Background/Aims: Anti-reflux mucosal ablation (ARMA) is a promising endoscopic intervention for proton pump inhibitor (PPI)-dependent gastroesophageal reflux disease (GERD). However, the effect of ARMA on esophageal motility remains unclear. Methods: Twenty patients with PPI-dependent GERD receiving ARMA were prospectively enrolled. Comprehensive self-report symptom questionnaires, endoscopy, 24-hour impedance-pH monitoring, and high-resolution impedance manometry were performed and analyzed before and 3 months after ARMA. Results: All ARMA procedures were performed successfully. Symptom scores, including GerdQ (11.16 ± 2.67 to 9.11 ± 2.64, P = 0.026) and reflux symptom index (11.63 ± 5.62 to 6.11 ± 3.86, P = 0.001), improved significantly, while 13 patients (65%) reported discontinuation of PPI. Total acid exposure time (5.84 ± 4.63% to 2.83 ± 3.41%, P = 0.024) and number of reflux episodes (73.05 ± 19.34 to 37.55 ± 22.71, P < 0.001) decreased significantly after ARMA. Improved esophagogastric junction (EGJ) barrier function, including increased lower esophageal sphincter resting pressure (13.89 ± 10.78 mmHg to 21.68 ± 11.5 mmHg, P = 0.034), 4-second integrated relaxation pressure (5.75 ± 6.42 mmHg to 9.99 ± 5.89 mmHg, P = 0.020), and EGJ-contractile integral(16.42 ± 16.93 mmHg · cm to 31.95 ± 21.25 mmHg · cm, P = 0.016), were observed. Esophageal body contractility also increased significantly (distal contractile integral, 966.85 ± 845.84 mmHg · s · cm to 1198.8 ± 811.74 mmHg · s · cm, P = 0.023). Patients with symptom improvement had better pre-AMRA esophageal body contractility. Conclusions ARMA effectively improves symptoms and reflux burden, EGJ barrier function, and esophageal body contractility in patients with PPIdependent GERD during short-term evaluation. Longer follow-up to clarify the sustainability of ARMA is needed.

Background/Aims: Anti-reflux mucosal ablation (ARMA) is a promising endoscopic intervention for proton pump inhibitor (PPI)-dependent gastroesophageal reflux disease (GERD). However, the effect of ARMA on esophageal motility remains unclear. Methods: Twenty patients with PPI-dependent GERD receiving ARMA were prospectively enrolled. Comprehensive self-report symptom questionnaires, endoscopy, 24-hour impedance-pH monitoring, and high-resolution impedance manometry were performed and analyzed before and 3 months after ARMA. Results: All ARMA procedures were performed successfully. Symptom scores, including GerdQ (11.16 ± 2.67 to 9.11 ± 2.64, P = 0.026) and reflux symptom index (11.63 ± 5.62 to 6.11 ± 3.86, P = 0.001), improved significantly, while 13 patients (65%) reported discontinuation of PPI. Total acid exposure time (5.84 ± 4.63% to 2.83 ± 3.41%, P = 0.024) and number of reflux episodes (73.05 ± 19.34 to 37.55 ± 22.71, P < 0.001) decreased significantly after ARMA. Improved esophagogastric junction (EGJ) barrier function, including increased lower esophageal sphincter resting pressure (13.89 ± 10.78 mmHg to 21.68 ± 11.5 mmHg, P = 0.034), 4-second integrated relaxation pressure (5.75 ± 6.42 mmHg to 9.99 ± 5.89 mmHg, P = 0.020), and EGJ-contractile integral(16.42 ± 16.93 mmHg · cm to 31.95 ± 21.25 mmHg · cm, P = 0.016), were observed. Esophageal body contractility also increased significantly (distal contractile integral, 966.85 ± 845.84 mmHg · s · cm to 1198.8 ± 811.74 mmHg · s · cm, P = 0.023). Patients with symptom improvement had better pre-AMRA esophageal body contractility. Conclusions ARMA effectively improves symptoms and reflux burden, EGJ barrier function, and esophageal body contractility in patients with PPIdependent GERD during short-term evaluation. Longer follow-up to clarify the sustainability of ARMA is needed.

Background/Aims: Anti-reflux mucosal ablation (ARMA) is a promising endoscopic intervention for proton pump inhibitor (PPI)-dependent gastroesophageal reflux disease (GERD). However, the effect of ARMA on esophageal motility remains unclear. Methods: Twenty patients with PPI-dependent GERD receiving ARMA were prospectively enrolled. Comprehensive self-report symptom questionnaires, endoscopy, 24-hour impedance-pH monitoring, and high-resolution impedance manometry were performed and analyzed before and 3 months after ARMA. Results: All ARMA procedures were performed successfully. Symptom scores, including GerdQ (11.16 ± 2.67 to 9.11 ± 2.64, P = 0.026) and reflux symptom index (11.63 ± 5.62 to 6.11 ± 3.86, P = 0.001), improved significantly, while 13 patients (65%) reported discontinuation of PPI. Total acid exposure time (5.84 ± 4.63% to 2.83 ± 3.41%, P = 0.024) and number of reflux episodes (73.05 ± 19.34 to 37.55 ± 22.71, P < 0.001) decreased significantly after ARMA. Improved esophagogastric junction (EGJ) barrier function, including increased lower esophageal sphincter resting pressure (13.89 ± 10.78 mmHg to 21.68 ± 11.5 mmHg, P = 0.034), 4-second integrated relaxation pressure (5.75 ± 6.42 mmHg to 9.99 ± 5.89 mmHg, P = 0.020), and EGJ-contractile integral(16.42 ± 16.93 mmHg · cm to 31.95 ± 21.25 mmHg · cm, P = 0.016), were observed. Esophageal body contractility also increased significantly (distal contractile integral, 966.85 ± 845.84 mmHg · s · cm to 1198.8 ± 811.74 mmHg · s · cm, P = 0.023). Patients with symptom improvement had better pre-AMRA esophageal body contractility. Conclusions ARMA effectively improves symptoms and reflux burden, EGJ barrier function, and esophageal body contractility in patients with PPIdependent GERD during short-term evaluation. Longer follow-up to clarify the sustainability of ARMA is needed.

Objective To observe the effect of Bushen Jianpi Prescription,a prescription with the actions of tonifying the kidney and strengthening the spleen,combined with short-term intensive insulin therapy on dedifferentiation of pancreatic beta-cells in patients with type 2 diabetes mellitus(T2DM)of spleen and kidney deficiency type.Methods Seventy patients with T2DM of spleen and kidney deficiency type were randomly divided into control group and observation group,with 35 cases in each group.The control group was treated with intensive insulin therapy,and the observation group was treated with Bushen Jianpi Prescription on the basis of treatment for the control group.The course of treatment lasted for 2 weeks.The changes of TCM syndrome score,and levels of blood glucose,serum high mobility group protein B1(HMGB1),interleukin 1β(IL-1β),tumor necrosis factor α(TNF-α)and the ratio of proinsulin to insulin(PI/I)in the two groups were observed before and after treatment.Results(1)During the treatment,one case in the control group and 2 cases in the observation group fell off.Eventually,34 cases in the control group and 33 cases in the observation group were included in the efficacy statistics.(2)After treatment,the scores of TCM syndromes in the two groups were significantly lower than those before treatment(P＜0.05),and the decrease in the observation group was significantly superior to that in the control group(P＜0.05).(3)After treatment,the levels of fasting plasma glucose(FPG)and 2-hour postprandial plasma glucose(2hPG)in the two groups were significantly lower than those before treatment(P＜0.05),and the decrease in the observation group was significantly superior to that in the control group(P＜0.05).(4)After treatment,the level of HMGB1 in the two groups was significantly lower than that before treatment(P＜0.05),and the decrease in the observation group was significantly superior to that in the control group(P＜0.05).(5)After treatment,the serum levels of inflammatory factors of IL-1β and TNF-α in the two groups were significantly lower than those before treatment(P＜0.05),and the decrease in the observation group was significantly superior to that in the control group(P＜0.05).(6)After treatment,the PI/I ratio of the two groups was significantly lower than that before treatment(P＜0.05),and the decrease of the observation group was significantly superior to that of the control group(P＜0.05).Conclusion Bushen Jianpi Prescription combined with short-term intensive insulin therapy can effectively improve the islet function of patients with T2DM of spleen and kidney deficiency type.The mechanism may be related to the relief of high-glucose toxicity and the decrease of the inflammatory factor levels,thus to inhibit the dedifferentiation of pancreatic beta-cells.

Background/Aims: Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. Methods: We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. Results: The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. Conclusions Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.

OBJECTIVES: To systematically evaluate the efficacy and safety of bosentan in the treatment of persistent pulmonary hypertension of the newborn (PPHN). METHODS: Chinese Journal Full-text Database, Weipu Database, Wanfang Data, China Biology Medicine disc, PubMed, Web of Science, Embase, and Cochrane Library were searched for literature on bosentan in the treatment of PPHN published up to August 31, 2021. RESULTS: A total of 8 randomized controlled trials were included for Meta analysis. The results of the Meta analysis showed that compared with the control group, the bosentan treatment group had a significantly lower treatment failure rate (RR=0.23, P<0.001), a significantly greater reduction in pulmonary artery pressure [mean difference (MD)=-11.79, P<0.001)], significantly greater increases in oxygen partial pressure (MD=10.21, P=0.006) and blood oxygen saturation (MD=8.30, P<0.001), and a significantly shorter length of hospital stay (MD=-1.35, P<0.001). The descriptive analysis showed that the bosentan treatment group had a lower degree of tricuspid regurgitation than the control group after treatment. The main adverse reactions of bosentan treatment included abnormal liver function, anemia and edema. The results of subgroup analysis based on treatment regimen, research area, and drug dose were consistent with those before stratification. CONCLUSIONS Bosentan is effective in the treatment of PPHN. However, when using bosentan, attention should be paid to adverse reactions such as abnormal liver function.
Bosentan/therapeutic use* ; China ; Humans ; Hypertension, Pulmonary/drug therapy* ; Infant, Newborn ; Treatment Failure

Objective: To analyze the course of disease and epidemiological parameters of COVID-19 and provide evidence for making prevention and control strategies. Methods: To display the distribution of course of disease of the infectors who had close contacts with COVID-19 cases from January 1 to March 15, 2020 in Guangdong Provincial, the models of Lognormal, Weibull and gamma distribution were applied. A descriptive analysis was conducted on the basic characteristics and epidemiological parameters of course of disease. Results: In total, 515 of 11 580 close contacts were infected, with an attack rate about 4.4%, including 449 confirmed cases and 66 asymptomatic cases. Lognormal distribution was fitting best for latent period, incubation period, pre-symptomatic infection period of confirmed cases and infection period of asymptomatic cases; Gamma distribution was fitting best for infectious period and clinical symptom period of confirmed cases; Weibull distribution was fitting best for latent period of asymptomatic cases. The latent period, incubation period, pre-symptomatic infection period, infectious period and clinical symptoms period of confirmed cases were 4.50 (95%CI:3.86-5.13) days, 5.12 (95%CI:4.63-5.62) days, 0.87 (95%CI:0.67-1.07) days, 11.89 (95%CI:9.81-13.98) days and 22.00 (95%CI:21.24-22.77) days, respectively. The latent period and infectious period of asymptomatic cases were 8.88 (95%CI:6.89-10.86) days and 6.18 (95%CI:1.89-10.47) days, respectively. Conclusion: The estimated course of COVID-19 and related epidemiological parameters are similar to the existing data.
COVID-19 ; Cohort Studies ; Contact Tracing ; Humans ; Incidence ; Prospective Studies

The tumor prescriptions contained in Dictionary of Tumor Formulas, Compendium of Good Tumor Formulas, Chinese Pharmacopoeia, Ministry of Health Drug Standards for Chinese Medicine Formulas and National Compilation of Standards for Proprietary Chinese Medicines were selected and organized to construct a database for tumor prescriptions, and the data mining techniques were applied to investigate the prescription regularity of colorectal cancer prescriptions. The formula data were extracted after screening in strict accordance with the inclusion and exclusion criteria, and were then analyzed with Microsoft Excel 2010 for frequency statistics, Apriori block provided by SPSS Clementine 12.0 software for correlation rule analysis, and arules and arulesViz packages in R 4.0.2 software for correlation rule visualization. In addition, SPSS 18.0 software was used for cluster analysis and factor analysis, in which cluster analysis was performed by Ochiai algorithm with bicategorical variables in systematic clustering method and factor analysis was performed mainly with principal component analysis. A total of 285 prescriptions were included in the statistical analysis, and the frequency statistics showed that 43 herbs had been used more than 16 times. The association rules analysis showed that 26 high-frequency me-dicine pair rules were obtained, and the association rules for those dispelling evil spirits, strengthening the body, resolving stasis, dispelling dampness, etc. were visualized. In the cluster analysis, we generated a dendrogram from which 7 groups of traditional Chinese medicines with homogeneity were extracted. 10 common factors were obtained in the factor analysis. The types of herbal medicines involved in the colorectal cancer prescription included anti-cancer antidotes, strengthening and tonifying medicines, blood-regulating medicines, and expectorant medicines, corresponding to the treatment for eliminating evil spirits, strengthening, resolving stasis, and expectorating dampness. The prescriptions for anti-cancer detoxification were normally based on the pairs composed of Scutellaria barbata-Hedyotis diffusa and Sophora flavescens, Sargentodoxa cuneata, S. barbata, often combined with stasis relieving drug and dampness eliminating drug, reflecting the characteristics of treatment for both toxicity and stasis, dampness and toxicity simultaneously. The prescriptions for strengthening the righteousness and tonifying the deficiency were composed of Astragalus membranaceus and Atractylodes macrocephala mainly, exerting the effect of benefiting Qi, strengthening the spleen and drying dampness, tonifying kidney and essence, tonifying blood and invigorating blood. Meanwhile, anti-cancer detoxification medicines shall be reduced as much as possible. The compatibility of the medicines for the intestinal tract reflected the principle of using the right medicine for the right condition and eliminating evil spirits or strengthening the body, as appropriate.
Colorectal Neoplasms/drug therapy* ; Data Mining ; Drug Prescriptions ; Drugs, Chinese Herbal/therapeutic use* ; Humans ; Medicine, Chinese Traditional

Objective:To take zebrafish embryo as the research object, in order to investigate the development toxicity, cardiotoxicity, liver toxicity and kidney toxicity of water extract of Jiaotaiwan (JTW) on zebrafish embryo. Method:Zebrafish embryos with normal development at 12 h (hpf) after fertilization were selected as model animals for the growth and cardiotoxicity experiments. The embryos were treated with 125, 250, 500 mg·L^-1 of JTW water extracts, and the effects of the drugs on the heart rate and morphology of the embryos and LD₅₀ were observed at 72 h (hpf) after fertilization. Zebrafish embryos with normal development at 72 h (hpf) after fertilization were used as model animals for the liver and kidney toxicity experiments. The embryos were treated with 125，250，500 mg·L^-1 of JTW water extracts, and the effect of the drugs on morphological changes, Alanine aminotransferase(ALT), Aspartate aminotransferase (AST) activity, and creatinine content of the larvae and LD₅₀ were observed at 72 d (dpf) after fertilization. Result:The zebrafish embryos in control group developed normally, the heart was well developed, and the heartbeat was even and powerful. The LD₅₀ of JTW water extract on zebrafish embryos for 72 h was 1 023 mg·L^-1. Compared with the embryos in the control group, 250，500 mg·L^-1 treatment groups in the development toxicity had a smaller head, shorter body lengths (P<0.05), and decreased eye size (P<0.05). Compared with the control group embryos, the pericardial edema was observed in the 500 mg·L^-1 group, the heart rate was significantly decreased in the 250，500 mg·L^-1 JTW water extract groups (P<0.01), the atrial and ventricular areas were significantly reduced (P<0.05), the distance of SV-BA became significantly larger (P<0.05), the distance of AV channel became significantly larger (P<0.01), and the in-flow distance was significantly shorter (P<0.01). In the acute toxicity experiment, the LD₅₀ of JTW water extract for zebrafish larvae for 72 h was 1 067 mg·L^-1. Compared with control group, JTW water extract significantly reduced ALT activity in zebrafish larvae (P<0.05). Conclusion:This experiment found that JTW has an obvious toxicity in embryonic development, which is mainly manifested as delayed growth and severe cardiotoxicity. Great attention shall be paid to clinical administration to pregnant women, lactating women and patients with heart disease.