Objective To investigate the effect of evodiamine on renal fibrosis in rats with chronic renal failure(CRF)by regulating sphingosine kinase 1(SphK1)/S1P signaling pathway.Methods CRF rat model was established by feeding 0.5％adenine diet.The rats after modeling were randomly divided into model group,evodiamine low-and high-dose groups,Niaoduqing Granules group and evodiamine high-dose+K6PC-5(SphK1 activator)group.At the end of intervention,the levels of 24-hour urinary protein(24 h-UTP),serum urea nitrogen(BUN)and serum creatinine(SCr)were detected.The levels of monocyte chemoattractant protein 1(MCP-1)and interleukin 6(IL-6)in serum of rats were detected by enzyme-linked immunosorbent assay(ELISA).The pathological changes of renal tissue and collagen volume fraction(CVF)were observed by hematoxylin-eosin(HE)and Masson staining.The mRNA expressions of transforming growth factor β1(TGF-β1)and type Ⅳcollagen(COL-Ⅳ)in renal tissue were detected by real-time quantitative polymerase chain reaction(qRT-PCR).The protein expressions of SphK1 and S1P in renal tissue were detected by Western Blot.Results Compared with the normal group,the model group showed obvious inflammatory infiltration and collagen fiber deposition,the number of glomeruli decreased in renal tissue,and the expression levels of SCr,BUN,24h-UTP,IL-6,MCP-1,CVF,mRNA expressions of TGF-β1 and COL-Ⅳ,protein expessions of SphK1 and S1P were significantly increased(P＜0.05).Compared with the model group,the histopathological changes of the low-dose and high-dose evodiamine groups and the Niaoduqing Granules group was improved,and the expression levels of SCr,BUN,24 h-UTP,IL-6,MCP-1,CVF,mRNA expressions of TGF-β1 and COL-Ⅳ,protein expessions of SphK1 and S1P were significantly decreased.For intergroup comparison of each index,there were differences between the low-dose evodiamine group and the high-dose evodiamine group(P＜0.05),but there was no significant difference between the high-dose evodiamine group and the Niaoduqing Granules group(P＞0.05).Compared with the high-dose evodiamine group,the histopathological changes of the high-dose evodiamine+K6PC-5 group was further aggravated,and the improvement effect of all indexes were reversed(P＜0.05).Conclusion Evodiamine improves renal fibrosis in CRF rats by inhibiting SphK1/S1P signaling pathway.

Objective:To evaluate the efficacy of visualized precise lung expansion for determining the intersegmental plane in thoracoscopic segmentectomy.Methods:Sixty-four American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ patients, regardless of gender, aged 33-77 yr, with body mass index of 16-34 kg/m 2, undergoing elective thoracoscopic segmentectomy under general anesthesia, were included. They were preoperatively reconstructed with 3D CT bronchovascularization to reconstruct the pulmonary vasculature, bronchus, and the virtual intersegmental planes of the lungs. The patients were divided into 2 groups ( n=32 each) using a random number table method: visualized precise lung expansion group (group V) and modified expansion and atrophy group (group E). Group V used visualized precision lung expansion to determine the intersegmental planes, and group E used the modified expansion and atrophy method to determine the intersegmental planes. The intraoperative intersegmental plane determination time, target segmental bronchus identification and treatment time, anesthesia time, operation time, postoperative air leakage, pulmonary atelectasis, fever, occurrence of lung infection, postoperative 24 h drainage volume, drain removal time and hospitalization time were recorded in the two groups. Results:Compared with group E, the intersegmental plane determination time, target segment bronchial identification and treatment time, anesthesia time and operation time were significantly shortened in group V( P<0.05).There were no significant differences between groups in the 24 h postoperative drainage volume, drain removal time, hospitalization time or incidence of postoperative pulmonary complications ( P>0.05). Conclusions:Compared with the modified expansion and atrophy method, visualized precise lung expansion can effectively shorten the intersegmental plane determination time in thoracoscopic segmentectomy.

DMRT, a gene family related to sexual determination, encodes a large group of transcription factors (DMRTs) with the double-sex and mab-3 (DM) domain (except for DMRT8), which is able to bind to and regulate DNAs. Current studies have shown that the DMRT gene family plays a critical role in the development of sexual organs (such as gender differentiation, gonadal development, germ cell development, etc.) as well as extrasexual organs (such as musculocartilage development, nervous system development, etc.). Additionally, it has been suggested that DMRTs may be involved in the cancer development and progression (such as prostate cancer, breast cancer, lung cancer, etc.). This review summarizes the research progress about the mammalian DMRTs' structure, function and its critical role in cancer development, progression and therapy (mainly in human and mice), which suggests that DMRT gene could be a candidate gene in the study of tumor formation and therapeutic strategy.
Male ; Animals ; Humans ; Mice ; Transcription Factors/genetics* ; Mammals/metabolism* ; Cell Differentiation ; Neoplasms/genetics*

Bone defects caused by different causes such as trauma, severe bone infection and other factors are common in clinic and difficult to treat. Usually, bone substitutes are required for repair. Current bone grafting materials used clinically include autologous bones, allogeneic bones, xenografts, and synthetic materials, etc. Other than autologous bones, the major hurdles of rest bone grafts have various degrees of poor biological activity and lack of active ingredients to provide osteogenic impetus. Bone marrow contains various components such as stem cells and bioactive factors, which are contributive to osteogenesis. In response, the technique of bone marrow enrichment, based on the efficient utilization of components within bone marrow, has been risen, aiming to extract osteogenic cells and factors from bone marrow of patients and incorporate them into 3D scaffolds for fabricating bone grafts with high osteoinductivity. However, the scientific guidance and application specification are lacked with regard to the clinical scope, approach, safety and effectiveness. In this context, under the organization of Chinese Orthopedic Association, the Expert consensus for the clinical application of autologous bone marrow enrichment technique for bone repair ( version 2023) is formulated based on the evidence-based medicine. The consensus covers the topics of the characteristics, range of application, safety and application notes of the technique of autologous bone marrow enrichment and proposes corresponding recommendations, hoping to provide better guidance for clinical practice of the technique.

OBJECTIVES: To survey the development status and actual needs of virtual autopsy technology in China and to clarify the applicability of forensic virtual autopsy laboratory accreditation. METHODS: The questionnaire was set up included three aspects：(1) the current status of virtual autopsy technology development; (2) the accreditation elements such as personnel, equipment, entrustment and acceptance, methods, environmental facilities; (3) the needs and suggestions of practicing institutions. A total of 130 forensic pathology institutions were surveyed by online participation through the Questionnaire Star platform. RESULTS: Among the 130 institutions, 43.08% were familiar with the characteristics of virtual autopsy technology, 35.38% conducted or received training in virtual autopsy, and 70.77% have establishment needs (including maintenance). Relevant elements were suitable for laboratory accreditation. CONCLUSIONS Virtual autopsy identification has gained social recognition. There is a demand for accreditation of forensic virtual autopsy laboratory. After the preliminary assessment, considering the characteristics and current situation of this technology, China National Accreditation Service for Conformity Assessment (CNAS) can first carry out the accreditation pilot of virtual autopsy project at large comprehensive forensic institutions with higher identification capability, and then CNAS can popularize the accreditation in a wide range when the conditions are suitable.
Autopsy ; Forensic Medicine ; Forensic Pathology ; Accreditation ; Surveys and Questionnaires

Objective: To investigate the clinicopathological characteristics, immunophenotype, and molecular signatures of oncocytic papillary renal cell carcinoma (OPRCC), and to compare these findings with those in type 1 papillary renal cell carcinoma (PRCC 1). Methods: The clinicopathologic data of 19 patients with OPRCC from the Affiliated Hospital of Qingdao University (16 patients) and the 971 Hospital of People's Liberation Army Navy (3 patients) from October 2003 to February 2021 were collected. Histologic, immunohistochemical (IHC) and molecular analyses, together with a control group of 15 cases of PRCC I diagnosed in the same period, were assessed. Results: The cohort included 15 males and 4 females, with a median age of 61 years (range, 47-78 years). In 13 patients the tumors were found at physical examination; four presented with painless gross hematuria and two with low back pain. As for the pathologic stage, 14 patients were pT1, one patient was pT2a, three patients were pT3a and one patient was pT4. The tumor size ranged from 1.7-14.0 cm, with clear boundary and soft texture. The cut surface was grayish-yellow and grayish-red. Microscopically, the tumor cells were mainly arranged in papillary (10%-100%) and acinar (tubular) patterns, with strongly eosinophilic cytoplasm, round or irregular nuclei, and prominent nucleoli (WHO/ISUP grade Ⅲ). Two cases showed sarcomatoid differentiation. Stromal foamy macrophages were visible in all cases. IHC staining showed diffuse strong positivity for AMACR in all cases. RCC (18/19), CD10 (17/19), vimentin (16/19) and PAX8 (17/19) were positive in most tumors. CK7 was expressed in about 50% of cases. Fluorescence in situ hybridization identified trisomy 7 in eight patients, trisomy 17 in seven patients, and the two aberrations occurred simultaneously in seven cases. Eight of 13 men had Y chromosome deletion. All patients were followed up for 8-120 months. Three patients died of metastases at 8, 62 and 82 months postoperatively, respectively, and one patient relapsed 36 months after surgery. Compared with PRCC1, OPRCC tended to have higher nuclear grade, and stromal foam cell aggregation was more commonly found (P<0.05). The expression of CD10 and EMA were different (P<0.01). There was no significant difference in the survival rate between the two groups (P=0.239). Conclusions: OPRCC has unique morphologic features, and its immunophenotype overlaps but differs from PRCC1. The molecular results support that it belongs to a morphologic variation of PRCC. This tumor has similar biologic behavior to PRCC1, and has a poor prognosis when sarcomatoid differentiation occurs.
Aged ; Biological Products ; Biomarkers, Tumor/analysis* ; Carcinoma, Renal Cell/genetics* ; Female ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Kidney Neoplasms/genetics* ; Male ; Middle Aged ; Neprilysin/analysis* ; Vimentin/analysis*

Objective: To explore the value of a two-stitch continuous suture in single- lumen ileostomy. Methods: This was a retrospective cohort study. Data for 98 patients who underwent single-lumen enterostomy were retrospectively collected between 1 January 2021 and 1 May 2022 at Zhujiang Hospital of Southern Medical University. All patients met the indications for prophylactic single-lumen ileostomy. Those older than 80 years of age, with complex underlying diseases, extremely poor systemic conditions who could not tolerate surgery, poor blood supply at the end of the bowel, and severe edema or severe infection at the end of the bowel were excluded. Among the included patients, patients who underwent surgery before 1 October 2021 underwent ileostomy with interrupted suture (control group, n=60), and patients operated on and after 1 October 2021 routinely underwent two-stitch continuous suture ileostomy (two-stitch stoma group, n=38). Two-stitch continuous suture ileostomy is performed as follows: the first continuous suture is used to suture the intestinal seromuscular layer, peritoneum, posterior sheath, and anterior sheath from deep to superficial layers. The bowel wall is then opened. The second continuous suture is used to suture the full thickness of the bowel and the skin. The differences in postoperative ostomy-related complications and operation time were compared between the groups. Results: There were no significant differences in baseline data between the groups (all, P>0.05). The operative time in the two-stitch stoma group was shorter than that of the control group (16.6±2.2 minutes vs. 25.1±2.4 minutes, respectively; t=-17.874;P<0.001). The incidences of mucocutaneous separation, dermatitis, and stoma rebound in the two-stitch stoma group were lower than those of the control group [5.3% (2/38) vs. 31.7% (19/60), χ²=9.633, P=0.002;5.3% (2/38) vs. 28.3% (17/60), χ²=7.923, P=0.005; and 2.6% (1/38) vs. 18.3% (11/60), P=0.026, respectively], while the incidences of parastomal hernia and stoma prolapse, and the postoperative visual analog scale scores in the two groups were similar (all P>0.05). Conclusion: Compared with traditional single-lumen ileostomy, two-stitch continuous suture ileostomy has the advantages of short operation time, simplicity, esthetic appearance of the stoma, and a significant reduction in the postoperative complications associated with ileostomy.
Humans ; Ileostomy/adverse effects* ; Retrospective Studies ; Suture Techniques/adverse effects* ; Surgical Stomas ; Sutures/adverse effects* ; Postoperative Complications/epidemiology*

Objective: To explore the association between weight gain during the first half of pregnancy and the risk of hypertension disorder of pregnancy (HDP). Methods: This prospective cohort study recruited singleton pregnant women in the first trimester from November 2016 to March 2019 at 19 community hospitals in Tianjin. According to pre-pregnancy body mass index (BMI), the cohort was divided into 3 groups: underweight(BMI<18.5 kg/m²), normal-weight(18.5-24.9 kg/m²), and overweight/obese(≥25.0 kg/m²). The basic information of the participants was gathered through questionnaires, and the height, weight, and blood pressure of the participants were measured along with routine pregnancy examinations. The rate of gestational weight gain (rGWG) in the 3 periods (0-13⁺⁶, 14⁺⁰-20⁺⁶, and 0-20⁺⁶ weeks) of the participants was calculated. To observe the occurrence of HDP, the participants were followed up to 42 days postpartum. Using a generalized linear model, the association between rGWG at the 3 periods during the first half of pregnancy and HDP after 20 weeks of gestation was evaluated. Results: A total of 9 805 pregnant women were finally included, with the age of (30.6±3.8) years old, 9 418 (96.1%) Han ethnicity, and 6 845 (69.8%) primipara. There were 1 184 (12.1%), 6 831 (69.7%) and 1 790 (18.3%) participants in the underweight, normal-weight, and overweight/obese groups. Five hundreds and eight pregnant women were diagnosed with HDP (5.2%). The incidences of HDP were 1.8% (21/1 184), 3.9% (269/6 831), and 12.2% (218/1 790), respectively, in underweight, normal-weight, and overweight/obese groups. Adjusted for age, pre-pregnancy BMI, primipara, and family history of hypertension, women in the entire cohort with rGWG ≥ 0.18 kg/week before 13⁺⁶ weeks of pregnancy had a 28% higher HDP risk than those with rGWG ≤ 0.00 kg/week (RR=1.28, 95%CI 1.04-1.55, P=0.015), and the risk of HDP was increased by 39% in the overweight/obese group (RR=1.39, 95%CI 1.04-1.85, P=0.026), while no correlation was found between rGWG and HDP in underweight and normal-weight pregnant women (P>0.05). Weight gain during 14⁺⁰-20⁺⁶ weeks of pregnancy in any group was not related to the risk of HDP (P>0.05).In the entire cohort, compared to rGWG ≤0.14 kg/week, rGWG≥0.28 kg/week prior to 20⁺⁶ weeks increased HDP risk by 36% (RR=1.36, 95%CI 1.11-1.67, P=0.003). Normal-weight pregnant women with rGWG≥0.29 kg/week faced a 46% higher risk of HDP than those with rGWG≤0.15 kg/week (RR=1.46, 95%CI 1.11-1.93, P=0.008).In the overweight/obese group, excessive weight gain before 20⁺⁶ weeks seemed to increased risk of HDP, but the difference was not statistically significant (RR=1.35,95%CI 0.99-1.85, P=0.059), while the connection was nonexistent in underweight women. Conclusions: Except for pre-pregnancy underweight women, excessive weight gain during the first half of pregnancy is associated with increased risk of HDP among pregnant women.
Female ; Pregnancy ; Humans ; Infant, Newborn ; Adult ; Overweight/complications* ; Thinness/epidemiology* ; Prospective Studies ; Risk Factors ; Weight Gain ; Body Mass Index ; Obesity/complications* ; Hypertension, Pregnancy-Induced/etiology* ; Cohort Studies ; Pregnancy Complications

For a long time, the cultivation of medical students’ scientific research and innovation abilitymainly depends on scattered extracurricular scientific research activities. With limited students, unsystematic teaching and inadequate administrative guarantee, it often results in obvious weakness andinefficiency. Since 2002, the Biochemistry and Molecular Biology teaching team in Shantou UniversityMedical College has been working on a “3+X” model to nurture the scientific research and innovationability of medical students. Guided by the concepts of complementary development of science andeducation, student-centeredness, and Problem-based Learning, a model is established based on the‘HEART” professionalism courses and the academy culture specific to Shantou University. We also takefull advantage of the first-tier disciplines of biology, basic medicine and clinical medicine in ShantouUniversity and collaborate with other professional teaching teams. It is conceptualized in a framework thatembraces the comprehensive connotation of scientific research and innovation ability and adopts a corecurriculum system that runs through the 5-year medical undergraduate education. In this model, " 3" means " whole-person training", " whole-process training" and " omni-directional training" for medicalstudents; " X" refers to several confirmatory dimensions of the operational effectiveness of the " 3+X" model, including organizing medical students to participate in various forms of national college students’ innovative experimental research competitions, international college students’ academic seminars, writingand publishing academic papers by medical undergraduates as the first author, etc. The model proves tobe effective in cultivating the scientific research and innovation ability of medical students, hence settinga good example to solve the current problems in the cultivation of medical students’ scientific researchand innovation ability.

Alternative polyadenylation(APA)is a crucial step in post-transcriptional regulation.Previous bioinformatic studies have mainly focused on the recognition of polyadenylation sites(PASs)in a given genomic sequence,which is a binary classification problem.Recently,computa-tional methods for predicting the usage level of alternative PASs in the same gene have been pro-posed.However,all of them cast the problem as a non-quantitative pairwise comparison task and do not take the competition among multiple PASs into account.To address this,here we propose a deep learning architecture,Deep Regulatory Code and Tools for Alternative Polyadenylation(DeeReCT-APA),to quantitatively predict the usage of all alternative PASs of a given gene.To accommodate different genes with potentially different numbers of PASs,DeeReCT-APA treats the problem as a regression task with a variable-length target.Based on a convolutional neural network-long short-term memory(CNN-LSTM)architecture,DeeReCT-APA extracts sequence features with CNN layers,uses bidirectional LSTM to explicitly model the interactions among com-peting PASs,and outputs percentage scores representing the usage levels of all PASs of a gene.In addition to the fact that only our method can quantitatively predict the usage of all the PASs within a gene,we show that our method consistently outperforms other existing methods on three different tasks for which they are trained:pairwise comparison task,highest usage prediction task,and rank-ing task.Finally,we demonstrate that our method can be used to predict the effect of genetic variations on APA patterns and sheds light on future mechanistic understanding in APA regulation.