A retrospective cohort study on the influencing factors for macrosomia in singleton pregnancies.

To explore the influencing factors of singletons with macrosomia, and to develop interventions for the prevention of macrosomia. A retrospective cohort study was conducted on 26,379 pregnant women who established the Maternal and Child Health Record and gave birth from January 1, 2019 to December 31, 2019 in a community health service center in Haidian district, Beijing. The study analyzed factors such as maternal age, ethnicity, education level, prepregnancy body mass index (BMI), parity, folic acid supplementation, gestational diabetes mellitus, gestational hyper, hypothyroidism in pregnancy (including subhypothyroidism), hyperthyroidism in pregnancy, and infant gender. Univariate analysis was performed using the χ2 test, and multivariate analysis was performed using non-conditional multivariate logistic regression analysis. Out of 26,379 live births, 5.8% (1522/26,379) were macrosomia and 94.2% (24,857/26,379) were non-macrosomia. Univariate analysis revealed that maternal age, prepregnancy BMI, education level, parity, hypothyroidism during pregnancy, and infant gender were identified as influencing factors for macrosomia (P < .05). Multivariate analysis showed that maternal age ≥ 35 years, education level of high school or below, pre-pregnancy BMI, hypothyroidism, male infant, and parity were all influencing factors for macrosomia (P < .05). Prepregnancy overweight or obesity, male infants, multiparity, and low education level are risk factors for macrosomia. Multiple factors can contribute to macrosomia, and therefore, maternal health care should be strengthened, and early interventions should be taken for the above-mentioned factors in the local area.

Prognostic marker CD27 and its micro-environmental in multiple myeloma.

BACKGROUND: The Cluster of Differentiation 27 (CD27) is aberrantly expressed in multiple myeloma (MM) -derived. This expression facilitates the interaction between tumor and immune cells within TME via the CD27-CD70 pathway, resulting in immune evasion and subsequent tumor progression. The objective of this study is to investigate the correlation between CD27 expression and the prognosis of MM, and to elucidate its potential relationship with the immune microenvironment. METHODS: In this research, CD27 expression in T cells within the 82 newly diagnosed MM microenvironment was assessed via flow cytometry. We then examined the association between CD27 expression levels and patient survival. Subsequent a series of bioinformatics and in vitro experiments were conducted to reveal the role of CD27 in MM. RESULTS: Clinical evidence suggests that elevated CD27 expression in T cells within the bone marrow serves as a negative prognostic marker for MM survival. Data analysis from the GEO database has demonstrated a strong association between MM-derived CD27 and the immune response, as well as the hematopoietic system. Importantly, patients with elevated levels of CD27 expression were also found to have an increased presence of MDSCs and macrophages in the bone marrow microenvironment. Furthermore, the PERK-ATF4 signaling pathway has been implicated in mediating the effects of CD27 in MM. CONCLUSIONS: We revealed that CD27 expression levels serve as an indicative marker for the prognosis of MM patients. The CD27- PERK-ATF4 is a promising target for the treatment of MM.

Comparing perioperative outcomes following off-pump multi-vessel minimally invasive via a single left intercostal space incision with median sternotomy coronary artery bypass grafting: A single-center retrospective cohort study.

BACKGROUND: The perioperative outcomes following off-pump multi-vessel minimally invasive surgery (MICS) coronary artery bypass grafting (CABG) via a single left intercostal space incision has not been well evaluated. METHOD: From July 2019 to January 2022, a total of 444 patients with multi-vessel coronary artery disease (CAD) were enrolled and divided into MICS (n = 179) and sternotomy CABG (n = 265). Perioperative outcomes were compared between these two groups, including intraoperative blood loss, postoperative first 24 h drainage, ventilation duration, length of stay (LOS) in ICU and total LOS in hospital. Intraoperative blood flow of graft vessels were measured by transit-time flow measurement after vascular anastomosis and mean flow (MF) and pulsatile index (PI) were compared. RESULTS: There were no significant differences in preoperative profiles between these two groups except younger and lower proportion of female in MICS. No significant difference in the number of graft vessels was observed between MICS (3.18 ± 0.74) and sternotomy CABG (3.28 ± 0.86). Compared to sternotomy CABG, patients with MICS showed longer operation duration [(4.33 ± 0.86) h versus (5.10 ± 1.09) h], fewer intraoperative blood loss [700 (600, 900) mL versus 500 (200, 700) mL], fewer postoperative first 24 h drainage [400 (250, 500) mL versus 300 (200, 400) mL], shorter postoperative ventilation duration [16.5 (12.5, 19.0) h versus 15.0 (12.0, 17.0) h], LOS in ICU [20.0 (16.0, 23.0) h versus 18.0 (15.0, 20.0) h] and total LOS in hospital [(14.5 ± 3.9) d versus (12.6 ± 2.7) d] (all p < .001). MI and PI of graft vessels were similar and no significant differences in major perioperative complications and mortality were observed between MICS and sternotomy CABG (all p > .05). CONCLUSION: Off-pump multi-vessel MICS may be an alternative treatment for patients with multi-vessel CAD with better perioperative outcomes than sternotomy CABG.

A study on the perioperative effects of obesity on minimally invasive coronary artery bypass grafting and its surgical techniques.

OBJECTIVES: The aim of this study was to discuss the perioperative effects of obesity on minimally invasive coronary artery bypass grafting (CABG) and its surgical techniques. METHODS: A total of 582 patients with multivessel lesion who underwent off-pump CABG by our medical group of Beijing Anzhen Hospital between January 2017 and January 2021 were divided into the minimally invasive cardiac surgery (MICS) group and the conventional group (median sternotomy) according to the surgical method used. The body mass index of the patients was calculated, based on which both groups were divided into obese (≥28 kg/m2) and non-obese subgroups (<28 kg/m2). First, the perioperative data of the obese subgroups of both MICS and conventional groups were compared. Second, the obese and non-obese subgroups were compared in the MICS group. RESULTS: Despite a higher proportion of diabetes in the MICS group, there was no significant difference in preoperative baseline nor in the incidence of major complications within 30 days after surgery between obese subgroups of the MICS and conventional groups. The MICS group had a significantly lower rate of poor wound healing, along with a higher predischarge Barthel Index. Also, the preoperative baseline between the obese and non-obese subgroups of the MICS group exhibited no statistical differences. The obese subgroup had longer postoperative ventilator assistance, while other intraoperative data and postoperative observation indexes exhibited no significant differences. CONCLUSIONS: MICS CABG method is safe and feasible for obese patients with multivessel lesion. Minimally invasive surgery is beneficial to wound healing in obese patients. However, it requires a thorough preoperative evaluation and adequate surgical experience and skills.

Mediating effect of kinesiophobia between self-efficacy and physical activity levels in post-CABG patients: protocol for a prospective, multicentre, cross-sectional study in China.

INTRODUCTION: Physical activity (PA) can improve cardiac function, exercise capacity, and quality of life, in addition to reducing mortality by 20%-30% and preventing the recurrence of adverse cardiovascular events in patients following coronary artery bypass graft (CABG). However, PA levels are low in patients after CABG. This study intends to explore the mediating effect of kinesiophobia between self-efficacy and PA levels in patients following CABG. METHODS AND ANALYSIS: The proposed study constitutes a prospective, multicentre and cross-sectional study comprising 413 patients. Four teaching hospitals with good reputations in CABG will be included in the study. All of them are located in Beijing, China, and provide medical service to the whole country. This study will assess the following patient-reported outcome measures: demographic information, International Physical Activity Questionnaire-Long, Social Support Rating Scale, Cardiac Exercise Self-Efficacy Instrument, Multidimensional Fatigue Inventory, Hospital Anxiety and Depression Scale, and Tampa Scale for Kinesiophobia Heart. ETHICS AND DISSEMINATION: This study conforms to the principles of the Declaration of Helsinki and relevant ethical guidelines. Ethical approval has been obtained from the Ethics Committee of The Sixth Medical Centre of PLA General Hospital (approval number: HZKY-PJ-2022-2). All study participants will provide written informed consent. Findings from this study will be published in Chinese or English for widespread dissemination of the results. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Register, ChiCTR2100054098.

Comparing patient outcomes following minimally invasive coronary artery bypass grafting surgery vs. coronary artery bypass grafting: a single-center retrospective cohort study.

Background: This present research was designed for comparing coronary artery disease (CAD) patient outcomes following minimally invasive coronary artery bypass grafting surgery (MICS) or coronary artery bypass grafting (CABG). Methods: From 2014-2017, 679 CAD patients underwent MICS (n=281) or CABG (n=398) and were evaluated for the present study. Patient data were analyzed using 1:1 propensity score-matched assessment and a multivariate Cox proportional hazards regression model, and primary study achievements comprised major adverse cardiac and cerebrovascular events (MACCEs), myocardial infarction (MI), cardiac death, heart failure (HF), revascularization, and stroke. The median follow-up period was 2.68 years. Results: CABG patients exhibited a trend towards higher cumulative overall rates of MACCEs at 2 years (CABG: 6.2% vs. MICS: 3.8%) and 4 years (CABG: 9.3% vs. MICS: 7.6%) [adjusted hazard ratio (HR): 1.33; 95% confidence interval (CI): 0.33-5.39 for CABG vs. MICS; P=0.687], although this difference was not significant. No significant differences in 2- or 4-year cardiac death rates were observed between groups (CABG: 3.5%, 5.6% vs. MICS 2.8%, 2.8%; adjusted HR: 0.23; 95% CI: 0.03-1.81 for CABG vs. MICS; P=0.160). Further, there existed no discrepancies in rates of MI (P=1.000), HF (adjusted HR: 4.76; 95% CI: 0.01-6.40 for CABG vs. MICS; P=0.996), stroke (adjusted HR: 9.58; 95% CI: 0.11-25.24 for CABG vs. MICS; P=0.320), or repeated revascularization (adjusted HR: 1.71; 95% CI: 0.01-7.21 for CABG vs. MICS; P=0.631) when comparing these patient groups. In a multivariable Cox proportional hazards regression analysis, patients that were male (adjusted HR: 5.28; 95% CI: 1.48-18.83; P=0.010) and cases with a history of previous MI epsiodes (adjusted HR: 3.20; 95% CI: 1.09-9.37; P=0.034) were found to be at a higher risk of MACCEs. Conclusions: Follow-up data indicated that the MICS and CABG treatments could achieve similar outcomes.

Comparison of early outcomes associated with coronary artery bypass grafting for multi-vessel disease conducted using minimally invasive or conventional off-pump techniques: a propensity-matched study based on SYNTAX score.

BACKGROUND: This study was designed to compare early outcomes associated with coronary artery bypass grafting for multi-vessel disease conducted using either minimally invasive or conventional off-pump techniques. METHODS: From January 2017 through January 2021, 582 patients with multi-vessel lesion coronary artery disease underwent either minimally invasive cardiac surgery coronary artery bypass grafting (MICS CABG) or conventional off-pump coronary artery bypass grafting (OPCABG) treatment by our team at Anzhen Hospital. Patients in the MICS CABG group were propensity score-matched with those in the OPCABG at a 1:1 ratio (MICS CABG = 172; OPCABG = 172), using epidemiological data, preoperative clinical characteristics, and SYNTAX score as covariates. Perioperative outcomes and 6-month computed tomography angiography findings were compared between these groups. RESULTS: No significant differences between groups were observed with respect to 30-day postoperative mortality, myocardial infarction, and stroke incidence. Surgical data indicated that the MICS CABG procedure was able to cover all three main arterial territories with a relatively low need for circulatory assistance. The MICS CABG procedure was associated with a longer operative duration, but was also associated with higher postoperative hemoglobin and activities of daily living index values as well as a shorter duration of postoperative hospitalization (P < 0.05). No differences in 6-month graft patency were observed between groups. CONCLUSIONS: MICS CABG is a safe, less invasive alternative to OPCABG when performing complete revascularization provided patients are properly selected, yielding similar in-hospital outcomes and 6-month graft patency rates together with an earlier return of physical function.

Biopharmaceutical and Pharmacokinetic Activities of Oxymatrine Determined by a Sensitive UHPLC-MS/MS Method.

BACKGROUND: Oxymatrine is known as one of the most promising alkaloids from Sophora flavescens for its excellent pharmacological effects. OBJECTIVE: The aim of this research is to assess the biopharmaceutical and pharmacokinetic activities of oxymatrine and clarify its mechanisms of absorption and metabolism. METHODS: The biological characteristics of oxymatrine were systematically investigated by UHPLC-MS/MS. The mechanisms of absorption and metabolism of oxymatrine were further clarified through incubation in rat liver microsomes and transport across the Caco-2 monolayer cell absorption model. RESULTS: It was found that the absolute oral bioavailability of oxymatrine was 26.43%, and the pharmacokinetic parameters Cmax, Tmax, and t1/2 were 605.5 ng/mL, 0.75 h, and 4.181 h after oral administration, indicating that oxymatrine can be absorbed quickly. The tissue distribution tests showed that oxymatrine distributed throughout all the organs, with the small intestine accumulating the highest level, followed by the kidney, stomach, and spleen. The Papp in Caco-2 cell line absorption model was over 1 × 10-5 and PDR 1.064, and t1/2 of oxymatrine in rat liver microsome in vitro was 1.042 h, indicating that oxymatrine can be absorbed easily through passive diffusion and CYP450 enzymes could be involved in its metabolism. The plasma protein binding rate of oxymatrine was 2.78 ± 0.85%. CONCLUSION: Oxymatrine can be absorbed into blood easily through passive diffusion, mainly distributed in the intestine, stomach, liver, and spleen in vivo, and CYP450 enzymes in the liver could be involved in its metabolism.

Acceptance of seasonal influenza vaccination and associated factors among pregnant women in the context of COVID-19 pandemic in China: a multi-center cross-sectional study based on health belief model.

BACKGROUND: Seasonal influenza can circulate in parallel with coronavirus disease (COVID-19) in winter. In the context of COVID-19 pandemic, the risk of co-infection and the burden it poses on healthcare system calls for timely influenza vaccination among pregnant women, who are the priority population recommended for vaccination. We aimed to evaluate the acceptance of influenza vaccination and associated factors among pregnant women during COVID-19 pandemic, provide evidence to improve influenza vaccination among pregnant women, help reduce the risk of infection and alleviate the burden of healthcare system for co-infected patients. METHODS: We conducted a multi-center cross-sectional study among pregnant women in China. Sociodemographic characteristics, health status, knowledge on influenza, attitude towards vaccination, and health beliefs were collected. Locally weighted scatterplot smoothing regression analysis was used to evaluate the trends in the acceptance of influenza vaccine. Logistic regression was applied to identify factors associated with vaccination acceptance. RESULTS: The total acceptance rate was 76.5% (95%CI: 74.8-78.1%) among 2568 pregnant women enrolled. Only 8.3% of the participants had a history of seasonal influenza vaccination. In the logistic regression model, factors associated with the acceptance of influenza vaccine were western region, history of influenza vaccination, high knowledge of influenza infection and vaccination, high level of perceived susceptibility, perceived benefit, cues to action and low level of perceived barriers. Among 23.5% of the participants who had vaccine hesitancy, 48.0% of them were worried about side effect, 35.6% of them lacked confidence of vaccine safety. CONCLUSIONS: Our findings highlighted that tailored strategies and publicity for influenza vaccination in the context of COVID-19 pandemic are warranted to reduce pregnant women's concerns, improve their knowledge, expand vaccine uptake and alleviate pressure for healthcare system.

Off-Pump Aortic Bypass for Hypoplastic Arch and Aortic Coarctation Via Anterolateral Thoracotomy.

We report the case of a 21-year-old woman who was referred with uncontrolled hypertension. Computed tomography angiography revealed aortic arch hypoplasia and severe aortic coarctation. An off-pump ascending-to-descending aortic bypass surgery using synthetic graft was performed via left anterolateral thoracotomy. The patient recovered well and was discharged home uneventfully after five days. This procedure was performed without touching the head vessels or any collateral vessels. We consider this a safe and less invasive alternative technique for adult coarctation patients who have aortic hypoplasia or interrupted aorta.

Surgical Challenges in Multi-Vessel Minimally Invasive Coronary Artery Bypass Grafting.

OBJECTIVES: Minimally invasive coronary artery bypass grafting (MICS CABG) has emerged as an alternative treatment for patients with multi-vessel coronary artery disease, but there are certain surgical challenges inherent in the adoption of this approach. The present study was conducted to provide insight regarding the outcomes associated with our first 118 cases, to discuss the surgical difficulties encountered in these patients, and to outline the potential countermeasures. METHODS: Between January 2017 and January 2020, 118 patients underwent multi-vessel MICS CABG. These patients were stratified into two groups based upon whether they did or did not experience surgical challenges, and early clinical outcomes were compared between these groups to assess the incidence of technical difficulties and associated factors. RESULTS: Surgical challenges arose in 38 of the 118 cases in this study, including 13 cases of exposure-related difficulties, 11 cases of proximal anastomosis-related difficulties, 15 cases of distal anastomosis-related difficulties, 4 cases of LITA-related difficulties, and 3 cases of lung-related difficulties. Relative to the other 80 patients, those patients for whom intraoperative technical challenges arose experience significant increases in operative duration (4.94 ± 0.89 vs. 5.59 ± 1.11 h, P=0.001), intraoperative blood loss (667 ± 313 vs. 892 ± 532 mL, P=0.005), length of the ICU admission (17.59 ± 3.51 vs. 22.59 ± 17.31 h, P=0.015), and the duration of postoperative hospitalization (5.96 ± 1.23 vs. 6.71 ± 1.92 days, P=0.012). There were no significant differences between these groups with respect to the mean graft number, major complications such as stroke or organ dysfunction, or one-year graft patency. CONCLUSIONS: There is a substantial learning curve associated with performing off-pump MICS CABG to treat multi-vessel disease. Surgical challenges encountered during this procedure may increase the operative duration, intraoperative blood loss, ICU admission, and the duration of postoperative hospitalization. However, these issues do not appear to compromise the efficacy of complete revascularization, and early clinical outcomes associated with this procedure remain acceptable.

A novel coumarin-based colorimetric and fluorescent probe for detecting increasing concentrations of Hg2+ in vitro and in vivo.

Mercury has complex biological toxicity and can cause a variety of physiological diseases and even death, so it is of great importance to develop novel strategies for detecting trace mercury in environmental and biological samples. In this work, we designed a new coumarin-based colorimetric and fluorescent probe CNS, which could be obtained from inexpensive starting materials with high overall yield in three steps. Probe CNS could selectively respond to Hg2+ with obvious color and fluorescence changes, and the presence of other metal ions had no effect on the fluorescence changes. Probe CNS also exhibited high sensitivity against Hg2+, with a detection limit as low as 2.78 × 10-8 M. More importantly, the behavioral tracks of zebrafish had no obvious changes upon treatment with 10 µM probe CNS, thus indicating its low toxicity. The probe showed potential application value and was successfully used for detecting Hg2+ in a test strip, HeLa cells and living zebrafish larvae.

Highly efficient and selective supramolecular hydrogel sensor based on rhodamine 6G derivatives.

A mercury ion sensitive fluorescent functional monomer was synthesized based on rhodamine 6G, and two highly-effective approaches about the research and development of novel macroscopic hydrogel sensor were reported. The monomer was utilized to synthesize hydrogel sensors by free radical polymerization and guest-host interaction. Hydrogel sensors have prominent selectivity to Hg2+ and can be tailored and reused, which are capable of detecting Hg2+ sensitively in flowing and standing water environment with satisfactory performance. This work is expected to open an avenue to construct novel fluorescent analysis method for Hg2+ detection.

Development of stimuli-responsive intelligent polymer micelles for the delivery of doxorubicin.

Doxorubicin is still used as a first-line drug in current therapeutics for numerous types of malignant tumours (including lymphoma, transplantable leukaemia and solid tumour). Nevertheless, to overcome the serious side effects like cardiotoxicity and myelosuppression caused by effective doses of doxorubicin remains as a world-class puzzle. In recent years, the usage of biocompatible polymeric nanomaterials to form an intelligently sensitive carrier for the targeted release in tumour microenvironment has attracted wide attention. These different intelligent polymeric micelles (PMs) could change the pharmacokinetics process of drugs or respond in the special microenvironment of tumour site to maximise the efficacy and reduce the toxicity of doxorubicin in other tissues and organs. Several intelligent PMs have already been in the clinical research stage and planned for market. Therefore, related research remains active, and the latest nanotechnology approaches for doxorubicin delivery are always in the spotlight. Centring on the model drugs doxorubicin, this review summarised the mechanisms of PMs, classified the polymers used in the application of doxorubicin delivery and discussed some interesting and imaginative smart PMs in recent years.

Effect of pravastatin treatment on circulating adiponectin: a meta-analysis of randomized controlled trials.

OBJECTIVE: Pravastatin has been suggested to increase circulating adiponectin in humans. However, results of randomized controlled trials (RCTs) are inconsistent. We aimed to systematically evaluate the influence of pravastatin on circulating adiponectin in humans by performing a meta-analysis of RCTs. MATERIALS AND METHODS: Studies were identified via systematic searching of PubMed, Embase, and Cochrane's Library databases. A random effect model was used to pool the results. Meta-regression and subgroup analyses were applied to explore the source of heterogeneity. RESULTS: Eight RCTs with nine comparisons of 595 participants were included. Pravastatin treatment was associated with a significant increased level of circulating adiponectin as compared with controls (weighted mean difference [WMD] =0.63 µg/mL; 95% CI, 0.17-1.09 µg/mL; P=0.007) with moderate heterogeneity (I2=28%). These results were confirmed by meta-analysis of double-blinded placebo-controlled RCTs (WMD =0.82 µg/mL; P=0.01). Meta-regression analyses indicated that proportions of males in each study were positively correlated with the effect of pravastatin on adiponectin (coefficient: 0.015, P=0.03). Subgroup analyses confirmed that pravastatin significantly increased adiponectin in studies of males (WMD =1.41 µg/mL; P=0.008), but not in those of females (WMD =-0.04 µg/mL; P=0.94). CONCLUSION: Pravastatin treatment is associated with increased circulating adiponectin. Gender difference may exist regarding the effect of pravastatin treatment on adiponectin.

Specific Activation In Vivo of HIV-1 by a Bromodomain Inhibitor from Monocytic Cells in Humanized Mice under Antiretroviral Therapy.

Combination antiretroviral therapy (cART) effectively suppresses HIV-1 replication and enables HIV­infected individuals to live long, productive lives. However, the persistence of HIV-1 reservoirs of both T and myeloid cells with latent or low-replicating HIV-1 in patients under cART makes HIV-1 infection an incurable disease. Recent studies have focused on the development of strategies to activate and purge these reservoirs. Bromodomain and extraterminal domain proteins (BETs) are epigenetic readers involved in modulating gene expression. Several bromodomain inhibitors (BETi) are reported to activate viral transcription in vitro in HIV-1 latency cell lines in a P-TEFb (CDK9/cyclin T1)-dependent manner. Little is known about BETi efficacy in activating HIV-1 reservoir cells under cART in vivo Here we report that a BETi (I-BET151) efficiently activated HIV-1 reservoirs under effective cART in humanized mice in vivo Interestingly, I-BET151 during suppressive cART in vivo activated HIV-1 gene expression only in monocytic cells and not in CD4+ T cells. We further demonstrate that BETi preferentially enhanced HIV-1 gene expression in monocytic cells rather than in T cells and that whereas CDK9 was involved in activating HIV-1 by I-BET151 in both monocytic and T cells, CDK2 enhanced HIV-1 transcription in monocytic cells but inhibited it in T cells. Our findings reveal a role for CDK2 in differential modulation of HIV-1 gene expression in myeloid cells and in T cells and provide a novel strategy to reactivate monocytic reservoirs with BETi during cART.IMPORTANCE Bromodomain inhibitors have been reported to activate HIV-1 transcription in vitro, but their effect on activation of HIV-1 reservoirs during cART in vivo is unclear. We found that BETi (I-BET151) treatment reactivated HIV-1 gene expression in humanized mice during suppressive cART. Interestingly, I-BET151 preferentially reactivated HIV-1 gene expression in monocytic cells, but not in CD4 T cells, in cART-treated mice. Furthermore, I-BET151 significantly increased HIV-1 transcription in monocytic cells, but not in HIV-1-infected CD4 T cells, via CDK2-dependent mechanisms. Our findings suggest that BETi can preferentially activate monocytic HIV-1 reservoir cells and that a combination of reservoir activation agents targeting different cell types and pathways is needed to achieve reactivation of different HIV-1 reservoir cells during cART.

Type I interferons suppress viral replication but contribute to T cell depletion and dysfunction during chronic HIV-1 infection.

The direct link between sustained type I interferon (IFN-I) signaling and HIV-1-induced immunopathogenesis during chronic infection remains unclear. Here we report studies using a monoclonal antibody to block IFN-α/ß receptor 1 (IFNAR1) signaling during persistent HIV-1 infection in humanized mice (hu-mice). We discovered that, during chronic HIV-1 infection, IFNAR blockade increased viral replication, which was correlated with elevated T cell activation. Thus, IFN-Is suppress HIV-1 replication during the chronic phase but are not essential for HIV-1-induced aberrant immune activation. Surprisingly, IFNAR blockade rescued both total human T cell and HIV-specific T cell numbers despite elevated HIV-1 replication and immune activation. We showed that IFNAR blockade reduced HIV-1-induced apoptosis of CD4+ T cells. Importantly, IFNAR blockade also rescued the function of human T cells, including HIV-1-specific CD8+ and CD4+ T cells. We conclude that during persistent HIV-1 infection, IFN-Is suppress HIV-1 replication, but contribute to depletion and dysfunction of T cells.

Minicircle HBV cccDNA with a Gaussia luciferase reporter for investigating HBV cccDNA biology and developing cccDNA-targeting drugs.

Chronic Hepatitis B Virus (HBV) infection is generally not curable with current anti-viral drugs. Virus rebounds after stopping treatment from the stable HBV covalently-closed-circular DNA (cccDNA). The development of drugs that directly target cccDNA is hampered by the lack of robust HBV cccDNA models. We report here a novel HBV cccDNA technology that will meet the need. We engineered a minicircle HBV cccDNA with a Gaussia Luciferase reporter (mcHBV-GLuc cccDNA), which serves as a surrogate to measure cccDNA activity. The mcHBV-GLuc cccDNA was easily produced in bacteria, and it formed minichromosomes as HBV cccDNA episome DNA does when it was transfected into human hepatocytes. Compared to non-HBV minicircle plasmids, mcHBV-GLuc cccDNA showed persistent HBV-GLuc activity and HBx-dependent gene expression. Importantly, the mcHBV-GLuc cccDNA showed resistance to interferons (IFN) treatment, indicating its unique similarity to HBV cccDNA that is usually resistant to long-term IFN treatment in chronic HBV patients. Most importantly, GLuc illuminates cccDNA as a surrogate of cccDNA activity, providing a very sensitive and quick method to detect trace amount of cccDNA. The mcHBV-GLuc cccDNA model is independent of HBV infection, and will be valuable for investigating HBV cccDNA biology and for developing cccDNA-targeting drugs.

PAK4 confers the malignance of cervical cancers and contributes to the cisplatin-resistance in cervical cancer cells via PI3K/AKT pathway.

BACKGROUND: Multiple protein or microRNA markers have been recognized to contribute to the progression and recurrence of cervical cancers. Particular those, which are associated with the chemo- or radio-resistance of cervical cancers, have been proposed to be promising and to facilitate the definition for cervical cancer treatment options. METHODS: This study was designed to explore the potential prognosis value of p21-activated kinase (PAK)-4 in cervical cancer, via the Kaplan-Meier analysis, log-rank test and Cox regression analysis, and then to investigate the regulatory role of PAK4 in the cisplatin resistance in cervical cancer cells, via the strategies of both PAK4 overexpression and PAK4 knockout. RESULTS: It was demonstrated that PAK4 was upregulated in cervical cancer tissues, in an association with the cancer's malignance variables such as FIGO stage, lymph node or distant metastasis and the poor histological grade. The high PAK4 expression was also independently associated with poor prognosis to cervical cancer patients. Moreover, PAK4 confers cisplatin resistance in cervical cancer Hela or Caski cells. In addition, the PI3K/Akt pathway has been implicated in the PAK4-confered cisplatin resistance. And the PI3K/Akt inhibitor, LY294002, markedly deteriorated the cisplatin-mediated viability reduction of Hela or Caski cells, indicating the involvement of PI3K/Akt pathway in the cisplatin resistance in cervical cancer cells. CONCLUSION: This study has confirmed the significant prognostic role of PAK4 level in cervical cancer patients and has recognized the regulatory role in cervical cancer progression. Moreover, our study has indicated that PAK4 also confers the chemoresistance of cervical cancer cells in a PI3K/Akt-dependent way. Thus, our study indicates PAK4 as a promising marker for cervical cancer treatment.

[Detection of cytochrome P450 3A4 gene polymorphism guides for labor analgesia with sufentanil medication].

OBJECTIVE: To investigate the relationship between single nucleotide polymorphisms (SNPs) of cytochrome P450 (CYP450) 3A4 rs2242480 and inter-individual differences of sufentanil consumption in accouchement sans douleur. METHODS: A total of 131 parturient women were collected. According to the distribution of genotypes and allele frequencies of rs2242480, the doses of sufentanil were individually designed. CC homozygotes were given the standard analgesia dose, CT heterozygotes and TT homozygotes were given 87.6% of standard sufentanil dose. RESULTS: Visual analogue score (VAS) between CC group and CT/TT group were 3.67±1.2 and 3.44±1.5, consistent with the expected analgesic standards. The difference was not statistically significant. CONCLUSION: The parturient women carrying CT heterozygotes and TT homozygotes of CYP3A4 rs2242480 required less sufentanil in accouchement sans douleur.