Objective: To examine the casual association between age at first sexual intercourse and gynecologic malignant tumors using Mendelian randomization (MR) approach. Methods: The single nucleotide polymorphisms (SNPs) associated with age at first sexual intercourse were obtained from a meta-analysis of genome-wide association study (GWAS), and the SNPs related to gynecologic malignant tumors (ovarian cancer, endometrial cancer, cervical cancer), and their subtypes were sourced from the IEU OpenGWAS database. Using age at first sexual intercourse as the exposure and gynecologic malignant tumors as the outcome, a MR analysis was performed with the inverse-variance weighted (IVW) method. Heterogeneity was assessed using Cochran's Q test, horizontal pleiotropy was evaluated using MR-Egger regression and MR-PRESSO test, and bias was examined using funnel plots. Results: The Mendelian randomization analysis demonstrated that younger age at first sexual intercourse was significantly associated with an increased risk of low-grade serous ovarian carcinoma (OR=0.553, 95%CI: 0.335-0.911), cervical cancer (OR=0.674, 95%CI: 0.466-0.974), endometrial cancer (OR=0.854, 95%CI: 0.730-0.999), and endometrioid carcinoma (OR=0.830, 95%CI: 0.690-0.998). No statistical association was found between the age at first sexual intercourse and ovarian cancer, high-grade serous ovarian cancer, mucinous ovarian cancer, endometrioid ovarian cancer, or non-endometrioid ovarian cancer (all P>0.05). Sensitivity analysis showed no evidence of undetected instrumental variable heterogeneity or horizontal pleiotropy (all P>0.05), and the funnel plot indicated no presence of bias. Conclusion Younger age at first sexual intercourse may be associated with an increased risk of certain gynecologic malignant tumors, highlighting the need to strengthen adolescent sex education.

PURPOSE: Emergency resuscitative thoracotomy (ERT) is a final salvage procedure for critically injured trauma patients. Given its low success rate and ambiguous indications, its use in blunt trauma scenarios remains highly debated. Consequently, our study seeks to ascertain the overall survival rate of ERT in blunt trauma patients and determine which patients would benefit most from this procedure. METHODS: A retrospective case-control study was conducted for this research. Blunt trauma patients who underwent ERT between January 2020 and December 2023 in our trauma center were selected for analysis, with the endpoint outcome being in-hospital survival, divided into survival and non-survival groups. Inter-group comparisons were conducted using Chi-square and Fisher's exact tests, the Kruskal-Wallis test, Student's t-test, or the Mann-Whitney U test. Univariate and multivariate logistic regression analyses were conducted to assess potential predictors of survival. Then, the efficacy of the predictors was assessed through sensitivity and specificity analysis. RESULTS: A total of 33 patients were included in the study, with 4 survivors (12.12%). Multivariate logistic regression analysis indicated a significant association between cardiac tamponade and survival, with an adjusted odds ratio of 33.4 (95% CI: 1.31 - 850.00, p = 0.034). Additionally, an analysis of sensitivity and specificity, targeting cardiac tamponade as an indicator for survivor identification, showed a sensitivity rate of 75.0% and a specificity rate of 96.6%. CONCLUSION The survival rate among blunt trauma patients undergoing ERT exceeds traditional expectations, suggesting that select individuals with blunt trauma can significantly benefit from the procedure. Notably, those presenting with cardiac tamponade are identified as the subgroup most likely to derive substantial benefits from ERT.
Adult ; Female ; Humans ; Male ; Middle Aged ; Case-Control Studies ; China ; Logistic Models ; Resuscitation/mortality* ; Retrospective Studies ; Survival Rate ; Thoracotomy/methods* ; Trauma Centers/statistics & numerical data* ; Wounds, Nonpenetrating/surgery*

OBJECTIVE: To investigate the effectiveness of Xuanshen Yishen Decoction (XYD) in the treatment of hypertension. METHODS: Hospital electronic medical records from 2019-2023 were utilized to emulate a randomized pragmatic clinical trial. Hypertensive participants were eligible if they were aged ⩾40 years with baseline systolic blood pressure (BP) ⩾140 mm Hg. Patients treated with XYD plus antihypertensive regimen were assigned to the treatment group, whereas those who followed only antihypertensive regimen were assigned to the control group. The primary outcome assessed was the attainment rate of intensive BP control at discharge, with the secondary outcome focusing on the 6-month all-cause readmission rate. RESULTS: The study included 3,302 patients, comprising 2,943 individuals in the control group and 359 in the treatment group. Compared with the control group, a higher proportion in the treatment group achieved the target BP for intensive BP control [8.09% vs. 17.5%; odds ratio (OR)=2.29, 95% confidence interval (CI)=1.68 to 3.13; P<0.001], particularly in individuals with high homocysteine levels (OR=3.13; 95% CI=1.72 to 5.71; P<0.001; P for interaction=0.041). Furthermore, the 6-month all-cause readmission rate in the treatment group was lower than in the control group (hazard ratio=0.58; 95% CI=0.36 to 0.91; P=0.019), and the robustness of the results was confirmed by sensitivity analyse. CONCLUSIONS XYD could be a complementary therapy for intensive BP control. Our study offers real-world evidence and guides the choice of complementary and alternative therapies. (Registration No. ChiCTR2400086589).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Antihypertensive Agents/pharmacology* ; Blood Pressure/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Hypertension/physiopathology* ; Patient Readmission ; Treatment Outcome

Abnormal amino acid metabolism promotes tumor progression by inducing malignant behaviors in tumor cells and altering the immune landscape within the tumor microenvironment. However, the underlying mechanisms remain unclear. In this study, we constructed colorectal cancer (CRC) organoids and patient-derived tumor xenograft (PDX) models, performing multifaceted validation to confirm that T-complex protein 1 subunit epsilon (CCT5), mediates the biosynthesis of aspartate and enhances sensitivity to anti-PD-L1 immunotherapy. Mechanistically, CCT5 directly binds to asparagine synthetase (ASNS) and promotes the synthesis of aspartate (Asn). The Asn-mTORC1 axis facilitates tumor cell proliferation while upregulating PD-L1 expression, which leads to a reduction in the number of effector CD8⁺ T cells. Treatment with l-asparaginase (ASNase) combined with anti-PD-L1 therapy effectively reverses the growth of CRC characterized by high CCT5 expression. In summary, we identify CCT5 as a potential biomarker to guide the combined use of ASNase and anti-PD-L1 antibodies in CRC treatment.

Objective To investigate the efficacy of therapeutic hypothermia on mild neonatal hypoxic-ischemic encephalopathy(HIE).Methods A prospective study was performed on 153 neonates with mild HIE who were born from September 2019 to September 2023.These neonates were randomly divided into two groups:therapeutic hypothermia(n=77)and non-therapeutic hypothermia group(n=76).The short-term clinical efficacy of the two groups were compared.Barkovich scoring system was used to analyze the severity of brain injury shown on magnetic resonance imaging(MRI)between the two groups.Results There were no significant differences in gestational age,gender,birth weight,mode of birth,and Apgar score between the therapeutic hypothermia and non-therapeutic hypothermia groups(P>0.05).There were no significant differences in the incidence rates of sepsis,arrhythmia,persistent pulmonary hypertension and pulmonary hemorrhage and the duration of mechanical ventilation within the first 72 hours after birth between the two groups.The therapeutic hypothermia group had longer prothrombin time within the first 72 hours after birth and a longer hospital stay(P<0.05).Compared with the non-therapeutic hypothermia group,the therapeutic hypothermia group had lower incidence rates of MRI abnormalities(30%vs 57%),moderate to severe brain injury on MRI(5%vs 28%),and watershed injury(27%vs 51%)(P<0.05),as well as lower medium watershed injury score(0 vs 1)(P<0.05).Conclusions Therapeutic hypothermia can reduce the incidence rates of MRI abnormalities and watershed injury,without obvious adverse effects,in neonates with mild HIE,suggesting that therapeutic hypothermia may be beneficial in neuroprotection in these neonates.

Objective To quantitatively analyze the impact of environmental hygiene on the occurrence of health-care-associated infections(HAI).Methods Monitoring data of HAI and environmental hygiene from a tertiary first-class hospital from January 2018 to December 2022 were collected,and the impact of environmental bacterial colony forming unit(CFU)on the occurrence of HAI was analyzed by a time-series generalized additive model.Results The single-contamination model showed a significant positive correlation between HAI and staff's hand bacterial CFU(β1=0.009,P=0.012).For an increase of 1 interquartile range(IQR)in the monthly mean CFU per dish(MCFU/Dish)of staffs'hand,the incidence of HAI increased by 13.28％(95％CI:2.82％-24.81％).Subgroup and lag effect analysis showed that when the monthly MCFU/Dish(after hand disinfection)of staffs'hand in-creased by one IQR,the excess risk(ER)of HAI for the month(lag0)was 16.26％(95％CI:15.45％-17.09％).In the multi-contamination model,the correlation between surface contamination and HAI was also statistically sig-nificant.Conclusion There is a significant correlation between hospital environmental hygiene and the occurrence of HAI.

Aim To observe the effects of Compound Dihuang Granules on α-syn,VAPB and PTPIP51 in the substantia nigra of Parkinson's disease(PD)rats with Yin deficiency and wind syndrome,and to explore the possible mechanisms of their actions.Methods The 6-hydroxydopamine-induced PD model of rats was constructed.The model rats were randomly divided into the model group,madopar group,CLD group,CMD group and CHD group,while the NC group did not re-ceive any treatment and the SO group was injected with ascorbic acid,with 13 rats in each group.The neurobe-havioral changes of the rats were observed,and the ex-pressions of α-syn,VAPB and PTPIP51 in the sub-stantia nigra were detected by Western blot,RT-PCR and Immunohistochemistry;the histopathological and morphological changes of the substantia nigra tissue were observed by HE staining,the changes of mito-chondrial ultrastructure in the substantia nigra cells were observed by transmission electron microscopy,and the changes of ATP content in substantia nigra tis-sue in each group were detected by ELISA.Results Compared with the NC and SO groups,rats in the model group showed that the number of rotational cir-cles and pole-climbing time increased,the expression of α-syn increased,the expression of VAPB and PTPIP 5 1 decreased,the number of neuronal cells decreased,the neuronal cells became crumpling,and mitochondrial swelling,disappearance of the mitochon-drial cristae,a larger distance between the ER-mito-chondrial contacts were observed;the ATP content de-creased.Compared with the model group,rats in Mado-par group and CLD group,CMD group and CHD group showed that the number of rotational circles and pole-climbing time decreased,the expression of α-syn de-creased,the expression of VAPB and PTPIP51 in-creased,the degree of neuronal damage was reduced,the morphology of mitochondria was improved and the content of ATP increased,showing the change of the difference in quantitative efficacy;the relative efficacy of Madopar group and CHD group was better,and there was no statistically significant difference.Con-clusions Compound Dihuang granules attenuate the behavioral symptoms in PD rats and may play a thera-peutic role in PD by down-regulating the expression ofα-syn,up-regulating the expression of PTPIP51 and VAPB and improving mitochondrial function.

Objective:To explore the early effects and safety of using a hybrid fixation strategy with 3D-printed porous tantalum metal augments to reconstruct substantial bone defects in complex primary total knee arthroplasty (TKA).Methods:A retrospective analysis was performed on the clinical data from August 2019 to September 2023, encompassing 20 patients (21 knees) with significant bone loss who underwent hybrid fixation with 3D-printed porous tantalum augments. The procedures were conducted at two medical centers: the First Affiliated Hospital, School of Medicine, Zhejiang University (11 cases) and Xiangya Hospital of Central South University (9 cases). The study cohort comprised 6 males (6 knees) and 14 females (15 knees), with a mean age of 61.05±11.23 years (range, 42-80 years). The distribution of cases was 7 on the left side and 14 on the right side. All cases were categorized as type 3 according to the Anderson Orthopaedic Research Institute (AORI) classification system. The cohort included 19 unilateral and 1 bilateral case, with 5 involving complex primary replacements (3 with Charcot arthropathy, 1 with syphilitic arthropathy, and 1 with severe valgus deformity) and 16 revision surgeries (13 for aseptic loosening and 3 for infection). Preoperative assessments included routine CT scans and digital three-dimensional reconstructions to identify large metaphyseal defects exceeding 50% of the metaphyseal area or those thicker than 10 mm. For such defects, 3D-printed standardized porous tantalum augments were implemented. In cases of extensive cavitary bone defects or severe metaphyseal defects where the medial and lateral defects collectively exceeded 80% of the metaphyseal region or where the residual bone stock was insufficient for screw fixation of standardized augments, 3D-printed personalized custom-made porous tantalum augments were employed for hybrid fixation and repair. Comparative analyses were conducted on pre- and postoperative imaging data (prosthesis positioning and complications), knee range of motion (ROM), visual analogue scale (VAS) for pain, and Knee Society score (KSS).Results:Of the cases, 17 were repaired using standardized 3D-printed porous tantalum augments, while 4 underwent repairs with customized augments for hybrid fixation. Follow-up averaged 26.5±15.0 months (range, 12-62 months). There was a significant increase in knee ROM, improving from 72.8°±31.9° preoperatively to 113.2°±6.8° at 12 months postoperatively ( P<0.05). VAS scores decreased from 6.6±1.4 preoperatively to 2.5±1.0 at 12 months postoperatively ( P<0.05). Similarly, KSS improved from 52.8±6.4 preoperatively to 80.7±7.9 at 12 months postoperatively ( P<0.05). There were no incidences of prosthesis displacement, poor bone integration, or postoperative infections. Conclusion:The hybrid fixation strategy employing 3D-printed porous tantalum augments has been found to be effective in addressing significant bone defects in TKA. The follow-up results indicate a satisfactory biological integration of the porous tantalum metal augments with the host bone, which has resulted in substantial improvements in pain relief and knee joint functionality.

AIM To rapidly screen xanthine oxidase(XOD)inhibitors from Smilax glabra Roxb.by enzyme-immobilized magnetic microspheres and LC-MS/MS,and to confirm the anti-uric acid constituents from S.glabra Roxb.METHODS The immobilized xanthine oxidase was prepared by covalent coupling with carboxyl magnetic beads as a carrier.The xanthine oxidase inhibitors in S.glabra were screened by the specific adsorption of immobilized enzyme.LC-MS/MS and standard substances were used for analysis and comparison,and the inhibitory activity and inhibition type of the screened and identified components were investigated.RESULTS The successful synthesis of immobilized xanthine oxidase was characterized by scanning electron microscopy and infrared spectroscopy.The enzyme loading was 70.50 μg/mg and the relative activity was 79.44%.Thirteen active compounds were screened from the extract of S.glabra,and eleven compounds were identified.The enzyme activity test showed that the inhibitory activites of engeletin and isoengeletin were the strongest,which was close to the positive control allopurinol.The IC50 value and inhibition type were 32.25 μg/mL,mixed inhibition,35.12 μg/mL,competitive inhibition.CONCLUSION The method is simple,rapid,accurate and suitable for directly screened active ingredients which can inhibit XOD from complex extract of traditional Chinese medicines.