Objective To explore the protective effect of L-carnitine on myocardial systolic dysfunction in sepsis and its underlying mechanism.Methods A mouse sepsis model was established by cecal ligation and puncture(CLP).Ten-week-old male SPF-grade C57BL/6 mice(body weight 20～30 g)were randomly divided into 5 groups via random number table:Sham group,Sepsis group,L-carnitine group,L-carnitine+Etomoxir(Eto)group,and Eto group.Echocardiography assessed cardiac function,ELISA measured serum creatine kinase isoenzyme MB(CK-MB)levels,and 72-hour survival rates were recorded to evaluate L-carnitine's effects on cardiac function.Cardiomyocytes were isolated,and a cell microtensiometer was used to detect cardiomyocyte contractile function and calcium transients.Myocardial tissues were collected from each group,and ELISA was used to determine the contents of triglyceride(TG),free fatty acid(FFA),and adenosine triphosphate(ATP).An in vitro sepsis model was constructed by stimulating HL-1 cardiomyocytes with lipopolysaccharide(LPS)for 12 hours,which was divided into 5 groups:control(CTRL)group,LPS group,L-carnitine group,L-carnitine+Eto group,and Eto group.ELISA was used to detect the contents of TG,FFA,and ATP as well as the activity of carnitine palmitoyltransferase 1A(CPT1A)in cardiomyocytes.A cellular energy metabolism analysis system was employed to measure fatty acid oxidation capacity,and Western blot was used to detect the protein expression of CPT1A in cardiomyocytes.BODIPY-FL-C16(green fluorescently labeled palmitic acid)was utilized to detect the distribution of fatty acids in the cytoplasm and mitochondria via immunofluorescence technology,thereby observing the ability of cells to transport fatty acids into mitochondria.Results Compared with the Sham group,cardiac function was significantly impaired in the Sepsis group,as evidenced by decreased ejection fraction and mean arterial pressure(P<0.05),along with elevated levels of the cardiac injury marker CK-MB(P<0.05).Treatment with L-carnitine significantly improved myocardial function,restored blood pressure in septic mice,and increased their survival rate from 12.50%to 81.25%(P<0.05).Compared with the Sham group,the contractile function and calcium transients of acutely isolated single cardiomyocytes were significantly reduced in the Sepsis group(P<0.05),while L-carnitine treatment remarkably restored the contractile function and calcium release capacity of septic cardiomyocytes(P<0.05).Both in vivo and in vitro experiments showed that TG and FFA levels were significantly increased(P<0.05),and ATP levels was significantly decreased(P<0.05)in the Sepsis and LPS groups—effects significantly reversed by L-carnitine treatment.Compared with the CTRL group,the basal oxidation rate and maximum oxidation capacity of fatty acids in cardiomyocytes of the LPS group were significantly reduced(P<0.05),and L-carnitine treatment notably improved these indicators.Compared with the CTRL group,the expression and activity of CPT1A in cardiomyocytes of the LPS group were significantly decreased(P<0.05),while L-carnitine treatment significantly increased the expression and activity of CPT1A(P<0.05).In LPS group cardiomyocytes,green fluorescently labeled palmitic acid primarily formed numerous granular/clumpy aggregates in the cytoplasm with minimal mitochondrial colocalization.In the L-carnitine group,the green fluorescent granules in the cytoplasm of cardiomyocytes were smaller,and colocalization with mitochondria was increased.However,the L-carnitine+Eto group exhibited similar phenomena to the LPS group.In addition,both in vivo and in vitro experiments demonstrated that treatment with the CPT1A inhibitor Eto reversed the effect of L-carnitine.Compared with the L-carnitine group,the ATP content in the L-carnitine+Eto group was significantly decreased(P<0.05),while the FFA content was significantly increased(P<0.05).Conclusion L-carnitine facilitates fatty acid entry into mitochondria for β-oxidation via a CPT1A-dependent mechanism,thereby ameliorating fatty acid oxidation dysfunction in septic cardiomyocytes and improving myocardial contractile function.

This study aims to describe the population and regional distribution characteristics of smoking behavior among adult twins in the China Twin Registry (CNTR), as well as the concordance rates for smoking behavior in monozygotic and dizygotic twins, and estimate the heritability. The study population included adult twins in CNTR who had smoking questionnaire data. A random-effects regression model was used to describe the distribution of smoking behavior among different subgroups based on various characteristics. The concordance of smoking behavior between different zygosity groups was calculated, and heritability was estimated. A total of 28 444 twin pairs were included in this study, with an average age of (36.6±12.0) years. Among male twins, 41.2% were current smokers, while only 1.2% of females smoked. Higher smoking rates were observed among male smokers in the 50-59 age group ( z=23.0, P<0.001), northern regions ( z=2.9, P<0.01), rural areas ( z=-5.2, P<0.001), those who were divorced/widowed ( z=3.8, P<0.001), and first-born twins ( z=-4.3, P<0.001), while lower smoking rates were found in those with higher education ( z=-16.1, P<0.001) and unmarried individuals ( z=-16.0, P<0.001). The smoking concordance rate for male monozygotic twins was 69.6%, significantly higher than the 57.3% concordance rate for dizygotic twins ( χ 2=105.0, P<0.05). The heritability of smoking behavior in male twins was estimated at 28.9% (95% CI: 24.3%-33.4%). Stratified analyses showed differences in heritability across regions and age groups: the heritability in northern regions was 32.6% (95% CI: 27.3%-38.0%), higher than the 21.0% (95% CI: 12.4%-29.5%) observed in southern regions; the highest heritability of 35.1% (95% CI: 26.3%-43.9%) was found in the 18-29 age group, with heritability decreasing with age. In conclusion, the smoking rate and influencing factors in the twin population are similar to those in the general population, with unique characteristics, such as higher smoking rates in first-born twins. Genetic factors have a significant impact on smoking behavior.

Objective To synthesize high-quality synthetic CT (sCT) images from cone beam CT (CBCT) by learning lung CT domain image features with a deep learning algorithm. Methods A sCT generation algorithm which employs perceptual loss-based cyclic generative adversarial network model (CycleGAN) and iterative registration was presented. CycleGAN model was trained to generate high-quality sCT images by combining perceptual loss and cycle consistency loss;and Elastix was used to register the generated sCT image and the planned CT (pCT) image,and iterate CycleGAN generator model. Results Experiments were conducted on the obtained pCT and CBCT data of 70 patients with lung tumors. From a quantitative perspective,the SSIM between sCT generated by the proposed algorithm and pCT was improved by 11.9％ as compared with that between CBCT and pCT,increasing from 0.825 to 0.923;additionally,RMSE dropped from 110.97 HU to 78.62 HU,PSNR increased from 32.21 dB to 34.74 dB,and mutual information increased from 1.187 to 1.418. The visual evaluation revealed that the proposed algorithm greatly eliminated the scattering artifacts of CBCT slices,highlighted the bone structure,and repaired the soft tissue structure. The comparisons with U-CycleGAN,R-CycleGAN and CUT models confirmed the effectiveness of the proposed algorithm. Conclusion Using the proposed algorithm for sCT images generation can effectively reduce the dose error and structural error between CBCT and pCT,making it possible to apply the proposed algorithm to accurate dose calculations and assist doctors in clinical diagnosis.

Objective To investigate the damage mechanism of extracellular vesicles(EVs)derived from ves-tibular schwannoma(VS)on HEI-OC1 cells and the protective effect of the ferroptosis inhibitor ferrostatin-1(Fer-1).Methods Tumor tissues and clinical data were collected from four patients with stage Ⅱ or Ⅲ VS,classified as grade D according to the AAO-HNS hearing classification.Primary VS cells were extracted,and their conditioned supernatant was collected.EVs were isolated using ultracentrifugation and identified.HEI-OC1 cells were cultured in vitro and divided into three groups:the control group(no treatment),the EVs group(treated with 3000 parti-cles/cell VS-EVs for 24 hours),and the EVs+Fer-1 group(pretreated with 20 μmol/L Fer-1 for 2 hours followed by co-culture with 3000 particles/cell VS-EVs for 24 hours).Cell viability was assessed using the CCK-8 assay,re-active oxygen species(ROS)levels were quantified using the DCFH-DA fluorescent probe,and lipid peroxidation was evaluated using the BODIPY 581/591 C11 probe.Results Compared with the control group,the EVs group showed significantly reduced cell viability(P＜0.001)and increased levels of ROS(P＜0.001)and lipid peroxides(P＜0.001).However,the EVs+Fer-1 group exhibited significantly restored cell viability(P＜0.001)and re-duced levels of ROS and lipid peroxidation(P＜0.001).Conclusion VS-derived EVs disrupts redox homeostasis,promotes intracellular accumulation of lipid peroxides and ROS,and induces ferroptosis in HEI-OC1 cells.Fer-1 significantly alleviates VS-EVs-induced ferroptosis,thereby protecting HEI-OC1 cells from damage.

Objective To investigate the effect of active muscle response on mechanical responses and injuries of human neck under high Gx loading.Methods A refined finite element model of the head and neck with active muscle response was established and validated based on the existing post-crash volunteer experiments.The effects of active muscle action on the kinematic and biomechanical responses of the neck were investigated under different G-value loads and at each tilting angle using this model.Results The stress distribution of vertebrae under high Gx load was dispersed from C4-7 to the whole vertebrae,and the active muscle action reduced the stress change,and the effect was significant under 8 G acceleration,which reduced the peak vertebral bone stress by 23.6％and 11.6％,and the peak intervertebral disc stress by 42.3％and 63.4％under 8 G and 10 G conditions,respectively.The maximum stress difference of 34.3 MPa was achieved by the active muscle action at 15° backward tilting.Conclusions The neck showed better stability by the active muscle action under the impact of high Gx loading.At different tilting angles,the active muscle action was more obvious in the backward tilting posture compared with the forward tilting and upright seated postures,and the backward tilting posture was safer to meet the impact when the same active muscle action was applied.The results can provide a reference for the subsequent studies related to the neck injury.

Traditional open thyroid surgery often leaves a scar on the neck,which can affect cosmetic outcomes.Therefore,various endoscopic thyroidectomy approaches via extra-cervical approaches have been developed.However,due to the unique anatomical characteristics of the neck and limitations of endoscopic instruments,conventional endoscopic techniques have certain drawbacks.Robot-assisted endoscopic thyroid surgery can help overcome these limitations.At present,robotic surgical systems remain expensive and the associated surgical costs are high,limiting their widespread adoption.Most surgeons are still relatively unfamiliar with the technique.Nevertheless,with ongoing technological advancements and cost reductions,robot-assisted surgery holds great promise for broader application.Based on years of large-scale experience in endoscopic thyroid surgery at our center,and drawing upon both domestic and international experiences with robotic thyroidectomy,this paper summarizes and proposes a seven-step protocol for robot-assisted endoscopic thyroidectomy via the bilateral axillo-breast approach,aiming to provide a practical reference for the clinical adoption of this technique.

Objective:To describe the distribution characteristics of alcohol consumption in adult twins in the Chinese National Twin Registry (CNTR), and further explore the influence of genetic factors on alcohol consumption in adult twins.Methods:The subjects of the study were twins registered by CNTR in 11 project areas across China from 2010 to 2018. A total of 56 966 twins (28 483 pairs) aged 18 years and above who answered questions about drinking behavior were included, and the random effect model was used to describe the population and regional distribution characteristics of alcohol consumption. Intra-pair analysis was performed to calculate the concordance rate and heritability of their alcohol consumption.Results:The age of all subjects was (36.6±12.0) years, and current drinkers accounted for 16.6% (9 461/56 966) of all subjects. In men, those aged 50-59 years, those in northern China, those living in rural area, those with low education level and those with high BMI, the proportions of current drinkers were higher. After excluding 468 pairs of twins who had stopped alcohol use and 21 764 pairs of twins who had no drink or had small amount drink, an intra-pair analysis was conducted in 4 929 pairs of same-sex twins, and found that the concordance rate of alcohol consumption was 64.0% (2 059/3 215) in monozygotic twins, and 52.6% (902/1 714) in dizygotic twins, the difference was significant ( P<0.001), and the heritability of alcohol consumption was 24.1% (95% CI: 18.9%- 29.3%). The further stratified analysis found that in southern men, the heritability was highest in those aged 40-49 years (36.1%, 95% CI: 21.6%-50.7%), while in northern men, the heritability was highest in those aged 50-59 years (34.2%, 95% CI: 18.1%-50.3%). Conclusions:In adult twins in China, there were population and regional differences in the distribution of alcohol consumption behavior, and alcohol consumption was influenced by genetic factors, and gender, age and region had potential modifying effects.

Objective To investigate the impact of the dominant deafness point mutation p.D179N on the oli-gomeric equilibrium state of Connexin 26(Cx26).Methods The wild-type Cx26 fusion protein(Cx26-WT-GFP)and mutant fusion proteins(Cx26-D179N-GFP,Cx26-D179C-GFP)were expressed in HEK293F cells.By using Fluorescence-detection size-exclusion chromatography(FSEC)and size-exclusion chromatography(SEC)to analysis the oligomeric state of the target protein based on malecular weight under the condition of solubilization and purifica-tion respectively.Cryo-electron microscopy(Cryo-EM)single particle analysis(SPA)was conducted to analysis the target protein's oligomeric states based on the 2D classification morphology of the protein particles.Results In vitro,the wild-type Cx26 protein(Cx26-WT)is almost exclusively dodecameric.The deafness mutation p.D179N protein(Cx26-D179N)exists as both dodecamers and hexamers,whereas the artificial mutation p.D179C protein(Cx26-D179C)does not form dodecamers.Conclusion The dominant deafness mutation GJB2 p.D179N could weaken the ability of docking between hexameric proteins,which could affect the balance between hexamers and do-decamers.

Objective To explore the diagnostic value of serum C-C motif chemokine ligand 3(CCL3)and Semaphorin 3A in patients with type 2 diabetes mellitus(T2DM)complicated by osteoporosis(OP).Methods A total of 125 patients with T2DM complicated by OP who visited the hospital from August 2022 to August 2023 were selected as the OP group,and another 125 patients with T2DM without OP who visited the hospital during the same period were selected as the T2DM group.The OP group was divided into Group A(T value>-1.0,but slightly lower than the normal value),Group B(T value between-2.5 and-1.0),and Group C(T value<-2.5)based on the measurement results of bone mineral density(BMD).The lev-els of serum CCL3 and Semaphorin 3A in each group were compared.Pearson correlation analysis was used to analyze the correlations between serum CCL3,Semaphorin 3A and BMD in patients with T2DM complicated by OP.Multivariate Logistic regression analysis was used to analyze the influencing factors of T2DM compli-cated by OP.The receiver operating characteristic(ROC)curve was used to analyze the diagnostic value of se-rum CCL3 and Semaphorin 3A for T2DM complicated by OP.Results Compared with the T2DM group,the serum CCL3 level in the OP group increased,and the Semaphorin 3A level decreased,and the difference was statistically significant(P<0.05).Compared with group A,the serum CCL3 levels in group B and group C increased,while the Semaphorin 3A level decreased,and the differences were statistically significant(P<0.05).Compared with group B,the serum CCL3 level in group C increased and the Semaphorin 3A level de-creased,and the difference was statistically significant(P<0.05).Compared with the T2DM group,the femo-ral neck bone BMD,lumbar spine BMD and total hip BMD in the OP group were significantly decreased,and the difference was statistically significant(P<0.05).The serum CCL3 level in patients with T2DM accompa-nied by OP was negatively correlated with femoral neck bone BMD,lumbar spine BMD and total hip BMD(P<0.05),and the serum Semaphorin 3A level was positively correlated with femoral neck bone BMD,lum-bar spine BMD and total hip BMD(P<0.05).The results of multivariate Logistic regression analysis showed that CCL3 was an independent risk factor for T2DM with OP(P<0.05),and Semaphorin 3A was an inde-pendent protective factor for T2DM with OP(P<0.05).The results of ROC curve analysis showed that the area under the curve(AUC)of serum CCL3,Semaphorin 3A and their combination diagnosis of T2DM accom-panied by OP were 0.810,0.802 and 0.869,respectively.The AUC of the combined diagnosis of T2DM ac-companied by OP was superior to their individual diagnoses(Zcombination-CCL3=2.235,Zcombination-Semaphorin 3A=2.021,P=0.025,0.043).Conclusion The serum CCL3 level is increased in patients with T2DM accompanied by OP,and the Semaphorin 3A level is decreased.The combination of the two has certain diagnostic value for T2DM accompanied by OP.

Objective To analyze the medication rules of traditional Chinese medicine in treating breast cancer based on real-world data mining.Methods Inpatients with breast cancer who received traditional Chinese medicine treatment at the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine from January 2017 to December 2021 were selected.Python 3.10 software was used to mine traditional Chinese medicine prescription data;SPSS 23.0 software was applied for descriptive analysis,and systematic cluster analysis was performed on high-frequency drugs.Results A total of 3026 consultation records of inpatients with breast cancer were collected.The main traditional Chinese medicine syndrome diagnosis of"predominantly liver depression and Qi stagnation"accounted for 60.94％of the total consultations.A total of 240 kinds of traditional Chinese medicine were used,with a cumulative frequency of 35 462 times.Among them,29 kinds of traditional Chinese medicine such as Danggui,Fuling,Baizhu,Chaihu had a cumulative usage frequency exceeding 300 times.Regarding the four natures of drugs,cold-natured(43.55％),warm-natured(30.05％),and neutral-natured(23.34％)drugs were predominant;In terms of five flavors,sweet(46.12％),bitter(30.91％),and pungent(20.02％)were the main ones.The most frequently used drugs were tonifying herbs(32.77％),followed by heat-clearing herbs(15.96％)and phlegm-resolving herbs(14.71％).Systematic cluster analysis yielded 7 groups of drug combinations.Conclusion In real-world clinical practice,traditional Chinese medicine for breast cancer mainly uses tonifying herbs,reflecting the traditional Chinese medicine principle of"strengthening healthy Qi and cultivating the root"in treating tumors.The four natures and five flavors of drugs follow syndrome differentiation and the combination of cold and heat.The clustered drug combinations have extensive therapeutic effects,covering various syndromes of breast cancer at different stages,which can provide a reference for clinical medication.