Integrative analysis reveals associations between oral microbiota dysbiosis and host genetic and epigenetic aberrations in oral cavity squamous cell carcinoma.

Dysbiosis of the human oral microbiota has been reported to be associated with oral cavity squamous cell carcinoma (OSCC) while the host-microbiota interactions with respect to the potential impact of pathogenic bacteria on host genomic and epigenomic abnormalities remain poorly studied. In this study, the mucosal bacterial community, host genome-wide transcriptome and DNA CpG methylation were simultaneously profiled in tumors and their adjacent normal tissues of OSCC patients. Significant enrichment in the relative abundance of seven bacteria species (Fusobacterium nucleatum, Treponema medium, Peptostreptococcus stomatis, Gemella morbillorum, Catonella morbi, Peptoanaerobacter yurli and Peptococcus simiae) were observed in OSCC tumor microenvironment. These tumor-enriched bacteria formed 254 positive correlations with 206 up-regulated host genes, mainly involving signaling pathways related to cell adhesion, migration and proliferation. Integrative analysis of bacteria-transcriptome and bacteria-methylation correlations identified at least 20 dysregulated host genes with inverted CpG methylation in their promoter regions associated with enrichment of bacterial pathogens, implying a potential of pathogenic bacteria to regulate gene expression, in part, through epigenetic alterations. An in vitro model further confirmed that Fusobacterium nucleatum might contribute to cellular invasion via crosstalk with E-cadherin/ß-catenin signaling, TNFα/NF-κB pathway and extracellular matrix remodeling by up-regulating SNAI2 gene, a key transcription factor of epithelial-mesenchymal transition (EMT). Our work using multi-omics approaches explored complex host-microbiota interactions and provided important insights into genetic and functional basis in OSCC tumorigenesis, which may serve as a precursor for hypothesis-driven study to better understand the causational relationship of pathogenic bacteria in this deadly cancer.

Cytotoxicity of 4 Wild Mushrooms in a Case of Yunnan Sudden Unexplained Death.

OBJECTIVES: To explore the cytotoxicity of four wild mushrooms involved in a case of Yunnan sudden unexplained death (YNSUD), to provide the experimental basis for prevention and treatment of YNSUD. METHODS: Four kinds of wild mushrooms that were eaten by family members in this YNSUD incident were collected and identified by expert identification and gene sequencing. Raw extracts from four wild mushrooms were extracted by ultrasonic extraction to intervene HEK293 cells, and the mushrooms with obvious cytotoxicity were screened by Cell Counting Kit-8 (CCK-8). The selected wild mushrooms were prepared into three kinds of extracts, which were raw, boiled, and boiled followed by enzymolysis. HEK293 cells were intervened with these three extracts at different concentrations. The cytotoxicity was detected by CCK-8 combined with lactate dehydrogenase (LDH) Assay Kit, and the morphological changes of HEK293 cells were observed under an inverted phase contrast microscope. RESULTS: Species identification indicated that the four wild mushrooms were Butyriboletus roseoflavus, Boletus edulis, Russula virescens and Amanita manginiana. Cytotoxicity was found only in Amanita manginiana. The raw extracts showed cytotoxicity at the mass concentration of 0.1 mg/mL, while the boiled extracts and the boiled followed by enzymolysis extracts showed obvious cytotoxicity at the mass concentration of 0.4 mg/mL and 0.7 mg/mL, respectively. In addition to the obvious decrease in the number of HEK293 cells, the number of synapses increased and the refraction of HEK293 cells was poor after the intervention of Amanita manginiana extracts. CONCLUSIONS: The extracts of Amanita manginiana involved in this YNSUD case has obvious cytotoxicity, and some of its toxicity can be reduced by boiled and enzymolysis, but cannot be completely detoxicated. Therefore, the consumption of Amanita manginiana is potentially dangerous, and it may be one of the causes of the YNSUD.

High GTSE1 expression promotes cell proliferation, metastasis and cisplatin resistance in ccRCC and is associated with immune infiltrates and poor prognosis.

Background: Clear cell renal cell carcinoma is the most common and fatal form of kidney cancer, accounting for 80% of new cases. Although it has been reported that GTSE1 is highly expressed in a variety of tumors and associated with malignant progression and poor clinical prognosis, its clinical significance, correlations with immune cell infiltration and biological function in ccRCC are still poorly understood. Methods: The gene expression, clinicopathological features, and clinical significance of GTSE1 were analyzed using multiple databases, including TCGA, GEO, TIMER, and UALCAN Kaplan-Meier survival analysis, gene set enrichment analysis gene ontology enrichment Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed. Tumor-infiltrating immune cells and immunomodulators were extracted and analyzed using TCGA-KIRC profiles. Protein‒protein interactions were built using the STRING website. The protein level of GTSE1 in ccRCC patients was detected by immunohistochemistry using a ccRCC tissue chip. Finally, MTT assays, colony-formation assays, cell flow cytometry analyses, EdU-staining assays, wound-healing assays, and transwell migration and invasion assays were conducted to assess the biological function of GTSE1 in vitro. Results: GTSE1 was overexpressed in ccRCC tissues and cells, and GTSE1 overexpression was associated with adverse clinical-pathological factors and poor clinical prognosis. Meanwhile, the functional enrichment analysis indicated that GTSE1 and its coexpressed genes were mainly related to the cell cycle, DNA replication, and immunoreaction, such as T-cell activation and innate immune response, through multiple signaling pathways, including the P53 signaling pathway and T-cell receptor signaling pathway. Furthermore, we observed a significant relationship between GTSE1 expression and the levels of infiltrating immune cells in ccRCC. Biological functional studies demonstrated that GTSE1 could promote the malignant progression of ccRCC by promoting cell proliferation, cell cycle transition, migration, and invasion capacity and decreasing the sensitivity of ccRCC cells to cisplatin. Conclusion: Our results indicate that GTSE1, serving as a potential oncogene, can promote malignant progression and cisplatin resistance in ccRCC. Additionally, high GTSE1 expression contributes to an increased level of immune cell infiltration and is associated with a worse prognosis, providing a potential target for tumor therapy in ccRCC.

Whole exome sequencing with a focus on cardiac disease-associated genes in families of sudden unexplained deaths in Yunnan, southwest of China.

OBJECTIVES: To explore the causes of sudden unexpected death (SUD) and to search for high-risk people, whole exome sequencing (WES) was performed in families with SUDs.  METHODS: Whole exome sequencing of 25 people from 14 SUD families were screened based on cardiac disease-associated gene variants, and their echocardiograms and electrocardiograms (ECG) were also examined. The protein function of mutated genes was predicted by SIFT, PolyPhen2 and Mutation Assessor. RESULTS: In the group of 25 people from 14 SUD families, 49 single nucleotide variants (SNVs) of cardiac disease-associated genes were found and verified by Sanger sequencing. 29 SNVs of 14 cardiac disorder-related genes were predicted as pathogens by software. Among them, 7 SNVs carried by two or more members were found in 5 families, including SCN5A (c.3577C > T), IRX4 (c.230A > G), LDB3 (c.2104 T > G), MYH6 (c.3G > A), MYH6 (c.3928 T > C), TTN (c.80987C > T) and TTN (c.8069C > T). 25 ECGs were collected. In summary, 4 people had J-point elevation, 2 people had long QT syndrome (LQTS), 4 people had prolonged QT interval, 3 people had T-wave changes, 3 people had sinus tachycardia, 4 people had sinus bradycardia, 4 people had left side of QRS electrical axis, and 3 people had P wave broadening. Echocardiographic results showed that 1 person had atrial septal defect, 1 person had tricuspid regurgitation, and 2 people had left ventricular diastolic dysfunction. CONCLUSIONS: Of the 14 heart disease-associated genes in 14 SUDs families, there are 7 possible pathological SNVS may be associated with SUDs. Our results indicate that people with ECG abnormalities, such as prolonged QT interval, ST segment changes, T-wave change and carrying the above 7 SNVs, should be the focus of prevention of sudden death.

Osteoprotective effect of denosumab on patients with chronic kidney disease / 中华肾脏病杂志

Osteoporosis is a comorbidity or complication of chronic kidney disease (CKD). Low bone mineral density, osteoporosis, and fractures are risk factors of poor prognosis in patients with CKD. Active prevention and treatment of osteoporosis is essential for patients with CKD. Denosumab is a fully human monoclonal antibody that targets receptor activator of nuclear factor-κB ligand (RANKL) and is not metabolized or excreted by the kidney. Clinical studies have shown that the use of denosumab in CKD (including dialysis and renal transplantation) patients with osteoporosis, can increase bone mineral density and reduce the incidence of fractures with acceptable safety. As hypocalcemia has been observed in patients with CKD, close monitoring and early supplementation of calcium and vitamin D are required before denosumab initiation, and serum calcium levels need to be monitored during treatment. The review summarized the published literature of denosumab in bone protection of CKD.

Functional analysis of HADH c.99C>G shows that the variant causes the proliferation of pancreatic islets and leu-sensitive hyperinsulinaemia.

A novel missense variant (NM_005327.7: c.99C>G, p.Ile33Met) was discovered in 3-hydroxyacyl-CoA dehydrogenase (HADH), which is involved in congenital hyperinsulinism (CHI). This variant may be damaging or deleterious, as assessed using protein prediction software. This study aimed at the impact of this variant on islets and if it caused the leu-sensitive insulin secretion. The adenoassociated virus containing the HADH missense variant (p.Ile33Met), wild-type (WT) HADH or empty vector (EV) was constructed, and the rats were infected with it. Three weeks after the transfection, 15 rats were dissected to observe the effect of the variant on the islet tissue. Then we treated the remaining rats with leucine or sodium carboxymethyl cellulose (CMC-Na) by gavage and drew blood from the rat tail vein to detect the variations in blood glucose, serum insulin and serum glucagon. Further, we dissected the rats to observe the fluctuation of insulin and glucagon contents in pancreatic islets under the combined action of leucine and p.Ile33Met. Insulin and glucagon were observed in the islet tissue under an inverted fluorescence microscope, serum insulin and glucagon were detected by ELISA, and the blood glucose value was determined using a Roche glucometer. The positive area and average gray value of islet fluorescence pictures were analysed using the software Image J (USA). Rats expressing p.Ile33Met showed significantly higher insulin and glucagon content, as well as the islet area, compared to WT and EV rats. Moreover, after intragastric administration of leucine, the serum insulin content of the variant rats increased but the blood sugar level decreased significantly. Meanwhile, there was an appreciable decrease in the insulin content in rat pancreatic islet tissues. Our results suggest that the variant NM_005327.7: c.99C>G promotes the proliferation of pancreatic islets, enhances the secretion of insulin, and induces leu-sensitive hyperinsulinaemia.

Determinants and Interactions of Oral Bacterial and Fungal Microbiota in Healthy Chinese Adults.

Numerous studies have examined the composition of and factors shaping the oral bacterial microbiota in healthy adults; however, similar studies on the less dominant yet ecologically and clinically important fungal microbiota are scarce. In this study, we characterized simultaneously the oral bacterial and fungal microbiomes in a large cohort of systemically healthy Chinese adults by sequencing the bacterial 16S rRNA gene and fungal internal transcribed spacer. We showed that different factors shaped the oral bacterial and fungal microbiomes in healthy adults. Sex and age were associated with the alpha diversity of the healthy oral bacterial microbiome but not that of the fungal microbiome. Age was also a major factor affecting the beta diversity of the oral bacterial microbiome; however, it only exerted a small effect on the oral fungal microbiome when compared with other variables. After controlling for age and sex, the bacterial microbiota structure was most affected by marital status, recent oral conditions and oral hygiene-related factors, whereas the fungal microbiota structure was most affected by education level, fruits and vegetables, and bleeding gums. Bacterial-fungal interactions were limited in the healthy oral microbiota, with the strongest association existing between Pseudomonas sp. and Rhodotorula dairenensis. Several bacterial amplicon sequence variants (ASVs) belonging to Veillonella atypica and the genera Leptotrichia, Streptococcus and Prevotella_7 and fungal ASVs belonging to Candida albicans and the genus Blumeria were revealed as putative pivotal members of the healthy oral microbiota. Overall, our study has facilitated understanding of the determining factors and cross-kingdom interactions of the healthy human oral microbiome. IMPORTANCE Numerous studies have examined the bacterial community residing in our oral cavity; however, information on the less dominant yet ecologically and clinically important fungal members is limited. In this study, we characterized simultaneously the oral bacterial and fungal microbial communities in a large cohort of healthy Chinese adults, examined their associations with an array of host factors, and explored potential interactions between the two microbial groups. We showed that different factors shape the diversity and structure of the oral bacterial and fungal microbial communities in healthy adults, with, for instance, sex and age only associated with the diversity of the bacterial community but not that of the fungal community. Besides, we found that bacterial-fungal interactions are limited in the healthy oral cavity. Overall, our study has facilitated understanding of the determining factors and bacterial-fungal interactions of the healthy human oral microbial community.

Silencing of Myh3 Gene by siRNA Inhibits Glycolysis in C2C12 Cells / 中国生物化学与分子生物学报

The Myh3 (myosin heavy chain 3) gene is a marker gene of muscle cell differentiation and regulates the utilization of energy in muscle cells, but whether it affects the glycolysis process of muscle cells in different states is rarely reported. In this paper, the expression patterns of Myh3 and glycolysis-related genes Pkm (M-type pyruvate kinse), Prkag3 (protein kinase adenosine monophosphate-activated γ3-subunit), and Gsk3β (glycogen synthase kinase-3β) were studied by the qRT-PCR (quantitative-Real-Time-PCR) method using C2C12 cells at different stages of myoblast and adipogenic differentiation as models. It was found that in the process of myoblast differentiation of C2C12 cells, the relative expression trends of Myh3 and glycolysis genes Prkag3 and Pkm were basically the same, and the relative expression levels first increased, reached the peak on the second day of differentiation, and then decreased; glycogen synthase the expression trend of the inhibitory gene Gsk3β was relatively stable. In the process of adipogenic differentiation of C2C12 cells, the relative expression trend of Myh3 and glycolysis genes Prkag3 and Pkm remained basically the same, and the relative expression gradually increased, reaching the highest value on the 8th day of differentiation; glycogen synthase inhibitory gene Gsk3β expression remained stable. In the myogenic differentiation state of C2C12 cells, qRT-PCR and Western blotting were used to detect the effects of interfering Myh3 on the mRNA and protein expressions of glycolysis-related genes Pkm, Prkag3, and Gsk3β. The results showed that after interfering with Myh3, the mRNA expressions of glycolysis genes Pkm and Prkag3 were significantly decreased (P 0.05). The protein levels of Myh3 and Pkm were significantly lower than those in the blank group and NC group. Under the adipogenic differentiation state of C2C12 cells, after interfering with Myh3, the mRNA levels of glycogen synthase inhibitor Gsk3β and glycolysis gene Prkag3 were significantly increased (P<0.01), and the mRNA level of glycolysis gene Pkm was decreased; the protein levels of Myh3 and Pkm in the Myh3 interference group were also lower than those in the blank group and NC group. Based on the above studies, there are significant differences in the levels of glycolysis in C2C12 cells in the myogenic and adipogenic states, and the expression patterns of Myh3 and glycolysis genes are similar. Further results showed that Myh3 suppression could inhibit the glycolysis of C2C12 cells in the myogenic state without affecting the glycogen synthesis. Unlike in the myogenic state, interfering expression of Myh3 in the adipogenic state of C2C12 cells inhibited both glycogen synthesis and glycolysis.

Restoration of the Oral Microbiota After Surgery for Head and Neck Squamous Cell Carcinoma Is Associated With Patient Outcomes.

OBJECTIVE: To evaluate the dynamics of the oral microbiome and associated patient outcomes following treatment of head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: This was a prospective cohort study at a tertiary academic center in Hong Kong SAR of patients with head and neck squamous cell carcinoma evaluating the oral microbiome in pre- and postsurgery oral rinses (at 1, 3, and 6 months) with 16S rRNA gene V3-V4 amplicon sequencing. RESULTS: In total, 76 HNSCC patients were evaluated. There was a significantly depressed alpha diversities of oral microbial communities observed in HNSCC oral rinse samples within the first 6 months post-surgery when compared to presurgery or healthy controls. Distant clustering between pre- and postsurgery was also observed (p < 0.022). Following treatment, eight oral bacterial genera showed a trend towards the restoration in the relative abundances that approximate healthy persons. In evaluating patient outcomes, the decreased relative abundance of three periodontal bacteria (Capnocytophaga, Prevotella 7, and Leptotrichia) and the increased relative abundance of two commensal bacteria (Streptococcus and Rothia) at 6 months postsurgery compared to presurgery showed a better 3-year disease-specific survival (a cutoff of Kaplan-Meier survival curve test p < 0.3 at 36 months). In particular, the postsurgery restoration of Prevotella 7 was statistically significant in the surveyed patients (survival rate of 84% vs. 56% at 36 months, p = 0.0065). CONCLUSIONS: Oral microbiome dysbiosis associated with HNSCC is dynamic. These dynamics of the oral microbiome postsurgery are also associated with patient treatment and outcomes and may serve as potential biomarkers for patient management in HNSCC.

Pneumonia, Multiple Pulmonary Infarction and Abscess Caused by a Bamboo Stick Accidentally Piercing into Chest: a Case Misdiagnosed as Pulmonary Tuberculosis.

Computed tomography (CT) examination is the major measure for detecting and diagnosis of foreign bodies in human body. Although CT has high sensitivity in diagnosis of foreign body, some interference factors may still lead to missed diagnosis or misdiagnosis. Here we report a rare case that a bamboo stick accidentally pierced into the left chest of a young man who was drunk and unware of this hurt. The patient experienced cough, chest pain, fever, hemoptysis, and was misdiagnosed as primary and secondary tuberculosis based on chest CT examinations at a local hospital, although no tubercular bacillus detected by sputum smear. He subsequently received anti-tuberculous treatments in the following three years, but no improvement of his symptoms was observed. Until one month before his death, the bamboo stick was detected by spiral CT examination as well as three-dimensional image reconstruction at another hospital. Postmortem examination revealed pneumonia, pulmonary infarction, and abscess as the causes of his death. We analyze the potential reasons of misdiagnosis in this case, aiming to provide reference for the diagnosis and treatment of pulmonary inflammation associated with foreign body in the future.

[Study on the Relationship between First-Time Complementary Feeding Practice and the Nutritional Status of Infants and Young Children in the Multi-Ethnic Rural Areas of Sichuan Province].

OBJECTIVE: To evaluate the current status of first food supplement and the nutrition of infants and young children in rural areas inhabited by people of Han, Tibetan, and Yi ethnicities in Sichuan Province, and to explore the relationship between the first ever feeding of food supplement and the nutritional status. METHODS: Using a multi-stage randomized cluster sampling method, we selected 2 Han counties, 2 Tibetan counties and 2 Yi counties in rural areas of Sichuan Province. These counties were previously defined as economically poor counties, but had since been lifted out of poverty. They were selected for this study before they came out of poverty. Infants and young children of 12-24 months old and their main caregivers from these counties were the subjects of the study. Structured questionnaires were used to collect information concerning the sociodemographic characteristics of infants and young children and their caregivers, and the first complementary feeding for infants and young children. Infant and young children weight scales and length/height tapes were used to collect the weight and length/height data of infants and young children. Unconditional logistic regression was used to analyze the correlation between the behavior of giving supplementary food for the first time to infants and young children and their nutritional status. RESULTS: A total of 1117 pairs of infants and children and their caregivers were investigated. Regarding the time of first supplementary food addition, nearly half of the caregivers in Han areas started adding supplementary food when the infants were 6 months old, accounting for 43.07% (171/397). Most of the caregivers in Yi and Tibetan areas started giving infants and young children supplementary food when they were less than 6 months old, accounting for 77.18% (301/390) and 47.58% (157/330), respectively. In terms of the types of supplementary food added for the first time, caregivers in Han areas mainly used homemade rice cereal, accounting for 41.56% (165/397), caregivers in Tibetan areas mainly used meat, vegetables or fruits and other complementary foods, accounting for 42.12% (139/330), and caregivers in Yi areas mainly used homemade rice cereal, accounting for 46.41% (181/390). The overall malnutrition rate of infants and young children was 28.83% (322/1117) and the malnutrition rate of infants and young children in Han, Tibetan, and Yi areas were 10.58% (42/397), 24.85 (82/330), and 50.77 (198/390), respectively. The regression analysis results show that after controlling for confounding factors, compared with Han areas, it is more likely for infants and young children in Yi areas to be malnourished ( OR=9.49, 95% CI 6.00-15.00). Compared with adding other types of complementary foods for the first time, infants and young children given iron-fortified rice cereal had a lower risk of malnutrition ( OR=0.54, 95% CI0.29-0.99). CONCLUSION: The multi-ethnic rural areas of Sichuan Province had problems that supplementary foods are added too early, and that the types of supplementary foods added for the first time were not appropriate. In addition, the nutritional status of local infants and young children in these areas was causing concerns. The malnutrition problem of infants and young children was especially prominent in the Yi ethnic areas. Adding iron-fortified rice cereal for the first time could reduce the possibility of malnutrition in infants and young children to a certain extent. It is recommended that attention should be given to the health education intervention of the first supplementary food for infants and young children to effectively improve the nutritional status of infants and young children in these areas.

[The Association Between Abdominal Obesity and Diabetes among Middle-aged and Older Adults with Normal BMI].

OBJECTIVE: To explore the relationship between abdominal obesity and diabetes among middle-aged and older adults with normal body mass index (BMI) and to provide reference information for formulating targeted diabetes prevention and control measures for this population. METHODS: Data were extracted from the China Health and Retirement Longitudinal Study (CHARLS) done in 2015. Middle-aged and older adults who were aged 45 and older and had normal BMI were included in the study. According to their status of diabetes, the subjects were divided into two groups, non-diabetes and diabetes groups. χ 2 test was used to investigate the difference between two groups. Logistic regression was used to do the multivariate analysis of factors influencing diabetes. RESULTS: A total of 5 197 middle-aged and older adults with normal BMI ranging between 18.5 and 24 kg/m 2 were included. The prevalence of diabetes was 11.26% (585/5 197) and the prevalence of abdominal obesity was 41.56% (2 160/5 197). Univariate analysis showed that the difference in age, residence, the status of hypertension, dyslipidemia and abdominal obesity between non-diabetic group and the diabetic group were statistically significant ( P<0.01). The prevalence of diabetes among adults with abdominal obesity was 14.2% (307/2 160) and that among people with no abdominal obesity was 9.2% (278/3 037). Compared with people with no abdominal obesity, the prevalence of diabetes among people with abdominal obesity was higher and the difference were statistically significant ( P<0.01). Multivariate logistic regression analysis showed that, among middle-aged and older adults with normal BMI, those with abdominal obesity, aged 60 years and older, living in urban areas, having hypertension and having dyslipidemia had higher probability of developing diabetes. CONCLUSION: Abdominal obesity and diabetes are becoming a serious problem among middle-aged and older adults with normal BMI and abdominal obesity may be related to higher risks of diabetes. It is recommended that more attention is given to abdominal obesity in this population to reduce the possibilities of diabetes.

The Intersection between Oral Microbiota, Host Gene Methylation and Patient Outcomes in Head and Neck Squamous Cell Carcinoma.

The role of oral microbiota in head and neck squamous cell carcinoma (HNSCC) is poorly understood. Here we sought to evaluate the association of the bacterial microbiome with host gene methylation and patient outcomes, and to explore its potential as a biomarker for early detection or intervention. Here we performed 16S rRNA gene amplicon sequencing in sixty-eight HNSCC patients across both tissue and oral rinse samples to identify oral bacteria with differential abundance between HNSCC and controls. A subset of thirty-one pairs of HNSCC tumor tissues and the adjacent normal tissues were characterized for host gene methylation profile using bisulfite capture sequencing. We observed significant enrichments of Fusobacterium and Peptostreptococcus in HNSCC tumor tissues when compared to the adjacent normal tissues, and in HNSCC oral rinses when compared to healthy subjects, while ten other bacterial genera were largely depleted. These HNSCC-related bacteria were discriminative for HNSCC and controls with area under the receiver operating curves (AUCs) of 0.84 and 0.86 in tissue and oral rinse samples, respectively. Moreover, Fusobacterium nucleatum abundance in HNSCC cases was strongly associated with non-smokers, lower tumor stage, lower rate of recurrence, and improved disease-specific survival. An integrative analysis identified that enrichment of F. nucleatum was associated with host gene promoter methylation, including hypermethylation of tumor suppressor genes LXN and SMARCA2, for which gene expressions were downregulated in the HNSCC cohort from The Cancer Genome Atlas. In conclusion, we identified a taxonomically defined microbial consortium associated with HNSCC that may have clinical potential regarding biomarkers for early detection or intervention. Host-microbe interactions between F. nucleatum enrichment and clinical outcomes or host gene methylation imply a potential role of F. nucleatum as a pro-inflammatory driver in initiating HNSCC without traditional risk factors, which warrants further investigation for the underlying mechanisms.

Elbasvir/grazoprevir treatment in an HCV-infected peritoneal dialysis patient.

Hepatitis C virus (HCV) infection is known to affect long-term patient survivals. Elbasvir/grazoprevir (EBR/GZR) has shown a high cure rate in hemodialysis patients with HCV infection. However, the combination is rarely used in peritoneal dialysis patients. Herein, we report a case of successful treatment with EBR/GZR in a peritoneal dialysis patient with HCV genotype 1 b infection. A 54-year-old woman on peritoneal dialysis（PD）with HCV genotype 1 b infection had been received EBR (100 mg) and GZR (50 mg) once daily for 12 weeks. Hepatitis C virus RNA was undetectable 4 weeks after the treatment. She achieved a sustained virological response at 12 weeks after the end of treatment. Only fatigue was reported as side effect during the treatment. Thus, elbasvir/grazoprevir was effective and safe in this PD patient with HCV genotype 1 b infection.

Risk factors analysis for surgical site infection following elective colorectal resection: a retrospective regression analysis.

BACKGROUND: A surgical site infection (SSI) is a major post-operative complication from elective colorectal surgery; however, few studies have focused on evaluating the risk factors for SSI. This study aimed to analyze the relative correlation of medical and environmental factors as well as patient-related factors that contribute to the incidence of all types of SSI. METHODS: A retrospective search for eligible patients was conducted using the patient database of the Gastrointestinal Surgery Center of the Third Affiliated Hospital of Sun Yat-sen University from January 2011 to August 2017. Pre-operative demographic and surgical data were extracted and recoded according to the study protocol. Univariate and multivariate analyses were performed to clarify factors affecting the incidence of SSI. Propensity analysis was conducted to minimize bias in the demographic characteristics to explore the prophylactic effect of pre-operative administration of oral antibiotics. RESULTS: Univariate analysis of the baseline characteristics revealed that younger age (odds ratio [OR]: 0.378; 95% confidence interval [CI]: 0.218-0.657) and pre-operative oral antibiotic use (OR: 0.465; 95% CI: 0.255-0.850) were protective factors, while pre-operative anemia (OR: 4.591; 95% CI: 2.567-8.211), neoadjuvant chemotherapy history (OR: 2.398; 95% CI: 1.094-5.256), and longer surgical duration (OR: 2.393; 95% CI: 1.349-4.246; P = 0.002) were identified as risk factors for SSI. Multivariate analysis indicated that age (P = 0.003), surgical duration (P = 0.001), and pre-operative oral antibiotic use (P < 0.001) were independent factors that affect the incidence of SSI. Furthermore, a propensity-matched analysis confirmed the protective effect of oral antibiotic use, with a 1-day course of oral antibiotic producing a similar effect to a 3-day course. CONCLUSIONS: Age, surgical duration, and pre-operative oral antibiotic use were associated with the incidence of SSI. However, pre-operative oral antibiotic use was the only controllable factor. From the results of our study, pre-operative oral antibiotic use is recommended before elective colorectal surgery and a 1-day course is enough to provide the protective effect.

Postmortem Analysis of 4 Mutation Hotspots of KCNQ1, KCNH2, and SCN5A Genes in Sudden Unexplained Death in Southwest of China.

Long QT syndrome (LQTS) is known to be involved in some sudden unexplained death (SUD) cases. To make clear whether the pathogenic genes of LQTS are involved in SUD in Yunnan province, southwest of China, we examined 4 mutation hotspot segments of KCNQ1, KCNH2, and SCN5A genes in 83 SUD cases using polymerase chain reaction and direct DNA sequencing. Genomic DNA was extracted from paraffin-embedded tissues in 83 cases of sudden cardiac death. One novel homozygous missense variant was identified in exon 3 of KCNQ1, c. 575G>T (p.R192L) in one case. One novel heterozygous missense variant was identified in exon 7 of KCNH2, c.1789T>A (p.Y597N) in 1 case. One novel heterozygous missense variant was identified in exon 7 of KCNH2, c.1800C>A (p.S600R) in 9 cases. In addition, 18 individuals were found to have heterozygous missense variant in exon 7 of KCNH2, c.1801G>A (p.G601S). Our study suggests that some SUDs in Yunnan province may be related with the pathogenic genes of LQTS.

Predictive models of adjuvant chemotherapy for patients with stage ii colorectal cancer: A retrospective study.

BACKGROUND: It remains controversial whether patients with Stage II colorectal cancer would benefit from adjuvant chemotherapy after radical resection. The aim of this study was to establish two mathematical models to identify the suitable patients for adjuvant chemotherapy. METHODS: The current study comprised of two steps. In the first step, 353 patients with Stage II colorectal cancer who underwent surgical procedures at the Third Affiliated Hospital of Sun Yat-sen University between June 2006 and December 2015 were entered and followed up for 6-120 months. Their clinical data were collected and enrolled into the database. We established two mathematical models by univariate and multivariate Cox regression analysis to identify the target patients; in the second step, 230 patients under the same standard between January 2012 and December 2016 were entered and followed up for 3-62 months to verify the two models' validation. RESULTS: In the first step, totally 340 surgical patients with Stage II colorectal cancer were finally enrolled in this study. Statistical analysis showed that tumor differentiation (TD) (P < 0.001), lymphovascular invasion (LVI) (P < 0.001), uncertain or positive margins (UPM) (P < 0.001), and fewer lymph nodes (LNs) (<12) retrieved (P < 0.001) were correlated with the overall survival (OS) and disease free survival (DFS). We obtained two models: (1) OS risk score = 1.116 × TD + 2.202 × LVI + 3.676 × UPM + 1.438 × LN - 0.493; (2) DFS risk score = 0.789 × TD + 2.074 × LVI + 3.183 × UPM + 1.329 × LN - 0.432. According to the models and cutoff points [(0.07, 1.33) and (-0.04, 1.30), respectively], patients can be divided into three groups: low-risk, moderate-risk, and high-risk. Moreover, the high-risk group patients could benefit from adjuvant chemotherapy. In the second step, totally 221 patients were finally used to verify the models' validation. The results proved that the models were accurate and feasible (P< 0.05). CONCLUSIONS: According to the predictive models, patients with Stage II colorectal cancer in the high-risk group are strongly recommended for adjuvant chemotherapy, thus facilitating the individualized and precise treatment.

Clinical Predictors of Outcome in Patients with Anti-neutrophil Cytoplasmic Autoantibody-related Renal Vasculitis: Experiences from a Single-center / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Primary anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) is a chronic autoimmune disease associated with multisystem dysfunction. Renal involvement is common and closely associated with outcome. The purpose of this study was to investigate the clinical determinants of mortality of patients with AAV-related renal injury in the first 2 years after diagnosis in a single West Chinese center.</p><p><b>METHODS</b>Demographic and laboratory parameters of 123 consecutive patients with AAV-related renal injury diagnosed in Renal Division and Institute of Nephrology, Sichuan Provincial People's Hospital between 2004 and 2012 were collected retrospectively. All patients were followed up for 2 years after diagnosis. Survivors were compared with nonsurvivors to identify the clinical baseline variables associated with mortality. Multivariate Cox regression model was used to determine the independent predictors of mortality.</p><p><b>RESULTS</b>Of the 123 patients, 46 (37.4%) died by the end of 2 years after diagnosis, with 41 (33.3%) patients dying within the first 12 months. In comparison with the survivors, Birmingham Vasculitis Activity Score (BVAS), the incidence of pulmonary hemorrhage and digestive system (DS) involvement, serum creatinine, and erythrocyte sedimentation rate were significantly higher in nonsurvivors, whereas lymphocyte counts, hemoglobin, and complement 3 (C3) were significantly lower. Renal replacement therapy was more common in nonsurvivors. High BVAS (hazard ratio [HR] = 1.058, 95% confidence interval [CI]: 1.002-1.117; P = 0.042), pulmonary hemorrhage (HR = 1.970, 95% CI: 1.033-3.757; P = 0.04), DS involvement (HR = 2.911, 95% CI: 1.212-6.911; P = 0.017), and serum creatinine >400 μmol/L (HR = 2.910, 95% CI: 1.271-6.664; P = 0.012) were independent predictors of death in patients with AAV-related renal injury.</p><p><b>CONCLUSIONS</b>Patients with AAV-related renal injury have high early mortality. Those with high BVAS (particularly with pulmonary or DS involvement) and serious renal dysfunction should receive aggressive therapy and careful monitoring to reduce the occurrence of adverse events and improve prognosis.</p>

Effect of preservation of Denonvilliers' fascia during laparoscopic resection for mid-low rectal cancer on protection of male urinary and sexual functions.

The aim of this study was to investigate the effect of preservation of Denonvilliers' fascia (DF) during laparoscopic resection for mid-low rectal cancer on protection of male urogenital function. Whether preservation of DF during TME is effective for protection of urogenital function is largely elusive.Seventy-four cases of male mid-low rectal cancer were included. Radical laparoscopic proctectomy was performed, containing 38 cases of preservation of DF (P-group) and 36 cases of resection of DF (R-group) intraoperatively. Intraoperative electrical nerve stimulation (INS) on pelvic autonomic nerve was performed and intravesical pressure was measured manometrically. Urinary function was evaluated by residual urine volume (RUV), International Prostatic Symptom Score (IPSS), and quality of life (QoL). Sexual function was evaluated using the International Index of Erectile Function (IIEF) scale and ejaculation function classification.Compared with performing INS on the surfaces of prostate and seminal vesicles in the R-group, INS on DF in the P-group exhibited higher increasing intravesical pressure (7.3 ±â€Š1.5 vs 5.9 ±â€Š2.4 cmH2O, P = 0.008). In addtion, the P-group exhibited lower RUV (34.3 ±â€Š27.2 vs 57.1 ±â€Š50.7 mL, P = 0.020), lower IPSS and QoL scores (7 days: 6.1 ±â€Š2.4 vs 9.5 ±â€Š5.9, P = 0.002 and 2.2 ±â€Š1.1 vs 2.9 ±â€Š1.1, P = 0.005; 1 month: 5.1 ±â€Š2.4 vs 6.6 ±â€Š2.2, P = 0.006 and 1.6 ±â€Š0.7 vs 2.1 ±â€Š0.6, P = 0.003, respectively), higher IIEF score (3 months: 10.7 ±â€Š2.1 vs 8.9 ±â€Š2.0, P = 0.000; 6 months: 14.8 ±â€Š2.2 vs 12.9 ±â€Š2.2, P = 0.001) and lower incidence of ejaculation dysfunction (3 months: 28.9% vs 52.8%, P = 0.037; 6 months: 18.4% vs 44.4%, P = 0.016) postoperatively.Preservation of DF during laparoscopic resection for selective male mid-low rectal cancer is effective for protection of urogenital function.