Protocol for detecting micro(nano)plastics released from intravenous infusion products.

Approaches for detecting micro(nano)plastics (MNPs) released from intravenous infusion products (IVIPs) are vital for evaluating the safety of both IVIPs and their derived MNPs on human health, yet current understanding is limited. Here, we present a protocol for detecting polyvinyl chloride (PVC) MNPs by combining Raman spectroscopy, scanning electron microscopy equipped with energy-dispersive X-ray spectroscopy (SEM-EDS), and pyrolysis-gas chromatography-mass spectrometry (Py-GC-MS). We describe steps for collecting, pretreating, and measuring PVC MNPs released from IVIPs. For complete details on the use and execution of this protocol, please refer to Li et al.1.

Agricultural drought-driven mechanism of coupled climate and human activities in the karst basin of southern China.

Timely and accurate agricultural drought monitoring and drought-driven mechanism analysis in karst basins in the context of global warming are highly important for drought disaster monitoring and sustainable ecological development in a basin. In this study, based on MODIS data, meteorological and topographic data and land use data from 2001 to 2020, we used the Sen slope, the Mann-Kendall test and a geographic detector to explore the driving mechanisms of agricultural drought caused by climate change and human activities in the karst basin of southern China from 2001 to 2020. The results showed that (1) the spatial distribution of the TVDI in the karst basin in southern China has obvious regional characteristics, showing a decreasing trend from west to east. (2) According to the interannual trend of drought, the degree of drought in the South China karst basin exhibited a weakening trend over the last 20 years, with the most severe drought occurring in 2003. Regarding the seasonal change in the TVDI, drought in spring, summer and autumn exhibited a decreasing trend, while that in winter exhibited an increasing trend, and the drought intensity decreased in the following order: spring (0.58) > autumn (0.53) > summer (0.5) > winter (0.48). (3) Single-factor detection the results showed that rainfall, temperature and elevation were the main factors driving aridification in the study area; multifactor coupling (mean) drove drought in descending order: rainfall (q = 0.424) > temperature (q = 0.340) > elevation (q = 0.219) > land use (q = 0.188) > population density (q = 0.061) > slope (q = 0.057). Therefore, revealing the mechanism of agricultural drought in karst basins through the study of this paper has important theoretical significance and provides technical guidance for drought relief in karst areas.

Nebivolol, an antihypertensive agent, has new application in inhibiting melanoma.

Repurposing existing drugs for cancer therapy has become an important strategy because of its advantages, such as cost reduction, effect and safety. The present study was designed to investigate the antimelanoma effect and possible mechanisms of action of nebivolol, which is an approved and widely prescribed antihypertensive agent. In this study, we explored the effect of nebivolol on cell proliferation and cell activity in melanoma in vitro and the potential antimelanoma mechanism of nebivolol through a series of experiments, including the analysis of the effects with regard to cell apoptosis and metastasis. Furthermore, we evaluated the antimelanoma effect on xenograft tumor models and inspected the antimelanoma mechanism of nebivolol in vivo using immunohistochemical and immunofluorescence staining assays. As results in this work, in vitro , nebivolol possessed a strong activity for suppression proliferation and cell cycle arrest on melanoma. Moreover, nebivolol significantly induced cell apoptosis in melanoma through a mitochondrial-mediated endogenous apoptosis pathway. Additionally, nebivolol inhibited melanoma cell metastasis. More importantly, nebivolol exhibited significantly effective melanoma xenograft models in vivo , which related to the mechanism of apoptosis induction, proliferation inhibition, metastasis blocking and angiogenesis arrest. Overall, the data of the present study recommend that nebivolol holds great potential in application as a novel agent for the treatment of melanoma.

Associations between the use of red yeast rice preparations and adverse health outcomes: An umbrella review of meta-analyses of randomized controlled trials.

BACKGROUND: Red yeast rice (RYR), a natural lipid-lowering agent, is widely used in clinical practice. However, the existing meta-analyses concerning the safety of RYR preparations have yielded inconsistent results, and the credibility of the evidence has not been quantified. OBJECTIVE: This study was designed to evaluate the existing evidence and offer a comprehensive understanding of the associations between the use of RYR preparations and various adverse health outcomes. SEARCH STRATEGY: Seven literature databases were searched from inception to May 5, 2023, using medical subject headings and free-text terms (e.g., "red yeast rice," "Xuezhikang," and "Zhibitai"). INCLUSION CRITERIA: Meta-analyses that investigated and quantitatively estimated associations between the use of RYR preparations and adverse health outcomes were included in this study. DATA EXTRACTION AND ANALYSIS: Two researchers independently extracted data using a standardized data collection table; any disagreements were resolved by consulting a third researcher. Based on the participant, intervention, comparator and outcome (PICO) framework in each eligible meta-analysis, a series of unique associations between the use of RYR preparations and adverse health outcomes were determined. The associations' effect estimates were re-evaluated using random-effect models. RESULTS: Fifteen meta-analyses, comprising 186 (164 unique) randomized controlled trials, were identified. Based on A MeaSurement Tool to Assess Systematic Reviews version 2, 3 (20%) and 12 (80%) of these meta-analyses had low and critically low confidence, respectively. A total of 61 unique associations between the use of RYR preparations and adverse health outcomes were extracted from eligible meta-analyses. Based on the random-effect models, 10 (16.4%) associations indicated a significant protective effect of RYR preparations against adverse health outcomes, while 5 (8.2%) indicated an increased risk of adverse health outcomes related to uric acid, alanine transaminase and aspartate transaminase levels. The other 46 (75.4%) associations showed no significant difference between the use of RYR preparations and control treatments. Regarding the credibility of the evidence, 21 (34.4%), 34 (55.7%) and 6 (9.8%) associations showed moderate, low and very low credibility, respectively. CONCLUSION: The evidence examined in this study suggests that RYR preparations are safe; however, the credibility of the evidence was not high. Further high-quality evidence is required. Please cite this article as: Ma ZY, Yang SP, Li Y, Xu TT, Yang YL, Yang HY, Li HB, Zhou LJ, Diao Y, Li SY. Associations between the use of red yeast rice preparations and adverse health outcomes: An umbrella review of meta-analyses of randomized controlled trials. J Integr Med. 2024; 22(2): 126-136.

Design, Synthesis, and Activity Evaluation of Fluorine-Containing Scopolamine Analogues as Potential Antidepressants.

This study aimed to develop novel rapid-acting antidepressants with sustained efficacy and favorable safety profiles. We designed and synthesized a series of fluorine-containing scopolamine analogues and evaluated their antidepressant potential. In vitro cytotoxicity assays showed that most of these compounds exhibited minimal toxicity against neuronal and non-neuronal mammalian cell lines (IC50 > 100 µM). The antidepressant activities of the compounds were evaluated using the tail suspension test, and S-3a was identified as a lead compound with potent and sustained antidepressant effects. Behaviorally, S-3a alleviated depressive symptoms in mice and displayed a higher cognitive safety margin than scopolamine. Toxicological assessments confirmed S-3a's safety, while pharmacokinetics showed a rapid clearance (half-life: 16.6 min). Mechanistically, S-3a antagonized M1 receptors and elevated BDNF levels, suggesting its potential as an antidepressant for further exploration.

Repurposing of Antidiarrheal Loperamide for Treating Melanoma by Inducing Cell Apoptosis and Cell Metastasis Suppression In Vitro and In Vivo.

BACKGROUND: Melanoma is the most common skin tumor worldwide and still lacks effective therapeutic agents in clinical practice. Repurposing of existing drugs for clinical tumor treatment is an attractive and effective strategy. Loperamide is a commonly used anti-diarrheal drug with excellent safety profiles. However, the affection and mechanism of loperamide in melanoma remain unknown. Herein, the potential anti-melanoma effects and mechanism of loperamide were investigated in vitro and in vivo. METHODS: In the present study, we demonstrated that loperamide possessed a strong inhibition in cell viability and proliferation in melanoma using MTT, colony formation and EUD incorporation assays. Meanwhile, xenograft tumor models were established to investigate the anti-melanoma activity of loperamide in vivo. Moreover, the effects of loperamide on apoptosis in melanoma cells and potential mechanisms were explored by Annexin V-FITC apoptosis detection, cell cycle, mitochondrial membrane potential assay, reactive oxygen species level detection, and apoptosis-correlation proteins analysis. Furthermore, loperamide-suppressed melanoma metastasis was studied by migration and invasion assays. What's more, immunohistochemical and immunofluorescence staining assays were applied to demonstrate the mechanism of loperamide against melanoma in vivo. Finally, we performed the analysis of routine blood and blood biochemical, as well as hematoxylin-eosin (H&E) staining, in order to investigate the safety properties of loperamide. RESULTS: Loperamide could observably inhibit melanoma cell proliferation in vitro and in vivo. Meanwhile, loperamide induced melanoma cell apoptosis by accumulation of the sub-G1 cells population, enhancement of reactive oxygen species level, depletion of mitochondrial membrane potential, and apoptosis-related protein activation in vitro. Of note, apoptosis-inducing effects were also observed in vivo. Subsequently, loperamide markedly restrained melanoma cell migration and invasion in vitro and in vivo. Ultimately, loperamide was witnessed to have an amicable safety profile. CONCLUSION: These findings suggested that repurposing of loperamide might have great potential as a novel and safe alternative strategy to cure melanoma via inhibiting proliferation, inducing apoptosis and cell cycle arrest, and suppressing migration and invasion.

Genetic Analysis of Adaptive Traits in Spring Wheat in Northeast China.

The dissection of the genetic architecture and the detection of the loci for adaptive traits are important for marker-assisted selection (MAS) for breeding. A spring wheat diversity panel with 251 cultivars, mainly from China, was obtained to conduct a genome-wide association study (GWAS) to detect the new loci, including the heading date (HD), maturating date (MD), plant height (PH), and lodging resistance (LR). In total, 41 loci existing in all 21 chromosomes, except for 4A and 6B, were identified, and each explained 4.3-18.9% of the phenotypic variations existing in two or more environments. Of these, 13 loci are overlapped with the known genes or quantitative trait loci (QTLs), whereas the other 28 are likely to be novel. The 1A locus (296.9-297.7 Mb) is a multi-effect locus for LR and PH, whereas the locus on chromosome 6D (464.5-471.0 Mb) affects both the HD and MD. Furthermore, four candidate genes for adaptive traits were identified, involved in cell division, signal transduction, and plant development. Additionally, two competitive, allele-specific PCR (KASP) markers, Kasp_2D_PH for PH and Kasp_6D_HD for HD, were developed and validated in another 162 spring wheat accessions. Our study uncovered the genetic basis of adaptive traits and provided the associated SNPs and varieties with more favorable alleles for wheat MAS breeding.

Direct entry of micro(nano)plastics into human blood circulatory system by intravenous infusion.

Understanding the pathways of human exposure to micro(nano)plastics (MNPs) is crucial for assessing their health impacts. Intravenous infusion can induce MNPs direct entry into the human blood, posing serious risks on human health, but remains unclear. Herein, we developed comprehensive analytical methods to detect polyvinyl chloride (PVC) MNPs down to 20 nm, and found about 0.52 µg equal to 105-1011 particles of PVC-MNPs released from intravenous infusion products (IVIPs) during each intravenous infusion of 250 mL injection. The released amounts of MNPs from IVIPs were dependent on the plastic materials, and the injection volume and composition. These findings indicated that the released MNPs should be directly introduced into the human blood circulatory system, causing serious impacts on human health. Our study reveals a previously ignored but important pathway of human exposure to MNPs, and calls for further research on the potential risks of these MNPs on human health.

Development and validation of a nomogram to predict the five-year risk of revascularization for non-culprit lesion progression in STEMI patients after primary PCI.

Background: Acute ST-segment elevation myocardial infarction (STEMI) patients after primary PCI were readmitted for revascularization due to non-culprit lesion (NCL) progression. Objective: To develop and validate a nomogram that can accurately predict the likelihood of NCL progression revascularization in STEMI patients following primary PCI. Methods: The study enrolled 1,612 STEMI patients after primary PCI in our hospital from June 2009 to June 2018. Patients were randomly divided into training and validation sets in a 7:3 ratio. The independent risk factors were determined by LASSO regression and multivariable logistic regression analysis. Multivariate logistic regression analysis was utilized to develop a nomogram, which was then evaluated for its performance using the concordance statistics, calibration plots, and decision curve analysis (DCA). Results: The nomogram was composed of five predictors, including age (OR: 1.007 95% CI: 1.005-1.009, P < 0.001), body mass index (OR: 1.476, 95% CI: 1.363-1.600, P < 0.001), triglyceride and glucose index (OR: 1.050, 95% CI: 1.022-1.079, P < 0.001), Killip classification (OR: 1.594, 95% CI: 1.140-2.229, P = 0.006), and serum creatinine (OR: 1.007, 95% CI: 1.005-1.009, P < 0.001). Both the training and validation groups accurately predicted the occurrence of NCL progression revascularization (The area under the receiver operating characteristic curve values, 0.901 and 0.857). The calibration plots indicated an excellent agreement between prediction and observation in both sets. Furthermore, the DCA demonstrated that the model exhibited clinical efficacy. Conclusion: A convenient and accurate nomogram was developed and validated for predicting the occurrence of NCL progression revascularization in STEMI patients after primary PCI.

Associations between teacher-student relationship and externalizing problem behaviors among Chinese rural adolescent.

The primary objective of this study is to present a fresh perspective on the correlation between teacher-student relationships and externalizing problem behaviors among adolescents. While previous research has examined this connection, there is still an insufficient understanding of the underlying mechanisms. Moreover, the crucial role of peer relationships, mental health, and parental knowledge has been overlooked. In this study, a total of 6,919 Chinese rural adolescents aged 13-19 years participated by completing an anonymous self-report questionnaire. The results show that: (1) teacher-student relationship has a protective effect against the development of externalizing problem behaviors; (2) peer relationship and mental health both have a mediating role in the relationship between teacher-student relationship and externalizing problem behaviors; (3) teacher-student relationship can indirectly affect externalizing problem behaviors through the chain mediation of peer relationship and mental health; (4) parental knowledge plays a moderating role between the teacher-student relationship and externalizing problem behaviors. As the level of parental knowledge increases among rural adolescents, the impact of the teacher-student relationship on externalizing problem behaviors becomes more pronounced; and (5) the impact of teacher-student relationship on externalizing problem behaviors has no significant gender differences. Given the study's empirical outcomes, we discuss potential explanations and advocate for a comprehensive pedagogical approach to mitigate rural adolescent externalizing behaviors. This entails nurturing teacher-student relations, fostering inclusive peer environments, emphasizing mental health literacy, and synergizing with caregivers for a holistic home-school intervention.

Association between triglyceride glucose-body mass index and heart failure in subjects with diabetes mellitus or prediabetes mellitus: a cross-sectional study.

Background: The triglyceride glucose-body mass index (TyG-BMI) is a surrogate indicator of insulin resistance. However, the association of TyG-BMI with heart failure (HF) in individuals with diabetes mellitus or prediabetes mellitus is unknown. Methods: This study included 7,472 participants aged 20-80 years old with prediabetes or diabetes from the National Health and Nutrition Examination Survey (2007-2018). The TyG-BMI was calculated as Ln [triglyceride (mg/dL) × fasting blood glucose (mg/dL)/2] × BMI, and individuals were categorized into tertiles based on TyG-BMI levels. The relationship of TyG-BMI with HF was analyzed using multiple logistic regression models. Subgroup analyses were stratified by gender, age, hypertension, and diabetes mellitus status. Results: This cross-sectional study had 7,472 participants (weighted n = 111,808,357), including 329 HF participants. Participants with a high TyG-BMI were prone to HF. The highest tertile group with a fully adjusted model was more likely to have HF compared to the lowest tertile group (odds ratio [OR], 2.645; 95% CI, 1.529-4.576). Restricted cubic spline analysis showed a significant dose-response relationship between TyG-BMI and HF (P < 0.001). In subgroup analyses, similar results were seen in terms of age (≥50 years old), gender, hypertension, and diabetes mellitus status. Conclusion: A high TyG-BMI is significantly associated with HF risk in participants with diabetes mellitus or prediabetes mellitus.

A nomogram for predicting the risk of intra-abdominal hypertension in critically ill patients based on ultrasound and clinical data.

Background: Intra-abdominal hypertension (IAH) is a common complication in critically ill patients. This study aimed to identify independent risk factors for IAH and generate a nomogram to distinguish IAH from non-IAH in these patients. Methods: We retrospectively analyzed 89 critically ill patients and divided them into an IAH group [intra-abdominal pressure (IAP) ≥12 mmHg] and a non-IAH group (IAP <12 mmHg) based on the IAP measured from their bladders. Ultrasound and clinical data were also measured. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors for IAH. The correlation between IAP and independent risk factors was also assessed. Results: Of these 89 patients, 45 (51%) were diagnosed with IAH. Univariate analysis showed there were significant differences in the right renal resistance index (RRRI) of the interlobar artery, the right diaphragm thickening rate (RDTR), and lactic acid (Lac) between IAH and non-IAH groups (P<0.001). Multivariate logistic regression analysis revealed that increasing RRRI, RDTR, and Lactic acid (Lac) were independent risk factors for IAH (P=0.001, P=0.001, and P=0.039, respectively). IAP was significantly correlated with RRRI, RDTR, and Lac (r=0.741, r=-0.774, and r=0.396, respectively; P<0.001). The prediction model based on regression analysis results was expressed as follows: predictive score = -17.274 + 31.125 × RRRI - 29.074 × RDTR + 0.621 × Lac. Meanwhile, the IAH nomogram prediction model was established with an area under the receiver operating characteristic (ROC) curve of 0.956 (95% confidence interval: 0.909-1.000). The nomogram showed good calibration for IAH with the Hosmer-Lemeshow test (P=0.864) and was found to be applicable within a wide threshold probability range, especially that higher than 0.40. Conclusions: The noninvasive nomogram based on ultrasound and clinical data has good diagnostic efficiency and can predict the risk of IAH. This nomogram may provide valuable guidance for clinical interventions to reduce IAH morbidity and mortality in critically ill patients.

Association between sun-protective behaviors and hypertension: a cross-sectional study from National Health and Nutrition Examination Survey 2009 to 2014.

BACKGROUND: In previous studies, sun-protective behaviors increased cardiovascular incidence. Our present article is to further analyze the potential relationship between sun-protective behaviors (staying in the shade, wearing long-sleeved clothing, and applying sunscreen) and hypertension. METHOD: The present cross-sectional study evaluated 8,613 participants (aged 20-60 years) from the National Health and Nutrition Examination Survey (NHANES) obtained between 2009 and 2014. We performed multiple logistic regression analysis to examine the relationship between sun-protective behaviors and hypertension. Subgroup analysis was then performed. Multiple linear regression analysis was utilized to examine the relationship of sun-protective behaviors and each sun-protective behavior with systolic and diastolic blood pressure, stratified by sex and race. RESULTS: A total of 8,613 participants (weighted n = 127,909,475) were applied in our study, including 1,694 hypertensive subjects. Our study demonstrated that sun-protective behaviors of the 2-3 category were associated with increased risk of hypertension, but not with higher systolic and diastolic blood pressure. In subgroup analysis, men, Mexican American, and 25 < BMI ≤ 30 who reported sun-protective behaviors (2-3) were prone to hypertension. Multiple linear regression models showed that non-Hispanic white men with sun-protective behaviors (2-3) were positively associated with systolic and diastolic blood pressure. The association between other-Hispanic men with frequent wearing long-sleeved clothing and diastolic blood pressure was positively correlated. CONCLUSION: Sun-protective behaviors of the 2-3 category could increase the incidence of hypertension, but not increase systolic and diastolic blood pressure. We only found that non-Hispanic white men who reported sun-protective behaviors (2-3) were positively associated with systolic and diastolic blood pressure. These findings suggested that excessive sun-protective behaviors should be avoided.

Establishment and comparison of piecewise linear regression models to measure thyroid volume by 2D and 3D ultrasound.

OBJECTIVE: Compared thyroid volumes measured by 2-D and 3-D US with those of resected specimens and proposed new models to improve measurement accuracy. METHODS: This study included 80 patients who underwent total thyroidectomy. One 2D_model and one 3D_model were developed using piecewise linear regression analysis. The accuracy of these models was compared using an ellipsoid model (2-D_US value × 0.5), 3-D_US value, and Ying's model [1.76 + (2-D_US value × 0.38)]. RESULTS: The new 2D_model was: V=2.66 + (0.71 * X1) - (1.51 * X2). In this model, if 2-D_US value <= 228.39, X1 = 2-D_US value and X2 = 0; otherwise, X1 = 2-D_US value and X2 = 2-D_US value - 228.39. The 3D_model was: V= 2.90 + (1.08 * X1) + (2.43 * X2). In this model, if 3-D_US value <= 102.06, X1 = 3-D_US value and X2 = 0; otherwise, X1 = 3-D_US value and X2 = 3-D_US value - 102.06. The accuracy of the new models was higher than that of the 3-D_US value, the ellipsoid model, and Ying's model (P<0.05). CONCLUSION: The models established are more accurate than the traditional ones and can accurately measure thyroid volume.

Can the ultrasound microcystic pattern accurately predict borderline ovarian tumors?

OBJECTIVE: To investigate whether the ultrasound microcystic pattern (MCP) can accurately predict borderline ovarian tumors (BOTs). METHODS: A retrospective collection of 393 patients who met the inclusion criteria was used as the study population. Indicators that could well identify BOT in different pathological types of tumors were derived by multivariate unordered logistic regression analysis. Finally, the correlation between ultrasound MCP and pathological features was analyzed. RESULTS: (1) MCP was present in 55 of 393 ovarian tumors, including 34 BOTs (34/68, 50.0%), 16 malignant tumors (16/88, 18.2%), and 5 benign tumors (5/237, 2.1%). (2) Univariate screening showed significant differences (P < 0.05) in patient age, CA-125 level, ascites, > 10 cyst locules, a solid component, blood flow, and MCP among BOTs, benign ovarian tumors, and malignant ovarian tumors. (3) Multivariate unordered logistic regression analysis showed that the blood flow, > 10 cyst locules, and MCP were significant factors in identifying BOTs (P < 0.05). (4) The pathology of ovarian tumors with MCP showed "bubble"- or "fork"- like loose tissue structures. CONCLUSION: MCP can be observed in different pathological types of ovarian tumors and can be used as a novel sonographic marker to differentiate between BOTs, benign tumors and malignant tumors. MCP may arise as a result of anechoic cystic fluid filling the loose tissue gap.

Development and validation of prediction models for the prognosis of colon cancer with lung metastases: a population-based cohort study.

Background: Current studies on the establishment of prognostic models for colon cancer with lung metastasis (CCLM) were lacking. This study aimed to construct and validate prediction models of overall survival (OS) and cancer-specific survival (CSS) probability in CCLM patients. Method: Data on 1,284 patients with CCLM were collected from the Surveillance, Epidemiology, and End Results (SEER) database. Patients were randomly assigned with 7:3 (stratified by survival time) to a development set and a validation set on the basis of computer-calculated random numbers. After screening the predictors by the least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression, the suitable predictors were entered into Cox proportional hazard models to build prediction models. Calibration curves, concordance index (C-index), time-dependent receiver operating characteristic (ROC) curves, and decision curve analysis (DCA) were used to perform the validation of models. Based on model-predicted risk scores, patients were divided into low-risk and high-risk groups. The Kaplan-Meier (K-M) plots and log-rank test were applied to perform survival analysis between the two groups. Results: Building upon the LASSO and multivariate Cox regression, six variables were significantly associated with OS and CSS (i.e., tumor grade, AJCC T stage, AJCC N stage, chemotherapy, CEA, liver metastasis). In development, validation, and expanded testing sets, AUCs and C-indexes of the OS and CSS prediction models were all greater than or near 0.7, which indicated excellent predictability of models. On the whole, the calibration curves coincided with the diagonal in two models. DCA indicated that the models had higher clinical benefit than any single risk factor. Survival analysis results showed that the prognosis was worse in the high-risk group than in the low-risk group, which suggested that the models had significant discrimination for patients with different prognoses. Conclusion: After verification, our prediction models of CCLM are reliable and can predict the OS and CSS of CCLM patients in the next 1, 3, and 5 years, providing valuable guidance for clinical prognosis estimation and individualized administration of patients with CCLM.

Combination of Chinese herbal medicine and conventional western medicine for coronavirus disease 2019: a systematic review and meta-analysis.

Objective: This study aimed to assess the efficacy and safety of Chinese herbal medicine (CHM) plus conventional western medicine (CWM) in comparison with CWM against COVID-19. Methods: We searched eight electronic databases and three trial registers spanning from January 1, 2020 to May 18, 2023. We included randomized controlled trials (RCTs) comparing the effectiveness and safety of CHM plus CWM and CWM against COVID-19 in our study. The Cochrane Risk of Bias tool 2.0 (RoB2) was applied to evaluate the methodological quality of the included RCTs. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system was employed to assess the certainty of evidence. Statistical analysis was implemented in R version 4.1.2. Results: Our study included 50 RCTs involving 11,624 patients. In comparison with sole CWM, CHM plus CWM against COVID-19 significantly enhanced clinical effective rate (RR = 1.18, 95% CI [1.13, 1.22]), improved chest image (RR = 1.19, 95% CI [1.11, 1.28]), inhibited clinical deterioration (RR = 0.45, 95% CI [0.33, 0.60]), lowered mortality (RR = 0.53, 95% CI [0.40, 0.70]), and reduced the total score of TCM syndrome (SMD = -1.24, 95% CI [-1.82, -0.66]). SARS-CoV-2 nucleic acid conversion time (MD = -2.66, 95% CI [-3.88, -1.44]), duration of hospitalization (MD = -2.36, 95% CI [-3.89, -0.82]), and clinical symptom (fever, cough, fatigue, and shortness of breath) recovery times were shorter in CHM plus CWM groups than in CWM groups. Further, CHM plus CWM treatment was more conducive for some laboratory indicators returning to normal levels. No statistical difference was found in the incidence of total adverse reactions between the two groups (RR = 0.97, 95% CI [0.88, 1.07]). We assessed the risk of bias for 246 outcomes, and categorized 55 into "low risk", 151 into "some concerns", and 40 into "high risk". Overall, the certainty of the evidence ranged from moderate to very low. Conclusions: Potentially, CHM listed in this study, as an adjunctive therapy, combining with CWM is an effective and safe therapy mode for COVID-19. However, more high-quality RCTs are needed to draw more accurate conclusions. Clinical trial registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=293963.

A novel benzothiazole derivative induces apoptosis via the mitochondrial intrinsic pathway producing antitumor activity in colorectal cancer.

Background: Colorectal cancer (CRC) is one of the most common malignancies causing the third highest mortality rate in the world. It is particularly urgent to explore effective therapeutic strategies to overcome this disease. We identified a novel benzothiazole derivative (BTD) that may serve as a potentially effective agent against CRC. Method: MTT assays, cell colony formation assays, EdU staining assays, flow cytometry, RNA-seq, Western blotting, and migration and invasion assays were used to examine the effects of BTD on cell proliferation, apoptosis, metastasis, and the cell cycle. The antitumor activity of BTD in vivo was investigated in a CT26 tumor-bearing mouse model. Immunohistochemistry (IHC) was performed to examine the protein expression in mouse tumors. Hematology, biochemical analysis, and H&E staining were used to assess the biosafety of BTD. Results: We observed that BTD suppressed cell proliferation and metastasis and promoted the apoptosis of tumor cells in vitro. Treatment with BTD at a tolerable dose significantly reduced tumor growth in CT26-tumor-bearing mice and appeared to be safe. Treatment of BTD induced apoptosis by increasing the generation of reactive oxygen species (ROS) and evoking the loss of mitochondrial transmembrane potential. Overall, BTD suppressed cell proliferation and metastasis, and induced apoptosis of colorectal tumor cells through the ROS-mitochondria-mediated apoptotic pathway. The preliminary proof of the antitumor activity and relative safety of BTD were validated in a mouse model. Conclusion: Our findings suggest that BTD could serve as a potentially safe and effective candidate for CRC treatment.

The Real-world Therapeutic Analysis of First-line Immunotherapy in Chinese Patients with Drive Gene Positive for Advanced Non-Small Cell Lung Cancer.

Background: Immune checkpoint inhibitors (ICIs) are widely used for treating advanced non-small cell lung cancer (NSCLC). However, some studies indicate that patients with genetic mutations do not benefit from immunotherapy. Hence, this study explored the efficacy of anti-programmed death-1 (PD-1) and anti-programmed death-ligand 1 (PD-L1) antibodies in the first-line treatment of advanced NSCLC with driver gene mutations in real-world settings. Methods: We retrospective analyzed patients with advanced NSCLC who treated with first-line anti-PD-1/PD-L1 antibodies at Shandong Provincial Hospital between May 2019 and October 2020. The patient's driver gene mutation status was identified using amplification refractory mutation system PCR (ARMS-PCR). The basic clinical characteristics, objective response rate (ORR), progression free survival (PFS), and other clinical data of patients were collected to evaluate the clinical efficacy and potential prognostic factors of treatment for patients with driver gene mutations. Results: A total of 430 patients' information was counted during this period, finally, 89 patients with NSCLC were enrolled in the study. The main pathological subtype of patients was adenocarcinoma (62.9%). The overall mutation rate was 44.9% (n = 40) and included following mutations: KRAS (n = 20), TP53 (n = 18), EGFR (n = 6), BRAF (n = 3), Her-2 (n = 3), MET (n = 3), ROS1 (n = 1), and NRAS (n = 1). The overall ORR was 44.30% and the disease control rate (DCR) was 82.23%. At the time of follow-up cut-off, the median PFS of all patients was 8.2 month. In NSCLC patients treated with ICI, median PFS was longer in mutation-negative patients than in mutation-positive patients (8.98 vs 7.07 months, P < 0.05). Survival benefit varied across mutational subgroups: KRAS patients could benefit from first-line immunotherapy (10.1 months, P < 0.05), patients with EGFR mutations have poor first-line immunotherapy outcomes, with a median PFS of only 3.0 months (P < 0.01), and patients with other mutation types having no significant difference in response from mutation-negative patients. In most mutation subgroups, immune combination therapy had longer PFS than immune monotherapy, and PD-L1 expression levels were positively correlated with clinical benefit in patients. Conclusion: In the real world, patients with KRAS mutations benefit from first-line immunotherapy, immune-combination modalities are more effective, and immune efficacy is positively correlated with PD-L1 expression; Patients with other driver mutations (BRAF, NRAS, Her2, MET, ROS1) benefit similarly to mutation-negative patients in first-line immunotherapy, and immunotherapy is recommended for first-line therapy; Immunotherapy is worse effective in patients with EGFR mutations, immunotherapy is not recommended in first-line therapy even patients with high PD-L1 expression.