Objective:To analyze the clinical features and genetic etiology of 17 Chinese pedigrees affected with X-linked intellectual disability (XLID).Methods:Seventeen pedigrees affected with unexplained intellectual disability which had presented at Henan Provincial People′s Hospital from May 2021 to May 2023 were selected as the study subjects. Clinical data of the probands and their pedigree members were collected. Trio-whole exome sequencing (Trio-WES), Sanger sequencing and X chromosome inactivation (XCI) analysis were carried out. Pathogenicity of candidate variants was predicted based on the guidelines from the American College of Medical Genetics and Genomics and co-segregation analysis.Results:The 17 probands, including 9 males and 8 females with an age ranging from 0.6 to 8 years old, had all shown mental retardation and developmental delay. Fourteen variants were detected by genetic testing, which included 4 pathogenic variants ( MECP2: c. 502C>T, MECP2: c. 916C>T/c.806delG, IQSEC2: c.1417G>T), 4 likely pathogenic variants ( MECP2: c. 1157_1197del/c.925C>T, KDM5C: c. 2128A>T, SLC6A8: c. 1631C>T) and 6 variants of uncertain significance ( KLHL15: c. 26G>C, PAK3: c. 970A>G/c.1520G>A, GRIA3: c. 2153C>G, TAF1: c. 2233T>G, HUWE1: c. 10301T>A). The PAK3: c.970A>G, GRIA3: c. 2153C>G and TAF1: c. 2233T>G variants were considered as the genetic etiology for pedigrees 12, 14 and 15 by co-segregation analysis, respectively. The proband of pedigree 13 was found to have non-random XCI (81: 19). Therefore, the PAK3: c. 1520G>A variant may underlie its pathogenesis. Conclusion:Trio-WES has attained genetic diagnosis for the 17 XLID pedigrees. Sanger sequencing and XCI assay can provide auxiliary tests for the diagnosis of XLID.

Objective To explore the mechanism of Gualou Xiebai Baijiu Decoction(GXB)in improving atherosclerosis(AS)in mice by regulating the gut microbiota(GM)and its metabolites.Methods Thirty-two male ApoE-/-mice were divided randomly into a Blank group,Model group,atorvastatin(Ato)group,and GXB group(n=8 mice per group).AS was established in all mice,except the Blank group,and the respective treatments were administered by gavage.Aortic plaques were detected by Oil red O staining and pathological changes in aortic tissue were detected by hematoxylin and eosin staining.The GM was analyzed using 16S rRNA gene sequencing technology,and mouse GM metabolites,including trimethylamine oxide(TMAO),short-chain fatty acids(SCFA),and serum levels of triglycerides(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),and nitric oxide(NO)were determined.Results Compared with the Blank group,mice in the Model and Ato groups showed an increase in AS plaque area(P＜0.05).Serum levels of TG,TC,and LDL-C were increased(P＜0.001)while levels of HDL-C and NO were decreased(P＜0.01,P＜0.001)in the Model group compared with the Blank group.The plaque area was decreased(P＜0.05),serum levels of TG,TC,and LDL-C were decreased(P＜0.001),and NO levels were increased(P＜0.01)in the Ato and GXB groups,while HDL-C levels were increased in the GXB group(P＜0.05)compared with the Model group.Plaque area was decreased(P＜0.05)and the NO level was increased(P＜0.01)in the GXB group compared with the Ato group.A total of 6345 characteristic sequences were obtained from 16S rRNA analysis.α-Diversity analysis indicated that GXB reduced the richness of the GM in AS mice(P＜0.001)and improved its uniformity(P＜0.05).β-Diversity analysis suggested that the microbial community structure in the GXB group was similar to that in the Blank group.The abundance of microbial communities differed among the groups at the phylum and genus levels.At the phylum level,the abundance of Proteobacteria was increased(P＜0.01)in AS mice,while GXB intervention reduced the abundance of Proteobacteria(P＜0.01)and increased the abundance of Verrucomimicrobiota(P＜0.05).At the genus level,GXB effectively increased the abundance of Akkermansia(P＜0.05).SCFAs were significantly increased(P＜0.01)and TMAO levels were significantly decreased(P＜0.01)in the GXB group compared with the Model group.Conclusions GXB can regulate the intestinal flora and intestinal flora metabolites SCFA and TMAO to improve AS.Akkermansia may be a key bacterial genus of the gut microbiota through which GXB may improve AS.

Objective: To investigate the mechanism of vascular endothelial growth factor(VEGF) inducing tolerogenic dendritic cells(DCs) in oral squamous cell carcinoma (OSCC). Methods: The DCs were divided into four groups: Control group (DC), VEGF group (VEGF added into DC), Co-culture group (DC co-cultured with SCC7) and Anti-VEGF group (anti-VEGF antibody added into DC co-cultured with SCC7). Flow cytometry (FCM) was used to detect DC surface markers. To detect the effect of DC on proliferation activity of T lymphocyte, the experiment included five groups: Nc group (T lymphocyte), Control group (T lymphocyte added into DC), VEGF group (T lymphocyte + DC + VEGF), Co-culture group (T lymphocyte + DC + supernatant of SCC7) and Anti-VEGF group (T lymphocyte + DC + supernatant of SCC7 + anti-VEGF antibody). Subsequently, the mixed lymphocyte reaction(MLR) was conducted. The expression levels of indole-2, 3-doxygenase(IDO)and programmed cell death 1 ligand 1(PD-L1)in DC were detected by western blot, real time PCR and FCM respectively. For the cytotoxic lymphocyte (CTL) assay, SCC7 cells and CTLs were mixed and CTL-mediated SCC7 cells cytotoxicity was tested. The experiment included four groups: Control group (T lymphocyte + DC), IDO inhibition group (T lymphocyte + DC + IDO inhibitor), Anti-PD-L1 antibody group (T lymphocyte + DC + anti-PD-L1 antibody) and Combination group (T lymphocyte + DC + IDO inhibitor + anti-PD-L1 antibody). The SCC7 tumor-bearing mice treated with IDO inhibitor and the anti-PD-L1 antibody were sacrificed and the tumor inhibition rate and the spleen index were determined. Results: Compared with Control group, exogenous VEGF or SCC7 co-culture inhibited the relative number of DC expressing CD11C, CD80, CD86, CD40 and MHC Ⅱ. The positive DCs were increased in the Anti-VEGF group compared with VEGF or Co-culture group. In VEGF or Co-culture group, the number of T cells stimulated by SCC7-pulsed DCs was decreased compared with Control group. However, the ability of Anti-VEGF group to induce T cell proliferation was significantly increased compared with VEGF or Co-culture group. Significantly increased expression of IDO and PD-L1 were observed in VEGF and Co-culture group. However, this was partially reversed by addition of anti-VEGF antibody into the co-culture system. Compared with Control group, the expressions of CD11C and CD86 in DC in both the IDO inhibition group and Anti-PD-L1 antibody group were increased, and were significantly higher in the Combination group compared with the single drug groups. The similar results were exhibited in MLR and CTL assay. In vivo, the results revealed that the tumors obtained from the mice in three experimental groups were smaller than those in the control group. Furthermore, the tumor volume of the Combination group was the smallest. The spleen index of each group was calculated and the results showed the spleen index of the three experimental groups was significantly higher than that of Control group. Conclusion VEGF in OSCC micro-environment inhibits the maturation and function of DC that are transformed into tolerogenic DC by high expression of IDO and PD-L1.

background The lead isotope ratios (LIR) differ among different sourced samples. Previous domestic and oversea studies on source tracing by LIR in human blood or urine mainly focused on the comparison of blood or urine samples from the same or different individuals, while few comparisons between biological and environmental samples, and the reported relative standard deviations (RSDs) of the main LIR (^207/206Pb and ^208/206Pb) fluctuate widely from 0.3% to 1%. Objective To optimize inductively coupled plasma mass spectrometry (ICP-MS), obtain a better RSD, and determine LIRs of human blood, urine, and related environmental samples. Methods The ICP-MS was optimized for operating conditions and parameters according to the sensitivity and RSD of LIR. The study subjects were 40 lead-exposed workers in a lead-acid battery factory and 2 lead poisoned children in a hospital. The samples included 40 blood and 40 urine samples from the workers before shift, 4 dust samples and 2 water samples in the workplace on the same day before shift, 2 blood and 3 urine samples from the children before hospital admission due to lead-poisoning, and 4 urine samples after medical treatment. After heating and acid digestion, the LIR (^207/206Pb and ^208/206Pb) of biological and environmental samples were determined by the optimized ICP-MS method. t-test and two-dimensional traceability graphics were adopted to analyze the detection results. Results The calibrated RSDs of the LIR (^207/206Pb and ^208/206Pb) of lead isotope standard solution were 0.11% and 0.08% respectively, and the NIST-SRM-981 actual values were 0.91531±0.00097 and 2.1670±0.0017, respectively. When the total concentration of lead was greater than 5 μg·L⁻¹, the RSD of each isotope ratio was stable gradually; when the total concentration of lead was between 10-80 μg·L⁻¹, the RSD was below 0.20%. There were statistically significant differences in the blood and urine LIR (^207/206Pb and ^208/206Pb) of the lead-exposed workers (t=5.831, P<0.001; t=21.021, P<0.001), the LIR (^207/206Pb and ^208/206Pb) between workplace dust samples and workers’ urine samples (t=−6.879, P=0.038; t=12.521, P<0.001), and the ^208/206Pb between workplace dust samples and workers’ blood samples (t=−10.46, P<0.001), except the ^207/206Pb between workplace dust samples and workers’ blood samples (t=−0.12, P=0.912). In the patients afflicted with lead poisoning, the projection points of LIR of blood and urine samples from the same individual were not at the same level in the two-dimensional model, nor was the LIR of urine samples before and after medical treatment of the same individual. Conclusion The optimized ICP-MS can control the RSD of main LIR (^207/206Pb and ^208/206Pb) below 0.20%. There are differences in the LIR distributions of different samples.

Objective:To explore the effect of core muscle stability exercise combined with biofeedback in the pelvic floor rehabilitation of patients after radical resection of early cervical cancer.Methods:From August 2018 to July 2021, convenience sampling was used to select 130 patients with cervical cancer who received gynecological surgery in the Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School as the research object. According to the random number table method, the patients were divided into the experimental group and the control group, 65 cases in each group. The control group conducted the conventional rehabilitation nursing, and the experimental group carried out rehabilitation nursing of core muscle stability exercise combined with biofeedback. The pelvic floor electrophysiological function, Pelvic Floor Distress Inventory-20 (PFDI-20) , and the Pelvic Floor Impact Questionnaire-7 (PFIQ-7) scores were compared between the two groups.Results:After the intervention, the values of the pelvic floor electromyography of the experimental group were higher than those of the control group, and the fatigue values of typeⅠ andⅡ muscle fibers were lower than those of the control group, and the differences were statistically significant ( P<0.01) . After intervention, the scores of PFDI-20 and PFIQ-7 in the experimental group were lower than those in the control group, and the differences were statistically significant ( P<0.01) . Conclusions:Core muscle stability exercise combined with biofeedback has a good effect on pelvic floor rehabilitation after radical resection of early cervical cancer, and it is worthy of clinical application.

The functional loss of the mismatch repair system is related to the occurrence of colorectal cancer. Some colorectal cancers have mismatch repair defects, however, the methylation of the MLH1 promoter cannot be detected, and germline mutations of the mismatch repair genes are not detected. Because this part of the group is very similar to Lynch syndrome, it is named Lynch-like syndrome. Lynch-like syndrome has certain genetic characteristics, but the pathogenesis has not been fully understood; and it cannot be simply classified as sporadic colorectal cancer or Lynch syndrome, and there is a lack of genetic knowledge and monitoring standards of these patients. This article introduces the progress of Lynch-like syndrome.

Objectives To evaluate the long-term outcomes of childhood low-or intermediate-risk neuroblastoma (NB) and their relevant prognostic factors. Methods A total of 70 new cases of low-or intermediate-risk NB diagnosed and treated by NB-99 protocol between 1999 and 2008 were analyzed retrospectively. Results Of these 70 NB patients, fourteen patients were in low-risk group and 56 were in intermediate-risk group. Sixty-seven patients reached complete remission (CR) or very good partial remission and 3 (5%) achieved partial remission. Ten patients relapsed. One patient occured second malignant neo-plasm. No patients died of chemotherapy-related adverse events or infections. The 5 year overall survival rate was 85.9%, event-free survival rate was 81.0%. Bone marrow infiltration, age at diagnosis, stage, lactate dehydrogenase level had a significant effect on prognosis. Conclusion Develop cytogenetic and molecular biology tests and pretreatment risk stratification are im-portant for further improvement of treatment protocol.

Objective To investigate the imaging features of adrenal rest tumor.Methods Twelve patients of adrenal rest tumor proved by surgery or clinical diagnosis were retrospectively analyzed.Among these 12 patients,12 were examined with ultrasound,11 with MR and 1 with CT. MR and CT were performed without and with intravenous injection of contrast material.The imaging features of adrenal rest tumor were retrospectively summarized and the relevant literatures reviewed. Results The adrenal rest tumors were found in testis in 10 of the 12 patients,and in ovaries and broad ligament in the remaining two.The imaging features of the testicular adrenal rest tumor were summarized as following:all patients had bilateral testicular masses without change of the testicular contour. On ultrasonography,the lesions were hypoechoic, with some hyperechoic areas and appeared highly vascularized on Colour Doppler ultrasonography.The masses showed iso-density on plain CT,and avid enhancement on post-contrast CT images.The masses ranging in size from0.7 cm×1.0 cm×2.2 cm to 2.3 cm ×2.7 cm ×2.9 cm with uniform signal intensity,lobulated margin on MRI.They exhibited iso- or slight hyperintensity on T1 WI and hypointensity on T2WI relative to normal testicular parenchyma.The tumors showed intense enhancement on post-contrast MR images. No abnormality was detected with Colour Doppler uhrasonography and MR in 2 patients of adrenal rest tumor in ovaries and broad ligament. Conclusion Combining imaging features with the typical clinical history,the diagnosis of adrenal rest tumor could be suggested pre-operatively.

Objective To investigate maternal risk factors for fetal congenital heart diseases (CHD). Methods A case-control study was conducted on 16 645 pregnant women who underwent cardiovascular malformation screening for fetal cardiovascular system,whose pregnancy outcomes were recorded,and whose newborns were scanned by an echocardiography in Peking University People's Hospital,Haidian,Changping,Mentougou and Daxing Maternal and Child Health Hospital from Nov.2006 to Oct.2009.One hundred and twelve pregnant women whose babies were found to be CHD (40 severe CHD and 72 simple CHD) before or after delivery were taken as study group.Women in control group (n =304) were randomly selected from those pregnant women who had infants without CHD.Logistic regression analysis and x2 test were used to analyze the maternal risk factors for fetal CHD. Results (1) The average age of women whose infants had severe CHD was 28.3 years (21-40 years),and it was 29.9 years (22-39 years) for women whose infants had simple CHD.There were no significant differences between the control group (29.5 years,20-44 years) and the above two groups (t=1.511 and -0.826,P=0.138 and 0.410 respectively).(2) Single factor analysis:during first trimester,the rate of upper respiratory infection (18/39,46.2 ％) and exposure to certain chemicals (13/40,32.5％) of severe CHD group were higher than those of control group [(14.9％ (45/303) and 2.0％ (6/304)] (x2 =22.399 and 62.678,OR=4.895 and 23.753,95％CI:2.419-9.905 and 8.358-67.506,P =0.000 respectively).Compared with control group (0.0％,0/304),the rate of pregnant women with CHD family history in simple CHD group was significantly higher (4.2％,3/72)(Fisher exact test,P=0.007).(3) Logistic regression analysis:maternal upper respiratory infections (OR =5.120,95％CI:2.340-11.206,P =0.000) and exposure to certain chemicals (f)R=23.030,95％CI:7.506-70.665,P=0.000) during first trimester were risk factors for fetal severe CHD. Conclusions Upper respiratory infection and exposure to certain chemicals during first trimester might play important roles in the occurrence of fetal severe CHD.Maternal family history of CHD might associate with fetal simple CHD.

Objective To analyze the professional psychological pressure and coping style of male nursing students during different learning stage,and discuss effective ways to solve these problems in order to promote physical and mental health development of male nursing students.Methods Using coping style questionnaire and the professional psychological pressure of nursing students questionnaire to survey 102 undergraduate male nursing students from grade 2005 to 2008 of a nursing college of certain province.Results The professional psychological pressure of undergraduate male nursing students was moderate.Male nursing students of different grades had different professional pressure,in which male nursing students of secondyear had lower professional psychological pressure than other students.Manners they adopted to cope with pressure were mature,that is,the "problem-solving-help" approach,in which ways taken by second-year students were more than others.Conclusions Social bias to male nurses should be corrected.Professional psychological education should be carried out to relieve their mental pressure according to characteristics of students in different stage and direct them to realize role change.