Boren Jiang

Serum Detection of Epidermal Growth Factor Receptor Gene Mutations Using Mutant-Enriched Sequencing in Chinese Patients with Advanced Non-Small Cell Lung Cancer

Epidermal growth factor receptor gene (EGFR) mutations are among the best predictive markers of the efficacy of EGFR tyrosine kinase inhibitor (EGFR-TKI) treatment. Mutations in the EGFR gene confer sensitivity to EGFR-TKIs in patients with advanced non-small cell lung cancer (NSCLC). This study determined the concordance rate of EGFR mutations in serum samples and tumour tissue from Chinese patients with advanced NSCLC and compared two detection methods: mutant-enriched polymerase chain reaction-based DNA sequencing and non-enriched sequencing. The EGFR mutation status in serum was consistent with that in paired tumour samples, with a concordance rate of 93.1% for mutant-enriched sequencing. In serum samples, mutant-enriched sequencing demonstrated sensitivity and specificity of 77.8% and 100%, respectively, and was more sensitive than the non-enriched assay. Mutant-enriched sequencing in serum may provide a non-invasive and sensitive method for detecting EGFR mutation status in patients with unresectable NSCLC.

Exposure to Famine in Early Life and Nonalcoholic Fatty Liver Disease in Adulthood.

CONTEXT Epidemiologic studies have indicated that early life nutrition influences later risk of obesity, type 2 diabetes, and metabolic syndrome. Nonalcoholic fatty liver disease (NAFLD) is also considered a metabolic disease. OBJECTIVE The aim was to explore the association between adult NAFLD and fetal or childhood exposure to Great Chinese Famine between 1959 and 1962 during fetal and childhood period. DESIGN AND SETTING In total, 5306 subjects from the Survey on Prevalence in East China for Metabolic Diseases and Risk Factors study were divided into a fetal-exposed (1959-1962), childhood-exposed (1949-1958), adolescence/young adult-exposed (1921-1948), and nonexposed (1963-1974, reference) group. MAIN OUTCOME MEASURE The degrees of steatosis of NAFLD were determined by ultrasonography. RESULTS The prevalences of NAFLD in the nonexposed (1963-1974), fetal-exposed, and childhood-exposed participants were 55.9%, 55.8%, and 55.4% in men and 33.0%, 46.3%, and 51.7% in women, respectively. Compared with those nonexposed, fetal- and childhood-exposed women but not men had a significantly higher prevalence of moderate-severe steatosis (P < .05). A significant association existed in women between increased alanine aminotransferase and both fetal and childhood exposure to famine, after adjusting for age, rural/urban residence, economic status, body mass index, diabetes, dyslipidemia, and hypertension (both P < .05). Famine exposure during the fetal period (odds ratio 1.77, 95% confidence interval 1.22, 2.57) and childhood (odds ratio 1.82, 95% confidence interval 1.35, 2.46) was associated with an increased prevalence of moderate-severe NAFLD in women in the above fully adjusted model. CONCLUSIONS Exposure to the Great Famine in early life had sex-specific association with moderate-severe NAFLD. This indicates that malnutrition in early life may influence the development of adult NAFLD; thus pregnant women and their infants and children may require the highest priority in obtaining nutritional relief.

Cervical necrotizing fasciitis due to methicillin-resistant Staphylococcus aureus: a case report

Cervical necrotizing fasciitis is an uncommon but potentially fatal infection characterized by rapidly progressive, widespread necrosis of the superficial fascia. The authors report a case of cervical necrotizing fasciitis of odontogenic origin in a male with uncontrolled diabetes mellitus. An early diagnosis was based on clinical examination, confirmed by computed tomography (CT) scan, which showed multiple collections of air in the left submandibular, submental and cervical region. Broad spectrum antibiotic therapy was started quickly followed by surgical drainage and debridement. Pus culture was positive for methicillin-resistant Staphylococcus aureus. Four days after admission, mediastinitis was revealed by CT and drainage was conducted through a transcervical incision. The patient was treated successfully with antimicrobial therapy, repeated surgical debridement and supportive care.

Exposure to severe famine in the prenatal or postnatal period and the development of diabetes in adulthood: an observational study

Aims/hypothesisLimited studies have compared the effect of prenatal or postnatal exposure to different severities of famine on the risk of developing diabetes. We aimed to measure the association between diabetes in adulthood and the exposure to different degrees of famine early in life (during the prenatal or postnatal period) during China’s Great Famine (1959–1962).MethodsData from 3967 individuals were included (a total of 2115 individuals from areas severely affected by famine, 1858 from moderately affected areas, 6 excluded due to missing data). A total of 2335 famine-exposed individuals were further divided into those exposed during the fetal stage, childhood or adolescence/young adulthood. We constructed a difference-in-differences model to compare HbA1c and fasting plasma glucose among the participants exposed to different degrees of famine intensity at different life stages. Logistic analyses were used as measures of the association between diabetes and the different levels of famine severity at different life stages.ResultsIndividuals who had been exposed to famine during the fetal period, childhood, and adolescence/adulthood and who had lived in a severely affected area had a 0.31%, 0.20% and 0.27% higher HbA1c, respectively, (all p < 0.01) compared with unexposed individuals. After adjusting for age, sex, smoking status, education level and waist circumference, participants exposed to severe famine during the fetal stage (OR 1.90, 95% CI 1.12, 3.21) and childhood (OR 1.44, 95% CI 1.06, 1.97) had significantly higher odds estimates. Unexposed participants living in severely and moderately affected areas had a comparable prevalence of diabetes (OR 1.22, 95% CI 0.80, 1.87). A significant interaction between famine exposure during the fetal and childhood periods and the level of severity in the area of exposure was found (p < 0.05).Conclusions/interpretationExposure to severe famine in the fetal or childhood period may predict a higher HbA1c and an increased diabetes risk in adulthood. These results from China indicate that both the prenatal and postnatal period may offer critical time windows for the determination of the risk of diabetes.

Follicle stimulating hormone, its novel association with sex hormone binding globulin in men and postmenopausal women

PurposeFollicle stimulating hormone plays direct roles in a variety of nongonadal tissues and sex hormone binding globulin is becoming the convergence of the crosstalk among metabolic diseases. However, no studies have explored the association between follicle stimulating hormone and sex hormone binding globulin. We aimed to study this association among men and women.MethodsSPECT-China is a population-based study conducted since 2014. This study included 4206 men and 2842 postmenopausal women. Collected serum was assayed for gonadotropins, sex hormone binding globulin, sex hormones etc. Regression analyses were performed to assess the relationship between sex hormone binding globulin and follicle stimulating hormone and other variables including metabolic factors, thyroid function and sex hormones. Treatment with follicle stimulating hormone at different concentrations of 0, 5, 50 and 100 IU/L for 24 h was performed in HepG2 cells.ResultsIn Spearman correlation, sex hormone binding globulin was significantly correlated with FSH, triglycerides, thyroxins, body mass index and blood pressure in men and postmenopausal women (all P < 0.05). In regression analyses, follicle stimulating hormone was a significant predictor of sex hormone binding globulin in men and postmenopausal women (P < 0.05), independent of above variables. Follicle stimulating hormone induced sex hormone binding globulin expression in a dose-dependent fashion in HepG2 cells.ConclusionSerum follicle stimulating hormone levels were positively associated with circulating sex hormone binding globulin levels in men and postmenopausal women. This association is independent of age, insulin resistance, hepatic function, lipid profile, thyroid function, adiposity, blood pressure, and endogenous sex hormones.

A unique exonic splicing mutation in the CYP17A1 gene as the cause for steroid 17α-hydroxylase deficiency

BACKGROUND 17α-Hydroxylase/17,20-lyase deficiency (17OHD) caused by a mutation in the CYP17A1 gene is characterized by hypertension, hypokalemia, and abnormal development of the genitalia. The majority of CYP17A1 mutations are located in the coding sequence, and several intronic splicing site mutations have been reported. OBJECTIVE A 2.5-year-old girl with 46,XY disordered sex development exhibited a nearly normal basal cortisol level and reduced sexual steroids. This study is aimed to explore the molecular basis and analyze its possible influence on the phenotype of the patient. METHODS AND RESULTS Mutation analysis revealed compound heterozygous CYP17A1 mutations, with c.985_987delinsAA in one allele and a synonymous substitution (c.1263G>A) in another allele. In vitro expression analysis of the allelic minigene showed that the novel nucleotide variation located in exon 8 induces a splicing signal, which results in an aberrant splicing of CYP17A1 mRNA and a missing portion of exon 8. The translation product includes the deletion of six or seven amino acids from residue position 415 without causing a frameshift. Consistent with the result of molecular modeling, functional studies in transiently transfected HEK-293T cells with the aberrantly spliced enzyme proteins showed that the deleted proteins completely abolished the enzyme activity. However, RT-PCR indicated the existence of a small fraction of normal, functionally intact enzyme, which may explain the partial masculinization of this patient. CONCLUSION This is the first description of an exonic splicing mutation in CYP17A1 relevant to the 17OHD phenotype. It also demonstrates the importance of studying synonymous change in such patients with less severe phenotype.

Arthroscopically guided removal of large solitary synovial chondromatosis from the temporomandibular joint.

Synovial chondromatosis of the joint is a rare benign condition characterized by the formation of metaplastic cartilage in the synovium of the joint resulting in numerous attached and unattached osteocartilagenous bodies. Involvement of the temporomandibular joint (TMJ) is uncommon. Arthrotomy is usually applied to remove the larger particles and the affected synovial tissues. The authors report the case of a 48-year-old female with a large solitary synovial chondroma in the left TMJ. The larger mass was removed successfully via an additional incision in the anterior wall of external auditory meatus under the guidance of arthroscopy. The patient has been symptom-free for 5 years postoperatively.

Are thyroid nodules associated with sex-related hormones? A cross-sectional SPECT-China study

Objective Little is known about the association between thyroid nodules (TNs) and endogenous sex hormones. We aimed to investigate the relationship between TNs and sex-related hormones among men in China. Setting The data were obtained from a cross-sectional study Survey on Prevalence in East China for Metabolic Diseases and Risk Factors (SPECT-China study, 2014–2015) based on the population. Participants In total, 4024 men over 18 years of age who were not using hormone replacement therapy and who underwent complete assays of the serum total testosterone (T), oestradiol (E2), follicle-stimulating hormone (FSH), luteinising hormone (LH) and sex hormone-binding globulin (SHBG) levels as well as thyroid ultrasonography (US) enrolled in this study. Results Of the 4024 participants (54.15±13.08 years old), 1667 participants (41.4%) had TNs. Men with TN(s) (TN(+) group) had significantly lower levels of total T and SHBG and higher E2/T levels compared with the men without TN(s) (TN(−) group) (p<0.05). The TN prevalence decreased with the quartiles of the SHBG level (p<0.05). Binary logistic analysis showed that lower quartiles of SHBG had a greater risk of TN(s) (all p for trend <0.05). This association persisted in the fully adjusted model (p for trend=0.017), in which, for the lowest compared with the highest quartile of SHBG, the OR of TN(s) was 1.42 (95% CI 1.07 to 1.89). No statistically significant association was found between sex-related hormones and US characteristics associated with malignancy (nodule >10 mm, microcalcification and a ‘taller’ than ‘wider’ shape). Conclusions TNs are highly prevalent in men in China. A lower SHBG level was significantly associated with TN among men. The potential role of SHBG in the pathogenesis of the TN remains to be elucidated.

Rosiglitazone protects diabetic rats from liver destruction

Aims: To investigate whether rosiglitazone (ROS) protects diabetic rats from destructive changes in the liver. Methods: Twenty-four Sprague Dawley rats were randomly divided into 3 groups: control (NC) group (no.=8), streptozocin (STZ)-treated diabetic (DM) group (no.=8), and STZ+ROStreated diabetic (RSG) group (no.=8). After 8 weeks, the liver structure was observed by light microscopy and transmission electron microscopy. Apoptosis was detected by TUNEL, and apoptosis index was calculated. The Fas ligand (FasL) mRNA expression of apoptosis-promoting gene and cyclooxygenase-2 (COX-2) mRNA in the liver were detected by RT-PCR. COX-2 protein in the liver was tested via immunohistochemical staining. Results: Compared to NC group, DM group showed a visible fatty degeneration and inflammatory cell infiltration in the liver under microscopy. Obvious hepatocyte swelling with atrophic mitochondria was observed, and the central zone of cholangiole was severely outstretched. Meanwhile, in RSG group, the hepatocyte steatosis and inflammatory cell infiltration decreased, and the hepatic ultra-structure was markedly improved. Hepatocyte apoptosis (p<0.05) and the expression levels for hepatic COX-2 mRNA (p<0.05), FasL mRNA (p<0.01), and COX-2 protein (p<0.05) were higher in DM group compared to the NC group, while the expression level of hepatic COX-2 mRNA (p<0.05), FasL mRNA (p<0.01), COX-2 protein (p<0.05), and hepatocyte apoptosis (p<0.05) in RSG group were decreased compared to DM group. Conclusion: Diabetes causes severe liver injury and ROS can protect diabetic rats from liver destruction, which may be related to inhibition of the expression of COX-2 and the hepatocyte apoptosis induced by FasL gene over expression.

Changes of pituitary and penile structure in male adult rats following castration and high-fat diet.

Aim: To investigate the influence of low androgen levels and high-fat diet on the structure of pituitary and penis in male rats. Methods: Ten-week-old adult male Sprague-Dawley rats were randomly divided into 2 groups, one fed a high-fat diet the other fed a normal diet; each group consisted of 3 subgroups: controls, castrated rats (with low androgen), and castrated rats given undecanoate replenishment. After 11 weeks, the structure of pituitary and penis were observed under light microcopy. Immunohistochemistry was used to assess the expression of FSH in pituitary and cyclooxygenase-2 (COX-2) in corpora cavernosa penis. Results: The structures of pituitary and penis in castrated rats were injured, and were more damaged in castration together with high-fat diet. Immunohistochemistry showed FSH expression in castrated rats pituitary while castrated rats on a high-fat diet had less positive staining than those on a normal diet. Vascular structure of corpora cavernosa penis, showed a strongly positive COX-2 expression in high-fat diet rats. Conclusions: Castration and high-fat diet could induce structural damages of pituitary and penis in male rats. Replacement with testosterone could partially restore the impaired structure. The positive expression of COX-2 implied inflammatory pathway existence on vascular structure of penis in high-fat diet and low-androgen male rats.