OBJECTIVE: To investigate the clinical and genetic characteristics of a family with Vissers-Bodmer Syndrome (VIBOS) and to review the relevant literature on VIBOS caused by CNOT1 gene variants. METHODS: A child diagnosed with VIBOS due to "growth retardation for over 6 years" at the Linyi People's Hospital on March 1, 2024 and her family members were selected as the study subjects. Clinical data of the family were collected. Peripheral venous blood samples were collected from the family members. Whole-exome sequencing (WES) was performed on the proband's peripheral blood, and Sanger sequencing was used for verification of the candidate variant in the family. Pathogenicity of the candidate variant was classified according to the "Standards and Guidelines for the Interpretation of Sequence Variants" established by the American College of Medical Genetics and Genomics American College of Medical Genetics (ACMG). Bioinformatics analysis, including pathogenicity prediction using Mutation Taster, three-dimensional protein structure modeling using SWISS-MODEL, and functional impact assessment using PyMOL, was performed. Relevant literature on VIBOS patients due to variants of the CNOT1 gene was retrieved from databases such as CNKI, Wanfang Data, and PubMed. The clinical phenotypes and genotypes of the patients were summarized. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: YX200303). RESULTS: The proband, a 6-year-and-7-month-old female, presented with short stature, distinctive facial features (esotropia, hypertelorism, prominent nasolabial folds), webbed neck, clinodactyly, and intellectual disability. WES revealed that she has carried a heterozygous c.736delG (p.V246*) variant of the CNOT1 gene, which was unreported previously. The proband's father exhibited borderline intellectual function but no short stature or distinctive facial features. Sanger sequencing confirmed that he has carried the same heterozygous variant. According to the ACMG guidelines, this genetic variant was predicted as "likely pathogenic" (PVS1+PM2_Supporting). The c.736delG (p.V246*) variant was predicted to have a deleterious effect by Mutation Taster. Subsequent homology modeling using SWISS-MODEL, coupled with structural visualization and comparison using PyMOL, confirmed that it may cause premature termination of translation and produce a truncated protein. Literature search has retrieved five articles on VIBOS due to CNOT1 gene variants, which included 45 cases. Together with the proband and her father, the common clinical features among these 47 patients included distinctive facial features (83.0%, 39/47), speech delay (70.2%, 33/47), motor delay (70.2%, 33/47), intellectual disability (59.6%, 28/47), and short stature (48.9%, 23/47). In terms of the types of the variants, missense variants were the most common (47.4%, 18/38), followed by frameshift variants (21.0%, 8/38). The variant sites have mainly located in exons 7, 25, and 31. No significant genotype-phenotype correlation was noted. CONCLUSION The c.736delG (p.V246*) frameshift variant of the CNOT1 gene is likely the genetic etiology of VIBOS in this proband. The clinical manifestations of the proband were more severe than in her fathers, which suggested phenotypic variability associated with this variant. This study has provided new evidence for the understanding of the genetic basis of VIBOS.
Child ; Female ; Humans ; Male ; Exome Sequencing ; Intellectual Disability/genetics* ; Mutation ; Pedigree ; Transcription Factors/genetics* ; East Asian People/genetics*

Objective To study the expression and clinical significance of neural Wiskott-Alrdich syndrome protein(N-WASP)in pla-centas with preeclampsia.Methods This study included a total of 65 pregnant women:15 in the early-onset preeclampsia group,15 in the early-onset control group,15 in the late-onset preeclampsia group,and 20 in the late-onset control group.Real-time fluorescence quan-titative PCR(RT-qPCR)was used to detect the relative expression of N-WASP mRNA in placental tissues.Western blotting and immu-nohistochemistry were used to detect the expression and position of N-WASP protein in placental tissues from each group.Results RT-qPCR revealed significantly lower N-WASP mRNA expression levels in the placental tissue of the early-onset preeclampsia group compared to those in the early-onset control group(0.50±0.19 vs.0.93±0.73,P＜0.05).The N-WASP mRNA expression levels in late-onset preeclampsia placenta were significantly lower than those in the late-onset control group(0.83±0.34 vs.1.15±0.34,P＜0.05).Western blotting revealed significantly lower N-WASP protein expression in the placental tissue of early-onset preeclampsia compared to that in the early-onset control group(0.35±0.17 vs.0.72±0.21,P＜0.05).The N-WASP protein expression in late-onset preeclampsia placenta was significantly lower than that in the late-onset control group(0.39±0.16 vs.0.76±0.20,P＜0.05).The N-WASP mRNA expression in the placenta negatively correlated with the occurrence of early-onset(r =-0.37,P = 0.042)and late-onset preeclampsia(r =-0.39,P = 0.019).Immunohistochemistry revealed that N-WASP protein was localized in the cytoplasm of syncytiotrophoblasts,cytotrophoblasts,villous stromal cells,and vascular endothelial cells.Conclusion The low expression of N-WASP may be closely associated with preeclampsia.

Objective:To investigate the impact of circular RanGTPase activating protein 1 (circRANGAP1) on the biological behavior of trophoblast cells in preeclampsia and its potential mechanisms.Methods:Placental tissues were collected from preeclampsia patients and age- and gestational age- matched control pregnant women admitted to Shengjing Hospital of China Medical University from August 2020 to December 2022 (eight cases each in the early-onset preeclampsia group and early-onset control group, and 24 cases each in the late-onset preeclampsia group and late-onset control group). The expression levels of circRANGAP1 and eukaryotic translation initiation factor 4A3 (EIF4A3) mRNA in placental tissues were detected by real-time quantitative polymerase chain reaction (RT-qPCR), and EIF4A3 protein expression was assessed by Western blotting. In HTR-8/Svneo cells, the proliferation, migration, and invasion abilities were evaluated by cell counting assay, scratch assay, Transwell invasion assay, and the regulatory effect of EIF4A3 on circRANGAP1 was examined by RNA binding protein immunoprecipitation (RIP). Changes of circRANGAP1 expression in HTR-8/Svneo cells were detected by RT-qPCR after EIF4A3 knockdown. Statistical analysis was performed using independent sample t-test, non-parametric Chi-square test, or Pearson correlation analysis. Results:(1) There was no significant difference in circRANGAP1 expression between the early-onset preeclampsia group and the early-onset control group. However, circRANGAP1 expression was higher in the late-onset preeclampsia group compared to the late-onset control group [(3.764±3.297) vs. (0.960±0.720), t=4.07, P<0.001]. In late-onset preeclampsia patients, circRANGAP1 expression was positively correlated with both systolic and diastolic blood pressure (systolic: r=0.639, P<0.01; diastolic: r=0.800, P<0.001). There was no significant difference in EIF4A3 mRNA and protein expression between the early-onset preeclampsia group and the early-onset control group, but EIF4A3 mRNA and protein expression were higher in the late-onset preeclampsia group compared to the late-onset control group [mRNA: (2.963±3.081) vs. (1.149±0.667), t=2.30, P=0.028; protein: (2.504±1.008) vs. (0.258±0.180), t=4.39, P=0.005]. (2) After small interfering (si) RNA knockdown, there was no significant difference in mRANGAP1 expression, but circRANGAP1 expression decreased [(1.000±0.004), (0.465±0.031), and (0.621±0.030)], with si-1 showing the highest knockdown efficiency ( t=23.59, P=0.002). Specific knockdown of circRANGAP1 resulted in increased proliferation [(1.297±0.058) vs. (1.456±0.030), t=－5.97, P<0.001], invasion [(94.400± 6.504) vs. (219.000±19.870), t=－13.32, P<0.001], and migration [(25.493±3.498)% vs. (58.456±3.277)%, t=－15.38, P<0.001] abilities of trophoblast cells. (3) There are six binding sites for EIF4A3 in the upstream region of circRANGAP1 pre-mRNA. EIF4A3 can bind through regions a and b, but not region c. After siRNA knockdown, EIF4A3 expression decreased [(1.003±0.101), (0.276±0.060), (0.398±0.074), and (0.184±0.017)], with si-3 showing the highest knockdown efficiency. After EIF4A3 knockdown, circRANGAP1 expression in trophoblast cells decreased [(1.004±0.118) vs. (0.480±0.039), t=5.96, P=0.027]. Conclusion:circRANGAP1, regulated by EIF4A3, inhibits the proliferation, migration, and invasion abilities of trophoblast cells, thereby participating in the pathogenesis of preeclampsia.

Objective: To evaluate the protective effect of influenza vaccine among people aged 70 years and older in Jiaxing City, Zhejiang Province, so as to provide a basis for formulating immunization strategies. Methods: The influenza-like illness (ILI) cases aged 70 years and older treated in influenza surveillance sentinel hospital in Jiaxing City from November 2022 to May 2023 were selected. The medical information and influenza vaccination information were collected by a questionnaire survey, and influenza virus was detected using the quantitative fluorescent real-time PCR assay. The test-negative design case-control study was used to analyze the influencing factors of influenza virus positive and evaluate vaccine effect (VE). Results: Totally 1 084 ILI cases were enrolled, including 535 males (49.35%) and 549 females (50.64%). There were 732 cases (67.53%) aged 70 to 79 years, and 352 cases (32.47%) aged 80 years and older. There were 689 cases with underlying diseases, accounting for 63.56%. A total of 224 influenza virus positive samples were detected, with a positive rate of 20.66%. Multivariable logistic regression analysis showed that a lower possibility of influenza virus positive was seen in ILI cases aged 80 years and older, with underlying diseases and with influenza vaccination in the current season (all P<0.05). A total of 345 cases were vaccinated against influenza in the current season, with a vaccination rate of 31.83%. The VE of influenza vaccine was 37.40% (95%CI: 12.40%-55.40%), of which the VE to A (H1N1) was 36.00% (95%CI: 7.50%-55.70%) and to A (H3N2) was 40.90% (95%CI: -26.00%-72.30%). The VE for ILI cases aged 70 to 79 years was 41.00% (95%CI: 13.90%-59.60%), and for ILI cases aged 80 years and older was 20.60% (95%CI: -64.60%-61.70%). Conclusions Influenza vaccine has a certain protective effect on cases aged 70 years and older. Free influenza vaccination for the elderly should be continuously promoted and the vaccination coverage should be increased.

Objective:To classified the fluid location of of grade B and C postoperative pancreatic fistula (POPF) and propose processing flow.Methods:Data from 232 patients who underwent pancreatic surgery from January 2018 to December 2022 at Department of General Surgery & Hepato-billo-pancreatic,Beijing Hospital were collected retrospectively. Forty-six patients who suffered from grade B and C POPF underwent ultrasound-guided drainage. There were 32 males and 14 females, with an age of (60.2±13.7)years (range:18 to 85 years). The imaging data of postoperative CT were collected and the the fluid location was classified. Then analyzed the drainage status when patents were diagnosed as POPF. Machine learning was performed and a random forest model was applied to construct the relationship between intervention time and mortality. The optimal intervention time was calculated. The patients were then divided into early and late intervention groups and clinical data and outcomes were compared using the t test,Mann-Whitney U test, χ2 test or Fisher′s exact test between the two groups. Results:Based on the results of the random forest model, the optimal puncture time was within 5.38 days after the diagnosis of POPF. Based on the optimal time, 21 patients were subsumed into early intervention group and 25 patients were subsumed into late intervention group. The location of fluid collection was classified into four types: peripancreatic (32.7%,15/46), extra-pancreatic and epigastric (41.3%,19/46), extra-pancreatic and hypogastic (13.0%,6/46) and diffused (13.0%,6/46). The status of the drainage included normal in 10 patients (21.8%), displaced drain in 18 patients (39.1%) and drain removed or blocked in 18 patients (39.1%). The perioperative mortality rate was 19.0% (4/21) in the early intervention group and 8.0%(2/25) in the late. The late intervention group had significantly higher rates of positive drainage fluid cultures (88.0%(22/25) vs. 42.9%(10/21), χ2=10.584, P=0.001), secondary surgery (24.0%(6/25) vs. 0(0/21), P=0.025), and readmission within 90 days(32.0%(8/25) vs. 4.8%(1/21), χ2=5.381, P=0.020) than the early group, and a significantly longer postoperative hospital stay( M(IQR))(24(20)days vs. 39(53)days, Z=3.023, P=0.003). Conclusions:The location of the POPF fluid collection is classified into four types. Early radiological evaluation can detect abdominal effusion promptly,and early puncture and drainage will be beneficial in improving outcomes in these patents.

Objective: To investigate the resistance of Mycobacterium tuberculosis to first-line anti-tuberculosis drugs in Jiaxing City, Zhejiang Province from 2017 to 2019, so as to provide insights into improvements of the therapeutic effect of pulmonary tuberculosis. Methods: Data pertaining to pulmonary tuberculosis in Jiaxing City from 2017 to 2019 were collected from the Tuberculosis Surveillance System of Chinese Disease Prevention and Control Information System, including demographics, treatment classification, sputum culture and drug resistance. The spectrum, types and prevalence of drug resistance in M. tuberculosis to four first-line tuberculosis drugs, including isoniazid (INH), rifampicin (RFP), streptomycin (SM) and ethambutol (EMB), was analyzed using a descriptive epidemiological method. Results: A total of 1 310 M. tuberculosis isolates were cultured from pulmonary tuberculosis patients in Jiaxing City from 2017 to 2019, and there were 259 M. tuberculosis isolates that were resistant to anti-tuberculosis drugs, with an overall drug resistance rate of 19.77%. The prevalence rates of drug resistance to INH, SM, RFP and EMB were 13.36%, 11.83%, 5.50% and 3.59%, respectively. The prevalence of drug resistance was lower in M. tuberculosis isolates from treatment-naïve patients than from retreated patients (18.45% vs. 34.58%, P<0.05). M. tuberculosis isolates presented high resistance to SM (4.50%) and INH alone (4.35%), the highest resistance to INH-SM combinations (3.28%), and the highest resistance to INH+RFP+SM combinations (1.83%). Sixteen isolates were resistant to all the four drugs, with a drug resistance rate of 1.22%. The proportions of resistance to a single drug, RFP resistance, multidrug resistance and resistance to two and more drugs were 10.31%, 5.50%, 4.73% and 4.73%, respectively. In addition, the prevalence of RFP resistance among all patients and treatment-naïve patients both showed a tendency towards a rise from 2017 to 2019 (P<0.05). The prevalence of RFP resistance (7.01% vs. 3.76%) and resistance to two and more drugs (6.01% vs. 3.25%) was both higher among interprovincial mobile tuberculosis patients than among local non-mobile patients (P<0.05). Conclusions The overall prevalence of drug resistance was lower in M. tuberculosis isolates in Jiaxing City from 2017 to 2019 than in Zhejiang Province, with INH and RFP resistance as predominant types.

Objective:To classified the fluid location of of grade B and C postoperative pancreatic fistula (POPF) and propose processing flow.Methods:Data from 232 patients who underwent pancreatic surgery from January 2018 to December 2022 at Department of General Surgery & Hepato-billo-pancreatic,Beijing Hospital were collected retrospectively. Forty-six patients who suffered from grade B and C POPF underwent ultrasound-guided drainage. There were 32 males and 14 females, with an age of (60.2±13.7)years (range:18 to 85 years). The imaging data of postoperative CT were collected and the the fluid location was classified. Then analyzed the drainage status when patents were diagnosed as POPF. Machine learning was performed and a random forest model was applied to construct the relationship between intervention time and mortality. The optimal intervention time was calculated. The patients were then divided into early and late intervention groups and clinical data and outcomes were compared using the t test,Mann-Whitney U test, χ2 test or Fisher′s exact test between the two groups. Results:Based on the results of the random forest model, the optimal puncture time was within 5.38 days after the diagnosis of POPF. Based on the optimal time, 21 patients were subsumed into early intervention group and 25 patients were subsumed into late intervention group. The location of fluid collection was classified into four types: peripancreatic (32.7%,15/46), extra-pancreatic and epigastric (41.3%,19/46), extra-pancreatic and hypogastic (13.0%,6/46) and diffused (13.0%,6/46). The status of the drainage included normal in 10 patients (21.8%), displaced drain in 18 patients (39.1%) and drain removed or blocked in 18 patients (39.1%). The perioperative mortality rate was 19.0% (4/21) in the early intervention group and 8.0%(2/25) in the late. The late intervention group had significantly higher rates of positive drainage fluid cultures (88.0%(22/25) vs. 42.9%(10/21), χ2=10.584, P=0.001), secondary surgery (24.0%(6/25) vs. 0(0/21), P=0.025), and readmission within 90 days(32.0%(8/25) vs. 4.8%(1/21), χ2=5.381, P=0.020) than the early group, and a significantly longer postoperative hospital stay( M(IQR))(24(20)days vs. 39(53)days, Z=3.023, P=0.003). Conclusions:The location of the POPF fluid collection is classified into four types. Early radiological evaluation can detect abdominal effusion promptly,and early puncture and drainage will be beneficial in improving outcomes in these patents.

Acute abdominal pain is one of the most frequent complaints of patients presenting to the emergency department. Timely diagnosis and correct treatment affect the prognosis of patients. Traditional diagnosis mostly depends on physical examination and radiology. In terms of treatment, some patients need exploratory laparotomy. In recent years, with the development of interventional ultrasound, new techniques such as contrast-enhanced ultrasound, ultrasound-guided biopsy, drainage have been gradually applied to the diagnosis and treatment of surgical acute abdomen, especially the surgeon-performed interventional ultrasound, which has effectively improved the diagnostic efficiency and broadened the treatment choice. In this article, we aim to review and evaluate the application and progress of interventional ultrasound in the diagnosis and treatment of surgical acute abdomen.

【Objective】 To investigate the unqualified rate of anti-HIV detection of blood screening laboratories in Beijing-Tianjin-Hebei region, and explore the differences in anti-HIV detection ability and influencing factors in each laboratory. 【Methods】 Through filling questionnaires via e-mail, the anti-HIV ELISA unqualified rate and confirmed (WB) positive results (data) from January to December 2018 from 15 blood screening laboratories in Beijing-Tianjin-Hebei region were collected. Our laboratory was responsible for data collection and confirmation, and statistics software SPSS22.0 was used for analysis. 【Results】 1) There was a statistically significant difference among the unqualified rate of anti-HIV ELISA(6.77‱~35.71‱) and confirmed positive rate(0.60‱~3.56‱) in 15 blood screening laboratories in Beijing-Tianjin-Hebei region (P<0.05); 2) There were significant differencse among the ELISA unqualified rate and the confirmed positive rate of 8 reagents for anti-HIV detection(P<0.01), and the sensitivity of the 4th generation detection reagent and the imported reagent was higher than that of the 3rd generation reagent and the domestic reagent. The anti-HIV ELISA unqualified rate of R5 was the highest (19.08‱). 3)There were significant differences in the anti-HIV ELISA unqualified rate of R1, R2, R3, R5 and R7 reagents among different blood station laboratories(P<0.05), and there were no significant differences in the anti-HIV ELISA unqualified rate of R4, R6 and R8 reagents among different blood station laboratories(P>0.05). 4)The unqualified rate of anti-HIV ELISA of laboratories using different regents showed significant differences(P<0.05), except H, J, M. The unqualified rate of imported reagent was significantly higher than that of domestic reagents of laboratories using imported and domestic reagents combinations(P<0.05), except O. 62.5% (5/8) laboratories using domestic 3^rd and 4^th generation reagent combination showed significant differences in the unqualified rates among different reagents(P<0.05); 5) The positive rate of single-reagent(62.02%~95.45%)in 15 blood screening laboratories showed significant difference(P<0.001), and A was the lowest (62.02%). 【Conclusion】 The anti-HIV detection ability among 15 blood screening laboratories in Beijing-Tianjin-Hebei region is quite different. The application of different reagents is the main factor for the difference, and other factors such as personnel, instruments and test strategies also has a great impact on the detection of anti-HIV. It is still necessary to promote the process of homogenization of blood testing quality among blood screening laboratories in Beijing-Tianjin-Hebei region.

Objective To evaluate the treatment effect of using preoperative embolization combined with microsurgery for the treatment of intracranial arteriovenous malformation.Methods From January 2005 to December 2015,57 consecutive patients with intracranial arteriovenous malformation (AVM ) admitted to the Department of Neurosurgery,Xuanwu Hospital,Capital Medical University were enrolled retrospectively. They were diagnosed by magnetic resonance imaging (MRI)and digital subtraction angiography (DSA). Glubran and/or Onyx embolization was used before the microsurgery. The clinical features,treatment, and occurrence of complications were recorded.Results In 57 patients,the Spetzler-Martin grade in 35 patients were gradeⅠ-Ⅱ,in 18 were Ⅲ,and in 4 were Ⅳ. The complications occurred in 11 patients (19. 3%),including 5 with Onyx,5 with Glubran,and 1 with Onyx+Glubran. After embilization,4 patients had hemorrhage,2 had intracranial hemorrhage,1 had postoperative intracranial infection,1 had postoperative neuro-logical dysfunction,and 3 had other systemic complications after procedure. The complication rates were 14. 3%(5/35)and 22. 2%(4/18)respectively according to the Spetzler-Martin grade Ⅰ-Ⅱ and Ⅲ. Two patients of Spetzler-Martin gradeⅣhad complications. The incidence of complications in the functional areas was 20. 0%(4/20)and that in non-functional areas was 18. 9%(7/37). One patient died. DSA revealed that 4 patients had residual lesions before discharge. The cure rate was 93. 0%. The mean modified Rankin scale (mRS)score at discharge was 1. 6 ± 1. 0. The patients of mRS 0-1 accounted for 59. 6%(34/57).The mRS scores in 7 patients at discharge were higher than before treatment.Conclusion For the high-grade AVM foci with larger volume and in the deep part of brain,the treatment with microsurgery combined with embolization can be considered.