A meta-analysis of associations of IL-10 gene polymorphisms with acute leukemia susceptibility.

BACKGROUND: Recently, increasing evidence has demonstrated that IL-10 single nucleotide polymorphisms (SNPs) are associated with the risk of acute leukemia (AL), but the findings of different articles remain controversial. Thus, we performed a meta-analysis to further investigate the exact roles of IL-10 SNPs in AL susceptibility. METHODS: Six common Chinese and English databases were utilized to retrieve eligible studies. The strength of the association was assessed by calculating odds ratios and 95 % confidence intervals. All analyses were carried out using Review Manager (version 5.3) and STATA (version 15.1). The registered number of this research is CRD42022373362. RESULTS: A total of 6391 participants were enrolled in this research. The results showed that the AG genotype of rs1800896 increased AL risk in the heterozygous codominant model (AG vs. AA, OR = 1.41, 95 % CI = 1.04-1.92, P = 0.03) and overdominant model (AG vs. AA + GG, OR = 1.32, 95 % CI = 1.04-1.70, P = 0.03). In the subgroup analysis, associations between the G allele, GG genotype, AG genotype, AG + GG genotype of rs1800896 and increased AL risk were also observed in the mixed population based on allelic, homozygote codominant, heterozygous codominant, dominant, and overdominant models. Furthermore, an association between the AC genotype of rs1800872 and increased AL risk was observed in the Caucasian population in the overdominant model. However, the rs1800871, rs3024489 and rs3024493 polymorphisms did not affect AL risk. CONCLUSION: IL-10 rs1800896 and rs1800872 affected the susceptibility of AL and therefore may be biomarkers for early screening and risk prediction of AL.

Effectiveness and Safety of Histamine H2 Receptor Antagonists: An Umbrella Review of Meta-Analyses.

Histamine H2 receptor antagonists (H2RAs) were widely used to inhibit gastric acid secretion, but its association with adverse events remains controversial and unclear. We conducted an umbrella review of meta-analyses to systematically assess the quality and credibility of the correlations between H2RA use with the risk of adverse outcomes through searching 4 major databases from inception to April 30, 2022. Forty-six individual meta-analyses were identified, including 29 meta-analyses of observation studies with 32 unique outcomes and 19 meta-analyses of randomized controlled trials with 3 unique outcomes for comparing the H2RA versus non-H2RA group. A Measurement Tool to Assess Systematic Reviews 2 rating for the included meta-analyses showed that 4 of 46 meta-analyses were assigned as high scores, 3 were assigned as "moderate," and 25 were assigned as low scores. Grading of Recommendations Assessment, Development and Evaluation assessment for combined results demonstrated that 6 outcomes were rated as "moderate," 9 outcomes were rated as "low," and 17 outcomes were rated as "very low." We confirmed significant associations of H2RA use with pneumonia, peritonitis, necrotizing enterocolitis, Clostridium difficile infection, liver cancer, gastric cancer, and hip fracture diseases. No associations for colorectal cancer, melanoma, kidney cancer, lung cancer, or common reproductive system cancer or renal, neurological, and cardiovascular system diseases were observed. We found a variety of evidence for the associations between H2RAs and adverse outcomes, which would give clinicians more positive guidance on prescription of H2RAs in clinical practice.

Cardiovascular effects associated with chimeric antigen receptor T cell therapy in cancer patients: A meta-analysis.

Background: Although numerous studies confirmed the marked efficacy of chimeric antigen receptor T cells (CAR-T cells) in many hematologic malignancies, severe cardiovascular toxicities remain to be a major obstacle when incorporating this technology. Furthermore, previous individual investigations regarding the cardiovascular toxicities of CAR-T cell therapy also reported controversial conclusions. Therefore, a meta-analysis was performed to further evaluate the impacts of CAR-T cell therapy on cardiovascular toxicities. Methods: The PubMed, Embase, Web of Science, and ClinicalTrials.gov databases were searched for eligible studies up to April 2022. All analyses were carried out using the R 4.1.0 software. Results: Eventually, 25 related studies consisting of 2,059 patients were enrolled in the current meta-analysis. We discovered that the pooled incidence rate of the all-cause mortality rate was 14.1% and that the pooled incidence rates of overall cardiovascular (CV) events and CV events with cytokine release syndrome (CRS) grade ≥ 2 were 25.6% and 14.2%, respectively. The pooled incidence of hypotension was 28.6%. Further analysis showed that the incidence rates of arrhythmias, cardiovascular dysfunction, heart failure (HF), CV deaths, acute coronary syndrome (ACS), cardiomyopathy, cardiac arrest, and other CV events were 19.2%, 8.0%, 5.3%, 1.8%, 2.5%, 2.9%, 1.3%, and 1.9%, respectively. Conclusion: Cancer patients treated with CAR-T cell therapy were at risk for cardiovascular toxicities, of which the most common cardiovascular events were arrhythmias, cardiovascular dysfunction, and heart failure. These findings would contribute to achieving more rational and individualized use of CAR-T cells in clinical treatment.

Synthesis of esters of ginsenoside metabolite M1 and their cytotoxicity on MGC80-3 cells.

Monoesters of ginsenoside metabolite M1 at the 3-OH, 4-OH and 6-OH positions of the glucose moiety at M1 were synthesized via the reaction of M1 with acyl chloride, or acid-N,N'-diisopropylcarbodiimide in the presence of DMAP. Their structures were fully characterized by spectral methods. The cytotoxicity of these compounds against then MGC80-3 human gastric cancer cell line was also assessed. High inhibitory effects were found at a concentration of 100 µg/mL.

Pathological significance of epidermal growth factor receptor expression and amplification in human gliomas.

AIMS: To investigate epidermal growth factor receptor (EGFR) expression and amplification in gliomas and to assess their association with survival. METHODS AND RESULTS: Immunohistochemistry and fluorescence in-situ hybridization were performed to analyse EGFR status in 158 cases of primary glioma. Kaplan-Meier survival and Cox regression analyses were performed to analyse the prognosis of patients. Overexpression of EGFR and expression of EGFR variant III (EGFRvIII) were found in 102 cases (64.6%) and 47 cases (29.7%), respectively. Overexpression of EGFR was significantly correlated with World Health Organization (WHO) grade and Karnofsky performance score (KPS) (both P < 0.05). Expression of EGFRvIII was significantly correlated with WHO grade, gender, age, and KPS (all P < 0.05). EGFR amplification was found in 46 cases (29.1%), and was significantly correlated with WHO grade, age, KPS and EGFR overexpression (all P < 0.05). Cox multifactor analysis showed that EGFR amplification was an independent unfavourable prognostic factor for human gliomas at all ages, and EGFRvIII was an independent prognostic factor in patients older than 60 years. CONCLUSION: EGFR amplification and EGFRvIII expression were associated with an unfavourable prognosis for patients of all ages, and for those older than 60 years, respectively. The differing significance of EGFR status in young and old glioma patients and its impact on prognosis needs further study.

Correlation of epidermal growth factor receptor overexpression with increased epidermal growth factor receptor gene copy number in esophageal squamous cell carcinomas.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most frequent malignancies in China and epidermal growth factor receptor (EGFR) is widely distributed in human epithelial cell membrane. The aim of this study was to investigate the protein overexpression and gene copy number of EGFR in ESCC, and help to identify patients who may benefit from EGFR targeted therapies. METHODS: Immunohistochemistry (IHC) was performed to analyze the expression of EGFR in 105 cases of ESCC, 16 cases of squamous epithelial atypical hyperplasia, and 11 cases of normal esophageal tissue. Fluorescence in situ hybridization (FISH) was performed to analyze the gene copy number in 80 cases of ESCC, eight cases of squamous epithelial atypical hyperplasia, and eight samples of normal esophageal tissue. RESULTS: The IHC-positive rates of EGFR in 105 cases of ESCC, 16 cases of squamous epithelial atypical hyperplasia, and 11 normal esophageal tissues were 97% (102/105), 44% (7/16), and 18% (2/11) respectively. The difference in the expression of EGFR among different esophageal tissue groups had statistically significance (P < 0.05). Among the 105 cases of ESCC, overexpression of EGFR was found in 90 cases (86%), of which 55 cases scored 3+ for EGFR staining and 35 cases scored 2+. In ESCC, the expression of EGFR was significantly correlated with depth of invasion and TNM stage (P < 0.05), but not with other parameters. The FISH-positive rates of EGFR in 80 cases of ESCC, the eight cases of squamous epithelial atypical hyperplasia, and eight samples of normal esophageal tissue were 31.3% (25/80), 0 (0/8) and 0 (0/8) respectively. In ESCC, EGFR gene amplification was found in 17 (21%) cases, high polysomy in 8 (10%) cases, disomy in 34 cases, low trisomy in 17 cases, and high trisomy in four cases. EGFR FISH-positive was significantly correlated with depth of invasion and lymph node metastasis (P < 0.05). EGFR FISH-positive was significantly associated with overexpression of EGFR. CONCLUSION: Protein overexpression and/or increased gene copy number of EGFR is common in ESCC, and EGFR targeted therapy may be appropriate for ESCC patients.

miR-29a and miR-142-3p downregulation and diagnostic implication in human acute myeloid leukemia.

Expression profiling of microRNAs (miRNAs) in most diseases might be popular and provide the possibility for diagnostic implication, but few studies have accurately quantified the expression level of dysregulated miRNAs in acute myeloid leukemia (AML). In this study, we analyzed the peripheral blood mononuclear cells (PBMCs) from 10 AML patients (subtypes M1 to M5) and six normal controls by miRNA microarray and identified several differentially expressed miRNAs. Among them miR-29a and miR-142-3p were selectively encountered in Northern blot analysis and their significantly decreased expression in AML was further confirmed. Quantitative real-time PCR in 52 primarily diagnosed AML patients and 100 normal controls not only verified the expression properties of these 2 miRNAs, but also established that the expression level of miR-142-3p and miR-29a in PBMCs could be used as novel diagnostic markers. A better diagnostic outcome was achieved by combining miR-29a and miR-142-3p with about 90% sensitivity, 100% specificity, and an area under the ROC curve (AUC) of 0.97. Our results provide insights into the involvement of miRNAs in leukemogenesis, and offer candidates for AML diagnosis and therapeutic strategy.

The targeted gene (KDRP-CD/TK) therapy of breast cancer mediated by SonoVue and ultrasound irradiation in vitro.

Suicide gene therapy has become an effective therapy for breast cancer, and ultrasound targeted microbubble destruction (UTMD) has become a popular topic in the gene therapy field. In this study, MCF-7 cells with the KDR promoter and LSl74T cells without the KDR promoter were transfected with the recombinant plasmid pEGFP-KDRP-CD/TK using UTMD. The recombinant plasmid pEGFP-KDRP-CD/TK was transfected into MCF-7 and LS174T cells successfully with no significant difference in transfection efficiency (p>0.05). By RT-PCR, the CD/TK fusion gene was shown to be expressed in MCF-7 cells but not expressed in LS174T cells. In a cytotoxicity experiment, transgenic MCF-7 cells were sensitive to the prodrugs 5-FC and GCV. When both 5-FC and GCV were administered, the rate of cellular inhibition was significantly greater than that achieved when only one of the prodrugs was administered (p<0.001). Moreover, the inhibition rates achieved administering 5-FC, GCV and both 5-FC and GCV were all significantly greater than the gene transfection rate of 21.92±3.64% (p<0.001). However, transgenic LS174T cells were not sensitive to any prodrug. These results demonstrated that UTMD is a safe, effective and targeted gene delivery system. Also, the KDR promoter can drive expression of the CD/TK double suicide gene target in MCF-7 cells, and the targeted killing effect of the KDRP-CD/TK gene on MCF-7 cells in vitro has good synergy with expression of the CD/TK fusion gene.

The influence of blood supply on high intensity focused ultrasound a preliminary study on rabbit hepatic VX2 tumors of different ages.

RATIONALE AND OBJECTIVES: The aim of this study was to explore the effects of blood supply on high-intensity focused ultrasound (HIFU) applied to rabbit hepatic VX2 tumors of different ages. MATERIALS AND METHODS: Eighteen rabbits with VX2 hepatic tumors were randomly divided into three groups according to the time of sacrifice after tumor implantation: 10, 15, or 20 days. Contrast-enhanced ultrasound was performed immediately before HIFU ablation. The same settings for HIFU dose parameters were used to ablate the central tumor area in each group, and the real-time temperature of the targeted site of the tumor was measured. After HIFU, the coagulation necrosis volumes of tumor tissue and the microvascular density of residual tumor tissue were determined. RESULTS: Histopathologic analysis showed that the extent of a tumor's blood supply followed the order 10-day group > 15-day group > 20-day group (P < .01). Contrast-enhanced ultrasound showed the same results. There was no statistically significant difference among the three groups in terms of temperature-increase parameters during HIFU treatment (P > .05). However, there were statistically significant differences between the groups in terms of temperature-decrease parameters during HIFU treatment and in terms of necrosis volumes after HIFU treatment (P < .05). Necrosis volume was inversely related to absolute enhanced intensity (r = -0.823, P < .001). CONCLUSIONS: The extent of a tumor's blood supply had a significant effect on the temperature-decrease phase but not on the temperature-increase phase during HIFU treatment. The longer the temperature-decrease phase, the more slowly heat dissipated after HIFU, resulting in larger coagulation necrosis volumes.

Enhanced lymph node retrieval from colorectal cancer resections using a simple lymphatic staining method.

BACKGROUND/AIMS: This study evaluated the effect of lymphatic staining on the number of lymph nodes (LNs) examined and staging in patients with colorectal cancer. METHODOLOGY: Sixty-two consecutive specimens from patients with colorectal cancer resected between February 2009 and April 2010 were randomized to the stained group or the control unstained. Differences in the retrieval, number and size of nodes, and time for retrieval were measured. RESULTS: LN harvest differed significantly with 30±12 and 13±5 (p<0.01) nodes in the stained and the control groups, respectively. Insufficient LN harvest (less than 12 nodes) occurred in 14 cases of the control group and only in 1 case of the stained group (p<0.01). Metastases were confirmed in 57 LNs occurring in 17 cases of the stained group and in 39 nodes occurring in 15 cases of the control group. The mean time for LN retrieval in the stained and control groups were comparable, 27.6±6.9min and 24.7±6.0min (p>0.05), respectively, yet there was a significant difference in the number of LNs (<2mm) (294 vs. 59, respectively, p<0.01) as well as in the number of LNs 2-5mm in size (474 vs. 220, respectively, p<0.01). CONCLUSIONS: By lymphatic staining method, more and smaller LNs could be detected, which significantly improved the LN harvest of resected colorectal specimens and reduced cases of insufficient LN harvest.

[Gastrointestinal adenocarcinomas with a micropapillary pattern: a clinicopathologic and immunohistochemical study].

OBJECTIVE: To study the clinicopathologic features and immunophenotype of gastrointestinal adenocarcinomas with a micropapillary pattern differentiation (GAMPD). METHODS: Seventy-three cases of GAMPD arising in gastrointestinal tract were retrospectively reviewed. Immunohistochemical study for epithelial membrane antigen (EMA), insulin-like growth factor II mRNA-binding protein-3 (IMP3) and E-cadherin was performed. RESULTS: Amongst the 73 cases studied, the micropapillary pattern accounted for 5% to 70% of the tumor component. It was often seen in a background of moderately differentiated adenocarcinoma. As compared with conventional adenocarcinoma, nodal metastasis was more frequently observed and the TNM tumor stage was statistically higher in GAMPD. The occurrence of micropapillary component in metastatic lymph nodes positively correlated with the proportion of micropapillary pattern in primary lesions. EMA staining on the stroma-facing surface of tumor micropapillae was demonstrated in 52.1% (38/73) of the cases. As compared with EMA-negative GAMPD, EMA-positive GAMPD was more in the stomach (P = 0.018), and with more metastatic lymph nodes (6.6 ± 5.8 vs 3.8 ± 4.7, P = 0.029). The rate of IMP3 expression in EMA-positive GAMPD was 86.8%(33/38), which was higher than that in conventional adenocarcinoma. In contrast, the rate of E-cadherin expression in GAMPD was lower than that in conventional adenocarcinoma. CONCLUSIONS: GAMPD is a distinctive variant of gastrointestinal adenocarcinomas and different from conventional adenocarcinoma in tumor morphology, immunophenotype and biologic behavior. It carries an aggressive clinical course and poor prognostic outcome. Immunohistochemical study for EMA, IMP3 and E-cadherin would be helpful in the diagnosis and prognostic evaluation of GAMPD.

Primary diffuse large B-cell lymphoma of the seminal vesicles: ultrasonography and computed tomography findings.

Primary tumors of the seminal vesicle are very rare. We reported a 35-year-old man with a rare primary diffuse large B-cell lymphoma of the seminal vesicles. By transrectal ultrasound (TRUS) imaging, ultrasonic elastography (UE), and computed tomography (CT) imaging, the tumor was defined to locate in seminal vesicles. By TRUS-guided biopsy and histopathological examinations, the patient was diagnosed with large B-cell lymphoma. To our knowledge, this finding has not been reported before. We present the ultrasound and CT appearances of a case of large B-cell lymphoma of the seminal vesicles.

[Diagnosis and treatment of parathyroid carcinoma: 9 cases report and literature review].

OBJECTIVE: To investigate the diagnosis and surgical treatment of parathyroid carcinoma. METHODS: The clinical data of 9 cases of parathyroid carcinoma treated from January 1967 to December 2009 was analyzed retrospectively with the review of related Chinese literatures. RESULTS: Parathyroid carcinoma accounted for 8.9% (8/90) of all patients with primary hyperparathyroidism in our hospital, and the other one case was transferred from another hospital. Of the patients, 8 cases were found with primary hyperparathyroidism. Primary surgery was carried out with small incision: 5 patients underwent en bloc resection, among which, 3 cases received central lymph node dissection; 2 patients received simple parathyroidectomy; one case underwent palliative tumor resection. The case from another hospital received subtotal thyroidectomy. Considering preoperative, intraoperative data and frozen sections pathology, all patients were diagnosed as parathyroid carcinoma. Nine patients were followed-up for 1 - 14 years, no recurrence occurred, and the patient received palliative resection died from carcinoma two years after the operation. In previous Chinese literatures and this group, there were total 146 patients reported as parathyroid carcinoma. Those patients were diagnosed through routine histopathology, accounted for 1.8% - 11.5% of patients with primary hyperparathyroidism. CONCLUSIONS: The diagnosis of parathyroid carcinoma is established according to severe hypercalcemia, clinical features, subset B-ultrasound and Tc(99m)-sestamibi scanning, intraoperative finding of adherence to close structures and histopathology. The initial surgical procedure of choice is en bloc resection of the tumor by minimally invasive small incision, including adjacent structures and ipsilateral thyroidectomy. The prognosis is favorable after the operation.

[Expression of BRG1 and BRM proteins in prostatic cancer].

OBJECTIVE: To study the effect of BRG1 and BRM, the catalytic subunits expressed by SWI/SNF, in benign and malignant prostatic tissues and to correlate the BRG1/BRM expression with the development and progression of prostatic cancer. METHODS: The expression levels of the BRG1 and BRM proteins in benign and malignant prostatic tissues were studied using semi-quantitative immunohisto-chemistry. The results correlated with various clinical and pathologic parameters. RESULTS: The average immuno-reactive score for BRG1 expression in prostatic cancer tissues was significantly higher than that in benign prostatic tissues (57+/-9.8 and 19+/-4.1, respectively, P = 0.000 17). The difference was more obvious in the high-grade cancer. On the other hand, BRM expression exhibited a heterogeneous pattern. The average immuno-reactive score for BRM expression was lower in cancer tissues than in benign tissues (112+/-17 and 151+/-19, respectively, P = 0.0047). BRG1 and BRM demonstrated a reciprocal expression pattern in benign and malignant tissues. The average immuno-reactive score for BRG1 expression was higher in the cancer cases with a larger tumor volume than in the cases with a smaller tumor volume (P = 0.0112). CONCLUSIONS: The expression of BRG1 and BRM correlates with the development of prostatic cancer. Increased BRG1 expression may have certain implications in tumor progression.

Detection of plasmid-mediated IMP-1 metallo-beta-lactamase and quinolone resistance determinants in an ertapenem-resistant Enterobacter cloacae isolate.

OBJECTIVE: To investigate the mechanism of carbapenem resistance and the occurrence of plasmid-mediated quinolone resistance determinants qnr and aac(6')-Ib-cr in a clinical isolate of Enterobacter cloacae. METHODS: An ertapenem-resistant E. cloacae ZY106, which was isolated from liquor puris of a female gastric cancer patient in a Chinese hospital, was investigated. Antibiotic susceptibilities were determined by agar dilution method. Conjugation experiments, isoelectric focusing, polymerase chain reaction (PCR), and DNA sequence analyses of plasmid-mediated carbapenemases and quinolone resistance determinants were preformed to confirm the genotype. Outer membrane proteins (OMPs) were examined by urea-sodium dodecyl sulfate-polyacrylamide gel electrophoresis (Urea-SDS-PAGE). RESULTS: Minimum inhibitory concentrations (MICs) of imipenem, meropenem, and ertapenem for ZY106 were 2, 4, and 16 microg/ml, respectively. Conjugation studies with Escherichia coli resulted in the transfer of significantly reduced carbapenem susceptibility. ZY106 produced IMP-1 metallo-beta-lactamase and CTX-M-3 extended-spectrum beta-lactamase, and E. coli transconjugant produced IMP-1. Plasmid-mediated quinolone resistance determinant qnrS1 was detected in ZY106. Transfer of the qnrS1-encoding-plasmid into E. coli by conjugation resulted in intermediate resistance to ciprofloxacin in E. coli transconjugant. Urea-SDS-PAGE analysis of OMPs showed that ZY106 lacked an OMP of approximately 38 kDa. CONCLUSION: It is the first IMP-1-producing Enterobacteriaceae in China and the first report of a clinical isolate that harbors both blaIMP and qnrS genes as well. The blaIMP-1, blaCTX-M-3, and qnrS1 are encoded at three different plasmids. IMP-1 combined with the loss of an OMP possibly resulted in ertapenem resistance and reduced imipenem and meropenem susceptibility in E. cloacae.

A case of primary malignant fibrous histiocytoma of the pancreas: CT and MRI findings.

Primary malignant fibrous histiocytoma (MFH) of the pancreas is rare and a distinct clinical entity. We report a case of recurrence of pancreatic MFH with computed tomography (CT) and magnetic resonance imaging (MRI) findings. A 67-year-old man presented with a history of decreased body weight over the past 6 mo. Abdominal CT revealed a large, multilocular cystic mass in the head of the pancreas with obvious atrophy in the body and tail of the pancreas. After 6 mo postoperatively, MRI demonstrated a recurrent large mass in the primary area of the head of the pancreas. The lesion was heterogeneous, hypointense to the liver on T1-weighted imaging, and heterogeneously hyperintense to the liver with a hypointense area in the central part of the tumor on fat-saturated T2-weighted imaging. Contrast-enhanced T1-weighted imaging demonstrated a large multilocular cystic mass with a cystic wall, fibrous septa and enhancement of solid components. To the best of our knowledge, this is the first report on recurrence of primary MFH of the pancreas, and the first with MRI findings.