As an important part of tumor microenvironment, neutrophils are poorly understood due to their spatiotemporal heterogeneity in tumorigenesis. Here we defined, at single-cell resolution, CD44-CXCR2- neutrophils as tumor-specific neutrophils (tsNeus) in both mouse and human gastric cancer (GC). We uncovered a Hippo regulon in neutrophils with unique YAP signature genes (e.g., ICAM1, CD14, EGR1) distinct from those identified in epithelial and/or cancer cells. Importantly, knockout of YAP/TAZ in neutrophils impaired their differentiation into CD54+ tsNeus and reduced their antitumor activity, leading to accelerated GC progression. Moreover, the relative amounts of CD54+ tsNeus were found to be negatively associated with GC progression and positively associated with patient survival. Interestingly, GC patients receiving neoadjuvant chemotherapy had increased numbers of CD54+ tsNeus. Furthermore, pharmacologically enhancing YAP activity selectively activated neutrophils to suppress refractory GC, with no significant inflammation-related side effects. Thus, our work characterized tumor-specific neutrophils in GC and revealed an essential role of YAP/TAZ-CD54 axis in tsNeus, opening a new possibility to develop neutrophil-based antitumor therapeutics.
Humans ; Animals ; Mice ; Adaptor Proteins, Signal Transducing/metabolism* ; Transcription Factors/metabolism* ; Stomach Neoplasms/pathology* ; Neutrophils/pathology* ; Signal Transduction/genetics* ; YAP-Signaling Proteins ; Tumor Microenvironment ; Hyaluronan Receptors/genetics*

Objective To analyze the changes in follicular helper T (Tfh) cells during HIV-1 in-fection, to investigate the influences of Tfh cells and Tfh-related molecules on HIV-1 progression and to pro-vide references for further research on using Tfh cells in highly active antiretroviral therapy ( HAART) and vaccines. Methods This study enrolled 33 patients with HIV-1 infection, including 11 long-term nonpro-gressors (LTNP), 10 rapid progressors (RP) and 12 typical progressors (TP), and 11 healthy subjects (normal controls, NC). Peripheral blood mononuclear cells were isolated from each subject. Multicolor flow cytometry was performed to detect CD4+CD45RA-CXCR5+Tfh and CD4+CD45RA-CXCR3-CXCR5+PD-1+Tfh subsets and the levels of inducible costimulatory molecule (ICOS), IFN-γ and IL-21. Moreover, the levels of IL-10 and the percentages of CD19+B cells in plasma samples of each group were also analyzed. Relationships among Tfh, CD4 and B cells were analyzed. Results The percentages of both Tfh subsets were higher in patients with HIV-1 infection than in NC. Compared with NC, LTNP had the highest percent-age of CD4+CD45RA-CXCR3-CXCR5+PD-1+Tfh cells (P<0. 05). Expression of Tfh-related molecules ICOS, IFN-γ and IL-21 were enhanced significantly upon Staphylococcus enterotoxin B ( SEB) stimulation, ICOS+Tfh cells were negatively related with HIV-1 progression, but had a positive correlation with CD19+B cells (r=-0. 49, P<0. 01; r=0. 60, P<0. 05). IL-10 level in plasma increased significantly in patients withHIV-1 infection , especially in TP and RP ( TP vs NC : P＜0. 01 ; RP vs NC : P<0. 05 ) . Conclusion HIV-1 patients and NC had significant differences in the expression of Tfh cells and Tfh-related molecules in peripheral blood. ICOS+Tfh cells were closely related to the progression of HIV-1 infection and the function of B cells.

OBJECTIVETo investigate the predictors that reduced the survival time on HIV positive TB patients during their first year's anti-TB therapy.

METHODSA retrospective study was conducted to review 519 TB/HIV co-infection patients from an Internet based TB surveillance system. We collected information of demography, HIV status, CD4+ lymphocytes count, antiretroviral therapy (ART), sputum smear results of diagnosis and around 2 months' initiation of anti-TB therapy, et al. Wilconxon rank sum test was used to compare the difference of age and CD4+ lymphocytes, count and Cox Uni-variable, and Multi-variable analysis were used to compare the different distribution of rest of risk elements between the groups of death and survival; survival function also has been used to evaluate the top 4 risk elements that have made negative impact on the survival time of HIV positive TB patients during their first year's anti-TB therapy.

RESULTSAmong 519 TB/HIV patients, 84 (16.18%) were dead, 435 (83.82%) survived. Median age (P50 (P25-P75)) in survival was 51.0 (41.0-65.0), while in death was 45.0 (35.0-60.0) (U=-2.68, P=0.007). There was significant difference between survival and death. Median CD4+ lymphocyte count in survival and death (P50 (P25-P75)) were 69.00 (26.00-131.20) and 114.50 (35.00-245.00), respectively, significant difference also has been observed. Based on the Cox analysis, patients with less than 2 months' intensive anti-TB therapy, poor treatment adherence, less than 4 months continue anti-TB therapy and sputum smear positive around 2 months initiation of anti-TB therapy had higher risk of death, the Relative Risk value (RR) were 1 100.40 (95% CI: 105.62-11,470.00), 52.91 (95% CI: 27.42-102.13), 49.43 (95% CI: 6.38-382.81), and 15.83 (95% CI: 2.55-98.40), respectively. Log-rank test results showed that there were significant difference between survival and death groups with anti-TB intensive therapy duration (Log-Rank value was 236.0, P<0.001), adherence (Log-Rank value was 302.9, P<0.001), and sputum smear results around 2 months' anti-TB initiation (Log-Rank value was 7.55, P=0.006).

CONCLUSIONKnown HIV positive, less CD4+ lymphocyte count, not initiation of ART, sputum smear positive, around 2 months' initiation of anti-TB therapy, not enough anti-TB therapy duration of intensive and continue period and poor treatment adherence were the predictors of death of HIV positive TB patients in the first year's anti-TB therapy.

Anti-HIV Agents ; CD4 Lymphocyte Count ; CD4-Positive T-Lymphocytes ; Coinfection ; Factor Analysis, Statistical ; HIV Infections ; Humans ; Life Expectancy ; Retrospective Studies ; Survival Rate ; Tuberculosis

OBJECTIVETo understand the general feature of patients with Mycobacterium tuberculosis (MTB) and human immunodeficiency virus (HIV) co-infectious (TB/HIV) in Guangxi, from 2007 to 2012.

METHODSInformation regarding individuals that the contributory causes of death were due to MTB infection among HIV as the underlying cause of death from the Vital Registration System, together with bacterium smear or culture results, onset of TB, time that TB was diagnosed and entered an Internet base TB surveillance system was collected and checked. Data including information on time of death, age, occupation, the underlying cause of death among TB patients, bacterium distribution, average age of death, interval from onset to death, percentage of TB/HIV co-infection patients among all the patients etc, were all analysed.

RESULTS203 patients died from HIV associated with TB from the Guangxi Vital Registration System were identified between 2007 and 2012. The average percentage of TB/HIV co-infection cases accounted for 8.24% (ranging from 3.94% in 2007 to 13.27% in 2012) among all the deaths of HIV infection while it accounted for 9.90% (ranging from 2.56% to in 2007 to 26.88% in 2012) among patients with MTB infection in the same period. The average percentage of deaths from TB/HIV co-infection in 2010 and 2012 accounted for 10.66% (ranging from 8.83% to 13.27%)and 22.17% (ranging from 20.60% to 26.88%)among patients died of HIV and TB infection respectively. The male-female ratio was 4.21 for 1, with the average age of death as 44.65 (44.65 ± 15.52) years;median time from TB symptoms onset to diagnosis as 37 (mean 94.31, standard deviation 206.07) days, record as (94.31 ± 206.07); median time from diagnosis to death as 46 (165.22 ± 282.19) days, 54.68% TB/HIV patients died within two months of being diagnosed with TB and the median time from TB symptoms onset to death as 131 (257.68 ± 340.79) days. 16.26% of the TB/HIV cases were bacterium confirmed TB cases.

CONCLUSIONCompare to those TB patients without HIV, less bacterium evidence was found in TB/HIV patients. High burden caused by HIV disease was seen if they were co-infected with TB. An increasing proportion of deaths was noticed among patients co-infected with HIV and TB in the last three years, suggesting that the coverage of antiretroviral therapy be scaled up together with the strengthening of the capability on early TB case-finding among people live with HIV.

Adult ; China ; epidemiology ; Coinfection ; mortality ; Female ; HIV Infections ; microbiology ; mortality ; Humans ; Male ; Middle Aged ; Tuberculosis ; mortality ; virology ; Young Adult

Objective To understand the general feature of patients with Mycobacterium tuberculosis(MTB)and human immunodeficiency virus(HIV)co-infectious(TB/HIV)in Guangxi, from 2007 to 2012. Methods Information regarding individuals that the contributory causes of death were due to MTB infection among HIV as the underlying cause of death from the Vital Registration System,together with bacterium smear or culture results,onset of TB,time that TB was diagnosed and entered an Internet base TB surveillance system was collected and checked. Data including information on time of death,age,occupation,the underlying cause of death among TB patients, bacterium distribution,average age of death,interval from onset to death,percentage of TB/HIV co-infection patients among all the patients etc,were all analysed. Results 203 patients died from HIV associated with TB from the Guangxi Vital Registration System were identified between 2007 and 2012. The average percentage of TB/HIV co-infection cases accounted for 8.24%(ranging from 3.94%in 2007 to 13.27%in 2012)among all the deaths of HIV infection while it accounted for 9.90%(ranging from 2.56%to in 2007 to 26.88%in 2012)among patients with MTB infection in the same period. The average percentage of deaths from TB/HIV co-infection in 2010 and 2012 accounted for 10.66%(ranging from 8.83% to 13.27%) and 22.17%(ranging from 20.60% to 26.88%) among patients died of HIV and TB infection respectively. The male-female ratio was 4.21 for 1,with the average age of death as 44.65 (44.65 ± 15.52)years;median time from TB symptoms onset to diagnosis as 37(mean 94.31,standard deviation 206.07)days,record as(94.31 ± 206.07);median time from diagnosis to death as 46(165.22 ± 282.19)days,54.68%TB/HIV patients died within two months of being diagnosed with TB and the median time from TB symptoms onset to death as 131 (257.68 ± 340.79) days. 16.26% of the TB/HIV cases were bacterium confirmed TB cases. Conclusion Compare to those TB patients without HIV,less bacterium evidence was found in TB/HIV patients. High burden caused by HIV disease was seen if they were co-infected with TB. An increasing proportion of deaths was noticed among patients co-infected with HIV and TB in the last three years,suggesting that the coverage of antiretroviral therapy be scaled up together with the strengthening of the capability on early TB case-finding among people live with HIV.

Objective To assess the relationship between BRAF gene mutations and clinical phenotype of malignant melanoma.Methods Tissue specimens were collected from the lesions of 80 patients with malignant melanoma,and from the normal skin of 30 patients with trauma in the Department of Plastic Surgery or General Surgery,and subjected to paraffin embedding and DNA extraction.PCR was performed to amplify the exon 11 and 15 of BRAF gene followed by DNA sequencing.Chi-square test and Fisher's exact test were carried out to assess the relationship between BRAF gene mutations and clinical phenotypes of malignant melanoma.Results BRAF gene mutations were found in 19 (23.8％) of the 80 malignant melanoma specimens.Among the 19 mutationpositive specimens,17 (88.2％) carried mutations in exon 15 of BRAF gene with V600E as the most frequent (88.2％,15/17) mutation type,and 2 (10.5％) carried mutations in exon 11.No mutation was found in any of the normal skin tissue specimens.The average age at onset was 57.5 years in these patients.The frequency of BRAF gene mutation was significantly higher in patients younger than 60 years than in those older than 60 years (37.1％ vs.13.3％,x2=6.613,P ＜ 0.05).A significant difference was observed in the frequency of BRAF gene mutation among tissue specimens of mueosal,acral and non-aeral malignant melanoma (18.2％ (4/21) vs.14.7％(5/34) vs.41.7％ (10/24),x2=6.167,P ＜ 0.05).There was no significant association between BRAF gene mutation and gender,race or lymph node metastasis (all P ＞ 0.05).Conclusions BRAF gene is a hot spot for mutations in patients with malignant melanoma in Xinjiang Uygur Autonomous Region,with V600E point mutation in exon 15 as the most frequent mutation type.BRAF gene mutations appear to be closely correlated with the age at onset of and lesional sites in,but uncorrelated with gender and race of or lymph node metastasis in,patients with malignant melanoma.

Objective: To study the therapeutic effect of secondary lymphoid tissue chemokine (SLC) combined with CpG oligodeoxynucleotide (CpG-ODN) in treatment of implanted mouse melanoma and the possible mechanism. Methods: SLC-Fc fusion protein was prepared and its chemotaxis of lymphocytes was detected by chemotaxis assay. Implanted melanoma mouse models were established and randomly divided into 4 groups: control group, SLC-Fc group, CpG-ODN group, and SLC-Fc+CpG-ODN group. The growth of implanted tumors in each group was observed after treatment. Subtype and infiltration of lymphocytes in implanted tumor tissues were examined by flow cytometry. Results: SLC-Fc protein was successfully prepared, and it dose-dependently attracted lymphocytes (0.03, 0.3, and 3 μg/L). Intra-tumor injection SLC-Fc and CpG-ODN alone or in combination significantly inhibited growth of B16-implanted tumors. Tumor size in SLC-Fc+CpG-ODN group was significantly smaller than that in control group (P<0.01), and animals in SLC-Fc+CpG-ODN group survived longer. Tumor-infiltrated CD4~+ T, CD~8+ T, and dendritic cells (DCs) in SLC-Fc+CpG-ODN group were markedly increased as compared with those in control group (P<0.05), and tumor draining lymph nodes were dramatically enlarged. Conclusion: SLC combined with CpG-ODN can inhibit the growth of implanted melanoma by attracting CD4~+ T and CD8~+ T and promoting proliferation of DCs.

Objective To know the current situation of drinking water quality and the influencing factors of provided for oneself water supply in rural schools in Guangxi.Methods According to the randomly proportionate stratification (economic,geography and topography etc.),43 and 50 counties were selected in 2007 and 2008 and the monitoring sites from 3 rural schools with provided for oneself water supply facility were taken out based on the proportion of water sources and technical patterns coverage in each county.The survey on water supply technical patterns,water sources and their coverage was conducted.One hundred and thirty,one hundred and fifty-three monitoring sites in rain season (July or August) and dry season (March or November) were monitored separately in 2007 and 2008.The monitoring results of drinking water were assessed according to Sanitary Standards for Drinking Water Quality (GB5749-2006).Results The groundwater was main drinking water source,which were 84.03% and 90.75% in 2007 and 2008.Most of water supply had not any water treatment,which was 75.86% in 2007 and 64.22% in 2008.The qualified rate in rain season (18.02%) was significant lower than dry season (31.80%) (P

Objective To investigate the quality of drinking water produced by safe drinking water projects in rural areas of Guangxi.Methods A survey of water quality was conducted from January to October 2008,in the drinking water projects funded by treasure bonds in 89 counties (cities and districts) of Guangxi.The water samples were collected from waterworks and tap water in dry season (March) and rainy season (July to August),respectively,and evaluated for aesthetic,microbiologic and chemical indexes.Results A total of 1 327 drinking water projects were surveyed.58.25% had a daily output under 100 tons,and only 2.71% had an output over 1 000 tons (enough for 10 000 persons).Only 12.28% adopted comprehensive water treatment process (i.e.coagulation,sedimentation,filtration and disinfection),whereas 62.85% did not provide any treatment.Up to 79.80% had no disinfection equipment and 90% failed to provide effective disinfection.25.21% and 21.48% of finished water,and 25.78% and 20.59% of tap water samples tested up to the standard respectively in the dry season and rainy season.Over 88% of water samples met the aesthetic,chemical and toxicological standards (100% up to standard for chronic,arsenic and fluoride),while 73.16%-80.78% met the standard for bacterial count,30.86%-36.17% for fecal coliforms and 41.86%-47.73% for thermotolerant coliforms.Conclusion The study results indicate that the inadequate supply of safe water,absence of water treatment facilities and poor drinking water quality have represented a potential health risk in Guangxi rural areas.

Objective To know the current status of the household lavatories in the countryside of Guangxi Province, China and to present the scientific data for the government to make decision in the lavatory improvement in the countryside. Methods A stratified cluster sampling was used in the investigation and 2 414 peasant households in 241 villages were selected in 2006. Results The popularization rate of sanitary lavatory was 43.79% and 50.95% of the peasant households used the non-sanitary lavatory, 5.26% had no household lavatory. The main types of the sanitary lavatories used in the investigated area were firedamp tank-like and three-case-cesspool, accounted for 50.14% and 33.96% respectively. The rate of dejecta treatment for the non-sanitary lavatories was only 13.74%. As the money spent on the sanitary lavatory in each household was no less than 810 Yuan (RMB), maybe the popularization rate of the sanitary household lavatory could reach 50%. Conclusion Although the popularization rate of sanitary household lavatory in the countryside of Guangxi province significantly increased in recent years, it still does not fulfill the requirement for controlling the intestinal infectious diseases and parasitism in this area.