Objective:To construct a prognostic model across multiple cancer types based on exhausted T cell(Tex)gene sets and to identify novel Tex cell markers.Methods:A pan-cancer single-cell dataset of CD8+T cells was utilized to identify the pan-cancer Tex gene set.Differential expression analysis and Cox regression analysis of TCGA data were performed to screen pan-cancer prognostic genes.These genes were then intersected with the Tex gene set,yielding a pan-cancer Tex prognostic gene set.Cox regression analysis was used to construct a pan-cancer prognostic model,and the model's performance was evaluated using Kaplan-Meier survival curve and receiver operating characteristic(ROC)curve analyses.In addition,correlation analysis was further applied to explore the role of TNFRSF18 in immunotherapy.Results:Cox regression analysis identified CXCL13,CDKN2A,TNFRSF18,and IL2RA as key prognostic genes,on which the prognostic model was constructed.Survival analysis showed that patients in the low-risk group exhibited significantly higher survival rates across various cancer types(P<0.05).Single-cell data analysis demonstrated that TNFRSF18 was specifically expressed in Tex cells and was significantly upregulated in tumor samples from various cancers(P<0.05).Conclusion:The pan-cancer Tex cell-based prognostic model showed robust predictive performance across various cancers.TNFRSF18 may function as a novel potential biomarker of Tex cells and play a role in cancer immunotherapy.

ObjectiveTo clone the gene of Marmota himalayana type ‍Ⅰ interferon receptor β subunit （mhIFNAR2）， and to perform antibody preparation and functional identification. MethodsRT-PCR was used for amplification in the spleen tissue of Marmota himalayana to obtain the sequence， which was cloned to the prokaryotic expression vector pRSET-B to express the recombinant protein. Electrophoresis and Western blot were used for identification. BALB/c mice were immunized with the recombinant protein to prepare the polyclonal antibody of its extracellular domain； immunohistochemistry， immunofluorescence assay， and Western Blot were used for identification， and the method of siRNA blockade was used to investigate its function. An analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for comparison between two groups. ResultsA fragment of mhIFNAR2 （149‍ ‍—‍ ‍1 ‍300 bp） was obtained from spleen tissue， which showed the highest homology of 98.05% in marmot. A prokaryotic expression plasmid was successfully constructed for expression of the extracellular domain of the mhIFNAR2_{（50-181aa）} and was named pRSET-B.mhIFNAR2， and the recombinant protein expressed by this plasmid had a molecular weight of 27 kD， a purity of about 95% after purification， and a concentration of 160 μg/mL. After BALB/c mice were immunized with the purified recombinant protein， 1∶1 000 specific polyclonal antibodies were obtained， and immunohistochemistry and immunofluorescence assay showed the expression in cell membrane and cytoplasm. Among the three siRNAs synthesized， the siRNA starting from the 277 locus （siRNA277） could silence the expression of target genes and weaken the interferon signaling pathway compared with the blank control group and the negative control group （both P<0.05）. ConclusionThe fragment of mhIFNAR2 is obtained， and the polyclonal antibody for the extracellular domain of mhIFNAR2 is successfully prepared， with relatively high titer and specificity， and can be used for immunohistochemistry， immunofluorescence assay， and Western blot.

Existing antidepressant treatments are generally suboptimal for patients with bipolar disorder(BD).Several studies have explored the efficacy of light therapy(LT)in patients with bipolar depression,along with investigating parameters,devices,and safety aspects of LT.This paper provides a review of these aspects.Numerous meta-analyses and randomized controlled trials have indicated that LT could significantly improve depressive symptoms in BD patients,with both low and high intensity white light having this effect,while the antidepressant effect of blue light remains unclear.LT takes effect rapidly,preferably in the morning,with each session lasting between 30 to 60 minutes,but there is no consensus on the most beneficial LT course for BD patients.The most commonly used device for LT is a lightbox.However further exploration is need regarding the safety of LT glasses.When LT devices that meet safety standards is selected,the overall safety of LT will be high and risk of manic or hypomanic switch will be low for BD patients.In conclusion,LT holds promise for patients with bipolar depression,and further research on LT for BD patients should be conducted to explore LT strategies and develop LT prescriptions.

OBJECTIVE: To investigate the correlation between the severity of obstructive sleep apnea syndrome (OSAS) and red cell distribution width (RDW) in elderly patients. METHODS: A cross-sectional study was conducted among 311 elderly patients diagnosed with OSAS in the snoring clinic between January, 2015 and October, 2016 and 120 healthy controls without OSAS from physical examination populations in the General Hospital of PLA. The subjects were divided into control group with apnea-hypopnea index (AHI) <5 (=120), mild OSAS group (AHI of 5.0-14.9; =90), moderate OSAS group (AHI of 15.0-29.9; =113) and severe OSAS group (AHI ≥ 30; =108). The clinical characteristics and the results of polysomnography, routine blood tests and biochemical tests of the subjects were collected. Multiple linear regression analysis was used to examine the correlation between OSAS severity and RDW. RESULTS: The levels of RDW and triglyceride were significantly higher in severe OSAS group than in the other groups ( < 0.01). The levels of fasting blood glucose and body mass index were significantly higher in severe and moderate OSAS groups than in mild OSAS group and control group ( < 0.05 or < 0.01). Multiple linear regression analysis showed that AHI was positively correlated with body mass index (β=0.111, =0.032) and RDW (β=0.106, =0.029). The area under ROC curve of RDW for predicting the severity of OSAS was 0.687 (=0.0001). CONCLUSIONS The RDW increases as OSAS worsens and may serve as a potential marker for evaluating the severity of OSAS.
Aged ; Cross-Sectional Studies ; Erythrocyte Indices ; Humans ; Polysomnography ; Severity of Illness Index ; Sleep Apnea, Obstructive

OBJECTIVE: To evaluate the changes of cardiac structure and function and their risk factors in elderly patients with obstructive sleep apnea syndrome (OSA) without cardiovascular complications. METHODS: Eighty-two elderly OSA patients without cardiovascular disease admitted between January, 2015 and October, 2016 were enrolled in this study. According to their apnea-hypopnea index (AHI, calculated as the average number of episodes of apnoea and hypopnoea per hour of sleep), the patients were divided into mild OSA group (AHI < 15) and moderate to severe OSA group (AHI ≥ 15). The demographic data and the general clinical data were recorded and fasting blood samples were collected from the patients on the next morning following polysomnographic monitoring for blood cell analysis and biochemical examination. Echocardiography was performed within one week after overnight polysomnography, and the cardiac structure, cardiac function and biochemical indexes were compared between the two groups. RESULTS: Compared with those with mild OSA group, the patients with moderate to severe OSA had significantly higher hematocrit (0.22±0.08 CONCLUSIONS Cardiac diastolic function impairment may occur in elderly patients with moderate or severe OSA who do not have hypertension or other cardiovascular diseases, and the severity of the impairment is positively correlated with AHI.
Aged ; Cardiovascular Diseases/etiology* ; Humans ; Risk Factors ; Severity of Illness Index ; Sleep Apnea, Obstructive/complications* ; Stroke Volume ; Ventricular Dysfunction, Left ; Ventricular Function, Left

To prepare and characterize Pluronic-PEI micelles as a drug/gene delivery system.We used the low-molecular-weight PEI as a cross-linking agent to prepare the Pluronic-PEI micelles. The particle size, zeta potential and critical micelle concentration (CMC) were measured by dynamic light scattering (DLS) and pyrene fluorescence probe. The cytotoxicity, transfection efficiency and the impact on the intracellular ATP and P-gp levels of Pluronic-PEI micelles were investigated at the cellular level.Pluronic-PEI micelles were successfully prepared with a suitable particle size (120-180 nm), zeta potential (+6-+9 mv), and a good ability to carry the drug/gene. Anstudy showed that Pluronic-PEI had low cytotoxicity, and the P123-PEI600 possessed high gene transfection efficiency and could downregulate the intracellular ATP and P-gp levels.Pluronic-PEI is a good drug/gene delivery system, and P123-PEI600 is an ideal vector, which may be used in the combination therapy for reversing multidrug resistance.

Objective To investigate whether myocardial perfusion impairment and left ventricular (LV) longituadinal systolic dysfunction had happened in patients with coronary slow flow(CSF),and to assess the relationship between them by myocardial contrast echocardiography(MCE) and speckle tracking imaging(STI).Methods A total of 55 patients underwent coronary angiography for angina were enrolled,of those 35 with coronary slow flow phenomenon as CSF group,20 patients with normal coronary angiography as control group.STI and MCE were performed from the apical 4-,3 and 2 chamber views at baseline and after low-dose dobutamine stress echocardiography (LDDSE) in CSF group and control group.STI derived LV global longitudinal strain(GLS) and GLS amplitude of variation(△GLS),and MCE derived myocardial blood flow(MBF),and myocardial flow reserve (MFR) were obtained.And the correlation between GLS/△GLS and MBF/MFR was analyzed.Results At baseline,the GLS and MBF were similar between CSF group and control group(P ＞0.05).After LDDSE,both GLS and MBF were significantly increased in two groups (P ＜0.05).The GLS,△GLS,MBF,and MFR in CSF group were significantly lower than those in control group(P ＜0.05).There was no significant correlation between GLS and MBF at baseline in the CSF group(r =-0.274,P =0.111).However,after LDDSE significant correlation existed between GLS and MBF(r =-0.630,P =0.000).Conclusions LV longituadinal systolic function is impaired in patients with CSF under dobutamine stress test,the impairment of MBF and MFR could be an important contributor to the decrease of LV longituadinal systolic function.

Objective To study the impact of human urinary kallidinogenase (HUK) on collateral circulation and blood perfusion in patients with acute cerebral ischemia (ACI) using multi-modality CT methods. Methods In a randomized controlled clinical trial, 75 patients diagnosed with ACI were enrolled and divided into experiment group (treated with HUK)and control group (untreated with HUK). All participants underwent computer technology perfusion (CTP) and computed tomographic angiography (CTA) examination before and fourteenth day after treatment. The CT cerebral perfusion imaging (CTP), CT cerebrovascular imaging (CTA) and National Institutes of Health Stroke Scale (NIHSS) score were analyzed in two groups. The NIHSS score, cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), and time to peak (TTP) were compared between the two groups before and after 14 days therapy. Results ① After treatment, The two group showed increased CBF and CBV values and decreased MTT and TTP values. The CBF improvement was significantly better in the HUK-treated group than in the control group (t=2.470,P<0.05).②MTT and TTP were shorter in the HUK-treated group than in the control group (t=2.126, t=2.213, P<0.05).③ CTA maximum intensity projection (MIP) sequence revealed that the number of patients collateral vessels was significantly increased in the HUK-treated group than in the control group ( x2=4.265, P<0.05). ④The NIHSS score improvement was significantly better in the HUK-treated group after 14 days treatment than in the control group (t=4.330, P<0.05). Conclusion Human urinary kallidinogenase can improve blood perfusion and ameliorates neurological deficits. It is a safe and effective drug for treating ACI patients. The multi-modality CT methods are effective measure to assess blood perfusion and collateral circulation in patients with acute cerebral ischemia.

Objective:To prepare and characterize Pluronic-PEI micelles as a drug/ gene delivery system.Methods:The low-molecular-weight PEI was used as a cross-linking agent to prepare Pluronic-PEI micelles.The particle size,zeta potential and critical micelle concentration (CMC) were measured by dynamic light scattering (DLS) and pyrene fluorescence probe.The cytotoxicity,transfection efficiency and the impact on the intracellular ATP and P-gp levels of Pluronic-PEI micelles were investigated at the cellular level.Results:Pluronic-PEI micelles were successfully prepared with a suitable particle size (120-180 nm),zeta potential (+ 6-+ 9 mV),and a good ability to carry the drug/gene.An in-vitro study showed that Pluronic-PEI had low cytotoxicity,and the P123-PEI600 possessed high gene transfection efficiency and could downregulate the intracellular ATP and P-gp levels.Conclusion:Pluronic-PEI is a good drug/gene delivery system,and P123-PEI600 is an ideal vector,which may be used in the combination therapy for reversing multidrug resistance.

OBJECTIVE: To investigate the risk factors associated with early miscarriage among intrauterine singleton pregnancies after treatment with in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI).
 METHODS: A retrospective case-control study was performed on all singleton pregnancies underwent IVF/ICSI from January, 2013 to May, 2014, in Xiangya Hospital. Ninety-six early miscarriage patients served as a case group and 593 pregnancies with live birth served as a control group. We analyzed factors for early miscarriage after IVF/ICSI in two groups.
 RESULTS: Multivariate logistic regression analysis demonstrated that the women age, miscarriage history, and sperm DAN fragmentation index (DFI) were the risk factors for early miscarriage (P<0.05).
 CONCLUSION Miscarriage after treatment with IVF/ICSI is affected by multiple factors. Women at elder age (>30 years old), women with a history of miscarriage or men with higher sperm DFI (≥15%) are the risk.
Abortion, Spontaneous ; Case-Control Studies ; Female ; Fertilization in Vitro ; Humans ; Male ; Pregnancy ; Retrospective Studies ; Risk Factors ; Sperm Injections, Intracytoplasmic ; Spermatozoa