Background In recent years, the increasingly widespread application of nuclear and medical radiation technologies has resulted in a large number of occupational populations exposed to low-dose ionizing radiation (LDIR). At present, there is no consistent conclusion on the effects of long-term exposure to LDIR on the metabolic health of the occupational population. Objective To explore the association between long-term exposure to LDIR and metabolic syndrome (MetS) among medical radiologists. Methods A cross-sectional study was conducted to enroll 6431 medical radiologists who ordered occupational health checkups from January 2022 to December 2023, and basic information such as demographic characteristics, occupational characteristics, lifestyles, and dietary habits was collected through questionnaires. Physical examinations were conducted using a standardized protocol. Individual dose equivalents of occupational external exposure were monitored by dosimeters worn by medical radiologists. Logistic regression model was used for identifying influencing factors of MetS and sensitivity analysis, and restricted cubic spline model was used to explore the dose-response relationship between cumulative effective dose and MetS. Two-stage linear regression was used to evaluate threshold effect of association between cumulative effective dose and MetS. Results The positive rate of MetS was 13.6% (877/6431) among the enrolled 6431 study participants. The logistic regression showed that gender, age, monthly income, body mass index (BMI), cumulative effective dose, and smoking were influencing factors for MetS. The risk of MetS was higher in males (OR=1.511, 95%CI: 1.209, 1.888); using the < 30 years old group as reference, the risk of MetS was higher in the 30-39 years old (OR=1.509, 95%CI: 1.095, 2.079), 40-49 years old (OR=2.214, 95%CI: 1.551, 3.161), and ≥50 years old (OR=3.480, 95%CI: 2.338, 5.181) groups; using the <10000 yuan group as reference, the risk of MetS was lower in the group with a monthly income of 10000-14999 yuan (OR=0.715, 95%CI: 0.582, 0.878); the risk of MetS was higher in the BMI ≥ 24 kg·m⁻² group (OR=7.548, 95%CI: 6.223, 9.156); using the < 0.76 mSv group as reference, the risk of MetS was higher in the cumulative effective dose of 0.76-2.73 mSv group (OR=1.270, 95%CI: 1.017, 1.586); the risk of MetS was higher in the smoking group (OR=1.734, 95%CI: 1.428, 2.107). The results of restricted cubic spline showed that the cumulative effective dose was nonlinearly correlated with MetS (P _{non-linearity}=0.028), with an inflection point of 1.25 mSv. The risk of developing MetS increased by 34.1% for each unit increase in cumulative effective dose up to 1.25 mSv, whereas above 1.25 mSv, the statistical association was not significant. The sensitivity analysis results showed that after excluding the self-reported hypertensive and diabetic patients, the cumulative effective dose 0.76-2.73 mSv group still had an increased risk of developing MetS compared with the < 0.76 mSv group (P < 0.05), and the results were robust. Conclusion Among medical radiologists, male, age, BMI, and smoking are positively correlated with MetS, and monthly income is negatively correlated with MetS; cumulative effective dose is non-linearly correlated with MetS among medical radiologists.

BACKGROUND: Chronic kidney disease (CKD)-associated anemia (CKD-anemia) is associated with poor survival, and hemoglobin targets are often not achieved with current therapies. Phase 3 trials have demonstrated the treatment efficacy of roxadustat for CKD-anemia. This phase 4 study aims to evaluate the long-term (52-week) safety and effectiveness of roxadustat in a broad real-world patient population with CKD-anemia with and without dialysis in China. METHODS: This Phase 4 multicenter, open-label, prospective study, conducted from 24 November 2020 to 11 November 2022, evaluated the long-term safety and effectiveness of roxadustat for CKD-anemia in China. Patients aged ≥18 years with CKD-anemia with or without dialysis were included. The initial oral dose was 70-120 mg (weight-based followed by dose adjustment) over 52 weeks. The primary endpoint was safety based on adverse events (AEs). The secondary endpoints were hemoglobin changes from baseline and the proportion of patients who achieved mean hemoglobin ≥100 g/L. Effectiveness evaluable populations 1 (EE1) and EE2 included roxadustat-naïve and previously roxadustat-treated patients, respectively. The safety analysis set (SAF) included all patients who received ≥1 occasion. RESULTS: The EE1, EE2, and SAF populations included 1804, 193, and 2021 patients, respectively. In the SAF, the mean age was 50 ± 14 years, and 1087 patients (53.8%) were male. Mean baseline hemoglobin was 96.9 ± 14.0 g/L in EE1 and 100.3 ± 12.9 g/L in EE2. In EE1, the mean (95% confidence interval) hemoglobin changes from baseline over weeks 24-36 and 36-52 were 14.2 (13.5-14.9) g/L and 14.3 (13.5-15.0) g/L, respectively. Over weeks 24-36 and 36-52, 83.3% and 86.1% of patients in EE1 and 82.7% and 84.7% in EE2 achieved mean hemoglobin ≥100 g/L, respectively. In the SAF, 1643 (81.3%) patients experienced treatment-emergent AEs (TEAEs). Overall, 219 (10.8%) patients experienced drug-related TEAEs. Thirty-eight (1.9%) patients died of TEAEs (unrelated to the study drug). Vascular access thrombosis was uncommon. CONCLUSIONS: Roxadustat (52 weeks) increased hemoglobin and maintained the treatment target in Chinese patients with CKD-anemia with acceptable safety, supporting its use in real-world settings. REGISTRATION Chinese Clinical Trial Registry ( www.chictr.org.cn ) ChiCTR2100046322; CDE ( www.chinadrugtrials.org.cn ) CTR20201568.
Humans ; Male ; Female ; Anemia/etiology* ; Middle Aged ; Renal Insufficiency, Chronic/complications* ; Glycine/adverse effects* ; Isoquinolines/adverse effects* ; Aged ; Prospective Studies ; Adult ; Hemoglobins/metabolism* ; Treatment Outcome ; China ; Registries ; East Asian People

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*

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.

Since the beginning of the 21st century, the severe respiratory infectious diseases worldwide [such as severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), influenza A H1N1 and novel coronavirus infection have attracted wide attention from all walks of life due to their superior pathogenicity and transmissibility. Aerosols-carrying pathogens are the main transmission route of many severe respiratory infectious diseases, which can lead to severe respiratory failure and even acute respiratory distress syndrome (ARDS) in infected individuals. Mechanical ventilation is the primary treatment for ARDS, and the small tidal volume, appropriate level of positive end-expiratory pressure based lung protective ventilation strategy can effectively reduce the incidence of ventilator-induced lung injury (VILI). However, in the process of clinical treatment, it is sometimes necessary to briefly disconnect the connection between the artificial airway and the ventilator circuit, which will not only cause the residual aerosol in the respiratory system to spill out and pollute the surrounding environment, increase the risk of nosocomial infection including medical staff, but also interfere with the implementation of lung protective ventilation strategy and aggravate ventilator-induced lung injury. In addition, studies have shown that a lot of medical staff have nosocomial infections, especially staff involved in tracheal intubation, extubation and other airway related operations. In addition to enhancing personal protective measures, it is crucial to safeguard healthcare workers from aerosol contamination and minimize associated risks during airway management. At present, there are few researches on the temporary sealing of airway lines and ventilator system, and there is a lack of clear guidance. This review summarizes the research status in related fields to provide a reference for corresponding solutions and programs.
Humans ; Respiratory Distress Syndrome/etiology* ; Respiration, Artificial ; Ventilator-Induced Lung Injury/prevention & control* ; Severe Acute Respiratory Syndrome ; COVID-19 ; Clinical Relevance

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.

ObjectiveTo construct a large language model （LLM）-based intelligent pre-consultation system for traditional Chinese medicine （TCM） to improve efficacy of clinical practice. MethodsA TCM large language model was fine-tuned using DeepSpeed ZeRO-3 distributed training strategy based on YAYI 2-30B. A weighted undirected graph network was designed and an agent-based syndrome differentiation model was established based on relationship data extracted from TCM literature and clinical records. An agent collaboration framework was developed to integrate the TCM LLM with the syndrome differentiation model. Model performance was comprehensively evaluated by Loss function， BLEU-4， and ROUGE-L metrics， through which training convergence， text generation quality， and language understanding capability were assessed. Professional knowledge test sets were developed to evaluate system proficiency in TCM physician licensure content， TCM pharmacist licensure content， TCM symptom terminology recognition， and meridian identification. Clinical tests were conducted to compare the system with attending physicians in terms of diagnostic accuracy， consultation rounds， and consultation duration. ResultsAfter 100 000 iterations， the training loss value was gradually stabilized at about 0.7±0.08， indicating that the TCM-LLM has been trained and has good generalization ability. The TCM-LLM scored 0.38 in BLEU-4 and 0.62 in ROUGE-L， suggesting that its natural language processing ability meets the standard. We obtained 2715 symptom terms， 505 relationships between diseases and syndromes， 1011 relationships between diseases and main symptoms， and 1 303 600 relationships among different symptoms， and constructed the Agent of syndrome differentiation model. The accuracy rates in the simulated tests for TCM practitioners， licensed pharmacists of Chinese materia medica， recognition of TCM symptom terminology， and meridian recognition were 94.09%， 78.00%， 87.50%， and 68.80%， respectively. In clinical tests， the syndrome differentiation accuracy of the system reached 88.33%， with fewer consultation rounds and shorter consultation time compared to the attending physicians （P＜0.01）， suggesting that the system has a certain pre- consultation ability. ConclusionThe LLM-based intelligent TCM pre-diagnosis system could simulate diagnostic thinking of TCM physicians to a certain extent. After understanding the patients' natural language， it collects all the patient's symptom through guided questioning， thereby enhancing the diagnostic and treatment efficiency of physicians as well as the consultation experience of the patients.