Influencing factors of survival benefit of patients after radical cystectomy and its correlation with preoperative AAPR / 国际外科学杂志

Objective:To investigate the influencing factors of survival benefit of patients after radical cystectomy and its correlation with preoperative albumin-to-alkaline phosphatase ratio (AAPR).Methods:The clinical data of 116 patients after radical cystectomy were retrospectively analyzed from January 2011 to January 2020 in Handan First Hospital. The influencing factors of survival benefit of patients after radical cystectomy were analyzed and the correlation between preoperative AAPR and overall survival time were evaluated. Kaplan-Meier method was used for survival analysis, and Log-rank test was used for comparison between groups. Cox proportional regression model was used to analyze the influencing factors of survival and prognosis and the correlation with preoperative AAPR. Trend Chi-square test was used to evaluate the level of preoperative AAPR.Results:Univariate Cox regression analysis showed that age, tumor diameter, pT stage, pN stage, histopathological grade, hydronephrosis, postoperative adjuvant chemotherapy and preoperative AAPR level were related to the overall survival time of patients after radical cystectomy( P<0.05). Multivariate Cox regression analysis showed that in calibration model Ⅰ and Ⅱ, the risk of death in high AAPR group was 0.351 and 0.433 times higher than low AAPR group( P<0.05). The risk of death decreased to 85.9% and 84.6% for every one unit increase of preoperative AAPR. The overall survival time of patients with high AARP level were significantly longer than patients with low and medium AARP level( P<0.05). Conclusion:The survival benefit of patients after radical cystectomy was independently related to the preoperative AAPR level; the higher the preoperative AAPR level, the longer the overall survival time.

Analysis of clinicopathological characteristics, therapeutic strategy and prognosis of 501 patients with gastric neuroendocrine neoplasms attending a single center / 中华胃肠外科杂志

Objective: To explore the clinicopathological features, treatment strategy and to analysis of prognosis-related risk factors of gastric neuroendocrine neoplasms(G-NEN). Methods: In this study, a retrospective observational study method was used to collect the clinicopathological data of patients diagnosed with G-NEN by pathological examination in the First Medical Center of PLA General Hospital from January 2000 to December 2021. The basic information of the patients, tumor pathological characteristics, and treatment methods were entered, and the treatment information and survival data after discharge were followed up and recorded. The Kaplan-Meier method was used to construct survival curves, and the log-rank test to analyze the differences in survival between groups. Cox Regression model analysis of risk factors affecting the prognosis of G-NEN patients. Results: Among the 501 cases confirmed as G-NEN, 355 were male and 146 were female, and their median age was 59 years. The cohort comprised 130 patients (25.9%) of neuroendocrine tumor (NET) G1, 54 (10.8%) of NET G2, 225 (42.9%) of neuroendocrine carcinoma (NEC), and 102 cases (20.4%) of mixed neuroendocrine-non-neuroendocrine(MiNEN). Patients NET G1 and NET G2 were mainly treated by endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR). The main treatment for patients with NEC/MiNEN was the same as that for gastric malignancies, namely radical gastrectomy+lymph node dissection supplemented with postoperative chemotherapy. There were significant differences in sex, age, maximum tumor diameter, tumor morphology, tumor numbers, tumor location, depth of invasion, lymph node metastasis, distant metastasis, TNM staging and expression of immunohistological markers Syn and CgA among NET, NEC, and MiNEN patients (all P<0.05). Further for NET subgroup analysis, there were significant differences between NET G1 and NET G2 in the maximum tumor diameter, tumor shape and depth of invasion(all P<0.05). 490 patients (490/501, 97.8%) were followed up with a median of 31.2 months. 163 patients had a death during follow-up (NET G1 2, NET G2 1, NEC 114, MiNEN 46). For NET G1, NET G2, NEC and MiNEN patients,the 1-year overall survival rates were 100%, 100%, 80.1% and 86.2%, respectively; the 3-year survival rates were 98.9%, 100%, 43.5% and 55.1%, respectively. The differences were statistically significant (P<0.001). Univariate analysis showed that gender, age, smoking history, alcohol history, tumor pathological grade, tumor morphology, tumor location, tumor size, lymph node metastasis, distant metastasis, and TNM stage were associated with the prognosis of G-NEN patients (all P<0.05). Multivariate analysis showed that age ≥60 years, pathological grade of NEC and MiNEN, distant metastasis, and TNM stage III-IV were independent factors influencing the survival of G-NEN patients (all P<0.05). 63 cases were stage IV at initial diagnosis. 32 of these were treated with surgery and 31 with palliative chemotherapy. Stage IV subgroup analysis showed that the 1-year survival rates were 68.1% and 46.2% in the surgical treatment and palliative chemotherapy groups, respectively, and the 3-year survival rates were 20.9% and 10.3%, respectively; the differences were statistically significant (P=0.016). Conclusions: G-NEN is a heterogeneous group of tumors. Different pathological grades of G-NEN have different clinicopathological features and prognosis. Factors such as age ≥ 60 years old, pathological grade of NEC/MiNEN, distant metastasis, stage III, IV mostly indicate poor prognosis of patients. Therefore, we should improve the ability of early diagnosis and treatment, and pay more attention to patients with advanced age and NEC/MiNEN. Although this study concluded that surgery improves the prognosis of advanced patients more than palliative chemotherapy, the value of surgical treatment for patients with stage IV G-NEN remains controversial.

Survey of prevalence of hepatitis C in people aged 1-69 years in Henan Province, 2020 / 中华流行病学杂志

Objective: To understand the infection status and epidemiological characteristics of hepatitis C in people aged 1-69 years in Henan Province in 2020. Methods: The estimated sample size was 5 827. From August to December 2020, multistage sampling was used to select 8 counties (districts) in Henan, and two survey sites were selected in each county (district), and a questionnaire survey was conducted in local people aged 1-69 years, blood samples were collected from them for anti-HCV, HCV RNA and genotype detections. Results: A total of 5 165 people aged 1-69 years completed the questionnaire survey. Men accounted for 44.76% (2 312/5 165), women accounted for 55.24% (2 853/5 165). In the people aged 1-69 years, the overall prevalence rates of anti-HCV and HCV RNA were 0.69% (95%CI: 0.68%-0.70%) and 0.20% (95%CI: 0.19%-0.21%) respectively. The prevalence rates of anti-HCV and HCV RNA were 0.48% (95%CI: 0.46%-0.50%), 0.09% (95%CI: 0.08%-0.10%) in men and 0.86% (95%CI: 0.85%-0.87%), 0.30% (95%CI: 0.28%-0.32%) in women. The prevalence rates of anti-HCV and HCV RNA increased with age. The prevalence rates of anti-HCV and HCV RNA were 0.87% (95%CI: 0.86%-0.88%), 0.28% (95%CI: 0.26%-0.30%) in urban residents and 0.53% (95%CI: 0.51%-0.55%), 0.14% (95%CI: 0.13%-0.15%) in rural residents. The genotyping results of 10 HCV RNA positive samples ware genotype 1b (4/10), genotype 2 (3/10), genotype 1b/3 (1/10), genotype 1b/3/6 (1/10) and genotype 2/6 (1/10). Conclusions: The prevalence of hepatitis C was low in Henan in 2020. It is necessary to strengthen hepatitis C surveillance in people aged 40 years and above. The major HCV genotypes were 1b and 2, and mixed genotype infection existed.

Down-regulation of the Smad signaling by circZBTB46 via the Smad2-PDLIM5 axis to inhibit type I collagen expression / 老年心脏病学杂志（英文版）

BACKGROUND@#Abnormal type I collagen (COL1) expression is associated with the development of many cardiovascular diseases. The TGF-beta/Smad signaling pathway and circRNAs have been shown to regulate COL1 gene expression, but the underlying molecular mechanisms are still not fully understood.@*METHODS@#Gain- and loss-of-function experiments were prformed to study the effect of circZBTB46 on the expression of alpha 2 chain of type I collagen (COL1A2). Co-immunoprecipitation assay was performed to observe the interaction between two proteins. RNA immunoprecipitation assay and biotin pull-down assay were performed to observe the interaction of circZBTB46 with PDLIM5.@*RESULTS@#In this study, we investigated the role of circZBTB46 in regulating COL1A2 expression in human vascular smooth muscle cells (VSMCs). We found that circZBTB46 is expressed in VSMCs and that TGF-beta inhibits circZBTB46 formation by downregulating KLF4 expression through activation of the Smad signaling pathway. CircZBTB46 inhibits the expression of COL1A2 induced by TGF-beta. Mechanistically, circZBTB46 mediates the interaction between Smad2 and PDLIM5, resulting in the inhibition of Smad signaling and the subsequent downregulation of COL1A2 expression. Furthermore, we found that the expression of TGF-beta and COL1A2 is decreased, while circZBTB46 expression is increased in human abdominal aortic aneurysm tissues, indicating that circZBTB46-mediated regulation of TGF-beta/Smad signaling and COL1A2 synthesis in VSMCs plays a crucial role in vascular homeostasis and aneurysm development.@*CONCLUSIONS@#CircZBTB46 was identified as a novel inhibitor of COL1 synthesis in VSMCs, highlighting the importance of circZBTB46 and PDLIM5 in regulating TGF-beta/Smad signaling and COL1A2 expression.

Acupuncture and moxibustion in treatment of chronic obstructive pulmonary disease at stable stage: a network Meta-analysis / 中国针灸

The efficacy on chronic obstructive pulmonary disease (COPD) at stable stage treated with different methods of acupuncture and moxibustion was evaluated using network Meta-analysis method. The articles of the randomized controlled trial (RCT) on stable COPD treated with acupuncture and moxibustion were searched electronically in CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Web of Science and Cochrane library. The search was conducted from the inception of the databases to March 20th, 2022. Data analysis was performed using R4.1.1, Stata16.0 and RevMan5.3 softwares. A total of 48 RCTs were included, involving 15 kinds of acupuncture and moxibustion interventions and a sample size of 3 900 cases. The results of network Meta-analysis showed that: ① For the forced expiratory volume in one second predicted (FEV1%), both the governor vessel moxibustion combined with conventional treatment (G+C therapy) and the yang-supplementing moxibustion combined with conventional treatment (Y+C therapy) obtained the better effect than that of the conventional treatment (P<0.05), and the G+C therapy was more effective compared with the thread-embedding therapy combined with conventional treatment (E+C therapy) and warm needling (P<0.05). ② Concerning to COPD assessment test (CAT) score, the results indicated that the Y+C therapy, and the mild moxibustion combined with conventional treatment (M+C therapy) were more effective when compared with the conventional treatment (P<0.05), and the effect of the Y+C therapy was better than that of the E+C therapy (P<0.05). ③ Regarding six-minute walking distance (6MWD), the effect of acupuncture combined with conventional treatment (A+C therapy) was better than that of either the E+C therapy or the conventional treatment (P<0.05). The effect of the G+C therapy was optimal for improving FEV1%, the Y+C therapy obtained the best effect for improving CAT score, and A+C therapy was the most effective for improving 6MWD. Due to the limitation of the quality and quantity of included studies, this conclusion needs to be further verified through high-quality RCT.

Short term efficacy of 3D printed individualized prosthesis for precise reconstruction of bone and joint defects after upper limb microsurgical repair / 中华显微外科杂志

Objective:To evaluate the efficacy of 3D printed individualised prosthesis in treating bone and joint defects in upper limbs remained after earlier microsurgical repairs.Methods:From June 2019 to September 2021, 12 patients were treated in the Institute of Orthopaedic Trauma of PLA, the 80th Group Army Hospital for bone and joint defects in upper limb that had been remained after earlier repairs with soft tissue flaps. The defects were: 1 in completely severed wrist, 2 defects of digit metacarpal bone, 4 defects of interphalangeal joint, 4 defects of bones in radiocarpal joint and 1 defect of lunate bone. The area of soft tissue defect ranged from 1.5 cm×3.0 cm to 12.0 cm×18.0 cm, and the length of bone defects ranged from 2.5 to 8.5(average 3.64) cm. For incompletely severed and completely severed limbs, replantation of severed limbs (digits) were performed in the primary surgery and the repair of soft tissue defects were performed in the second stage surgery. The remaining defects of bone and joint were reconstructed by 3D printed individualised prostheses in the third stage surgery. Finger soft tissue defects were covered with a local flap in the primary surgery, and bone and joint defects were reconstructed with a 3D printed prosthesis in the second surgery. Finger soft tissue defects were covered with a local flap in the first phase, and bone and joint defects were reconstructed with a 3D printed prosthesis in the second phase. After the surgery, the bone integration between the broken end of the bone joint defect and the prosthesis was determined based on the X-ray results and the Paley fracture healing score standard. Simultaneously measured the Total Active Motion(TAM) of the forearm and hand joints. At 1, 2, 3, 6, 9 and 12 months after hospital discharge. Follow-up X-ray examinations were taken followed by examinations on the recovery of soft tissues and bones. The upper limb function was graded according to the Evaluation Trial Standards of Upper Limb Partial Functional of Hand Surgery of Chinese Medical Association.Results:Postoperative follow-up at outpatient clinic lasted for 6 to 26 months, with an average of 11.5 months. All flaps were free from necrosis and infection, also there was no infection in bones and joints. According to the Paley fracture healing scale, 10 patients were in excellent and 2 in good. In addition, according to the Evaluation Trial Standards of Upper Limb Partial Functional of Hand Surgery of Chinese Medical Association, 5 patients achieved upper limb function in excellent, 5 in good and 2 in fair. The ranges of motion of the affected wrists were 30°-42°(average 37.3°) for the implanted prostheses of distal end of radius and the radial shaft. Wrist flexion 40° to 55°(average 43.5°). The range of motion of finger and wrist was 60° to 70°(average 65.7°) with a metacarpal and phalangeal bone prosthesis.Conclusion:3D printed individually customised prostheses are safe, accurate and effective in repair of the remained bone and joint defects in upper limbs after primary and early stages of microsurgical flap repairs. It can effectively restore anatomical structures of bone and joint in upper limbs.

Multiple mitochondrial dysfunction syndrome 2 caused by BOLA3 gene mutation: a case report and literature review / 中华神经科杂志

Objective:To report cases of multiple mitochondrial dysfunction syndrome 2 (MMDS2) caused by BOLA3 gene mutation, hoping to help clinical diagnosis. Methods:The medical records of a child with MMDS2 admitted to the Department of Neurology, Guangzhou Women and Children′s Medical Center in November 2021 were analyzed, and the clinical, imaging characteristics and prognosis of MMDS2 were summarized by literature review.Results:This 1 year and 9 months old male had a disease that started in childhood, with motor function regression and hyperlactatemia. Head magnetic resonance imaging indicated white matter lesions, and gene examination indicated the homozygous variation of BOLA3 gene c.295C>T(p.Arg99Trp). The diagnosis of MMDS2 was clear for the child. After treatment, the clinical symptoms and imaging of the child recovered significantly. Through literature review, 13 children with MMDS2 reported in 7 English literatures were reviewed. These cases had similar manifestations with the case reported in this study. Among them, 1 case recovered and 8 cases died in infancy. Conclusions:MMDS2 patients often show nervous system dysfunction such as motor regression, elevated lactate and white matter lesions, which often cause multiple system disorders. Some children die early, but some of them can be recovered.

Establishment and validation of a nomogram for predicting prognosis of gastric neuroendocrine neoplasms based on data from 490 cases in a single center / 南方医科大学学报

OBJECTIVE@#To develop and validate a nomogram for predicting outcomes of patients with gastric neuroendocrine neoplasms (G-NENs).@*METHODS@#We retrospectively collected the clinical data from 490 patients with the diagnosis of G-NEN at our medical center from 2000 to 2021. Log-rank test was used to analyze the overall survival (OS) of the patients. The independent risk factors affecting the prognosis of G-NEN were identified by Cox regression analysis to construct the prognostic nomogram, whose performance was evaluated using the C-index, receiver-operating characteristic (ROC) curve, area under the ROC curve (AUC), calibration curve, DCA, and AUDC.@*RESULTS@#Among the 490 G-NEN patients (mean age of 58.6±10.92 years, including 346 male and 144 female patients), 130 (26.5%) had NET G1, 54 (11.0%) had NET G2, 206 (42.0%) had NEC, and 100 (20.5%) had MiNEN. None of the patients had NET G3. The numbers of patients in stage Ⅰ-Ⅳ were 222 (45.3%), 75 (15.3%), 130 (26.5%), and 63 (12.9%), respectively. Univariate and multivariate analyses identified age, pathological grade, tumor location, depth of invasion, lymph node metastasis, distant metastasis, and F-NLR as independent risk factors affecting the survival of the patients (P < 0.05). The C-index of the prognostic nomogram was 0.829 (95% CI: 0.800-0.858), and its AUC for predicting 1-, 3- and 5-year OS were 0.883, 0.895 and 0.944, respectively. The calibration curve confirmed a good consistency between the model prediction results and the actual observations. For predicting 1-year, 3-year and 5-year OS, the TNM staging system and the nomogram had AUC of 0.033 vs 0.0218, 0.191 vs 0.148, and 0.248 vs 0.197, respectively, suggesting higher net benefit and better clinical utility of the nomogram.@*CONCLUSION@#The prognostic nomogram established in this study has good predictive performance and clinical value to facilitate prognostic evaluation of individual patients with G-NEN.

Characteristics of attentional bias in Wilson disease patients with different levels of state-trait anxiety / 中华行为医学与脑科学杂志

Objective:To investigate the characteristics of attention bias in Wilson disease(WD) patients with different levels of state-trait anxiety.Methods:The emotional Stroop paradigm and the state-trait anxiety inventory(STAI) were used to evaluate the anxiety level and the characteristics of attention bias in 49 inpatients with WD.SPSS 25.0 software was used for statistical analysis.Independent sample t-test was used for comparison between the two groups.Multiple linear regression analysis was used to evaluated the influencing factors of attentional bias response time. Results:(1) In WD patients, the response times measured under the positive, negative and neutral words in the high trait anxiety group((867.0±172.1)ms, (877.0±167.7)ms, (898.4±169.8)ms, respectively) were significantly higher than the low trait anxiety group((771.9±128.9)ms, (770.9±110.4)ms, (778.4±120.1)ms, respectively) and the differences were statistically significant( t=-2.183, -2.605, -2.847, all P<0.05). The response times under the positive, negative and neutral word measured in the high state anxiety group((866.9±171.9)ms, (867.8±173.8)ms, (889.8±173.5)ms, respectively) were higher than those of the low state anxiety group((771.9±129.2)ms, (780.4±109.3)ms, (787.3±123.0)ms, respectively) and the differences were statistically significant( t=-2.177, -2.116, -2.378, all P<0.05). (2) Multiple linear regression analysis showed that the total score of trait anxiety ( B=4.584, 4.671, 5.376, P=0.020, 0.015, 0.008) and age ( B=9.314, 7.864, 7.505, P=0.002, 0.008, 0.014) were the influencing factors of response times measured under the positive, negative and neutral emotion words. Conclusion:Anxiety will lead patients with WD to show more negative attention bias, and trait anxiety can significantly predict the characteristics of attention bias.

Impact of bicuspid aortic valve or tricuspid aortic valve on hemodynamics and left ventricular reverse remodeling in patients after transcatheter aortic valve replacement / 中华心血管病杂志

Objective: To compare the impact of bicuspid aortic valve (BAV) or tricuspid aortic valve (TAV) on hemodynamics and left ventricular reverse remodeling after transcatheter aortic valve replacement (TAVR). Methods: We retrospectively analyzed the clinical data of patients who underwent TAVR in our hospital from January 2019 to March 2021. Patients were divided into BAV group and TAV group according to aortic contrast-enhanced CT. Each patient was followed up by N-terminal pro B-type natriuretic peptide (NT-proBNP) and echocardiography at four time points, namely before TAVR, 24 hours, 1 month and 6 months after TAVR. Echocardiographic data, including mean pressure gradient (MPG), aortic valve area (AVA), left ventricular ejection fraction (LVEF), left ventricle mass (LVM) and LV mass index (LVMi) were evaluated. Results: A total of 41 patients were included. The age was (75.0±8.6) years, and male patients accounted for 53.7%. There were 19 BAV patients and 22 TAV patients in this cohort. All patients undergoing TAVR using a self-expandable prosthesis Venus-A valve. MPG was (54.16±21.22) mmHg(1 mmHg=0.133 kPa) before TAVR, (21.11±9.04) mmHg at 24 hours after TAVR, (18.84±7.37) mmHg at 1 month after TAVR, (17.68±6.04) mmHg at 6 months after TAVR in BAV group. LVEF was (50.42±13.30)% before TAVR, (53.84±10.59)% at 24 hours after TAVR, (55.68±8.71)% at 1 month after TAVR and (57.42±7.78)% at 6 months after TAVR in BAV group. MPG and LVEF substantially improved at each time point after operation, and the difference was statistically significant (all P<0.05) in BAV group. MPG in TAV group improved at each time point after operation, and the difference was statistically significant (all P<0.05). LVMi was (164.13±49.53), (156.37±39.11), (146.65±38.84) and (134.13±39.83) g/m2 at the 4 time points and the value was significantly reduced at 1 and 6 months post TAVR compared to preoperative level(both P<0.05). LVEF in the TAV group remained unchanged at 24 hours after operation, but it was improved at 1 month and 6 months after operation, and the difference was statistically significant (all P<0.05). LVMi in TAV group substantially improved at each time point after operation, and the difference was statistically significant (all P<0.05). NT-proBNP in both two groups improved after operation, at 1 month and 6 months after operation, and the difference was statistically significant (all P<0.05). MPG in TAV group improved better than in BAV group during the postoperative follow-up (24 hours after TAVR: (11.68±5.09) mmHg vs. (21.11±9.04) mmHg, P<0.001, 1 month after TAVR: (10.82±3.71) mmHg vs. (18.84±7.37) mmHg, P<0.001, 6 months after TAVR: (12.36±4.42) mmHg vs. (17.68±6.04) mmHg, P=0.003). There was no significant difference in NT-proBNP between BAV group and TAV group at each time point after operation (all P>0.05). There was no significant difference in paravalvular regurgitation and second prosthesis implantation between the two groups (all P>0.05). Conclusions: AS patients with BAV or TAV experience hemodynamic improvement and obvious left ventricular reverse remodeling after TAVR, and the therapeutic effects of TAVR are similar between BAV and TAV AS patients in the short-term post TAVR.

Highly penetrable nanoparticles co-loading doxorubicin and IDO1 siRNA enhance tumor immunotherapy / 药学学报

There are two serious obstacles to tumor immunotherapy. Firstly, the immune response of the tumor is seriously reduced due to immunosuppressive tumor microenvironment (ITM) and low immunogenicity of tumor. The second obstacle is the dense and complex heterogeneous structures, which seriously prevent the nanoparticles (NPs) from penetrating deeper into tumor tissue. Immunogenic cell death (ICD) induced by doxorubicin (DOX) is an effective method to enhance tumor immune activity. However, interferon-γ (IFN-γ) secreted by cytotoxic T lymphocytes (CTL) after ICD induction would increase the expression of indoleamine 2,3-dioxygenase 1 (IDO1) and enhance ITM. IDO1 siRNA would reduce the expression of IDO1 protein, regulate the tumor immunosuppressive microenvironment and regulate ITM, so as to enhance the ICD effect of DOX. In this paper, a novel charge conversional, particle size reduction and highly penetrable NPs based on a pH sensitive copolymer poly(ethylene glycol)-poly-L-lysine-2,3-dimethylmaleic anhydride (mPEG-PLL-DMA, PLD) and polyamidoamine (PAMAM) dendrimers to achieve deep delivery of tumor tissue. DOX and IDO1 siRNA were encapsulated to achieve efficient tumor immunotherapy. Preparation and cell level experiments showed that PLD material had significant pH sensitivity. Results of 3D tumor penetrable experiment in vitro showed that adding the pH sensitive material PLD significantly improved the permeability of the preparation. In addition, 4T1 tumor model was established for BALB/c mice and all animal experiments were displayed in according with the requirements of the Animal Experiment Ethics Committee of Shenyang Pharmaceutical University. The results of in vivo efficacy experiments and tissue experiments evaluated that IDO1 siRNA significantly improved the ICD effect owing to DOX, so as to significantly inhibit tumor growth.

The world’s first malaria vaccine: Hope and challenge / 中国血吸虫病防治杂志

The RTS,S/AS01 is a subunit malaria vaccine against the pre-erythrocytic stage of Plasmodium falciparum. After over 30 years of research and development and clinical trials, this vaccine has been recommended by the WHO for use among children living in highly malaria endemic areas. Although the RTS, S/AS01 vaccine suffers from problems of a low protective efficacy (about 30%), need of four doses and short duration of protective immunity, this malaria vaccine is expected to save tens of thousands of children’s lives, and avoid tens of millions of malaria cases annually, because there have been tens of thousands of childhood deaths due to malaria recently. The introduction of the RTS, S/AS01 vaccine is therefore, widely accepted as a milestone in the history of battle against malaria, which brings a hope to contain malaria and even eventually eliminate malaria. Although there are still multiple challenges in the development of a satisfactory malaria vaccine, the success of the RTS, S/AS01 malaria greatly facilitates the progress towards the development of parasitic disease vaccines, and a more perfect malaria vaccine deserves expectations.

Analysis of factors associated with the structure of the gut microbial community in HIV/AIDS patients in some areas of Henan province / 中华流行病学杂志

Objective: To investigate the related factors associated with the structure of the gut microbial community in HIV infection/AIDS cases (HIV/AIDS) in Henan province. Methods: The convenience sampling method was used to select 122 cases who were receiving Antiviral Treatment (ART) or ART-naive in Henan. Whole blood and stool specimens were collected. Genomic DNA of stool samples was extracted, and the V3-V4 hypervariable regions of the 16S rRNA gene were sequenced using Illumina NovaSeq 6000 high-throughput sequencing system. The analysis was performed mainly at the genus level, and the 30 genera with the highest abundance were selected as a measure of the gut microbial community structure. The correlation between community structure and related factors was analyzed using redundancy analysis and Envfit function. Results: 122 cases were finally completed sequencing and analysis, the average BMI was (23.62±2.78) kg/m2 and the average age was (47±13) years. Among them, male accounted for 66.39% (81/122), and heterosexual transmission route constituted the largest ratio, accounting for 51.64% (63/122). 36 cases were treatment naive (29.51%, 36/122). The top five dominant genera of the total population (122 cases) were Prevotella, Roseburia, Megamonas, Bacteroides and Faecalibacterium and the top five dominant genera of the ART population (86 cases) were Prevotella, Megamonas, Bacteroides, Roseburia and Faecalibacterium. The top five dominant genera of the ART-naive population (36 cases) appeared as Prevotella, Faecalibacterium, Roseburia, Bacteroides and Megamonas. In the total population, ART (P<0.001) was the most significant factors of community structure. Other significant factors were: duration of diagnosis (P=0.009), viral load (P=0.022) and anti-HCV (P=0.018). ART was positively correlated with Megamonas and negatively correlated with Prevotella, Roseburia and Faecalibacterium, while the other three factors of duration of diagnosis, viral load and anti-HCV were positively correlated with Prevotella, Roseburia and Faecalibacterium and negatively correlated with Megamonas. In the ART-naive population, duration of diagnosis (P=0.003) were the factors significantly associated with community structure. Duration of diagnosis was positively correlated with Roseburia, Faecalibacterium, Megamonas and Prevotella and negatively correlated with Bacteroides. Conclusion: ART and duration of diagnosis were factors significantly associated with gut microbial community structure and had a significant impact on multiple high-abundance genera.

Trend and prediction of hepatitis C cases in children aged 14 years old and younger in Henan province, 2005-2020 / 中华流行病学杂志

Objective: To explore the time series characteristics of hepatitis C cases in children aged ≤14 years old in Henan and predict their epidemic situation with effective model. Methods: Hepatitis C reported data among children aged ≤14 years old in Henan from 2005 to 2020 were collected from China information system for diseases control and prevention. Descriptive and time series analyses were used to demonstrate characteristics of time trend, decomposition methods were used to show the seasonality by using seasonal indices and the long-term trend by using a linear regression model. An auto-regressive integrated moving average (ARIMA) model was established. Results: From 2005 to 2020, a total of 5 355 hepatitis C cases in children were reported in Henan, the seasonal index range of the hepatitis C was lower than 1, and no obvious seasonality characteristics was observed. The average of monthly incidence of 2005-2011 showed increase trend (0.351 case/month), and the incidence of 2012-2020 decreased (-0.474 case/month). The predicted reported case number of hepatitis C in children in Henan from January 2005 to December 2020 fitted by ARIMA model was consistent with the actual number, the RMSE of the number of reported cases in the current year and the existing number of children cases was 10.240, 10.558, the MAPE was 35.566, 0.659, and the MAE was 6.688, 7.156, respectively. Conclusion: Time series analysis on surveillance data is useful for the better understanding of the epidemic situation of hepatitis C in children aged ≤14 years. ARIMA model can be used in the short-term prediction and dynamic analysis of the incidence of hepatitis C in children in Henan.

A new classification on location of hepatolithiasis in guiding treatment with percutaneous transhepatic choledochoscopic lithotripsy / 中华肝胆外科杂志

Objective:To study the clinical application of a new classification on location of hepatolithiasis in guiding treatment using percutaneous transhepatic choledochoscopic lithotomy (PTCSL).Methods:The clinical data of 85 consecutive patients with preoperatively diagnosed hepatolithiasis who underwent PTCSL at the First Affiliated Hospital of Nanjing Medical University from January 2017 to July 2021 were prospectively collected. There were 27 males and 58 females, aged from 15 to 86(62±14) years. Hepatolithiasis was classified into five types of stone location based on preoperative imagings: type Ⅰ ( n=12) , stones located in central bile duct, including hilar bile duct and common hepatic duct; type Ⅱ ( n=17) in unilateral hepatic duct with multiple branches; type Ⅲ ( n=24) in unilateral hepatic duct with multiple branches plus central bile duct; type Ⅳ ( n=31) in bilateral hepatic ducts with multiple branches; and type Ⅴ ( n=1) in unilateral hepatic duct with a single branch. Fistulation path, number of procedures, number of bile duct fistula, and complications were recorded. The residual stone rate and stone recurrence rate were compared among the five types. The follow-up was performed to analyse prognosis. Results:A total of 99 biliary fistulae were performed, with one single tract created in 74 patients, two tracts in 9 patients, three tracts in 1 patient, and four tracts in 1 patient. The fistulation path was B2 in 12 patients, B3 in 18 patients, B4 in 1 patient, B5 in 4 patients, B6 in 10 patients, B7 in 4 patients, and B8 in 50 patients. Altogether, 151 choledochoscopic lithotomy procedures were performed (1-3 times per patient, mean 1.78 times). For the 9 patients with residual stones (10.6%, 9/85), there were 3 patients with type Ⅱ and 6 patients with type Ⅳ. There were significant differences in the residual stone rates among the 5 types (χ 2=11.13, P=0.025). Stone recurrence developed in 33 (38.8%) patients, including 2 patients with type Ⅰ, 7 patients with type Ⅱ, 10 patients with type Ⅲ and 14 patients with type Ⅳ (χ 2=9.07, P=0.046). The total intraoperative and postoperative complications rates was 28.2% (24/85). The follow-up period was 4-58 months with the median follow-up time of 30 months. Twelve patients died during the follow-up period, including 1 patient who died from postoperative bleeding, 3 cholangiocarcinoma, 7 biliary cirrhosis-related liver failure, and 1 stone-unrelated disease. Conclusion:Type Ⅳ in the location classification of hepatolithiasis based on PTCSL had significantly higher rates of residual stones and stone recurrence. This new classification is helpful for clinicaians to determine the optimal path using a smaller number of fistulation tracts to clear stones. It improved the efficacy of PTCSL in treating hepatolithiasis.

Eye tracking studies related to social attention deficits in autism spectrum disorders / 中华行为医学与脑科学杂志

Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders.Impaired social functioning is a core characteristic of individuals with ASD.Social attention deficits are important manifestation of their impaired social functioning.And it mainly reflected in the gaze on faces and social interactions.Eye movement technology is an objective and sensitive non-invasive measurement tool.Its application makes the measurement of individual core characteristics of ASD more accurate and objective.A review of recent studies revealed that the type of eye-movement stimuli for social attention in patients with AD gradually shifted from face image processing to social interaction scenes, and developed from static presentation to dynamic presentation.Dimensional embodiment of the progress of eye-movement studies of social attention in individuals with ASD.These studies suggest that individuals with ASD are less likely to gaze at the face region and the eye region of the face.More studies are currently using eye-tracking technology, and the analysis of emotional face gaze reveals that, the reduction in eye gaze in individuals with ASD is due to the discomfort associated with threatening faces.These findings validate the " gaze aversion" hypothesis regarding impaired social attention in individuals with ASD.Related neural mechanism studies have found a general lack of attention to social cues in the environment in individuals with ASD.Brain regions such as the amygdala, cingulate gyrus, superior temporal sulcus and anterior insula are associated with social attention in individuals with ASD.Especially with the superior temporal sulcus, the dorsal and ventral sides of the anterior insula, and so on.Future research should explore the cognitive neural mechanisms of social attention deficits in ASD, and the application of advanced information technology, such as eye-tracking technology, in the rehabilitation of patients with ASD.

Anti-tumor Mechanism of Active Ingredients of Glycyrrhizae Radix et Rhizoma and Its Combined Use in Anti-tumor Treatment： A Review / 中国实验方剂学杂志

As a traditional Chinese medicinal material， Glycyrrhizae Radix et Rhizoma has been extensively used in various formulae. According to modern pharmacological research， it has anti-tumor， anti-inflammatory， anti-viral， liver-protecting， anti-heart failure， immunoregulatory， and anti-fibrosis effects. Caused by the interaction of various factors， cancer features complex pathogenesis. It is a global challenge and one of the main causes of death in China. Statistics show that the morbidity and mortality of malignant tumors have been on the rise， particularly for the young， which threaten the health of human beings. At the moment， radiotherapy and chemotherapy are the main countermeasures. Most clinical anti-tumor drugs demonstrate non-selective toxicity. To be specific， they damage normal cells while killing tumor cells， thus injuring vital organs. In addition， long-term medication will reduce the sensitivity of tumor cells. However， traditional Chinese medicine， which is characterized by treatment based on syndrome differentiation， multiple components， and multiple targets， is superior in the treatment of tumor. Studies have shown that the combination of anti-tumor drugs with Chinese medicine can not only enhance the anti-tumor effect but also alleviate toxicity. Therefore， it has been a research hotspot to develop anti-tumor drugs based on traditional Chinese medicine. In recent years， major headway has been made in the research on active ingreddients of Glycyrrhizae Radix et Rhizoma in anti-liver cancer， anti-breast cancer， anti-lung cancer， and anti-colon cancer and the combination with other drugs for anti-tumor. On this basis， we summarized the mechanisms of active ingredients of Glycyrrhizae Radix et Rhizoma in inducing apoptosis， interfering with cell cycle， inducing autophagy， inhibiting glycolysis， regulating immunity， and modulating miRNA and signaling pathways， as well as the combination with other drugs in anti-tumor efficiency， toxicity reduction， and sensitivity enhancement， hoping to lay a theoretical basis for the further development and clinical application of active ingredients of Glycyrrhizae Radix et Rhizoma.

Targeting GATA1 and p2x7r Locus Binding in Spinal Astrocytes Suppresses Chronic Visceral Pain by Promoting DNA Demethylation / 神经科学通报·英文版

Irritable bowel syndrome is a gastrointestinal disorder of unknown etiology characterized by widespread, chronic abdominal pain associated with altered bowel movements. Increasing amounts of evidence indicate that injury and inflammation during the neonatal period have long-term effects on tissue structure and function in the adult that may predispose to gastrointestinal diseases. In this study we aimed to investigate how the epigenetic regulation of DNA demethylation of the p2x7r locus guided by the transcription factor GATA binding protein 1 (GATA1) in spinal astrocytes affects chronic visceral pain in adult rats with neonatal colonic inflammation (NCI). The spinal GATA1 targeting to DNA demethylation of p2x7r locus in these rats was assessed by assessing GATA1 function with luciferase assay, chromatin immunoprecipitation, patch clamp, and interference in vitro and in vivo. In addition, a decoy oligodeoxynucleotide was designed and applied to determine the influence of GATA1 on the DNA methylation of a p2x7r CpG island. We showed that NCI caused the induction of GATA1, Ten-eleven translocation 3 (TET3), and purinergic receptors (P2X7Rs) in astrocytes of the spinal dorsal horn, and demonstrated that inhibiting these molecules markedly increased the pain threshold, inhibited the activation of astrocytes, and decreased the spinal sEPSC frequency. NCI also markedly demethylated the p2x7r locus in a manner dependent on the enhancement of both a GATA1-TET3 physical interaction and GATA1 binding at the p2x7r promoter. Importantly, we showed that demethylation of the p2x7r locus (and the attendant increase in P2X7R expression) was reversed upon knockdown of GATA1 or TET3 expression, and demonstrated that a decoy oligodeoxynucleotide that selectively blocked the GATA1 binding site increased the methylation of a CpG island in the p2x7r promoter. These results demonstrate that chronic visceral pain is mediated synergistically by GATA1 and TET3 via a DNA-demethylation mechanism that controls p2x7r transcription in spinal dorsal horn astrocytes, and provide a potential therapeutic strategy by targeting GATA1 and p2x7r locus binding.

Oxygen Metabolism-induced Stress Response Underlies Heart-brain Interaction Governing Human Consciousness-breaking and Attention / 神经科学通报·英文版

Neuroscientists have emphasized visceral influences on consciousness and attention, but the potential neurophysiological pathways remain under exploration. Here, we found two neurophysiological pathways of heart-brain interaction based on the relationship between oxygen-transport by red blood cells (RBCs) and consciousness/attention. To this end, we collected a dataset based on the routine physical examination, the breaking continuous flash suppression (b-CFS) paradigm, and an attention network test (ANT) in 140 immigrants under the hypoxic Tibetan environment. We combined electroencephalography and multilevel mediation analysis to investigate the relationship between RBC properties and consciousness/attention. The results showed that RBC function, via two independent neurophysiological pathways, not only triggered interoceptive re-representations in the insula and awareness connected to orienting attention but also induced an immune response corresponding to consciousness and executive control. Importantly, consciousness played a fundamental role in executive function which might be associated with the level of perceived stress. These results indicated the important role of oxygen-transport in heart-brain interactions, in which the related stress response affected consciousness and executive control. The findings provide new insights into the neurophysiological schema of heart-brain interactions.

Application of ultrasound-guided endoscopic retrograde appendicitis therapy in children with appendix-related chronic abdominal pain / 中国当代儿科杂志

OBJECTIVES@#To study the clinical efficacy of ultrasound-guided endoscopic retrograde appendicitis therapy in children with appendix-related chronic abdominal pain.@*METHODS@#A retrospective analysis was performed on the medical data of 30 children with the chief complaint of chronic abdominal pain who were admitted from August 2019 to May 2021. All the children were found to have inflammation of the appendix or intracavitary stool and fecalith by ultrasound and underwent ultrasound-guided endoscopic retrograde appendicitis therapy. The medical data for analysis included clinical manifestations, endoscopic findings, white blood cell count, neutrophil percentage, length of hospital stay, and cure rate.@*RESULTS@#Among the 30 children with chronic abdominal pain, there were 13 boys (43%) and 17 girls (57%), with a mean age of (9±3) years (range 3-15 years) at diagnosis. The median duration of the disease was 12 months, and the median length of hospital stay was 3 days. The children had a median white blood cell count of 6.7×109/L and a neutrophil percentage of 50%±13%. Fecalith and a large amount of feces were flushed out of the appendix cavity for 21 children (70%) during surgery. The follow-up rate was 97% (29/30), and the median follow-up time was 11 months (range 5-26 months). Of the 29 children, abdominal pain completely disappeared in 27 children (93%).@*CONCLUSIONS@#Ultrasound-guided endoscopic retrograde appendicitis therapy is effective in children with chronic abdominal pain caused by feces or fecalith in the appendix cavity.