Objective To explore the effects of Tepp-46, a pyruvate kinase M2 (PKM2) agonist, on the skin fibrosis of patients with systemic scleroderma (SSc) and its therapeutic effect on the SSc mouse models. Methods Full-thickness skin tissues of SSc patients and healthy controls were taken, and the expression levels of PKM2 and α-smooth muscle actin (α-SMA) were detected using immunohistochemical staining. The skin primary fibroblasts were isolated from the tissues, and the PKM2 protein expression was detected using Western blotting. SSc fibroblasts were stimulated with Tepp-46 of different concentrations, and Western blotting was used to measure the expression of PKM2, collagen type Ⅰα1 (ColⅠα1) and α-SMA protein after the stimulation. The C57BL/6 mice were randomly divided into three groups: control group, bleomycin (BLM) group and Tepp-46 group. BLM was injected subcutaneously to establish the SSc mouse model, at the same time, Tepp-46 treatment initiated in the Tepp-46 group. At 21 d after modeling, the mice were executed and their skins were taken. HE staining and Masson staining were used to analyze morphological changes of the skin. The immunohistochemical staining was used to examine the expression of PKM2 and α-SMA protein in the mouse skin. Western blotting was used to analyze the expression of ColⅠα1 and PKM2 in the mouse skin. Results Compared with the healthy controls, α-SMA protein expression in the dermis of SSc patients was higher, and PKM2 protein expression in the epidermis and dermis of SSc patients increased (P＜0.000 1). PKM2 protein expression in primary fibroblasts of SSc skin was higher than that of healthy controls (P＜0.01); after Tepp-46 stimulation, the levels of ColⅠα1 and α-SMA in SSc fibroblasts decreased (P＜0.01), but PKM2 protein was not affected. In the mice, HE and Masson stainings showed that compared with BLM group, the pathological changes of skin were alleviated in the Tepp-46 group. The immunohistochemical staining results showed the levels of PKM2 and α-SMA in the skin of Tepp-46 group were lower than those of the BLM group (P＜0.000 1). Western blotting results showed the level of ColⅠα1 in the Tepp-46 group was lower than that in the BLM group (P＜0.001). Conclusions The expression of PKM2 protein in SSc skin tissue and primary fibroblasts is up-regulated, and PKM2 agonist Tepp-46 can inhibit SSc skin fibrosis.

Objective: To explore the effect of cardiorespiratory fitness (CRF) on cardiometabolic health and physical activity among obese adolescents, in order to provide a scientific basis for health promotion of obese adolescents. Methods: From July to August 2021 and 2022, 140 obese adolescents aged 10-17 were recruited in a residential weight loss camp. Sedentary behavior (SB), low intensity physical activity (LPA), total physical activity (TPA) and moderate to vigorous physical activity (MVPA) were measured by ActiGraph GT3X+ triaxial motion accelerometer, and CRF levels were measured by 20 meter shuttle run test. Cardiometabolic risk Z score (CMR- Z ) was constructed by measuring the cardiometabolic health indicators of obese adolescents, including waist circumference (WC), sagittal abdominal diameter (SAD), systolic blood pressure (SBP), diastolic blood pressure (DBP), average blood pressure (ABP), fasting insulin (FINs), fasting plasma glucose (FPG), total cholesterol (TC), and high density lipoprotein cholesterol (HDL-C). The mediating effect analysis was conducted by using the SPSS Process plug in compiled. Results: Cardiovascular health indicators WC, SAD, SBP, DBP, ABP, FINs, FPG, TC, HDL-C and CMR-Z were (93.21± 11.51 )cm, (21.77±2.71)cm, (111.24±11.86)mmHg, (66.08±9.03)mmHg and (88.66±8.97)mmHg, (8.98±6.42)μU/mL, ( 4.42 ±0.62)mmol/L, (4.43±0.97)mmol/L, (1.29±0.28)mmol/L, -0.43(-1.83,1.78)min, respectively. In the daily activity behavior indicators, the duration of SB, LPA, MVPA and TPA were (345.16±78.47, 267.35±62.65, 64.77±39.52, 677.30±57.63)min, respectively. SB, LPA and MVPA accounted for 50.96%, 39.47% and 9.56%, respectively. The indicator VO 2max of CRF was (37.95±4.96)mL/(kg min). Mediation analysis showed that CRF played a fully mediating role between LPA and waist to height ratio (WHtR), accounting for 44.2%. It exhibited a suppressing effect between LPA and ABP accounting for 31.5%, with a suppressing effect between MVPA and SAD accounting for 43.2% and a suppressing effect between MVPA and CMR- Z accounting for 96.0%. Conclusions CRF may be an important factor in the relationship between physical activity and cardiometabolic health of obese adolescents. Improving CRF level may be conducive to promoting cardiometabolic health of obese adolescents.

Caspofungin is the firs t echinocandin antifungal drug approved for serious fungal infections caused by Candida or Aspergillus. Currently ，caspofungin has been recommended as the first-line treatment for invasive Candida and the second-line treatment for invasive Aspergillus，for its safety and tolerability. However ，there are still probability of pharmacokinetic variability and the risk of low exposure in different populations. Herein the population pharmacokinetics-pharmacodynamics studies of caspofungin in children and adults were reviewed. The results indicate that the body surface area was the main factor affecting the distribution and clearance of caspofungin in pediatric patients. In adults ，the two-compartment model fits the caspofungin behavior best in vivo with the primary covariates of body weight and albumin level. The efficacy of caspofungin might be related to pharmacokinetics-pharmacodynamics parameters ，such as the ratio of area under blood concentration time curve to minimum inhibitory concentration （AUC/MIC），the ratio of peak concentration to minimum effective concentration （cmax/MEC）.

Objective To explore the correlation between homocysteine(Hcy),lipids amd type 2 diabetes mellitus (T2DM). Methods The laboratory test results of 533 cases of patients with T2DM(T2DM group)and 362 cases of healthy individuals (healthy control group)were retrospectively analyzed.Results The serum levels of Hcy and rates of abnormal serum cholesterol (TC),triacylglycerol(TG),low density lipoprotein cholesterol(LDL-C),high density lipoprotein cholesterol(HDL-C)levels in the T2DM group were higher than those in the healthy control group,had statistically significant differences(P <0.05).Conclusion The high serum level of Hcy and abnormal lipid metabolism are correlated with T2DM,which might be risk factors of diabetes mel-litus and cardiovascular disease.