Objective:To develop and validate a nomogram prediction model for major adverse cardiovascular events (MACE) in elderly patients with chronic heart failure (CHF) based on the ratio of homocysteine to free triiodothyronine (HCY/FT3).Methods:This research was a prognostic study. A total of 1 301 elderly patients with CHF admitted to the Department of General Practice of Shanghai Fifth People′s Hospital Affiliated to Fudan University from January 2018 to January 2023 were enrolled and divided into MACE group ( n=564) and non-MACE group ( n=737) according to whether MACE occurred at the end of the follow-up. Baseline clinical data was collected. The follow-up period was 18 months, with the follow-up deadline being June 30, 2024. The primary endpoint was the occurrence of MACE, including death from any cause or re-hospitalization due to heart failure. Multivariate logistic regression analysis was used to determine the independent risk factors for MACE of elderly patients with CHF ( P<0.05). All patients included were randomly allocated into a training cohort ( n=913) and a validation cohort ( n=388) in a 7∶3 ratio. A nomogram prediction model was developed. The model was internally validated by bootstrapping. The discriminative ability of the model was assessed by calibration curves and receiver operating characteristic (ROC) curves. Results:Multivariable logistic regression analysis demonstrated that atrial fibrillation history, lower diastolic blood pressure, elevated uric acid, elevated free thyroxine (FT4), higher HCY/FT3 ratio, and lower left ventricular ejection fraction (LVEF) were independent predictors of MACE in elderly CHF patients ( P<0.05). A nomogram model incorporating these factors was developed. Internal validation using bootstrapping showed good calibration, as both training and validation cohort calibration curves closely approximated the ideal line. ROC curve analysis indicated an area under the curve of 0.721 (95% CI: 0.661-0.782) for the nomogram in predicting MACE. Conclusions:We developed and internally validated a nomogram incorporating the HCY/FT3 ratio to predict MACE risk in elderly CHF patients. This model demonstrated acceptable discrimination and good calibration, suggesting potential clinical utility for risk stratification.

OBJECTIVE: To analyze the current status and temporal trends of the disease burden of spinal fractures in China from 1990 to 2021 based on data from the Global Burden of Disease Study 2021 (GBD 2021), aiming to provide evidence for developing prevention and treatment strategies. METHODS: Epidemiological data on spinal fractures in China, the United States of America (USA), and globally were extracted from the GBD 2021 database. Joinpoint regression models were applied to analyze temporal trends. Age-standardized incidence, prevalence, and disability-adjusted life years (DALYs) rates were calculated, with comparisons of gender- and age-group disparities. RESULTS: In 2021, the number of incident cases, prevalent cases, and DALYs of spinal fractures in China increased by 52.28%, 113.68%, and 106.98%, respectively, compared to 1990. The age-standardized incidence, prevalence, and DALYs rates rose by 11.80%, 16.11%, and 14.79%, respectively. The disease burden escalated significantly with age, peaking in individuals aged ≥75 years. Males exhibited higher age-standardized incidence and DALYs rates than females. Comparative analysis revealed that the age-standardized DALYs rate in China (4.19/100 000) was lower than that in globally (6.62/100 000) and USA (15.92/100 000). However, China showed an upward trend [annual average percentage change (AAPC)=0.19%], contrasting with a declining trend in the USA (AAPC=-0.08%). CONCLUSION The escalating disease burden of spinal fractures in China is closely linked to population aging, gender disparities, and insufficient targeted prevention policies. Future strategies should integrate age- and gender-specific interventions, including strengthened osteoporosis prevention, trauma risk control, and big data-driven precision measures, to mitigate this burden.
Humans ; China/epidemiology* ; Global Burden of Disease/trends* ; Male ; Female ; Spinal Fractures/epidemiology* ; Middle Aged ; Aged ; Disability-Adjusted Life Years ; Prevalence ; Incidence ; Adult ; Young Adult ; Adolescent ; Aged, 80 and over ; United States/epidemiology* ; Cost of Illness ; Quality-Adjusted Life Years ; Child

Objective To explore the causal association between immune cells and allergic rhi-nitis using Mendelian randomization(MR)approach.Methods GWAS data for 731 types of im-mune cells and allergic rhinitis were obtained from genome-wide association study(GWAS)databas-es.A two-sample bidirectional MR analysis was conducted,with the inverse-variance weighted(IVW)method as the primary analytical approach,and the weighted median method,MR-Egger re-gression,simple mode method,and weighted mode method as supplementary approaches.Sensitivity analyses,including heterogeneity tests,pleiotropy tests,and the leave-one-out method,were per-formed.Bonferroni correction was applied to the preliminary results to enhance their reliability and rigor.Results The two-sample forward MR analysis revealed correlations between 67 immune cell phenotypes and allergic rhinitis.After Bonferroni correction,four immune cell phenotypes were finally identified.Among them,the expression of CD3 on CD39-positive activated CD4 regulatory T cells(OR=0.953,95％CI,0.931 to 0.978,P＜0.001,Padj=0.007),the expression of herpesvirus entry mediator(HVEM)on CD45RA-negative CD4+T cells(OR=0.965,95％CI,0.948 to 0.983,P＜0.001,Padj=0.008),and the percentage of human leukocyte antigen class DR(HLA-DR)-high-expressing monocytes among leukocytes(OR=0.929,95％CI,0.885 to 0.974,P=0.002,Padj=0.157)were protective factors for allergic rhinitis.In contrast,the percentage of transitional B cells among B cells(OR=1.094,95％CI,1.032 to 1.161,P=0.003,Padj=0.183)was a risk factor for allergic rhinitis.The reverse MR analysis showed no causal relationship between allergic rhinitis and the four immune cell phenotypes.Conclusion The two-sample forward MR analysis confirms a caus-al link between immune cells and allergic rhinitis.MR analysis has the advantages of reducing con-founding factor interference and avoiding reverse causation,providing a theoretical basis for in-depth research on immune mechanisms,sensitive biomarkers,and drug treatment targets of allergic rhinitis.

Objective:To develop and validate a nomogram prediction model for major adverse cardiovascular events (MACE) in elderly patients with chronic heart failure (CHF) based on the ratio of homocysteine to free triiodothyronine (HCY/FT3).Methods:This research was a prognostic study. A total of 1 301 elderly patients with CHF admitted to the Department of General Practice of Shanghai Fifth People′s Hospital Affiliated to Fudan University from January 2018 to January 2023 were enrolled and divided into MACE group ( n=564) and non-MACE group ( n=737) according to whether MACE occurred at the end of the follow-up. Baseline clinical data was collected. The follow-up period was 18 months, with the follow-up deadline being June 30, 2024. The primary endpoint was the occurrence of MACE, including death from any cause or re-hospitalization due to heart failure. Multivariate logistic regression analysis was used to determine the independent risk factors for MACE of elderly patients with CHF ( P<0.05). All patients included were randomly allocated into a training cohort ( n=913) and a validation cohort ( n=388) in a 7∶3 ratio. A nomogram prediction model was developed. The model was internally validated by bootstrapping. The discriminative ability of the model was assessed by calibration curves and receiver operating characteristic (ROC) curves. Results:Multivariable logistic regression analysis demonstrated that atrial fibrillation history, lower diastolic blood pressure, elevated uric acid, elevated free thyroxine (FT4), higher HCY/FT3 ratio, and lower left ventricular ejection fraction (LVEF) were independent predictors of MACE in elderly CHF patients ( P<0.05). A nomogram model incorporating these factors was developed. Internal validation using bootstrapping showed good calibration, as both training and validation cohort calibration curves closely approximated the ideal line. ROC curve analysis indicated an area under the curve of 0.721 (95% CI: 0.661-0.782) for the nomogram in predicting MACE. Conclusions:We developed and internally validated a nomogram incorporating the HCY/FT3 ratio to predict MACE risk in elderly CHF patients. This model demonstrated acceptable discrimination and good calibration, suggesting potential clinical utility for risk stratification.

Abstract: Mosquitoes and mosquito-borne illnesses remain one of the major public threats which is intensified by the emergence and resurgence of new and existing vector species. Mosquito control is often the only sustainable measure to combat mosquito-borne diseases due to lack or limitation in vaccinations and/or effective medications. Among mosquito control interventions, larviciding to target aquatic habitats is more cost-effective and feasible as opposite to adulticiding which focuses on air-borne adult stages. The available mosquito larvicides are at a historical low owing to numerous reasons. Currently, available larvicides are based on microbial agents, insect growth regulators (IGRs), and a few others of botanical origins. In the IGR arena, juvenile hormone mimics have drawn a lot of attention in research, development, and application. Pyriproxyfen (PPF) was first developed in the early 1970s by Sumitomo Chemical Co. Ltd. (SCC). Its great potential and safety profile to control a wide variety of arthropod pests have been recognized ever since. The current review provides general information and highlights the following advantages of PPF: unique mode of action to mimic the action of natural juvenile hormone (JH) in mosquitoes, broad target spectrum against many mosquito species, the highest bioactivity against mosquitoes as compared with all other known or potential mosquito larvicides, low risk in resistance development and lack of cross-resistance with other larvicides studied, and high activity against species in Stegomyia group. Recently, more potential uses of PPF against adult mosquitoes in bait, barrier treatment, and bed net treatment have been on the horizon. Environmental concerns about PPF residues and their metabolites are also discussed. In general, PPF is one of the critical tools in combating mosquito species of public health importance for now and the foreseeable future.

An essential treatment for atlantoaxial dislocation is posterior atlantoaxial fusion. The current intra-articular fusion of the atlantoaxial lateral mass joint demonstrates a higher bone fusion rate, requires a smaller amount of bone graft, and has a lower incidence of complications. Although it has been employed in clinical practice, the atlantoaxial lateral mass intra-articular fusion cage is not yet widely utilized. Atlantoaxial instability and reducible atlantoaxial dislocation can be managed with simple posterior reduction, fixation, and atlantoaxial lateral mass intra-articular fusion. For patients with irreducible atlantoaxial dislocation, such as those with severe basilar invagination or obstructive anterior bone structures, transoral release is necessary, and anterior fusion cage placement is also feasible. Both posterior and anterior atlantoaxial lateral mass intra-articular fusion have seen significant improvements in surgical techniques, bone graft materials, and fusion cages. Among them, the procedure is evolving from the classic open approach to a more minimally invasive one. Bone graft materials include massive iliac bone, granular cancellous bone, fibula, autologous bone harvested from the C 1 posterior arch and C 2 lamina, and allogeneic bone, reflecting an increasingly diverse selection. Fusion cages have evolved from simple spacers to titanium blocks and further to cages that are anatomically adapted to the atlantoaxial joint, offering high bone fusion rates and various specifications of width and height. In anterior fusion cages, the circular design facilitates easy placement, while the wedge-shaped cage, when inserted transorally, better conforms to the physiological structure of the atlantoaxial lateral mass joint, resulting in improved surgical outcomes.The 3D-printed locking cage provides robust anterior support for fixation and fusion without the need for additional bone grafting. Anterior fusion cages are particularly suitable for patients with partial irreducible atlantoaxial dislocation requiring transoral release. Posterior cages, such as the cylindrical threaded cage, offer immediate stability. Customized cages exhibit more uniform stress distribution and can reduce cage subsidence. The posterior fusion cage has broad applicability and is suitable for patients with basilar invagination and atlantoaxial dislocation. The continuous advancements of fusion cages, bone graft materials, and surgical techniques will be from the aspects of stability, safety, and fusion rate to optimize the atlantoaxial lateral mass intra-articular fusion.

Objective To investigate the causal association between bronchial asthma and bone mineral density at different sites using a two-sample Mendelian randomization (MR) approach. Methods Summary data for exposure factors and outcome were obtained from different genome-wide association studies.Single nucleotide polymorphisms strongly associated with bronchial asthma were selected as instrumental variables,and those in linkage disequilibrium were excluded.The inverse-variance weighted (IVW) method was used as the primary method for MR analysis,complemented by weighted median,simple mode,weighted mode,and MR-Egger regression methods.Sensitivity analyses were conducted to assess the stability of the results. Results The random-effects model of IVW analysis showed that heel bone mineral density (OR=0.986;95% CI,0.974 to 0.998;P=0.023) as the outcome dataset had a reverse causal effect with bronchial asthma,while lumbar spine bone mineral density (OR=1.031;95% CI,0.984 to 1.081;P=0.195),femoral neck bone mineral density (OR=1.014;95% CI,0.973 to 1.057;P=0.505),and forearm bone mineral density (OR=1.011;95% CI,0.935 to 1.094;P=0.775) as outcome datasets showed no causal effect with bronchial asthma.The MR-Egger intercept test results indicated that the P-values for the intercepts of lumbar bone mineral density,femoral neck bone mineral density,forearm bone mineral density,and calcaneal bone mineral density were all over 0.05,suggesting no horizontal pleiotropy and relatively stable results. Conclusion MR analysis reveals a reverse causal effect between bronchial asthma and heel bone mineral density,suggesting that clinicians should strengthen the monitoring of heel bone mineral density in patients with bronchial asthma to timely detect and intervene osteoporosis.

An essential treatment for atlantoaxial dislocation is posterior atlantoaxial fusion. The current intra-articular fusion of the atlantoaxial lateral mass joint demonstrates a higher bone fusion rate, requires a smaller amount of bone graft, and has a lower incidence of complications. Although it has been employed in clinical practice, the atlantoaxial lateral mass intra-articular fusion cage is not yet widely utilized. Atlantoaxial instability and reducible atlantoaxial dislocation can be managed with simple posterior reduction, fixation, and atlantoaxial lateral mass intra-articular fusion. For patients with irreducible atlantoaxial dislocation, such as those with severe basilar invagination or obstructive anterior bone structures, transoral release is necessary, and anterior fusion cage placement is also feasible. Both posterior and anterior atlantoaxial lateral mass intra-articular fusion have seen significant improvements in surgical techniques, bone graft materials, and fusion cages. Among them, the procedure is evolving from the classic open approach to a more minimally invasive one. Bone graft materials include massive iliac bone, granular cancellous bone, fibula, autologous bone harvested from the C 1 posterior arch and C 2 lamina, and allogeneic bone, reflecting an increasingly diverse selection. Fusion cages have evolved from simple spacers to titanium blocks and further to cages that are anatomically adapted to the atlantoaxial joint, offering high bone fusion rates and various specifications of width and height. In anterior fusion cages, the circular design facilitates easy placement, while the wedge-shaped cage, when inserted transorally, better conforms to the physiological structure of the atlantoaxial lateral mass joint, resulting in improved surgical outcomes.The 3D-printed locking cage provides robust anterior support for fixation and fusion without the need for additional bone grafting. Anterior fusion cages are particularly suitable for patients with partial irreducible atlantoaxial dislocation requiring transoral release. Posterior cages, such as the cylindrical threaded cage, offer immediate stability. Customized cages exhibit more uniform stress distribution and can reduce cage subsidence. The posterior fusion cage has broad applicability and is suitable for patients with basilar invagination and atlantoaxial dislocation. The continuous advancements of fusion cages, bone graft materials, and surgical techniques will be from the aspects of stability, safety, and fusion rate to optimize the atlantoaxial lateral mass intra-articular fusion.

Using chemoproteomic techniques, we first identified EIF2AK2, eEF1A1, PRDX3 and VPS4B as direct targets of berberine (BBR) for its synergistically anti-inflammatory effects. Of them, BBR has the strongest affinity with EIF2AK2 via two ionic bonds, and regulates several key inflammatory pathways through EIF2AK2, indicating the dominant role of EIF2AK2. Also, BBR could subtly inhibit the dimerization of EIF2AK2, rather than its enzyme activity, to selectively modulate its downstream pathways including JNK, NF-κB, AKT and NLRP3, with an advantage of good safety profile. In EIF2AK2 gene knockdown mice, the inhibitory IL-1β, IL-6, IL-18 and TNF-α secretion of BBR was obviously attenuated, confirming an EIF2AK2-dependent anti-inflammatory efficacy. The results highlight the BBR's network mechanism on anti-inflammatory effects in which EIF2AK2 is a key target, and inhibition of EIF2AK2 dimerization has a potential to be a therapeutic strategy against inflammation-related disorders.

A series of new monobactam sulfonates is continuously synthesized and evaluated for their antimicrobial efficacies against Gram-negative bacteria. Compound 33a (IMBZ18G) is highly effective in vitro and in vivo against clinically intractable multi-drug-resistant (MDR) Gram-negative strains, with a highly druglike nature. The checkerboard assay reveals its significant synergistic effect with β-lactamase inhibitor avibactam, and the MIC values against MDR enterobacteria were reduced up to 4-512 folds. X-ray co-crystal and chemoproteomic assays indicate that the anti-MDR bacteria effect of 33a results from the dual inhibition of the common PBP3 and some class A and C β-lactamases. Accordingly, preclinical studies of 33a alone and 33a‒avibactam combination as potential innovative candidates are actively going on, in the treatment of β-lactamase-producing MDR Gram-negative bacterial infections.