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 investigate the genetic characteristics of fetuses carrying a small supernumerary marker chromosome (sSMC) derived from chromosome 15.Methods:This was a retrospective study involving three fetuses who were diagnosed with microdeletions or microduplications by non-invasive prenatal testing (NIPT) and confirmed to carry sSMC derived from chromosome 15 through prenatal diagnosis at the Center of Prenatal Diagnosis, Jinan Maternity and Child Care Hospital Affiliated to Shandong First Medical University from June to October 2023. Clinical data, including NIPT results and ultrasound findings, were collected. Genetic tests for the fetuses and their parents were performed using genetic karyotype analysis, fluorescence in situ hybridization (FISH), and single nucleotide polymorphisms array (SNP-array). All data were analyzed using descriptive statistics. Results:(1) The mothers of the three fetuses were aged 36, 37, and 41 years, and all of them were multiparous with no family history of genetic disorders. The fetuses exhibited duplications of 8.80, 8.17, and 8.80 Mb in the 15q11.2q13.3 region, respectively. Amniotic fluid karyotyping revealed a 47,XN,+mar karyotype in all three cases. The abnormal sSMC contained two centromeres. One of them was pycnotic, deeply stained, but remained active, while the other was enlarged and formed a band, losing its activity. Both were pseudo-dicentric structures. (2) FISH was not performed on Fetus 1. FISH results for both Fetus 2 and Fetus 3 were ish idic(15)( D15Z1++, SNRPN++, PML-), indicating the presence of two copies of the D15Z1 and SNRPN probes on the sSMC, with no PML probe signal. The D15Z1 probe was located at both ends of the sSMC, while the SNRPN probe was near the center. (3) SNP-array results were arr[GRCh37] 15q11.2q13.2(22 770 422-31 098 691)×4 for Fetus 1, covering 29 OMIM genes including UBE3A and 38 protein-coding genes; arr[GRCh37] 15q11.2q13.3(22 770 422-32 915 723)×4 for Fetus 2, covering 36 OMIM genes including UBE3A and 50 protein-coding genes; and arr[GRCh37] 15q11.2q13.1 (22 770 422-28 560 664)×4 and arr[GRCh37] 15q13.1q13.3(29 009 041-32 444 043)×3 for Fetus 3, covering 24 OMIM genes including UBE3A and 20 protein-coding genes. Additionally, Fetus 3 had a 3.435 Mb duplication in 15q13.1q13.3, covering 11 OMIM genes including CHRNA7 and 20 protein-coding genes. (4) No significant abnormalities were found in the peripheral blood karyotyping for the parents of Fetus 1 or in the SNP-array analysis for the parents of Fetus 3. (5) All three families opted for pregnancy termination. There were no obvious abnormalities in the appearance of Fetus 1 and Fetus 3 after induction, while details of Fetus 2 were unavailable. Conclusion:The three fetuses carried a psu idic(15)(q13)-derived sSMC, leading to increased copy numbers in the 15q11q13 region.

OBJECTIVE To observe the fever-reducing effect of pricking-cupping method on endotoxin-induced fever in rab-bits,and to further explore the fever-reducing mechanism of pricking-cupping method from the perspective of skeletal muscle mito-chondrial energy metabolism.METHODS A total of 72 rabbits were randomly divided into blank group,model group,Western medi-cine group,pricking group,cupping group and pricking-cupping group,with 12 rabbits in each group.The rabbit model of endotoxin-in-duced fever was reproduced and the corresponding therapeutic intervention was carried out.The body temperature of rabbits was recor-ded continuously for 6 h.The mitochondrial structure was observed by transmission electron microscopy.Oxygraph-2k system was used to detect mitochondrial function.ATP content in thigh muscle tissue of rabbits in each group was detected.The expression of uncoupling protein 2(UCP2)and mitochondrial fusion protein 2(Mfn2)in thigh muscle of rabbits was detected by Wes automated western blot quantitative analysis system.RESULTS The model was successfully replicated,and the body temperature of rabbits in the four treatment groups was lower than that in the model group.The skeletal muscle mitochondrial morphology of rabbits in the blank group was intact,and the mitochondrial morphology was closest to normal after the treatment of pricking-cupping.Moreover,the oxygen con-sumption of mitochondrial CII OXPHOS stage in the pricking-cupping group was significantly higher than that in the model group.Compared with the model group,the ATP content in the muscle tissue of rabbits in the pricking-cupping group was significantly increased,Mfn2 protein expression was significantly increased,and UCP2 protein expression was significantly decreased.CONCLU-SION The pricking-cupping method has a good fever-reducing effect on endotoxin-induced fever in rabbits,and its mechanism may be related to inhibiting UCP2 protein expression in skeletal muscle,promoting Mfn2 protein expression,promoting the oxidative phos-phorylation process in skeletal muscle mitochondria,and increasing ATP synthesis in mitochondria.

Objective:To observe any influence of combining proprioceptive training with core stability training in rehabilitation motor functioning and balance after extensive burns.Methods:Sixty patients with lower limb motor and balance disorders after extensive burns were randomly divided into a treatment group and a control group, each of 30. Both groups underwent skin grafting on the lower limbs. After the wounds had healed, both groups were given routine rehabilitation treatment, including joint stretching and muscle strength training, but the treatment group was additionally provided with proprioception and core stability training. Before and after 12 weeks of treatment, both groups′ lower limb motor function and walking ability were evaluated using the Fugl-Meyer Assessment (L-FMA), and static and dynamic balance were quantified using Holden Functional Ambulation Classification (FAC). The duration of standing on one leg with the eyes closed was recorded, along with Timed " Up & Go" Test (TUGT) times. After the treatment, each patient′s satisfaction was assessed using a self-designed questionnaire.Results:Significant improvement was observed in the average L- FMA and FAC scores after the treatment, as well as in the ability to stand on one leg with the eyes closed. The average TUGT time in both groups was shorter, but there had been significantly greater improvement of the treatment group than among the controls. Reported satisfaction was significantly higher among the treated group than among the controls.Conclusions:Supplementing basic rehabilitation with proprioception training and core stability training can further improve the motor functioning, balance and walking of persons who have suffered extensive burns.

Objective:To observe the clinical efficacy of different treatment methods in treating older patients with oral papilloma.Methods:A randomized controlled study was conducted on 40 older patients with oral papilloma who visited the Department of Stomatology of Beijing Hospital from August 2022 to November 2024.They were randomly divided into a surgical resection group and a 5-aminolevulinic acid (ALA) application group.There were 15 males and 25 females, with ages ranging from 60 to 82 (70.20 ± 6.53) years old.The ALA application group received ALA photodynamic therapy (PDT), while the surgical resection group underwent surgical resection of the papilloma.Visual analog scale (VAS) and self-assessment anxiety and depression scale were used to evaluate the two groups of patients at different periods.Results:All lesions in both groups achieved complete healing, with no recurrence observed during the 6-month follow-up period.Although the ALA application group received more treatment sessions than the surgical resection group, postoperative VAS scores and the duration of postoperative pain were both significantly lower [VAS score: (2.95±0.83) vs. (4.95±1.32) points; pain duration: (4.65±0.67) vs.(6.20±1.06) days]( t=5.755 and 5.540, respectively; both P<0.001). Before treatment, there was no statistically significant difference in either self- assessed anxiety or self- assessed depression scores between the two groups (both P>0.05). Six months after treatment, the self- assessed anxiety score in the ALA application group was significantly higher than that in the surgical resection group ( P<0.05), whereas no significant difference was observed in the self- assessed depression score ( P>0.05). Conclusions:Both ALA-PDT and surgical resection can effectively treat oral papilloma in older patients.However, ALA-PDT has lighter and shorter duration of postoperative pain, making it more suitable for treating lesions in special anatomical areas such as the corners of the mouth and the duct openings of the parotid glands.

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.

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 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.