Reproductive system diseases are among the primary contributors to the decline in social fertility rates and the intensification of aging, posing significant threats to both physical and mental health, as well as quality of life. Recent research has revealed the substantial potential of the gut microbiota in improving reproductive system diseases. Under healthy conditions, the gut microbiota maintains a dynamic balance, whereas dysfunction can trigger immune-inflammatory responses, metabolic disorders, and other issues, subsequently leading to reproductive system diseases through the gut-gonadal axis. Reproductive diseases, in turn, can exacerbate gut microbiota imbalance. This article reviews the impact of the gut microbiota and its metabolites on both male and female reproductive systems, analyzing changes in typical gut microorganisms and their metabolites related to reproductive function. The composition, diversity, and metabolites of gut bacteria, such as Bacteroides, Prevotella, and Firmicutes, including short-chain fatty acids, 5-hydroxytryptamine, γ-aminobutyric acid, and bile acids, are closely linked to reproductive function. As reproductive diseases develop, intestinal immune function typically undergoes changes, and the expression levels of immune-related factors, such as Toll-like receptors and inflammatory cytokines (including IL-6, TNF-α, and TGF-β), also vary. The gut microbiota and its metabolites influence reproductive hormones such as estrogen, luteinizing hormone, and testosterone, thereby affecting folliculogenesis and spermatogenesis. Additionally, the metabolism and absorption of vitamins can also impact spermatogenesis through the gut-testis axis. As the relationship between the gut microbiota and reproductive diseases becomes clearer, targeted regulation of the gut microbiota can be employed to address reproductive system issues in both humans and animals. This article discusses the regulation of the gut microbiota and intestinal immune function through microecological preparations, fecal microbiota transplantation, and drug therapy to treat reproductive diseases. Microbial preparations and drug therapy can help maintain the intestinal barrier and reduce chronic inflammation. Fecal microbiota transplantation involves transferring feces from healthy individuals into the recipient’s intestine, enhancing mucosal integrity and increasing microbial diversity. This article also delves into the underlying mechanisms by which the gut microbiota influences reproductive capacity through the gut-gonadal axis and explores the latest research in diagnosing and treating reproductive diseases using gut microbiota. The goal is to restore reproductive capacity by targeting the regulation of the gut microbiota. While the gut microbiota holds promise as a therapeutic target for reproductive diseases, several challenges remain. First, research on the association between gut microbiota and reproductive diseases is insufficient to establish a clear causal relationship, which is essential for proposing effective therapeutic methods targeting the gut microbiota. Second, although gut microbiota metabolites can influence lipid, glucose, and hormone synthesis and metabolism via various signaling pathways—thereby indirectly affecting ovarian and testicular function—more in-depth research is required to understand the direct effects of these metabolites on germ cells or granulosa cells. Lastly, the specific efficacy of gut microbiota in treating reproductive diseases is influenced by multiple factors, necessitating further mechanistic research and clinical studies to validate and optimize treatment regimens.

Objective To investigate the effect of Qingyi Decoction enema on the toll-like recep-tor(TLR)4/nuclear factor(NF)-κB signaling pathway in patients with acute pancreatitis(AP).Methods A total of 100 patients with mild AP were selected as the study objects,and randomly di-vided into control group(n=50)and observation group(n=50).The control group received con-ventional western medicine therapy combined with ulinastatin,while the observation group was treated with Qingyi Decoction retention enema on the basis of control group.Clinical efficacy,symptom re-lief,traditional Chinese medicine syndrome scores,pancreatic function indicators,inflammatory mark-ers as well as TLR4 mRNA and NF-κB mRNA expression levels were compared between the two groups.Results The clinical effective rate in the observation group was 92.00％which was significantly higher than 76.00％in the control group(P＜0.05).The observation group had significantly shorter times for abdominal distension pain relief,first bowel movement,recovery of bowel sounds and normalization of amylase(AMS)levels compared to the control group(P＜0.05).After 10 days of treatment,both groups showed significantly lower scores for abdominal pain,tenderness,fullness,dryness,nausea,vomiting and short red urine syndrome compared to before treatment,with the observation group showing significantly lower scores than the control group(P＜0.05).After 10 days of treat-ment,serum AMS and lipase(LPS)levels were significantly lower in both groups compared to be-fore treatment,with the observation group showing significantly lower levels than the control group(P＜0.05).After 10 days of treatment,serum tumor necrosis factor(TNF)-α,triggering receptor expressed on myeloid cells(TREM)-1,microtubule-associated protein 1 light chain 3(MAP1-LC3)and intercellular adhesion molecule(ICAM)-1 levels were significantly lower in both groups com-pared to before treatment,with the observation group showing significantly lower levels than the con-trol group(P＜0.05).After 10 days of treatment,TLR4 mRNA and NF-κB mRNA expression lev-els were significantly lower in both groups compared to before treatment,with the observation group showing significantly lower levels than the control group(P＜0.05).Conclusion Qingyi Decoc-tion can effectively improve the clinical symptoms of AP patients such as abdominal pain andabdomi-nal distension,inhibit inflammatory response,and promote the recovery of pancreatic function,which may be related to the inhibition of TLR4/NF-κB signaling pathway.

Objective To construct and evaluate the rat model of thyroid nodule liver-qi depression syndrome with the combination of disease and syndrome,so as to lay a foundation for the exploration of the mechanism and clinical research of traditional Chinese medicine in the treatment of thyroid nodule.Methods 36 rats were randomly divided into three groups.The model was induced by chronic unpredictable mild stress(CUMS)stimulation combined with propylthiouracil(PTU).The rats in the blank group were fed with saline at the dose of 1 mL·100 g-1·d-1,and the rats in the PTU group were fed with 0.1%PTU solution at the dose of 1 mL·100 g-1·d-1.The rats in the CUMS+PTU group were fed with CUMS stimulation in a single cage and intragastric administration of 0.1%PTU solution according to the dose of 1 mL·100 g-1·d-1,and the modeling time lasted for 6 weeks.After the establishment of the model,the model of combination of disease and syndrome was evaluated comprehensively by means of animal behavior detection,ultrasonic image,apparent morphology observation,pathological staining and serum hormone index detection.Results Compared with control group and PTU group,the total distance in the open field was significantly shortened,the sucrose preference rate was significantly decreased,and the swimming suspension time was significantly prolonged in the CUMS+PTU group,showing obvious symptoms of liver qi stagnation.In addition,compared with the other two groups,the thyroid gland of CUMS+PTU group showed obvious enlargement and nodule formation,thyroid index significantly increased,and thyroid follicular epithelial cells showed a high phase of proliferation.In terms of hormone levels,compared with control group,the serum levels of free triiodothyronine(FT3)and free thyroxine(FT4)in CUMS+PTU group were significantly lower,while the level of thyroid stimulating hormone(TSH)was significantly higher,which was in line with the current evaluation criteria of thyroid nodule model.Conclusion The method of CUMS stimulation combined with PTU drug induction can successfully prepare the rat model of thyroid nodule liver-qi depression syndrome,and the comprehensive evaluation method is stable and reliable,which is helpful to improve the scientific nature of the disease-syndrome combination model.

Based on the teaching concept of constructivism, this study aims to promote independent inquiry-based learning and clinical thinking among students and establish the guiding ideology of "full participation, process control, in-depth discussion, and expansion of thinking". A blending learning model was adopted with offline inquiry-based group learning and in-class defense and comment, as well as online teacher-student interaction and supervision to promote learning. Case-problem-based learning (CPBL) of pathophysiology was carried out among the medical students in the class of 2017, and process management was strengthened to effectively manage the two key links of data retrieval and group discussion. The analysis of 176 teaching evaluations collected at the end of the semester show that in terms of the overall evaluation of CPBL teaching, 162 students (92.05%) had high evaluation on teaching objectives, organization, cases, and personal gains and held a very or relatively favorable attitude. There were more negative feedbacks on "appropriate time allocation"; 21 students (11.93%) held a relatively or very disapproving attitude, and 149 students (84.66%) "felt very tired". In terms of teaching effect evaluation, 150 students (85.23%) strongly or relatively agreed that CPBL teaching may help to understand professional knowledge, stimulate learning enthusiasm and initiative, improve problem solving ability, emphasize clinical practice to cultivate clinical thinking, supervise and promote learning, and enhance team cooperation and teacher-student communication. In terms of the evaluation of teachers, 167 students (94.89%) thought that teachers were rigorous, responsible, and enthusiastic in teaching, attached importance to process management, and did well in effective guidance and thinking inspiration (strongly or relatively agree). The above results suggest that the CPBL teaching reform of pathophysiology based on process management can effectively promote in-depth inquiry-based independent learning and the cultivation of clinical thinking and improve teaching effectiveness, but further improvement is needed for teaching arrangement and time allocation.

The characteristic genetic abnormality of neuroendocrine neoplasms (NENs), a heterogeneous group of tumors found in various organs, remains to be identified. Here, based on the analysis of the splicing variants of an oncogene Focal Adhesion Kinase (FAK) in The Cancer Genome Atlas datasets that contain 9193 patients of 33 cancer subtypes, we found that Box 6/Box 7-containing FAK variants (FAK^6/7) were observed in 7 (87.5%) of 8 pancreatic neuroendocrine carcinomas and 20 (11.76%) of 170 pancreatic ductal adenocarcinomas (PDACs). We tested FAK variants in 157 tumor samples collected from Chinese patients with pancreatic tumors, and found that FAK^6/7 was positive in 34 (75.6%) of 45 pancreatic NENs, 19 (47.5%) of 40 pancreatic solid pseudopapillary neoplasms, and 2 (2.9%) of 69 PDACs. We further tested FAK splicing variants in breast neuroendocrine carcinoma (BrNECs), and found that FAK^6/7 was positive in 14 (93.3%) of 15 BrNECs but 0 in 23 non-NEC breast cancers. We explored the underlying mechanisms and found that a splicing factor serine/arginine repetitive matrix protein 4 (SRRM4) was overexpressed in FAK^6/7-positive pancreatic tumors and breast tumors, which promoted the formation of FAK^6/7 in cells. These results suggested that FAK^6/7 could be a biomarker of NENs and represent a potential therapeutic target for these orphan diseases.
Female ; Humans ; Alternative Splicing ; Breast Neoplasms/metabolism* ; Carcinoma, Pancreatic Ductal/pathology* ; Focal Adhesion Protein-Tyrosine Kinases/therapeutic use* ; Nerve Tissue Proteins/genetics* ; Neuroendocrine Tumors/genetics* ; Oncogenes ; Pancreatic Neoplasms/metabolism*

8-hydroxy-2'-deoxyguanosine (8-OHdG) is a sensitive and stable biomarker for evaluating DNA oxidative damage. A rapid and sensitive colloidal gold immunochromatographic strip was developed for 8-OHdG detection by a competitive method. The sample pad (glass cellulose film), bonding pad (glass cellulose film), nitrocellulose film and absorbent pad were pasted on the polyvinyl chloride (PVC) base plate to construct the test strip. Colloidal gold (AuNPs) was prepared by the reduction of chloroauric acid with sodium citrate. 8-OHdG antibody (Ab) was coated on the outer layer of AuNPs to form Ab@AuNPs as a probe. Bovine serum albumin (BSA) and 8-OHdG were conjugated with carbodiimide hydrochloride to prepare an artificial antigen, which was used as the coating antigen of detection line. Goat anti mouse polyclonal antibody IgG was used as the coating antibody of control line. The experimental parameters were optimized including the type of nitrocellulose membrane, the formula of loading solution, and the spraying amount of gold labeled antibody. The results showed that the appropriate nitrocellulose membrane was CN 95. The optimal loading solution included BSA (1%), Tween-20 (3%), sucrose (3%) and NaCl (0.9%). The optimal spraying amount of gold labeled antibody was 4 μL. 8-OHdG can be detected by the strip under visible light, and the level of 8-OHdG in urine can be preliminarily determined by comparing the color intensity of T line and C line. The 8-OHdG concentration in urine was further calculated by the gray value of T line and the threshold of detection was 2.55 μg/L. This colloidal gold immunochromatographic strip is simple, rapid and specific for detecting 8-OHdG in human urine to preliminarily evaluate the human status.
8-Hydroxy-2'-Deoxyguanosine ; Animals ; Antibodies, Monoclonal ; Gold ; Gold Colloid/chemistry* ; Metal Nanoparticles ; Mice ; Sensitivity and Specificity

Ebola virus (EBOV) is an enveloped negative-sense RNA virus and a member of the filovirus family. Nucleoprotein (NP) expression alone leads to the formation of inclusion bodies (IBs), which are critical for viral RNA synthesis. The matrix protein, VP40, not only plays a critical role in virus assembly/budding, but also can regulate transcription and replication of the viral genome. However, the molecular mechanism by which VP40 regulates viral RNA synthesis and virion assembly/budding is unknown. Here, we show that within IBs the N-terminus of NP recruits VP40 and is required for VLP-containing NP release. Furthermore, we find four point mutations (L692A, P697A, P698A and W699A) within the C-terminal hydrophobic core of NP result in a stronger VP40-NP interaction within IBs, sequestering VP40 within IBs, reducing VP40-VLP egress, abolishing the incorporation of NC-like structures into VP40-VLP, and inhibiting viral RNA synthesis, suggesting that the interaction of N-terminus of NP with VP40 induces a conformational change in the C-terminus of NP. Consequently, the C-terminal hydrophobic core of NP is exposed and binds VP40, thereby inhibiting RNA synthesis and initiating virion assembly/budding.
Ebolavirus/physiology* ; HEK293 Cells ; HeLa Cells ; Humans ; Nucleocapsid Proteins/metabolism* ; RNA, Viral/metabolism* ; Viral Matrix Proteins/metabolism* ; Virion/metabolism* ; Virus Assembly

Objective: To investigate the effect of micro steel plate internal fixation combined with traditional Chinese medicine medicated bath in the treatment of proximal phalanx fractures. Methods: From January 2012 to December 2012, 100 patients with proximal phalanx fracture in Ningbo Mingzhou Hospital were selected and randomly divided into control group and observation group, according to the digital table, with 50 cases in each group.The control group was treated by simple miniature steel plate internal fixation, the observation group was treated by microplate internal fixation combined with traditional Chinese medicine medicated bath.The clinical treatment effect was compared between the two groups. Results: The hospitalization time and fracture healing time in the observation group were (8.35±1.62)d and (49.35±3.85)d, respectively, which were significantly shorter than those in the control group [(8.95±1.48)d, (57.82±6.12)d], the differences were statistically significant (t=5.032, 6.114, all P<0.05). The postoperative total active flexion degree and incidence rate of adverse reactions of the observation group (16.00%) was lower than that in control group (34.00%), the difference was statistically significant (χ²=18.485, P<0.05). Conclusion Microplate internal fixation combined with traditional Chinese medicine medicated bath in the treatment of proximal phalanx fractures has better treatment effect, and it has shorter treatment time and less complications.

Transient osteoporosis of the hip(TOH) is classified as a type of bone marrow edema syndrome. TOH is lack of previous study and there is still controversy about his pathogenesis. In recent years, with the development of multi-discipline, such as imaging, pathology, molecular biology, the study has found that the pathological mechanism is complex, while its mechanism is still not clear, which need further research. This paper summarizes the research progress on the pathogenesis of TOH from neurogenic, osteonecrosis, abnormal vascular function, subchondral fracture, heredity and regional acceleration and son on.

Objective To evaluate the effect of hyperbaric oxygen (HBO) therapy on postoperative cognitive dysfunction (POCD) in elderly patients undergoing general anesthesia.Methods A total of 112 patients,aged 65-75 yr,of American Society of Anesthesiologists physical status Ⅱ or Ⅲ,undergoing elective non-cardiac surgery with general anesthesia,were randomly divided into control group (C group,n =54) and HBO group (n =58).Patients were exposed to hyperbaric oxygen in a hyperbaric oxygen chamber once a day from day 3 to day 12 after surgery in both groups.Pressure was slowly increased to 2 atmosphere absolute within 20 min,pure oxygen was inhaled for 35 min by mask,5 min later pure oxygen was inhaled for another 35 min,oxygen inhalation was then stopped and pressure was slowly increased to 1 atmosphere absolute in HBO group.Patients inhaled air at 1 atmosphere absolute for 70 min in C group.Cognitive function score was assessed using Mini-Mental State Examination,language ability test,visual identification function test,digit span backwards task and Hasegawa's Dementia Scale (HDS) at 2 days before surgery and 7 and 13 days after surgery.The development of POCD was recorded.Results Compared with the baseline at 2 days before surgery,language ability test,digit span backwards task and HDS scores were significantly decreased at 7 and 13 days after surgery in C group,and digit span backwards task scores were significantly decreased at 7 days after surgery in HBO group (P＜0.05 or 0.01).The language ability test and HDS scores were significantly higher,and the incidence of POCD was lower at 7 and 13 days after surgery in HBO group than in C group (P＜0.05).Conclusion HBO therapy can reduce POCD in elderly patients undergoing general anesthesia.