Durable natural killer cell response after three doses of SARS-CoV-2 inactivated vaccine in HIV-infected individuals / 中华医学杂志(英文版)

BACKGROUND@#Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine can induce a potent cellular and humoral immune response to protect against SARS-CoV-2 infection. However, it was unknown whether SARS-CoV-2 vaccination can induce effective natural killer (NK) cell response in people living with human immunodeficiency virus (PLWH) and healthy individuals.@*METHODS@#Forty-seven PLWH and thirty healthy controls (HCs) inoculated with SARS-CoV-2 inactivated vaccine were enrolled from Beijing Youan Hospital in this study. The effect of SARS-CoV-2 vaccine on NK cell frequency, phenotype, and function in PLWH and HCs was evaluated by flow cytometry, and the response of NK cells to SARS-CoV-2 Omicron Spike (SARS-2-OS) protein stimulation was also evaluated.@*RESULTS@#SARS-CoV-2 vaccine inoculation elicited activation and degranulation of NK cells in PLWH, which peaked at 2 weeks and then decreased to a minimum at 12 weeks after the third dose of vaccine. However, in vitro stimulation of the corresponding peripheral blood monocular cells from PLWH with SARS-2-OS protein did not upregulate the expression of the aforementioned markers. Additionally, the frequencies of NK cells expressing the activation markers CD25 and CD69 in PLWH were significantly lower than those in HCs at 0, 4 and 12 weeks, but the percentage of CD16 + NK cells in PLWH was significantly higher than that in HCs at 2, 4 and 12 weeks after the third dose of vaccine. Interestingly, the frequency of CD16 + NK cells was significantly negatively correlated with the proportion of CD107a + NK cells in PLWH at each time point after the third dose. Similarly, this phenomenon was also observed in HCs at 0, 2, and 4 weeks after the third dose. Finally, regardless of whether NK cells were stimulated with SARS-2-OS or not, we did not observe any differences in the expression of NK cell degranulation markers between PLWH and HCs.@*CONCLUSION@#s:SARS-CoV-2 vaccine elicited activation and degranulation of NK cells, indicating that the inoculation of SARS-CoV-2 vaccine enhances NK cell immune response.

Weak SARS-CoV-2-specific responses of TIGIT-expressing CD8 + T cells in people living with HIV after a third dose of a SARS-CoV-2 inactivated vaccine / 中华医学杂志(英文版)

BACKGROUND@#T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domains (TIGIT), an inhibitory receptor expressed on T cells, plays a dysfunctional role in antiviral infection and antitumor activity. However, it is unknown whether TIGIT expression on T cells influences the immunological effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inactivated vaccines.@*METHODS@#Forty-five people living with HIV (PLWH) on antiretroviral therapy (ART) for more than two years and 31 healthy controls (HCs), all received a third dose of a SARS-CoV-2 inactivated vaccine, were enrolled in this study. The amounts, activation, proportion of cell subsets, and magnitude of the SARS-CoV-2-specific immune response of TIGIT + CD4 + and TIGIT + CD8 + T cells were investigated before the third dose but 6 months after the second vaccine dose (0W), 4 weeks (4W) and 12 weeks (12W) after the third dose.@*RESULTS@#Compared to that in HCs, the frequency of TIGIT + CD8 + T cells in the peripheral blood of PLWH increased at 12W after the third dose of the inactivated vaccine, and the immune activation of TIGIT + CD8 + T cells also increased. A decrease in the ratio of both T naïve (T N ) and central memory (T CM ) cells among TIGIT + CD8 + T cells and an increase in the ratio of the effector memory (T EM ) subpopulation were observed at 12W in PLWH. Interestingly, particularly at 12W, a higher proportion of TIGIT + CD8 + T cells expressing CD137 and CD69 simultaneously was observed in HCs than in PLWH based on the activation-induced marker assay. Compared with 0W, SARS-CoV-2-specific TIGIT + CD8 + T-cell responses in PLWH were not enhanced at 12W but were enhanced in HCs. Additionally, at all time points, the SARS-CoV-2-specific responses of TIGIT + CD8 + T cells in PLWH were significantly weaker than those of TIGIT - CD8 + T cells. However, in HCs, the difference in the SARS-CoV-2-specific responses induced between TIGIT + CD8 + T cells and TIGIT - CD8 + T cells was insignificant at 4W and 12W, except at 0W.@*CONCLUSIONS@#TIGIT expression on CD8 + T cells may hinder the T-cell immune response to a booster dose of an inactivated SARS-CoV-2 vaccine, suggesting weakened resistance to SARS-CoV-2 infection, especially in PLWH. Furthermore, TIGIT may be used as a potential target to increase the production of SARS-CoV-2-specific CD8 + T cells, thereby enhancing the effectiveness of vaccination.

Targeting the HIV reservoir: chimeric antigen receptor therapy for HIV cure / 中华医学杂志(英文版)

Although antiretroviral therapy (ART) can reduce the viral load in the plasma to undetectable levels in human immunodeficiency virus (HIV)-infected individuals, ART alone cannot completely eliminate HIV due to its integration into the host cell genome to form viral reservoirs. To achieve a functional cure for HIV infection, numerous preclinical and clinical studies are underway to develop innovative immunotherapies to eliminate HIV reservoirs in the absence of ART. Early studies have tested adoptive T-cell therapies in HIV-infected individuals, but their effectiveness was limited. In recent years, with the technological progress and great success of chimeric antigen receptor (CAR) therapy in the treatment of hematological malignancies, CAR therapy has gradually shown its advantages in the field of HIV infection. Many studies have identified a variety of HIV-specific CAR structures and types of cytolytic effector cells. Therefore, CAR therapy may be beneficial for enhancing HIV immunity, achieving HIV control, and eliminating HIV reservoirs, gradually becoming a promising strategy for achieving a functional HIV cure. In this review, we provide an overview of the design of anti-HIV CAR proteins, the cell types of anti-HIV CAR (including CAR T cells, CAR natural killer cells, and CAR-encoding hematopoietic stem/progenitor cells), the clinical application of CAR therapy in HIV infection, and the prospects and challenges in anti-HIV CAR therapy for maintaining viral suppression and eliminating HIV reservoirs.

Virome in immunodeficiency: what we know currently / 中华医学杂志(英文版)

Over the past few years, the human virome and its complex interactions with microbial communities and the immune system have gained recognition as a crucial factor in human health. Individuals with compromised immune function encounter distinctive challenges due to their heightened vulnerability to a diverse range of infectious diseases. This review aims to comprehensively explore and analyze the growing evidence regarding the role of the virome in immunocompromised disease status. By surveying the latest literature, we present a detailed overview of virome alterations observed in various immunodeficiency conditions. We then delve into the influence and mechanisms of these virome changes on the pathogenesis of specific diseases in immunocompromised individuals. Furthermore, this review explores the clinical relevance of virome studies in the context of immunodeficiency, highlighting the potential diagnostic and therapeutic gains from a better understanding of virome contributions to disease manifestations.

Research on mechanism of opioid receptors in pharmacological effects of ketamine / 中国药理学通报

Ketamine has been used clinically as an analgesic and anesthetic since 1970. Recently, it has been concerned due to its rapid and effective antidepressant effect. However, the psychiatric adverse reactions caused by ketamine such as addiction and hallucination limit its clinical application, yet the mechanism of the adverse reactions is still unclear. At present, it is generally believed that the pharmacological effects of ketamine are mainly mediated by N-methyl-D-aspartate acid (NMDA) receptors, but increasing numbers of research evidences suggest that the opioid receptor also play an important role in the pharmacological effects of ketamine. This review, based on the relevant literature published publicly in the past 20 years, summarizes the mechanisms of opioid receptors in the pharmacological effects of ketamine, such as anesthesia, analgesia, anti-depressant, anti-addiction and addiction, providing reference for revealing the mechanism of ketamine, and making beneficial exploration for solving the clinical side effects of ketamine.

Research progress of 5-HT / 中国药理学通报

The serotonin 2A receptor(5-HT

Protein phosphorylation involved in psychedelic-induced head-twitch response in rats / 中国药理学通报

Aim To investigate the potential protein post-translational modifications of psychedelic-induced Head-twith response and underling mechanism. Methods Psychedelics LSD, DOM, or Psilocin was administered to rats by intraperitoneal injection to induce head-twitch response, then the most effective dosage was identified to create animal models of head-twitch behavior. Western blot was performed in detecting the protein phosphorylation, acetylation, and ubiquitination in prefrontal cortex of SD rats after 10 min or 30 min injection. Results LSD (0.025 mg • kg~, i. p.), DOM (3 mg•kg

Early Enteral Nutrition and Sepsis-Associated Acute Kidney Injury: A Propensity Score Matched Cohort Study Based on the MIMIC-III Database

Purpose@#We aimed to analyze the optimal timing of enteral nutrition (EN) in the treatment of sepsis and its effect on sepsis-associated acute kidney injury (SA-AKI.) Materials and Methods: The MIMIC-III database was employed to identify patients with sepsis who had received EN. With AKI as the primary outcome variable, receiver operating characteristic (ROC) curves were utilized to calculate the optimal cut-off time of early EN (EEN). Propensity score matching (PSM) was employed to control confounding effects. Logistic regressions and propensity score-based inverse probability of treatment weighting were utilized to assess the robustness of our findings. Comparisons within the EEN group were performed. @*Results@#2364 patients were included in our study. With 53 hours after intensive care units (ICU) admission as the cut-off time of EEN according to the ROC curve, 1212 patients were assigned to the EEN group and the other 1152 to the delayed EN group. The risk of SA-AKI was reduced in the EEN group (odds ratio 0.319, 95% confidence interval 0.245–0.413, p<0.001). The EEN patients received fewer volumes (mL) of intravenous fluid (IVF) during their ICU stay (3750 mL vs. 5513.23 mL, p<0.001). The mediating effect of IVF was significant (p<0.001 for the average causal mediation effect). No significant differences were found within the EEN group (0–48 hours vs. 48–53 hours), except that patients initiating EN within 48 hours spent fewer days in ICU and hospital. @*Conclusion@#EEN is associated with decreased risk of SA-AKI, and this beneficial effect may be proportionally mediated by IVF volume.

Pediatric myofibroma/myofibromatosis of the soft tissue and bone: a clinicopathological analysis of 28 cases / 中华病理学杂志

Objective: To investigate the clinicopathological features, diagnosis and differential diagnosis of pediatric myofibroma/myofibromatosis of the soft tissue and bone. Methods: All cases of pediatric myofibroma/myofibromatosis of the soft tissue and bone diagnosed between January 2011 and December 2018 were retrieved from the surgical pathology records in the Department of Pathology, Beijing Jishuitan Hospital, Beijing, China. Clinical and radiological data were collected. H&E and immunohistochemistry were used to examine histological and immunophenotypic features and to make the diagnosis and differential diagnosis. The relevant literature was also reviewed. Results: Twenty-eight cases of pediatric myofibroma/myofibromatosis of the soft tissue and bone were respectively collected. The patients' ages ranged from 2 months to 14 years, with a mean age of 7 years. There were 7 females and 21 males. There were 12 cases located in soft tissue, including the finger (n=9), upper arm (n=1) and foot (n=2). There were 14 cases located in the bone of limb, including the femur (n=8), tibia (n=4), clavicle (n=2), fibula (n=2) and radius (n=1). There were 2 cases of myofibromatosis involving multiple bones. Radiology showed lytic lesions in the bone. The proliferation of spindle-shaped myofibroblasts arranged in fascicles with indistinct eosinophilic cytoplasm and bland nuclei, with no pleomorphism and cytological atypia. The characteristic histologic structure was the biphasic nodular growth pattern with cellular and paucicellular regions. The tumors might arrange in a hemangiopericytoma-like pattern. The stroma varied between dense fibrosis and myxoid changes. The reactive new bone formation and inflammatory cell infiltration also existed. Immunohistochemical study showed that the SMA was positive. The surgical resections were performed. One of the patients had tumor recurrence as a result of 11-month follow-up. Conclusions: The pediatric myofibroma/myofibromatosis of the soft tissue and bone is a very rare benign tumor and has a good prognosis. It has a characteristic morphology and its differential diagnosis from other spindle cell tumors could be made with the immunohistochemical analysis.

An exoskeleton robot can help improve the walking ability of stroke survivors / 中华物理医学与康复杂志

Objective:To explore the efficacy of a flat ground exoskeleton robot in improving the walking ability of stroke survivors.Methods:Fifty-eight stroke survivors with mobility difficulties were randomly divided into a robot group ( n=29) and a control group ( n=29). In addition to routine rehabilitation, the control group received conventional walking training, while the robot group underwent exoskeleton robot-assisted gait training. The 30-minute training sessions were held twice a day, 5 days per week for 5 weeks. Before as well as after 2 and 4 weeks of treatment, everyone′s walking ability was tested using the 6-minute walk test (6MWT) and functional ambulation scale (FAC). General lower limb motor function was quantified using the Fugl-Meyer Lower Extremity assessment (FMA-LE). Moreover, gait analysis was conducted before and after 4 weeks of treatment. Results:After 2 and 4 weeks of treatment, the average 6MWT times of both groups were significantly better than before the treatment, with the improvement of the robot group significantly greater than that of the control group after 2 weeks. After 2 and 4 weeks the average FMA-LE and FAC scores of both groups had improved significantly compared with before treatment. After 4 weeks the stride frequency and gait cycle of both groups had improved significantly.Conclusions:Exoskeleton robot-assisted gait training can improve walking ability and lower limb motor function of stroke survivors about as well as conventional walking training.

Effect of antiplatelet strategy on prognosis of in patients with diabetes mellitus and acute coronary syndrome with different CYP2C19 genotype / 国际生物医学工程杂志

Objective:To investigate the effect of different P2Y12 inhibitors on the long-term prognosis of patients with diabetes mellitus (DM) and acute coronary syndrome (ACS), with or without the CYP2C19 loss-of-function (LOF) gene. Method:266 consecutive ACS patients undergoing percutaneous coronary intervention (PCI) were enrolled. According to the CYP2C19 LOF genotype, the patients were divided into rapid metabolizing-type (without the CYP2C19 LOF gene) and moderate-slow metabolizing type (with the CYP2C19 LOF gene). Each type was divided into the A group (with diabetes) and the B group (without diabetes). Each group was divided into the ticagrelor subgroup and the clopidogrel subgroup according to the type of P2Y12 platelet inhibitor. The MACE events were recorded for each subgroup over 3 years, and the prognostic impact of the CYP2C19 LOF genotype and the type of P2Y12 used were analyzed. Results:There were no significant differences in MACE, revascularization, stroke, heart failure rehospitalization, major bleeding, or all-cause mortality among subgroups of patients with rapid metabolizing type at 3 years after PCI (all P>0.05). In patients with moderate-slow metabolizing-type, the use of tegretol significantly reduced the probability of MACE events and cardiac revascularization (all P<0.01) and significantly reduced the reoccurrence of heart attack in patients with DM. Conclusions:In DM combined with ACS patients with rapid metabolizing type, the choice of different P2Y12 inhibitors after PCI had no significant effect on their prognosis. In DM combined with ACS patients with moderate-slow metabolizing type, tegretol not only significantly reduced the incidence of MACE, revascularization, and reinfarction, but also did not increase the risk of major bleeding. In terms of reducing the reoccurrence of heart attack, the benefit of using tegretol in the DM patients was greater than in the non-DM patients.

Clinical application of local anesthesia for TiRobot-assisted removal of sacroiliac screws / 中华创伤骨科杂志

Objective:To explore the feasibility and advantages and disadvantages of local anesthesia for TiRobot-assisted removal of sacroiliac screws by comparison with general anesthesia for TiRobot-assisted removal of sacroiliac screws.Methods:A retrospective study was performed in 39 patients with posterior pelvic ring fracture-dislocation who had undergone removal of percutaneous sacroiliac screws after fracture union from January 2017 to December 2020 at Department of Orthopaedic Surgery, Hospital Affiliated to Chengdu University. Their sacroiliac screws were removed with TiRobot assistance under local anesthesia (LA group) or general anesthesia (GA group). In the LA group of 18 cases, there were 10 males and 8 females, aged (43.3 ± 8.4) years (from 25 to 58 years); in the GA group of 21 cases, there were 12 males and 9 females, aged (44.9 ± 9.0) years (from 23 to 60 years). The 2 groups were compared in terms of time for planning screw removal path, fluoroscopy frequency, fluoroscopy time, operation time, anesthesia time, anesthesia cost, postoperative visual analogue scale (VAS) and postoperative ambulation time.Results:There was no statistically significant difference in baseline data between the 2 groups, showing comparability ( P>0.05). Follow-ups revealed grade A wound healing in all patients. There were no significant differences between the 2 groups in time for planning screw removal path, fluoroscopy frequency, fluoroscopy time or operation time ( P>0.05). The anesthesia time [(41.6 ± 8.3) min], anesthesia cost [(653.5 ± 102.6) yuan] and postoperative ambulation time [(2.6 ± 0.6) h] in the LA group were significantly less than those in the GA group [(52.3 ± 9.5) min, (2,475.6 ± 261.8) yuan and (8.7 ± 2.4) h] while the VAS score in the former group (3.8 ± 1.5) was significantly higher than that in the latter group (2.5 ± 1.3) (all P<0.05). Conclusions:It is feasible to use local anesthesia for TiRobot-assisted removal of sacroiliac screws. In TiRobot-assisted removal of sacroiliac screws, compared with general anesthesia, local anesthesia may lead to shorter anesthesia time, lower anesthesia cast and shorter ambulation time, but the patients need to be compliant enough.

Advances in signaling pathway of 5-HT / 中国药理学通报

Classic serotonergic hallucinogens(also known as psychedelics)are powerful psychoactive substances that can induce profound alterations of human consciousness,emotion,and cognition. It is generally believed that the main target of psychedelics for their hallucinogenic effect is 5-hydroxytryptamine 2A receptor(5-HT

Associations of Plasma Glucagon Levels with Estimated Glomerular Filtration Rate, Albuminuria and Diabetic Kidney Disease in Patients with Type 2 Diabetes Mellitus

Background@#Type 2 diabetes mellitus (T2DM) is characterized by elevated fasting glucagon and impaired suppression of postprandial glucagon secretion, which may participate in diabetic complications. Therefore, we investigated the associations of plasma glucagon with estimated glomerular filtration rate (eGFR), albuminuria and diabetic kidney disease (DKD) in T2DM patients. @*Methods@#Fasting glucagon and postchallenge glucagon (assessed by area under the glucagon curve [AUCgla]) levels were determined during oral glucose tolerance tests. Patients with an eGFR <60 mL/min/1.73 m2 and/or a urinary albumin-to-creatinine ratio (UACR) ≥30 mg/g who presented with diabetic retinopathy were identified as having DKD. @*Results@#Of the 2,436 recruited patients, fasting glucagon was correlated with eGFR and UACR (r=–0.112 and r=0.157, respectively; P<0.001), and AUCgla was also correlated with eGFR and UACR (r=–0.267 and r=0.234, respectively; P<0.001). Moreover, 31.7% (n=771) presented with DKD; the prevalence of DKD was 27.3%, 27.6%, 32.5%, and 39.2% in the first (Q1), second (Q2), third (Q3), and fourth quartile (Q4) of fasting glucagon, respectively; and the corresponding prevalence for AUCgla was 25.9%, 22.7%, 33.7%, and 44.4%, respectively. Furthermore, after adjusting for other clinical covariates, the adjusted odds ratios (ORs; 95% confidence intervals) for DKD in Q2, Q3, and Q4 versus Q1 of fasting glucagon were 0.946 (0.697 to 1.284), 1.209 (0.895 to 1.634), and 1.521 (1.129 to 2.049), respectively; the corresponding ORs of AUCgla were 0.825 (0.611 to 1.114), 1.323 (0.989 to 1.769), and 2.066 (1.546 to 2.760), respectively. Additionally, when we restricted our analysis in patients with glycosylated hemoglobin <7.0% (n=471), we found fasting glucagon and AUCgla were still independently associated with DKD. @*Conclusion@#Both increased fasting and postchallenge glucagon levels were independently associated with DKD in T2DM patients.

Alterations in the oral microbiome in HIV infection: causes, effects and potential interventions / 中华医学杂志(英文版)

A massive depletion of CD4+ T lymphocytes has been described in early and acute human immunodeficiency virus (HIV) infection, leading to an imbalance between the human microbiome and immune responses. In recent years, a growing interest in the alterations in gut microbiota in HIV infection has led to many studies; however, only few studies have been conducted to explore the importance of oral microbiome in HIV-infected individuals. Evidence has indicated the dysbiosis of oral microbiota in people living with HIV (PLWH). Potential mechanisms might be related to the immunodeficiency in the oral cavity of HIV-infected individuals, including changes in secretory components such as reduced levels of enzymes and proteins in saliva and altered cellular components involved in the reduction and dysfunction of innate and adaptive immune cells. As a result, disrupted oral immunity in HIV-infected individuals leads to an imbalance between the oral microbiome and local immune responses, which may contribute to the development of HIV-related diseases and HIV-associated non-acquired immunodeficiency syndrome comorbidities. Although the introduction of antiretroviral therapy (ART) has led to a significant decrease in occurrence of the opportunistic oral infections in HIV-infected individuals, the dysbiosis in oral microbiome persists. Furthermore, several studies with the aim to investigate the ability of probiotics to regulate the dysbiosis of oral microbiota in HIV-infected individuals are ongoing. However, the effects of ART and probiotics on oral microbiome in HIV-infected individuals remain unclear. In this article, we review the composition of the oral microbiome in healthy and HIV-infected individuals and the possible effect of oral microbiome on HIV-associated oral diseases. We also discuss how ART and probiotics influence the oral microbiome in HIV infection. We believe that a deeper understanding of composition and function of the oral microbiome is critical for the development of effective preventive and therapeutic strategies for HIV infection.

Analysis on the law of height growth spurt in adolescence of children and adolescents in Zhongshan City / 北京大学学报(医学版)

OBJECTIVE@#To analyze the characteristics of the age at peak height velocity and peak height velocity of primary and middle school students in Zhongshan City, Guangdong Province, and to explore the law of the sudden increase in adolescent height in this area, and to understand the law of height growth spurt in adolescence by longitudinal tracking of the height of children and adolescents in Zhong-shan City.@*METHODS@#Based on the physical examination database of primary and middle school students in Zhongshan City, Guangdong Province from 2005 to 2016, individuals who had been continuously tracked for more than 6 times were selected as research samples. SITAR model was used to fit the height data of the sample population, and the age at peak height velocity and peak height velocity were calcula-ted.@*RESULTS@#A total of 49 579 subjects were included in this study, including 26 524 boys and 26 008 urban students. The median follow-up ages of boys and girls were 7.74 and 7.72 years, respectively. The boy's height spurt peak age was (12.72±0.89) years, and later than the girls at the age of (10.98±0.95) years (t=207.639, P < 0.001), the boy's height spurt peak velocity of (10.12±1.49) cm/year, higher than the girls of (8.35±1.12) cm/year (t=150.826, P < 0.001). The gender differences of height spurt peak age and height spurt peak speed in urban and rural students were consistent with the whole sample. The height surge peak age of urban male students was earlier than that of rural male students, and the height surge peak speed of urban female students was lower than that of rural female students.@*CONCLUSION@#The peak age of the surge of girls was earlier than that of boys, but the peak rate of the surge of girls was lower than that of boys, the peak age of urban students was earlier than that of rural students, but the peak rate of urban boys was lower than that of rural boys in Guangdong Province.

Genetic characteristics of hemagglutinin gene of H9N2 avian influenza viruses isolated from live poultry markets in Anhui Province from 2013 to 2018 / 中华疾病控制杂志

@#Objective To analyze genetic characteristics of hemagglutinin( HA) gene of H9N2 avian influenza viruses( AIVs) circulating in Anhui Province from 2013 to 2018． Methods All H9N2 positive samples tested by real－time polymerase chain reaction( PCＲ) were inoculated into specific patho- gen free ( SPF) chicken eggs for isolation and purification． Viral ＲNA was reversely transcribed into cD- NA and then amplified with gene specific primers． PCＲ products were sequenced and the gene sequences were analyzed using molecular and bioinformatics software． The DATAMONKEY online server was conducted to analyze selection pressure，and protein structure homology modelling was computed by the SWISS－MODEL server． Ｒesults 33 H9N2 AIVs isolated from live poultry markets belonged to h9．4．2．5 in the phylogenetic tree． The receptor binding sites of HA gene at 183，226 and 227 position were mutated into N，L and M，respectively． Meanwhile 189 and 190 sites presented with genetic polymorphism． Since 2015，all H9N2 viruses in this study carried 6 potential N－linked glycosylation sites． It was found that po- sition 160 of HA gene was subjected greater positive selection pressure，presented 7 spatial conformations at least． Conclusions The H9N2 viruses isolated from live poultry markets in Anhui Province possess the molecular characteristics of infecting mammals and the ability of antigenic drift，so we need to pay more attention to the genetic characteristics of the viruses．

Effect of CYP2C19 polymorphism and different P2Y 12 inhibitors on the long-term prognosis of patients with acute coronary syndromes / 国际生物医学工程杂志

Objective:To explore the relationship between the selection of different P2Y 12 inhibitors and the long-term prognosis of acute coronary syndrome (ACS) patients with and without CYP2C19 defect gene. Method:289 consecutive ACS patients who underwent percutaneous coronary intervention (PCI) at Tianjin Third Central Hospital from March 2016 to October 2016 were selected for CYP2C19 gene polymorphism detection. According to the detection results, the patients were divided into group A (with CYP2C19 loss-of-function gene, 199 cases) and group B (without CYP2C19 loss-of-function gene, 90 cases). After PCI, different P2Y 12 inhibitors were selected. The patients were followed up for 3 years, and 23 cases were lost to follow-up. Finally, 182 cases were enrolled in group A and 84 cases were enrolled in group B. According to whether there were major adverse cardiovascular events (MACE) within 3 years, the patients in groups A and B were divided into MACE subgroups (58 cases, 32 cases) and non-MACE subgroups (124 cases, 52 cases). The single factor analysis of the two subgroups in groups A and B was carried out based on the patient's clinical data, coronary artery disease and intervention status, and postoperative drug treatment plan. Risk factors with statistical significance ( P<0.05) were selected, and multivariate logistic regression analysis was performed on groups A and B to compare the effects of different P2Y 12 inhibitors on the prognosis of the two groups. Results:The differences in platelet volume, fasting blood glucose, HbA1c, left ventricular end-diastolic diameter, proportion of single-branch lesions, proportion of intervention for left main lesions, and dual antiplatelet therapy were statistically significant between the two subgroups in group A (all P<0.05). The differences in low-density lipoprotein (LDL), left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter, proportion of two-branch lesions, proportion of three-branch lesions, and proportion of using tirofeben were statistically significant between the two subgroups in group B (all P<0.05). In the group A, the choice of different P2Y 12 inhibitors was the independent risk factor for the long-term prognosis. Compared with patients treated with Ticagrelor, the probability of long-term MACE was 11.971 times larger ( OR=12.971, 95% CI: 5.028~33.464, P<0.001) among patients treated with Clopidogrel 75 mg/day, and 5.029 times larger ( OR=6.029, 95%CI: 2.278~15.958) among patients treated with Clopidogrel 100 mg/day. No significant correlation was witnessed between different P2Y 12 inhibitors and long-term prognosis in group B. In the group B, different P2Y 12 inhibitors have no significant correlation with their long-term prognosis of patients( P>0.05). Conclusions:For ACS patients with CYP2C19 loss-of-function gene, the choice of P2Y 12 inhibitors is associated with their long-term MACE events after PCI. Ticagrelor therapy brings the lowest risk of long-term MACE. For those without CYP2C19 loss-of-function gene, the correlation between the choice of different P2Y 12 inhibitors and their prognosis is not significant.

Efficacy and safety of the long-acting fusion inhibitor albuvirtide in antiretroviral-experienced adults with human immunodeficiency virus-1: interim analysis of the randomized, controlled, phase 3, non-inferiority TALENT study / 中华医学杂志(英文版)

BACKGROUND@#Albuvirtide is a once-weekly injectable human immunodeficiency virus (HIV)-1 fusion inhibitor. We present interim data for a phase 3 trial assessing the safety and efficacy of albuvirtide plus lopinavir-ritonavir in HIV-1-infected adults already treated with antiretroviral drugs.@*METHODS@#We carried out a 48-week, randomized, controlled, open-label non-inferiority trial at 12 sites in China. Adults on the World Health Organization (WHO)-recommended first-line treatment for >6 months with a plasma viral load >1000 copies/mL were enrolled and randomly assigned (1:1) to receive albuvirtide (once weekly) plus ritonavir-boosted lopinavir (ABT group) or the WHO-recommended second-line treatment (NRTI group). The primary endpoint was the proportion of patients with a plasma viral load below 50 copies/mL at 48 weeks. Non-inferiority was prespecified with a margin of 12%.@*RESULTS@#At the time of analysis, week 24 data were available for 83 and 92 patients, and week 48 data were available for 46 and 50 patients in the albuvirtide and NRTI groups, respectively. At 48 weeks, 80.4% of patients in the ABT group and 66.0% of those in the NRTI group had HIV-1 RNA levels below 50 copies/mL, meeting the criteria for non-inferiority. For the per-protocol population, the superiority of albuvirtide over NRTI was demonstrated. The frequency of grade 3 to 4 adverse events was similar in the two groups; the most common adverse events were diarrhea, upper respiratory tract infections, and grade 3 to 4 increases in triglyceride concentration. Renal function was significantly more impaired at 12 weeks in the patients of the NRTI group who received tenofovir disoproxil fumarate than in those of the ABT group.@*CONCLUSIONS@#The TALENT study is the first phase 3 trial of an injectable long-acting HIV drug. This interim analysis indicates that once-weekly albuvirtide in combination with ritonavir-boosted lopinavir is well tolerated and non-inferior to the WHO-recommended second-line regimen in patients with first-line treatment failure.@*TRIAL REGISTRATION@#ClinicalTrials.gov Identifier: NCT02369965; https://www.clinicaltrials.gov.Chinese Clinical Trial Registry No. ChiCTR-TRC-14004276; http://www.chictr.org.cn/enindex.aspx.

Increased early activation of CD56dimCD16dim/- natural killer cells in immunological non-responders correlates with CD4+ T-cell recovery / 中华医学杂志(英文版)

BACKGROUND@#Natural killer (NK) cells play a critical role in suppressing human immunodeficiency virus-1 (HIV-1) infection, but knowledge on whether and how NK cells affect immune reconstitution in HIV-1-infected individuals who receive antiretroviral therapy (ART) is limited.@*METHODS@#We performed a case-control study with 35 healthy individuals and 66 HIV-1-infected patients including 32 immunological non-responders (INRs) with poor CD4+ T-cell recovery (500 cells/μL after 4 years of ART). NK cell phenotype, receptor repertoire, and early activation in INRs and IRs were investigated by flow cytometry.@*RESULTS@#A significantly higher proportion of CD56dimCD16dim/- NK cells was observed in INRs than IRs before ART and after 4 years of ART. The number of CD56dimCD16dim/- NK cells was inversely correlated with CD4+ T-cell counts in INRs before ART (r = -0.344, P = 0.050). The more CD69-expressing NK cells there were, the lower the CD4+ T-cell counts and ΔCD4, and these correlations were observed in INRs after ART (r = -0.416, P = 0.019; r = -0.509, P = 0.003, respectively). Additionally, CD69-expressing CD56dimCD16dim/- NK cells were more abundant in INRs than those in IRs (P  = 0.018) after ART, both of which had an inverse association trend towards significance with CD4+ T-cell counts. The expression of the activating receptors NKG2C, NKG2D, and NKp46 on CD56dimCD16dim/- NK cell subsets were higher in IRs than that in INRs after 4 years of ART (all P < 0.01). Strong inverse correlations were observed between CD69 expression and NKG2C, NKG2A-NKG2C+, NKG2D, and NKp46 expression on CD56dimCD16dim/- NK cells in INRs after ART (NKG2C: r = -0.491, P = 0.004; NKG2A-NKG2C+: r = -0.434, P = 0.013; NKG2D: r = -0.405, P = 0.021; NKp46: r = -0.457, P = 0.008, respectively).@*CONCLUSIONS@#INRs had a larger number of CD56dimCD16dim/- NK cells characterized by higher activation levels than did IRs after ART. The increase in the CD56dimCD16dim/- NK cell subset may play an adverse role in immune reconstitution. Further functional studies of CD56dimCD16dim/- NK cells in INRs are urgently needed to inform targeted interventions to optimize immune recovery.