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 quality of diagnosis and treatment guidelines and expert consensuses on childhood immune thrombocytopenic purpura （ITP） published domestically and internationally， in order to provide reference for clinical practice and future guideline/expert consensus development and improvement. METHODS A systematic search was conducted across multiple databases， including PubMed， Cochrane Library， Embase， CNKI， Wanfang data， VIP， CBM； additionally， supplementary searches were carried out on websites such as Medlive， the Chinese Medical Association’s official website， and National Institute for Health and Clinical Excellence in the UK. The retrieval time ranged from the inception to September 2， 2024. Researchers who had undergone systematic training independently evaluated the methodology and report quality included in the guideline/consensus using the Appraisal of Guidelines Research and Evaluation Ⅱ （AGREE Ⅱ） and the Reporting Items for Practice Guidelines in Healthcare （RIGHT）. RESULTS A total of 11 guidelines/consensuses were included. The average scores for the six domains of AGREE Ⅱ tool respectively were “range and purpose” （[ 66.67±17.98）% ]， “participants” [58.33% （13.89%，73.61%）]， “rigor” （[ 41.81±23.85）% ]， “clarity”（[ 69.57±19.35）%]， “applicability” （[ 35.98±17.83）%]， and “independence” [27.08% （0，75.00%）]； out of 11 articles， 9 had a recommendation level of B， 2 had a recommendation level of C， and there were no A-level articles. The average reporting rates of the 7 areas in the RIGHT tool were “basic information” （[ 72.35±12.95）% ]， “background” （[ 54.55±15.40）%]，“ evidence” （[ 36.36±24.81）%]，“ recommended opinions” （[ 53.25±19.20）%]，“ review and quality assurance” [0 （0， 25.00%）]， “funding and conflict of interest statement and management” [12.50%（0，25.00%）]， and other aspects [8.33%（0， 50.00%）]. In addition， there was no statistically significant difference in the AGREE Ⅱ and RIGHT scores between the guidelines and consensuses （P＞0.05）. CONCLUSIONS The overall quality of the guidelines and consensuses included in this study is not high， with a recommended level of B or C. It is recommended that clinical decision-making prioritize referring to the relatively high-quality guideline/consensus among them. The quality of evidence in the existing traditional Chinese medicine guidelines for children with ITP needs to be improved， and there is no integrated guideline/consensus for traditional Chinese and Western medicine. It is recommended to revise or write relevant guideline/consensus according to the requirements of AGREE Ⅱ and RIGHT in various fields to guide clinical practice.

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disease characterized by structural or functional abnormalities of motile cilia. It often presents clinically with recurrent respiratory infections, situs inversus, hydrocephalus, and infertility. Currently, there is no clinical treatment to directly restore ciliary motility in PCD patients.In recent years, researchers have explored gene therapy methods such as gene replacement, gene editing, and RNA replacement in vitro and in mouse models, offering potential new strategies for PCD treatment. This paper comprehensively reviews the current status of PCD gene therapy research, evaluates the potential of different gene therapies, and provides an outlook on the future treatment directions for this disease.

ObjectiveTo compare the clinical features of patients with hepatitis B virus （HBV）-related early-onset liver cancer and those with late-onset liver cancer， to assess the severity of the disease， and to provide a theoretical basis for the early diagnosis and treatment of liver cancer. MethodsA retrospective analysis was performed for 695 patients who were diagnosed with HBV-related liver cancer for the first time in Guangzhou Eighth People’s Hospital， Guangzhou Medical University， from January 2019 to August 2023， among whom 93 had early-onset liver cancer （defined as an age of50 years for female patients and40 years for male patients） and 602 had late-onset liver cancer （defined as an age of ≥50 years for female patients and ≥40 years for male patients）. Related clinical data were collected， including demographic data， clinical symptoms at initial diagnosis， comorbidities， smoking history， drinking history， family history， routine blood test results， biochemical parameters of liver function， serum alpha-fetoprotein（AFP）， virological indicators， coagulation function， and imaging findings. The pan-inflammatory indices neutrophil-to-lymphocyte ratio （NLR）， platelet-to-lymphocyte ratio （PLR）， and lymphocyte-to-monocyte ratio （LMR） were calculated， as well as FIB-4 index， aspartate aminotransferase-to-platelet ratio index （APRI）， S index， Model for End-Stage Liver Disease （MELD） score， Child-Turcotte-Pugh （CTP） score， albumin-bilirubin （AIBL） grade， and Barcelona Clinic Liver Cancer （BCLC） stage. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test or Fisher’s exact test were used for comparison of categorical data between two groups. ResultsThere were significant differences between the two groups in the proportion of male patients and the incidence rates of diabetes， hypertension， and fatty liver disease （χ²=6.357， 15.230， 11.467， and 14.204， all P0.05）， and compared with the late-onset liver cancer group， the early-onset liver cancer group had a significantly higher proportion of patients progressing to liver cancer without underlying cirrhosis （χ²=24.657， P0.001） and a significantly higher proportion of patients with advanced BCLC stage （χ²=6.172， P=0.046）. For the overall population， the most common clinical symptoms included abdominal distension， abdominal pain， poor appetite， weakness， a reduction in body weight， edema of both lower limbs， jaundice， yellow urine， and nausea， and 55 patients （7.9%） had no obvious symptoms at the time of diagnosis and were found to have liver cancer by routine reexamination， physical examination suggesting an increase in AFP， or radiological examination indicating hepatic space-occupying lesion； compared with the late-onset liver cancer group， the patients in the early-onset liver cancer group were more likely to have the symptoms of abdominal distension， abdominal pain， and jaundice （all P0.05）. Compared with the late-onset liver cancer group， the early-onset liver cancer group had a significantly larger tumor diameter （Z=2.845， P=0.034）， with higher prevalence rates of multiple tumors and intrahepatic， perihepatic， or distant metastasis （χ²=5.889 and 4.079， both P0.05）， and there were significant differences between the two groups in tumor location and size （χ²=3.948 and 11.317， both P0.05）. Compared with the late-onset liver cancer group， the early-onset liver cancer group had significantly lower FIB-4 index， proportion of patients with HBsAg ≤1 500 IU/mL， and levels of LMR and Cr （all P0.05）， as well as significantly higher positive rate of HBeAg and levels of log₁₀ HBV DNA， AFP， WBC， Hb， PLT， NLR， PLR， TBil， ALT， Alb， and TC （all P0.05）. ConclusionCompared with late-onset liver cancer， patients with early-onset liver cancer tend to develop liver cancer without liver cirrhosis and have multiple tumors， obvious clinical symptoms， and advanced BCLC stage， which indicates a poor prognosis.

Cancer stem cells (CSCs) are widely acknowledged as primary mediators to the initiation and progression of tumors. The association between microbial infection and cancer stemness has garnered considerable scholarly interest in recent years. Porphyromonas gingivalis (P. gingivalis) is increasingly considered to be closely related to the development of oral squamous cell carcinoma (OSCC). Nevertheless, the role of P. gingivalis in the stemness of OSCC cells remains uncertain. Herein, we showed that P. gingivalis was positively correlated with CSC markers expression in human OSCC specimens, promoted the stemness and tumorigenicity of OSCC cells, and enhanced tumor formation in nude mice. Mechanistically, P. gingivalis increased lipid synthesis in OSCC cells by upregulating the expression of stearoyl-CoA desaturase 1 (SCD1) expression, a key enzyme involved in lipid metabolism, which ultimately resulted in enhanced acquisition of stemness. Moreover, SCD1 suppression attenuated P. gingivalis-induced stemness of OSCC cells, including CSCs markers expression, sphere formation ability, chemoresistance, and tumor growth, in OSCC cells both in vitro and in vivo. Additionally, upregulation of SCD1 in P. gingivalis-infected OSCC cells was associated with the expression of KLF5, and that was modulated by P. gingivalis-activated NOD1 signaling. Taken together, these findings highlight the importance of SCD1-dependent lipid synthesis in P. gingivalis-induced stemness acquisition in OSCC cells, suggest that the NOD1/KLF5 axis may play a key role in regulating SCD1 expression and provide a molecular basis for targeting SCD1 as a new option for attenuating OSCC cells stemness.
Porphyromonas gingivalis/pathogenicity* ; Stearoyl-CoA Desaturase/metabolism* ; Humans ; Carcinoma, Squamous Cell/pathology* ; Mouth Neoplasms/metabolism* ; Animals ; Neoplastic Stem Cells/microbiology* ; Mice, Nude ; Mice ; Nod1 Signaling Adaptor Protein/metabolism* ; Kruppel-Like Transcription Factors/metabolism* ; Cell Line, Tumor

Objective To discuss the application value of comfort medical mode in patients with uterine fibroids receiving interventional embolization therapy during hospitalization.Methods A total of 27 patients with uterine fibroids,who received interventional embolization at the Third Affiliated Hospital of Zhengzhou University of China,were enrolled in this study.The patient's basic data,including age,the sum of the maximum diameter of the measurable uterine fibroids and the hemoglobin level at admission,were collected.After admission and before discharge,the self-efficacy scale score,Becker anxiety scale score,and positive and negative emotions scale score were determined in all the patients.According to the different medical management mode adopted during the hospitalization,the patients were divided into study group(n=14)and control group(n=13).Comfort medical mode guided by quantitative evaluation strategy was employed for the patients of the study group,while conventional management mode was adopted for the patients of the control group.SPSS 26.0 software was used for data analysis.Measurement data within group were analyzed by independent sample t-test,and measurement data between groups were analyzed by paired sample t-test,and P＜0.05 was defined as a statistically significant difference.Results There were no statistically significant differences in the basic data between the two groups,and no statistically significant differences in the self-efficacy scale score,Becker anxiety scale score,and positive and negative emotions scale score at admission existed between the two groups.In the study group,the self-efficacy score and positive emotion score at discharge were strikingly higher than those at admission(P＜0.001),and the anxiety degree and negative emotion score at discharge were obviously lower than those at admission(P＜0.001).In the control group,the scores of the above-mentioned scales at discharge did not differ from those at admission.Conclusion The comfort medical mode guided by quantitative evaluation strategy has better clinical effect in patients with uterine fibroids receiving interventional embolization therapy,it can improve patient's comfortableness degree during hospitalization period.

Objective To screen the influencing factors associated with adverse clinical out-comes in hospitalized elderly patients with Alzheimer's disease(AD)using LASSO-Logistic regression analysis and to construct a nomogram prediction model.Methods A retrospective selection of 214 hospitalized elderly patients with AD who visited the Department of Geriatric Medicine in the hospital from February 2021 to March 2023 was conducted,and clinical data of all patients were collected.Patients were divided into adverse events group(n=53)and non-adverse events group(n=161)based on the occurrence of adverse clinical outcomes.After variable screening using LASSO regres-sion,multivariate Logistic regression analysis was performed to identify independent factors influen-cing adverse clinical outcomes in hospitalized elderly patients with AD.A Nomogram model for pre-dicting adverse clinical outcomes in these patients was established based on the results of multivariate analysis.The predictive performance,calibration,and clinical utility of the Nomogram model were evaluated using the concordance index,calibration curve,and decision curve analysis(DCA).The diagnostic performance of the Nomogram model for adverse clinical outcomes in hospitalized elderly patients with AD was assessed using the receiver operating characteristic(ROC)curve and the area under the curve(AUC).Results LASSO-Logistic regression analysis revealed that the Mini-Men-tal State Examination(MMSE)score was an independent protective factor against adverse clinical outcomes in hospitalized elderly patients with AD(P＜0.05),while the Charlson Comorbidity In-dex(CCI score),creatinine,urea,and fasting blood glucose(FBG)levels were all independent risk factors for adverse clinical outcomes in these patients(P＜0.05).The Nomogram model con-structed based on the influencing factors screened by LASSO-Logistic regression analysis showed a concordance index of 0.994(95％CI,0.958 to 1.000)for predicting adverse clinical outcomes in hospitalized elderly patients with AD.The Hosmer-Lemeshow test results indicated x2=1.909,P=0.984,suggesting good model fit.The DCA result demonstrated that the model had favorable threshold probabilities and net clinical benefits.Conclusion The Nomogram model for predicting clinical outcomes in elderly inpatients with AD constructed based on LASSO-Logistic regression anal-ysis exhibits high predictive value,and can be used to forecast the occurrence of adverse clinical outcomes in these patients.

Objective To explore the application effect of the dual-track nursing intervention model in the treatment process of children with lobar pneumonia.Methods A total of 186 children with lobar pneumonia were selected and randomly divided into control group and intervention group u-sing a double-blind method,with 93 cases in each group.The control group received conventional nursing intervention,while the intervention group implemented the dual-track nursing intervention model on the basis of conventional nursing.This model included the establishment and training of nurs-ing teams,personalized nursing plans,health education,and psychological support.Outside the hos-pital,it emphasized family support,regular follow-up guidance,and community-based collaborative ed-ucation.Both groups received a 3-week intervention.The improvement times of clinical symptoms,hos-pital stay,pulmonary function indicators before and after nursing,treatment compliance,and family members' satisfaction with nursing were compared and analyzed between the two groups.Results The fever resolution time[(3.89±0.96)d],cough relief time[(6.21±1.34)d],disappearance time of pulmonary rales[(7.89±1.56)d],and hospital stay duration[(9.45±1.89)d]in the intervention group were all shorter than those in the control group[(5.23±1.14),(7.45±1.67),(9.32±2.01),and(11.28±2.35)d,respectively],with statistically significant differences(P＜0.05).After nursing,the forced expiratory volume in one second(FEV1)[(1.51±0.22)L],forced vital capacity(FVC)[(1.75±0.25)L],and FEV1/FVC[(94.12±5.65)％]in the intervention group were all higher than those in the control group[(1.42±0.15)L,(1.66±0.22)L,and(85.73±8.41)％,respectively],with statistically significant differences(P＜0.05).The scores for exami-nation cooperation[(23.91±3.82)points],nursing cooperation[(24.19±4.03)points],standardized medication use[(24.26±3.94)points],and rational diet[(23.77±3.62)points]in the intervention group were higher than those in the control group[(20.16±3.53),(19.64±3.46),(23.05±3.68),and(18.85±3.41)points,respectively],with statistically significant differences(P＜0.05).The satisfaction rate of family members with nursing work in the intervention group was higher than that in the control group,with a statistically significant difference(98.92％versus 89.25％,P＜0.05).Conclusion The dual-track nursing intervention model has a signifi-cant application effect in children with lobar pneumonia.It can accelerate their recovery process,improve treatment compliance,promote pulmonary function improvement,and enhance family mem-bers' satisfaction.

Tuberous sclerosis complex(TSC)is a rare genetic disease that can lead to benign dysplasia in multiple organs such as the skin, brain, eyes, oral cavity, heart, lungs, kidneys, liver, and bones. Its main symptoms include epilepsy, intellectual disabilities, skin depigmentation, and facial angiofibromas, whilst incidence is approximately 1 in 10 000 to 1 in 6000 newborns. This case presents a middle-aged woman who initially manifested with epilepsy and nodular depigmentation. Later, she developed a lower abdominal mass, elevated creatinine, and severe anemia. Based on clinical features and whole exome sequencing, the primary diagnosis was confirmed as TSC. Laboratory and imaging examinations revealed that the lower abdominal mass originated from the uterus. CT-guided biopsy pathology and surgical pathology suggested a combination of leiomyoma and abscess. With the involvement of multiple organs and various complications beyond the main diagnosis, the diagnostic and therapeutic process for this patient highlights the importance of rigorous clinical thinking and multidisciplinary collaboration in the diagnosis and treatment of rare and challenging diseases.

Objective To investigate the clinical significance of the expression of antioxidant 1 copper chaperone protein(ATOX1)in hepatocellular carcinoma(HCC)and its relationship with tumor proliferation,migration and invasion.Methods The expression of ATOX1 mRNA in HCC cancer tissue and normal liver tissue was analyzed using the Human Genome Atlas database.Immunohistochemical experiment was used to detect the expression of ATOX1 in 15 cases of HCC cancer tissue and adjacent tissue.Human HCC cell lines Hep3B and HepG2 were divided into the control group(NC),the ATOX1 knockdown group 1(si-ATOX1#1)and the ATOX1 knockdown group 2(si-ATOX1#2).The effects of ATOX1 knockdown on the malignant biological behavior of HCC cells were observed through CCK-8 cell proliferation experiment,scratch experiment and Transwell invasion experiments.A nude mouse xenograft tumor model was constructed to analyze the effect of ATOX1 knockdown on the quality and volume of transplanted tumors.Western blot assay was used to detect the relationship between ATOX1 and JAK2/STAT3 pathway protein expression.Results Bioinformatics analysis showed that expression of ATOX1 mRNA in HCC cancer tissue was higher than that in adjacent normal tissue(P＜0.05).The immunohistochemical staining results showed that the positive rate of ATOX1 protein was higher in HCC cancer tissue than that in adjacent tissue(93.33%vs.13.33%,P＜0.01).In vitro experimental results showed that siRNA knockdown of ATOX1 protein expression in Hep3B and HepG2 cells significantly reduced the proliferation,migration and invasion abilities of cancer cells(P＜0.05).In vivo experiments in mice showed that the volume and weight of subcutaneous xenograft tumors were significantly smaller in the sh-ATOX1 group than those in the sh-con group(P＜0.05).The expression levels of JAK2/STAT3 pathway-related proteins p-JAK2,p-STAT3,CyclinD1 and MMP2 were significantly lower in the subcutaneous transplanted tumor tissue of the sh-ATOX1 group than that of the sh-con group(P＜0.05).Conclusion ATOX1 can promote the proliferation,migration and invasion of HCC through JAK2/STAT3 pathway,which can potentially become a potential tumor marker and therapeutic target.