Impact of Helicobacter pylori Infection and Outcome of Anti-Helicobacter pylori Therapy in Patients with Reflux Laryngopharyngitis.

Objectives: This study was designed to explore the relationship between Helicobacter pylori (Hp) infection and reflux laryngopharyngitis (RLP) and to evaluate the outcome of anti-Hp therapy in improving RLP symptoms. Methods: A total of 410 patients with RLP were enrolled and tested for Hp infection. The association of Hp infection with reflux symptom index (RSI) and reflux finding score (RFS) was determined. Hp-positive patients received either a proton pump inhibitor (PPI) omeprazole alone (control group) or a combination regimen (experimental group) consisting of omeprazole, mosapride citrate, amoxicillin, and clarithromycin. Therapeutic outcomes were compared 4 weeks later. Results: Of the 410 participants, 290 were Hp-positive and 120 Hp-negative. Both RSI and RFS were significantly higher in Hp-positive patients than in Hp-negative patients. Hp infection status was positively correlated with RSI (P < 0.05) and RFS (P < 0.05). The overall response rate was higher in the experimental group than in the control group. Both the groups had a significant reduction in RSI and RFS after therapy, with a greater improvement in the experimental group (P < 0.05). Conclusion: Our findings establish a link between Hp infection and RLP. Anti-Hp therapy improves RSI and RFS in RLP patients. Therefore, Hp eradication drugs may be added to the PPI-based regimen in the treatment of RLP.

Effect of Thymosin on Inflammatory Factor Levels, Immune Function, and Quality of Life in Lung Cancer Patients Undergoing Radical Thoracoscopic Surgery.

Purpose: To explore the effect of thymosin on inflammatory factor levels, immune function, and quality of life in patients undergoing radical thoracoscopic lung cancer surgery. Methods: One hundred and twenty patients admitted to the Surgical Oncology Department of the First Hospital of Jiaxing from January 2018 to January 2019 were randomized into the study group and the control group using the random number table method, with 60 cases in each group. The control group was treated with radical thoracoscopic lung cancer surgery, and the study group was treated with radical thoracoscopic lung cancer surgery combined with thymosin. The clinical efficiency, inflammatory factors, immune function, and quality of life between the two groups of patients were compared. Results: There was no significant difference between the two groups in terms of pathological stage, tissue type, maximum tumor diameter, and perioperative indicators such as operative time, intraoperative bleeding, pleural drainage, hospital stay, and the number of intraoperative lymph nodes removed. The levels of CD4 (+%), CD8 (+%), CD4+/CD8+, and natural killer cell (NK) (%) were significantly decreased in both groups after treatment, with significantly higher results in the study group than in the control group. The study group had significantly lower serum interleukin-6 (IL-6) levels and higher interleukin-10 (IL-10) levels than the control group. After treatment, patients in the study group had better postoperative physiological status and overall score than the control group. There was no significant difference in postoperative survival and adverse reactions between the two groups. Conclusion: The use of thymosin treatment in lung cancer patients undergoing radical thoracoscopic surgery significantly improves immune function, mitigates inflammatory response, and enhances the quality of life, which is worthy of clinical application.

Mulberrin confers protection against hepatic fibrosis by Trim31/Nrf2 signaling.

Mulberrin (Mul) is a key component of the traditional Chinese medicine Romulus Mori with various biological functions. However, the effects of Mul on liver fibrosis have not been addressed, and thus were investigated in our present study, as well as the underlying mechanisms. Here, we found that Mul administration significantly ameliorated carbon tetrachloride (CCl4)-induced liver injury and dysfunction in mice. Furthermore, CCl4-triggerd collagen deposition and liver fibrosis were remarkably attenuated in mice with Mul supplementation through suppressing transforming growth factor ß1 (TGF-ß1)/SMAD2/3 signaling pathway. Additionally, Mul treatments strongly restrained the hepatic inflammation in CCl4-challenged mice via blocking nuclear factor-κB (NF-κB) signaling. Importantly, we found that Mul markedly increased liver TRIM31 expression in CCl4-treated mice, accompanied with the inactivation of NOD-like receptor protein 3 (NLRP3) inflammasome. CCl4-triggered hepatic oxidative stress was also efficiently mitigated by Mul consumption via improving nuclear factor E2-related factor 2 (Nrf2) activation. Our in vitro studies confirmed that Mul reduced the activation of human and mouse primary hepatic stellate cells (HSCs) stimulated by TGF-ß1. Consistently, Mul remarkably retarded the inflammatory response and reactive oxygen species (ROS) accumulation both in human and murine hepatocytes. More importantly, by using hepatocyte-specific TRIM31 knockout mice (TRIM31Hep-cKO) and mouse primary hepatocytes with Nrf2-knockout (Nrf2KO), we identified that the anti-fibrotic and hepatic protective effects of Mul were TRIM31/Nrf2 signaling-dependent, relieving HSCs activation and liver fibrosis. Therefore, Mul-ameliorated hepatocyte injury contributed to the suppression of HSCs activation by improving TRIM31/Nrf2 axis, thus providing a novel therapeutic strategy for hepatic fibrosis treatment.

The mechanism of triptolide in the treatment of connective tissue disease-related interstitial lung disease based on network pharmacology and molecular docking.

BACKGROUND: Interstitial lung disease (ILD) is associated with substantial morbidity and mortality, which is one of the key systematic manifestations of connective tissue disease (CTD). Tripterygium wilfordii, known as Leigongteng in Chinese, has been applied to treat connective tissue disease-related interstitial lung disease (CTD-ILD) for many years. Triptolide is a key effective component from Tripterygium wilfordii. But the molecular mechanism of Triptolide for treating CTD-ILD is not yet clear. METHODS: Gaining insight into the molecular mechanism of Triptolide intervention CTD-ILD, we used the method of network pharmacology. And then we conducted drug-target networks to analyse the potential protein targets between Triptolide and CTD-ILD. Finally, AutoDock Vina was selected for molecular docking. RESULTS: By analysing the interaction genes between Triptolide and CTD-ILD, 242 genes were obtained. The top 10 targets of the highest enrichment scores were STAT3, AKT1, MAPK1, IL6, TP53, MAPK3, RELA, TNF, JUN, JAK2. GO and KEGG enrichment analysis exhibited that multiple signalling pathways were involved. PI3K-Akt, multiple virus infections, cancer signalling, chemokine, and apoptosis signalling pathway are the main pathways for Triptolide intervention CTD-ILD. And it is related to various biological processes such as inflammation, infection, cell apoptosis, and cancer. Molecular docking shows Triptolide can bind with its target protein in a good bond by intermolecular force. CONCLUSIONS: This study preliminarily reveals the internal molecular mechanism of Triptolide interfere with CTD-ILD through multiple targets, multiple access, validated through molecular docking.KEY MESSAGESTriptolide intervention CTD-ILD, which are related to various biological processes such as inflammation, infection, cell apoptosis, and cancer.PI3K-Akt, multiple virus infections, and apoptosis signalling pathway are the main pathways for Triptolide intervention CTD-ILD.Triptolide can bind with related target protein in a good bond by Intermolecular force, exhibiting a good docking activity.

Biomimetic Ca2+ nanogenerator based on ions interference strategy for tumour-specific therapy.

Intracellular Ca2+ ions as second messenger played key role in cell behaviour, which was often overlooked in traditional antitumor treatment. Disrupting Ca2+ ion homeostasis by Ca2+ overload might switch ions signal from 'regulating' to 'destroying'. Inspired by this, a biomimetic Ca2+ nanogenerator was constructed. Briefly, the curcumin (CUR) was loaded into mesoporous calcium carbonate nanoparticles (MCC NPs), and then coated with platelet (PLT) membrane. Upon reaching tumour cells by PLT membrane-mediated tumour targeting effect, PLT@MCC/CUR would instantaneously decompose in acidic lysosomes, concurrently accompanying with Ca2+ generation and CUR release. The CUR could further facilitate Ca2+ release from endoplasmic reticulum (ER) and inhibit Ca2+ efflux, aggravating Ca2+ overload to disrupt mitochondrial Ca2+ homeostasis for mitochondria apoptosis signalling pathway activation. Interestingly, such effect was ineffective in normal cells, realising the tumour-specific therapeutic therapy. Based on ions interference strategy, PLT@MCC/CUR herein offered synergistic combination of Ca2+ overload therapy and chemotherapy, which would pave the way towards more effective nanotherapeutics.

Effect of traditional Chinese medicine emotional therapy on post-stroke depression: A protocol for systematic review and meta-analysis.

BACKGROUND: Post-stroke depression has seriously affected the rehabilitation and quality of life of patients, and there is no reliable treatment plan at present. Nursing plays an important role in the recovery of patients, some studies have pointed out that traditional Chinese medicine emotional therapy has advantages in improving post-stroke depression and promoting rehabilitation, but it is lack of evidence-based basis. The purpose of this study is to systematically evaluate the effect of traditional Chinese medicine emotional therapy on the improvement of post-stroke depression. METHOD: We will search CNKI, Wanfang, VIP and CBM, PubMed, Embase, Web of Science and the Cochrane Library database, and search the randomized controlled trial on traditional Chinese medicine emotional therapy in patients with post-stroke depression from the establishment of the database to February 2021. The language is limited to English and Chinese. The quality of the included study is independently extracted and the literature quality is evaluated by 2 researchers. And meta-analysis is performed on the included literature using RevMan5.3 software. RESULT: In this study, the effect of traditional Chinese medicine emotional therapy on the improvement of post-stroke depression is evaluated by patient psychiatric scale score, compliance evaluation, quality of life evaluation and other indicators. CONCLUSION: This study will provide reliable evidence-based basis for establishing a reasonable and effective nursing scheme for patients with post-stroke depression. ETHICS AND DISSEMINATION: Private information from individuals will not be published. This systematic review also does not involve endangering participant rights. Ethical approval will not be required. The results may be published in a peer-reviewed journal or disseminated at relevant conferences. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/KA7G3.

Preferences for Artificial Intelligence Clinicians Before and During the COVID-19 Pandemic: Discrete Choice Experiment and Propensity Score Matching Study.

BACKGROUND: Artificial intelligence (AI) methods can potentially be used to relieve the pressure that the COVID-19 pandemic has exerted on public health. In cases of medical resource shortages caused by the pandemic, changes in people's preferences for AI clinicians and traditional clinicians are worth exploring. OBJECTIVE: We aimed to quantify and compare people's preferences for AI clinicians and traditional clinicians before and during the COVID-19 pandemic, and to assess whether people's preferences were affected by the pressure of pandemic. METHODS: We used the propensity score matching method to match two different groups of respondents with similar demographic characteristics. Respondents were recruited in 2017 and 2020. A total of 2048 respondents (2017: n=1520; 2020: n=528) completed the questionnaire and were included in the analysis. Multinomial logit models and latent class models were used to assess people's preferences for different diagnosis methods. RESULTS: In total, 84.7% (1115/1317) of respondents in the 2017 group and 91.3% (482/528) of respondents in the 2020 group were confident that AI diagnosis methods would outperform human clinician diagnosis methods in the future. Both groups of matched respondents believed that the most important attribute of diagnosis was accuracy, and they preferred to receive combined diagnoses from both AI and human clinicians (2017: odds ratio [OR] 1.645, 95% CI 1.535-1.763; P<.001; 2020: OR 1.513, 95% CI 1.413-1.621; P<.001; reference: clinician diagnoses). The latent class model identified three classes with different attribute priorities. In class 1, preferences for combined diagnoses and accuracy remained constant in 2017 and 2020, and high accuracy (eg, 100% accuracy in 2017: OR 1.357, 95% CI 1.164-1.581) was preferred. In class 2, the matched data from 2017 were similar to those from 2020; combined diagnoses from both AI and human clinicians (2017: OR 1.204, 95% CI 1.039-1.394; P=.011; 2020: OR 2.009, 95% CI 1.826-2.211; P<.001; reference: clinician diagnoses) and an outpatient waiting time of 20 minutes (2017: OR 1.349, 95% CI 1.065-1.708; P<.001; 2020: OR 1.488, 95% CI 1.287-1.721; P<.001; reference: 0 minutes) were consistently preferred. In class 3, the respondents in the 2017 and 2020 groups preferred different diagnosis methods; respondents in the 2017 group preferred clinician diagnoses, whereas respondents in the 2020 group preferred AI diagnoses. In the latent class, which was stratified according to sex, all male and female respondents in the 2017 and 2020 groups believed that accuracy was the most important attribute of diagnosis. CONCLUSIONS: Individuals' preferences for receiving clinical diagnoses from AI and human clinicians were generally unaffected by the pandemic. Respondents believed that accuracy and expense were the most important attributes of diagnosis. These findings can be used to guide policies that are relevant to the development of AI-based health care.

Proteomic analysis of oridonin-induced apoptosis in multiple myeloma cells.

Oridonin is a diterpenoid compound isolated from the medicinal herb Rabdosia rubescens, and has shown marked antitumor effects against different types of cancer. However, the definitive systematic molecular mechanism underlying the antitumor activity of oridonin in multiple myeloma remains to be elucidated. In the present study, cell viability and cytotoxicity were examined to determine the appropriate concentration for proteomic investigation. In addition, cell apoptosis was evaluated using flow cytometry and transmission electron microscopy. A proteomic investigation using a two­dimensional electrophoresis system and mass spectrometry was performed to identify and characterize the global proteome of the apoptosis induced by oridonin. Of the proteins identified, seven were involved in the anticancer effects of oridonin. Regulation of the expression and function of target proteins, stathmin, dihydrofolate reductase and pyruvate dehydrogenase E1ß, may be potential, therapeutic strategies to effectively treat multiple myeloma. These findings provide novel information on the molecular mechanisms underlying the anticancer properties of oridonin in multiple myeloma.

Tetramethylpyrazine Protects against Early Brain Injury after Experimental Subarachnoid Hemorrhage by Affecting Mitochondrial-Dependent Caspase-3 Apoptotic Pathway.

This study was to test the hypothesis that tetramethylpyrazine (TMP) protected against early brain injury after subarachnoid hemorrhage (SAH) by affecting the mitochondrial-dependent caspase-3 apoptotic pathway. TMP was administrated after the rats' prechiasmatic SAH mode. Animal neurobehavioral functions were assessed and the mitochondrial morphology, mitochondrial and cytoplasmic calcium, and mitochondrial membrane potential changes (Δψm) of the brain tissues were measured. The expressions of cytoplasmic cytochrome c (cyt c), second mitochondria-derived activator of caspases (Smac), and cleaved caspase-3 B-cell lymphoma 2 (bcl-2) in cells were determined and cellular apoptosis was detected. The treatment of TMP resulted in less apoptotic cells and milder mitochondrial injury and potentially performed better in the neurobehavioral outcome compared to those with saline. Also, TMP ameliorated calcium overload in mitochondria and cytoplasm and alleviated the decrease of Δψm. In addition, TMP inhibited the expression of cytoplasmic cyt c, Smac, and cleaved caspase-3, yet it upregulated the expression of bcl-2. These findings suggest that TMP exerts an antiapoptosis property in the SAH rat model and this is probably mediated by the caspase-3 apoptotic pathway triggered by mitochondrial calcium overload. The finding offers a new therapeutic candidate for early brain injury after SAH.

A Bilobalide-Producing Endophytic Fungus, Pestalotiopsis uvicola from Medicinal Plant Ginkgo biloba.

For screening bilobalide (BB)-producing endophytic fungi from medicinal plant Ginkgo biloba, a total of 57 fungal isolates were isolated from the internal stem, root, leaf, and bark of the plant G. biloba. Fermentation processes using BB-producing fungi other than G. biloba may become a novel way to produce BB, which is a terpene trilactones exhibiting neuroprotective effects. In this study, a BB-producing endophytic fungal strain GZUYX13 was isolated from the leaves of G. biloba grown in the campus of Guizhou University, Guiyang city, Guizhou province, China. The strain produced BB when grown in potato dextrose liquid medium. The amount of BB produced by this endophytic fungus was quantified to be 106 µg/L via high-performance liquid chromatography (HPLC), substantially lower than that produced by the host tissue. The fungal BB which was analyzed by thin layer chromatography (TLC) and HPLC was proven to be identical to authentic BB. The strain GZUYX13 was identified as Pestalotiopsis uvicola via morphology and ITS rDNA phylogeny. To the best of our knowledge, this is the first report concerning the isolation and identification of endophytic BB-producing Pestalotiopsis spp. from the host plant, which further proved that endophytic fungi have the potential to produce bioactive compounds.

Minimally invasive surgery for patients with bulky bladder stones and large benign prostatic hyperplasia simultaneously: a novel design.

OBJECTIVE: To determine the efficacy and safety of a novel minimally invasive design for treating bulky vesical calculi and large benign prostatic hyperplasia (BPH) simultaneously. METHODS: 76 patients with large bladder stones (>4 cm) and large BPH (≥50 cm³) were treated from August 2008 to January 2011. 38 patients (group 1) underwent transurethral cystolithotripsy followed by transurethral resection of the prostate (TURP), 38 patients (group 2) received percutaneous cystolithotripsy within a laparoscopic entrapment bag and TURP by two surgeons simultaneously. 72 patients were followed up for 1 year. Patient demographics, perioperative parameters and follow-up data were compared. RESULTS: Patient baseline characteristics were comparable in the two groups. In group 1, 3 patients converted to open surgery and received blood transfusion, 4 patients had postoperative fever, 2 had residual stones and 1 developed urethral stricture postoperatively. In group 2, the mean total operative and the operative times for stone management were 71.6 and 30.1 min, respectively, the mean hemoglobin decrease was 0.80 g/dl, no patients received blood transfusion and no complications occurred, significantly superior to group 1. CONCLUSIONS: Percutaneous cystolithotripsy using a laparoscopic entrapment bag associated with TURP by two surgeons simultaneously is a highly effective, safe and minimally invasive method for managing large vesical calculi and large BPH.

Intragastric administration of evodiamine suppresses NPY and AgRP gene expression in the hypothalamus and decreases food intake in rats.

Evodiamine (Evo), an alkaloidal component extracted from the fruit of Evodiae fructus (Evodia rutaecarpa Bentham, Rutaceae), decreases the body weight of rats through a poorly defined mechanism. The hypothalamus is one of the areas in the brain linked to the control of food intake and energy expenditure. We postulate that Evo mediates this activity by modulating feeding-related peptides in the hypothalamus. We investigated the effects of Evo on food intake, body weight, the mRNA expression and peptide level of feeding-related peptides in the hypothalamus, in male rats. The juvenile rats of 5 weeks old were used at the start of the experiment. Evo (40 mg/kg or 4 mg/kg) was administered intragastrically for 25 days, and food intake and body weight of rats were recorded daily. Blood samples were collected for leptin radioimmunoassay (RIA). Real-Time PCR was used to analyze the mRNA expression. Western Blotting and immunohistochemistry were used to analyze the peptide. Our results show that intragastric administration of Evo (40 mg/kg) decreased rate of food intake and body weight increase following rat growth, reduced orexigenic neuropeptide Y (NPY) and agouti-gene related protein (AgRP) mRNA levels and NPY peptide level in the arcuate nucleus (ARC) of the hypothalamus, but it increases the circulating level of leptin. Intragastric administration of a smaller dose of Evo (4 mg/kg) was ineffective. These data suggest that Evo decreases food intake, and therefore body weight, partly by down-regulating NPY and AgRP mRNA expression and peptide expression in the ARC of the hypothalamus.

[The change of certain biochemical indexes and apotosis protein (Fas/FasL) expression in rat liver of selenium and iodine deficiency].

OBJECTIVE: To investigate the effect of selenium (Se) and iodine (I) deficiency on certain biochemical indexes and apotosis protein (Fas/FasL) expression. METHOD: Healthy SD rats were divided into 4 groups at random, including control group, Se deficient group, I deficient group and both Se and I deficient group.The rats in each group were given different man-made feeds containing different levels of Se and I to breed. The second generation rats were chosen as research subjects. The GPX-Px activity and MDA and NO contents and expression of apoptosis protein (Fas/FasL) in liver were determined by chromometry and western blot. RESULT: GPX-Px of rat liver in Se deficient group significantly reduced, MDA and NO content s and expression of apoptosis of Fas/FasL increased. There were no apparent change in GPX-Px activities and NO contents of rat liver in I deficient group, while the contents of MDA and Fas/FasL expressions were much higher. The changes of GSH-Px activities and contents of MDA, NO as well as the Fas/FasL expressions in both Se and I deficiency groups are much higher than those of Selenium and Iodine deficiency groups. CONCLUSION: Se deficiency can cause the decrease of GPX-Px activities of rat liver and the increase of contents of MDA and NO. It can also lead to over expression of Fas/FasL. It seems that I deficiency can enhance the effect of selenium deficiency.

[Dynamic observation on the relationship between the Keshan disease incidence and some element in internal and external environment in Shanxi Province].

OBJECTIVE: To observe the dynamic changes of condition in Keshan Disease (KSD) and trace element in internal and external environment. METHODS: Based on the standard of KSD surveillance and diagnosis, surveillances site of KSD was set up in Huangling country and all local residents were listed as surveillance subjects. Dynamic changes of condition in KSD were observe. Meanwhile, the hair samples of children and cereals in surveillances sites were selected, and the content of Se, Cu, Ze, Fe and Mn in above samples were determined by atomic absorption spectrometry and fluorospectrophotometry respectively. RESULTS: (1) There were 447 cases of Latent KSD were diagnosed during 15 years. The incidence rates of KSD among people mainly monitored were 3.6%-10.9%. (The average incidence rate was 6.14%). The incidence rates of KSD were risen slowly and were reached steadily. The numbers of new diagnosed cases of latent KSD were 25. The new incidence rates were 0-55.6/ten thousand. The average incidence rate was 34.34/ten thousand, which was decreased slowly. (2) The Se level of wheat in endemic area was significantly lower than that in non-endemic, the hair Se level of children in endemic area was risen yearly and could already reach and steadily stabilize with non-endemic since 1995. Hair Fe level of children in endemic area was significantly higher than that in non-endemic. CONCLUSION: The decline and stabilization of KSD could be associated with increase of Se level in inside environment among the residents in endemic area. However, even if the Se level in inside environment of residents in endemic area could reach the level in non-endemic area, new cases of latent KSD patients were still found in these areas, which suggested that Se could be an important factor that can cause KSD rather than the only factor.