N6-methyladenosine modification of hypoxia-inducible factor-1α regulates Helicobacter pylori-associated gastric cancer via the PI3K/AKT pathway.

BACKGROUND: Helicobacter pylori (H. pylori) colonizes the human gastric mucosa and is implicated in the development of gastric cancer (GC). The tumor microenvironment is characterized by hypoxia, where hypoxia-inducible factor-1α (HIF-1α) plays a key role as a transcription factor, but the mechanisms underlying H. pylori-induced HIF-1α expression and carcinogenesis remain unclear. AIM: To explore the underlying mechanism of H. pylori-induced HIF-1α expression in promoting the malignant biological behavior of gastric epithelial cells (GES-1). METHODS: The study was conducted with human GES-1 cells in vitro. Relative protein levels of methyltransferase-like protein 14 (METTL14), HIF-1α, main proteins of the PI3K/AKT pathway, epithelial-mesenchymal transition (EMT) biomarkers, and invasion indicators were detected by Western blot. Relative mRNA levels of METTL14 and HIF-1α were detected by quantitative reverse transcription-polymerase chain reaction. mRNA stability was evaluated using actinomycin D, and the interaction between METTL14 and HIF-1α was confirmed by immunofluorescence staining. Cell proliferation and migration were evaluated by cell counting kit-8 assay and wound healing assay, respectively. RESULTS: H. pylori promoted HIF-1α expression and activated the PI3K/AKT pathway. Notably, METTL14 was downregulated in H. pylori-infected gastric mucosal epithelial cells and positively regulated HIF-1α expression. Functional experiments showed that the overexpression of HIF-1α or knockdown of METTL14 enhanced the activity of the PI3K/AKT pathway, thereby driving a series of malignant transformation, such as EMT and cell proliferation, migration, and invasion. By contrast, the knockdown of HIF-1α or overexpression of METTL14 had an opposite effect. CONCLUSION: H. pylori-induced underexpression of METTL14 promotes the translation of HIF-1α and accelerates tumor progression by activating the PI3K/AKT pathway. These results provide novel insights into the carcinogenesis of GC.

Epidemiological investigation on the local epidemic situation in Zhengzhou High-Tech Zone caused by SARS-CoV-2 Delta variant / 中华预防医学杂志

This study collected epidemic data of COVID-19 in Zhengzhou from January 1 to January 20 in 2022. The epidemiological characteristics of the local epidemic in Zhengzhou High-tech Zone caused by the SARS-CoV-2 Delta variant were analyzed through epidemiological survey and big data analysis, which could provide a scientific basis for the prevention and control of the Delta variant. In detail, a total of 276 close contacts and 599 secondary close contacts were found in this study. The attack rate of close contacts and secondary close contacts was 5.43% (15/276) and 0.17% (1/599), respectively. There were 10 confirmed cases associated with the chain of transmission. Among them, the attack rates in close contacts of the first, second, third, fourth and fifth generation cases were 20.00% (5/25), 17.86% (5/28), 0.72% (1/139) and 14.81% (4/27), 0 (0/57), respectively. The attack rates in close contacts after sharing rooms/beds, having meals, having neighbor contacts, sharing vehicles with the patients, having same space contacts, and having work contacts were 26.67%, 9.10%, 8.33%, 4.55%, 1.43%, and 0 respectively. Collectively, the local epidemic situation in Zhengzhou High-tech Zone has an obvious family cluster. Prevention and control work should focus on decreasing family clusters of cases and community transmission.

Predictive value of systemic immune-inflammation index (SII) for short-term prognosis in patients with sepsis complicated with acute kidney injury receiving CRRT / 中华内分泌外科杂志

Objective:To evaluate the predictive value of systemic immune inflammation index (SII) for short-term prognosis in patients with sepsis complicated with acute kidney injury who received continuous renal replacement therapy (CRRT) .Methods:From Feb. 2018 to Jan. 2022, 90 patients with sepsis complicated with acute kidney injury who received CRRT in Hangzhou Cancer Hospital were included as the research objects. According to the survival of patients within 90 days, they were grouped into a survival group of 60 cases and a death group of 30 cases. The clinical baseline data such as age, sequential organ failure assessment (SOFA) score, acute physiological function and chronic health status scoring system II (APACHE II), albumin (ALB) were recorded. Automatic blood cell analyzer was applied to detect lymphocyte count, platelet count and neutrophil count in peripheral venous blood of patients with sepsis complicated with acute kidney injury who received CRRT, and the SII was calculated; Pearson correlation analysis was performed to analyze the correlation between SII and clinical baseline data in dead patients with sepsis complicated with acute kidney injury receiving CRRT; ROC curve was drawn to analyze and compare the predictive value of SII, SOFA score and APACHEII for death in patients with sepsis complicated with acute kidney injury receiving CRRT; Kaplan-Meier curve was performed to describe the changes in patient survival; multivariate Cox regression analysis was performed to analyze the factors affecting 90-day death in patients with sepsis complicated with acute kidney injury receiving CRRT.Results:SII (2636.74), C-reactive protein (CRP) [ (92.45±29.74) mg/L], SOFA score (12.83±3.24) and APACHEII (28.30±7.51) in the death group were higher than those in the survival group [341.92, (50.24±16.13) mg/L, 10.00±3.12, 25.13±6.87], and ALB [ (2.50±0.53) g/dl] was lower than that in the survival group [ (2.79±0.61) g/dl] ( P<0.05). SII was significantly positively correlated with CRP, SOFA score and APACHEII, and significantly negatively correlated with ALB in patients with sepsis complicated with acute kidney injury who received CRRT ( P<0.05). The areas under the curve (AUC) of SII, SOFA score, and APACHEII for predicting death in patients with sepsis complicated with acute kidney injury who received CRRT were 0.936, 0.827, and 0.736, respectively, and AUC of SII prediction was greater than that of SOFA score and APACHEII ( P<0.05). The 90-day survival rate of patients with sepsis complicated with acute kidney injury who received CRRT in the high SII group (23/46, 50.00%) was lower than that in the low SII group (37/44, 84.09%) ( P<0.05). SII was an independent risk factor for death within 90 days in patients with sepsis complicated with acute kidney injury who received CRRT ( P<0.05) . Conclusion:SII can better predict the 90-day mortality risk of patients with sepsis complicated with acute kidney injury receiving CRRT, and assist clinical assessment of short-term prognosis.

New endocrine therapy with abiterone for metastatic hormone sensitive prostate cancer: a case report and literature review / 中华泌尿外科杂志

To investigate the clinical characteristics of metastatic hormone sensitive prostate cancer and explore the strategy of combination of new endocrine drugs.In April 2019, an 69-year-old man was admitted to the First People’s hospital of Changzhou with "gross hematuria" . Physical examination showed prostatic hyperplasia with an unsmooth hard surface. CT showed a mass in bladder and possible metastasis in right lung. Diagnostic TUR-Bt pathology showed prostatic acinar adenocarcinoma, and PET-CT showed malignant lesion of prostate with bladder invasion, multiple pelvic lymph node metastasis and lung metastasis. The diagnosis of mHSPC with lymphatic and lung metastasis was considered. The patient was treated with bicalutamide and then switched to goserelin plus acetate abiraterone with prednisone. Total prostate specific antigen (tPSA) decreased to 0.705 ng/ml after 1 month of ADT+ AAP treatment, and decreased to 0.007 ng/ml after 4 months, and then maintained at 0.003 ng/ml until January 2021. Serum testosterone decreased to 0ng/dl and maintained the whole follow-up period. After 3 months of treatment, the pulmonary metastasis was not obvious. Till the last follow-up at January 2021, the patient reported good quality of life with no serious adverse events. The efficacy of ADT combined with acetate abiraterone in the treatment of mHSPC with lung cancer was significant.

Role of Renin-Angiotensin System in Acute Lung Injury Caused by Viral Infection.

The renin-angiotensin system (RAS) is the most important regulatory system of electrolyte homeostasis and blood pressure and acts through angiotensin-converting enzyme (ACE)/angiotensin II (Ang II)/Ang II type 1 (AT1) receptor axis and angiotensin-converting enzyme 2 (ACE2)/angiotensin (1-7)/MAS receptor axis. RAS dysfunction is related to the occurrence and development of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) and causes a serious prognosis and even death. ALI/ARDS can be induced by various ways, one of which is viral infections, such as SARS-CoV, SARS-CoV-2, H5N1, H7N9, and EV71. This article reviews the specific mechanism on how RAS dysfunction affects ALI/ARDs caused by viral infections. SARS-CoV and SARS-CoV-2 enter the host cells by binding with ACE2. H5N1 and H7N9 avian influenza viruses reduce the ACE2 level in the body, and EV71 increases Ang II concentration. Treatment with angiotensin-converting enzyme inhibitor and angiotensin AT1 receptor blocker can alleviate ALI/ARDS symptoms. This review provides suggestions for the treatment of lung injury caused by viral infections.

Overexpression of the peanut CLAVATA1-like leucine-rich repeat receptor-like kinase AhRLK1 confers increased resistance to bacterial wilt in tobacco.

Bacterial wilt caused by Ralstonia solanacearum is a devastating disease affecting hundreds of plant species, yet the host factors remain poorly characterized. The leucine-rich repeat receptor-like kinase gene AhRLK1, characterized as CLAVATA1, was found to be up-regulated in peanut upon inoculation with R. solanacearum. The AhRLK1 protein was localized in the plasma membrane and cell wall. qPCR results showed AhRLK1 was induced in a susceptible variety but little changed in a resistant cultivar after inoculated with R. solanacearum. Hormones such as salicylic acid, abscisic acid, methyl jasmonate, and ethephon induced AhRLK1 expression. In contrast, AhRLK1 expression was down-regulated under cold and drought treatments. Transient overexpression of AhRLK1 led to a hypersensitive response (HR) in Nicotiana benthamiana. Furthermore, AhRLK1 overexpression in tobacco significantly increased the resistance to R. solanacearum. Besides, the transcripts of most representative defense responsive genes in HR and hormone signal pathways were significantly increased in the transgenic lines. EDS1 and PAD4 in the R gene signaling pathway were also up-regulated, but NDR1 was down-regulated. Accordingly, AhRLK1 may increase the defense response to R. solanacearum via HR and hormone defense signaling, in particular through the EDS1 pathway of R gene signaling. These results provide a new understanding of the CLAVATA1 function and will contribute to genetic enhancement of peanut.

Posture analysis and intervention can improve the lower limb motor function of hemiplegic stroke survivors / 中华物理医学与康复杂志

Objective To investigate the effect of the posture analysis and intervention on the lower limb motor function of hemiplegic stroke survivors. Methods Forty hospitalized stroke survivors with hemiplegia were di-vided at random into a control group and an experimental group. The control group (n＝20) received conventional re-habilitation training. The experimental group (n＝20) additionally received therapy based on posture analysis. Before the treatment and after 2 and 4 weeks of treatment, Holden walking function grading was applied, along with Fugl-Meyer motor function rating, and the timed up and go test ( TUGT) was administered. Results After 2 weeks of treatment there were no statistically significant differences between the groups in terms of any of the measures. After 4 weeks of treatment the average Holden and Fugl-Meyer scores of the experimental group were significantly better than those of the control group, though there was still no significant difference in the two groups' average TUGT times. Conclusion Posture analysis-based intervention can improve the lower limb motor function of stroke patients with hemiplegia.

Emergence and mechanism of carbapenem-resistant Escherichia coli in Henan, China, 2014.

The emergence and dissemination of carbapenem-resistant Escherichia coli (E. coli) strains is a main risk for global public health, but little is known of carbapenemase producing E. coli in Henan, China. The study was undertaken to investigate the prevalence and mechanism of carbapenem-resistant E. coli strains in a hospital in Xinxiang, Henan, China, 2014. A total of 5 carbapenemase-producing E. coli strains were screened from 1014 isolates. We found that they were all resistant to meropenem and imipenem. Amikacin showed the best sensitivity, with gentamicin coming up next. The positive rate of blaNDM was 80% (4/5). The sequencing results showed that two isolates belonged to blaNDM-1 whereas other 2 isolates carried the blaNDM-5. Other carbapenemase genes including blaIMP,blaVIM, blaKPC and blaOXA-48 were not detected. The blaCTX-M-15,blaTEM-1,sul2, aad, and aac(6")-Ib-cr were also detected. MLST analysis showed that NDM-producing E. coli were sporadic. Conjugation test indicated blaNDM could be transferred. In conclusion, the blaNDM was the principal resistance mechanism of carbapenem-resistant E. coli in the hospital, Henan, China.

Pathogenic mechanisms of the oncoprotein CagA in H. pylori-induced gastric cancer (Review).

Infection with Helicobacter pylori is the strongest risk factor for the development of chronic gastritis, gastric ulcer and gastric carcinoma. The majority of the H. pylori-infected population remains asymptomatic, and only 1% of individuals may progress to gastric cancer. The clinical outcomes caused by H. pylori infection are considered to be associated with bacterial virulence, genetic polymorphism of hosts as well as environmental factors. Most H. pylori strains possess a cytotoxin-associated gene (cag) pathogenicity island (cagPAI), encoding a 120-140 kDa CagA protein, which is the most important bacterial oncoprotein. CagA is translocated into host cells via T4SS system and affects the expression of signaling proteins in a phosphorylation-dependent and independent manner. Thus, this review summarizes the results of relevant studies, discusses the pathogenesis of CagA-mediated gastric cancer.

Role of Helicobacter pylori infection in pathogenesis of gastric carcinoma.

Gastric cancer (GC) is one of the most common carcinoma and the second leading cause of cancer-related deaths worldwide. Helicobacter pylori (H. pylori) infection causes a series of precancerous lesions like gastritis, atrophy, intestinal metaplasia and dysplasia, and is the strongest known risk factor for GC, as supported by epidemiological, preclinical and clinical studies. However, the mechanism of H. pylori developing gastric carcinoma has not been well defined. Among infected individuals, approximately 10% develop severe gastric lesions such as peptic ulcer disease, 1%-3% progresses to GC. The outcomes of H. pylori infection are determined by bacterial virulence, genetic polymorphism of hosts as well as environmental factors. It is important to gain further understanding of the pathogenesis of H. pylori infection for developing more effective treatments for this common but deadly malignancy. The recent findings on the bacterial virulence factors, effects of H. pylori on epithelial cells, genetic polymorphism of both the bacterium and its host, and the environmental factors for GC are discussed with focus on the role of H. pylori in gastric carcinogenesis in this review.

Determination of Patulin in Health Foods Containing Hawthorn by HPLC / 中国药师

Objective:To establish an HPLC method for the determination of patulin in health foods containing hawthorn to im-prove the quality control of patulin in related health foods. Methods:An Agilent TC-C18(2)(250 mm ×4.6 mm, 5 μm) column was used with the temperature of 30℃. The mobile phase consisted of 0. 8% tetrahydrofuran and the flow rate was 1. 0 ml·min-1 . The detection wavelength was set at 276nm. Results:The calibration curve of patulin was linear within the range of 1-20ng(r=1. 000 0), the average recovery was 92. 1% and RSD was 2. 2%(n=6). Conclusion:The method is simple, reliable and accurate, which can be used in the content determination of patulin in health foods containing hawthorn.

Transgenic peanut (Arachis hypogaea L.) expressing the urease subunit B gene of Helicobacter pylori.

Helicobacter pylori (H. pylori) has been identified as the main pathogenic factors of chronic gastritis and peptic ulcer, and the Class I carcinogen of gastric cancer by WHO. Vaccine has become the most effective measure to prevent and cure H. pylori infection. The UreB is the most effective and common immunogen of all strains of H. pylori and may stimulate the immunoresponse protecting the human body against the challenge of H. pylori. UreB antigen gene was cloned into the binary vector pBI121 which contains a seed-specific promoter Oleosin of peanut and a kanamycin resistance gene, and then UreB gene was transformed into peanut embryo leaflets by Agrobacter-mediated method. The putative transgenic plants were examined for the presence of UreB in the nuclear genome of peanut plants by PCR analysis. Expression of UreB gene in plants was identified by RT-PCR and Western blot analysis. These results suggest that the UreB transgenic peanut can be potentially used as an edible vaccine for controlling H. pylori.