Global Prevalence of Helicobacter pylori Infection and Incidence of Gastric Cancer Between 1980 and 2022.

BACKGROUND & AIMS: We aimed to assess the secular trend of the global prevalence of Helicobacter pylori (H pylori) infection in adults and children/adolescents and to show its relation to that of gastric cancer incidence. METHODS: We performed a systematic review and meta-analysis to calculate overall prevalence, adjusted by multivariate meta-regression analysis. The incidence rates of gastric cancer were derived from the Global Burden of Disease Study and Cancer Incidence in Five Continents. RESULTS: Of the 16,976 articles screened, 1748 articles from 111 countries were eligible for analysis. The crude global prevalence of H pylori has reduced from 52.6% (95% confidence interval [CI], 49.6%-55.6%) before 1990 to 43.9% (95% CI, 42.3%-45.5%) in adults during 2015 through 2022, but was as still as high as 35.1% (95% CI, 30.5%-40.1%) in children and adolescents during 2015 through 2022. Secular trend and multivariate regression analyses showed that the global prevalence of H pylori has declined by 15.9% (95% CI, -20.5% to -11.3%) over the last 3 decades in adults, but not in children and adolescents. Significant reduction of H pylori prevalence was observed in adults in the Western Pacific, Southeast Asian, and African regions. However, H pylori prevalence was not significantly reduced in children and adolescents in any World Health Organization regions. The incidence of gastric cancer has decreased globally and in various countries where the prevalence of H pylori infection has declined. CONCLUSIONS: The global prevalence of H pylori infection has declined during the last 3 decades in adults, but not in children and adolescents. The results raised the hypothesis that the public health drive to reduce the prevalence of H pylori as a strategy to reduce the incidence of gastric cancer in the population should be confirmed in large-scale clinical trials.

In vivo selection reveals autophagy promotes adaptation of metastatic ovarian cancer cells to abdominal microenvironment.

Peritoneal dissemination is the most frequent metastatic route of ovarian cancer. However, due to the high heterogeneity in ovarian cancer, most conventional studies lack parental tumor controls relevant to metastases and, thus, it is difficult to trace the molecular changes of cancer cells along with the selection by the abdominal microenvironment. Here, we established an in vivo mouse peritoneal dissemination scheme that allowed us to select more aggressive sublines from parental ovarian cancer cells, including A2780 and SKOV-3. Microarray and gene profiling analyses indicated that autophagy-related genes were enriched in selected malignant sublines. Detection of LC3-II, p62 and autophagic puncta demonstrated that these malignant variants were more sensitive to autophagic induction when exposed to diverse stress conditions, such as high cell density, starvation and drug treatment. As compared with parental A2780, the selected variant acquired the ability to grow better under high-density stress; however, this effect was reversed by addition of autophagic inhibitors or knockdown of ATG5. When analyzing the clinical profiles of autophagy-related genes identified to be enriched in malignant A2780 variant, 73% of them had prognostic significance for the survival of ovarian cancer patients. Taken together, our findings indicate that an increase in autophagic potency among ovarian cancer cells is crucial for selection of metastatic colonies in the abdominal microenvironment. In addition, the derived autophagic gene profile can not only predict prognosis well but can also be potentially applied to precision medicine for identifying those ovarian cancer patients suitable for taking anti-autophagy cancer drugs.

Interacting trends of colorectal cancer incidence: the combined effects of screening and birth cohort.

BACKGROUND: Colorectal cancer remains a major global public health challenge. Its incidence is shaped by a complex interplay of screening programmes and age, period and cohort factors. METHODS: We introduce a novel Age-Period-Cohort-Screening (APCS) model to analyse trends in colorectal cancer incidence in Taiwan from 2000 to 2019. RESULTS: In 2010, the incidence of colorectal cancer in Taiwan increased by 19.2% (95% CI: 13.5%, 25.3%) for men and 15.6% (95% CI: 9.2%, 22.4%) for women. This was followed by annual declines of 3.4% (95% CI: 2.8%, 4.1%) and 3.1% (95% CI: 2.4%, 3.9%), respectively. By 2015 for men and 2014 for women, the age-standardized incidence had fallen below the levels projected in a no-screening scenario. By 2019, the incidence had further declined by 12.4% (95% CI: 11.8%, 13.1%) for men and 11.6% (95% CI: 10.7%, 12.6%) for women, compared with the no-screening scenario. Cohort effects have shown a persistent rise from 1920 to 1980: incidence increased 5.8-fold for men and 3.1-fold for women. The trend began to plateau after 1980, with a noticeable decline in women. CONCLUSION: Through its screening programme, Taiwan has successfully reduced colorectal cancer incidence by 10% as of 2019. Furthermore, the incidence due to cohort effects has plateaued and even begun to decline. However, continued monitoring remains crucial. The advanced APCS model could serve as a robust analytical tool for other researchers and policy makers evaluating the impacts of cancer screening programmes on incidence trends.

Predicting readmission due to severe hyperglycemia after a hyperglycemic crisis episode.

AIM: This study aimed to investigate the readmission pattern and risk factors for patients who experienced a hyperglycemic crisis. METHODS: Patients admitted to MacKay Memorial Hospital for diabetic ketoacidosis (DKA) or hyperglycemic hyperosmolar state (HHS) between January 2016 and April 2019 were studied. The timing of the first readmission for hyperglycemia and other causes was recorded. Kaplan-Meier analysis was used to compare patients with hyperglycemia and all-cause readmissions. Cox regression was used to identify independent predictors for hyperglycemia and all-cause readmission post-discharge. RESULTS: The study cohort included 410 patients, and 15.3 % and 46.3 % of them had hyperglycemia and all-cause readmissions, respectively. The DKA and HHS group showed a similar incidence for hyperglycemia, with the latter group showing a higher incidence of all-cause readmissions. The significant predictors of hyperglycemia readmissions included young age, smoking, hypoglycemia, higher effective osmolality, and hyperthyroidism in the DKA group and higher glycated hemoglobin level in the HHS group. CONCLUSIONS: Patients who experienced DKA and HHS had similar hyperglycemia readmission rates; however, predictors in the DKA group were not applicable to the HHS group. Designing different strategies for different types of hyperglycemic crisis is necessary for preventing readmission.

Inhibition of lipopolysaccharide-induced inducible nitric oxide synthase and cyclooxygenase-2 gene expression by 5-aminoimidazole-4-carboxamide riboside is independent of AMP-activated protein kinase.

Recent studies suggest AMP-activated protein kinase (AMPK), an enzyme involved in energy homeostasis, might be a novel signaling pathway in regulating inflammatory response, but the precise intracellular mechanisms are not fully understood. In this study, we have demonstrated that 5-aminoimidazole-4-carboxamide riboside (AICAR), an activator of AMPK, inhibited lipopolysaccharide (LPS)-induced protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in macrophages and microglial cells at the gene transcription level. Data obtained from electrophoretic mobility shift assay (EMSA) and promoter activity assay have further confirmed the ability of AICAR to block LPS-mediated NF-kappaB, AP-1, CREB, and C/EBPbeta activation. However, AICAR did not affect LPS-mediated IKK, ERK, and p38 activation. Regardless of the ability of AICAR to activate AMPK, the inhibitory effects of AICAR on iNOS and COX-2 expression were not associated with AMPK. An adenosine kinase inhibitor 5'-iodotubercidin, which effectively abolished AMPK activation caused by AICAR, did not reverse the anti-inflammatory effect of AICAR. Moreover, another AMPK activator metformin was not able to mimic the effects of AICAR. Direct addition of AICAR in EMSA assay interrupted binding of NF-kappaB, CREB, and C/EBPbeta to specific DNA elements. Taken together, this study demonstrates that the anti-inflammatory effects of AICAR against LPS-induced iNOS and COX-2 gene transcription are not associated with AMPK activation, but might be resulting from the direct interference with DNA binding to transcription factors.

Surface electromyography analysis of blepharoptosis correction by transconjunctival incisions.

Upper eyelid movement depends on the antagonistic actions of orbicularis oculi muscle and levator aponeurosis. Blepharoptosis is an abnormal drooping of upper eyelid margin with the eye in primary position of gaze. Transconjunctival incisions for upper eyelid ptosis correction have been a well-developed technique. Conventional prognosis however depends on clinical observations and lacks of quantitatively analysis for the eyelid muscle controlling. This study examines the possibility of using the assessments of temporal correlation in surface electromyography (SEMG) as a quantitative description for the change of muscle controlling after operation. Eyelid SEMG was measured from patients with blepharoptosis preoperatively and postoperatively, as well as, for comparative study, from young and aged normal subjects. The data were analyzed using the detrended fluctuation analysis method. The results show that the temporal correlation of the SEMG signals can be characterized by two indices associated with the correlation properties in short and long time scales demarcated at 3ms, corresponding to the time scale of neural response. Aging causes degradation of the correlation properties at both time scales, and patient group likely possess more serious correlation degradation in long-time regime which was improved moderately by the ptosis corrections. We propose that the temporal correlation in SEMG signals may be regarded as an indicator for evaluating the performance of eyelid muscle controlling in postoperative recovery.

Synthesis and biological evaluation of geminal disulfones as HIV-1 integrase inhibitors.

Integration of HIV-1 viral DNA into the host genome is carried out by HIV-integrase (IN) and is a critical step in viral replication. Although several classes of compounds have been reported to inhibit IN in enzymatic assays, inhibition is not always correlated with antiviral activity. Moreover, potent antiviral IN inhibitors such as the chicoric acids do not act upon the intended enzymatic target but behave as entry inhibitors instead. The charged nature of the chicoric acids contributes to poor cellular uptake, and these compounds are further plagued by rapid ester hydrolysis in vivo. To address these critical deficiencies, we designed neutral, nonhydrolyzable analogues of the chicoric acids. Herein, we report the synthesis, enzyme inhibition studies, and cellular antiviral data for a series of geminal disulfones. Of the 10 compounds evaluated, 8 showed moderate to high inhibition of IN in purified enzyme assays. The purified enzyme data correlated with antiviral assays for all but two compounds, suggesting alternative modes of inhibition. Time-of-addition studies were performed on these analogues, and the results indicate that they inhibit an early stage in the replication process, perhaps entry. In contrast, the most potent member of the correlative group shows behavior consistent with IN being the cellular target.

Strontium-impregnated bioabsorbable composite for osteoporotic fracture fixation.

Osteoporosis impairs the bone-healing process as well as bone fracture fixation. The intervention of osteoporosis is considered to be one part of bone fracture treatment. Thus, orthopedic fixators impregnated with antiosteoporosis regimens will improve fracture fixation in osteoporotic bone. In this study, the strontium (Sr) and calcium phosphate ceramic (CPC) were mixed first and then mixed with poly(ε-caprolactone) (PCL) to fabricate a bioactive and bioabsorbable bone fixators. The prepared Sr-CPC/PCL screws were implanted into the distal femur of ovariectomized rabbits. The results showed that Sr-CPC/PCL composite had the appropriate mechanical properties, good biocompatibility, and radio-opacity. The Sr addition created a porous structure and accelerated the degradation of bone screws, but the degradation products did not acidify the surrounding environment. For osteoporotic animals, favorable osteointegration around the Sr-CPC/PCL screws was found, and the total porosity of trabecular bone was decreased under the inspections of micro-computerized tomography. Compared with PCL or CPC/PCL screw, animals which received Sr-CPC/PCL were found to have better results in terms of trabecular number, thickness, and separation. This study reveals that the Sr-impregnated bone fixator improves osseointegration in osteoporotic animals. Sr-CPC/PCL composite is a good candidate material for osteofixation in osteoporotic patients.