Objective To construct 5 machine-learning models and compare their performance in predicting the associations between pre-pregnancy socio-psycho-behavioral exposures of both spouses and preconception outcomes.Methods Based on Chongqing Preconception Reproductive Health and Birth Outcome Cohort of volunteers recruited from Chongqing Health Center for Women and Children during January 2019 and March 2022,5 447 couples were recruited and surveyed through interviewer-interview for the demographic and social-psychological-behavioral data of both spouses(221 variables).According to the inclusion and exclusion criteria,4 097 couples were finally included,and randomly assigned into a training set(n=2 867 spouses)and a validation set(n=1 230 spouses)at a ratio of 7∶3.Feature analysis and collinear screening were applied to select the potential exposure factors.In consideration of difficulty to carry out semen parameters analysis in primary healthcare institutions,feature Set 1 including sperm parameters and feature Set 2 excluding semen parameters were constructed by including or excluding sperm quality simultaneously in the training set and the validation set.Five algorithms,that is,Logistic Regression,Naive Bayes,Random Forest,Gradient Boosting Machine,and Support Vector Machine,were used to construct preconception outcome prediction models,and the parameters of each model were optimized using random search combined with grid search.The predictive performance of each model was compared using precision,recall,F1 score,area under the receiver operating characteristic curve(AUC),and calibration curve.The optimal model was then selected by comparing the changes in the predictive ability of the questionnaire data for fertility outcomes with or without semen parameters.Results There were 24 variables screened out in feature Set 1,and 16 variables in feature Set 2.In feature Set 1,the gradient boosting machine performed better,with a relatively higher AUC value(0.651)and better F1 score(0.61).The logistic regression model performed stably(AUC value=0.647)and was suitable as the reference model.The random forest(AUC value=0.641),Naive Bayes(AUC value=0.641),and support vector machine(AUC value=0.634)performed second-best.By utilizing the gradient boosting machine,comparable results were found between the predictions from feature sets with or without semen parameters,as in feature Set 1,the AUC value of its validation set was 0.651(95%CI:0.629～0.681),the prediction accuracy was 0.63,the recall rate was 0.65,and the average precision value F1 was 0.61;and in feature Set 2,the AUC value of its validation set was 0.649(95%CI:0.624～0.663),and both the calibration curves were close to the ideal curve.The prediction results indicated that in feature Set 1,the features highly negatively correlated with preconception outcomes were female age,male age,and no pregnancy within 1 year without contraception,while the features highly positively correlated with preconception outcomes were female pregnancy history,total sperm vitality,and use of contraceptive measures before enrollment.Conclusion Among the 5 machine-learning algorithms performed in this cohort data,the gradient boosting machine shows slightly better performance.There are 24 factors being associated with preconception outcomes in both spouses,and the performance of the simplified model excluding semen parameters is not significantly declined.It is feasible to use machine-learning methods to predict human preconception outcomes through social-psychological-behavioral questionnaires.

BACKGROUND:Abnormal extracellular matrix accumulation and excessive proliferation of fibroblasts are the main manifestations of pathological scars.Excessive proliferation of fibroblasts leads to the production of large amounts of collagen-based extracellular matrix.Therefore,to investigate the role of fibroblast fibrosis in the formation of pathological scar will provide a new idea for revealing the mechanism of pathological scar and biological therapy. OBJECTIVE:To investigate the effect of RAS-selective lethal small molecule 3(RSL3)on the fibrosis of human pathological scar fibroblasts. METHODS:Then cases of pathological scar tissue and normal skin tissue samples from the same individuals,provided by the Department of Burn Plastic Surgery,General Hospital of Ningxia Medical University,were collected.Fibroblasts of human pathological scar and human normal skin were extracted and used in the following experiments.The general condition of the pathological scar tissue and the normal skin tissue was detected by hematoxylin-eosin staining.The appearance of fibroblasts from pathological scar and normal skin were observed by inverted microscope.The fibroblasts were verified by immunofluorescence assay.The cells were treated with different concentrations of RSL3(1,3,5,7,9,11,13 μmol/L).The inhibitory concentration of RSL3 on fibroblasts was detected by cell counting kit-8.Control group(without treatment)and RSL3 intervention group(treated with 7 μmol/L RSL3 for 24 hours)were set up.The mRNA and protein expressions of glutathione peroxidase 4,type Ⅰ collagen,type Ⅲ collagen and α-smooth muscle actin were detected by Qrt-PCR and western blot,respectively.Level of malondialdehyde in cells was detected.The residual scratch area was measured by cell scratch test after 24 hours to calculate the percentage of residual scratch area. RESULTS AND CONCLUSION:The expression of glutathione peroxidase 4 in the pathological scar group was higher than that in the normal skin group(Mrna:t=3.252,P<0.01;protein:t=5.075,P<0.01).The expression of glutathione peroxidase 4 in the pathological scar fibroblast group was higher than that in the normal skin fibroblast group(Mrna:t=10.32,P<0.01;protein:t=26.22,P<0.01).Compared with the control group,the expression of glutathione peroxidase 4 was decreased(Mrna:t=2.798,P<0.05;protein:t=4.643,P<0.01),the content of malondialdehyde was increased(t=2.917,P<0.05),the expression of type Ⅰ collagen(Mrna:t=15.84,P<0.01;protein:t=4.610,P<0.01),type Ⅲ collagen(Mrna:t=28.86,P<0.01;protein:t=7.713,P<0.01)and α-smooth muscle actin(Mrna:t=2.671,P<0.05;protein:t=7.417,P<0.01)were decreased in the RSL3 intervention group.Compared with the control group,the migration ability was weakened in the RSL3 intervention group(t=14.06,P<0.01).To conclude,RSL3 can inhibit the expression of glutathione peroxidase 4 and then inhibit the ability of fibrosis and migration of pathological scar fibroblasts.

Objective To investigate the effect of chronic psychological stress on testicular cell senescence in rats and the role of glucocorticoid receptor(GR)in the process.Methods Thirty-two male SD rats(4～6 weeks old,weighing 120～140 g)were randomly assigned into dimethyl sulfoxide(DMSO)group,mifepristone(RU486)group,chronic unpredictable mild stress(CUMS)group,and CUMS+RU486 group.DMSO of 0.5 ml/(kg·d)was injected subcutaneously into the rats of DMSO group.After the rats of the CUMS group were exposed to CUMS,mifepristone of 1 mg/(kg·d)was given to the rats of the RU486 group and CUMS+RU486 group.All the above 4 groups were inflicted for 42 consecutive days.After modeling,the psychological stress status of rats was evaluated with animal behavioral experiments.Computer-aided sperm analysis(CASA)system was used to detect sperm density.ELISA was employed to measure the serum levels of corticosterone(CORT),sex hormones and inflammation factors.The contents of malondialdehyde(MDA),H2O2,NAD+/NADH and ATP in the testicular tissues were tested with corresponding reagent kits.Western blotting was utilized to detect protein levels of[3-gal,p16,and GR in testicular tissue,and transmission electron microscopy was used to observe mitochondrial structure of spermatogenic cells.Results Compared with the DMSO group,the sperm density,serum levels of testosterone(T),luteinizing hormone(LH)and follicle stimulating hormone(FSH)were decreased while those of CORT and estradiol(E2)were increased in the CUMS group(all P＜0.001).Serum pro-inflammatory factors IL-6 and TNF-α concentrations were increased while anti-inflammatory factor IL-10 concentration was decreased in the CUMS group than the DMSO group(all P＜0.05).And,ATP content and NAD+/NADH ratio were decreased while MDA and H2O2 levels were elevated in testicular tissues in the CUMS group(all P＜0.05).Moreover,the protein levels of testicular cell aging markers β-gal,p16 and GR were significantly enhanced in the CUMS group(all P＜0.01),accompanied by swelling and vacuolization of mitochondrial structures in spermatogenic cells.RU486 treatment effectively improved sperm density and increased CORT level and down-regulated the testicularβ-gal,p16 and GR protein level(all P＜0.05).Conclusion Chronic psychological stress induces testicular damage in rats,presenting declines in sperm density and CORT level,which is possibly associated with GR-mediated cell senescence.

OBJECTIVES: To design and prepare silk fibroin/hyaluronic acid composite hydrogel. METHODS: The thiol modified silk fibroin and the double-bond modified hyaluronic acid were rapidly cured into gels through thiol-ene click polymerization under ultraviolet light condition. The grafting rate of modified silk fibroin and hyaluronic acid was characterized by ¹H NMR spectroscopy; the gel point and the internal microstructure of hydrogels were characterized by rheological test and scanning electron microscopy; the mechanical properties were characterized by compression test; the swelling rate and degradation rate were determined by mass method. The hydrogel was co-cultured with the cells, the cytotoxicity was measured by the lactate dehydrogenase method, the cell adhesion was measured by the float count method, and the cell growth and differentiation on the surface of the gel were observed by scanning electron microscope and fluorescence microscope. RESULTS: The functional group substitution degrees of modified silk fibroin and hyaluronic acid were 17.99% and 48.03%, respectively. The prepared silk fibroin/hyaluronic acid composite hydrogel had a gel point of 40-60 s and had a porous structure inside the gel. The compressive strength was as high as 450 kPa and it would not break after ten cycles. The water absorption capacity of the composite hydrogel was 4-10 times of its own weight. Degradation experiments showed that the hydrogel was biodegradable, and the degradation rate reached 28%-42% after 35 d. The cell biology experiments showed that the cytotoxicity of the composite gel was low, the cell adhesion was good, and the growth and differentiation of the cells on the surface of the gel were good. CONCLUSIONS The photocurable silk fibroin/hyaluronic acid composite hydrogel can form a gel quickly, and has excellent mechanical properties, adjustable swelling rate and degradation degree, good biocompatibility, so it has promising application prospects in biomedicine.
Fibroins/chemistry* ; Hydrogels/chemistry* ; Hyaluronic Acid/chemistry* ; Biocompatible Materials/chemistry* ; Click Chemistry ; Sulfhydryl Compounds ; Silk/chemistry*

Objective To study the inhibitory effect of recombinant human interferon α1b (IFN-α1b) on enterovirus 71 (EV71) in vitro and to investigate the antiviral mechanism of IFN-α1b.Methods The cytotoxity of IFN-α1b and the inhibition of IFN-α1b on cytopathic effect before and after EV71 infection were measured in rhabdomyosarcoma (RD) cell line.The in vitro inhibition of IFN-α1b on EV71 RNA and VP1 protein,and the protection of IFN-α1b on EV71 infected cells were also investigated.Then the EV71 invasion prevention of IFN-α1b induced transmembrane protein IFITM3 was evaluated.Results When treated 12h before or 1h after EV71 infection,IFN-α1b presented a IC50 258.53IU/ml and 2113.58IU/ml with SI>16497 and >3271,respectively,suggesting that IFN-α1b had obvious anti EV71 activity,and IFN-α1b treatment before EV71 infection was more effective.This study also showed that IFN-α1b significantly inhibited EV71 RNA replication and protein synthesis,and delayed the progeny virus release,which might prevent EV71 invasion by inducing IFITM3 expression.Conclusion IFN-α1b has anti EV71 activity and can act as an antiviral agent by influencing the viral life cycle including invasion,replication,assembly and release.

Inflammation response is the most crucial link in the pathogeneses of spinal cord injury (SCI),and is the basis of secondary damage. NF-κB Signalling pathway is activated excessively after SCI,so that numerous NF-κB possessing biological activities is quickly translocated into the nuclear and regulates the target genes,resulting in heightened inflammation and further tissue damage. Suppressing NF-κB signalling pathway and controlling inflammation response effectively are effective approaches to promoting SCI repair. It is found that curcumin has multiple target molecules to suppress NF-κB signalling pathway,block the excessive activation of NF-κB and reduce the expression of proinflammation cytokines,which plays an important role in SCI repair. This article discusses NF-κB signalling pathway,the contribution of NF-κB signalling pathway to SCI and the role of curcumins inhibition of NF-κB signalling pathway in SCI.

Objective To observe the effect of laparoscopic operation( LPS) for the treatment of endometrio-sis(EMS) infertile serum matrix metalloproteinase in patients of matrix metalloproteinases-9(MMP-9),tissue inhibi-tors of metalloproteinase-1(TIMP-1) and interleukin-2 (IL-2),interleukin-10(IL-10) .Methods 80 patients with EMS in 2012 August to 2013 August to accept the choice of operation cases,according to the different operation modes for the observation group(received LPS operation therapy) and control group(received open operation treatment), 40 cases in each group.The changes of serum MMP9, TIMP-1, MMP-9/TIMP-1 and IL-2, IL-10, IL-2/IL-10 and 6 months after operation in the two groups were observed before and after treatment,the pregnancy situation were ob-served.Results The MMP-9 levels of the patients in the observation group[(51.21 ±24.01)μg/L] than before treatment[(261.88 ±190.11)μg/L] decreased significantly,and the observation group decreased more obviously than that in the control group;the observation group the level of TIMP-1[ (45.88 ±11.02)μg/L] than in the control group[(25.32 ±6.67)μg/L]increased significantly (t =4.846,P <0.05);observation group MMP-9/TIMP-1 decreased significantly compared with the control group,the difference was statistically significant ( t=3.636,P<0.05);the two group after treatment,IL-2,IL-10,IL-2/IL-10,the difference was statistically significant ( t=4.228, 4.415,3.396,all P<0.05);the observation group the pregnancy rate was 65%,the abortion rate 7.7%,30.0%and the 33.3%was better than that of the control group (χ2 =9.825,4.060,all P<0.05).Conclusion LPS is an effective method in treating EMS,which can increase the serum TIMP-1 and IL-2 levels,reduce MMP9 and IL-10 level;improve the immune index,improve the patient's fertility.

Objective To explore the clinical characteristics and management of urinary tract injuries incidental in gynecologic surgery. Methods Urinary tract injuries in gynecologic surgery during the past 10 years were reviewed retrospectively.The clinical features of initial operations including the types of disease,operative procedures and the methods of diagnosis and treatment was studied. Results 21 urological injuries were incurred during the performance of 6075 gynecologic surgical procedures,an incidence of 0.35% including of 10 ureter injuries and 11 bladder injuries with incidence of 0.16% and 0.18% respectively. The time of diagnosis from 0 to 23 days postoperatively.As for operation way,Laparoscopic surgery 10 cases(48%),radical surgery for cancer 7 cases(33%),other surgery 4 cases.injury of urinary tract was found intraoperatively in 15 patients(67%) and postoperatively in 7 patients(33%).Urinary fistulae occurred in 6 patients(29%).Urinary tract injuries were mainly diagnosed methylene blue infusion,via excretory urogram(IVP),CTU.An appropriate repair during operation,putting the doubleJ-catheter and catheterization was useful. Conclusion The rate of urinary tract injury is increased as more patients received laparoscopic surgery.Most of urinary tract injuries in gynecologic surgery had optimal results when they were diagnosed early and managed correctly.