Objective To investigate the changes in eosinophil counts and the activation of microglial cells in the brain tissues of mice at different stages of Angiostrongylus cantonensis infection, and to examine the role of microglia in regulating the progression of angiostrongyliasis and unravel the possible molecular mechanisms. Methods Fifty BALB/c mice were randomly divided into the control group and the 7-d, 14-d, 21-day and 25-d infection groups, of 10 mice in each group. All mice in infection groups were infected with 30 stage III A. cantonensis larvae by gavage, and animals in the control group was given an equal amount of physiological saline. Five mice were collected from each of infection groups on days 7, 14, 21 d and 25 d post-infection, and 5 mice were collected from the control group on the day of oral gavage. The general and focal functional impairment was scored using the Clark scoring method to assess the degree of mouse neurological impairment. Five mice from each of infection groups were sacrificed on days 7, 14, 21 d and 25 d post-infection, and 5 mice from the control group were sacrificed on the day of oral gavage. Mouse brain tissues were sampled, and the pathological changes of brain tissues were dynamically observed using hematoxylin and eosin (HE) staining. Immunofluorescence staining with eosinophilic cationic protein (ECP) and ionized calcium binding adaptor molecule 1 (Iba1) was used to assess the degree of eosinophil infiltration and the counts of microglial cells in mouse brain tissues in each group, and the morphological parameters of microglial cells (skeleton analysis and fractal analysis) were quantified by using Image J software to determine the morphological changes of microglial cells. In addition, the expression of M1 microglia markers Fcγ receptor III (Fcgr3), Fcγ receptor IIb (Fcgr2b) and CD86 antigen (Cd86), M2 microglia markers Arginase 1 (Arg1), macrophage mannose receptor C-type 1 (Mrc1), chitinase-like 3 (Chil3), and phagocytosis genes myeloid cell triggering receptor expressed on myeloid cells 2 (Trem2), CD68 antigen (Cd68), and apolipoprotein E (Apoe) was quantified using real-time quantitative reverse transcription PCR (RT-qPCR) assay in the mouse cerebral cortex of mice post-infection. Results A large number of A. cantonensis larvae were seen on the mouse meninges surface post-infection, and many neuronal nuclei were crumpled and deeply stained, with a large number of bleeding points in the meninges. The median Clark scores of mouse general functional impairment were 0 (interquartile range, 0), 0 (interquartile range, 0.5), 6 (interquartile range, 1.0), 14 (interquartile range, 8.5) points and 20 (interquartile range, 9.0) points in the control group and the 7-d, 14-d, 21-d and 25-d groups, respectively (H = 22.45, P < 0.01), and the median Clark scores of mouse focal functional impairment were 0 (interquartile range, 0), 2 (interquartile range, 2.5), 7 (interquartile range, 3.0), 18 (interquartile range, 5.0) points and 25 (interquartile range, 6.5) points in the control group and the 7-d, 14-d, 21-d and 25-d groups, respectively (H = 22.72, P < 0.01). The mean scores of mice general and focal functional impairment were all higher in the infection groups than in the control group (all P values < 0.05). Immunofluorescence staining showed a significant difference in the eosinophil counts in mouse brain tissues among the five groups (F = 40.05, P < 0.000 1), and the eosinophil counts were significantly higher in mouse brain tissues in the 14-d (3.08 ± 0.78) and 21-d infection groups (5.97 ± 1.37) than in the control group (1.00 ± 0.28) (both P values < 0.05). Semi-quantitative analysis of microglia immunofluorescence showed a significant difference in the counts of microglial cells among the five groups (F = 17.66, P < 0.000 1), and higher Iba1 levels were detected in mouse brain tissues in 14-d (5.75 ± 1.28), 21-d (6.23 ± 1.89) and 25-d infection groups (3.70 ± 1.30) than in the control group (1.00 ± 0.30) (all P values < 0.05). Skeleton and fractal analyses showed that the branch length [(162.04 ± 34.10) μm vs. (395.37 ± 64.11) μm; t = 5.566, P < 0.05] and fractal dimension of microglial cells (1.30 ± 0.01 vs. 1.41 ± 0.03; t = 5.266, P < 0.05) were reduced in mouse brain tissues in the 21-d infection group relative to the control group. In addition, there were significant differences among the 5 groups in terms of M1 and M2 microglia markers Fcgr3 (F = 48.34, P < 0.05), Fcgr2b (F = 55.46, P < 0.05), Cd86 (F = 24.44, P < 0.05), Arg1 (F = 31.18, P < 0.05), Mrc1 (F = 15.42, P < 0.05) and Chil3 (F = 24.41, P < 0.05), as well as phagocytosis markers Trem2 (F = 21.19, P < 0.05), Cd68 (F = 43.95, P < 0.05) and Apoe (F = 7.12, P < 0.05) in mice brain tissues. Conclusions A. cantonensis infections may induce severe pathological injuries in mouse brain tissues that are characterized by massive eosinophil infiltration and persistent activation of microglia cells, thereby resulting in progressive deterioration of neurological functions.

Objective:Preliminary explore the safety and efficacy of using only vitamin K antagonists without antiplatelet therapy after left ventricular assist devices (LVAD) implantation.Methods:This is a cohort study. Patients who underwent HeartCon LVAD implantation in TEDA International Cardiovascular Hospital from September 2020 to September 2022 were included. Oral warfarin sodium was given on postoperative days 1 to 2, with the target international standardized ratio (INR) of 2.0 to 2.5. Follow-up until September 2022, survival, INR level and occurrence of bleeding and thrombosis were recorded. Survival analysis was performed by the Kaplan-Meier method (censored for heart transplantation).Results:A total of 22 patients, including 16 male patients (72.7%), aged (51.0±13.3) years, were included. The duration of HeartCon LVAD support was (458±166) days and the INR during support was 2.28±0.26. One patient underwent the heart transplant at 307 d after implantation. One patient (4.5%) occured cardiac tamponade, two patients (9.1%) occured hemorrhagic stroke, five patients (22.7%) occured gastrointestinal bleeding, four patients (18.2%) occured gingival hemorrhage, two patients (9.1%) occured epistaxis, one patient (4.5%) occurred ischemic stroke, one patient (4.5%) occured pump thrombosis, and one patient (4.5%) occured aortic valve thrombosis. The survival rates were 100%, 95%, 95%, and 95% at 3 months, 6 months, 1 year, 2 years after implantation respectively.Conclusion:The single antithrombotic strategy using warfarin (target INR 2.0-2.5) without antiplatelet for patients with implantations of HeartCon type LVAD may be safe and effective.

For a long time, macrolides have been the first choice for the antibacterial treatment for pertussis.However, in the past decade, resistance to macrolide antimicrobials has been common in clinically isolated Bordetella pertussis in China, which is in contradiction with the recommended macrolide treatment.Therefore, Trimethoprim-Sulfamethoxazole (TMP-SMZ) is suggested as the first choice for antibacterial treatment for pertussis in China, with a dosage determined according to age and body weight, lasting 14 days.If TMP-SMZ cannot be used, full-dose and full-course β-lactam antimicrobials may be used, of which the effects should be assessed carefully.The impact of other antibacterial drugs, such as quinolones and tetracyclines, on the elimination of Bordetella pertussis should also be evaluated as soon as possible to treat adult pertussis and potential cases caused by drug-resistant bacteria in future.

Objective:To determine the erythromycin resistance of Bordetella pertussis isolates and their ptxP1 and ptxP3 phenotypic composition and compare clinical manifestations of children with pertussis caused by the two types of strains. Methods:This was a cross-sectional study, the pertussis cases diagnosed using bacterial culture from January 2019 to December 2022 in Beijing Children′s Hospital and the First People′s Hospital of Wuhu were collected.Any suspected Bordetella pertussis colonies were identified by the slide agglutination test.The susceptibility of isolates to erythromycin was detected by the E-test and K-B test.The ptxP gene was amplified by polymerase chain reaction and sequenced to determine its genotype. t-test, Mann-Whitney U-test, Chi-square test and Fisher′s exact test were use to statistical analysis. Results:A total of 192 strains of Bordetella pertussis were identified, including 188 (97.9%) erythromycin-resistant strains.Among the 188 strains, 30.3%(57/188) belonged to the ptxP1 genotype and 69.7%(131/188) belonged to the ptxP3 genotype.In children aged below 1 year old, the incidence of paroxysmal cough caused by infection with the ptxP3 strain was higher than that with the ptxP1 strain (57.1% vs.29.4%, P<0.05), and children infected with the ptxP3 strain were more likely to develop apnea or asphyxia (23.8% vs.17.6%), post-tussive vomiting (44.4% vs.32.4%), whooping cough (72.0% vs.50.0%) and pneumonia or bronchitis (85.7% vs.73.5%) compared to those infected with the ptxP1 strain, but the differences were not statistically significant(all P>0.05). In children aged 1 year old and above, the white blood cell count of children infected with the ptxP1 strain was higher than that of infections with the ptxP3 strain [13.5(9.9, 24.5)×10 9/L, 10.3 (7.0, 16.4)×10 9/L, P<0.05], and children infected with the ptxP1 strain were more likely to contract other pathogen infections than those infected with the ptxP3 strain (17.4% vs.4.4%, P>0.05). Conclusions:ptxP3 erythromycin-resistant Bordetella pertussis has become the main pathogen of pertussis.Infants with pertussis caused by the ptxP3 erythromycin-resistant strain show more significant manifestations and a higher possibility of severe symptoms than those infected with the ptxP1 erythromycin-resistant strain.

Objective:To assess respondents' understanding of the items in the Neck Dissection Impairment Index (NDII) through cognitive interviews and to revise the items accordingly.Methods:Totally 30 postoperative neck dissection patients returning for follow-up at Department of Otolaryngology-Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University from November 2023 to February 2024, were selected by purposive sampling for two rounds of cognitive interviews. Based on the interview results, the Chinese version of the NDII was revised.Results:The Chinese version of the NDII included ten items. The first round of interviews identified issues such as "incomplete expression, abstract language, and written form, " leading to revisions of five items. The second round of interviews showed that all respondents understood the revised items, and no new suggestions for modification were made.Conclusions:Cognitive interviews can improve respondents' comprehension of the Chinese version of the NDII, identify cognitive biases caused by cultural differences and improper linguistic expressions during the translation process, and enhance the understanding and acceptance of the scale's content among the target population.

Research into human drug metabolism,liver disease modeling as well as drug screening heavily depend on cell cultures for in vitro validation and experimental animal models for in vivo analysis.However,these methods are not without limitations.Cell stability is often compromised in vitro,and the species-specific differences between experimental animals and humans restrict the accuracy of these models in replicating in vivo drug metabolism and the pathophysiological features of human liver diseases.Humanized liver chimeric mouse models,developed through the transplantation and expan-sion of human liver cells into the livers of live mice,replicate the specific functionalities of the human liver.This replication is instrumental in fulfilling a variety of research objectives,including the replication of hepatitis viruses within mice,the modeling of liver metabolic disorders,the screening of liver cell-targeted therapeutic agents,and the evaluation of drug-induced hepatotoxicity.As such,these models are regarded as optimal for the preclinical validation of drug efficacy and safety assessment.This paper presents a comprehensive review and a vision of three representative humanized liver chimeric mouse models in terms of classification,construction principles,limitations,and current applications,thereby offering reference for the selection of appropriate models in research.

BACKGROUND: China bears the biggest atrial fibrillation (AF) burden in the world. However, little is known about the incidence and predictors of AF. This study aimed to investigate the current incidence of AF and its electrocardiographic (ECG) predictors in general community individuals aged over 60 years in China. METHODS: This was a prospective cohort study, recruiting subjects who were aged over 60 years and underwent annual health checkups from April to July 2015 in four community health centers in Songjiang District, Shanghai, China. The subjects were then followed up from 2015 to 2019 annually. Data on sociodemographic characteristics, medical history, and the resting 12-lead ECG were collected. Kaplan-Meier curve was used for showing the trends in AF incidence and calculating the predictors of AF. Associations of ECG abnormalities and AF incidence were examined using Cox proportional hazard models. RESULTS: This study recruited 18,738 subjects, and 351 (1.87%) developed AF. The overall incidence rate of AF was 5.2/1000 person-years during an observation period of 67,704 person-years. Multivariable Cox regression analysis indicated age (hazard ratio [HR], 1.07; 95% confidence interval [CI]: 1.06-1.09; P < 0.001), male (HR, 1.30; 95% CI: 1.05-1.62; P = 0.018), a history of hypertension (HR, 1.55; 95% CI: 1.23-1.95; P < 0.001), a history of cardiac diseases (HR, 3.23; 95% CI: 2.34-4.45; P < 0.001), atrial premature complex (APC) (HR, 2.82; 95% CI: 2.17-3.68; P < 0.001), atrial flutter (HR, 18.68; 95% CI: 7.37-47.31; P < 0.001), junctional premature complex (JPC) (HR, 3.57; 95% CI: 1.59-8.02; P = 0.002), junctional rhythm (HR, 18.24; 95% CI: 5.83-57.07; P < 0.001), ventricular premature complex (VPC) (HR, 1.76; 95% CI: 1.13-2.75, P = 0.012), short PR interval (HR, 5.49; 95% CI: 1.36-22.19; P = 0.017), right atrial enlargement (HR, 6.22; 95% CI: 1.54-25.14; P = 0.010), and pacing rhythm (HR, 3.99; 95% CI: 1.57-10.14; P = 0.004) were independently associated with the incidence of AF. CONCLUSIONS The present incidence of AF was 5.2/1000 person-years in the studied population aged over 60 years in China. Among various ECG abnormalities, only APC, atrial flutter, JPC, junctional rhythm, short PR interval, VPC, right atrial enlargement, and pacing rhythm were independently associated with AF incidence.
Humans ; Male ; Middle Aged ; Aged ; Atrial Fibrillation/epidemiology* ; Prospective Studies ; Incidence ; Atrial Flutter/complications* ; Risk Factors ; China/epidemiology* ; Electrocardiography

Objective To investigate the safety and efficacy of endoscopic thyroid surgery through axillary approach in the treatment of unilateral papillary thyroid carcinoma.Methods A total of 135 patients admitted to Yunnan Cancer Hospital from April 2022 to November 2022 were selected.According to the surgical method,69 patients were in the endoscopic group and 66 patients were in the open surgery group.The clinical data,operation time,intraoperative blood loss,postoperative drainage volume,postoperative hospitalization stay,complications,cosmetic satisfaction,scar evaluation,postoperative swallowing pain and blood calcium,blood phosphorus,PTH levels of the two groups were observed.Results There were no significant differences in general data,pathological features,number of lymph node dissection,and perioperative complications between the two groups(P>0.05).The operation time and postoperative drainage volume in the endoscopic group were significantly higher than those in the open surgery group.The intraoperative blood loss,postoperative hospital stay,pain score,serum calcium,serum phosphorus,PTH levels and cosmetic satisfaction in the endoscopic group were significantly better than those in the open group(P<0.05).Conclusion Transaxillary approach endoscopic thyroid surgery for the treatment of single-sided papillary thyroid carcinoma is safe,feasible,and provides better protection of the parathyroid glands,postoperative swallowing pain,and cosmetic satisfaction.

Objective:To analyze the characteristics of nerve injury in patients with diabetic peripheral neuropathy (DPN) and explore the diagnostic value of current perception threshold (CPT) and nerve conduction velocity (NCV) for DPN.Methods:One hundred and thirty-six DPN patients admitted to Beijing Puren Hospital from June 2017 to December 2019 were selected, and 130 diabetic non-DPN patients admitted during the same period were used as controls. All the subjects were tested by CPT and NCV. Among them, the detection of NCV included sensory nerve conduction velocity (SCV) and motor nerve conduction velocity (MCV). Statistical analysis was performed on the relevant indicators of the two groups of subjects.Results:The CPT values of the upper limb median nerve and ulnar nerve at 2 000 Hz, 250 Hz, and 5 Hz, the superficial peroneal nerves at 250 Hz, and 5 Hz, and the CPT values of the sural nerve at 2 000 Hz and 250 Hz were higher than those of non-DPN patients, DPN injury mainly occurred in myelinated nerve fibers in the lower extremities [60.29%(82/136)], and the difference were statistically significant ( P<0.05). The SCV and MCV of the median nerve, ulnar nerve, and common peroneal nerve in the DPN group were lower than those in the non-DPN group, the SCV abnormal rate was higher than the MCV: 55.88%(76/136) vs. 37.50%(51/136); 58.82%(80/136) vs. 41.18% (56/136); 67.65%(92/136) vs. 50.00%(68/136), and the differences were statistically significant ( P<0.05). The area under the predictive value curve (AUC) of CPT for DPN was 0.815 (95% CI 0.735 ~ 0.895). The AUC of NCV for DPN was 0.875 (95% CI 0.813 ~ 0.944). The AUC of CPT and NCV for DPN was 0.923 (95% CI 0.876 ~ 0.970). Conclusions:DPT patients have abnormal CPT and NCV, and nerve damage occurs mostly in myelinated nerve fibers and SCV. Diagnosing DPN by combining CPT and NCV is helpful to improve the detection rate of DPN.

Objective:To investigate the predictive value of MRI radiomics model in assessing the early response to concurrent chemoradiotherapy for locally advanced cervical squamous cell carcinoma.Methods:A total of 367 patients with pathologically proven locally advanced cervical squamous cell carcinoma (International Federation of Gynecology and Obstetrics stage ⅡB-ⅣA) in Liaoning Cancer Hospital & Institute from January 2013 to June 2019 were retrospectively collected. The patients were unable to undergo surgery and received complete concurrent chemoradiotherapy. Pelvic plain MRI, DWI and dynamic contrast-enhanced MRI were performed within 2 weeks before treatment and at the end of the 4th week of treatment. Patients were divided into complete response (CR) group ( n=247) and non-CR group ( n=120) according to response evaluation criteria in solid tumors 1.1. The patients were divided into a training set ( n=256) and a validation set (n=111) via a randomized split method at a ratio of 7∶3. Two radiologists drew the region of interest on the DWI, T 2WI and contrast-enhanced T 1WI (delayed phase) images before treatment to form the volume of interest finally. Totally 1 906 radiomics features were extracted from 3 single sequence images, respectively. Feature correlation analysis and tree model were used for feature selection. Three classifier learning algorithms, namely logistic regression (LR), support vector machine and random forest, were used for machine learning and the best classifier was selected. Based on the best classifier, 3 single sequence radiomics models were built, and a multi-sequence combined model was obtained by multivariate LR analysis. The differences in the area under the receiver operating characteristic curve (AUC) of the 3 single sequence models and the multi-sequence combined model were compared by DeLong test. The clinical application value of the multi-sequence combined model was evaluated by decision analysis curve. Results:In the training set and validation set, the LR classifier model had the best performance. Based on the LR classifier, AUCs of DWI, T 2WI, contrast-enhanced T 1WI and combined sequences in the training set were 0.77, 0.74, 0.79 and 0.86, respectively, and AUCs in the validation set were 0.71, 0.66, 0.75 and 0.77, respectively. In the training set, the AUC of multi-sequence combined model was higher than those of DWI, T 2WI and contrast-enhanced T 1WI sequence models, and the differences were statistically significant ( Z=3.01, 3.56, 2.83; P=0.003, 0.001, 0.005). In the validation set, the AUC of multi-sequence combined model and T 2WI model had significant difference ( Z=2.46, P=0.015). The decision analysis curve showed that when the threshold probability was in the range of 0.44 to 0.88, the multi-sequence combined model yielded a net benefit. Conclusion:Based on the LR classifier, the combined model built by radiomics features of multi-sequence MRI images has predictive value for assessing the early response of concurrent chemoradiotherapy for locally advanced cervical squamous cell carcinoma.