ObjectiveTo understand the whole genome characteristics and the information for genetic evolution in the two coxsackievirus A2 (CVA2) strains isolated from patients with herpangina in Shanghai, and to provide a scientific basis for the prevention and treatment of herpetic angina. MethodsTwo CAV2 strains isolated from patients with herpetic angina in Shanghai were performed whole genome sequencing and analysis for phylogenetics, nucleotide homology, and evolution. ResultsA phylogenetic analysis of the VP1 region revealed that the two Shanghai strains both belonged to CVA2 genotype D, with the highest homology to OL357660, a strain from Yunnan. The average nucleotide identity (ANI) of the whole genome between the two Shanghai strains was 98.88%, and the ANI of the whole genome comparisons to other CVA2 genotype D strains and CVA2 genotypes A-C strains ranged from 84.64% to 97.42% and from 79.21% to 84.20%, respectively. The two Shanghai strains had low homology in the 3D region compared to the existing CVA2 strains. The phylogenetic analysis and sliding window nucleotide similarity analysis indicated that the two Shanghai strains and the Yunnan OL357660 strain might constitute a new genetic lineage. ConclusionThe two CVA2 strains isolated for the first time in Shanghai are assigned to genotype D (GenBank: PQ130039 and PQ130040), which is identical to the existing subtype prevalent in China. As represented by the Shanghai strains, a new CVA2 genetic lineage is been identified. This study has enriched the data on genetic evolution and genetic variation of CVA2 in Shanghai, indicating the requirement to strengthen surveillance for the epidemiological pattern of CVA2.

Simultaneous management of intestinal mucosal barrier dysfunction and gut microbiota dysregulation represents a significant challenge in the treatment of inflammatory bowel disease (IBD). Herein, we report a novel system that integrates multi-enzyme mimicking cerium single-atom nanocatalysts (CeSACs) with Lactobacillus reuteri probiotics (LR@CeSACs) for multipronged management of IBD. In this system, CeSACs demonstrate robust multi-enzyme activities across a broad pH range, effectively scavenging elevated reactive oxygen species, downregulating pro-inflammatory cytokines, and suppressing the expression of fibrosis-related genes. Moreover, probiotics promote the targeting and retention of the CeSACs for sustained catalytic antioxidant therapy. In turn, the inflammation relief enabled by CeSACs promotes bacterial viability, allowing for the rapid reshaping of intestinal barrier function and the restoration of gut microbiota. Therefore, LR@CeSACs exhibit excellent catalytic anti-inflammatory and anti-fibrotic therapeutic effects, as well as a certain prophylactic effect, as demonstrated in several murine models.

Objective To investigate the epidemiological characteristics and spatial distribution characteristics of Clonorchis sinensis human infections in Guangdong Province from 2016 to 2022, so as to provide insights into formulation of the clonorchiasis control measures in the province. Methods Xinhui District of Jiangmen City, Longmen County of Huizhou City and Wengyuan County of Shaoguan City in Guangdong Province were selected as fixed surveillance sites for human clonorchiasis from 2016 to 2022, and additional 10% to 15% counties (districts) endemic for clonorchiasis were sampled from Guangdong Province as mobile surveillance sites each year from 2016 to 2022. A village (community) was randomly selected from each surveillance site according to the geographical orientations of east, west, south, north and middle, and subjects were randomly sampled from each village (community). C. sinensis eggs were detected in subjects’ stool samples using the Kato-Katz technique, and the prevalence and intensity of C. sinensis infections were calculated. In addition, subjects’ gender, age, ethnicity, educational level and occupation were collected. The Guangdong Provincial 1:1 million electronic map in vector format was downloaded from the National Geomatics Center of China, and kernel density analysis and spatial autocorrelation analysis of C. sinensis human infections in Guangdong Province from 2016 to 2022 were performed using the software ArcGIS 10.7. Results A total of 153 188 residents were tested for C. sinensis infections in Guangdong Province from 2016 to 2022, including 75 596 men (49.35%) and 77 592 women (50.65%), and there were 5 369 residents infected with C. sinensis, with 3.50% overall prevalence of infections. The prevalence rates of severe, moderate and mild C. sinensis infections were 0.76%, 7.26% and 91.97% among C. sinensis-infected residents in Guangdong Province from 2016 to 2022, and there were age-, gender-, ethnicity-, occupation- and educational level-specific prevalence of C. sinensis human infections (χ² = 2 578.31, 637.33, 52.22, 2 893.28 and 1 139.33, all P values < 0.05). Global spatial autocorrelation analysis showed a cluster in the prevalence of C. sinensis human infections in Guangdong Province (Moran’s I = 0.63, Z = 27.31, P < 0.05). Kernel density analysis showed that the prevalence of C. sinensis human infections with a high kernel density in Guangdong Province was mainly distributed along the Zhujiang River basin in Pearl River Delta areas, followed by in eastern and northern Guangdong Province. In addition, local spatial autocorrelation analysis identified 73 high-high clusters of the prevalence of C. sinensis human infections in Guangdong Province. Conclusions The prevalence of C. sinensis human infections was high in Guangdong Province from 2016 to 2022, and mild infection was predominant among all clonorchiasis cases, with spatial clusters identified in the prevalence of C. sinensis human infections. Targeted clonorchiasis control measures are required among high-risk populations and areas.

Objective: To explore the clinical dosimetry advantages of automated plan of IMRT for postoperative esophageal cancer and the dose prediction accuracy of the constructed 3D U-Res-Net model． Methods: A total of 110 postoperative esophageal cancer (middle and upper) cases treated by IMRT were considered in the study，of which 90 cases were randomly selected for training of deep learning prediction model．The deep learning prediction model and Auto-Plan module ( Philips pinnacle3 16. 2 ) were used to predict the three-dimension dose distribution and redesigned the remaining 20 cases respectively ，and the results obtained were compared with manual plan. Results : The average DSC value between the deep learning prediction plan and the manual plan was greater than 0. 92 in isodose surface，and the average Hausdorff distance HD95 of the isodose surface was 0. 58－0. 62 cm ; The V20 ，V30 ，Dmean of total lung were slightly lower than those of manual plan (P ＜0. 05 ) for the prediction model， meanwhile，the D2 ，D50 ，Dmean，HI of the target area and V30 of total lungs were better than those of manual plan(P ＜0. 05) for Auto-Plan ; Three-dimensional dose distribution of the three groups and the corresponding DVH curve showed that the three-dimensional dose distribution of the three groups had a little differences，and the DVH curves of the target area and organs at risk had a good agreement． Conclusion Auto-Plan can realize the design of automated plan for postoperative esophageal cancer，while the deep learning prediction model can realize the accurate prediction of the 3D dose distribution.

Objective:To investigate the clinicopathological characteristics, treatment methods and prognosis of renal primary neuroendocrine neoplasms.Methods:The clinical data of 42 patients with renal neuroendocrine neoplasms admitted to the First Affiliated Hospital of Zhengzhou University from October 2011 to June 2021 were retrospectively analyzed.There were 17 males and 25 females. The median age was 60.0 (50.0, 67.0) years old.The CT enhancement scan lesion was slightly intensified with less intensification than normal renal parenchyma.The clinic manifestation included lumbar abdominal pain in 7 cases, hematuria in 3 cases, abdominal distension in 1 cases, and asymptomatic in 8 cases. The average diameter of tumor was 8.0 (4.0, 10.0) cm. The tumor of 13 cases was in the left, and 6 cases was in the right. 6 cases were in T 1 stage, 11 cases were in T 2, 11 cases were in T 3, and 14 cases were in T 4.17 cases had lymph node metastasis, 11 cases had distant metastasis.The surgical method was radical nephrectomy in 27 cases, nephrectomy in 5 cases and interventional embolization in 4 case, and no operation in 6 cases, including 5 with chemotherapy alone and 1 with supportive care.Patients were classified by WHO Classification of renal tumors of the urinary system and the male reproductive organs (2016) into high-differentiated renal neuroendocrine tumors (NET, including carcinoid and atypical carcinoids) and high-grade renal neuroendocrine carcinoma (NEC, including small cell neuroendocrine carcinoma and large cell neuroendocrine carcinoma). The clinicopathological characteristics and prognosis of the 2 groups were compared, and the Cox proportional regression risk model was used to analyze the clinical factors affecting the prognosis. Results:In the NET group, 12 cases were carcinoids and 7 cases were atypical carcinoids. In the NEC group, 23 cases were small cell carcinomas.The mean Ki-67 index of 42 cases was 35% (4.5%, 62.5%). The proportion of positive expression of the neuroendocrine markers CD56, chromogranin A (CgA), and synapsin (Syn) were (37/42), (15/42), and (38/42), respectively. A total of 42 patients were followed up, and the median follow-up time was 60 (35, 99) months, and the median survival time was 25 (15, 60) months. The 3-year and 5-year overall survival rates were 40.0% and 21.2%. The 3-year and 5-year overall survival rates in the NET group were 72.6% and 42.3%.The 3-year and 5-year overall survival rates in the NEC groups were 6.3% and 0, respectively. The mean Ki-67 index was 3% (2%, 10%) in the NET group, 2 patients received postoperative chemotherapy and 3 patients had early progression after initial treatment.The mean Ki-67 index in the NEC group was 60% (40%, 80%), 15 patients received postoperative chemotherapy, and 13 patients had early progression of initial treatment.There were statistically differences in treatment method, postoperative chemotherapy, Ki-67 index, and early disease progression (all P <0.05) between the two groups.The results of univariate analysis showed that sex, age, early progression, treatment method, tumor differentiation, and Ki-67 index were all factors influencing patient prognosis (all P <0.05). Cox multivariate analysis showed that poorly differentiated NEC ( HR=13.964, P=0.003) and early progression ( HR=3.626, P=0.018) were independent risk factors for patient survival, and renal radical surgery ( HR=0.197, P=0.033) was independent protective factors for patient survival. Further subgroup analysis showed that the median survival time of the NEC patients with adjuvant chemotherapy after surgery was significantly longer compared with the patients without adjuvant chemotherapy (21 and 9 months, P=0.012). Conclusions:Primary renal neuroendocrine tumors are clinically rare, often manifested as lumbar and abdominal pain, and radical renal surgical treatment is preferred.The NET has a better prognosis and NEC prognosis is extremely poor, but NEC patients can have survival benefit from chemotherapy. NEC and early progression of the disease are independent prognostic risk factors, and radical renal surgical treatment is an independent protective factor for prognosis.

Objective To compare the therapeutic effects between three-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiotherapy (IMRT) in patients with stage Ⅱ/Ⅲ esophageal cancer and investigate the prognostic factors.Methods Medical record of 2 132 patients with stage Ⅱ/Ⅲ esophageal cancer who underwent definitive radiotherapy with/without chemotherapy in 10 hospitals from January 2002 to December 2016 from were retrospectively analyzed.Among these patients,37.9％ of them were aged ≥ 70 years,33.9％ with neck and upper esophageal tumors and 66.1％ with middle and lower esophageal and borderline tumors.The median gross tumor volume (GTV) and lymph node gross tumor volume (GTVnd) was 41.6 cm3.Among them,32％ were stage Ⅱ] and 68％ were stage Ⅲ.A total of 723 patients received 3DCRT and 1 409 cases received IMRT.Patients received an equivalent dose in 2 Gy (EQD2) ≥ 60 Gy accounted for 86.1％,and 41.1％ of them received concurrent chemoradiotherapy.Results The median follow-up time was 60.8 months.The 1-,3-and 5-year overall survival (OS) of all patients was 73.9％,41.7％ and 32.6％,and the 1-,3-and 5-year progression-free survival (PFS) was 62.2％,37.3％ and 32％,respectively.Multivariate analysis demonstrated that age,primary tumor location,clinical stage,tumor target volume,EQD2 and concurrent chemoradiotherapy were the independent prognostic factors for OS.Age,primary tumor location,clinical stage,tumor target volume and EQD2 were the independent prognostic factors for PFS.The OS and PFS did not significantly differ among the low-risk,low-/moderate-risk,moderate-/high-risk and high-risk groups according to age≥70 years,tumor diameter＞5 cm,tumor volume ≥41.6 cm3 and stage Ⅲ (P＜0.001).After the propensity score matching (PSM) method,neither 3DCRT nor IMRT yielded significant advantages in OS or PFS (P=0.971;P=0.658).However,IMRT tended to yield survival benefits in low-risk patients (P=0.125).Conclusions Both 3DCRT and IMRT yield relatively high OS rate in patients with stage Ⅱ/Ⅲ esophageal cancer.The prognosis model established in this investigation can properly predict the survival of patients.Low-risk patients tend to obtain survival benefits from IMRT.

Objective To evaluate the clinical efficacy and safety of ritonavir-boosted danoprevir (DNVr) combined with daclatasvir (DCV) in the treatment of patients with genotype 1b chronic hepatitis C (CHC).Methods Thirty-three patients with genotype 1b CHC admitted in the Department of Infectious Diseases of the First Affiliated Hospital of Nanchang University from August 2018 to February 2019 were enrolled.All the patients received DNVr +DCV antiviral treatment.HCV RNA levels were detected before and 2, 4, 12 weeks after treatment, and after drug withdrawal , respectively.Indicators of liver and kidney function and adverse events were observed.ANOVAV of repeated measurement was used to analyze the data. Results The baseline viral loads of 33 patients ranged from 1.12×104 to 1.76×107 IU／mL.Two weeks after treatment the viral loads of all patients were down to the lowest limit of detection (＜500 IU／mL). Serum ALT, AST and TBil levels returned to norml ( F＝58.26, 14.49 and 20.16, all P＜0.05) and sustained virologic response reached 100%12 weeks after drug withdrawal.Three cases had minor adverse reactions during the treatment.Conclusion DNVr combined with DCV can achieve a rapid and strong virological response in the treatment of patients with genotype 1b CHC with good safety.

Aim To investigate the relationship between the brain targeting effect and P-glycoprotein(P-gp)expression level of Danshensu borneol ester(DBE)and the combination use of sodium Danshensu and borneol(SDSS-B).Methods The liquid chromatography mass spectrometry(LC-MS)method was applied to investigate the accumulation of Danshensu(DSS)in rat brain tissues after intravenous injection of DBE,SDSS-B and SDSS.Also their effect on regulating the expression level of P-gp in rat hippocampus was investigated using Western blot.Results The brain targeting effect of DBE,SDSS-B was qualitatively analyzed through the brain distribution of DSS,and the result was DBE(SDSS-B)>SDSS(P<0.01).Meanwhile,the brain distribution of DBE group was slightly lower than SDSS-B group at 15 min,while at 30 min DBE was higher than that of SDSS-B.DBE demonstrated a better slow release property compared to SDSS-B.Western blot analysis indicated that DBE,SDSS-B were more effective in inhibiting the expression of P-gp than SDSS in rat hippocampus(P<0.01 vs control or SDSS group),and the lowest P-gp expression was obtained with(47.58±2.28)％and(46.54±1.41)％at 45 min after administration of DBE or SDSS-B.Once the administration time was extended to 60 min,the inhibitory effect on P-gp expression of DBE was stronger than SDSS-B[(85.04±1.42)％vs(95.29±0.98)％].However,no significant inhibition of P-gp expression in rat hippocampus was found throughout the treatment of SDSS(P>0.05 at 5,15,45,60 min,vs control group).Conclusion An attenuated expression level of P-gp can be realized by DBE and SDSS-B,which is advantageous to their brain targeting.

Important/potential value of macrolides has been proved in the management of chronic respiratory diseases by increasing basic and clinical trials.Through three face-to-face discussions,10 experts examined important data and drafted this consensus related to macrolides:(1) mechanism of nonantiinfective effects;(2) clinical use in chronic respiratory diseases;(3) cautions of long-term use.The mechanism out of non-antiinfective effects includes anti-inflammatory effect,modifying airway secretion,immune-regulation related to antibacterial effect,corticoid saving effect and anti-viral effect.The efficacy of long-term use of low-dose macrolides is definitely confirmed in diffuse panbronchiolitis,chronic rhinosinusitis.It is considerably used in bronchiectasia,cystic fibrosis,severe asthma and chronic obstructive pulmonary disease.Further studies should be conducted in cryptogenic organizing pneumonia and respiratory viral infection.It should be paid attention to its possible adverse effects (including drug interactions,cardiac toxicity,ototoxicity and disturbance of intestinal flora) and drug resistance in long-term use.A Chinese consensus for non-antiinfective effects and clinical use of macrolides is developed for the first time,which aims to expand their rational use and the further research.

Objective To study the influence of pregnant rats' prenatal chronic stress (PS) on learning and memory of their offspring rats and its possible molecular mechanisms.Methods Pregnant females were individually restrained for 45 min 3 times a day during pregnancy from day 14 to day 21.Control pregnant females were left undisturbed in their home cages.The rat offsprings were randomly assigned to PS group or control group.Males and females were kept for the study separately.The learning and memory of the developing rat offspring in the Morris water maze were examined.The basal levels of corticosterone (COR) and adreno-cortico-tropic-hormone (ACTH) were analyzed by using radioimmunoassay.The Golgi-Cox impregnation technique was used to compare density and morphology of the CA1 hippocampal dendritic spines.Results The escape latency (EL) to find the platform in the control group was significantly less than that in the PS group in female rat offspring (F =4.533,P ＜ 0.05),and the difference was statistically significant on the 5th day (t =2.788,P ＜ 0.01).EL to find the platform in the control group was significantly less than that in the PS group in male rat offspring (F =6.101,P ＜0.05),and the difference was statistically significant on the second day (t =3.051,P ＜ 0.01).In the space exploration experiments of the water maze,the retention time observed for the control group and the PS group in the goal quadrant was similar(P ＞ 0.05).The basal levels of the serum COR in the PS group were higher than those in the control group of female rat offspring(t =3.658,P ＜ 0.01) and the basal levels of the serum ACTH in the PS group were higher than those in the control group of male rat offsprings(t =2.319,P ＜ 0.05).A simplified pattern was observed in the CA1 hippocampal dendritic spines in the PS group,showing a less extent of dendritic arborization and the density was significantly lower than that in the control group(t =-3.072,P ＜ 0.01).Conclusions Altered function of the hypothalamic-pituitary-adrenal axis in the offspring mediates the cognitive alterations observed following prenatal stress should to be associated with the lower density and simplified pattern of CA1 dendritic spines.