[Effect of CD4-positive T lymphocyte expression rate on pain control and prognosis in stage â £ non-small cell lung cancer patients with cancerous pain].

Objective: To investigate the effect of CD4-positive T lymphocyte expression rate on the pain control and prognosis of stage Ⅳ non-small cell lung cancer (NSCLC) patients with cancerous pain. Methods: The clinical data of 128 stage Ⅳ NSCLC patients with cancerous pain who were admitted to the Affiliated Cancer Hospital of Zhengzhou University from January to December 2020 were retrospectively analyzed, including 92 males and 36 females, with a male-to-female ratio of 23∶9 and an average age of (56±21) years old. The expression rate of CD4-positive T lymphocytes in peripheral blood was routinely detected on admission, and the expression rate of CD4-positive T lymphocytes ≥45% was defined as the CD4 high expression group, and<45% was defined as the low expression group. The differences in the time required for pain control, the dosage of opioids and the incidence of adverse reactions between the two groups were compared and analyzed. Survival analysis was performed by Kaplan-Meier method, and the overall survival (OS) time and progression-free survival (PFS) time of the two groups were calculated. Cox regression model was used to analyze the influencing factors of patients' OS time and PFS time. Results: The median time required for pain control in the high CD4 expression group [M (Q1, Q3)] was 18.6 (4.6, 21.5) h, which was lower than that in the low CD4 expression group [28.2 (7.1, 38.9) h] (P=0.012). The dosage of morphine in the CD4 high expression group [M (Q1, Q3)] was 88.6 (42.5, 295.0) mg, which was lower than that in the low expression group [145.8 (82.5, 442.5) mg] (P=0.010). There was no significant difference in the incidence of adverse reactions such as nausea and vomiting, constipation, urinary retention, intestinal obstruction, and respiratory depression between the two groups (all P>0.05). The OS time and PFS time in the CD4 high expression group [M (Q1, Q3)] were 12.5 (8.1, 13.8) months and 8.5(3.1, 9.4) months, respectively, which were higher than those in the CD4 low expression group [8.6 (4.1, 12.9) months and 6.5 (2.1, 7.9) months, respectively] (all P<0.01). Cox multivariate analysis showed that high expression of CD4 was a protective factor affecting OS (HR=0.876, 95%CI: 1.224-6.641, P=0.004) and PFS (HR=0.675, 95%CI: 1.742-5.930, P=0.031) Conclusion: The stage Ⅳ NSCLC patients with cancerous pain and high expression of CD4-positive T lymphocytes have shorter pain control time, less morphine dosage, and longer OS and PFS time.

[Follow up analysis of 6 patients with severe trimethyltin chloride poisoning for 4 years].

Objective: Objective to investigate the health changes of patients with severe trimethyltin chloride (TMT) poisoning in four years. Methods: Six patients with severe TMT poisoning treated in the First Affiliated Hospital of Gannan Medical College in August 2016 were numbered 1, 2, 3, 4, 5 and 6 respectively. The patients were followed up 0.5, 2 and 4 years after poisoning and compared and analyzed. The follow-up contents include: symptom degree, score of simple mental intelligence examination scale (MMSE) and modified Rankin Scale (MRS) , cranial magnetic resonance imaging (MRI) , EEG, etc. Results: The symptoms of dizziness, headache, chest tightness, palpitation, nausea and vomiting decreased gradually in 6 patients. The symptoms of speech disorder and memory decline in No.1, 2 and 3 patients gradually increased, and the scores of MMSE and Mrs gradually decreased; Patients No.4, 5 and 6 had improved speech disorder, but their memory decreased, MMSE and Mrs scores were still flat, and mild cognitive impairment. The brain atrophy of No.1, 2 and 3 patients was aggravated, which showed obvious atrophy of hippocampus, temporal lobe, insular lobe and cerebellum and enlargement of ventricle; There was no significant change in brain atrophy in No.4, 5 and 6 patients. Conclusion: The neurotoxic symptoms in the later stage of severe TMT poisoning are still serious, and the neurotoxic time is long.

Coordination of primary metabolism and virulence factors expression mediates the virulence of Vibrio parahaemolyticus towards cultured shrimp (Penaeus vannamei).

AIMS: Acute hepatopancreatic necrosis disease (AHPND) caused by Vibrio parahaemolyticus has emerged as a severe bacterial disease of cultured shrimp. To identify the key virulence factors, two AHPND-causing V. parahaemolyticus (VpAHPND ) strains (123 and 137) and two non-VpAHPND strains (HZ56 and ATCC 17082) were selected. METHODS AND RESULTS: Challenge tests showed that the four strains exhibited different virulence towards shrimp with cumulative mortalities at 48 h postinfection (hpi) ranging from 10 to 92%. The expression of pirABVP in strain 123 and 137 was not significantly different. Genomic analysis revealed that the two VpAHPND strains contain a plasmid with the PirABVP toxins (pirABVP ) flanked by the insertion sequence (ISVal1) that has been identified in various locations of chromosomes in VpAHPND strains. The two VpAHPND strains possessed almost identical virulence factors, while ISVal1 disrupted three genes related to flagellar motility in strain 137. Phenotype assay showed that strain 123 possessed the highest growth rate and swimming motility, followed by strain 137, suggesting that the disruption of essential genes mediated by ISVal1 significantly affected the virulence level. Transcriptome analysis of two VpAHPND strains (123 and 137) further suggested that virulence genes related to the capsule, flagella and primary metabolism were highly expressed in strain 123. CONCLUSIONS: Here for the first time, it is demonstrated that the virulence of VpAHPND is not only determined by the expression of pirABVP , but also is mediated by ISVal1 which affects the genes involved in flagellar motility and primary metabolism. SIGNIFICANCE AND IMPACT OF THE STUDY: The genomic and transcriptomic analysis of VpAHPND strains provides valuable information on the virulence factors affecting the pathogenicity of VpAHPND.

Effects of water deficiency on preference and performance of an insect herbivore Ostrinia furnacalis.

With further climate change still expected, it is predicted to increase the frequency with plants will be water stressed, which subsequently influences phytophagous insects, particularly Lepidoptera with limited mobility of larvae. Previous studies have indicated that oviposition preference and offspring performance of Lepidoptera insects are sensitive to drought separately. However, the integration of their two properties is not always seen. Here, we evaluated changes in oviposition selection and offspring fitness of a Lepidoptera insect under three water-stressed treatments using a model agroecosystem consisting of maize Zea mays, and Asian corn borer Ostrinia furnacalis. Results found that female O. furnacalis preferred to laying their eggs on well-watered maize, and then their offspring tended to survive better, attained bigger larvae mass, and developed more pupae and adults on the preferred maize. Oviposition selection of O. furnacalis positively correlated with height and leaf traits of maize, and offspring fitness positively related with water content and phytochemical traits of hosts. Overall, these results suggest that oviposition choice performed by O. furnacalis reflects the maximization of offspring fitness, supporting preference-performance hypothesis. This finding further highlights that the importance of simultaneous evaluation of performance and performance for water driving forces should be involved, in order to accurately predict population size of O. furnacalis under altered precipitation pattern.

[Changes of coagulation factor activity and its clinical significance in tumor patients with abnormal coagulation function].

Objective: To investigate the changes and clinical significance of coagulation factor activity in tumor patients with abnormal coagulation function. Methods: The clinical data of cancer patients who were hospitalized in Henan Cancer Hospital from January 2020 to June 2021 was collected. Thromboelastography (TEG) was used to monitor the coagulation function of tumor patients. Accordingly, 196 tumor patients with abnormal coagulation function were in the test group, and 36 tumor patients with normal status were in the control group. According to the coagulation index (CI) value of the TEG test results, the test group was divided into two groups: hypercoagulability test group (n=104): CI value>3; hypocoagulation test group (n=92): CI value<-3. Meanwhile, each test group was divided into 3 subgroups according to the R value, K value, α angle and MA value of the TEG results, namely hypercoagulable group one (n=37), hypercoagulable group two (n=34), and hypercoagulable group three (n=33); hypocoagulation group one (n=33), hypocoagulation group two (n=30), and hypocoagulation group three (n=29). The activities of coagulation factors (F) Ⅱ, Ⅴ, Ⅶ, Ⅷ, Ⅸ, Ⅹ, Ⅺ, Ⅻ and von willebrand factor (vWF) were measured and compared for all patients in the test groups and the control group in the same period. Results: Compared with the normal control group, the hypercoagulable group one showed higher FⅡ, FⅤ, FⅦ, FⅧ, FⅪ and vWF activity, and the values were (1 105±281), (1 352±326), (1 628±397), (1 795±314), (1 389±288) and (1 908±486) U/L, respectively (P<0.01). The hypercoagulable group two showed higher FⅡ, FⅤ, FⅦ, FⅧ FⅩ and vWF activity, and the values were (1 068±189), (1 194±205), (1 529±394), (1 562±241), (1 150±196) and (1 722±415) U/L, respectively (P<0.05). Hypercoagulable group three showed higher FⅦ, FⅩ and vWF activity, and the values were (1 411±196), (1 212±327) and (1 713±457) U/L, respectively (P<0.01). In contrast, the hypocoagulation group one showed lower FⅤ, FⅧ, FⅨ, FⅫ and vWF activity, and the values were (732±96), (695±64), (1 216±191), (832±128) and (1 088±117) U/L, respectively (P<0.05). Hypocoagulation group two showed lower FⅤ, FⅦ, FⅧ and FⅫ activity, and the values were (714±102), (1 125±108), (783±95) and (912±111) U/L, respectively (P<0.01). Hypocoagulation group three had lower FⅪ, FⅫ and vWF activity, and the values were (812±92), (827±179) and (916±76) U/L, respectively (P<0.01). Conclusions: Only part of the coagulation factor activity changes significantly in the tumor patients with abnormal coagulation function. In tumor patients with hypercoagulable state, the high activity of FⅡ and FⅩ becomes an important factor in anticoagulant therapy, while high FⅤ, FⅧ activity can cause deep vein thrombosis. In the hypocoagulation state, the significant decreases of FⅤ and FⅧ activity often cause bleeding or oozing.

[Comparison of effects of celiac plexus block alone or in combination with retroperitoneal metastatic lymph node injection for pancreatic cancer-related pain].

Objective: To analyze the analgesic effect of CT-guided celiac nerve plexus destruction or celiac plexus destruction combined with absolute ethanol injection on retroperitoneal enlarged lymph nodes in patients with pancreatic cancer with retroperitoneal lymph node metastasis (combined therapy). Methods: Retrospective analysis of clinical data of 187 patients with pancreatic cancer and retroperitoneal lymph node metastasis admitted to Zhengzhou University Cancer Hospital from January 2014 to December 2018 due to poor abdominal pain control. According to the treatment method, they were divided into 2 groups: Group A (n=48) , treated with CT-guided celiac plexus destruction; Group B (n=139) , treated with CT-guided combined therapy. The analgesic effect, morphine application dose, and adverse reactions were compared before surgery, 1 week, 1 month, and 3 months after surgery. Results: The oral morphine doses of patients in Group A before surgery and 1 day, 1 week, 1 month, and 3 months after surgery were (107±34) , (65±23) , (35±12) , (48±18) , (81±25) mg. The oral morphine doses of patients in Group B before surgery and 1 day, 1 week, 1 month, and 3 months after surgery were (112±37) , (53±17) , (27±14) , (42±16) , (63±20) mg. Compared with that before surgery, the oral morphine doses were significantly reduced at 1 day, 1 week, 1 month, and 3 months after surgery in both groups (P<0.05 or P<0.01) . The effective rate and excellent rate of pain treatment in Group A at 1 week after operation were 83.3% and 60.4%, in Group B were 95.7% and 75.5%, respectively. The effective rate and excellent rate of pain treatment in Group A at one month after operation were 71.7% and 45.6%, in Group B were 89.0% and 67.6%, respectively; The effective rate and excellent rate of pain treatment in Group A at three months after operation were 48.6% and 25.7%, respectively, in Group B were 72.6% and 47.0%; Compared with Group A, the effective rate and excellent rate of pain treatment in Group B were increased, and the differences were statistically significant (P<0.05 or P<0.01). There was no significant difference in the incidence of nausea and vomiting between the two groups of patients before and 1 day after surgery, but the incidence of nausea and vomiting at 1 week, 1 month, and 3 months after surgery in Group B was significantly reduced, and the differences were statistically significant (P<0.05 or P<0.01). Compared with that before surgery, the incidence of nausea and vomiting in Group A was significantly reduced at 1 week and 1 month after operation, and the difference was statistically significant (P<0.01); The incidence of nausea and vomiting in Group B was significantly reduced at 1 day, 1 week, 1 month, and 3 months after operation, and the differences were statistically significant (P<0.01). Compared with 1 day after surgery, the incidence of nausea and vomiting in Group A was significantly reduced at 1 week and 1 month after surgery (P<0.05 or P<0.01). The incidence of nausea and vomiting in Group B was significantly reduced at 1 week, 1 month, and 3 months after operation, and the differences were statistically significant (P<0.01). Compared with 1 week after surgery, the incidence of nausea and vomiting in the two groups increased at 3 months after surgery, and the differences were statistically significant (P<0.05 or P<0.01). Compared with 1 month after surgery, the incidence of nausea and vomiting in Group A increased at 3 months after surgery, and the difference was statistically significant (P<0.05). There was no significant difference in the incidence of transient hypotension after surgery in the two groups. The difference in the incidence of postoperative diarrhea was not statistically significant. The incidence was highest within 1 day after surgery and generally recovered within 7 days after surgery. Conclusions: The two schemes can effectively relieve pain in patients with pancreatic cancer with retroperitoneal lymph node metastasis, reduce morphine dose. The combination therapy has higher efficiency and excellent rate, lower morphine dosage after surgery, and lower incidence of nausea and vomiting.

[Study on the relationships between precollege sexual abuse experiences at different stages and adult attachment in college students].

Objective: To explore the association between precollege sexual abuse experiences at different periods and adult attachment in college students. Methods: In October 2018,a total of 4 034 college students were selected from 4 colleges in Hefei City by using the stratified cluster sampling method. A self-designed questionnaire was used to investigate the demographic characteristics, sexual abuse experience, and attachment style of participants. Multivariate linear regression analysis was performed to analyze the association between different periods, types of precollege sexual abuse experiences and attachment style in college students. Results: The rate of total precollege sexual abuse, noncontact sexual abuse, and contact sexual abuse was 14.1% (569), 12.7% (512) and 5.4% (219), respectively. Multivariate linear regression analysis showed that secure attachment [ß(95%CI)=-0.205 (-0.292, -0.117)] was negatively correlated with total precollege sexual abuse experiences, whereas anxiety attachment [ß(95%CI)=0.211 (0.110, 0.310)], avoidant attachment [ß(95%CI)=0.117 (0.020, 0.216)] were positively correlated with total precollege sexual abuse experiences. The number of periods of precollege noncontact sexual abuse was negatively correlated with secure attachment [ß(95%CI)=-0.106(-0.171, -0.041)]and positively correlated with anxiety attachment [ß(95%CI)=0.158 (0.084, 0.231)]and avoidant attachment [ß(95%CI)=0.080 (0.008, 0.152)]. The noncontact [ß(95%CI)=0.427 (0.018, 0.775)] and contact sexual abuse [ß(95%CI)=0.468 (0.251, 0.687)] in high school were positively correlated with anxiety attachment (P<0.05). Conclusion: Different periods, types of precollege sexual abuse experiences were all associated with adult attachment in college students.

Jia-Wei-Si-Miao-Wan alleviates acute gouty arthritis by targeting NLRP3 inflammasome.

Gout is a common metabolic disease and acute gouty arthritis (AGA) is one of the important complications. Jia-Wei-Si-Miao-Wan is a newly developed drug for treating acute gouty arthritis, but the molecular mechanism has not been completely clarified. Thus, this study was aimed to explore the regulation of Jia-Wei-Si-Miao-Wan on NLRP3 inflammasome and TLR/NF-κB signaling, which are two important signaling pathways in inflammation. AGA rat model was established by injecting monosodium urate into the right knee. Colchicine and Jia-Wei-Si-Miao-Wan were administrated by gavage. The circumference of the knee was measured. IL-1ß and IL-18 level in the flushing fluid was detected by enzyme linked immunosorbent assay (ELISA). Western blot, immunohistochemistry and quantitative real-time RT-PCR were used to detect the protein and mRNA expression of TLR4, NLRP3, ASC, caspase-1, NF-κB and p-NF-κB. The results showed that IL-1ß and IL-18 level in the flushing fluid was increased and TLR4, NLRP3, ASC, caspase-1, NF-κB and p-NF-κB expressions were up-regulated after the establishment of AGA rat model. Colchicine and Jia-Wei-Si-Miao-Wan administration could alleviate the inflammation in the knee by inhibiting NLRP3 inflammasome and TLR/NF-κB signaling. In vivo data showed that the therapeutic effect of Jia-Wei-Si-Miao-Wan could be comparable with colchicine but had lower hepatic and renal toxicity. In conclusion, Targeting NLRP3 inflammasome and TLR/NF-κB signaling by Jia-Wei-Si-Miao-Wan could be effective in treating AGA.

Problems and challenges: development of blood transfusion services in Mainland China within the context of health-care system reform.

OBJECTIVE: To evaluate the development of blood transfusion services in Mainland China within the context of health-care system reform. BACKGROUND: China launched a health-care reform program in 2009 to redistribute health-care resources, which are currently over-concentrated in well-developed cities. A geographically equitable blood transfusion service is key to achieving this goal. METHODS: Based on the national survey of blood establishments in July 2015, total blood collection, whole-blood donations per 1000 population and the supply and demand relationship were analysed at the administrative region level. Areas at different developmental levels were compared in terms of total blood collection and human resources. RESULTS: In 2014, Mainland China's 31 provinces showed wide variation, with total blood collection in blood facilities ranging from about 1000 units to over 600 000 units (each 200 mL), and the whole-blood donation rate per 1000 population, ranging from 1·48 to 17·09. 69% of the country's total collection, was concentrated in 29 provincial capitals, and 31% was in 311 non-capital cities. Of 97 personnel with doctorates, 74 worked in 32 provincial blood establishments, whereas the remaining 23 worked at the other 318 blood stations. In most provinces, per permanent resident donation was within 2-4 mL, and blood volume per inpatient was 10-35 mL regardless of the development of the transfusion service. CONCLUSION: In 2014, China had an imbalanced development and insufficient access to blood transfusion services. This service must be redeployed at the national level to facilitate health-care reform in China.

The Impact of Cryopreservation-Thawing Conditions on Umbilical Cord Blood Quality and Transplantation Outcomes.

BACKGROUND: Cord blood units (CBUs) go through the cryopreservation-thawing process for storage before use in transplantation. The differences in the cryopreservation-thawing process affect the quality of CBUs. The effects of the cryopreservation-thawing process on the final outcomes of CBU transplantation has not been defined well. OBJECTIVE: To study the impact of differences in the cryopreservation-thawing process on the quality of CBUs and the final clinical outcomes of transplantation. MATERIALS AND METHODS: The differences in cryopreservation-thawing conditions were analyzed to determine their effect on the quality and clinical outcomes of transplanted CBUs. CBUs were detected using the same reagents, instruments and methods for minimizing experimental errors. RESULTS: The differences in the cryopreservation-thawing process did not change cell survival, TNCC recovery (CD34+ and CFUs), the implantation rates and recovery time of neutrophils/100-day platelets. CONCLUSION: The present study shows that the differences in the cryopreservation-thawing conditions do not influence the quality and transplantation outcomes of CBUs.

[Effect of opioid-related gene polymorphisms on patients with high-dose opioid-tolerant cancer pain].

Objective: To investigate the relationship between single nucleotide polymorphisms of opioid-related genes and high-dose opioid tolerance in patients with cancer pain. Methods: Twenty patients (high-dose opioid tolerance group, group A) who were hospitalized in Henan Cancer Hospital from June 2016 to June 2018 and who received high-dose opioid for pain control for more than 1 week were selected as case groups (group A). Thirty patients with stage Ⅳ tumors who were hospitalized in Henan Cancer Hospital and did not have opioid tolerance were randomly selected as the control group (group B). The peripheral blood samples of two groups were taken for DNA extraction. Gene polymorphisms were detected in 15 single nucleotide polymorphisms (SNP) (rs1799971, rs754891060, rs200637194, rs1045642, rs7438135, rs7439366, rs2242480, rs1080985, rs529520, rs581111, rs2234918, rs4680, rs6276, rs3732765, rs9859538) of the nine opioid receptor-related genes (OPRM1,ABCB1,UGT2B7,CYP3A4,CYP2D6,OPRD1, COMT,DRD2,P2RY12) which most likely to affect high-dose opioid tolerance in patients with cancer pain. Results: The distribution of different genotypes of rs7438135 locus in UGT2B7 gene were statistically significant between the two groups (χ(2)=9.68, P=0.004). The difference in the distribution of the different genotypes of the rs3732765 locus of the P2RY12 gene in the two groups were at the significant edge (χ(2)=5.57, P=0.05). A correlation analysis between the relevant SNP locus and the risk of high-dose opioid tolerance in cancer patients indicated that individuals with rs7438135 GA genotype in cancer patients were at 6.19 times more likely to have high doses of opioid tolerance than individuals with AA genotypes. Conclusions: The rs7438135 locus gene polymorphism of UGT2B7 gene may be a risk predictor for high-dose opioid tolerance. The rs3732765 site of the P2RY12 gene may be a potential predictor of high-dose opioid tolerance.

[The expression of LINC00052 during glycidyl methacrylate-induced malignant transformation of 16HBE cells].

Objective: To investigate the expression and role of LINC00052 during glycidyl methacrylate (GMA) -induced malignant transformation of 16HBE cells. Methods: Human bronchial epithelial (16HBE) cells were divided into GMA transformation group and corresponding DMSO control group, and the 10th, 20th and 30th generation cells of each group were collected LncRNA microarrays were used to analysis expression of LINC00052 in different stage of malignant transformation. Bioinformatics analysis was applied and the relative expression of LINC00052 and its potentially target genes was detected by real-time quantification PCR (qPCR) . Results: The results of microarray analysis showed that LINC00052 was up-regulated by 1.32-fold, down-regulated by 1.64-fold and down-regulated by 4.92-fold in the malignant transformation early (P10) , middle term (P20) and late (P30) , respectively, The results of qPCR showed that compared with the DMSO control group, the expression of LINC00052 was up-regulated by 1.55 times, down-regulated by 1.20 times and down-regulated by 2.35 times in P10, P20 and P30, respectively, and the difference was statistically significant (P<0.05) . There was a statistically significant difference in the relative expression of NTRK3 between the GMA transformation group of P10 and P30 generations with the corresponding DMSO control group (P<0.05) . Conclusion: LINC00052 is highly expressed in early time of GMA-induced malignant transformation of 16HBE, and down-regulated in the middle and last stage of malignant transformation and may play a protective role in GMA-induced malignant transformation of 16HBE by influencing the expression of its target gene NTRK3.

Growth and laser properties of Nd3+-doped Bi4Ge3O12 single-crystal fiber.

The Nd3+-doped Bi4Ge3O12 (BGO) single-crystal fiber (SCF) was successfully grown by the micro-pulling-down method with the resistance heating system. The fluorescence spectrum and transmission spectrum of the Nd:BGO SCF were measured. Excited by a continuous-wave 808-nm laser diode, a fluorescence peak around 1064 nm was observed. At an absorbed pump power of 15.25 W, the Nd:BGO SCF laser delivered a power of 3.37 W with a slope efficiency of 31.2%.

[Correlation of baseline serum interleukin-6, 10 and its ratio with 7-year all-cause mortality in 11 communities of Beijing].

Objective: To evaluate whether baseline interleukin-6 (IL-6), interleukin-10 (IL-10) as well as their ratio was associated with overall mortality risk over 7 years of follow-up in 11 communities of Beijing. Methods: Data from a prospective cohort study conducted between 2005 and 2012 in 11 communities of Beijing was analyzed to examine the above associations. Serum IL-6 and IL-10 were analyzed using enzyme-linked immunosorbent assay (ELISA) kits. Follow-up surveys were conducted in 2007, 2010 and 2012 to collect data about participant's survival. Cox regression model was used to estimate the impact of IL-6, IL-10 and their ratio on overall mortality risk. Results: Among 1 539 eligible participants (10 263 total person-years), 77 deaths occurred in 7 years of follow-up. The rates of all-cause death were 4.86, 7.24, and 10.56 per 1 000 person-years (P=0.009) in the first, second, and third tertile of IL-6, respectively. The corresponding age-sex-adjusted hazard ratios (HR) were 1.00, 1.18 (95% CI: 0.64-2.19), and 1.80 (95% CI: 1.01-3.23) and full-adjusted HR were 1.00, 1.17 (95% CI: 0.63-2.19) and 1.87 (95% CI: 1.04-3.36). The corresponding rates of all-cause deaths were not significantly different among three tertiles of IL-10. The age-sex and full-adjusted HR were not significantly different in Cox model. The rates of all-cause death were 4.63, 8.99, and 8.93 per 1 000 person-years (P=0.043) in the first, second, and third tertile of IL-6/IL-10 ratio, respectively. The corresponding age-sex-adjusted HR were 1.00, 1.67 (95% CI: 0.91-3.06), and 1.98 (95% CI: 1.08-3.64) and full-adjusted HR were 1.00, 1.66 (95% CI: 0.90-3.06), and 2.09 (95% CI: 1.13-3.87). Conclusion: High IL-6 and IL-6/IL-10 ratio may be new risk factors to all-cause death. However, IL-10 is not significantly associated with death.

[Efficacy and safety of paritaprevir/ritonavir/ombitasvir combined with dasabuvir in non-cirrhotic Asian adult patients with newly diagnosed and treated chronic HCV genotype 1b infection: a randomized, double-blind, placebo-controlled study - China data].

Objective: To evaluate the safety and efficacy of ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) 25/150/100 mg once daily combined with dasabuvir 250mg, twice daily in non-cirrhotic Chinese adult patients with newly diagnosed and treated chronic HCV genotype 1b infection. Methods: A randomized, double-blind, placebo-controlled, multicenter phase 3 clinical trial was conducted in mainland China, Korea, and Taiwan.Safety and efficacy of OBV/PTV/r plus DSV administered for 12 weeks were evaluated in a newly diagnosed and treated (interferon alpha /pegylated interferon alpha) and ribavirin non-cirrhotic adults with chronic HCVgenotype 1b infection. Patients randomly received OBV/PTV/r plus DSV for 12 weeks (Group A), or placebo for 12 weeks (Group B) followed by an open-label phase of OBV/PTV/r plus DSV for 12 weeks. Sustained response (SVR12) rate obtained at 12 weeks and (SVR24) 24 weeks after discontinuation of treatment, and the incidence of adverse events and laboratory abnormalities after double-blind and open-label phase treatment were assessed. Results: A total of 410 cases of Chinese patients were included and randomly assigned to group A and B (with 205 cases in each group) in a 1:1 ratio. The rates of SVR12 and SVR24 were 99% (95% CI: 94.8% - 99.8%) in the newly diagnosed patients in group A (205 patients) and the rates of SVR12 and SVR24 were 100% in treated patients (95% CI: 96.3% - 100%). Different baseline characteristics had no effect on SVR12 and SVR24 rates. Most of the adverse events occurred were mild, asymptomatic, and≥ 3 laboratory abnormalities during treatment were rare, including elevation of alanine aminotransferase (2 cases in double-blind stage A group), aspartate aminotransferase (Double-blind stage A (3 cases) and total bilirubin (1 case in open-label phase B group); however, those mild adverse events could be recovered after drug withdrawal or discontinuation. only1 person discontinued drugs due to adverse events (Group B, open-label phase). Conclusion: The 12 weeks treatment course of OBV/PTV/r combined with DSV produced 99% ~ 100% rates of SVR12 and SVR24 in non-cirrhotic Asian adult patients with newly diagnosed and treated chronic HCV genotype 1b infection, and the tolerance and safety were good.

Decreased frequencies and impaired functions of the CD31+ subpopulation in Treg cells associated with decreased FoxP3 expression and enhanced Treg cell defects in patients with coronary heart disease.

Coronary heart disease (CHD) is one of the most common types of organ lesions caused by atherosclerosis, in which CD4+ CD25+ forkhead box protein 3 (FoxP3+ ) regulatory T cells (Treg ) play an atheroprotective role. However, Treg cell numbers are decreased and their functions are impaired in atherosclerosis; the underlying mechanisms remain unclear. CD31 plays an important part in T cell response and contributes to maintaining T cell tolerance. The immunomodulatory effects of CD31 are also implicated in atherosclerosis. In this study, we found that decreased frequencies of the CD31+ subpopulation in Treg cells (CD31+ Tr cells) correlated positively with decreased FoxP3 expression in CHD patients. Cell culture in vitro demonstrated CD31+ Tr cells maintaining stable FoxP3 expression after activation and exhibited enhanced proliferation and immunosuppression compared with the CD31- subpopulation in Treg cells (CD31- Tr cells). We also confirmed impaired secretion of transforming growth factor (TGF)-ß1 and interleukin (IL)-10 in CD31+ Tr cells of CHD patients. Further analysis revealed reduced phospho-SHP2 (associated with CD31 activation) and phospho-signal transducer and activator of transcription-5 (STAT-5) (associated with FoxP3 transcription) levels in CD31+ Tr cells of CHD patients, suggesting that decreased FoxP3 expression in CD31+ Tr cells might be because of attenuated SHP2 and STAT-5 activation. These data indicate that decreased frequencies and impaired functions of the CD31+ Tr subpopulation associated with decreased FoxP3 expression give rise, at least in part, to Treg cell defects in CHD patients. Our findings emphasize the important role of the CD31+ Tr subpopulation in maintaining Treg cell normal function and may provide a novel explanation for impaired immunoregulation of Treg cells in CHD.

Narcissus yellow stripe virus and Narcissus mosaic virus detection in Narcissus via multiplex TaqMan-based reverse transcription-PCR assay.

AIMS: Development of a multiplex TaqMan RT-qPCR assay to simultaneously detect Narcissus yellow stripe virus (NYSV) and Narcissus mosaic virus (NMV), frequently causing mixed narcissus infection. Feasibility verification was confirmed in natural samples. METHODS AND RESULTS: Primers and probes were designed based on the conserved CP gene regions of NYSV or NMV and their suitability for singleplex and multiplex TaqMan RT-qPCR assays as well as for conventional RT-PCR. Conventional RT-PCR, singleplex and multiplex TaqMan RT-qPCR assays proved to be NYSV and NMV specific. P-values and coefficients of variation of TaqMan RT-qPCR assays indicated high reproducibility. Significantly increased sensitivity was achieved compared to conventional RT-PCR. The detection limit of both viruses was 103 copies with superior correlation coefficients and linear standard curve responses between plasmid concentrations and Ct values. NYSV and NMV infection of narcissus leaves, petals and bulbs could successfully be detected via our multiplex RT-qPCR method at 1·25 mg. CONCLUSION: Our multiplex TaqMan RT-qPCR assay provides rapid, specific, sensitive and reliable testing to simultaneously detect NYSV and NMV, supplying useful routine monitoring for different narcissus samples. SIGNIFICANCE AND IMPACT OF THE STUDY: Efficient identification and discrimination of the narcissus viruses provides reliable information for scientists and conventional growers. Furthermore, it enriches the information of NYSV, NMV and other narcissus viruses.

Isolation, identification and pathogenicity of Vibrio harveyi, the causal agent of skin ulcer disease in juvenile hybrid groupers Epinephelus fuscoguttatus × Epinephelus lanceolatus.

The hybrid grouper, Epinephelus fuscoguttatus (♀) × Epinephelus lanceolatus (♂), is a newly bred cultivated marine fish species of high economic value. However, a skin ulcer disease with high mortality has occurred, and the responsible pathogen remains unknown. In this study, we summarized the epidemic status and external signs of this disease. We screened potential pathogens and finally isolated one bacterial strain ML01 from affected fish. We subjected healthy juvenile hybrid groupers to bacterial challenge tests with the isolate by immersion, immersion after dermal abrasion and intraperitoneal injection, respectively. Within 14 days post-infection, the isolate ML01 caused mass mortality of juveniles infected via immersion after dermal abrasion or intraperitoneal injection. Diseased juveniles displayed obvious signs of skin ulcers. The median lethal dose of ML01 by intraperitoneal injection was 1.10 × 105 colony-forming units. ML01 was identified as Vibrio harveyi by bacterial morphology, analytical profile index identification, 16S rDNA sequencing and multilocus sequence analysis. Antibiotic susceptibility tests showed that ML01 was sensitive to ceftriaxone, doxycycline and minocycline. The results of this study suggest that V. harveyi is the causal agent of skin ulcer disease in juvenile hybrid groupers, thus providing a basis for effective control and prevention of this disease.

[Oxidative damage effects induced by CdTe quantum dots in mice].

Objective: To investigate Oxidative damage effects induced by CdTe Quantum Dots (QDs) in mice. Methods: 40 ICR mice were randomly divided into 5 groups: one control group (normal saline) ; four CdTe QDs (exposed by intravenous injection of 0.2 ml of CdTe QDs at the concentration of 0、0.5、5.0、50.0 and 500.0 nmol/ml respectively) . After 24 h, the mice were decapitated and the blood was collected for serum biochemically indexes、hematology indexes, the activities of SOD、GSH-Px and the concentration of MDA were all detected. Results: The results showed in the four CdTe QDs exposure groups, the level of CRE、PLT and the concentration of MDA were all significantly lower than those of the control group (P<0.05 or P<0.01) ; the activities GSH-Px in 50.0 and 500.0 nmol/ml CdTe QDs group were significantly higher than those of control group (P<0.01) . Conclusion: It was suggested that CdTe QDs at 0.5 nmol/ml could induce Oxidative damage effects in mice.

An outbreak of multiple norovirus strains on a cruise ship in China, 2014.

AIMS: To determine the cause of an outbreak of acute gastroenteritis that occurred on a cruise ship sailing along the Yangzi River from Chongqing to Nanjing, China. METHODS AND RESULTS: Noroviruses were identified by reverse transcription-PCR (RT-PCR) in rectal swabs from 34 of 54 subjects tested (63·0%). Sequencing and genotyping showed that noroviruses of up to seven different genotypes circulated in this outbreak: noroviruses GI.1, GI.2, GI.3, GI.4, GI.8, GI.9 and an uncommon strain GII.17. Common genotypes were not identified in this event. None of the food or water samples were tested positive for noroviruses. CONCLUSIONS: We suspected that it was a point-source infection due to contaminated water or food harvested from contaminated water, taking account of the co-existence of diverse norovirus genotypes. SIGNIFICANCE AND IMPACT OF THE STUDY: In this study, we presented the molecular investigation of a norovirus outbreak on a cruise in China. We revealed that the outbreak was caused by several different norovirus genotypes and analysed the possible source of infection as well, thus facilitating the evaluation of epidemiological issues regarding noroviruses in this area.