Timely removal of oxidatively damaged proteins is critical for cells exposed to oxidative stresses; however, cellular mechanism for clearing oxidized proteins is not clear. Our study reveals a novel type of protein modification that may play a role in targeting oxidized proteins and remove them. In this process, DSS1 (deleted in split hand/split foot 1), an evolutionally conserved small protein, is conjugated to proteins induced by oxidative stresses in vitro and in vivo, implying oxidized proteins are DSS1 clients. A subsequent ubiquitination targeting DSS1-protein adducts has been observed, suggesting the client proteins are degraded through the ubiquitin-proteasome pathway. The DSS1 attachment to its clients is evidenced to be an enzymatic process modulated by an unidentified ATPase. We name this novel protein modification as DSSylation, in which DSS1 plays as a modifier, whose attachment may render target proteins a signature leading to their subsequent ubiquitination, thereby recruits proteasome to degrade them.
Free Radicals ; metabolism ; HeLa Cells ; Humans ; Oxidation-Reduction ; Oxidative Stress ; genetics ; Proteasome Endopeptidase Complex ; genetics ; metabolism ; Protein Binding ; Protein Modification, Translational ; genetics ; Ubiquitin ; metabolism ; Ubiquitination ; genetics

Objective: To investigate the evolution and clinical significance of HER2 low expression status in HER2 negative patients in primary and recurrent/metastatic breast cancers. Methods: The data and archived sections of 259 breast cancer patients with recurrence/metastasis and HER2-negative primary foci were collected from January 2015 to January 2022 at the Fourth Hospital of Hebei Medical University, and the HER2 status of primary and recurrence/metastasis foci was determined by immunohistochemistry (IHC), among which IHC 2+patients were subject to fluorescence in situ hybridization (FISH). The HER2 status was classified as HER2-0 group; patients with IHC 1+, IHC 2+and no FISH amplification were classified as HER2 low expression group; and patients with IHC 3+, IHC 2+and FISH amplified were classified as HER2-positive group. The changes of HER2 status in patients with HER2 low expression in primary versus recurrent/metastatic breast cancer foci were compared, and their clinicopathologic characteristics and prognosis were analyzed. Results: The overall concordance rate between primary and recurrent/metastatic HER2 status in breast cancer was 60.6% (157/259, κ=0.178). A total of 102 patients (102/259, 39.4%) had inconsistent primary and recurrent/metastatic HER2 status; 37 patients (37/259, 14.3%) had HER2-0 at the primary foci and HER2-low expression at the recurrent/metastatic; and 56 patients (56/259, 21.6%) had HER2-low expression in the primary foci and HER2-0 in the recurrent/metastatic. The recurrent/metastatic foci became low-expressing compared with the recurrent/metastatic foci which remained HER2-0 patients, with longer overall survival time, higher ER and PR positivity, lower Ki-67 positivity index, and lower tumor histological grade; all with statistically significant differences (all P<0.05). In the primary HER2-low group, patients with recurrent/metastatic foci became HER2-0 while those with recurrent/metastatic foci remained low expression; there were no statistically significant differences in clinicopathological features and overall survival time (all P>0.05). Conclusions: Unstable HER2 status in patients with HER2-0 and low expression in primary versus recurrent/metastatic breast cancer foci, and HER2-0 in the primary foci but low HER2 expression status in recurrence/metastasis is associated with favourable prognosis, and testing HER2 status in recurrence/metastasis can provide more treatment options for such patients.
Humans ; Breast Neoplasms/genetics* ; Clinical Relevance ; In Situ Hybridization, Fluorescence ; Female

Coal ; Coal Mining ; Dust/analysis* ; Humans ; Male ; Miners ; Occupational Diseases ; Occupational Exposure/adverse effects*

Objective: To explore distribution of HIV gene subtypes among newly reported HIV/AIDS cases from China and Myanmar in Dehong Dai and Jingpo prefecture of Yunnan province in 2016. Methods: We conducted DNA extractions from newly reported HIV/AIDS cases in 2016. The gag, env and pol genes were amplified by using reverse transcription-PCR (RT-PCR) and sequenced to identify HIV subtypes. Results: A total of 1 112 newly diagnosed HIV cases were reported in Dehong in 2016, and the HIV subtypes were identified for 860 cases. Subtype C was predominant (33.6%), followed by unique recombinant forms (URFs) (28.4%), CRF01_AE (18.6%) and so on. URFs include four recombination, among which the recombination of CRF01_AE and C subtype were predominant. The HIV subtype distribution was associated with nationality and transmission route in HIV/AIDS cases from Myanmar. Conclusions: The gene subtypes of C, URFs and CRF01_AE were mainly distributed; distribution of URFs remained complex and diverse among newly reported HIV/AIDS cases in Dehong in 2016.
Base Sequence ; China/epidemiology* ; Ethnicity/genetics* ; Genes, pol ; Genotype ; HIV Infections/genetics* ; HIV-1/genetics* ; Humans ; Male ; Phylogeny ; Polymerase Chain Reaction/methods* ; Serogroup

Objective: To explore the survival factors and construct a prognostic index (PI) for oral squamous cell carcinoma (OSCC). Methods: From January 2004 to June 2016, a total of 634 patients with pathologically confirmed OSCC were recruited in a hospital of Fujian. The clinical and follow-up data of all the patients with pathologically confirmed OSCC were collected to identify the factors influencing the prognosis of OSCC. All the patients were randomly divided into two groups: modeling group (modeling dataset, n=318) and validation group (validation dataset, n=316). Randomization was carried out by using computer-generated random numbers. In the modeling dataset, survival rates were calculated using Kaplan-Meier method and compared using the log-rank test. Cox regression model was used to estimate the hazard ratio (HRs) and 95% confidence intervals (CIs) of prognosis factors. An PI for OSCC patients prognostic prediction model was developed based on β value of each significant variable obtained from the multivariate Cox regression model. Using the tertile analysis, patients were divided into high-risk group, moderate-risk group, and low-risk group according to the PI, the Akaike information criterion (AIC) and Harrell's c-statistic (C index) were used to evaluated the model's predictability. Results: Results from the multivariate Cox regression model indicated that aged ≥55 years (HR=2.22, 95%CI: 1.45-3.39), poor oral hygiene (HR=2.12, 95%CI: 1.27-3.54), first diagnosis of lymph node metastasis (HR=5.78, 95%CI: 3.60-9.27), TNM stage Ⅲ-Ⅳ (stage Ⅰ as reference) (HR=2.43, 95%CI: 1.10-5.37) and poor differentiation (well differentiation as reference) (HR=2.53, 95%CI: 1.60-4.01) were the risk factors influencing the prognosis of OSCC. The PI model had a high predictability in modeling group and validation group (AIC and C index were 1 205.80, 0.700 2 and 1 150.47, 0.737 3). Conclusion: Age, poor oral hygiene, first diagnosis of lymph node metastasis, TNM stage and histological grade were factors associated with the prognosis of OSCC, and the PI model has a certain significance in the clinical treatment of OSCC.
Carcinoma, Squamous Cell/therapy* ; China/epidemiology* ; Humans ; Lymphatic Metastasis ; Middle Aged ; Mouth Neoplasms/therapy* ; Prognosis ; Proportional Hazards Models ; Risk Factors ; Survival Rate ; Treatment Outcome

Objective: To understand the characteristics on major strain subtypes of hepatitis C virus among HIV/HCV co-infected patients, so as to explore the molecular transmission clusters and related risk factors of HCV strains. Methods: A total of 336 newly reported HIV-infected patients were diagnosed as HIV/HCV co-infection in Dehong Dai and Jingpo autonomous prefecture (Dehong) in 2016. We used Nested PCR to amplify CE1 and NS5B genes among 318 samples with plasma levels above 200 μl, before using the combining phylogenetic tree and constructing molecular propagation network method to analyze the related data. Results: A total of 267 HIV/HCV co-infection patients who had met the HCV genotyping requirements were screened the gene subtypes were diversified. Among these genotypes, proportions of 3b, 6n, 6u, 1a, 3a and other subtypes appeared as 32.6% (87/267), 18.4% (49/267), 15.7%(42/267), 13.1%(35/267), 11.2%(30/267) and 9.0%(24/267) respectively. Molecular transmission network of five major HCV genotypes was constructed with a clustering rate of 39.1% (95/243). The clustering rate of subtype 1a was the highest, as 71.4% (25/35). Results from the multivariate logistic regression showed that ethnic minorities other than the Yi and Jingpo (vs. the Han, OR=0.17, 95%CI: 0.04-0.71), the married spouses (vs. the unmarried, OR=0.42, 95%CI: 0.18-0.94), the 6n and 3a subtype (vs. the 3b subtype, OR=0.34, 95%CI: 0.12-0.95; OR=0.22, 95%CI: 0.05-0.93) were more difficult to form transmission clusters. However, the 6u and 1a subtype (vs. the 3b subtype, OR=3.10, 95%CI: 1.21-7.94; OR=4.00, 95%CI: 1.32-12.11) seemed more likely to form the transmission clusters. Conclusion: Ethnicity, marital status and genetic subtypes were factors significantly associated with the formation of transmission clusters related to the major HCV gene subtypes among newly reported HIV/HCV co-infection in Dehong.
AIDS-Related Opportunistic Infections/virology* ; Asian People ; China/epidemiology* ; Coinfection ; Genotype ; HIV Infections/virology* ; Hepacivirus/isolation & purification* ; Hepatitis C/virology* ; Humans ; Phylogeny ; Polymerase Chain Reaction

Objective: To investigate the distribution patterns of mosquitoes, midges and related arboviruses in Sichuan province. Methods: Blood-sucking insects were collected from houses and pens, using the ultraviolet lights. Mosquito samples were classified according to morphologic characteristics and then stored at liquid nitrogen. All samples were incubated with BHK-21 and C6/36 cells for virus isolation and then detected for their viral genes. Sequences of the virus were identified and analyzed by molecular biological software, such as BioEdit 7.0.5.3, MEGA 6.0. Results: In total, 17 019 mosquitoes from 3 genera and 4 species and 12 700 midges were collected from the southeast regions of Sichuan province in 2016 and 2017. Among them, 79.4% (13 519/17 019) belonged to Culex tritaeniorhynchus with 11.1% (1 897/17 019) as Armigeres subalbatus, 5.5% (930/17 019) were Anopheles sinensis and 4.0% (673/17 019) were Anopheles sinensis 3 virus strains that isolated from Culex tritaeniorhynchus were identified as typeⅠ Japanese encephalitis virus. Seven pools of mosquitoes isolated from Hejiang county were identified Japanese encephalitis virus gene positive through PCR amplification. With 4 pool midges were detected positive for Akabane virus through PCR gene amplification while midges samples didn't have virus isolates. Conclusions: Culex tritaeniorhynchus appeared the predominant species in the southeast regions of Sichuan. Japanese encephalitis virus transmitted by mosquitoes and Akabane virus by midges were prevalent in southeast Sichuan province.
Animals ; Arboviruses ; Culicidae ; Encephalitis Virus, Japanese/isolation & purification* ; Encephalitis, Japanese/diagnosis* ; Genes, Viral ; Nucleic Acid Amplification Techniques ; Phylogeny ; Polymerase Chain Reaction

Objective: To investigate the association between alcohol consumption and lung cancer risk in Chinese males. Methods: Information on alcohol consumption and outcomes were collected on a biennial basis among males in Kailuan Cohort (2006-2015). In addition, electronic databases of hospitals affiliated to Kailuan Community, Insurance Systems of Kailuan Community and Tangshan were also used for supplementary information retrieval. Cox proportional hazards regression models were used to evaluate the hazard ratio (HR) and 95%CI of baseline frequency and type of alcohol consumption associated with lung cancer risk in males. Non-drinkers were used as control group. Results: A total of 101 751 males were included and 913 new lung cancer cases were identified in the Kailuan male cohort study, with a total follow-up time of 808 146.56 person-years and a median follow-up time of 8.88 years by 31 December 2015. After adjusting for potential confounding factors, the HR of former drinkers, occasional drinkers (<1/day) and drinkers (≥1/day) were 1.30 (95%CI: 0.90-1.88), 0.80 (95%CI: 0.64-1.01) and 1.04 (95%CI: 0.85-1.27), respectively, compared with non-drinkers. In addition, drinking beer/red wine (HR=0.91, 95%CI: 0.69-1.20) and white wine (HR=0.99, 95%CI: 0.83-1.19) showed no significant association with lung cancer. The results were similar when stratified analysis were conducted. Conclusion: Our study results don't support the hypothesis that alcohol consumption is significantly associated with the risk of lung cancer in males.
Adult ; Alcohol Drinking/epidemiology* ; China/epidemiology* ; Cohort Studies ; Humans ; Lung Neoplasms/epidemiology* ; Male ; Middle Aged ; Proportional Hazards Models ; Prospective Studies ; Risk Factors

Objective: To assess the association and intensity of baseline TC level with the incidence of lung cancer in men in China. Methods: Since May 2006, all the male workers, including the employees and the retirees in Kailuan Group were recruited in the Kailuan male dynamic cohort study. Information about demographics, medical history, anthropometry and TC level were collected at the baseline interview, as well as the information of newly-diagnosed lung cancer cases during the follow-up period. According to guidelines for blood lipids in Chinese adults and the distribution in the population, TC level was classified into five groups as followed: <160, 160-, 180-, 200- and ≥240 mg/dl, with the second quintile group (160- mg/dl) serving as the referent category. Cox proportional hazards regression model and restricted cubic spline (RCS) model were used to evaluate the association and the nonlinear association between baseline TC level and the risk of lung cancer in the men. Results: By December 31, 2014, for the 109 884 men, a follow up of 763 819.25 person-years was made with a median follow-up period of 7.88 years. During the follow up, 808 lung cancer cases were identified. After adjustment for age, education level, income level, smoking status, alcohol consumption level, history of dust exposure, FPG level and BMI, HR (95%CI) of lung cancer for men with lower TC level (<160 mg/dl) and higher TC level (≥240 mg/dl) were 1.34 (1.04- 1.72) and 1.45 (1.09-1.92), respectively, compared with men with normal TC level (160- mg/dl). The results didn't change significantly after exclusion of newly diagnosed cancer cases within 2 years of follow up and subjects with the history of hyperlipidemia. Conclusion: Our results showed that TC might be associated with higher risk of lung cancer. Men with lower TC level or higher TC level had higher risk for lung cancer. Keep moderate TC level might be one of the effective precaution for the prevention of lung cancer.
Adult ; Asian People ; China/epidemiology* ; Cholesterol/blood* ; Cohort Studies ; Humans ; Incidence ; Lipids ; Lung Neoplasms/ethnology* ; Male ; Proportional Hazards Models ; Prospective Studies ; Risk Factors