Network meta-analysis of probiotics, prebiotics, and synbiotics for the treatment of chronic constipation in adults.

OBJECTIVE: To compare the outcomes associated with the use of probiotics, prebiotics, and synbiotics for the treatment of chronic constipation in adults. METHODS: We searched eight electronic databases from database inception to July 11, 2023, to identify randomized controlled trials (RCTs) that report efficacy and safety for the treatment of chronic constipation. The risk of bias in the included RCTs was evaluated according to the Cochrane tool, and the certainty of the evidence was assessed using the Confidence in Network Meta-Analysis framework. The analysis was conducted using R version 4.3.0. RESULTS: Out of the 37 RCTs, a total of 21 different types of interventions were reported, involving 3,903 patients. This NMA demonstrated that both prebiotics and synbiotics resulted in an increase in frequency of stool movements per week. Compared to placebo, lactulose (Mean difference [MD] = 3.39, 95% Confdence interval [CI] [1.13, 5.65], moderate certainty), mix2 (consisting of Lactulose and Bacillus coagulans) (MD = 3.63, 95% CI [1.37, 5.89], moderate certainty), mix6 (consisting of Lactulose and Bifidobacterium coagulans) (MD = 4.30, 95% CI [1.04, 7.54], low certainty), and mix7 (consisting of Lactulose, Bifidobacterium subtilis, and Enterococcus faecium) (MD = 4.58, 95% CI [1.35, 7.78], moderate certainty) exhibited a significant effect. Notably, mix7 demonstrated the highest probability of being the most effective intervention (94.8%). Furthermore, when compared to L. plantarum, four probiotics and two synbiotics showed significant advantages in the Patient Assessment of Constipation Symptoms (PAC-SYM) score. L. reuteri (MD = -13.74, 95% CI [-22.20, -4.66], very low certainty) exhibited a significant effect in improving the Patient Assessment of Constipation Quality of Life (PAC-QoL) score. In terms of safety, there were no statistically significant differences between the intervention and control groups in all adverse event analyses. CONCLUSIONS: Moderate to very low evidence supports the use of lactulose and synbiotics to increase the number of weekly stool movements in patients, particularly highlighting the significant impact of synbiotics in increasing the number of weekly stool movements in patients with constipation. The use of L. paracasei showed improvements in PAC-SYM scores, while L. reuteri demonstrated enhancements in PAC-QoL scores.

TMT-based quantitative proteomics analysis of Sprague-Dawley rats liver reveals Triphenyltin induced liver damage and lipid metabolism disorders.

Triphenyltin (TPT) is a widely used pesticide that has a negative impact on biological health and production efficiency. In addition, TPT poses a threat to human health through the food chain and environmental pollution. However, the exact mechanism of TPT toxicity remains unclear. In this study, we investigated the hepatotoxicity of TPT and its effects on lipid metabolism using male SD rats as an animal model. Our results from HE and serum biochemical analysis suggested that TPT could damage liver structure and function, resulting in disruption of lipid metabolism. We therefore proceeded to analyze the proteomic response of rat liver tissue after 28 days of treatment with 2 mg/kg/d TPT. Our study demonstrates that TPT has a variety of effects on liver protein expression in rats. Through bioinformatic analysis, we observed significant changes in proteins related to fatty acid oxidation and synthesis due to TPT exposure. Furthermore, western blot and RT-qPCR experiments confirmed that TPT can affect lipid metabolism through the PPAR pathway. These findings suggest that TPT exposure can lead to liver damage, lipid accumulation and metabolic disorders.

Comparison of effectiveness and safety of lasmiditan and CGRP-antagonists for the acute treatment of migraine in adults: systematic review and network meta-analysis of randomised trials.

OBJECTIVE: To compare the outcomes associated with the use of lasmiditan, rimegepant, ubrogepant, and zavegepant for the acute management of migraine headaches. METHODS: We searched four electronic databases from database inception to August 31, 2023, to identify randomized controlled trials (RCTs) that report efficacy and safety for the acute treatment of migraine. The risk of bias in the included RCTs was evaluated according to the Cochrane tool, and the certainty of evidence using the CINeMA approach. We conducted frequentist network meta-analyses (NMA) to summarise the evidence. Data were analyzed using R-4.3.1. RESULTS: A total of 18 eligible studies including 10 different types of interventions with 22,429 migraine patients were included. NMA results showed that compared to ubrogepant (25 mg and 50 mg) and zavegepant, lasmiditan (100 mg and 200 mg) exhibits an elevated probability of achieving pain relief within a 2-hour interval. Similarly, relative to zavegepant, rimegepant (75 mg) and ubrogepant (50 mg and 100 mg) demonstrate an enhanced likelihood of sustaining pain relief over a 24-hour period. Furthermore, in contrast to ubrogepant (25 mg) and lasmiditan (50 mg), rimegepant (75 mg) presents a heightened probability of achieving freedom from photophobia within 2 h. Regarding safety, lasmiditan carries the highest risk of adverse events, which are associated with an increased incidence of adverse effects, including dizziness, somnolence, asthenia, paresthesia, and fatigue. CONCLUSIONS: In this NMA, a spectrum of evidence ranging from very low to high levels underscores the favorable efficacy and tolerability of rimegepant 75 mg and ubrogepant 100 mg, positioning them as potential candidates for the acute management of migraine. Concurrently, lasmiditan (100 mg and 200 mg) exhibits notable efficacy, albeit accompanied by an increased susceptibility to adverse events. These findings should still be approached with caution, primarily due to the intrinsic limitations associated with indirect comparisons.

Non-pharmacological interventions for smoking cessation: analysis of systematic reviews and meta-analyses.

BACKGROUND: Although non-pharmacological smoking cessation measures have been widely used among smokers, current research evidence on the effects of smoking cessation is inconsistent and of mixed quality. Moreover, there is a lack of comprehensive evidence synthesis. This study seeks to systematically identify, describe, and evaluate the available evidence for non-pharmacological interventions in smoking populations through evidence mapping (EM), and to search for best-practice smoking cessation programs. METHODS: A comprehensive search for relevant studies published from the establishment of the library to January 8, 2023, was conducted in PubMed, Web of Science, Embase, the Cochrane Library, CNKI, CBM, Wan Fang, and VIP. Two authors independently assessed eligibility and extracted data. The PRISMA statement and AMSTAR 2 tool were used to evaluate the report quality and methodology quality of systematic reviews/meta-analyses (SRs/MAs), respectively. Bubble plots were utilized to display information, such as the study population, intervention type, evidence quality, and original study sample size. RESULTS: A total of 145 SRs/MAs regarding non-pharmacological interventions for smoking cessation were investigated, with 20 types of interventions identified. The most commonly used interventions were cognitive behaviour education (n = 32, 22.07%), professional counselling (n = 20, 13.79%), and non-nicotine electronic cigarettes (e-cigarettes) (n = 13, 8.97%). Among them, counselling and behavioural support can improve smoking cessation rates, but the effect varies depending on the characteristics of the support provided. These findings are consistent with previous SRs/MAs. The general population (n = 108, 74.48%) was the main cohort included in the SRs/MAs. The total score of PRISMA for the quality of the reports ranged from 8 to 27, and 13 studies (8.97%) were rated as high confidence, and nine studies (6.21%) as moderate confidence, in the AMSTAR 2 confidence rating. CONCLUSIONS: The abstinence effect of cognitive behaviour education and money incentive intervention has advantages, and non-nicotine e-cigarettes appear to help some smokers transition to less harmful replacement tools. However, the methodological shortcomings of SRs/MAs should be considered. Therefore, to better guide future practice in the field of non-pharmacological smoking cessation, it is essential to improve the methodological quality of SRs and carry out high-quality randomized controlled trials (RCTs).

The effects of active workstations on reducing work-specific sedentary time in office workers: a network meta-analysis of 23 randomized controlled trials.

BACKGROUND: Active workstations have been proposed as a feasible approach for reducing occupational sedentary time. This study used a network meta-analysis (NMA) to assess and compare the overall efficacy of active workstation interventions according to type and concomitant strategy for reducing work-specific sitting time in office workers. METHODS: PubMed, Web of Science, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched from database inception until May 2022 to obtain randomized controlled trials (RCTs) assessing the efficacy of active workstations with or without concomitant strategies for reducing occupational sedentary time in office workers. The risk of bias of the RCTs included in this study was assessed according to the Cochrane Handbook. An NMA with STATA 15.1 was used to construct a network diagram, league figures, and the final surface under the cumulative ranking curve (SUCRA) values. The certainty of evidence was assessed using the grading of recommendations, assessment, development, and evaluation (GRADE) approach. RESULTS: A total of 23 eligible studies including eight different types of interventions with 1428 office workers were included. NMA results showed that compared to a typical desk, multicomponent intervention (standardized mean difference (SMD) = - 1.50; 95% confidence interval (CI) - 2.17, - 0.82; SUCRA = 72.4%), sit-stand workstation + promotion (Reminders of rest breaks, posture variation, or incidental office activity) (SMD = - 1.49; 95%CI - 2.42, - 0.55; SUCRA = 71.0%), treadmill workstation + promotion (SMD = - 1.29; 95%CI - 2.51, - 0.07; SUCRA = 61.6%), and sit-stand workstation (SMD = - 1.10, 95%CI - 1.64, - 0.56; SUCRA = 50.2%) were effective in reducing occupational sedentary time for office workers. CONCLUSIONS: Multicomponent intervention, sit-stand workstation + promotion, treadmill workstation + promotion, and sit-stand workstation appear to be effective in reducing work-specific sedentary time for office workers. Furthermore, multicomponent interventions and active workstations + promotion better reduced work-specific sedentary time than active workstation alone. However, the overall certainty of the evidence was low. TRIAL REGISTRATION: Our study protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO); registration number: CRD42022344432.

Preferences for training needs of village doctors in China: a systematic review.

BACKGROUND: Village doctors, as gatekeepers of the health system for rural residents in China, are often confronted with adversity in providing the basic public healthcare services. OBJECTIVE: We sought to summarize the training contents, training method, training location, and training costs most preferred by village doctors in China and hope to provide evidence and support for the government to deliver better training in the future. METHODS: Eight databases were searched to include studies that reported on the training needs of village doctors in China. We undertook a systematic review and a narrative synthesis of data. RESULTS: A total of 38 cross-sectional studies including 35,545 participants were included. In China, village doctors have extensive training needs. "Clinical knowledge and skill" and "diagnosis and treatment of common disease" were the most preferred training content; "continuing medical education" was the most preferred delivery method; above county- and county-level hospitals were the most desirable training locations, and the training costs were expected to be low or even free. CONCLUSION: Village doctors in various regions of China have similar preferences for training. Thus, future training should focus more on the training needs and preferences of village doctors.

Efficacy and safety of antidepressants for smoking cessation: A systematic review and network meta-analysis.

To evaluate the effectiveness, safety and tolerability of antidepressants in helping smokers quit tobacco dependence, five databases were searched for randomized controlled trials (RCTS ) on different antidepressant interventions involving smoking cessation in populations (September 2022). The STATA 15.1 software was used to perform network meta-analysis. The Cochrane bias risk tool was used to assess the risk of bias, and CINeMA was used to evaluate the evidence credibility for the effect of different interventions on smoking cessation. In all, 107 RCTs involving 42 744 patients were included. Seven studies were rated as having a low risk of bias. All trials reported 18 interventions and 153 pairwise comparisons were generated. The network meta-analysis showed that compared with placebo, varenicline + bupropion (OR = 3.53, 95% CI [2.34, 5.34]), selegiline + nicotine replacement therapy (NRT) (OR = 3.78, 95% CI [1.20, 11.92]), nortriptyline + NRT (OR = 2.33, 95% CI [1.21, 4.47), nortriptyline (OR = 1.58, 95% CI [1.11,2.26]), naltrexone + bupropion (OR = 3.84, 95% CI [1.39, 10.61]), bupropion + NRT (OR = 2.29, 95% CI [1.87, 2.81]) and bupropion (OR = 1.70, 95% CI [1.53, 1.89]) showed benefits with respect to smoking cessation. In addition, bupropion + NRT showed better effects than bupropion (OR = 1.35, 95% CI [1.12, 1.64]) and NRT (OR = 1.38, 95% CI [1.13, 1.69]) alone. The final cumulative ranking curve showed that varenicline + bupropion was the most likely to be the best intervention. There was moderate- to very-low-certainty evidence that most interventions showed benefits for smoking cessation compared with placebo, including monotherapy and combination therapies. Varenicline + bupropion had a higher probability of being the best intervention for smoking cessation.

Accurate quantification of alkalinity of sintered ore by random forest model based on PCA and variable importance (PCA-VI-RF).

The alkalinity of sintered ore has an important impact on the quality, output, and energy consumption of blast furnace smelting, and there is an urgent need for a method for accurate quantifying of the alkalinity of sintered ore. The present work explores the combination of the laser-induced breakdown spectroscopy (LIBS) technique and random forest (RF) based on principal component analysis (PCA) and variable importance for the quantitative analysis of the alkalinity of sintered ore. Sixteen sintered ore samples were used in this study, and the characteristic lines of LIBS spectra for sintered ore samples can be identified based on the National Institute of Standards and Technology (NIST) database. At first, abnormal spectra are identified and rejected by PCA coupled with Mahalanobis distance (MD). Then, the input variable for the RF calibration model is optimized according to the variable importance threshold obtained by the RF model, and two RF model parameters of ${{n}_{\rm tree}}$ntree and ${{m}_{\rm try}}$mtry are determined by out-of-bag estimate. Finally, the PCA-VI-RF model is built under the optimal model parameters. In order to verify the predictive ability of the quantitative model, the PCA-VI-RF model prediction results were compared with the RF model, partial least-squares model, and least-squares support vector machine model. The result demonstrated that PCA-VI-RF shows better analytical performance than other methods. Compared with the RF model with the original spectrum as input, the averaged relative errors of test results decreased from 5.82% to 3.94%, coefficients of determination (${R^2}$R2) of the test set increased from 0.8957 to 0.9814, and the root mean square error decreased from 0.1502% to 0.0860%. The speed of modeling and prediction has also been greatly improved, and the modeling time was reduced from 4675.56 to 16.86 s. The stability of the PCA-VI-RF model was verified by the relative standard deviation (RSD) of the test data prediction results, and the RSD reached below 4.74%. This study shows LIBS combining PCA-VI-RF is an effective method for accurate quantification of the alkalinity of sintered ore. It has great significance for the potential application of real-time online analysis of the alkalinity of sintered ore.

Polygala tenuifolia: a source for anti-Alzheimer's disease drugs.

Context: Alzheimer's disease (AD) is a chronic neurodegenerative disease that originates from central nervous system lesions or recessions. Current estimates suggest that this disease affects over 35 million people worldwide. However, lacking effective drugs is the biggest handicap in treating AD. In traditional Chinese medicine (TCM), Polygala tenuifolia Willd. (Polygalaceae) is generally used to treat insomnia, memory dysfunction and neurasthenia.Objective: This review article explores the role of P. tenuifolia and its active components in anti-Alzheimer's disease.Methods: Literature for the last ten years was obtained through a search on PubMed, SciFinder, CNKI, Google Scholar, Web of Science, Science Direct and China Knowledge Resource Integrated with the following keywords: Polygala tenuifolia, polygalasaponin XXXII (PGS 32), tenuifolin, polygalacic acid, senegenin, tenuigenin, Alzheimer's disease.Results: Polygala tenuifolia and its active components have multiplex neuroprotective potential associated with AD, such as anti-Aß aggregation, anti-Tau protein, anti-inflammation, antioxidant, anti-neuronal apoptosis, enhancing central cholinergic system and promote neuronal proliferation.Conclusions: Polygala tenuifolia and its active components exhibit multiple neuroprotective effects. Hence, P. tenuifolia is a potential drug against Alzheimer's disease, especially in terms of prevention.

Ethnobotany, Phytochemistry and Pharmacological Effects of Plants in Genus Cynanchum Linn. (Asclepiadaceae).

Genus Cynanchum L. belongs to the family Asclepiadaceae, which comprise more than 200 species distributed worldwide. In Chinese medical practice, numerous drugs (such as tablets and powders) containing different parts of plants of this genus are used to treat snake bites, bruises, osteoblasts, rheumatoid arthritis and tumors. A search for original articles published on the cynanchum genus was performed by using several resources, including Flora of China Official Website and various scientific databases, such as PubMed, SciFinder, the Web of Science, Science Direct, and China Knowledge Resource Integrated (CNKI). Advances in the botanical, ethnomedicinal, phytochemical, and pharmacological studies of this genus are reviewed in this paper. Results showed that more than 440 compounds, including C21 steroids, steroidal saponins, alkaloids, flavonoids and terpene, have been isolated and identified from Cynanchum plants up to now. In vivo and in vitro studies have shown that plants possess an array of biological activities, including anti-tumor, neuroprotective and anti-fungal effects. Popular traditional prescription of Cynanchum sp. was also summed up in this paper. However, many Cynanchum species have received little or no attention. Moreover, few reports on the clinical use and toxic effects of Cynanchum sp. are available. Further attention should be focused on the study of these species to gather information on their respective toxicology data and relevant quality-control measures and clinical value of the crude extracts, active compounds, and bioactive metabolites from this genus. Further research on Cynanchum sp. should be conducted, and bioactivity-guided isolation strategies should be emphasized. In addition, systematic studies of the chemical composition of plants should be enhanced.

Development of serum parameters panels for the early detection of pancreatic cancer.

Early detection of pancreatic cancer is promising for improving clinical outcome; however, no effective biomarker has yet been identified. Here, we detected 61 clinical serum parameters in 200 healthy controls (Ctrls), 163 pancreatic ductal adenocarcinoma (PDAC) patients and 109 benign pancreatitis patients (Benign) in the training group. A metropolis algorithm with Monte Carlo simulation was used for identifying parameter panels. Sera from 183 Ctrl, 129 PDAC and 95 Benign individuals were used for cross-validation. Samples from 77 breast, 72 cervical, 101 colorectal, 138 gastric, 108 prostate and 132 lung cancer patients were collected for evaluating cancer selectivity. A panel consisting of carbohydrate antigen (CA)19-9, albumin (ALB), C-reactive protein (CRP) and interleukin (IL)-8 had the highest diagnostic value for discriminating between PDAC and Ctrl. The sensitivity (SN) was 99.39% for all-stage, 96.10% for early-stage and 98.80% for advanced-stage PDAC at 90% specificity (SP). In the validation group, the sensitivities were 93.80, 93.10 and 94.40%, respectively, at 90% SP. This panel also identified 80.52% of the breast cancer, 66.67% cervical cancer, 86.14% colorectal cancer, 89.86% gastric cancer, 71.30% prostate cancer and 93.85% lung cancer samples as non-PDAC. The panel consisting of CA19-9, carbon dioxide, CRP and IL-6 panel had the highest diagnostic value for discriminating between PDAC and Benign. The SN was 74.23% for all-stage, 75.30% for early-stage and 74.40% for advanced-stage PDAC at 90% SP. In the validation group, the sensitivities were 72.10, 76.10 and 67.20%, respectively, at 90% SP. Our parameter panels may aid in the early detection of PDAC to improve clinical outcome.

Remodeling of intestinal epithelium derived extracellular vesicles by nanoparticles and its bioeffect on tumor cell migration.

Extracellular vesicles (EVs) are an effective tool to elucidate the bioeffect of nanomedicines. To clarify the interaction between oral nanomedicines and intestinal epithelial cells, and their bioeffects on downstream cells, polystyrene nanoparticles (PS-NPs) with different sizes were used as the model nanomedicines for EVs induction. Caco-2 monolayers were selected as the model of the intestinal epithelium and DLD-1 cells as the colorectal cancer model proximal to the gastrointestinal tract. It is found that compared with small-sized (25, 50, 100 nm) PS-NPs, the large-sized (200 and 500 nm) exhibited higher co-localization with multivesicular bodies and lysosomes, and more significant reduction of lysosomal acidification in Caco-2 cells. Proteomic and western-blotting analysis showed that the EVs remodeled by large-sized PS-NPs exhibited a higher extent of protein expression changes. The in vitro and in vivo signaling pathway detection in DLD-1 cells and DLD-1 cell xenograft nude mice showed that the remodeled EVs by large-sized PS-NPs inhibited the activation of multiple signaling pathways including Notch3, EGF/EGFR, and PI3K/Akt pathways, which resulted in the inhibition of tumor cell migration. These results primarily clarify the regulation mechanisms of nanomedicines-EVs-receptor cells chain. It provides a new perspective for the rational design and bioeffect evaluation of oral drug nanomaterials and sets up the fundamental knowledge for novel tumor therapeutics in the future.

SILAC proteomics based on 3D cell spheroids unveils the role of RAC2 in regulating the crosstalk between triple-negative breast cancer cells and tumor-associated macrophages.

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, and is characterized by a high infiltration of tumor-associated macrophages (TAMs). TAMs contribute significantly to tumor progression by intricately interacting with tumor cells. Deeply investigating the interaction between TNBC cells and TAMs is of great importance for finding potential biomarkers and developing novel therapeutic strategies to further improve the clinical outcomes of TNBC patients. In this study, we confirmed the interplay using both 3D and 2D co-culture models. The stable-isotype labeling by amino acids in cell culture (SILAC)-based quantitative proteomics was conducted on 3D cell spheroids containing TNBC cells and macrophages to identify the potential candidate in regulating the crosstalk between TNBC and TAMs. Ras-related C3 botulinum toxin substrate 2 (RAC2) was identified as a potential molecule for further exploration, given its high expression in TNBC and positive correlation with M2 macrophage infiltration. The suppression of RAC2 inhibited TNBC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) in vitro. Meanwhile, knocking down RAC2 in TNBC cells impaired macrophage recruitment and M2 polarization. Mechanistically, RAC2 exerted its roles in TNBC cells and TAMs by regulating the activation of P65 NF-κB and P38 MAPK, while TAMs further elevated RAC2 expression and P65 NF-κB activation by secreting soluble mediators including IL-10. These findings highlight the significance of RAC2 as a crucial molecule in the crosstalk between TNBC and TAMs, suggesting it could be a promising therapeutic target in TNBC.

Taraxacum: A Review of Ethnopharmacology, Phytochemistry and Pharmacological Activity.

Taraxacum refers to the genus Taraxacum, which has a long history of use as a medicinal plant and is widely distributed around the world. There are over 2500 species in the genus Taraxacum recorded as medicinal plants in China, Central Asia, Europe, and the Americas. It has traditionally been used for detoxification, diuresis, liver protection, the treatment of various inflammations, antimicrobial properties, and so on. We used the most typically reported Taraxacum officinale as an example and assembled its chemical makeup, including sesquiterpene, triterpene, steroids, flavone, sugar and its derivatives, phenolic acids, fatty acids, and other compounds, which are also the material basis for its pharmacological effects. Pharmacological investigations have revealed that Taraxacum crude extracts and chemical compounds contain antimicrobial infection, anti-inflammatory, antitumor, anti-oxidative, liver protective, and blood sugar and blood lipid management properties. These findings adequately confirm the previously described traditional uses and aid in explaining its therapeutic applications.

Comprehensive pan-cancer analysis identifies centromere-associated protein E as a novel prognostic and immunological biomarker in human tumors.

Centromere-associated protein E (CENP-E), a core component of the kinetochore, mediates chromosome congression and spindle microtubule capture during mitosis. Partial experimental evidence has illustrated the carcinogenic effects of CENPE in tumors, but the corresponding pan-cancer analysis of CENPE still lacking. Based on public databases, including the Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Human Protein Atlas (HPA), we take an array of bioinformatics methods to investigate the potential oncogenic roles of CENPE. Then, we validated CENPE, cell cycle-related proteins, and immune checkpoint molecule findings expression in clinical colon cancer samples by western blot. Our results showed that CENPE was up-regulated in almost all tumors, and the expression level of CENPE was associated with worse overall survival (OS) and disease-specific survival (DSS) in patients. The strong relationship between CENPE with gene mutation and MMR has also been validated. Moreover, CENPE gene expression was positively correlated with immune checkpoint molecular, and reversely correlated with infiltration levels of most immune cells. In the human colon cancer tissues, the expression of CENPE, cell cycle-related proteins, and immune checkpoint molecules were significantly higher than in the adjacent normal tissues. Our results indicated that CENPE can function as an oncogene in various cancers, and may be regarded as a promising prognostic and diagnostic biomarker in cancer treatment.

[Application of homemade antibiotic bone cement rod in tibial screw canal osteomyelitis].

Objective: To investigate the effectiveness of homemade antibiotic bone cement rod in the treatment of tibial screw canal osteomyelitis by Masquelet technique. Methods: A clinical data of 52 patients with tibial screw canal osteomyelitis met the criteria between October 2019 and September 2020 was retrospectively analyzed. There were 28 males and 24 females, with an average age of 38.6 years (mean, 23-62 years). The tibial fractures were treated with internal fixation in 38 cases and external fixation in 14 cases. The duration of osteomyelitis was 6 months to 20 years with a median of 2.3 years. The bacterial culture of wound secretions showed 47 positive cases, of which 36 cases were infected with single bacteria and 11 cases were infected with mixed bacteria. After thorough debridement and removal of internal and external fixation devices, the locking plate was used to fixed the bone defect. The tibial screw canal was filled with the antibiotic bone cement rod. The sensitive antibiotics were given after operation and the 2nd stage treatment was performed after infection control. The antibiotic cement rod was removed and the bone grafting in the induced membrane was performed. After operation, the clinical manifestations, wound, inflammatory indexes, and X-ray films were monitored dynamically, and the postoperative bone infection control and bone graft healing were evaluated. Results: Both patients successfully completed the two stages of treatments. All patients were followed up after the 2nd stage treatment. The follow-up time was 11 to 25 months (mean, 18.3 months). One patient had poor wound healing and the wound healed after enhanced dressing change. X-ray film showed that the bone grafting in the bone defect healed and the healing time was 3-6 months, with an average of 4.5 months. The patient had no recurrence of infection during the follow-up period. Conclusion: For the tibial screw canal osteomyelitis, the homemade antibiotic bone cement rod can reduce the recurrence rate of infection and obtain a good effectiveness, and has the advantages of simple operation and less postoperative complications.

Effectiveness of Multicomponent Interventions in Office-Based Workers to Mitigate Occupational Sedentary Behavior: Systematic Review and Meta-Analysis.

BACKGROUND: Sedentary time in workplaces has been linked to increased risks of chronic occupational diseases, obesity, and overall mortality. Currently, there is a burgeoning research interest in the implementation of multicomponent interventions aimed at decreasing sedentary time among office workers, which encompass a comprehensive amalgamation of individual, organizational, and environmental strategies. OBJECTIVE: This meta-analysis aims at evaluating the effectiveness of multicomponent interventions to mitigate occupational sedentary behavior at work compared with no intervention. METHODS: PubMed, Web of Science, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched from database inception until March 2023 to obtain randomized controlled trials (RCTs) assessing the efficacy of multicomponent interventions on occupational sedentary behavior among office-based workers. Two reviewers independently extracted the data and assessed the risk of bias by using the Cochrane Collaboration's risk of bias tool. The average intervention effect on sedentary time was calculated using Stata 15.1. Mean differences (MDs) with 95% CIs were used to calculate the continuous variables. Subgroup analyses were performed to determine whether sit-stand workstation, feedback, and prompt elements played an important role in multicomponent interventions. Further, the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) system was used to evaluate the certainty of evidence. RESULTS: A total of 11 RCTs involving 1894 patients were included in the analysis. Five studies were rated as low risk of bias, 2 as unclear risk of bias, and 4 as high risk. The meta-analysis results showed that compared with no intervention, multicomponent interventions significantly reduced occupational sitting time (MD=-52.25 min/8-h workday, 95% CI -73.06 to -31.44; P<.001) and occupational prolonged sitting time (MD=-32.63 min/8-h workday, 95% CI -51.93 to -13.33; P=.001) and increased occupational standing time (MD=44.30 min/8-h workday, 95% CI 23.11-65.48; P<.001), whereas no significant differences were found in occupational stepping time (P=.06). The results of subgroup analysis showed that compared with multicomponent interventions without installment of sit-stand workstations, multicomponent interventions with sit-stand workstation installment showed better effects for reducing occupational sitting time (MD=-71.95 min/8-h workday, 95% CI -92.94 to -51.15), increasing occupational standing time (MD=66.56 min/8-h workday, 95% CI 43.45-89.67), and reducing occupational prolonged sitting time (MD=-47.05 min/8-h workday, 95% CI -73.66 to -20.43). The GRADE evidence summary showed that all 4 outcomes were rated as moderate certainty. CONCLUSIONS: Multicomponent interventions, particularly those incorporating sit-stand workstations for all participants, are effective at reducing workplace sedentary time. However, given their cost, further research is needed to understand the effectiveness of low-cost/no-cost multicomponent interventions.

Marsdenia tenacissima extract induces endoplasmic reticulum stress-associated immunogenic cell death in non-small cell lung cancer cells through targeting AXL.

ETHNOPHARMACOLOGICAL RELEVANCE: Marsdenia Tenacissima (Roxb.) Wight et Arn. is a traditional Chinese medicine. Its standardized extract (MTE), with the trade name Xiao-Ai-Ping injection, is widely used for cancer treatment. The pharmacological effects of MTE-inducing cancer cell death have been primarily explored. However, whether MTE triggers tumor endoplasmic reticulum stress (ERS)-associated immunogenic cell death (ICD) is unknown. AIM OF THE STUDY: To determine the potential role of endoplasmic reticulum stress in the anti-cancer effects of MTE, and uncover the possible mechanisms of endoplasmic reticulum stress-associated immunogenic cell death induced by MTE. MATERIAL AND METHODS: The anti-tumor effects of MTE on non-small cell lung cancer (NSCLC) were examined through CCK-8 and wound healing assay. Network pharmacology analysis and RNA-sequencing (RNA seq) were performed to confirm the biological changes of NSCLCs after MTE treatment. Western blot, qRT-PCR, reactive oxygen species (ROS) assay, and mitochondrial membrane potential (MMP) assay were used to explore the occurrence of endoplasmic reticulum stress. Immunogenic cell death-related markers were tested by ELISA and ATP release assay. Salubrinal was used to inhibit the endoplasmic reticulum stress response. SiRNA and bemcentinib (R428) were used to impede the function of AXL. AXL phosphorylation was regained by recombinant human Gas6 protein (rhGas6). The effects of MTE on endoplasmic reticulum stress and immunogenic cell death response were also proved in vivo. The AXL inhibiting compound in MTE was explored by molecular docking and confirmed by Western blot. RESULTS: MTE inhibited cell viability and migration of PC-9 and H1975 cells. Enrichment analysis identified that differential genes after MTE treatment were significantly enriched in endoplasmic reticulum stress-related biological processes. MTE decreased mitochondrial membrane potential (MMP) and increased ROS production. Meanwhile, endoplasmic reticulum stress-related proteins (ATF6, GRP-78, ATF4, XBP1s, and CHOP) and immunogenic cell death-related markers (ATP, HMGB1) were upregulated, and the AXL phosphorylation level was suppressed after MTE treatment. However, when salubrinal (an endoplasmic reticulum stress inhibitor) and MTE were co-treated cells, the inhibitory effects of MTE on PC-9 and H1975 cells were impaired. Importantly, inhibition of AXL expression or activity also promotes the expression of endoplasmic reticulum stress and immunogenic cell death-related markers. Mechanistically, MTE induced endoplasmic reticulum stress and immunogenic cell death by suppressing AXL activity, and these effects were attenuated when AXL activity recovered. Moreover, MTE significantly increased the expression of endoplasmic reticulum stress-related markers in LLC tumor-bearing mouse tumor tissues and plasma levels of ATP and HMGB1. Molecular docking illustrated that kaempferol has the strongest binding energy with AXL and suppresses AXL phosphorylation. CONCLUSION: MTE induces endoplasmic reticulum stress-associated immunogenic cell death in NSCLC cells. The anti-tumor effects of MTE are dependent upon endoplasmic reticulum stress. MTE triggers endoplasmic reticulum stress-associated immunogenic cell death by inhibiting AXL activity. Kaempferol is an active component that inhibits AXL activity in MTE. The present research revealed the role of AXL in regulating endoplasmic reticulum stress and enriched the anti-tumor mechanisms of MTE. Moreover, kaempferol may be considered a novel AXL inhibitor.

Targeting Ferroptosis in Cancer by Natural Products: An Updated Review.

Ferroptosis is a new cell death process characterized by massive iron accumulation and lipid peroxidation. Emerging evidence demonstrates that ferroptosis plays a crucial role in the development and progression of tumorigenesis. Targeting it is a potentially effective cancer prevention and treatment strategy in the clinic. A comprehensive review of molecular mechanisms of targeting ferroptosis in cancer by natural products needs to be re-summarized and updated due to the advances in research. We searched and reviewed relevant literature through the database Web of Science, mainly focusing on the regulatory effects of natural products and their active compounds in treating or preventing cancer by regulating ferroptosis. A total of 62 kinds of natural products and their active compounds were reported to exert antitumor effects via causing ferroptosis of cancer cells by regulating the System Xc--GPX4 axis and lipid, mitochondrial, and iron metabolism. Natural products have advantages in improving chemotherapy's therapeutic effects by causing cancer cell ferroptosis through their polypharmacological actions. These molecular mechanisms of ferroptosis regulation by natural products will pave the way for developing natural antitumor drugs based on regulating ferroptosis.