Lifestyle-based subtypes of childhood obesity and their association with cardiometabolic factors: A cluster analysis.

BACKGROUND: Lifestyle factors play an important role in the development and management of childhood obesity and its related cardiometabolic complications. OBJECTIVE/METHODS: We aimed to explore childhood obesity subtypes based on lifestyle factors and examine their association with cardiometabolic health. We included 1550 children with obesity from the National Health and Nutrition Examination Survey. Cluster analysis identified obesity subtypes based on four lifestyle factors (physical activity, diet quality, sedentary time and smoking). Multiple linear regression assessed their association with cardiometabolic factors. RESULTS: Five subtypes of childhood obesity were identified: unhealthy subtype (n = 571; 36.8%), physically active subtype (n = 185; 21.1%), healthy diet subtype (n = 404; 26.1%), smoking subtype (n = 125; 8.1%) and non-sedentary subtype (n = 265; 17.1%). Compared with the unhealthy subtype, the physically active subtype had lower insulin and HOMA-IR levels, and smoking subtype was associated with lower HDL levels. When compared with children with normal weight, all obesity subtypes had worse cardiometabolic profile, except the physically active subtype who had similar DBP, HbA1c and TC levels; smoking subtype who had similar TC levels; and healthy diet and non-sedentary subtypes who had similar DBP levels. CONCLUSION: Children of different lifestyle-based obesity subtypes might have different cardiometabolic risks. Our new classification system might help personalize assessment of childhood obesity.

CA1 Modulates the Osteogenic Differentiation of Dental Follicle Stem Cells by Activating the BMP Signaling Pathway In Vitro.

BACKGROUND: Carbonic anhydrase 1 (CA1) has been found to be involved in osteogenesis and osteoclast in various human diseases, but the molecular mechanisms are not completely understood. In this study, we aim to use siRNA and lentivirus to reduce or increase the expression of CA1 in Dental follicle stem cells (DFSCs), in order to further elucidate the role and mechanism of CA1 in osteogenesis, and provide better osteogenic growth factors and stem cell selection for the application of bone tissue engineering in alveolar bone fracture transplantation. METHODS: The study used RNA interference and lentiviral vectors to manipulate the expression of the CA1 gene in DFSCs during in vitro osteogenic induction. The expression of osteogenic marker genes was evaluated and changes in CA1, alkaline phosphatase (ALP), Runt-related transcription factor 2 (RUNX2), and Bone morphogenetic proteins (BMP2) were measured using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting (WB). The osteogenic effect was assessed through Alizarin Red staining. RESULTS: The mRNA and protein expression levels of CA1, ALP, RUNX2, and BMP2 decreased distinctly in the si-CA1 group than other groups (p < 0.05). In the Lentivirus-CA1 (LV-CA1) group, the mRNA and protein expressions of CA1, ALP, RUNX2, and BMP2 were amplified to varying degrees than other groups (p < 0.05). Apart from CA1, BMP2 (43.01%) and ALP (36.69%) showed significant upregulation (p < 0.05). Alizarin red staining indicated that the LV-CA1 group produced more calcified nodules than other groups, with a higher optical density (p < 0.05), and the osteogenic effect was superior. CONCLUSIONS: CA1 can impact osteogenic differentiation via BMP related signaling pathways, positioning itself upstream in osteogenic signaling pathways, and closely linked to osteoblast calcification and ossification processes.

Global analysis of an age-structured tuberculosis model with an application to Jiangsu, China.

Diagnostic delay for TB infected individuals and the lack of TB vaccines for adults are the main challenges to achieve the goals of WHO by 2050. In order to evaluate the impacts of diagnostic delay and vaccination for adults on prevalence of TB, we propose an age-structured model with latent age and infection age, and we incorporate Mycobacterium TB in the environment and vaccination into the model. Diagnostic delay is indicated by the age of infection before receiving treatment. The threshold dynamics are established in terms of the basic reproduction number R 0 . When R 0 < 1 , the disease-free equilibrium is globally asymptotically stable, which means that TB epidemic will die out; When R 0 = 1 , the disease-free equilibrium is globally attractive; there exists a unique endemic equilibrium and the endemic equilibrium is globally attractive when R 0 > 1 . We estimate that the basic reproduction number R 0 = 0.5320 (95% CI (0.3060, 0.7556)) in Jiangsu Province, which means that TB epidemic will die out. However, we find that the annual number of new TB cases by 2050 is 1,151 (95%CI: (138, 8,014)), which means that it is challenging to achieve the goal of WHO by 2050. To this end, we evaluate the possibility of achieving the goals of WHO if we start vaccinating adults and reduce diagnostic delay in 2025. Our results demonstrate that when the diagnostic delay is reduced from longer than four months to four months, or 20% adults are vaccinated, the goal of WHO in 2050 can be achieved, and 73,137 (95%CI: (23,906, 234,086)) and 54,828 (95%CI: (15,811, 206,468)) individuals will be prevented from being infected from 2025 to 2050, respectively. The modeling approaches and simulation results used in this work can help policymakers design control measures to reduce the prevalence of TB.

circular RNA circ-231 promotes protein biogenesis of TPI1 and PRDX6 through mediating the interaction of eIF4A3 with STAU1 to facilitate unwinding of secondary structure in 5' UTR, enhancing progression of human esophageal squamous cell carcinoma (ESCC).

Background: The nuclear cap-binding complex (CBC)-dependent translation (CT) is an important initial translation pathway for 5'-cap-dependent translation in normal mammal cells. Eukaryotic translation initiation factor 4A-III (eIF4A3), as an RNA helicase, is recruited to CT complex and enhances CT efficiency through participating in unwinding of secondary structure in the 5' UTR. However, the detailed mechanism for eIF4A3 implicated in unwinding of secondary structure in the 5' UTR in normal mammal cells is still unclear. Specially, we need to investigate whether the kind of mechanism in normal mammal cells extrapolates to cancer cells, e.g. ESCC, and further interrogate whether and how the mechanism triggers malignant phenotype of ESCC, which are important for identifying a potential therapeutic target for patients with ESCC. Methods: Bioinformatics analysis, RNA immunoprecipitation and RNA pulldown assays were performed to detect the interaction of circular RNA circ-231 with eIF4A3. In vitro and in vivo assays were performed to detect biological roles of circ-231 in ESCC. RNA immunoprecipitation, RNA pulldown, mass spectrometry analysis and co-immunoprecipitation assays were used to measure the interaction of circ-231, eIF4A3 and STAU1 in HEK293T and ESCC. In vitro EGFP reporter and 5' UTR of mRNA pulldown assays were performed to probe for the binding of circ-231, eIF4A3 and STAU1 to secondary structure of 5' UTR. Results: RNA immunoprecipitation assays showed that circ-231 interacted with eIF4A3 in HEK293T and ESCC. Further study confirmed that circ-231 orchestrated with eIF4A3 to control protein expression of TPI1 and PRDX6, but not for mRNA transcripts. The in-depth mechanism study uncovered that both circ-231 and eIF4A3 were involved in unwinding of secondary structure in 5' UTR of TPI1 and PRDX6. More importantly, circ-231 promoted the interaction between eIF4A3 and STAU1. Intriguingly, both circ-231 and eIF4A3 were dependent on STAU1 binding to secondary structure in 5' UTR. Biological function assays revealed that circ-231 promoted the migration and proliferation of ESCC via TPI1 and PRDX6. In ESCC, the up-regulated expression of circ-231 was observed and patients with ESCC characterized by higher expression of circ-231 have concurrent lymph node metastasis, compared with control. Conclusions: Our data unravels the detailed mechanism by which STAU1 binds to secondary structure in 5' UTR of mRNAs and recruits eIF4A3 through interacting with circ-231 and thereby eIF4A3 is implicated in unwinding of secondary structure, which is common to HEK293T and ESCC. However, importantly, our data reveals that circ-231 promotes migration and proliferation of ESCC and the up-regulated circ-231 greatly correlates with tumor lymph node metastasis, insinuating that circ-231 could be a therapeutic target and an indicator of risk of lymph node metastasis for patients with ESCC.

Inhibiting MMP13 Attenuates Deep Vein Thrombosis in a Mouse Model by Reducing the Expression of Pdpn.

OBJECTIVE: Matrix metalloproteinase 13 (MMP13) is an extracellular matrix protease that affects the progression of atherosclerotic plaques and arterial thrombi by degrading collagens, modifying protein structures and regulating inflammatory responses, but its role in deep vein thrombosis (DVT) has not been determined. The purpose of this study was to investigate the potential effects of MMP13 and MMP13-related genes on the formation of DVT. METHODS: We altered the expression level of MMP13 in vivo and conducted a transcriptome study to examine the expression and relationship between MMP13 and MMP13-related genes in a mouse model of DVT. After screening genes possibly related to MMP13 in DVT mice, the expression levels of candidate genes in human umbilical vein endothelial cells (HUVECs) and the venous wall were evaluated. The effect of MMP13 on platelet aggregation in HUVECs was investigated in vitro. RESULTS: Among the differentially expressed genes, interleukin 1 beta, podoplanin (Pdpn), and factor VIII von Willebrand factor (F8VWF) were selected for analysis in mice. When MMP13 was inhibited, the expression level of PDPN decreased significantly in vitro. In HUVECs, overexpression of MMP13 led to an increase in the expression level of PDPN and induced platelet aggregation, while transfection of PDPN-siRNA weakened the ability of MMP13 to increase platelet aggregation. CONCLUSIONS: Inhibiting the expression of MMP13 could reduce the burden of DVT in mice. The mechanism involves downregulating the expression of Pdpn through MMP13, which could provide a novel gene target for DVT diagnosis and treatment.

Revealing the variances in color formation and bioactivities of seven catechin monomers throughout the enzymatic reaction by colorimetric and mass spectrometry.

The capacity differences of seven catechin monomers to produce colors after treating with catechin-free extract were investigated. After 240-min reaction, only (-)-epicatechin (EC) and (+)-catechin (C) presented obvious luminous red color with L* values of 63.32-71.73, a* values of 37.13-46.44, and b* values of 65.64-69.99. Meanwhile, the decrease rate of EC and C was 43.52 %-50.35 %, which were significantly lower than those of other catechin monomers (85.91 %-100 %). The oxidized products of catechin monomers were analyzed by ultra-high performance liquid chromatography-quadrupole-time of flight-mass spectrometry coupled with diode array detector, wherein dehydro-dimers and -trimers (oxidative coupling products of catechins' A-B ring) were found to be the major chromogenic compounds of EC and C. Additionally, the antioxidant capacity of catechin monomers only decreased after 30-min reaction, while along with further enzymatic reaction, catechin monomers presented comparable oxyradical scavenging ability (e.g., the DPPH inhibitory rates of catechin monomers were in the range of 24.42 %-50.77 %) to vitamin C (positive control, DPPH inhibitory rate was 27.66 %). Meanwhile, the inhibitory effects of most catechin monomers on α-glucosidase were enhanced in different degrees. These results provided basis for the development of enzymatically-oxidized catechin monomers as functional food color additives.

Regional gap and sustainable development of interpreting level in mainland China: A statistics and GIS-based study.

Against the backdrop of globalization, interpreting, a translation communicative activity in a verbal way, plays an increasingly important role in international communications and exchanges. In response to this world pattern, the Chinese government attaches great importance to the interpreting industry. However, due to the national condition of uneven regional development, the English interpreting level across China is also unbalanced. Confronting this circumstance, previous research only stagnates at the level of recognizing the problem, but very few studies have attempted to solve the problem. Thus, the current study aims to figure out the regional interpreting level in mainland China by establishing and utilizing an innovative indicator system based on statistics and geography technologies. Based on the literature review and empirical questionnaire survey from different stakeholders, the study proposes an indicator system containing 3 first-level factors and 7 second-level factors to measure regional English interpreting levels. The weight of each indicator and scoring method is laid down based on factor analysis and interval marking. In addition, putting the innovative indicator system into practice, a total of 38 groups of regional data are collected to rank the regional interpreting level across China. Integrating with GIS and statistical techniques, the result visually shows that the English interpreting level across China is uneven at present: higher in the southern and eastern parts of China compared to that of northern and western China, which is unfriendly to sustainable development in the future. Facing this reality, a following-up analysis has been made for offering explanations of the results and suggestions for regional interpreting sustainable development.

A Randomized Trial Comparing Standard of Care to Bayesian Warfarin Dose Individualization.

The quality of warfarin treatment may be improved if management is guided by the use of models based upon pharmacokinetic-pharmacodynamic theory. A prospective, two-armed, single-blind, randomized controlled trial compared management aided by a web-based dose calculator (NextDose) with standard clinical care. Participants were 240 adults receiving warfarin therapy following cardiac surgery, followed up until the first outpatient appointment at least 3 months after warfarin initiation. We compared the percentage of time spent in the international normalized ratio acceptable range (%TIR) during the first 28 days following warfarin initiation, and %TIR and count of bleeding events over the entire follow-up period. Two hundred thirty-four participants were followed up to day 28 (NextDose: 116 and standard of care: 118), and 228 participants (114 per arm) were followed up to the final study visit. Median %TIR tended to be higher for participants receiving NextDose guided warfarin management during the first 28 days (63 vs. 56%, P = 0.13) and over the entire follow-up period (74 vs. 71%, P = 0.04). The hazard of clinically relevant minor bleeding events was lower for participants in the NextDose arm (hazard ratio: 0.21, P = 0.041). In NextDose, there were 89.3% of proposed doses accepted by prescribers. NextDose guided dose management in cardiac surgery patients requiring warfarin was associated with an increase in %TIR across the full follow-up period and fewer hemorrhagic events. A theory-based, pharmacologically guided approach facilitates higher quality warfarin anticoagulation. An important practical benefit is a reduced requirement for clinical experience of warfarin management.

Warfarin-A natural anticoagulant: A review of research trends for precision medication.

BACKGROUND: Warfarin is a widely prescribed anticoagulant in the clinic. It has a more considerable individual variability, and many factors affect its variability. Mathematical models can quantify the quantitative impact of these factors on individual variability. PURPOSE: The aim is to comprehensively analyze the advanced warfarin dosing algorithm based on pharmacometrics and machine learning models of personalized warfarin dosage. METHODS: A bibliometric analysis of the literature retrieved from PubMed and Scopus was performed using VOSviewer. The relevant literature that reported the precise dosage of warfarin calculation was retrieved from the database. The multiple linear regression (MLR) algorithm was excluded because a recent systematic review that mainly reviewed this algorithm has been reported. The following terms of quantitative systems pharmacology, mechanistic model, physiologically based pharmacokinetic model, artificial intelligence, machine learning, pharmacokinetic, pharmacodynamic, pharmacokinetics, pharmacodynamics, and warfarin were added as MeSH Terms or appearing in Title/Abstract into query box of PubMed, then humans and English as filter were added to retrieve the literature. RESULTS: Bibliometric analysis revealed important co-occuring MeShH and index keywords. Further, the United States, China, and the United Kingdom were among the top countries contributing in this domain. Some studies have established personalized warfarin dosage models using pharmacometrics and machine learning-based algorithms. There were 54 related studies, including 14 pharmacometric models, 31 artificial intelligence models, and 9 model evaluations. Each model has its advantages and disadvantages. The pharmacometric model contains biological or pharmacological mechanisms in structure. The process of pharmacometric model development is very time- and labor-intensive. Machine learning is a purely data-driven approach; its parameters are more mathematical and have less biological interpretation. However, it is faster, more efficient, and less time-consuming. Most published models of machine learning algorithms were established based on cross-sectional data sourced from the database. CONCLUSION: Future research on personalized warfarin medication should focus on combining the advantages of machine learning and pharmacometrics algorithms to establish a more robust warfarin dosage algorithm. Randomized controlled trials should be performed to evaluate the established algorithm of warfarin dosage. Moreover, a more user-friendly and accessible warfarin precision medicine platform should be developed.

Efficacy of ceftazidime-avibactam in the treatment of carbapenem-resistant Klebsiella pneumoniae infections: Focus on solid organ transplantation recipients.

INTRODUCTION: Ceftazidime-avibactam (CAZ-AVI) is a new option to treat KPC- and OXA-48 carbapenem-resistant Klebsiella pneumoniae (CRKP) infections. However, clinical evidence is limited regarding its use in treating CRKP infections, especially in solid organ transplantation (SOT) recipients. In this study, we assessed the efficacy of CAZ-AVI in treating CRKP infections in both the general population and the SOT recipients in comparison with other antibiotic regimens. METHODS: This is a single-centre retrospective cohort study of patients admitted between January 1, 2018 and June 30, 2021 with the diagnosis of CRKP infections receiving either CAZ-AVI or other regimens ≥ 72 hours and clinical outcomes were analysed. RESULTS: Of 200 patients with CRKP infections, 67 received CAZ-AVI, 133 received other regimens, and 50 were SOT recipients. In the SOT cohort, 30 patients received CAZ-AVI, and 20 received other regimens. The overall 30-day mortality was 38% in the SOT cohort. Compared with patients receiving other regimens, CAZ-AVI therapy resulted in lower 30-day mortality (23.3% vs. 60%, P = 0.014) and 90-day mortality (35.7% vs. 86.7%, P = 0.003), higher clinical cure (93.3% vs. 40%, P < 0.001) and microbiological clearance. Similar promising results of CAZ-AVI were also shown in the whole population cohort. Moreover, clinical outcomes of SOT recipients receiving CAZ-AVI were not inferior to those without SOT. CONCLUSIONS: CAZ-AVI therapy was associated with better clinical outcomes in CRKP infections in both the general population and SOT recipients. Considering the limitations of the present study, well-conducted RCTs are still warranted to confirm these findings.

CD39 expression defines exhausted CD4+ T cells associated with poor survival and immune evasion in human gastric cancer.

Objectives: CD4+ T cell helper and regulatory function in human cancers has been well characterised. However, the definition of tumor-infiltrating CD4+ T cell exhaustion and how it contributes to the immune response and disease progression in human gastric cancer (GC) remain largely unknown. Methods: A total of 128 GC patients were enrolled in the study. The expression of CD39 and PD-1 on CD4+ T cells in the different samples was analysed by flow cytometry. GC-infiltrating CD4+ T cell subpopulations based on CD39 expression were phenotypically and functionally assessed. The role of CD39 in the immune response of GC-infiltrating T cells was investigated by inhibiting CD39 enzymatic activity. Results: In comparison with CD4+ T cells from the non-tumor tissues, significantly more GC-infiltrating CD4+ T cells expressed CD39. Most GC-infiltrating CD39+CD4+ T cells exhibited CD45RA-CCR7- effector-memory phenotype expressing more exhaustion-associated inhibitory molecules and transcription factors and produced less TNF-α, IFN-γ and cytolytic molecules than their CD39-CD4+ counterparts. Moreover, ex vivo inhibition of CD39 enzymatic activity enhanced their functional potential reflected by TNF-α and IFN-γ production. Finally, increased percentages of GC-infiltrating CD39+CD4+ T cells were positively associated with disease progression and patients' poorer overall survival. Conclusion: Our study demonstrates that CD39 expression defines GC-infiltrating CD4+ T cell exhaustion and their immunosuppressive function. Targeting CD39 may be a promising therapeutic strategy for treating GC patients.

Modelling the impact of human behavior using a two-layer Watts-Strogatz network for transmission and control of Mpox.

PURPOSE: This study aims to evaluate the effectiveness of mitigation strategies and analyze the impact of human behavior on the transmission of Mpox. The results can provide guidance to public health authorities on comprehensive prevention and control for the new Mpox virus strain in the Democratic Republic of Congo as of December 2023. METHODS: We develop a two-layer Watts-Strogatz network model. The basic reproduction number is calculated using the next-generation matrix approach. Markov chain Monte Carlo (MCMC) optimization algorithm is used to fit Mpox cases in Canada into the network model. Numerical simulations are used to assess the impact of mitigation strategies and human behavior on the final epidemic size. RESULTS: Our results show that the contact transmission rate of low-risk groups and susceptible humans increases when the contact transmission rate of high-risk groups and susceptible humans is controlled as the Mpox epidemic spreads. The contact transmission rate of high-risk groups after May 18, 2022, is approximately 20% lower than that before May 18, 2022. Our findings indicate a positive correlation between the basic reproduction number and the level of heterogeneity in human contacts, with the basic reproduction number estimated at 2.3475 (95% CI: 0.0749-6.9084). Reducing the average number of sexual contacts to two per week effectively reduces the reproduction number to below one. CONCLUSION: We need to pay attention to the re-emergence of the epidemics caused by low-risk groups when an outbreak dominated by high-risk groups is under control. Numerical simulations show that reducing the average number of sexual contacts to two per week is effective in slowing down the rapid spread of the epidemic. Our findings offer guidance for the public health authorities of the Democratic Republic of Congo in developing effective mitigation strategies.

CD39hi identifies an exhausted tumor-reactive CD8+ T cell population associated with tumor progression in human gastric cancer.

The ectonucleotidase CD39 has been regarded as a promising immune checkpoint in solid tumors. However, the expression of CD39 by tumor-infiltrating CD8+ T cells as well as their potential roles and clinical implications in human gastric cancer (GC) remain largely unknown. Here, we found that GC-infiltrating CD8+ T cells contained a fraction of CD39hi cells that constituted about 6.6% of total CD8+ T cells in tumors. These CD39hi cells enriched for GC-infiltrating CD8+ T cells with features of exhaustion in transcriptional, phenotypic, metabolic and functional profiles. Additionally, GC-infiltrating CD39hiCD8+ T cells were also identified for tumor-reactive T cells, as these cells expanded in vitro were able to recognize autologous tumor organoids and induced more tumor cell apoptosis than those of expanded their CD39int and CD39-CD8+ counterparts. Furthermore, CD39 enzymatic activity controlled GC-infiltrating CD39hiCD8+ T cell effector function, and blockade of CD39 efficiently enhanced their production of cytokines IFN-γ and TNF-α. Finally, high percentages of GC-infiltrating CD39hiCD8+ T cells correlated with tumor progression and independently predicted patients' poor overall survival. These findings provide novel insights into the association of CD39 expression level on CD8+ T cells with their features and potential clinical implications in GC, and empowering those exhausted tumor-reactive CD39hiCD8+ T cells through CD39 inhibition to circumvent the suppressor program may be an attractive therapeutic strategy against GC.

The complete mitochondrial genome of cattle tick clade C reveals the genetic relationship within Rhipicephalus microplus complex.

Cattle ticks (Rhipicephalus microplus) are important economic ectoparasites causing direct and indirect damage to cattle and leading to severe economic losses in cattle husbandry. It is common knowledge that R. microplus is a species complex including five clades; however, the relationships within the R. microplus complex remain unresolved. In the present study, we assembled the complete mitochondrial genome of clade C by next-generation sequencing and proved its correctness based on long PCR amplification. It was 15,004 bp in length and consisted of 13 protein genes, 22 transfer genes, and two ribosomal genes located in the two strains. There were two copies of the repeat region (pseudo-nad1 and tRNA-Glu). Data revealed that cox1, cox2, and cox3 genes were conserved within R. microplus with small genetic differences. Ka/Ks ratios suggested that 12 protein genes (excluding nad6) may be neutral selection. The genetic and phylogenetic analyses indicated that clade C was greatly close to clade B. Findings in the current study provided more data for the identification and differentiation of the R. microplus complex and made up for the lack of information about R. microplus clade C.

Facile Fabrication of Hollow Nanoporous Carbon Architectures by Controlling MOF Crystalline Inhomogeneity for Ultra-Stable Na-Ion Storage.

Hollow nanoporous carbon architectures (HNCs) present significant utilitarian value for a wide variety of applications. Facile and efficient preparation of HNCs has long been pursued but still remains challenging. Herein, we for the first time demonstrate that single-component metal-organic frameworks (MOFs) crystals, rather than the widely reported hybrid ones which necessitate tedious operations for preparation, could enable the facile and versatile syntheses of functional HNCs. By controlling the growth kinetics, the MOFs crystals (STU-1) are readily engineered into different shapes with designated styles of crystalline inhomogeneity. A subsequent one-step pyrolysis of these MOFs with intraparticle difference can induce a simultaneous self-hollowing and carbonization process, thereby producing various functional HNCs including yolk-shell polyhedrons, hollow microspheres, mesoporous architectures, and superstructures. Superior to the existing methods, this synthetic strategy relies only on the complex nature of single-component MOFs crystals without involving tedious operations like coating, etching, or ligand exchange, making it convenient, efficient, and easy to scale up. An ultra-stable Na-ion battery anode is demonstrated by the HNCs with extraordinary cyclability (93 % capacity retention over 8000 cycles), highlighting a high level of functionality of the HNCs.

Clinical and Radiologic Outcomes of Arthroscopic Rotator Cuff Repair in Medial Bursal-Side Fosbury Flop Tears Compared With Tendinous Avulsion Lesions.

Purpose: To determine the clinical and radiologic outcomes after surgical repair of medial bursal-side Fosbury flop rotator cuff tears compared with traditional avulsion of tendinous attachments lesions. Methods: A retrospective cohort study was performed. All patients who had undergone arthroscopic posterosuperior repair were recruited. Patients with previous shoulder rotator cuff surgery were excluded. Recruited patients were divided into 2 groups: one presenting Fosbury flop tears and the other presenting with standard avulsion lesions. Preoperative demographics such as age, gender, and arm dominance were recorded. Range of motion (ROM), visual analog scale (VAS) for pain and satisfaction, Constant score, Single Alpha-Numeric Evaluation score, and American Shoulder and Elbow Surgeons score were evaluated at 3 points in time: preoperatively, and at 6 months and minimum 1-year postoperatively. The healing of repaired cuffs was evaluated by ultrasound at 6 months. Results: Two hundred thirty-six patients were recruited, with 27 (11.4%) Fosbury flop tears and 209 (88.6%) tendon avulsions. Although there was no significant difference in gender or arm dominance between the groups, Fosbury flop tears had significantly older patients (P < .05) with a mean age 61.6 years (standard deviation 9.0), compared with tendon avulsions with a mean age of 56.1 years (standard deviation 9.1). There was no significant difference in tendon retraction between the groups. Both groups demonstrated significant improvement in ROM, visual analog scale, American Shoulder and Elbow Surgeons, Single Alpha-Numeric Evaluation, and Constant score postoperatively at 6 months and minimum 1 year. The groups demonstrated no significant difference in the ROM and clinical scores. There was a nonsignificant difference in re-tear rate of 7.4% (2/27) in Fosbury flop tears compared with 2.8% (6/209) in tendon avulsions (P = .361). Conclusions: Arthroscopic rotator cuff repair of medial bursal side Fosbury Flop rotator cuff tears results in favorable clinical and radiologic outcomes at 4 years after surgery. These outcomes are comparable with surgically repaired avulsion lesions, with an acceptable retear rate after arthroscopic repair. Level of Evidence: Level III, retrospective comparative prognostic trial.

Enhancement of ester biosynthesis in blueberry wines through co-fermentation via cell-cell contact between Torulaspora delbrueckii and Saccharomyces cerevisiae.

This study investigated the effects of co-fermentation of T. delbrueckii and S. cerevisiae on the volatile composition and sensory characteristics of blueberry wines. Mixed fermentation led to higher levels of terpenes, higher alcohols, and esters compared to wines fermented with each yeast individually. Conversely, when T. delbrueckii were physically separated from S. cerevisiae in the double-compartment fermenter, contrasting outcomes emerged. The stronger fruity aroma induced by mixed fermentation were linked to higher ester concentrations, including isoamyl acetate, ethyl isovalerate, ethyl hexanoate, and diethyl succinate. The enhanced esters in mixed fermentation can be attributed to the upregulated alcohol acyltransferase activity and the expressions of ACC1, FAS2, ELO1 and ATF1 genes in late fermentation stage via the cell-cell contact between T. delbrueckii and S. cerevisiae. These findings can deepen the understanding of the interaction between non-Saccharomyces and S. cerevisiae in ester production, assisting wineries in effectively controlling wine aroma through mixed fermentations.

[Clinical Features and Prognosis of Acute T-cell Lymphoblastic Leukemia in Children--Multi-Center Data Analysis in Fujian].

OBJECTIVE: To evaluate the efficacy of acute T-cell lymphoblastic leukemia (T-ALL) in children and explore the prognostic risk factors. METHODS: The clinical data of 127 newly diagnosed children with T-ALL admitted to five hospitals in Fujian province from April 2011 to December 2020 were retrospectively analyzed, and compared with children with newly diagnosed acute precursor B-cell lymphoblastic leukemia (B-ALL) in the same period. Kaplan-Meier analysis was used to evaluate the overall survival (OS) and event-free survival (EFS), and COX proportional hazard regression model was used to evaluate the prognostic factors. Among 116 children with T-ALL who received standard treatment, 78 cases received the Chinese Childhood Leukemia Collaborative Group (CCLG)-ALL 2008 protocol (CCLG-ALL 2008 group), and 38 cases received the China Childhood Cancer Collaborative Group (CCCG)-ALL 2015 protocol (CCCG-ALL 2015 group). The efficacy and serious adverse event (SAE) incidence of the two groups were compared. RESULTS: Proportion of male, age≥10 years old, white blood cell count (WBC)≥50×109/L, central nervous system leukemia, minimal residual disease (MRD)≥1% during induction therapy, and MRD≥0.01% at the end of induction in T-ALL children were significantly higher than those in B-ALL children (P <0.05). The expected 10-year EFS and OS of T-ALL were 59.7% and 66.0%, respectively, which were significantly lower than those of B-ALL (P <0.001). COX analysis showed that WBC≥100×109/L at initial diagnosis and failure to achieve complete remission (CR) after induction were independent risk factors for poor prognosis. Compared with CCLG-ALL 2008 group, CCCG-ALL 2015 group had lower incidence of infection-related SAE (15.8% vs 34.6%, P =0.042), but higher EFS and OS (73.9% vs 57.2%, P EFS=0.090; 86.5% vs 62.3%, P OS=0.023). CONCLUSIONS: The prognosis of children with T-ALL is worse than children with B-ALL. WBC≥100×109 /L at initial diagnosis and non-CR after induction (especially mediastinal mass has not disappeared) are the risk factors for poor prognosis. CCCG-ALL 2015 regimen may reduce infection-related SAE and improve efficacy.

Pelvic floor muscle strength and influencing factors based on vaginal manometry among healthy women at different life stages: A multicentre cross-sectional study.

OBJECTIVE: To assess pelvic floor muscle (PFM) strength and influencing factors among healthy women at different life stages. DESIGN: Multicentre cross-sectional study. SETTING: Fourteen hospitals in China. POPULATION: A total of 5040 healthy women allocated to the following groups (with 1680 women per group): premenopausal nulliparous, premenopausal parous and postmenopausal. METHODS: The PFM strength was evaluated by vaginal manometry. Multivariate logistic regression was used to determine the influencing factors for low PFM strength. MAIN OUTCOME MEASURES: Maximum voluntary contraction pressure (MVCP). RESULTS: The median MVCP values were 36, 35 and 35 cmH2O in premenopausal nulliparous (aged 19-51 years), premenopausal parous (aged 22-61 years), and postmenopausal (aged 40-86 years) women, respectively. In the premenopausal nulliparous group, physical work (odds ratio, OR 2.05) was the risk factor for low PFM strength, which may be related to the chronic increased abdominal pressure caused by physical work. In the premenopausal parous group, the number of vaginal deliveries (OR 1.28) and diabetes (OR 2.70) were risk factors for low PFM strength, whereas sexual intercourse (<2 times per week vs. none, OR 0.55; ≥2 times per week vs. none, OR 0.56) and PFM exercise (OR 0.50) may have protective effects. In the postmenopausal group, the number of vaginal deliveries (OR 1.32) and family history of pelvic organ prolapse (POP) (OR 1.83) were risk factors for low PFM strength. CONCLUSIONS: Physical work, vaginal delivery, diabetes and a family history of POP are all risk factors for low PFM strength, whereas PFM exercises and sexual life can have a protective effect. The importance of these factors varies at different stages of a woman's life.

Ticagrelor alleviates pyroptosis of myocardial ischemia reperfusion-induced acute lung injury in rats: a preliminary study.

Pulmonary infection is highly prevalent in patients with acute myocardial infarction undergoing percutaneous coronary intervention. However, the potential mechanism is not well characterized. Myocardial ischemia-reperfusion injury (MIRI) induces acute lung injury (ALI) related to pulmonary infection and inflammation. Recent studies have shown that pyroptosis mediates ALI in several human respiratory diseases. It is not known whether MIRI induces pyroptosis in the lungs. Furthermore, ticagrelor is a clinically approved anti-platelet drug that reduces ALI and inhibits the expression levels of several pyroptosis-associated proteins, but the effects of ticagrelor on MIRI-induced ALI have not been reported. Therefore, we investigated whether ticagrelor alleviated ALI in the rat MIRI model, and its effects on pyroptosis in the lungs. Sprague-Dawley rats were randomly divided into four groups: control, MIRI, MIRI plus low ticagrelor (30 mg/kg), and MIRI plus high ticagrelor (100 mg/kg). Hematoxylin and Eosin (HE) staining was performed on the lung sections, and the HE scores were calculated to determine the extent of lung pathology. The wet-to-dry ratio of the lung tissues were also determined. The expression levels of pyroptosis-related proteins such as NLRP3, ASC, and Cleaved caspase-1 were estimated in the lung tissues using the western blot. ELISA was used to estimate the IL-1ß levels in the lungs. Immunohistochemistry was performed to determine the levels of MPO-positive neutrophils as well as the total NLRP3-positive and Cleaved caspase-1-positive areas in the lung tissues. The lung tissues from the MIRI group rats showed significantly higher HE score, wet-to-dry ratio, and the MPO-positive area compared to the control group, but these effects were attenuated by pre-treatment with ticagrelor. Furthermore, lung tissues of the MIRI group rats showed significantly higher expression levels of pyroptosis-associated proteins, including NLRP3 (2.1-fold, P < 0.05), ASC (3.0-fold, P < 0.01), and Cleaved caspase-1 (9.0-fold, P < 0.01). Pre-treatment with the high-dose of ticagrelor suppressed MIRI-induced upregulation of NLRP3 (0.46-fold, P < 0.05), ASC (0.64-fold, P < 0.01), and Cleaved caspase-1 (0.80-fold, P < 0.01). Immunohistochemistry results also confirmed that pre-treatment with ticagrelor suppressed MIRI-induced upregulation of pyroptosis in the lungs. In summary, our data demonstrated that MIRI induced ALI and upregulated pyroptosis in the rat lung tissues. Pre-treatment with ticagrelor attenuated these effects.