Analysis of the heavy metal contents' effect on steroidal saponins and the anti-breast cancer activity of Paris polyphylla var. yunnanensis.

Background: P. polyphylla var. yunnanensis, as a near-threatened and ethnic medicine in China, used to be a key ingredient in traditional Chinese medicine in treatment of traumatic injuries, sore throat, snakebites, and convulsions for thousands of years. However, there were no reports on the inverse relationship between the contents of heavy metals and saponins and its anti-breast cancer pharmacological activity in P. polyphylla var. yunnanensis. Methods: The present study aimed to reveal the characteristics of heavy metal contents and saponins and its anti-breast cancer pharmacological activity and their interrelationships in P. polyphylla var. yunnanensis from different production areas. The contents of heavy metal and steroidal saponins in P. polyphylla var. yunnanensis were analyzed by inductively coupled plasma mass spectrometry (ICP-MS) and the high-performance liquid chromatography technique, respectively. The Pearson correlation was used to study the correlation between saponins and heavy metals. 4T1 mouse mammary tumor cells were selected and cultivated for antitumor studies in vitro. Cell Counting Kit-8 (CCK-8) assay, Hoechst staining, and flow cytometry analysis were used for the examination of the proliferation and apoptosis of 4T1 tumor cells. Mouse breast cancer 4T1 cells were subcutaneously injected into BALB/c mice to construct a tumor model to explore the in vivo inhibitory effect on breast cancer. TUNEL assay and immunohistochemistry were used for the examination of the effect of P. polyphylla var. yunnanensis from different origins on cancer cell proliferation and apoptosis induction in 4T1 tumor mice. Results: Heavy metal contents were highly correlated with the content of steroidal saponins. The overall content of 10 metals in the three producing origins was of the order C3 >C2 >C1. The total content of eight steroidal saponins in the extracts of P. polyphylla var. yunnanensis from three different origins was C1 >C2 >C3. The Pearson correlation study showed that in all of the heavy metals, the contents of Cd and Ba were positively correlated with the main steroidal saponins in P. polyphylla var. yunnanensis, while Al, Cr, Cu, Fe, Zn, As, Hg, and Pb showed a negative correlation. In vitro experiments showed that the extracts of P. polyphylla var. yunnanensis from three origins could inhibit the proliferation and induce cell apoptosis of 4T1 cells in a concentration- and time-dependent manner, especially in the C1 origin. In vivo experiments showed that the extract of P. polyphylla var. yunnanensis from the three origins could inhibit the growth of tumors and induce the apoptosis of tumor cells. In the three origins, C1 origin had the lowest total heavy metal level but the highest total steroidal saponin level. Therefore, it showed a better effect in reducing the expression of the human epidermal growth factor receptor 2 (HER2) and Kiel 67 (Ki67) and increasing the expression of p53 in tumor tissues compared to the other origins. In conclusion, in the three origins, C1 origin exhibits antitumor pharmacological effects in vivo and in vitro which are better than those in the other origins. Conclusion: In this study, we found that with the increase of the heavy metal content, the content of steroid saponins and anti-breast cancer activity decreased. The results showed that the high content of the total heavy metals may not be conducive to the accumulation of steroidal saponins in P. polyphylla var. yunnanensis and lead to the low anti-breast cancer activity. The results of this study suggest that the content of heavy metals should be controlled in the artificial cultivation process of P. polyphylla var. yunnanensis.

Is endoscopic retrograde appendicitis therapy a better modality for acute uncomplicated appendicitis? A systematic review and meta-analysis.

BACKGROUND: Previous studies had shown endoscopic retrograde appendicitis therapy (ERAT) is an effective treatment for acute appendicitis. However, different studies reported conflicting outcomes regarding the effectiveness of ERAT in comparison with laparoscopic appendectomy (LA). AIM: To compare the effectiveness of ERAT with LA. METHODS: Randomized controlled trials (RCTs) and retrospective studies of ERAT for acute uncomplicated appendicitis were searched in PubMed, Cochrane Library, Web of Science, Embase database, China National Knowledge Infrastructure (CNKI), the WanFang Database, and Chinese Scientific Journals Database (VIP) from the establishment date to March 1 2021. Heterogeneity was assessed using the I-squared statistic. Pooled odds ratios (OR), weighted mean difference (WMD), and standard mean difference (SMD), with 95% confidence intervals (CI) were calculated through either fixed-effects or random-effects model. Sensitivity analysis was also performed. Publication bias was tested by Egger's test, and Begg's test. The quality of included RCT were evaluated by the Jadad scale, while Newcastle-Ottawa scale is adopted for assessing the methodological quality of case-control studies. All statistical analysis was performed using Stata 15.1 statistical software. All statistical analysis was performed using Stata 15.1 statistical software. This study is registered with PROSPERO, CRD42021243955. RESULTS: After screening, 10 RCTs and 2 case-control studies were included in the current systematic review. Firstly, the length of hospitalizations [WMD = -1.15, 95%CI: -1.99, -0.31; P = 0.007] was shorter than LA group. Secondly, the level of post-operative CRP [WMD = -10.06, 95%CI: (-17.39, -2.73); P = 0.007], TNF-α [WMD = -7.70, 95%CI: (-8.47, -6.93); P < 0.001], and IL-6 Levels [WMD = -9.78, 95%CI: (-10.69, -8.88); P < 0.001; P < 0.001] in ERAT group was significantly lower than LA group. Thirdly, ERAT group had a lower incidence of intestinal obstruction than LA group. [OR = 0.19, 95%CI: (0.05, 0.79); P = 0.020]. Moreover, the quality of 10 RCTs were low with 0-3 Jadad scores, while the methodological quality of two case-control studies were fair with a score of 2 (each). CONCLUSION: Compared with LA, ERAT reduces operation time, the level of postoperative inflammation, and results in fewer complications and shorter recovery time, with preserving the appendix and its immune and biological functions.

[Effect of Banxia Xiexin Decoction on intestinal flora of mice with ulcerative colitis induced by dextran sodium sulfate].

The aim of this paper was to investigate the effect of Banxia Xiexin Decoction(BXD) on inflammatory factors and intestinal flora in a dextran sulfate sodium induced ulcerative colitis(DSS-UC) mouse model, and to explore the mechanism of BXD in treating ulcerative colitis from the perspective of flora disorder. Forty C57 BL/6 J mice were randomly divided into control group, model group and BXD group. A 2.5% DSS-induced ulcerative colitis model was established. On the 8 th day, normal saline, normal saline, and BXD were given daily for 14 days. After 14 days, HE staining was used to observe histopathological changes of the colon. Serum inflammatory factor content was detected by ELISA, and the change of intestinal flora in mice feces was detected by 16 S rRNA sequencing technology. Compared with control group, the colonic tissue of mice in model group was damaged seriously, and the contents of IL-6 and TNF-α in serum were significantly increased(P<0.05). Compared with model group, mice in BXD group had less colonic damage, and the contents of IL-6, TNF-α in serum were decreased significantly(P<0.05). After creation, the richness of Patescibacteria was increased significantly at the phylum level(P<0.05). At the same time, the richness of Faecalibaculum(P<0.01), norank_f_Muribaculaceae(P<0.01) were decreased significantly at the genus level, while the richness of Turicibacter(P<0.01), Romboutsia(P<0.01), Clostridium_sensu_stricto_1(P<0.01) were increased significantly. After the intervention with BXD, the content of Patescibacteria was significantly reduced at the phylum level(P<0.05), and the contents of Lactobacillus(P<0.01), Clostri-dium_sensu_stricto_1(P<0.01), Enterorhabdus(P<0.01), Candidatus_Saccharimonas(P<0.05), Eubacterium_fissicatena_group(P<0.05) were decreased significantly at the genus level, while the contents of Dubosiella, Bacteroides and Allobaculum were increased significantly. Therefore, BXD could significantly improve the symptoms of DSS-UC mice. It not only could reduce the contents of IL-6 and TNF-α, but also could reduce the richness of Patescibacteria at the phylum level, and those of Clostridium_sensu_stricto_1, Candidatus_Saccharimonas, Eubacterium_fissicatena_group at the genus level. Inaddition, BXD could increase the richness of Bacteroides and Bifidobacterium. It suggested that BXD could play a role in the treatment of ulcerative colitis partially through reducing inflammatory factors and regulating the structure of the gut microbiota.

METTL3 Is Suppressed by Circular RNA circMETTL3/miR-34c-3p Signaling and Limits the Tumor Growth and Metastasis in Triple Negative Breast Cancer.

Despite N6-methyladenosine (m6A) is functionally important in various biological processes, its role in the underlying regulatory mechanism in TNBC are lacking. In this study, we investigate the pathological role and the underlying mechanism of the m6A methylated RNA level and its major methyltransferase METTL3 in the TNBC progression. We found that the m6A methylated RNA was dramatically decreased in TNBC tissues and cell lines. Functionally, we demonstrated that METTL3 inhibits the proliferation, migration, and invasion ability of TNBC cells. Moreover, we found METTL3 is repressed by miR-34c-3p in TNBC cells. On the mechanism, we found that circMETTL3 could act as a sponge for miR-34c-3p and inhibits cell proliferation, invasion, tumor growth and metastasis by up-regulating the expression of miR-34c-3p target gene METTL3. In conclusion, our study demonstrates the functional importance and regulatory mechanism of METTL3 in suppressing the tumor growth of TNBC.

Assessing risk factors for SARS-CoV-2 infection in patients presenting with symptoms in Shanghai, China: a multicentre, observational cohort study.

Background: The outbreak of COVID-19 has led to international concern. We aimed to establish an effective screening strategy in Shanghai, China, to aid early identification of patients with COVID-19. Methods: We did a multicentre, observational cohort study in fever clinics of 25 hospitals in 16 districts of Shanghai. All patients visiting the clinics within the study period were included. A strategy for COVID-19 screening was presented and then suspected cases were monitored and analysed until they were confirmed as cases or excluded. Logistic regression was used to determine the risk factors of COVID-19. Findings: We enrolled patients visiting fever clinics from Jan 17 to Feb 16, 2020. Among 53 617 patients visiting fever clinics, 1004 (1·9%) were considered as suspected cases, with 188 (0·4% of all patients, 18·7% of suspected cases) eventually diagnosed as confirmed cases. 154 patients with missing data were excluded from the analysis. Exposure history (odds ratio [OR] 4·16, 95% CI 2·74-6·33; p<0·0001), fatigue (OR 1·56, 1·01-2·41; p=0·043), white blood cell count less than 4 × 109 per L (OR 2·44, 1·28-4·64; p=0·0066), lymphocyte count less than 0·8 × 109 per L (OR 1·82, 1·00-3·31; p=0·049), ground glass opacity (OR 1·95, 1·32-2·89; p=0·0009), and having both lungs affected (OR 1·54, 1·04-2·28; p=0·032) were independent risk factors for confirmed COVID-19. Interpretation: The screening strategy was effective for confirming or excluding COVID-19 during the spread of this contagious disease. Relevant independent risk factors identified in this study might be helpful for early recognition of the disease. Funding: National Natural Science Foundation of China.

Synergistic effects of temperature and humidity on the symptoms of COPD patients.

This panel study investigates how temperature, humidity, and their interaction affect chronic obstructive pulmonary disease (COPD) patients' self-reported symptoms. One hundred and six COPD patients from Shanghai, China, were enrolled, and age, smoking status, St. George Respiratory Questionnaire (SGRQ) score, and lung function index were recorded at baseline. The participants were asked to record their indoor temperature, humidity, and symptoms on diary cards between January 2011 and June 2012. Altogether, 82 patients finished the study. There was a significant interactive effect between temperature and humidity (p < 0.0001) on COPD patients. When the indoor humidity was low, moderate, and high, the indoor temperature ORs were 0.969 (95% CI 0.922 to 1.017), 0.977 (0.962 to 0.999), and 0.920 (95% CI 0.908 to 0.933), respectively. Low temperature was a risk factor for COPD patients, and high humidity enhanced its risk on COPD. The indoor temperature should be kept at least on average at 18.2 °C, while the humidity should be less than 70%. This study demonstrates that temperature and humidity were associated with COPD patients' symptoms, and high humidity would enhance the risk of COPD due to low temperature.

Prognostic value of CD133 expression in cancer patients treated with chemoradiotherapy: a meta-analysis.

Many studies evaluated the correlations of CD133 expression with the clinical outcomes in patients treated with chemoradiotherapy (CRT) but yielded controversial results. This meta-analysis was performed to identify the impacts of CD133 expression on the prognosis of cancer patients treated with CRT. Electronic databases updated up to March 2014 were searched to find relevant studies. Relevant literatures without any language restrictions were searched via electronic databases as follows: Web of Science (1945 ~ 2013), the Cochrane Library Database (Issue 12, 2013), PubMed (1966 ~ 2013), EMBASE (1980 ~ 2013), CINAHL (1982 ~ 2013), and the Chinese Biomedical Database (CBM) (1982 ~ 2013). STATA software was used for the current meta-analysis. Hazard ratios (HR) and its corresponding 95% confidence interval (95% CI) were calculated. Six studies were identified with a total of 470 cancer patients treated with CRT. The meta-analysis results showed that CD133-positive patients had poorer overall survival (OS) than that of CD133-negative patients (HR = 2.13, 95% CI = 1.20 ~ 3.07, P < 0.001). Furthermore, CD133-positive patients displayed shorter disease-free survival (DFS) than that of CD133-negative patients (HR = 1.74, 95% CI = 0.08 ~ 3.40, P = 0.039). Ethnicity-stratified analysis indicated that CD133 expression positively correlated with shorter OS among the Japanese, Chinese, and Spanish populations (all P < 0.05). In conclusion, our findings suggest that CD133 expression may be positively correlated with poorer prognosis in cancer patients treated with CRT.

[Clinical effects of sub-maximum ergometry exercise rehabilitation in patients with chronic obstructive pulmonary disease].

OBJECTIVE: To study the rehabilitation effects ergometry on COPD patients. METHODS: Thirty COPD out-patients in our Hospital were randomly divided into 2 groups. Rehabilitation group, 15 patients, performed leg ergometry exercise of 80% peak Watt x 30min/d x 3d/w x 12w. Another 15 patients were control group without exercise. All patients received conventional therapy. Pulmonary function testing (PFT), cardiopulmonary exercise testing (CPET), arterial blood gas analysis (ABG), Borg and CAT sores were done at both baseline and 12 w. RESULTS: There was no statistically difference in lung function testing, blood gas analysis and cardiopulmonary exercise test when pre- exercises between 2 sub-groups. The IC, peak VO2 and peak, W of rehabilitation group significantly increased (P < 0.05); and Borg and CAT.scores significantly decreased (P < 0.05) from baseline; and other PFT and ABG did not change (P > 0.05). While there was no difference in control group (P > 0.05). CONCLUSION: Leg submaximal ergometry rehabilitation improves health condition and ameliorate dyspnea symptoms in COPD patients.

The ability of volumetric capnography to distinguish between chronic obstructive pulmonary disease patients and normal subjects.

PURPOSE: The aim of our study was to evaluate volumetric capnography (VCap) in the differentiation between chronic obstructive pulmonary disease (COPD) patients and normal subjects. PATIENTS AND METHODS: Thirty-nine healthy male volunteers and 60 male COPD patients were enrolled. Regression equations between VCap indices and age, weight, height, and tidal volume in healthy volunteers were established by stepwise regression analysis. Predicted normal values of VCap indices in COPD patients were calculated. A paired t test was used to compare the difference between observed and predicted values for VCap indices in COPD patients. Receiver operating characteristic (ROC) curve analysis was used to evaluate the power of each VCap index alone in differentiating COPD patients and normal subjects. The power of the combination of VCap indices was assessed by discriminant analysis. RESULTS: All regression equations were significant (P < 0.01) as were the differences between the observed and predicted normal VCap indices in COPD patients (P < 0.001). ROC curve analysis showed that the volume between 25 and 50% of F CO2et (Vm25-50), slope of Phase II (dC2/dV), and slope of Phase III (dC3/dV) were valuable predictors. Nearly all (90.9%) subjects were correctly classified by discriminant analysis. CONCLUSION: Vm25-50, dC2/dV, or dC3/dV alone are valuable for differentiating COPD patients and normal subjects, but more powerful are the combinations of Vm25-50, dC2/dV, and dC3/dV, the ratio of dC2/dV to dC3/dV (SR23), dead space according to the Bohr method (VDB), and dead space according to the Wolff and Brunner methods (PIE).

Detection of the airway obstruction stage in asthma using impulse oscillometry system.

OBJECTIVE: Although spirometry is the most common method for evaluating the airway obstruction stage in asthma patients, it is difficult to perform in some patients. The aim of this study was to evaluate whether impulse oscillometry, an easy-to-perform technique, can detect asthmatic airway obstruction stage. METHODS: A total of 80 subjects, including healthy volunteers and patients with asthma, were enrolled in this study. The asthma patients were classified into three groups according to American Thoracic Society (ATS)/European Respiratory Society (ERS)-2005: the mild group (forced expiratory volume in 1 second (FEV(1)) ≥ 70% predicted (Pred), n = 20), the moderate group (50% Pred ≤ FEV(1) <70% Pred, n = 20), and the severe group (FEV(1) < 50% Pred, n = 20). Spirometry and impulse oscillometry (IOS) parameters were obtained from every subject. Correlation analysis was used to compare spirometry measurements and IOS parameters. One-way analysis of variance (ANOVA) was performed to compare IOS parameters among different groups. The potential of using all individual IOS parameters to detect the different stages of asthmatic airway obstruction was evaluated by the receiver operating characteristic (ROC) curve analysis. RESULTS: The correlation analysis showed that IOS parameters, such as respiratory resistance at 5 Hz (R(5)), respiratory resistance at 10 Hz (R(10)), respiratory resistance at 20 Hz (R(20)), difference in resistance between 5 Hz and 20 Hz (R(5-20)), impedance at 5 Hz (Z(5)), resonant frequency (Fres), and area of reactance (AX) were negatively correlated with FEV(1) and peak expiratory flow (PEF), while reactance at 5 Hz (X(5)) was positively correlated with FEV(1) and PEF. The increase in R(5), R(10), R(20), Z(5), R(5-20), Fres, (-X(5)), and AX parameters corresponded significantly with an increase in the airway obstruction stage, as determined by one-way ANOVA . ROC curve analysis revealed that all the IOS parameters studied, except for Fres, were capable of classifying asthmatic airway obstruction. R(5), R(5-20), and Z(5) were the most accurate parameters. CONCLUSION: IOS provides an accurate, reliable, and patient-friendly technique for classifying asthmatic airway obstruction.