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.

Lung cancer is the deadliest form of cancer globally, with millions of new cases diagnosed each year. Although rapid advancements in surgical techniques, targeted therapies, and immunotherapy have significantly improved patient outcomes, the overall 5-year survival rate remains disappointingly low. Recent studies have highlighted the vital role of gut microbiota in maintaining host health and its close association with the onset and progression of lung cancer through various mechanisms. This article provides a systematic analysis of the role of gut microbiota in lung cancer, focusing on its immunomodulatory and metabolic functions, as well as its potential applications in treatment, while also exploring its prospects for clinical use.
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Humans ; Lung Neoplasms/therapy* ; Gastrointestinal Microbiome ; Animals

OBJECTIVES: To investigate the protective effects of dexmedetomidine (DEX) against heat stress (HS)-induced oncosis in human skeletal muscle cells (HSKMCs) and its underlying mechanisms. METHODS: A HSKMC model of HS-induced oncosis were established by 43 ℃ water bath for 4 h, and the effects of treatments with 30 μmol/L DEX, ML385 (a Nrf2 inhibitor) +DEX, si-Nrf2+HS, and si-Nrf2+DEX prior to modeling on cell viability was assessed using CCK-8 assay. Oncosis characteristics were evaluated using transmission electron microscopy and Annexin V-FITC/PI flow cytometry. The oxidative stress markers (GSH, GSH-Px, MDA, SOD and ROS), mitochondrial membrane potential, energy metabolism, and inflammatory cytokines (TNF-α, IL-6 and IL-1β) in the cells were quantified using standard kits, and the expressions of porimin, caspase-3 and Nrf2 pathway proteins were analyzed using Western blotting and qRT-PCR. RESULTS: HS induced typical oncotic features in HSKMCs including organelle swelling and cytoplasmic vacuolization. DEX pretreatment significantly attenuated these changes, reduced Annexin V⁺/PI⁺ cell ratio and cellular porimin expression, and lowered the levels of ROS and MDA while restoring GSH and SOD levels. DEX pretreatment also significantly increased the mitochondrial membrane potential and ATP level, upregulated the expressions of Nrf2, p-Nrf2, HO-1 and NQO1, and suppressed the expressions of TNF-α, IL-6 and IL-1β. The protective effects of DEX were obviously attenuated by interventions with ML385 or si-Nrf2. CONCLUSIONS DEX mitigates HS-induced HSKMC oncosis by activating the Nrf2/HO-1 pathway to relieve oxidative stress, mitochondrial dysfunction, and inflammatory responses.
Humans ; Dexmedetomidine/pharmacology* ; NF-E2-Related Factor 2/metabolism* ; Oxidative Stress/drug effects* ; Heat-Shock Response/drug effects* ; Signal Transduction/drug effects* ; Membrane Potential, Mitochondrial ; Muscle, Skeletal/cytology* ; Heme Oxygenase-1/metabolism* ; Apoptosis/drug effects*

This study aims to investigate the medication rules of patented traditional Chinese medi-cine(TCM)compound formulas and molecular mechanisms of core drugs for treating sepsis using data mining and network pharmacology approaches.In the present study,we first searched the PubMed database,Web of Science database,and the China National Knowledge Infrastructure(CNKI)since the establishment of the library to April 30,2024 for the relevant literature on the treatment of sepsis by traditional Chinese medicine.The prescriptions were then statistically ana-lyzed for drug frequency and association analysis to obtain the core drugs.Then we screened the ef-fective active ingredients of the core drugs by TCMSP and other database platforms,obtained sep-sis-related genes in GeneCards and other databases,and statistically intersected targets,and predic-ted the mechanism of action of the core TCMs by subjecting the intersected targets to PPI analy-sis,GO function and KEGG pathway enrichment analysis.Finally,the relationship between key tar-gets and herbal components was examined in reverse by molecular docking method.The results showed that 64 compound formulas were obtained,with a total of 150 Chinese medicines,which were mostly sweet in taste,cold in nature,and belonged to the spleen,stomach and intestinal me-ridians.According to the association rules,the core drugs were identified as"mirabilite-peach ker-nel-rheum officinale".There were 79 intersecting targets between the core drugs and sepsis,with core targets such as IL-1β,EGFR and SRC.MAPK,TNF,IL-17 and other signaling pathways are involved to mediate inflammatory responses,apoptosis and other biological processes to exert ther-apeutic effects on sepsis.The molecular docking results indicated that the docking activity of the key targets with the main components of the drug,and sennoside E_qt has the lowest binding ener-gy and the best docking activity with SRC.In conclusion,this study showed that the prescription of Chinese medicine for sepsis is mostly based on tonifying the spleen and clearing heat.The mecha-nism of action of the core drug"mirabilite-peach kernel-rheum officinale"in the treatment of sep-sis is multilevel and multifaceted,which provides a certain theoretical basis for the treatment of sepsis by traditional Chinese medicine.

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 systematically review the advantages and disadvantages of capping and non-capping decannulation strate-gies in adult tracheostomized patients.Methods The PICO framework was developed.Literatures on decannulation measures in adult tracheostomized patients were searched in PubMed,EMbase,Cochrane Library,CNKI,Wanfang Database and SinoMed from establish-ment to February 1st,2025.The non-capping group included patients who underwent decannulation after passing the assessment,without≥24 hours of tube capping.The capping group included patients who underwent≥24 hours of tube occlusion before decannulation.Study types included randomized controlled trial(RCT),cohort studies,and case-control studies.The Newcastle-Ottawa Scale(NOS)was used to evaluate the quality of non-ran-domized studies,while the Cochrane Risk of Bias Tool was applied to assess RCTs.The GRADE was used to evaluate the evidence quality of outcome measures.Relevant information was extracted from the included studies for systematic review.Results A total of six studies were ultimately included,published between 2003 and 2020,originating from Spain,Chi-na,Nepal,and Israel,involving 745 patients.Non-RCT studies scored six to eight points on NOS.Among RCT,one study had a low risk of bias,while another had a moderate risk based on the Cochrane Risk of Bias Tool.Capping strategies included complete capping for 24 to 48 hours before decannulation,stepwise tube downsizing followed by capping,and progressive capping prior to decannulation.Non-capping strategies involved immediate decannulation after passing the assessment or following endoscopic evaluation.Compared with the capping strat-egy,non-capping decannulation significantly reduced decannulation time and incidence of adverse events.No sig-nificant differences were observed in decannulation success rates or pulmonary infection rates between the two strategies.However,findings on pulmonary infections and adverse events were inconsistent across studies.Ac-cording to the GRADE assessment,the strength of evidence was rated as low for decannulation success rate and decannulation time,and very low for incidence of pulmonary infection and adverse events.Conclusion For adult tracheostomized patients,non-capping decannulation strategy appears superior to capping strategy,demonstrating shorter decannulation time and reduced adverse events.No significant difference were observed in decannulation success rates and pulmonary infection rates between the two strategies.

[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.

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.

Tumor-associated neutrophils(TAN)are key components of the tumor microenvironment(TME)that exert dual regulatory roles in tumor progression through highly heterogeneous functional phenotypes.This review systematically addresses the dynamic balance of TAN in pro-tumor and anti-tumor mechanisms:TAN can directly kill tumor cells or collaborate with immune cells to activate anti-tumor re-sponses;however,in contrast,they can accelerate tumor progression by promoting angiogenesis,remodeling the extracellular matrix,and mediating immune evasion.Studies have shown that the functional heterogeneity of TAN is precisely regulated by multiple signaling net-works within the TME,and that the plasticity transformation of different subsets directly influences tumor progression.In-depth analyses of TAN subset characteristics,transformation mechanisms,and their clinical relevance will provide a theoretical basis for the development of inhibitors targeting pro-tumor neutrophils as well as advance the establishment of precise patient selection strategies for TAN subtype-based immunotherapy.

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.