Objective To identify the disease-causing gene mutation in families with anterior segment dysgenesis (ASD).Methods Two ASD families coming from Henan and Hebei provinces were enrolled in this study.Ocular examinations were performed,and periphery blood specimens were collected from each family member under the informed consent.The blood samples of 2 patients and 1 normal person in family 1 and 1 patient and 1 normal person in family 2 were analyzed by the whole exome sequences.The candidate genes were verified by Sanger sequence and predicted damages by PolyPhen-2 and SIFT Human Splicing Finder software.Results Family 1 including 9 patients were examined in serial 3 passages,which conformed to autosomal dominant inheritance pattern.Clinical examination revealed binocular anterior segment dysgenesis in the 9 patients.There were 13 SNV and 55 InDel candidate mutations.And missense mutation c.T2A(p.M1K)on PAX6 gene was found.Family 2 included 8 members,and 2 patients were examined.The splicing mutation c.357 + 1g ＞ c on the same gene was found.Conclusion T2A(p.M1 K) and c.357 + 1 g ＞ c mutations in PAX6 gene are responsible for ASD.Whole exome sequence provides a new approach to detect diseasecausing mutation of ASD with diversity clinical phenotypes.

Abstract Vaccine-hypervariable poliovirus type Ⅲ was detected in an acute flaccid paralysis infant at age of 6 months in Zhejiang Province in June, 2021, and the isolated and incubated virus had six nucleotide variations in the VP1 region as compared to the poliovirus Sabin vaccine strain. The infant had a history of three-dose poliovirus vaccination, and grade 2 muscle strength of the left upper limb upon onset. He was clinically diagnosed with cellulitis of the left shoulder, and recovered to normal following treatment. No abnormality was detected in the nervous system, and the infant was cured and discharged from hospital. No vaccine-hypervariable poliovirus was detected in subsequent infant' clinical samples or in close contacts, and no similar cases were identified during the active case detection by county/district medical institutions and among community populations. Since the infant did not present poliomyelitis-related clinical symptoms caused by vaccine-hypervariable poliovirus, poliomyelitis was excluded. The vaccine-hypervariable poliovirus was not spread because of timely identification and effective responses, suggesting the urgent need to maintain the sensitivity of the acute flaccid paralysis surveillance system and improve the coverage of poliovirus vaccination, so as to inhibit the transmission of poliovirus.

Objective To establish a noninvasive prenatal testing(NIPT) method based on the chromosome specific site sequencing instead of the conventional whole genome sequencing.Methods Blood plasma samples from 200 pregnant women with known fetus karyotypes were collected.First,the specific loci on chromosome 13,18 and 21 were selected by the database filter.Then,these specific loci were captured by probes,and were performed sequencing.Finally,chromosome aneuploidy was identified by the Z-score.ResultsSeven fetuses with 21-trisomy syndrome,3 with 18-trisomy syndrome and 1 with 13-trisomy syndrome were detected by the chromosome specific site sequencing,and the results were accordant with those of the whole genome sequencing method.Conclusion The NIPT method based on the chromosome specific site sequencing has the advantages of low cost and high throughput,which may replace the NIPT method based on the whole genome sequencing.

OBJECTIVE To analyze the data of non-invasive prenatal testing based on specific loci of circulating cell-free fetal DNA (cffDNA). METHODS Selected loci of target chromosomes were analyzed by sequence capture and sequencing. Meanwhile, 600 loci were selected from other chromosomes for determining the concentration of cffDNA. RESULTS A total of 768 specific loci were captured on chromosomes 21 and 18, and used to determine whether the two were abnormal. When the minimum concentration of detected cffDNA was set at 3% and the threshold of Z score was set to [-6,6], the specificity of the analysis was 99.37% and the sensitivity was 100%. CONCLUSION A reliable, convenient and low-cost analytical method has been developed. The method requires less sequencing data for non-invasive prenatal testing, and can accurately detect abnormalities of fetal chromosomes 21 and 18, and simultaneously determine the concentration of cffDNA.

Objective:To study the use of the Glissonean pedicle approach based on the triangular area among the right anterior pedicle, the right posterior pedicle and the right hepatic vein ( "APR triangle" ), followed by indocyanine green fluorescence negative staining in laparoscopic anatomical resection of right hepatic segments.Methods:The clinical data of 34 patients with liver tumors who underwent laparoscopic anatomical right hepatic segmentectomy at the Chinese Academy of Medical Sciences and Peking Union Medical College from September 2020 to September 2021 were analyzed retrospectively. Of the 34 patients, there were 24 males and 10 females, aged (58.3±10.3) years old. Data on completion of operation, operation time, intraoperative blood loss, intraoperative blood transfusion, postoperative complications and postoperative hospital stay were collected.Results:All the 34 patients had malignant liver tumors, and they were successfully operated using total laparoscopic surgery. There was no conversion to open surgery. Three patients underwent segment V resection, 3 patients segment VI resection, 5 patients segment VII resection, 2 patients segment V + segment VI resection, 9 patients segment VI + segment VII resection, 3 patients segment V + segment VII resection, 5 patients segment V dorsal segment + segment VI + segment VII resection, 3 patients right posterior section resection + anterior dorsal segment resection and 1 patient anterior dorsal section resection. The operation time was (275.58±82.28) min, the amount of intraoperative blood loss was 100(100, 300) ml, and there were no patients requiring blood transfusion during the operation. Liquid food was started on the first day after operation, and out-of bed activities were carried out on the second to third days after operation. The Clavien Dindo classification of postoperative complications was grade I in 32 patients and grade III in 2 patients. The postoperative hospital stay was (7.23±3.10) d. All tumor margins were negative for malignancy. All the 34 patients were followed-up for (8.94±2.94) months. By the end of follow-up, 34 patients had survived without tumor recurrence.Conclusion:The right Glisson pedicle approach based on the "APR triangle" and the anatomical resection of right hepatic segments with fluorescence negative staining were safe and feasible.

Objective:To explore the effect of family doctor system on the risk stratification of community hypertensive population by application of Markov modelMethods:Retrospective investigation was conducted on hypertensive patients under continuing management from 13 community health service centers in Shanghai Xuhui District from January 2014 to December 2016. Among 98 996 subjects, 50 920 (51.45%) were contracted to family doctors (contracted group) and 48 046 (48.55%) did not contracted to family doctors (non-contracted group). According to the risk stratification of hypertension, the four-state Markov model (low-risk, medium-risk, high-risk, and extremely high-risk) was established. The prediction effect of the model was validated, and the changes in the risk stratification status of hypertension in the study subjects from 2017 to 2020 was predicted by using the Markov model.Results:Among all subjects the number of medium-risk and extremely high-risk accounted for the majority(>80%). Compared with 2014, in 2016 the number of low-risk patients with hypertension was decreased from 9 042 cases (17.76%) to 6 851 cases (13.45%) in contracted group; and from 9 971 cases (20.75%) to 7 906 cases (16.46%) in non-contracted group; the number of people at extremely high risk of hypertension was increased from 15 609 cases (30.65%) to 17 639 cases (34.64%) in the contracted group; from 13 847 cases (28.82%) to 15 641 cases (32.55%) in the non-contracted group. According to the Markov model one year after the risk stratification, the risk status of most subjects remained in the original one. There was not transform from extremely high-risk to low-risk state (0%), but there was transform from low-risk to extremely high-risk state in some extend, and the degree of transform in non-contracted group [2.06%(205/9 971)] was higher than the contracted group [1.85%(167/9 042)]. Predicted by the Markov model, between 2017 and 2020 the number and proportion of the medium-risk>extremely high-risk>low-risk>high-risk in both contracted group and non-contracted group. With the extension of time, low-risk proportion is gradually reduces, and the rate of reduction of the contracted group was lower than that of the non-contracted group, while proportion of medium-risk, high-risk and extremely high-risk is gradually increased.Conclusions:The constructed Markov model is accruable and stable, which can be used in the study of hypertension prognosis. The study indicates that the contracted services of family doctor have positive effects on the management of community hypertensive patients.

Objective:To explore the characteristics of echocardiographic parameters among the many parameters of two-dimensional transthoracic echocardiography(2D-TTE) and three-dimensional speckle tracking imaging (3D-STI) that can be used for early identification of familial hypertrophic cardiomyopathy(FHCM) mutation gene carriers, and construct a Nomogram prediction model, in order to provide a diagnostic method for early identification of G+ P- patients for clinical practice.Methods:A total of 15 FHCM families admitted to the General Hospital of Ningxia Medical University from November 2017 to August 2022 were enrolled.Whole exome sequencing and Sanger sequencing technology were used for gene detection, among which 54 were G+ P- and 75 were G-P-. Stratified random sampling was used to divide the subjects into training set ( n=90) and test set ( n=39) according to the ratio of 7∶3. Philips iE33 ultrasonic diagnostic instrument and TomTec offline software were used to obtain relevant ultrasonic parameters. Lasso regression and Logistic regression were used to screen echocardiographic parameters and obtain independent risk factors for early prediction of G+ P-, based on which a Nomogram prediction model was established. Results:①Lasso-Logistic regression showed that global longitudinal strain(GLS) ( OR=1.739, 95% CI=1.305-2.316) and left ventricular outflow trac velocity time integral(LVOT-VTI) ( OR=1.358, 95% CI=1.072-1.722) could be used as independent risk factors for early prediction of G+ P-. ②The Nomogram prediction model was established based on the above indicators. After 1000 internal verifications of Bootstrap self-sampling, the C-indices of the training set and the test set were 0.885 (95% CI=0.816-0.954), 0.878 (95% CI=0.764-0.992), which had good internal consistency. ③The results of the calibration curve showed that the risk of G+ P- predicted by the Nomogram model was basically consistent with the actual risk (training set P=0.990, test set P=0.961); the clinical decision curve shows that under different threshold probabilities, using this prediction model to provide patients with clinical decision-making could bring benefits to patients. Conclusions:Echocardiographic parameters GLS and LVOT-VTI can be used as independent risk factors to predict FHCM mutation gene carriers. The Nomogram prediction model has good discrimination, goodness of fit and clinical benefit in identifying whether the family members of FHCM patients carry the mutation gene, and it can provide a new idea and evaluation method for the early identification of FHCM mutation gene carriers by echocardiography.

Objective: To detect pathogenic gene variants in two Chinese families with cone-rod dystrophy(CORD). Methods: After the informed consent and comprehensive ophthalmic examinations for the patients, 3 mL peripheral blood was taken from the patients’ blood vessel and DNA was extracted. The DNA was sequenced by whole-exome sequencing technology and variants were analyzed. Results: Two novel compound heterozygous AIPL1 variants were detected in two patients, which were c. 923T>C(p.L308P) and c. 421C>T(p.Q141X) variants in Family 1, c. 572T>C(p.L191P) and c. 421C>T(p.Q141X) in Family 2 . Conclusion The results supported that AIPL1 gene variants are the main cause of the two CORD families. Whole-exome sequencing technology is a useful tool in the clinical differentiated diagnosis and genetic counseling for CORD patients.

Objective:To explore the clinical effect of laparoscopic anatomical hepatic segment Ⅷ (S8) resection.Methods:Of 16 patients with liver cancer who underwent laparoscopic anatomical hepatic S8 resection at the National Cancer Center from October 2020 to October 2022 were were enrolled, including 13 males and 3 females, aged (59.1±10.9) years. The operation time, intraoperative blood loss, occurrence of intraoperative blood transfusion, and postoperative complications were retrospectively analyzed. Recurrence and survival were followed up by outpatient and telephone reviews.Results:Laparoscopic anatomical hepatic S8 resection was successfully performed in 16 patients without conversion to laparotomy. Among them, 10 patients underwent the intraoperative ultrasound guided hepatic parenchymal approach, and 6 underwent laparoscopic Glissonean pedicle puncture for the positive staining of S8 using indocyanine green. The operation time was (274.8±82.8) min, and the intraoperative blood loss was [ M( Q1, Q3)] 100.0 (50.0, 200.0) ml. There were no intraoperative blood transfusion or postoperative complication. The drainage tube was successfully removed and the patients were discharged 5 to 7 days after surgery. The patients were followed up for 5 to 24 months and all survived. Two patients had tumor recurrence. Conclusion:Laparoscopic anatomical S8 resection is safe and feasible.