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 explore the safety and efficacy of high-dose etoposide (VP-16) combined with recombinant human granulocyte colony-stimulating factor (rhG-CSF) as salvage mobilization for peripheral blood stem cells (PBSC) in newly diagnosed multiple myeloma (NDMM) patients. METHODS: From April 2021 to May 2023, eight NDMM patients who had failed to yield sufficient PBSC during initial mobilization with high-dose cyclophosphamide (CTX) combined with rhG-CSF underwent salvage mobilization with 1.2 g/m2 etoposide combined with rhG-CSF 10 μg/(kg·d). The effects and adverse reactions of initial mobilization and salvage mobilization were analyzed. RESULTS: For salvage mobilization and initial mobilization, the numbers of PBSC collections were 16 and 18, respectively. The mean value of total collected CD34⁺ cells were (11.90±5.75)×10⁶/kg and (1.67±0.75)×10⁶/kg (P =0.0010) in salvage mobilization group and initial mobilization group, respectively. The proportion of patients with a total collection of CD34⁺ cell count≥2×10⁶/kg were 100% and 37.5% (P =0.0625), and the proportion of patients with a total collection of CD34⁺ cell count≥5×10⁶/kg were 87.5% and 0% (P =0.0156) in salvage mobilization group and initial mobilization group, respectively. For five patients who underwent high-dose CTX initial mobilization but had a total CD34⁺ cell count < 2×10⁶/kg, successful collection was achieved through salvage mobilization with high-dose VP-16. Salvage mobilization with high-dose VP-16 was scheduled 2-3 weeks after failure of CTX mobilization. Adverse reactions of high-dose VP-16 mobilization did not increase compared to the initial mobilization with high-dose CTX. CONCLUSION As a salvage mobilization regimen, VP-16 1.2 g/m² combined with rhG-CSF is safe and highly effective in NDMM patients who failed to initial mobilization with high-dose CTX combined with rhG-CSF.
Humans ; Multiple Myeloma/therapy* ; Etoposide/therapeutic use* ; Hematopoietic Stem Cell Mobilization/methods* ; Cyclophosphamide/therapeutic use* ; Granulocyte Colony-Stimulating Factor ; Salvage Therapy ; Peripheral Blood Stem Cells ; Male ; Middle Aged ; Female ; Peripheral Blood Stem Cell Transplantation

Acute mitochondrial damage and the energy crisis following axonal injury highlight mitochondrial transport as an important target for axonal regeneration. Syntaphilin (Snph), known for its potent mitochondrial anchoring action, has emerged as a significant inhibitor of both mitochondrial transport and axonal regeneration. Therefore, investigating the molecular mechanisms that influence the expression levels of the snph gene can provide a viable strategy to regulate mitochondrial trafficking and enhance axonal regeneration. Here, we reveal the inhibitory effect of microRNA-146b (miR-146b) on the expression of the homologous zebrafish gene syntaphilin b (snphb). Through CRISPR/Cas9 and single-cell electroporation, we elucidated the positive regulatory effect of the miR-146b-snphb axis on Mauthner cell (M-cell) axon regeneration at the global and single-cell levels. Through escape response tests, we show that miR-146b-snphb signaling positively regulates functional recovery after M-cell axon injury. In addition, continuous dynamic imaging in vivo showed that reprogramming miR-146b significantly promotes axonal mitochondrial trafficking in the pre-injury and early stages of regeneration. Our study reveals an intrinsic axonal regeneration regulatory axis that promotes axonal regeneration by reprogramming mitochondrial transport and anchoring. This regulation involves noncoding RNA, and mitochondria-associated genes may provide a potential opportunity for the repair of central nervous system injury.
Animals ; Zebrafish ; MicroRNAs/genetics* ; Nerve Regeneration/physiology* ; Mitochondria/metabolism* ; Zebrafish Proteins/genetics* ; Axons/metabolism* ; Signal Transduction/physiology* ; Axonal Transport/physiology* ; Nerve Tissue Proteins/genetics*

Objective To develop a deep learning model based on fundus retinal images to improve the detection rate of mild cognitive impairment(MCI)in patients with coronary heart disease,achieve early intervention and improve prognosis.Methods The study was a single-center cross-sectional study that retrospectively included patients diagnosed with coronary heart disease(CHD)by coronary angiography(≥50％ stenosis of at least one coronary vessel)from Beijing Anzhen Hospital between November 2021 and December 2022.The whole data set was randomly divided into the training set and the testing set according to the ratio of 8∶2 for model development.After that,the patient data of the same center from January 2023 to April 2023 were included in the time verification method to verify the model.The diagnostic criteria for MCI were MMSE＜27 or MoCA＜26.Four kinds of convolutional neural network(CNN)architectures were used to train fundus images,and a comprehensive vision model of MCI detection was established through model integration.The area under the curve(AUC),sensitivity and specificity of the receiver operating curve(ROC)were used to evaluate the performance of the AI model.Results We collected 5 880 eligible fundus images from 3 368 CHD patients.Based on the results of the MMSE scale,the algorithm was labeled,including 2 898 males and 527 MCI patients.The AUC of the deep learning model in the test group is 0.733(95％CI 0.688-0.778),and the sensitivity of the algorithm in the test group is 0.577(95％CI 0.528-0.625)by using the operating point with the maximum sum of sensitivity and specificity.With a specificity of 0.758(95％CI 0.714-0.802),corresponding to a validated AUC of 0.710(95％CI 0.601-0.818).Based on the results of the MoCA scale,the algorithm labels 2 437 males and 1 626 MCI patients.The AUC of the deep learning model in the test group was 0.702(95％CI 0.671-0.733).The operating point with the maximum sum of sensitivity and specificity was selected,and the sensitivity of the algorithm was 0.749(95％CI 0.719-0.778)and the specificity was 0.561(95％CI 0.527-0.595),corresponding to the AUC value of the verification group was 0.674(95％CI 0.622-0.726).Conclusions The deep learning algorithm model based on fundus images has good diagnostic performance,and may be used as a new non-invasive,convenient and rapid screening method for MCI in CHD population.

Objective To investigate the effect and mechanism of edaravone(Eda)on myocardial injury in chronic heart failure(CHF)rats by regulating Notch/Hes-1 signaling pathway.Methods The CHF rat model was established and the rats were separated into sham surgery(S)group,model(M)group,low dose Eda(Eda-L)group,medium dose Eda(Eda-M)group,high dose Eda(Eda-H)group,and Eda-H+Notch signal pathway inhibitor DAPT(Eda-H+DAPT)group,with 25 rats in each group.Echocardiography was applied to detect the levels of left ventricular end diastolic diameter(LVEDd),left ventricular end-systolic diameter(LVEDs),and left ventricular ejection fraction(LVEF)in rats.ELISA was applied to detect levels of tumor necrosis factor-α(TNF-α),interleukin(IL)-1β,IL-6,malondialdehyde(MDA),superoxide dismutase(SOD),and angiotensin Ⅱ(Ang Ⅱ)in serum.Myocardial infarction was observed by 2,3,5-triphenyl tetrazolium chloride(TTC)staining.HE staining,TUNEL staining and Masson staining were applied to observe the morphological changes of myocardial tissue,myocardial cell apoptosis and myocardial fibrosis respectively.immunohistochemistry was applied to detect the expression of collagen Ⅰ and angiotensin converting enzyme 2(ACE2)proteins in myocardial tissue.Western blotting was applied to detect the expression of Notch 1,Hes-1,transforming growth factor-β1(TGF-β1),Bcl-2,Bax,and Caspase-3 proteins in myocardial tissue.Results Compared with the sham group,the distribution of cardiomyocytes in model group was disordered,and severe inflammatory symptoms.There was a large amount of blue collagen deposition between the perivascular area and the myocardium.The LVEDd,LVEDs,TNF-α,IL-1β,IL-6,MDA and Ang Ⅱ levels,myocardial infarction size,cardiomyocyte apoptosis rate,Collagen Ⅰ,Bax,Caspase-3 and TGF-β1 protein expressions increased obviously(P＜0.05),the LVEF,SOD levels,ACE2,Bcl-2,Notch 1,and Hes-1 protein expressions were obviously reduced(P＜0.05).Compared with the model group,the myocardial tissue damage was reduced in the Eda-L,Eda-M,and Eda-H groups,with reduced inflammatory cell infiltration and collagen deposition;The LVEDd,LVEDs,TNF-α,IL-1β,IL-6,MDA and Ang Ⅱ levels,myocardial infarction size,cardiomyocyte apoptosis rate,collagen Ⅰ,Bax,Caspase-3 and TGF-β1 protein expressions reduced obviously(P＜0.05),the LVEF,SOD levels,ACE2,Bcl-2,Notch 1,and Hes-1 protein expressions increased obviously(P＜0.05).Notch signaling pathway inhibitor DAPT reversed the protective effect of edaravone on myocardial injury in rats with CHF(P＜0.05).Conclusion Edaravone may improve myocardial injury in CHF rats by activating Notch/Hes-1 signaling pathway.

Objective:To analyze the clinical characteristics and cytokines expression characteristics in infants with mild and severe respiratory syncytial virus (RSV) infection.Methods:From May 2023 to December 2023, plasma samples and clinical information were collected from 16 infants with RSV infection and 14 control infants. Cytek Aurora flow cytometry (Cytek, America) and Enzyme linked immunosorbent assay (ELISA) were used to detect the expression levels of 25 cytokines after mild and severe RSV infection.Results:Cough and nasal obstruction were the main clinical manifestations in infants with mild RSV infection, accompanied by polypnea, wheezing and other symptoms. The main symptoms of severe RSV infection were cough and rales, accompanied by fever and polypnea. In comparison with the control group, the expression levels of IL-2, IL-4, IL-5, IL-6, IL-9, IL-13, IL-22, TNF-α, IFN-α, IFN-β, MIP-1β, I-TAC, ENA-78, GROα, Eotaxin, and MCP-1 in the RSV infection group all exhibited an upregulation trend. Both IP-10 and MIP-3α demonstrated a downward trend in the RSV infection group; however, there was no statistically significant difference ( P>0.05). The levels of IL-10, IFN-γ, MIP-1α, and IL-8 in the RSV infection group were significantly higher than those in the control group, whereas the levels of MIG, TARC, and RANTES in the RSV infection group were significantly lower than those in the control group ( P<0.05). The levels of IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-13, IL-22, IFN-β, IFN-γ, TNF-α, IL-8, I-TAC, MIP-1β, Eotaxin, and MCP-1 in the mild RSV infection group were significantly higher than those in the severe RSV infection group ( P>0.05). Among these, the levels of MIG, RANTES, TARC, MIP-3α, and ENA-78 in the mild infection group were all lower than those in the severe infection group. The expressions of ENA-78 and MIP-1α in the severe infection group were significantly higher than those in the mild infection group and also higher than those in the control group. There was no significant difference in IP-10 and GROα between the mild and severe RSV infection groups ( P>0.05). Conclusions:The differences in clinical features and cytokines between infants with mild and severe RSV infection provide important data support for the prevention and treatment of RSV infection in infants.

Objective:To explore the therapeutic effect of drug-coated balloon(DCB)combined drug-eluting stent(DES)on coronary bifurcation lesions.Methods:A total of 108 patients with coronary bifurcation lesions admitted in Shanghai Ninth People's Hospital Huangpu Branch,Shanghai Jiaotong University School of Medicine between February 2021 and March 2023 were enrolled in this randomized controlled study.Patients were randomly divided into combined treatment group(n=54,DCB was implanted in the sub-branch,and DES was implanted in the main branch)and DES group(n=54,DES were implanted in both main branch and sub-branch).Clinical therapeutic effect,coronary angiography quantitative parameters before,instant and 9 months after operation and clinical out-comes during 1-year follow-up after operation were compared between two groups.Results:The total effective rate of combined treatment group was significantly higher than that of DES group(96.30％vs.87.04％,P=0.030).Compared to those in DES group,instant and 9 months after operation,patients in the combined treatment group had significant higher diameters of main branch vessel[(3.13±0.31)mm vs.(3.01±0.25)mm,(2.99±0.33)mm vs.(2.84±0.23)mm],sub-branch vessel[(2.51±0.26)mm vs.(2.42±0.13)mm,(2.44±0.24)mm vs.(2.29±0.36)mm],and significant lower main branch stenosis rate[(6.05±0.21)％vs.(6.24±0.31)％,(9.06±0.23)％vs.(10.12±0.12)％]and sub-branch stenosis rate[(7.38±0.42)％vs.(7.63±0.18)％,(8.07±0.39)％vs.(11.25±0.22)％](P＜0.05 or＜0.01).There were no significant difference in incidence of target lesion revascularization,cardiogenic death and major adverse cardiovascular events between two groups(P＞0.05 all).Conclusion:Drug-eluting stent combined drug-coated balloon may promote vascular branch dilation of coro-nary artery lesions,increase the minimum lumen diameter of sub-branch vessels,and reduce the occurrence of ste-nosis in the treatment of coronary bifurcation lesion,which had similar effectiveness and safety with drug-eluting stent technique.

Objective To explore the improvement effect of ultrasound microbubble blasting assisted bone marrow mesenchymal stem cells(BMSC)transplantation on diabetic nephropathy(DN)in terms of inflammatory response and renal function via the Toll like receptor 4(TLR-4)/nuclear factor-kappa B(NF-κB)signaling pathway,as well as its specific mechanism.Methods A rat DN model was estab-lished and randomly grouped into the following:Model group,BMSC group,BMSC+microbubble group,and BMSC+microbubble+TLR-4/NF-κB pathway activator lipopolysaccharide(LPS)group,with 12 rats in each group.Additionally,12 rats were selected as the control(CK)group.Biochemical and biuret analysis,HE and Masson staining,ELISA,and Western blotting testing were employed to detect fasting blood glucose(FBG),total cholesterol(TC),triglyceride(TG),serum creatinine(sCr),blood urea nitrogen(BUN),24-hour urinary total protein(24 h-UTP),pathological changes in renal tissue,fibrosis status,and the expression of interleukin-1 β(IL-1β),tumor necrosis factorα(TNF-α),TLR-4,and NF-κB proteins of rats in each group.Results The renal tissue in the CK group was structurally normal with few collagen fibers.The Model group showed obvious renal tissue lesions and severe collagen fiber deposition;the lesions in the BMSC group and BMSC+microvesicle group were alleviated in turn,while the lesions were aggravated after the addition of LPS compared with the BMSC+microvesicle group.Compared with the CK group,the levels of FBG,TC,TG,sCr,BUN,24 h-UTP,as well as the expression of IL-1β,TNF-α,TLR-4,and NF-κB proteins were increased in the Model group(P＜0.05).Compared with the Model group,the above-men-tioned indices and protein expression were decreased in the BMSC group(P＜0.05).Compared with the BMSC group,the above-men-tioned indices and protein expression were further decreased in the BMSC+microvesicle group(P＜0.05).Compared with the BMSC+mi-crovesicle group,the above-mentioned indices and protein expression were increased in the BMSC+microvesicle+LPS group(P＜0.05).Conclusion The improvement effect of ultrasound microbubble blasting-assisted BMSC transplantation on DN rats may be related to the inhibition of the TLR-4/NF-κB signaling pathway.

Objective To explore the improvement effect of ultrasound microbubble blasting assisted bone marrow mesenchymal stem cells(BMSC)transplantation on diabetic nephropathy(DN)in terms of inflammatory response and renal function via the Toll like receptor 4(TLR-4)/nuclear factor-kappa B(NF-κB)signaling pathway,as well as its specific mechanism.Methods A rat DN model was estab-lished and randomly grouped into the following:Model group,BMSC group,BMSC+microbubble group,and BMSC+microbubble+TLR-4/NF-κB pathway activator lipopolysaccharide(LPS)group,with 12 rats in each group.Additionally,12 rats were selected as the control(CK)group.Biochemical and biuret analysis,HE and Masson staining,ELISA,and Western blotting testing were employed to detect fasting blood glucose(FBG),total cholesterol(TC),triglyceride(TG),serum creatinine(sCr),blood urea nitrogen(BUN),24-hour urinary total protein(24 h-UTP),pathological changes in renal tissue,fibrosis status,and the expression of interleukin-1 β(IL-1β),tumor necrosis factorα(TNF-α),TLR-4,and NF-κB proteins of rats in each group.Results The renal tissue in the CK group was structurally normal with few collagen fibers.The Model group showed obvious renal tissue lesions and severe collagen fiber deposition;the lesions in the BMSC group and BMSC+microvesicle group were alleviated in turn,while the lesions were aggravated after the addition of LPS compared with the BMSC+microvesicle group.Compared with the CK group,the levels of FBG,TC,TG,sCr,BUN,24 h-UTP,as well as the expression of IL-1β,TNF-α,TLR-4,and NF-κB proteins were increased in the Model group(P＜0.05).Compared with the Model group,the above-men-tioned indices and protein expression were decreased in the BMSC group(P＜0.05).Compared with the BMSC group,the above-men-tioned indices and protein expression were further decreased in the BMSC+microvesicle group(P＜0.05).Compared with the BMSC+mi-crovesicle group,the above-mentioned indices and protein expression were increased in the BMSC+microvesicle+LPS group(P＜0.05).Conclusion The improvement effect of ultrasound microbubble blasting-assisted BMSC transplantation on DN rats may be related to the inhibition of the TLR-4/NF-κB signaling pathway.

OBJECTIVE To analyze the characteristics of imported malaria cases in West China Hospital of Sichuan University in recent years and to provide reference for the prevention and control of imported infectious diseases.METHOD A retrospective analysis of 62 cases of imported malaria from abroad reported in West China Hospital of Sichuan University from 2012 to 2023 were retrospectively analyzed.RESULTS From 2012 to 2023,62 cases of imported malaria were reported,including 49 cases(79.03％)of falciparum malaria,10 cases(16.13％)of vivax malaria,and 3 cases(4.84％)of ovale malaria.Among the imported malaria cases,9 cases were severe malaria,with 8(16.33％,8/49)severe cases caused by falciparum malaria,of which 6 cases(75.00％,6/8)were cere-bral malaria.The cases were mainly Chinese citizens and young-to-middle-aged adults,with the highest concentra-tion in the 40-49 age group(37.10％,23/62).There were more males than females,with a male-to-female sex ratio of 11.4∶1;the predominant occupation was worker(38.71％,24/62).The primary region of importation was Africa(90.32％,56/62).There was importation throughout the year,with no distinct seasonal distribution pattern.Two of the admitted cases died(severe cases of falciparum malaria,which developed into cerebral malari-a),while the rest were improved and discharged from the hospital after standardized treatment.CONCLUSIONS Cases of imported malaria from abroad are characterized by Chinese nationality,males,young adults and workers.The type of malaria is mainly falciparum malaria,and the prognosis for most cases is relatively good.It is necessary to strengthen the construction of joint prevention and control systems and other long-term mechanisms,and to continuously and scientifically implement various strategies and measures to prevent the re-emergence of malaria through imported ca-ses,in order to avoid the occurrence of secondary cases resulting from imported infections.