Mammalian male germline development depends on a specialized gonadal somatic microenvironment. However, itsin vitro reconstruction remains challenging. Major barriers include the generation of appropriate supporting-cell lineages, organized tissue architecture, and culture conditions that sustain germ-cell maturation. Yoshino et al. established a mouse pluripotent stem cell-derived testicular organoid model. This model reconstitutes the sex-determining region Y (Sry)-SRY-box transcription factor 9 (Sox9)‑mediated sex-determination program and generates testicular somatic cell-like cells (TesLCs). When assembled with primordial germ cell-like cells (PGCLCs), TesLCs formed seminiferous tubule-like structures and supported male germline progression toward prospermatogonia and germline stem cell-like cells (GSCLCs). After transplantation into infertile recipient testes, organoid-derived GSCLCs produced fertilization-competent sperm and generated fertile offspring. The major significance of this work extends beyond sperm production. It integrates sex determination, germ-cell fate transition, and testicular niche self-organization into an experimentally tractable organoid system. This commentary discusses the technical strategy, sex-determination mechanism, value of testicular niche reconstruction, and translational limitations of this study. It also highlights its implications for in vitro gametogenesis, male infertility modeling, and reproductive medicine.

This paper summarizes Professor WU Mianhua's clinical experience in the staged treatment of radiation-induced brain injury （RIBI） based on the stasis-heat theory. It is believed that radiation fire-toxin is the initiating pathogenic factor of RIBI， and the core pathogenesis consists of the intermingling of stasis and heat， obstruction of collaterals by wind-phlegm， dual deficiency of qi and yin， as well as impairment of essence and depletion of marrow. In the early stage， the disease is mainly manifested as stasis-heat with fluid retention and obstruction of collaterals by wind-phlegm， with the lesion located in the brain collaterals. The therapeutic principle is to cool the blood and dissipate stasis， extinguish wind and unblock collaterals， and simultaneously eliminate phlegm and promote urination， according to which self-designed Liangxue Tongluo Formula （凉血通络方） is selected for treatment.In the middle stage， the key pathological features are the binding of phlegm， stasis and heat， and consumption of kidney essence， with the lesion invading the kidney essence. The therapeutic principle is to resolve phlegm and remove stasis， clear and relieve latent heat， replenish essence and tonify marrow， and the self-designed Qinghua Tianjing Formula （清化填精方） is selected for treatment. In the advanced stage， the disease is mostly manifested as dual deficiency of qi and yin and toxin-induced marrow exhaustion， with the lesion involving the brain marrow. The therapeutic principle is to replenish qi and nourish yin， remove toxin and tonify marrow， and the self-designed Yangyin Jiedu Formula （养阴解毒方） is selected for treatment.

BACKGROUND:With aging,the regenerative capacity and differentiation function of bone marrow mesenchymal stem cells progressively decline,reducing bone tissue repair efficacy.Thus,identifying bone marrow mesenchymal stem cell subpopulations with enhanced osteogenic potential is of significant importance for advancing bone tissue engineering.OBJECTIVE:To evaluate the osteogenic differentiation potential differences between STRO-1 positive and negative bone marrow mesenchymal stem cells under osteogenic induction conditions.METHODS:SD rat bone marrow mesenchymal stem cells were isolated and cultured.The expression of CD29,CD45,CD90,and STRO-1 was identified via flow cytometry and immunofluorescence.Immunomagnetic cell sorting was used to separate STRO-1 positive and negative bone marrow mesenchymal stem cells.The cells of two groups were subjected to osteogenic induction for 7 and 14 days.qRT-PCR and western blotting were performed to analyze differences in osteogenesis-related gene expression(Collagen I,Runt-related transcription factor 2,osteoprotegerin,and osteocalcin)and protein levels.Alizarin red staining and alkaline phosphatase staining were used to observe calcium nodule formation.RESULTS AND CONCLUSION:Flow cytometry showed high expression levels of CD29 and CD90 and low expression of CD45,with a positive STRO-1 expression rate of 12.8％.Immunofluorescence results were consistent with those of flow cytometry.After magnetic cell sorting,STRO-1 positive cells demonstrated a higher colony formation rate than STRO-1 negative cells.On day 14,STRO-1 positive cells showed significantly higher osteogenic differentiation potential than on day 7,with significantly elevated osteogenesis-related marker levels compared to STRO-1 negative cells(P＜0.01).The findings indicate that STRO-1 positive bone marrow mesenchymal stem cells exhibit significant advantages in osteogenic potential,providing a theoretical basis for their selection as ideal seed cells in bone tissue engineering.In future applications,they may represent a promising therapeutic approach for bone defect repair.

BACKGROUND:With aging,the regenerative capacity and differentiation function of bone marrow mesenchymal stem cells progressively decline,reducing bone tissue repair efficacy.Thus,identifying bone marrow mesenchymal stem cell subpopulations with enhanced osteogenic potential is of significant importance for advancing bone tissue engineering.OBJECTIVE:To evaluate the osteogenic differentiation potential differences between STRO-1 positive and negative bone marrow mesenchymal stem cells under osteogenic induction conditions.METHODS:SD rat bone marrow mesenchymal stem cells were isolated and cultured.The expression of CD29,CD45,CD90,and STRO-1 was identified via flow cytometry and immunofluorescence.Immunomagnetic cell sorting was used to separate STRO-1 positive and negative bone marrow mesenchymal stem cells.The cells of two groups were subjected to osteogenic induction for 7 and 14 days.qRT-PCR and western blotting were performed to analyze differences in osteogenesis-related gene expression(Collagen I,Runt-related transcription factor 2,osteoprotegerin,and osteocalcin)and protein levels.Alizarin red staining and alkaline phosphatase staining were used to observe calcium nodule formation.RESULTS AND CONCLUSION:Flow cytometry showed high expression levels of CD29 and CD90 and low expression of CD45,with a positive STRO-1 expression rate of 12.8％.Immunofluorescence results were consistent with those of flow cytometry.After magnetic cell sorting,STRO-1 positive cells demonstrated a higher colony formation rate than STRO-1 negative cells.On day 14,STRO-1 positive cells showed significantly higher osteogenic differentiation potential than on day 7,with significantly elevated osteogenesis-related marker levels compared to STRO-1 negative cells(P＜0.01).The findings indicate that STRO-1 positive bone marrow mesenchymal stem cells exhibit significant advantages in osteogenic potential,providing a theoretical basis for their selection as ideal seed cells in bone tissue engineering.In future applications,they may represent a promising therapeutic approach for bone defect repair.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective:To investigate the potential causes of the rising epidemic of severe fever with thrombocytopenia syndrome (SFTS) in Weifang, Shandong province.Methods:The temporal trend of SFTS epidemic was segmented using Joinpoint regression analysis. Changes in epidemiological characteristics across different periods were compared, and correlation analysis was conducted to identify meteorological factors influencing the epidemic trend.Results:Joinpoint regression revealed two distinct periods for SFTS epidemic in Weifang: 2015-2021 and 2022-2024. No significant trend was observed during 2015-2021 ( P=0.634), while a sharp annual increase of 46.69% occurred from 2022 to 2024 ( P=0.006). Spatial autocorrelation analysis demonstrated a global Moran’s I of 0.42 ( Z=8.55, P<0.001) for 2015-2021, with 15 high-high clustering areas identified. For 2022-2024, the global Moran’s I decreased to 0.37 ( Z=7.31, P<0.001), with 13 high-high clusters, including newly emerging hotspots in Anqiu and Zhucheng in the southeastern region. High-risk populations remained individuals aged ≥50 in mountainous and hilly areas, with a marked rise in incidence in these groups. The male-to-female ratio of cases was higher in plain areas than in mountainous/hilly regions. Autumn (September-November) temperatures from the preceding year showed a positive correlation with annual case numbers ( P=0.004, r=0.82). The linear regression expression is y=40.61x-580.78 (y is the annual incidence, and x is the average daily temperature of last autumn). Conclusions:The SFTS epidemic in Weifang is showing a rising trend. There is a linear correlation between the temperature of the previous autumn and the scale of SFTS epidemic in the following year. This correlation allows for predicting the subsequent year′s epidemic, thereby enabling early warning of SFTS.

Objective:To analyze the current status and trends in the clinical management and outcomes of respiratory distress syndrome (RDS) in preterm infants <32 weeks′ gestation admitted to the Chinese Neonatal Network (CHNN) from 2019 to 2023.Methods:A cross-sectional study was conducted from November 2024 to January 2025 using the CHNN cohort of very preterm and extremely preterm infants. A total of 30 869 RDS infants with gestational age <32 weeks were admitted within 1 day after birth to CHNN centers from 2019 to 2023. Data on demographics, perinatal management, early complications within 7 days of age, and in-hospital outcomes were collected. Yearly groups were defined by admission year. Trends by year were evaluated by Cochran-Armitage trend test, linear regression model and median regression model.Results:The gestational age at birth of 30 869 RDS infant was 28.9 (27.1, 30.7) weeks and the birth weight was 1 259 (932, 1 586) g. Males account for 56.5% (17 363/30 757). From 2019 to 2023, the prevalence of RDS was 73.8% (5 503/7 461), 74.5% (5 490/7 368), 79.8% (5 884/7 372), 81.6% (6 435/7 889), and 86.0% (7 557/8 789), respectively, showing an increasing trend year by year ( P<0.001). The overall rate of pulmonary surfactant administration was 72.4% (22 359/30 869), fluctuating between 71.2% (5 381/7 557) and 74.3% (4 089/5 503) over the 5-year period. Antenatal corticosteroids were administered to 82.3% (24 357/29 597) mothers of RDS infants and 23.6% (7 218/30 565) RDS infants received noninvasive positive end-expiratory pressure support in the delivery room, both showing a increasing trend over the 5 years (both P<0.001). The incidence of pneumothorax and the use rate of inhaled nitric oxide within 7 days of age were 1.3% (393/30 846) and 1.4% (436/30 869), respectively, both showing increasing trends over the 5 years (both P<0.001). The rate of complete course of antenatal corticosteroids administration was 64.6% (14 458/22 382), the rates of discharge against medical advice and mortality within 7 days of age were 5.3% (1 635/30 869) and 2.7% (724/26 803), respectively, all showing a decreasing trend over time (all P<0.05). Regarding in-hospital outcomes, mortality rate of RDS infants was 4.6% (1 228/26 803), showing a downward trend year by year ( P=0.005). The incidence of bronchopulmonary dysplasia (BPD) was 35.0% (9 417/26 919), and the combined incidence of death or BPD was 36.4% (9 763/26 803), both showing an increasing trend year by year (both P<0.001). Conclusions:RDS prevalence increased annually in preterm infants <32 weeks′ gestation from 2019 to 2023, with declining mortality but rising BPD rates. While antenatal steroid use and noninvasive positive end-expiratory pressure support application improved, full-course antenatal steroid compliance decreased. These findings highlight the need for standardized perinatal management protocols to improve the clinical management of RDS.

Background and purpose:Thyroid cancer is the most common malignant endocrine tumor,particularly prevalent among the Asian population.The overall survival for thyroid cancer patients is relatively high,but there are significant survival differences among patients.Based on long-term hospital-based cancer registry database,this study analyzed the 10-year observed overall survival(OS)rate of thyroid cancer cases and the distribution of causes of death,providing real-world evidences to further survival management of thyroid cancer in China.Methods:A total of 55343 thyroid cancer patients who underwent treatment at Fudan University Shanghai Cancer center from 2005 to 2021 were included in this study.Clinical information and the follow-up endpoint data were collected through medical records review,telephone visits and death registry data linkage.The last follow-up date was October 31,2024.Kaplan-Meier method was applied in evaluating the OS rate,and survival data were described by different subgroups as age group,gender,treatment period,tumor staging and pathological characteristics.The standardized mortality ratio(SMR)and absolute excess risk(AER)were calculated using general Shanghai population as the reference,and the mortality risk was described by gender,age at diagnosis and histological subtype.Results:With a median follow-up time of 63.01 months,the overall 1-,3-,5-and 10-year OS rates of thyroid cancer patients were 99.67%(95%CI:99.62%-99.72%),99.11%(95%CI:99.03%-99.19%),98.48%(95%CI:98.36%-98.60%)and 95.81%(95%CI:95.50%-96.11%),respectively.The 10-year OS rates of stage Ⅰ,Ⅱ,Ⅲ and Ⅳ were 97.99%(95%CI:97.70%-98.28%),89.80%(95%CI:87.24%-92.37%),77.84%(95%CI:70.76%-84.92%)and 62.95%(95%CI:55.37%-70.54%),respectively.The differences in OS among patients with different age,gender and histological classification were significant.1256(2.27%)deaths occurred,of which 18.63%,50.88%and 7.32%were attributable to thyroid cancer,other cancers and cardiovascular disease(CVD),respectively.Compared with the general population,patients with different subtypes of thyroid cancer had higher all-cause mortality rates,progressively increasing with papillary,follicular,medullary and anaplastic thyroid carcinoma/poorly differentiated carcinoma.Compared with general population,the death risk was 2.24 times higher in papillary thyroid cancer patients(95%CI:2.06-2.44),9.94 times higher in follicular thyroid cancer patients(95%CI:6.79-14.09),12.16 times higher in medullary thyroid cancer patients(95%CI:8.05-17.69),and the highest risk was observed in patients with anaplastic thyroid carcinoma/poorly differentiated carcinoma[SMR=79.67(95%CI:58.38-106.31),AER=766.01/1 000 person-years].Conclusion:The 10-year long survival data and cause of death for thyroid cancer patients with different histological types were reported in China based on a large single institution hospital-based cancer registry database.Staging and histological characteristics were the most important factors directly affected the survival.Early diagnosis and individualized treatment are crucial for improving prognosis.

This study investigates the effects of pseudorabies virus(PRV)infection on the antiviral immune signaling pathways and type Ⅰ interferon factors in mouse trigeminal ganglion(TG)cells.In this experiment,primary TG cells were infected with PRV at a multiplicity of infection(MOI)of 1,while mice were infected via a drop-nose method using 106,29 TCID50 of PRV.Real-time fluorescence quantitative PCR(qPCR),Western blot and ELISA were used to assess gene tran-scription,protein expression,and the secretion of IFN-α and IFN-β.The results indicated that PRV infection of mouse TG primary cells led to alterations in the gene and protein expression of RIG-Ⅰ,MAVS,and IRF3,as well as the phosphorylation of IRF3 and IKBα both in vivo and ex vivo.ELISA results showed that PRV infection could regulate the secretion of IFN-α and IFN-β in mouse primary TG cells and mouse TGs.The results of RIG-Ⅰ signaling pathway-related proteins and the secretion of IFN-a and IFN-β were analyzed using Western blot after using siRNA to interfere with RIG-Ⅰ expression in TG cells.The results showed that siRIG-Ⅰ successfully inter-fered with RIG-Ⅰ protein expression in TG cells and caused changes in the expression of down-stream proteins such as MAVS and IRF3,and also regulated the secretion of IFN-α and IFN-β in TG cells.Furthermore,the results indicated that PRV infection induced the expression of RIG-Ⅰ in mouse TG progenitor cells,regulating the antiviral immune response of type Ⅰ interferon factors in TG cells through the RIG-Ⅰ-MAVS-IRF3 signaling axis.Notably,PRV inhibited the expression of IRF3 in TG cells while significantly upregulating the expression of IFN-β during the later stages of infection,which may be an important factor in the important reason for the rapid mortality ob-served in mice during the late stages of PRV infection.This experiment elucidates part of the anti-viral immune mechanism mediated by the RIG-Ⅰ-MAVS-IRF3 signaling pathway in regulating type Ⅰ interferon factor after PRV infection of mouse TG cells,as well as the discovery of differ-ent trends of IRF3 protein changes in vivo and ex vivo,laying the groundwork for future in-depth studies.

Objectives:This study aims to investigate the association between Chinese visceral adiposity index(CVAI)and the risk of cardiovascular disease(CVD),and explore the sex differences.Methods:Participants were screened from the three sub-cohorts of Prediction for Atherosclerotic Cardiovascular Disease Risk in China(China-PAR)project,baseline information on body measure and biochemistry examinations were collected from 1998,2000-2001,and 2007-2008,separately.Participants were followed up to 2015.Cohort-stratified Cox proportional risk models were used to analyze the relationship between CVAI,both in continuous(per standard deviation increase)and categorical(quartiles,with Q1 as reference)scales,and CVD risk in the total population,men and women.The multiplicative interaction between sex and CVAI on CVD risk were calculated.Restricted cubic spline regression was employed to investigate the dose-response relationship.Results:A total of 98 464 participants without CVD at baseline were included.During the 723 508 person-years of follow-up,3 605 CVD events were recorded.After multivariate adjustment,the HRs(95％CIs)of CVD were 1.25(1.20-1.29),1.09(1.04-1.15),and 1.54(1.46-1.64)for per standard deviation increment in CVAI in the general population,men and women,respectively.Besides,compared with Q1 group,the HRs(95％CIs)in Q4 group were 1.87(1.67-2.10),1.33(1.14-1.54)and 3.84(3.09-4.78),correspondingly,and the effect of CVAI on the risk of CVD was significantly higher in women than in men(Pinteraction<0.05).Additionally,there was a positive dose-response relationship between CVAI and the risk of CVD.Conclusions:Elevated CVAI is an independent risk factor for CVD,especially in women.