Protective effect of Liujing Toutong Tablets on rats with permanent cerebral ischemia via NF-κB signaling pathway / 中国中药杂志

This study investigated the neuroprotective effects and underlying mechanism of Liujing Toutong Tablets(LJTT) on a rat model of permanent middle cerebral artery occlusion(pMCAO). The pMCAO model was established using the suture method. Eighty-four male SPF-grade SD rats were randomly divided into a sham operation group, a model group, a nimodipine group(0.020 g·kg~(-1)), and high-, medium-, and low-dose LJTT groups(2.8, 1.4, and 0.7 g·kg~(-1)). The Longa score, adhesive removal test and laser speckle contrast imaging technique were used to evaluate the degree of neurological functional impairment and changes in local cerebral blood flow. The survival and mortality of rats in each group were recorded daily. After seven days of continuous administration following the model induction, the rats in each group were euthanized, and brain tissue and blood samples were collected for corresponding parameter measurements. Nissl staining was used to examine pathological changes in brain tissue neurons. The levels of tumor necrosis factor-alpha(TNF-α), interleukin-6(IL-6), IL-1β, vascular endothelial growth factor(VEGF), calcitonin gene-related peptide(CGRP), beta-endorphin(β-EP), and endogenous nitric oxide(NO) in rat serum were measured using specific assay kits. The entropy weight method was used to analyze the weights of various indicators. The protein expression levels of nuclear factor kappa-B(NF-κB), inhibitor kappaB alpha(IκBα), phosphorylated IκBα(p-IκBα), and phosphorylated inhibitor of NF-κB kinase alpha(p-IKKα) in brain tissue were determined using Western blot. Immunohistochemistry was used to detect the protein expression of chemokine-like factor 1(CKLF1) and C-C chemokine receptor 5(CCR5) in rat brain tissue. Compared with the sham operation group, the model group showed significantly higher neurological functional impairment scores, prolonged adhesive removal time, decreased cerebral blood flow, increased neuronal damage, reduced survival rate, significantly increased levels of TNF-α, IL-1β, IL-6, CGRP, and NO in serum, significantly decreased levels of VEGF and β-EP, significantly increased expression levels of NF-κB p65, p-IκBα/IκBα, and p-IKKα in rat brain tissue, and significantly upregulated protein expression of CKLF1 and CCR5. Compared with the model group, the high-dose LJTT group significantly improved the neurological functional score of pMCAO rats after oral administration for 7 days. LJTT at all doses significantly reduced adhesive removal time and restored cerebral blood flow. The high-and medium-dose LJTT groups significantly improved neuronal damage. The LJTT groups at all doses showed reduced levels of TNF-α, IL-1β, IL-6, CGRP, and NO in rat serum, increased VEGF and β-EP levels, and significantly decreased expression levels of NF-κB p65, p-IκBα/IκBα, p-IKKα, and CCR5 protein in rat brain tissue. The entropy weight analysis revealed that CGRP and β-EP were significantly affected during the model induction, and LJTT exhibited a strong effect in reducing the release of inflammatory factors such as TNF-α and IL-1β. LJTT may exert a neuroprotective effect on rats with permanent cerebral ischemia by reducing neuroinflammatory damage, and its mechanism may be related to the inhibition of the NF-κB signaling pathway and the regulation of the CKLF1/CCR5 axis. Additionally, LJTT may exert certain analgesic effects by reducing CGRP and NO levels and increasing β-EP levels.

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.

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.

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.

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.

Correlation between sarcopenia,sarcopenic obesity and osteoporosis in adults of Han nationality in Liaoning province / 解剖学报

Objective To understand the prevalence of sarcopenia,sarcopenic obesity and osteoporosis, and to analyze the influence of sarcopenia and sarcopenic obesity on osteoporosis. Methods After all the people signed the informed research agreement, the experimental subjects were selected from Han people over 20 years old in Liaoning region, and a total of 1266 cases were included. The distribution of muscle mass, fat mass and bone mineral density in different parts of adults were measured by bioelectrical impedance analyzer (BIA) and bone densitometer, and the correlation between sarcopenia and sarcopenic obesity and osteoporosis in adults was studied. Results With the increase of age, the muscle mass of limbs, trunk, total muscle mass and body weight of the Han adults in Liaoning showed a trend of increasing at first and then decreasing. There was no significant difference in the prevalence of sarcopenia and sarcopenic obesity between men and women, but there was a significant difference in the prevalence of osteoporosis between men and women. The prevalence of all three groups reached the peak in the age group above 60, and the difference was statistically significant.The risk factor for osteoporosis was sarcopenia and sarcopenic obesity. Conclusion Among adults of Han nationality in Liaoning, the prevalence of sarcopenic obesity,sarcopenia and osteoporosis is significantly different in age. Bone condition is affected by fat mass and muscle mass.

Hippo-YAP pathway is involved in the effect of NaAsO / 中国药理学通报

Aim To explore the effects of NaAsO

The protective effect of orcinol glucoside on dexamethasone induced osteoblast cell damage through inhibition of glucocorticoid receptor nucleus translocation / 中国药理学通报

Aim To investigate the protective effect of orcinol glucoside on dexamethasone(DEX)-induced osteoblast injury and its mechanism. Methods Primary osteoblasts were extracted from calvaria of neonatal mice and cultured in medium with DEX(1 μmol•L

Efficacy and safety of Kangxian Huanji Granule as adjunctive treatment in acute exacerbation of idiopathic pulmonary fibrosis: An exploratory randomized controlled trial / 中西医结合学报

BACKGROUND@#Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is an important occurrence in the natural history of idiopathic pulmonary fibrosis (IPF), associated with high hospitalization rates, high mortality and poor prognosis. At present, there is no effective treatment for AE-IPF. Chinese herbal medicine has some advantages in treating IPF, but its utility in AE-IPF is unclear.@*OBJECTIVE@#The treatment of AE-IPF with Kangxian Huanji Granule (KXHJ), a compound Chinese herbal medicine, lacks an evidence-based justification. This study explores the efficacy and safety of KXHJ in patients with AE-IPF.@*DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS@#We designed a randomized, double-blind, placebo-controlled, exploratory clinical trial. A total of 80 participants diagnosed with AE-IPF were randomly assigned to receive KXHJ or a matching placebo; the treatment included a 10 g dose, administered twice daily for 4 weeks, in addition to conventional treatment. Participants were followed up for 12 weeks after the treatment.@*MAIN OUTCOME MEASURES@#The primary endpoints were treatment failure rate and all-cause mortality. Secondary endpoints included the length of hospitalization, overall survival, acute exacerbation rate, intubation rate, the modified British Medical Research Council (mMRC) score, and the St George's Respiratory Questionnaire for IPF (SGRQ-I) score.@*RESULTS@#The rate of treatment failure at 4 weeks was lower in the intervention group compared to the control group (risk ratio [RR]: 0.22; 95% confidence interval [CI]: 0.051 to 0.965, P = 0.023). There was no significant difference in all-cause mortality at 16 weeks (RR: 0.75; 95% CI: 0.179 to 3.138; P > 0.999) or in the acute exacerbation rate during the 12-week follow-up period (RR: 0.69; 95% CI: 0.334 to 1.434; P = 0.317). The intervention group had a shorter length of hospitalization than the control group (mean difference [MD]: -3.30 days; 95% CI, -6.300 to -0.300; P = 0.032). Significant differences in the mean change from baseline in the mMRC (between-group difference: -0.67; 95% CI: -0.89 to -0.44; P < 0.001) and SGRQ-I score (between-group difference: -10.36; 95% CI: -16.483 to -4.228; P = 0.001) were observed after 4 weeks, and also in the mMRC (between-group difference: -0.67; 95% CI: -0.91 to -0.43; P < 0.001) and SGRQ-I (between-group difference: -10.28; 95% CI, -15.838 to -4.718; P < 0.001) at 16 weeks. The difference in the adverse events was not significant.@*CONCLUSION@#KXHJ appears to be effective and safe for AE-IPF and can be considered a complementary treatment in patients with AE-IPF. As a preliminary exploratory study, our results provide a basis for further clinical research.@*TRIAL REGISTRATION@#Chinese Clinical Trial Registry (ChiCTR1900026289). Please cite this article as: Li JS, Zhang HL, Guo W, Wang L, Zhang D, Zhao LM, Zhou M. Efficacy and safety of Kangxian Huanji Granule as adjunctive treatment in acute exacerbation of idiopathic pulmonary fibrosis: an exploratory randomized controlled trial. J Integr Med. 2023; 21(6): 543-549.

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.

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.

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.

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.

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.

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.