[Genetic diagnosis of microcephaly].

Objective: To explore the diagnostic value of chromosome karyotype analysis, chromosomal microarray analysis (CMA) and whole exome sequencing (WES) in microcephaly. Methods: A total of 9 cases of microcephaly fetuses diagnosed by prenatal ultrasound or children with microcephaly diagnosed after birth were selected from the Sixth Affiliated Hospital of Guangzhou Medical University from January 2014 to August 2022.Karyotype analysis and/or CMA were used to detect. The cases with negative karyotype analysis and CMA results were further sequenced by trio-based WES (Trio-WES). Then the coding genes contained in the pathogenic copy number variation (CNV) fragments were analyzed by gene ontology (GO) enrichment. The genes related to the development of the central nervous system contained in the pathogenic CNV and the pathogenic genes found by Trio-WES were combined for gene interaction network analysis. Results: In this study, 9 cases of microcephaly were recruited, with the time of diagnosis ranged from 23 weeks of gestation to 7 years after birth, and the head circumference of fetus or children ranged from 18.3 to 42.5 cm (-7SD to -2SD). Karyotype analysis was detected in all 9 cases and no abnormality result was found. Eight cases were detected by CMA, and one abnormal was found. Five cases were detected by Trio-WES, and two cases were detected with likely pathogenic genes. The GO enrichment analysis of the coding gene in the 4p16.3 microdeletion (pathogenic CNV) region showed that: in biological process, it was mainly concentrated in phototransduction, visible light; in terms of molecular function, it was mainly concentrated in fibroblast growth factor binding; in terms of cell components, it was mainly concentrated in rough endoplasmic reticulum. Gene interaction network analysis suggested that CDC42 gene could interact with CTBP1, HTT and ASPM gene. Conclusions: CMA could be used as a first-line detection technique for microcephaly. When the results of chromosome karyotype analysis and/or CMA are negative, Trio-WES could improve the detection rate of pathogenicity of microcephaly.

[Prenatal genetic diagnosis of the fetuses with isolated corpus callosum abnormality].

Objective: To explore the application value of chromosome karyotype analysis, chromosomal microarray analysis (CMA) and whole exome sequencing (WES) in prenatal diagnosis of isolated corpus callosum abnormality (CCA) fetus. Methods: Fetuses diagnosed with isolated CCA by ultrasound and MRI and receiving invasive prenatal diagnosis in Guangzhou Women and Children's Medical Center and Qingyuan People's Hospital from January 2010 to April 2021 were selected. Karyotype analysis and/or CMA [or copy number variation sequencing (CNV-seq)] were performed on all fetal samples, and WES was performed on fetal samples and their parents whose karyotype analysis and/or CMA (or CNV-seq) results were not abnormal. Results: Among 65 fetuses with isolated CCA, 38 cases underwent karyotype analysis, and 3 cases were detected with abnormal karyotypes, with a detection rate of 8% (3/38). A total of 49 fetuses with isolated CCA underwent CMA (or CNV-seq) detection, and 6 cases of pathogenic CNV were detected, the detection rate was 12% (6/49). Among them, the karyotype analysis results were abnormal, and the detection rate of further CMA detection was 1/1. The karyotype results were normal, and the detection rate of further CMA (or CNV-seq) detection was 14% (3/21). The detection rate of CMA as the first-line detection technique was 7% (2/27). A total of 25 fetuses with isolated CCA with negative results of karyotyping and/or CMA were tested by WES, and 9 cases (36%, 9/25) were detected with pathogenic genes. The gradient genetic diagnosis of chromosomal karyotyping, CMA and WES resulted in a definite genetic diagnosis of 26% (17/65) of isolated CCA fetuses. Conclusions: Prenatal genetic diagnosis of isolated CCA fetuses is of great clinical significance. The detection rate of CMA is higher than that of traditional karyotyping. CMA detection could be used as a first-line detection technique for fetuses with isolated CCA. WES could increase the pathogenicity detection rate of fetuses with isolated CCA when karyotype analysis and/or CMA test results are negative.

Incidence and mortality of nasopharyngeal carcinoma: interim analysis of a cluster randomized controlled screening trial (PRO-NPC-001) in southern China.

BACKGROUND: Previous mass screening studies have shown that IgA antibodies against Epstein-Barr Virus (EBV) can facilitate early detection of nasopharyngeal carcinoma (NPC), but the impact of EBV-antibody screening for NPC-specific mortality remains unknown. PATIENTS AND METHODS: A prospective, cluster randomized, controlled trial for NPC screening (PRO-NPC-001) was conducted in 3 selected towns of Zhongshan City and 13 selected towns of Sihui City in southern China beginning in 2008. Serum samples of the screening group were tested for two previously selected anti-EBV antibodies. Subjects with serological medium risk were subsequently retested annually for 3 years, and those with serological high risk were referred to otorhinolaryngologists for diagnostic check-up. An interim analysis was carried out to evaluate the primary end points of the NPC-specific mortality and the early diagnostic rate, and the secondary end point of the NPC incidence, through linkage with the database of Zhongshan City. RESULTS: Among 70 296 total subjects, 29 413 screened participants (41.8% of the total subjects) in the screening group and 50 636 in the control group, 153 (43.3 per 100 000 person-year), 62 (55.3 per 100 000 person-year) and 99 (33.1 per 100 000 person-year) NPC cases were identified. The early diagnostic rates of NPC were significantly higher in the participants (79.0%, P < 0.0001) and the screening group (45.9%, P < 0.0001) compared with the control group (20.6%). Although no differences were found between NPC-specific mortality of the screening group and the control group [relative risk (RR)= 0.82, 95% confidence interval (CI) 0.37-1.79], lower NPC-specific mortality was noticed among participants from the screening group versus the control group (RR = 0.22, 95% CI 0.09-0.49). CONCLUSION: IgA antibodies against EBV can identify high-risk population and was effective in screening for early asymptomatic NPC. Although the mortality reduction was not significant in the primary end point, we noted encouraging evidence of a mortality reduction in screening participants in this interim analysis. CLINICAL TRIAL NUMBER: NCT00941538.

Clinical significance of fascin-1 and laminin-5 in non-small cell lung cancer.

Lung cancer is the leading cause of cancer death in men and the second leading cause of cancer death in women worldwide. Fascin-1 and laminin-5 were associated with the invasiveness and prognoses of several cancers. The expression and the serum levels of fascin-1 and laminin-5 in patients with non-small cell lung cancer (NSCLC) were analyzed in this study. The expression of fascin-1 and laminin-5 were examined in 378 patients and their serum level was measured in 154 patients. The health of all patients was followed post-surgery. The expression of fascin-1 (P = 0.000) and lanminin-5 (P = 0.001) and the serum levels of fascin-1 (P = 0.015) and laminin-5 (P = 0.046) were related to the relapse of patients with NSCLC. Both serum levels and expression of fascin-1 and laminin-5 can be used to effectively evaluate the prognoses of patients with NSCLC.

Relationship between genetic polymorphisms in MCP-1, CCR-2, and non-small-cell lung cancer in the Han nationality of Northern China.

Lung cancer is a common malignant tumor worldwide and is now the leading cause of cancer-related deaths. Monocyte chemoattractant protein 1 (MCP-1) and its receptor chemokine receptor 2 (CCR-2) are important chemokines. We examined the polymorphisms of 338 unrelated patients with non-small cell lung carcinoma (NSCLC) and 200 unrelated healthy controls of Han nationality in Northern China using polymerase chain reaction-restriction fragment length polymorphism. We found a significant increase in the frequency of the MCP-1 AA genotype [0.293 vs 0.195, odds ratio (OR) = 1.71, 95% confidence interval (CI) = 1.13-2.60] and a significant decrease in the frequency of the GG genotype (0.290 vs 0.41, OR = 0.64, 95%CI = 0.47-0.87) in NSCLC patients compared to controls. The frequencies of AA-ww (0.151 vs 0.090, P = 0.041, OR = 1.80, 95%CI = 1.33-2.43) and AA-wm (0.136 vs 0.080, P = 0.049, OR = 1.81, 95%CI = 1.01-3.27) were higher in lung cancer patients than in healthy controls; the frequency of GG-wm (0.121 vs 0.190, P = 0.030, OR = 0.60, 95%CI = 0.38-0.95) was lower in lung cancer patients than in healthy controls. Based on these results, the polymorphism in MCP-1 may be correlated with the development of NSCLC in the Han nationality of Northern China. However, the polymorphism in CCR-2 is not involved in NSCLC.

Extensive thrombosis of the portal vein and vena cava after orthotopic liver transplantation with cavoportal hemitransposition: a case report.

We report herein a case of orthotopic liver transplantation (OLT) with cavoportal hemitransposition. The patient underwent OLT for hepatitis B virus-related cirrhosis with diffused portomesenteric vein thrombosis (PVT). The unique feature of this case was that 1 month after the operation, because of extensive thrombosis of the portal vein and vena cava in the allografted liver, the hepatic artery was the only vessel to supply the liver. Percutaneous pulse spray thrombolysis through a femoral vein access was incompletely successful with the result that the cavoportal anastomosis stoma occluded and the allografted liver was supplied only by the hepatic artery; the portal vein served no function. Yet the patient survived and was eventually discharged in good condition with normal liver and kidney functions. The patient is alive and well with persistent normalization of hepatic function during 1.5 years follow-up.

University of California at San Francisco criteria can be applied to living donor liver transplantation for hepatocellular carcinoma: single-center preliminary results in 27 patients.

BACKGROUND: Living donor liver transplantation (LDLT) can provide life-saving therapy for many patients with hepatocellular carcinoma (HCC), who otherwise would succumb due to tumor progression. However, donor risk must be balanced against potential recipient benefit. METHODS: From January 2002 to December 2006, a total of 27 LDLT were performed for HCC patients in our center, including 25 right lobe grafts, and 2 dual grafts. Twenty-four (88.89%) met the University of California at San Francisco (UCSF) criteria, whereas 3 (11.11%) did not. RESULTS: Of our 29 donors, the overall complication rate was 17.24%. Two (6.90%) experienced major complications including intra-abdominal bleeding and portal vein thrombosis in 1, respectively; 3 (10.34%) experienced minor complications: wound steatosis, pleural effusion, and transient chyle leakage in 1, respectively. We did not observe any donor mortality; all donors fully recovered and returned to their previous occupations. No recipient developed small-for-size syndrome. The overall HCC patient survival rates at 1- and 3-years were 84.01% and 71.40%, respectively, similar to those of patients undergoing LDLT for various nonmalignant diseases during the same period (P > .05). CONCLUSIONS: Although further study is needed to fully assess the risks and benefits of LDLT for both HCC patients and donors, our preliminary results suggested that LDLT offered an acceptable chance and duration of survival for HCC patients. It was not only a relatively safe procedure provided that every effort was taken to minimize donor morbidities, but also beneficial for HCC recipients.

Arterial complications after living-related liver transplantation: single-center experience from West China.

Vascular complications after liver transplantation remain a major source of morbidity and mortality for recipients. In particular, patients receiving living-related liver transplantation (LRLT) experience a higher rate of vascular complications owing to the complex vascular reconstruction. Between July 2001 and December 2005, LRLTs were performed in our center on 33 patients with end-stage liver diseases. The 23 men and 10 women had a mean age of 32.6 +/- 11.3 years (range = 5 to 58 years). Of the 33 patients, the percentage of vascular complications was 9.09% (3 cases), including hepatic arterial thrombosis (HAT), hepatic arterial stenosis (HAS), or hepatic artery pseudoaneurysm (HAP) in one patient, respectively. No portal vein or hepatic vein complication occurred in our patients. Thrombectomy was performed in the patient with thrombosis. The patient with stenosis was treated with balloon angioplasty and endoluminal stent placement. The pseudoaneurysm was also successfully embolized to restore the blood flow toward the donor liver. Mean follow-up for all patients after LRLT was 18.0 +/- 5.4 months. The overall postoperative 30-day mortality rate was 6.06% (2/33). The 1-year survival rate was 86.36% in 22 patients with benign diseases and 72.73% in 11 patients with malignant diseases. However, no death was associated with vascular complications. Careful preoperative evaluation and intraoperative microsurgical technique for hepatic artery reconstructions are the keys to prevent vascular complications following LRLT. Immediate surgical intervention is required for acute vascular complications, whereas late complications may be treated by balloon angioplasty and endoluminal stent placement. Embolization may be a safe and effective approach in the treatment of a pseudoaneurysm of the hepatic artery.

Safety of donor in adult-to-adult living donor liver transplantation using right lobe graft.

BACKGROUND: The growing gap between the number of patients awaiting liver transplantation and available organs has continued to be the primary issue facing the transplant community. To overcome the waiting list mortality, living donor liver transplantation has become an option, in which the greatest concern is the safety of the donor, especially in adult-to-adult living donor liver transplantation (A-A LDLT) using a right lobe liver graft. OBJECTIVE: We evaluated the safety of donors after right lobe liver donation for A-A LDLT performed in our center. METHODS: From January 2002 to March 2006, 26 patients underwent A-A LDLT using right lobe liver grafts in our center. Seven donors were men and 19 were women (range, 19-65 years; median age, 38 years). The right lobe liver grafts were obtained by transecting the liver on the right side of the middle hepatic vein without interrupting the vascular blood flow. The mean follow-up time for these donors was 9 months. RESULTS: These donor residual liver volumes ranged from 30.5% to 60.3%. We did not experience any donor mortality. Two cases (7.69%) experienced major complications: intra-abdominal bleeding and portal vein thrombosis in one each and three (11.54%), minor ones: wound steatosis in two, and transient chyle leak in one. All donors were fully recovered and returned to their previous occupations. CONCLUSIONS: A-A LDLT using a right lobe liver graft has become a standard option. The donation of right lobe liver for A-A LDLT was a relatively safe procedure in our center.