OBJECTIVE: To explore the role of DNAM-1 in the activation, proliferation and function of type Ⅰ regulatory T cells (Tr1 cells). METHODS: Anti-CD3/CD28 antibodies were used to stimulate mouse T cells derived from the spleen of wild-type (WT) mice, and the expression level of DNAM-1 in resting and activated Tr1 cells was evaluated with flow cytometry. Na?ve CD4⁺ T cells isolated by magnetic cell sorting from the spleens of WT mice and DNAM-1 knockout (KO) mice were cultured in Tr1 polarizing conditions for 3 days, after which CD25 and CD69 expressions were measured using flow cytometry. The induced Tr1 cells were labelled with CFSE and cultured in the presence of anti-CD/CD28 antibodies for 3 days, and their proliferative activity was analyzed. The expressions of IL-10 and p-STAT5 in DNAM-1-deficient Tr1 cells were detected before and after IL-2 stimulation. RESULTS: The expression level of DNAM-1 was significantly upregulated in CD4⁺ T cells and Tr1 cells after stimulation with anti-CD3/CD28 antibodies (P < 0.05). DNAM-1 knockout did not cause significant changes in the number or proportion of Tr1 cells, but but significantly increased the expression levels of the activation markers CD69 and CD25 (P < 0.05). Compared with WT Tr1 cells, DNAM-1-deficient Tr1 cells exhibited reduced proliferative activity in vitro (P < 0.05) with downregulated IL-10 production (P < 0.05) and decreased expressions of Il-10 and Gzmb mRNA (P < 0.05). In DNAM-1-deficient Tr1 cells, IL-2 stimulation significantly reduced IL-10 secretion level and the expression of p-STAT5 as compared with WT Tr1 cells. CONCLUSION DNAM-1 participate in the activation and proliferation of Tr1 cells and affect the biological functions of Tr1 cells through the IL-2/STAT5 pathway.
Animals ; Antigens, Differentiation, T-Lymphocyte ; CD28 Antigens/metabolism* ; Cell Proliferation ; Cells, Cultured ; Interleukin-10 ; Interleukin-2/metabolism* ; Mice ; RNA, Messenger ; STAT5 Transcription Factor/metabolism* ; T-Lymphocytes, Regulatory

Since 2015 when the transmission of schistosomiasis was controlled in China, the country has been moving towards elimination of schistosomiasis, with the surveillance-response as the main interventions for schistosomiasis control. During the period of the 13th Five-Year Plan, the transmission of schistosomiasis had been interrupted in four provinces of Sichuan, Jiangsu, Yunnan and Hubei and the prevalence of schistosomiasis has been at the historically lowest level in China. As a consequence, the goal set in The 13th Five-Year National Schistosomiasis Control Program in China is almost achieved. However, there are multiple challenges during the stage moving towards elimination of schistosomiasis in China, including the widespread distribution of intermediate host snails and complicated snail habitats, many types of sources of Schistosoma japonicum infections and difficulty in management of bovines and sheep, unmet requirements for the current schistosomiasis control program with the currently available tools, and vulnerable control achievements. During the 14th Five-Year period, it is crucial to consolidate the schistosomiasis control achievements and gradually solve the above difficulties, and critical to provide the basis for achieving the ultimate goal of elimination of schistosomiasis in China. Based on the past experiences from the national schistosomiasis control program and the challenges for schistosomiasis elimination in China, an expert consensus has been reached pertaining to the objectives, control strategy and measures for The 14th Five-Year National Schistosomiasis Control Program in China, so as to provide insights in to the development of The 14th Five-Year National Schistosomiasis Control Program in China.

Objective To investigate the distribution characteristics of Oncomelania hupensis in Guangxi Zhuang Autonomous Region, so as to provide insights into the assessment of the risk of schistosomiasis transmission and the scientific formulation of the schistosomiasis surveillance strategy. Methods From 2015 to 2019, a total of 19 national schistosomiasis surveillance sites were assigned in Guangxi Zhuang Autonomous Region, including 4 fixed sites and 15 mobile sites. Snail survey was performed by means of systematic sampling in combination with environmental sampling, and the infection of Schistosoma japonicum was detected by the crushing method combined with loop-mediated isothermal amplification (LAMP) assay. Results From 2015 to 2019, snail habitats were detected at areas of 17 040 to 39 527 m², including 6 214 m² emerging snail habitats and 16 563 m² re-emerging snail habitats. The overall mean density of living snails was 0.019 2 snails/0.1 m² and the occurrence of frames with snails was 1.11% in the national schistosomiasis surveillance sites; however, no S. japonicum infection was identified in snails. The area of snail habitats increased by 121.46% in the national surveillance sites in 2019 as compared to that in 2015; however, 50.34% (Z = −0.422, P > 0.05) and 42.85% (χ² = 130.41, P < 0.01) reductions were seen in the overall means density of living snails and the occurrence of frames with snails. All snail habitats were distributed in the 4 fixed surveillance sites, and were mainly found in ditches, paddy fields and dry lands, with weeds as the primary vegetation type. Conclusions There are still risk factors leading to re-emergent transmission of schistosomiasis in Guangxi Zhuang Autonomous Region, such as local snail spread, and the monitoring of schistosomiasis remains to be reinforced to further consolidate the achievements of schistosomiasis elimination in the region.

The relationship between areca nut as a primary carcinogen and oral cancer has been widely concerned. Areca can change the levels of reactive oxygen species (ROS) and autophagy in cells, and the levels of ROS and autophagy are closely related to the occurrence and development of tumors. This paper reviewed the relationships among areca nut, intracellular ROS, and autophagy.
Areca ; Autophagy ; Humans ; Mouth Neoplasms ; Nuts ; Oral Submucous Fibrosis ; Reactive Oxygen Species

Objective To investigate the application and advantages of alternative vascular hemihepatic occlusion in anatomic mesohepatectomy.MethodsThe clinical data of 57 patients with liver cancer who underwent operation in hepatobiliary surgery of Fuzhou general hospital from January 2014 to December 2017 were retrospectively analyzed.According to the surgery method, the patients were divided into observation group and control group, 34 cases in observation group were performed anatomic mesohepatectomy with alternative hemihepatic occlusion, 23 cases in control group were treated with non-anatomical liver lobectomy.The clinical effect of two groups were compared.Results The observation group was significantly better than the control group in terms of operation time, intraoperative blood loss, length of hospital stay, hospitalization costs, ALB at 1, 3, 5 days after surgery, ALT and AST at 1, 3, 5, 7 days after surgery, the differences were significant (P＜0.05).There was no perioperative deaths in the two groups.ConclusionApplied alternative hemihepatic vascular occlusion in anatomic mesohepatectomy can achieve good short-term curative effect and high safety.

Objective To assess the clinical significance of transient elastography (Fibroscan) in detection of clonorchiasis, so as to provide new insights into the assessment of therapeutic efficacy of deworming. Methods The liver stiffness measurement (LSM) values were measured in parasitologically diagnosed clonorchiasis patients using FibroScan before and after deworming, and the patients’age, gender, body mass index (BMI), duration of raw fish consumption and total amount of raw fish consumption were collected for correlation analyses. Results The clonorchiasis patients’age, gender, BMI, duration of raw fish consumption and total amount of raw fish consumption had no associations with pre-treatment LSM values (r/rs = 0.189, 0.073, 0.180; 0.071, –0.098, 0.033; 0.166, 0.309, 0.172; 0.235, 0.247, 0.209; 0.164, 0.277, 0.088; all P values > 0.05). There was a significant difference in the LSM values from the seventh, eighth and ninth intercostal space prior to deworming (F = 3.259, P < 0.05), and no significant difference was detected after deworming (F = 0.851, P > 0.05). The LSM values from the seventh, eighth and ninth intercostal space were significantly lower pre-deworming than post-deworming (t = 6.724, 5.603, 2.884; all P values < 0.05). Conclusion FibroScan is feasible to assess the therapuetic efficacy of deworming in patients with clonorchiasis; however, measurement at various sites affects the LSM value.

BACKGROUNDPrecise evaluation of the live donor's liver is the most important factor for the donor's safety and the recipient's prognosis in living donor liver transplantation (LDLT). Our study assessed the clinical value of computer-assisted three-dimensional quantitative assessment and a surgical planning tool for donor evaluation in LDLT.

METHODSComputer-assisted three-dimensional (3D) quantitative assessment was used to prospectively provide quantitative assessment of the graft volume for 123 consecutive donors of LDLT and its accuracy and efficiency were compared with that of the standard manual-traced method. A case of reduced monosegmental LDLT was also assessed and a surgical planning tool displayed the precise surgical plan to avoid large-for-size syndrome.

RESULTSThere was no statistically significant difference between the detected graft volumes with computer-assisted 3D quantitative assessment and manual-traced approaches ((856.76 ± 162.18) cm(3) vs. (870.64 ± 172.54) cm(3), P = 0.796). Estimated volumes by either method had good correlation with the actual graft weight (r-manual-traced method: 0.921, r-3D quantitative assessment method: 0.896, both P < 0.001). However, the computer-assisted 3D quantitative assessment approach was significantly more efficient taking half the time of the manual-traced method ((16.91 ± 1.375) minutes vs. (39.27 ± 2.102) minutes, P < 0.01) to estimate graft volume. We performed the reduced monosegmental LDLT, a pediatric case, with the surgical planning tool (188 g graft in the operation, which was estimated at 208 cm(3) pre-operation). The recipient recovered without large-for-size syndrome.

CONCLUSIONSComputer-assisted 3D quantitative assessment provided precise evaluation of the graft volume. It also assisted surgeons with a better understanding of the hepatic 3D anatomy and was useful for the individual surgical planning tool.

Computer Simulation ; Humans ; Image Processing, Computer-Assisted ; Imaging, Three-Dimensional ; In Vitro Techniques ; Liver ; diagnostic imaging ; surgery ; Liver Transplantation ; Living Donors ; Organ Size ; Tomography, X-Ray Computed

BACKGROUNDRecombinant human parathyroid hormone (1-34) (rhPTH (1-34)) is the first agent in a unique class of anabolic therapies acting on the skeleton. The efficacy and safety of long-term administration of rhPTH (1-34) in Chinese postmenopausal women had not been evaluated. This study compared the clinical efficacy and safety of rhPTH (1-34) with elcatonin for treating postmenopausal women with osteoporosis in 11 urban areas of China.

METHODSA total of 453 postmenopausal women with osteoporosis were enrolled in an 18-month, multi-center, randomized, controlled study. They were randomized to receive either rhPTH (1-34) 20 µg (200 U) daily for 18 months, or elcatonin 20 U weekly for 12 months. Lumbar spine (L1-4) and femoral neck bone mineral density (BMD), fracture rate, back pain as well as biochemical markers of bone turnover were measured. Adverse events were recorded.

RESULTSrhPTH (1-34) increased lumbar BMD significantly more than did elcatonin after 6, 12, and 18 months of treatment (4.3% vs. 1.9%, 6.8% vs. 2.7%, 9.5% vs. 2.9%, P < 0.01). There was only a small but significant increase of femoral neck BMD after 18 months (2.6%, P < 0.01) in rhPTH groups. There were larger increases in bone turnover markers in the rhPTH (1-34) group than those in the elcatonin group after 6, 12, and 18 months (serum bone-specific alkaline phosphatase (BSAP) 93.7% vs. -3.6%; 117.8% vs. -4.1%; 49.2% vs. -5.8%, P < 0.01; urinary C-telopeptide/creatinine (CTX/Cr) 250.0% vs. -29.5%; 330.0% vs. -41.4%, 273.0% vs. -10.6%, P < 0.01). rhPTH (1-34) showed similar effect of pain relief as elcatonin. The incidence of clinical fractures was 5.36% (6/112) in elcatonin group and 3.2% (11/341) in rhPTH (1-34) group (P = 0.303). Both treatments were well tolerated. Hypercaluria (9.4%) and hypercalcemia (7.0%) in rhPTH (1-34) group were transient and caused no clinical symptoms. Pruritus (8.2% vs. 2.7%, P = 0.044) and redness of injection site (4.4% vs. 0, P = 0.024) were more frequent in rhPTH (1-34). Nausea/vomiting (16.1% vs. 6.2%, P = 0.001) and hot flushes (7.1% vs. 0.6%, P < 0.001) were more common in elcatonin group.

CONCLUSIONSrhPTH (1-34) was associated with greater increases in lumbar spine BMD and bone formation markers. It could increase femoral BMD after 18 months of treatment. rhPTH could improve back pain effectively. The results of the present study indicate that rhPTH (1-34) is an effective, safe agent in treating Chinese postmenopausal women with osteoporosis.

Aged ; Bone Density ; drug effects ; Calcitonin ; analogs & derivatives ; therapeutic use ; China ; Female ; Humans ; Middle Aged ; Osteoporosis, Postmenopausal ; drug therapy ; Parathyroid Hormone ; therapeutic use ; Treatment Outcome

OBJECTIVETo investigate the sensitivity of imatinib mesylate (IM) on Sup-B15 Ph⁺ acute lymphoblastic leukemia (ALL) cells knockdown of VE-cadherin (CD144), and to further explore its mechanism.

METHODSCD144 in Sup-B15 leukemia cells was stably knock downed via lentivirus-mediated RNA interference (named as Sup-B15/shVEC). The inhibitory effects of IM on Sup-B15/shVEC and Sup-B15 leukemia cells were measured by CCK-8 test, and the apoptosis of those cells was determined by AnnexinV/7-AAD dyeing using flow cytometry, the percentage of CD34⁺CD38⁻ leukemia cells also by flow cytometry. ALDH1 mRNA levels were detected by real-time RT-PCR, and protein levels of CD144, CD133, Bcr-abl and β-catenin by Western blot.

RESULTSIM treatment presented inhibitory effects on Sup-B15/shVEC and Sup-B15 leukemia cells at multiple concentrations of IM. The IC50 of IM on Sup-B15/shVEC and Sup-B15 leukemia cells were 25.1μmol/L and 18.7μmol/L, respectively (P<0.05). After 48h of 20 μmol/L IM treatment, the percentages of apoptosis cell in Sup-B15/shVEC cells and Sup-B15 cell were (13.52±2.06)% and (3.03±0.72) %, respectively (P<0.05). The percentage of CD34⁺CD38⁻ cells in Sup-B15 cells was significantly higher than in Sup-B15/shVEC cells [(2.39±0.28)% vs (0.96±0.07)%, P<0.05). As compared to Sup-B15 cells, the transcription of ALDH1 in Sup-B15/shVEC was remarkably downregulated, and the CD133 protein level was also downregulated in Sup-B15/shVEC cells. Both cytoplasmic and nucleic β-catenin protein levels (but not for Bcr-abl levels) decreased in Sup-B15/shVEC cells as compare to Sup-B15 cells.

CONCLUSIONKnockdown of CD144 sensitized Sup-B15 Ph+ ALL cells to IM. The possible mechanisms underlying this phenomenon might be via inhibiting β-catenin nucleic translocation and facilitating β-catenin degradation.

Antigens, CD ; genetics ; Benzamides ; pharmacology ; Cadherins ; genetics ; Cell Line, Tumor ; Drug Resistance, Neoplasm ; genetics ; Endothelium, Vascular ; drug effects ; metabolism ; Gene Knockdown Techniques ; Humans ; Imatinib Mesylate ; Piperazines ; pharmacology ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; genetics ; metabolism ; Pyrimidines ; pharmacology ; RNA Interference ; beta Catenin ; metabolism

BACKGROUNDBloodstream infections (BSIs) remain a major cause of morbidity and mortality in patients undergoing surgery. This study aimed at elucidating the clinical characteristics of community-acquired BSIs (CABs) and nosocomial BSIs (nBSIs) in patients admitted to the surgical wards of a teaching hospital in Beijing, China.

METHODSThis cross-sectional study compared 191 episodes of BSIs in 4074 patients admitted to the surgical wards between January 2008 and December 2011. Cases of BSIs were classified as CABs or nBSIs, and the characteristics, relevant treatments, and outcomes of CABs and nBSIs were compared.

RESULTSOf the 191 BSIs, 52 (27.2%) and 139 (72.8%) were CABs and nBSIs, respectively. Escherichia coli, coagulasenegative staphylococci, and Klebsiella spp, were the most frequently isolated microorganisms. There were significant differences between CABs and nBSIs with respect to the use of hormonal drugs, ventilation, acute physiology and chronic health evaluation (APACHE) II and American Society of Anesthesiologists scores, and prevalence of cancer (P < 0.05). Empirical antibacterial therapy did not decrease the crude mortality, but multivariate analysis showed that high APACHE II was independently associated with a risk of mortality (odds ratio = 0.97, 95% confidence interval: 0.93-1.02 for APACHE II).

CONCLUSIONSWe found significant differences in the clinical characteristics of surgical patients with CABs and nBSIs. The outcome of patients seems to be related to high APACHE II scores.

Anti-Bacterial Agents ; Bacteremia ; epidemiology ; China ; Community-Acquired Infections ; epidemiology ; microbiology ; Cross Infection ; epidemiology ; microbiology ; Cross-Sectional Studies ; Escherichia coli ; pathogenicity ; Female ; General Surgery ; statistics & numerical data ; Hospitals ; Humans ; Male ; Staphylococcus ; pathogenicity