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 investigate the expression of peroxiredoxin 4 (PRDX4) in oral squamous cell carcinoma (OSCC) and its effect on the proliferation, migration, and invasion of OSCC cells. Methods: The Cancer Genome Atlas(TCGA) database was used to analyze the expression of PRDX4 in OSCC. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western Blot (WB) were used to detect the mRNA and protein expression of PRDX4 in OSCC cell lines and normal oral mucosal epithelial cells. PRDX4 was knocked down in CAL-27 cells and divided into two groups: the si-PRDX4 group and si-NC group. SCC-9 cells overexpressing PRDX4 were divided into two groups: the PRDX4 overexpression group (transfected with pcDNA3.1-PRDX4 plasmid) and the vector group (the control group; transfected with pcDNA3.1-NC plasmid). A cell counting kit-8 (CCK-8) and plate colony formation assay were used to detect cell proliferation. Transwell assay and cell scratch test were used to detect cell invasion and migration ability. WB was used to detect the effects of knockdown or overexpression of PRDX4, p38MAPK agonist or inhibitor on the expression of p38MAPK-related signaling pathway proteins, and epithelial mesenchymal transition proteins in OSCC cells. Results: PRDX4 was highly expressed in OSCC tissues and cell lines. The results of qRT-PCR and WB showed that PRDX4 was highly expressed in OSCC cell lines compared with normal oral mucosal epithelial cells. The CCK-8 assay showed that the si-PRDX4 group had significantly lower OD values than the si-NC group at 24, 48, and 72 h (P<0.05). The PRDX4 overexpression group had a significantly higher OD value than the vector group at 24, 48, and 72 h (P<0.05). The plate colony formation assay showed that the si-PRDX4 group had a significantly lower number of colonies than the si-NC group (P<0.05). The number of colonies formed in the PRDX4 overexpression group was significantly higher than that in the vector group (P<0.05). The cell scratch test showed that the wound healing area of the si-PRDX4 group was less than that of the si-NC group (P<0.05). The scratch healing area of the PRDX4 overexpression group was significantly higher than that of the vector group (P<0.05). The Transwell invasion assay showed that the number of transmembrane cells in the si-PRDX4 group was lower than that in the si-NC group (P<0.05). The number of transmembrane cells in the PRDX4 overexpression group was significantly higher than that in the vector group (P<0.05). The WB results showed that knockdown and overexpression of PRDX4 could downregulate and upregulate the expression of the p38MAPK signaling pathway and epithelial-mesenchymal transition related proteins, respectively, and the addition of p38MAPK agonist and inhibitor could significantly reverse the expression of related proteins. Conclusion PRDX4 is highly expressed in OSCC. Knocking down the expression of PRDX4 in OSCC cells can downregulate the expression of p38 MAPK signal axis and EMT-related signal proteins, thereby inhibiting the proliferation, migration, invasion, and epithelial-mesenchymal transition of cells.

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 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.

Based on the theory of “manifestation-body and spirit-qi”， it is considered that the pathogenesis of tic disorders （TD） involves three manifestations of “wind， phlegm and fire”， with wind as the leading factor and phlegm and fire as the accompanying factors. It is advocated to identify the abnormality of body and spirit， summarize the evolution of manifestation， and prescribe flexibly based on qi movement of zang-fu organs. Among them， the common symptoms related to tics are mostly belong to wind symptoms， which originated from lung qi failing to purify and liver qi over-ascent. The method of soothing liver wood and purifying lung gold is adopted， and modified Xiaochaihu Decoction （小柴胡汤） and Cangerzi Powder （苍耳子散） are recommended； Patients with prolonged illness and strange symptoms are often mixed with phlegm， which stemmed from the fact that spleen failing to rise clear and stomach failing to downward turbid. The method of raising spleen-earth and lowering stomach-earth is adopted， and modified Yigong Powder （异功散） and Erchen Decoction （二陈汤） are recommended； Patients with severe symptoms are often mixed with fire symptoms， which originated from discordance of water and fire and hyperactivity of heart fire. The method of interacting heart and kidney and coordinating water and fire is adopted， and modified Xiegan Pill （泻肝丸） and Liuwei Dihuang Pill （六味地黄丸） are recommended， in order to regulate qi movement， harmonize body and spirit， and improve the symptoms.

Objective To analyze the clinical risk factors for chronic complications in patients with type 2 diabetes and their correlation with bone mineral density and 1,25-dihydroxyvitamin D3. Methods A total of 163 patients with type 2 diabetes mellitus were selected as research subjects and were divided into complication group and non-complication group according to the presence or absence of chronic complications. The independent related factors for chronic complications in patients with type 2 diabetes mellitus were analyzed. Spearman rank correlation analysis was used to evaluate the correlation between bone mineral density, 1,25-dihydroxyvitamin D3 and chronic complications. Results Among the 326 patients with type 2 diabetes mellitus, 202 developed chronic complications (61.96%), including 71 cases of cardiovascular disease, 59 cases of neuropathy, 33 cases of renal lesion, and 28 cases of retinopathy. There were statistically significant differences in the duration of diabetes mellitus, fasting blood glucose, systolic blood pressure, glycosylated hemoglobin, triglyceride, low density lipoprotein cholesterol, serum creatinine, bone mineral density, and 1,25-dihydroxyvitamin D3 between the complication group and the non-complication group (P<0.05). Logistic multivariate regression analysis showed that the duration of diabetes mellitus, systolic blood pressure, glycosylated hemoglobin, ow density lipoprotein cholesterol, serum creatinine, bone mineral density, and 1,25-dihydroxyvitamin D3 were all independent related factors for the occurrence of chronic complications in patients with type 2 diabetes mellitus (P<0.05). Spearman correlation analysis showed that bone mineral density and 1,25-dihydroxyvitamin D3 were negatively correlated with chronic complications (P<0.05). Conclusion Bone mineral density and 1,25-dihydroxyvitamin D3 in patients with type 2 diabetes mellitus are closely related to chronic complications.

BACKGROUND:In vitro fertilization-embryo transfer is commonly used to solve infertility,but its success rate is not high,the more common reasons are poor endometrial receptivity,poor egg quality,etc.The follicular fluid melatonin can inhibit the aging of the ovary,to a certain extent,can promote the development of embryos,improve the probability of conception,but whether there is a correlation between the two is not known. OBJECTIVE:To explore the correlation between follicular fluid melatonin level and pregnancy rate of single-cycle in vitro fertilization-embryo transfer women. METHODS:A total of 112 female patients who received in vitro fertilization-embryo transfer treatment in the First Affiliated Hospital of Anhui Medical University from December 2020 to April 2021 were selected as the study subjects.They were divided into quartile array(Q1-Q5)according to the follicular fluid melatonin level from low to high.Among them,the melatonin level of group Q1 was<6.99 ng/L(n=18),that of group Q2 was 7.00-9.99 ng/L(n=26),that of group Q3 was 10.00-11.99 ng/L(n=27),and that of group Q4 was 12.00-13.99 ng/L(n=18);and melatonin levels in group Q5 were 14.00-19.99 ng/L(n=23).Clinical data characteristics of the five groups were compared.Multi-factor Logistic regression was used to analyze the correlation between follicular fluid melatonin level and pregnancy rate of women with single-cycle in vitro fertilization-embryo transfer and embryo transfer.A restricted cubic spline Logistic regression model was established to analyze the dose-response relationship,and the model was evaluated by clinical decision curve. RESULTS AND CONCLUSION:(1)Compared with the study population with the lowest melatonin quintile(Q1),with the increase of melatonin level(Q2-Q5),the levels of egg harvest and pregnancy success were gradually increased,and the body mass index was gradually decreased,and the differences were significant(P<0.05).(2)Multivariate Logistic regression analysis showed that after adjusting for confounding factors such as global mass index,number of eggs retrieved,luteinizing hormone,estradiol,progesterone and other confounding factors,follicular fluid melatonin level was still independently correlated with pregnancy rate of single-cycle in vitro fertilization-embryo transfer women(OR=1.538,95%CI:1.032-1.837,P<0.05),and there was significant difference in trend test of follicular fluid melatonin level from low to high quintile array(Ptrend<0.05).(3)The sensitivity test analysis showed that E value was 2.117.Subgroup analysis showed that the study population with higher levels of luteinizing hormone in follicular fluid had a more significant association between follicular fluid melatonin and pregnancy rate in single-cycle in vitro fertilization-embryo transfer women(P interaction=0.008).(4)The results of restricted cubic spline model analysis showed that there was a nonlinear dose-response relationship between follicular fluid melatonin level and pregnancy rate of single-cycle in vitro fertilization-embryo transfer women(P<0.05),and there was an overall positive correlation between follicular fluid melatonin level and pregnancy rate of single-cycle in vitro fertilization-embryo transfer women.(5)The results of clinical decision curve analysis showed that the follicular fluid melatonin level had important clinical value in predicting the pregnancy rate of single-cycle in vitro fertilization-embryo transfer women.(6)Follicular fluid melatonin level is closely related to the pregnancy rate of single-cycle in vitro fertilization-embryo transfer women,and with the decrease of follicular fluid melatonin level,the pregnancy rate of single-cycle in vitro fertilization-embryo transfer women also decreases.

Objective To investigate the factors influencing the pregnancy outcomes during frozen-thawed embryo transfer(FET)cycles in patients with polycystic ovary syndrome(PCOS).Methods A retrospective analysis was conducted on patients'data from 882 FET cycles.According to the pregnancy outcome,the patients were divided into non-implantation group(Group A),abortion group(Group B1)and live birth group(Group B2).Clinical data and laboratory parameters were compared among the three groups,and ordered Logistic regression analysis was used to study the factors influencing pregnancy outcomes after FET.Patients were also divided into four groups(C1-C4)based on the number of high-quality embryos obtained(0-3,4-6,7-10,≥11),and their clinical data and laboratory parameters were compared.Results The clinical pregnancy rate,live birth rate,and miscar-riage rate in the 882 treatment cycles were 71.09%(627/882),61.68%(544/882),and 13.24%(83/627),respectively.Single-factor analysis showed significant differences in body mass index(BMI),infertility type,hu-man chorionic gonadotropin(hCG)day estradiol(E2)level,number of retrieved oocytes,and number of high-quality embryos among Groups A,B1,and B2(P<0.05).Further multiple Logistic regression analysis revealed that BMI(OR=1.046,95%CI:1.001-1.093,P=0.044)and a history of previous pregnancy(OR=1.417,95%CI:1.030-1.950,P=0.032)were independent risk factors for successful FET in PCOS patients,while an in-creased number of high-quality embryos was an independent protective factor for successful pregnancy.Based on the results of Group B2,compared to Group A,OR=0.920,95%CI:0.880-0.962,P=0.000;compared to Group B1,OR=0.923,95%CI:0.862-0.988,P=0.022.Compared with the other three groups(C1-C3),the total amount of gonadotropin(Gn)in the C4 group was the lowest and the number of oocytes obtained was the high-est(P<0.05).Multiple comparisons showed that Group C4 had lower BMI,follicle-stimulating hormone(FSH),very low-density lipoprotein(vLDL)levels,a higher luteinizing hormone and follicle-stimulating hormone(LH/FSH)ratio compared to Group C1(P<0.05).Group C4 had lower fasting insulin(FINS)and homeostasis model assessment of insulin resistance(HOMA-IR)levels compared to Group C3,and higher high-density lipoprotein-cholesterol(HDL-C)and apolipoprotein A1(Apo A1)levels compared to Groups C2 and C3(P<0.05).Con-clusion BMI,the history of previous pregnancy and the number of high-quality embryos were both independent factors for predicting pregnancy outcomes in PCOS patients undergoing FET cycles.Patients with a higher number of high-quality embryos have a higher clinical pregnancy rate during FET cycles.