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.

Objective To evaluate the effect of pneumatic logistics transport system(PTS)on the trans-portation efficiency of the transferred samples and the accuracy of the results.Methods The transportation speed,temperature and humidity change of PTS were analyzed by temperature and humidity transmitter.Anti-coagulant samples containing disodium ethylenediaminetetraacetate(EDTA-K2),sodium citrate,lithium hepa-rin and samples containing inert separation gel coagulant were selected.and used respectively for complete blood cell analysis,prothrombin time(PT),activated partial prothrombin time(APTT),troponin T(TnT)and other myocardial markers,as well as the detection of items such as glucose(Glu)and lactate dehydrogen-ase(LDH).According to the transfer mode,they were divided into the manual transfer group and the PTS transfer group,and according to the number of PTS transfers,they were divided into the one-time transfer group,the three-time transfer group and before transfer(control).The differences among each group were statistically analyzed,and 1/3 allowable total error(1/3TEa)was adopted as the criterion for determining the clinical application value.Results There was no statistically significant difference in the changes of tempera-ture and humidity during the transportation process of PTS compared with manual transportation(P＞0.05),but it was significantly faster than manual transportation in terms of transportation time(P＜0.05).Com-pared with before transfer,the differences between the PT,APTT,Glu and LDH items in the one-time trans-fer group and the three-time transfer group were statistically significant(P＜0.01),and their deviations were all much greater than 1/3TEa.However,in the plasma samples,compared with before transport,there were statistically significant differences in Glu and LDH between the one-time transfer group and the three-time transfer group(P＜0.05),but the deviations were all less than 1/3TEa.For the items of TnT,red blood cell count and hematocrit,compared with before transfer,there were statistically significant differences between some groups of the one-time transfer group and the three-time transfer group(P＜0.05),but the deviations were all less than 1/3TEa.Conclusion PTS can significantly improve the transportation efficiency of sam-ples,but it significantly affects the detection of Glu and LDH in plasma samples,which can be improved by u-sing serum sample transportation instead.In addition,PTS also affects the detection of PT and APTT,and it is not recommended to use PTS to transport coagulation specimen.

Objective To explore the effect of bionic electrical stimulation(BES)combined with resistance tightening leg training on postpartum pelvic floor dysfunction(PFD).Methods A total of 205 patients with PFD were divided into the BES group(n=102)and the combined group(n=103)by random number table method.All subjects received routine pelvic floor muscle training.In addition,the BES group was treated with BES intervention,and the combined group was treated with BES combined with resistance tightening leg training,with 8 weeks of treatment.The classification of pelvic floor muscle strength,electrophysiological indexes of pelvic floor function,urodynamics and stress urinary incontinence(SUI)classification/pelvic organ prolapse(POP)degree were compared between the two groups before and after treatment.Results After treatment,the pelvic floor muscle strength classification,SUI classification and POP degree in the combined group were significantly better than those in the BES group(P<0.05).After treatment,ClassⅠ/ClassⅡmuscle fiber fatigue,vaginal dynamic pressure and maximal electromyography(EMG)value of fast muscle in the combined group were(-1.20±0.35)%,(-0.90±0.30)%,(76.30±5.51)cmH2 O,(43.00±5.82)μV,respectively,which were all significantly higher than those in the BES group(P<0.05).After treatment,the indexes of urodynamics in both groups were significantly improved,and the combined group was better than the BES group(P<0.05).Conclusions BES combined with resistance tightening leg training can significantly improve pelvic floor muscle strength,muscle fiber fatigue and urodynamics in patients with PFD,thus alleviating SUI/POP symptoms.

Type 2 diabetes (T2D) is an independent risk factor for cognitive impairment. The dysregulation of hypoxia inducible factor (HIF) signaling in T2D patients results in impaired adaptive responses to hypoxia, thereby accelerating the progression of complications. However, limited knowledge is available regarding its precise function in diabetes-associated cognitive impairment (DACI). Here, elevated HIF-1α levels were observed in brain endothelial cells (ECs) of db/db mice. Functionally, brain ECs-specific knockdown of H if1 a significantly ameliorated T2D-induced memory loss and neuronal damage. Glycolysis in brain ECs was inhibited in this process, as indicated by RNA-seq, leading to decreased hippocampal lactate production through reduced LDHA expression. Notably, T2D patients showed increased cerebrospinal fluid lactate levels, which were strongly associated with their cognitive dysfunction. Intrahippocampal injection of lactate accelerated cognitive dysfunction and impaired adult hippocampal neurogenesis (AHN) in db/db mice. Conversely, reducing hippocampal lactate levels through the intrahippocampal injection of oxamate delayed the onset of memory deficits. Furthermore, asiatic acid was discovered to protect db/db mice from cognitive impairment by decreasing brain endothelial HIF-1α expression and subsequently reducing hippocampal lactate-induced AHN damage. Overall, this study elucidates the inhibiting role played by endothelial HIF-1α-driven lactate in AHN and highlights a potential tactic of targeting HIF-1α in brain ECs for treating cognitive impairment.

Retinopathy of prematurity (ROP) is a vision-threatening disorder that leads to pathological growth of the retinal vasculature due to hypoxia. Here, we investigated the potential effects of alamandine, a novel heptapeptide in the renin-angiotensin system (RAS), on hypoxia-induced retinal neovascularization and its underlying mechanisms. In vivo, the C57BL/6J mice with oxygen-induced retinopathy (OIR) were injected intravitreally with alamandine (1.0 μmol/kg per eye). In vitro, human retinal microvascular endothelial cells (HRMECs) were utilized to investigate the effects of alamandine (10 μg/mL) on proliferation, apoptosis, migration, and tubular formation under vascular endothelial growth factor (VEGF) stimulation. Single-cell RNA sequencing (scRNA-seq) matrix data from the Gene Expression Omnibus (GEO) database and RAS-related genes from the Molecular Signatures Database (MSigDB) were sourced for subsequent analyses. By integrating scRNA-seq data across multiple species, we identified that RAS-associated endothelial cell populations were highly related to retinal neovascularization. The liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis revealed a significant decrease in alamandine levels in both the serum and retina of OIR mice compared to those in the control group. Next, alamandine ameliorated hypoxia-induced retinal pathological neovascularization and physiologic revascularization in OIR mice. In vitro, alamandine effectively mitigated VEGF-induced proliferation, scratch wound healing, and tube formation of HRMECs primarily by inhibiting the hypoxia-inducible factor-1α (HIF-1α)/VEGF pathway. Further, coincubation with D-Pro⁷ (Mas-related G protein-coupled receptor D (MrgD) antagonist) hindered the beneficial impacts of alamandine on hypoxia-induced pathological angiogenesis both in vivo and in vitro. Our findings suggested that alamandine could mitigate retinal neovascularization by targeting the MrgD-mediated HIF-1α/VEGF pathway, providing a potential therapeutic agent for OIR prevention and treatment.
Animals ; Retinal Neovascularization/prevention & control* ; Mice, Inbred C57BL ; Vascular Endothelial Growth Factor A/metabolism* ; Humans ; Mice ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Oligopeptides/therapeutic use* ; Signal Transduction/drug effects* ; Cell Proliferation/drug effects* ; Endothelial Cells/drug effects* ; Retinopathy of Prematurity/drug therapy* ; Apoptosis/drug effects* ; Cell Movement/drug effects* ; Renin-Angiotensin System/drug effects* ; Cells, Cultured

Patients with periodontal disease often require combined periodontal-orthodontic interventions to restore periodontal health, function, and aesthetics, ensuring both patient satisfaction and long-term stability. Managing these patients involving orthodontic tooth movement can be particularly challenging due to compromised periodontal soft and hard tissues, especially in severe cases. Therefore, close collaboration between orthodontists and periodontists for comprehensive diagnosis and sequential treatment, along with diligent patient compliance throughout the entire process, is crucial for achieving favorable treatment outcomes. Moreover, long-term orthodontic retention and periodontal follow-up are essential to sustain treatment success. This expert consensus, informed by the latest clinical research and practical experience, addresses clinical considerations for orthodontic treatment of periodontal patients, delineating indications, objectives, procedures, and principles with the aim of providing clear and practical guidance for clinical practitioners.
Humans ; Consensus ; Orthodontics, Corrective/standards* ; Periodontal Diseases/complications* ; Tooth Movement Techniques/methods* ; Practice Guidelines as Topic

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

ADC189 is a novel drug of cap-dependent endonuclease inhibitor. In our study, its antiviral efficacy was evaluated in vitro and in vivo, and compared with baloxavir marboxil and oseltamivir. A first-in-human phase I study in healthy volunteers included single ascending dose (SAD) and food effect (FE) parts. In the preclinical study, ADC189 showed potent antiviral activity against various types of influenza viruses, including H1N1, H3N2, influenza B virus, and highly pathogenic avian influenza, comparable to baloxavir marboxil. Additionally, ADC189 exhibited much better antiviral efficacy than oseltamivir in H1N1 infected mice. In the phase I study, ADC189 was rapidly metabolized to ADC189-I07, and its exposure increased proportionally with the dose. The terminal elimination half-life (T_1/2) ranged from 76.69 to 98.28 hours. Of note, food had no effect on the concentration, clearance, and exposure of ADC189. It was well tolerated, with few treatment-emergent adverse events (TEAEs) reported and no serious adverse events (SAEs). ADC189 demonstrated excellent antiviral efficacy both in vitro and in vivo. It was safe, well-tolerated, and had favorable pharmacokinetic characteristics in healthy volunteers, supporting its potential for single oral dosing in clinical practice.
Humans ; Antiviral Agents/therapeutic use* ; Animals ; Male ; Adult ; Mice ; Female ; Endonucleases/antagonists & inhibitors* ; Influenza, Human/drug therapy* ; Young Adult ; Dibenzothiepins/pharmacology* ; Oseltamivir/pharmacology* ; Middle Aged ; Triazines/pharmacology* ; Thiepins/pharmacology* ; Influenza B virus/drug effects* ; Influenza A Virus, H1N1 Subtype/drug effects* ; Pyridines/pharmacology* ; Morpholines ; Pyridones

Objective:To explore the impact of previous cytomegalovirus (CMV), herpes simplex virus (HSV), and rubella virus (RV) infection on pregnancy outcomes in infertile women undergoing the first in vitro fertilization/intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) treatment. Methods:A retrospective cohort study was conducted to analyze the clinical data of women who underwent IVF/ICSI-ET for the first time at the Reproductive Medicine Center, the First Affiliated Hospital of Zhengzhou University from December 2017 to December 2022. The patients were divided into CMV-IgG (+) group ( n=154), RV-IgG (+) group ( n=86), HSV-IgG (+) group ( n=93) and IgG all-negative group ( n=172). The pregnancy outcomes of the patients in the virus-only infection group and the IgG all-negative group were compared. Patients who were previously co-infected with CMV and HSV were classified as the CMV+HSV-IgG (+) group ( n=344), and the pregnancy outcomes of patients with previous CMV and HSV co-infection and those with infection alone were further compared. Results:The two pronuclei (2PN) fertilization rate [63.90% (1 195/1 870)], the clinical pregnancy rate [51.30% (79/154)], and the live birth rate [45.45% (70/154)] of the CMV-IgG (+) group were significantly lower than those of the IgG completely negative group [68.68% (1 469/2 139), P=0.001; 68.60% (118/172), P=0.001; 61.05% (105/172), P=0.005]. The 2PN fertilization rate [61.62% (729/1 183)], the clinical pregnancy rate [50.54% (47/93)], and the live birth rate [43.01% (40/93)] of the HSV-IgG (+) group were significantly lower than those of the IgG completely negative group [68.68% (1 469/2 139), P=0.001; 68.60% (118/172), P=0.004; 61.05% (105/172), P=0.005]. There were no statistical differences in the 2PN fertilization rate, the clinical pregnancy rate, and the live birth rate between the RV-IgG (+) group and the IgG completely negative group (all P>0.05). Compared with the IgG completely negative group, there were no significant differences in the risk of complications such as gestational diabetes, hypertensive disorders of pregnancy and neonatal outcomes in the CMV-IgG (+) group, RV-IgG (+) group, and HSV-IgG (+) group (all P>0.05). Multivariate logistic regression analysis showed that CMV-IgG (+) ( OR=0.453, 95% CI: 0.280-0.734, P=0.001; OR=0.515, 95% CI: 0.321-0.825, P=0.006), HSV-IgG (+) ( OR=0.425, 95% CI: 0.245-0.738, P=0.002; OR=0.447, 95% CI: 0.259-0.771, P=0.004) and CMV+HSV-IgG (+) ( OR=0.491, 95% CI: 0.329-0.733, P=0.001; OR=0.528, 95% CI: 0.357-0.780, P=0.001) were all independent influencing factors of patients' clinical pregnancy and live birth. There were no statistical differences in the clinical outcomes between the previous CMV and HSV co-infection group and the single infection group ( P>0.05). Conclusion:Previous CMV or HSV infection alone reduced the fertilization rate, the clinical pregnancy rate and the live birth rate of patients undergoing IVF/ICSI-ET treatment, but had no significant impact on pregnancy complications and neonatal outcomes. Pregnancy outcomes of patients with previous CMV and HSV co-infection were similar to those with infection alone.

As a critical component of global agriculture,the dairy industry is essential for the food security and economic development.In China,the dairy sector in plateau regions plays an important role in addressing the nutritional needs of residents,boosting farmers' incomes,and fostering re-gional economic growth.However,the harsh high-altitude conditions,such as low oxygen,low at-mospheric pressure,and severe climate,pose significant challenges to the health and survival of dairy cows.This article summarizes the changes in physiological characteristics,metabolic perform-ance,production performance,and health status of dairy under high altitude areas,providing in-sights for the identification of adaptive traits in dairy to plateau.Also,the genetic and epigenetic mechanisms behind these phenotypic adaptations are discussed,and future directions and strategies for enhancing adaptability of dairy of dairy n plateau regions are outlined,thereby guiding re-searchers in adaptation evolution and breeding of dairy cattle.