ObjectiveTePixD (Tll0078) is a blue light-using flavin (BLUF) photoreceptor protein from Thermosynechococcus elongatus BP-1. TePixD protein has a conserved Tyr8-Gln50-Met93 triad around the FAD pocket to mediate the proton-coupled electron transfer (PCET) process. But the detailed light response mechanism needs further study. We aimed to elucidate the structure and biochemical properties of TePixD mutants at key light response sites to analyze the light response process of TePixD. MethodsWe employed X-ray crystallography to resolve the crystal structure of the TePixD Y8F mutant. The side chain of Tyr8 is involved in PCET while Phe8 in mutation loses the function due to the loss of its hydroxyl group. We compared the structure of TePixD Y8F mutation to TePixD wild type (WT) and its homology protein SyPixD Y8F. Using multi-angle light scattering (MALS), we analyzed the oligomerization of multiple TePixD mutations (Y8F, Q50L, W91F, Y8F/W91F, and Q50L/W91F), focusing specifically on mutational sites that are critical residues for the protein’s photo response to dark and light conditions. ResultsWe resolved the crystal structure of TePixD Y8F mutant at a resolution of 2.54 Å and found that it shares a similar overall structure with the TePixD WT but exhibits significant differences from the SyPixD Y8F structure. Biochemical analysis revealed differences in molecular mass and elution profiles between the TePixD mutants and the WT under dark and light conditions, indicating the perturbation on the light-induced conformational change by the mutants. ConclusionOur structure determination and biochemical analyses will add information to reveal the light response mechanism of BLUF proteins.

Objective: To investigate the association between the distribution of tumor infiltrating lymphocytes (TIL) in EBV associated lymphoepitheliomatoid carcinoma (LELC) and the pathological subtypes of LELC, as well as the clinical significance of TIL distribution. Methods: The LELC patients with sufficient tumor tissues, complete clinical data and positive EBER, who visited Zhejiang Cancer Hospital, Hangzhou, China from January 2006 to October 2018, were selected. Various immunohistochemical markers (CD20, CD138, CD4, CD8, CD56 and FOXP3) were examined for TIL typing. Two pathologists reviewed the hematoxylin and eosin (HE) staining sections and interpreted the immunohistochemical results. Correlation analysis was used to evaluate the relationship between the distribution of TIL subgroups and LELC's pathological characteristics. Survival analyses were conducted to study the prognostic values of TIL subgrouping. Results: A total of 102 patients with EBV related LELC were included. 46 of them were classic LELC (c-LELC) with rich interstitial TIL, and 56 were non-classic LELC (n-LELC) with relatively fewer interstitial TIL. The results of TIL analysis showed that all subtypes of c-LELC were rich in TIL, with B lymphocytes as the dominant subgroup. The number of TIL in n-LELC was fewer than that in c-LELC, with T lymphocytes as the dominant subgroup. There was no significant difference in the distribution of plasma cells between the two groups. Survival analysis showed that the total number of TIL, and the infiltrations of CD20⁺B cells, CD4⁺T cells, and FOXP3⁺Treg cells were associated with better overall survivals (P=0.004, 0.003, 0.008 and 0.025, respectively) and disease-free survivals (P=0.011, 0.003, 0.038 and 0.041, respectively) in patients with LELC. Conclusions: The morphologic subtypes of EBV-related LELC have different tumor immune characteristics. The total number of TIL in the stroma of c-LELC is significantly higher than that of n-LELC. Interestingly, B lymphocytes are the dominant TIL in c-LELC, while T lymphocytes are the dominant TIL in n-LELC. The infiltration of TIL, CD20⁺B cells, CD4⁺T cells and FOXP3⁺Treg cells in LELC may suggest a better prognosis.
Humans ; Lymphocytes, Tumor-Infiltrating ; Herpesvirus 4, Human ; Clinical Relevance ; Prognosis ; Carcinoma, Squamous Cell/pathology* ; Forkhead Transcription Factors

Objective: To examine a predictive model that incorporating high risk pathological factors for the prognosis of stage Ⅰ to Ⅲ colon cancer. Methods: This study retrospectively collected clinicopathological information and survival outcomes of stage Ⅰ~Ⅲ colon cancer patients who underwent curative surgery in 7 tertiary hospitals in China from January 1, 2016 to December 31, 2017. A total of 1 650 patients were enrolled, aged (M(IQR)) 62 (18) years (range: 14 to 100). There were 963 males and 687 females. The median follow-up period was 51 months. The Cox proportional hazardous regression model was utilized to select high-risk pathological factors, establish the nomogram and scoring system. The Bootstrap resampling method was utilized for internal validation of the model, the concordance index (C-index) was used to assess discrimination and calibration curves were presented to assess model calibration. The Kaplan-Meier method was used to plot survival curves after risk grouping, and Cox regression was used to compare disease-free survival between subgroups. Results: Age (HR=1.020, 95%CI: 1.008 to 1.033, P=0.001), T stage (T3:HR=1.995,95%CI:1.062 to 3.750,P=0.032;T4:HR=4.196, 95%CI: 2.188 to 8.045, P<0.01), N stage (N1: HR=1.834, 95%CI: 1.307 to 2.574, P<0.01; N2: HR=3.970, 95%CI: 2.724 to 5.787, P<0.01) and number of lymph nodes examined (≥36: HR=0.438, 95%CI: 0.242 to 0.790, P=0.006) were independently associated with disease-free survival. The C-index of the scoring model (model 1) based on age, T stage, N stage, and dichotomous variables of the lymph nodes examined (<12 and ≥12) was 0.723, and the C-index of the scoring model (model 2) based on age, T stage, N stage, and multi-categorical variables of the lymph nodes examined (<12, 12 to <24, 24 to <36, and ≥36) was 0.726. A scoring system was established based on age, T stage, N stage, and multi-categorical variables of lymph nodes examined, the 3-year DFS of the low-risk (≤1), middle-risk (2 to 4) and high-risk (≥5) group were 96.3% (n=711), 89.0% (n=626) and 71.4% (n=313), respectively. Statistically significant difference was observed among groups (P<0.01). Conclusions: The number of lymph nodes examined was an independent prognostic factor for disease-free survival after curative surgery in patients with stage Ⅰ to Ⅲ colon cancer. Incorporating the number of lymph nodes examined as a multi-categorical variable into the T and N staging system could improve prognostic predictive validity.
Male ; Female ; Humans ; Prognosis ; Neoplasm Staging ; Retrospective Studies ; Nomograms ; Lymph Nodes/pathology* ; Risk Factors ; Colonic Neoplasms/surgery*

OBJECTIVE: To examine the impact of COVID-19 pandemic on the epidemic status of imported malaria and national malaria control program in China, so as to provide insights into post-elimination malaria surveillance. METHODS: All data pertaining to imported malaria cases were collected from Anhui Province, Hubei Province, Henan Province, Zhejiang Province and Guangxi Zhuang Autonomous Region during the period from January 1, 2018 through December 31, 2021. The number of malaria cases, species of malaria parasites, country where malaria parasite were infected, diagnosis and treatment after returning to China, and response were compared before (from January 1, 2018 to January 22, 2020) and after the COVID-19 pandemic (from January 23, 2020 to December 31, 2021). RESULTS: A total of 2 054 imported malaria cases were reported in Anhui Province, Hubei Province, Henan Province, Zhejiang Province and Guangxi Zhuang Autonomous Region during the period from January 1, 2018 to December 31, 2021, and there were 1 722 cases and 332 cases reported before and after the COVID-19 pandemic, respectively. All cases were reported within one day after definitive diagnosis. The annual mean number of reported malaria cases reduced by 79.30% in Anhui Province, Hubei Province, Henan Province, Zhejiang Province and Guangxi Zhuang Autonomous Region after the COVID-19 pandemic (171 cases) than before the pandemic (826 cases), and the number of monthly reported malaria cases significantly reduced in Anhui Province, Hubei Province, Henan Province, Zhejiang Province and Guangxi Zhuang Autonomous Region since February 2020. There was a significant difference in the constituent ratio of species of malaria parasites among the imported malaria cases in Anhui Province, Hubei Province, Henan Province, Zhejiang Province and Guangxi Zhuang Autonomous Region before and after the COVID-19 pandemic (χ² = 146.70, P < 0.05), and P. falciparum malaria was predominant before the COVID-19 pandemic (72.30%), while P. ovale malaria (44.28%) was predominant after the COVID-19 pandemic, followed by P. falciparum malaria (37.65%). There was a significant difference in the constituent ratio of country where malaria parasites were infected among imported malaria cases in Anhui Province, Hubei Province, Henan Province, Zhejiang Province and Guangxi Zhuang Autonomous Region before and after the COVID-19 pandemic (χ² = 13.83, P < 0.05), and the proportion of malaria cases that acquired Plasmodium infections in western Africa reduced after the COVID-19 pandemic that before the pandemic (44.13% vs. 37.95%; χ² = 4.34, P < 0.05), while the proportion of malaria cases that acquired Plasmodium infections in eastern Africa increased after the COVID-19 pandemic that before the pandemic (9.58% vs. 15.36%; χ² = 9.88, P = 0.02). The proportion of completing case investigation within 3 days was significantly lower after the COVID-19 pandemic than before the pandemic (96.69% vs. 98.32%; χ²= 3.87, P < 0.05), while the proportion of finishing foci investigation and response within 7 days was significantly higher after the COVID-19 pandemic than before the pandemic (100.00% vs. 98.43%; χ² = 3.95, P < 0.05). CONCLUSIONS The number of imported malaria cases remarkably reduced in Anhui Province, Hubei Province, Henan Province, Zhejiang Province and Guangxi Zhuang Autonomous Region of China during the COVID-19 pandemic, with a decreased proportion of completing case investigations within 3 days. The sensitivity of the malaria surveillance-response system requires to be improved to prevent the risk of secondary transmission of malaria due to the sharp increase in the number of imported malaria cases following the change of the COVID-19 containment policy.
Humans ; Pandemics ; China/epidemiology* ; Incidence ; COVID-19/epidemiology* ; Malaria/prevention & control* ; Malaria, Falciparum/epidemiology*

OBJECTIVE: To understand the clinical and epidemiological characteristics of human ocular thelaziasis patients in China. METHODS: Case reports regarding human ocular thelaziasis cases in China were retrieved in international and national electronic databases, including CNKI, VIP, CBM, Traditional Chinese Medical Literature Analysis and Retrieval System, Wanfang Database, PubMed and Web of Science from 2011 to 2022. Patients' gender, age, clinical symptoms, treatment, recurrence, site of infections, time of onset, affected eye, affected sites, number of infected Thelazia callipaeda, sex of T. callipaeda and source of infections were extracted for descriptive analyses. RESULTS: A total of 85 eligible publications were included, covering 101 cases of human ocular thelaziasis, including 57 males (56.44%) and 44 females (43.56%) and aged from 3 months to 85 years. The main clinical manifestations included foreign body sensation (56 case-times, 22.49%), eye itching (38 case-times, 15.26%), abnormal or increased secretions (36 case-times, 14.46%), tears (28 case-times, 11.24%) and eye redness (28 case-times, 11.24%), and conjunctival congestion (50 case-times, 41.67%) was the most common clinical sign. The most common main treatment (99/101, 98.02%) was removal of parasites from eyes using ophthalmic forceps, followed by administration with ofloxacin and pranoprofen. In publications presenting thelaziasis recurrence, there were 90 cases without recurrence (97.83%) and 2 cases with recurrence (2.17%). Of all cases, 51.96% were reported in four provinces of Hubei, Shandong, Sichuan, Hebei and Henan, and ocular thelaziasis predominantly occurred in summer (42.19%) and autumn (42.19%). In addition, 56.45% (35/62) had a contact with dogs. CONCLUSIONS The human thelaziasis cases mainly occur in the continental monsoon and subtropical monsoon climate areas such as the Yellow River and the Yangtze River basin, and people of all ages and genders have the disease, with complex clinical symptoms and signs. Personal hygiene is required during the contact with dogs, cats and other animals, and individual protection is required during outdoor activities to prevent thelaziasis.
Animals ; Dogs ; Female ; Humans ; Male ; Bibliometrics ; China/epidemiology* ; Seasons ; Spirurida Infections/epidemiology* ; Thelazioidea ; Eye Diseases/parasitology*

The nucleocapsid (N) protein of SARS-CoV-2 has been reported to have a high ability of liquid-liquid phase separation, which enables its incorporation into stress granules (SGs) of host cells. However, whether SG invasion by N protein occurs in the scenario of SARS-CoV-2 infection is unknow, neither do we know its consequence. Here, we used SARS-CoV-2 to infect mammalian cells and observed the incorporation of N protein into SGs, which resulted in markedly impaired self-disassembly but stimulated cell cellular clearance of SGs. NMR experiments further showed that N protein binds to the SG-related amyloid proteins via non-specific transient interactions, which not only expedites the phase transition of these proteins to aberrant amyloid aggregation in vitro, but also promotes the aggregation of FUS with ALS-associated P525L mutation in cells. In addition, we found that ACE2 is not necessary for the infection of SARS-CoV-2 to mammalian cells. Our work indicates that SARS-CoV-2 infection can impair the disassembly of host SGs and promote the aggregation of SG-related amyloid proteins, which may lead to an increased risk of neurodegeneration.
Amyloidogenic Proteins/metabolism* ; Amyotrophic Lateral Sclerosis/genetics* ; Animals ; COVID-19 ; Cytoplasmic Granules/metabolism* ; Mammals ; SARS-CoV-2 ; Stress Granules

Adult ; Brain ; Brain Diseases ; Heat Stroke ; Humans ; Magnetic Resonance Imaging ; Male ; Retrospective Studies

Juvenile dermatomyositis (JDM) is an autoimmune disease manifesting as proximal muscle weakness and skin rash and can involve multiple systems and visceral organs. Myositis-specific autoantibodies (MSAs) are highly associated with various complications and prognosis in JDM. Patients with anti-Mi-2 antibodies tend to have good prognosis and typical clinical symptoms. Patients with anti-MDA5 antibodies often have diffuse interstitial lung disease and skin ulcer, with mild symptoms of myositis. Patients with anti-NXP2 antibodies often have calcinosis, and such antibodies are associated with gastrointestinal bleeding and perforation. Patients with anti-TIF1-γ antibodies have diffuse and refractory skin lesions. Anti-SAE antibodies are rarely detected in children, with few reports of such cases. This article reviews the features of clinical phenotypes in JDM children with these five types of MSAs, so as to provide a basis for the clinical treatment and follow-up management of children with JDM.
Autoantibodies ; Dermatomyositis ; Humans ; Lung Diseases, Interstitial/etiology* ; Myositis ; Prognosis

To understand the mutational characteristics of ATP7B gene of hepatolenticular degeneration in Xinjiang region. 24 cases were diagnosed as hepatolenticular degeneration and the exon of ATP7B gene was detected in some of their siblings and parents. A total of 45 ATP7B gene mutations (93.75%) were detected in 24 cases, of which 14 cases were homozygous mutations or compound heterozygous mutations, six cases were heterozygous mutations and four cases were no mutations. A total of 24 gene mutations and 14 SNPS were detected, including 8 new mutations: c.251C > A, c.121A > c, c.2945C > A, c.2194C > T, c.2947T > c, c.3626T > A, c.3662_3664del, c.3557G > T. The most common mutations were c.2621C > T (p.A874V) [16.7% (4/24)] and c.2333G > T (p.R778L) [12.5% ​​(3/24)]. A total of 4 cases were diagnosed as pre-symptomatic. In this study, the most common mutation in the ATP7B gene is A874V. The most common genetic mutations in Han and Uyghur patients were different. The most common mutation in Han and Uyghur patients is R778L and A874V. Exon 11 is the gene mutations hot spot for patients with hepatolenticular degeneration in Xinjiang region, and is one of the priority exons to be detected when screening patients with suspected hepatolenticular degeneration.

To understand the hepatitis C virus (HCV) genotype distribution characteristics in Xinjiang region. 6462 cases with chronic HCV infection that were treated at the First Affiliated Hospital of Xinjiang Medical University from January 2013 to September 2018 were selected, and repeated testers were excluded. A total of 4773 cases with HCV genotypes were efficiently included. PCR-reverse dot hybridization method was used to retrospectively analyze the genotypes distribution. (2) test or F-test was used for intergroup comparison. < 0.05 was considered as statistically significant. Five genotypes were detected in 4 773 samples: genotype 1b 2928 cases (61.3%), genotype 2a 1241 cases (26%), and genotype 3a 375 cases (7.9%), genotype 3b 205 cases (4.3%), and genotype 6a 24 cases (0.5%). Patients were 48.14 ± 13.93 years old. Genotype 1b was mainly detected in all age groups. There were 2 965 cases of Han ethnicity and 1808 cases of 19 ethnic minorities, of which 1798 cases (60.6%) and 1130 cases (62.5%) were genotype 1b, and 235 cases (7.9%) and 345 cases (19.1%) were genotype 3, respectively. Among the ethnic minorities, Uyghur were the predominant, and genotype 6a could be detected; however, no other ethnic groups had detected genotype 6a. There were 704 Uyghur of genotype 1b (62.1%), 269 Uyghur of genotype 3 (23.7%), and 235 Hans of genotype 3 (7.9%). There were 2 413 males and 2 360 females, of which 1 418 males (58.8%), and 1 510 females (64%) were of genotype 1b, and 424 males (17.6%), and 156 females (6.6%) were of genotype 3. There was a statistically significant difference between the gender of patients with genotype 1b and non-genotype 1b ( < 0.05). There was a statistically significant difference in the detection rate of genotype 2a, 3a, 3b, 6a between Han and ethnic minority patients ( < 0.05). HCV genotypes distribution in Xinjiang region is diverse, and is mainly type 1b. An ethnic minority has higher proportion of HCV genotype 3 than that of Han ethnicity. HCV genotypes detection in Xinjiang region enriches the distribution characteristics of HCV genotypes and provides a basis for individualizing treatment for patients in China.
Adult ; China ; Ethnic Groups ; Female ; Genotype ; Hepacivirus ; genetics ; Hepatitis C ; Humans ; Male ; Middle Aged ; Minority Groups ; Retrospective Studies