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 determine the potential genetic causal relationship between sleep related phenotypes and female pubertal onset using the two sample Mendelian randomization approach. Methods: Genetic instrumental variables for sleep and age at menarche were sourced from FinnGen, IEU Open GWAS and GWAS Catalog three publicly available Genome Wide Association Study databases. Causal effects were estimated using the inverse variance weighted method, supplemented by sensitivity analyses and tests for heterogeneity, pleiotropy, and direction. Results: Genetically predicted sleep duration was positively associated with age at menarche ( β =0.61, 95% CI =0.30-0.91, P <0.01). Conversely, overall sleep problems ( β =-0.13, 95% CI =-0.20 to -0.07 ), two specific types of sleep disorders (sleep apnea: β =-0.10, 95% CI =-0.16 to -0.03; insomnia: β =-0.40, 95% CI = -0.69 to -0.11) were causally associated with earlier age at menarche (all P <0.01). Sensitivity analyses confirmed the robustness of these findings with consistent effect directions and no evidence of significant directional pleiotropy. Conclusions The study reveales a genetic causal relationship between sleep and pubertal onset. Adequate sleep duration appears to have a protective effect. These findings suggest that sleep may have a critical regulatory role in the initiation of pubertal development.

OBJECTIVE To explore the influencing factors and improvement pathways for the effectiveness of China’s pharmaceutical information traceability system construction， and to provide references for regulating the pharmaceutical market order， ensuring the security of medical insurance funds， and safeguarding public health.METHODS Based on the technology-organization-environment （TOE） theoretical framework， six conditional variables were selected， including the level of big data development， interdepartmental coordination mechanisms， regulatory exposure intensity， quality of traceability personnel， government financial investment， and degree of public attention. The fuzzy set qualitative comparative analysis （fsQCA） method was employed to collect policies related to pharmaceutical information traceability systems issued by 31 provinces（autonomous regions， municipalities） in China， and to explore the condition configurations and optimization pathways for promoting the construction of pharmaceutical information traceability systems. RESULTS &CONCLUSIONS No single condition exerts a decisive influence on the construction of pharmaceutical information traceability systems. However， the level of big data development， quality of traceability personnel， regulatory exposure intensity， and degree of public attention play key roles in the configuration pathways. There are four pathways for efficiently promoting the construction of pharmaceutical information traceability systems， namely the competence enhancement type， the technological breakthrough type， the technology-focused type， and the environment-driven type； the consistencies of all pathways were higher than 0.750, with an solution consistency of 0.790 and an solution coverage of 0.897. Each province can select an appropriate path according to its own conditions. It is recommended to promote the high-quality construction of pharmaceutical information traceability systems through technological innovation， strengthening interdepartmental coordination and full-chain regulation， and optimizing the environment for system construction. Meanwhile， attention should also be paid to the implementation difficulties faced by medical institutions so as to reduce their implementation costs.

To investigate whether Tasquinimod can influence cisplatin resistance in drug-resistant ovarian cancer (OC) cell lines by regulating histone deacetylase 4 (HDAC4) or p21, we explored its effects on the cell cycle, and associated mechanisms.RT-PCR and Western blot analyses, flow cytometry, CCK8 assay, and immunofluorescence were utilized to investigate the effects of Tasquinimod on gene expression, cell cycle, apoptosis, viability, and protein levels in OC cells. The results showed that Tasquinimod inhibited cell viability and promoted apoptosis in SKOV3/DDP (cisplatin) and A2780/DDP cells more effectively than DDP alone. In combination with cisplatin, Tasquinimod further enhanced cell apoptosis and reduced cell viability in these cell lines, an effect that could be reversed following HDAC4 overexpression. Tasquinimod treatment down-regulated HDAC4, Bcl-2, and cyclin D1, and CDK4 expression and up-regulated the cleaved-Caspase-3, and p21 expression in SKOV3/DDP and A2780/ DDP cells. Additionally, Tasquinimod inhibited DDP resistance in OC/DDP cells. These effects were similarly observed in OC mouse models treated with Tasquinimod. In conclusion, Tasquinimod can improve OC cells' sensitivity to DDP by down-regulating the HDAC4/p21 axis, offering insights into potential strategies for overcoming cisplatin resistance in OC.

Background Prenatal chronic psychological stress may increase the risk of allergic diseases in children, and eczema is the most common allergic disease in children, the pathogenesis of which is not yet fully understood. Objective To preliminarily clarify the changes in offspring intestinal flora after chronic stress exposure during pregnancy in rats that increases offspring immune imbalance and eczema susceptibility. Methods Thirty SPF-grade adult female SD rats were selected and randomly divided into a model group and a control group (n=15). Sixteen male rats were randomly divided into a model mating group and a control mating group (n=8). A 28-day chronic unpredictable mild stress (CUMS) model during pregnancy was established. On the 7th day of stress, male and female rats were caged in a ratio of 3:1. Blood samples were collected from female rats in each group via angular vein on the 1st day before stress, and on the 7th, 14th, 21st, and 28th days after stress. The content of plasma corticosterone during pregnancy was determined by enzyme-linked immunosorbent assay (ELISA). For the offspring rats, an eczema model was constructed using 2,4-dinitrochlorobenzene (DNCB). The number of scratching times of the offspring rats within 5 min was recorded. The offspring rats were divided into 4 groups: DNCB-CUMS group (MM), DNCB-control group (MC), solvent control-CUMS group (CM), and blank control group (CC), with 8 rats in each group. The eczema was induced once every 3 days, and the induction period was 12 d. The expression level of immunoglobulin E (IgE) in the serum of offspring rats after the eczema induction experiment were determined by ELISA. The concentrations of tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-2 (IL-2), interleukin-4 (IL-4), and interleukin-13 (IL-13) in the serum were quantified by multi-parameter flow cytometry. The composition and abundance of intestinal microbiota in the feces of offspring rats were detected by 16S rRNA high-throughput sequencing technology. Results The plasma corticosterone concentrations in the model group were higher than those in the control group on the 7th and 21st days of stress (P<0.05). On the 14th and 21st days of stress, the 1% sucrose preference percentages of female rats in the model group were lower than that in the control group. On the 7th, 14th, and 21st days of stress, the horizontal movement scores of female rats in the model group and the vertical movement scores on the 7th and 14th days were lower than those in the control group (P<0.05). After 6, 9, and 12 d of model building, the scratching frequencies in the MC group and MM group were significantly higher than those in the CC group and CM group (P<0.05). Moreover, there were differences in the contents of cytokines including IFN-γ, IL-2, TNF-α, IL-4, IL-13, and IgE among the offspring rat groups (P<0.05). The CM group and MM group led to an increase in the contents of TNF-α, IL-4, IL-13, and IgE cytokines (P<0.05), while the MM group caused a decrease in the contents of IFN-γ and IL-2 (P<0.05). After the eczema induction experiment, the α-diversity analysis showed that the Simpson index and Shannon index in the CM were higher than those in the CC (P<0.05), indicating that CUMS during the pregnancy of female rats could increase the species abundance of their offspring. The abundances of Prevotella and Lactobacillus in the CM group decreased (P<0.05). Conclusion Intestinal dysbiosis in offspring due to chronic prenatal psychological stress, which may be one of the mechanisms linking maternal stress to immune imbalance and increased susceptibility to eczema in offspring.

Objective: To investigate characteristics of colorectal cancer incidence and mortality in registration areas of Guangdong Province in 2020, so as to provide a basis for optimizing regional prevention and control strategies. Methods: Data on incidence and mortality of colorectal cancer in cancer registration areas of Guangdong Province in 2020 were collected from the Cancer Follow-up Registration System and the All-Cause Mortality Registration Reporting System of the Guangdong Provincial Center for Disease Control and Prevention. The crude incidence, crude mortality, truncated rate for 35 to 64 years, and cumulative rate for 0 to 64 years were calculated, and standardized using the Segi's world standard population. Descriptive epidemiological methods were applied to analyze the characteristics of colorectal cancer incidence and mortality by different genders, urban/rural areas and ages. Results: A total of 14 771 cases of colorectal cancer were reported in Guangdong Province in 2020. The crude incidence, world population-standardized incidence, truncated incidence for 35 to 64 years and cumulative incidence for 0 to 64 years were 35.18/100 000, 24.84/100 000, 38.87/100 000 and 1.37%, respectively. A total of 5 384 deaths of colorectal cancer were reported, with crude incidence, world population-standardized incidence, truncated incidence for 35 to 64 years and cumulative incidence for 0 to 64 years were 14.55/100 000, 8.83/100 000, 10.39/100 000 and 0.37%, respectively. The crude incidence and mortality were higher in males than in females (40.35/100 000 vs. 29.88/100 000, 16.51/100 000 vs. 12.54/100 000, both P<0.05). The crude incidence and mortality were higher in urban areas than in rural areas (38.94/100 000 vs. 26.10/100 000, 16.60/100 000 vs. 10.42/100 000, both P<0.05). The crude incidence of colorectal cancer initially increased with advancing age (P<0.05), reaching a peak of 239.36/105 in the 80-<85 age group, followed by a marked decline after 85 years. The crude mortality of colorectal cancer increased with advancing age (P<0.05), reaching a peak of 174.25/100 000 in the ≥85 years age group. Conclusions In 2020, the incidence and mortality of colorectal cancer in registration areas of Guangdong Province were higher than the national averages. There were differences in the characteristics of incidence and mortality among genders, urban/areas and age. Therefore, it is necessary to strengthen the comprehensive prevention and control efforts for colorectal cancer in males, urban areas, and the elderly population.

Objective: To investigate the epidemiological characteristics of lung cancer in cancer registration areas of Guangdong Province in 2020, so as to provide the evidence for improving prevention and control strategies of lung cancer. Methods: Data of incidence and mortality in 2020 from 30 cancer registries in Guangdong Province were collected from the Cancer Follow-up Registration System and the All-Cause Mortality Registration Reporting System of the Guangdong Provincial Center for Disease Control and Prevention. The crude incidence, crude mortality, and cumulative rate for 0 to 74 years were calculated. The Chinese population-standardized rate and world population-standardized rate were calculated using the age structure of the standard population from the Fifth National Population Census in 2000 and Segi's world standard population. The incidence and mortality characteristics of lung cancer in different genders, urban/rural areas and ages were described. Results: In 2020, there were 25 357 new cases of lung cancer in Guangdong Province. The crude incidence, Chinese population-standardized incidence, world population-standardized incidence, and cumulative incidence for 0 to 74 years were 60.40/100 000, 43.75/100 000, 43.26/100 000, and 5.30%, respectively. There were 14 366 lung cancer deaths. The crude mortality, Chinese population-standardized mortality, world population-standardized mortality, and cumulative mortality for 0 to 74 years were 38.82/100 000, 24.49/100 000, 24.36/100 000, and 2.88%, respectively. The crude incidence and crude mortality of lung cancer in males were higher than those in females (71.19/100 000 vs. 49.42/100 000, 52.94/100 000 vs. 24.36/100 000, both P<0.05). The crude incidence and crude mortality of lung cancer in urban areas were higher than those in rural areas (66.37/100 000 vs. 45.95/100 000, 40.68/100 000 vs. 35.07/100 000, both P<0.05). The crude incidence and crude mortality of lung cancer exhibited upward trends with increasing age (both P<0.05), peaking in the age of 80-<85 years (347.97/100 000 and 342.14/100 000). Conclusions Comparing to the national data, the incidence of lung cancer in registration areas of Guangdong Province remained relatively high, while mortality remained relatively low. Males, urban residents and the elderly constitute the key populations for lung cancer prevention and control. It is recommend to optimize the allocation of medical resources between urban and rural areas and strengthen lung cancer screening among high-risk groups.

Cardiac fibrosis(CF) is a cardiac pathological process characterized by excessive deposition of extracellular matrix(ECM). When the heart is damaged by adverse stimuli, cardiac fibroblasts are activated and secrete a large amount of ECM, leading to changes in cardiac fibrosis, myocardial stiffness, and cardiac function declines and accelerating the development of heart failure. There is a close relationship between heart yin deficiency and cardiac fibrosis, which have similar pathogenic mechanisms. Heart Yin deficiency, characterized by insufficient Yin fluids, causes the heart to lose its nourishing function, which acts as the initiating factor for myocardial dystrophy. The deficiency of body fluids leads to stagnation of blood flow, resulting in blood stasis and water retention. Blood stasis and water retention accumulate in the heart, which aligns with the pathological manifestation of excessive deposition of ECM, as a tangible pathogenic factor. This is an inevitable stage of the disease process. The lingering of blood stasis combined with water retention eventually leads to the generation of heat and toxins, triggering inflammatory responses similar to heat toxins, which continuously stimulate the heart and cause the ultimate outcome of CF. Considering the syndrome of heart Yin deficiency, traditional Chinese medicine capable of nourishing Yin, activating blood, and promoting urination can reduce myocardial cell apoptosis, inhibit fibroblast activation, and lower the inflammation level, showing significant advantages in combating CF.
Humans ; Fibrosis/drug therapy* ; Animals ; Yin Deficiency/metabolism* ; Myocardium/metabolism* ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/therapeutic use*

BACKGROUND: The use of inserted sham acupuncture as a placebo in randomized controlled trials (RCTs) is controversial, because it may produce specific effects that cause an underestimation of the effect of acupuncture treatment. OBJECTIVE: This systematic survey investigates the magnitude of insert-specific effects of sham acupuncture and whether they affect the estimation of acupuncture treatment effects. SEARCH STRATEGY: PubMed, Embase and Cochrane Central Register of Controlled Trials were searched to identify acupuncture RCTs from their inception until December 2022. INCLUSION CRITERIA: RCTs that evaluated the effects of acupuncture compared to sham acupuncture and no treatment. DATA EXTRACTION AND ANALYSIS: The total effect measured for an acupuncture treatment group in RCTs were divided into three components, including the natural history and/or regression to the mean effect (controlled for no-treatment group), the placebo effect, and the specific effect of acupuncture. The first two constituted the contextual effect of acupuncture, which is mimicked by a sham acupuncture treatment group. The proportion of acupuncture total effect size was considered to be 1. The proportion of natural history and/or regression to the mean effect (PNE) and proportional contextual effect (PCE) of included RCTs were pooled using meta-analyses with a random-effect model. The proportion of acupuncture placebo effect was the difference between PCE and PNE in RCTs with non-inserted sham acupuncture. The proportion of insert-specific effect of sham acupuncture (PIES) was obtained by subtracting the proportion of acupuncture placebo effect and PNE from PCE in RCTs with inserted sham acupuncture. The impact of PIES on the estimation of acupuncture's treatment effect was evaluated by quantifying the percentage of RCTs that the effect of outcome changed from no statistical difference to statistical difference after removing PIES in the included studies, and the impact of PIES was externally validated in other acupuncture RCTs with an inserted sham acupuncture group that were not used to calculate PIES. RESULTS: This analysis included 32 studies with 5492 patients. The overall PNE was 0.335 (95% confidence interval [CI], 0.255-0.415) and the PCE of acupuncture was 0.639 (95% CI, 0.567-0.710) of acupuncture's total effect. The proportional contribution of the placebo effect to acupuncture's total effect was 0.191, and the PIES was 0.189. When we modeled the exclusion of the insert-specific effect of sham acupuncture, the acupuncture treatment effect changed from no difference to a significant difference in 45.45% of the included RCTs, and in 40.91% of the external validated RCTs. CONCLUSION The insert-specific effect of sham acupuncture in RCTs represents 18.90% of acupuncture's total effect and significantly affects the evaluation of the acupuncture treatment effect. More than 40% of RCTs that used inserted sham acupuncture would draw different conclusions if the PIES had been controlled for. Considering the impact of the insert-specific effect of sham acupuncture, caution should be taken when using inserted sham acupuncture placebos in RCTs. Please cite this article as: Luo XC, Liu JL, Yao MH, Chen YM, Fan AY, Liang FR, Zhao JP, Zhao L, Zhou X, Zhong XY, Yang JH, Li B, Zhang Y, Sun X, Li L. Specific effect of inserted sham acupuncture and its impact on the estimation of acupuncture treatment effect in randomized controlled trials: A systematic survey. J Integr Med. 2025; 23(6):630-640.
Acupuncture Therapy/methods* ; Humans ; Randomized Controlled Trials as Topic ; Placebo Effect ; Placebos ; Treatment Outcome