Objective To study the clinical characteristics, diagnosis, treatment and its effectiveness of vulvar intraepithelial neoplasm Ⅲ(VIN Ⅲ).Methods Clinical data, including age of the patients, mode of surgical operation, pathological features, results of post-operation follow-up, of 12 cases of VIN Ⅲ admitted to the Peking Union Medical College Hospital(PUMCH)during January 1984 to December2006 were retrospectively analyzed.Results Mean age of the 12 cases was 40.3(ranging from 23 to 56)years.All the patients had symptoms of vulvar itching, three with VUlVar ulcer and one with vulvar pain.There was single neoplasm focus in two cases and multiple focuses in 10 cases, five cases with neoplasm in other sites and five with human papilloma virus(HPV)infection.All the 12 patients received surgical operation, three with simple vulvectomy(one with some residue at perianal incisal edge)and other nine with lumpectomy(four with some residue at incisal edge).Eight cases were followed-up for 9.0 months in average(ranging 1～22 months)after surgical operation, including three with some residue at incisal edge.Relapse was found in two cases three and 11 months after operation, respectively, who received re-operation, including one with residue at incisal edge and one without residue.Conclusions It is necessary to attach more importance to biopsy for the cases of suspected VIN Ⅲ, as well as colposcopic diagnosis for those with vaginal or vulvar neoplasm and testing for HPV infection.Surgical operation, including simple vulvectomy and lumpectomy with or without adjunctive measures, are main treatment for patients of VIN Ⅲ and follow-up is also important for all those with VIN Ⅲ.

Objective:To explore the effects of macrophages after influenced by tuberculosis antigen Ag85 on the proliferation and apoptosis of Hodgkin lymphoma cells, and to discuss the possible role of tuberculosis infection in the progression of Hodgkin lymphoma.Methods:The indirect co-culture system between Hodgkin lymphoma cell line KM-H2 and human monocytic leukemia cell line THP-1 (simulated macrophage) was established by using Transwell nesting. KM-H2 cells were cultured as KM-H2 group alone, KM-H2 cells interfered with Ag85 were taken as KM-H2+Ag85 group, and KM-H2 cells co-cultured with THP-1 cells were taken as KM-H2+THP-1 group. The co-culture system of KM-H2 cells and THP-1 cells interfered by Ag85 was taken as KM-H2+THP-1+Ag85 group. The proliferation of KM-H2 cells in each group was detected by using CCK-8 assay, and the growth curve was drawn. The apoptosis of cells in each group was detected by using flow cytometry. The mRNA expression levels of p53, c-myc, bcl-2 and vascular endothelial growth factor receptor 3 (VEGFR3) in each group were detected by using quantitative real-time fluorescence polymerase chain reaction (qRT-PCR). The expressions of bax and bcl-2 proteins were detected by using Western blotting.Results:The cell proliferation ability of KM-H2+Ag85 group was higher than that of KM-H2 group (all P = 0.001) after 24 and 48 h culture, but the cell proliferation ability of KM-H2+THP-1 group was lower than that of KM-H2 group after 24 h, 48 h and 72 h culture (all P < 0.05). The cell proliferation ability of KM-H2+THP-1+Ag85 group was lower than that of KM-H2 group after 48 h and 72 h culture (all P < 0.05), but the cell proliferation ability of KM-H2+THP-1+Ag85 group was enhanced after 24 h and 48 h culture compared with KM-H2+THP-1 group, and there was no statistically significant difference between the two groups after 72 h culture ( P > 0.05). The apoptosis rate of KM-H2+Ag85 group was lower than that of KM-H2 group [(0.92±0.80)% vs. (6.02±1.63)%, P < 0.001], and the apoptosis rate of KM-H2+THP-1 group [(8.57±0.57)%] was higher than that of KM-H2 group ( P < 0.05). The apoptosis rate [(0.60±0.13)%] in KM-H2+THP-1+Ag85 group was lower than that in KM-H2+THP-1 group ( P < 0.001). The relative expression of bcl-2 and VEGFR3 mRNA in KM-H2+Ag85 group was higher than that in KM-H2 group ( P = 0.018, P = 0.017), while the relative expression of c-myc mRNA in KM-H2+Ag85 group was lower than that in KM-H2 group ( P = 0.016), and there was no statistically significant difference of p53 mRNA relative expression level between the both groups ( P > 0.05).The relative expression of p53 mRNA in KM-H2+THP-1+Ag85 group was lower than that in KM-H2+THP-1 group ( P = 0.048), while the relative expressions of bcl-2 and VEGFR3 mRNA in KM-H2+THP-1+Ag85 group were higher than those in KM-H2+ THP-1 group ( P = 0.016; P = 0.021). The expression of bax protein in KM-H2+Ag85 group was lower than that in KM-H2 group ( P = 0.019), and bcl-2 protein was more than that in KM-H2 group ( P = 0.001). The expression of bax protein in KM-H2+THP-1+Ag85 group was lower than that in KM-H2+THP-1 group ( P = 0.011), but there was no statistically significant difference in the expression of bcl-2 protein between the two groups ( P > 0.05). Conclusions:Tuberculosis antigen Ag85 may inhibit the apoptosis of Hodgkin lymphoma KM-H2 cells and enhance the proliferative activity by affecting the function of macrophages.

Objective:To investigate the prevalence of enterovirus infection and its clinical characteristics in neonatal febrile cases.Methods:A total of 308 neonates in the neonatal ward of Kunming Children′s Hospital with febrile symptoms from March 2018 to February 2019 were selected for the study.Fecal specimens and some (271) cerebrospinal fluid specimens were collected from all neonates.Enterovirus was respectively detected in feces and cerebrospinal fluid by using reverse transcription-polymerase chain reaction (RT-PCR) method.The rate of enterovirus infection in febrile neonates was clarified.They were divided into enterovirus infection group ( n=91) and no enterovirus infection group ( n=217). The clinical data of the subjected neonates in the two groups were analyzed and the clinical manifestations of the neonates and their laboratory findings were compared statistically. Results:Ninety-one enteroviruses (90 enterovirus were general type, and 1 was coxsackievirus A16 type) were detected in 308 children, accounting for 29.55% of all neonates.Viral RNA was detected in only 1 case [0.37% (1/271)]of all examined cerebrospinal fluid specimens, which was significantly lower than the detection rate of 29.55% (91/308) in fecal specimens.There were no fatal cases, but there was one severe case in enterovirus infection group.Except for the severe case which was discharged automatically, all of them improved or healed and discharged from hospital.The clinical manifestations of the enterovirus infection group were non-specific statistically compared with the non-enterovirus infection group(all P>0.05), except for respiratory symptoms and skin rash(all P<0.05). The incidence of enterovirus infection was significantly seasonal[83.52%(76/91)in summer and autumn]. Conclusion:In the epidemic season of enterovirus, it is recommended to list fecal enterovirus as a routine test item to improve the accuracy and timeliness of diagnosis and treatment, and avoid the application of unnecessary antibiotics and the outbreak of enterovirus in the neonatal ward.

OBJECTIVE: To define genetic profiling of homologous recombination (HR) deficiency in Chinese ovarian cancer patients. METHODS: we have applied next-generation sequencing to detect deleterious mutations through all exons in 31 core HR genes. Paired whole blood and frozen tumor samples from 50 Chinese women diagnosed with epithelial ovarian carcinomas were tested to identify both germline and somatic variants. RESULTS: Deleterious germline HR-mutations were identified in 36% of the ovarian cancer patients. Another 5 patients had only somatic mutations. BRCA2 was most frequently mutated. Three out of the 5 somatic mutations were in RAD genes and a wider distribution of other HR genes was involved in non-serous carcinomas. BRCA1/2-mutation carriers had favorable platinum sensitivity (relative risk, 1.57, p<0.05), resulting in a 100% remission probability and survival rate. In contrast, mutations in other HR genes predicted poor prognosis. However, multivariate analysis demonstrated that platinum sensitivity and optimal cytoreduction were the independent impact factors influencing survival (hazards ratio, 0.053) and relapse (hazards ratio, 0.247), respectively. CONCLUSION: our results suggest that a more comprehensive profiling of HR defect than merely BRCA1/2 could help elucidate tumor heterogeneity and lead to better stratification of ovarian cancer patients for individualized clinical management.
Asian Continental Ancestry Group* ; Exons ; Female ; Homologous Recombination* ; Humans ; Multivariate Analysis ; Ovarian Neoplasms* ; Platinum ; Population Characteristics ; Prognosis ; Recurrence ; Survival Rate

Objective To investigate personal identification of mixed seminal stain of two individuals, we combined the detection of genotyping autosomal, Y and X STR and sequencing mtDNA hypervariable Ⅰ (HV Ⅰ ) region. Methods We analyzed autosomal, Y and X STR with commercial kit and separating and sequencing HVⅠfragments of mixed seminal stain from two males by SSCP electrophoresis. Results Four genetic markers of the high amount sample can be obtained when mixed ratio is more than 1:10. When the proportion of two samples is close, the suspect could be excluded or, to some extent, identified by comparing with our results. Conclusion The combined detection of four genetic marker systems can, to some degree, solve the personal identification from mixed seminal stain of two individuals.

Objective In this study,a multiplex PCR amplification system was constructed based on fluorescent labeling PCR and LDR,to provide a new strategy for analyzing severely degraded DNA.Methods Eight SNP loci (rs10802248,rs10516197,rs10488372,rs2278945,rs4757318,rs4887255,rs4889002,and rs9304473) were selected.Their LDR probes and PCR primers of linked products were designed and synthesized.Ligase detection reaction,PCR amplification,and capillary gel electrophoresis (CEG) were performed to establish the multiplex LDR-PCR amplification system.Results The genotypes of these 8 loci were obtained simultaneously by the fluorescence-labeled multiplex LDR-PCR amplification method.The loci profiles obtained by fluorescence-labeled multiplex LDR-PCR amplification were in accordance with those obtained by direct sequencing of the polymorphic regions in samples from all individuals.By fluorescence-labeled multiplex LDR-PCR amplification,the 8 SNP loci were efficiently amplified from the severely degraded FFPET DNA.Conclusion Eight SNP loci results could be obtained simultaneously by using the multiplex LDR-PCR amplification system,which is a simple,efficient,and practical SNP genotyping method with accurate and reliable results for highly degraded samples.

Objective To demonstrate the clinicopathological characteristics and determine the prognostic factors for women with synchronous primary endometrial and ovarian cancer(SEOC). Methods A retrospective analysis of 63 pathologically proven cases of SEOC diagnosed in Peking Union Medical College Hospital from January 2000 to May 2018 was carried out. Results (1)Clinical features: mean age at diagnosis was(48.3±10.0)years, and the mean body mass index(BMI)was(23.4±3.7)kg/m2. The most common presenting symptom was abnormal uterine bleeding with a ratio of 73%(46/63). Forty-three patients(68%,43/63)were premenopausal, and 30%(19/63)were nulliparous.(2)Pathological features:for the endometrial cancer, 90% patients were diagnosed at stageⅠ, and 81% were low grade tumors(G1- G2). The histological type of endometrial cancer was mainly endometrioid carcinoma(86%)and majority (81%)of patients were proved without or with superficial myometrial invasion. For the ovarian cancer, 70% patients were diagnosed at stage Ⅰand 65% were low grade tumors(G1-G2). Sixty-two percent of ovarian cancers were endometrioid carcinoma and 68% of patients had unilateral involvement of the ovaries.(3) Treatment and prognosis: all patients underwent surgery, of which 56 (89%) underwent staging surgery including retroperitoneal lymphadenectomy, and 57(90%)received postoperative adjuvant therapy. The median follow-up time was 48.0 months(range, 2-176 months), and 13% of the patients experienced tumor recurrence during the follow-up period. The median time to recurrence was 38.5 months, and 6 patients (10%)died of tumor recurrence. The 5-year progression-free survival(PFS)and 5-year overall survival(OS) for all patients were 69% and 80%, respectively.(4)Prognostic factors: univariate analysis showed that the presence of lymphovascular space invasion(LVSI), non-endometrioid histology of ovarian cancer and stage of ovarian cancer above stageⅠwere associated with significantly worse PFS(P<0.05). LVSI, high grade of endometrial cancer, and above stage Ⅰof ovarian cancer were associated with significantly worse OS(P<0.05). On multivariate analysis, LVSI, non-endometrioid type ovarian cancer and stage of ovarian cancer above stageⅠwere associated with significantly worse PFS(P<0.05). In addition, LVSI and stage of ovarian cancer above stage Ⅰwere also associated with significantly worse OS(P<0.05). Conclusions Women with SEOC are young, premenopausal and have a favorable overall prognosis. Presence of LVSI, non-endometrioid type ovarian cancer and stage of ovarian cancer above stageⅠare independent prognostic factors for PFS,and stage of ovarian cancer above stageⅠare independent prognostic factors for OS.

Objective:To analyze the clinical efficacy and pregnancy outcomes of gonadotropin-releasing hormone agonist (GnRH-a) based fertility-sparing re-treatment in women with endometrial carcinoma (EC) and atypical endometrial hyperplasia (AEH) who failed with oral progestin therapy.Methods:Forty cases with EC or AEH who failed to respond to oral progestin were included from January 2012 to December 2020 at Peking Union Medical College Hospital. Combination of GnRH-a with levonorgestrel-releasing intrauterine system (group GLI: a subcutaneous injection of GnRH-a every 4 weeks and LNG-IUS insertion constantly) or the combination of GnRH-a with aromatase inhibitor (group GAI: a subcutaneous injection of GnRH-a every 4 weeks and oral letrozole 2.5 mg, daily) were used for these patients. Histological evaluation were performed at the end of each course (every 3-4 months) by hysteroscopy and curettage. After the complete remission (CR), all patients were followed up regularly.Results:(1) Clinical characteristics:among the 40 patients with EC or AEH, the median age at diagnosis was 31 years (range: 22-40 years) and the median body mass index was 24.7 kg/m 2 (range: 18.9-39.5 kg/m 2). (2) Efficacy of fertility-sparing re-treatment: 37 (92%, 37/40) patients achieved CR, 6 (6/7) in AEH and 31 (94%, 31/33) in EC patients. The CR rate was 93% (26/28) and 11/12 in group GLI and GAI, respectively. The median time to CR was 5 months (range: 3-12 months). At the end of the first therapy course, the CR rates in AEH and EC were 5/7 and 42% (14/33), at the second course, the CR rates were 6/7 and 82% (27/33), respectively. (3) Recurrence: after 25 months of median follow-up duration (range: 10-75 months), 8 (22%, 8/37) women developed recurrence, 1/6 in AEH and 7 (23%, 7/31) in EC patients, with the median recurrence time of 18 months (range: 9-26 months). Among them, two cases who had completed childbirth chose to receive hysterectomy directly. Six patients met the criteria of fertility-preserving therapy and received conservative treatment again and 5 (5/6) of them achieved CR. (4) Pregnancy: of the 37 patients with CR, 33 desired to conceive. Ten women attempted to get pregnancy spontaneously and 23 cases with assisted reproductive technology. Fourteen (42%, 14/33) patients became pregnant, including 9 (27%, 9/33) live births, 3 (9%, 3/33) missed abortions, and 2 (6%, 2/33) miscarriages at the second trimester. Conclusions:GnRH-a based fertility-sparing re-treatment in AEH or EC patients who failed with oral progestin therapy achieved good treatment effect and reproductive outcomes. It is an encouraging alternative regime for patients who failed with oral progestin therapy.

Objective To investigate the association between periconceptional folic acid supplementation and small for gestational age (SGA) birth based on maternal pre-pregnancy body mass index (BMI) and provide evidence for the development of comprehensive prevention programs on SGA birth.Methods Between March,2012 and September,2016,a total of 8 523 pregnant women delivering in the First Affiliated Hospital of Shanxi Medical University were surveyed to collect the information about their demographic characteristics,folic acid supplementation before and during pregnancy and about their infants.Among their infants,1 066 were small for gestational age (case group),7 457 were appropriate for gestational age (AGA) (control group).Unconditional logistic regression model was used to evaluate the association between periconceptional folic acid supplementation and SGA birth in the context of different pre-pregnancy BMI.Results The overall incidence of SGA birth was 12.51％ (1 066/8 523).After adjusting the confounding factors,prepregnancy BMI＜ 18.5 kg/m2 was a risk factor for SGA birth (OR=1.22,95％ CI:1.01-1.47),prepregnancy BMI≥24.0 kg/m2 was associated with a reduced risk of SGA birth (OR=0.81,95％CI:0.68-0.97).After adjusting confounding factors,periconceptional folic acid supplementation was a protective factor for SGA birth (OR=0.82,95％CI:0.68-0.98).After stratified by pre-pregnancy BMI,periconceptional folic acid supplementation was associated with the reduced risk of SGA birth in overweight group (24.0 kg/m2≤BMI＜28.0 kg/m2) with OR of 0.55 (95％CI:0.36-0.85).No significant association was observed in other groups.When examined by folic acid supplement type,periconceptional single folic acid supplementation (400 μg per tablet) was a protective factor for SGA birth (OR=0.82,95％ CI:0.69-0.99).After stratified by pre-pregnancy BMI,periconceptional single folic acid supplementation (400 μg per tablet) was associated with the reduced risk of SGA birth in overweight groups (OR =0.56,95 ％ CI:0.36-0.86).No association was observed between periconceptional folic acid containing multivitamin supplementation and SGA birth.Conclusions Periconceptional folic acid supplementation (400 μg) was associated with reduced risk of SGA birth in women with prepregnancy BMI≥24.0 kg/m2 and ＜28.0 kg/m2.No association between folic acid supplementation and SGA was observed in other groups.This study suggests that pre-pregnancy BMI might modify the influence of folic acid supplementation on the risk of SGA birth.

In recent years, the prevalence of metabolic diseases, including obesity, diabetes, nonalcoholic fatty liver disease, and metabolic syndrome, increased significantly. Fatigue is common in metabolic diseases and may lead to functional disability. This complicated feeling imposes a huge influence on patients with metabolic diseases physically and psychologically, which seriously affects the quality of life and brings serious burden to the social economy. There were an increasing number of researches on fatigue and metabolic diseases. This article reviews the evidences of the linkages between fatigue and metabolic diseases.