OBJECTIVES: To analyze the distribution of Y chromosome azoospermia factor (AZF) microdeletions and their association with testicular development in male pediatric patients with congenital reproductive system disorders, including hypospadias, cryptorchidism, and disorders of sex development (DSD). METHODS: A prospective cohort study was conducted on pediatric patients admitted to the Department of Urology of Shanghai Children's Hospital from November 2021 to December 2023. The observation group included boys with hypospadias, cryptorchidism, or DSD, while the control group comprised boys with phimosis, indirect inguinal hernia, or hydrocele. Blood samples were collected for AZF microdeletion analysis using multiplex PCR to detect 15 sequence-tagged sites. Testicular ultrasound was performed to record testicular position and volume. Propensity score matching (PSM) was used to balance the groups. After matching, testicular volume differences were assessed. Stratified analyses compared testicular volume among children with AZF microdeletions, the control group, and children without micro-deletions in observation group. RESULTS: A total of 493 children were enrolled (observation group: 463; control group: 30). No Y chromosome microdeletions were detected in the control group. Four boys in the observation group had AZF microdeletions: one with cryptorchidism (AZFc+AZFd), one with isolated hypospadias (AZFc), and two with DSD (one with AZFb+AZFc+AZFd and one with AZFa). Ultrasonography measured 888 testicles. After PSM, testicular volume was significantly smaller in the observation group than in the control group (P<0.01). Stratified analysis revealed that among children under 9 years, those with AZF microdeletions tended to be older but had smaller testicular volumes compared to the control group and those without microdeletions in the observation group, although differences were not statistically significant (all P>0.05). Among children over 9 years, ages were comparable, but children with AZF microdeletions had smaller testicular volumes than the other two groups (statistical analysis was not performed due to small sample size). CONCLUSIONS The prevalence of Y chromosome microdeletions is higher in male children with congenital reproductive system disorders compared to the general population, particularly in those with DSD. Hypospadias, cryptorchidism, DSD, and AZF microdeletions may be associated with delayed testicular development in these children.

Objective To develop an enteral nutrition management system for critically ill patients and assess its application outcomes to standardize enteral nutrition management.Methods Based on relevant guidelines and indicator systems,a management system for enteral nutrition in critically ill patients was constructed,consisting of 4 modules:nutritional screening and assessment,nutritional implementation,nutritional monitoring,and statistical analysis.A convenience sampling method was used to select enteral nutrition patients and healthcare staff from the ICU of a tertiary hospital in Ningbo.Data from January to February 2024 served as an experimental group,while data from January to February 2023 constituted a control group.The 2 groups were compared regarding nutritional risk screening rate,feeding interruption rate,completion rate of the enteral nutrition plan,and incidence of complications.At the same time,the system's effectiveness was assessed by healthcare professionals using the clinical nursing information system effectiveness evaluation form.Results The study included 111 patients in the experimental group and 101 patients in the control group.The experimental group exhibited a significantly higher nutritional risk screening rate and enteral nutrition plan completion rate,as well as significantly lower feeding interruption rate and incidence of mechanical complications compared to the control group(P＜0.05).The system received a high effectiveness rating,with an average score of 104.73±9.34.Conclusion The application of the enteral nutrition management system effectively improves the nutritional risk screening rate and completion rate of enteral nutrition plans,while reducing both the feeding interruption rate and the incidence of mechanical complications.Healthcare staff highly rated the system.

Objective:To investigate the interaction between non-alcoholic fatty liver disease (NAFLD) and overweight/obesity on the risk of mild cognitive impairment (MCI) in elderly individuals.Methods:This cross-sectional study was based on the Hubei Memory and Aging Cohort Study (HMACS). Cluster random sampling was used to select 5 661 elderly individuals aged≥65 years in Wuhan from 2018 to 2023. Standardized neuropsychological assessments and clinical examinations results were collected. The NAFLD was diagnosed by abdominal ultrasound. The logistic regression analysis was used to analyze the association of NAFLD and overweight/obesity with MCI. The impacts of interaction between NAFLD and overweight/obesity on the risk of MCI were analyzed using both multiplicative and additive models.Results:Among the 5 661 elderly individuals included in the analysis, 2 563 were male and 3 098 were female, with a mean age of (72.24±5.51) years. A total of 2 239 participants (39.6%) resided in rural areas, 2 841 (50.2%) were overweight/obesity, 2 390 (42.2%) had NAFLD, and 1 694 (29.9%) were diagnosed with MCI. The risk of MCI in elderly individuals with NAFLD and overweight/obesity was 2.975 times ( OR=2.975, 95% CI: 2.489-3.557, P<0.001) of that in non-overweight/obese individuals without NAFLD. There was a multiplicative interaction between NAFLD and overweight/obesity on MCI ( OR=1.508, 95% CI: 1.169-1.944, P=0.002). NAFLD and overweight/obesity had an additive interaction effect on the risk of MCI, and the relative excess risk of interaction, attributable proportion of interaction and the synergy index was 1.099 (95% CI: 0.630-1.593), 0.369 (95% CI: 0.222-0.487), 2.256 (95% CI: 1.457-3.492), respectively. Conclusion:There is an interaction between NAFLD and overweight/obesity in elderly individuals, and the co-existence of NAFLD and overweight/obesity increases the risk of MCI in this population.

Protein arginine methyltransferase 5 (PRMT5) exhibits elevated expression levels in a variety of cancers and has emerged as a critical target for cancer therapy in recent years. However, first-generation PRMT5 inhibitors have exhibited inadequate selectivity, leading to significant hematological toxicity, thus limiting their clinical utility. The second-generation PRMT5 inhibitors have shown marked improvement in safety and efficacy by selectively targeting MTAP-null tumor cells without impacting normal cells. This review systematically summarizes the biological and functional roles of PRMT5 in MTAP-deficient tumor cells, and comprehensively analyzes the research and development process, molecular binding mechanisms, and the latest advancements in clinical trials of the five second-generation PRMT5 inhibitors currently under investigation, aiming to provide valuable insights for further in-depth studies in this field.

Objective To investigate the clinical efficacy of Xiaoluo Granules combined with an-tituberculosis drugs in the treatment of patients with cervical lymph node tuberculosis.Methods A retrospective analysis was conducted on the clinical data of 118 patients with cervical lymph node tu-berculosis who were treated in our hospital from January 2021 to January 2023.The patients were di-vided into control group(57 patients receiving conventional antituberculosis drug treatment)and ob-servation group(61 patients receiving Xiaoluo Granules combined with antituberculosis drug treat-ment)based on their treatment methods.The efficacy,traditional Chinese medicine(TCM)symptom scores,peripheral blood T-cell subsets,and type 1/type 2 helper T cell(Th1/Th2)-related cytokine levels,including tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),interleukin-10(IL-10),and interferon-γ(IFN-γ),were compared between the two groups.Results After 6 months of treat-ment,the total effective rate in the observation group was higher than that in the control group(P＜0.05).After 6 months of treatment,the scores for pain,low fever,fatigue,anorexia,and night sweats decreased in both groups,and the scores for these symptoms in the observation group were lower than those in the control group(P＜0.05).After 6 months of treatment,CD3+,CD4+,and CD4+/CD8+increased,while CD8+decreased in both groups.Additionally,CD3+,CD4+,and CD4+/CD8+were higher,while CD8+was lower in the observation group than those in the control group(P＜0.05).After 6 months of treatment,TNF-α,IL-6,and IFN-γ levels decreased,while IL-10 levels increased in both groups.Furthermore,TNF-α,IL-6,and IFN-γ levels were lower in the observa-tion group than in the control group,while IL-10 levels were higher(P＜0.05).Conclusion Xia-oluo Granules combined with antituberculosis drugs can significantly improve the efficacy in the treatment of cervical lymph node tuberculosis and enhance immune function by upregulating CD3+,CD4+,CD4+/CD8+,and IL-10 levels and downregulating CD8+,TNF-α,IL-6,and IFN-γ levels.

[Objective] To explore the risk factors of postoperative fever in primary aldosteronism (PA) patients. [Methods] Clinical data of 116 PA patients undergoing adrenalectomy in Peking University People's Hospital during Jan.2018 and Jul.2021 were retrospectively analyzed.Based on postoperative body temperature, the patients were divided into fever group (body temperature ≥38.0 ℃, n=41) and non-fever group (body temperature <38.0 ℃, n=75). Clinical features were analyzed between the two groups.The fever group was subdivided into low fever group (38.0 ℃≤body temperature <38.5 ℃, n=19) and high fever group (body temperature ≥38.5 ℃, n=22). The clinical data of the subgroups were compared. [Results] The incidence of postoperative fever was 35.3%.Logistic regression analysis showed that lower lowest potassium on records (OR=0.419, 95%CI: 0.196-0.894, P=0.025), lower high-density lipoprotein cholesterol (HDL-C) (OR=0.112, 95%CI: 0.018-0.687, P=0.018), and postoperative adrenal insufficiency (OR=4.158, 95%CI: 1.731-9.989, P=0.001) were independent risk factors for postoperative fever.There was no difference between the high and low fever groups.After surgery, infection occurred in 1 patient, adrenal insufficiency in 40 (34.5%) patients, but long-term follow-up indicated that no patients needed lifelong glucocorticoid replacement. [Conclusion] Fever is a common postoperative complication in PA patients, most likely due to transient adrenal insufficiency.Glucocorticoid supplementation should be administered appropriately and timely based on laboratory tests and clinical manifestations.Evaluation of adrenal function is highly recommended for patients undergoing adrenalectomy.

Background Injury poses a serious threat to human health. As global warming continues to intensify, there is an urgent need to explore the impact of temperature changes on injury deaths. However limited research has focused on this issue. Objective To investigate the relationship between daily mean temperature change (Tm) and injury death, as well as to estimate the associated future death burden in Hunan Province. Methods We employed an individual-level, time-stratified case-crossing design to establish a conditional logistic regression model to analyze the exposure-response relationship between daily mean temperature change and injury death in Hunan Province from 2013 to 2018. Consequently, we conducted subgroup analysis of gender, age group, and injury type. Finally, we estimated the excess burden of injury death attributable to temperature changes under a sustainable development path [low emission scenario (SSP1-2.6)], regional competition path [high emission scenario (SSP3-7.0)], or fossil fuel development path [very high emission scenario (SSP5-8.5)]. Results The study collected 155577 injury deaths in Hunan Province. The results indicated that for each 1 ℃ increment in daily mean temperature, the cumulative excess risk (CER) of injury mortality among Hunan residents increased by 0.71% (95%CI: 0.53%, 0.90%). Notably, the CER for intentional injuries (1.06%, 95%CI: 0.51%, 1.61%) was higher than that for unintentional injuries (0.66%, 95%CI: 0.46%, 0.87%). Warmer temperatures were positively associated with CER of mortality due to drowning, falls, transport injuries, assaults, and suicides, while they were negatively associated with mortality due to poisoning. Compared with 2010–2019, for 2090–2099, the excess mortality rate (EMR) due to ambient temperature increase in Hunan Province under the SSP5-8.5 scenario (14.62/100000, 95%CI: 10.81/100000, 18.40/100000) would be higher than that of the SSP3-7.0 scenario (10.28/100000, 95%CI: 7.58/100000, 12.97/100000) and the SSP1-2.6 scenario (3.35/100000, 95%CI: 2.46/100000, 4.23/100000); the EMR would be around 2.5 times among men (20.64/100000, 95%CI: 14.44/100000, 26.8/100000) than that among women (8.33/100000, 95%CI: 3.98/100000, 12.6/100000). Among unintentional injuries, the leading contributors to EMR would be drowning (4.46/100000), falls (3.96/100000), and transport injuries (2.96/100000). And among intentional injuries, the EMR for suicide (2.08/100000) would be higher than that for assault (0.47/100000). Conclusion Climate warming will increase the total burden of injury-related deaths among residents in Hunan Province, especially in the absence of effective mitigation strategies and measures. It is necessary to strengthen the prevention and control of severe injuries closely related to temperature changes, such as drowning, falls, traffic, and suicides injuries, in order to reduce injury deaths associated with climate change.

AIM:To investigate the effect of Biejiajian pill(BJJP)in reducing carbon tetrachloride(CCl4)-in-duced liver fibrosis in rats and to explore the underlying mechanism of the TLR4-NF-κB signaling pathway.METHODS:A total of 40 male Wistar rats were randomly assigned to 4 groups:control group,model group,low-dose BJJP group,and high-dose BJJP groups,with 10 rats per group.The rat model of liver fibrosis was established by intraperitoneal injection of CCl4,and two doses of BJJP(2.2 g/kg and 0.55 g/kg)were administered simultaneously.After 8 weeks of modeling and BJJP administration,the enzyme-linked immunosorbent assay(ELISA)was used to measure liver injury indicators,including alanine aminotransferase(ALT)and aspartate aminotransferase(AST).Masson trichrome staining and Sirius red staining were performed to assess the fibrin deposition in liver tissue.Immunohistochemistry and Western blot analysis were conducted to detect the expression of extracellular matrix produced by hepatic stellate cells(HSCs).The expression of fibrosis-related proteins was examined using morphological assessment and Western blot.Finally,Western blot analysis was performed to detect the expression of proteins related to the Toll-like receptor 4(TLR4)/myeioid differentiation factor 88(MyD88)/NF-κB signaling pathway.RESULTS:The ELISA results indicated that BJJP treatment significantly re-duced ALT and AST levels in the serum of rats with liver fibrosis(P<0.01).Hematoxylin-eosin staining confirmed the protective effect of BJJP on liver tissue.Morphological analysis using Masson trichrome staining,Sirius Red staining,and alpha smooth muscle actin(α-SMA)immunohistochemical staining demonstrated that BJJP effectively reduced fibrin depo-sition in CCl4-induced rat liver fibrosis.Furthermore,the decreased expression of other markers associated with hepatic stellate cell activation,including fibronectin,collagen type Ⅰ,and α-SMA(P<0.01).Additionally,BJJP treatment sig-nificantly inhibited the activation of the TLR4/MyD88/NF-κB signaling pathway induced by CCl4(P<0.05).CONCLU-SION:BJJP alleviates CCl4-induced liver injury and fibrosis in rats.This effect may be attributed to its inhibition of the TLR4-NF-κB signaling pathway,which subsequently suppressed the HSCs activation.

Objective To quantitatively analyze the effect of long-term ultrahigh-altitude and mid-high-altitude expo-sure on fundus microcirculation.Methods In the cross-sectional study,healthy residents from ultrahigh-altitude areas(＞3 500-5 500 m)and those from mid-high-altitude areas(＞1 500-3 500 m)were included as subjects.Meanwhile,healthy residents from plain areas were included as the control group.All subjects underwent optical coherence tomography angiography(OCTA)and spectral domain optical coherence tomography(SD-OCT)scans.Fundus images were quantified using ImageJ,and fundus microcirculation metrics were calculated and compared among these groups.Retinal microcircu-lation metrics included retinal vessel density(RVD),retinal skeleton density(RSD),fractal dimension(FD),foveal avas-cular zone(FAZ)area,and ganglion cell complex(GCC)thickness.Choroidal microcirculation metrics included subfoveal choroidal thickness(SFCT),luminal area(LA),total choroidal area(TCA),and choroidal vascularity index(CVI).Results In the ultra-high altitude group,the RVD was(32.52±3.57)％,the RSD was(15.05±4.24)％,and the FD was 1.68±0.08,all of which were significantly lower compared with the control group(all P＜0.001).The average thick-ness of GCC in the ultrahigh-altitude group was(98.76±10.26)μm,which was significantly thinner than the average thickness of GCC in the control group(P＜0.001).The TCA in the ultrahigh-altitude group was(2.15±0.49)mm2,the LA was(1.17±0.36)mm2,and the SFCT was(318.12±76.50)μm,all of which were significantly higher compared with the control group(all P＜0.001).However,the CVI was significantly decreased in the ultrahigh-altitude group compared with the control group(P＜0.001).There were no significant differences in fundus microcirculation metrics between the mid-high-altitude group and the control group(all P＞0.05).Conclusion Long-term ultrahigh-altitude exposure may induce ischemia and hypoxia in the fundus,primarily characterized by a decrease in the retinal and choroidal blood flow density,whereas long-term mid-high-altitude exposure cannot cause changes in the fundus microcirculation.

[Objective]To explore the correlation between general anesthesia and mild cognitive impairment in older adults so as to provide new ideas for early prevention and timely intervention of mild cognitive impairment(MCI).[Methods]Based on the baseline survey of the Hubei memory and aging cohort study(2018-2023),the participants completed a thorough neuropsychological assessment and physical examination,and self-reported a history of general anesthesia and surgery.The association of general anesthesia and MCI in the elderly was analyzed using the logistic regression model.In addition,the stratification and interaction analysis of anesthesia history,anesthesia number and physical intellectual exercise were conducted separately.[Results]A total of 5 069 older adults aged 65 and above were included in this study,including 3 692 city dwellers and 1 377 rural people,among whom were 2 584 women(51%).Out of the 1 472 participants with history of general anesthesia,249 people(17.4%)had MCI.After controlling for confounding factors,there was a 39.6%increased risk of MCI in older adults who underwent general anesthesia[OR=1.396,95%CI(1.169,1.668),P<0.001],suggesting that general anesthesia may be an independent influence on MCI.For the older adults who had one general anesthesia[OR=1.235,95%CI(1.001,1.523),P=0.049],two general anesthesia[OR=1.779,95%CI(1.292,2.450),P<0.001],and three OR more general anesthesia[OR=2.395,95%CI(1.589,3.610),P<0.001],their risks of MCI were increased by 23.5%,77.9%,and 139.5%,respectively.Compared with the older adults without a history of general anesthesia who did not exercise,the risk of developing MCI was significantly negatively correlated with the exercise group,cognitive exercise group,and combined exercise and cognitive exercise groups(all P<0.001).The risk of developing MCI in the exercise group was 60.2%of that in the no exercise group[OR=0.602,95%CI(0.456,0.795)],the risk in the cognitive exercise group was 42.4%of that in the no exercise group[OR=0.424,95%CI(0.294,0.613)],and the risk in the combined exercise and cognitive exercise group was 27.0%of that in the no exercise group[OR=0.270,95%CI(0.208,0.353)].In the older adults with a history of general anesthesia,compared with the no exercise group,the risk of developing MCI was significantly negatively correlated with the cognitive exercise group and the combined exercise and cognitive exercise group(all P<0.05).The risk of developing MCI in the cognitive exercise group was 47.7%of that in the no exercise group[OR=0.477,95%CI(0.256,0.892)],the risk in the combined exercise and cognitive exercise group was 34.5%of that in the no exercise group[OR=0.345,95%CI(0.220,0.540)],while the risk in the exercise-only group did not show a significant difference.[Conclusion]The risk of MCI increased significantly in older adults with a history of general anesthesia,and this risk increased with the times of anesthesia.Physical and mental exercise reduces the risk of MCI.it is recommended that older adults with a history of anesthesia incorporate physical and mental exercise into their daily lives to prevent mild cognitive impairment.