Objective:To explore the impact of CACNA1C rs58619945 genotype on the cortical thickness of attentional networks in patients with Bipolar 1 disorder type (BD-Ⅰ). Methods:From August 2013 and August 2019, a total of 155 BD-Ⅰ patients were recruited from the outpatient and inpatient Departments of the Affiliated Brain Hospital of Guangzhou Medical University, along with 82 healthy controls (HC) from the community and university. Genotype for the CACNA1C rs58619945 locus was determined for all BD-I patients and HC subjects, followed by 3.0 T magnetic resonance imaging scans to measure the cortical thickness in the alert, orienting, and executive control subnetworks. General linear models (GLMs) were used to evaluate the impact of CACNA1C rs58619945 on the cortical thickness of attentional networks. Concurrently, attentional dimension functions were assessed using repeatable battery for the assessment of neuropsychological status (RBANS) and Cambridge neuropsychological test automated battery rapid visual information processing (CANTAB RVP) test. This study was approved by the Medical Ethics Committee of the Affiliated Brain Hospital of Guangzhou Medical University(Ethics No. 2023-056). Results:Compared with the HC group, the BD-Ⅰ patients had shown reduced thickness in bilateral prefrontal cortex, bilateral posterior cingulate cortex, and bilateral superior temporal cortex( P<0.05). A significant interaction between the CACNA1C genotype and the cortical thickness(HC vs.BD) of right prefrontal cortex, right posterior parietal cortex and right superior temporal cortex was noted( P<0.05). Partial correlation analysis has demonstrated a significant correlation between CANTAB RVP and RBANS attention indices and cortical thickness in the right prefrontal cortex, right posterior cingulate cortex( P<0.05), and right superior temporal cortex predominantly among carriers of the BD-Ⅰ G allele. Conclusion:The G allele of CACNA1C rs58619945 is associated with cortical thickness of the right prefrontal cortex, right posterior cingulate cortex, and right superior temporal cortex in BD-Ⅰ, which are part of the alerting and orienting network.

Objective To investigate the effect of exosomes derived from Echinococcus multilocularis on macrophage polarization after treatment for different durations and concentrations. Methods A total of 60 BALB/c mice were used for modeling, among which 4 mice were selected to observe the growth of abdominal lesions on 7.0T MRI. The mice for modeling were dissected, and the protoscoleces was taken from the abdominal lesion and cultured in vitro ; ultracentrifugation was used to extract the exosomes from the supernatant, and transmission electron microscopy and Western blotting were used for the characterization of exosomes. The macrophages without exosome treatment were established as control group, and the macrophages co-cultured with different concentrations of exosomes derived from Echinococcus multilocularis were established as experimental group (10 μg/mL group and 50 μg/mL group) and were cultured for 48 and 72 hours. The morphological changes of macrophages were observed under a microscope, and flow cytometry and ELISA were used to observe polarization state. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the least significant difference t -test was used for further comparison between two groups. Results The results of 7.0T MRI showed the formation of diffuse lesions with different sizes in the abdominal cavity of mice, and the exosomes derived from Echinococcus multilocularis were approximately 100 nm in diameter and were cup-shaped or saucer-shaped, with the positive expression of the surface markers CD9, TSG101, and CD63. After co-culture, most of the cells in the experimental group were elongated with an irregular and polygonal shape. Flow cytometry showed that after 48 hours of co-culture, the positive rates of CD16/32, CD206, and CD369 in the control group were 99.53%±0.06%, 90.27%±0.21%, and 2.40%±0.20%, respectively; compared with the control group, except that the 10 μg/mL exosome group had a significant reduction in the positive rate of CD369 (0.80%±0.00%) ( P < 0.05), all the other groups had a significant increase in the positive rates of CD16/32, CD206, and CD369 (all P < 0.000 1); after 72 hours of co-culture, the positive rates of CD16/32, CD206, and CD369 in the control group were 99.67%±0.06%, 85.47%±0.55%, and 6.60%±0.20%, respectively, and compared with the control group, the experimental group had significant increases in the positive rates of CD16/32, CD206, and CD369 (all P < 0.05). ELISA showed that after 48 hours of co-culture, the levels of IL-6 and TNFα in the control group were 58.53±15.52 pg/mL and 320.70±5.30 pg/mL, respectively, and when the exosome concentration was 50 μg/mL, the level of IL-6 in the experimental group was 98.81±15.55 pg/mL, which was higher than that in the control group ( P < 0.05); after 72 hours of co-culture, the levels of IL-6 and TNFα in the control group were 76.22±9.68 pg/mL and 323.90±87.37 pg/mL, respectively, and when the exosome concentration was 10 μg/mL, the level of TNFα was 164.20±14.17 pg/mL, which was significantly lower than that in the control group ( P < 0.05); when the exosome concentration was 50 μg/mL, the level of IL-6 was 99.52±8.35 pg/mL, which was significantly higher than that in the control group ( P < 0.05). Conclusion Exosomes derived from Echinococcus multilocularis can regulate macrophage polarization and induce M2-like polarization of macrophages after co-culture at a concentration of 10 μg /mL for 72 hours, and further studies are needed to clarify the specific method.

Objective:To investigate the risk factors and establish a prediction model of primary non-response (PNR) to anti-tumor necrosis factor-α(TNF-α) monoclonal antibody in Crohn′s disease (CD) patients.Methods:From December 1, 2018 to July 31, 2022, 103 patients with CD treated with the anti-TNF-α monoclonal antibody in Renmin Hospital of Wuhan University were enrolled (modeling group), and at the same time, 109 patients with CD treated with anti-TNF-α monoclonal antibody in Zhongnan Hospital of Wuhan University were selected (validation group). The baseline clinical data of all the patients before the first treatment of anti-TNF-α monoclonal antibody were collected, which included C-reactive protein (CRP), the simplified Crohn′s disease activity index (CDAI), and modified multiplier simple endoscopic score for Crohn′s disease (MM-SES-CD), etc. Multivariate logistic regression was used to screen the independent risk factors of PNR in patients with CD treated with the anti-TNF-α monoclonal antibody, and to establish the nomograms prediction model. The area under the curve (AUC) of the receiver operating characteristic curve (ROC), the net reclassification index (NRI), integrated discrimination improvement index (IDI), and decision curve analysis (DCA) were used to evaluate the predictive efficacy and clinical application value of the prediction model. DeLong test was used for statistical analysis.Results:The results of multivariate logistic regression analysis showed that high level of CRP ( OR=1.030, 95% confidence interval (95% CI) 1.002 to 1.059), simplified CDAI ( OR=1.399, 95% CI 1.023 to 1.913), and MM-SES-CD ( OR=1.100, 95% CI 1.025 to 1.181) in baseline were independent risk factors of PNR in patients with CD treated with the anti-TNF-α monoclonal antibody ( P=0.033, 0.036 and 0.008). The results of ROC analysis showed that the AUCs of CRP, simplified CDAI, MM-SES-CD, and the prediction model in the modeling group and the validation group were 0.697(95% CI 0.573 to 0.821), 0.772(95% CI 0.666 to 0.879), 0.819(95% CI 0.725 to 0.912), 0.869 (95% CI 0.786 to 0.951) and 0.856 (95% CI 0.756 to 0.955), respectively. The AUC of the prediction model in the modeling group was greater than those of CRP and simplified CDAI, and the differences were statistically significant ( Z=3.00 and 2.75, P=0.003 and 0.006), while compared with MM-SES-CD and the validation group, the differences were not statistically significant (both P>0.05). However, compared with MM-SES-CD, the NRI and IDI of the prediction model in the modeling group were 0.205(95% CI 0.002 to 0.409, P=0.048) and 0.098(95% CI 0.022 to 0.174, P=0.011), respectively, suggesting that the predictive ability of the prediction model was better than that of MM-SES-CD. The results of DCA indicated that the prediction model had significant clinical benefits in both the modeling group and the validation group. Conclusions:A prediction model was successfully constructed based on the independent risk factors for PNR in patients with CD treated with the anti-TNF-α monoclonal antibody. After verification, the prediction model has good prediction performance and significant clinical benefits.

Alveolar echinococcosis, caused by Echinococcus multilocularis infection, is a highly deadly zoonotic parasitic disease. As a benzimidazole compound, albendazole has a strong and broad-spectrum anti-parasitic action. For alveolar echinococcosis patients that are unwilling to receive surgical treatment, lose the timing for surgery, or are intolerant to surgery due to poor physical status, administration of albendazole may delay disease progression. Recently, a large number of advances have been achieved in experimental studies on alveolar echinococcosis. In order to increase the understanding of the therapeutic efficacy of albendazole for alveolar echinococcosis, this review summarizes the advances in albendazole treatment for alveolar echinococcosis, so as to provide insights into the clinical treatment of alveolar echinococcosis with albendazole.

Virtual reality (VR) is a technology, which can simulate human vision, touch, hearing and other sensory functions, and it synthesizes a computer-generated 3D world to provide immersive experiences.VR technology has the characteristics of interactivity, immersion and imagination, and its application in medical education and simulation training improves the quality and efficiency of learning.At the same time, VR technology also plays a certain role in clinical treatment such as surgery, rehabilitation, psychology, sedation and analgesia.With the development of VR technology, its application in pediatric medicine field is expected to solve some difficulties of pediatric practitioners.For example, the application of virtual standard patient in pediatric training, and VR technology relieving pain and anxiety.

Objective:To explore the long-term effect of endoscopic radiofrequency ablation for the treatment of unresectable ampullary carcinoma.Methods:Clinical data of patients with ampullary carcinoma who received endoscopic radiofrequency ablation in the Third Affiliated Hospital of Naval Medical University from January 2012 to May 2019 were retrospectively collected, including basic information, frequency of radiofrequency ablation, the type of biliary stent, postoperative complications, and follow-up. Kaplan-Meier method was used to analyze the survival of patients after endoscopic radiofrequency ablation. Relationship between frequency of radiofrequency ablation, type of biliary stent and overall survival time was analyzed.Results:A total of 50 patients were enrolled, including 31 males and 19 females, aged 73.0±9.7 years. Twenty-five patients (50.0%) underwent 1 radiofrequency ablation treatment, while 25 patients (50.0%) underwent radiofrequency ablation treatments more than twice. Postoperative complications occurred in 6 patients (12.0%), all of which were mild symptoms. The average follow-up was 22.3 months, with a total of 39 (78.0%) deaths, 5 (10.0%) lost to follow-up, and 6 (12.0%) surviving. The median overall survival time was 16.9 (95% CI: 9.1-24.8) months, with cumulative survival rates of 62.0%, 38.5%, 27.0%, and 12.6% at 1, 2, 3, and 5 years, respectively. The median overall survival time of those treated with radiofrequency ablation ≥2 times showed a trend of prolongation compared to patients treated once, but the difference was not statistically significant [26.7 (95% CI: 9.7-43.7) months VS 12.6 (95% CI: 4.9-20.3) months, χ2=3.049, P=0.081]. Plastic stents were used in 32 patients (64.0%) and metal stents in 18 patients (36.0%). There was no significant difference in median overall survival time between patients using metal and plastic stents [17.1 (95% CI: 6.1-28.0) months VS 15.9 (95% CI: 6.9-24.9) months， χ2=0.029， P=0.865]. Conclusion:Endoscopic radiofrequency ablation is a safe treatment for unresectable ampullary carcinoma, and multiple consecutive treatments may increase the survival benefit.

Objective:To investigate the efficacy of endoscopic stent placement for patients with Bismuth type Ⅳ hilar cholangiocarcinoma.Methods:Data of 229 patients with unresectable Bismuth type Ⅳ hilar cholangiocarcinoma who successfully underwent endoscopic stent placement at the Department of Endoscopy, the Third Affiliated Hospital of Naval Medical University from January 2002 to January 2019 were retrospectively analyzed. Outcomes included clinical success rate, complication incidence, stent patency period and overall survival time. The patency of stents and overall survival time of patients were estimated by using the Kaplan-Meier method. The independent predictors for stent patency and overall survival of patients were analyzed by a multivariate Cox proportional regression model.Results:The overall clinical success rate was 78.2% (179/229). The incidence of early cholangitis after endoscopic retrograde cholangiopancreatography was 20.5% (47/229). The median stent patency and overall survival time were 5.7 (95% CI: 4.8-6.7) months and 5.1 (95% CI: 4.2-6.0) months, respectively. Further multivariate Cox regression analysis showed that metal stent ( P<0.001, HR=0.452, 95% CI: 0.307-0.666) and bilateral stents with bilateral angiography ( P=0.036, HR=0.644, 95% CI: 0.427-0.971) were independent predictors of stent patency; total bilirubin>200 μmol/L ( P=0.001, HR=1.627, 95% CI: 1.208-2.192), metal stent ( P=0.004, HR=0.636, 95% CI: 0.467-0.866) and antitumor therapy ( P<0.001, HR=0.439, 95% CI:0.308-0.626) were independent predictors of overall survival. Conclusion:There is high incidence of cholangitis in patients with unresectable Bismuth type Ⅳ hilar cholangiocarcinoma treated with endoscopic stenting. Longer stent patency can be achieved with metal stent placement and bilateral drainage. In addition, metal stent for drainage and antitumor therapy can also help increase the survival benefit.

Objective:To investigate the level of endogenous hydrogen sulfide (H 2S) in contrast-induced acute kidney injury (CIAKI), as well as the potential role of H 2S against CIAKI by down-regulating NLRP3 inflammasome. Methods:Twenty-four healthy male Sprague-Dawley rats, weighing 180-220 g, were randomly divided into three groups according to the random number table method: control group, CIAKI group (iopromide 2.9 g/kg) and CIAKI+NaHS group (NaHS 4 mg/kg for three days before 2.9 g/kg iopromide injection). Kidneys were collected for whole-genome sequencing and bioinformatic analysis. HE and PAS staining were used for kidney histological examination. TUNEL assays were applied to detect renal tubular epithelial injury. Expressions of NLRP3 inflammasome (NLRP3, ASC and caspase-1) were evaluated by immunofluorescence staining. The role of H 2S in contrast (iopromide 200 mgI/kg)-induced injury on human renal tubular epithelium (HK-2 cells) was investigated, and CCK-8 assay was used to detect cellular viability. Results:Compared with the control group, the expression of endogenous H 2S synthetases-related genes [cystathionine β-synthase ( CBS), cystathionine-γ-lyase ( CSE) and 3-mercaptopyruvate sulfurtransferase ( 3- MST)] was lower in CIAKI group (all P<0.05). The gene expression levels of CBS, CSE and 3- MST were negatively correlated with renal function biomarkers serum creatinine, blood urea nitrogen and cystatin-C (all P<0.05). Compared with the CIAKI group, CIAKI+NaHS group showed alleviated creatinine, blood urea nitrogen and cystatin-C, improved histological changes, reduced apoptosis. Moreover, the expression levels of NLRP3, ASC and caspase-1 in CIAKI+NaHS group were lower than those in CIAKI group (all P<0.05). In HK-2 cells, compared with the contrast group, the cellular viability was higher in the contrast+NaHS group; reducing endogenous H 2S by CBS inhibitor could enhance contrast-induced cell viability ( P<0.05). Conclusions:Injury of endogenous H 2S system is pivotal to CIAKI pathogenesis. Up-regulation of H 2S ameliorates renal injury of CIAKI rats, which may be related to regulation of NLRP3 inflammasome.

Objective:To investigate the infiltration and polarization of macrophages in mice during Chlamydia muridarum ( Cm) respiratory infection. Methods:C57BL/6 mice were intranasally infected with 1×10 3 inclusion-forming units (IFU) of Cm to establish the mouse model of Cm respiratory tract infection. The percentages of CD45 + F4/80 + cells and the macrophages expressing CD86, major histocompatibility complex Ⅱ (MHC), inducible nitric oxide synthase (iNOS) and CD206 were detected by flow cytometry. Expression of iNOS, CD206 and CCL2 at mRNA level was detected by real-time quantitative PCR. Results:Cm respiratory tract infection induced the increase of macrophages in mouse lung tissues. Compared with uninfected group, CD45 + F4/80 + macrophages were increased significantly from day 3 and reached the peak on day 7 after Cm infection. Moreover, the expression of CD86, MHCⅡ and CCL2 was increased, and the macrophages were polarized to M1 phenotype. However, the expression of M2 macrophage marker CD206 was decreased gradually. Further studies showed that iNOS expression, the indicator of M1 macrophage activation, was increased after Cm infection and reached to the top on day 7. Conclusions:Cm respiratory infection could induce the infiltration of macrophages in lung tissues and promote the polarization of macrophages to M1 phenotype.

Objective: To explore the effect of vaccination on viral negative conversion of children with COVID-19. Methods: A retrospective cohort study was conducted. A cohort of 189 children aged 3-14 years with COVID-19 admitted to Renji Hospital (South branch) of Shanghai Jiao Tong University School of Medicine from April 7^th to May 19^th 2022 was enrolled in the study. According to the vaccination status, the infected children were divided into an unvaccinated group and a vaccinated group. Age, gender, severity, clinical manifestations, and laboratory tests, etc. were compared between groups, by rank sum test or chi-square test. The effects of vaccination on viral negative conversion were analyzed by a Cox mixed-effects regression model. Additionally, a questionnaire survey was conducted among the parents of unvaccinated children to analyze the reasons for not being vaccinated. Results: A total of 189 children aged 3-14 years were enrolled, including 95 males (50.3%) and 94 females (49.7%), aged 5.7 (4.1,8.6) years. There were 117 cases (61.9%) in the unvaccinated group and 72 cases (38.1%) in the vaccinated group. The age of the vaccinated group was higher than that of the unvaccinated group (8.8 (6.8, 10.6) vs. 4.5 (3.6, 5.9) years, Z=9.45, P<0.001). No significant differences were found in clinical manifestations, disease severity, and laboratory results between groups (all P>0.05), except for the occurrence rate of cough symptoms, which was significantly higher in the vaccinated group than in the non-vaccinated group (68.1% (49/72) vs. 50.4% (59/117),χ²=5.67, P=0.017). The Kaplan-Meier survival curve and Cox mixed-effects regression model showed that the time to the viral negative conversion was significantly shorter in the vaccinated group compared with the unvaccinated group (8 (7, 10) vs. 11 (9, 12) d, Z=5.20, P<0.001; adjusted HR=2.19 (95%CI 1.62-2.97)). For questionnaire survey on the reasons for not receiving a vaccination, 115 questionnaires were distributed and 112 valid questionnaires (97.4%) were collected. The main reasons for not being vaccinated were that parents thought that their children were not in the range of appropriate age for vaccination (51 cases, 45.5%) and children were in special physical conditions (47 cases, 42.0%). Conclusion: Vaccination can effectively shorten the negative conversion time of children with COVID-19 and targeted programs should be developed to increase eligible children's vaccination rate for SARS-CoV-2 vaccination.
Child ; Female ; Male ; Humans ; COVID-19/prevention & control* ; COVID-19 Vaccines ; Retrospective Studies ; SARS-CoV-2 ; China/epidemiology* ; Vaccines