Objective To investigate the epidemiological characteristics and mutation spectrum of monogenic diseases in Chinese population through a large-scale,multicenter carrier screening.Methods This study was conducted among a total of 33 104 participants(16 610 females)from 12 clinical centers across China.Carrier status for 223 genes was analyzed using high-throughput sequencing and different PCR methods.Results The overall combined carrier frequency was 55.58%for 197 autosomal genes and 1.84%for 26 X-linked genes in these participants.Among the 16 669 families,874 at-risk couples(5.24%)were identified.Specifically,584 couples(3.50%)were at risk for autosomal genes,306(1.84%)for X-linked genes,and 16 for both autosomal and X-linked genes.The most frequently detected autosomal at-risk genes included GJB2(autosomal recessive deafness type 1A,393 couples),HBA1/HBA2(α-thalassemia,36 couples),PAH(phenylketonuria,14 couples),and SMN1(spinal muscular atrophy,14 couples).The most frequently detected X-linked at-risk genes were G6PD(G6PD deficiency,236 couples),DMD(Duchenne muscular dystrophy,23 couples),and FMR1(fragile X syndrome,17 couples).After excluding GJB2 c.109G>A,the detection rate of at-risk couples was 3.91%(651/16 669),which was lowered to 1.72%(287/16 669)after further excluding G6PD.The theoretical incidence rate of severe monogenic birth defects was approximately 4.35‰(72.5/16 669).Screening for a battery of the top 22 most frequent genes in the at-risk couples could detect over 95%of at-risk couples,while screening for the top 54 genes further increased the detection rate to over 99%.Conclusion This study reveals the carrier frequencies of 223 monogenic genetic disorders in the Chinese population and provides evidence for carrier screening strategy development and panel design tailored to the Chinese population.In carrier testing,genetic counseling for specific genes or gene variants can be challenging,and the couples need to be informed of these difficulties before testing and provided with options for not screening these genes or gene variants.

Objective To analyze the clinical characteristics of patients with acute esophageal injuries in order to improve clinicians'diagnosis and treatment of such diseases.Methods The general data and treatment methods of 61 patients with acute esophageal injury from January 2013 to March 2023 were retrospectively analyzed.Results Majority of the patients with esophageal and cardia mucosal tear syndrome were male(72.2%),age(52.04±17.96)years,triggering factor was gastroscopy in 29 patients(53.7%),and vomiting of blood and black stools was the main clinical manifestation(63.0%),the average length of hospital stay was(6.39±3.53)d and 13(24.1%)patients had anaemic complications,blood transfusion was given to 8 patients(14.8%),39 patients(72.2%)were discharged after conservative treatment with transfusion,and only 15 patients(27.8%)required endoscopic hemostasis.1 case of esophageal hematoma combined with esophageal cardia mucosal tear syndrome was an elderly male patient with a history of hypertension,cerebral infarction,and long term use of oral aspirin,complicated by severe anemia,who was given desiprofloxacin to stop the hemostasis endoscopically,the total length of hospital stay was 22 d.4 patients with esophageal hematoma were young and middle-aged males,2 patients had a predisposing factor of poor diet prior to the onset of the disease,2 patients presented with vomiting of blood,1 with chest pain and 1 with a foreign body sensation in the throat,2 patients were discharged with endoscopic intervention,and the remaining 2 patients were discharged after conservative treatment.2 patients with spontaneous esophageal rupture were young and middle-aged males,clinical manifestations were chest tightness or retrosternal discomfort,and one patient had esophageal rupture with left-sided liquid pneumothorax,esophageal rupture repair+pleural adhesion branding+open thoracic hemostasis+intrathoracic foreign body removal was performed,and an esophageal stent was placed endoscopically after the operation,and the patient was discharged from the hospital after 52 d,in another case,the patient's esophageal fistula was small,and a three-lumen nutrient tube was placed under gastroscopic guidance,the patient's esophagus recovered well after 7 d,and the patient was discharged from the hospital.Conclusion Acute esophageal injury is a clinical emergency,among them,esophageal hematoma and spontaneous esophageal rupture are relatively rare.Prompt endoscopic clot removal is a viable option for patients with ruptured esophageal hematomas who have failed conservative treatment,and patients with spontaneous esophageal rupture who have surgically placed esophageal stents have good mucosal recovery.Clinicians need to be vigilant for patients with esophageal injuries that are associated with anemia,or even require blood transfusion,should make a clear diagnosis at an early stage,with timely endoscopic or surgical intervention to avoid progression of the disease.

Objective To investigate the epidemiological characteristics and mutation spectrum of monogenic diseases in Chinese population through a large-scale,multicenter carrier screening.Methods This study was conducted among a total of 33 104 participants(16 610 females)from 12 clinical centers across China.Carrier status for 223 genes was analyzed using high-throughput sequencing and different PCR methods.Results The overall combined carrier frequency was 55.58%for 197 autosomal genes and 1.84%for 26 X-linked genes in these participants.Among the 16 669 families,874 at-risk couples(5.24%)were identified.Specifically,584 couples(3.50%)were at risk for autosomal genes,306(1.84%)for X-linked genes,and 16 for both autosomal and X-linked genes.The most frequently detected autosomal at-risk genes included GJB2(autosomal recessive deafness type 1A,393 couples),HBA1/HBA2(α-thalassemia,36 couples),PAH(phenylketonuria,14 couples),and SMN1(spinal muscular atrophy,14 couples).The most frequently detected X-linked at-risk genes were G6PD(G6PD deficiency,236 couples),DMD(Duchenne muscular dystrophy,23 couples),and FMR1(fragile X syndrome,17 couples).After excluding GJB2 c.109G>A,the detection rate of at-risk couples was 3.91%(651/16 669),which was lowered to 1.72%(287/16 669)after further excluding G6PD.The theoretical incidence rate of severe monogenic birth defects was approximately 4.35‰(72.5/16 669).Screening for a battery of the top 22 most frequent genes in the at-risk couples could detect over 95%of at-risk couples,while screening for the top 54 genes further increased the detection rate to over 99%.Conclusion This study reveals the carrier frequencies of 223 monogenic genetic disorders in the Chinese population and provides evidence for carrier screening strategy development and panel design tailored to the Chinese population.In carrier testing,genetic counseling for specific genes or gene variants can be challenging,and the couples need to be informed of these difficulties before testing and provided with options for not screening these genes or gene variants.

Objective:To analyze circRNAs specifically differentially expressed in esophageal squamous cell carcinoma (ESCC) based on high-throughput sequencing data.Methods:Six patients with pathologically confirmed ESCC in Tangdu Hospital of Air Force Medical University from March 2018 to March 2019 were selected as the research subjects, among which 3 were stage Ⅰ ESCC and 3 were stage Ⅲ ESCC. High-throughput sequencing technology was used to analyze the difference in the expression of circRNA in cancer tissues and adjacent tissues of patients. GO enrichment analysis, KEGG enrichment analysis and Venn analysis were performed on differentially expressed genes. The circRNA-miRNA-mRNA network was constructed using Cytoscape software. The most significantly differentially expressed genes in cancer tissues were verified in cells and tissues, and the relationships between circRNAs and clinical pathological indicators of patients were analyzed.Results:A total of 553 differentially expressed circRNAs were screened in paracancerous tissues and cancer tissues of 3 stage Ⅰ ESCC patients, of which 413 were up-regulated and 140 were down-regulated in cancer tissues; A total of 425 differentially expressed circRNAs were screened in paracancerous tissues and cancer tissues of 3 stage Ⅲ ESCC patients, of which 276 were up-regulated and 149 were down-regulated in cancer tissues. GO enrichment analysis showed that the host genes of differential circRNAs in patients with stage Ⅰ ESCC were mainly enriched in cell cycle-related biological processes such as mitotic G 2/M transition. The host genes of differential circRNAs in patients with stage Ⅲ ESCC were mainly enriched in biological processes related to cell division and tumor development, such as mitotic spindle checkpoint and cell matrix adhesion. KEGG enrichment analysis showed that the differential circRNAs in cancer tissues of stage Ⅰ and stage Ⅲ ESCC patients were mainly enriched in cancer-related biological pathways such as cell adhesion. The results of Venn analysis showed that in stage Ⅰ ESCC patients and stage Ⅲ ESCC patients, 2 and 8 circRNAs that were only specifically expressed in paracancerous tissues and had significant differences were screened out respectively, and were only specifically expressed in cancer tissues with significant differences were 11 and 14 respectively. The circRNA-miRNA-mRNA network showed that the cancer tissue-related circRNA-miRNA-mRNA network in stage Ⅰ ESCC patients consisted of 7 circRNA nodes, 10 miRNA nodes and 28 mRNA nodes, and the cancer tissue-related circRNA-miRNA-mRNA network in stage Ⅲ ESCC patients consisted of 7 circRNA nodes, 9 miRNA nodes and 49 mRNA nodes. The most significantly differentially expressed hsa-circ-0060927 and hsa-circ-0109301 in cancer tissues of patients with stage Ⅰ ESCC and stage Ⅲ ESCC were selected for cytological and histological verification. The results showed that the relative expression levels of hsa-circ-0060927 in ESCC cell lines TE1, TE13, KYSE30, KYSE170, and human normal esophageal epithelial cell line HEEC were 7.82±1.96, 12.69±2.68, 12.78±2.74, 7.53±1.75, and 2.43±0.17, respectively, with a statistically significant difference ( F=4.68, P=0.004). The relative expression levels of hsa-circ-0060927 in ESCC cell lines TE1, TE13, KYSE30, and KYSE170 were higher than that in human normal esophageal epithelial cell line HEEC, with statistically significant differences ( P=0.009; P=0.003; P=0.003; P=0.007). The relative expression levels of hsa-circ-0109301 in ESCC cell lines TE1, TE13, KYSE30, KYSE170, and human normal esophageal epithelial cell line HEEC were 5.16±1.32, 6.28±1.57, 4.89±1.13, 8.92±2.12, and 22.56±4.13, respectively, with a statistically significant difference ( F=4.31, P=0.022). The relative expression levels of hsa-circ-0109301 in ESCC cell lines TE1, TE13, KYSE30, and KYSE170 were lower than that in human normal esophageal epithelial cell line HEEC, with statistically significant differences ( P=0.027; P=0.015; P=0.024; P=0.008). The expression level of hsa-circ-0060927 in cancer tissues of 13 early ESCC patients was 12.89±2.67, significantly higher than 5.73±1.18 in paracancerous tissue, and there was a statistically significant difference ( t=15.02, P<0.001) ; the expression level of hsa-circ-0109301 in cancer tissues of 19 patients with advanced ESCC was 7.78±2.17, significantly lower than 16.32±3.15 in paracancerous tissue, and there was a statistically significant difference ( t=9.73, P<0.001). The expression of hsa-circ-0109301 was related to the degree of tumor differentiation in advanced ESCC patients ( P=0.023) . Conclusion:One circRNA (hsa-circ-0060927 and hsa-circ-0109301) with the most significanty differential expression is selected in early and advanced ESCC patients respectively, in which hsa-circ-0060927 is highly expressed in ESCC cancer tissues and hsa-circ-0109301 is lowly expressed in ESCC cancer tissues, and the expression of hsa-circ-0109301 is correlated with the degree of tumor differentiation.

Objective:To explore the effect of mind mapping teaching of gastroenterology in the standardized training for general practitioners, and provide new ideas for general practice education.Methods:A total of 65 physicians who were enrolled in the standardized training of general practice from January to December 2017 were collected as the control group, and the traditional teaching method was adopted; another 58 physicians from January to December 2018 were selected as the experimental group, and the mind mapping was adopted based on the traditional teaching method. The learning effect (theoretical and operational results) and the satisfaction questionnaire of trainees and teachers were used as evaluation indicators. SPSS 21.0 was used for t test and chi-square test. Results:The theory exam and clinical skills examination results of experimental group (80.80±5.30, 82.66±5.90) were significantly higher than those of the control group (71.60±5.20, 75.72±4.57), and the difference was statistically significant ( P<0.05). Compared with the control group, the experimental group had better understanding of knowledge points of this discipline, clinical thinking ability, higher learning interest, teamwork ability, innovation ability and teacher satisfaction, with statistical significance ( P<0.05). Conclusion:The mind mapping has more advantages than traditional teaching methods in the standardized training for general practitioners, which can be further extended.

Objective:To explore the effect of evidence-based nursing based on the ACE-Star model as the theoretical framework for incision management of patients undergoing transoral endoscopic thyroidectomy.Methods:Convenience sampling was used to select 40 patients with thyroid tumor in General Surgery of Nanyang Central Hospital in Henan Province from June 2019 to June 2020 as the control group, and received routine thyroidectomy nursing. A total of 32 patients admitted from July 2020 to June 2021 were selected as the observation group, and were given evidence-based nursing with the ACE-Star model as the theoretical framework, including body position management, incision anti-infection management, and headgear usage management. The total drainage volume, extubation time, hospital stay, Visual Analogue Scale (VAS) score, incidence of complications (infection, facial edema, subcutaneous congestion) , and patient satisfaction were compared between the two groups, and the implementation rate of evidence-based items in the observation group was recorded.Results:The total drainage volume, extubation time, hospital stay, and VAS score of the observation group were lower than those of the control group, and the differences were statistically significant ( P<0.05) . The incidence of complications in the observation group was lower than that in the control group, and the difference was statistically significant (χ 2=6.57, P<0.05) . The patients in the observation group had higher satisfaction with nursing than the control group, and the difference was statistically significant (χ 2=6.68, P<0.05) . In the observation group, the implementation rates of three evidence-based management items, including body position management, incision anti-infection management, and headgear usage management, were 96.88%, 96.88%, and 93.75%, respectively, and the implementation rates were all higher than 90%. Conclusions:Evidence-based nursing with the ACE-Star model as the theoretical framework is used for the incision management of transoral endoscopic thyroidectomy, which is beneficial to reduce postoperative complications and improve patient satisfaction, and has certain clinical guiding significance.

Objective:To build a three-dimensional evaluation model of single bed efficiency in an obstetrics and gynecology hospital and provide reference for bed management in hospital.Methods:The sample ward and key indicators were determined through interviews. A two-level database was built according to patients′ data from hospital information system. K-means cluster analysis was used to get the beds classified by annual average vacancy(x), annual average turnover(y) and annual average case-mix index per capita(z). The authors built the three-dimensional bed efficiency model with x, y, z as boundaries and analyzed the bed efficiency by comparing the within group average point A k( x k, y k, z k) with the overall average point A0( x, y, z). Whereafter the bed efficiency of each medical work team was analyzed. Results:Thirty-six beds were classified into 4 categories according to utilization efficiency. 50% of the beds(18 beds) were well used, 28%(10 beds) had room for improvement, and 19%(7 beds) may have resource waste. Significant differences existed in bed efficiency among medical work teams.Conclusions:The model in our study can realize in-depth exploration by evaluating bed efficiency from two aspects of the whole ward and each medical work team. This model, which is mainly applicable to the situation where beds are under the charge of fixed medical work groups or doctors, can be adjusted and extended to meet different strategic needs of hospitals.

Objective To evaluate the clinical value of holographic image navigation in urological laparoscopic and robotic surgery.Methods The data of patients were reviewed retrospectively for whom accepted holographic image navigation laparoscopic and robotic surgery from Jan.2019 to Dec.2019 in Beijing United Family Hospital and other 18 medical centers,including 78 cases of renal tumor,2 cases of bladder cancer,2 cases of adrenal gland tumor,1 cases of renal cyst,1 case of prostate cancer,1 case of sweat gland carcinoma with lymph node metastasis,1 case of pelvic metastasis after radical cystectomy.All the patients underwent operations.In the laparoscopic surgery group,there were 27 cases of partial nephrectomy,1 case of radical prostatectomy,2 cases of radical cystectomy and 2 cases of adrenalectomy.In the da Vinci robotic surgery group of 54 cases,there were 51 cases of partial nephrectomy,1 case of retroperitoneal lymph node dissection,1 case of retroperitoneal bilateral renal cyst deroofing and 1 case of resection of pelvic metastasis.There were 41 partial nephrectomy patients with available clinical data for statistic,with a median age of 53.5 years (range 24-76),including 26 males and 15 females.The median R.E.N.A.L score was 7.8 (range 4-11).Before the operation,the engineers established the holographic image based on the contrast CT images and reports.The surgeon applied the holographic image for preoperative planning.During the operation,the navigation was achieved by real time fusing holographic images with the laparoscopic surgery images in the screen.Results All the procedures had been complete uneventfully.The holographic images helped surgeon in understanding the visual three-dimension structure and relation of vessels supplying tumor or resection tissue,lymph nodes and nerves.By manipulating the holographic images extracorporeally,the fused image guide surgeons about location vessel,lymph node and other important structure and then facilitate the delicate dissection.For the 41 cases with available clinical data including 23 cases of robotic-assisted partial nephrectomy and 18 cases of laparoscopic nephrectomy,the median operation time was 140 (range 50-225) min,the median warm ischemia time was 23 (range 14-60) min,the median blood loss was 80(range 5-1 200) ml.In the robotic surgery group,the median operation time was 140 (range 50-215)min,the median warm i schemia time was 21 (range 17-40)min,the median blood loss was 150(range 30-1 200)ml.In the laparoscopic surgery group,the median operation time was 160(range 80-225)min,the median warm ischemia time was 25 (range 14-60)min,the median blood loss was 50 (range 5-1 200) ml.All the patients had no adjacent organ injury during operation.There were 2 cases with Clavien Ⅱ complications.One required transfusion and the other one suffered hematoma post-operation.However,the tumors were located in the renal hilus for these 2 cases and the R.E.N.A.L scores were both 11.Conclusions Holographic image navigation can help location and recognize important anatomic structures during the surgical procedures..This technique will reduce the tissue injury,decrease the complications and improve the success rate of surgery.

OBJECTIVE: To investigate the value of positive lymph node ratio (LNR) in predicting the prognosis of patients with esophageal cancer. METHODS: We retrieved the data of a total of 862 patients with esophageal cancer with complete clinical pathology data archived in SEER database in 2010 to 2015. The best cutoff point of LNR was selected using X-tile software. Univariate and multivariate COX proportional hazard models were used to assess the value of LNR in predicting the prognosis of patients after propensity score matching (PSM). RESULTS: The best cut-off point of LNR determined using X-tile 3.6.1 software was 0.16. The patients with LNR < 0.16 and those with LNR≥0.16 showed significant differences in the number of positive lymph nodes, pathological type, T stage and M stage. After 1:1 propensity score matching, the two groups showed no significant difference in the clinical data or pathological parameters. Matched univariate and multivariate COX regression analyses showed that LNR, primary tumor site and M staging were all independent risk factors affecting the prognosis of patients, and among them LNR had the most significant predictive value (LNR < 0.16 LNR≥0.16: HR=1.827, 95% : 1.140-2.929; =0.000). The median survival time of patients with LNR < 0.16 was 31 months (95%: 22.556-39.444 months), as compared with 16 months (95%: 12.989-19.011) in patient with LNR≥0.16 (Log Rank χ=27.392, < 0.0001). LNR had a better accuracy than N stage for assessing the patients' prognosis with an area under the ROC curve of 0.617 (95%: 0.567-0.666), as compared with 0.515 (95%: 0.463-0.565) of N stage (=3.008, =0.0026). CONCLUSIONS LNR≥0.16 is an independent risk factor affecting the prognosis of patients with esophageal cancer and has better prognostic value than N stage.
Esophageal Neoplasms ; Humans ; Lymph Node Excision ; Lymph Node Ratio ; Lymph Nodes ; Lymphatic Metastasis ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Risk Factors

Objective To investigate pathogenic genes related to the phenotype of fetus with severely short limbs in the first and second trimester by whole exome sequencing (WES). Methods Thirteen fetuses with severely short limbs detected by ultrasonography in the first and second trimester admitted in Chinese PLA General Hospital from September 2016 to June 2018 were collected. All cases were performed induced abortion, 6 of which were carried out karyotype analysis of amniotic fluid at the same time. WES and copy number variations (CNV) were performed on specimens from fetal tissues after labor induction. The suspected pathogenic mutations were validated by Sanger sequencing reactions. Results No abnormal karyotypes or pathological CNV were found. In 10 fetuses, pathogenic or possibly pathogenic mutations were detected in the following genes: COL2A1, FGFR3, COL1A1, COL1A2, DYNC2LI1 and TRIP11, all of which were essential to skeletal development. The diagnostic yield of WES in the fetuses with severe short limbs was 10/13. Conclusions In the first and second trimester, most of the fetuses with extremely short limbs suffer from monogenic diseases. WES is likely to be a valuable diagnostic testing option for the fetuses with severe short limbs.