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.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

Aim To investigate the high expression of LINC00626 in colorectal cancer,and explore the effects of LINC00626 on the proliferation,apoptosis,and drug sensitivity of colorectal cancer SW480 cells,as well as its underlying mechanisms.Methods Flu-orescence in situ hybridization(FISH)was used to de-tect the expression levels of LINC00626 in 38 colorec-tal cancer tissues and their corresponding adjacent nor-mal tissues.The JASPAR database was utilized to pre-dict co-expressed genes and their possible binding sites.Cell transfection technology was employed to knockdown LINC00626.Western blot and qRT-PCR techniques were used to verify the transfection efficien-cy.CCK-8 assay,cell apoptosis and necrosis staining,and Western blot were used to detect the changes in the proliferation,apoptosis,drug sensitivity,and ap-optotic proteins of SW480 cells,respectively.Results The FISH results indicated that LINC00626 was highly expressed in colorectal cancer tissues(P＜0.05).The expression of LINC00626 was not associat-ed with the age or gender of patients,but was related to the TNM stage and the presence of lymph node me-tastasis($ P＜0.05 $).The results of CCK-8 assay and cell apoptosis and necrosis staining showed that af-ter knockdown of LINC00626,the proliferation ability of SW480 cells decreased,the apoptosis level in-creased,and the drug resistance decreased(P＜0.05).Western blot results showed that with the de-crease in the expression level of LINC00626,the ex-pression of caspase-3 protein decreased,the expression of cleaved caspase-3 protein increased,and the expres-sion of Bcl-2 protein decreased(P＜0.05).Conclu-sions LINC00626 is highly expressed in colorectal cancer and is associated with the TNM stage and the presence of lymph node metastasis.LINC00626 can af-fect the proliferation,apoptosis,and drug sensitivity of SW480 cells and alter the expression of apoptotic pro-teins.

Aim To investigate the effects of Congrong San(CRS)on learning and memory ability,hippocam-pal neuronal injury,and ferroptosis in rats with Alzhei-mer's disease(AD)and to explore the related mecha-nisms.Methods AD rat models were established and divided into Sham,Model,CRS low-dose,CRS medium-dose,CRS high-dose,and memantine groups.After treatment,Morris water maze,HE and Nissl staining,transmission electron microscopy,immunofluorescence staining,Western blot,and kit assays were performed to assess learning and memory ability,hippocampal neuro-nal injury,ferroptosis-related indicatorsand glucose reg-ulated protein 78 ku(GRP78)-(proteinkinaseR-li-keERkinase)PERK-(activating transcription factor 4)ATF4 pathway protein expression.Results Com-pared with the model group,rats in the CRS medium-and high-dose groups and the memantine group showed significant improvement in learning and memory abili-ty,reduced hippocampal neuronal injury,increased number of Nissl bodies,and ameliorated endoplasmic reticulum swelling and mitochondrial damage.In addi-tion,the expressions of GRP78,p-PERK/PERK,and ATF4 were downregulated,while GPX4 expression was upregulated in the CRS medium-and high-dose groups and the memantine group.Moreover,MDA content de-creased,and SOD and GSH-PX levels increased in these groups.Conclusions CRS can improve the learning and memory ability in AD rats,reduce hipp-ocampal neuronal injury and ferroptosis,and its mecha-nism may be related to the inhibition of the GRP78-PERK-ATF4 pathway,enhancement of GPX4 expres-sion,and reduction of oxidative stress levels,providing a new approach for the clinical treatment of AD.

Objective To investigate the mechanism of autophagy induced by House dust mites(HDM)on airway epithelial tight junction through β-catenin-Snail signaling pathway.Methods Human bronchial epithelial cells(16HBE)were stimulated with HDM at different time points(0,3,6,12,24,48 h)and different concen-trations(0,40,100,200 μg/mL)to screen the appropriate stimulation concentration and stimulation time.16HBE cells were treated with oxidative stress inhibitor N-acetylcysteine(NAC),autophagy inhibitor 3-methylad-enine(3-MA),HDM,and their combinations.Cells were transfected with mCherry-EGFP-LC3B,Beclin-1-siRNA,and ATG14-siRNA lentivirus and then stimulated with NAC and HDM.Immunofluorescence was used to detect the expression levels of autophagy-related protein LC3B,tight junction-related proteins Occludin,and ZO-1 in airway epithelial cells.The level of reactive oxygen species(ROS)was detected by using DCFH-DA in each group.The protein expression levels of Occludin,ZO-1,LC3B,Beclin-1,ATG5,ATG14,P62,Snail,β-catenin and p-β-catenin were detected by Western blot method.Results Immunofluorescence results showed that compared with the control group,200 μg/mL HDM stimulation induced cellular autophagy,increased the expression level of LC3B protein,and promoted the level of ROS,all with statistical significances(all P<0.05).Compared with the HDM group,the HDM+3-MA,HDM+ATG14-si,and HDM+Beclin-1-si groupsall showed significantincreases in the expression levels of tight junction-related proteins Occludin and ZO-1(P<0.05).The HDM+NAC group demonstrated significant decreases both in the level of ROS andin the expression level of LC3B protein.Western blot results revealed that compared with HDM,3-MA and autophagy protein low-expression beads(Beclin-1-si,ATG14-si)attenuated HDM-induced cellular autophagy(P<0.05),inhibited HDM-induced upregulation of Snail and p-β-catenin expression,and improved HDM-induced decreases in Occludin and ZO-1(P<0.05).Moreover,compared with the HDM group,the NAC+HDM group exhibited significant decreases both in the conversion of LC3BⅠ to LC3BⅡ(P<0.001)in the protein levels of Snail,p-β-catenin,Beclin-1 and ATG14(P<0.01),but significant increases in the protein levels of Occludin and ZO-1(P<0.05).Conclusion HDM affects the tight connections between airway epithelial cells by inducing autophagy,which may be attributed to the β-catenin-Snail signaling pathway.

Objective:To conduct a comprehensive global review of research on toxic leadership behavior among nursing managers and to analyze the current research status.Methods:Literature related to toxic leadership behavior among nursing managers was retrieved from PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, VIP Chinese Science and Technology Journal Database, and China Biomedical Literature Database. The search period extended from the inception of each database to February 15, 2025. The included literature was then organized, analyzed, and summarized.Results:A total of 28 studies were included. There were 23 studies reported the occurrence of toxic leadership behavior among nursing managers, the incidence of toxic leadership behavior was almost at a moderately low level. There were 8 studies reported the influencing factors of toxic leadership behavior, its influencing factors encompassed three primary aspects: the organizational level, the personal characteristics of nursing managers, and characteristics of the nursing staff group. Assessment tools of toxic leadership behavior included the Toxic Leadership Behaviors of Nurse Managers, the Abuse Management Questionnaire, etc. The adverse consequences included increased nurse turnover intention, decreased nursing quality, and reduced organizational trust, etc. Interventions were planned and implemented from three perspectives: the hospital managers, nursing managers, and the nurses.Conclusions:The factors influencing toxic leadership behavior among nursing managers and its adverse consequences require further exploration. Therefore, more intervention studies are warranted to provide new insights and methods for preventing and reducing toxic leadership behavior.

OBJECTIVE To investigate the clinical distribution and dynamic change of drug resistance of K.pneu-moniae and carbapenem-resistant Klebsiella pneumoniae(CRKP)isolated from a three-A hospital of Suzhou so as to provide scientific bases for prevention and control of hospital-associated infections and reasonable application of antibiotics.METHODS The K.pneumoniae and CRKP strains that were isolated from the submitted specimens were collected from the patients who treated in the Affiliated Suzhou Hospital of Nanjing Medical University from 2019 to 2023.The clinical characteristics of the patients with infection and the trend of drug resistance were statis-tically analyzed.RESULTS Totally 5631 strains of K.pneumoniae were isolated,1205(21.40％)of which were CRKP,and the isolation rate of CRKP showed an upward trend in the five years(x2=236.352,P＜0.001).Among the K.pneumoniae isolates,51.59％were isolated from sputum,13.51％from urine;19.43％were isolated from intensive care unit(ICU),7.64％from emergency department,and 7.19％from respiratory department.There were significant differences in gender,age and season between the patients detected with CRKP and the patients detected with non-CRKP(P＜0.05).The drug resistance rates of the K.pneumoniae strains to cephalosporins,quinolones and carbapenems con-tinuously increased from 2019 to 2023(P＜0.001),the drug resistance rate to imipenem increased from 11.69％to 34.24％,meropenem from 10.92％to 34.24％.CONCLUSIONS The K.pneumoniae isolates show severe drug re-sistance from 2019 to 2023,and the isolation rate of CRKP strains rises increasingly.It is necessary for the hospi-tal to focus on the continuous monitoring of key populations and departments and optimize the management of an-tibiotics and infection control strategies so as to provide guidance for reasonable clinical use of antibiotics,effective control of transmission of drug-resistant strains and cope with the increasingly severe drug resistance.

Objective To analyze the effects of circular RNA CSPP1(circCSPP1)and microRNA-642a-5p(miR-642a-5p)on the biological behaviors of retinoblastoma Y-79 cells.Methods A total of 47 patients with retinoblastoma(47 eyes)who were admitted at Zhengzhou Central Hospital from June 2019 to October 2022 were included in this study,and the tumor tissues and paraneoplastic tissues of these patients were collected during surgery.The human retinoblastoma cell line Y-79 was cultured in vitro and then divided into seven groups based on different transfectants:the Con group(nor-mally cultured Y-79 cells),sh-NC group(transfected with sh-NC),sh-circCSPP1 group(transfected with sh-circCSPP1),miR-NC group(transfected with miR-NC),miR-642a-5p group(transfected with miR-642a-5p mimics),sh-circCSPP1+an-ti-miR-NC group(co-transfected with sh-circCSPP1 and anti-miR-NC),and sh-circCSPP1+anti-miR-642a-5p group(co-transfected with sh-circCSPP1 and anti-miR-642a-5p).The real-time quantitative polymerase chain reaction(RT-qPCR)was used to measure the expression level of circCSPP1 and miR-642a-5p in retinoblastoma tissues,paraneoplastic tissues,and Y-79 cells.The proliferation,migration,and invasion of Y-79 cells were assessed via the cell counting kit-8(CCK-8)assay,scratch wound healing assay,and Transwell chamber assay,respectively.The targeting relationship between cir-cCSPP1 and miR-642a-5p was verified by the dual-luciferase reporter assay.Western blot was performed to quantify the ex-pression level of E-cadherin and N-cadherin.Results Compared with paraneoplastic tissues,the expression of circCSPP1 was up-regulated,that of miR-642a-5p was downregulated in retinoblastoma tissues,and the differences were statistically significant(both P＜0.05).Compared with the Con group and the sh-NC group,the sh-circCSPP1 group showed a reduced scratch healing rate,decreased invasive cell count,up-regulated relative protein expression of E-cadherin,and down-regu-lated relative protein expression of N-cadherin,and the differences were statistically significant(all P＜0.05).Compared with the Con group and the miR-NC group,the miR-642a-5p group exhibited a reduced scratch healing rate,decreased in-vasive cell count,up-regulated protein expression of E-cadherin,and down-regulated protein expression of N-cadherin,and the differences were statistically significant(all P＜0.05).The dual luciferase reporter assay demonstrated that cir-cCSPP1 negatively regulated the expression level of miR-642a-5p.Compared with the sh-circCSPP1+anti-miR-NC group,the sh-circCSPP1+anti-miR-642a-5p group displayed an increased scratch healing rate,increased invasive cell count,down-regulated protein expression of E-cadherin,and up-regulated protein expression of N-cadherin,and the differences were statistically significant(all P＜0.05).Conclusion Silencing circCSPP1 may suppress the proliferation,migration,and invasion of Y-79 cells by up-regulating the expression of miR-642a-5p,suggesting that circCSPP1 may become a poten-tial therapeutic target for retinoblastoma.

Objective:To explore the influence of artificial intelligence(AI)-assisted compressive sensing(ACS)technique with different acceleration factors on the image quality and scan time of three dimensional time-of-flight magnetic resonance angiography(3D-TOF-MRA)for brain.Methods:Thirty participants who underwent brain magnetic resonance imaging(MRI)at Tongzhou Branch of Beijing Friendship Hospital were recruited.All subjects underwent imaging scans about four different parameters:a non-accelerated technique(control group),ACS technique integrated with acceleration factor of 4.03(ACS4 group),ACS technique integrated with acceleration factor of 5.02(ACS5 group),and ACS technique integrated with acceleration factor of 6.06(ACS6 group).The image clarity,ranking of imaging capabilities of distal branch blood vessels and the ratio of pseudo-stenosis were qualitatively analyzed.The signal-to-noise ratio(SNR),contrast-to-noise ratio(CNR),edge sharpness,and scan time were quantitatively analyzed.Results:There was not difference in vessel clarity among three ACS groups at the proximal and middle intracranial segments.For distal segments of blood vessel,the ACS4 group[3.0(3.0,3.0)]and ACS5 group[3.0(3.0,3.0)]were better than ACS6[2.5(2.0,3.0)](q=29.800,27.500,P<0.05).The imaging capabilities of distal-branch vessel of ACS4 group and ACS5 group were better than ACS6 group.There was no stenosis in the proximal and middle segments of the images of the three ACS group,and there were no stenosis in the images of distal vessels of ACS4 group and ACS5 group.A total of 5 cases were pseudo-stenosis in the distal vessels of ACS6 group.Compared with the control group,the incidence of pseudo-stenosis in the distal vessels of ACS6 group was 16.7%.The SNR and CNR values of quantitative analysis for proximal vessels in ACS6 group were higher than them in ACS4 group(q=27.800,26.200,P<0.05),and there was not significant difference in them among ACS4 group,ACS6 group and ACS5 group(P>0.05).The differences of SNR and CNR values in the middle and distal segments of blood vessels among different groups were not significant(P>0.05).There was not significant difference in the edge sharpness of blood vessels among ACS4 group,ACS5 group,and ACS6 group(P>0.05),while all of them were higher than those of control group,and the differences were significant(q=48.150,53.367,44.883,P<0.001).Compared with control group,the scan-time of ACS4 group was reduced by 55.19%,and that of ACS5 group was reduced by 64.07%,and that of ACS6 group was reduced by 70%.Conclusion:ACS technique can accelerate the imaging speed of brain 3D-TOF-MRA and ensure image quality.It is clinically recommended to set the ACS acceleration factor as 5.02 to undergo brain 3D-TOF-MRA scans.