Ulcerative colitis (UC) is a chronic inflammatory disease that damages colonic and rectal mucosa, and pharmacotherapy is the primary measure. However, the UC drug presents several notable problems, including low therapeutic efficacy, side effects, and high cost. Sophora moorcroftiana (S. moorcroftiana) is a plant native to the Tibetan Plateau. It is recorded that the aqueous extract of the seeds is used for treating digestive tract diseases, and the main alkaloids possess anti-inflammatory properties. Therefore, it is suggested that the water-soluble alkaloid (E2) from S. moorcroftiana may be a potential therapeutic agent against UC. The main alkaloids of the extract (E2, E2-a, and E2-b) were detected and identified by liquid chromatography-mass spectrometry (LC-MS). UC mice were induced with dextran sulfate sodium (DSS), followed by treatment with extract from S. moorcroftiana seeds. Disease activity index (DAI) scores and H&E staining were used to determine which extract has a therapeutic effect. The proportion of Tregs/Th17 cells was detected by flow cytometry, the levels of IL-6, TNF-α, IL-1β, and IL-28B in colon tissue were measured by ELISA, and the expression of p-STAT3, p-p65, p-IκBα, and p-p38 was detected with western blot. The main alkaloids of the extract were identified; there are 7 distinct alkaloids in E2, with E2-a and E2-b each containing 4, and piperine is present only in E2. Compared with the DSS group, mice treated with E2-b or E2 exhibited less severe damage, based on the milder DAI scores, longer colon length, and less pathological injury. In contrast, E2-a failed to alleviate the progression of UC. Further research revealed that both E2-b and E2 reduced the population of IL-17 A+ cells, while E2 upregulated the population of Tregs. In addition, all extracts induced a low level of IL-6, and E2 decreased the level of IL-1β. Moreover, the protein expression of p-STAT3 was significantly inhibited by E2. In the extracts of S. moorcroftiana seeds, the water-soluble alkaloid (E2) exhibits the best therapeutic efficacy in UC mice, suggesting that the compounds present in the extract is a potential therapeutic agent in UC.

CONTEXT:Vitamin C has been used as an essential antioxidant to reduce the inflammatory response associated with pneumonia and acute respiratory distress syndrome in patients with the 2019 coronavirus disease (COVID-19), but its effect on clinical outcomes remains controversial and inconclusive. OBJECTIVE:The purpose of this study was to conduct a meta-analysis and systematic review to assess the effects of vitamin C supplementation on the severity of COVID-19 in hospitalized patients. DATA SOURCES:Web of Science, Embase, Cochrane Library, PubMed, CNKI, CSTJ, Wan fang, and CBM databases were searched for publications between January 2020 and December 2023 that met the inclusion criteria. DATA EXTRACTION:The meta-analyses of outcomes in more than one study were performed using Review Manager software. Heterogeneity was evaluated using the I2 statistic. A randomized controlled trial, cohort studies, and retrospective studies in which vitamin C supplementation was supplemented as monotherapy or in combination, compared with placebo, no treatment, or other standard treatment without vitamin C were included. DATA ANALYSIS:After screening, 22 studies, with a total of 3429 patients, were selected for assessment. Odds ratios (ORs) with 95% CIs were calculated using fixed- and random-effects models. The meta-analysis showed significant effects of vitamin C on alleviating clinical outcomes in patients with COVID-19 (OR = 0.76, 95% CI = 0.65-0.89, P = .0007) but no shortening of the length of hospitalization (MD = 1.16, 95% CI = -0.13-2.44, P = .08) compared with the control group. Notably, vitamin C supplements significantly reduced the mortality risk (OR = 0.64, 95% CI = 0.51-0.80, P = .0001) and the incidence of severity (OR = 0.59, 95% CI = 0.43-0.80, P = .0006) in COVID-19 patients. CONCLUSION:The findings suggest that vitamin C supplements may have a beneficial effect on clinical outcomes, as well as reducing severity and mortality in COVID-19 patients, but more clinical randomized controlled trials are needed to evaluate the role of vitamin C in treating COVID-19. SYSTEMATIC REVIEW REGISTRATION:PROSPERO registration no. CRD42023491517.

Ensuring food safety and extending the shelf life of perishable products remain major challenges for the global food industry. The escalating consumer demand for natural food preservatives has intensified research into biological alternatives to chemical additives. Probiotics, traditionally recognized for their health-promoting effects, have recently gained attention for their capacity to improve food preservation. Beyond their direct competitive exclusion of pathogens, probiotics produce a wide range of antimicrobial peptides (AMPs), including bacteriocins, enzymes, and peptide-based inhibitors, which exhibit potent activity against foodborne spoilage and pathogenic microorganisms. Individually, both probiotics and their AMPs have been explored as natural biopreservatives; however, growing evidence suggests that their synergistic application offers enhanced efficacy. The synergy arises from the multi-targeted approach: probiotics colonize the food matrices, creating a protective biofilm, while simultaneously producing a spectrum of AMPs that disrupt bacterial cell membranes, inhibit cell wall synthesis, and suppress virulence gene expression. This combination extends the shelf life of various food products, including dairy, meats, and vegetables, by effectively controlling microbial load and delaying spoilage. Furthermore, the use of probiotic-derived AMPs, often exhibiting thermal and pH stability, offers a natural label-friendly option for the food industry. Despite these advancements, challenges remain regarding strain specificity, scalability, regulatory approval, and sensory impacts on food products. This review comprehensively examines the mechanisms of action, efficacy in various food matrices, and potential for industrial application, concluding that the strategic integration of probiotics and their antimicrobial proteins represents a potent, natural, and synergistic strategy for ensuring food safety and sustainability.

Introduction:Forsythia suspensa leaves (FSL), a traditional Chinese ethnomedicinal herbal material used to prepare health-promoting infusions and pharmacologically noted for their robust anti-inflammatory, antioxidant, and broad-spectrum antiviral activities, nevertheless have an as-yet-uncharacterized molecular mechanism of action against human adenovirus (HAdV). Methods:Ultra-high-performance liquid chromatography coupled with Q-Exactive Orbitrap mass spectrometry (UHPLC-Q-Exactive-Orbitrap/MS) was employed to identification of FSL components. Publicly available GEO datasets were mined to identify HAdV-associated differentially expressed genes (DEGs). An integrated analysis of GEO datasets and network pharmacology to predict the key molecular targets of FSL flavonoids against HAdV. Ensemble molecular docking and molecular dynamics simulations assessed the stability of flavonoid-protein interactions. In vitro antiviral assays quantified FSL's effect on HAdV replication, viral gene expression, and E1A protein levels. Flow cytometry and RT-qPCR examined cell cycle distribution and expression of cell-cycle regulators. Results:Thirty-nine active components were identified in FSL, predominantly organic acids, terpenoids, flavonoids, and lignans. An integrated analysis of GEO data revealed 990 adenovirus-associated DEGs, with network pharmacology and functional enrichment analyses further demonstrating FSL flavonoids' preferential targeting of cell cycle regulators. In silico docking and simulation confirmed the stable binding of FSL-derived flavonoids to core cell cycle proteins. In vitro, FSL inhibited HAdV replication in a dose-dependent manner, significantly reducing viral gene transcripts and E1A protein expression. Mechanistic studies demonstrated that FSL induced G2/M phase arrest, accompanied by the downregulation of CDC25A expression and upregulation of CCNB2, AURKA, CHEK1, and CCNA2 expression, thereby blocking progression into S-phase and impairing viral DNA synthesis. Discussion:These findings establish a pharmacological foundation for developing FSL-derived phytotherapeutics against adenoviral infections.

BACKGROUND:Cystic echinococcosis (CE), a zoonosis caused by Echinococcus granulosus sensu lato (EG), is a major public health burden in western China. The study aimed to evaluate the current status of KAP about CE among undergraduate students from western areas of China, and to provide a basis for developing health education strategies for college students on the prevention of CE. METHODS:A cross-sectional study was conducted from September 2023 to April 2024 in China. A cluster sampling method was used to enroll participants of undergraduate students. The Cronbach's alpha coefficient of the questionnaire, the χ2 test for comparing rates, the independent sample T test for KAP scores, and linear regression analyses were conducted in the study. RESULTS:A total of 724 students were included in the study. Approximately 65% (471) of the participants were female students and 35% (253) were male students, and most of them were non-medical (90%) students and from rural areas (60%). The total score of KAP was from 21 to 57, and the mean score of KAP was 41.92±5.78, and less than one fifth of undergraduate students had higher level knowledge (14.8%), positive attitudes (15.5%), and low-risk practices (8.6%). The education level was a significant factor in predicting knowledge, and upper-year students (junior/senior) had a higher level of knowledge about CE than lower-year students (OR = 1.59, p = 0.01). Both residence (OR = 0.57, p < 0.05) and knowledge (OR = 2.26, p<0.05) were significant predicting attitude factors, and students with more knowledge had a positive attitude. But the significant predictors of practice were gender (OR = 3.26, p < 0.05), education level (OR = 0.75, p < 0.05) and attitude (OR = 2.25, p = 0.05). CONCLUSION:The KAP level and pass rate for knowledge of CE among Chinese students in western areas is low, and most participants showed insufficient or poor CE knowledge. It is necessary to strengthen the health education in school or by multimedia communication platforms on CE for college students in western areas and those with identified related factors.

Ethnopharmacological relevance: Paeoniae Radix Rubra (PRR) is the dried root of Paeonia lactiflora Pall, which has been widely used to anti-thrombotic, lipid-lowering, anti-spasmodic, antioxidant, antibacterial, hepatoprotective, and anti-tumor in Chinese clinical practice. Recent research has demonstrated that PRR plays a significant anti-tumor role in animal models of tumor-bearing. Aim of the study: There has not been the evaluation of the anti-tumor effects of PRR. This study conducts a metaanalysis to assess the anti-tumor efficacy of PRR on animal models, providing scientific evidence for clinical application of PRR in the adjuvant therapy of tumors. Materials and methods: English databases (PubMed, The Cochrane Library, Embase, and Web of Science) and Chinese databases (CNKI, WanFang, SinoMed, CTSJ-VIP) were used to search all pertinent animal studies investigating the anti-tumor effects of PRR and its extracts. The quality of the included studies was evaluated using the SYRCLE animal experiment risk assessment tool, and statistical analysis was carried out using Revman 5.3 software. Egger's test and funnel plots were used to assess potential publication bias in the studies. Results: The initial search produced a total of 3905 potentially pertinent studies, and 24 studies met the inclusion criteria. These studies included animal tumor models of hepatocellular carcinoma, lung cancer, sarcoma, bladder cancer, leukemia, colon cancer, glioblastoma, and pancreatic cancer. The meta-analysis findings demonstrated that both PRR and its extracts significantly inhibited tumor growth in animals. Compared with the control group, PRR substantively inhibited tumor volume (SMD, -3.09; 95% CI, [-4.05, -2.13]; P < 0.0001), reduced tumor weight (SMD, -1.08; 95% CI, [-1.37, -0.78]; P < 0.0001), decreased tumor number (SMD, -2.16; 95% CI, [-3.45, -0.86]; P = 0.001), and prolonged the survival duration time (SMD, 0.97; 95% CI, [0.23, 1.71]; P = 0.01) on the experimental animals. Conclusions: PRR displayed a potential therapeutic efficacy on eight tumors in animal models including hepatocellular carcinoma, lung cancer, sarcoma, bladder cancer, leukemia, colon cancer, glioblastoma, and pancreatic cancer. However, the quality and quantity of included studies may affect the accuracy of positive results. In the future, more high-quality randomized controlled animal experiments are need for meta-analysis.

BackgroundMore than 200 diseases are caused by eating food contaminated and the burden of foodborne disease is considered to be high worldwide. Foodborne diseases are an important public health issue, and the knowledge, attitudes and practices among college students are crucial in preventing outbreaks.ObjectiveThis study aimed to evaluate the current knowledge, attitudes, and practices (KAP) toward foodborne diseases among Chinese college students and to identify the factors influencing practice actions.MethodsA cross-sectional study was conducted from April to November in 2023. A cluster random sampling method was used to enroll participants at Xihua University. The questionnaire including 47 items was used to collect the foodborne diseases information. An offline questionnaire was used to generate the surveys. Multiple linear regression was used to analyze the factors associated with foodborne disease knowledge, attitudes and practices.ResultsA total of 445 college students with a mean age of 19.76 ± 1.24 years were included in the study. The majority of participants were female (59.1%), of Han Chinese (95.1%), and nearly two-thirds were lower-year undergraduates (66.7%). Most participants (78.9%) were non-medical students, and 64.7% of participants were from rural areas. The KAP score of foodborne diseases was 79.21 ± 6.84. The knowledge, attitudes, and practices scores toward foodborne diseases were 8.76 ± 0.95, 10.50 ± 1.63, and 59.94 ± 6.48, respectively. In particular, there was a notable decrease in practice scores toward foodborne diseases among male students, ethnic minority students, and non-medical students. The significant predictors of practices were included gender (β = 0.11, p < 0.05), nationality (β = −0.12, p < 0.05), specialization type (β = −0.13, p < 0.05), residence (β = −0.11, p < 0.05).ConclusionThese results revealed gaps in knowledge, attitudes, and practices regarding foodborne diseases, and the knowledge was at an insufficient level, the attitude was positive and practice was at a moderate and acceptable level. In general, the level of KAP was at a moderate and acceptable level. Gender, nationality, education level, specialization type, and residence were identified as crucial influencers on practices toward foodborne diseases. It is necessary to provide foodborne disease health education targeting this population in western areas, which can help improve students’ knowledge, attitudes, and practices.

Fully online learning has become a common option in many universities worldwide in the post-COVID-19 era. The study aimed to evaluate the dimensions and characteristics of the fully online learning self-efficacy among Chinese undergraduate medical and nonmedical students. A cross-sectional study was conducted from January to August 2023 at Xihua University in China. A stratified cluster sampling method was used to enroll participants of undergraduate students. The Chinese version of the online learning self-efficacy scale (OLSES) was used to collect the demographic information. Cronbach’s alpha coefficient, exploratory factor analyses, confirmatory factor analyses, and linear regression analyses were conducted in the study. A total of 203 college students were included in the study. One hundred and twenty (59.1

Objective:Nanomedicine represents a transformative approach in biomedical applications. This study aims to delineate the application of nanomedicine in the biomedical field through the strengths, weaknesses, opportunities, and threats (SWOT) analysis to evaluate its efficacy and potential in clinical applications. Methods:The SWOT analysis framework was employed to systematically review and assess the internal strengths and weaknesses, along with external opportunities and threats of nanomedicine. This method provides a balanced consideration of the potential benefits and challenges. Results:Findings from the SWOT analysis indicate that nanomedicine presents significant potential in drug delivery, diagnostic imaging, and tissue engineering. Nonetheless, it faces substantial hurdles such as safety issues, environmental concerns, and high development costs. Critical areas for development were identified, particularly concerning its therapeutic potential and the uncertainties surrounding long-term effects. Conclusion:Nanomedicine holds substantial promise in driving medical innovation. However, successful clinical translation requires addressing safety, cost, and regulatory challenges. Interdisciplinary collaboration and comprehensive strategic planning are crucial for the safe and effective application of nanomedicine.

Coronavirus disease 2019 (COVID-19), beginning in December 2019, has spread worldwide, leading to the death of millions. Owing to the absence of definitive treatment, vaccination against COVID-19 emerged as an effective strategy against the spread of the pandemic. Acceptance of the COVID-19 vaccine has advanced considerably, and vaccine-related research has significantly increased over the past three years. This study aimed to evaluate the content and external characteristics of COVID-19 vaccine-related literature for tracking research trends related to the global COVID-19 vaccine with the means of bibliometrics and visualization maps. A total of 18,285 records in 3499 journals were retrieved in the Web of Science Core Collection database and included in the final analysis. China was the first to focus on COVID-19 vaccine research, while European and American countries started late but developed rapidly. The USA and the UK are the top contributors to COVID-19 vaccine development, with the largest number of publications. The University of Washington and Harvard Medical School were the leading institutions, while Krammer, F. from Icahn School of Medicine at Mount Sinai was the author most active and influential to the topic. The New England Journal of Medicine had the highest number of citations and the highest TLS, and was the most cited and influential journal in the field of COVID-19 vaccine research. COVID-19 vaccine research topics and hotspots focused on populations’ attitudes towards vaccination, immunity-related information analysis of spike proteins, the effectiveness and side effects of the COVID-19 vaccine, and the public management of epidemic transmission. The findings of this study provide the global status, research hotspots and potential trends in the field of COVID-19 vaccine research, which will assist researchers in mastering the knowledge structure, and evaluating and guiding future developmental directions of COVID-19 vaccine

BackgroundHepatocellular carcinoma (HCC) is one of the most prevalent and deadly malignant tumors with serious clinical and socioeconomic consequences. Although gene therapy holds great promise in the treatment of hepatoma, its clinical applications are hindered by uncontrolled gene transmission and transcription.MethodsThe pY-ads-8-5HRE-cfosp-IFNG plasmid was constructed and identified by double enzyme digestion and gene sequencing. The expression of pYr-ads-8-5HRE-cfosp-IFNG in HepG2 cells was detected by quantitative PCR. PEI-Fe3O4/pYr-ads-8-5HRE-cfosp-IFNG albumin nanospheres were prepared and characterized. In vitro heating test of magnetic albumin nanospheres in an alternating magnetic field (AMF) was carried out. The therapeutic effect of PEI-Fe3O4/pYr-ads-8-5HRE-cfosp-IFNG albumin nanospheres on hepatocellular carcinoma was investigated by cell and animal experiments. After treatment, mice blood was collected for clinical biochemical analysis and histopathological evaluation of major organs was performed to assess potential adverse effects of treatment.ResultsDouble enzyme digestion and gene sequencing showed that the pY-ads-8-5HRE-cfosp-IFNG plasmid was constructed successfully. QPCR results showed that the IFNγ transcript level in the PEI-Fe3O4/pYr-ads-8-5HRE-cfosp-IFNG group was higher than that in the PEI-Fe3O4/pYr-ads-8-cfosp-IFNG group after being treated with hypoxia (P<0.05). TEM revealed that the self-prepared PEI-Fe3O4/pYr-ads-8-5HRE-cfosp-IFNG albumin nanospheres exhibit an approximately spherical or elliptical shape. The hydrodynamic size of the albumin nanospheres was 139.7 nm. The maximum temperature of 0.25 mg/mL solution is stable at about 44°C, which is suitable for tumor thermal therapy without damaging normal tissues. The relative cell inhibition rate of the radiation-gene therapy and MFH combination group was higher than that of other control groups in CCK8 experiment. (P<0.05) Flow cytometry showed that the apoptosis rate and necrosis rate of the combined treatment group were 42.32% and 35.73%, respectively, higher than those of the other groups. (P<0.05) In animal experiments, the mass and volume inhibition rates of the combined treatment group were 66.67% and 72.53%, respectively, higher than those of other control groups. (P<0.05) Clinical biochemical analysis and histopathological evaluation showed no abnormality.ConclusionsThe results indicated the successful construction of the radiation-induced plasmid and demonstrated that the hypoxia enhancer could augment the expression of INFγ in a hypoxia environment. Gene therapy combined with magnetic fluid hyperthermia (MFH) has exhibited excellent outcomes in both cell and animal studies. Our experiments demonstrated that the PEI-Fe3O4/pYr-ads-8-5HRE-cfosp-IFNG albumin nanospheres system is a comprehensive treatment method for hepatoma, which can effectively combine immune genre therapy with hyperthermia.

In the coronavirus disease 2019 (COVID-19) pandemic, vaccinations were essential in preventing COVID-19 infections and related mortality in older adults. The objectives of this study were to evaluate the effectiveness and safety of the COVID-19 vaccines in older adults. We systematically searched the electronic bibliographic databases of PubMed, Web of Science, Embase, Cochrane Library, ClinicalTrials.gov, Research Square, and OpenGrey, as well as other sources of gray literature, for studies published between January 1, 2020, and October 1, 2022. We retrieved 22 randomized controlled trials (RCTs), with a total of 3,404,696 older adults (aged over 60 years) participating, that were included in the meta-analysis. No significant publication bias was found. In the cumulative meta-analysis, we found that the COVID-19 vaccines were effective in preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (OR = 0.38, 95% CI = 0.23-0.65, p = 0.0004) and in reducing the number of COVID-19-related deaths (OR = 0.16, 95% CI = 0.10-0.25, p < 0.00001) in elderly people. Antibody seroconversion (AS) and geometric mean titer (GMT) levels significantly increased in vaccinated older adults [OR = 24.42, 95% CI = 19.29-30.92; standardized mean difference (SMD) = 0.92, 95% CI = 0.64-1.20, respectively]. However, local and systemic adverse events after COVID-19 vaccine administration were found in older adults (OR = 2.57, 95% CI = 1.83-3.62, p < 0.00001). Although vaccination might induce certain adverse reactions in the elderly population, the available evidence showed that the COVID-19 vaccines are effective and tolerated, as shown by the decrease in COVID-19-related deaths in older adults. It needs to be made abundantly clear to elderly people that the advantages of vaccination far outweigh any potential risks. Therefore, COVID-19 vaccination should be considered as the recommended strategy for the control of this disease by preventing SARS-CoV-2 infection and related deaths in older adults. More RCTs are needed to increase the certainty of the evidence and to verify our conclusions.

In the coronavirus disease 2019 (COVID-19) pandemic, vaccinations were essential in preventing COVID-19 infections and related mortality in older adults. The objectives of this study were to evaluate the effectiveness and safety of the COVID-19 vaccines in older adults. We systematically searched the electronic bibliographic databases of PubMed, Web of Science, Embase, Cochrane Library, ClinicalTrials.gov, Research Square, and OpenGrey, as well as other sources of gray literature, for studies published between January 1, 2020, and October 1, 2022. We retrieved 22 randomized controlled trials (RCTs), with a total of 3,404,696 older adults (aged over 60 years) participating, that were included in the meta-analysis. No significant publication bias was found. In the cumulative meta-analysis, we found that the COVID-19 vaccines were effective in preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (OR = 0.38, 95% CI = 0.23–0.65, p = 0.0004) and in reducing the number of COVID-19-related deaths (OR = 0.16, 95% CI = 0.10–0.25, p < 0.00001) in elderly people. Antibody seroconversion (AS) and geometric mean titer (GMT) levels significantly increased in vaccinated older adults [OR = 24.42, 95% CI = 19.29–30.92; standardized mean difference (SMD) = 0.92, 95% CI = 0.64–1.20, respectively]. However, local and systemic adverse events after COVID-19 vaccine administration were found in older adults (OR = 2.57, 95% CI = 1.83–3.62, p < 0.00001). Although vaccination might induce certain adverse reactions in the elderly population, the available evidence showed that the COVID-19 vaccines are effective and tolerated, as shown by the decrease in COVID-19-related deaths in older adults. It needs to be made abundantly clear to elderly people that the advantages of vaccination far outweigh any potential risks. Therefore, COVID-19 vaccination should be considered as the recommended strategy for the control of this disease by preventing SARS-CoV-2 infection and related deaths in older adults. More RCTs are needed to increase the certainty of the evidence and to verify our conclusions. Systematic review registration https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022319698, identifier CRD42022319698.

IL-28B, belonging to type III interferons (IFN-λs), exhibits a potent antitumor activity with reduced regulated T cells (Tregs) population, yet the effect of IL-28B on the tumor microenvironment (TME) and if IL-28B can downregulate Tregs directly in vitro are still unknown. In this study, we investigated the effects of IL-28B on Tregs in the spleen and TME in H22 tumor-bearing mice and verified the downregulation of IL-28B on Tregs in vitro. We found that rAd-mIL-28B significantly inhibited tumor growth and reduced the frequency of splenic CD4+Foxp3+ T cells. The levels of CXCL13, ICAM-1, MCP-5, and IL-7 in the serum, and the levels of IL-15 and sFasL in the tumor tissue decreased significantly after rAd-mIL-28B treatment relative to rAd-EGFP. Furthermore, the percentage of CD8+ cells in the TME was significantly increased in the rAd-mIL-28B group compared with the untreated group. In vitro, splenocytes were stimulated with anti-CD3/CD28 and IL-2 in the presence of TGF-β with or without IL-28B for three days and followed by flow cytometric, RT-PCR, and IL-10 production analysis. The results showed that IL-28B significantly reduced the proportion of induced Foxp3+ cells. It demonstrated that IL-28B may be used as a promising immunotherapy strategy against cancer.

Echinococcus multilocularis , the causative agent of alveolar echinococcosis (AE), severely threats human health and livestock farming. The first line of chemotherapeutic drug for AE is albendazole, which limits rapid extension of E. multilocularis metacestodes, but is rarely curative for AE, with severe side effects in long-term use, thus development of new anti-echinococcal drugs is mandated. Pseudolaric acid B (PAB) has long been used to treat fungal-infected dermatosis, and exerted anti-tumor, -fertility, -angiogenesis, -tubulin and antiparasitic activity. However, the effect of PAB against Echinococcus spp. remains unclear. The present study is to understand the effect of PAB against E. multilocularis in vitro and in vivo , and identify potential anti-echinococcal mechanism, as well as its toxicity. After exposure to PAB at 20 μg/ml, significant reduction of the survival rate and substantial ultrastructural destructions in E. multilocularis protoscoleces were observed in vitro . Furthermore, the wet weight of E. multilocularis cysts in the infected mice was significantly decreased after treatment with PAB (40, 20 or 10 mg/kg) for 12 weeks. Meanwhile, significant increase of both protein and mRNA expression of transforming growth factor beta 1 (TGF-β1) was detected in the serum and liver of the infected mice, whereas PAB administration lowered its expression significantly. The toxicity tests demonstrated that PAB displayed lower cytotoxicity to human liver and kidney cells (HL-7702 and HK-2 cell) with IC 50 = 25.29 and 42.94 μg/ml than albendazole with IC 50 = 3.71 and 21.22 μg/ml in vitro , and caused lower hepatoxicity and nephrotoxicity in mice than ABZ. Our findings indicated that PAB possesses potent anti-echinococcal effect, with lower toxicity than albendazole, implying a potential chemotherapeutic agent for AE. Additionally, the present study demonstrated that the suppressive effect of PAB on the parasite may involve down-regulation of TGF-β1 signaling.

The BOPPPS teaching strategy has been used recently in many medical courses as an improved and more practical pedagogy in China. Nevertheless, the effectiveness of this pedagogy has not been fully assessed in terms of knowledge and skill outcomes in medical education. This meta-analysis aimed to evaluate the effectiveness of the BOPPPS strategy compared with traditional lecture-based learning (LBL) in Chinese medical education. The English electronic databases of Web of Science, PubMed, Embase, and the Cochrane Library and the Chinese electronic databases of CNKI, CQVIP, Wanfang, and CBM were used to search the publications related to the BOPPPS teaching strategy before 6 Jun 2022. Eligibility publications were retrieved and the data were extracted by two researchers independently according to the predefined inclusion and exclusion criteria. Quality analysis was performed using the Cochrane risk-of-bias tool, and the meta-analysis was performed using RevMan 5.3 and StataSE. We retrieved 367 records and 41 studies with a total of 5,042 medical students in the meta-analysis, which included 34 randomized controlled trials (RCTs) and 7 Cohort studies. In the cumulative meta-analysis, BOPPPS strategy significantly increased skill scores (SS) (SMD: 1.15, 95% CI: 1.00–1.30, P < 0.00001), knowledge examination scores (KES) (SMD: 1.56, 95% CI: 1.24–1.89, P < 0.00001), comprehensive ability scores (CAS) (SMD: 1.22, 95%CI: 0.85–1.59; P < 0.00001), and teaching satisfaction (TS) (OR: 3.64; 95%CI: 2.97–4.46; P < 0.0001) compared to the LBL model among those medical students. Statistically similar results were obtained in the sensitivity analysis. These results showed that the BOPPPS method is an effective teaching strategy for Chinese medical students to improve SS, knowledge scores, CAS, and TS when compared with LBL in medical education. Because of the limited quantity and quality of the included studies, further rigorous studies are needed to conclude with more confidence.

Background Liver cancer, particularly hepatocellular carcinoma (HCC), is the fourth leading cause of cancer-related death worldwide. Sorafenib is a crucial drug for the treatment of advanced HCC, but it is difficult to meet the challenge of increasing clinical demands due to its severe side effects and drug resistance. Hence, development of novel antitumor drugs is urged. Previous studies showed that pseudolaric acid B (PAB) could reduce the expression of protein kinase B (PKB/Akt), a downstream effector of Notch signaling, facilitating cell apoptosis in HCC. The disruption of Notch signaling was verified to exacerbate malignant progression and drug resistance, however, the antitumor effect of PAB on Notch signaling in HCC remains unclear. Thus, this study aims to investigate the anti-HCC effect of PAB in association with the regulation of Notch1/Akt signaling. Methods CCK-8 assay and transwell assay were used to examine the cell proliferation and invasion in Huh7 cells after treatment with PAB and a Notch inhibitor DAPT. Moreover, the cell cycle of Huh7 cells after treatment with PAB was analyzed using flow cytometry. Finally, the changes of Notch1, Jagged1, Hes1, and Akt expression at the protein and mRNA level in Notch1/Akt signaling in Huh7 cells after treatment with PAB and DAPT were analyzed using immunofluorescence assay and real-time qPCR. Results The proliferation rate of Huh7 cells exposed to PAB of 0.5, 1, 2, 4, 8, 10, 20, 40, 80, 100, and 200 μmol/L revealed a time-and dose-dependent decrease in vitro, showing cell cycle arrest at G2/M phase (P < 0.05). Furthermore, compared with the untreated group, at the concentration of 40 μmol/L, the proliferation rate and invasion rate of Huh7 cells in PAB, DAPT, and PAB-DAPT combination (PAB + DAPT) group were significantly decreased (P < 0.05), but the PAB + DAPT showed no synergistic antiproliferation and anti-invasion effect in comparison with PAB treatment alone (P > 0.05). In addition, compared with the untreated group, PAB and DAPT alone significantly downregulated the expression of Notch1, Jagged1, Hes1, Akt mRNA, or/and protein in Huh7 cells (P < 0.05), but there was no significant difference in synergistic downregulated effect between the PAB + DAPT group and the PAB group (P > 0.05). Conclusion PAB can suppress proliferation and invasion of HCC cells through downregulating the expression of Notch1/Akt signaling protein and mRNA, and may be a potential novel antitumor drug candidate for the clinical treatment of HCC in the future.

Chronic inflammation plays a positive role in the development and progression of colitis-associated colorectal cancer (CAC). Medicinal plants and their extracts with anti-inflammatory and immunoregulatory properties may be an effective treatment and prevention strategy for CAC. This research aimed to explore the potential chemoprevention of paeoniflorin (PF) for CAC by network pharmacology, molecular docking technology, and in vivo experiments. The results showed that interleukin-6 (IL-6) is a key target of PF against CAC. In the CAC mouse model, PF increased the survival rate of mice and decreased the number and size of colon tumors. Moreover, reduced histological score of colitis and expression of Ki-67 and PCNA were observed in PF-treated mice. In addition, the chemoprevention mechanisms of PF in CAC may be associated with suppression of the IL-6/STAT3 signaling pathway and the IL-17 level. This research provides experimental evidence of potential chemoprevention strategies for CAC treatment.

Echinococcosis, which is caused by the larvae of cestodes of the genus Echinococcus, is a parasitic zoonosis that poses a serious threat to the health of humans and animals globally. Albendazole is the drug of choice for the treatment of echinococcosis, but it is difficult to meet clinical goals with this chemotherapy due to its low cure rate and associated side effects after its long-term use. Hence, novel anti-parasitic targets and effective treatment alternatives are urgently needed. A previous study showed that verapamil (Vepm) can suppress the growth of Echinococcus granulosus larvae; however, the mechanism of this effect remains unclear. The aim of the present study was to gain insight into the anti-echinococcal effect of Vepm on Echinococcus with a particular focus on the regulatory effect of Vepm on calcium/calmodulin-dependent protein kinase II (Ca2+/CaM-CaMKII) in infected mice. The anti-echinococcal effects of Vepm on Echinococcus granulosus protoscoleces (PSC) in vitro and Echinococcus multilocularis metacestodes in infected mice were assessed. The morphological alterations in Echinococcus spp. induced by Vepm were observed by scanning electron microscopy (SEM), and the changes in calcium content in both the parasite and mouse serum and liver were measured by SEM-energy dispersive spectrometry, inductively coupled plasma mass spectrometry and alizarin red staining. Additionally, the changes in the protein and mRNA levels of CaM and CaMKII in infected mice, and in the mRNA levels of CaMKII in E. granulosus PSC, were evaluated after treatment with Vepm by immunohistochemistry and/or real-time quantitative polymerase chain reaction. In vitro, E. granulosus PSC could be killed by Vepm at a concentration of 0.5 μg/ml or higher within 8 days. Under these conditions, the ultrastructure of PSC was damaged, and this damage was accompanied by obvious calcium loss and downregulation of CaMKII mRNA expression. In vivo, the weight and the calcium content of E. multilocularis metacestodes from mice were reduced after treatment with 40 mg/kg Vepm, and an elevation of the calcium content in the sera and livers of infected mice was observed. In addition, downregulation of CaM and CaMKII protein and mRNA expression in the livers of mice infected with E. multilocularis metacestodes was found after treatment with Vepm. Vepm exerted a parasiticidal effect against Echinococcus both in vitro and in vivo through downregulating the expression of Ca2+/CaM-CaMKII, which was over-activated by parasitic infection. The results suggest that Ca2+/CaM-CaMKII may be a novel drug target, and that Vepm is a potential anti-echinococcal drug for the future control of echinococcosis.