ObjectiveTo investigate the association between endothelin receptor type A gene （EDNRA） and congenital bilateral absence of the vas deferens （CBAVD）. MethodsThis case-control study consisted of 124 subjects with CBAVD and 100 fertile controls.Two single nucleotide polymorphisms （SNPs： rs5335 and rs1801708） in the EDNRA gene were genotyped via PCR， PCR-RFLP analysis， and direct sequencing. ResultsNo significant differences existed between EDNRA polymorphisms and CBAVD phenotype （rs1801708： P=0.220 2， 0.163 2； rs5335： P=0.805 8， 0.818 6）. However， the rs1801708-rs5335 haplotype AG was notably associated with an increased risk of CBAVD （P=0.008 6， OR=2.178， 95% CI： 1.207-3.929）. A significantly protective effect of rs1801708-rs5335 haplotype GG on CBAVD （P=0.038 5， OR= 0.671， 95% CI： 0.460-0.980） was observed. After Bonferroni correction， the result for haplotype A-G remained significant （P =0.008 6<0.012 5）， while haplotype G-G was not significant. ConclusionThe rs1801708-rs5335 AG haplotype of EDNRA is a potential risk factor for CBAVD development in Han Chinese.

Purpose: The genomic characteristics of uterine sarcomas have not been fully elucidated. This study aimed to explore the genomic landscape of the uterine sarcomas (USs). Materials and Methods: Comprehensive genomic analysis through RNA-sequencing was conducted. Gene fusion, differentially expressed genes (DEGs), signaling pathway enrichment, immune cell infiltration, and prognosis were analyzed. A deep learning model was constructed to predict the survival of US patients. Results: A total of 71 US samples were examined, including 47 endometrial stromal sarcomas (ESS), 18 uterine leiomyosarcomas (uLMS), three adenosarcomas, two carcinosarcomas, and one uterine tumor resembling an ovarian sex-cord tumor. ESS (including high-grade ESS [HGESS] and low-grade ESS [LGESS]) and uLMS showed distinct gene fusion signatures; a novel gene fusion site, MRPS18A–PDC-AS1 could be a potential diagnostic marker for the pathology differential diagnosis of uLMS and ESS; 797 and 477 uterine sarcoma DEGs (uDEGs) were identified in the ESS vs. uLMS and HGESS vs. LGESS groups, respectively. The uDEGs were enriched in multiple pathways. Fifteen genes including LAMB4 were confirmed with prognostic value in USs; immune infiltration analysis revealed the prognositic value of myeloid dendritic cells, plasmacytoid dendritic cells, natural killer cells, macrophage M1, monocytes and hematopoietic stem cells in USs; the deep learning model named Max-Mean Non-Local multi-instance learning (MMN-MIL) showed satisfactory performance in predicting the survival of US patients, with the area under the receiver operating curve curve reached 0.909 and accuracy achieved 0.804. Conclusion USs harbored distinct gene fusion characteristics and gene expression features between HGESS, LGESS, and uLMS. The MMN-MIL model could effectively predict the survival of US patients.

Purpose: The genomic characteristics of uterine sarcomas have not been fully elucidated. This study aimed to explore the genomic landscape of the uterine sarcomas (USs). Materials and Methods: Comprehensive genomic analysis through RNA-sequencing was conducted. Gene fusion, differentially expressed genes (DEGs), signaling pathway enrichment, immune cell infiltration, and prognosis were analyzed. A deep learning model was constructed to predict the survival of US patients. Results: A total of 71 US samples were examined, including 47 endometrial stromal sarcomas (ESS), 18 uterine leiomyosarcomas (uLMS), three adenosarcomas, two carcinosarcomas, and one uterine tumor resembling an ovarian sex-cord tumor. ESS (including high-grade ESS [HGESS] and low-grade ESS [LGESS]) and uLMS showed distinct gene fusion signatures; a novel gene fusion site, MRPS18A–PDC-AS1 could be a potential diagnostic marker for the pathology differential diagnosis of uLMS and ESS; 797 and 477 uterine sarcoma DEGs (uDEGs) were identified in the ESS vs. uLMS and HGESS vs. LGESS groups, respectively. The uDEGs were enriched in multiple pathways. Fifteen genes including LAMB4 were confirmed with prognostic value in USs; immune infiltration analysis revealed the prognositic value of myeloid dendritic cells, plasmacytoid dendritic cells, natural killer cells, macrophage M1, monocytes and hematopoietic stem cells in USs; the deep learning model named Max-Mean Non-Local multi-instance learning (MMN-MIL) showed satisfactory performance in predicting the survival of US patients, with the area under the receiver operating curve curve reached 0.909 and accuracy achieved 0.804. Conclusion USs harbored distinct gene fusion characteristics and gene expression features between HGESS, LGESS, and uLMS. The MMN-MIL model could effectively predict the survival of US patients.

Purpose: The genomic characteristics of uterine sarcomas have not been fully elucidated. This study aimed to explore the genomic landscape of the uterine sarcomas (USs). Materials and Methods: Comprehensive genomic analysis through RNA-sequencing was conducted. Gene fusion, differentially expressed genes (DEGs), signaling pathway enrichment, immune cell infiltration, and prognosis were analyzed. A deep learning model was constructed to predict the survival of US patients. Results: A total of 71 US samples were examined, including 47 endometrial stromal sarcomas (ESS), 18 uterine leiomyosarcomas (uLMS), three adenosarcomas, two carcinosarcomas, and one uterine tumor resembling an ovarian sex-cord tumor. ESS (including high-grade ESS [HGESS] and low-grade ESS [LGESS]) and uLMS showed distinct gene fusion signatures; a novel gene fusion site, MRPS18A–PDC-AS1 could be a potential diagnostic marker for the pathology differential diagnosis of uLMS and ESS; 797 and 477 uterine sarcoma DEGs (uDEGs) were identified in the ESS vs. uLMS and HGESS vs. LGESS groups, respectively. The uDEGs were enriched in multiple pathways. Fifteen genes including LAMB4 were confirmed with prognostic value in USs; immune infiltration analysis revealed the prognositic value of myeloid dendritic cells, plasmacytoid dendritic cells, natural killer cells, macrophage M1, monocytes and hematopoietic stem cells in USs; the deep learning model named Max-Mean Non-Local multi-instance learning (MMN-MIL) showed satisfactory performance in predicting the survival of US patients, with the area under the receiver operating curve curve reached 0.909 and accuracy achieved 0.804. Conclusion USs harbored distinct gene fusion characteristics and gene expression features between HGESS, LGESS, and uLMS. The MMN-MIL model could effectively predict the survival of US patients.

Objective To explore the role and mechanism of warm malate ringer's solution(MR)in resuscitation of the lethal triad caused by severe trauma.Methods A rat model of severe trauma was established in SPF-grade SD rats(half male and half female,weighing 200～220 g)using combined multiple injuries and hemorrhagic shock,and the rats were randomly divided into 8 groups(n=8):Sham group,only arterial and venous catheterization;Trauma(Tra)groups with different time points(10,30,60,90,120,180 min)and a Trauma group that were observed without any treatment for 180 min after model establishment.The changes of activated clotting time(ACT),reaction time(R),maximum amplitude(MA),and rate of blood clot formation(Angle)at different time points were detected by using thromboelastography,and tail bleeding,core body temperature and arterial blood gas parameters,were also observed and detected.The plasma von Willebrand Factor(vWF)level,mitochondrial respiratory control ratio in pulmonary venous endothelium,and expression levels of vascular endothelial cadherin(VE-Cadherin),peroxisome proliferator activating receptor gamma coactivator 1α(PGC1α),dynamin-related protein 1(Drp1),p-Drp1,and mitofusin 2(Mfn2)were detected to evaluate the vascular endothelial injury and mitochondrial dysfunction.Another group of SD rats were randomly divided into severe trauma group(no treatment for 180 min after injury),and MR solution at room temperature and at 37 ℃ groups.MR solution at room temperature or at 37 ℃ was given to the rats using a medical blood transfusion apparatus at 60 min post-trauma.Above indicators were observed and detected to investigate the resuscitation effect of the MR solution.Results Compared with the Sham group,the severely traumatic rats at 180 min after injury had significantly prolonged ACT and R values(P＜0.05),shortened MA and decreased Angle values(P＜0.05),extended tail bleeding time(P＜0.05),lower partial pressure of carbon dioxide(PCO2)and HCO3-and base excess(BE)levels(P＜0.05),and continuously increasing K+(P＜0.05)and decreasing Na+(P＜0.05)and Ca2+levels(P＜0.05).Additionally,plasma vWF level(P＜0.05)and protein levels of VE-cadherin,PGC1α and Mfn2 in pulmonary vein endothelium were significantly reduced(P＜0.05),the expression of p-Drp1 was enhanced and the mitochondrial respiration control rate was declined in the rats at 180 min after injury(P＜0.05).MR solution resuscitation shortened tail bleeding time(P＜0.05),increased core body temperature(P＜0.05),elevated plasma vWF level(P＜0.05),increased protein levels of VE-cadherin,PGC1α and Mfn2(P＜0.05),and decreased that of p-Drp1 protein expression(P＜0.05)when compared with the rats at 180 min after severe traumatic injury.The above effects were more significant in the rats infused with the solution at 37 ℃ than those at room temperature.Conclusion Warm MR solution significantly improves the lethal triad in rats after severe trauma,which may be associated with its improving mitochondrial function and attenuating vascular endothelial damage.

To explore the differences in biological gas production in the waterlogged zone of a coal seam fire-affected area, in this study the in-situ gas production experiment was conducted with the mine water from aquitard layers in coal seam fire zones in Xinjiang. The results showed that the biogas production first increased and then decreased with the increase in distance, and the highest gas production reached 216.55 mL. The changes in key metabolic pathways during the anaerobic fermentation of coal were analyzed, which showed that as the distance from the aquitard layer in the coal seam fire zone increased, the methanogenesis pathways gradually shifted from acetic acid decarboxylation and carbon dioxide reduction to acetic acid decarboxylation and methylamine methanogenesis. The significant variability in the in-situ mine water reservoir conditions contributed to the differences. In addition, the reservoir pressure and temperature increased as the distance from the fire zone became longer, and the salinity of the farthest mine water in the reverse fault was the highest due to the lack of groundwater supply. Pearson correlation analysis revealed significant correlations of microbial communities with key functional genes and the types and concentrations of ions. The ions significantly influencing microbial enzymatic metabolic activities included Al³⁺, Fe²⁺, Co²⁺, Ni²⁺, Cu²⁺, Zn²⁺, Mg²⁺, PO₄^3-, and Mo⁶⁺. The differences in metabolic pathways were attributed to the integrated effects of a co-occurring environment with multiple ions. The gas production simulation experiments and metagenomic analyses provide data support for the practical application of in-situ biogas experiments, laying a foundation for engineering applications.
Biofuels ; Coal ; Methane/biosynthesis* ; Fires ; Groundwater ; Coal Mining ; Fermentation ; China ; Anaerobiosis

Objective To explore the relationship between peripheral blood levels of phosphoryla-ted Tau181(p-Tau181)and β-amyloid(Aβ)42 and microstructure of white matter in elderly pa-tients with different types of dementia.Methods A total of 64 elderly dementia patients admitted to our department between January 2022 and December 2023 were enrolled and according to dif-ferent types of dementia,they were divided into Alzheimer's disease(AD)group(38 cases)and vascular dementia(VaD)group(26 cases).Another 30 healthy individual taking physical examina-tion during the same period were subjected and served as control group.All participants under-went MRI examination and detection of peripheral blood indicators.The cognitive level[mini-mental state examination(MMSE),Montreal cognitive assessment(MoCA)],diffusion tensor imaging parameters in different white matter areas[fractional anisotropy(FA),mean diffusion coefficient(MD)[,and peripheral blood indicators(p-Tau181,Aβ42)were compared among the three groups.Spearman correlation analysis was applied to analyze the relationship between peripheral blood Tau181 and Aβ42 levels and microstructure of white matter in AD group and VaD group.Results The scores of MMSE and MoCA were significantly higher in the control group than the AD group and the VaD group(28.13±0.72 vs 11.25±2.37 and 10.98±2.59,27.84±0.62 vs 10.37±2.64 and 10.58±2.87,P＜0.05).In the VaD group,the MD values of anterior and pos-terior horns of left and right lateral ventricles were obviously greater than the AD group and the control group,while the FA values were notably lower than the two groups(P＜0.05).The levels of p-Tau181 and Aβ42 were remarkably higher in the AD group and the VaD group than the con-trol group,and the level of p-Tau181 was significantly higher and that of Aβ42 was significantly lower in the AD group than the VaD group(P＜0.05).Spearman correlation analysis showed that in the VaD group,the peripheral blood level of p-Tau181 was positively correlated with the FA value and negatively with the MD value of brain white matter,while that of Aβ42 was negatively with the FA value and positively correlated with the MD value of brain white matter(P＜0.01).Conclusion There are significant differences in microstructure damage of white matter and pe-ripheral blood levels of p-Tau181 and Aβ42 among elderly patients with different types of dementi-a,and the levels of the two indicators are correlated with the microstructure damage.Clinically,peripheral blood indicators can be applied to evaluate microstructure damage of white matter.

Objective:To investigate the status of allostatic load (AL) in patients with polycystic ovary syndrome (PCOS) and its influence on the clinical outcomes of in vitro fertilization-embryo transfer.Methods:This was a prospective study. By using convenient sampling method, 421 patients with PCOS (PCOS group) and 372 control infertility patients (control group) in the Reproductive Center of the First Affiliated Hospital of Anhui Medical University from April 2022 to January 2024 were investigated for basic information, physical examination, laboratory examination and follow-up of clinical outcomes. The total score of AL was calculated using 16 related indicators of cardiovascular system, metabolic system and immune system, and AL>3 was used as the judgment criteria for the high level AL group and the low level AL group. The differences in general data, embryo development and clinical outcomes between the groups were compared.Results:There were 222 cases (52.7%, 222/421) in PCOS low level AL group and 199 cases (47.3%, 199/421) in PCOS high level AL group. There were 214 patients (57.5%, 214/372) in the control low level AL group and 158 patients (42.5%, 158/372) in the control high level AL group. Embryo development outcomes: number of oocytes retrieved (median: 12, 12, 19, 14, respectively; P<0.001), number of two pronuclei (median: 8, 7, 11, 8, respectively; P<0.001), number of fertilization (median: 9, 9, 13, 10, respectively; P<0.001), number of metaphase of meiosis Ⅱ oocytes (median: 9, 8, 13, 10, respectively; P<0.001), number of transferable embryos (median: 5, 5, 7, 6, respectively; P<0.001), number of high-quality embryos (median: 4, 3, 6, 5, respectively; P<0.001), gonadotropin(Gn) starting dosage (median: 150, 200, 150, 200 U, respectively; P<0.001), total dosage of Gn (median: 1 800, 2 075, 1 575, 2 025 U, respectively; P<0.001), duration of Gn used (median: 10, 10, 10, 10 days, respectively; P=0.027) in the control low level AL group, control high level AL group, PCOS low level AL group and PCOS high level AL group were significantly different. Pairings between groups showed that number of oocytes retrieved, number of two pronuclei, number of fertilization, number of metaphase of meiosis Ⅱ oocytes and number of transferable embryos in PCOS high level AL group were lower than those in PCOS low level AL group (all P<0.05); Gn starting dosage and total dosage of Gn in PCOS low level AL group were lower than those in the other three groups (all P<0.05); duration of Gn used in PCOS high level AL group was higher than that PCOS low level AL group ( P<0.05). Clinical outcomes: the control low level AL group, control high level AL group, PCOS low level AL group and PCOS high level AL group underwent fresh transplantation [27.4% (57/208), 24.4% (38/156), 15.1% (32/212), 17.1% (33/193), respectively; P=0.006] and the proportion of transplanted day 5 embryos [82.7% (172/208), 77.6% (121/156), 91.0% (193/212), 86.5% (167/193), respectively; P=0.018] were statistically significant. There were no significant differences in fertilization rate, biochemical pregnancy rate, clinical pregnancy rate, multiple pregnancy rate and early abortion rate among the four groups (all P>0.05). Conclusion:The high level of AL in PCOS patients may affect the outcomes of embryo development, and more attention should be paid to AL in PCOS patients to reduce stress.

Objective To investigate the protective effects of remimazolam(Remi),a novel benzodiazepine sedative,on intestinal barrier function in septic mice.Methods A mouse model of sepsis was established using cecal ligation and puncture(CLP).A total of 96 SPF-grade adult male C57BL/6 mice were randomized into sham operation(Sham),sepsis(Sepsis),and sepsis with Remi intervention(Sepsis+Remi)groups.Survival rate and survival time were recorded within 72 h after modeling.Intestinal pathological alterations,barrier functional indicators,ZO-1 expression,and macrophage polarization status were observed and detected to evaluate the effects of Remi.Lipopolysaccharide(LPS)was used to treat RAW264.7 cells for 24 h to simulate in vitro sepsis model.The cells were divided into control(Control),LPS,and LPS+Remi groups.Immunofluorescence staining was performed to assess macrophage phenotype,mitochondrial morphology,and mitochondrial reactive oxygen species(MtROS),and Western blotting was applied to detect the protein expression of iNOS and CD206.Results Compared with the sepsis group,Remi intervention significantly improved the survival rate of septic mice from 12.50%to 68.75%and markedly prolonged survival duration(P<0.05).Histopathological analysis demonstrated partial restoration of intestinal villus architecture,accompanied with attenuated interstitial edema and reduced inflammatory cell infiltration after Remi intervention.Furthermore,the intervention group demonstrated significant improvement in functional indicators.Both in vivo and in vitro experiments demonstrated elevated iNOS and decreased CD206 expression in the septic mice and LPS-stimulated macrophages(P<0.05),which were partially reversed after Remi intervention.Furthermore,LPS-stimulated macrophages exhibited fragmented mitochondria and elevated MtROS level,whereas Remi intervention ameliorated these conditions(P<0.05).Conclusion Remi protects intestinal barrier function in septic mice by mitigating mitochondrial dynamics imbalance-induced oxidative damage and ameliorating inflammatory macrophage activation.

Objective:To explore the clinical characteristics of neonatal necrotizing enterocolitis（NEC）and analyze the risk factors for early-onset NEC.Methods:A total of 220 children with NEC admitted to the Department of Pediatrics，Tianjin Medical University General Hospital from January 1st，2018 to February 29th，2024 were retrospectively selected as the research objects. According to the time of onset，the early-onset group（ n=120）and the late-onset group（ n=100）were established，and the clinical characteristics of the two groups were compared. Another 150 cases of normal healthy newborns born in this hospital in the same period were selected as the control group，and the clinical data of the control group were collected. The clinical characteristics of the early-onset group and the control group were compared，and the risk factors of early-onset NEC were analyzed by multivariate Logistic regression. Results:Compared with the late-onset group，the early-onset group had fever［50.0%（60/120）vs. 40%（40/100）， χ2=7.333， P=0.007］，apnea［39.17%（47/120）vs. 28%（28/100）， χ2=7.568， P=0.006］，no rise in body temperature［56.67%（68/120）vs. 39%（39/100）， χ2=6.815， P=0.009］，abdominal distension［25%（30/120）vs. 40%（40/100）， χ2=13.200， P<0.001］，vomiting［30.83%（37/120）vs. 45%（45/100）， χ2=12.797， P<0.001］was significantly different（all P<0.05）；Multivariate Logistic regression analysis：weight<1 500 g（ OR=5.871，95% CI：3.153～9.673， P<0.001），gestational age<30 weeks（ OR=4.256，95% CI：2.641～7.896， P=0.007），hemodynamically significant patent ductus arteriosus（hs-PDA）（ OR=3.113，95% CI：1.865～5.133， P=0.033），severe anemia（ OR=3.057，95% CI：2.165～4.802， P=0.001），feeding intolerance（ OR=4.215，95% CI：1.579～10.802， P=0.005），amniotic fluid pollution（ OR=2.452，95% CI：1.579～3.111， P<0.001）were the independent risk factors for early-onset NEC（all P<0.05）. Conclusion:Weight<1 500 g，gestational age<30 weeks，hs-PDA，severe anemia，feeding intolerance，and amniotic fluid contamination are independent risk factors for early-onset NEC. In clinical practice，more attention should be paid to these factors for disease prevention，early identification，and timely intervention in newborns to reduce the occurrence of NEC.