基于网络药理学和临床试验探讨前列消汤对ⅢA型前列腺炎IL-17与Foxp3表达影响研究＊

目的 基于网络药理学进行前列消汤治疗慢性前列腺炎的预测，同时采用临床试验进行验证，证明前列消汤对ⅢA型前列腺炎患者的临床疗效及对前列腺液（Expressed Prostatic Secretion， EPS）中白细胞介素17（interleukin 17， IL-17）及双头叉转录因子p3（Forkhead box p3， Foxp3）表达的影响。方法 采用网络信息学分析方法，筛选出前列消汤在ⅢA型前列腺炎治疗中发挥疗效的主要作用靶点，采用临床随机非盲法，将符合纳入标准的80例ⅢA型前列腺炎湿热下注证患者随机分为观察组和对照组各40例，观察组口服自拟前列消汤，对照组口服银花泌炎灵片。观察治疗前后两组的症状及证候评分情况、前列腺按摩液以及其IL17、Foxp3表达的差异。取40例正常男性前列腺液为正常对照。结果 网络药理学分析结果提示IL17信号通路为前列消汤治疗慢性前列腺炎的重要通路之一，临床试验结果提示经治疗后观察组有效率达89.19%，较对照组的73.68%为优（P < 0.05）。两组患者服药后的临床表现、前列腺按摩液WBC、症状及证候评分均存在明显改善。观察组和对照组IL-17水平较治疗前下降，Foxp3表达较治疗前升高（P < 0.05）。观察组对降低IL-17表达和提升Foxp3表达上较对照组差异更大（P < 0.05）。观察组治疗后与正常组IL-17和Foxp3水平比较差异较小（P > 0.05）。结论 网络药理学能一定程度上预测中药作用于疾病的相应靶点，前列消汤对ⅢA型前列腺炎湿热下注证患者的临床症状有明显改善作用，并能降低IL-17表达，对Foxp3表达有提升作用，在总有效率和对细胞因子的影响上较银花泌炎灵片组明显。     

Factors Associated with Hepatitis B Surface Antigen Kinetics and Responses in Pegylated Interferon Alpha-2a Monotherapy for Patients with Chronic Hepatitis B

Objective Pegylated-interferon monotherapy is the standard treatment for patients with chronic hepatitis B; however, the factors associated with its therapeutic effects remain unclear. Methods Patients with chronic hepatitis B were treated with pegylated interferon α-2a for 48 weeks. We evaluated the kinetics of hepatitis B surface antigen (HBsAg) during treatment and follow-up periods and the factors associated with an HBsAg response (defined as a change in HBsAg of ≥-1 log IU/mL from baseline). Results The study population comprised 50 patients. The median baseline levels of hepatitis B virus DNA and HBsAg were 5.00 and 3.40 log IU/mL. The median values of HBsAg reduction from baseline were -0.44 (n=48), -0.41 (n=40), and -0.68 (n=11) log IU/mL at the end of treatment and at 48 and 144 weeks post-treatment, respectively. The rates of HBsAg response were 24.0% and 22.5% at the end of treatment and at 48 weeks post-treatment, respectively. A multivariate analysis identified HBsAg <3.00 log IU/mL as an independent baseline factor contributing to the HBsAg response at the end of treatment and 48 weeks post-treatment (p=1.07×10^-2 and 4.42×10^-2, respectively). There were significant differences in the reduction of the HBsAg levels at 12 weeks of treatment and in the incidence of serum ALT increase during treatment between patients with and without an HBsAg response. Conclusion These findings suggest that the baseline HBsAg level, HBsAg kinetics at 12 weeks of treatment, and ALT increase during treatment are important factors contributing to the HBsAg response in pegylated interferon α-2a monotherapy for patients with chronic hepatitis B.     

Defining the dimensions of circulating tumor cells in a large series of breast,prostate, colon,and bladder cancer patients

Circulating tumor cells (CTCs) in the blood of cancer patients are of high clinical relevance. Since detection and isolation of CTCs often rely on cell dimensions, knowledge of their size is key. We analyzed the median CTC size in a large cohort of breast (BC), prostate (PC), colorectal (CRC), and bladder (BLC) cancer patients. Images of patient‐derived CTCs acquired on cartridges of the FDA‐cleared CellSearch^® method were retrospectively collected and automatically re‐analyzed using the accept software package. The median CTC diameter (μm) was computed per tumor type. The size differences between the different tumor types and references (tumor cell lines and leukocytes) were nonparametrically tested. A total of 1962 CellSearch^® cartridges containing 71 612 CTCs were included. In BC, the median computed diameter (CD) of patient‐derived CTCs was 12.4 μm vs 18.4 μm for cultured cell line cells. For PC, CDs were 10.3 μm for CTCs vs 20.7 μm for cultured cell line cells. CDs for CTCs of CRC and BLC were 7.5 μm and 8.6 μm, respectively. Finally, leukocytes were 9.4 μm. CTC size differed statistically significantly between the four tumor types and between CTCs and the reference data. CTC size differences between tumor types are striking and CTCs are smaller than cell line tumor cells, whose size is often used as reference when developing CTC analysis methods. Based on our data, we suggest that the size of CTCs matters and should be kept in mind when designing and optimizing size‐based isolation methods.

Abbreviations

ACCEPT

Automated CTC Classification, Enumeration, and PhenoTyping software

BC

breast cancer

BLC

bladder cancer

CD

computed diameter

CEL

cultured tumor cell (cell line)

CK

cytokeratin

CRC

colorectal cancer

CTC‐L

circulating tumor cells derived from cerebrospinal fluid (liquor)

CTCs

circulating tumor cells

DAPI

4′6‐diamidino‐2‐phenylindole

EMT

epithelial–mesenchymal transition

EpCAM

epithelial cell adhesion molecule

IQR

interquartile range

KW test

Kruskal–Wallis test

MWU test

Mann–Whitney U test

NCR

nucleus/cytoplasm ratio

P2A

perimeter to area

PC

prostate cancer

TIF

tagged Image Format files

TXT

text file

μm

micrometer

µm²

square micrometers

     

两种保留自主神经D3根治术治疗中低位直肠癌的安全性及生存质量比较

目的比较腹腔镜保留自主神经D3根治术与开腹术治疗中低位直肠癌的安全性及生存质量差异。 方法回顾性分析2015年6月至2017年8月间84例低位直肠癌患者资料，根据手术方式不同分为腹腔镜组(n＝46)和开腹组(n＝38)，应用SPSS21.0软件完成数据分析。手术相关指标采用( ±s)表示，独立样本t检验；并发症发生率、复发率及生存率等指标采用χ²检验；P<0.05为差异有统计学意义。 结果腹腔镜组患者的手术时间长于开腹组(P<0.05)，而术中出血量、住院时间、尿管保留时间、肛门排气时间均短于开腹组(均P<0.05)。腹腔镜组术后并发症总发生率为6.5%低于开腹组的26.3%(χ²＝4.6517，P<0.05)。两组患者1年局部复发率及生存率差异均无统计学意义(均P>0.05)。腹腔镜组患者术后10 d排尿功能、术后2个月勃起功能、术后2个月射精功能均优于开腹组(均P<0.05)。 结论腹腔镜保留自主神经D3根治术治疗中低位直肠癌安全性较高，复发率及生存率与开腹术相当，并能显著提高患者的生存质量，值得推广应用。     

The utility of neuropsychological consultation in identifying medical inpatients with suspected cognitive impairment at risk for greater hospital utilization

Objective: This was a retrospective study designed to examine the relationship between inpatient neuropsychological status and future utilization costs. Methods: We completed a retrospective chart review of 280 patients admitted to a large academic medical center who were referred for bedside neuropsychological evaluation. Patients were grouped based on neuropsychological recommendation regarding level of supportive needs post-discharge (low, moderate, high). Level of support was used as a gross surrogate indicator of cognitive status in this heterogeneous sample. We also included patients who refused assessment. Outcome variables included time to readmission, number of emergency department visits, inpatient admissions, length of hospitalization, and total costs of hospitalizations, 30 days and 1 year following discharge. Results: Multivariate analysis indicated patients who refused assessment had higher inpatient service utilization (number of ED visits, number of admissions, and total cost of hospitalization) compared to those with moderate needs. Also, high needs patients had higher total cost of hospitalization at 1 year, and those with low needs used the ED more, compared to those with moderate needs. Conclusions: Our findings replicate prior studies linking refusal of neuropsychological evaluation to higher service utilization costs, and suggest a nonlinear relationship between cognitive impairment severity and future costs for medical inpatients (different groups incur different types of costs). Results preliminarily highlight the potential utility of inpatient neuropsychological assessment in identifying patients at risk for greater hospital utilization, which may allow for the development of appropriate interventions for these patients.     

Intravenous subdissociative-dose ketamine versus morphine for acute geriatric pain in the Emergency Department: A randomized controlled trial

Study objective

We compare the analgesic efficacy and safety of subdissociative intravenous-dose ketamine (SDK) versus morphine in geriatric Emergency Department (ED) patients.

Effect of carbon-rich biochar on mechanical properties of PLA-biochar composites

Agricultural biomass residues are emerged from harvesting and processing of agricultural crops. When the crop production increases, a large amount of biomass residues is produced and remained after cutting of peel, bunch, straw and stalk of crops. In this work, agricultural biomass residues (cassava rhizome, durian peel, pineapple peel and corncob) were selected as feedstock for carbon-rich biochar (CRB) production using a facile pyrolysis method. Proximate analysis and thermogravimetric analysis (TGA) were used to characterize biomass feedstock. The results showed that the percentage of fixed carbon in biomass feedstock ranged between 11.91% and 17.51%. Characteristic differences of the CRB were investigated using scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS), Fourier transform infrared spectroscopy (FTIR) and Raman spectroscopy. The carbon content in the CRB was found to significantly depend on biomass origin. Interestingly, cassava rhizome, which has a higher percentage of fixed carbon, is a superior precursor for CRB production. The study of different pyrolysis temperature indicated that the carbon content of cassava rhizome derived CRB is increased with pyrolysis temperature. The tensile properties of composite between poly(lactic acid) PLA and different types of biomass-derived CRB were investigated. PLA composite incorporated with a higher carbon content-CRB tended to exhibit improved mechanical properties. Specifically, the elastic modulus and impact energy of PLA/CRB composite specimens increased remarkably with the incorporation of CRB powder. The current research indicates that CRB prepared from agricultural biomass residues could be a sustainable material for utilization in PLA biocomposites.     

Partner Discussion as a Mediator of the Effects of Mass Media Exposure to FP on Contraceptive Use among Young Nigerians: Evidence from 3 Urban Cities

Evidence suggests that despite high knowledge of family planning (FP), unwanted pregnancies and birth rates remain high among young Nigerians. There is a critical gap in understanding the nexus between exposure to FP information and contraception practices among this population. This study aimed to fill this gap and tested a pathway of the impact of media exposure to FP messages on modern contraceptive use. Data came from a 2018 cross-sectional baseline survey of young people aged 15–24 in three urban centers in Nigeria – Lagos, Kaduna, and Kano. This was part of an impact evaluation of a television-based drama designed to improve contraceptive use among young individuals. The study was limited to 777 young men and women who were sexually active. We found evidence of the mediation effect of media exposure to FP messages on partner discussion about FP, which in turn was associated with an increased likelihood of modern contraceptive use. Contraceptive self-efficacy also had positive associations with contraception. Our study elucidated a potential pathway through which media communication programs can significantly contribute to increased modern contraceptive use and underlined the importance of providing young people in Nigeria with opportunities to learn and practice obtaining and using contraception.     

氯氮平片辅助治疗PD合并精神障碍患者的有效性及不良反应研究

目的:对氯氮平片在帕金森病(Parkinson’s disease,PD)合并精神障碍辅助治疗中的应用价值予以探讨。方法:选取50例我院2013年1月1日—2019年6月30日接诊的PD合并精神障碍患者进行研究,按照随机数表法分为对照组和观察组。对照组用多巴丝肼,观察组联合氯氮平片,对比治疗效果。结果:观察组疾病治疗总有效率96.00%(24/25)高于对照组68.00%(17/25),差异有统计学意义(P<0.05),不良反应发生率8.00%(2/25)与对照组20.00%(5/25)差异无统计学意义(P>0.05);观察组UPDRD评分、VGI-S评分和BPRS评分明显低于对照组,差异有统计学意义(P<0.05)。结论:氯氮平片辅助治疗PD合并精神障碍患者,既可提高临床疗效,也不会增加用药后不良反应,安全性高,值得推广。     

Clinicopathological analysis of immunohistochemical expression of CD47 and SIRPα in adult T-cell leukemia/lymphoma

The interaction of CD47 and signal-regulatory protein alpha (SIRPα) induces “don't eat me signal”, leading suppression of phagocytosis. This signal can affect the clinical course of malignant disease. Although CD47 and SIRPα expression are associated with clinicopathological features in several neoplasms, the investigation for adult T-cell leukemia/lymphoma (ATLL) has not been well-documented. This study aimed to declare the association between CD47 and SIRPα expression and clinicopathological features in ATLL. We performed immunostaining on 73 biopsy samples and found that CD47 is primarily expressed in tumor cells, while SIRPα is expressed in non-neoplastic stromal cells. CD47 positive cases showed significantly higher FoxP3 (P = .0232) and lower CCR4 (P = .0214). SIRPα positive cases presented significantly better overall survival than SIRPα negative cases (P = .0132). SIRPα positive cases showed significantly HLA class I (P = .0062), HLA class II (P = .0133), microenvironment PD-L1 (miPD-L1) (P = .0032), and FoxP3 (P = .0229) positivity. In univariate analysis, SIRPα expression was significantly related to prognosis (Hazard ratio [HR] 0.470; 95% confidence interval [CI] 0.253-0.870; P = .0167], although multivariate analysis did not show SIPRα as an independent prognostic factor. The expression of SIRPα on stromal cells reflects activated immune surveillance mechanism in tumor microenvironment and induce good prognosis in ATLL. More detailed studies for gene expression or genomic abnormalities will disclose clinical and biological significance of the CD47 and SIRPα in ATLL.