Objective: To explore the causal association between dietary components (carbohydrate, fat, protein, and sugar) and 119 genera of known gut microbiota using Mendelian randomization (MR) methods. Methods: Genome-wide association study (GWAS) data for dietary components were collected from the DietGen, while GWAS data for gut microbiota were collected from the MiBioGen. Single nucleotide polymorphism (SNP) loci associated with the four dietary components were used as instrumental variables, and 119 known gut microbiota genera were used as the outcomes. MR analysis was performed using inverse variance weighted (IVW) method. Heterogeneity was evaluated using Cochran's Q test, horizontal pleiotropy and exclude outliers were tested using MR-Egger regression and MR-PRESSO test. Common genetic pleiotropic genes between dietary components and gut microbiota were identified by MAGMA and PLACO analyses. Results: The MR analysis revealed causal associations between carbohydrates and 4 gut microbiota genera, fats and 14 genera, proteins and 14 genera, and sugars and 11 genera (all P<0.05). The MR-Egger regression analysis showed no horizontal pleiotropy among the selected SNPs, and the MR-PRESSO test did not identify any outliers (all P>0.05). The MAGMA and PLACO analyses revealed that 74.42% (32/43) of the causal associations had pleiotropic genes, with 1 to 10 pleiotropic genes identified. Multiple causal association groups shared the same pleiotropic genes. Conclusion There are potential genetic and causal associations between dietary components and gut microbiota.

Objective: To investigate the association between childhood obesity and type 2 diabetes mellitus (T2DM) as well as coronary artery heart disease (CHD). Methods: Genome-wide association study (GWAS) data for childhood obesity were collected from the ECG consortium, encompassing information on children aged 2 to 18 years, including 18 613 cases and 12 696 controls. GWAS data for T2DM were collected from the DIAGRAM consortium, including 242 283 cases and 1 569 734 controls. GWAS data for CHD were collected from the CARDIoGRAMplusC4D consortium, including 10 801 cases and 137 371 controls. Pleiotropic genes associated with both T2DM and CHD were analyzed using the MAGMA, PLACO and conditional false discovery rate (cFDR) methods. Mendelian randomization (MR) analysis was performed using inverse variance weighted (IVW) method, exploring the causal relationships among childhood obesity, T2DM and CHD. Heterogeneity was evaluated using Cochran's Q test, horizontal pleiotropy and exclude outliers were tested using MR-Egger regression and MR-PRESSO test. The mediating variables among the three diseases were investigated by using a mediation analysis. Results: The results of MAGMA, PLACO and cFDR analyses identified 80 pleiotropic genes associated with both T2DM and CHD, primarily distributed on chromosomes 3, 17 and 19. The MR analysis revealed that childhood obesity increased the risk of T2DM (OR=1.151, 95%CI: 1.033-1.283) and CHD (OR=1.158, 95%CI: 1.068-1.255), T2DM increased the risk of CHD (OR=1.182, 95%CI: 1.139-1.227), and CHD increased the risk of T2DM (OR=1.124, 95%CI: 1.055-1.198). The MR-Egger regression analysis showed no horizontal pleiotropy, and the MR-PRESSO test did not identify any outliers (all P>0.05). Mediation analysis indicated that childhood obesity directly increased the risk of CHD (effect value=0.096, 95%CI: 0.012-0.180) and indirectly increased the risk of CHD through T2DM (effect value=0.023, 95%CI: 0.005-0.041), with the mediation effect accounting for 15.65% of the total effect. Conclusions There are potential causal associations between childhood obesity and T2DM as well as CHD, with a bidirectional causal relationship between T2DM and CHD. T2DM also plays a mediating role in the association between childhood obesity and CHD.

BACKGROUND:Gold nanoparticles are of great significance in the development of multifunctional transdermal drug delivery systems.Smaller gold nanoparticles can penetrate the dermis through the intercellular pathway,but are limited to their easy agglomeration and colloidal morphology,which makes it difficult to exert effects on low delivery efficiency. OBJECTIVE:To develop an ultrasound-optimized hydrogel delivery system by combining phase change nanodroplets with bio-adhesive hydrogel for percutaneous delivery of gold nanoparticles. METHODS:The ultrasound-responsive nanodroplets loaded with gold nanoparticles were prepared by the emulsion solvent evaporation method and loaded into the polydopamine-modified methylacryloyl gelatin hydrogel to prepare a composite hydrogel scaffold.The structure and chemical composition of the ultrasound-responsive nanogold carrier were characterized.The microstructure,porosity,permeability,rheology,in vitro hemostasis,and antibacterial properties of the composite hydrogel were characterized.The cell compatibility of the hydrogel scaffold was evaluated by live/dead staining,and the optimization effects of low-intensity pulsed ultrasound on the permeability,porosity,and mechanical properties of hydrogel were evaluated. RESULTS AND CONCLUSION:(1)Transmission electron microscopy and ultraviolet-visible spectroscopy proved the successful construction of nanogold carriers.The particle size and potential results demonstrated that the synthesized nanoscaled ultrasonic responsive carrier had good stability.(2)Live/dead cell staining proved that the prepared composite hydrogel scaffold had certain biocompatibility.(3)Scanning electron microscopy exhibited that the prepared composite hydrogel scaffold had a porous network structure,and numerous pores of about 2 μm appeared inside the macropores after the addition of nanodroplets and ultrasonic irradiation.The permeability experiment displayed that low-intensity pulsed ultrasound could optimize the porosity and permeability of hydrogel materials.The hemostatic performance of the composite hydrogel scaffold was better than that of the hemostatic sponge and polydopamine@methylacrylylated gelatin hydrogel scaffold.Under the irradiation of low-intensity pulsed ultrasound,the composite hydrogel scaffolds had good antioxidant effects and antibacterial properties.(4)Thermal imaging results manifested that gold nanoparticles were encapsulated in ultrasound-responsive nanobubbles,and more uniform dispersion could be obtained under ultrasonic excitation.(5)The results of the mechanical property test demonstrated that the storage modulus of the hydrogel increased before and after loading gold nanoparticles-nanodroplets,which showed stronger mechanical properties.The elongation at break was 122%,and the ductility was better than that without gold nanoparticles-nanodroplets(P<0.05).(6)These findings indicate that the composite hydrogel scaffold has good biocompatibility,antibacterial property,oxidation resistance,and hemostatic effect.

OBJECTIVE To evaluate the effictiveness and safety of recombinant human endostatin combined with afatinib and teggio in the treatment of advanced lung squamous cell carcinoma. METHODS A total of 25 patients with driver-negative advanced lung squamous cell carcinoma were included in this single-arm prospective study, and the enrolled patients were treated with recombinant human endostatin combined with afatinib and teggio as scheduled. Progression-free survival(PFS), overall survival(OS), disease control rate(DCR), objective response rate(ORR), and adverse reactions(AR) were observed and analyzed. RESULTS The 25 enrolled patients received at least 2 cycles of second-line treatment, and were followed up as of March 31, 2023. Among them, 4 patients had partial remission, 17 patients had stable disease, and 4 patients experienced progressive disease. The ORR confirmed by the researchers was 16%(95%CI, 4.5%−36.1%), DCR was 84%(95%CI, 63.9%−95.5%), and median PFS was 5.3 months(95%CI, 3.5−6.9 months). The median OS had not yet been achieved. The entire group of patients had good treatment tolerance, and the most common level Ⅲ or Ⅳ adverse events related to treatment were leukopenia(20%) and rash(12%), with no reported treatment-related deaths. CONCLUSION Recombinant human endostatin combined with afatinib and teggio in the second line treatment of advanced lung squamous cell carcinoma can prolong the progression free survival period of patients and is relatively safe, which is worth further exploration and promotion.

Replacement of the temporomandibular joint (RTJ) has undergone decades of technological improvements and is now an important treatment for end-stage temporomandibular joint (TMJ) disease. The main complications of RTJ include aseptic loosening, heterotopic ossification, postsurgical infection, hypersensitivity reaction, prosthesis loosening or malposition, nerve injury and severe bleeding. Improvement in clinical technique is now the key to resolving complications. In the future, improvements in prosthetic materials may be an important development for newer iterations. With the development and popularity of TMJ surgical techniques, prosthesis-related complications will increasingly come into clinical view. This article provides a systematic review of the complications of RTJ prosthesis replacement and the measures to deal with them, and looks forward to the direction of the development of this field from the perspective of reducing complications, so as to provide a reference for clinical work.

Objective:To explore the impact of transcatheter edge-to-edge repair (TEER) devices on mitral valve regurgitant flow convergence post-procedure using computational fluid dynamics(CFD), and to seek solutions for accurately measuring effective regurgitant orifice area(EROA) after TEER.Methods:Multimodal fusion was conducted based on preoperative cardiac CT images and intraoperative three-dimensional transesophageal echocardiography(3DTEE) of 33 patients with mitral valve regurgitation undergoing TEER at Renmin Hospital of Wuhan University from January 2020 to August 2023. Using this data, CFD models of mitral valve regurgitation post-TEER, including with and without the TEER device, were constructed. The distance (D) from the midpoint of the mitral regurgitation orifice to the TEER device was measured. The proximal isovelocity surfice area(PISA) radius with and without the TEER device was measured, and the corresponding EROA1 and EROA2 based on this was calculated. The EROA correction factor CC=EROA2/EROA1 was calculated.Results:A total of 42 sets of CFD models with mild or greater residual mitral regurgitation, both with and without the TEER device, and 50 sets of PISA were obtained. Based on the relative position of PISA to the TEER device, four types of PISA were observed: Type 1: PISA away from the TEER device (D>R, 14 cases), with a CC of 0.93±0.07; Type 2: PISA adjacent to the TEER device (D

In order to further strengthen the training and management of clinical teachers, broaden the career development channels of clinical teachers, and truly stimulate their teaching enthusiasm and initiative, this study further classifies clinical teachers according to the principle of the Snell model, focuses on the training of educational clinicians, and explores the training mechanism of teaching talents in line with the actual development needs of hospitals affiliated to universities from the aspects of selection, training, incentive, and assessment. The results of practice show that related practices have a good effect, and the mean number of teaching achievements was 1.98 for the 56 educational physicians, which was 3.9 times that for non-educational physicians. The per capita teaching achievements of educational physicians tended to increase every year compared with those of non-educational physicians. The training path for educational physicians provides useful experience for the construction of clinical teaching team and the high-quality development of education and teaching, and at the same time, it is necessary to further strengthen the dynamic adjustment of talent echelon, the improvement of operating mechanism, and the introduction of new technology.

Objective:To explore the prognostic predictive value of deep neural network (DNN) assisted myocardial contrast echocardiography (MCE) quantitative analysis of ST-elevated myocardial infarction (STEMI) patients after successful percutaneous coronary intervention(PCI).Methods:A retrospective analysis was performed in 97 STEMI patients with thrombolysis in myocardial infarction-3 flow in infarct vessel after primary PCI in Renmin Hospital of Wuhan University from June to November 2021. MCE was performed within 48 h after PCI. Patients were followed up to 120 days. The adverse events were defined as cardiac death, hospitalization for congestive heart failure, reinfarction, stroke and recurrent angina. The framework consisted of the U-net and hierarchical convolutional LSTMs. The plateau myocardial contrast intensity (A), micro-bubble rate constant (β), and microvascular blood flow (MBF) for all myocardial segments were obtained by the framework, and then underwent variability analysis. Patients were divided into low MBF group and high MBF group based on MBF values, the baseline characteristics and adverse events were compared between the two groups. Other variables included biomarkers, ventricular wall motion analysis, MCE qualitative analysis, and left ventricular ejection fraction. The relationship between various variables and prognosis was investigated using Cox regression analysis. The ROC curve was plotted to evaluate the diagnostic efficacy of the models, and the diagnostic efficacy of the models was compared using the integrated discrimination improvement index (IDI).Results:The time-cost for processing all 3 810 frames from 97 patients was 377 s. 92.89% and 7.11% of the frames were evaluated by an experienced echocardiographer as "good segmentation" and "correction needed". The correlation coefficients of A, β, and MBF ranged from 0.97 to 0.99 for intra-observer and inter-observer variability. During follow-up, 20 patients met the adverse events. Multivariate Cox regression analysis showed that for each increase of 1 IU/s in MBF of the infarct-related artery territory, the risk of adverse events decreased by 6% ( HR 0.94, 95% CI =0.91-0.98). There was a 4.5-fold increased risk of adverse events in the low MBF group ( HR 5.50, 95% CI=1.55-19.49). After incorporating DNN-assisted MCE quantitative analysis into qualitative analysis, the IDI for prognostic prediction was 15% (AUC 0.86, sensitivity 0.78, specificity 0.73). Conclusions:MBF of the area supplied by infarct-related artery after STEMI-PCI is an independent protective factor for short-term prognosis. The DNN-assisted MCE quantitative analysis is an objective, efficient, and reproducible method to evaluate microvascular perfusion. Assessment of culprit-MBF after PCI in STEMI patients adds independent short-term prognostic information over qualitative analysis.It has the potential to be a valuable tool for risk stratification and clinical follow-up.

Objective: To investigate the epidemiological characteristics of hemorrhagic fever with renal syndrome (HFRS) in Shaoxing City from 2006 to 2022, so as provide insights into improvements of the HFRS control strategy. Methods: Data pertaining to HFRS cases in Shaoxing City from 2006 to 2022 were captured from the Surveillance System of China Information System for Disease Control and Prevention. The temporal, population and regional distributions of HFRS were analyzed using the descriptive epidemiological method, and the trends in incidence of HFRS were evaluated using annual percent change (APC). Results: Totally 1 022 HFRS cases were reported in Shaoxing City from 2006 to 2022, with annual average incidence of 1.22/105 and three deaths. The incidence of HFRS appeared a tendency towards a decline in Shaoxing City from 2006 to 2022 (APC=-11.101%, t=-9.930, P<0.001), and the incidence of HFRS peaked from May to June and from November to January of the next year. A higher incidence of HFRS was seen in men than in women (1.76/105 vs. 0.68/105; χ2=201.361, P<0.001). There were 714 HFRS cases at ages of 30 to 59 years (69.86%), and farmers were the predominant occupation (78.18%). The three counties with the largest number of HFRS cases included Zhuji (366 cases), Xinchang (263 cases) and Shengzhou (134 cases). The incidence of HFRS was lower in urban districts (Yuecheng, Keqiao and Shangyu) than in counties (Zhuji, Shengzhou and Xinchang) (0.58/105 vs. 1.96/105; χ2=326.880, P<0.001). Conclusion The incidence of HFRS appeared a tendency towards a decline in Shaoxing City from 2006 to 2022, and the incidence was high in late spring, early summer and winter. The HFRS cases were mainly males, young and middle-aged people, and farmers, and predominantly distributed in counties. Targeted control measures are needed.

Objective: To investigate the epidemiological and etiological characteristics of viral diarrhea among children under 5 years of age in Shaoxing City, Zhejiang Province, so as to provide insights into management of viral diarrhea. Methods: The surveillance data on viral diarrhea among children under 5 years of age in Shaoxing City from 2019 to 2022 were collected, including demographics and stool testing results. The epidemiological and etiological characteristics of viral diarrhea were analyzed using a descriptive epidemiological method. Results: A total of 763 diarrheal children under 5 years of age were reported in Shaoxing City from 2019 to 2022, and 236 children were tested positive for virus (30.93%). The detection of virus was 49.01%, 31.61%, 20.43% and 21.89% from 2019 to 2022, which appeared an overall tendency towards a decline (P<0.05). The incidence of viral diarrhea peaked from November to March of the next year and from May to July, and the detection of virus was lower among children with diarrhea living in urban areas (Yuecheng District, Keqiao District and Shangyu District) than among those in suburb areas (Zhuji City, Shengzhou City and Xinchang County) (30.22% vs. 52.00%, P<0.05). There were 206 children tested positive for a single virus, and the detection rates of rotavirus (RV), enteric adenovirus (EAdV), norovirus (NoV), and sapovirus (SaV) were 9.57%, 8.91%, 8.39%, and 0.13%, respectively. There were 25 children with virus co-infections, and the positive rates of EAdV and NoV, RV and EAdV and RV and NoV co-infections were 1.31%, 1.18% and 0.79%, respectively. There were 5 children with triple infections of RV, EAdV and NoV (0.66%). The highest detection of EAdV was seen in April, the highest detection of RV and NoV was seen in January, while SaV was only detected in April. Conclusion The incidence of viral diarrhea among children under 5 years of age peaked in winter and spring in Shaoxing City from 2019 to 2022, and the cases predominantly occurred in urban areas. The detection of virus appeared an overall tendency towards a decline, with high detection of RV, EAdV and NoV.