Epidemiologic changes of a longitudinal surveillance study spanning 51 years of scrub typhus in mainland China.

Scrub typhus may be one of the world's most prevalent, neglected and serious, but easily treatable, febrile diseases. It has become a significant potential threat to public health in China. In this study we used national disease surveillance data to analyze the incidence and spatial-temporal distribution of scrub typhus in mainland China during 1952-1989 and 2006-2018. Descriptive epidemiological methods and spatial-temporal epidemiological methods were used to investigate the epidemiological trends and identify high-risk regions of scrub typhus infection. Over the 51-year period, a total of 182,991 cases and 186 deaths were notified. The average annual incidence was 0.13 cases/100,000 population during 1952-1989. The incidence increased sharply from 0.09/100,000 population in 2006 to 1.93/100,000 population in 2018 and then exponentially increased after 2006. The incidence was significantly higher in females than males (χ2 = 426.32, P < 0.001). Farmers had a higher incidence of scrub typhus than non-farmers (χ2 = 684.58, P < 0.001). The majority of cases each year were reported between July and November with peak incidence occurring during October each year. The trend surface analysis showed that the incidence of scrub typhus increased gradually from north to south, and from east and west to the central area. The spatial autocorrelation analysis showed that a spatial positive correlation existed in the prevalence of scrub typhus on a national scale, which had the characteristic of aggregated distribution (I = 0.533, P < 0.05). LISA analysis showed hotspots (High-High) were primarily located in the southern and southwestern provinces of China with the geographical area expanding annually. These findings provide scientific evidence for the surveillance and control of scrub typhus which may contribute to targeted strategies and measures for the government.

[Response Characteristics of Soil Fungal Community Structure to Long-term Continuous Cropping of Pepper].

This study aimed to clarify the effect of long-term continuous cropping of pepper on soil fungal community structure, reveal the mechanism of continuous cropping obstacles, and provide a theoretical basis for the ecological safety and sustainable development of pepper industry. We took the pepper continuous cropping soil in the vegetable greenhouse planting base of Tongren City as the research object. The diversity and community structure of fungi in farmland soil were analyzed using Illumina MiSeq high-throughput sequencing, the responses of soil physio-chemical properties and fungal community characteristics to long-term continuous pepper cropping were discussed, and the relationships between the characteristics of fungal community structure and environmental factors were determined using CCA and correlation network analysis. The results showed that with the extension of pepper continuous cropping years, the soil pH value and organic matter (OM) content decreased, total phosphorus (TP) and available phosphorus (AP) contents increased, hydrolyzed nitrogen (AN) and available potassium (AK) contents decreased first and then increased, and total nitrogen (TN) and total potassium (TK) contents did not change significantly. Long-term continuous cropping decreased the Chao1 index and observed species index and decreased the Shannon index and Simpson index. The change in continuous cropping years had a significant effect on the relative abundance of soil fungal dominant flora. At the phylum level, the relative abundance of Mortierellomycota decreased with the extension of pepper continuous cropping years, the relative abundance of Ascomycota increased first and then decreased, and the relative abundance of Basidiomycota decreased first and then increased. At the genus level, with the increasing of pepper continuous cropping years, the relative abundance of Fusarium increased, and the relative abundance of Mortierella and Penicillium decreased. In addition, long-term continuous cropping simplified the soil fungal symbiosis network. CCA analysis indicated that pH, OM, TN, AN, AP, and AK were the driving factors of soil fungal community structure, and correlation network analysis showed that pH, OM, TN, TP, TK, AN, AP, and AK were the driving factors of soil fungal community structure, including Fusarium, Lophotrichus, Penicillium, Mortierella, Botryotrichum, Staphylotrichum, Plectosphaerella, and Acremonium. In conclusion, continuous cropping changed the soil physical and chemical properties, affected the diversity and community structure of the soil fungal community, changed the interaction between microorganisms, and destroyed the microecological balance of the soil, which might explain obstacles associated with continuous cropped pepper.

Ruthenium-dihydroartemisinin complex: a promising new compound for colon cancer prevention via G1 cell cycle arrest, apoptotic induction, and adaptive immune regulation.

BACKGROUND: Artemisinin (ART) and its derivatives are important antimalaria agents and have received increased attention due to their broad biomedical effects, such as anticancer and anti-inflammation activities. Recently, ruthenium-derived complexes have attracted considerable attention as their anticancer potentials were observed in preclinical and clinical studies. METHODS: To explore an innovative approach in colorectal cancer (CRC) management, we synthesized ruthenium-dihydroartemisinin complex (D-Ru), a novel metal-based artemisinin derivative molecule, and investigated its anticancer, anti-inflammation, and adaptive immune regulatory properties. RESULTS: Compared with its parent compound, ART, D-Ru showed stronger antiproliferative effects on the human CRC cell lines HCT-116 and HT-29. The cancer cell inhibition of D-Ru comprised G1 cell cycle arrest via the downregulation of cyclin A and the induction of apoptosis. ART and D-Ru downregulated the expressions of pro-inflammatory cytokines IL-1ß, IL-6, and IL-8. Although ART and D-Ru did not suppress Treg cell differentiation, they significantly inhibited Th1 and Th17 cell differentiation. CONCLUSIONS: Our results demonstrated that D-Ru, a novel ruthenium complexation of ART, remarkably enhanced its parent compound's anticancer action, while the anti-inflammatory potential was not compromised. The molecular mechanisms of action of D-Ru include inhibition of cancer cell growth via cell cycle arrest, induction of apoptosis, and anti-inflammation via regulation of adaptive immunity.

Ligamentum teres hepatis as a graft for portal and/or superior mesenteric vein reconstruction: From bench to bedside.

BACKGROUND: Pancreaticoduodenectomy combined with portal vein (PV) and/or superior mesenteric vein (SMV) resection in patients with pancreaticobiliary malignancy has become a common surgical procedure. There are various grafts currently used for PV and/or SMV reconstruction, but each of these grafts have certain limitations. Therefore, it is necessary to explore novel grafts that have an extensive resource pool, are low cost with good clinical application, and are without immune response rejection or additional damage to patients. AIM: To observe the anatomical and histological characteristics of the ligamentum teres hepatis (LTH) and evaluate PV/SMV reconstruction using an autologous LTH graft in pancreaticobiliary malignancy patients. METHODS: In 107 patients, the post-dilated length and diameter in resected LTH specimens were measured. The general structure of the LTH specimens was observed by hematoxylin and eosin (HE) staining. Collagen fibers (CFs), elastic fibers (EFs), and smooth muscle (SM) were visualized by Verhoeff-Van Gieson staining, and the expression of CD34, factor VIII-related antigen (FVIIIAg), endothelial nitric oxide synthase (eNOS), and tissue type plasminogen activator (t-PA) were detected using immunohistochemistry in LTH and PV (control) endothelial cells. PV and/or SMV reconstruction using the autologous LTH was conducted in 26 patients with pancreaticobiliary malignancies, and the outcomes were retrospectively analyzed. RESULTS: The post-dilated length of LTH was 9.67 ± 1.43 cm, and the diameter at a pressure of 30 cm H2O was 12.82 ± 1.32 mm at the cranial end and 7.06 ± 1.88 mm at the caudal end. Residual cavities with smooth tunica intima covered by endothelial cells were found in HE-stained LTH specimens. The relative amounts of EFs, CFs and SM in the LTH were similar to those in the PV [EF (%): 11.23 ± 3.40 vs 11.57 ± 2.80, P = 0.62; CF (%): 33.51 ± 7.71 vs 32.11 ± 4.82, P = 0.33; SM (%): 15.61 ± 5.26 vs 16.74 ± 4.83, P = 0.32]. CD34, FVIIIAg, eNOS, and t-PA were expressed in both LTH and PV endothelial cells. The PV and/or SMV reconstructions were successfully completed in all patients. The overall morbidity and mortality rates were 38.46% and 7.69%, respectively. There were no graft-related complications. The postoperative vein stenosis rates at 2 wk, 1 mo, 3 mo and 1 year were 7.69%, 11.54%, 15.38% and 19.23%, respectively. In all 5 patients affected, the degree of vascular stenosis was less than half of the reconstructed vein lumen diameter (mild stenosis), and the vessels remained patent. CONCLUSION: The anatomical and histological characteristics of LTH were similar to the PV and SMV. As such, the LTH can be used as an autologous graft for PV and/or SMV reconstruction in pancreaticobiliary malignancy patients who require PV and/or SMV resection.

Effects of different fertilization treatments on soil microbial functional diversity of dry tableland wheat field in south Shanxi Province.

Understanding the effects of different fertilization treatments on microbial functional diversity in loess tableland wheat soil in south Shanxi Province can provide the theoretical basis from the perspective of microbial functional diversity for chemical fertilizer reduction, wheat yield increase, and soil fertility improvement in dryland soil. We conducted a long-term field experiment with seven fertilization treatments in winter wheat cultivation area of loess tableland in south Shanxi Province, including straw charcoal fertilizer (SF), bacterial fertilizer (BF), organic fertilizer (OF), humic acid fertilizer (HF), monitoring fertilizer (MF), farmer fertilizer (FF) and no fertilizer (CK). We employed Biolog-ECO microplate technique to investigate the differences of carbon source utilization capacity and functional diversity of soil microorganisms. The results showed that all the fertilization treatments could improve the metabolic activity and functional diversity of soil microbial community. Carbon source utilization was the most efficient in SF, with the overall soil microbial utilization ability of the 31 carbon sources and the utilization ability of different guilds of carbon sources being improved. Functional diversity, richness, and dominance based on microbial carbon sources utilization were significantly higher in SF treatment than that under other five treatments, and the evenness was higher than BF. Results of principal component analysis (PCA) and biclustering heatmap analysis showed that different fertilization treatments had significant effects on the metabolic function of microbial community. SF treatment could promote the functional diversity of soil microbial community, especially for the utilization of carbohydrates, carboxylic acids and amino acids. In conclusion, straw charcoal fertilizer had positive effects on soil microbial activity in wheat soil of loess tableland in south Shanxi Province.

Hemiplegia due to hypoglycaemia followed by haemicorea after correction of glycaemic values.

A 69-year-old man suffered from hemiplegia of the left limb due to hypoglycaemia. After 3 h of oral supplementation with sugar water, the patient recovered from hemiplegia but then presented symptoms of haemichorea. To our knowledge, a case of abnormal glucose metabolism complicated with two types of motor disturbance has not been reported previously.

Factors influencing thrombelastography in pregnancy / 中南大学学报(医学版)

OBJECTIVES@#The number of gestational women has been increased in recent years, resulting in more adverse pregnancy outcomes. It is crucial to assess the coagulation function of pregnant women and to intervene in a timely manner. This study aims to analyze the influencing factors on thrombelastography (TEG) and explore the evaluation of TEG for gestational women.@*METHODS@#A retrospective study was conducted on 449 pregnant women who were hospitalized in the obstetrics department in Xiangya Hospital of Central South University from 2018 to 2020. We compared the changes on the TEG parameters among normal pregnant women between different age groups, different ingravidation groups, and different stages of pregnancy groups. The influence on TEG of hypertensive disorders in pregnancy (HDP) and gestational diabetes mellitus (GDM) as well as two diseases synchronization was explored.@*RESULTS@#Compared with the normal second trimester women, the R values and K values of TEG were increased, and α angle, CI values and LY30 values were decreased in third trimester women (all P<0.05). Compared with normal group, the R values and CI values of TEG of the HDP group have significant difference (both P<0.05). There were no significant difference of TEG between the GDM group, the HDP combined with GDM group and the normal group (all P>0.05). Multiple linear regression analysis showed that the influencing factors for R value in TEG were weeks of gestation (P<0.001) and mode of conception (P<0.05), for α angle was weeks of gestation (P<0.05), for MA value was mode of conception (P<0.05), and for CI value was weeks of gestation (P<0.05). The analysis of correlation between TEG with platelet (PLT) and coagulation routines represented that there was a correlation between TEG R values and activated partial thromboplastin time (APTT) (P<0.01), and negative correlation between TEG CI values and APTT (P<0.05). There was a negative correlation between TEG K values and FIB (P<0.05). The correlation of α angle (P<0.05), MA values (P<0.01) and CI values (P<0.05) with FIB were positive respectively.@*CONCLUSIONS@#The TEG parameters of 3 stages of pregnancy were different. The different ingravidation approach has effect on TEG. The TEG parameters were consistent with conventional coagulation indicators. The TEG can be used to screen the coagulation status of gestational women, recognize the abnormalities of coagulation and prevent the severe complication timely.

Preliminary study of PPARA regulate the ferroptosis of hepatocellular carcinoma to prevent disease deterioration / 中华预防医学杂志

To explore whether PPARA is involved in the process of ferroptosis in hepatoma cells, peroxisome proliferator activated receptor (PPARA) was comprehensively analyzed in hepatocellular carcinoma (HCC) through public database and experimental data, including the expression, the functions and the potential roles of tumor progression. The research design is experimental research,data analysis based on bioinformatics and cell experiment. From January 2022 to August 2022, relevant cell experiments were conducted in the Basic Medical Laboratory of the General Hospital of the Southern Theatre of the Chinese People's Liberation Army. The expression and the correlation with clinicopathologic features of PPARA in HCC were analyzed by The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. To study the protein expression of PPARA in HCC and normal tissues through the Human Protein Atlas (HPA). The protein-protein interaction (PPI) network between PPARA and the core factor of ferroptosis was constructed based on Search Tool for the Retrival of Interacting Genes/Protein (STRING) database, then, the correlation between PPARA and the core gene Glutamate-cysteine Ligase Catalytic Subunit (GCLC) was analyzed by Gene Expression Profiling Interactive Analysis (GEPIA). Assessed the expression of PPARA in HCC cell lines SK-HEP-1, SMMC-7721, MHCC-97H, BEL-7402 and normal liver cell L02 by Western Blot (WB) and the changes of PPARA expression after 48h treatment with ferroptosis inducer Erastin were observed. Single factor analysis of variance was used to compare the expression of PPARA between groups in GEPIA database. The expression of PPARA in GSE25097 and GSE112790 data was compared by rank sum test. Survival analysis was performed using time series test method. The difference of PPARA expression between clinical and pathological features was compared using the Kruskal-Wallis test. The correlation between the expression of GCLC and PPARA was compared by the method of Spearman correlation. The expression of PPARA in cell lines was compared by paired T test. The results showed that the RNA and protein expression of PPARA in HCC was lower than that in normal tissues (P<0.05). PPARA alterations were correlated with patient clinicopathological features and prognosis (P<0.05). The PPI constructed by STRING database suggests that PPARA interact with the key factors of ferroptosis, such as NFE2 like bZIP transcription factor 2 (NFE2L2), Heme Oxygenase 1 (HMOX1), Tumor Protein P53 (TP53), GCLC, Dipeptidyl Peptidase 4 (DPP4), Citrate Synthase (CS), Arachidonate 15-Lipoxygenase (ALOX15) and Acyl-CoA Synthetase Long Chain Family Member 4 (ACSL4). Furthermore, the PPARA was significantly associated with GCLC validated via GEPIA database(R=0.6, P<0.05). The expression of PPARA increased after treatment with ferroptosis inducer Erastin for 48 h by WB. In conclusion, the expression of PPARA is lower in HCC with a poor prognosis. PPARA interacts with GCLC in regulating ferroptosis in HCC.

Association between clinical phenotypes of hypertrophic cardiomyopathy and Ca2+ gene variation gene variation / 中华心血管病杂志

Objective: To observe the association between clinical phenotypes of hypertrophic cardiomyopathy (HCM) patients and a rare calcium channel and regulatory gene variation (Ca2+ gene variation) and to compare clinical phenotypes of HCM patients with Ca2+ gene variation, a single sarcomere gene variation and without gene variation and to explore the influence of rare Ca2+ gene variation on the clinical phenotypes of HCM. Methods: Eight hundred forty-two non-related adult HCM patients diagnosed for the first time in Xijing Hospital from 2013 to 2019 were enrolled in this study. All patients underwent exon analyses of 96 hereditary cardiac disease-related genes. Patients with diabetes mellitus, coronary artery disease, post alcohol septal ablation or septal myectomy, and patients who carried sarcomere gene variation of uncertain significance or carried>1 sarcomere gene variation or carried>1 Ca2+ gene variation, with HCM pseudophenotype or carrier of ion channel gene variations other than Ca2+ based on the genetic test results were excluded. Patients were divided into gene negative group (no sarcomere or Ca2+ gene variants), sarcomere gene variation group (only 1 sarcomere gene variant) and Ca2+ gene variant group (only 1 Ca2+ gene variant). Baseline data, echocardiography and electrocardiogram data were collected for analysis. Results: A total of 346 patients were enrolled, including 170 patients without gene variation (gene negative group), 154 patients with a single sarcomere gene variation (sarcomere gene variation group) and 22 patients with a single rare Ca2+ gene variation (Ca2+ gene variation group). Compared with gene negative group, patients in Ca2+ gene variation group had higher blood pressure and higher percentage of family history of HCM and sudden cardiac death (P<0.05); echocardiographic results showed that patients in Ca2+ gene variation group had thicker ventricular septum ((23.5±5.8) mm vs. (22.3±5.7) mm, P<0.05); electrocardiographic results showed that patients in Ca2+ gene variation group had prolonged QT interval ((416.6±23.1) ms vs. (400.6±47.2) ms, P<0.05) and higher RV5+SV1 ((4.51±2.26) mv vs. (3.50±1.65) mv, P<0.05). Compared with sarcomere gene variation group, patients in Ca2+ gene variation group had later onset age and higher blood pressure (P<0.05); echocardiographic results showed that there was no significant difference in ventricular septal thickness between two groups; patients in Ca2+ gene variation group had lower percentage of left ventricular outflow tract pressure gradient>30 mmHg (1 mmHg=0.133 kPa, 22.8% vs. 48.1%, P<0.05) and the lower early diastolic peak velocity of the mitral valve inflow/early diastolic peak velocity of the mitral valve annulus (E/e') ratio ((13.0±2.5) vs. (15.9±4.2), P<0.05); patients in Ca2+ gene variation group had prolonged QT interval ((416.6±23.1) ms vs. (399.0±43.0) ms, P<0.05) and lower percentage of ST segment depression (9.1% vs. 40.3%, P<0.05). Conclusion: Compared with gene negative group, the clinical phenotype of HCM is more severe in patients with rare Ca2+ gene variation; compared with patients with sarcomere gene variation, the clinical phenotype of HCM is milder in patients with rare Ca2+ gene variation.

Safety and efficacy of transcatheter closure of Fontan fenestration with atrial septal occluder / 中华心血管病杂志

Objective: To assess the safety and efficacy of transcatheter fenestration closure following Fontan procedure with an atrial septal occluder. Methods: This is a retrospective study. The study sample consists of all consecutive patients who underwent closure of a fenestrated Fontan baffle at Shanghai Children's Medical Center Affiliated to Shanghai Jiaotong University School of Medicine between June 2002 and December 2019. The indications of Fontan fenestration closure included that normal ventricular function, targeted drugs for pulmonary hypertension and positive inotropic drugs were not required prior the procedure; and the Fontan circuit pressure was less than 16 mmHg (1 mmHg=0.133 kPa) and no more than a 2 mmHg increase during test occlusion of the fenestration. Electrocardiogram and echocardiography were reviewed at 24 hours, 1, 3, 6 months and annually thereafter post procedure. Follow-up information including clinical events and complications related to Fontan procedure was recorded. Results: A total of 11 patients, including 6 males and 5 females, aged (8.9±3.7) years old were included. The types of Fontan were extracardiac conduits (7 cases) and intra-atrial duct (4 cases). The interval between percutaneous fenestration closure and the Fontan procedure was (5.1±2.9) years. One patient reported recurrent headache after Fontan procedure. Successful fenestration occlusion with atrial septal occluder was achieved in all patients. Compared with prior closure, Fontan circuit pressure ((12.72±1.90) mmHg vs. (12.36±1.63) mmHg, P<0.05), and aortic oxygen saturation ((95.11±3.11)% vs. (86.35±7.26)%, P<0.01) were increased. There were no procedural complications. At a median follow-up of (3.8±1.2) years, there was no residual leak and evidence of stenosis within the Fontan circuit in all patient. No complication was observed during follow-up. One patient with preoperative headache did not have recurrent headache after closure. Conclusions: If the Fontan pressure is acceptable by test occlusion during the catheterization procedure, Fontan fenestration could be occluded with the atrial septum defect device. It is a safe and effective procedure, and could be used for occlusion of Fontan fenestration with varying sizes and morphologies.

Research progress in brain computer interface technology applied to motor recovery after spinal cord injury / 中华创伤杂志

Most patients with spinal cord injury suffer from limb motor dysfunction. Given drugs, surgery and other conventional treatments are often not effective, the patients can only rely on a wheelchair to move or even lie in bed for a long time, seriously affecting their quality of life. Brain computer interface (BCI) technology provides a non-muscular pathway for the recovery of motor function in patients with spinal cord injury, which allows the patients to recover partial motor function through the normal function of their own non-diseased spinal cord or external mechanical devices. After decades of development of BCI technology, signal collection devices can identify and collect the motor signals of the brain more accurately, transform the signal by characteristic analysis, and implement the brain command by using the output device. A large number of experimental and clinical studies have also proved that the application of BCI technology in patients with spinal cord injury can partially improve the motor function of upper and lower limbs. Therefore, BCI technology has attracted more and more attention. The authors summarized the BCI technology and its influence on motor function rehabilitation in patients with spinal cord injury, so as to provide a reference for the rehabilitation of motor function in patients with spinal cord injury.

Physical health status and influencing factors of preschool children in Tibet / 中国学校卫生

Objective@#To explore physical health status and influencing factors of preschool children in Tibet, so as to provide a scientific reference and theoretical basis for the healthy development of physical fitness.@*Methods@#Data were collected from children (3-6 years old) of Xizang national physical fitness monitoring, and a total of 1 521 preschool children were recruited who received questionnaire survey and physical fitness test. Independent sample t-test and one-way ANOVA were used to compare the differences in physical fitness indexes of preschool children in different groups. Chi square test and binary Logistic regression model were used to analyze the factors affecting physical health of preschool children.@*Results@#The total qualified rate of physical fitness was 79.75%, among which the excellent rate was 3.16%, the good rate was 15.12%, the qualified rate was 61.47% and the unqualified was 20.25%. From the perspective of BMI, the excellent physical fitness rate (3.74%) and good physical fitness rate ( 17.47% ) were highest in healthy weight preschool children, and the qualified physical fitness rate of overweight preschool children (69.03%) was higher than that of obese (55.88%) and healthy weight preschool children (60.68%)( χ 2=53.56, P <0.01). From the perspective of ethnic, Tibetan children s physique proficiency (3.69%), good rate ( 17.13% ) than with the elevation of the Han nationality (0.74%, 5.88%), fraction defective (16.97%), lower than that of Han nationality (35.29%) ( χ 2=53.71, P <0.01); The results of chest circumference, skinfold thickness, body fat percentage, tennis throw distance, continuous jump of both feet, sitting forward bend and balance beam walking of Tibetan children were higher than those of Han children, and the results of quiet heart rate and standing long jump were lower than those of Han children ( t = 2.72 , 10.95, 9.66, 3.68, 3.88, 8.04, 3.56, 8.70, -4.39 , -4.40, P <0.01). Binary Logistic regression analysis showed that Tibetans ( OR =2.29), breastfeeding ( OR =1.51), body dynamics outdoor daily exercise duration 30-90 min (30-<60 min ;OR = 2.03 ; 60-90 min: OR =2.22) were positively correlated with physical health of preschool children ( P <0.05).@*Conclusions@#The total physical qualification rate of preschool children aged 3-6 years old in Tibet is lower than the national average. Ethnic group, feeding pattern during infancy, and physical activity are all factors that affected the physical fitness of preschool children in Tibet. It is of great significance to improve the physique of preschool children in Tibet to promote their sustainable and healthy development.

Mixing Characteristic and High-Throughput Synthesis of Cadmium Sulfide Nanoparticles with Cubic Hexagonal Phase Junctions in a Chaotic Millireactor.

A four-stage oscillating feedback millireactor with splitters (S-OFM) was designed to improve the mixing performance based on chaotic advection. Three-dimensional CFD simulations were used to investigate its flow characteristics and mixing performance, and the generation mechanisms of secondary flows were examined. The results show that the mixing index (MIcup) increased with the increase in the Reynolds number (Re), and MIcup could reach 99.8% at Re = 663. Poincaré mapping and Kolmogorov entropy were adopted to characterize the chaotic advection intensity, which indicates that there is a intensity increase with the increase in Re. In addition, the results of Villermaux-Dushman experiments demonstrate that S-OFM performs excellently, and the mixing time could reach 1.04 ms at Re = 2764. Finally, S-OFM was successfully used to synthesize CdS nanoparticles with cubic hexagonal phase junctions. At a flow rate of 180 mL/min, the average particle size was 10.5 nm and the particle size distribution was narrow (with a coefficient of variation of 0.14).

[Effect of WRAP53 ß Targeted Co-Inhibitory Pathways Based on Comprehensive Bioinformatics Analysis in Treating Squamous Cell Carcinoma of the Head and Neck].

Objective: To investigate the association between WD40-encoding RNA antisense to p53 ( WRAP53 ß), a telomerase new core subunit, and the clinical, genomic and immune infiltration characteristics of squamous cell carcinoma of the head and neck (HNSC), and to explore for potential joint targeted therapy of HNSC. Methods: Tumor IMmune Estimation Resource (TIMER) online modules were adopted to predict the association between WRAP53 ß expression and the clinical features, oncogene, and immune infiltration of HNSC in the Cancer Genome Atlas (TCGA) cohort. Tumor Immune Single-cell Hub (TISCH) was used to analyze WRAP53 ß expression at the single cell level. Analysis of the small molecule inhibitors potentially targeting WRAP53 ß was carried out by Computational Analysis of REsistance (CARE). In the in vitro verification experiment, recombinant lentiviral particles with the sh WRAP53 ß sequence were synthesized. Then, the oral squamous cell carcinoma cell line Cal27 (the sh WRAP53 ßgroup) stably expressing sh WRAP53 ß were constructed, and two control groups were set up (the shNC group consisting of Cal27 cells added with lentiviral particles containing non-specific control sequences and the Con group consisting of untreated Cal27 cells). MTT assay was done to examine the proliferation of cells in the three groups. Cellular immunofluorescence assay was done for further qualitative examination of the expression of P53 protein in the cells of the sh WRAP53 ß group and the shNC group. Western blot was done to measure the expression of WRAP53ß and γ-H2AX, a DNA damage protein, in the 18 th, 23 rd and 28 th passages of the sh WRAP53 ß group and the shNC group. Finally, specimens of 13 cases of oral squamous cell carcinoma and 7 cases of oral mucosal inflammation were collected, and the expression of WRAP53ß and γ-H2AX in the clinical specimens of oral squamous cell carcinoma was verified with immunohistochemistry. Resluts: TIMER analysis revealed that the expression level of WRAP53 ß in HNSC tissues was significantly higher than that in normal tissues. There was a significant positive correlation between WRAP53 ß expression and multiple genes in the p53 pathway, including CCNB1, CCNB2 and CDK1. Although no significant correlation between WRAP53 ß expression and infiltrating immune cells was found, WRAP53 ß was significantly positively correlated with the inflammatory factors IFN-γ and IL23A, and negatively correlated with IL-1A and IL-6 in HPV-positive carcinoma of the head and neck. TISCH single cell sequencing datasets also showed higher expression of WRAP53 ß in malignant cells, and very low or zero expression in immune cells. According to the CARE scores, the most potent WRAP53 ß co-inhibitory drugs were ATM, CDK1 and MDM4 targeted inhibitors. In vitro cell experiments showed that the proliferation ability of Cal27 cells decreased significantly in the sh WRAP53 ß group as compared with that of the control group between Day 5 and Day 7 ( P<0.05). Furthermore, the expression of P53 decreased significantly in the sh WRAP53 ß group. As compared with the control group, the expression of WRAP53ß in sh WRAP53 ß group significantly decreased in the 18 th, 23 rd and 28 th passages ( P<0.05), while γ-H2AX expression only decreased in the 18 th and 28 th passages ( P<0.05) according to the results of Western blot. Clinical specimens showed rather high positive expression rate of γ-H2AX in oral squamous cell carcinoma tissues (12/13), while the expression of WRAP53ß was not detected in oral mucositis samples (0/7). Conclusions: WRAP53 ß showed significantly higher expression level in HSNC, and was significantly associated with p53 pathway genes. ATM, CDK1 and MDM4 inhibitors may be potential WRAP53 ß co-inhibitory agents. RNA interference of WRAP53 ß expression may cause inhibition of DNA damage, thereby indicating therapeutic potential for HNSC.

[Comparison of functional recovery of distal radius fracture by suture of pronator muscle through modified Henry approach].

OBJECTIVE: To investigate the effect of suture of pronator muscle on forearm function after modified Henry approach for distal radius fractures. METHODS: from January 2018 to December 2020, 220 patients with distal radius fractures were treated with open reduction and locking plate internal fixation through the modified Henry approach. They were divided into two groups according to different suture methods. There were 112 cases in the intraoperative suture group, including 35 males and 77 females;The age ranged from 37 to 65(48.5±7.4) years;AO classification of fracture, 46 cases of type B and 66 cases of type C;After fracture reduction and locking plate fixation, the pronator muscle was opened and sutured. There were 108 cases in the non suture group, 32 males and 76 females;The age ranged from 34 to 67(47.6±7.8) years;There were 41 cases of fracture type B and 67 cases of fracture type C;After fracture reduction and locking plate fixation, the open pronator muscle was not sutured, and it was laid on the surface of the plate in situ. The range of wrist motion (pronation, supination, palmar inclination and dorsiflexion), the score of disability of arm shoulder and hand dash and visual analog scale(VAS) were compared between the two groups at 6 weeks and 6 months after operation. RESULTS: All 220 patients were followed up for 6 to 18 (8.5±1.3) months. There was no significant difference in the range of motion and DASH score of forearm and wrist between the two groups 6 weeks after operation (P>0.05);There was significant difference in VAS score between suture group (2.6±1.2) and non suture group (5.8±2.3)(P<0.05). Six months after operation, there was no significant difference in the range of motion, DASH score and VAS score of forearm and wrist between the two groups(P>0.05). CONCLUSION: The modified Henry approach has no obvious advantages in the range of wrist movement and upper limb function, but the intraoperative suture of pronator can reduce the early postoperative pain. It is suggested that the pronator should be sutured during the operation.

Epidemiological characteristics and spatiotemporal patterns of scrub typhus in Yunnan Province from 2006 to 2017.

Scrub typhus is an acute infectious disease in humans. A temporal, spatial and epidemiologic study was conducted to understand the characteristics of scrub typhus in Yunnan, to assist public health prevention and control measures. Based on the data on all cases reported in Yunnan during 2006-2017, we characterized the epidemiological features. Spatio-temporal patterns and Q-type cluster method were adopted to analyze the incidence of scrub typhus in Yunnan. In total, 27,838 scrub typhus cases were reported in Yunnan during 2006-2017. Of these, 49.53% (13,787) were male and 50.47% (14,051) were female (P > 0.05). Most patients were farmers (71.70%) (P < 0.05) and children aged 0-5 years (13.16%) (P < 0.01), which accounted for 84.86% of the total cases. An almost 20-fold increase in the number of patients was observed in 2017 (6,337 cases) compared to 2006 (307 cases). Baoshan and Lincang had the most cases accounting for 41.94%, while Diqing had the lowest incidence (only 3 cases). Sixteen municipalities infected were classified into three groups numbered in sequence. The incidence of scrub typhus in Yunnan is high and the annual incidence increased noticeably over time. Our results also indicate that surveillance and public education need to be focused on Baoshan, Lincang and Dehong.

Effects of dihydroartemisinin, a metabolite of artemisinin, on colon cancer chemoprevention and adaptive immune regulation.

BACKGROUND: Artemisinin (ART) is an anti-malaria natural compound with a moderate anticancer action. As a metabolite of ART, dihydroartemisinin (DHA) may have stronger anti-colorectal cancer (CRC) bioactivities. However, the effects of DHA and ART on CRC chemoprevention, including adaptive immune regulation, have not been systematically evaluated and compared. METHODS: Coupled with a newly-established HPLC analytical method, enteric microbiome biotransformation was conducted to identify if the DHA is a gut microbial metabolite of ART. The anti-CRC potential of these compounds was compared using two different human CRC cell lines for cell cycle arrest, apoptotic induction, and anti-inflammation activities. Naive CD4+ T cells were also obtained for testing the compounds on the differentiation of Treg, Th1 and Th17. RESULTS: Using compound extraction and analytical methods, we observed for the first time that ART completely converted into its metabolites by gut microbiome within 24 h, but no DHA was detected. Although ART did not obviously influence cancer cell growth in the concentration tested, DHA very significantly inhibited the cancer cell growth at relatively low concentrations. DHA included G2/M cell cycle arrest via upregulation of cyclin A and apoptosis. Both ART and DHA downregulated the pro-inflammatory cytokine expression. The DHA significantly promoted Treg cell proliferation, while both ART and DHA inhibited Th1 and Th17 cell differentiation. CONCLUSIONS: As a metabolite of ART, DHA possessed stronger anti-CRC activities. The DHA significantly inhibited cell growth via cell cycle arrest, apoptosis induction and anti-inflammation actions. The adaptive immune regulation is a related mechanism of actions for the observed effects.

Efficacy of percutaneous jejunal drainage in treatment of hepatolithiasis after choledochojejunostomy / 中华肝胆外科杂志

Objective:To study the feasibility and safety of percutaneous jejunal drainage in treatment of hepatolithiasis after choledochojejunostomy.Methods:The clinical data of 24 patients with hepatolithiasis after choledochojejunostomy treated by percutaneous jejunal drainage at the Cholelithiasis Center, Shanghai East Hospital Affiliated to Tongji University from May 2021 to May 2022 were retrospectively analyzed. There were 16 males and 8 females, aged (50.46±10.89) years old. Ultrasound and X ray guided percutaneous jejunography was performed under local anesthesia for patients with hepatolithiasis after choledochojejunostomy. Then the fistula was directly dilated to 16.0Fr, and percutaneous jejunal choledochoscopy was performed 3 days later. The success rate, complication rate and stone removal rate were analysed.Results:Twenty-four patients were treated with percutaneous jejunography, with a success rate of 79.2%(19/24), including 19 patients after anterior colonic cholangiojejunostomy with a success rate of 94.7%(18/19), and 5 patients after retrocolonic cholangiojejunostomy with a success rate of 20.0%(1/5). There was no complication including bleeding, intestinal leakage and bile leakage. In 19 patients with successful percutaneous jejunography, the success rate of fistula dilation was 100%(19/19), and there was no complication. Five patients with failed percutaneous jejunography underwent open choledocholithotomy through the jejunal output-loop, and bile leakage occurred in one patient. Thirteen patients with anastomotic stenosis, 5 with intrahepatic biliary strictures, and 6 with anastomotic and intrahepatic biliary strictures were diagnosed by choledochoscopy and selective cholangiography in these 24 patients. After choledochoscopic electrotomy, cylindrical balloon dilation, stone removal, stenting and other treatments, the stenosis relief rate was 100%(24/24), and the clearance rate of intrahepatic bile duct stones was 91.7%(22/24).Conclusion:Percutaneous jejunal drainage was a feasible, safe and minimally invasive method for treatment of hepatolithiasis after choledochojejunostomy. The procedure was especially suitable for patients with anterior colonic cholangiojejunostomy.

Therapeutic Effect of Mesenchymal Stem Cells Overexpressing Interleukin-10 on Inflammatory Bowel Disease / 中国生物化学与分子生物学报

Inflammatory bowel disease (IBD) is an, intractable inflammatory autoimmune disease characterized by T-cell infiltration to the colon. Mesenchymal stem cells (MSCs), owing to their immunosuppressive capabilities, have the potential to rescue IBD. But the therapeutic effectiveness of MSCs is sometime thwarted by their variable immunomodulatory ability in vivo. In the present study, we produced engineered MSCs that secrete interleukin10 (IL-10) and evaluated their therapeutic potential in IBD mouse model. The MSCs maintained the phenotype and cell proliferation rate after overexpression of IL-10 by lentivirus (LV) infection. Immune cells and MSCs in vitro co-culture systems exhibited that relative to unmodified MSCs, immune cells co-cultured with IL-10-overexpressing MSCs had significantly lower numbers of T helper 1 cells (Th1) and T helper 17 cells (Th17) (P0.05). Overall, LV induced MSCs overexpressing IL-10 might be a promising alternative therapeutic option for the treatment of IBD.

Generation of Kidney Directed Differentiation Platform from Human Pluripotent Stem Cells / 中国生物化学与分子生物学报

Kidney is an essential organ in human body with multiple physiological functions. However, there is 10 % population worldwide with renal disease. It is urgent to generate a model which is more similar with kidney at structural and functional level to study renal disease. The rise of in vitro differentiation technology from pluripotent stem cells gives regeneration medicine and precise medicine new energy. This study mimics kidney development in vitro by inducing human pluripotent stem cells including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) into kidney progenitor cells, and further forming nephrons, which is the structure and function unit in kidney. Human pluripotent stem cells were differentiated into primitive streak through activating WNT pathway while inhibiting TGF-(B signaling. Afterward, the primitive streak spontaneously differentiated into intermediate mesoderm. Then, we induced intermediate mesoderm cells into kidney progenitor cells through FGF pathway. The FACS analysis data indicated kidney progenitor cells were up to 51. 5%-61. 9% in total cell population. Immuno-stai-ning results showed these structures contained podocytes of glomerulus, proximal tubule, and distal tubule. This kidney differentiation protocol is stable, high-efficient, and well repeatable. This research provides a novel platform for early human kidney development study, kidney disease modeling, and drug screening.