Application of next-generation sequencing in detection of BRCA1/2 and homologous recombination repair pathway multi-genes germline mutation and correlation analysis / 中华预防医学杂志

Objective: To investigate the germline mutation status of related genes in breast cancer patients and high-risk individuals by next-generation sequencing. To analyze the correlations between homologous recombination repair (HR) pathway gene mutation status and clinicopathological characteristics of breast cancer patients. To supplement the database of breast cancer related gene mutations in Chinese population. Methods: This study is a cross-sectional study. From October 2020 to September 2021, whole blood samples were collected from 350 breast cancer patients and 49 high-risk individuals, admitted to Peking University People's Hospital and accepted genetic testing voluntarily. Germline mutations in 32 breast cancer related genes were detected by NGS. The clinicopathological characteristics, including age at the onset, family history, unilateral/bilateral tumor, Luminal typing (Luminal A subtype, Luminal B subtype, HER2-enriched subtype and triple negative breast cancer), tumor size and metastasis, were analyzed, and the correlations between HR pathway gene mutation status and clinicopathological characteristics were analyzed by Chi-squared test and Fisher's exact probability test. Results: Among 350 breast cancer patients, 64 (18.3%) cases carried gene pathogenic mutations (including pathogenic and likely pathogenic mutations), including 47 (13.4%) in BRCA1/2, 16 (4.6%) in non-BRCA1/2 genes, 1 (0.3%) in BRCA2 and FANCL. Among 49 high-risk individuals, 7 (14.3%) cases carried gene pathogenic mutations, including 6 (12.3%) in BRCA1/2 and 1 (2%) in ATM genes. BRCA1/2 pathogenic mutations were associated with age at the onset (18%, 8.7%, χ²=6.346, P=0.012), and the BRCA1/2 pathogenic mutation frequency was higher in patients diagnosed at age ≤45 years. HR pathway gene mutations (including pathogenic, likely pathogenic and uncertain significance mutations) were correlated with unilateral/bilateral tumor (49.5%, 68.4%, χ²=4.841, P=0.028) and Luminal typing (45.7%, 62.2%, 32%, 60%, χ²=12.004, P=0.007), and the HR mutation frequencies were higher in patients with bilateral tumor, Luminal B breast cancer and triple negative breast cancer (TNBC). Conclusion: The BRCA1/2 pathogenic mutation frequency in high-risk individuals is similar to that in breast cancer patients, and BRCA1/2 testing is helpful to guide breast cancer screening and prevention in high-risk individuals. Patients with early onset breast cancer, bilateral breast cancer, Luminal B breast cancer and TNBC have higher mutation frequencies of HR pathway genes, and HR pathway genes testing should be conducted as soon as possible to provide laboratory evidence for diagnosis, treatment, prognosis and risk evaluation of breast cancer.

Correlation of Social-psychological Health and Joint Function in Patients during Rehabilitation for Joint Impairment / 中国康复理论与实践

Objective:To explore the influence of social-psychological factors on outcome of joint rehabilitation. Methods:From October, 2015 to April, 2017, 64 inpatients accepting joint rehabilitation were divided into anxiety group and non-anxiety group, and depression group and non-depression group, according to the scores of Hamilton Anxiety Scale and Hamilton Depression Scale. They were assessed with routine joint scores as initial and final stages of joint rehabilitation, as well as Symptom Checklist-90 (SCL-90) and World Health Organization Disability Assessment Schedule 2.0 (WHO-DAS 2.0). The correlation of joint scores to scores of SCL-90 and WHO-DAS 2.0 was analyzed with Spearman correlation analysis. Results:There were significant differences in joint scores between the depression and the non-depression groups initially and finally (|t| > 2.106, P < 0.05). The joint score at the initial stage was negatively correlated with the interpersonal factor score of SCL-90 (r = -0.257, P < 0.05). The joint score at the final stage was negatively correlated (P < 0.05) with the dimension one (r = -0.257) and four (r = -0.278) of WHO-DAS 2.0, total score (r = -0.263), and interpersonal (r = -0.328) and hostile (r = -0.385) factor scores of SCL-90. Improvement of joint score negative correlated with dimension one of WHO-DAS 2.0 score (r = -0.249, P < 0.05). Conclusion:The social-psychological factors affect the outcome of joint rehabilitation. It is necessary to explore the way to take the the social-psychological assessment into the routine three stage evaluation of the joint rehabilitation protocol.

Inhaled iloprost during acute pulmonary vasodilator testing for preoperative assessment of surgical operability of congenital heart disease with severe pulmonary hypertension / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy of iloprost in acute vasodilatation test during cardiac catheterization and to explore a useful hemodynamic indication regarding operability in the patients with severe pulmonary hypertension (PH) related to congenital heart disease (CHD).</p><p><b>METHODS</b>The clinical data of 46 patients [mean age (12 ± 9) years] with severe PH related to CHD from June 2006 to December 2008 was retrospectively analyzed. All patients underwent standard right and left cardiac catheterization and a trial of inhaled iloprost test during cardiac catheterization. The mean pulmonary arterial pressure was (80 ± 13) mm Hg (1 mm Hg = 0.133 kPa) and pulmonary vascular resistance index was (17 ± 10) wood.m². A positive response to inhaled iloprost was defined as a decrease of at least 20% in pulmonary vascular resistance index (PVRI) without changes on systemic artery pressure. Patients with positive response to iloprost underwent cardiac surgical repair. The pulmonary artery pressure and PVRI was monitored by Swan-Ganz catheter postoperatively.</p><p><b>RESULTS</b>Of the 46 patients, 29 (63.1%) showed a positive response after iloprost inhalation, defined by a significant reduction in PVRI from (15 ± 6) wood.m(2) at baseline to (9 ± 4) wood.m² in response to iloprost inhalation therapy (P < 0.05). The ratio of pulmonary to systemic resistance (Rp/Rs) decreased from 0.7 ± 0.2 to 0.4 ± 0.2 (P < 0.05). Seventeen patients (36.9%) didn't respond to iloprost displayed only little changes in PVRI [from (21 ± 10) wood.m(2) to (19 ± 9) wood.m²] and Rp/Rs (from 1.0 ± 0.5 to 0.9 ± 0.5). Out of 29 positive patients, 21 (72%) underwent successful cardiac surgical repair with a reduction of mean pulmonary arterial pressure (mPAP) to an average of (27 ± 10) mm Hg after the operation. Only 2 patients out of the 17 patients from the negative group were referred to surgery. Their mPAP was greater than 45 mm Hg.</p><p><b>CONCLUSIONS</b>A significant reduction in pulmonary artery pressure after cardiac surgery was observed in patients with positive response to inhaled iloprost. Inhaled iloprost may be a valuable tool in the preoperative evaluation of patients with severe PH related to CHD.</p>

Linkage analysis of a Chinese family with autosomal dominant congenital retinaochoroidal coloboma / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To map the candidate gene by linkage analysis in a Chinese family with autosomal dominant congenital retinaochoroidal coloboma.</p><p><b>METHODS</b>A detailed clinical examination was performed for all patients in the family. The genomic DNA of all family members was extracted from peripheral blood leukocytes. Linkage analysis and genome-wide linkage screening was conducted using fluorescent detection of 398 microsatellite markers representing all autosomes at an average resolution of approximately 10 cM. Polymerase chain reaction was carried out to amplify all 398 microsatellite markers. The allele sizes were determined on ABI 3130-Avant genetic analyzer according to an internal size standard, and the results were analyzed using Genescan 3.1 and Genotyper 2.0 software.</p><p><b>RESULTS</b>Linkage analysis showed the markers D2S2382-D2S301-D2S2244-D2S163 co-segregated with the disease locus in all affected members. The maximum Lod score was 3.01(D2S2382).</p><p><b>CONCLUSION</b>The candidate region of the disease gene in the family was located in 2q34-2q35.</p>

Assessment of the young rat model of visceral hypersensitivity by measuring electrical discharge of external oblique / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the value of measuring electrical discharge of external oblique in assessment of young rat model of visceral hypersensitivity.</p><p><b>METHODS</b>Eight-day-old neonatal Sprague-Dawley rats were randomly assigned to two groups: an experimental group and a control group (n=16 each). Rats in the experimental group were subjected to mechanical colorectal irritation daily for 7 consecutive days, while the rats in the control group did not received colorectal irritation treatment. On the 6th week of their lives, the spike amplitude of external oblique were measured to evaluate the bowel sensitivity.</p><p><b>RESULTS</b>When the colorectal distention (CRD) pressure was 30 and 45 mmHg, the 95% confidence interval of the spike amplitude in the experimental group was significantly higher than that in the control group (P<0.01). When the CRD pressure were 60 and 75 mmHg, the 95% confidence interval of the spike amplitude in female rats was significantly higher than that in males (P<0.05).</p><p><b>CONCLUSIONS</b>The electrical discharge of external oblique confirmed that chronic colorectal irritation in neonatal rats can result in a chronic visceral hypersensitivity in the juvenile stage, with gender differences. Electrophysiological assessment is a quantitative test, and can objectively reflect visceral sensibility of pain.</p>