ObjectiveTo observe the clinical efficacy and possible mechanisms of Xianglian Huazhuo Granules （香连化浊颗粒， XHG） in the treatment of chronic atrophic gastritis with intestinal metaplasia. MethodsA total of 140 patients with chronic atrophic gastritis and intestinal metaplasia were randomly divided into a treatment group and a control group， with 70 cases in each group. The treatment group received 12.5 g of XHG orally， twice daily. The control group received 12.5 g of placebo orally， twice daily. Both groups were treated for 6 months. The traditional Chinese medicine （TCM） symptom scores， pathological types， serum tumor markers of the digestive system， and serum bile acids （TBA）， interleukin-23 （IL-23）， and Dickkopf-related protein 1 （DKK-1） levels were observed before and after treatment. Safety indicators and adverse events were recorded. After treatment， TCM syndrome efficacy and pathological types were evaluated， and patients were followed up for 18 months with gastric endoscopy and pathological results， which were compared with the results after treatment finished. ResultsTwo patients dropped out in the control group， and a total of 168 cases were included in the final analysis， 70 in the treatment group and 68 in the control group. The treatment group showed a significant reduction in TCM symptom scores， serum TBA， IL-23， and DKK-1 levels， and a significant increase in alpha-fetoprotein （AFP）， carbohydrate antigen 125 （CA125）， carbohydrate antigen 199 （CA199） levels； in the control group， carcinoembryonic antigen （CEA）， CA125， CA199 levels significantly increased （P＜0.05 or P＜0.01）； and carbohydrate antigen 242 （CA242） level in both the treatment group and the control group decreased significantly （P＜0.01）. The treatment group had lower TCM symptom scores and lower levels of serum TBA， IL-23， and DKK-1 compared to the control group （P＜0.05）. The effective rate for TCM syndrome efficacy in the treatment group was 80.00% （56/70）， significantly higher than the 20.59% （14/68） in the control group （P < 0.05）. The effective rate for pathological classification in the treatment group was 72.73% （8/11） for mixed intestinal metaplasia， significantly better than 46.15% （6/13） in the control group （P＜0.05）. No adverse events were reported in either group. Among 40 patients who had a follow-up endoscopy after one year， 21 were from the treatment group， of whom 11 showed reduced intestinal metaplasia， 9 showed no significant changes， and 1 had worsened； while 19 patients in the control group had 4 with reduced intestinal metaplasia， 13 with no significant changes， and 2 with worsened conditions. No cancer was detected in either group. The treatment group showed significantly better improvement in intestinal metaplasia on follow-up gastric endoscopy pathology than the control group （P＜0.05）. ConclusionXHG can significantly improve the clinical symptoms in patients with chronic atrophic gastritis and intestinal metaplasia and reduce the degree of mixed intestinal metaplasia. The mechanism may involve lowering serum TBA， DKK-1， and IL-23 levles， thus delaying the progression from inflammation to cancer.

The rich club, as a community of highly interconnected nodes, serves as the topological center of the network. However, the similarities and differences in how the rich club supports functional integration and segregation in the brain across different species remain unknown. In this study, we first detected and validated the rich club in the structural networks of mouse, monkey, and human brains using neuronal tracing or diffusion magnetic resonance imaging data. Further, we assessed the role of rich clubs in functional integration, segregation, and balance using quantitative metrics. Our results indicate that the presence of a rich club facilitates whole-brain functional integration in all three species, with the functional networks of higher species exhibiting greater integration. These findings are expected to help to understand the relationship between brain structure and function from the perspective of brain evolution.
Animals ; Humans ; Brain/diagnostic imaging* ; Mice ; Male ; Nerve Net/diagnostic imaging* ; Macaca ; Female ; Neural Pathways/diagnostic imaging* ; Magnetic Resonance Imaging ; Biological Evolution ; Adult ; Diffusion Magnetic Resonance Imaging ; Brain Mapping ; Species Specificity ; Mice, Inbred C57BL

Objective To evaluate the effects of combining immune checkpoint inhibitors,trastuzumab,and chemotherapy on the left and right ventricular function in patients with advanced gastric adenocarcinoma expressing human epidermal growth factor receptor 2(HER2).Methods 25 patients with advanced HER2-positive gastric adenocarcinoma who received HER2-ASTRUM therapy(sruili monoclonal antibody combined with trastuzumab and DOS regimen)underwent echocardiographic examinations at baseline(T1),after completion of 4 cycles(T2),and 6 cycles(T3)of chemotherapy.Left ventricular strain,left ventricular myocardial work,right ventricular strain,and ejection fraction were further analyzed.Results Compared with T1,both T2 and T3 showed a decrease in left ventricular ejection fraction(LVEF),(T1,T2,and T3 were[67.3±2.7]％,[63.0±2.9]％and[61.3±3.2]％,P＜0.05).T3 showed a decrease in right ventricular ejection fraction(RVEF),([59.3±7.8]％vs[43.7±6.6]％,P＜0.05),while T2 showed no significant change in RVEF.Both right ventricular global longitudinal strain(RVGLS),(T1,T2,and T3 were[-25.7±5.7]％,[-22.4±5.3]％and[-19.1±3.6]％,respectively;P＜0.05)and right ventricular free-wall longitudinal strain(RVFWLS),(T1,T2,and T3 were[-20.9±4.7]％,[-18.9±4.1]％and[-16.1±3.9]％,P＜0.05)decreased in all three time points.The global work index(GWI)was lower in T2 and T3 than in T1(P＜0.05),while the global constructive work(GCW),global wasted work(GWW),and global work efficiency(GWE)did not show significant changes.Conclusions Combination of trastuzumab,immune checkpoint inhibitors,and chemotherapy has an impact on left ventricular strain,LVEF,and right ventricular strain,as well as GWI,in HER2-positive patients with gastric adenocarcinoma.Left ventricular global longitudinal strain(LVGLS),RVFWLS,and RVGLS can more sensitively monitor cardiac function and detect cardiac dysfunction related to cancer treatment in a timely manner.

Objective To construct and validate a risk prediction model for poor inhalation in chronic obstructive pulmonary disease(COPD)patients receiving inhaler therapy,providing a decision support tool for personalized prevention of poor inhalation.Methods A cross-sectional study was conducted to collect data related to COPD patients receiving inhaler therapy,forming a dataset.The dataset was randomly divided into a training set and a test set in a ratio of 4∶1.Four different methods for missing value imputation,3 methods for variable feature selection,and 18 machine learning algorithms were employed to successfully construct 216 models on the training set.The monte carlo simulation method was used for resampling in the test set to validate the models,with the area under curve(AUC),accuracy,precision,recall,and F1 score used to evaluate model performance.The optimal model was selected to build the poor inhalation prediction platform.Results A study involving 308 patients with COPD found that 135(43.8%)were at risk of adverse inhalation.Using 33 predictor variables,216 risk prediction models were developed.Of these models,the ensemble learning algorithm yielded the highest average AUC of 0.844,with a standard deviation of 0.058[95%CI=(0.843,0.845)].The differences in predictive performance among the 216 models were statistically significant(P＜0.01).Under the ensemble learning algorithm,adherence to inhaler use(38.087 4%),inhaler satisfaction(25.680 1%),literacy(24.031 3%),number of inhalers(5.482 3%),age(4.204 5%)and number of acute exacerbations in the past year(2.184 7%)contributed most to the predictive model.The model exhibited superior performance,with an AUC of 0.869 3,an accuracy of 83.87%,a precision of 86.96%,a recall of 74.07%,and an F1 score of 0.8.Conclusion This study has developed a predictive model for poor inhalation risk in COPD inhaler therapy patients using machine learning algorithms,which exhibits strong predictive capabilities and holds potential clinical application value.

Acceleration of tooth movement during orthodontic treatment is challenging,with osteoclast-mediated bone resorption on the compressive side being the rate-limiting step.Recent studies have demonstrated that mechanoreceptors on the surface of monocytes/macrophages,especially adhesion G protein-coupled receptors(aGPCRs),play important roles in force sensing.However,its role in the regulation of osteoclast differentiation remains unclear.Herein,through single-cell analysis,we revealed that CD97,a novel mechanosensitive aGPCR,was expressed in macrophages.Compression upregulated CD97 expression and inhibited osteoclast differentiation;while knockdown of CD97 partially rescued osteoclast differentiation.It suggests that CD97 may be an important mechanosensitive receptor during osteoclast differentiation.RNA sequencing analysis showed that the Rap1a/ERK signalling pathway mediates the effects of CD97 on osteoclast differentiation under compression.Consistently,we clarified that administration of the Rap1a inhibitor GGTI298 increased osteoclast activity,thereby accelerating tooth movement.In conclusion,our results indicate that CD97 suppresses osteoclast differentiation through the Rap1a/ERK signalling pathway under orthodontic compressive force.

Background::A phase II trial on recombinant human tenecteplase tissue-type plasminogen activator (rhTNK-tPA) has previously shown its preliminary efficacy in ST elevation myocardial infarction (STEMI) patients. This study was designed as a pivotal postmarketing trial to compare its efficacy and safety with rrecombinant human tissue-type plasminogen activator alteplase (rt-PA) in Chinese patients with STEMI.Methods::In this multicenter, randomized, open-label, non-inferiority trial, patients with acute STEMI were randomly assigned (1:1) to receive an intravenous bolus of 16 mg rhTNK-tPA or an intravenous bolus of 8 mg rt-PA followed by an infusion of 42 mg in 90 min. The primary endpoint was recanalization defined by thrombolysis in myocardial infarction (TIMI) flow grade 2 or 3. The secondary endpoint was clinically justified recanalization. Other endpoints included 30-day major adverse cardiovascular and cerebrovascular events (MACCEs) and safety endpoints.Results::From July 2016 to September 2019, 767 eligible patients were randomly assigned to receive rhTNK-tPA ( n = 384) or rt-PA ( n = 383). Among them, 369 patients had coronary angiography data on TIMI flow, and 711 patients had data on clinically justified recanalization. Both used a –15% difference as the non-inferiority efficacy margin. In comparison to rt-PA, both the proportion of patients with TIMI grade 2 or 3 flow (78.3% [148/189] vs. 81.7% [147/180]; differences: –3.4%; 95% confidence interval [CI]: –11.5%, 4.8%) and clinically justified recanalization (85.4% [305/357] vs. 85.9% [304/354]; difference: –0.5%; 95% CI: –5.6%, 4.7%) in the rhTNK-tPA group were non-inferior. The occurrence of 30-day MACCEs (10.2% [39/384] vs. 11.0% [42/383]; hazard ratio: 0.96; 95% CI: 0.61, 1.50) did not differ significantly between groups. No safety outcomes significantly differed between groups. Conclusion::rhTNK-tPA was non-inferior to rt-PA in the effect of improving recanalization of the infarct-related artery, a validated surrogate of clinical outcomes, among Chinese patients with acute STEMI.Trial registration::www.ClinicalTrials.gov (No. NCT02835534).

【Objective】 To investigate and analyze the current situation of blood donors’ complaints in Changsha Blood Center, find out the reasons and characteristics of the complaints, aimed at improving the satisfaction of blood donors and the quality of blood donation service. 【Methods】 The healthcare complaint analysis tool (HCAT) was used to encode and statistically analyze the complaints against our center from 2020 to 2022, and then a three-level framework for complaint management classification was constructed. 【Results】 Blood donors had relatively more appeals to the management of primary classification, accounting for 61.77%(126/204). For secondary classification, complaints mainly focused on the working system and process, accounting for 24.02%(49/204), and the problems related to policies and regulations such as free blood use and voluntary blood donation incentive mechanism, accounting for 22.55%(46/204), and the problems related to environment and facilities such as the adjustment of blood donation centers and blood donation time was not announced timely and not updated synchronously on the Baidu map, accounting for 15.2%(31/204). 【Conclusion】 In response to the demands of blood donors, blood centers should optimize the working process and improve the service model of " Internet + voluntary blood donation" and the service awareness of the staff. Further more, the complaint process should be gradually improved to solve the demands of blood donors in time.

Objective To explore the left and right ventricular myocardial strain and dyssynchrony in patients with Micra AV leadless pacing implantation,and to further analyze the impact of implantation site on myocardial strain and dyssynchrony.Methods A retrospective study was conducted on 43 patients with Micra AV implantation and 20 patients with high-degree atrioventricular block(Ⅱdegree typeⅡandⅢdegree atrioventricular block)at the Department of Cardiology,Zhongshan Hospital from April 2023 to December 2023.The demographic information and clinical characteristics of the patients were collected.Echocardiography and speckle tracking imaging techniques were used to obtain conventional echocardiographic parameters,myocardial strain,and dyssynchrony indices of patients in the two groups,including global longitudinal strain(GLS),free wall longitudinal strain(FWLS),peak strain dispersion(PSD)of 18 left ventricular segments,PSD of 6 right ventricular segments,and other indices.According to the implantation location of Micra AV,the patients were further divided into middle group(right ventricular septum),high group(right ventricular inflow tract),and low group(apical region),and the differences in myocardial strain and dyssynchrony indices among the three subgroups were compared.Results The left ventricular GLS(LVGLS),right ventricular GLS(RVGLS),and right ventricular FWLS(RVFWLS)of the Micra AV group were significantly lower than those of the conduction block group(P＜0.001),and the right ventricular dyssynchrony of the Micra AV group was significantly higher than that of the conduction block group(P＜0.05).Comparison of myocardial strain and dyssynchrony at different implantation sites showed that the LVGLS of the high implantation group was significantly higher than that of the middle and low implantation groups,and the left ventricular dyssynchrony index Yu was significantly lower than that of the middle group(P＜0.05);the right ventricular ejection fraction(RVEF)of the low implantation group was significantly lower than that of the high group,and the right ventricular 6-segment PSD was significantly higher than that of the middle and high implantation groups(P＜0.05).Conclusions Compared with patients with high-degree atrioventricular block,patients with Micra AV leadless pacing have reduced left and right ventricular strain,and the implantation of low position had greater effect.

Objective:To investigate the effectiveness and safety of ultrasound-guided endovascular therapy for autogenous arteriovenous fistula (AVF) thrombosis.Methods:It was a single-center retrospective cohort study. Data of patients undergoing ultrasound-guided intravascular therapy due to AVF thrombosis in the First Hospital of Hebei Medical University from August 2018 to June 2021 were analyzed. According to different surgical procedures, the patients were divided into two groups. Patients treated with percutaneous transluminal angioplasty (PTA) + drilling thrombectomy were in group A, and patients treated with PTA only were in group B. After 1 year of follow-up, the surgical technique success rate, primary patency rate, secondary patency rate and complications were compared between the two groups.Results:A total of 152 patients were enrolled, including 74 in group A and 78 in group B. There were no significant differences in gender, age, proportion of patients with diabetes and hypertension, and thrombosis time of AVF between the two groups (all P>0.05). Compared with group B, the diameter and length of thrombus in group A were larger [13.0(9.0, 16.0) mm vs. 6.0(5.0, 6.5) mm, Z=-9.362, P<0.001; 12(8, 15) cm vs. 3(3, 4) cm, Z=-10.061, P<0.001], and the establishment time of AVF was longer [5(2, 7) years vs. 2(1, 5) years, Z=-2.698, P=0.007]. Among the overall patients, the success rate of surgery was 96.7% (147/152), and the success rate of surgery was 95.9% (71/74) in group A and 97.4% (76/78) in group B respectively, with no statistical difference ( χ2=0.004, P=0.952). Kaplan-Meier survival analysis showed that, overall, the primary patency rate at 3rd, 6th and 12th month after operation was 87.1%, 71.4% and 56.6%, and the secondary patency rate was 97.1%, 96.4% and 94.1%, respectively. The primary patency rate of group A at 3rd, 6th and 12th month was 82.4%, 66.7% and 53.6%, and the secondary patency rate was 95.7%, 94.2% and 89.7%, respectively. The primary patency rate of group B at 3rd, 6th and 12th month was 91.5%, 73.2% and 59.7%, and the secondary patency rate was 98.6%, 98.6% and 98.5%, respectively. There was no significant difference in the primary and secondary patency rate between group A and group B at 3rd, 6th and 12th month (all P>0.05). The duration of operation in group A was longer than that in group B [2.0(1.9, 2.0) h vs. 2.0(1.0, 2.0) h, Z=-5.181, P<0.001], but no serious complications occurred in both groups. Conclusion:The two surgical methods are effective, safe and reliable in the treatment of AVF thrombosis, and have high clinical application value.

Objective To investigate the effect of circular RNA(circRNA)ACAP2 on myocardial injury in MI rats by regulating the miR-421/B cell translocation gene 2(BTG2)axis.Methods A rat MI model and an H9c2 myocardial cell model were constructed.A total of 80 rats were divided into sham operation group,MI group,small interfering RNA-negative control(si-NC)group,si-circACAP2 group,overexpression control(pcDNA3.1)group,pCDNA3.1-circACAP2 group,pCDNA3.1-circACAP2+mimic NC group,and pCDNA3.1-circACAP2+miR-421 mimic group,with 10 rats in each group.H9c2 cells were divided into hypoxia group,hypoxia+si-NC group,hypoxia+si-circACAP2 group,hypoxia+pcDNA3.1 group,hypoxia+pcDNA3.1 circACAP2 group,hypoxia+pcDNA3.1 circACAP2+mimic NC group,hypoxia+pcDNA3.1 circACAP2+miR-421 mimic group,and control group.LVEF,LVFS,myocardial infarction,pathological chan-ges of myocardial tissue,and circACAP2,miR-421 and BTG2 mRNA expression,LDH,CK-MB activity,H9c2 cardiomyocyte viability and apoptosis,BTG2 protein expression in myocardial tis-sue,and BTG2 protein expression in H9c2 cardiomyocytes were detected in each group.Results Compared with the sham operation group,higher mRNA levels of circACAP2(1.84±0.21 vs 1.00±0.10)and BTG2(1.68±0.17 vs 1.00±0.10),larger infarct size,stronger activities of CK-MB and LDH,while decreased expression of miR-421(0.49±0.05 vs 1.00±0.11)and LVFS and LVEF values were observed in the MI group(P＜0.05).Compared with the si-NC group,the si-circACAP2 group had alleviated myocardial injury,increased LVFS and LVEF values,and decreased infarct size and CK-MB and LDH activities(P＜0.05).Significantly increased cell via-bility,and reduced apoptotic rate and CK-MB and LDH activities were observed in the hypoxia+si-circACAP2 group than the hypoxia+si-NC group(P＜0.05).Compared with the pcDNA3.1 group,myocardial injury was aggravated,LVFS and LVEF were decreased,and infarct size and CK-MB and LDH activities were increased in the pcDNA3.1-circACAP2 group(P＜0.05);Com-pared with the hypoxia+pcDNA3.1 group,the hypoxia+PCDNA3.1-circACAP2 group signifi-cantly decreased cell viability,and enhanced apoptotic rate and CK-MB and LDH activities(P＜0.05).Conclusion circACAP2 is up-regulated in MI rats and H9c2 cells,and silencing circACAP2 may improve cardiac function,reduce myocardial injury,and increase cardiomyocyte viability by regulating miR-421/BTG2 axis.