[Clinical and genetic spectrum of 6 cases with asparagine synthetase deficiency].

Objective: To explore the clinical and genetic characteristics of asparagine synthase deficiency. Methods: Case series studies. Retrospective analysis and summary of the clinical data of 6 cases with asparagine synthase deficiency who were diagnosed by genetic testing and admitted to the Third Affiliated Hospital of Zhengzhou University from May 2017 to April 2023 were analyzed retrospectively. The main clinical features, laboratory and imaging examination characteristics of the 6 cases were summarized, and the gene variation sites of them were analyzed. Results: All of the 6 cases were male, with onset ages ranging from 1 month to 1 year and 4 months. All of the 6 cases had cognitive and motor developmental delay, with 3 cases starting with developmental delay, 3 cases starting with convulsions and later experiencing developmental arrest or even regression. All of 6 cases had epilepsy, in whom 2 cases with severe microcephaly developed epileptic encephalopathy in the early stages of infancy with spasms as the main form of convulsions, 4 cases with mild or no microcephaly gradually evolved into convulsions with no fever after multiple febrile convulsions with focal seizures, tonic clonic seizures and tonic seizure as the main forms of convulsions. Three cases of 4 gradually developed into stagnation or even regression of development and ataxia after multiple convulsions with no fever. There were normal cranial imaging in 2 cases, dysplasia of the brains in 1 cases, frontal lobe apex accompanied by abnormal white matter signal in the frontal lobe and thin corpus callosum in 1 case, thin corpus callosum and abnormal lateral ventricular morphology in 1 case, and normal in early stage, but gradually developing into cerebellar atrophy at the age of 5 years and 9 months in 1 case. Two cases underwent visual evoked potential tests, the results of which were both abnormal. Three cases underwent auditory evoked potential examination, with 1 being normal and 2 being abnormal. All of 6 cases had variations in the asparagine synthase gene, with 2 deletion variations and 7 missense variations. The variations of 2 cases had not been reported so far, including c.1341_1343del and c.1283A>G, c.1165_1167del and c.1075G>A. The follow-up time ranged from 3 months to 53 months. Two cases who had severe microcephaly died in infancy, while the other 4 cases with mild or no microcephaly were in survival states until the follow-up days but the control of epilepsy was poor. Conclusions: Asparagine synthase deficiency has a certain degree of heterogeneity in clinical phenotype. Children with obvious microcephaly often present as severe cases, while children with mild or no microcephaly have relatively mild clinical manifestations. The variation of asparagine synthetase gene is mainly missense variation.

Chapter 11: Astrobiology Education, Engagement, and Resources.

Although astrobiology is a relatively new field of science, the questions it seeks to answer (e.g., "What is life?" "What does life require?") have been investigated for millennia. In recent decades, formal programs dedicated specifically to the science of astrobiology have been organized at academic, governmental, and institutional scales. Constructing educational programs around this emerging science relies on input from broad expertise and backgrounds. Because of the interdisciplinary nature of this field, career pathways in astrobiology often begin in more specific fields such as astronomy, geology, or biology, and unlike many other sciences, typically involve substantial training outside one's primary discipline. The recent origin of astrobiology as a field of science has led to strong collaborations with education research in the development of astrobiology courses and offers a unique instructional laboratory for further pedagogical studies. This chapter is intended to support students, educators, and early career scientists by connecting them to materials and opportunities that the authors and colleagues have found advantageous. Annotated lists of relevant programs and resources are included as a series of appendices in the supplementary material.

[Analysis of prognostic factors of extranodal NK/T-cell lymphoma treated with pegaspargase/L-asparaginase: a multicenter retrospective study].

Objective: To explore the prognostic factors of extracellular NK/T cell lymphoma (ENKTL) treated with pegaspargase/L-asparaginase. Methods: The clinical data of 656 ENKTL patients diagnosed at 11 medical centers in the Huaihai Lymphoma Working Group from March 2014 to April 2021 were retrospectively analyzed. The patients were randomly divided into two groups: a training set (460 cases) and a validation set (196 cases) at 7∶3, and the prognostic factors of the patients were analyzed. A prognostic scoring system was established, and the predictive performance of different models was compared. Results: Patients' median age was 46 (34, 57) years, with 456 males (69.5% ) and 561 nasal involvement (85.5% ). 203 patients (30.9% ) received a chemotherapy regimen based on L-asparaginase combined with anthracyclines, and the 5-year overall survival rate of patients treated with P-GEMOX regimen (pegaspargase+gemcitabine+oxaliplatin) was better than those treated with SMILE regimen (methotrexate+dexamethasone+cyclophosphamide+L-asparaginase+etoposide) (85.9% vs 63.8% ; P=0.004). The results of multivariate analysis showed that gender, CA stage, the Eastern Cooperative Oncology Group performance status (ECOG PS) score, HGB, and EB virus DNA were independent influencing factors for the prognosis of ENKTL patients (P<0.05). In this study, the predictive performance of the prognostic factors is superior to the international prognostic index, Korean prognostic index, and prognostic index of natural killer lymphoma. Conclusion: Gender, CA stage, ECOG PS score, HGB, and EB virus DNA are prognostic factors for ENKTL patients treated with pegaspargase/L-asparaginase.

[Evaluation of effects of comprehensive intervention based on key persons on AIDS-related high-risk behaviors in male sex workers in entertainment venues].

Objective: To evaluate the effect of comprehensive intervention model based on key persons in entertainment venues on the incidence of AIDS-related high-risk behaviors in male sex workers (MSW). Data from this study thus can be used to provide compelling evidence for the wider implementation of the intervention model. Methods: In this randomized controlled trial, MSW were recruited and followed-up from May to December, 2021 in entertainment venues in Wuxi, Jiangsu Province, with an estimated sample size of 320. The MSW in the intervention group were provided with comprehensive interventions via key persons in entertainment venues compared with the control group receiving routine interventions. The effect of the intervention model was assessed by comparing the behavioral differences between these two groups and in the intervention group before and after intervention. Results: A total of 330 MSW were recruited at baseline survey, in which 168 were divided into intervention group and 162 into control group. There was no significant difference in socio-demographic characteristics between two groups (all P>0.05). After intervention for 6 months, the rate of consistent condom use in commercial homosexual activities in the intervention group was 79.5% (101/127), higher than 63.2% (74/117) in the control group, and in the intervention group, 90.1% (73/81) of MSW used condom consistently in heterosexual activities, higher than in the control group (59.6%, 59/99) . Compared with 30.8% (36/117) of MSW with drug abuse history in the control group, a lower proportion of 9.4% (12/127) was observed in the intervention group. Differences in all of aforementioned variables were significant (all P<0.05). After intervention, the incidence of group sex was 3.9% (5/127) in the intervention group and 9.4% (11/117) in the control group, the incidence of anal sex post-alcohol consumption was 40.2% (51/127) in the intervention group and 32.5% (38/117) in control group, the differences were not significant (all P>0.05). Conclusions: The intervention model based on key persons in entertainment venues could promote consistent condom use in MSW in both commercial homosexual and heterosexual activities and help them reduce drug abuse, but had no significant effect on decreasing group sex and anal sex after alcohol consumption. It is crucial to improve the intervention model according to the specific characteristics of MSW in order to enhance the effects of comprehensive intervention.

[Preliminary studies on the role of mast cells in the phenotype and immune activation of type 2 inflammatory cytokine release of atopic dermatitis].

Objective: To investigate the role of mast cells in atopic dermatitis (AD) phenotype and the immune activation of type 2 inflammatory cytokine release. Methods: Nine AD skin samples were obtained from the Department of Dermatology, the Second Affiliated Hospital of Xi'an Jiaotong University, and nine healthy skin control samples were obtained from the surgical excision of excess normal skin by orthopedic surgery, the Second Affiliated Hospital of Xi'an Jiaotong University, which were subjected to toluidine blue staining and fluorescence staining to clarify the mast cell degranulation activation status of the AD skin lesions. We investigated whether MC903 could directly activate mast cells in vivo through the toe swelling and exudation assay in wild-type mice; we constructed the MC903-AD model using wild-type and KitW-sh/W-sh mast cell-deficient mice in order to investigate whether mast cells affected the phenotype, histopathology, and the level of type 2 inflammatory factors in AD mice; we extracted mouse peritoneal mast cells and the ability of MC903 to activate mast cells to release inflammatory mediators in vitro was explored by calcium imaging, tryptase and ß-aminohexokinase release assays, and MCP-1 and CXCL-2 release assays. Results: The number of degranulated mast cells in an activated state was increased in skin lesions of AD patients compared to healthy controls, with (5.40±1.14) and (2.20±0.84), respectively (P<0.001). KitW-sh/W-sh mast cell-deficient AD mice had an attenuated phenotype with ADI scores of (5.50±1.05), compared to wild-type AD mice with (10.00±0.89) (P<0.001). The release of type 2 inflammatory factors in wild-type AD mice was higher than those in KitW-sh/W-sh mast cell-deficient AD mice, with IL-4 levels of (29.50±1.87) and (15.33±1.86) pg/mg (P<0.001), IL-13 levels were (6.32±0.25) and (3.93±0.22) pg/mg (P<0.001), IL-31 levels were (9.73±0.38) and (6.89±0.27) pg/mg (P<0.001), and TSLP levels were (206.00±4.43) and (99.00±4.86) pg/mg (P<0.001), respectively. MC903 could cause mast cell activation in wild-type mice, leading to increased swelling and exudation in the toes of mice, and MC903 could activate mast cells in vitro, leading to increased degranulation and release of inflammatory factors such as MCP-1 and CXCL-2. Conclusions: The number of activated mast cells was increased in skin lesions of AD patients than in healthy controls. KitW-sh/W-sh mast cell-deficient AD mice showed significantly reduced phenotype, histopathology, and type 2 inflammatory factor levels compared with wild-type AD mice. MC903 activates mast cells in vivo and in vitro. Mast cells play a key role in AD phenotype and immune activation.

[Progress in methodology of the Global Burden of Disease Study and its impact on the disease burden of parasitic diseases].

Currently, the Global Burden of Disease Study (GBD) is the most comprehensive, systematic, and largest-scale global observational epidemiological project, which measures the national, regional and global mortality and disability of diseases, injuries and risk factors that threaten human health using unified indicators, such as disability-adjusted life year. This review describes the development history, assessment process and methodological advances of GBD, and discusses the impact of GBD on the burden of parasitic diseases, aiming to provide insights into the widespread use of GBD.

[Temporal trends in disease burden of major human parasitic diseases in China from 1990 to 2019].

OBJECTIVE: To analysize the temporal trends in the disease burden of major human parasitic diseases in China from 1990 to 2019, so as to provide the evidence for improving the parasitic disease control strategy in China. METHODS: The disability-adjusted life years (DALYs) of malaria, intestinal nematode infections, schistosomiasis, food-borne trematodiases, cysticercosis and echinococcosis in China from 1990 to 2019 were captured from the Global Burden of Disease Study 2019 (GBD 2019), and age- and gender-specific DALYs of parasitic diseases were estimated. The temporal trends in DALYs of malaria, intestinal nematode infections, schistosomiasis, food-borne trematodiases, cysticercosis and echinococcosis were evaluated in China from 1990 to 2019 using average annual percent change (AAPC) with Joinpoint regression analysis. RESULTS: The DALYs were 643 836.42 person-years due to food-borne trematodiases, 156 853.03 person-years due to cysticercosis, 79 764.62 person-years due to schistosomiasis, 70 989.73 person-years due to intestinal nematode infections, 4 258.61 person-years due to echinococcosis and 264.86 person-years due to malaria in China in 2019, respectively. The overall DALYs of six parasitic diseases were higher among men (546 441.93 person-years) than among women (409 525.33 person-years), and were greater among adults at ages of 14 to 65 years (684 780.84 person-years) than among children at 14 years and lower (35 437.38 person-years) and the elderly at ages of 65 years and older (235 749.04 person-years). During the period from 1990 to 2019, food-borne trematodiases were the leading cause of DALYs among the six parasitic diseases, and cysticercosis shifted from the fourth leading cause in 1990 to the second leading cause of DALYs in China in 2019, while intestinal nematode infections shifted from the second leading cause in 1990 to the fourth leading cause of DALYs in 2019. The DALYs of major human parasitic diseases appeared an overall tendency towards a decline in China from 1990 to 2019, with the fastest drop seen in DALYs due to malaria (AAPC = -19.6%, P = 0.003), followed by due to intestinal nematode infections (AAPC = -8.2%, P < 0.001) and schistosomiasis (AAPC = -3.1%, P < 0.001), and a slow decline was seen in the DALYs of food-borne trematodiases (AAPC = -1.0%, P < 0.001), while there were no significant decrease in the DALYs of echinococcosis (AAPC = -0.5%, P = 0.264) and the DALYs of cysticercosis appeared a tendency towards a rise (AAPC = 0.7%, P < 0.001). CONCLUSIONS: The disease burden of major human parasitic diseases appeared an overall tendency towards a decline in China from 1990 to 2019, with a high disease burden seen due to food-borne parasitic diseases, no remarkable reduction seen in echinococcosis, and a tendency towards a rise seen in cysticercosis. It is recommended to focus on echinococcosis control, and continue to consolidate the control achievements of other major human parasitic diseases in China; meanwhile, the surveillance and prevention of food-borne parasitic diseases should be reinforced.

[Global distribution and transmission of Fasciola].

As a global zoonotic disease, fascioliasis is a serious threat to human and animal health and animal husbandry development. The complexity of the classification and identification of Lymnaeidae, the intermediate host of Fasciola, notably the emergence of its sibling species, leads to misunderstanding of geographical distribution and transmission potential of Fasciola. This review introduces the classification of flukes of the family Fasciolidae, describes the geographical distribution of F. hepatica and F. gigantic, and discusses the co-evolution of Fasciola and Lymnaeidae host snails, and the effects of human activities and ruminant migration on global spread and transmission of Fasciola. In addition, we revisit the intermediate host snails of Fasciola in Africa based on the latest molecular biological evidence.

[Numerical simulation study on dust transport law in antibiotic raw material drug powder screening workshop].

To study the distribution pattern of drug dust in the antibiotic raw material drug powder screening workshop and improve the working environment, we used COMSOL Multiphysics 6.0 software to simulate and study the airflow distribution and dust transport law in the powder screening workshop. The results indicated that the dust in the powder screening workshop diffused rapidly with the airflow and reached a stable state at the 100th second. After the dust migrated to a stable state, the area with excessive dust concentration (dust concentration>6 mg/m(3)) widely distributed, mainly distributed in the middle and lower parts of the wall opposite the air inlet from the rotary vibrating screen. The distribution of dust showed a characteristic of local aggregation, and dust transport was related to airflow movement, which was prone to aggregation in areas with low airflow velocity and eddy currents. On the plane of the human respiratory belt height (h=1.5 m), the concentration near the dust producing surface was high, with local concentrations exceeding 32 mg/m(3). It was the key area for dust prevention and control. And the working environment can be improved by changing the air flow distribution in the workshop or other dust reduction methods.

[Taxonomic rank of human parasites].

Biological category is effective to indicate the evolution of organism populations between past and present. Conventional taxonomy of human parasites mainly depends on important morphological features, which suffers from a problem of categorizing related-genera species with similar morphological characteristics. With recent advances in molecular biological technologies, the effective applications of mitochondrial and ribosomal biomarkers and sequencing greatly improve the development of the taxonomic rank of human parasites. Worldwide, the classification of human parasites have been continuously revised and improved. Hereby, we re-categorize parasitic Protozoa, Trematoda, Cestoda and Nematoda, so as to provide insights into the researches on molecular systematics and genetic evolution of human parasites.

[Diagnostic efficacy of indirect haemagglutination assay for detection of Schistosoma japonicum infections among boatmen and fishermen in the Dongting Lake region].

OBJECTIVE: To evaluate the diagnostic efficacy of indirect haemagglutination assay (IHA) for detection of Schistosoma japonicum infections among boatmen and fishermen in Dongting Lake region, so as to provide insights into improving the schistosomiasis surveillance program among boatmen and fishermen. METHODS: The boatmen and fishermen were detected for S. japonicum infections using IHA and Kato-Katz technique or miracidium hatching test nylon gauze simultaneously at schistosomiasis testing sites in the anchor sites for boatmen and fishermen in the Dongting Lake region during the period from 2014 to 2016, and using IHA for serological screening followed by parasitological testing of seropositives during the period from 2017 to 2019. The sensitivity and specificity of IHA were evaluated for detection of S. japonicum infections among boatmen and fishermen, with the 2014-2016 parasitological testing results as a gold standard. In addition, the seroprevalence of S. japonicum infections was compared among boatmen and fishermen with different characteristics and among years. RESULTS: A total of 306 schistosomiasis testing sites were assigned for boatmen and fishermen, and a total of 143 360 person-time boatmen and fishermen were tested for S. japonicum infections in the Dongting Lake region from 2014 to 2019. The sensitivity and specificity of IHA were 69.9%, 97.3% and 96.1% (χ2 = 74.6, P < 0.05), and 70.9%, 74.5% and 71.9% for detection of S. japonicum infections from 2014 to 2016 (χ2 = 29.4, P < 0.05), respectively. The seroprevalence of S. japonicum infections reduced from 30.3% in 2014 to 1.8% in 2019 among boatmen and fishermen, appearing an overall tendency towards a decline (Z = 1 552.4, P < 0.05). In addition, male, individuals at ages of 45 to 60 years, full-time boatmen and fishermen were more likely to be seropositive for S. japonicum infections (all P values < 0.05). CONCLUSIONS: The seroprevalence of S. japonicum infections appeared a tendency towards a decline among boatmen and fishermen in the Dongting Lake region year by year from 2014 to 2019. IHA presented a high efficacy for screening of S. japonicum infections among boatmen and fishermen in the Dongting Lake region.

[Clinical and genetic spectrum of SCN2A gene associated epilepsy and episodic ataxia].

Objective: To explore the clinical manifestations and genetic characteristics of patients with epilepsy and episodic ataxia caused by SCN2A gene variation. Methods: The clinical data of seizure manifestation, imaging examination and genetic results of 5 patients with epilepsy and (or) episodic ataxia because of SCN2A gene variation admitted to the Department of Pediatrics, the Third Affiliated Hospital of Zhengzhou University from July 2017 to January 2021 were analyzed retrospectively. Results: Among 5 patients, 4 were female and 1 was male. The onset age of epilepsy ranged from 4 days to 8 months. There were 2 cases of benign neonatal or infantile epilepsy and 3 cases of epileptic encephalopathy, in whom 1 case had development retardation,1 case transformed from West syndrome to infantile spasm and another one transformed from infantile spasm to Lennox-Gastaut syndrome. One case of benign neonatal-infantile epilepsy was characterized by neonatal onset seizures and episodic ataxia developed at the age of 78 months. Electroencephalograms at first visit of 5 cases showed that 2 cases were normal, 1 case had focal epileptic discharge, and 2 cases had multi-focal abnormal discharge with peak arrhythmia. The brain magnetic resonance imaging (MRI) of 3 cases were nomal, 1 case was abnormal (brain atrophy with decreased white matter) and the results of 1 case was unknown. The follow-up time ranged from 17 months to 89 months. Four cases of epilepsy were controlled and 1 case died at 2 years of age. Two cases had normal intelligence and motor development, 2 had moderate to severe intelligence retardation and motor critical state, and 1 had moderate to severe intelligence and motor development retardation. SCN2A gene variations were identified in all cases. There were 4 missense variations and 1 frameshift variation. Three variations had not been reported so far, including c.4906A>G,c.3643G>T,c.638delT. Conclusions: Variations in SCN2A gene can cause benign neonatal or infantile epilepsy and epileptic encephalopathy. Some children develop episodic ataxia with growing age. The variation of SCN2A gene is mainly missense variation.

[Risk factors of carbapenem resistant Acinetobacter baumannii infection in intensive care unit].

Objective: This study will analyze the clinical characteristics and risk factors that may be related to the 30-day mortality of patients infected with CRAB in intensive care unit (ICU), and explore the resistance of CRAB and its influence on mortality. Methods: From December 2012 to February 2021, 173 ICU patients with CRAB infection in the Fifth Medical Center of PLA General Hospital were selected as the research objects, and the relevant data were collected for retrospective analysis. There were 119 cases (68.8%) in survival group and 54 cases (31.2%) in the non-survival group. Patients with CRAB infection were (52.9±13.5) years old, including 140 males (80.9%) and 33 females (19.1%).The first detected CRAB was collected, and antibiotic sensitivity test was conducted after the strain was resuscitated to analyze the antibiotic resistance. Univariate and multivariate Cox models were used to analyze independent risk factors associated with 30-day mortality in patients with CRAB infection. Results: Univariate and multivariate Cox analysis showed that acute physiology and chronic health evaluation scoring system Ⅱ(APACHE Ⅱ)(HR=1.058, 95%CI:1.012-1.106, P=0.013) and septic shock (HR=6.240, 95%CI:2.227-17.483, P<0.001) were independent risk factors related to 30-day mortality in ICU patients with CRAB. Treatment with ß-lactamase inhibitor (HR=0.496, 95%CI: 0.275-0.893, P<0.019) can reduce the 30-day mortality of patients with CRAB infection in ICU. The resistance rate of CRAB to cephalosporins, carbapenems, aminoglycosides and quinolones were more than 80%. The survival rate of patients infected by aminoglycoside resistant CRAB is low(χ²=4.012,P<0.05). Conclusion: The APACHE Ⅱ score, septic shock and use of ß-lactamase inhibitors were independent factors associated with the 30-day mortality in ICU patients with CRAB infection.

[Application of health economics assessment techniques in the prevention and control of important infectious diseases: a review].

Due to the relative shortage of health resources, rational allocation and utilization of health resources is critical to achieving the maximum economic benefits in developing countries, which requires a health economic assessment to meet the needs to balance the competitive requirements of cost reduction and effectiveness enhancement. This review describes the advances in applications of health economic assessment techniques in four major infectious diseases, including AIDS, tuberculosis, hepatitis B and schistosomiasis. Currently, there is no standard economic assessment in the prevention and control of infectious diseases, and notably, the transparency of cost research is limited, which may affect the popularization of the study conclusions. Further health economic assessments of infectious diseases are required to improve the quality, standard and transparency of the economic evaluation through formulating strategies, to improve the standardization of studies, to improve the popularization of the study conclusions and to improve the applicability of the economic evaluation for policies.

[Conversion of serum anti-Schistosoma japonicum antibodies detected by immunological tests following treatment with praziquantel: a meta-analysis].

OBJECTIVE: To evaluate the conversion of serum antibodies against Schistosoma japonicum in humans and livestock detected by immunological tests following treatment with praziquantel. METHODS: The studies pertaining to serological tests of schistosomiasis japonica published from 1991 to 2020 were retrieved in electronic databases, including Chinese National Knowledge Infrastructure, WanFang Data, PubMed and ScienceDirect. Data were extracted from included studies. The publication bias was assessed with funnel plots using the software RevMan version 5.3, and the conversion of antibodies against S. japonicum was evaluated through meta-analysis. RESULTS: A total of 40 publications were included in the final meta-analysis, consisting of 33 Chinese publications and 7 English publications, and all immunological tests were performed with indirect hemagglutination test (IHA) and enzyme-linked immunosorbent assay (ELISA). Pooled analysis showed that the negative rates of serum anti-S. japonicum antibody were 45.36% [95% confidential interval (CI): (43.96%, 46.76%)] and 20.83% [95% CI: (19.69%, 21.97%)] detected by ELISA and IHA within 6 months post praziquantel treatment, 62.95% [95% CI: (61.59%, 64.31%)] and 55.61% [95% CI: (54.21%, 57.01%)] within 6 to 12 months after treatment and 85.92% [95% CI: (84.94%, 86.90%)] and 86.90% [95% CI: (85.95%, 87.85%)] over 12 months after treatment, respectively. CONCLUSIONS: The negative rate of the serum anti-S. japonicum antibody by IHA and ELISA increased with the time of post-treatment with praziquantel. The overall negative rates of anti-S. japonicum antibody detected by IHA and ELISA are low within 12 months post praziquantel treatment. However, a high negative rate of anti-S. japonicum antibody is detected if there is no new contact with infested water after 12 months of praziquantel treatment.

Hyperlipidemia Impairs Osseointegration via the ROS/Wnt/ß-Catenin Pathway.

The influence of hyperlipidemia on titanium implant osseointegration and the underlying mechanisms is not well understood. This study investigates the changes in osseointegration and explores the potential mechanisms in hyperlipidemia conditions. In vivo, specialized titanium implants were implanted in the femurs of diet-induced or genetic hyperlipidemia mice. In vitro, primary murine osteoblasts were cultured on the titanium surface in high-fat medium. Results showed that hyperlipidemia led to poor osseointegration in both types of mice in vivo, and high-fat medium impaired the osteogenic differentiation of primary osteoblasts on the titanium surface in vitro. In addition, high-fat medium caused significant overproduction of reactive oxygen species (ROS) and inhibition of the Wnt/ß-catenin pathway in osteoblasts. Both N-acetyl-L-cysteine (NAC, an ROS antagonist) and Wnt3a (an activator of the Wnt/ß-catenin pathway) attenuated the poor osteogenic ability of osteoblasts. In addition, NAC reactivated the Wnt/ß-catenin pathway in osteoblasts under high-fat stimulation. These results demonstrate that hyperlipidemia impairs osseointegration via the ROS/Wnt/ß-catenin pathway and provide support for the ROS or Wnt/ß-catenin pathway as a promising therapeutic target for the development of novel drugs or implant materials to improve the osseointegration of implants in hyperlipidemic patients.

Blood glucose fluctuations in patients with coronary heart disease and diabetes mellitus correlates with heart rate variability: A retrospective analysis of 210 cases.

AIM: This retrospective analysis aims to evaluate the correlation between blood glucose fluctuation (BGF) and heart rate variability (HRV) in patients with coronary heart disease (CHD) and type 2 diabetes mellitus (T2DM). SUBJECTS AND METHODS: In total, 210 patients with CHD and T2DM from January 2014 to January 2019 admitted to Wenling Hospital of Traditional Chinese Medicine were enrolled in this study. Based on whether BGF existed, patients were allocated to BG control group and BG fluctuation group. The HRV parameters, frequency of adverse events, and Gensini score between groups were recorded and Pearson analysis was performed. RESULTS: Results displayed that no significant differences in age, gender, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), alcohol consumption history, drinking history, or serum lipid were found between groups (P > 0.05 for all items). However, the BGF parameters were significantly higher while the HRV parameters were significantly lower in BG fluctuation group, compared with BG control group (P < 0.05 for all items). Pearson analysis showed that despite mean blood glucose (MBG) and mean amplitude of glycemic excursions (MAGE) both correlated with a standard deviation of NN intervals (SDNN) level, the correlation coefficient of MAGE-SDNN was much higher (-0.705 vs -0.185). Additionally, the frequencies of adverse events and Gensini scores were also significantly higher in the BG fluctuation group than the BG control group. CONCLUSIONS: It suggests that BGF strongly correlated with HRV in patients with CHD and T2DM. It also provides experimental instructions for clinical practice.

[Study on synthetic drug use and associated factors among men who have sex with men at high risk of HIV infection].

Objective: To understand the current status of synthetic drug use and associated factors among men who have sex with men (MSM) at high risk of HIV infection. Methods: A cross- sectional study was conducted in Guangzhou, Wuxi and Shenzhen through January to August 2017. MSM at high risk of HIV infection were recruited from attendants at the health clinics, through internet advertisement and snowball sampling method. Eligible MSM were the ones who had met the following criteria: ≥18 years old, having either 2 male sex partners, or condomless anal sex with a casual male sex partner, or a STD historg during the past 6 months. Data regarding demographic, sexual behavior, HIV/STD testing history and previous drug use were collected by sely-administered questionnaires. Blood was also drawn for HIV testing. Results: Of the 603 MSM at high risk of HIV, 25.5% (154/603, 95%CI: 22.0%-29.0%) of them had used drugs in the past 6 months, including 29.1% (88/302, 95%CI: 24.0%-34.3%) in Guangzhou, 26.3% (40/152, 95%CI: 19.2%-33.4%) in Shenzhen, and 17.4% (26/149, 95%CI: 11.3%-23.6%) in Wuxi. 'Rush' (85.1%, 131/154) was the most commonly used drug. Results from the multivariable logistic regression revealed that drug use was associated with the following factors: having multiple casual sexual partners (aOR=3.24, 95%CI: 1.29-7.43) and alcohol use (aOR=1.78, 95%CI: 1.12-2.80) in the past 6 months after adjusting for age, education and monthly income. Conclusions: Drug use seemed common among MSM population at high risk of HIV infection and was associated with higher risk behavior that leading to HIV infection. Synthetic drug use among MSM deserved more attention.

LncRNA NEAT1 accelerates the occurrence and development of diabetic nephropathy by sponging miR-23c.

OBJECTIVE: LncRNA nuclear enriched abundant transcript 1 (NEAT1) has been reported to play an oncogenic role in the occurrence and development of diabetic nephropathy (DN). The aim of our study was to investigate the potential mechanism by which NEAT1 facilitates the progression of DN. PATIENTS AND METHODS: Quantitative Real-time polymerase chain reaction (qRT-PCR) was carried out to determine the abundance of NEAT1, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), proliferating cell nuclear antigen (PCNA), Cyclin D1, P38, apoptosis signal-regulating kinase 1 (ASK1), Fibronectin, α smooth muscle actin (α-SMA) and miR-23c in the serum of DN patients, normal patients and mouse mesangial cells (MMCs). Cell proliferation was assessed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), qRT-PCR and Western blot assays. Flow cytometry and Western blot were applied to measure apoptosis of MMCs. Cell fibrosis and epithelial-to-mesenchymal transition (EMT) were analyzed by qRT-PCR and Western blot. The binding sites between miR-23c and NEAT1 were predicted by starBase bioinformatics software, and the relationship was verified by dual-luciferase reporter assay. RESULTS: The enrichment of NEAT1 was elevated in the serum of DN patients and MMCs induced by high concentration of glucose. NEAT1 overexpression accelerated proliferation, fibrosis and EMT and restrained apoptosis of MMCs induced by high concentration of glucose. MiR-23c bound to NEAT1, and the inhibition of miR-23c counteracted the suppressive effect of NEAT1 depletion on proliferation, fibrosis and EMT of MMCs induced by high concentration glucose. CONCLUSIONS: LncRNA NEAT1 promoted proliferation, fibrosis and EMT while impeded apoptosis of MMCs through sponging miR-23c. LncRNA NEAT1 and miR-23c might be underlying therapeutic targets for the treatment of DN.