Changes of T lymphocyte subsets in patients with HIV-negative symptomatic neurosyphilis.

OBJECTIVES: The host immune response could be an imperative factor in the pathogenesis of neurosyphilis, but the role of T lymphocyte subsets remains unclear. In the present study, we assessed the CD4+ T and CD8+ T cell subsets in the peripheral blood of patients with HIV-negative symptomatic neurosyphilis and then explored the clinical application value of neurosyphilis. METHODS: In total, 24 patients with HIV-negative symptomatic neurosyphilis and 22 patients with syphilis/non-neurosyphilis were included in this study and cerebrospinal fluid (CSF) and blood samples were obtained. Th1, Th2, Th17, Th9, CD8+IFN-γ+, CD8+IL-4+, CD8+IL-9+, and CD8+IL-17 + cells were identified by flow cytometry. RESULTS: The levels of CD8+IFN-γ+ were significantly increased in the peripheral blood of neurosyphilis patients compared to that in syphilis/non-neurosyphilis patients, but it was opposite to Th2, Th9, CD8+IL-4+, CD8+IL-9+, and CD8+IL-17 + cells. Dendritic cells (DCs) of neurosyphilis matured by T. pallidum induced the development of a combination of IFN-γ-producing Th1 cells. The number of CD8+IL-17 + cells was significantly correlated with the CSF RPR and CSF TPPA levels. ROC curve analysis revealed that the number of CD8+IFN-γ+ cells could be a potential biomarker for neurosyphilis from non-neurosyphilis/syphilis. CONCLUSIONS: High expression of CD8+IFN-γ+ cells and low expression of CD8+IL-17 + cells in patients with symptomatic neurosyphilis, which explains the pathogenesis of symptomatic neurosyphilis, meanwhile CD8+IFN-γ+ cells may be a better indicator in classifying symptomatic neurosyphilis from non-neurosyphilis/syphilis among patients without HIV infection.

LncRNA-ENST00000421645 promotes T cells to secrete IFN-γ by sponging PCM1 in neurosyphilis.

Aim: Neurosyphilis patients exhibited significant expression of long noncoding RNA (lncRNA) in peripheral blood T lymphocytes. In this study, we further clarified the role of lncRNA-ENST00000421645 in the pathogenic mechanism of neurosyphilis. Methods: lncRNA-ENST00000421645 was transfected into Jurkat-E6-1 cells, namely lentivirus (Lv)-1645 cells. RNA pull-down assay, flow cytometry, RT-qPCR, ELISA (Neobioscience Technology Co Ltd, Shenzhen, China) and RNA immunoprecipitation chip assay were used to analyze the function of lncRNA-ENST00000421645. Results: The expression of IFN-γ in Lv-1645 cells was significantly increased compared to that in Jurkat-E6-1 cells stimulated by phorbol-12-myristate-13-acetate (PMA). Then, it was suggested that lncRNA-ENST00000421645 interacts with PCM1 protein. Silencing PCM1 significantly increased the level of IFN-γ in Lv-1645 cells stimulated by PMA. Conclusion: This study revealed that lncRNA-ENST00000421645 mediates the production of IFN-γ by sponging PCM1 protein after PMA stimulation.

Lay abstract The mechanisms underlying Treponema pallidum (a type of bacterium that causes syphilis) invasion into the CNS have not yet been established. In this study, we further clarified the role of long noncoding RNA (lncRNA) in the pathogenic process causing nerve damage. The results suggested that lncRNA-ENST00000421645 interacts with an important protein named PCM1. Suppressing the expression of PCM1 significantly increased the level of IFN-γ cytokines (substances secreted by immune cells that effect other cells) with an increased level of lncRNA-ENST00000421645 when immune cells were stimulated by phorbol-12-myristate-13-acetate a specific activator of the PKC signaling enzyme involved in gene transcription pathways. This study revealed that lncRNA-ENST00000421645 mediates the production of IFN-γ by interacting with PCM1 protein.

Comparison of the efficacy and safety of levetiracetam and phenytoin in the treatment of established status epilepticus: A systematic review and meta-analysis.

Status epilepticus (SE) is the second most critical neurological illness after cerebrovascular disease. Phenytoin has traditionally been considered the second-line drug of first choice after failure of first-line treatment using benzodiazepines. In recent years, levetiracetam has been proposed as a potential substitute for phenytoin. To comprehensively evaluate the efficacy and safety of levetiracetam and phenytoin in the treatment of patients with established SE, we integrated the data from 11 eligible studies and conducted a systematic review and meta-analysis. The PubMed, Web of Science, Cochrane Library, and Embase databases were searched to identify eligible articles reporting outcomes including clinical seizure cessation within 60 min, clinical recurrence rate within 24 h, good final outcome at discharge, and adverse events (AEs) of treatment with levetiracetam and phenytoin. Our study included a total of 11 trials including a total of 1933 patients. The outcomes showed that the pooled Risk Raito (RR) of clinical seizure cessation within 60 min was 1.08 (95% CI = 1.02-1.14, P = 0.01). The pooled RR of clinical recurrence rate within 24 h was 1.03 (95% CI = 0.66-1.59, P = 0.91). The pooled RR of AEs was 0.83 (95% CI = 0.57-1.21, P = 0.34). The pooled RRs of life-threatening hypotension and acute respiratory depression were 0.29 (95% CI = 0.10-0.81, P = 0.02) and 0.63 (95% CI = 0.40-0.98, P = 0.04), respectively. Levetiracetam might be more effective than phenytoin for the treatment of established SE and is associated with a lower incidence of more serious AEs. Levetiracetam can be used as an alternative to phenytoin for the treatment of benzodiazepine-refractory SE.

Prenatal exposure to fine particulate matter and fetal growth: a cohort study from a velocity perspective.

BACKGROUND: Reduced growth velocity before birth increases the risk of adverse health outcomes in adult life. However, until recently, there has been a lack of studies demonstrating the impact of prenatal PM2.5 exposure on fetal growth velocity. METHODS: The current study was embedded in a previous cohort built between January 1, 2014, and April 30, 2015, in Shanghai First Maternity and Infant Hospital, China, in 6129 eligible singleton pregnancies. The PM2.5 concentration was estimated by an inverse distance weighted method according to the residential addresses of the participants. Repeated fetal biometry measurements, including head circumference (HC), abdominal circumference (AC), femur length (FL), and biparietal diameter (BPD), were measured through ultrasound between 14 and 41 gestational weeks. A principal component analysis through conditional expectation for sparse longitudinal data was used to estimate the corresponding velocities. RESULTS: A total of 22782 ultrasound measurements were conducted among 6129 participants with a median of 2 and a maximum of 9 measurements. With each 10 µg/m3 increase in cumulative PM2.5 exposure, the velocity of HC, AC FL and BPD decreased by 0.12 mm/week, 0.17 mm/week, 0.02 mm/week and 0.02 mm/week, respectively, on average. The results of the Generalized Functional Concurrent Model showed that the velocity decreased significantly with PM2.5 exposure between 22 and 32 gestational weeks, which might be the potential sensitive exposure window. CONCLUSIONS: There are negative associations between prenatal exposure to PM2.5 and fetal growth velocity, and the late second trimester and early third trimester might be the potential sensitive window.

Study on detection rate of polyps and adenomas in artificial-intelligence-aided colonoscopy.

BACKGROUND/AIM: To study the impact of computer-aided detection (CADe) system on the detection rate of polyps and adenomas in colonoscopy. MATERIALS AND METHODS: A total of 1026 patients were prospectively randomly scheduled for colonoscopy with (the CADe group, CADe) or without (the control group, CON) the aid of the CADe system, together with visual notification and voice alarm, so as to compare the detection rate of polyp. RESULTS: Compared with group CON, the detection rate of adenomas increased in group CADe, the average number of adenomas increased, the number of small adenomas increased, the number of proliferative polyps increased, and the differences were statistically significant (P < 0.001), but the comparison for the number of larger adenomas showed no significant difference between the groups (P> 0.05). CONCLUSIONS: The CADe system is feasible for increasing the detection of polyps and adenomas in colonoscopy.

Treponemapallidum Dysregulates Monocytes and Promotes the Expression of IL-1ß and Migration in Monocytes Through the mTOR Signaling Pathway.

Monocytes are widely involved in the body's defense response, and abnormally regulated monocyte subsets are closely related to the pathogenesis of various diseases. It is unclear whether Treponema pallidum (Tp) dysregulates monocyte subsets and impacts the functions of monocytes. This study aims to analyze the distribution of monocyte subsets in syphilis patients and the effect of Tp on monocyte functions to explore the pathogenesis of syphilis. Flow cytometry was employed to detect monocyte subsets. With or without pre-treatment with rapamycin, THP-1 cell migration stimulated by Tp was investigated by a Transwell migration assay, and THP-1 cell phagocytosis was studied using fluorescent microspheres. IL-1ß and TNF-α expression was quantified by PCR and flow cytometry, while LC3 and mTOR were investigated in Tp-exposed THP-1 cells using western blotting. Tp infection led to an increase in the proportion of CD14++CD16+ monocytes and a decrease in the proportion of CD14++CD16- monocytes. In addition, Tp promoted monocyte (THP-1) CD14 and CD16 expression in vitro, induced the expression of IL-1ß and TNF-α in a dose-dependent manner and promoted the migration and autophagy of monocytes. Furthermore, mTOR phosphorylation on monocytes was stimulated by Tp, and the levels peaked at 30 min. Pre-treatment with rapamycin (mTOR inhibitor) attenuated the expression of IL-1ß and migration in Tp-exposed THP-1 cells. Tp abnormally regulates monocyte subsets and promotes migration, autophagy, and the expression of IL-1ß and TNF-α in THP-1 cells. Meanwhile, the mTOR affected the expression of IL-1ß and migration in Tp-exposed THP-1 cells. This study is important as it sheds light on the mechanism by which monocytes interact with Tp during infection.

Tp47 induces cell death involving autophagy and mTOR in human microglial HMO6 cells.

BACKGROUND: Tp47 can induce immune cells to produce numerous inflammatory factors, some of which can trigger autophagy. Increased autophagy has a dual effect on cell survival. However, whether Tp47 induces autophagy in microglia is unknown. OBJECTIVE: To evaluate the potential role of Tp47 in microglia. METHODS: After treatment with Tp47, autophagy-related proteins were assessed in HMO6 human microglial cells by flow cytometry, Western blotting and immunofluorescence. Cell death was assessed by flow cytometry and trypan blue staining. Changes in mTOR pathway proteins were explored by using Western blotting. RESULTS: After treatment with Tp47, a gradual increase in total LC3 expression was observed as a dose- and time-dependent accumulation of its active form, LC3-II (P < 0.05), but P62 expression was downregulated (P < 0.05). Moreover, microglial mortality gradually increased in a dose- and time-dependent manner. 3-Methyladenine (3-MA), a specific inhibitor of PI3KC3, reversed autophagy and cell death. The mortality rate of HMO6 microglial cells treated with Tp47 was approximately 13.7 ±â€¯2%, and the basal expression of p-mTOR, p-p70s6k and p-S6 in these cells was significantly downregulated by Tp47. Moreover, the mortality rate of microglia was significantly reduced after mTOR agonist intervention. CONCLUSION: In human microglial HMO6 cells, Tp47 induces autophagy- and mTOR pathway-dependent cell death.

Body mass index and all-cause mortality in patients with atrial fibrillation: insights from the China atrial fibrillation registry study.

BACKGROUND: Impact of body mass index (BMI) on all-cause mortality in atrial fibrillation (AF) patients remains controversial. METHODS: A total of 10,942 AF patients were prospectively enrolled and categorized into four BMI groups: underweight (BMI < 18.5 kg/m2), normal weight (BMI 18.5-24 kg/m2), overweight (BMI 24-28 kg/m2) and obesity (BMI ≥ 28 kg/m2). The primary outcome was all-cause mortality. Different Cox proportional hazards models were performed to evaluate the association between BMI and all-cause mortality. RESULTS: During a median follow-up of 30 months (IQR 18-48 months), 862 deaths events occurred. Compared to normal BMI, higher BMI was associated with a lower mortality risk (overweight: HR 0.70; 95% CI 0.61-0.81, P < 0.0001 and obesity: HR 0.54; 95% CI 0.44-0.67, P < 0.0001) and lower BMI was associated with a higher mortality risk (HR 2.23, 95% CI 1.67-2.97, P < 0.0001). CONCLUSION: A reversed relationship between BMI and all-cause mortality in AF patients was found. Higher risk of mortality was observed in underweight patients compared to patients with a normal BMI, while overweight and obese patients had a lower risk of all-cause mortality. CLINICAL TRIAL REGISTRATION: URL: http://www.chictr.org.cn/showproj.aspx?proj=5831. Unique identifier: ChiCTR-OCH-13003729.

[Characteristics of canopy stomatal conductance of Platycladus orientalis and its responses to environmental factors in the mountainous area of North China]. / åŽåŒ—å±±åŒºä¾§æŸå† å±‚æ°”å­”å¯¼åº¦ç‰¹å¾åŠå ¶å¯¹çŽ¯å¢ƒå› å­çš„å“åº”.

Canopy stomatal conductance (gs) is an important biological parameter to measure water vapor flux in canopy atmosphere interface. Exploring characteristics of canopy stomatal conductance and its responses to environmental factors can offer theoretical evidence for conducting mechanism based study of vapor exchange process in forest canopy. SF-L thermal dissipation probe was adopted to measure sap flow density (Js) of Platycladus orientalis in 2014. The environmental factors including photosynthetically active radiation (PAR), vapor pressure deficit (VPD) and air temperature (T) were simultaneously observed. The canopy stomatal conductance was calculated, and the responses of gs to environmental factors were analyzed. The results showed that the daily variation of sap flow density was of two peak pattern curve, and the Js in growing season was higher than in non-growing season. And the bigger DBH was, the higher Js would be. The daily variation of canopy stomatal conductance was similar to the canopy transpiration of per leaf area (EL), which was of two peak pattern curve. The gs and EL in growing season were higher than those in non growing season. The canopy stomatal conductance and air temperature presented parabolic relation, and gs reached peak valley at around 10 ℃. Taking the value of 400 µmol·m-2·s-1 as the PAR thre shold, when PAR was under this threshold, gs was positively correlated with PAR. When PAR was beyond this threshold, the correlation between gs and PAR would be small. The relationship between canopy stomatal conductance and vapor pressure deficit was negative logarithmic function. As VPD increasing, gs decreased gradually. Higher air temperature and photosynthetically active radiation, and lower vapor pressure deficit contributed to higher canopy stomatal conductance of P. orientalis and could promote greater canopy transpiration.

[Influences of shallow groundwater on sap flow of riparian poplar plantations in northern China.] / æµ å±‚åœ°ä¸‹æ°´å¯¹åŽåŒ—åœ°åŒºæ²³å²¸æ¨æ ‘æž—æ ‘å¹²æ¶²æµçš„å½±å“.

Water use strategy in growing seasons plays a great role in the management of riparian poplar plantations in northern China. The research was conducted on a poplar (Populus × euramericana cv. '74/76') plantation located near the floodplain of Chaobai River in the northeastern su-burb of Beijing. The influencing factors of poplar sap flow (SF) were presented based on the measurements on the stem SF with thermal dissipation sap flow probe (TDP), soil volumetric water content (VWC) with time-domain-reflectometer (TDR) and environmental factors with eddy cova-riance system from June to July, 2014, to explore the impact of shallow ground water on SF. The results showed that the diurnal variation of SF presented single or double peaks depending on the varia-tion of solar radiation (R). The SF density decreased in soil water relative deficient period (RDP), and the peak time advanced to 12:30 from 14:00, while the time lag between the SF density and R showed no obvious change. The solar radiation and air vapor pressure deficit were the predominant factors of SF during soil water relative sufficient period (RSP), while soil water became the limiting factor in RDP. During the RDP, the daily water consumption of individual poplar tree was significantly negatively correlated with soil VWC at the depth of 100 cm, and significantly positively correlated with soil VWC of the other depths. The shallow ground water (at the depth of ≥150 cm where the soil water content showed little change) might move to the upper soil layer controlled by the capillary force and supply for poplar growth during the soil water-relatively deficient period.

Synthesis of a new cyclosporine-based stationary phase and separation behaviors toward aromatic positional isomers by high-performance liquid chromatography.

A new cyclosporine-bonded stationary phase has been synthesized through the Staudinger reaction between azido cyclosporine A (CsA) and aminopropyl silica gel and applied in separations of six disubstituted aromatic analytes by high-performance liquid chromatography. For dimethyl phthalate, nitroaniline and chloronitrobenzene, their positional isomers were well-separated on this CsA stationary phase, in which the separation factor for m-/o-dimethyl phthalates was the biggest. For nitrotoluene, dichlorobenzene and benzenediol, the m-/o-isomers were co-eluted. Then, effects of chromatographic conditions (such as types and content of alcoholic modifiers) on separation of nitroaniline positional isomers have been investigated. Retention behaviors of nitroaniline isomers on the column exhibited the strengthening trend along with increasing carbon number of alcohols, from ethanol to 1-propanol, and to 1-butanol. A similar phenomenon was observed by lowering the content of alcohol.

Comparative HPLC enantioseparation on substituted phenylcarbamoylated cyclodextrin chiral stationary phases and mobile phase effects.

Two new cyclodextrin-derived chiral stationary phases with multiple urea linkages were prepared through the Staudinger reactions between aminopropyl silica gel and cyclodextrin derivatives, namely, heptakis(6-azido-6-deoxy-2,3-di-O-3,5-dimethylphenylcarbamoylated)-ß-cyclodextrin and heptakis(6-azido-6-deoxy-2,3-di-O-3,5-dichlorophenylcarbamoylated)-ß-cyclodextrin, respectively. HPLC separation behaviors toward 46 chiral analytes have been investigated under multimodal elution. They exhibited good separation performances for these analytes and also showed some complimentary enantioselectivity to each other, due to different electron-donating (methyl)/withdrawing (chlorine) groups in the phenylcarbamate moieties. Among these analytes, aromatic alcohols and N-(2,4-dinitrophenyl)-derived carboxylic acids were better resolved on the π-basic chiral stationary phase than the π-acidic. The proton pump inhibitors, the 5-hydroxytryptamine receptor antagonists, and the analytes with carbonyl groups easily formed stereoselective interactions with the π-acidic chiral stationary phase, further leading to better enantioseparation. Elution order reversal for palonosetron and N-(2,4-dinitrophenyl) glutamine was observed in three chiral stationary phases, probably induced by the difference of phenylcarbamate groups. Moreover, mobile phase effects on retention behaviors of analytes have been studied in detail.