Objective: To characterize perioperative dynamic changes in immune-cell phenotypes and inflammatory cytokines in patients undergoing CPB (cardiopulmonary bypass) cardiac surgery, and to explore their associations with postoperative outcomes. Methods: In this prospective cohort study, 120 adult patients who underwent elective cardiac surgery under CPB at West China Hospital from May 2022 to March 2023 were enrolled. Perioperative immune-cell phenotypes and concentrations of 40 inflammation-related cytokines were measured. The primary outcomes were the sequential organ failure assessment (SOFA) score at 24 h after surgery and ΔSOFA (the peak SOFA score within 48 h after surgery minus the preoperative SOFA score). Secondary outcomes included major adverse cardiovascular events (MACE), acute kidney injury (AKI), respiratory failure, severe liver injury, and infection. Results: The mean age of enrolled patients was 57±10 years. Of these, 52% (62/120) were male and 90% (108/120) underwent valve surgery. During the rewarming to the end of CPB, neutrophil counts rapidly increased (7.39×10 /L vs preoperative 3.07×10 /L, P<0.001), with significant upregulation of CD11b (7.30×10 /L vs preoperative 3.05×10 /L, P<0.001) and CD54 (7.15×10 /L vs preoperative 2.99×10 /L, P<0.001). Lymphocyte counts increased at the end of CPB (1.75×10 /L vs preoperative 1.12×10 /L, P<0.001) but decreased significantly at 24 h after surgery (0.59×10 /L vs preoperative 1.12×10 /L, P<0.001). Plasma analysis showed that multiple pro-inflammatory cytokines increased during CPB and remained elevated up to 24 h after surgery; five chemokines and the anti-inflammatory cytokine IL-10 peaked at the end of CPB. The SOFA score increased from 1 (1, 2) preoperatively to 7 (5, 10) at 24 h after surgery, with a ΔSOFA of 6 (4, 8). Within 30 days after surgery, 48 patients (40.0%) developed AKI, 17 (14.2%) developed infection, 4 (3.3%) developed severe liver injury, 3 (2.5%) developed respiratory failure, and 3 (2.5%) experienced MACE. During the 2-year follow-up, 8 patients (6.7%) experienced MACE and 5 (4.2%) died. Conclusion: Multi-organ dysfunction is common after cardiac surgery under CPB (median ΔSOFA, 6), accompanied by perioperative activation of multiple immune-cell subsets and upregulation of pro-inflammatory, anti-inflammatory, and chemotactic mediators. This study provides data-driven evidence and research clues for further investigation of the associations between CPB-related immune perturbations and postoperative organ dysfunction and clinical outcomes.

ObjectiveTo investigate the association between metabolic associated fatty liver disease （MAFLD） and the risk of atherosclerotic cardiovascular disease （ASCVD）， and to provide data support for the prevention and treatment of such metabolic-associated diseases in clinical practice. MethodsAn observation cohort was established for the workers of Kailuan who underwent physical examination for the first time from June 2006 to October 2007 and had complete liver assessment data， without the history of malignant tumor， MAFLD or ASCVD. According to the presence or absence of MAFLD， the patients were divided into non-MAFLD group with 67 565 patients and MAFLD group with 29 004 patients， and according to the presence or absence of ASCVD， the patients were divided into non-ASCVD group with 69 141 patients and ASCVD group with 481 patients. The group t-test or the Wilcoxon rank-sum test was used for comparison of continuous data between the two groups. The χ² test was used for comparison of categorical data between the two groups. The life-table method was used to calculate the cumulative incidence rates of new-onset ASCVD and MAFLD； the Kaplan-Meier method was used to plot the survival curves of the cumulative incidence rates of ASCVD in the MAFLD group and the non-MAFLD group and the cumulative incidence rates of MAFLD in the ASCVD group and the non-ASCVD group， and the log-rank test was used for comparison of cumulative incidence rates between two groups. A multivariate Cox proportional-hazards regression model analysis was used to investigate the impact of MAFLD on the risk of ASCVD and the impact of ASCVD on the risk of MAFLD. ResultsCompared with the non-MAFLD group， the MAFLD group had significantly higher levels of body mass index （BMI）， waist circumference， systolic blood pressure （SBP）， diastolic blood pressure （DBP）， resting heart rate， alanine aminotransferase， uric acid （UA）， fasting blood glucose （FBG）， triglyceride （TG）， total cholesterol， low-density lipoprotein cholesterol， and high sensitivity C-reactive protein （hs-CRP）， as well as significanty lower levels of estimated glomerular filtration rate （eGFR） and high-density lipoprotein cholesterol （all P <0.05）. Compared with the non-ASCVD group， the ASCVD group had significantly higher levels of BMI， waist circumference， SBP， DBP， UA， FBG， TG， and hs-CRP and a significantly lower level of eGFR （all P<0.05）. The incidence rate of new-onset ASCVD continued to increase over time in the MAFLD group and the non-MAFLD group， while the incidence rate of new-onset MAFLD firstly increased and then remained stable over time in the ASCVD group and the non-ASCVD group. There were 4 263 cases （14.70%） of new-osnet ASCVD in the MAFLD group， with an incidence density of 12.90 per 1 000 person-years， while there were 6 529 cases （9.66%） of new-osnet ASCVD in the non-MAFLD group， with an incidence density of 8.24 per 1 000 person-years， and there were significant differences in the incidence density and cumulative incidence rate of ASCVD between the two groups （χ²=519.09 and 531.80， both P<0.05）. There were 148 cases （30.77%） of new-onset MAFLD in the ASCVD group， with an incidence density of 40.10 per 1 000 person-years， while there were 32 194 cases （46.56%） of new-onset MAFLD in the non-ASCVD group， with an incidence density of 57.59 per 1 000 person-years， and there were significant differences in the incidence density and cumulative incidence rate of MAFLD between the two groups （χ²=19.29 and 30.78， both P<0.05）. The corrected multivariate Cox proportional-hazards regression model analysis showed that MAFLD was a risk factor for new-onset ASCVD （hazard ratio ［HR］=1.11， 95% confidence interval ［CI］： 1.06 — 1.16， P<0.001）， while ASCVD was a protective factor against new-onset MAFLD （HR=0.72， 95%CI： 0.61 — 0.85， P<0.001）. ConclusionThere is a significant association between MAFLD and ASCVD， with an increase in the risk of ASCVD in the MAFLD population and a reduction in the risk of MAFLD in the ASCVD population.

OBJECTIVE: To analyze the clinical characteristics and genetic profile of patients with 46,XY Disorders of sex development (DSD) and a female phenotype in order to provide insights for the diagnosis and management of similar cases. METHODS: A retrospective analysis was conducted on 36 children with 46,XY DSD and a female phenotype who were treated at the Department of Endocrinology, Genetics and Metabolism of Henan Children's Hospital between March 1, 2016, and June 30, 2024. The evaluations included external genitalia scoring using the Prader scale and External Masculinization Score (EMS), imaging studies to assess gonadal development, and assessments of adrenal and gonadal function via adrenal hormone levels, sex hormone levels, and human chorionic gonadotropin (hCG) stimulation testing. Gender role behavior was assessed using gender role scales and sandplay therapy. Whole exome sequencing and Sanger sequencing were used to identify and validate genetic variants. A multidisciplinary team (MDT) comprehensively determined gender rearing based on molecular genetic diagnosis. This study was approved by the Medical Ethics Committee of Henan Children's Hospital (Ethics No.: 2024-K-105). RESULTS: The median age at initial consultation was 3 years and 1 month (range: 7 days to 16 years). Common symptoms included primary amenorrhea, clitoromegaly, and inguinal hernia. Fully feminized external genitalia were observed in 52.7% of the cases, and 80.5% had absence of the uterus. Internal gonads included absent gonads (5.6%), ovotestes (8.3%), streak gonads (5.6%), cryptorchidism (75.0%), and normally positioned testes (5.6%). At initial diagnosis, median luteinizing hormone (LH) was 1.305 IU/L, with elevated LH in 14 cases. Median follicle-stimulating hormone (FSH) was 4.87 IU/L, with elevated FSH in 17 cases. Median testosterone was 0.025 ng/mL. Median dihydrotestosterone (DHT) was 36.90 pg/mL. After hCG stimulation, median testosterone was 0.984 ng/mL and median DHT was 71.69 pg/mL. The testosterone/DHT ratio was elevated in one case (35.7). Testosterone levels remained below 1 ng/mL after hCG stimulation in 18 cases. Anti-Müllerian hormone (AMH) was decreased in 15 cases and increased in 3 cases. Inhibin B (InhB) was increased in 7 cases and decreased in 4 cases. Pathogenic variants were detected in 88.9% of the patients, involving AR (11 cases), CYP17A1 (4 cases), GATA4 (1 case), NR0B1 (1 case), NR5A1 (7 cases), SRD5A2 (1 case), WT1 (2 cases), STAR (4 cases), and LHCGR (1 case), totaling 34 variant sites. Among these, 9 variants were de novo, and 23 were inherited from parents. Sixteen variant sites were previously unreported. Gender assignment was male in 11 cases (30.6%) and female in 25 cases (69.4%). CONCLUSION Common symptoms in 46,XY DSD patients with a female phenotype include primary amenorrhea, clitoromegaly, and inguinal hernia. Elevated FSH, androgen deficiency, and decreased AMH and InhB may indicate testicular dysgenesis or impaired androgen synthesis. Adrenal insufficiency should raise suspicion for defects in steroid hormone synthesis pathway enzymes.
Humans ; Female ; Disorder of Sex Development, 46,XY/diagnosis* ; Child ; Male ; Phenotype ; Child, Preschool ; Retrospective Studies ; Adolescent ; Infant

Objective To investigate the effects of Zuogui Jiangtang Tongmai Prescription on short-chain fatty acids(SCFAs)and G protein-coupled receptor 109A(GPR109A)in diabetic atherosclerotic mice;To explore its mechanism of improving diabetic atherosclerosis.Methods ApoE-/-mice were fed with high sugar and high fat diet and intraperitoneal injection of streptozotocin to establish atherosclerosis model of diabetes.After modeling,the mice were randomly divided into the model group,Western medicine group(metformin hydrochloride+atorvastatin),and Zuogui Jiangtang Tongmai Prescription low-,medium-and high-dosage groups(19,38,76 g/kg);and the other C57BL/6J mice were set as the control group,with 6 mice in each group.Each group was given solution for gavage,once a day for 4 weeks.Blood glucose of the mice were detected,HE staining was used to observe the morphology of the aorta,TG,TC,LDL-C and HDL-C contents were detected by fully automated biochemistry analyzers,ELISA was used to detect the contents of serum HbA1c,fasting insulin(FINS),interleukin(IL)-1β,IL-6 and tumor necrosis factor(TNF)-α,gas chromatography was used to detect the content of intestinal SCFAs,and RT qPCR and Western blot were used to detect the mRNA and protein expressions of GPR109A in ileal tissue and nuclear factor(NF)-κB p65 in aortic tissue,respectively.Results Compared with the control group,obvious plaques and inflammatory cells infiltration were seen in the aorta of the model group,the blood glucose and serum HbA1c,TG,TC,LDL-C,IL-1β,IL-6 and TNF-α contents increased(P<0.01),FINS and HDL-C content decreased(P<0.01),intestinal acetate,propionate,butyric acid,isobutyric acid and isovaleric acid contents decreased(P<0.01),GPR109A mRNA and protein expression in ileal tissue decreased,NF-κB p65 mRNA and protein expression in aortic tissue increased(P<0.01).Compared with the model group,the aortic plaque area and inflammatory cells infiltration were significantly improved in each drug intervention group,the blood glucose and serum HbA1c,TG,TC,LDL-C,IL-1β,IL-6 and TNF-α contents decreased(P<0.05,P<0.01);the FINS and HDL-C content increased(P<0.05,P<0.01),intestinal acetic,propionic,butyric acid,isobutyric acid and isovaleric acid contents increased(P<0.05,P<0.01),GPR109A mRNA and protein expression in ileal tissue increased and NF-κB p65 mRNA and protein expression in ileal tissue decreased decreased(P<0.05,P<0.01).Conclusion Zuogui Jiangtang Tongmai Prescription can improve glucolipid metabolism and inflammatory response in diabetic atherosclerotic mice,which may be related to regulating SCFAs/GPR109A pathway.

Radiotherapy (RT) is one of the main treatment methods for malignant tumors. However, how to improve the efficacy of RT while reducing its side effects is still facing great challenges. The progress of nanomedicine has provided the possibility of improving the curative effect of RT for tumors. Nanomaterials not only act as radiosensitizers to enhance radiation energy, but also act as nanomaterials to provide therapeutic methods against tumor radiation. This may help to explore the new direction of clinical translation of nanoparticle radiosensitizers. In this article, the combination of nanomaterials-based radiotherapy and photothermal therapy for cancer was reviewed. The use of nanomaterials to counter anti-tumor radiation responses was highlighted, and the mutual enhancement of these synergistic therapies was described. In addition, the potential challenges and future prospects of radiation nanomedicine were explored.

Objective To investigate polyp miss rate and influencing factors during colonoscopy using the opportunity of short-interval repeat examinations in day surgery settings.Methods This single-center retrospective cohort study consecutively enrolled 1 005 patients undergoing polypectomy at the Endoscopy Center of Army Medical University First Affiliated Hospital(March-June 2023).All patients received initial diagnostic colonoscopy followed by therapeutic colonoscopy(repeat examination).Using repeat examination findings as reference,we calculated patient miss rate,polyp miss rate,and adenoma patient miss rate.Multivariable logistic regression analyzed operator-and patient-related factors influencing patient miss rates.Results Patient miss rate,polyp miss rate,and adenoma miss rate were 26.67%(95%CI:23.95～29.52),16.45%(95%CI:15.26～17.70),and 15.52%(95%CI:13.34～17.91),respectively.Multivariable analysis identified independent risk factors—operator-related:initial procedure by junior endoscopists(OR=2.07,95%CI:1.42～3.03,P<0.001)and afternoon procedures(13:30-16:00;OR=1.68,95%CI:1.01～2.81,P=0.047);Patient-related:inadequate bowel preparation(OR=4.16,95%CI:2.28～7.61,P<0.001)and flat-type lesions(OR=4.33,95%CI:2.49～7.52,P<0.001).Reduced miss rates occurred with polyps 0.3～0.5 cm(OR=0.30,95%CI:0.21～0.41,P<0.001)and 0.6～0.9 cm(OR=0.10,95%CI:0.04～0.22,P<0.001).Inadequate preparation during therapeutic examination decreased polyp detection(OR=0.23,95%CI:0.10～0.53,P<0.001).Conclusion Colonoscopy exhibits significant polyp miss rates influenced by operator and patient factors.Standardized repeat examinations in day surgery settings effectively detect missed lesions,supporting long-term quality control.

Glutathione(GSH)is a tripeptide containing sulfhydryl groups,which has the function of antioxidant,detoxifying,and immune enhancing effects,and its expression is closely associated with many diseases such as cancer,etc.Therefore,it is of great significance for clinical diagnosis by developing a highly sensitive,simple,and rapid method for detecting GSH.Herein,two-dimensional(2D)Zn-TCPP(Fe)nanosheets employing Zn2+and Fe-bound tetrakis(4-carboxyphenyl)porphyrin ligands were obtained by a surfactant-assisted synthetic method.The 2D Zn-TCPP(Fe)nanosheets exhibited excellent peroxidase-like activity,which allowed the catalysis of the H2O2-initiated oxidation of colorless 3,3',5,5'-tetramethylbenzidine(TMB)to blue oxidized TMB(ox-TMB).In the presence of GSH,GSH underwent a reduction reaction with oxTMB,resulting in the blue color of the solution fading.The proposed colorimetric sensor exhibited favorable sensitivity for GSH in the linear range of 0.1-200 μmol/L with a limit of detection(S/N=3)of 0.042 μmol/L,indicating excellent selectivity.The developed sensor was successfully applied to detect GSH level in the human serum samples with recoveries of 93.0％-107.7％,showing satisfactory results.The developed colorimetric sensor provided a new approach for detecting GSH.

Objective:To evaluate the effectiveness of opioid-free anesthesia on postoperative outcomes in elderly patients following laparoscopic cholecystectomy.Methods:In this randomized controlled trial, 90 patients of either sex, aged 65-75 yr, with a body mass index of 18.5-23.9 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, scheduled for elective laparoscopic cholecystectomy, were divided into 2 groups ( n=45 each) using a table of random numbers: conventional general anesthesia group (GA group) and opioid-free anesthesia group (OFA group). Anesthesia was induced with intravenous etomidate, sufentanil and cisatracurium besylate and maintained with infusion of propofol and remifentanil combined with inhalation of sevoflurane in GA group. In OFA group, bilateral ultrasound-guided transversus abdominis plane block was performed via the posterior gluteal approach (injection of 0.25% ropivacaine 20 ml respectively) before anesthesia induction, anesthesia was induced with intravenous dexmedetomidine, esketamine, etomidate and cisatracurium besylate and maintained with infusion of dexmedetomidine, esketamine and propofol combined with inhalation of sevoflurane. In both groups, mechanical ventilation was performed with a laryngeal mask airway after anesthesia induction, and ketorolac tromethamine 30 mg (for postoperative analgesia) and metoclopramide 10 mg (to prevent postoperative nausea and vomiting) were intravenously injected at the end of surgery. The intraoperative adverse cardiovascular events, emergence time, laryngeal mask airway removal time, time of postanesthesia care unit stay, and postoperative rescue analgesia, nausea and vomiting and delirium were recorded. Results:No gallbladder cardiac reflex was found during operation in either group. Compared with GA group, the incidence of intraoperative bradycardia (11% versus 22%) was significantly increased ( P<0.05), the incidence of intraoperative hypotension and postoperative nausea, vomiting and delirium (17% versus 8%, 29% versus 16%, 16% versus 4% and 18% versus 4%), and requirements for rescue analgesia and antiemetics (31% versus 7% and 13% versus 4%) were decreased ( P<0.05), the postoperative emergence time, time of laryngeal mask airway removal and time of postanesthesia care unit stay were prolonged ( P<0.05), and no statistically significant difference was found in discharge time in OFA group ( P>0.05). Conclusions:The results of this study, as a single-center, small-sample randomized controlled trial, indicate that referenced to conventional general anesthesia, opioid-free anesthesia (esketamine-dexmedetomidine based anesthesia combined with bilateral transversus abdominis plan block) can improve the short-term postoperative outcomes to a certain extent in elderly patients following laparoscopic cholecystectomy.

Objective:To analyze the characteristics and changes in incidence and mortality of ischemic and hemorrhagic stroke among Chinese residents from 2015 to 2019.Methods:The incidence and mortality data of ischemic and hemorrhagic stroke from 2015 to 2019 were collected from the China Registry of Cardiovascular Events (China RACE), which was established in 2014 and covered 100 counties (cities and districts) in 31 provinces in China. The age-standardized incidence rate (ASIR) was calculated using the Seventh National Census data as the standard population. The ratio of the incidence rate of ischemic stroke to hemorrhagic stroke was calculated. The subtype-specific mortality-to-incidence ratio (M/I) was calculated by the ratio of the number of deaths to the reported incidence cases. The relative ratio (RR) of M/I for ischemic to hemorrhagic stroke was calculated. The Joinpoint model was used to analyze the annual percentage change (APC) and trend of the incidence rate of stroke.Results:From 2015 to 2019, a total of 1 354 614 new stroke cases were reported, including 1 077 244 (79.52%) ischemic stroke and 277 370 (20.48%) hemorrhagic stroke cases, respectively. A total of 248 620 stroke deaths were reported, including 119 819 (48.19%) ischemic stroke deaths and 128 801 (51.81%) hemorrhagic stroke deaths. The incidence ratio of ischemic/hemorrhagic stroke from 2015 to 2019 was 3.50∶1, 3.76∶1, 3.63∶1, 4.23∶1, and 4.35∶1, respectively. From 2015 to 2019, there was no statistically significant annual trend of ASIR of ischemic stroke in overall, urban and rural areas and males ( Ptrend>0.05), while there was a downward trend in females (APC=-1.02%, Ptrend=0.042). The incidence of hemorrhagic stroke in the whole population, rural areas, males and females showed a downward trend ( Ptrend<0.05). Patients aged 45-49 years had an upward trend in the incidence rate of ischemic stroke (APC=3.82%, Ptrend=0.011), while those aged 70-74 years (APC=-7.37%, Ptrend=0.034), 80-84 years (APC=-9.75%, Ptrend=0.001) and 85 years and over (APC=-11.22%, Ptrend=0.017) presented a downward trend in the incidence of hemorrhagic stroke. During the period, the overall relative ratio of M/I (RR) for ischemic to hemorrhagic stroke was 4.2∶1, which was lower in urban than in rural areas (3.8 vs. 4.3). The largest gap between urban and rural areas was in the 55-59 age group (6.8 vs. 9.3). Conclusion:The incidence and mortality of ischemic and hemorrhagic stroke among Chinese residents are severe from 2015 to 2019, and there are regional and population differences.

Objective:To investigate the differences in clinical and imaging characteristics of patients with recent small subcortical infarct (RSSI) stratified by different etiological subtypes.Methods:A retrospective, consecutive analysis was conducted on 696 RSSI patients admitted to the West China Hospital, Sichuan University, from January 2019 to May 2024. Based on clinical and imaging data, patients were stratified into 3 etiological subgroups: presumed cerebral small vessel disease (CSVD)-related RSSI, coexisting carrier large artery stenosis, and coexisting proximal extracranial/intracranial large artery stenosis. The clinical characteristics, vascular risk factors, infarct imaging features, and CSVD markers were compared across the 3 groups. Additionally, the differences in clinical and imaging features based on the location of infarcts (anterior vs posterior circulation) and infarct size (<15 mm vs ≥15 mm) were examined. Results:Among the 696 patients, 557 (80.0%) had presumed CSVD-related RSSI, 68 (9.8%) had coexisting carrier large artery stenosis, and 71 (10.2%) had coexisting proximal extracranial/intracranial large artery stenosis. The patients with presumed CSVD-related RSSI were the youngest [60 (53, 69) years], followed by those with coexisting carrier large artery stenosis [64 (55, 69) years] and those with coexisting proximal extracranial/intracranial large artery stenosis [69 (55, 75) years; H=9.523, P=0.013]. Among RSSI patients with coexisting proximal extracranial/intracranial large artery stenosis, the proportion of those with diabetes (38/71, 53.5%) was the highest, whereas the proportion was 210/557 (37.7%) in the presumed CSVD-related group and 31/68 (45.6%) in the group with coexisting carrier large artery stenosis (χ 2=8.027, P=0.023). Patients with RSSI combined with proximal extracranial/intracranial large artery stenosis had more infarction sites in the pons and a higher proportion of proximal infarction. However, there were no significant differences among the 3 groups in terms of infarct size, or CSVD imaging markers. In the anterior versus posterior circulation comparison, patients with posterior circulation RSSI ( n=360) had a significantly higher age of onset [63(55, 72) years vs 60(52, 59) years, U=51 335.500, P<0.001], had higher prevalence of hypertension and diabetes, and showed higher NIHSS scores [3(2, 6) vs 3(1, 5), U=57 840.500, P=0.028]. The anterior circulation group ( n=366) showed a higher proportion of lacunas [152/336 (45.2%) vs 118/360 (32.8%), χ2=11.364, P<0.001], while the posterior circulation group had a greater prevalence of severe perivascular spaces in the basal ganglia [254/360 (70.6%) vs 203/336 (60.4%), χ2=7.879, P=0.005] and deep white matter hyperintensities grading≥2 [124/360 (34.4%) vs 90/336 (26.8%), χ2=4.787, P=0.029]. There were no statistically significant differences in the distribution of infarcts between anterior and posterior circulations or in CSVD imaging markers between RSSI patients with infarction lesions ≥15 mm ( n=290) and <15 mm ( n=406). Conclusions:Approximately 20% of RSSI cases are related to large artery stenosis. These patients tend to be older at onset and have a higher prevalence of diabetes. Compared to presumed CSVD-related RSSI cases, RSSI cases related to large artery stenosis show no significant differences in infarct imaging features and CSVD imaging markers, suggesting that large artery stenosis in RSSI may be an epiphenomenon rather than a direct causative factor.