the relapsed group was significantly lower than that in the remission group and the control group (P< 0.05). The expression level of exosomal miR-181b-5p in T-ALL children was higher than that in B-ALL children (P<0.05). The expression level of plasma exosomal miR-181b-5p in male children was higher than that in female children (P<0.01). CONCLUSION Exosome derived miR-181b-5p changes dynamically in the course of ALL children, and can be used as a marker miRNA to monitor disease status. Exosomes can transmit information in the tumor microenvironment and serve as a potential carrier for biomolecular targeted therapy.
Humans ; Male ; Female ; Child ; Exosomes/metabolism* ; Clinical Relevance ; MicroRNAs/genetics* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/metabolism* ; Tumor Microenvironment

OBJECTIVE: To investigate the factors related to renal impairment in patients with diabetic kidney disease (DKD) from the perspective of integrated Chinese and Western medicine. METHODS: Totally 492 patients with DKD in 8 Chinese hospitals from October 2017 to July 2019 were included. According to Kidney Disease Improving Global Outcomes (KDIGO) staging guidelines, patients were divided into a chronic kidney disease (CKD) 1-3 group and a CKD 4-5 group. Clinical data were collected, and logistic regression was used to analyze the factors related to different CKD stages in DKD patients. RESULTS: Demographically, male was a factor related to increased CKD staging in patients with DKD (OR=3.100, P=0.002). In clinical characteristics, course of diabetes >60 months (OR=3.562, P=0.010), anemia (OR=4.176, P<0.001), hyperuricemia (OR=3.352, P<0.001), massive albuminuria (OR=4.058, P=0.002), atherosclerosis (OR=2.153, P=0.007) and blood deficiency syndrome (OR=1.945, P=0.020) were factors related to increased CKD staging in patients with DKD. CONCLUSIONS Male, course of diabetes >60 months, anemia, hyperuricemia, massive proteinuria, atherosclerosis, and blood deficiency syndrome might indicate more severe degree of renal function damage in patients with DKD. (Registration No. NCT03865914).
Humans ; Male ; Diabetes Mellitus, Type 2 ; Diabetic Nephropathies ; Hyperuricemia ; Kidney ; Proteinuria ; Renal Insufficiency, Chronic/complications*

Objective: To investigate the distribution of blood pressure and analyze the associated factors of blood pressure of the elderly with type 2 diabetes in Jiangsu Province. Methods: The elderly over 60 years old participants with type 2 diabetes in the communities of Huai'an City and Changshu City, Jiangsu Province were selected in this study. They were divided into two groups: taking antihypertensive drugs and not taking antihypertensive drugs. The demographic characteristics, such as age and sex, and relevant factors were collected by questionnaire. The systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured by physical examination. The percentile of SBP and DBP in each age group of men and women were described. The kernel density estimation curve was used to show the blood pressure distribution. The trend of blood pressure with age was fitted by locally weighted regression. The logistic regression model was used to analyze relevant factors of blood pressure. Results: A total of 12 949 participants were included in this study, including 7 775 patients in the antihypertensive drug group and 5 174 patients in the group without antihypertensive drugs. The SBP of participants was concentrated at 140-160 mmHg, and their DBP was concentrated at 75-85 mmHg. There were significant differences in the distribution of blood pressure among the subgroups of body mass index (BMI) and rural areas whether taking antihypertensive drugs and not. For participants aged under 80 years old, the SBP showed an increasing trend with age and the DBP showed a decreasing trend with age. Age, BMI ≥24 kg/m², fasting blood glucose ≥7.0 mmol/L, living in rural areas and no smoking were influencing factors of the elevated SBP; BMI ≥24 kg/m², male, living in rural areas, no smoking, drinking alcohol and not receiving drug hypoglycemic treatment were influencing factors of the elevated DBP. Conclusion: The SBP of older diabetic adults in Jiangsu Province is at a high level, and the distribution of blood pressure is significantly different between men and women in taking antihypertensive drugs group. The SBP presents a rising trend and the DBP is decreasing at the age of 60-80 years. The blood pressure level of this population are mainly affected by age, BMI, urban and rural areas, smoking.
Adult ; Aged ; Humans ; Male ; Female ; Middle Aged ; Aged, 80 and over ; Blood Pressure/physiology* ; Diabetes Mellitus, Type 2/epidemiology* ; Antihypertensive Agents/therapeutic use* ; Smoking ; Body Mass Index ; Hypertension/epidemiology*

Objective: Compare and analyze the results of the domestic Lanyi AH600 glycated hemoglobin analyzer and other different detection systems to understand the comparability of the detection results of different detectors, and establish the best cut point of Lanyi AH600 determination of haemoglobin A1c (HbA1c) in the diagnosis of diabetes. Methods: Multi center cohort study was adopted. The clinical laboratory departments of 18 medical institutions independently collected test samples from their respective hospitals from March to April 2022, and independently completed comparative analysis of the evaluated instrument (Lanyi AH600) and the reference instrument HbA1c. The reference instruments include four different brands of glycosylated hemoglobin meters, including Arkray, Bio-Rad, DOSOH, and Huizhong. Scatter plot was used to calculate the correlation between the results of different detection systems, and the regression equation was calculated. The consistency analysis between the results of different detection systems was evaluated by Bland Altman method. Consistency judgment principles: (1) When the 95% limits of agreement (95% LoA) of the measurement difference was within 0.4% HbA1c and the measurement score was≥80 points, the comparison consistency was good; (2) When the measurement difference of 95% LoA exceeded 0.4% HbA1c, and the measurement score was≥80 points, the comparison consistency was relatively good; (3) The measurement score was less than 80 points, the comparison consistency was poor. The difference between the results of different detection systems was tested by paired sample T test or Wilcoxon paired sign rank sum test; The best cut-off point of diabetes was analyzed by receiver operating characteristic curve (ROC). Results: The correlation coefficient R² of results between Lanyi AH600 and the reference instrument in 16 hospitals is≥0.99; The Bland Altman consistency analysis showed that the difference of 95% LoA in Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180) was -0.486%-0.325%, and the measurement score was 94.6 points (473/500); The difference of 95% LoA in the Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant II) was -0.727%-0.612%, and the measurement score was 89.8 points; The difference of 95% LoA in the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT) was -0.231%-0.461%, and the measurement score was 96.6 points; The difference of 95% LoA in the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT) was -0.469%-0.479%, and the measurement score was 91.9 points. The other 14 hospitals, Lanyi AH600, were compared with 4 reference instrument brands, the difference of 95% LoA was less than 0.4% HbA1c, and the scores were all greater than 95 points. The results of paired sample T test or Wilcoxon paired sign rank sum test showed that there was no statistically significant difference between Lanyi AH600 and the reference instrument Arkray HA8180 (Z=1.665,P=0.096), with no statistical difference. The mean difference between the measured values of the two instruments was 0.004%. The comparison data of Lanyi AH600 and the reference instrument of all other institutions had significant differences (all P<0.001), however, it was necessary to consider whether it was within the clinical acceptable range in combination with the results of the Bland-Altman consistency analysis. The ROC curve of HbA1c detected by Lanyi AH600 in 985 patients with diabetes and 3 423 patients with non-diabetes was analyzed, the area under curve (AUC) was 0.877, the standard error was 0.007, and the 95% confidence interval 95%CI was (0.864, 0.891), which was statistically significant (P<0.001). The maximum value of Youden index was 0.634, and the corresponding HbA1c cut point was 6.235%. The sensitivity and specificity of diabetes diagnosis were 76.2% and 87.2%, respectively. Conclusion: Among the hospitals and instruments currently included in this study, among these four hospitals included Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180), Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant Ⅱ), the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT), and the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT), the comparison between Lanyi AH600 and the reference instruments showed relatively good consistency, while the other 14 hospitals involved four different brands of reference instruments: Arkray, Bio-Rad, DOSOH, and Huizhong, Lanyi AH600 had good consistency with its comparison. The best cut point of the domestic Lanyi AH600 for detecting HbA1c in the diagnosis of diabetes is 6.235%.
Pregnancy ; Child ; Humans ; Female ; Glycated Hemoglobin ; Cohort Studies ; Diabetes Mellitus/diagnosis* ; Sensitivity and Specificity ; ROC Curve

Objective: To investigate the association between long-term fasting blood glucose (FPG) variability and all-cause mortality in patients with type 2 diabetes. Methods: A total of 7 174 type 2 diabetic patients included in National Basic Public Health Service Program in Changshu of Jiangsu Province were recruited as participants. Long-term glucose variability was assessed using standard deviation (SD), coefficient of variation (CV), average real variability (ARV), and variability independent of the mean (VIM) across FPG measurements at the more than three visits. Death information were mainly obtained from the death registry system in Jiangsu. Then Cox proportional hazards regression models were used to estimate the associations of four variability indicators and all-cause mortality's hazard ratios (HRs) and their 95%CIs. Results: Among 55 058.50 person-years of the follow-up, the mean follow-up time was 7.67 years, and 898 deaths occurred during the follow-up period. After adjustment, compared with T₁ group, the Cox regression model showed that HRs of T₃ group in SD, CV, ARV and VIM were 1.24 (95%CI: 1.03-1.49), 1.20 (95%CI: 1.01-1.43), 1.28 (95%CI: 1.07-1.55) and 1.20 (95%CI:1.01-1.41), respectively. HRs of per 1 SD higher SD, CV, ARV and VIM were 1.13 (95%CI: 1.06-1.21), 1.08 (95%CI: 1.01-1.15), 1.05 (95%CI: 1.00-1.12) and 1.09 (95%CI: 1.02-1.16) for all-cause mortality, respectively. In the stratified analysis, age, gender, hypoglycemic agent and insulin uses had no effect on the above associations (all P for interaction >0.05). Conclusion: Long-term FPG glycemic variability was positively associated with the risk of all-cause mortality in type 2 diabetes patients.