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Li Li,1,* Xuemei Zhong,1,* Aifang Zheng,1 Chen JianKun,2,3 Ayiguzali A Budukadeer,1 Paierda Aini,1 Maimaitiaili Tuerxun,1 Mukeremu Yasen,1 Tao Ma,1 Jie Ren,1 Rukeyamu Semaiti,1 Chengxin Xie,1 Feifei Li,1 Mireban Rexiati,1 Lifeng Tang,1 Gulanbaier Abudurexiti,1 Dayong Zheng,1 Ji-Qiang Li1– 3 1Department of Respiratory and Critical Care Medicine, The First People’s Hospital of Kashi Prefecture, Kashi, Xinjiang, People’s Republic of China; 2The Second Clinical College, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 3The Third Comprehensive Department, The Second Affiliated Hospital, Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dayong ZhengDepartment of Respiratory and Critical Care Medicine, The First People’s Hospital of Kashi Prefecture, 120 Yingbin Road, Kashi City, Xinjiang, 844000, People’s Republic of ChinaTel +13570029702Email zdy525679@163.comJi-Qiang LiThe Second Clinical College, Guangzhou University of Chinese Medicine, 232 Waihuan East Road, Guangzhou University City, Panyu District of Guangzhou, Guangzhou, 510120, People’s Republic of ChinaTel +13527675982Email Ljq525679@126.comObjective: To investigate the prevalence and the risk factors of COPD in the Uyghur population in the Kashi region.Methods: From August 2018 to March 2019, we recruited participants of Uyghur ethnicity and aged ≥ 40 years old from the Kashi region using a combined cluster sampling and random sampling method. We collected potential risk factors using questionnaire, and conduced lung function using a portable pulmonary function instrument.Results: A total of 2963 participants were included in this analysis, of whom 1268 were males and 1695 were females. There were 504 participants with COPD, generating a prevalence of 17.01%. With the increase of age, the prevalence of COPD in different genders increased significantly. The results of different regions were χ2= 627.89, p < 0.01, indicating significant differences in the prevalence in different regions. Among them, based on the existing survey data, it is speculated that Shache county has the highest crude prevalence, but the sample size needs to be further expanded. The participants with high age, smoking, lower BMI, high waist circumference, systolic blood pressure, fried cooking and barbecue share more COPD than those who partake of fruits and vegetables in this study.Conclusion: The prevalence of COPD among the Uyghur population in the Kashi region is higher than the national rural average. Among them, high age, smoking, low BMI, high waist circumference, high systolic blood pressure, cooking methods that may be stir-fried and deep-fried barbecue are risk factors for COPD, and vegetable and fruit intake may be a protective factor for COPD.Keywords: Uyghur population, chronic obstructive pulmonary disease, prevalence, risk factors, epidemiology study

Epigenetic gene silencing by aberrant DNA methylation is one of the important mechanisms leading to loss of key cellular pathways in tumorigenesis. Methyl‐CpG‐targeted transcriptional activation (MeTA) reactivates hypermethylation‐mediated silenced genes in a different way from DNA‐demethylating agents. Microarray coupled with MeTA (MeTA‐array) identified seven commonly hypermethylation‐mediated silenced genes in 12 pancreatic ductal adenocarcinoma (PDAC) cell lines. Among these, we focused on IRX4 (Iroquois homeobox 4) because IRX4 is located at chromosome 5p15.33 where PDAC susceptibility loci have been identified through genome‐wide association study. IRX4 was greatly downregulated in all of the analyzed 12 PDAC cell lines by promoter hypermethylation. In addition, the IRX4 promoter region was found to be frequently and specifically hypermethylated in primary resected PDACs (18/28: 64%). Reexpression of IRX4 inhibited colony formation and proliferation in two PDAC cell lines, PK‐1 and PK‐9. In contrast, knockdown of IRX4 accelerated cell proliferation in an IRX4‐expressing normal pancreatic ductal epithelial cell line, HPDE‐1. Because IRX4 is a sequence‐specific transcription factor, downstream molecules of IRX4 were pursued by microarray analyses utilizing tetracycline‐mediated IRX4 inducible PK‐1 and PK‐9 cells; CRYAB, CD69, and IL32 were identified as IRX4 downstream candidate genes. Forced expression of these genes suppressed colony formation abilities for both PK‐1 and PK‐9. These results suggest that DNA methylation‐mediated silencing of IRX4 contributes to pancreatic tumorigenesis through aberrant transcriptional regulation of several cancer‐related genes., IRX4 was found as a commonly hypermethylation‐mediated silenced gene in pancreatic ductal adenocarcinoma (PDAC) using the methyl‐CpG targeted transcriptional activation (MeTA) method. Promoter hypermethylation of IRX4 was seen in PDAC, reexpression of IRX4 inhibited proliferation in PDAC cell lines, and forced expression of IRX4 downstream genes suppressed colony formation abilities. These results suggest that DNA methylation‐mediated silencing of IRX4 contributes to pancreatic tumorigenesis through aberrant transcriptional regulation of several cancer‐related genes.

Background Prostate cancer is characterized by aberrant lipid metabolism, including elevated fatty acid oxidation. Carnitine palmitoyltransferase 1B (CPT1B) catalyzes the rate-limiting step of fatty acid oxidation. This study aimed to determine if CPT1B has a critical role in prostate cancer progression and to identify its regulatory mechanism. Methods CPT1B expression data from The Cancer Genome Atlas and Gene Expression Omnibus databases was compared with patient survival data. A tissue microarray was constructed with 60 samples of prostate cancer and immunohistochemically stained for CPT1B. Castration-resistant prostate cancer (CRPC) cell lines 22RV1 and C4-2 in which CPT1B expression had been stably knocked down were established; and cell proliferation, cell cycle distribution, and invasion were investigated by Cell Counting Kit-8 (CCK-8) and colony formation assays, flow cytometry, and Transwell assays, respectively. To examine the impact of androgen receptor (AR) inhibition on CPT1B expression, JASPAR CORE was searched to identify AR-binding sites in CPT1B. Dual luciferase and ChIP assays were performed to confirm CPT1B activity and AR binding, respectively. Differentially expressed genes (DEGs) in prostate cancer underwent gene set enrichment analysis (GSEA). Enzalutamide-resistant C4-2 cells were generated and the mechanism of enzalutamide resistance and downstream signaling pathway changes of CPT1B to C4-2 was explored through CCK-8 test. Results CPT1B expression was upregulated in human prostate cancer compared with normal prostate tissue and was associated with poor disease-free survival and overall survival. Silencing of CPT1B resulted in downregulated cell proliferation, reduced S-phase distribution, and lower invasive ability, whereas the opposite was observed in CRPC cells overexpressing CPTB1. DEGS in prostate cancer were correlated with G-protein-coupled receptor signaling, molecular transducer activity, and calcium ion binding. AR may regulate CPT1B expression and activity via specific binding sites, as confirmed by dual luciferase and ChIP assays. The CCK-8 experiment demonstrated that CPT1B overexpression in C4-2 cells did not significantly increase the ability of enzalutamide resistance. However, overexpression of CPT1B in C4-2R cells significantly increased the enzalutamide resistance. Upregulation of CPT1B expression increased AKT expression and phosphorylation. Conclusions CPT1B is upregulated in prostate cancer and is correlated with poor prognosis, indicating its potential as a biomarker. AR inhibits the transcription of CPT1B. In the CRPC cell line, overexpression of CPT1B alone cannot promote enzalutamide resistance, but in the drug-resistant line C4-2R, overexpression of CPT1B can promote the resistance of C4-2R to enzalutamide.

Epigenetic gene silencing by aberrant DNA methylation leads to loss of key cellular pathways in tumorigenesis. DNA methylation-mediated silenced genes in pancreatic cancer were searched for using the methyl-CpG targeted transcriptional activation (MeTA) method, and LHX6 (LIM homeobox 6), a transcription factor involved in embryogenesis and head development, was selected as a strong candidate gene. LHX6 was downregulated in most of the pancreatic cancer cell lines (83%, 10/12), mainly through promoter hypermethylation and histone deacetylation. Furthermore, LHX6 was methylated in primary pancreatic cancer specimens (57%, 16/28) in a tumor-specific manner. Re-expression of LHX6 inhibited colony formation and proliferation in LHX6 low-expressing pancreatic cancer cell lines, PK-1 and PK-9. In contrast, knockdown of LHX6 accelerated cell proliferation in LHX6 high-expressing pancreatic cancer cell lines, PCI-35 and MIA PaCa-2. In order to analyze LHX6 downstream genes, we performed microarray analyses using LHX6 inducible PK-1 and PK-9 and found that LHX6 induction upregulated several genes that had tumor suppressive functions. Among these, we focused on TFPI2 (Tissue factor pathway inhibitor-2) and found that TFPI2 was greatly downregulated in all twelve pancreatic cancer cell lines. Our present results suggest that epigenetic inactivation of LHX6 plays an important role in pancreatic tumorigenesis by promoting cell proliferation through aberrant transcriptional regulation of several cancer-related genes.

The present study investigated the clinical significance afforded by locoregional surgery in improving the prognosis of primary metastatic testicular cancer (pMTC). The population-based Surveillance, Epidemiology and End Results database was used as the primary source of data in the present study. Stratification analysis was employed to identify the effects of testicular surgery on testicular cancer-specific survival and overall survival. Propensity score matching and Cox regression models were then employed to find and evaluate the extent of improvements to the survival of patients with pMTC by testicular surgery. The median testicular cancer-specific survival and overall survival in the surgery group were 10% higher than those in the group without surgery. Testicular surgery was demonstrated to have provided a survival advantage for patients with a single metastasis in the bone or brain, but not in the liver or lung. When combined with radiotherapy and chemotherapy, surgery significantly improved the survival of patients. However, according to the surgical outcome based on molecular subtypes, when deciding on the surgery for patients with metastatic testicular cancer, only human chorionic gonadotropin and lactate dehydrogenase, and not α-fetoprotein should be considered. Surgery serves a significant role in the management of non-seminoma, whereas its role in the management of seminoma is far more limited. The effects of locoregional surgery have been neglected when treating patients with pMTC. Surgical procedures should be considered more seriously when planning combination treatments for patients with pMTC with a single bone or brain metastasis.

Objective The aim of the study was to determine an appropriate follow-up schedule for human papillomavirus (HPV) detection by evaluating the clearance time of HPV after treatment. Materials and Methods A retrospective study was conducted on 97 high-grade squamous intraepithelial lesion (HSIL) (cervical intraepithelial neoplasia 2–3) patients and 437 early invasive cervical cancer (CC) (stages Ia–IIa) patients who received radical surgery at the Affiliated Tumor Hospital of Xinjiang Medical University. Patient medical information, including personal information, pathological diagnosis, HPV infection status, and therapeutic methods, was obtained through the hospital's historical medical records management system. The clearance time of HPV was determined using Kaplan-Meier method analysis, and clearance time of HPV among different age groups, different grades, and different clinical stages were compared using the log-rank test. Results The median clearance time of all patients was 10.4 months. The median clearance time was longer in HSIL patients than in early invasive CC patients (p < .05). No statistical significance was found among different HSIL grades, CC stages, or patient age groups (P > 0.05). Conclusions Delaying first posttreatment follow-up to 9 months in patients at high risk of noncompliance could potentially reduce burden of cost and repeated clinical visits. This follow-up approach could be consistently applied to all women regardless of age, severity, and extent of disease.

We aimed to analyse clinical characteristics and identify risk factors predicting all-cause mortality in older patients with severe coronavirus disease 2019 (COVID-19). A total of 281 older patients with severe COVID-19 were categorized into two age groups (60–79 years and ≥ 80 years). Epidemiological, clinical, and laboratory data, and outcome were obtained. Patients aged ≥ 80 years had higher mortality (63.6%) than those aged 60–79 years (33.5%). Anorexia and comorbidities including hypertension, diabetes and COPD, higher levels of lactate dehydrogenase (LDH), osmotic pressure, C-reactive protein, D-dimer, high-sensitivity troponin I and procalcitonin, and higher SOFA scores were more common in patients aged > 80 years than those aged 60–79 years and also more common and higher in non-survivors than survivors. LDH, osmotic pressure, C-reactive protein, D-dimer, high-sensitivity troponin I, and procalcitonin were positively correlated with age and sequential organ failure assessment (SOFA), whereas CD8+ and lymphocyte counts were negatively correlated with age and SOFA. Anorexia, comorbidities including hypertension, diabetes, and chronic obstructive pulmonary disease (COPD), LDH, osmotic pressure, and SOFA were significantly associated with 28-day all-cause mortality. LDH, osmotic pressure and SOFA were valuable for predicting 28-day all-cause mortality, whereas the area under the receiver operating characteristic curve of LDH was the largest, with sensitivity of 86.0% and specificity of 80.8%. Therefore, patients with severe COVID-19 aged ≥ 80 years had worse condition and higher mortality than did those aged 60–79 years, and anorexia and comorbidities including hypertension, diabetes, COPD, elevated plasma osmotic pressure, LDH, and high SOFA were independent risk factors associated with 28-day all-cause mortality in older patients with severe COVID-19. LDH may have the highest predictive value for 28-day all-cause mortality in all examined factors.

Clear cell renal cell carcinoma (ccRCC) is the most common subtype among renal cancer, and more and more researches find that the occurrence of ccRCC is associated with genetic changes, but the molecular mechanism still remains unclear. The present study aimed to identify aggregation trend of differentially expressed genes (DEGs) in ccRCC, which would be beneficial to the treatment of ccRCC and provide research ideas using a series of bioinformatics approach. Gene ontology (GO) and Kyoto Encyclopedia of Gene and Genomes (KEGG) analysis were used to get the enrichment trend of DEGs of GSE53757 and GSE16449. Draw Venn Diagram was applied for co-expression of DEGs. Cytoscape with the Retrieval of Interacting Gene (STRING) datasets and Molecular Complex Detection (MCODE) were performed protein-protein interaction (PPI) of DEGs. The Kaplan–Meier Plotter analysis of top 15 upregulated and top 15 downregulated were selected in Gene Expression Profiling Interactive Analysis (GEPIA). Then, the expression level of hub genes between normal renal tissue and different pathological stages of ccRCC tissue, which significantly correlated with overall survival in ccRCC patients, were also analyzed by Ualcan based on The Cancer Genome Atlas (TCGA) database. In this study, we got 167 co-expression DEGs, including 72 upregulated DEGs and 95 downregulated DEGs. We identified 11 hub genes had significantly correlated with overall survival in ccRCC patients. Among them, KIF23, APLN, ADCY1, GREB1, TLR4, IRF8, CXCL1, CXCL2, deserved our attention.

ObjectiveTo compare the knee shape and bone parameters between knee prosthesis products from overseas companies and a Chinese patient’s knee, and to apply the anatomical basis for Chinese knee prosthesis design.MethodsThree-dimensional digital models were built, including prosthesis products for a normal adult. The relevant anatomy index was measured, and physical parameter, radiographic, geometric, knee kinematic, and distal geometry data were collected on the femur and tibia.ResultsThe width of the femoral condyle (WFC), width of the medial femoral condyle (WMFC), width of the lateral femoral condyle (WLFC), depth of the intercondylar fossa (DICF), sagittal length of the medial femoral condyle (SLMFC), sagittal length of the lateral femoral condyle (SLLFC), angle of the medial femoral condyle (AMFC), and angle of the lateral femoral condyle (ALFC) in the femur and the transverse diameter (ML) and anteroposterior diameter (AP) of the tibial bone were measured. These parameters were significantly lower in the normal group compared with the prosthesis product model group.ConclusionWhen using an imported knee prosthesis, the osteotomy angle may not fit perfectly. Use of an imported prosthesis may be an important factor in the increasing failure of knee arthroplasty in China.

Mierxiati Abudurexiti,1,2,* Jun Wang,1,2,* Ning Shao,1,2 Fang-Ning Wan,1,2 Yao Zhu,1,2 Bo Dai,1,2 Ding-Wei Ye1,2 1Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China *These authors contributed equally to this work Purpose: Urethral carcinoma (UC), as a rare tumor, is not widely studied. There have been no systematic studies of rare pathological types of UC. We conducted this study to further investigate rare pathological types of primary urethral carcinoma (PUC).Materials and methods: We used the population-based Surveillance, Epidemiology, and End Results (SEER) database to evaluate prognostic factors in rare pathological types of PUC. From 1978 to 2015, 2,651 and 257 cases were identified in the SEER database as common and rare pathological types of PUC, respectively. Overall and cancer-specific survival (CSS) times were computed using the Kaplan–Meier method, and the Cox proportional hazards analysis was used to evaluate patient age at diagnosis, gender, race, and TNM stage.Results: The median overall survival (OS) rates were 36 and 59 months for rare and common pathological groups, respectively, and their respective 10-year OS rates were 31.9% and 42.4%, respectively. The median CSS rate was 61 months for the rare pathological group. Through multivariate analysis, it was found that age, race, T stage, and M stage were independent prognostic risk factors for rare pathological type of urethral cancer. In the age group, the HR ratio of patients aged older than 60 years and younger or equal to 60 years was 2.778 (P

Essential hypertension (EH) is a principal contributing factor in worldwide cardiovascular disease mortality. Although interventions that minimize environmental risk factors for EH are associated with reduced cardiovascular disease, such approaches are limited for individuals with high genetic EH risk. In this study, we investigated possible associations between ACE2 polymorphisms and hypertension-related target organ damages in south Xinjiang, China. Four hundred and two hypertensive patients were enrolled as study participants in an EH group, and 233 normotensive individuals were enrolled as control subjects. Participants were recruited from the south Xinjiang region. Fourteen ACE2 polymorphisms were genotyped by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Risk genotypes of rs2074192 (TT+CT, OR = 1.72, 95% CI: 1.17-2.53), rs2106809 (TT, OR = 1.71, 95% CI: 1.13-2.58), rs4240157 (CC+CT, OR = 1.99, 95% CI: 1.17-3.41), rs4646155 (TT+CT, OR = 1.94, 95% CI: 1.06-3.54), rs4646188 (TT+CT, OR = 3.25, 95% CI: 1.95-5.41), rs4830542 (CC+CT, OR = 1.88, 95% CI: 1.10-3.23), and rs879922 (CC+CG, OR = 4.86, 95% CI: 2.74-8.64) were associated with EH. Hypertensive patients carrying the control genotype of rs2074192 (CC, OR = 2.37, 95% CI: 1.28-4.39) were associated with CAS ≥50%, while those carrying a high-EH-risk genotype of rs4240157 (OR = 2.62, 95% CI: 1.24-5.54), rs4646155 (OR = 2.44, 95% CI: 1.16-5.10), or rs4830542 (CC+CT, OR = 2.20, 95% CI: 1.03-4.69) were associated with atrial fibrillation (AF), larger left atrial diameter, and higher levels of renin-angiotensin-aldosterone system (RAAS) activation (renin and angiotensin I/II). In conclusion, the ACE2 variant rs2074192 was associated with EH and EH with CAS ≥50%, while 3 ACE2 variants (rs4240157, rs4646155, and rs4830542) were associated with EH- and hypertension-related AF and left atrial remodeling in south Xinjiang, China.

Background Cardiovascular benefits by reversing environmental risks factors for essential hypertension (EH) and dyslipidemia could be weaken by high genetic risk. We investigated possible associations between ACE2 polymorphisms and dyslipidemia in patients with EH. Methods Four hundred and two hypertensive patients were enrolled in an EH group and 233 normotensive individuals were enrolled as control group from the Xinjiang region of China. Fourteen ACE2 polymorphisms were genotyped by Matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Results Participants carrying T allele (TT + CT) of rs2074192 (P = 0.006), rs4646155 (P = 0.030) and rs4646188 (P

Clinical studies have confirmed that indomethacin (Indo) can reduce the incidence and severity of post-endoscopicretrogradecholangio-pancreatography pancreatitis (PEP) effectively. However, the role of Indo on severe acute pancreatitis (SAP) is not clear. In the present study, we aimed to explore the effects of Indo treatment on SAP model induced by caerulein combined with lipopolysaccharide. After intraperitoneal injection of Indo in mice, both the severity of SAP and the serum levels of amylase, lipase, and proinflammatory cytokines were decreased. Furthermore, the mRNA and protein levels of NLRP3 inflammasome pathway (NLRP3,ASC and IL-1β) in pancreatic tissues were down-regulated. In vitro experiments, by isolating the pancreatic acinar cells (PACs) from mice, we found that Indo significantly reduced lactate dehydrogenase(LDH) excretion, increased the cell activity, and inhibited the NLRP3 inflammasome pathway of PACs. Taken together, our data showed that Indo could protect pancreatic acinar cell from injury by inhabiting NLRP3 pathway and decreased the severity of SAP accordingly.

Castration-resistant prostate cancer (CRPC) displays a higher 18F-FDG PET SUVmax than hormone-sensitive prostate cancer, which suggests a greater need for glucose metabolism in CRPC. Targeting glucose metabolism in cancer cells remains attractive for cancer treatment. Glucose transporters (GLUTs) meditate the first and rate-limiting step of glucose metabolism. Here, we investigated the key mediator of glucose transporters and evaluated its therapeutic value in a preclinical model of CRPC. 18F-FDG PET showed a higher SUVmax in CRPC than in hormone-sensitive prostate cancer, and GLUT1 expression positively correlated with SUVmax and was associated with a worse CRPC outcome. GLUT1 inhibition significantly suppressed cell growth, glycolysis and tumor volume in a xenograft model both in CRPC and enzalutamide-resistant prostate cancer. Chromatin immunoprecipitation and dual luciferase reporter assay showed that androgen receptor (AR) directly bound to the GLUT1 gene promoter to promote GLUT1 transcription. Combining GLUT1 inhibition and enzalutamide remarkably suppressed proliferation and glycolysis and induced apoptosis in CRPC cells. Our results suggest that GLUT1 is an AR target and displays synergistic effects with enzalutamide. GLUT1 may act as a promising therapeutic target in CRPC and enzalutamide-resistant prostate cancer.

Background: Existing data on the association of metastatic sites and prognosis of patients with metastatic testicular malignancy are limited. In this study, the association of survival outcome and the prognostic value of different metastatic sites in patients with metastatic testicular cancer was investigated.Methods: A dataset from the Surveillance, Epidemiology and End Results (SEER) survey was selected for a retrospective metastatic testicular cancer cohort study. Patients with different metastatic sites were divided into corresponding groups for further analysis. Kaplan-Meier analysis with log-rank test was implemented for comparison of the survival distribution of cases. Multivariate Cox regression models were then applied to analyze the association of distant metastases with survival for all selected patients and subgroup based on different histological type with a single metastatic site.Results: A total of 1,661 patients treated for metastatic testicular malignant tumors between 2010 to 2016 were enrolled in this cohort study. Upon initial diagnosis, 61.9, 15.2, 6.7, 6.4, and 36.2% of patients were found to have lung, liver, bone, brain, and distant lymph nodes metastatic sites, respectively. Patients with lung, liver, or bone metastases showed more undesirable prognosis for overall survival (OS) and cancer-specific survival (CSS), in contrast with those with distant lymph node metastases (all P < 0.05). In comparison with patients with more than one metastatic site, those with a single metastasis had extended OS and CSS (both P < 0.001). In patients with a single metastatic site, Kaplan-Meier analysis and multivariate Cox regression demonstrated the association of bone and liver with the worst two groups of OS and CSS. Multivariate Cox models based on histological type showed different prognostic values of metastases in patients with seminoma or non-seminomatous germ cell tumors.Conclusion: There is much heterogeneity in the oncological outcome of site-specific metastatic patients. Metastatic profiles and the prognostic value of metastases are dependent on the histological type in TC patients. Distant lymph nodes and lung metastases indicate favorable prognostic factors, while bone and liver metastases indicate negative survival outcomes in TC.

Purpose: We aimed to develop and validate a novel gene signature from published data and improve the prediction of survival in muscle-invasive bladder cancer (MIBC).Methods: We searched the published gene signatures associated with the overall survival (OS) of MIBC and compiled all 274 genes to develop a novel gene signature. RNAseq data of TCGA (the Cancer Genome Atlas) bladder cohort were downloaded. All genes were included in a univariate Cox hazard ratio model. We then used a reduced multivariate Cox regression model, which included only genes achieving P < 0.05 in the univariate model. A total of 172 patients at Fudan University Shanghai Cancer Center (FUSCC) and 61 patients from GEO datasets were used as an external validation set.Results: A total of 327 patients in the TCGA cohort were enrolled. We identified 274 genes from eight published papers on the OS of MIBC. Using the TCGA database, we identified 12 genes that correlated with OS (P < 0.05 in both univariate and multivariate analyses). By integrating these genes with the RT-qPCR data in our validation dataset and GEO datasets, we confirmed that the power for predicting OS of the 12-gene panel (AUC of 0.741 and 0.727, respectively) was higher than just clinical data (including gender, age, T stage, grade, and N stage) alone in the TCGA and FUSCC cohort (AUC of 0.667 and 0.631, respectively). Additionally, upon combining the clinical data and 12-gene panel together, the AUC increased to 0.768, 0.757, and 0.88 in the TCGA, FUSCC and GSE13507 cohorts, respectively.Conclusions: Applying published gene signatures and TCGA data, we successfully built and externally validated a novel 12-gene signature for the survival of MIBC.Brief ExplanationWe systemically reviewed all published prognostic gene signatures of muscle-invasive bladder cancer (MIBC) and integrated the genes in the TCGA MIBC cohort. This new gene panel was validated in a newly established MIBC cohort in GEO and FUSCC. This method can help update the previous established panels in a new way.

Background: As conditional survival could provide more relevant prognostic information at each follow-up time, the present study aimed to assess conditional overall survival (COS) based on two cohorts and assess the risks of death due to renal cell carcinoma (RCC) vs. other causes. Methods: The Fudan University Shanghai Cancer Center (FUSCC) and Surveillance, Epidemiology, and End Results (SEER) database were used as the source of data for our analysis. COS and cancer-specific survival were evaluated using the Kaplan–Meier method. Results: A total of 90,927 patients (SEER cohort = 88,807, FUSCC cohort = 2,120) were enrolled. Our results suggest that hazards of other causes-related death were always higher than that of cancer-specific death in low-risk RCC patients, but lower in metastatic RCC patients. It exceeded that of cancer-specific death by 8 years in high-risk RCC patients. Only in metastatic RCC patients, the COS improved markedly with survivorship increasing. After surviving 1, 2, 3, 4, and 5 years, the 5 years COS increased by +10, +18, +23, +29, and 35% (the observed 5 years OS: 12%), respectively. Conclusions: COS can better help patients with metastatic RCC rather than other RCC patients. Additionally, COS brings optimism for metastatic RCC patients with expected poorer prognosis psychologically.

OBJECTIVE Serine palmitoyltransferase, long chain base subunit 1 (SPTLC1) catalyzes the first step in sphingolipid synthesis and has been implicated in the progression of various cancers. However, its role in clear cell renal cell carcinoma (ccRCC) remains unclear. Here, we investigated the expression and prognostic value of SPTLC1 in ccRCC. METHODS Three ccRCC patient cohorts were studied. ccRCC and adjacent normal kidney tissue samples were obtained from 183 patients at the Fudan University Shanghai Cancer Center (FUSCC) and subjected to immunohistochemical staining and quantitative reverse-transcription polymerase chain reaction to evaluate SPTLC1 protein and messenger RNA (mRNA) expression. Two validation cohorts consisting of mRNA and clinicopathological data sets from patients with ccRCC were obtained from the Cancer Genome Atlas (TCGA, n = 429) and Oncomine (n = 178) databases. Associations between low and high SPTLC1 mRNA and protein expression and survival were evaluated using the Kaplan-Meier method and log-rank test. Independent prognostic factors were identified using univariate and multivariate Cox regression analysis. RESULTS SPTLC1 mRNA or protein were expressed at significantly lower levels in ccRCC tissues compared with normal kidney tissues in all three patient cohorts (P

Background The rarities of primary neuroendocrine prostate cancer (NEPC) and primary adenocarcinoma with neuroendocrine differentiation (NE differentiation) mean that their clinical characteristics have not been fully elucidated. Materials and methods A total of 449 patients with NEPC, including 352 cases of pure NEPC and 97 cases of NE differentiation, together with 408 629 cases of prostate adenocarcinoma at diagnosis were retrieved from the Surveillance, Epidemiology, and End Results program (2010-2015). Clinical parameters and prognoses were compared between patients with different histological types of NEPC using the χ2 test and Kaplan-Meier analysis, respectively. The prognostic value of prostate-specific antigen (PSA) in NEPC and adenocarcinoma was evaluated using Cox regression and the Kaplan-Meier method. Results Pure NEPC had higher rates of visceral metastases (brain, lung, and liver: 4.58%, 26.72%, and 36.64%, respectively) but a lower rate of bone metastasis (65.65%) compared with NE differentiation and prostate adenocarcinoma. Moreover, patients diagnosed with pure NEPC had a poorer outcome (median survival time: 10 months) compared with patients with NE differentiation (26 months) and prostate adenocarcinoma (median survival time not reached). Using PSA 4.1 to 10 ng/mL as the reference, the adjusted hazard ratios (HRs) for PSA lower than or equal to 4.0 ng/mL were 2.24 (95% confidence interval [CI]: 1.11-4.55, P = .025) in the NE differentiation group and 1.57 (95% CI: 1.11-2.23, P = .011) in the pure NEPC group. Conclusions Patients with NE differentiation had different clinical characteristics and a better prognosis than patients with pure NEPC. In addition, low-serum PSA levels were associated with a poorer prognosis in patients with either NEPC or NE differentiation.

Objective. The effect of adiposity on hypertension among Uyghur Chinese is not clear. This study aimed to compare the effect of BMI and its optimal cut-off value in identifying hypertension in Uyghur and Han adults in China. Methods. By using a multistage stratified sampling method, 3072 Uyghur and 3195 Han adults underwent questionnaire interview, physical examination, and biochemical tests. Age- and sex-standardized prevalence of hypertension was calculated. Adjusted odds ratios for adiposity associated with hypertension were estimated. ROC analyses were used for assessing the ethnic and sex specific optimal BMI cut-off values in identifying hypertension. Results. Both in Uyghur and Han, increased BMI was consistent with the elevated systolic and diastolic blood pressure. Although more Uyghur were overweight/obese, their standardized prevalence of hypertension (17.87%) was lower than that of Han (20.28%). Han adults had 1.42 times odds than Uyghur of hypertension. The adjusted ORs of overweight and obesity were 2.67 and 6.04 in Uyghur and 2.74 and 7.58 in Han. In male, the optimal cut-off values of BMI identifying hypertension in Uyghur and Han were 24.6 kg/m2 and 24.9 kg/m2 , respectively, but the correspond values in Uyghur and Han females were 27.2 kg/m2 and 25.0 kg/m2. Conclusions. Adiposity had strong effect on hypertension, but this effect was less strong in Uyghur female than in Han female.

Seipin deficiency is responsible for type 2 congenital generalized lipodystrophy with severe loss of adipose tissue and can lead to hepatic steatosis, insulin resistance (IR), and dyslipidemia in humans. Adipose tissue secretes many adipokines that are central to the regulation of metabolism. In this study, we investigated whether transplantation of normal adipose tissue could ameliorate severe hepatic steatosis, IR, and dyslipidemia in lipoatrophic seipin knockout (SKO) mice. Normal adipose tissue from wild-type mice was transplanted into 6-wk-old SKO mice. At 4 mo after adipose tissue transplantation (AT), the transplanted fat survived with detectable blood vessels, and the reduced levels of plasma leptin, a major adipokine, were dramatically increased. Severe hepatic steatosis, IR, and dyslipidemia in SKO mice were ameliorated after AT. In addition, abnormal hepatic lipogenesis and β-oxidation gene expression in SKO mice were improved after AT. Our results suggest that AT may be an effective treatment to improve lipodystrophy-associated metabolic disorders.

Background Cervical cancer incidence and mortality is high in Uyghur ethnics. Their life style and dietary habit were different from other ethnics living together. Study on the role of trace elements in HPV infection and cervical lesion of Uyghur minority is needed for future intervention and prevention work. Methods In total, 833 Uyghur women were randomly selected from the screening site and hospital. The concentrations of the trace elements As, Fe, Cd, Ni, Cu, Zn, Mn, and Se were determined by atomic absorption spectrophotometry and inductively coupled plasma atomic emission spectroscopy. Univariate analysis was performed with chi-squared test between the HPV-positive and HPV-negative groups and between the case group and the control group. Multivariate analysis was performed with logistic regression. Results An As concentration ≥ 0.02 mg/kg was a risk factor for HPV infection (OR > 1, P 1, P

Background Type 2 diabetes mellitus (T2D), rapidly increasing to epidemic proportions, globally escalates cardiovascular disease risk. Although intensive interventions and comprehensive management of environmental risks factors for T2D are associated with reduced cardiovascular disease, such approaches are limited for individuals with high genetic T2D risk. In this study we investigated possible associations of ACE2 polymorphisms and cardiovascular risks in Uygur patients with T2D. Methods 275 Uygur T2D patients and 272 non-diabetic Uygur individuals were enrolled as study participants. 14 ACE2 polymorphisms were genotyped by Matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Results ACE2 SNP rs1978124, rs2048683, rs2074192, rs233575, rs4240157, rs4646156, rs4646188 and rs879922 were associated with T2D (all P

Background Accumulated evidence suggests that metastatic prostate cancer (mPCa) with a low prostate-specific antigen (PSA) level may be a unique entity. However, its clinical features and prognosis have not been fully evaluated. Objective To investigate the clinical features of low-PSA mPCa and the impact of low PSA level on overall survival (OS) and PCa-specific mortality (PCSM) of mPCa. Design, setting, and participants A total of 8479 mPCa patients were retrieved from the Surveillance, Epidemiology, and End Results program (2010–2015). The median follow-up was 18 mo. Outcome measurements and statistical analysis Cox regression and Fine-Gray competing risk were used to calculate the hazard ratio (HR) and subdistribution hazard ratio (sHR) for OS and PCSM, respectively. Results and limitations A higher rate of T4 stage disease (19.8%) and visceral metastasis (18.2%) and the shortest median OS (34 mo) were observed in mPCa patients with Gleason 8–10 and PSA ≤4 ng/ml. In the Cox regression model, PSA ≤4 ng/ml was a significant predictor of OS for Gleason 8–10 disease. The distribution of PCSM by PSA was U-shaped for Gleason score 8–10 (PSA 4.1–10 ng/ml as the referent), with an adjusted sHR of 1.52 for PSA ≤4.0 ng/ml (95% confidence interval: 1.17–1.96) versus 0.99 for PSA 10.1–20 ng/ml and 1.35 for PSA >20 ng/ml. In contrast, the distribution of PCSM by PSA was linear for Gleason 5–7. Sensitivity analyses showed similar results in Gleason 9–10 and Gleason 10 subgroup. The study is limited by its retrospective design. Conclusions Low PSA, high-grade mPCa has a higher proportion of T4 stage disease, visceral metastasis, and PCSM. Patient summary We found that 2.8% of high-grade metastatic prostate cancer has a prostate-specific antigen level ≤4 ng/ml at diagnosis. This population has aggressive clinical features and a poor cancer-specific outcome. Our results highlighted this under-reported population, and the management of these patients warrants further research.

ObjectiveThis study was performed to compare the effectiveness and safety of percutaneous endoscopic lumbar discectomy (PELD) versus micro-endoscopic discectomy (MED) in the treatment of patients with lumbar disk herniation.MethodsIn total, 216 patients treated for lumbar disk herniation in our center from January 2016 to July 2017 were prospectively divided into two groups according to the treatment received. One group was treated with PELD and the other group was treated with MED. The surgical duration, intraoperative blood loss, total hospital stay, visual analog scale (VAS) pain score, and Oswestry disability index (ODI) score before and after the surgery were compared between the groups.ResultsThe surgical duration was significantly longer in the PELD than MED group. The intraoperative blood loss volume was significantly larger in the MED than PELD group. The total hospital stay was significantly longer in the MED than PELD group. The decline in the VAS pain score and increase in the ODI score after surgery were not significantly different between the two groups.ConclusionsAlthough PELD is associated with a longer surgical duration than MED, it should still be considered superior to MED because of less intraoperative hemorrhage and a significantly shorter hospitalization time.

Objective To evaluate the application and therapeutic effects of debridement from a single posterior approach for bone grafting and internal fixation treatment of lumbosacral tuberculosis. Methods From January 2010 to December 2016, 96 patients with lumbosacral tuberculosis were treated by single posterior debridement and internal fixation with bone graft. Among these patients, there were 9 cases involving the L3–L4 segment, 57 involving L4–L5, and 30 involving L5–S1. Interlaminar debridement was applied in 60 cases and transforaminal debridement was applied in 36 cases. Evaluation of therapeutic effects included the Prolo scale and visual analogue scale. The kyphotic angle and height loss of the vertebral body in the affected region of the lumbosacral segment were measured radiologically. Results All patients were followed up for 12–24 months. In the interlaminar group, the mean preoperative, postoperative, and final kyphotic angles were −24.1 ± 5.5°, −34.6 ± 5.6°, and −32.1 ± 5.1°, respectively. In contrast, those in the transforaminal group were −25.1 ± 5.9°, −35.0 ± 6.6°, and −33.3 ± 5.9°, respectively. There was significant improvement of the postoperative angle compared with the preoperative angle. The result of the modified Prolo scale was 93.8%. According to the visual analogue scale, the preoperative and postoperative scales were 7.8 and 2.7, indicating a significant alleviation of pain. Conclusions Debridement from single posterior approach is an effective technique for the internal fixation of lumbosacral regional spinal tuberculosis. An appropriate selection of indications, careful evaluation of radiology, and thorough debridement were the key to a successful operation.

Background Glutaric aciduria type II (GA II) is an autosomal recessive disorder affecting fatty acid and amino acid metabolism. The late-onset form of GA II disorder is almost exclusively associated with mutations in the electron transfer flavoprotein dehydrogenase (ETFDH) gene. Till now, the clinical features of late-onset GA II vary widely and pose a great challenge for diagnosis. The aim of the current study is to characterize the clinical phenotypes and genetic basis of a late-onset GAII patient. Methods In this study, we described the clinical and biochemical manifestations of a 23-year-old female Chinese patient with late-onset GA II, and performed genomic DNA-based PCR amplifications and sequence analysis of ETFDH gene of the whole pedigree. We also used in-silicon tools to analyze the mutation and evaluated the pathogenicity of the mutation according to the criteria proposed by American College of Medical Genetics and Genomics (ACMG). Results The muscle biopsy of this patient revealed lipid storage myopathy. Blood biochemical test and urine organic acid analyses were consistent with GA II. Direct sequence analysis of the ETFDH gene (NM_004453) revealed compound heterozygous mutations: c.250G > A (p.A84T) on exon 3 and c.920C > G (p.S307C) on exon 8. Both mutations were classified as “pathogenic” according to ACMG criteria. Conclusions In conclusion, our study described the phenotype and genotype of a late-onset GA II patient, reiterating the importance of ETFDH gene screening in these patients. Electronic supplementary material The online version of this article (10.1186/s12944-017-0576-5) contains supplementary material, which is available to authorized users.

Summary: Glucose-stimulated insulin secretion from islet β cells is mediated by KATP channels. However, the role of non-KATP K+ channels in insulin secretion is largely unknown. Here, we show that a non-KATP K+ channel, KCNH6, plays a key role in insulin secretion and glucose hemostasis in humans and mice. KCNH6 p.P235L heterozygous mutation co-separated with diabetes in a four-generation pedigree. Kcnh6 knockout (KO) or Kcnh6 p.P235L knockin (KI) mice had a phenotype characterized by changing from hypoglycemia with hyperinsulinemia to hyperglycemia with insulin deficiency. Islets from the young KO mice had increased intracellular calcium concentration and increased insulin secretion. However, islets from the adult KO mice not only had increased intracellular calcium levels but also had remarkable ER stress and apoptosis, associated with loss of β cell mass and decreased insulin secretion. Therefore, dysfunction of KCNH6 causes overstimulation of insulin secretion in the short term and β cell failure in the long term. : Yang et al. show that KCNH6 plays a key role in insulin secretion and glucose hemostasis in humans and mice. Dysfunction of KCNH6 results in a hyperinsulinemia phenotype in the short term and hypoinsulinemia and diabetes in the long term. Keywords: maturity-onset diabetes of the young, MODY, monogenic diabetes, type 2 diabetes, islet, insulin secretion, KCNH6, KCNH2, KATP, Cas9

Aim Atherosclerosis-prone apolipoprotein E (apoE) or low-density lipoprotein receptor (LDL-R) knockout (KO) mice are generally resistant to developing coronary atherosclerosis (CA) and ischemic heart disease (IHD). However, studies have demonstrated the occurrence of spontaneous CA and IHD in scavenger receptor class B type 1 (SR-BI)/apoE double KO (dKO) mice, which suggests that SR-BI could be a potential target for the prevention and therapy of CA and IHD. This possibility was later investigated in SR-BI/LDL-R dKO mice, but no signs of CA or IHD was identified when mice were fed a normal western-type diet. Here we explored whether SR-BI deletion could result in CA and IHD in LDL-R KO mice when fed a modified western-type diet containing higher (0.5%) cholesterol. Methods Cardiac functions were detected by electrocardiography, single photon emission computed tomography (SPECT), echocardiography (Echo) and 2,3,5-triphenyltetrazolium chloride staining. CA was visualized by hematoxylin-eosin staining. Results After 12 weeks on the modified diet, SR-BI/LDL-R dKO mice developed cardiac ischemia/infarction, together with systolic dysfunction and left ventricular dilatation. CA was most severe at the aortic sinus level to an extent that no dKO mice survived to 20 weeks on the modified diet. None of control mice, however, developed CA or IHD. Conclusions SR-BI deletion led to CA and IHD in LDL-R KO mice when fed the modified western-type diet. We established SR-BI/LDL-R dKO mice as a diet-induced murine model of human IHD and developed detection methods, using a combination of SPECT and Echo, for effective in vivo evaluation of cardiac functions.

The hamster has been shown to share a variety of metabolic similarities with humans. To replicate human acute pancreatitis with hamsters, we comparatively studied the efficacy of common methods, such as the peritoneal injections of caerulein, L-arginine, the retrograde infusion of sodium taurocholate, and another novel model with concomitant administration of ethanol and fatty acid. The severity of pancreatitis was evaluated by serum amylase activity, pathological scores, myeloperoxidase activity, and the expression of inflammation factors in pancreas. The results support that the severity of pathological injury is consistent with the pancreatitis induced in mice and rat using the same methods. Specifically, caerulein induced mild edematous pancreatitis accompanied by minimal lung injury, while L-arginine induced extremely severe pancreatic injury including necrosis and neutrophil infiltration. Infusion of Na-taurocholate into the pancreatic duct induced necrotizing pancreatitis in the head of pancreas and lighter inflammation in the distal region. The severity of acute pancreatitis induced by combination of ethanol and fatty acids was between the extent of caerulein and L-arginine induction, with obvious inflammatory cells infiltration. In view of the advantages in lipid metabolism features, hamster models are ideally suited for the studies of pancreatitis associated with altered metabolism in humans.

Background The severe forms of hypertriglyceridemia are usually caused by genetic defects. In this study, we described a Chinese female with severe hypertriglyceridemia caused by a novel homozygous mutation in the APOC2 gene. Methods Lipid profiles of the pedigree were studied in detail. LPL and HL activity were also measured. The coding regions of 5 candidate genes (namely LPL, APOC2, APOA5, LMF1, and GPIHBP1) were sequenced using genomic DNA from peripheral leucocytes. The ApoE gene was also genotyped. Results Serum triglyceride level was extremely high in the proband, compared with other family members. Plasma LPL activity was also significantly reduced in the proband. Serum ApoCII was very low in the proband as well as in the heterozygous mutation carriers. A novel mutation (c.86A > CC) was identified on exon 2 of the APOC2 gene, which converted the Asn codon at position 29 into Ala, followed by a termination codon (TGA). Conclusions This study presented the first case of ApoCII deficiency in the Chinese population, with a novel mutation c.86A > CC in the APOC2 gene identified. Serum ApoCII protein might be a useful screening test for identifying mutation carriers.