Adverse events of vonoprazan in the treatments of acid-related diseases: a systematic review and meta-analysis.

BACKGROUND AND AIMS: vonoprazan, a novel potassium-competitive acid blocking agent, has better clinical outcomes in the treatment of acid-related diseases. However, some adverse events have been associated with vonoprazan for the treatment of acid-associated diseases. Therefore, this systematic review and meta-analysis aimed to explore the safety and tolerability of vonoprazan for acid-associated diseases. METHODS: electronic databases were retrieved to determine randomized controlled trials (RCTs) of vonoprazan for acid-associated diseases with any adverse effects and discontinuation. RESULTS: this systematic review and meta-analysis conforming to the selection criteria included 18 RCTs with a total of 7,932 participants. Compared with proton pump inhibitors, oral vonoprazan treatment showed no significant increase in the incidence of adverse effects (95 % CI = 0.987-1.095, p = 0.141). Diarrhea or loose stools analysis showed that there was a statistically significant difference between vonoprazan and proton pump inhibitors (PPIs) treatment (95 % CI = 0.661-0.966, p = 0.021). However, there was no significant difference in constipation, rash or eruption, nausea or vomiting, bloating or abdominal pain, dysgeusia, nasopharyngitis, neurological disorders, upper respiratory tract infection and abnormal investigations between vonoprazan and PPIs treatment. CONCLUSION: vonoprazan, which has better tolerability and safety, may significantly decrease diarrhea and loose stools in acid-related patients compared with PPIs. Our meta-analysis led to safer strategies for treating acid-related diseases. More high-quality studies with larger sample sizes are needed to further elucidate its efficacy and safety.

Metal-free, oxidative decarboxylation of aryldifluoroacetic acid with the formation of the ArS-CF2 bond.

A metal-free, oxidative decarboxylative reaction of aryldifluoroacetic acids with diaryl disulfides or thiols under mild reaction conditions has been developed. This is an efficient and straightforward radical cross-coupling method for the synthesis of diverse aryldifluoromethylthio ethers in moderate to excellent yields.

Visible-light mediated stereospecific C(sp2)-H difluoroalkylation of (Z)-aldoximes.

A visible light mediated stereospecific C(sp2)-H difluoroalkylation of (Z)-aldoximes to (E)-difluoroalkylated ketoximes has been described. In this reaction, (hetero)-aromatic and aliphatic difluoroalkylated ketoximes could be obtained with the retention of the configuration of the starting aldoximes. A preliminary mechanism study showed that a difluoromethyl radical via an SET pathway was involved.

Diffuse panbronchiolitis: A case report from a Chinese consanguineous marriage family and literature review.

Diffuse panbronchiolitis (DPB) is a chronic diffuse airway inflammatory disease, which is strongly associated with the class I human leukocyte antigen (HLA) alleles. Here, we report a pair of sisters who have been suffering from chronic cough, expectoration and wheezing for many years. They were previously misdiagnosed as chronic bronchitis and bronchial asthma, and were recently diagnosed as diffuse panbronchiolitis. The 36-year-old elder sister suffered from diffuse panbronchiolitis complicated with pulmonary tuberculosis. The 30-year-old younger sister suffered from diffuse panbronchiolitis complicated with bronchial asthma and bronchiectasis. We have performed HLA genotyping research on the two sisters, their parents and younger brother. The results showed that all family members were positive for HLA-A24 and HLA-B13. The younger sister and mother were positive for HLA-A2. The younger brother and father were positive for HLA-A11. We suspect that the two sisters' disease susceptibility may be caused by their parents' consanguineous marriage. In this study, we reported the clinical characteristics of the two sisters with diffuse panbronchiolitis and shared the associated HLA genotyping results of this family cluster, hoping to provide reference for the etiology, diagnosis and treatment of this disease.

Comparative Analysis of 95 Patients with Different Severity in the Early Outbreak of COVID-19 in Wuhan, China.

OBJECTIVE: To explore the clinical characteristics of patients with different severity in the early outbreak of COVID-19, hoping to provide reference for clinical diagnosis and treatment. METHODS: We retrospectively analyzed the clinical data of 95 COVID-19 patients in Wuhan Red Cross Hospital of China from January 17 to February 13, 2020. All patients were investigated with epidemiological questionnaires. Outcomes were followed up until April 1, 2020. RESULTS: There were 53 males and 42 females, aged 22-84 years (mean 57.3 years). Clinical classification included 54 cases of common type, 27 cases of severe type, and 14 cases of critical type. Six patients had been exposed to the local Huanan seafood market. There were 38 clusters of COVID-19, including 27 family clusters and 11 work unit clusters. Common symptoms included fever (86 (90.5%) of 95), cough (73 (76.8%)), and fatigue (50 (52.6%)). Laboratory findings showed that the most common abnormalities were lymphopenia (75 (78.9%)), elevated D-dimer (60 (63.2%)), and elevated C-reactive protein (56 (58.9%)) on admission. All patients had abnormal chest computed tomography, showing patchy shadows or ground-glass opacities. Severe and critical cases were older, more likely to have shortness of breath, more likely to have underlying comorbidities, and more likely to have abnormal laboratory findings than common cases. The prognosis of patients with different degrees of severity was significantly different. All common and severe patients (100%) were cured and discharged from the hospital, while 10 (71.4%) of 14 critical patients died. CONCLUSIONS: COVID-19 has fast transmission speed and high pathogenicity. We must assess the severity of the disease and take corresponding treatment measures as early as possible.

Aspirin use improves the biochemical control of prostate cancer in Chinese men.

PURPOSE: Aspirin may improve treatment outcomes and increase the survival of patients with prostate cancer, but the results remain controversial. METHODS: This study consisted of 483 patients who underwent radical prostatectomy for localized prostate cancer, 231 of whom were in the aspirin group. The associations between aspirin use and freedom from biochemical failure (FFBF), overall survival (OS) and relative factors were evaluated. RESULTS: Multivariate analysis showed that aspirin therapy, T classification, Gleason score (GS), and prostate-specific antigen (PSA) were associated with biochemical failure. The aspirin group had a significantly better FFBF rate (91.1%) at 5 years than the control group (82.3%, p=0.000). Among patients with high-risk disease, the FFBF rate for patients in the aspirin group was 79.1% at 5 years compared to 52.2% in the control group (p=0.000). CONCLUSIONS: We demonstrate that the use of aspirin may be beneficial for the biochemical control of prostate cancer. The mechanism of the antineoplastic effect of aspirin is not fully understood. Further clinical trials and large-scale studies will be necessary to confirm the relationship between aspirin use and prostate cancer risk.

The association between smoking and blood pressure in men: a cross-sectional study.

BACKGROUND: Cigarette smoking is a known risk factor for cardiovascular disease (CVD), but the association between smoking and blood pressure is unclear. Thus, the current study examined the association between cigarette smoking and blood pressure in men. METHODS: Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and pulse pressure (PP) were examined using digital blood pressure measuring device, and smoking status was determined with China National Health Survey. RESULTS: The ANCOVA showed that the adjusted DBP and MAP were lower in current smokers versus nonsmokers and the adjusted SBP was lower in current smokers versus former smokers (P < 0.05). Additionally, the adjusted PP tend to be decreased steadily as the pack·years increased in current smokers. In a fully adjusted logistic regression model, former smokers had increased ORs (95% CI) of 1.48 (1.01, 2.18) of hypertension and current smokers had not increased ORs (95% CI) of 0.83 (0.61, 1.12), compared with never smokers. CONCLUSIONS: The findings revealed that the adjusted blood pressure were lower in current smokers versus nonsmokers and former smokers. No significant dose-dependent effect of current smoking on blood pressure indices except PP was observed. Smoking cessation was significantly associated with an increased risk of hypertension. However, current smoking was not a risk factor of hypertension.

Prevalence, awareness, treatment, control and risk factors related to hypertension among urban adults in Inner Mongolia 2014: differences between Mongolian and Han populations.

BACKGROUND: Han and Mongolian populations constitute approximately 96% of the population of Inner Mongolia Autonomous Region, and the two ethnic groups have different genetic backgrounds and lifestyle. We aim to assess the prevalence, awareness, treatment, control, and related risk factors of hypertension among urban adults in Inner Mongolia, with the comparison of the differences between Mongolian and Han populations in this respect. METHODS: Three thousand two hundred fifty-one individuals aged 20-80 years (2326 Han and 925 Mongolian) were selected using a multistage cluster sampling method from Inner Mongolia in 2014. The adjusted prevalence, awareness, treatment and control of hypertension were evaluated by the Logistic regression. In addition, possible interactions were also tested. When interactions were found significant, strata-specific analysis were performed. Multivariate logistic regression was used for estimating independent associations between risk factors and hypertension. RESULTS: The prevalence of hypertension was 27.47% for Han population, 31.46% for Mongolian population. The adjusted prevalence, awareness, treatment and control of hypertension were 26.45, 65.43, 78.24 and 48.28% in Han, and 31.30, 68.22, 85.57 and 50.55% in Mongolian, respectively. There was no significant difference in the adjusted awareness, treatment and control of hypertension among Mongolian and Han adult residents (all P >0.05). Lower prevalence of hypertension was associated with younger age and healthy weight in both Mongolian and Han adults. Within Han adults, high education, moderate physical activity and non-alcohol drinkers were additionally associated with lower prevalence of hypertension, whereas within Mongolian adults, lower prevalence was associated with being female. Among residents with medium education level, nondrinkers had 0.60 times lower odds of having hypertension than current drinkers (OR = 0.60, 95% CI: 0.44-0.82); among residents with high education level, nondrinkers has 0.65 times lower odds of having hypertension than current drinkers (OR = 0.65, 95% CI: 0.43-0.97). CONCLUSIONS: Mongolian population had a higher prevalence of hypertension than Han population. There were no significant difference between Mongolian and Han population in awareness, treatment and control of hypertension, which suggested that there was no difference between the two ethnicities in the distribution of health resources.

Treatment of gastric ulcer, traditional Chinese medicine may be a better choice.

ETHNOPHARMACOLOGICAL RELEVANCE: Gastric ulcer (GU) is the injury of the gastric mucosa caused by the stimulation of various pathogenic factors penetrating the deep mucosal muscle layer. An increasing number of studies have shown that traditional Chinese medicine (TCM) is highly effective in treating GU due to its multitarget, multilevel, and multi-pathway effects. AIM OF THE STUDY: To review the latest research progress in the treatment of GU by TCM, including clinical and experimental studies, focusing on the target and mechanism of action of drugs and providing a theoretical basis for the treatment of GU by natural herbs. MATERIALS AND METHODS: Electronic databases (PubMed, Elsevier, Springer, Web of Science, and CNKI) were searched using the keywords "gastric ulcer", "gastric mucosal lesion", "TCM" and or paired with "peptic ulcer" and "natural drugs" for studies published in the last fifteen years until 2023. RESULTS: TCM, including single components of natural products, Chinese patent medicines (CPM), and TCM decoction, is expected to treat GU by regulating various mechanisms, such as redox balance, inflammatory factors, angiogenesis, gastric mucosal protective factors, intestinal flora, apoptosis, and autophagy. CONCLUSIONS: We discussed and summarized the mechanism of TCM in the treatment of GU, which provided a sufficient basis for TCM treatment of GU.

Secreted Glycoproteins That Regulate Synaptic Function: the Dispatchers in the Central Nervous System.

Glycoproteins are proteins that contain oligosaccharide chains. As widely distributed functional proteins in the body, glycoproteins are essential for cellular development, cellular function maintenance, and intercellular communication. Glycoproteins not only play a role in the cell and the membrane, but they are also secreted in the intercell. These secreted glycoproteins are critical to the central nervous system for neurodevelopment and synaptic transmission. More specifically, secreted glycoproteins play indispensable roles in neurite growth mediation, axon guiding, synaptogenesis, neuronal differentiation, the release of synaptic vesicles, subunit composition of neurotransmitter receptors, and neurotransmitter receptor trafficking among other things. Abnormal expressions of secreted glycoproteins in the central nervous system are associated with abnormal neuron development, impaired synaptic organization/transmission, and neuropsychiatric disorders. This article reviews the secreted glycoproteins that regulate neuronal development and synaptic function in the central nervous system, and the molecular mechanism of these regulations, providing reference for research about synaptic function regulation and related central nervous system diseases.

Hesperidin inhibits lung fibroblast senescence via IL-6/STAT3 signaling pathway to suppress pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and fatal lung disease with obscure pathogenesis. Increasing evidence suggests that cellular senescence is an important mechanism underlying in IPF. Clinical treatment with drugs, such as pirfenidone and nintedanib, reduces the risk of acute exacerbation and delays the decline of pulmonary function in patients with mild to moderate pulmonary fibrosis, and with adverse reactions. Hesperidin was previously shown to alleviate pulmonary fibrosis in rats by attenuating the inflammation response. Our previous research indicated that the Citrus alkaline extracts, hesperidin as the main active ingredient, could exert anti-pulmonary fibrosis effects by inhibiting the senescence of lung fibroblasts. However, whether hesperidin could ameliorate pulmonary fibrosis by inhibiting fibroblast senescence needed further study. PURPOSE: This work aimed to investigate whether and how hesperidin can inhibit lung fibroblast senescence and thereby alleviate pulmonary fibrosis METHODS: Bleomycin was used to establish a mouse model of pulmonary fibrosis and doxorubicin was used to establish a model of cellular senescence in MRC-5 cells in vitro. The therapeutic effects of hesperidin on pulmonary fibrosis using haematoxylin-eosin staining, Masson staining, enzyme-linked immunosorbent assay, immunohistochemistry, western blotting and quantitative Real-Time PCR. The anti-senescent effect of hesperidin in vivo and in vitro was assessed by western blotting, quantitative Real-Time PCR and senescence-associated ß-galactosidase RESULTS: We demonstrated that hesperidin could alleviate bleomycin-induced pulmonary fibrosis in mice. The expression level of senescence marker proteins p53, p21, and p16 was were downregulated, along with the myofibroblast marker α-SMA. The number of senescence-associated ß-galactosidase-positive cells was significantly reduced by hesperidin intervention in vivo and in vitro. In addition, hesperidin could inhibit the IL6/STAT3 signaling pathway. Furthermore, suppression of the IL-6/STAT3 signaling pathway by pretreatment with the IL-6 inhibitor LMT-28 attenuating effect of hesperidin on fibroblast senescence in vitro. CONCLUSIONS: These data illustrated that hesperidin may be potentially used in the treatment of IPF based on its ability to inhibit lung fibroblast senescence.

Xiangshao Decoction alleviates gastric mucosal injury through NRF2 signaling pathway and reduces neuroinflammation in gastric ulcer rats.

BACKGROUND: A type of gastric mucosal injury disease known as gastric ulcer (GU) is clearly connected to the aberrant release of gastric acid. Traditional botanicals have the potential for anti-inflammation, anti-oxidation, and other multitarget therapies, as well as being safe. PURPOSE: The purpose of this study was to investigate the potential effects of Xiangshao Decoction (XST) on gastric mucosal injury in GU rats and to explore the possible molecular mechanisms. METHODS: After identifying XST and its components, we established GU rats and cell models by acetic acid and H2O2 induction, respectively. SOD and MDA indexes in gastric tissues and GES-1 cells, and the serum levels of BDNF, ALT, and AST were detected with relevant kits, changes of the gastric mucosa were observed and recorded, and gastric tissue pathology was observed by H&E staining. The production of ROS in GES-1 cells was detected by fluorescent probes. Cell transfection techniques were used to silence or overexpress NRF2. The mRNA or protein expressions of NRF2, KEAP1, NQO1, HO-1, SOD2, IL-1ß, IL-6, TNF-α, IBA1, GFAP, or γ-H2AX in the gastric tissue, hippocampus, or GES-1 cells were measured via qPCR, Western blot, immunofluorescence staining, or immunohistochemical staining. RESULTS: The pH of gastric acid, ulcer score, and pathological damage score in GU rats could be reversed by XST administration. Expressions of IL-1ß, IL-6, and TNF-α in the gastric mucosal tissues and the hippocampus of GU rats after administration of XST were down. Expressions of NRF2, NQO1, HO-1, SOD2, etc. in the gastric mucosal tissues and BDNF in the hippocampus were up-regulated. The production of ROS and MDA and the expressions of IL-1ß, IL-6, TNF-α, and KEAP1 in H2O2-induced GES-1 cells were significantly reduced after XST intervention, while the activities of SOD and the expression of NRF2, NQO1, HO-1, and SOD2 were significantly increased, and these could be blocked by silencing NRF2 expression. CONCLUSIONS: XST can improve oxidative stress injury and inflammatory response in GU rats and cell models, and its mechanism is mediated by the NRF2 signaling pathway.

Identification of a Nomogram with an Autophagy-Related Risk Signature for Survival Prediction in Patients with Glioma.

BACKGROUND: Glioma is a common type of tumor in the central nervous system characterized by high morbidity and mortality. Autophagy plays vital roles in the development and progression of glioma, and is involved in both normal physiological and various pathophysiological progresses. PATIENTS AND METHODS: A total of 531 autophagy-related genes (ARGs) were obtained and 1738 glioma patients were collected from three public databases. We performed least absolute shrinkage and selection operator regression to identify the optimal prognosis-related genes and constructed an autophagy-related risk signature. The performance of the signature was validated by receiver operating characteristic analysis, survival analysis, clinic correlation analysis, and Cox regression. A nomogram model was established by using multivariate Cox regression analysis. Schoenfeld's global and individual test were used to estimate time-varying covariance for the assumption of the Cox proportional hazard regression analysis. The R programming language was used as the main data analysis and visualizing tool. RESULTS: An overall survival-related risk signature consisting of 15 ARGs was constructed and significantly stratified glioma patients into high- and low-risk groups (P < 0.0001). The area under the ROC curve of 1-, 3-, 5-year survival was 0.890, 0.923, and 0.889, respectively. Univariate and multivariate Cox analyses indicated that the risk signature was a satisfactory independent prognostic factor. Moreover, a nomogram model integrating risk signature with clinical information for predicting survival rates of patients with glioma was constructed (C-index=0.861±0.024). CONCLUSION: This study constructed a novel and reliable ARG-related risk signature, which was verified as a satisfactory prognostic marker. The nomogram model could provide a reference for individually predicting the prognosis for each patient with glioma and promoting the selection of optimal treatment.

Evaluation of carotid atherosclerosis and related risk factors using ultrasonic B-Flow technology in elderly patients.

OBJECTIVE: This study was performed to identify the risk factors for carotid atherosclerotic plaque formation using B-Flow ultrasound. METHODS: In total, 120 patients who underwent bilateral carotid ultrasound examination were enrolled in this cross-sectional study. The intima-media thickness was measured, and the risk factors for carotid atheromatous plaque formation were investigated. RESULTS: Age, sex, medical history of hypertension, coronary heart disease, and diabetes were risk factors for carotid atheromatous plaque formation. Multivariate logistic regression analysis revealed that the main risk factors for carotid atheromatous plaque formation were male sex, advanced age, a high hemoglobin concentration, a high red cell distribution width, and a high low-density lipoprotein cholesterol concentration. CONCLUSION: The risk factors for carotid atheromatous plaque formation were basically the same as those for stroke. Early ultrasound examination of the carotid artery enables the identification of risk factors associated with stroke.

Secular Trends of the Impact of Overweight and Obesity on Hypertension in Yi People: Yi Migrant Study, 1996-2015.

BACKGROUND: Rising hypertension prevalence, coupled with increasing overweight and obesity rates, has been observed in Yi people. Moreover, the growing blood pressure level among Yi people was mostly attributable to the continuous increase of body mass index (BMI). However, little is known about the trend of association between them. METHODS: Consequently, we investigated the impact of overweight/obesity on hypertension over three periods (1996, 2007-2008, 2015) using data from Yi Migrant Study (n = 8749). The Yi Migrant Study incorporated three successive cross-sectional studies which were implemented by the same team with consistent protocols. RESULTS: Compared with period 1 (1996), the influence of overweight/obesity on hypertension risk significantly increased in period 2 (2007-2008) and period 3 (2015); relative excess risk due to interaction (RERI) was 1.59 (95% CI: 0.12, 3.05) and 1.41 (95% CI: 0.30, 2.78), respectively. Meanwhile, the overweight/obese population in period 3 did not show hypertension risk higher than that in period 2 (RERI = 0.15; 95% CI: -0.76, 1.07). Additionally, we observed a continuously growing trend of hypertension risk among normal weight Yi people. CONCLUSIONS: During the past two decades, there was a significant increase in the association between overweight/obesity and hypertension in Yi people, whereas the increasing trend has leveled off in more recent years. These findings suggest that overweight/obesity and hypertension are becoming more epidemic comorbidity over time. Interventions to prevent hypertension should focus not only on the overweight/obese population, but also on those with normal weight.

[Protective effects of n-butanol extract of Potentilla anserina on acute myocardial ischemic injury in mice].

OBJECTIVE: To investigate the protective effects of the n-butanol extract of Potentilla anserina L. (NP) on pituitrin-induced acute myocardial ischemic injury in mice. METHODS: Ninety healthy female mice were randomly divided into normal control group, untreated group, Salvia miltiorrhiza group and low-, medium- and high-dose NP groups. Except for the normal control group, the mice were intraperitoneally injected with pituitrin (20 U/kg) to induce acute myocardial ischemic injury. Thirty minutes after induction, electrocardiogram was monitored, and height of the J spot was measured also. Activities of lactate dehydrogenase (LDH), creatine kinase (CK) and superoxide dismutase (SOD) and content of malondialdehyde (MDA) in serum of the mice were detected. The degree of myocardial ischemic injury in mice was observed by Nagar-Olsen staining. RESULTS: The moving up of J spots in the treated groups was significantly inhibited when comparing with the untreated group (P<0.01). Compared with untreated group, high- and medium-dose NP and Salvia miltiorrhiza could significantly decrease the activities of LDH, CK (P<0.01, P<0.05), increase the SOD activity (P<0.01) and decrease the content of MDA (P<0.05). However, no significant difference was observed between low-dose NP group and untreated group (P>0.05). Nagar-Olsen staining showed that high- and medium-dose NP and Salvia miltiorrhiza could significantly diminish the areas of cardiac muscles injured by ischemia, but low-dose NP had no effect on that. CONCLUSION: NP has a remarkable protective effect on acute myocardial ischemic injury in mice.

Twenty-year time trends in hypertension prevalence in Yi people of China: three successive cross-sectional studies, 1996-2015.

OBJECTIVE: To explore the trend of hypertension prevalence and related factors in Yi people from 1996 to 2015. METHODS: Three successive cross-sectional surveys were conducted in Liangshan Yi Autonomous Prefecture in 1996, 2007 and 2015, respectively. A total of 8448 participants aged 20-80 years (5040 Yi farmers, 3408 Yi migrants) were included in final analysis. RESULTS: Overall, the age-standardised prevalence of hypertension in migrants was significantly higher than in farmers. Furthermore, the age-standardised prevalence rates increased from 10.1% to 15.3% to 19.6% in Yi migrants and from 4.0% to 6.3% to 13.1% in Yi farmers during 1996 to 2007 to 2015. The highest 2015-to-1996 ratio of age-standardised hypertension prevalence was in male farmers (ratio=4.30), whereas despite the highest prevalence of hypertension, the equivalent figure in male migrants was 1.57. The older age, overweight and obesity were persistent risk factors of hypertension in three periods. After adjusted for age and body mass index, the difference of hypertension prevalence between 1996 and 2015 then vanished in male migrants (OR=1.335; 95% CI: 0.884 to 2.015) and female farmers (OR=1.267; 95% CI: 0.590 to 2.719). The disparities of hypertension prevalence between Yi migrants and farmers were not statistically significant in all subgroups when adjusted for age, body mass index and education. CONCLUSIONS: Over the past two decades, the hypertension prevalence in Yi people has significantly increased. Yi migrants were more likely to be hypertensive than Yi farmers which was predominantly driven by the discrepancy of body mass index between them.

[Expression of TMV coat protein gene RNAi in transgenic tobacco plants confer immunity to tobacco mosaic virus infection].

RNAi technique has been proved as a powerful tool for plant breeding. In this paper, the coat protein of tobacco mosaic virus (TMV) was used for constructing the RNAi interference vector. The tobacco varieties K326 and Longjiang 911 were transformed via Agrobacterium tumefaciens-mediated transformation, and transgenic plants were generated. The expression analysis with real-time PCR indicated that TMV RNA had been degraded varied in different transgenic lines. Field assay revealed that 83% and 90 % transgenic plants showed immunity resistance to TMV in K326 and Longjiang 911 respectively.