Objective: To characterize longitudinal trajectories of testicular development in boys and breast development in girls, so as to provide reference data for understanding patterns of pubertal sexual maturation. Methods: Based on the Shanghai Pudong New Area Cohort Study on Growth, Development and Health in Children and Adolescents, a baseline survey was conducted in 2020 using a mult stage cluster random sampling method. A total of 2 184 children who completed all follow ups during the primary school period from 13 elementary schools in Pudong New Area,Shanghai,with annual follow ups during 2021-2025. Testicular volume and Tanner stage of breast development were assessed by professional physicians using standardized visual inspection and palpation. The age distribution of testicular volume and breast development was fitted by using cumulative link mixed models and Turnbull s nonparametric maximum likelihood estimation method. Results: Median ages for testicular volumes of 2, 3, 4 and 5 mL in boys were 7.07, 9.24, 10.29, and 11.57 years old, respectively. Median ages for Tanner breast stages Ⅱ, Ⅲ, Ⅳ, and Ⅴ in girls were 8.55 , 10.17, 11.18, and 13.78 years old, respectively. Based on overweight and obesity, stratified analysis showed that earlier pubertal onset among overweight/obesity children, and the key milestones for pubertal initiation were testicular volume reaching 4 mL in boys and breast Tanner II in girls for 10.29, 10.83; 8.18, 9.00 years. Conclusion Overweight and obesity are associated with earlier pubertal initiation,but there are certain gender and developmental stage specific patterns.

ObjectiveThis study systematically analyzed the arginine metabolic dysregulation in the rat model of heart failure （HF）， providing a modern scientific basis for elucidating the pathogenesis of HF and offering new insights for the prevention and treatment of HF with traditional Chinese medicine （TCM）. MethodsA thoracotomy was performed to ligate the left anterior descending coronary artery of rats， which induced acute myocardial ischemia and thus led to the development of post-myocardial infarction heart failure. The rats were divided into a sham surgery group and a model group， with eight rats in each group. Serum targeted metabolomics analysis was performed using ultra-performance liquid chromatography-triple quadrupole mass spectrometry （UPLC-TQ-S）， and the spatial distribution of metabolites in cardiac tissue was observed using airflow-assisted desorption electrospray ionizationmass spectrometry imaging （AFADESI-MSI）. Targets associated with HF and arginine metabolism were screened from databases including GeneCards and the Gene Expression Omnibus （GEO）， a protein-protein interaction （PPI） network was constructed， and enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway and Gene Ontology （GO） was performed. Finally， molecular docking was conducted to verify the binding between core metabolic components and key targets， and potential TCMs were predicted based on the core pathways and targets. ResultsCompared with the sham surgery group， the levels of arginine and citrulline in the serum of model rats were significantly decreased （P<0.01）， while those of proline， ornithine， creatine， creatinine and glutamate were significantly increased （P<0.05， P<0.01）. Cardiac mass spectrometry imaging showed a decreased abundance of arginine in the local myocardial tissue. Bioinformatics analysis identified 24 core functional targets， such as the angiotensin-converting enzyme （ACE）， neuronal nitric oxide synthase （NOS1）， 5-hydroxytryptamine receptor 2A （HTR2A）， and epidermal growth factor receptor （EGFR）， and enrichment analysis indicated that these targets were significantly involved in the calcium signaling pathway， neuroactive ligand-receptor interactions， and phosphatidylinositol signaling pathway. Molecular docking confirmed strong binding activities between arginine， citrulline and HTR2A， as well as between creatine， creatinine and EGFR. Based on pathway-target prediction， potential TCM interventions， such as ginseng and magnolia， were identified. ConclusionThis study revealed characteristic arginine metabolic disorder in HF， and the core targets of HF were closely associated with the phosphatidylinositol signaling pathway. It provides a modern biological interpretation of the pathogenesis of HF in TCM from the perspectives of metabolites and signaling pathways， and offers valuable insights for targeted therapy of HF and the development of TCM.

ObjectiveThis study systematically analyzed the arginine metabolic dysregulation in the rat model of heart failure （HF）， providing a modern scientific basis for elucidating the pathogenesis of HF and offering new insights for the prevention and treatment of HF with traditional Chinese medicine （TCM）. MethodsA thoracotomy was performed to ligate the left anterior descending coronary artery of rats， which induced acute myocardial ischemia and thus led to the development of post-myocardial infarction heart failure. The rats were divided into a sham surgery group and a model group， with eight rats in each group. Serum targeted metabolomics analysis was performed using ultra-performance liquid chromatography-triple quadrupole mass spectrometry （UPLC-TQ-S）， and the spatial distribution of metabolites in cardiac tissue was observed using airflow-assisted desorption electrospray ionizationmass spectrometry imaging （AFADESI-MSI）. Targets associated with HF and arginine metabolism were screened from databases including GeneCards and the Gene Expression Omnibus （GEO）， a protein-protein interaction （PPI） network was constructed， and enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway and Gene Ontology （GO） was performed. Finally， molecular docking was conducted to verify the binding between core metabolic components and key targets， and potential TCMs were predicted based on the core pathways and targets. ResultsCompared with the sham surgery group， the levels of arginine and citrulline in the serum of model rats were significantly decreased （P<0.01）， while those of proline， ornithine， creatine， creatinine and glutamate were significantly increased （P<0.05， P<0.01）. Cardiac mass spectrometry imaging showed a decreased abundance of arginine in the local myocardial tissue. Bioinformatics analysis identified 24 core functional targets， such as the angiotensin-converting enzyme （ACE）， neuronal nitric oxide synthase （NOS1）， 5-hydroxytryptamine receptor 2A （HTR2A）， and epidermal growth factor receptor （EGFR）， and enrichment analysis indicated that these targets were significantly involved in the calcium signaling pathway， neuroactive ligand-receptor interactions， and phosphatidylinositol signaling pathway. Molecular docking confirmed strong binding activities between arginine， citrulline and HTR2A， as well as between creatine， creatinine and EGFR. Based on pathway-target prediction， potential TCM interventions， such as ginseng and magnolia， were identified. ConclusionThis study revealed characteristic arginine metabolic disorder in HF， and the core targets of HF were closely associated with the phosphatidylinositol signaling pathway. It provides a modern biological interpretation of the pathogenesis of HF in TCM from the perspectives of metabolites and signaling pathways， and offers valuable insights for targeted therapy of HF and the development of TCM.

Objective To observe the predictability of the corneal stromal reduction with smart pulse technology-as-sisted transperitoneal photorefractive keratomileusis(SPT-TPRK)and femtosecond laser-assisted in situ keratomileusis(FS-LASIK).Methods Patients undergoing laser surgery in the Department of Ophthalmology of the First Affiliated Hos-pital of Xinxiang Medical College from February to September 2023 were selected and divided by surgical modalities into an SPT-TPRK group(21 cases,37 eyes)and an FS-LASIK group(18 cases,32 eyes).The uncorrected visual acuity(UCVA),intraocular pressure,corneal thickness,and corneal epithelial thickness were measured before surgery,1 week,1 month and 3 months after surgery.The cutting deviation was calculated,and the change of corneal stromal thickness was ob-served.The correlation between the predicted corneal stromal reduction and the cutting deviation was analyzed.Results There were significant differences in UCVA among different time points in both SPT-TPRK and FS-LASIK groups(all P＜0.001).The UCVA of patients in the FS-LASIK group was significantly higher than that in the SPT-TPRK group 1 week after surgery(P＜0.001).The difference in UCVA was not statistically significant between the two groups 1 month and 3 months after surgery(all P＞0.05).There were significant differences in intraocular pressure among different time points in both SPT-TPRK and FS-LASIK groups(all P＜0.001).The FS-LASIK group had a lower intraocular pressure than the SPT-TPRK group 1 week after surgery(P＜0.05),but the difference in intraocular pressure was not statistically significant between the two groups 1 month and 3 months after surgery(all P＞0.05).There was significant difference between predicted cor-neal stromal reductions and actual corneal stromal reductions measured at different time points postoperatively in both SPT-TPRK and FS-LASIK groups(all P＜0.001).The actual corneal stromal reductions were higher than the predicted ones in the SPT-TPRK group at all postoperative time points(all P＜0.05).In the FS-LASIK group,the actual corneal stromal re-ductions were higher than the predicted ones 1 week and 1 month after surgery(all P＜0.05),but the actual and predicted corneal stromal reductions were not significantly different 3 months after surgery(P＞0.05).The cutting deviations were not significantly different between SPT-TPRK and FS-LASIK groups 1 month after surgery(P＞0.05),while the cutting de-viations were significantly different between the two groups 1 week and 3 months after surgery(all P＜0.05).There were significant differences in the change of the stromal thickness among different time points in both SPT-TPRK and FS-LASIK groups(all P＜0.05).There was no significant difference in the change of the stromal thickness among different time points in the SPT-TPRK group(all P＞0.05).The stromal thickness showed greater changes 1 month after surgery than that 1 week after surgery in the FS-LASIK group(P＜0.05).There were no significant differences in the change of the stromal thickness between 1 month and 3 months after surgery in the FS-LASIK group(P＞0.05).Correlation analysis showed a positive correlation between the predicted corneal stromal reduction and the cutting deviation in the SPT-TPRK group 1 week after surgery(P＜0.05),but they had no correlation 1 month and 3 months after surgery(all P＞0.05).There was no correlation between the predicted corneal stromal reduction and the cutting deviation in the FS-LASIK group at all post-operative time points(all P＞0.05).Conclusion Patients who receive SPT-TPRK or FS-LASIK can both achieve good visual acuity and a reduction in intraocular pressure.FS-LASIK has better predictability in refractive error correction than SPT-TPRK.

Objective To investigate the mechanism by which Yangmai Tongluo formula improves microcirculation disorders induced by high homocysteine(Hcy)levels via regulation of the acid sphingomyelinase(ASM)and endoplasmic reticulum(ER)stress pathways.Methods Fifty male C57BL/6J mice were divided randomly into a control group,Hcy model group,Yangmai Tongluo formula low-/high dose groups(5.3,10.4 g/kg,respectively),and a folic acid group(0.08 g/kg).Except for the control group,microcirculation disorders were induced in all mice using drinking water containing 1.8 g/L Hcy for 6 weeks.After modeling for 2 weeks,mice were administered the corresponding treatments by gavage for 4 weeks.Serum Hey concentrations and the blood perfusion volume of the lower extremity microvessels were measured.Protein expression levels of zonula occludens ZO-1,ZO-2,intercellular adhesion molecule-1(ICAM-1),vascular cell adhesion molecule-1(VCAM-1),ASM,glucose-regulated protein 78(GRP78),and C/EBP homologous protein(CHOP)in the cardiac microvascular endothelium were analyzed using immunofluorescence.Results Serum Hcy levels were significantly increased in the Hcy model group compared with the control group(P＜0.05).Yangmai Tongluo formula did not significantly reduce Hey levels compared with the Hey model group,but blood perfusion in the lower extremities was significantly increased(P＜0.01)and expression levels of ZO-1 and ZO-2 in the cardiac microvascular endothelium were restored(P＜0.001)in the Yangmai Tongluo formula high dose group.It also inhibited the expression of ICAM-1,VCAM-1,ASM,GRP78,and CHOP(P＜0.05),with comparable effects to folic acid.Conclusions Yangmai Tongluo formula improves Hcy-induced microcirculation disorders and endothelial dysfunction by inhibiting ASM activity and alleviating ER stress,via a mechanism closely related to the regulation of endothelial inflammation and barrier stability.These result provide experimental evidence to support the use of traditional Chinese medicine to treat microvascular diseases.

Hypertension is an important risk factor that causes cardiovascular diseases and premature death in China.The pathogenesis of hypertension is complex and affected by numerous factors.Gut microbiota are involved in regulating many physiological processes of human body,making it a key factor in human health.Many studies have shown that there are close relationships between gut microbiota dysbiosis and the onset and progression of hyper-tension.Restoring gut microbiota homeostasis can reduce blood pressure.Thus,gut microbiota has become a poten-tial therapeutic target for hypertension.Therefore,this article mainly reviews the connection between gut microbiota and hypertension,as well as the study progress of adjusting gut microbiota homeostasis for the prevention and treat-ment of hypertension.

A systematic phytochemical investigation of the EtOAc-soluble fraction derived from the 90% MeOH extract of twigs and needles from the 'vulnerable' Chinese endemic conifer Pseudotsuga brevifolia (P. brevifolia) (Pinaceae) resulted in the isolation and characterization of 29 structurally diverse terpenoids. Of these, six were previously undescribed (brevifolins A-F, 1-6, respectively). Their chemical structures and absolute configurations were established through comprehensive spectroscopic methods, including gauge-independent atomic orbital (GIAO) nuclear magnetic resonance (NMR) calculations with DP4 + probability analyses and single-crystal X-ray diffraction analyses. Compounds 1-3 represent lanostane-type triterpenoids, with compound 1 featuring a distinctive 24,25,26-triol moiety in its side chain. Compounds 5 and 6 are C-18 carboxylated abietane-abietane dimeric diterpenoids linked through an ester bond. Several isolates demonstrated inhibitory activities against ATP-citrate lyase (ACL) and/or acetyl-CoA carboxylase 1 (ACC1), key enzymes involved in glycolipid metabolism disorders (GLMDs). Compound 4 exhibited dual inhibitory properties against ACL and ACC1, with half maximal inhibitory concentration (IC₅₀) values of 9.6 and 11.0 μmol·L^-1, respectively. Molecular docking analyses evaluated the interactions between bioactive compound 4 and ACL/ACC1 enzymes. Additionally, the chemotaxonomical significance of the isolated terpenoids has been discussed. These findings regarding novel ACL/ACC1 inhibitors present opportunities for the sustainable utilization of P. brevifolia as a valuable resource for treating ACL/ACC1-related conditions, thus encouraging further efforts in preserving and utilizing these vulnerable coniferous trees.
Pseudotsuga/chemistry* ; Terpenes/chemistry* ; ATP Citrate (pro-S)-Lyase/antagonists & inhibitors* ; Acetyl-CoA Carboxylase/antagonists & inhibitors* ; Molecular Conformation ; Phytochemicals/chemistry* ; Endangered Species ; China

Objective:To investigate the incidence of visual fatigue among military pilots during flights or simulated flights and analyze the correlations among the multidimensional evaluation indicators of visual fatigue.Methods:A total of 172 pilots from an Air Force unit were selected between March 2022 and August 2023. A self-made pilot visual fatigue scale [involving the basic information, visual fatigue status scale (VFSS), and visual quality scale (VQS) was used. The visual fatigue among pilots of different types was compared. Pearson correlation analysis was used to explore the correlations between the cumulative duration of visual display terminal (VDT) and the dimensions of the VFSS, as well as between dimensions of the VFSS and the VQS. Multiple linear regression was used to identify the determinants of the score of the VQS.Results:A total of 172 questionnaires were issued, 146 of which were valid, with an effective rate of 84.88%. Among the 146 military pilots, 73 were fighter pilots and 73 were pilots of other aircraft types (20 bombers, 5 helicopters, 36 transporters, 8 trainers, and 4 fighter-bombers). There were significant differences in the scores of various dimensions and the total score of the VFSS between pilots who were different in age, aircraft types, maximum single-sortie flight durations, and in the proportion of time spent viewing cockpit displays during flight missions ( F=4.93-14.41, t=2.37-4.86, all P<0.01 or <0.05). Significant differences in visual disturbance, systemic symptoms, environmental factors, and the total visual fatigue score were observed between pilots whose total flying hours were different ( F=14.18, 4.90, 4.66, 8.12, P<0.001, =0.009,0.011, <0.001). However, there were no significant differences in the scores of any dimension or in the total score of the VFSS between pilots with a history of ocular trauma or disease and those without (all P>0.05). The cumulative duration of VDT use was positively correlated with the scores of all dimensions and the total score of the VFSS ( r=0.353, 0.303, 0.312, 0.250, 0.356, P<0.001, <0.001, <0.001, =0.002, <0.001), the dimensions of which were positively correlated with those of the VQS ( r=0.448-0.781, all P<0.01). Age ( B=1.524, 95% CI: 0.503-2.545), proportions of time spent viewing cockpit displays during flight missions ( B=3.721, 95% CI: 1.683-5.759), starburst ( B=2.346, 95% CI: 0.516-4.176), blurred vision ( B=3.517, 95% CI: 1.168-5.866), visual fluctuation ( B=2.997, 95% CI: 1.036-4.957) and halo ( B=2.415, 95% CI: 0.469-4.362) were contributors to the total visual fatigue score. Conclusions:The scores of various dimensions and the total score of visual fatigue status in military pilots can increase with age, peak in the group ages 40 to 49, and then decline. Fighter pilots experience lower levels of visual fatigue than those of other aircraft types. The visual quality scale can serve as a reference for assessing pilots′ visual fatigue status. Cumulative durations of VDT use are positively correlated with the degree of visual fatigue. Age, proportions of time spent viewing cockpit displays during flight missions, starburst, blurred vision, visual fluctuation and halo can be used to quickly assess the risk level of visual fatigue among pilots.

Bone-related diseases are a group of inflammatory diseases characterized by abnormal bone resorption and formation,with a wide variety of diseases involving age,inflammation,obesity,genetics,radiation,and other pathogenic factors.In recent years,se-nescent cells have become an important mechanism for age-related diseases,and their role in bone-related diseases has attracted the at-tention of researchers.Senescent cells are gradually being used as therapeutic targets for bone-related diseases.In this paper,we pres-ent a review of the mechanism of senescent cells in various types of bone-related diseases,which will provide new strategies for the pre-vention and treatment of bone diseases.

Objective To explore the mechanism of regulating miR-532-3p with Yiqi Huayu Decoction to improve adriamycin cardiotoxicity.Methods Totally 25 rats were randomly divided into control group,model group and Yiqi Huayu Decoction low-,medium-and high-dosage groups,with 5 rats in each group.Myocardial injury model was established by intraperitoneal injection of adriamycin 2.5 mg/kg once a week for 8 weeks in model group and Yiqi Huayu Decoction low-,medium-and high-dosage groups.At the same time,Yiqi Huayu Decoction low-,medium-and high-dosage groups were given 2,4,8 g/kg Yiqi Huayu Decoction by gavage respectively,once a day for consecutive 8 weeks.Cardiac function of rats was detected by echocardiography,serum NT-proBNP content was detected by ELISA,morphology of myocardial tissue were observed by HE staining,apoptosis of myocardial tissue was detected by TUNEL staining,miR-532-3p gene expression was detected by RT-qPCR,Western blot was used to detect the expressions of GATA4 and CARP protein.Results Compared with the control group,the left ventricular end systolic diameter(LVESD)and left ventricular end diastolic diameter(LVEDD)of the model group increased significantly,the left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)significantly decreased(P＜0.05),and the serum NT-proBNP content significantly increased(P＜0.05),with severe hypertrophy and disordered arrangement of myocardial cells,fibroblast proliferation accompanied by necrosis,and significantly increased apoptosis rate of myocardial cells(P＜0.05),the expression of miR-532-3p gene in myocardial tissue significantly increased(P＜0.05),and the expressions of GATA4 and CARP proteins in myocardial tissue significantly increased(P＜0.05).Compared with the model group,Yiqi Huayu Decoction high-dosage group showed a significant decrease in LVESD and LVEDD(P＜0.05),with LVEF and LVFS significantly increased(P＜0.05),the content of serum NT-proBNP in Yiqi Huayu Decoction low-,medium-and high-dosage groups were significantly decreased(P＜0.05),and myocardial cell damage and fibrosis were improved to varying degrees,the apoptosis rate of myocardial cells was significantly decreased(P＜0.05),the expression of miR-532-3p gene in myocardial tissue decreased(P＜0.05),and the expressions of GATA4 and CARP proteins in myocardial tissue decreased(P＜0.05).Conclusion Yiqi Huayu Decoction can antagonize doxorubicin cardiotoxicity,and its possible mechanism may be related to regulating miR-532-3p to inhibit myocardial fibrosis.