[Epidemioloical characteristics and economic burden analysis of palmoplantar pustulosis in urban areas of China].

Objective: To analyze the epidemiological characteristics and economic burden of palmoplantar pustulosis (PPP) in China. Methods: A population-based retrospective study was conducted using the data from China's Urban Basic Medical Insurance data from January 1, 2012, to December 31, 2016. International Classification of Diseases code and diagnoses in Chinese for PPP were used to identify cases and estimate the prevalence, incidence, and cost. Subgroup analyses were performed according to age and sex, and sensitivity analyses were conducted to evaluate the robustness of the results. Age-adjusted prevalence rates were calculated based on the 2010 national census data. Results: The crude prevalence and incidence rate of PPP in 2016 were 2.730/100 000 (95%CI: 2.218/100 000-3.242/100 000) and 1.556/100 000 (95%CI: 1.154/100 000-1.958/100 000), and the prevalence rate of females (2.910/100 000) was higher than that of males (2.490/100 000, χ2=97.48, P=0.001). The incidence rate of females (1.745/100 000) was also higher than that of males (1.418/100 000, χ2=85.02, P=0.001). The age peak of incidence and prevalence of patients with PPP was in the 30-39-year age group and a small peak existed in the 0-3-year age group among people under 20 years old. From 2012 to 2016, the average number of visits was (2.44±0.04) per patient, and the total per-capita cost per year was (982.40±39.19) yuan. Conclusion: In 2016, the prevalence and incidence rate of PPP in China were higher in females than in males, and the highest age peak was in the 30-39-year age group.

Obstetric and offspring outcomes in isolated maternal hypothyroxinaemia: a systematic review and meta-analysis.

OBJECTIVE: To examine the association between isolated maternal hypothyroxinaemia (IMH) and adverse obstetric outcomes and offspring outcomes and also investigate the effects of levothyroxine therapy on IMH for the above outcomes. METHODS: We systematically searched PubMed, EMBASE, and Cochrane Library, and the reference lists of key reviews were hand searched on June 9, 2021. Two authors independently screened titles/abstracts. Full articles were further assessed if the information suggested that the study met the inclusion/exclusion criteria, and two researchers performed data extraction and risk-of-bias assessment using standardized tables. Summary relative risks or the mean difference between maternal effects and offspring outcomes were calculated by a random-effects model. RESULTS: We identified 38 eligible articles (35 cohort studies and two randomized controlled trials [RCT]). Meta-analysis showed that maternal IMH was associated with increased gestational diabetes mellitus, preterm premature rupture of membranes, preterm birth, fetal distress, and macrosomia outcomes in IMH compared to euthyroid women, and the relative risks were 1.42 (1.03-1.96), 1.50 (1.05-2.14), 1.33 (1.15-1.55), 1.75 (1.16-2.65) and 1.62 (1.35-1.94), respectively. IMH was not associated with placenta previa, gestational hypertension, pre-eclampsia, intrauterine growth restriction, and offspring outcomes like birth weight, low birth weight infants, fetal macrosomia, neonatal intensive care, neonatal death, or fetal head circumference. In addition, we did not find an association between IMH and adverse offspring cognitive defects. Due to insufficient data for meta-analysis, it failed to pool the evidence of levothyroxine's therapeutic effect on IMH and their offspring. CONCLUSIONS AND RELEVANCE: IMH in pregnancy may relate to a few maternal and offspring outcomes. Moreover, there is currently no sufficient evidence that levothyroxine treatment during pregnancy reduces adverse maternal outcomes and disability in offspring. Further investigation to explore the beneficial effects of levothyroxine therapy is warranted.

[Comparison of application effects of colonoscopy, fecal immunochemical test and a novel risk-adapted screening approach in colorectal cancer screening in Xuzhou population].

Objective: To compare the application effect of the colonoscopy, fecal immunochemical test (FIT) and novel risk-adapted screening approach in colorectal cancer screening in Xuzhou population. Methods: From May 2018 to April 2019, 4 280 subjects aged 50-74 were recruited from Gulou district, Yunlong district and Quanshan district of Xuzhou. They were randomly assigned to the colonoscopy group (n=863), FIT group (n=1 723) and novel risk-adapted screening approach group (n=1 694) according to the ratio of 1∶2∶2. For the novel risk-adapted screening approach group, after the risk assessment, high-risk subjects were invited to undergo colonoscopy and low-risk subjects were invited to undergo FIT examination. All FIT positive subjects were invited to undergo colonoscopy. Colonoscopy participation rate [(the number of colonoscopies completed/the number of colonoscopies invited to participate)×100%], detection rate of colorectal lesions [(the number of diagnosed patients/the number of colonoscopies completed)×100%], colonoscopy resource load (the number of colonoscopies completed/the number of diagnosed advanced tumors) and FIT resource load in each group were calculated and compared. Results: The age of all subjects was (61±6) years old, including 1 816 males (42.43%). There was no statistically significant difference in the socio-demographic characteristics of the subjects in different screening groups. The colonoscopy participation rate was 22.60% (195/863) in the colonoscopy group, 57.04% (77/135) in the FIT group, and 33.94% (149/439) in the novel risk-adapted screening approach group, respectively. The colonoscopy participation rate was higher in the FIT group than in the colonoscopy group and the novel risk-adapted screening approach group (P<0.001). The colonoscopy participation rate of novel risk-adapted screening group was significantly higher than the colonoscopy group (P<0.001). The detection rates of advanced tumors were 6.67% (13/195), 9.09% (7/77) and 8.72% (13/149), respectively, and the difference was not statistically significant (P>0.05). The colonoscopy resource load (95%CI) was 15 (13-17) in the colonoscopy group, 11 (9-14) in the FIT group and 11 (10-13) in the novel risk-adapted screening approach group, respectively. Among them, the colonoscopy resource load of high-risk individuals in the novel risk-adapted screening approach group was 12 (9-15). FIT resource loads (95%CI) were 207 (196-218) and 88 (83-94) in the FIT group and the novel risk-adapted screening approach group. Conclusion: The combined application of risk-adapted screening approach and FIT may have a good application effect in colorectal cancer screening.

[Analysis of the performance of a multi-view fusion and active contour constraint based deep learning algorithm for ossicles segmentation on 10 µm otology CT].

Objective: To explore the performance of a deep learning algorithm that combined multi-view fusion with active contour constrained for ossicles segmentation on the 10 µm otology CT images. Methods: The 10 µm otology CT image data from 79 cases (56 cases were from volunteers and 23 cases were from specimens) were retrospectively collected in the Radiology Department of Beijing Friendship Hospital from October 2019 to December 2020. An annotation of malleus, incus, and stapes were conducted. Then the datasets were established and were divided into training set (n=55), validation set (n=8), and test set (n=16). Using the rapid localization of the region of interest combined with the precise segmentation algorithm, the malleus, incus and stapes were segmented and fused from three perspectives of coronal, sagittal and cross-sectional views. Besides, an active contour loss was designed simultaneously for the segmentation of stapes. Dice similarity coefficient (DSC) was used as the objective evaluation metric for the evaluation of the segmentation results. The inter group DSC of the proposed method was compared with that of the basic method and other methods. Results: The average DSC values of the multi-view fusion segmentation algorithm for malleus, incus and stapes reached up to 94.2%±2.7%, 94.6%±2.6% and 76.0%±5.5%, respectively. After adopting the constraint of active contour loss method, the average DSC of stapes was improved (76.4%±5.4% vs 76.0%±5.5%). The visualization results also demonstrated that the segmentation results of the stapes were more complete. Conclusions: Multi-view fusion algorithm based on 10 µm otology CT images can realize accurate segmentation of malleus and incus. Combined with the constraint of active contour loss method, the segmentation accuracy of stapes can be further improved.

[Epidemiological study of bone and joint injury based on urban medical insurance database].

OBJECTIVE: To estimate the prevalence rate of bone and joint injury in China and to describe the three-dimension distribution of the disease (area, time and people). METHODS: Based on a cross-sectional design, a retrospective study was conducted by using Chinese basic medical insurance database from January 1, 2013 to December 31, 2017 to analyze the epidemiological characteristics of bone and joint injury. The prevalence rate of bone and joint injury in each city was calculated, and then using meta-analyses to estimate the pooled prevalence of each area and the whole country. The pooled prevalence rates were compared among the different groups of populations, in terms of geographical area, time and population characteristics (age and gender). RESULTS: A total of 28 419 264 subjects were included in this study, including 705 793 patients with bone and joint injury. From 2013 to 2017, in Chinese basic medical insurance database, the overall prevalence rate of bone and joint injury was 141.5(95%CI: 90.4－203.7) per 10 000 population, and the prevalence rates of non-specific or polyarticular disease, knee disease, and shoulder disease were 101.6 (95%CI: 63.5－148.4)per 10 000 population, 22.5(95%CI:15.1－31.4)per 10 000 population and 10.9 (95%CI: 6.4－16.4)per 10 000 population. The prevalence rates varied across the areas, the highest rate was observed in North China, with the prevalence of 310.6 (95%CI: 12.6－989.7) per 10 000 population, and the lowest rate was observed in Southwest China, with the prevalence of 59.0 (95%CI: 37.5－85.2) per 10 000 population. The prevalence rate of bone and joint injury increased over the study period, from 111.1 (95%CI: 56.0－182.5)per 10 000 population in 2013 to 175.5 (95%CI: 116.8－245.5)per 10 000 population in 2017. The prevalence of bone and joint injury in the female population was 149.1 (95%CI: 94.2－215.9) per 10 000 population, which was higher than that of men [133.6(95%CI: 86.2－190.9) per 10 000 population]. The higher prevalence of knee disease, unspecified or polyarticular disease, and bone and joint injury were observed in people aged 60 years and older, while the prevalence of shoulder disease peaked in 40－59 years old people [20.6 (95%CI: 12.5－30.5) per 10 000 population]. CONCLUSION: This study reported a relative low prevalence of bone and joint injury in China from 2013 to 2017. The prevalence increased over the study period, and the highest prevalence rate was observed in North China. The prevalence rate showed differences among different groups of populations, and higher rates were observed in females and people aged 60 years and older.

[COâ and 16S rDNA Sequence Identification of Common Necrophagous Flies in Fujian Province].

ABSTRACT: Objective To identify the species of common necrophagous flies in Fujian Province by gene fragment sequences of mitochondrial cytochrome c oxidase subunit Ⅰ （COⅠ） and 16S ribosomal deoxyribonucleic acid （16S rDNA）, and to explore the identification efficacy of these two molecular markers. Methods In total 22 common necrophagous flies were collected from the death scenes in 9 different regions in Fujian Province and DNA was extracted from the flies after morphological identification. The gene fragments of COⅠ and 16S rDNA were amplified and sequenced. All the sequences were uploaded to GeneBank and BLAST and MEGA 10.0 software were used to perform sequence alignment, homology analysis and intraspecific and interspecific genetic distance analysis. The phylogenetic trees of DNA fragment sequences of COⅠ and 16S rDNA of common necrophagous flies in Fujian Province were established by unweighted pair-group method with arithmetic means （UPGMA）, respectively. Results The flies were classified into 6 species, 5 genera and 3 families by morphological identification. The results of gene sequence analysis showed that the average number of interspecific and intraspecific genetic distance of 16S rDNA ranged from 1.8% to 8.9% and 0.0% to 2.4%, respectively. The average number of interspecific and intraspecific genetic distance of COⅠ ranged from 7.2% to 13.6% and 0.0% to 6.3%, respectively. Conclusion The gene sequences of COⅠ and 16S rDNA can accurately identify the species of different necrophagous flies, and 16S rDNA showed higher value in species identification of common calliphoridae necrophagous flies in Fujian Province.

[Clinical analysis of 43 cases of retroperitoneal laparoscopic renal biopsy].

Objective: Percutaneous renal biopsycurrently is the most important and widely used method of renal biopsy. However, there still are some patients in whom a percutaneous approach may be considered a major risk. In these patients, renal biopsy under direct vision is a reliable alternative. We described our personal technique and experience in a series of Chinese patients who underwent retroperitoneal laparoscopic renal biopsy. Methods: We retrospectively reviewed the patients who had performed retroperitoneal laparoscopic renal biopsy over a 4-year period (Jan 2013 to Jan 2017).Forty-three patients with renal dysfunction were involved inour center.Especially some patients showed atrophic kidney and poor visualization on ultrasonography. The patients' abnormal conditions includeddialysis (10 cases), morbid obesity (5 cases), deaf-mutes (2 cases) and uncontrolled severe hypertension. The kidney was approached via alaparoscopic retroperitoneal route using athree-ports technique. Then biopsies were performed bya 16-gaugebiopsy needle, and hemostasis was achieved by compression.In less cases, a topical spray hemostatic gel was required. Results: Biopsy was performed successfully in all cases and adequate renal tissue was acquired.Mean operative time was 59.4 minutes, mean blood loss was 36.5 ml.Under general anesthesia, no anesthetic accidents and related complications were recorded. Forty-onepatients were discharged within 24 h after operation. Onepatient occurred disseminated intravascular coagulationduring operation. Red blood cell transfusion and fresh-frozen plasma infusion were performed. Injury at hilum of kidney was detected in another patient. And extrapyelogenic repair surgery was performed. Conclusions: The retroperitoneallaparoscopic renal biopsy is a safe, reliable, minimallyinvasive alternative renal biopsy method with better haemostasis, fewer complications and a rapid recovery. As the helpful supplement of percutaneous renal biopsy, this technique may have to be used more often in the future.

[Clinicopathologic features of lipoprotein glomerulopathy: observation of 6 cases].

Objective: To investigate the clinicopathologic features of lipoprotein glomerulopathy (LPG). Methods: A total of 6 cases (5 males and 1 female, with a mean age of 27.5 years and age range of 11-53 years) of lipoprotein glomerulopathy with complete clinicopathologic data were enrolled. Except for light microscope, immunofluorescence and electron microscopic examination, renal biopsy tissues were checked by oil red O staining. The gene map of apolipoprotein E (ApoE) of 2 cases were analyzed. Results: All 6 cases presented with heavy proteinuria or nephrotic syndrome, and high level of low-density lipoprotein (LDL), very low-density lipoprotein (vLDL), ApoE. Family history of LPG was found in 3 cases, and 2 patients progressed to uremia, or even to death. Pathologic features showed that lipoprotein deposited in glomerulus capillary lumen and renal tubular epithelial cells. Gene analysis demonstrated that 2 cases expressed abnormal ApoE gene (162G>C and 455G>C). Conclusions: Lipoprotein glomerulopathy is autosomal-recessive disease with mutation of ApoE. Common clinical manifestations of LPG are heavy proteinuria or nephrotic syndrome, with a poor prognosis. Renal biopsy pathologic diagnosis can confirm this kidney disease. Emboli of lipoprotein being observed in glomerulus capillary lumen is the pathological feature of LPG.

[The role of heme oxygenase-1 on oxidative stress injury induced by zinc oxide nanoparticles in human umbilical vein endothelial cells line EA.hy926 cells].

Objective: To explore the effect of heme oxygenase-1 (HO-1) on level of reactive oxygen species (ROS) induced by zinc oxide nanoparticles (ZnO-NPs) in Human umbilical vein endothelial cells line EA.hy926. Methods: The EA.hy926 cells in logarithmic growth phase were incubated with 0.0, 2.5, 5.0, 10.0 and 15.0 mg/L ZnO-NPs respectively. The ROS level, reflected by mean fluorescence intensity (MFI), was examined by flow cytometer after 4 hours exposure, the protein expression of HO-1 which was determined by Western Blot after exposed to ZnO-NPs for 24 hours. Cells incubated with 15.0 mg/L were set as the ZnO-NPs group; a blank control group was set at the same time. Cells were pretreated with HO-1 inhibitor zinc protoporphyrin (ZnPPIx) and HO-1 activator cobalt protoporphyrin (CoPPIx), they were classified as ZnPPIx group and CoPPIx group. 15 mg/L ZnO-NPs was chosen to conduct the experiment of HO-1 activation and inhibition. Cells were classified as ZnPPIX+ ZnO-NPs group and CoPPIx+ ZnO-NPs group after pretreated with 10 µmol/L ZnPPIx or CoPPIx for 1 h, added 15 mg/L ZnO-NPs to cell culture medium. In all groups ROS levels were detected after exposed to ZnO-NPs for 4 hours, the protein expression of HO-1 was detected after exposed to ZnO-NPs for 24 hours. Results: With the increased dose of ZnO-NPs, levels of ROS and HO-1 in EA.hy926 cells were clearly elevated (the MFI of 0.0, 2.5, 5.0, 10.0 and 15.0 mg/L ZnO-NPs incubated groups was 22 627.22±718.27, 24 726.47±568.52, 31 141.75±1 312.24, 39 824.82±4 774.74, 50 569.03±1 497.63 respectively, and HO-1 relative expression were 0.16±0.01, 0.19±0.02, 0.16±0.01, 0.23±0.02, 0.92±0.06 respectively). HO-1 expression in ZnPPIx pretreatment group decreased compared with ZnO-NPs group (1.05±0.05 vs. 1.12±0.01, P<0.05), meanwhile ROS level enhanced (62 683.95±2 589.59 vs. 53 654.53±2 229.01, P<0.05). However, CoPPIx pretreatment had higher HO-1 level and lower level of ROS compared with ZnO-NPs group (HO-1: 1.74±0.11 vs. 0.22±0.03, P<0.05; ROS: 32 845.04±993.48 vs. 53 654.53±2 229.01, P<0.05). Conclusions: Exposure to ZnO-NPs significantly induced ROS generation in EA.hy926 cells in a dose-dependent manner. HO-1 regulated ZnO-NPs-induced oxidative stress.

The miR-93 promotes proliferation by directly targeting PDCD4 in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the second leading cause of cancer mortality worldwide. Although advances have made in treatment of HCC, the overall survival rate remains low and the molecular pathogenesis of HCC is still poorly understood. The purpose of this study was to explore the molecular pathogenesis of HCC. A total of 89 patients were involved in the study. MicroRNA-93 (miR-93) was aberrantly up-regulated in HCC tissues as determined by qRT-PCR. The high level of miR-93 was closely associated with larger tumor size (p < 0.05) and poor overall survival (p < 0.05). In in vitro and in vivo assays, we demonstrated that high miR-93 levels enhanced cell growth of HCC. The luciferase activity assay showed that PDCD4 was a direct target of miR-93 and its expression was down-regulated by miR-93. Re-expression of PDCD4 inversely correlated with the level of miR-93 and attenuated the miR-93-induced promotion of cell growth in HCC. Taken together, our data indicate that miR-93 may function as an oncogenic factor in HCC, and promotes HCC cell proliferation by targeting PDCD4.

[Effect of nano-TiO2 on intestinal glucose absorption in young rat on the everted gut sac model].

OBJECTIVE: To study the effect of titanium dioxide (TiO2) nanoparticles on intestinal glucose absorption in young rats and its size effect. METHODS: In the study, 63 small intestine segments were isolated from 63 Sprague-Dawley rats (SD rats, 4-week-old) to prepare the everted gut sac model. In the first part of our work, the everted sacs were exposed to 0, 50 mg/L TiO2 nanoparticles (24 nm) for 2 h with the presence of a series of glucose concentrations (10, 25, 50, 100, 200, 400, and 800 mmol/L), and the glucose absorbing function of the everted sacs were assessed in the process. On the basis of the work, utilizing the same method, further study was carried out to compare the effects of TiO2 nanoparticles (24 nm) and fine-particles (120 nm) on intestinal glucose absorbing function with the presence of 400 mmol/L glucose and 0, 10, 50, 200 mg/L TiO2. 3 intestine segments were used in each group. RESULTS: The cumulative glucose absorption increased with time extension and increased glucose concentration. In the first part of our work, with the presence of 400 mmol/L glucose, the group treated with 50 mg/L TiO2 nanoparticles showed significantly lower cumulative glucose absorption and glucose absorbing rate than the control group at the exposure time of 30 min (tcumulative absorption=3.254, P<0.05; tglucose absorbing rate=3.958, P<0.05), 90 min (tcumulative absorption=3.323, P<0.05; tglucose absorbing rate=3.063, P<0.05) and 120 min (tcumulative absorption=2.834, P<0.05; tglucose absorbing rate=3.002, P<0.05). At other glucose concentrations, statistically significant differences in cumulative glucose absorption or glucose absorbing rates were not found between the TiO2 nanoparticle exposed group and the control group. In the second part of our work, when compared with the control group, no significant downregulations in cumulative glucose absorption or glucose absorbing rates were observed in both TiO2 nano-particle treated group and TiO2 fine particle treated group. Differences between the TiO2 nanoparticle treated group and the TiO2 fine particle treated group were not statistically significant. CONCLUSION: Short-term exposure to TiO2 nanoparticles may downregulate the intestinal glucose absorbing function in young rats, and the difference with TiO2 fine particlesis is not obvious.

[Investigation of the cognition and behavior on drug safety in Beijing middle school students].

OBJECTIVE: To understand the cognition and behavior of drug safety in Beijing middle school students and provide advice for relevant education. METHODS: A cross-sectional survey using paper questionnaires was carried out on the student body of nine Beijing middle schools. Multi-stage proportionate stratified cluster sampling was adopted to enroll participants. In addition to demographic questions, the questionnaire included 17 questions assessing the cognition and behavior of safe drug use, prioritizing questions that aligned with the health education guideline for primary and secondary school students from Chinese Ministry of Education. Descriptive statistical methods were applied using the SAS 9.2 software. RESULTS: Of the 4 220 students investigated, 2 097(49.7%) were males and 2 123(50.3%) were females. The average age was (14.3±1.7) years. 2 030(48.1%) students were from downtown areas, 1 511(35.8%) were from urban-rural linking areas and 679(16.1%) were from rural areas. Half (51.5%) of the respondents were junior high school students, and the others were from senior high schools (34.2%) and vocational high schools (14.3%). Most of the students (89.6%) lived off campus. The awareness rate of drug safety knowledge was 74.4%, the median score of drug safety behavior was 4 points (full score was 5 points) and there was a statistically positive correlation between the two (Spearman's correlation coefficient was 0.156, P<0.001). Both the awareness rates and the drug safety behavior scores were statistically different among the students in different regions, different school types and different residence types (P<0.001). Multiple factors analysis demonstrated the correlation between the cognition degrees of both drug safety knowledge, behavior and the above factors. Of all the students, 80.4% agreed that any drug could have adverse drug reactions; 40.5% were aware that antibiotics couldn't kill viruses; as many as 49.6% mistook aspirin as antibiotic; 97.4% would read drug instructions before taking them; Only 42.4% put expired drugs into special recycling bins; 49.8% would deviate from the suggested dosage and frequency of their medication when they were sick with common diseases. CONCLUSION: Overall, the cognition of drug safety in Beijing middle school students is good, but problems still exist in medication adherence, the management of expired drugs and the antibiotics cognition, which need to be fixed through specific, pointed way of education. And more efforts should be made to improve the cognition in rural regions, vocational high schools and on campus students.

[Estradiol inhibits differentiation of mouse macrophage into a pro-inflammatory phenotype by upregulating the IRE1α-XBP1 signaling axis].

OBJECTIVE: To explore the mechanism by which estradiol modulates the immunophenotype of macrophages through the endoplasmic reticulum stress pathway. METHODS: Peritoneal macrophages isolated from C57 mice were cultured in the presence of 60 ng/mL interferon-γ (IFN-γ) followed by treatment with estradiol (1.0 nmol/L) alone, estradiol with estrogen receptor antagonist (Acolbifene, 4 nmol/L), estradiol with IRE1α inhibitor (4 µ 8 C), or estradiol with IRE1α agonist. After the treatments, the expression levels of MHC-Ⅱ, iNOS and endoplasmic reticulum stress marker proteins IRE1α, eIF2α and ATF6 in the macrophages were detected with Western blotting, and the mRNA levels of TGF-ß, IL-6, IL-10 and TNF-α were detected with RT-PCR. RESULTS: Estrogen treatment of the macrophages significantly decreased the expressions of M1-related proteins MHC-Ⅱ (P=0.021) and iNOS (P < 0.001) and the mRNA expressions of TNF-α (P=0.003) and IL-6 (P=0.004), increased the mRNA expression of TGF-ß (P=0.002) and IL-10 (P=0.008), and up-regulated the protein expressions of IRE1α (P < 0.001) and its downstream transcription factor XBP-1 (P < 0.001). Addition of the estrogen inhibitor obviously blocked the effect of estrogen. Compared with estrogen treatment alone, combined treatment of the macrophages with estrogen and the IRE1α inhibitor 4 µ 8 C significantly up-regulated the protein expressions of MHC-Ⅱ (P=0.002) and iNOS (P=0.003) and the mRNA expressions of TNF-α (P=0.003) and IL-6 (P=0.024), and obviously down-regulated the mRNA expression of TGF-ß (P < 0.001) and IL-10 (P < 0.001); these changes were not observed in cells treated with estrogen and the IRE1α agonist. CONCLUSION: Estrogen can inhibit the differentiation of murine macrophages into a pro-inflammatory phenotype by up-regulating the IRE1α-XBP-1 signaling axis, thereby producing an inhibitory effect on inflammatory response.

[Methodology progress and challenges on assessing the appropriateness of real-world data].

From the perspective of data users, ensuring the relevance and reliability of big data in healthcare and medicine via assessments on data appropriateness is a prerequisite for generating high-quality real-world evidence, which could guarantee good representativeness and generalizability of real-world studies. This review summarized the quality dimensions, definitions, evaluation indexes and calculating methods of assessment on the appropriateness of real-world data (RWD) according to guidance from different countries and international organizations, as well as exploring the opportunities and challenges for better assessing RWD appropriateness.

[A qualitative systematic review and enlightenment of teaching models and evaluation in the general education of epidemiology in China and abroad].

Objective: This study aims to systematically sort out the effectiveness evaluation of the general education teaching models in epidemiology at home and abroad and provide a reference for the development and reform of epidemiology education. Methods: A systematic search of English databases such as PubMed, Embase, and Web of Science and Chinese databases such as CNKI, Sinomed, Wanfang, etc., were used to screen out the literature on different general teaching models of education in epidemiology. Each literature's teaching effect will be summarized and evaluated to conduct a systematic qualitative review in the narrative integration method, Results: A total of 45 articles (28 in Chinese and 17 in English) were included in this study, involving 14 teaching models, including mixed teaching models, PBL (problem-based learning), project designing models, and CBL (case-based learning) and other teaching models. Except for some teaching models such as project design, network platform, and flipped classroom model, the teaching effect of other innovative models is better than that of the traditional model. The distribution of teaching models was different in Chinese and foreign literature. Foreign teaching models were diverse, mainly concentrated in mixed teaching models and software/network platform learning. Domestic teaching models were relatively fixed. The mixed teaching model and PBL model were the most widely used in China, and there were fewer comparative studies between different teaching models than in foreign countries. Conclusion: General education in epidemiology is still in the early exploration stage. Compared with the traditional lecture model, the effect of various innovative teaching models has been improved. According to teaching objectives and student characteristics, we encourage extensive use of different teaching strategies, combining theoretical knowledge with practical applications and integrating epidemiological knowledge with inter-professional knowledge. Thus, students who can apply what they learn are becoming interdisciplinary talents our society needs.

Inhibition of hyaluronan retention by 4-methylumbelliferone suppresses osteosarcoma cells in vitro and lung metastasis in vivo.

BACKGROUND: Hyaluronan (HA) plays crucial roles in the tumourigenicity of many types of malignant tumours. 4-Methylumbelliferone (MU) is an inhibitor of HA synthesis. Several studies have shown its inhibitory effects on malignant tumours; however, none have focused on its effects on osteosarcoma. METHODS: We investigated the effects of MU on HA accumulation and tumourigenicity of highly metastatic murine osteosarcoma cells (LM8) that have HA-rich cell-associated matrix, and human osteosarcoma cell lines (MG-63 and HOS). RESULTS: In vitro, MU inhibited HA retention, thereby reducing the formation of functional cell-associated matrices, and also inhibited cell proliferation, migration, and invasion. Akt phosphorylation was suppressed by MU (1.0 mM). In vivo, although MU showed only a mild inhibitory effect on the growth of the primary tumour, it markedly inhibited (75% reduction) the development of lung metastasis. Hyaluronan retention in the periphery of the primary tumour was markedly suppressed by MU. CONCLUSION: These findings suggested that MU suppressed HA retention and cell-associated matrix formation in osteosarcoma cells, resulting in a reduction of tumourigenicity, including lung metastasis. 4-Methylumbelliferone is a promising therapeutic agent targeting both primary tumours and distant metastasis of osteosarcoma, possibly via suppression of HA retention.

[The enlightenment of foreign MD-MPH double degree program to the cultivation of high-level applied public health talents in China].

Objective: To understand the current status of foreign dual-degree programs of Medical Doctor (MD) and Master of Public Health (MPH) and provide evidence-based decision-making reference for promoting the education of high-level applied public health talents in China. Methods: The list of involved institutions and information of foreign MD-MPH dual-degree programs was collected through literature retrieval, online information searching, and additional survey of key figures. We extracted the details of each project regarding professional fields, core competence, length of schooling, teaching and learning arrangement, internship eligibility, and graduation assessment. Python 3.8.0 was used for data cleaning, and the occurrence frequency of related items in each dimension was calculated. Results: A total of 99 MD-MPH programs from 104 foreign institutions were included, among which 97.1% of them were implemented in universities from the United States. The School of Public Health provided 42.4% (42/99) of the programs. Epidemiology was the major discipline set up among most programs, accounting for 12.0% (29/241) of all the specialties involved. Epidemiological research methods, health policy management and practice, and public health practice were the top 3 core competencies to be mastered. Of the 99 programs, 87 gave information on the length of the program, of which 74.7% (65/87) were five years, 6.9% (6/87) were four years, and 18.4% (16/87) included both 4-year and 5-year programs. Conclusions: The international MD-MPH programs were sophisticated and mainly organized by the School of Public Health alone or in conjunction with the School of Medicine. Epidemiology is the core course and competence objective, with a length of 4-5 years. Through learning experience from international MD-MPH programs and the Chinese unique medical development background, China should optimize its medical education system to develop a suitable talent training strategy for MD-MPH dual-degree programs in the new era.

Polymorphisms rs763110 in FASL is linked to hepatitis C virus infection among high-risk populations.

BACKGROUND: The Fas cell surface death receptor (FAS) and Fas ligand (FASL) can participate in the apoptosis of immune cells and target cells infected with a virus through the FAS-FASL signalling pathway. The decoy receptor 3 (DCR3) can competitively inhibit the binding of FAS to FASL. Our aim is to investigate the effect of single nucleotide polymorphisms (SNPs) in FAS, FASL and DCR3 on hepatitis C virus (HCV) infection. METHODS: Four SNPs (rs763110 in FASL, rs1324551 and rs2234767 in FAS and rs2257440 in DCR3) were genotyped in 1495 controls free of HCV, 522 individuals with spontaneous HCV clearance and 732 patients with hepatitis C virus infection. The RegulomeDB database and RNAfold web servers were used to explore potential biological functions of SNPs. RESULTS: FASL rs763110 was associated with susceptibility to HCV infection, and not to CHC. The odds ratio (95% confidence interval) of HCV infection in high-risk populations carrying FASL rs763110-TT was 1.82 (1.36-2.51, P < 0.001) compared to that of CC genotypes and 1.93 (1.43-2.60, P < 0.001) higher than that of CC + CT genotypes. Based on computer simulation, FASL rs763110-T may affect the transcription of mRNA by affecting the binding of a transcription factor, leading to structural changes in mRNA. CONCLUSION: The genetic variant in FASL is linked with HCV infection, but not to spontaneous HCV clearance.

[Developing process of guide on methodological standards in pharmacoepidemiology (T/CPHARMA 002-2019)].

Pharmacoepidemiology refers to the use of epidemiological research methods in studying the application and use of drugs in large populations to evaluate the safety and efficacy of medical products. Therefore, standardized pharmacoepidemiology research is the basis of the above work. Based on systematic reviews of national and international pharmacoepidemiological methodological standards and guidelines, and in combination with Chinese medical and health practice and experts' opinions, the Professional Committee of Pharmacoepidemiology of Chinese Pharmaceutical Association developed the group standard, guide on methodological standards in pharmacoepidemiology (T/CPHARMA 002-2019), to better guide the work of pharmacoepidemiology. The guideline was designed to provide advice and reference for pharmacoepidemiology research by government, regulatory agencies, research institutions, and pharmaceutical manufacturers in China.

[Study on thyroid hormone levels and influence factors in drug users in a drug rehabilitation center in Jiangsu province].

Objective: To understand the serum levels of thyroid stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), triiodothyronine (T3), and thyroxine (T4) and identify the related influencing factors of thyroid dysfunction in drug users. Methods: From June to August 2018, a face-to-face questionnaire survey was conducted in 788 male drug users in a drug rehabilitation center in Jiangsu province to collect their socio-demographic information. Then, venous blood sample was collected from each participant for the detection of various hematological indicators, such as thyroid hormones. Results: The abnormal rates of T3, T4, FT3, FT4 and TSH were 4.57%, 1.27%, 0.51%, 0.38% and 0.89%, respectively, in the male drug users. HCV infection was an influencing factor for abnormal T3 level in the male drug users (OR=8.52, 95%CI: 2.36-30.74, P=0.001). And serum T3 (P<0.001) and T4 (P=0.048) levels increased with increasing HCV viral load. Conclusions: HCV infection was an influencing factor for the abnormality of serum T3 level in drug users. Therefore, thyroid-related knowledge should be added in the health education for drug users, and the monitoring of thyroid function should be strengthened for drug users infected with HCV.