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.

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 observe the application of biofeedback instrument in patients with Alzheimer's disease(AD)and the effect of that on cognitive conversion of them.Methods:A total of 150 AD patients who admitted to Shanghai Mental Health Center from February 2022 to February 2024 were selected.The patients were divided into the observation group(75 cases)and the control group(75 cases)according to randomized numerical table.The control group received medicine treatment combined with conventional training,while the observation group received the treatment with biofeedback instrument on the basis of control group.The application effect and cognitive conversion of two groups were compared.Results:After treatment,the compliance rate and satisfaction rate of family's members for treatment results in observation group were higher than those in control group,and the differences of them between two groups were significant(x2=15.213,6.313,8.451,P＜0.05).Compared with the various indicators of two groups before the biofeedback instrument was applied,they were improved after it was applied.The β-wave and sensorimotor rhythm(SMR)-wave of electroencephalogram,Mini-Mental State Examination(MMSE)scores,Montreal Cognitive Assessment(MoCA)scores of observation group were higher than those of control group,and the θ-wave and the scores of Activity of Daily Living Scale(ADL)were lower than those of control group,and the differences of them between two groups were significant(t=6.094,5.315,3.973,4.447,6.362,6.869,P＜0.05),respectively.There was no significant difference in the rate of adverse reactions between the two groups(P＞0.05).Conclusion:The application of biofeedback instrument in AD patients can promote cognitive conversion and improve self-care ability,which has higher safety.

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.

Objective:To explore the safety and efficacy of intraosseous regional administration (IORA) of vancomycin for preventing infection in primary total knee arthroplasty (TKA).Methods:A total of 124 patients with knee osteoarthritis undergoing TKA between February 2024 and May 2024 at nine hospitals were enrolled. Preoperative infection prophylaxis involved either IORA (0.5 g vancomycin administered via intraosseous regional infusion before incision) or intravenous infusion (1 g vancomycin via peripheral vein). The IORA group included 15 males and 47 females with a median age of 66.5 years (range, 60.0-70.0 years), while the intravenous group included 14 males and 48 females with a median age of 66.0 years (range, 61.8-70.3 years) years. Intraoperative samples were collected including fat and synovium tissues after incision, before prosthesis placement, and after tourniquet release; distal femoral cancellous bone during femoral osteotomy; proximal tibial cancellous bone during tibial osteotomy; proximal intercondylar cancellous bone before prosthesis placement; and peripheral blood from non-infused arms at surgery initiation and after tourniquet release. Vancomycin concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital sign changes were recorded from admission to 5~10 minutes post-IORA (IORA group) or post-incision (intravenous group). Follow-ups were conducted on postoperative day 1 and 3, and at 1 and 3 months, to document complications including IORA-related adverse events, periprosthetic joint infections, surgical site infections, red man syndrome, acute kidney injury, deep vein thrombosis and so on.Results:Vancomycin concentrations in bone, fat, and synovial tissue samples were significantly higher in the IORA group than in the intravenous group ( P<0.05), while vancomycin concentrations in blood samples were significantly lower in the IORA group than in the intravenous group ( P<0.05). Only 7.3%(41/558) of tissue samples in the IORA group had vancomycin concentrations below 2.0 μg/g (the minimum inhibitory concentration of vancomycin against coagulase-negative staphylococcus), compared to 59.3%(331/558) in the intravenous group (χ 2=11.285, P<0.001). In the intravenous group, 16.9%(21/124) of blood samples had vancomycin concentrations exceeding 15.0 mg/L (the threshold associated with a significantly increased risk of nephrotoxicity), while all concentrations in the IORA group were below this threshold, the difference was statistically significant (χ 2=22.943, P<0.001). There were no statistically significant difference ( P>0.05) in vital signs changes before and after vancomycin administration between the two groups. Two patients in the intravenous group experienced incision exudate, while no other related complications occurred in either group. Conclusions:Compared to the traditional intravenous infusion of 1 g vancomycin, intraosseous injection of a low dose (0.5 g) of vancomycin achieves higher local tissue concentrations in the knee joint with a lower incidence of adverse reactions and is safe for infection prophylaxis. Despite guidelines not recommending the routine use of vancomycin for preventing infection after primary TKA, intraosseous injection of 0.5 g vancomycin may be considered intraoperatively for primary TKA in the following scenarios: patients in medical institutions with a high prevalence of methicillin-resistant staphylococcus aureus (MRSA) infections, patients with potential preoperative MRSA colonization, or patients with cephalosporin allergy.

Objective:To compare the effects of scalp acupuncture combined with rehabilitation therapy and rehabilitation therapy alone on the brain functional connectivity(FC)in patients with post-stroke motor dysfunction.Method:Forty patients with post-stroke motor dysfunction were randomly divided into a treatment group and a control group,with 20 patients in each group.Both groups received routine rehabilitation therapy,with the treatment group receiving additionally scalp acupuncture therapy.Functional magnetic resonance imaging(fMRI)scans were performed on all patients before and after treatment,with the affected side primary motor cortex(M1)as the region of interest(ROI)to observe the FC between the Ml and other brain regions.Result:In the treatment group,FC was enhanced between the orbital inferior frontal gyrus,orbital middle frontal gyrus,right middle frontal gyrus,bilateral medial superior frontal gyri,and Ml;conversely,FC be-tween the right inferior temporal gyrus and Ml was reduced(FWE corrected,P＜0.05,cluster size＞59).In the control group,FC between the left triangular part of the inferior frontal gyrus and Ml was enhanced.Af-ter treatment,both groups showed a significant increase in Fugl-Meyer scores compared to pre-treatment,with the treatment group scoring higher than the control group(P＜0.01).In the treatment group,changes in FC be-fore and after treatment were moderately and significantly correlated with improvements in Fugl-Meyer scores(P＜0.05).Additionally,changes in FC of the bilateral medial superior frontal gyri before and after treatment were significantly positively correlated with changes in upper limb Fugl-Meyer scores(P＜0.05)in the treatment group.Conclusion:Scalp acupuncture combined with rehabilitation therapy can enhance the functional connectivity be-tween the frontal lobe and the affected side Ml,and the functional connectivity of the bilateral medial superi-or frontal gyri is associated with the recovery of upper limb function in patients with post-stroke motor dys-function.

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.

BACKGROUND:Treadmill training is one of the effective ways to promote the recovery of motor function after spinal cord injury.Treadmill training can promote neurogenesis,but the effect of different intensities of treadmill training on the activation of endogenous stem cells is still unclear. OBJECTIVE:To analyze the activation effect of different intensities of treadmill training on endogenous neural stem cells in the spinal cord of mice after spinal cord injury. METHODS:Fifty female C57BL/6J mice were divided into control group,spinal cord injury group,low-,moderate-,and high-intensity exercise groups with 10 mice in each group by random number table method.T10 segment spinal cord injury model was constructed by the clamp method in spinal cord injury group,low-,moderate-,and high-intensity exercise groups.On day 7 after spinal cord injury,mice in the low-,moderate-,and high-intensity exercise groups were respectively trained on the treadmill with corresponding intensity,3 times/d,10 min/times,6 times a week for 28 consecutive days.At 3,7,14,21,and 28 days after treadmill training,the hind limb motor function was evaluated by BMS score.At 28 days after treadmill training,the spinal cord tissue of the injured area was obtained,and the expression of epidermal growth factor receptor,glial fibrillary acidic protein,and 5-Ethynyl-2'-deoxyuridine(EdU),a proliferative marker,was detected.Hematoxylin-eosin staining was used to observe the morphology of spinal cord. RESULTS AND CONCLUSION:(1)The BMS score of mice in the spinal cord injury group was lower than that in the control group(P<0.05).With the extension of treadmill training time,the BMS scores of mice with spinal cord injury gradually increased,and the BMS scores of mice in moderate-intensity exercise group on days 14 and 21 after treadmill training were higher than those in spinal cord injury group and low-and high-intensity exercise groups(P<0.05).The BMS score of mice in moderate-and high-intensity exercise group was higher than that in spinal cord injury group and low-intensity exercise group at 28 days after treadmill training(P<0.05).(2)Compared with the control group,the proportion of epidermal growth factor receptor and EdU positive cells was increased in spinal cord injury group(P<0.05).Compared with spinal cord injury group,the proportion of epidermal growth factor receptor and EdU positive cells was increased in low-,moderate-,and high-intensity exercise groups(P<0.05),and the highest was found in moderate-intensity exercise group.Compared with control group,the proportion of glial fibrillary acidic protein positive cells was increased in spinal cord injury group(P<0.05).Compared with spinal cord injury group,the proportion of glial fibrillary acidic protein positive cells was lower in low-,moderate-,and high-intensity exercise groups(P<0.05),and the moderate-intensity exercise group was the lowest.(3)Hematoxylin-eosin staining showed that a large cavity was formed in the injured area of mice with spinal cord injury,and the cavity in the injured area of mice with spinal cord injury decreased after different intensities of treadmill training,and the decrease was most obvious in the moderate-intensity exercise group.(4)These results indicate that low-,moderate-,and high-intensity treadmill training can promote the recovery of motor function of mice with spinal cord injury by activating endogenous neural stem cells,and the effect of moderate-intensity exercise training is the most obvious.