The COVID-19 Vaccines Evaluation Program: Implementation, Management, and Experiences, 2021-2023.

In 2021, China's domestically produced coronavirus disease 2019 (COVID-19) vaccines received approval from regulatory bodies and were administered worldwide. Due to a low number of infections within China during that period, it became imperative to evaluate the vaccines' real-world effectiveness through international studies. To facilitate this, China CDC launched the COVID-19 Vaccines Evaluation Program (COVEP). This program formed research collaboration agreements with health institutes across five World Health Organization regions, addressing key questions about vaccine performance through ten cooperative agreements. The findings from COVEP projects reinforced confidence, both domestically and globally, in the effectiveness of the vaccines produced in China. Moreover, the outcomes observed internationally were frequently mirrored by later studies conducted within China. COVEP thus pioneered a novel approach for fostering cross-national research collaborations, addressing significant public health issues and exemplifying a framework for international cooperation. This approach is in line with the strategic objectives and other development efforts of China CDC's national disease control and prevention initiatives.

Protosappanin A Protects DOX-Induced Myocardial Injury and Cardiac Dysfunction by Targeting ACSL4/FTH1 Axis-Dependent Ferroptosis.

Doxorubicin (DOX) is an effective anticancer agent, but its clinical utility is constrained by dose-dependent cardiotoxicity, partly due to cardiomyocyte ferroptosis. However, the progress of developing cardioprotective medications to counteract ferroptosis has encountered obstacles. Protosappanin A (PrA), an anti-inflammatory compound derived from hematoxylin, shows potential against DOX-induced cardiomyopathy (DIC). Here, it is reported that PrA alleviates myocardial damage and dysfunction by reducing DOX-induced ferroptosis and maintaining mitochondrial homeostasis. Subsequently, the molecular target of PrA through proteome microarray, molecular docking, and dynamics simulation is identified. Mechanistically, PrA physically binds with ferroptosis-related proteins acyl-CoA synthetase long-chain family member 4 (ACSL4) and ferritin heavy chain 1 (FTH1), ultimately inhibiting ACSL4 phosphorylation and subsequent phospholipid peroxidation, while also preventing FTH1 autophagic degradation and subsequent release of ferrous ions (Fe2+) release. Given the critical role of ferroptosis in the pathogenesis of ischemia-reperfusion (IR) injury, this further investigation posits that PrA can confer a protective effect against IR-induced cardiac damage by inhibiting ferroptosis. Overall, a novel pharmacological inhibitor is unveiled that targets ferroptosis and uncover a dual-regulated mechanism for cardiomyocyte ferroptosis in DIC, highlighting additional therapeutic options for chemodrug-induced cardiotoxicity and ferroptosis-triggered disorders.

Research on cognitive impairment and potential risk factors in peritoneal dialysis patients: An observational study.

The objective of this study is to investigate the associated risk factors and their effects on cognitive impairment (CI) in patients undergoing peritoneal dialysis. A retrospective analysis was conducted on the basic information of 268 patients who underwent continuous ambulatory peritoneal dialysis (CAPD) at our hospital from January 2020 to September 2023. Cognitive function was assessed using the Montreal Cognitive Assessment Scale during their subsequent dialysis visits. Participants were categorized into a CI group and a cognitively normal group. Blood and other biological samples were collected for relevant biomarker analysis. Subsequently, we analyzed and compared the factors influencing CI between the 2 groups. The prevalence of CI among CAPD patients was 58.2%. Compared to the cognitively normal group, the CI group had a higher prevalence of alcohol consumption, lower levels of education, and reduced serum uric acid levels (P < .05). There was also a higher incidence of autoimmune diseases such as systemic lupus erythematosus in the CI group (P < .05). In terms of dialysis efficacy, the residual kidney Kt/V and residual kidney Ccr were significantly lower in the CI group compared to the cognitively normal group. In blood parameters, the CI group showed elevated total cholesterol levels and lower serum calcium concentrations (P < .05). Logistic regression analysis identified male gender, older age, lower educational attainment, hypercholesterolemia, and elevated high-sensitivity C-reactive protein levels as independent risk factors for CI in CAPD patients (P < .05). Additionally, in this patient cohort, dialysis duration and residual renal function were protective factors against CI (P < .05). CI is prevalent among PD patients. Elevated high-sensitivity C-reactive protein levels, male gender, older age, lower educational attainment, and hypercholesterolemia constitute an independent risk factor for CI in CAPD patients, whereas residual renal function acts as a protective element.

Alterations and associations between lung microbiota and metabolite profiles in silica-induced lung injury.

Silicosis, caused by silica exposure, is the most widespread and deadliest occupational disease. However, effective treatments are lacking. Therefore, it is crucial to elucidate the mechanisms and targets involved in the development of silicosis. We investigated the basic processes of silicosis development and onset at different exposure durations (2 or 4 weeks) using various techniques such as histopathology, immunohistochemistry, Enzyme linked immunosorbent assay(ELISA),16 S rRNA, and untargeted metabolomics.These results indicate that exposure to silica leads to progressive damage to lung tissue with significant deterioration observed over time. Time-dependent cytokines such as the IL-4, IL-13, and IL-6 are detected in lung lavage fluid, the model group consistently exhibited elevated levels of these cytokines, indicating a persistent and worsening inflammatory response in the lungs. Meanwhile, HE and Masson results show that 4-week exposure to silica causes more obvious lung injury and pulmonary fibrosis. Besides, the model group consistently exhibited a distinct lung bacterial population, known as the Lachnospiraceae_NK4A136_group, regardless of exposure duration. However, with increasing exposure duration, specific temporal changes were observed in lung bacterial populations, including Haliangium, Allobaculum, and Sandaracinus (at 4 weeks; p < 0.05). Furthermore, our study revealed a strong correlation between the mechanism of silica-induced lung injury and three factors: oxidative stress, impaired lipid metabolism, and imbalanced amino acid metabolism. We observed a close correlation between cytokine levels, changes in lung microbiota, and metabolic disturbances during various exposure periods. These findings propose that a possible mechanism of silica-induced lung injury involves the interplay of cytokines, lung microbiota, and metabolites.

Exploring the Burden of PM2.5-Related Deaths and Economic Health Losses in Beijing.

Air pollution is one of the major global public health challenges. Using annual fine particulate matter (PM2.5) concentration data from 2016 to 2021, along with the global exposure mortality model (GEMM), we estimated the multi-year PM2.5-pollution-related deaths divided by different age groups and diseases. Then, using the VSL (value of statistical life) method, we assessed corresponding economic losses and values. The number of deaths attributed to PM2.5 in Beijing in 2021 fell by 33.74 percent from 2016, while health economic losses would increase by USD 4.4 billion as per capita disposable income increases year by year. In 2021, the average annual concentration of PM2.5 in half of Beijing's municipal administrative districts is less than China's secondary ambient air quality standard (35 µg/m3), but it can still cause 48,969 deaths and corresponding health and economic losses of USD 16.31 billion, equivalent to 7.9 percent of Beijing's GDP. Therefore, it is suggested that more stringent local air quality standards should be designated to protect public health in Beijing.

Not only phosphorus: dauciform roots can also influence aboveground biomass through root morphological traits and metal cation concentrations.

Background: Phosphorus in the soil is mostly too insoluble for plants to utilize, resulting in inhibited aboveground biomass, while Carex can maintain their aboveground biomass through the presence of dauciform roots. However, dauciform roots lead to both morphological and physiological changes in the root system, making their primary mechanism unclear. Methods: A greenhouse experiment was conducted on three Carex species, in which Al-P, Ca-P, Fe-P, and K-P were employed as sole phosphorus sources. The plants were harvested and assessed after 30, 60 and 90 days. Results: (1) The density of dauciform roots was positively correlated with root length and specific root length, positively influencing aboveground biomass at all three stages. (2) The aboveground phosphorus concentration showed a negative correlation with both dauciform root density and aboveground biomass in the first two stages, which became positive in the third stage. (3) Aboveground biomass correlated negatively with the aboveground Al concentration, and positively with Ca and Fe concentration (except Al-P). (4) Root morphological traits emerged as critical factors in dauciform roots' promotion of aboveground biomass accumulation. Conclusion: Despite the difference among insoluble phosphorus, dauciform roots have a contributing effect on aboveground growth status over time, mainly by regulating root morphological traits. This study contributes to our understanding of short-term variation in dauciform roots and their regulatory mechanisms that enhance Carex aboveground biomass under low available phosphorus conditions.

[Spatiotemporal Interaction Characteristics and Transition Mechanism of Carbon Intensity in China's Transportation Industry].

This research was conducted using many spatial analysis approaches to dissect the spatiotemporal interactive characteristics of carbon emission intensity within the transportation sector from 2002 to 2020. An in-depth exploration of their transition mechanisms was conducted by nesting the obtained timewarp types with the panel quantile model. Finally, the geodetector model aligned with different transition mechanisms was employed to investigate and analyze the interaction effects among various factors influencing carbon intensity in the transportation sector. The results indicated that:① The carbon emission intensity of the transportation sector in 30 provinces and regions of China showed an overall downward trend with fluctuations, and the spatial clustering level was relatively stable. ② The spatiotemporal interactive features of ESTDA revealed that the relationship between the northwest region and its adjacent spatial units was unstable, with significant variations and fluctuations. In contrast, economically developed areas such as coastal cities in the eastern part had established mature transportation networks, resulting in a relatively stable local spatial pattern, though a few areas still exhibited spatiotemporal competitiveness. ③ The spatiotemporal transition of carbon intensity in the transportation sector could be categorized into four driving or constraining modes(the population economy urbanization constraint model, population economy urbanization facility constraint model, technology consumption industry-driven model, and technology industry regulation-driven model). Most provinces were influenced by the low quantile constraint and high quantile drive modes, with only a few affected by the high quantile constraint and low quantile drive modes, the majority of which were located in the northwest or southwest regions. ④ Further, we introduced the geographical detector model based on the identified mechanism of carbon emission intensity transition in the transportation sector, emphasizing the coordinated development of multiple factors and strengthening inter-regional collaborative governance.

Low-intensity pulsed ultrasound protects from inflammatory dilated cardiomyopathy through inciting extracellular vesicles.

AIMS: CD4+ T cells are activated during inflammatory dilated cardiomyopathy (iDCM) development to induce immunogenic responses that damage the myocardium. Low-intensity pulsed ultrasound (LIPUS), a novel physiotherapy for cardiovascular diseases, has recently been shown to modulate inflammatory responses. However, its efficacy in iDCM remains unknown. Here, we investigated whether LIPUS could improve the severity of iDCM by orchestrating immune responses and explored its therapeutic mechanisms. METHODS AND RESULTS: In iDCM mice, LIPUS treatment reduced cardiac remodelling and dysfunction. Additionally, CD4+ T cell inflammatory responses were suppressed. LIPUS increased Treg cells while decreasing Th17 cells. LIPUS mechanically stimulates endothelial cells, resulting in increased secretion of extracellular vesicles (EVs), which are taken up by CD4+ T cells and alter their differentiation and metabolic patterns. Moreover, EVs selectively loaded with microRNA (miR)-99a are responsible for the therapeutic effects of LIPUS. The hnRNPA2B1 translocation from the nucleus to the cytoplasm and binding to caveolin-1 and miR-99a confirmed the upstream mechanism of miR-99a transport. This complex is loaded into EVs and taken up by CD4+ T cells, which further suppress mTOR and TRIB2 expression to modulate cellular differentiation. CONCLUSION: Our findings revealed that LIPUS uses an EV-dependent molecular mechanism to protect against iDCM progression. Therefore, LIPUS is a promising new treatment option for iDCM.

Long-Term Follow-Up of Patients Undergoing Thalidomide Therapy for Transfusion-Dependent ß-Thalassaemia: A Single-Center Experience.

Objective: We evaluated the long-term safety and efficacy of thalidomide in the treatment of transfusion-dependent ß-thalassemia (TDT). Methods: Fifty patients with TDT were treated with thalidomide and followed-up for 5 years. Thalidomide at a 50 mg dose was administered once a day after dinner. The dose was increased to 150 mg/d after 3 d if well tolerated. After 1 year of treatment, the hemoglobin (Hb) level was stabilized at its maximum, and thalidomide was gradually reduced and maintained at the minimum dose. The hematological response, transfusion dependence, and haemolytic indicators were assessed. Results: At 9 month of follow-up, 38 (76%) patients achieved an excellent response, 1 (2%) a good response, 4(8%) a minor response, and 7(14%) did not show a response. The overall response rate was 86%. At 9 months, the Hb level increased from 79.0 ± 13.2 g/L at baseline to 99.0 ± 13.7g/L (P<0.001). Patients who achieved excellent response continued to show an increase in Hb levels during follow-up. At 48 months, the mean Hb level was 98.99 ± 10.3g/L; 21 patients (84.0%) became transfusion independent. Thalidomide was reduced and maintained to 25 mg/d in three of these patients. Moreover, five patients completed 60 months of follow-up, and with a mean Hb level of 99.8 ± 6.7g/L. During follow-up, grade 1-2 adverse drug reactions were noted; however, no grade 3 or higher adverse event was reported. However, no decrease in hemolytic indicators was observed. Conclusion: Thalidomide was well tolerated in the long term, while it significantly improved Hb levels and reduced the transfusion burden.

Elucidating transport dynamics and regional division of PM2.5 and O3 in China using an advanced network model.

Air pollution exhibits significant spatial spillover effects, complicating and challenging regional governance models. This study innovatively applied and optimized a statistics-based complex network method in atmospheric environmental field. The methodology was enhanced through improvements in edge weighting and threshold calculations, leading to the development of an advanced pollutant transport network model. This model integrates pollution, meteorological, and geographical data, thereby comprehensively revealing the dynamic characteristics of PM2.5 and O3 transport among various cities in China. Research findings indicated that, throughout the year, the O3 transport network surpassed the PM2.5 network in edge count, average degree, and average weighted degree, showcasing a higher network density, broader city connections, and greater transmission strength. Particularly during the warm period, these characteristics of the O3 network were more pronounced, showcasing significant transport potential. Furthermore, the model successfully identified key influential cities in different periods; it also provided detailed descriptions of the interprovincial spillover flux and pathways of PM2.5 and O3 across various time scales. It pinpointed major pollution spillover and receiving provinces, with primary spillover pathways concentrated in crucial areas such as the Beijing-Tianjin-Hebei (BTH) region and its surrounding areas, the Yangtze River Delta, and the Fen-Wei Plain. Building on this, the model divided the O3, PM2.5, and synergistic pollution transmission regions in China into 6, 7, and 8 zones, respectively, based on network weights and the Girvan Newman (GN) algorithm. Such division offers novel perspectives and strategies for regional joint prevention and control. The validity of the model was further corroborated by source analysis results from the WRF-CAMx model in the BTH area. Overall, this research provides valuable insights for local and regional atmospheric pollution control strategies. Additionally, it offers a robust analytical tool for research in the field of atmospheric pollution.

Individual-centralized seeding strategy for influence maximization in information-limited networks.

Peer effects can directly or indirectly rely on interaction networks to drive people to follow ideas or behaviours triggered by a few individuals, and such effects can be largely improved by targeting the so-called influential individuals. In this article, we study the current most promising seeding strategy used in field experiments, the one-hop strategy, where the underlying interaction networks are generally too impractical or prohibitively expensive to be obtained, and propose an individual-centralized seeding approach to target influential seeds in information-limited networks. The presented strategy works by reasonable follow-up questions to respondents, such as Who do you think has more connections/friends?, and constructs the seeding set by those nodes with the most nominations. In this manner, the proposed method could acquire more information about the studied interaction network from the inference of respondents without surveying additional individuals. We evaluate our strategy on networks from various experimental datasets. Results show that the obtained seeds are much more influential compared to the one-hop strategy and other methods. We also show how the proposed approach could be implemented in field studies and potentially provide better interventions in real scenarios.

Atrial fibrillation ablation compared to pacemaker therapy in patients with tachycardia-bradycardia syndrome: A systematic review and updated meta-analysis.

BACKGROUND: Tachycardia-bradycardia syndrome (TBS) is a subtype of sick sinus syndrome characterized by prolonged sinus pause (≥3 s) following termination of tachyarrhythmias, primarily atrial fibrillation (AF). There is controversy regarding whether the long-term prognosis of AF ablation is superior to pacemaker implantation. This study aimed to compare the effects of AF ablation and pacemaker therapy in patients with TBS. METHODS: We conducted a comprehensive search of electronic databases, including PubMed, Cochrane, EmBase, Web of Science, and Chinese BioMedical, up until December 1, 2023. We included studies that reported the effects of AF ablation vs pacemaker therapy in patients with TBS. From this search, we identified 5 studies comprising 843 participants with TBS who underwent catheter AF ablation or pacemaker therapy. RESULTS: Our meta-analysis revealed that AF ablation and pacemaker therapy had similar effects on cardiovascular death (odds ratio [OR] = 0.62 and 95% confidence interval [CI]: 0.14-2.65), procedural complications (OR = 1.53 and 95% CI: 0.67-3.48), and cardiovascular rehospitalization (OR = 0.57 and 95% CI: 0.26-1.22). However, AF ablation provided greater benefits than pacemaker therapy in terms of all-cause mortality (OR = 0.37 and 95% CI: 0.17-0.82), thromboembolism (OR = 0.25 and 95% CI: 0.12-0.49), stroke (OR = 0.28 and 95% CI: 0.13-0.57), heart failure (OR = 0.27 and 95% CI: 0.13-0.56), freedom from AF (OR = 23.32 and 95% CI: 7.46-72.92), and prevention of progression to persistent AF (OR = 0.12 and 95% CI: 0.06-0.24). Furthermore, AF ablation resulted in a reduced need for antiarrhythmic agents (OR = 0.21 and 95% CI: 0.08-0.59). CONCLUSION: AF ablation can effectively reduce the risk of all-cause mortality, thromboembolism, stroke, heart failure, and progression to persistent AF in patients with TBS. Additionally, it may eliminate the need for further pacemaker therapy in most cases after ablation. Therefore, AF ablation is considered superior to pacemaker therapy in the management of patients with TBS.

Efficient isomerization of glucose into fructose by MgO-doped lignin-derived ordered mesoporous carbon.

The conversion of glucose into fructose can transform cellulose into high-value chemicals. This study introduces an innovative synthesis method for creating an MgO-based ordered mesoporous carbon (MgO@OMC) catalyst, aimed at the efficient isomerization of glucose into fructose. Throughout the synthesis process, lignin serves as the exclusive carbon precursor, while Mg2+ functions as both a crosslinking agent and a metallic active center. This enables a one-step synthesis of MgO@OMC via a solvent-induced evaporation self-assembly (EISA) method. The synthesized MgO@OMCs exhibit an impeccable 2D hexagonal ordered mesoporous structure, in addition to a substantial specific surface area (378.2 m2/g) and small MgO nanoparticles (1.52 nm). Furthermore, this catalyst was shown active, selective, and reusable in the isomerization of glucose to fructose. It yields 41 % fructose with a selectivity of up to 89.3 % at a significant glucose loading of 7 wt% in aqueous solution over MgO0.5@OMC-600. This performance closely rivals the current maximum glucose isomerization yield achieved with solid base catalysts. Additionally, the catalyst retains a fructose selectivity above 60 % even after 4 cycles, a feature attributable to its extended ordered mesoporous structure and the spatial confinement effect of the OMCs, bestowing it with high catalytic efficiency.

Acceptance and willingness to pay for DTaP-HBV-IPV-Hib hexavalent vaccine among parents: A cross-sectional survey in China.

DTaP-HBV-IPV-Hib hexavalent vaccine has been used in high-income countries for many years to prevent diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis, and invasive Haemophilus influenzae type b disease. Currently, no hexavalent vaccines have been approved for use in China. Evidence of parental acceptance and interest in hexavalent vaccines can help policy makers and manufacturers make decisions about entering the vaccine market and the immunization program in China. We measured parental acceptance and willingness-to-pay (WTP) for a hexavalent vaccine to provide such evidence. We conducted a cross-sectional survey of children's caregivers in 16 vaccination clinics in seven cities in China and obtained information on socio-demographics, knowledge of disease, confidence in vaccines, previous vaccination experience, and acceptance of and WTP for hexavalent vaccine. Multivariate logistic regression was used to determine factors influencing acceptance, and multivariate tobit regression was used to identify factors impacting WTP. Between April 28 and June 30, 2023, a total of 581 parents of children aged 0-6 years participated in the survey; 435 (74.87%, 95% CI:71.3%-78.4%) parents indicated acceptance of hexavalent vaccine. Residence location, parents' education level, experience paying for vaccination, and disease knowledge scores were key factors affecting parents' choices for vaccination. Mean (SD) and median (IQR) willingness to pay for full 4-dose course vaccination were 2266.66 (1177.1) CNY and 2400 (1600-2800) CNY. Children's age (p < .001), parents' education level (p = .024), and perceived price barriers (p < .001) were significantly associated with WTP. Parents have high acceptance and willingness to pay for hexavalent vaccine. The less money parents have to pay out of pocket, the more willing they can be to accept the vaccine. Therefore, acceptance may increase even further if the vaccine is covered by medical insurance, provided free of charge by the government, or if its price is reduced. Our results provide reference for optimizing and adjusting immunization strategies in China.

B1 Power Modification for Amide Proton Transfer Imaging in Parotid Glands: A Strategy for Image Quality Accommodation and Evaluation of Tumor Detection Feasibility.

BACKGROUND: In the application of APTw protocols for evaluating tumors and parotid glands, inhomogeneity and hyperintensity artifacts have remained an obstacle. This study aimed to improve APTw imaging quality and evaluate the feasibility of difference B1 values to detect parotid tumors. METHODS: A total of 31 patients received three APTw sequences to acquire 32 lesions and 30 parotid glands (one patient had lesions on both sides). Patients received T2WI and 3D turbo-spin-echo (TSE) APTw imaging on a 3.0 T scanner for three sequences (B1 = 2 µT, 1 µT, and 0.7 µT in APTw 1, 2, and 3, respectively). APTw image quality was evaluated using four-point Likert scales in terms of integrity and hyperintensity artifacts. Image quality was compared between the three sequences. An evaluable group and a trustable group were obtained for APTmean value comparison. RESULTS: Tumors in both APT2 and APT3 had fewer hyperintensity artifacts than in APT1. With B1 values decreasing, tumors had less integrity in APTw imaging. APTmean values of tumors were higher than parotid glands in traditional APT1 sequence though not significant, while the APTmean subtraction value was significantly different. CONCLUSIONS: Applying a lower B1 value could remove hyperintensity but could also compromise its integrity. Combing different APTw sequences might increase the feasibility of tumor detection.

Home-based vs center-based exercise on patient-reported and performance-based outcomes for knee osteoarthritis: a systematic review with meta-analysis.

Background: Home-based exercise (HBE) represents an alternative to increase the accessibility of rehabilitation programs and relieve the burden on the health care system for people with knee osteoarthritis. Objectives: To summarize for the first time the effectiveness of HBE as compared to center-based exercise (CBE), both with and without HBE, on patient-reported and performance-based outcomes in people with KOA. Methods: Searches were conducted on PubMed, Cochrane, Embase, Web of Science, and Scopus until March 10, 2023, without date or language restrictions. Randomized controlled trials investigating HBE versus CBE or HBE combined with CBE for people with KOA were eligible. The primary outcomes were patient-reported: pain, physical disability, and quality of life. The secondary outcomes were performance-based: walking ability, lower limb muscle strength, and balance function. Risk of bias was assessed with the Cochrane Risk of Bias tool and quality of evidence according to the GRADE. Results: Eleven trials involving 956 participants were included. There was no difference in short-term pain (SMD, 0.22 [95% CI, -0.04 to 0.47], p = 0.09; I2 = 0%), physical disability (SMD, 0.17 [95% CI, -0.19 to 0.54], p = 0.35; I2 = 0%), walking ability (SMD, -0.21 [95% CI, -0.64 to 0.22], p = 0.33; I2 = 35%) and lower limb muscle strength (SMD, -0.24 [95% CI, -0.88 to 0.41], p = 0.47; I2 = 69%) between HBE and CBE. HBE combined with CBE has better benefits compared with HBE alone in short-term pain (SMD, 0.89 [95% CI, 0.60 to 1.17], p < 0.001; I2 = 11%) and physical disability (SMD, 0.25 [95% CI, 0.00 to 0.50], p = 0.05; I2 = 0%). Conclusion: Based on limited evidence, HBE is as effective as CBE on short-term pain, physical disability, walking ability, and lower limb muscle strength in people with knee osteoarthritis. Furthermore, combining HBE with CBE may enhance the overall efficacy of the intervention. Systematic review registration: PROSPERO, CRD42023416548.

Leukemia inhibitory factor protects against experimental periodontitis through immuno-modulations of both macrophages and periodontal ligament fibroblasts.

BACKGROUND: To explore the role of leukemia inhibitory factor (LIF) in periodontitis via in vivo and in vitro experiments. METHODS: The second upper molar of LIF knockout mice and their wild-type littermates were ligated for 8 days. Micro-computed tomography (micro-CT), histological analysis, and quantitative real-time polymerase chain reaction (qRT-PCR) were performed. The expression levels of proinflammatory cytokines were examined in mouse bone marrow derived macrophages and human periodontal ligament fibroblasts (HPDLFs) after lipopolysaccharide (LPS) treatment. RESULTS: LIF deficiency promoted alveolar bone loss, inflammatory cells infiltration, osteoclasts formation and collagen fiber degradation in ligature-induced mouse, along with higher expressions of proinflammatory cytokines, including interleukin-6 (IL6), IL-1ß (IL1B), tumor necrosis factor-α (TNFA), matrix metalloproteinase 13 (MMP13), and RANKL/OPG ratio. Additionally, LIF deletion led to higher expression levels of these proinflammatory cytokines in mouse bone marrow-derived macrophages from both femur and alveolar bone and HPDLFs when treated with LPS. Administration of recombined LIF attenuated TNFA, IL1B, and RANKL/OPG ratio in HPDLFs. CONCLUSIONS: These findings indicate that LIF deficiency promotes the progress of periodontitis via modulating immuno-inflammatory responses of macrophages and periodontal ligament fibroblasts, and the application of LIF may be an adjunctive treatment for periodontitis to resolute inflammation.

The Effectiveness of Exercise-Based Rehabilitation in People With Hand Osteoarthritis: A Systematic Review With Meta-analysis.

OBJECTIVE: To investigate the effectiveness of exercise-based rehabilitation programs compared with nonexercise intervention or no intervention for people with hand osteoarthritis (OA). DESIGN: Intervention systematic review with meta-analysis. LITERATURE SEARCH: We searched 5 databases on July 23, 2023. STUDY SELECTION CRITERIA: We included randomized controlled trials that compared the effectiveness of rehabilitation programs that included an exercise component, with nonexercise intervention or no intervention for people with hand OA. DATA SYNTHESIS: Standardized mean differences (SMDs) were pooled using a random-effects model. The risk of bias was assessed using the Cochrane Risk of Bias 2.0 tool. The certainty of the evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach. RESULTS: Fourteen trials were included in the meta-analysis (n = 1341 participants). In the immediate term (<24 weeks), there was low-certainty evidence of an effect of exercise-based rehabilitation on improving pain (13 trials; SMD = -0.65; 95% CI: -1.06, -0.25), function (11 trials; SMD = -0.35; 95% CI: -0.54, -0.15), and grip strength (14 trials; SMD = 0.21; 95% CI: 0.03, 0.38). There was moderate-certainty evidence of an effect on reducing stiffness (7 trials; SMD = -0.33; 95% CI: -0.51, -0.16). There was low-certainty evidence of no effect on improving pinch strength and quality of life. For the long term (≥24 weeks), there was low-certainty evidence that exercise-based rehabilitation had no additional effect on improving pain, function, and stiffness. CONCLUSION: Exercise-based rehabilitation improved pain, function, stiffness, and grip strength in people with hand OA in the immediate term; the benefits were not maintained in the long term. J Orthop Sports Phys Ther 2024;54(7):1-11. Epub 20 March 2024. doi:10.2519/jospt.2024.12241.

Exploration of the Mechanisms Underlying Yu's Enema Formula in Treating Ulcerative Colitis by Blocking the RhoA/ROCK Pathway based on Network Pharmacology, High-performance Liquid Chromatography Analysis, and Experimental Verification.

BACKGROUND: The traditional Chinese medicine formula, Yu's Enema Formula (YEF), has demonstrated potential in the treatment of Ulcerative Colitis (UC). OBJECTIVE: This study aimed to unveil the anti-UC mechanisms of YEF. METHODS: Utilizing public databases, we obtained YEF and UC-related targets. GO and KEGG analyses were conducted via clusterProfiler and Reactome. The STRING database facilitated the construction of the PPI network, and hub targets were selected using cytoHubba. We used R software for differential expression and correlation analyses, and molecular docking was performed with PyMOL and AutoDock. HPLC analysis identified the compounds in YEF. For in vivo validation, a UC rat model was employed. RESULTS AND DISCUSSION: 495 YEF-UC overlapping targets were identified. GO and KEGG analyses indicated enrichment in exogenous stimuli response, peptide response, positive MAPK cascade regulation, interleukin- related signaling, and the TLR4 cascade. Hub targets included CTNNB1, JUN, MAPK1, MAPK3, SRC, STAT3, TLR4, TP53, and RELA, which were often interconnected. Molecular docking revealed quercetin's strong binding affinity with CTNNB1, MAPK1, MAPK3, SRC, STAT3, TLR4, and TP53, consistent with HPLC analysis. In vivo experiments suggested that YEF has the potential to alleviate UC symptoms and protect the intestinal mucosal barrier by inhibiting the RhoA/ROCK pathway. CONCLUSION: YEF may safeguard the intestinal mucosal barrier in UC by targeting CTNNB1, MAPK1, MAPK3, SRC, STAT3, TLR4, and TP53, while blocking the RhoA/ROCK pathway.