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.

The current study aimed to clarify the roles of apolipoprotein A5 (ApoA5) and milk fat globule-epidermal growth factor 8 (Mfge8) in regulating myocardial lipid deposition and the regulatory relationship between them. The serum levels of ApoA5 and Mfge8 in obese and healthy people were compared, and the obesity mouse model induced by the high-fat diet (HFD) was established. In addition, primary cardiomyocytes were purified and identified from the hearts of suckling mice. The 0.8 mmol/L sodium palmitate treatment was used to establish the lipid deposition cardiomyocyte model in vitro. ApoA5-overexpressing adenovirus was used to observe its effects on cardiac function and lipids. The expressions of the fatty acid uptake-related molecules and Mfge8 on transcription or translation levels were detected. Co-immunoprecipitation was used to verify the interaction between ApoA5 and Mfge8 proteins. Immunofluorescence was used to observe the co-localization of Mfge8 protein with ApoA5 or lysosome-associated membrane protein 2 (LAMP2). Recombinant rMfge8 was added to cardiomyocytes to investigate the regulatory mechanism of ApoA5 on Mfge8. The results showed that participants in the simple obesity group had a significant decrease in serum ApoA5 levels (P < 0.05) and a significant increase in Mfge8 levels (P < 0.05) in comparison with the healthy control group. The adenovirus treatment successfully overexpressed ApoA5 in HFD-fed obese mice and palmitic acid-induced lipid deposition cardiomyocytes, respectively. ApoA5 reduced the weight of HFD-fed obese mice (P < 0.05), shortened left ventricular isovolumic relaxation time (IVRT), increased left ventricular ejection fraction (LVEF), and significantly reduced plasma levels of triglycerides (TG) and cholesterol (CHOL) (P < 0.05). In myocardial tissue and cardiomyocytes, the overexpression of ApoA5 significantly reduced the deposition of TG (P < 0.05), transcription of fatty acid translocase (FAT/CD36) (P < 0.05), fatty acid-binding protein (FABP) (P < 0.05), and fatty acid transport protein (FATP) (P < 0.05), and protein expression of Mfge8 (P < 0.05), while the transcription levels of Mfge8 were not significantly altered (P > 0.05). In vitro, the Mfge8 protein was captured using ApoA5 as bait protein, indicating a direct interaction between them. Overexpression of ApoA5 led to an increase in co-localization of Mfge8 with ApoA5 or LAMP2 in cardiomyocytes under lipid deposition status. On this basis, exogenous added recombinant rMfge8 counteracted the improvement of lipid deposition in cardiomyocytes by ApoA5. The above results indicate that the overexpression of ApoA5 can reduce fatty acid uptake in myocardial cells under lipid deposition status by regulating the content and cellular localization of Mfge8 protein, thereby significantly reducing myocardial lipid deposition and improving cardiac diastolic and systolic function.
Animals ; Humans ; Mice ; Myocytes, Cardiac/metabolism* ; Obesity/physiopathology* ; Male ; Apolipoprotein A-V/blood* ; Lipid Metabolism/physiology* ; Milk Proteins/blood* ; Myocardium/metabolism* ; Diet, High-Fat ; Antigens, Surface/physiology* ; Mice, Inbred C57BL ; Cells, Cultured ; Female

Metal ion-promoted chemodynamic therapy(CDT) combined with photodynamic therapy(PDT) offers broad application prospects for enhancing anti-tumor effects. In this study, glycyrrhizic acid(GA), copper ions(Cu~(2+)), and norcantharidin(NCTD) were co-assembled to successfully prepare a natural small-molecule, carrier-free hydrogel(NCTD Gel) with excellent material properties. Under 808 nm laser irradiation, NCTD Gel responded to the tumor microenvironment(TME) and acted as an efficient Fenton reagent and photosensitizer, catalyzing the conversion of endogenous hydrogen peroxide(H_2O_2) within the tumor into oxygen(O_2), and hydroxyl radicals(·OH, type Ⅰ reactive oxygen species) and singlet oxygen(~1O_2, type Ⅱ reactive oxygen species), while depleting glutathione(GSH) to stabilize reactive oxygen species and alleviate tumor hypoxia. In vitro and in vivo experiments demonstrated that NCTD Gel exhibited significant CDT/PDT synergistic therapeutic effects. Further safety evaluation and metabolic testing confirmed its good biocompatibility and safety. This novel hydrogel is not only simple to prepare, safe, and cost-effective but also holds great potential for clinical transformation, providing insights and references for the research and development of metal ion-mediated hydrogel-based anti-tumor therapies.
Hydrogels/chemistry* ; Animals ; Photochemotherapy ; Humans ; Mice ; Antineoplastic Agents/administration & dosage* ; Photosensitizing Agents/chemistry* ; Neoplasms/metabolism* ; Female ; Copper/chemistry* ; Reactive Oxygen Species/metabolism* ; Tumor Microenvironment/drug effects* ; Cell Line, Tumor ; Male

OBJECTIVE: To investigate the prognostic value of peripheral blood absolute monocyte count(AMC) in non-severe aplastic anaemia(NSAA) patients. METHODS: 178 patients with NSAA who attended the Affiliated Hospital of Xuzhou Medical University from April 2008 to September 2020 were retrospectively analyzed, and the optimal cut-off value of peripheral blood AMC was determined by the receiver operating characteristic curve of the subjects, and they were divided into low AMC group (48 patients) and normal AMC group (130 patients), and the differences in clinical characteristics between the two groups were compared. Overall survival(OS) and progression-free survival(PFS) were analyzed by Kaplan-Meier. Univariate and multivariate Cox regression analysis were used to determine the independent prognostic value of AMC. RESULTS: Among 178 NSAA patients, 105(59.0%) were male and 73(41.0%) were female, with a median age of 31(18-87) years old, a median follow-up time of 58 months (range: 6 months-175 months), and a median AMC of 0.15×10⁹/L ［range: (0.01-0.59)×10⁹/L)］. The proportion of granulocytes (27.5% vs 36.0%, P < 0.05), and the proportion of mature monocytes (1% vs 2%, P < 0.05) in the low AMC group were lower than that in the normal AMC group; the proportion of mature lymphocytes in the low AMC group was higher than that in the normal AMC group (54% vs 50%, P < 0.05). However, there was no significantly different in the proportion of erythropoietic cells and stages of the erythropoietic cells between the two groups ( P >0.05). CR (27.7% vs 10.4%) and ORR (75.4% vs 56.3%) in the normal AMC group were higher than that in the low AMC group. Compared with patients in the low AMC group, AA patients in the normal AMC had better 5-year OS (98.5% vs 86.9%, P < 0.01), and the 5-year PFS (86.0% vs 58.9%, P < 0.01). Also, the 10-year survival rate of patients in the normal AMC group was higher than that in the low AMC group (98.5% vs 60.5%,P < 0.01). Univariate analysis showed that age, reticulocyte count, AMC<0.1×10⁹/L and the proportion of bone marrow mature monocytes were related with patients survival. Multivariate Cox regression analysis showed that monocyte count reduction was not an independent poor prognostic factor in NSAA patients （HR =4.474，95%CI ：0.508-44.390； P =0.172）. CONCLUSION Low AMC level at initial diagnosis is not an independent prognostic factor for NSAA patients, but still suggest potential prognostic value of AMC.
Humans ; Anemia, Aplastic/diagnosis* ; Female ; Male ; Prognosis ; Monocytes ; Adult ; Middle Aged ; Retrospective Studies ; Adolescent ; Aged ; Young Adult ; Aged, 80 and over ; Leukocyte Count

BACKGROUND: The association of systemic inflammatory response index (SIRI) with prognosis of coronary artery disease (CAD) patients has never been investigated in a large sample with long-term follow-up. This study aimed to explore the association of SIRI with all-cause and cause-specific mortality in a nationally representative sample of CAD patients from United States. METHODS: A total of 3386 participants with CAD from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 were included in this study. Cox proportional hazards model, restricted cubic spline (RCS), and receiver operating characteristic curve (ROC) were performed to investigate the association of SIRI with all-cause and cause-specific mortality. Piece-wise linear regression and sensitivity analyses were also performed. RESULTS: During a median follow-up of 7.7 years, 1454 all-cause mortality occurred. After adjusting for confounding factors, higher lnSIRI was significantly associated with higher risk of all-cause (HR = 1.16, 95% CI: 1.09-1.23) and CVD mortality (HR = 1.17, 95% CI: 1.05-1.30) but not cancer mortality (HR = 1.17, 95% CI: 0.99-1.38). The associations of SIRI with all-cause and CVD mortality were detected as J-shaped with threshold values of 1.05935 and 1.122946 for SIRI, respectively. ROC curves showed that lnSIRI had robust predictive effect both in short and long terms. CONCLUSIONS SIRI was independently associated with all-cause and CVD mortality, and the dose-response relationship was J-shaped. SIRI might serve as a valid predictor for all-cause and CVD mortality both in the short and long terms.

Objective To observe the effect of electric stimulation on nuclear factor-κB(NF-κB)/NOD-like receptor protein 3(NLRP3)signaling pathway and microglial cell morphology in mice with lipopolysaccharide(LPS)induced chronic neuroinflammation,and to explore the protective mechanism of electric stimulation on brain of mice.Methods C57BL/6 mice were randomly divided into blank control group(n=8),model group(n=12),sham electroacupuncture group(n=6)and electroacupuncture group(n=6).Except blank control group,mice in other groups were injected intraperitoneally with LPS(0.25 mg/kg)for 7 consecutive days.On the 8th day,mice in the sham electroacupuncture group and electroacupuncture group were treated with acupuncture or Zusanli electroacupuncture for 7 consecutive days.The mice were weighed before the experiment,on the 7th and 14th days.On the 13th day,the elevated cross maze test was performed on the mice.The open field test was performed on the 14th day.After the experiment,immunofluorescence assay was used to determine the expression of microglial ionized calcium binding adaptor molecule-1(Iba-1)in prefrontal cortex region.The mRNA expression of NF-κB,inducible nitric oxide synthase(iNOS),tumor necrosis factor-α(TNF-α),Caspase-1 and interleukin(IL)-18 were detected by Real-time PCR.The protein expression levels of NF-κB,iNOS,NLRP3,apoptosis-associated speck-like protein containing a CARD(ASC),Caspase-1,IL-1βand IL-18 were detected by Western blotting.Results Weight change,On the 7th day,compared with the control group,the body weight of mice in model group,sham electroacupuncture group and electroacupuncture group decreased(P＜0.0001),respectively;On the 14th day,compared with the control group,the weight of mice in the model group decreased(P＜0.0001);Compared with the sham electroacupuncture group,the body weight of mice in the electroacupuncture group increased(P＜0.05).Elevated cross maze experiment,compared with the control group,the total distance and open arm retention time of mice in model group decreased,while the closed arm retention time increased(P＜0.05).The open field experiment showed that compared with the control group,the model group mice showed a decrease in total distance traveled,slower movement speed,and fewer entries into the central area(P＜0.001);Compared with the model group,the electroacupuncture group showed an increase in all three indicators(P＜0.01);Compared with the sham electroacupuncture group,the total distance and motion speed of mice in electroacupuncture group both increased(P＜0.05).Immunofluorescence assay,compared with the control group,the relative fluorescence of Iba-1 in prefrontal cortex area of mice in model group increased(P＜0.05).Compared with the model and sham electroacupuncture group,the relative fluorescence of Iba-1 in prefrontal cortex area of mice in electroacupuncture group decreased(P＜0.05).Real-time PCR showed that compared with the control group,mRNA expressions of NF-κB,iNOS,TNF-α,Caspase-1 and IL-18 in the model group increased(P＜0.05);Compared with the model group,mRNA expressions of NF-κB,iNOS,TNF-α,Caspase-1 and IL-18 in electroacupuncture group decreased(P＜0.05).Western blotting indicated that compared with the control group,the protein expressions of NF-κB,iNOS,Caspase-1,IL-1β and IL-18 in model group increased(P＜0.05);Compared with model group,the protein expressions of NF-κB,iNOS,NLRP3,ASC,Caspase-1,IL-1β and IL-18 in electroacupuncture group decreased(P＜0.05);Compared with the sham electroacupuncture group,IL-18 protein in electroacupuncture group decreased(P＜0.05).Conclusion Electroacupuncture can improve the behavioral performance of mice and inhibit the activation of microglia in the cortical region of mice,which may play an anti-inflammatory and protective role by regulating NF-κB/NLRP3 pathway.

Objective:To analyze the prognostic value of del(1p32)in patients with newly diagnosed multiple myeloma(MM).Methods:The clinical data of 341 newly diagnosed MM attended in Jiangsu Province Hospital were retrospective analyzed.Clinical characteristic combined with genetic features,especially del(1p32),were analyzed for survival and prognostic of patients.Results:Among the 341 patients with newly diagnosed MM,24(7.0％)patients were del(1p32)positive.The progression-free survival(PFS)and overall survival(OS)were significantly shorter in MM patients with del(1p3 2)than those without de1(1p32)(PFS:P＜0.001;OS:P＜0.001).The COX proportional-hazards model showed that del(1 p32)was an independent risk factor for PFS and OS of patients with MM.The patients with both 1q21 gain/amplification and del(1p32),as"double-hit chromosome 1",have worse prognosis than those with only 1q21 gain/amplification or only del(1 p32)(PFS:P＜0.001;OS:P＜0.001).Conclusion:Del(1p32)is an independent risk factor for PFS and OS of patients with MM.Del(1p32)detection should be widely used in the prognostic analysis for newly diagnosed MM patients.

Objective To assess the risk factors for carbapenem-resistant Acinetobacter baumannii(CRAB)bloodstream infection(BSI)and 28-day short-term mortality in elderly patients,and provide reference for the pre-vention and treatment of CRAB BSI.Methods Clinical data of patients aged ≥60 years and diagnosed with AB BSI in a hospital in Yulin City from January 2013 to December 2022 were retrospectively analyzed,including demogra-phic and microbiological characteristics,as well as clinical outcomes of the patients.Variables which were significant in univariate analysis were selected for multivariate analysis using binary logistic regression model and Cox propor-tional hazards model.Independent risk factors for infection were further determined,and survival analysis was per-formed using Kaplan-Meier curve.Results A total of 150 patients were included in the study,out of which 16 pa-tients(10.7％)had CRAB BSI and 134 had carbapenem-sensitive AB(CSAB)BSI.The 28-day short-term mortali-ty of AB BSI in elderly patients was 15.3％(23/150,95％CI:9.6％-21.1％),and the short-term mortality of CRAB BSI was higher than that of CSAB([56.3％,9/16]vs[10.4％,14/134]).Deep venous catheterization(OR:15.598,95％CI:1.831-132.910)and combined infections of other sites(OR:15.449,95％CI:1.497-159.489)were related to CRAB BSI in elderly patients.The independent risk factors for 28-day mortality in elderly patients with AB BSI were hemodialysis(OR:11.856,95％CI:2.924-48.076),intensive care unit admission(OR:9.387,95％CI:1.941-45.385),and pulmonary infection being suspected source of bacteremia(OR:7.019,95％CI:1.345-36.635).Conclusion The occurrence of CRAB BSI in elderly patients is related to the combined infection of other sites and deep vein catheterization.Hemodialysis,admission to ICU,and pulmonary infection being suspected source of bacteremia are independent risk factors for the prognosis of AB BSI in elderly patients.

Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.

Objective To explore the regulatory mechanism of Macelignan on oxidative stress-mediated neuronal injury in autophagy and apoptosis.Methods Murine hippocampal neuronal HT22 cells were treated with 2.5 mmol·L-1 glutamic acid(Glu)to establish an oxidative stress cell model.The cells were divided into normal group(normal cultured cells),model group(2.5 mmol·L-1 Glu)and experimental-L,-M,-H groups(2.5,5,10 μmol·L-1Macelignan treatment),inhibitor group(2.5 mmol·L-1 Glu+10 μmol·L-1 Macelignan+10 μmol·L-1 LY294002).Aoptosis rate was detected by flow cytometry;the protein expression level of autophagy-related protein LC3B(LC3B),anti-SQSTM1/p62(p62),p21,B-cell lymphoma-2(Bcl-2)and Bcl-2 associated X protein(Bax)was detected by Western blot.Results The apoptosis rates in the normal group,model group and experimental-L,-M,-H groups were(4.58±1.25)％,(8.75±0.55)％,(6.30±1.71)％,(5.97±2.27)％and(5.49±1.71)％.The difference between model group and normal group was statistically significant(P＜0.01).The difference between experimental-L,-M,-H groups and model group was statistically significant(all P＜0.01).The levels of LC3B in normal group,model group,experimental-L,experimental-M,experimental-H groups and inhibitor group were 0.28±0.02,0.74±0.02,1.02±0.04,0.70±0.03,0.26±0.02 and 0.21±0.01;p62 levels were 0.49±0.08,0.33±0.03,0.50±0.07,0.59±0.01,0.64±0.13 and 0.65±0.06;p21 levels were 0.87±0.02,1.18±0.03,0.98±0.03,0.88±0.03,0.72±0.06 and 0.81±0.02;Bcl-2/Bax levels were 1.74±0.23,1.11±0.10,1.38±0.05,1.66±0.26,1.58±0.29 and 1.53±0.09,respectively.The differences between model group and normal group,between model group and experimental-H group,between model group and inhibitor group,were also statistically significant(all P＜0.01).Conclusion Macelignan can reduce the damage of hippocampal neurons induced by glutamate acid by regulating the process of autophagy and apoptosis,and has obvious neuroprotective effect.