No evidence for a causal link between Helicobacter pylori infection and Irritable bowel syndrome: a Mendelian randomization study.

Background: Although clinical studies have revealed a potential link between Helicobacter pylori (H. pylori) infection and irritable bowel syndrome (IBS), the causal relationship between them remains unknown. The objective of this study was to investigate whether H. pylori infection is causally associated with IBS. Method: A two-sample Mendelian randomization (MR) analysis using the inverse variance weighted (IVW), weighted mode, weighted median and MR-Egger methods was performed. We used the publicly available summary statistics data sets of genome-wide association studies (GWAS) for H. pylori infection in individuals of European descent (case = 1,058, control = 3,625) as the exposure and a GWAS for non-cancer illness code self-reported: IBS (case = 10,939, control = 451,994) as the outcome. Results: We selected 10 single nucleotide polymorphisms at genome-wide significance from GWASs on H. pylori infection as the instrumental variables. The IVW, weighted mode, weighted median and MR-Egger methods all provided consistent evidence that suggests a lack of causal association between H. pylori and IBS. MR-Egger regression revealed that directional pleiotropy was unlikely to be biasing the result (intercept = -1e-04; P = 0.831). Cochran's Q-test and the funnel plot indicated no evidence of heterogeneity and asymmetry, indicating no directional pleiotropy. Conclusion: The results of MR analysis support that H. pylori infection may not be causally associated with an increased risk of IBS.

Deubiquitinating enzyme 4 facilitates chemoresistance in glioblastoma by inhibiting P53 activity.

Glioblastoma is a malignant primary brain tumor with poor prognosis with a median survival of only 12-15 months. The high mortality rate of this disease is mainly due to the chemoresistance resulting from various reasons. Ubiquitin-specific protease 4 (USP4) has recently been found to be elevated in various types of cancer through regulating P53 activity. However, whether USP4 is responsible for chemoresistance in glioblastoma is not clear. In the present study, the expression of USP4 in glioblastoma tissues and cell lines, as well as its association with temozolomide (TMZ) chemoresistance was analyzed. The results demonstrated that USP4 was significantly upregulated in glioblastoma tissues and cell lines at the mRNA and protein levels. Notably, USP4 knockdown alone did not affect glioblastoma cell viability; however, when USP4 knockdown cells were treated with TMZ, the cell viability was decreased significantly. In addition, the results revealed that cleaved poly(ADP-ribose) polymerase level increased when USP4 was knocked down in glioblastoma cells treated with TMZ. It was also observed that P53 was increased in U251 and U87 cells with USP4 knockdown. Following treatment with a P53 specific inhibitor, the results suggested that USP4 mediated chemoresistance through inhibiting apoptosis in a P53-dependent manner. In conclusion, the data revealed the critical role of USP4 in TMZ resistance in glioblastoma and provided new insight for future drug development for the treatment of this disease.

A pilot study of neuromuscular electrical stimulation for neuropathic pain caused by spinal cord injury.

This pilot study retrospectively investigated the feasible effect and safety of neuromuscular electrical stimulation (NMES) for the management of neuropathic pain (NPP) caused by spinal cord injury (SCI).A total of 54 patient cases with NPP after SCI were included. Of these, 27 cases underwent carbamazepine plus NMES treatment, and were assigned to an NMES group; while the other 27 cases received carbamazepine only, and were assigned to a control group. The primary outcome of pain intensity was measured by numerical rating scale (NRS). The secondary outcome of quality of life was measured by the Short Form 36 (SF-36) Scale. Furthermore, adverse events were also documented in this study. All outcomes were measured and analyzed before and after 3-month treatment.After 3-month treatment, the cases in the NMES group neither reduced the pain intensity of NPP, measured by the NRS (P > .05), nor improved the quality of life, measured by the SF-36 (P > .05), compared with cases in the control group. Moreover, both groups had similar adverse events.The results of this study showed that NMES might be not efficacious for NPP caused by SCI after 3 months treatment with quite low intervention dose.

Immunohistochemical detection of E7 human papillomavirus protein in pre­malignant and malignant lesions of the uterine cervix.

Human papillomavirus (HPV) E7 protein expression is caused by HPV viral DNA integration into human cellular DNA, and is a prerequisite for the development and progression of cervical cancer. The present study aimed to evaluate the role of E7 protein as a biomarker for identification of transformed cervical epithelial cells during the early stages of cervical cancer. Specific monoclonal antibodies to the E7 protein of high­risk HPVs were generated and characterized for applications in immunocytochemistry and immunohistochemistry using cervical epithelial cells or biopsy tissue slides. The specificity and feasibility for detecting precancerous cells in cervical exfoliated epithelial cells was demonstrated. In addition, antibody staining of cervix biopsies indicated the pathological grades of cervical cancer and precancerous lesions. The results of the present study demonstrated the potential benefit of using E7 protein as a novel and specific clinical diagnostic marker to distinguish transient HPV infections from malignant and pre­malignant lesions.