Objective:To analyze and determine the clinical and genetic characteristics of children with Helsmoortel-Van der Aa syndrome(HVDAS).Methods:Clinical data of 6 children with HVDAS treated at the First Hospital of Peking University from November 2018 to October 2022 and their family members were collected and analyzed retrospectively.Whole exome sequencing was performed on children and their family members to identify the genetic variants.Genotype and phenotype correlation was analyzed.Results:(1) Clinical analysis results: among the 6 children, there were 5 boys and 1 girl, and their age at diagnosis ranged from 11 months and 17 days to 12 years and 9 months.Six patients all presented with developmental delays/intellectual disabilities; (2) Genetic analysis results: 6 de novo ADNP variants were discovered in 6 children, including 1 initial codon deletion variant c. 1_2del, 2 nonsense variants c. 1175dup, p.(Tyr392*) and c. 2213C>G, p.(Ser738*), and 3 frameshift variants c. 2632dup, p.(Ser878Lysfs*3), c.1695_1696insATGGTATGTATGTATGTATG, p.(Val566Metfs*8) and c. 2120_2123del, p.(Asn707Serfs*8).All variants were classified as pathogenic variants by the American College of Medical Genetics and Genomics.Except the c. 2213C>G, p.(Ser738*), the other 5 variants are all novel variants that have not been reported before. Conclusions:All of the 6 cases of HVDAS showed typical clinical manifestations, and expanded the phenotype spectrum of microcephaly and tall stature.Six de novo mutations were discovered, expanding the ADNP mutation spectrum and providing accurate genetic counseling and prenatal genetic diagnosis of the disease.

Objective To analyze the influencing factors of poor anal function after laparoscopic intersphincteric resection(Lap-ISR)for extremely low rectal cancer,and to construct and verify a prediction model based on this model,in order to provide guidance for improving the anal function of patients with extremely low rectal cancer after Lap-ISR.Method A total of 127 patients with extremely low rectal cancer who underwent Lap-ISR in Taizhou People's Hospital from June 2020 to June 2022 were retrospectively selected.Patients were followed up for 12 months after surgery,and postoperative anal function was evaluated by the anal incontinence score(Wexner).According to Wexner score,the patients were divided into good anal function group(106 cases)and poor anal function group(21 cases).The clinical data of patients were collected and the risk factors affecting postoperative poor anal dysfunction were analyzed,and a Nomogram model was constructed to predict the risk of postoperative anal dysfunction in patients after Lap-ISR,and the receiver operating characteristic curve(ROC)was drawn.The area under the curve(AUC)was used to analyze the predictive efficacy of the prediction model for poor anal dysfunction after Lap-ISR.Result The incidence of anal dysfunction after Lap-ISR in patients with extremely low rectal cancer was 16.54％(21/127).Univariate analysis showed that there was no significant difference in gender,age,body mass index,clinical stage,combined underlying diseases,operation time,intraoperative blood loss,anastomosis method,and the distance from the lower edge of the tumor to the dentate line between the two groups(P＞0.05).The proportion of tumor diameter≥5 cm,the proportion of neoadjuvant chemotherapy,the distance between anastomosis and anal verge＜2 cm,and the proportion of anastomotic leakage in the anal dysfunction group were higher than those in the good anal function group(P＜0.05).Cox multivariate regression analysis showed that tumor diameter≥5 cm(OR=5.124),neoadjuvant chemotherapy(OR=5.761)and anastomotic leakage(OR=6.881)were risk factors for postoperative anal function(P＜0.05).Wexner score of patients with tumor diameter ≥5 cm was higher than that of patients with tumor diameter＜5 cm,Wexner score of patients with neoadjuvant chemotherapy was higher than that of patients without neoadjuvant chemotherapy,and Wexner score of patients with anastomotic leakage was higher than that of patients without anastomotic leakage(P＜0.05).Internal validation of Bootstrap method showed that the C-index was 0.785(95％CI:0.692-0.851).The results of ROC curve showed that the sensitivity and specificity of the nomogram model in predicting postoperative poor anal function of patients were 85.70％and 88.70％,respectively,and the AUC was 0.895(95％CI:0.795-0.984).Conclusion Tumor diameter,neoadjuvant chemotherapy and anastomotic leakage are risk factors for poor anal function after Lap-ISR in patients with extremely low rectal cancer.The nomogram risk prediction model based on the above risk factors has a good risk efficiency in evaluating the risk of postoperative anal dysfunction in patients.

Objective To investigate radiation resources in medical diagnosis and treatment and their use frequency in medical institutions in Hangzhou, China, and to provide a basis for relevant departments to rationally allocate and scientifically supervise the resources. Methods From April 1, 2019 to March 31, 2020, a survey was conducted on the basic information, radiation staff, equipment configuration, and frequency of radiation diagnosis and treatment of all medical institutions in Hangzhou using a questionnaire. Results There were 1001 institutions with radiation services in Hangzhou, with 6714 radiation staff members and 2742 pieces of radiation equipment. The frequency of conventional X-ray diagnosis was 788.43 per 1000 population. The frequency of computed tomography diagnosis was 531.93 per 1000 population. The frequency of mammography and dental photography diagnosis was 246.34 per 1000 population. The frequency of interventional diagnosis and treatment was 10.01 per 1000 population. The frequency of radiotherapy was 2.39 per 1000 population. The frequency of nuclear medicine diagnosis was 8.90 per 1000 population. The frequency of nuclear medicine treatment was 0.99 per 1000 population. Conclusion Medical institutions have developed rapidly in Hangzhou, but with an unbalanced situation. In order to better protect the health of examinees, we recommend relevant departments optimize resource allocation and strengthen supervision on radiation protection in medical institutions.

Sterols are a class of cyclopentano-perhydrophenanthrene derivatives widely present in living organisms. Sterols are important components of cell membranes. In addition, they also have important physiological and pharmacological activities. With the development of synthetic biology and metabolic engineering technology, yeast cells are increasingly used for the heterologous synthesis of sterols in recent years. Nevertheless, since sterols are hydrophobic macromolecules, they tend to accumulate in the membrane fraction of yeast cells and consequently trigger cytotoxicity, which hampers the further improvement of sterols yield. Therefore, revealing the mechanism of sterol transport in yeast, especially understanding the working principle of sterol transporters, is vital for designing strategies to relieve the toxicity of sterol accumulation and increasing sterol yield in yeast cell factories. In yeast, sterols are mainly transported through protein-mediated non-vesicular transport mechanisms. This review summarizes five types of sterol transport-related proteins that have been reported in yeast, namely OSBP/ORPs family proteins, LAM family proteins, ABC transport family proteins, CAP superfamily proteins, and NPC-like sterol transport proteins. These transporters play important roles in intracellular sterol gradient distribution and homeostasis maintenance. In addition, we also review the current status of practical applications of sterol transport proteins in yeast cell factories.
Saccharomyces cerevisiae/genetics* ; Sterols ; Phytosterols ; Biological Transport ; ATP-Binding Cassette Transporters/genetics*

Enterotoxigenic Escherichia coli（ETEC）infection can induce watery diarrhea，leading to dehydration，electrolyte disturbance，and even death in severe cases. Recombinant B subunit/inactivated whole-cell cholera（rBS/WC）vaccine is effective in preventing ETEC infectious diarrhea. On the basis of the latest evidence on etiology and epidemiology of ETEC，as well as the effectiveness，safety，and health economics of rBS/WC vaccine，National Clinical Research Center for Child Health（The Children’s Hospital，Zhejiang University School of Medicine）and Zhejiang Provincial Center for Disease Control and Prevention invited experts to develop expert consensus on rBS/WC vaccine in prevention of ETEC infectious diarrhea. It aims to provide the clinicians and vaccination professionals with guidelines on using rBS/WC vaccine to reduce the incidence of ETEC infectious diarrhea.

Objective:To compare the clinical outcomes of a double purse-string and bridging technique versus duct-to-mucosal pancreaticojejunostomy in laparoscopic pancreaticoduodenectomy.Methods:The clinical data of patients who underwent laparoscopic pancreaticoduodenectomy using the double purse-string and bridging pancreaticojejunostomy technique versus those who underwent duct-to-mucosa pancreaticojejunostomy at the Affiliated Jinhua Hospital of Zhejiang University School of Medicine from January 2016 to August 2021 were retrospectively analyzed. Of the 93 patients who underwent laparoscopic pancreaticoduodenectomy, there were 48 males and 45 females, with age of (62±10) years old. These patients were divided into two groups: patients who underwent double purse-string and bridging pancreaticojejunostomy (the double purse-string group, n=51), and patients who underwent duct-to-mucosa pancreaticojejunostomy (the duct-to-mucosa group, n=42). The clinical data of the two groups were compared. Results:All the 93 patients underwent laparoscopic pancreaticoduodenectomy successfully, and there were no deaths within 3 months of operation. Compared with the duct-to-mucosa group, the double purse-string group had significantly shorter time of pancreaticojejunal anastomosis [(32.41±8.75) vs. (47.62±8.90) min] and time of operation [(365.75±43.74) vs. (389.07±45.31) min] (all P<0.05). The postoperative pancreatic fistula rates were 9.8% (5/51) in the double purse-string group and 7.1% (3/42) in the duct-to-mucosa group. There was no significant difference between the two groups ( P>0.05). In the double purse-string group, there were 18 patients with a pancreatic duct diameter >3 mm, and 3 of these patients developed grade B pancreatic fistula, giving a grade B pancreatic fistula rate of 16.6% (3/18). In the duct-to-mucosa group, there were 11 patients with a pancreatic duct diameter >3 mm, and no patients developed grade B pancreatic fistula, giving a pancreatic fistula rate of 0(0/11). Conclusion:Compared with the duct-to-mucosa anastomosis, the double purse string and bridging pancreaticojejunostomy was technically simpler. It shortened the time of pancreaticojejunostomy in laparoscopic pancreaticoduodenectomy, especially for patients with a non-dilated pancreatic duct.

OBJECTIVE: To carry out amniocyte karyotyping analysis and chromosomal microarray analysis (CMA) for women with anomalies revealed by fetal echocardiography. METHODS: From January 2019 to December 2021, genetic testing was carried out for 205 fetuses including 97 with soft marker anomalies and 108 with structural heart abnormalities. Among these, 138 only had abnormal fetal echocardiography, whilst 38 and 29 were complicated with extracardiac soft marker anomalies and extracardiac structural malformation, respectively. RESULTS: No significant difference was detected in the detection rate of genetic anomalies between fetuses with heart-related soft markers and those with abnormal heart structures (P > 0.05). Compared with those with abnormal fetal echocardiography alone, the detection rates of chromosomal aneuploidies in those with abnormal extracardiac soft markers or abnormal extracardiac structures were significantly higher (P < 0.05). Twenty-eight chromosomal aneuploidies (including a rare mosaicism), 2 balanced translocations and 1 supernumerary marker chromosome were detected by karyotyping analysis. Twenty-seven aneuploidies, 19 copy number variations (CNVs) and 1 uniparental disomy were detected by CMA. CONCLUSION Prenatal diagnosis has attached great importance to the suggestive role of fetal heart-related soft markers, and chromosomal aneuploidies are more common among fetuses with abnormal extracardiac soft markers and extracardiac structural abnormalities. Chromosomal Karyotyping is useful for the detection of balanced translocations and mosaicisms. CMA is helpful for the detection of CNVs. Identification of the genetic causes can facilitate genetic counseling for the affected couples.
Pregnancy ; Female ; Humans ; DNA Copy Number Variations ; Prenatal Diagnosis ; Fetus ; Echocardiography ; Aneuploidy ; Mosaicism ; Translocation, Genetic

Objective:To understand the current situation of nurses in 52 hospitals in China on mastery of knowledge about skin injury in the elderly based on the background of mixed-mode homogenization training.Methods:Using the convenient sampling method, a total of 1 067 nurses from 52 hospitals in China were selected as the research objects in January 2021. A self-designed questionnaire on knowledge of skin injury in the elderly was used to investigate the nurses through the questionnaire star and univariate analysis was used to analyze the influencing factors. A total of 1 067 questionnaires were distributed and 1 067 valid questionnaires were recovered, and the effective recovery rate was 100%.Results:The knowledge scores of pressure injury, incontinence-associated dermatitis, skin tear and xerosis cutis among 1067 nurses were (95.66±7.37) , (95.65±9.15) , (91.37±15.45) and (87.67±15.91) , respectively. The results of univariate analysis showed that hospital grade was the influencing factor of nurses' knowledge score of pressure injury, skin tear and incontinence-associated dermatitis ( P<0.05) , educational background was the influencing factor of nurses' knowledge score of skin tear ( P<0.05) , professional title was the influencing factor of nurses' knowledge scores of pressure injury, incontinence-associated dermatitis and xerosis cutis ( P<0.05) . Conclusions:Hospitals at all levels need to strengthen the theoretical and practical knowledge training for nurses on skin xerosis and skin tear in the elderly, especially for nurses with primary titles and lower education in grassroots hospitals.

Objective:To investiagte the ability of albumin-indocyanine green (ALICE) score, albumin-bilirubin (ALBI) score and Child-Pugh score in predicting postoperative liver failure (PHLF) in patients with hepatocellular carcinoma, and to determine the clinical value of ALICE score.Methods:The clinical data of 397 patients with hepatocellular carcinoma who underwent hepatectomy in the Department of Hepatobiliary and Pancreatic Surgery, Jinhua Hospital Affiliated to Zhejiang University from June 2015 to June 2021 were retrospectively analyzed, including 350 males and 47 females, aged (58.9±11.2) years. Univariate and multivariate logistic regression were used to analyze the risk factors of PHLF. The predictive ability of ALICE score for PHLF was evaluated by receiver operating characteristic (ROC) curve, and compared with ALBI score and Child-Pugh score.Results:There were 74 patients with PHLF and 323 patients without PHLF. Multivariate logistic regression analysis showed that Child-Pugh score ( OR=1.630, 95% CI: 1.251-2.486, P=0.034), ALBI score ( OR=1.863, 95% CI: 1.028-3.119, P=0.049) and ALICE score ( OR=1.759, 95% CI: 1.216-3.078, P=0.038) were independent risk factors for PHLF in patients with hepatocellular carcinoma, and the risk of PHLF increased with the increase of grade. The area under the ROC curve of ALICE score predicting PHLF in patients with hepatocellular carcinoma was 0.613 (95% CI: 0.564-0.662), the area under the ALBI score was 0.612 (95% CI: 0.563-0.661), and the area under the Child-Pugh score was 0.555 (95% CI: 0.505-0.605). The ALICE score was better than the Child-Pugh score, and the difference was statistically significant ( z=2.04, P=0.041). In small liver resection patients, ALICE score was better than Child-Pugh score ( z=2.61, P=0.009). There was no significant difference betwenn ALICE score and ALBI score ( z=0.06, P=0.954). Conclusion:ALICE score can predict the occurrence of PHLF in patients with hepatocellular carcinoma, especially in patients with small liver resection, its value is similar to ALBI score, but better than Child-Pugh score.

Objective:To analyze the causes of SARS-CoV-2 nosocomial infection among healthcare workers (HCWs) and explore the effective precaution strategies in Emergency Center.Methods:The data of SARS-CoV-2 infected HCWs from January 5 to March 2, 2020 were retrospectively analyzed and compared under different conditions in Emergency Center of Zhongnan Hospital of Wuhan University.Results:Totally 13 SARS-CoV-2 infected HCWs (12 confirmed cases and 1 suspected case) were included in this study. The overall infection rate was 17.8% (13/73). The infection rates in outpatient/rescue room, isolation observation room and isolationin patient ward were 11.8% (4/34), 20.0% (3/15), 25% (6/24), respectively. The infection rate of physician was 13.0% (3/23), and the infection rate of nurse was 20.0% (10/50). All the infected HCWs had the definite exposure with confirmed or suspected COVID-19 patients. One asymptomatic cases were identified by laboratory findings of SARS-CoV-2 infection screening. There was no new confirmed SARS-CoV-2 infected HCWs after February 5, 2020. All the infected HCWs were cured.Conclusions:Under the epidemic of COVID-19, HCWs of Emergency Center have a high risk of occupational exposure and infection, especially for staffs working in COVID-19 isolation units. Scientific prevention and control management can effectively reduce the risk of SARS-CoV-2 infections and ensure the occupational safety for HCWs in Emergency Center.