Objective:To explore genetic counseling and prenatal diagnosis strategies for women who have androgen insensitivity syndrome (AIS) family history or pregnancy history of AIS proband.Methods:Three families of complete AIS (CAIS) were retrospectively reported and summarized. The subsequent pregnancies and processes of prenatal diagnosis were followed up.Results:Among three CAIS families, one family had androgen receptors (AR) gene mutation diagnosis; the other two families were diagnosed clinically without gene diagnosis. All three mothers of CAIS probands were in pregnant again when they sought counseling, with gestational weeks between 7－13 weeks. They underwent chorionic villi sampling or amniocentesis in their second trimester (at 12, 16, 17 weeks respectively). Chromosome gender of all three fetuses were 46,XY, which was inconsistent with the ultrasonographic phenotype of external genitalia. All patients chose selective abortion in their second trimester. The external genitalia of all aborted fetuses were female phenotype, which supported the diagnosis of CAIS.Conclusion:Genetic counseling and prenatal diagnosis should be provided to high-risk patients with family history of AIS or proband pregnancy history, so as to achieve the goal of good childbearing and sound childrearing.

A 44-year-old pregnant woman (G5P3) who had delivered two children with DMD was admitted and underwent prenatal diagnosis at Peking Union Medical College Hospital in 2019. (1) The karyotype of the fetus in 2019 was 47,XXY. The fluorescence in situ hybridization (FISH) result showed a nucish(CSPX×2, CSPY×1)[100] and multiplex ligation-dependent probe amplification (MLPA) suggested sex chromosome abnormality. Based on the above results, the fetus was diagnosed with Klinefelter syndrome. Fetal short tandem repeat (STR) linkage analysis and Sanger sequencing indicated a heterozygous mutation of c.9543delG(p.Trp3181CysfsTer2). (2) Sanger sequencing of the proband found a novel frameshift mutation of c.9543delG(p.Trp3181CysfsTer2 ) in exon 65 of the DMD gene. (3) The male fetus performing prenatal diagnosis in 2008 was found to have the same maternal gene markers as the proband with the same genotype. While the genotype of the fetus in 2009 obtained a different maternal gene marker from the proband and did not detect the same DMD gene mutation. This fetus was delivered at full term and was good during follow-up. (4) The elder brother and cousin of the proband had the same frameshift mutation in exon 65 of the DMD gene as the proband. The mother of the proband was a heterozygous carrier of the mutation.

Objective: To investigate the resistance to rifampicin and isoniazid and the changing trends among patients with pulmonary tuberculosis in Luohu District, Shenzhen City, Guangdong Province from 2012 to 2022, so as to provide insights into improving drug-resistant pulmonary tuberculosis control and prevention strategies. Methods: Basic information, treatment classification and drug resistance data of patients with pulmonary tuberculosis and positive pathogenic detection in Luohu District from 2012 to 2022 were collected through the Tuberculosis Surveillance System of Chinese Disease Prevention and Control Information System, and resistance rates of rifampicin and isoniazid and the changing trends were analyzed. Results: A total of 2 126 patients with pulmonary tuberculosis were collected and had a median age of 34 (interquartile range, 25) years, including 1 334 males (62.75%) and 792 females (37.25%). There were 302 patients with drug-resistance in Luohu District from 2012 to 2022, with a resistance rate of 14.21%. Among them, 60 patients were monoresistant to rifampicin (2.82%), 113 patients were monoresistant to isoniazid (5.32%), and 129 patients were multidrug resistant (6.07%). The rate of rifampicin monoresistance showed a downward trend from 2012 to 2022, while the rate of multidrug resistance showed an upward trend (both P<0.05). There was no significant tendency in the rate of isoniazid monoresistance (P>0.05). The rate of multidrug resistance among patients without Shenzhen residence was higher than that among patients with Shenzhen residence; the rates of rifampicin resistance and multidrug resistance among retreated patients were higher than those among treatment-naïve patients (all P<0.05). Conclusions The rate of rifampicin monoresistance appeared a downward trend and the rate of multidrug resistance appeared an upward trend among patients with pulmonary tuberculosis in Luohu District from 2012 to 2022. Attention should be given to non-Shenzhen residence and retreated patients.

Objective To investigate the predictive value of preoperative serum human epididymis protein 4 (HE4) and CA125 in patients with high risk of stage Ⅰ endometrial cancer (EC)and to identify the optimal cutoff values. Methods Clinical and pathological data of 231 patients with stage Ⅰ EC were included in this study. Patients were divided into high risk group (n=96) and low risk group (n=135). The preoperative serum levels of HE4 and CA125 were measured, and their correlations with clinical pathological features were analyzed. The ROC curves were generated to determine optimal cutoff values of HE4 and CA125 levels with the maximum Youden index for prediction of high risk EC. Results There were significant differences in serum levels of HE4 and CA125 between patients with different depths of myometrial invasion, with or without vascular invasion, with or without lower uterine segment involvement, with different diameters of tumor and different risk classifications of stage ⅠEC (P<0.05). There were significant differences in serum levels of HE4 between patients with different menopausal status, hypertension, pathological types, histological grading and the involvement of cervical endometrial glands (P<0.05). The preoperative serum levels of HE4 and CA125 were positive correlated (r=0.262, P<0.05). The AUC value of HE4 for diagnosing stageⅠEC was 0.794(95%CI:0.734-0.854),the cutoff value was 74 pmol/L, the sensitivity was 75.0%, specificity was 83.0%, positive predictive value was 75.8%, negative predictive value was 82.4% and the accuracy rate was 79.7%. The AUC value of CA125 for diagnosing stage Ⅰ EC was 0.696 (95%CI: 0.624-0.767), the cutoff value was 17 kU/L, the sensitivity was 56.3%, specificity was 85.9%, positive predictive value was 74.0%, negative predictive value was 73.4%and the accuracy rate was 73.6%, respectively. The AUC value of combination of both markers was 0.847 (95%CI: 0.796-0.899), the corresponding values were 95.8%, 77.0%, 74.8%, 96.3%and 84.8%, respectively. Conclusion The best cutoff values of HE4 and CA125 are 74 pmol/L and 17 kU/L for detecting high risk stageⅠEC. The combined detection is better than that of the single detection in sensitivity, negative predictive value and accuracy rate.

Objective To investigate efficient diagnosis and treatment of 17α-hydroxylase (17OHD) deficiency by summarizing clinical characteristics of those patients.Methods From January 1983 to January 2010,48 cases with 17OHD in Peking Union Medical College Hospital were studied retrospectively.Results Among 48 patients with 17OHD,karyotype analysis showed,12 cases with 46,XX and 36 cases with 46,XY.The 46,XX karyotype and 46,XY karyotype with complete 17OHD had typical clinical presentation of amenorrhea [ 12/12,100％ ( 36/36 ) ],no typical spontaneous puberty [ 12/12,13.9％ (5/36) ],Hypertension [ 11/12,100％ ( 36/36 ) ],hypokalemia [ K +:( 2.6 ± 0.7 ),( 2.8 ± 0.7 )mmol/L],hypergonadotropin [ follicle-stimulatinghormone ( FSH ):( 51 ± 35 ),( 79 ± 46 ) U/L,luteinizing hormone( LH ):( 27 ± 14 ),(49 ± 37 ) U/L ],impaired production of sex hormones [ testosterone(T):0.003,0.005 nmol/L; estradiol ( E2 ):26.86,10.64 pmol/L ],hyper-progesterone [ (P):( 32 ± 15 ),( 29 ± 23) nmol/L],impaired production of 17α-hydroxyprogesterone ( 17α-OHP ) [ ( 2.5 ± 1.1 ),( 2.4 ±1.7) nmol/L],ACTH hypersecreation (91.8,114.0 pmol/L).ACTH stimulating test did not elevated in 17α-OHP and cortisol.Conclusion When patients with elevated basal serum levels of progesterone higher than that of ovulation period in addition to clinical symptoms,examination about 17OHD should be warranted.

Objective To investigate the drug resistance and its distribution induced by β-lactamases and class Ⅰ integrons with the deficiency of Omp genes in Enterobacter cloacaes.Methods Totally 112 strains of Enterobacter cloacaes were isolated during January 2008 and May 2011.The identification of strains was performed by using Vitek-2 Compact automatic system; and antibiotic susceptibility was determined by K-B method.Isolates of E.cloacae were screened for carbapenemases by modified Hodge test,improved three dimensional test and EDTA-meropenem synergy test.Genes encoding AmpC β-lactamase,metallo-β-1actamases (MBLs) and OXA-like β-1actamases were screened by multiple PCR.Single PCR was used to detect ISEcpl,OmpK35/36,NDM-1 and OXA-48.The variable regions of class Ⅰ integrons were amplified and sequenced.Results Among 112 isolates,6 (5.4％) demonstrated positive in the modified Hodge test and 14 ( 12.5％ ) were positive in the improved three-dimensional test.No carbapenemases gene was found.There were 29(25.9％ ) strains positive for ESBLs genes,ISEcpl was found in the upstream of all the CTX-M-type ESBLs; OXA-1 ESBLs were detected in 2 isolates.AmpC β-lactamase genes were positive in 45 (40.2％) strains,and 82.2％ (37/45) were MIR-3 type.Twenty two isolates carried class Ⅰ integrons,and four different cassettes arrangements were identified within 16 strains:9 isolates harbored aadB-aadA2 ( 1 000 bp),5 isolates with dfrAl5 (700 bp),2 isolates with aadAl ( 1 000 bp).One isolate harbored all the above gene cassettes.The deficiency of OmpK35/36 was found in all strains.Conclusion ESBL,AmpC β-lactamase and the deficiency of OmpK35/36 are correlated with the resistance to carbapenems in Enteobacter clocace,and class Ⅰ integrons may also partly account for the multidrug-resistance.

It is kno wn that 8-Br-cAMP is one of selective bi nding site analogues for cAMP RIIα to af fect cell growth through regulation of g ene expression.The p16,p21wafl,p53 a nd Rb are antioncogenes which affect cel l growth through control of cell cycle.T he aim of this study is to investigate t he 8-Br-cAMP effect on the expression of antioncogenes in human HXO-Rb44 cells. Methods Cultured HXO-Rb44 cells in RPMI -1 640 medium were divided into two aliquot s.8-Br-cAMP (2×10-5mol/L) was added i nto one aliquot for 24h as the experime ntal group(EG),the another aliquot witho ut 8-Br-cAMP as the control group(CG).Af ter 24h,the cell suspension was dropped onto the nitrocellulose membrane.The mR NA of p16,p21wafl,wild type(w)p53,mut ant type(m) p53 and Rb were used respec tively with biotin-labeled cDNA probes b y intact cell RNA dot blot.The immunorea ctivity(IR) of P16,P21wafl,PRb,PCN A,cdk2 and cdk4 were detected respecti vely with specific monoclonal antibodies on dot blot.ResultsThe mRNA dot blot s ignals of mp53 and protein dot blot of cdk2-IR,cdk4-IR and PCNA-IR in EG were weaker than those in CG(P＜0.05～0.01). W hile,the mRNA signals of p16,p21wafl,wp53 and Rb in EG were stronger than tho se in CG(P＜0.05～0.01).The intensity of ea ch protein dot blot was consistent with that of their RNA dot blot (except for w P53-IR and mP53-IR not to be done).Conc lusions(1)8-Br-cAMP could up-regul ate expression of antioncogenes includin g p16,p21wafl,wp53,Rb,and protein exp ression of P16,P21wafl and PRb.(2) 8-Br-cAMP could down-regulate mp53 gene expression and protein expression of cd k2,cdk4 and PCNA.The results suggest t hat 8-Br-cAMP could inhibit human HXO-Rb 44 cell growth through interfering rela ted gene expression of cell cycle.

BACKGROUND:Recently, the effects of human umbilical cord mesenchymal stem cel s (hUCMSCs) and placenta-derived mesenchymal stem cel s (PDMSCs) on treatment of acute graft versus host disease (aGVHD) have been confirmed in some in vitro studies or animal models. But there are stil no reports comparing the therapeutic effects of these two cel types. OBJECTIVE:To compare the immunosuppressive function of hUCMSCs and PDMSCs in vitro or in a mouse aGVHD model. METHODS:(1) In vitro experiment. Human peripheral blood mononuclear cel s (PBMCs) were isolated and divided into four groups:PBMCs cultured alone, PBMCs stimulated with phytohaemagglutinin (PHA), PHA stimulated-PBMCs cocultured with hUCMSCs, PHA stimulated-PBMCs cocultured with PDMSCs. After 5 days, PBMCs proliferation and interferon-γlevel in cel supernatant were measured. (2) In vivo experiment. Fifty-seven BABL/C(H-2d) mice exposed to 8.5 Gy irradiation were randomly divided into five groups:only saline injection group, syngeneic bone marrow transplantation group, al ogeneic bone marrow transplantation group, aGVHD group, hUCMSCs treatment group, PDMSCs treatment group. The clinical aGVHD score, histopathology of skin, liver, and smal intestine, and survival time were analyzed at days 11, 14, 21 after transplantation. RESULTS AND CONCLUSION:(1) In vitro test:compared with the hUCMSCs, PDMSCs had stronger anti-inflammatory function. (2) In vivo test:The clinical scores on acute graft versus host disease were significantly lower in the hUCMSCs and PDMSCs treatment groups than that in the aGVHD group (P<0.05). The survival rates of mice were significantly increased in the hUCMSCs and PDMSCs treatment groups compared to the aGVHD group (P<0.05). Evident skin lesions were not found in al groups. Although smal intestine mucosal lesions were found in al groups, the damage level seemed similar. Notably, significant difference was found in the liver that multifocal necrosis and a large number of inflammatory cel s were seen in the aGVHD group, but less necrosis and inflammatory cel s in the hUCMSC and PDMSC treatment groups. In conclusion, hUCMSC and PDMSC are comparably effective in the treatment of aGVHD in mice.

Lactic acid is the main substance produced by Lactobacillus and plays an important role in maintaining a healthy vaginal microecology. Recent studies indicates that both L- and D-chiral isomers of lactic acid can be protonated and destroy the cell membranes of pathogens, thereby inhibiting bacterial vagi-nosis- and aerobic vaginitis-related pathogens. Lactic acid also can inhibit the pathogens of sexually transmit-ted diseases such as Chlamydia trachomatis and human immunodeficiency virus. Moreover, lactic acid acts as an immunomodulator to inhibit the inflammatory responses caused by pathogenic microorganisms and as an epigenetic regulator regulating gene expression in vaginal epithelial cells. In this paper, we reviewed the pro-gress in lactic acid-mediated maintenance of a healthy vaginal microbiology in recent years for providing ref-erence for further research.

Group B Streptococcus ( GBS) is a leading infectious cause of adverse pregnancy out-comes such as preterm birth. GBS colonizes the vagina during pregnancy and can ascend into the uterus and then infect the fetus. It encodes a series of virulence factors such as adhesion and invasion factors, hemolytic pigments and hyaluronidase, which are important to vaginal colonization and immune evasion. Immune re-sponses to GBS cause the release of a multiple of inflammatory mediators, leading to the premature rupture of membranes, preterm birth and fetal injury. This paper reviews the pathogenesis of GBS vaginal colonization and ascending infection causing adverse pregnancy outcomes.