Decreased expression of claudin-18.2 in alpha-fetoprotein-producing gastric cancer compared to conventional gastric cancer

BackgroundAlpha-fetoprotein-producing gastric cancer (AFPGC) is a subtype of gastric cancer (GC) with more aggressive biological behavior. As a highly specific tight junction component exclusively present in gastric mucosa and gastric adenocarcinomas, claudin-18.2 (CLDN18.2) has become an emerging target in GC. In this study, we aimed to provide insight into AFPGC and investigate the expression and the clinical implications of CLDN18.2 in AFPGC.MethodsWe retrospectively collected 98 cases of AFPGC and reviewed their clinical, morphological, and immunohistochemical features. Another 356 patients with stage-matched conventional GC (cGC) were enrolled as a control group. We further surveyed CLDN18.2 expression by immunohistochemistry (IHC) in 51 AFPGC tissues and explained its association with the clinicopathological parameters of AFPGC.ResultsOur results showed that AFPGC was a unique GC type with elevated serum alpha-fetoprotein (AFP), which was a predictor of a worse prognosis. AFPGC showed typical morphological features and positive staining of at least 1 hepatocytic or enteroblastic marker. The expression rate of CLDN18.2 was low, with a positivity rate of 21.6%, which was much lower than that observed in cGC tissues (38.5%). A significant correlation was found between CLDN18.2 expression and the differentiation of AFPGC. CLDN18.2 expression was negatively correlated with the serum AFP level of AFPGC. We also found that AFPGC with a hepatoid type (HPT) component showed a significantly lower CLDN18.2 expression than those without.ConclusionsThis study demonstrated that CLDN18.2 was significantly decreased in AFPGC and was negatively correlated with the patient’s preoperative serum AFP level. The negative correlation between AFP and CLDN18.2 could be explained by retro-differentiation of AFPGC. Special treatment strategies might be needed for this unique tumor type.     

Development and evaluation of time‐resolved fluorescent immunochromatographic assay for quantitative detection of SARS‐CoV‐2 spike antigen

BackgroundThe spread of COVID‐19 worldwide caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has necessitated efficient, sensitive diagnostic methods to identify infected people. We report on the development of a rapid 15‐minute time‐resolved fluorescent (TRF) lateral flow immunochromatographic assay for the quantitative detection of the SARS‐CoV‐2 spike protein receptor‐binding domain (S1‐RBD).ObjectivesOur objective was to develop an efficient method of detecting SARS‐CoV‐2 within 15 min of sample collection.MethodsWe constructed and evaluated a portable, disposable lateral flow device, which detected the S1‐RBD protein directly in nasopharyngeal swab samples. The device emits a fluorescent signal in the presence of S1‐RBD, which can be captured by an automated TRF instrument.ResultsThe TRF lateral flow assay signal was linear from 0 to 20 ng/ml and demonstrated high accuracy and reproducibility. When evaluated with clinical nasopharyngeal swabs, the assay was performed at >80% sensitivity, >84% specificity, and > 82% accuracy for detection of the S1‐RBD antigen.ConclusionThe new S1‐RBD antigen test is a rapid (15 min), sensitive, and specific assay that requires minimal sample preparation. Critically, the assay correlated closely with PCR‐based methodology in nasopharyngeal swab samples, showing that the detected S1‐RBD antigen levels correlate with SARS‐CoV‐2 virus load. Therefore, the new TRF lateral flow test for S1‐RBD has potential application in point‐of‐care settings.     

Increasing nodal vulnerability and nodal efficiency implied recovery time prolonging in patients with supplementary motor area syndrome

Supplementary motor area (SMA) syndrome is a surgery‐related complication that commonly occurs after removing SMA glioma, and needs weeks to recover. However, susceptible factors of patients suffering from SMA syndrome remain unknown. Graphic theory was applied to reveal topological properties of sensorimotor network (SMN) by processing resting‐state functional magnetic resonance images in 66 patients with SMA gliomas. Patients were classified into SMA and non‐SMA groups based on whether they suffered from SMA syndrome. We collected recovery time and used causal mediation analysis to find association between topological properties and recovery time. Compared with the non‐SMA group, higher vulnerability (left: p = .0018; right: p = .0033) and lower fault tolerance (left: p = .0022; right: p = .0248) of the whole SMN were found in the SMA group. Moreover, higher nodal properties of lesional‐hemispheric cingulate cortex (nodal efficiency: left, p = .0389; right, p = .0169; nodal vulnerability: left, p = .0185; right, p = .0085) and upper limb region of primary motor cortex (PMC; nodal efficiency: left, p = .0132; right, p = .0001; nodal vulnerability: left, p = .0091; right, p = .0209) were found in the SMA group. Nodal efficiency and nodal vulnerability of cingulate cortex and upper limb region of PMC were important predictors for SMA syndrome occurring and recovery time prolonging. Neurosurgeons should carefully deal with upper limb region of PMC and cingulate cortex, and protect them if these two region were unnecessary to damage during SMA glioma resection.     

疏血通注射液治疗缺血性脑卒中78例

目的 评价疏血通注射液治疗缺血性脑卒中的疗效。方法 将137例缺血性脑卒中患者分为两组，治疗组78例，对照组59例，均予阿司匹林、银杏叶注射液及基础治疗，治疗组加用疏血通8mL静脉滴注，1次／d，分别于治疗前及治疗后第7，14，21天时对患者进行欧洲卒中量表（ESS）评分、日常生活活动能力评定量表（ADL）及常规检查。结果 治疗后第14，21天时，两组ESS及ADL评分有显著差异（P〈0．05）。结论 疏血通能明显改善缺血性脑卒中的预后，且不增加缺血性卒中后出血的风险。     

Awareness of and compliance with recommended dietary supplement among age-related macular degeneration patients

BACKGROUND: The age-related eye disease study suggested that taking zinc and anti-oxidants supplements could reduce the progression of age-related macular degeneration (AMD). In Australia, the available supplement is Macu-Vision. The study aimed to assess the awareness of and compliance with taking this supplement and the public health implication. METHODS: The fundus photograph database of patients aged 55 years and older at the ophthalmology department of a public teaching hospital in Adelaide, Australia was reviewed. In total, 125 patients with category 3 and 4 AMD were identified. A total of 100 patients participated in this cross-sectional study. RESULTS: In total, 53% of participants were aware of the availability of the formulae available in Australia, 38% were taking the supplement and only 1% were taking the correct dose. Of those taking the supplement 95% (36/38) were taking half the recommended dosage. Among those who were aware of the supplement but not taking it, cost was the most common reason (31%). Another 31% were not taking it because of actual side-effects experienced, fear of potential side-effect and/or fear of interaction with other medications. There was no predictive factor for failing to take the formulae available in Australia among age, sex, smoking status, living arrangement and category of AMD. CONCLUSIONS: Clinicians need to emphasize that the recommended dosage is twice that on the supplement label. If the trend demonstrated here of underutilizing the formulae available in Australia among public hospital patients continues, it is unlikely to have any major public health impact in similar settings in Australia.     

麦门冬汤加减治疗特发性肺间质纤维化32例临床观察

笔者自2001年9月～2007年5月采用麦门冬汤加减治疗特发性肺间质纤维化32例,并与西药治疗的16例对比观察,获效满意,现报道如下.     

不同方法治疗围绝经期及绝经后妇女抑郁症的疗效分析

目的 探讨抗抑郁药物及性激素治疗围绝经期及绝经后妇女抑郁症的临床效果.方法 采用汉米尔顿抑郁量表(HRSD)及自评抑郁量表(SDS)对86例围绝经期及绝经后抑郁症妇女进行抑郁症程度评价,然后随机分为2组,每组43例.对照组应用抗抑郁药物,其中轻、中度(29例)患者应用氟哌噻吨美利曲辛(其他名称:黛力新)1～2片/d;重度患者(14例)应用盐酸氟西汀(其他名称:百忧解)20 mg/d;性激素治疗(HRT)组(轻、中度31例,重度12例)应用替勃龙1.25 mg/d.入选者每4周随访1次,共计12周.结果 (1)有效率:对照组轻、中度抑郁症患者,治疗总有效率为96%;HRT组治疗总有效率为93%.两组比较,差异无统计学意义(P＞0.05).重度抑郁症的治疗有效率对照组为93%,HRT组为42%,两组比较,差异有统计学意义(P＜0.01).(2)HRSD评分:轻、中度抑郁症患者用药前、用药第4、8、12周时,对照组分别为(26.8±5.7)、(10.7±3.6)、(6.4±3.6)、(3.5±2.5)分;HRT组分别为(25.3±4.7)、(15.2±5.3)、(11.4±4.4)、(4.4±3.8)分.两组内治疗后各时间点HRSD评分与治疗前比较,差异均有统计学意义(P＜0.01);对照组与HRT组用药前及用药第12周时HRSD评分比较,差异无统计学意义(P＞0.05).重度抑郁症患者用药前、用药第4、8、12周时,HRSD评分对照组分别为(37.6±5.6)、(21.4±5.2)、(14.2±4.2)、(7.3±2.3)分;HRT组分别为(38.2±4.8)、(32.6±5.4)、(28.2±4.6)、(24.3±4.5)分.对照组内治疗后各时间点比较,差异有统计学意义(P＜0.01),HRT组用药前与用药第12周比较,差异也有统计学意义(P＜0.05).两组用药后各时间点HRSD评分比较,差异有统计学意义(P＜0.01).(3)SDS评分:对照组轻、中、重度患者用药前与用药第4、8、12周各时间点SDS评分比较,差异均有统计学意义(P＜0.01).HRT组轻、中度患者用药前与用药第4、8、12周各时间点SDS评分比较,差异也有统计学意义(P＜0.01);HRT组重度抑郁症患者用药前与用药第12周比较,差异有统计学意义(P＜0.05).在重度抑郁症患者中,对照组用药后HRSD、SDS评分与HRT组比较,明显降低,差异有统计学意义(P＜0.01).结论 HRT可用于治疗围绝经期及绝经后轻、中度抑郁症,对于重度抑郁症患者,抗抑郁药物的治疗效果优于性激素.     

Novel immune‐related signature based on immune cells for predicting prognosis and immunotherapy response in clear cell renal cell carcinoma

BackgroundClear cell renal cell carcinoma (ccRCC) is the most common malignant tumor of the kidney and is characterized by poor prognosis. We sought to build an immune‐related prognostic signature and investigate its relationship with immunotherapy response in ccRCC.MethodsImmune‐related genes were identified by ssGSEA and WGCNA. The prognostic signature was conducted via univariate, least absolute shrinkage and selection operator, and multivariable Cox regression analyses. Kaplan‐Meier analysis, PCA, t‐SNE, and ROC were used to evaluate the risk model.ResultsA total of 119 immune‐related genes associated with prognosis were screened out. Six immune‐related genes (CSF1, CD5L, AIM2, TIMP3, IRF6, and HHLA2) were applied to construct a prognostic signature for KIRC. Kaplan–Meier analysis showed that patients in high‐risk group had a poorer survival outcome than in low‐risk group. The 1‐, 3‐ and 5‐year AUC of the prognostic signature was 0.754, 0.715, and 0.739, respectively. Univariate and multivariate Cox regression models demonstrated that the risk signature was an independent prognostic factor for KIRC survival. GSEA analysis suggested that the high‐risk group was concentrated on immune‐related pathways. The high‐risk group with more regulatory T‐cell infiltration showed a higher expression of immune negative regulation genes. The risk score had positively relationship with TIDE score and negatively with the response of immunotherapy. The IC50 values of axitinib, sunitinib, sorafenib, and temsirolimus were lower in the high‐risk group.ConclusionOur study defined a robust signature that may be promising for predicting clinical outcomes and immunotherapy and targeted therapy response in ccRCC patients.     

Comparative analysis of transient receptor potential channel 5 opposite strand-induced gene expression patterns and protein-protein interactions in triple-negative breast cancer

In patients with triple-negative breast cancer (TNBC), high tumour mutation burden and aberrant oncogene expression profiles are some of the causes of poor prognosis. Therefore, it is necessary to identify aberrantly expressed oncogenes, since they have the potential to serve as therapeutic targets. Transient receptor potential channel 5 opposite strand (TRPC5OS) has been previously shown to function as a novel tumour inducer. However, the underlying mechanism of TRPC5OS function in TNBC remain to be elucidated. Therefore, in the present study TRPC5OS expression was first measured in tissue samples of patients with TNBC and a panel of breast cancer cell lines (ZR-75-1, MDA-MB-453, SK-BR-3, JIMT-1, BT474 and HCC1937) by using qRT-PCR and Western blotting. Subsequently, the possible effects of TRPC5OS on MDA-MB-231 cells proliferation were determined using Cell Counting Kit-8 and 5-Ethynyl-2′-deoxyuridine assays after Lentiviral transfection of MDA-MB-231. In addition, potential interaction partners of TRPC5OS were explored using liquid chromatography-mass spectrometry (LC-MS)/MS. Gene expression patterns following TRPC5OS overexpression were also detected in MDA-MB-231 cells by using High-throughput sequencing. Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) analysis were then used to systematically verify the potential interactions among the TRPC5OS-regulated genes. The potential relationship between TRPC5OS-interacting proteins and gene expression patterns were studied using Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) analysis. TRPC5OS expression was found to be significantly higher in TNBC tumour tissues and breast cancer cell lines compared with luminal tumour tissues and ZR-75-1. In addition, the overexpression of TRPC5OS significantly increased cell proliferation. High-throughput sequencing results revealed that 5,256 genes exhibited differential expression following TRPC5OS overexpression, including 3,269 upregulated genes and 1,987 downregulated genes. GO analysis results indicated that the functions of these differentially expressed genes were enriched in the categories of ‘cell division’ and ‘cell proliferation’ regulation. KEGG analysis showed that the TRPC5OS-regulated genes were associated with processes of ‘homologous recombination’ and ‘TNF signalling pathways’. Subsequently, 17 TRPC5OS-interacting proteins were found using LC-MS/MS and STRING analysis. The most important protein among interacting proteins was ENO1 which was associated with glycolysis and regulated proliferation of cancer. In summary, data from the present study suggest that TRPC5OS overexpression can increase TNBC cell proliferation and ENO1 may be a potential target protein mediated by TRPC5OS. Therefore, TRPC5OS may serve as a novel therapeutic target for TNBC.