BACKGROUND:Several observational studies have found a close relationship between thyroid function levels and sarcopenia,but the causal relationship between thyroid function levels and the onset of sarcopenia is not yet clear. OBJECTIVE:To investigate the causal relationship between thyroid function levels and sarcopenia using a two sample Mendelian randomization method. METHODS:A two sample Mendelian randomization analysis was conducted using genome-wide association study data on thyrotropin,free triiodothyronine,free tetraiodothyronine,subclinical hyperthyroidism,subclinical hypothyroidism,and four related phenotypes of sarcopenia-lefthand grip strength,right hand grip strength,limb lean mass,and gait speed.The inverse-variance weighted method,weighted median method,simple mode method,weighted median estimator method,and MR Egger regression method were used as analysis methods,while heterogeneity test,pleiotropy test,MR-PRESSO,leave-one-out method,funnel plot and other methods were used for sensitivity analysis. RESULTS AND CONCLUSION:Elevated levels of thyroid-stimulating hormone increased left-(β=0.02,SE=0.01,P=0.01)and right-handed grip strength(β=0.02,SE=0.01,P=0.01),an increase in free triiodothyronine decreased left-(β=-0.06,SE=0.02,P=9.5×10-5)and right-handed grip strength(β=-0.07,SE=0.02,P=9.3×10-5),and subclinical hyperthyroidism decreased gait speed(β=-4.4×10-3,SE=1.7×10-3,P=0.01).The sensitivity analysis results were basically consistent with the main analysis results.To conclude,an increase in thyroid-stimulating hormone is a protective factor for sarcopenia,and elevation of free triiodothyronine and subclinical hyperthyroidism may increase the risk of sarcopenia.

Objective:To prepare heparin (Hep)-modified gelatin methacryloyl (GelMA) microspheres and to investigate their application in liver-targeted delivery of adipose-derived mesenchymal stem cells (ADSCs).Methods:GelMA microspheres were modified with Hep to obtain GelMA-Hep microspheres. The surface morphology of the GelMA-Hep microspheres was observed by scanning electron microscopy. The changes of carbon atoms, nitrogen atoms and sulfur atoms on the surface of the GelMA-Hep microspheres were detected by X-ray photoelectron spectroscopy. The surface chemical group composition of the GelMA-Hep microspheres was analyzed by Fourier transform infrared spectrometer. The swelling properties of the GelMA-Hep microspheres were detected by water absorption swelling experiment. Human liver HL-7702 cells transfected with lentivirus were co-cultured with GelMA, GelMA-dopamine (GelMA-dop) and GelMA-Hep microspheres. The effects of microspheres on cell proliferation activity were evaluated by cell counting kit-8 method and live/dead cell staining experiment. The adhesion of microspheres to cells was observed by confocal microscopy. The GelMA-Hep microspheres loaded with ADSCs were injected into C57BL/6 mice through the tail vein, and its efficiency of liver-targeted delivery of ADSCs was observed by a small animal in vivo imaging system. The data were compared by independent sample t test or one-way analysis of variance. Results:The GelMA-Hep microspheres were prepared by modifying the GelMA microspheres with Hep. Compared with the GelMA microspheres, the size of the GelMA-Hep microspheres did not change significantly, and the surface did not collapse and showed some crystalline particles. The binding energy of sulfur atoms on the surface of the GelMA-Hep microspheres increased from 166 eV to 168 eV. On the surface of the GelMA-Hep microspheres, the characteristic peaks of sulfonic acid and sulfate groups of Hep were detected at 1 490 cm ?1 and from 1 135 cm ?1 to 1 050 cm ?1, respectively. The swelling rate of the GelMA-dop microspheres was uniform, while the swelling rate of the GelMA microspheres and the GelMA-Hep microsphere was quite different, but the final swelling mass of the three microspheres tended to be consistent at 5 min. After 12, 24, 36 and 48 h of culture, the relative proliferation of cells in the GelMA-Hep group (1.61±0.29, 1.78±0.05, 2.27±0.08, 2.26±0.33) were higher than those in the negative control group (1.00±0.00, 1.28±0.06, 1.39±0.02, 1.41±0.04) (all P<0.05). After 36 h of culture, the relative proliferation of cells in the GelMA-Hep group was higher than that in the GelMA-dop group (1.63±0.21), with significant difference ( P<0.05). Live/dead cell staining experiment showed that after 12 h of cell culture in the GelMA-Hep group, only a few microspheres had cell adhesion; at 24 h, the cells were densely distributed on the surface of the microspheres. After 36 h, the number of cells increased further. At 48 h, live cells were distributed throughout the microspheres. Confocal microscopy showed that after 24 h of culture, cells adhered to the surface of the microspheres in the GelMA-Hep group and showed a stretched morphology. The liver of the GelMA-Hep+ADSCs group showed strong fluorescence at 0.5 h, and the fluorescence brightness continued to 48.0 h. The number of ADSCs reaching the liver was more than that of ADSCs group and GelMA+ADSCs group. Conclusions:GelMA-Hep microspheres were successfully prepared, which can improve the efficiency of liver-targeted delivery of ADSCs.

Left atrial appendage closure(LAAC)is an important intervention method for preventing thromboembolic events in patients with non-valvular atrial fibrillation(NVAF).However,incomplete endothelialization following the procedure can impact its long-term efficacy and safety.This article proposes the view of qi flourishment promoting tissue regeneration based on the traditional Chinese medicine(TCM)theory of qi and blood,and explores diagnostic and therapeutic strategies for post-LAAC incomplete endothelialization by examining the theoretical connotation of qi flourishment promoting tissue regeneration and the relationship between qi and vascular endothelial cells.It is proposed that the primary pathogenesis in patients after LAAC is due to qi deficiency.Guided by the view of qi flourishment promoting tissue regeneration,therapeutic approaches such as tonifying qi to promote granulation,supplementing qi to activate blood circulation,and harmonizing the viscera can be employed to address incomplete endothelialization in NVAF patients following LAAC.Clinically,the qi-supplementing and blood-activating classic formula Neituo Shengji San,mainly composed of Astragali Radix,Glycyrrhizae Radix et Rhizoma,Olibanum,Myrrha,Paeoniae Radix Alb,Trichosanthis Radix,Salviae Miltiorrhizae Radix et Rhizoma,etc.,is usually utilized for modified use.Depending on the specific symptom patterns or pathogenesis characteristics of patients with incomplete endothelialization,this basic formula may be used by combining with Shengmai San or augmented with qi-supplementing and blood-activating herbs such as Chuanxiong Rhizoma,Fici Simplicissimae Radix,and Notoginseng Radix et Rhizoma to promote endothelialization.Diagnosing and treating post-LAAC incomplete endothelialization in NVAF patients following the view of qi flourishment promoting tissue regeneration,it is expected to offer a novel TCM perspective and therapeutic strategy to enhance post-LAAC outcomes and address the challenge of incomplete endothelialization.This approach can further serve as a reference for TCM clinicians to manage endothelialization issues following implantation procedures.

Sonodynamic therapy (SDT) can potentially induce immunogenic cell death in tumor cells, leading to the release of ATP, and facilitating the initiation of an immune response. Nevertheless, the enzymes CD39 and CD73 can swiftly convert ATP into immunosuppressive adenosine (ADO), resulting in an immunosuppressive tumor microenvironment (TME). This study introduced a nanomedicine (QD/POM1@NP@M) engineered to reprogram TME by modulating the CD39/CD73/ADO pathway. The nanomedicine encapsulated sonosensitizers silver sulfide quantum dots, and the CD39 inhibitor POM1, while also incorporating homologous tumor cell membranes to enhance targeting capabilities. This integrated approach, on the one hand, stimulates the release of ATP via SDT, thereby initiating the immune response. In addition, it reduced the accumulation of ADO by inhibiting CD39 activity, which ameliorated the immunosuppressive TME. Upon administration, the nanomedicine demonstrated substantial anti-tumor efficacy by facilitating the infiltration of anti-tumor immune cells, while reducing the immunosuppressive cells. This modulation effectively transformed the TME from an immunologically "cold" state to a "hot" state. Furthermore, combined with the checkpoint inhibitor α-PDL1, the nanomedicine augmented systemic anti-tumor immunity and promoted the establishment of long-term immune memory. This study provides an innovative strategy for combining non-invasive SDT and ATP-driven immunotherapy, offering new ideas for future cancer treatment.

Cardiac fibrosis is characterized by an elevated amount of extracellular matrix (ECM) within the heart. However, the persistence of cardiac fibrosis ultimately diminishes contractility and precipitates cardiac dysfunction. Circular RNAs (circRNAs) are emerging as important regulators of cardiac fibrosis. Here, we elucidate the functional role of a specific circular RNA CELF1 in cardiac fibrosis and delineate a novel feedback loop mechanism. Functionally, circ-CELF1 was involved in enhancing fibrosis-related markers' expression and promoting the proliferation of cardiac fibroblasts (CFs), thereby exacerbating cardiac fibrosis. Mechanistically, circ-CELF1 reduced the ubiquitination-degradation rate of BRPF3, leading to an elevation of BRPF3 protein levels. Additionally, BRPF3 acted as a modular scaffold for the recruitment of histone acetyltransferase KAT7 to facilitate the induction of H3K14 acetylation within the promoters of the Celf1 gene. Thus, the transcription of Celf1 was dramatically activated, thereby inhibiting the subsequent response of their downstream target gene Smad7 expression to promote cardiac fibrosis. Moreover, Celf1 further promoted Celf1 pre-mRNA transcription and back-splicing, thereby establishing a feedback loop for circ-CELF1 production. Consequently, a novel feedback loop involving CELF1/circ-CELF1/BRPF3/KAT7 was established, suggesting that circ-CELF1 may serve as a potential novel therapeutic target for cardiac fibrosis.

Local anesthetics (LAs), such as articaine (AT), exhibit limited efficacy in inflammatory environments, which constitutes a significant limitation in their clinical application within oral medicine. In our prior research, we developed AT-17, which demonstrated effective properties in chronic inflammatory conditions and appears to function as a novel oral LA that could address this challenge. In the present study, we further elucidated the beneficial effects of AT-17 in acute inflammation, particularly in oral acute inflammation, where mitochondrial-related apoptosis played a crucial role. Our findings indicated that AT-17 effectively inhibited lipopolysaccharide (LPS)-induced nerve cell apoptosis by ameliorating mitochondrial dysfunction in vitro. This process involved the inhibition of mitochondrial reactive oxygen species (mtROS) production and the subsequent activation of the NRF2 pathway. Most notably, improvements in mitochondria-related apoptosis were key contributors to AT-17's inhibition of voltage-gated sodium channels. Additionally, AT-17 was shown to reduce mtROS production in nerve cells through the Na⁺/NCLX/ETC signaling axis. In conclusion, we have developed a novel local anesthetic that exhibits pronounced anesthetic functionality under inflammatory conditions by enhancing mitochondria-related apoptosis. This advancement holds considerable promise for future drug development and deepening our understanding of the underlying mechanisms of action.

Objective:To examine the distribution of pathogens that cause postoperative nosocomial infections in patients with rectal cancer(RC)and to construct a predictive nomogram for nosocomial infection.Methods:The clinical data of 1537 RC patients admitted to Sir Run Run Shaw Hospital between January 2021 and December 2022 were collected.Patients were assigned 1∶1 by propensity score matching(PSM)to the infection group(n=83)and control group(n=83)based on the occurrence of nosocomial infection.The dis-tribution and drug resistance of bacteria in patients with nosocomial infection were analyzed.Risk factors for postoperative nosocomial infection were identified by least absolute shrinkage and selection operator(LASSO)regression,and a predictive nomogram was con-structed using multivariate logistics regression.The predictive performance of the model was evaluated by receiver operating character-istic(ROC)curve,calibration curve,and decision curve analysis(DCA).Results:A total of 93 strains of pathogens were isolated from the 83 infected patients,including 62 strains of Gram-negative bacteria(66.67%;predominantly Escherichia coli and Pseudomonas ae-ruginosa),25 strains of Gram-positive bacteria(26.88%;mainly Enterococcus faecalis),and 6 strains of fungi(6.45%;all Candida albicans).LASSO and multivariate logistics regression showed that smoking(odds ratio[OR]=3.97,95%CI=1.27-12.43),the dwelling time of drainage tube(OR=1.19,95%CI=1.08-1.30),difference in preoperative and postoperative neutrophil counts(OR=1.23,95%CI=1.01-1.49),and difference between preoperative and postoperative C-reactive protein levels(OR=1.05,95%CI=1.03-1.07)were inde-pendent risk factors for postoperative nosocomial infection in RC patients.The area under the ROC curve of the nomogram constructed based on the above factors was 0.933(95%CI=0.896-0.969).The calibration curve showed that the predicted risk was in good agree-ment with the actual observed risk of infection.In addition,DCA demonstrated that the nomogram has good clinical utility and high net clinical benefits in predicting nosocomial infection.Conclusion:The nomogram constructed in this study has a good predictive perfor-mance in postoperative nosocomial infection in RC patients.

Objective:To understand the epidemiological characteristics and spatiotemporal distribution of viral encephalitis in children and adolescents in Henan Province from 2012 to 2023.Methods:The information about viral encephalitis cases from October 1, 2012 to July 26, 2023 were collected from Zhengzhou Children's Hospital (National Children's Regional Medical Center),Henan Provincial Children's Hospital for the analyses on temporal distribution the cases, the severe illness rate, age distribution, pathogen type and imaging findings of the cases.Results:A total of 6 276 cases of viral encephalitis were included in this study after excluding cases with incomplete information. The cases mainly originated from Zhengzhou (38.96%), followed by Zhoukou (9.93%), Xuchang (8.68%), Zhumadian (7.90%) and Pingdingshan (7.39%). The cases in boys accounted for 62.13% and the cases in girls accounted for 37.87%. Most cases (72.45%) occurred in age group 7-13 years. The overall rate of severe illness cases was 4.51% from 2012 to 2023. There were significant differences in severe illness cases among different areas and years ( χ2=5.33, P=0.021; χ2=48.14, P<0.001). Enteroviruses were mainly detected (31.57%), in which Coxsackie virus was predominant (58.37%). Imaging findings showed that cerebral hemisphere damage was most common in children and adolescents with viral encephalitis (54.93%). Conclusions:From 2012 to 2023, more cases of viral encephalitis occurred in boys in Henan. Children and adolescents aged 7-13 years were the main affected group. The prevention of enteroviruses infection, especially Coxsackie virus, needs to be strengthened. Special attention should be paid to the prevention of cerebral hemisphere damage after viral encephalitis diagnosis.

Pulmonary fibrosis(PF)is a chronic progressive end-stage lung disease.However,the mechanisms un-derlying the progression of this disease remain elusive.Presently,clinically employed drugs are scarce for the treatment of PF.Hence,there is an urgent need for developing novel drugs to address such diseases.Our study found for the first time that a natural source of Prismatomeris connata Y.Z.Ruan(Huang Gen,HG)ethyl acetate extract(HG-2)had a significant anti-PF effect by inhibiting the expression of the transforming growth factor beta 1/suppressor of mothers against decapentaplegic(TGF-β1/Smad)pathway.Network pharmacological analysis suggested that HG-2 had effects on tyrosine kinase phosphorylation,cellular response to reactive oxygen species,and extracellular matrix(ECM)disassembly.Moreover,mass spec-trometry imaging(MSI)was used to visualize the heterogeneous distribution of endogenous metabolites in lung tissue and reveal the anti-PF metabolic mechanism of HG-2,which was related to arginine biosyn-thesis and alanine,asparate and glutamate metabolism,the downregulation of arachidonic acid meta-bolism,and the upregulation of glycerophospholipid metabolism.In conclusion,we elaborated on the relationship between metabolite distribution and the progression of PF,constructed the regulatory metabolic network of HG-2,and discovered the multi-target therapeutic effect of HG-2,which might be conducive to the development of new drugs for PF.

Objective: : Blood-blister aneurysms (BBAs) of the internal carotid artery (ICA) are challenging lesions with high morbidity and mortality rates. Although research on BBAs is well documented in different populations, the study of BBAs in the Tibetan population is extremely rare. This study aimed to evaluate the characteristics of BBAs and analyze the treatment modalities and long-term outcomes in the Tibetan population in comparison with the Han population. Methods: : The characteristics of patients with BBAs of the ICA from January 2009 to January 2021 at our institution were reviewed. The features of aneurysms, treatment modalities, complications, and follow-up outcomes were retrospectively analyzed. Results: : A total of 130 patients (41 Tibetan and 89 Han patients) with BBAs of the ICA who underwent treatment were enrolled. Compared with the Han group, the Tibetan group significantly demonstrated a high ratio of BBAs among ICAs (8.6%, 41/477 vs. 1.6%, 89/5563; p<0.05), a high ratio of vasospasm (34.1%, 14/41 vs. 6.7%, 6/89; p=0.001), a high risk of ischemic events (43.9%, 18/41 vs. 22.5%, 20/89; p<0.05), and a low ratio of good outcomes (modified Rankin scale, 0–2) at the 1-year follow-up (51.2%, 21/41 vs. 74.2%, 66/89; p<0.05). The multivariate regression model showed that ischemic events significantly contributed to the prediction of outcomes at 1 year. Further analysis revealed that microsurgery and vasospasm were associated with ischemic events. Conclusion : In comparison with Han patients, the Tibetan population had a high ratio of BBA occurrence, a high incidence of ischemic events, and a high ratio of poor outcomes. The endovascular approach showed more benefits in BBA patients.