Objective To explore the influencing factors of pregnancy outcome after re-pregnancy in patients with unexplained recurrent spontaneous abortion based on ultrasound endometrial receptability parameters and lymphocyte immunophenotype.Methods A total of 166 re-pregnant patients with unexplained recurrent spon-taneous abortion admitted to Nantong Maternal and Child Health Hospital from April to August 2022 were included in the study.According to the pregnancy outcome,the patients were divided into the delivery group and the abortion group.The endometrial receptability parameters and peripheral blood T lymphocytes were detected to screen the influencing factors of abortion.Results Among 166 patients,102 cases(61.45%)had successful delivery and 64 cases(38.55%)had abortion again.The delivery group showed thicker endometrial thickness,larger endometrial volume,and higher VFI,but lower CD4+ and CD4+/CD8+ compared to the abortion group(P<0.05).CD4+ and CD4+/CD8+ were observed to be the risk factors for pregnancy failure(P<0.05),and endometrial thickness,endo-metrial volume,and vascularized flow index(VFI)were found to be the protective factors for pregnancy failure(P<0.05).Conclusion The pregnancy outcome of patients with unexplained recurrent spontaneous abortion is related to endometrial thickness,endometrial volume,VFI,CD4+,and CD4+/CD8+.

Microglial surveillance plays an essential role in clearing misfolded proteins such as amyloid-beta, tau, and α-synuclein aggregates in neurodegenerative diseases. However, due to the complex structure and ambiguous pathogenic species of the misfolded proteins, a universal approach to remove the misfolded proteins remains unavailable. Here, we found that a polyphenol, α-mangostin, reprogrammed metabolism in the disease-associated microglia through shifting glycolysis to oxidative phosphorylation, which holistically rejuvenated microglial surveillance capacity to enhance microglial phagocytosis and autophagy-mediated degradation of multiple misfolded proteins. Nanoformulation of α-mangostin efficiently delivered α-mangostin to microglia, relieved the reactive status and rejuvenated the misfolded-proteins clearance capacity of microglia, which thus impressively relieved the neuropathological changes in both Alzheimer's disease and Parkinson's disease model mice. These findings provide direct evidences for the concept of rejuvenating microglial surveillance of multiple misfolded proteins through metabolic reprogramming, and demonstrate nanoformulated α-mangostin as a potential and universal therapy against neurodegenerative diseases.

Objective: To understand the prevalence and pattern of abnormal uterine bleeding (AUB) among female medical college students in Shanghai，to provide a basis for menstrual health intervention for female college students. Methods: A total of 912 female medical students from a university in Shanghai were selected through cluster sampling. An anonymous questionnaire survey on menstrual history and related factors was conducted in March 2021. Results: The prevalence of AUB among female medical college students was 39.9%, with cycle disordered and non cycle disordered AUB of 24.7% and 15.2%, respectively. Among female college students with AUB, 21.7% had two or three abnormal menstrual symptoms. Multivariate Logistic analysis showed that sleep quality was associated with both types of AUB, and female undergraduates with poorer and poor sleep quality were at increased risk of both cyclic disordered AUB ( OR =2.05) and non cyclic disordered AUB ( OR =2.00). Low BMI ( OR =1.66) and weight gain and loss ( OR =1.76) were associated with cycle disordered AUB. Frequent insomnia ( OR =2.45) was associated with non cyclic disordered AUB( P <0.05). Conclusion Abnormal uterine bleeding (AUB) is common in female college students, female medical college students with AUB have multiple concurrent abnormal bleeding patterns. Factors associated with AUB varied according to the type of AUB, with sleep quality correlates with both types of AUB.

ObjectiveTo develop a self-assessment questionnaire for menstrual abnormalities and test its reliability and validity. To provide an assessment tool for self-identification of abnormal menstruation in young women and to investigate the health seeking situation of abnormal menstruation in the population. MethodsFifteen physicians with clinical experience were invited to participate in the Delphi expert consultations. Medical indications for menstrual abnormalities were constructed and questionnaires were formed based on domestic and international literature， expert meetings and 2 rounds of Delphi expert consultations. A whole-group sampling was used to select 923 female college students from a medical school in Shanghai for the survey， and 306 of them were retested. The internal consistency， retest correlation， researcher-investigator evaluation correlation， and structural and response validity of the questionnaire were examined. ResultsThe questionnaire formed 6 dimensions with 17 indications. The positive coefficients for the two rounds of consulting experts were >90%. The mean authority coefficient was 0.857. The Kendall W coordination coefficient was 0.465 and 0.455， respectively （P<0.001）. The questionnaire Cronbach's alpha coefficient was 0.622. The retest correlation coefficient was 0.459. The correlation coefficient between the researcher's score and the respondents' self-assessment was 0.562. The five common factors extracted by factor analysis were consistent with the structure of the questionnaire， and the cumulative contribution of variance was 54.4%. Total questionnaire scores were moderately to highly correlated with each dimension score （0.409 to 0.699）. There was low correlation between the dimensions （-0.002 to 0.203）. Girls who had sought medical care had higher scores on the total questionnaire， category A， category B， cycle dimension， menstrual dimension， and dysmenorrhea/PMS dimension than girls who had not sought medical care （P<0.01）， and the difference between the two groups in menstrual volume dimension scores was not statistically significant. ConclusionThe self-assessment questionnaire for menstrual abnormalities developed in this study has acceptable reliability， good structure validity and response validity. It can provide a self-examination tool and medical consultation guidance for young women with abnormal menstruation.

Objective:Human leukocyte antigen(HLA)B27 is a susceptibility allele of ankylosing spondylitis(AS),and HLA-B27 antigen typing is an important indicator for clinical diagnosis of AS,but current typing methods such as sequence specific primer polymerase chain reaction(PCR-SSP)still possess limitation.Therefore,this study aims to analyze the correlation between B27 subtypes and susceptibility to AS in Hunan Province by applying high-resolution polymerase chain reaction-sequence-based typing(PCR-SBT). Methods:Peripheral blood of 116 patients with suspected AS(suspected AS group)and 121 healthy volunteers(control group)admitted to the Second Xiangya Hospital from January 2020 to December 2020 were collected for HLA-B genotyping by PCR-SBT.Among the patients in the suspected AS group,23 patients were finally diagnosed with AS(confirmed AS group),and the remaining 93 undiagnosed patients served as the non-confirmed AS group.PCR-SBT and PCR-SSP were used to detect HLA-B27 typing in 116 patients with suspected AS,and the results of the 2 methods were compared. Results:The HLA-B27 allele frequency in the suspected AS group was significantly higher than that in the control group[11.63%vs 2.48%;P<0.001,odds ratio(OR)=5.18,95%confidence interval(CI)2.097 to 12.795].B*27:04,B*27:05,B*27:06,and B*27:07 were detected in the suspected AS group and the control group.The frequency of the B*27:04 allele in the suspected AS group was significantly higher than that in the control group(9.48%vs 1.24%;P<0.001,OR=8.346,95%CI 2.463 to 28.282).The positive rate of B27 in the suspected AS group and the confirmed AS group(B27+/+ and B27+/-)was significantly higher than that in the control group(χ2=16.579,P<0.001;χ2=94.582,P<0.001,respectively).Among the confirmed AS group,21 were HLA-B27 carriers,and the B27 positive rate in the confirmed AS group was 91.3%.PCR-SBT could achieve high resolution typing of the HLA-B gene locus,with higher sensitivity,specificity,positive predictive value,negative predictive value,and accuracy than PCR-SSP. Conclusion:PCR-SBT typing analysis shows a strong correlation between HLA-B * 27:04 and AS in Hunan province.The PCR-SBT method can be used as the preferred option for the auxiliary diagnosis of clinical AS.

Aggressive angiomyxoma (AAM) is a rare clinical entity. A case of AAM was reported in this paper. The patient presented with severe hydronephrosis of the left kidney and was diagnosed with a pelvic mass compressing the ureter. The patient underwent laparoscopic resection of the pelvic mass. The postoperative pathology and immunohistochemistry confirmed the diagnosis of AAM. The patient had no recurrence and metastasis after 9 months of follow-up.

Objective:To explore the risk factors for depression in patients with cognitive impairment and construct a prediction model to preliminarily validate the predictive performance of the model, aiming to provide medical and nursing staff with a screening tool for high-risk groups.Methods:From January 2020 to December 2021, convenience sampling was used to select 1 130 patients with cognitive impairment admitted to the Affiliated Brain Hospital of Nanjing Medical University as the research subject. The research subjects were divided into a modeling group ( n=791) and a validation group ( n=339) at a ratio of 7∶3. The influencing factors of depression in patients with cognitive impairment were determined using binomial Logistic regression and a risk prediction model was established. The predictive performance of the prediction model was tested using the receiver operating characteristic (ROC) curve. Results:The incidence of depression in 1 130 patients with cognitive impairment was 51.3% (580/1 130). Binomial Logistic regression analysis showed that the influencing factors for depression in patients included age, Activities of Daily Living Scale score, Hamilton Anxiety Scale score, Pittsburgh Sleep Quality Index score, and Lewy Body Composite Risk score ( P<0.05). In the modeling group, the area under the ROC curve was 0.921, the Youden index was 0.716, the sensitivity was 0.834, the specificity was 0.882, and the prediction accuracy was 0.858. In the validation group, the area under the ROC curve was 0.896, the Youden index was 0.651, the sensitivity was 0.824, the specificity was 0.827, and the prediction accuracy was 0.825. Conclusions:The depression risk prediction model can effectively predict the risk of depression in patients with cognitive impairment, and can provide a screening tool for high-risk groups for medical and nursing staff.

Objective:To analyze the changes in biological characteristics including infectivity, growth and pathogenicity of Chlamydia muridarum ( Cm) after serial passage in vitro in special conditions in order to provide reference for screening attenuated live vaccines and virulence-related genes. Methods:Wild-type Cm strain (G0) was cultured for several passages using conventional cell culture method under alternate unassisted and assisted culture conditions. Then, the 28th generation (G28) of Cm was selected and compared with the parental G0 strain in terms of centrifugation dependence, attaching ability, intracellular growth curve, plaque size and fallopian tube lesions after genital tract infection in a mouse model. Results:Compared with the parental G0 strain, the G28 strain showed significantly decreased dependence on centrifugation during cell infection ( P<0.05) and increased attachment capacity to cells ( P<0.05). No significant differences were observed in the growth curves 32 h after cell infection or in the plaque sizes between the parental G0 and G28 strains. In the in vivo virulence test, fallopian tube lesions were observed in 87.5% of G0-infected mice and 37.5% of G28-infected mice ( P<0.05). Conclusions:Compared with the parental G0 strain, the G28 strain showed significantly enhanced in vitro infection ability, but decreased in vivo pathogenicity, which brought hope for further identification of virulence genes, isolation of attenuated strains with single genotype and development of live attenuated Chlamydia vaccines.

Objective? To explore the quality of life in patients with cognitive disorder and to discuss its influencing factors so as to provide a reference for improving the quality of life in patients with cognitive disorder. Methods? Totally 1 398 neurological patients from a neuropsychiatric hospital in Nanjing were screened using cluster sampling and 125 patients with cognitive disorder were selected as subjects between January and December 2017. The subjects received a cross-sectional study with Quality of Life in Alzheimer＇s Disease (QOL-AD), Montreal Cognitive Assessment Scale (MoCA), Activities of Daily Living Scale (ADL), Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS) and the general information questionnaire. Variance analysis, Pearson correlation analysis and multivariate linear regression analysis were used for statistical analysis. Results? The morbidity of cognitive disorder in neurological patients from our hospital was 9.3%. Their QOL-AD score was (31.88±6.54). Sex, educational background, nature of work, household income, sleep and bad social relations are factors affecting the quality of life of the subjects (P＜0.05). According to multivariate linear regression analysis, MoCA, SAS and SDS were main factors affecting the quality of life of the subjects (P＜0.05). Conclusions? Male patients with lower education, physical work and bad social relations are high-risk patients with lower quality of life. Cognitive disorder, anxiety and depression are main risk factors affecting the quality of life in patients with cognitive disorder. Nursing workers should improve and maintain the patients＇cognitive ability, enrich their cultural life and social activities, and enhance their mental health, thereby improving their quality of life.

Mitochondrial diseases are maternally inherited heterogeneous disorders that are primarily caused by mitochondrial DNA (mtDNA) mutations. Depending on the ratio of mutant to wild-type mtDNA, known as heteroplasmy, mitochondrial defects can result in a wide spectrum of clinical manifestations. Mitochondria-targeted endonucleases provide an alternative avenue for treating mitochondrial disorders via targeted destruction of the mutant mtDNA and induction of heteroplasmic shifting. Here, we generated mitochondrial disease patient-specific induced pluripotent stem cells (MiPSCs) that harbored a high proportion of m.3243A>G mtDNA mutations and caused mitochondrial encephalomyopathy and stroke-like episodes (MELAS). We engineered mitochondrial-targeted transcription activator-like effector nucleases (mitoTALENs) and successfully eliminated the m.3243A>G mutation in MiPSCs. Off-target mutagenesis was not detected in the targeted MiPSC clones. Utilizing a dual fluorescence iPSC reporter cell line expressing a 3243G mutant mtDNA sequence in the nuclear genome, mitoTALENs displayed a significantly limited ability to target the nuclear genome compared with nuclear-localized TALENs. Moreover, genetically rescued MiPSCs displayed normal mitochondrial respiration and energy production. Moreover, neuronal progenitor cells differentiated from the rescued MiPSCs also demonstrated normal metabolic profiles. Furthermore, we successfully achieved reduction in the human m.3243A>G mtDNA mutation in porcine oocytes via injection of mitoTALEN mRNA. Our study shows the great potential for using mitoTALENs for specific targeting of mutant mtDNA both in iPSCs and mammalian oocytes, which not only provides a new avenue for studying mitochondrial biology and disease but also suggests a potential therapeutic approach for the treatment of mitochondrial disease, as well as the prevention of germline transmission of mutant mtDNA.
Animals ; DNA, Mitochondrial ; genetics ; Humans ; Induced Pluripotent Stem Cells ; cytology ; metabolism ; MELAS Syndrome ; genetics ; Male ; Mice ; Microsatellite Repeats ; genetics ; Mitochondria ; genetics ; metabolism ; Mutation ; genetics