Extensive studies have identified potential adverse effects on semen quality of obesity, based on body mass index, but the association between body fat distribution, a more relevant indicator for obesity, and semen quality remains less clear. We conducted a longitudinal study of 4304 sperm donors from the Guangdong Provincial Human Sperm Bank (Guangzhou, China) during 2017-2021. A body composition analyzer was used to measure total and local body fat percentage for each participant. Generalized estimating equations were employed to assess the association between body fat percentage and sperm count, motility, and morphology. We estimated that each 10% increase in total body fat percentage (estimated change [95% confidence interval, 95% CI]) was significantly associated with a 0.18 × 10 6 (0.09 × 10 6 -0.27 × 10 6 ) ml and 12.21 × 10 6 (4.52 × 10 6 -19.91 × 10 6 ) reduction in semen volume and total sperm count, respectively. Categorical analyses and exposure-response curves showed that the association of body fat distribution with semen volume and total sperm count was stronger at higher body fat percentages. In addition, the association still held among normal weight and overweight participants. We observed similar associations for upper limb, trunk, and lower limb body fact distributions. In conclusion, we found that a higher body fat distribution was significantly associated with lower semen quality (especially semen volume) even in men with a normal weight. These findings provide useful clues in exploring body fat as a risk factor for semen quality decline and add to evidence for improving semen quality for those who are expected to conceive.
Humans ; Male ; Adult ; Semen Analysis ; China ; Body Fat Distribution ; Longitudinal Studies ; Sperm Count ; Sperm Motility ; Body Mass Index ; Tissue Donors ; Obesity/complications* ; Spermatozoa ; Young Adult ; Middle Aged ; East Asian People

OBJECTIVE: To study the effects and mechanisms of juglone on the proliferation and apoptosis of acute myeloid leukemia (AML) cells. METHODS: Juglone and AML targets were collected from public databases, and the intersecting target clusters were taken for functional enrichment analysis to explore the potential mechanism of juglone in the treatment of AML. Then wet experiments were performed to verify. AML cell lines including KG-1a, MV-411, THP-1 and MOLM-13 were treated with different concentrations of juglone for 24 h. MTT assay was used to detect cell viability and determine the IC₅₀, and the most sensitive cell line was screened for subsequent experiments. Flow cytometry was used to detect the apoptosis of cells treated with different concentrations of juglone. Western blot was performed to check the expression of relevant proteins. RESULTS: Eleven targets were obtained as potential targets for juglone in the treatment of AML, and the top ten significantly enriched pathways were intrinsic pathway of apoptosis, programmed cell death, cytochrome c-mediated apoptotic response, apoptosis, apoptotic factor-mediated response, regulated necrosis, cytokine signaling in immune system, signaling by interleukins, oncogene induced senescence, and signal transduction. The cell viability of KG-1a, MV-411, THP-1 and MOLM-13 was decreased with increasing juglone concentration after 24 h of juglone treatment (r =-0.992, -0.886, -0.956, -0.910). Among them, MOLM-13 was the most sensitive to juglone. The results of flow cytometry showed that the apoptosis rate of MOLM-13 tended to significantly increase with the increasing concentration of juglone (r =0.99). At the same time point, p-RIPK1/RIPK1, p-RIPK3/RIPK3, and p-MLKL/MLK were decreased in each juglone concentration group compared with control group. CONCLUSION Juglone inhibits the viability of KG-1a, MV-411, THP-1 and MOLM-13 cells, and induces apoptosis of MOLM-13 cells, the mechanism of which may be related to the inhibition of RIPK1/RIPK3/MLKL signaling pathway.
Humans ; Naphthoquinones/pharmacology* ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Leukemia, Myeloid, Acute/pathology* ; Cell Line, Tumor ; Receptor-Interacting Protein Serine-Threonine Kinases/metabolism* ; Protein Kinases/metabolism* ; Signal Transduction ; Cell Survival/drug effects*

ObjectiveTo investigate the effect of transplantation of bone marrow mesenchymal stem cells （BMSCs） co-cultured with bone marrow-derived M2 macrophages （M2-BMDMs）， named as BMSC^M2， on a rat model of liver cirrhosis induced by carbon tetrachloride （CCl₄）/2-acetaminofluorene （2-AAF）. MethodsRat BMDMs were isolated and polarized into M2 phenotype， and rat BMSCs were isolated and co-cultured with M2-BMDMs at the third generation to obtain BMSC^M2. The rats were given subcutaneous injection of CCl₄ for 6 weeks to establish a model of liver cirrhosis， and then they were randomly divided into model group （M group）， BMSC group， and BMSC^M2 group， with 6 rats in each group. A normal group （N group） with 6 rats was also established. Since week 7， the model rats were given 2-AAF by gavage in addition to the subcutaneous injection of CCl₄. Samples were collected at the end of week 10 to observe liver function， liver histopathology， and hydroxyproline （Hyp） content in liver tissue， as well as changes in the markers for hepatic stellate cells， hepatic progenitor cells， cholangiocytes， and hepatocytes. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the N group， the M group had significant increases in the activities of serum alanine aminotransferase （ALT） and aspartate aminotransferase （AST） （P<0.01）； compared with the M group， the BMSC and BMSC^M2 groups had significant reductions in ALT and AST （P<0.01）， and the BMSC^M2 group had significantly better activities than the BMSC group （P<0.05）. Compared with the N group， the M group had significant increases in Hyp content and the mRNA and protein expression levels of alpha-smooth muscle actin （α-SMA） in the liver （P<0.01）； compared with the M group， the BMSC and BMSC^M2 groups had significant reductions in Hyp content and the expression of α-SMA （P<0.05）， and the BMSC^M2 group had a significantly lower level of α-SMA than the BMSC group （P<0.01）. Compared with the N group， the M group had significant increases in the mRNA expression levels of the hepatic progenitor cell markers EpCam and Sox9 and the cholangiocyte markers CK7 and CK19 （P<0.01） and significant reductions in the expression levels of the hepatocyte markers HNF-4α and Alb （P<0.01）； compared with the M group， the BMSC and BMSC^M2 groups had significant reductions in the mRNA expression levels of EpCam， Sox9， CK7， and CK19 （P<0.05） and significant increases in the mRNA expression levels of HNF-4α and Alb （P<0.05）， and compared with the BMSC group， the BMSC^M2 group had significant reductions in the mRNA expression levels of EpCam and CK19 （P<0.05） and significant increase in the expression level of HNF-4α （P<0.05）. ConclusionM2-BMDMs can enhance the therapeutic effect of BMSCs on CCl₄/2-AAF-induced liver cirrhosis in rats， which provides new ideas for further improving the therapeutic effect of BMSCs on liver cirrhosis.

Objective:To summarize the incidence of cerebral venous reflux (CVR) in patients with recent small subcortical infarct (RSSI) and explore its correlation with enlarged perivascular spaces (EPVS).Methods:Patients with RSSI in the lenticulostriate artery admitted to the Department of Neurology of the First Affiliated Hospital of Zhengzhou University from January 2019 to December 2022 were included. The baseline demographic data, medical history, and laboratory results of the patients were collected. CVR was assessed by time-of-flight magnetic resonance angiography. Patients were stratified into 2 groups based on the presence (CVR group) or absence of CVR (non-CVR group), and baseline characteristics as well as laboratory test results were compared between the 2 groups. The location and number of EPVS were evaluated using a visual grading scale, with EPVS with higher scores defined as high-grade EPVS (HEPVS). Simultaneous evaluation of cerebral white matter hyperintensities and lacunar infarctions was conducted, followed by intergroup comparisons. The relationship between EPVS and CVR was studied using multiple Logistic regression analysis.Results:A total of 571 patients with RSSI in the lentiform artery area were ultimately included, including 180 females (31.5%). Their age was (59.37±12.87) years. Among them, 73 patients (12.8%) exhibited CVR based on imaging findings, so the incidence of CVR was 12.8%. In comparison between the CVR group ( n=73) and the non-CVR group ( n=498), the proportion of females [21.9% (16/73) vs 32.9% (164/498), χ 2=3.578, P=0.059] was lower and the proportion of history of smoking [38.4% (28/73) vs 27.7% (138/498), χ 2=3.499, P=0.061] was higher in the CVR group, but without statistical significance. Additionally, the history of alcohol consumption [34.2% (25/73) vs 21.7% (108/498), χ 2=5.621, P=0.018] and the proportion of patients with concomitant HEPVS in the basal ganglia area [41.1% (30/73) vs 25.3% (126/498), χ 2=7.999, P=0.005] was higher in the CVR group with statistical significance. Multiple Logistic regression analysis showed that HEPVS in the basal ganglia region remained independently associated with CVR ( OR=1.988, 95% CI 1.190-3.320, P=0.009). Conclusion:EPVS in the basal ganglia region is significantly associated with CVR in the RSSI population, suggesting that venous dysfunction may be closely related to the formation of EPVS.

Objective To investigate the effect and mechanism of Yiguan Decoction(YGJD)on the efficacy of M1 bone marrow-derived macrophages(M1-BMDMs)in the treatment of rats with liver cirrhosis induced by 2-AAF/CCl4.Methods BMDMs were isolated and induced into M1-BMDMs by lipopolysaccharide.A total of 50 male Wistar rats were randomly divided into normal group with 5 rats and model group with 45 rats.The rats for modeling were given subcutaneous injection of 50%CCl4 twice a week.Since week 7,the rats for modeling were randomly divided into model group(M group),YGJD group,M1-BMDM group,M1-BMDM+YGJD group,and sorafenib(SORA)group,and they were given subcutaneous injection of 30%CCl4 to maintain the progression of liver cirrhosis and intragastric administration of 2-AAF.CCR2 inhibitors were added to the drinking water,and each group was given the corresponding intervention.Related samples were collected at week 9.The rats were observed in terms of serum liver function parameters,liver pathology,hydroxyproline(Hyp)content in liver tissue,hepatic stellate cell activation,hepatic fibrosis and inflammation factors,and the expression levels of molecules associated with the Wnt signaling pathway.A one-way analysis of variance was used for comparison of continuous data between multiple groups,and the least significant difference t-test was used for further comparison between two groups.Results Compared with the M group,the M1-BMDM+YGJD group had significant reductions in the serum levels of alanine aminotransferase,aspartate aminotransferase,and total bilirubin(TBil)(all P<0.05)and a significant increase in the content of albumin(Alb)(P<0.05),and compared with the M1-BMDM group,the M1-BMDM+YGJD group had a significant reduction in the serum level of TBil(P<0.05)and a significant increase in the serum level of Alb(P<0.05).Compared with the M1-BMDM group,the M1-BMDM+YGJD group had significant reductions in the expression levels of CD68 and TNF-α(P<0.05).Compared with the M1-BMDM group,the M1-BMDM+YGJD group had significant reductions in Hyp content and Sirius red positive area(P<0.05).As for the non-canonical Wnt signaling pathway molecules,compared with the M1-BMDM group,the M1-BMDM+YGJD group had significantly lower mRNA and protein expression levels of Wnt5a(P<0.05)and mRNA expression level of Fzd2(P<0.05),as well as significant reductions in the mRNA expression levels of Wnt4,Wnt5b,and Fzd3(P<0.05),while there were no significant changes in the mRNA expression levels of the canonical Wnt signaling pathway molecules β-catenin,LRP5,LRP6,Fzd5,and TCF.Conclusion YGJD can enhance the therapeutic effect of M1-BMDMs on rats with liver cirrhosis induced by 2-AAF/CCl4,possibly by inhibiting the non-canonical Wnt5a/Fzd2 signaling pathway,which provides new ideas for the synergistic effect of traditional Chinese medicine on M1-BMDMs in the treatment of liver cirrhosis.

Objective:To investigate the correlation between serum growth differentiation factor 11 (GDF11) level and coronary artery lesions in patients with ST-segment elevation myocardial infarction (STEMI), and the predictive efficacy of nomogram risk prediction model based on GDF11 combined with traditional risk factors on the occurrence of STEMI.Methods:This study was a retrospective cross-sectional study. Patients hospitalized in the Department of Cardiology of the 904th Hospital of Joint Logistic Support Force of People′s Liberation Army of China from 2016 to 2018 were selected and divided into control group and STEMI group. The demographic data, blood lipid level, laboratory indicators of blood and GDF11 level were collected. Logistic regression analysis screened out independent correlated factors for the occurrence of STEMI. Spearman correlation analysis clarified the correlation of each indicator with the SYNTAX or Gensini scores. A nomogram risk prediction model for the risk of STEMI occurrence and the receiver operating characteristic curve was used to compare the prediction efficiency of each model.Results:A total of 367 patients were enrolled, divided into control group ( n=172) and STEMI group ( n=195), age (66.5±11.8), male 222 (60.49%). The serum GDF11 level of STEMI group was significantly lower than that of the control group (36.20 (16.60, 70.75) μg/L vs. 85.00 (53.93, 117.10) μg/L, P<0.001). The results of multivariate logistic regression analysis showed serum GDF11( OR=0.98, 95% CI: 0.97-0.99) and traditional independent risk factors such as smoking, diabetes, C-reactive protein, homocysteine, lipoprotein (a) and apolipoprotein A1/B were independent correlate factors for the occurrence of STEMI ( P<0.05). Spearman correlation analysis showed that serum GDF11 was negatively correlated with SYNTAX score and Gensini score ( P<0.05). The nomogram model constructed by serum GDF11 combined with traditional independent risk factors (AUC=0.85, 95% CI: 0.81-0.89) had better predictive value for the occurrence of STEMI than the traditional nomogram model constructed by independent risk factors(AUC=0.80, 95% CI:0.75-0.84) or serum GDF11 (AUC=0.76, 95% CI: 0.72-0.81), all P<0.01. Conclusions:Serum GDF11 is an independent correlate factor in the occurrence of STEMI and is negatively correlated with the severity of coronary artery lesions in patients with STEMI. The nomogram model constructed based on GDF11 combined with traditional risk factors can be a good predictor for the occurrence of STEMI.

AIM To study the phenylpropanoids from Brandisia hancei Hook.f.and their antioxidant activities.METHODS The extract from B.hancei was isolated and purified by Rp-C18,MCI,semi-preparative HPLC,silica gel and Sephadex LH-20,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The cytotoxicities was determined by MTT method,and the antioxidant activities were determined by DPPH and ABTS+free radical scavenging methods.RESULTS Fifteen phenylpropanoids were isolated and identified as(+)-pinonesinol(1),(-)-medioresinol(2),(-)-syringaresinol(3),buddlenol D(4),(7R,7'R,7″S,8S,8'S,8″S)-4',5″-dihydroxy-3,5,3',4″-tetramethoxy-7,9':7',9-diepoxy-4,8″-oxy-8,8'-sesquineo-lignan-7″,9″-diol(5),(-)-(7R,7'R,7″R,8S,8'S,8″S)-4',4″-dihydroxy-3,3',3″,5-tetramethoxy-7,9':7',9-diepoxy-4,8″-oxy-8,8'-sesquineolignan-7″,9″-diol(6),hedyotol A(7),dracunculifoside R(8),acteoside(9),isoacteoside(10),arenarioside(11),isomartynoside(12),curcasinlignan B(13),erythro-2,3-bis(4-hydroxy-3-methoxyphenyl)-3-ethoxypropan-l-ol(14),citrusin C(15).Compounds 1-4 and 9-10 had no obvious cytotoxicity to HepG2 hepatoma cells.Compounds 1,3,9,10 and 12 had strong scavenging activities against DPPH radicals.Compounds 1-3,9-10,12 and 14 showed strong scavenging activities against ABTS+radical.CONCLUSION Compounds 1-8 and 12-15 are isolated from genus Brandisia for the first time.The phenylpropanoids from B.hancei show strong antioxidant activities.

OBJECTIVE: This study was aimed at investigating the carrier rate of, and molecular variation in, α- and β-globin gene mutations in Hunan Province. METHODS: We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan Province. Hematological screening was performed, and molecular parameters were assessed. RESULTS: The overall carrier rate of thalassemia was 7.1%, including 4.83% for α-thalassemia, 2.15% for β-thalassemia, and 0.12% for both α- and β-thalassemia. The highest carrier rate of thalassemia was in Yongzhou (14.57%). The most abundant genotype of α-thalassemia and β-thalassemia was -α ^3.7/αα (50.23%) and β ^IVS-II-654/β ^N (28.23%), respectively. Four α-globin mutations [CD108 (ACC>AAC), CAP +29 (G>C), Hb Agrinio and Hb Cervantes] and six β-globin mutations [CAP +8 (C>T), IVS-II-848 (C>T), -56 (G>C), beta nt-77 (G>C), codon 20/21 (-TGGA) and Hb Knossos] had not previously been identified in China. Furthermore, this study provides the first report of the carrier rates of abnormal hemoglobin variants and α-globin triplication in Hunan Province, which were 0.49% and 1.99%, respectively. CONCLUSION Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan population. The results should facilitate genetic counselling and the prevention of severe thalassemia in this region.
Humans ; beta-Thalassemia/genetics* ; alpha-Thalassemia/genetics* ; Hemoglobinopathies/genetics* ; China/epidemiology* ; High-Throughput Nucleotide Sequencing

ObjectiveTo investigate the analgesic effect and mechanism of Osteoking （OK） on nerve compression in lumbar disc herniation. MethodThe rat model of chronic compression of dorsal root ganglion （CCD） was established to simulate clinical lumbar disc herniation. The CCD rats were randomly divided into model group， low， medium， and high dose OK groups （1.31， 2.63， 5.25 mL·kg^-1·d^-1）， and pregabalin group （5 mg·kg^-1）， with eight rats in each group. Another eight SD rats were taken as the blank group， and the same volume of normal saline was given by gavage. Behavioral tests， side effect evaluation， network analysis， Western blot， immunofluorescence， and antagonist application were used to explore the effect. ResultCompared with the blank group， the mechanical hyperalgesia threshold， thermal hyperalgesia threshold， and the expression of inflammatory factors in the spinal dorsal horn of the model group are significantly increased （P<0.01）， and the related indicators of the affected foot footprints are significantly down-regulated （P<0.01）. The expression of signal transducer and activator of transcription 3 （STAT3）， vascular endothelial growth factor A （VEGFA）， and phosphorylated extracellular regulated protein kinase （p-ERK） in microglia in the spinal dorsal horn is significantly increased in the model group （P<0.01）. Compared with the model group， low， medium， and high dose OK groups can increase the mechanical hyperalgesia and thermal hyperalgesia thresholds of CCD rats （P<0.05， P<0.01） in a dose-dependent manner， improve the gait of CCD rats （P<0.05， P<0.01）， and reduce the expression of inflammatory factors in the spinal dorsal horn （P<0.05， P<0.01）. The expression of STAT3， VEGFA， and p-ERK in the spinal dorsal horn microglia of CCD rats is significantly decreased （P<0.05， P<0.01）， and the acetic acid-induced nociceptive response in rats is effectively reduced （P<0.05， P<0.01）. In addition， there is no tolerance. The results of the body mass test， organ index， forced swimming， and rotation show that OK has no obvious toxic or side effects. Further antagonist experiments show that MRS1523 and RS127445 can reverse the transient analgesic effect of OK compared with the high dose OK group （P<0.01）. ConclusionOK has a good analgesic effect on the CCD model without obvious toxic side effects， and its mechanism may be related to the activation of ADORA3 and HTR2B and the inhibition of STAT3， VEGFA， p-ERK， and other elements in microglia.

Animals ; Rats ; Diabetes Mellitus ; Vascular Endothelial Growth Factor A