Curcumin alleviates myocardial inflammation, apoptosis, and oxidative stress induced by acute pulmonary embolism by regulating microRNA-145-5P/insulin receptor substrate 1 axis.

The treatment of patients with acute pulmonary embolism (APE) is extremely challenging due to the complex clinical presentation and prognosis of APE related to the patient's hemodynamic status and insufficient arterial blood flow and right ventricular overload. Protective efficacy against cardiovascular diseases of curcumin, a common natural polyphenolic compound, which has antithrombotic properties and reduces platelet accumulation in the circulation by inhibiting thromboxane synthesis has been demonstrated. However, the direct effect of curcumin on APE has rarely been studied. Therefore, the present study aimed to investigate the therapeutic potential of curcumin in APE and associated myocardial injury to provide new insights into curcumin as a promising competitive new target for the treatment of APE. A suspension of 12 mg/kg microspheres was injected intravenously into rats. An APE rat model was built. Before modeling, intragastric 100 mg/kg curcumin was given, and/or lentiviral plasmid vector targeting microRNA-145-5p or insulin receptor substrate 1 (IRS1) was injected. Pulmonary artery pressure was measured to assess right ventricular systolic pressure (RVSP). Hematoxylin and eosin (H&E) staining was performed on liver tissues and myocardial tissues of APE rats. TUNEL (terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling) staining and immunohistochemical (IHC) staining were conducted to measure apoptosis and CyPA-CD147 expression in the myocardium, respectively. Inflammatory indices interleukin-1beta (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) were measured by ELISA in cardiac tissues. RT-qPCR and Western blot were performed to determine the expression levels of related genes. In addition, by dual luciferase reporter assay and RIP assay, the relationship between microRNA-145-5p and insulin receptor substrate 1 (IRS1) was confirmed. In results: curcumin improved APE-induced myocardial injury, reduced myocardial tissue edema, and thrombus volume. It attenuated APE-induced myocardial inflammation and apoptosis, as well as reduced lung injury and pulmonary artery pressure. Curcumin promoted microRNA-145-5p expression in APE rat myocardium. MicroRNA-145-5p overexpression protected against APE-induced myocardial injury, and microRNA-145-5p silencing abolished the beneficial effects of curcumin in APE-induced myocardial injury. IRS1 was targeted by microRNA-145-5p. IRS1 silencing attenuated APE-induced myocardial injury, and enhanced therapeutic effect of curcumin on myocardial injury in APE rats. In conclusion, curcumin alleviates myocardial inflammation, apoptosis, and oxidative stress induced by APE by regulating microRNA-145-5p/IRS1 axis.

[Application of V-Y advancement flap with facial artery perforator for the repair of midface skin defects].

Objective: To investigate the efficacy of V-Y advancement flap with facial artery perforator for the repair of midface skin defects. Methods: A retrospective analysis was performed on 18 patients with facial skin cancer, including 11 males and 7 females, aged 65-83 years, who underwent the repair of midface skin defects using V-Y advancement flap with facial artery perforator in the Department of Head and Neck Surgery, Affiliated Cancer Hospital of Nantong University from January 2020 to April 2023. Medium, large or complex midface skin defects developed after surgical resections of the primary lesions. According to the defect site, size, location information of facial vessels, a V-Y advancement flap with appropriate shape was designed for each case. During the operation, the facial vessels and their perforators were retained in the pedicle of the flap, the facial nerve branches were dissected and protected, and the further denuded pedicle was determined according to actual amount of advancement. After the flap was advanced, the facial defect area was repaired without tension, and the anatomical positions and functions of the eyes, nose and mouth were restored as far as possible. Postoperative follow-ups were conducted to observe the survival rate of the flaps, postoperative complications, recurrences and metastases of tumors. Results: Midface defects of 3.0 cm×3.5 cm-6.5 cm×7.5 cm were observed after tumor resections, which involved one or more subregions. The sizes of the flaps were 3.5 cm×9.0 cm-7.0 cm×18.0 cm. All flaps were completely alive except for one with temporary local bruising. With following-up of 4-40 months, 5 of the 12 patients with lower eyelid and inner canthus invasions had lower eyelid ectropion, but no exposed keratitis was found; one case with poorly differentiated squamous cell carcinoma had lymph node metastasis in the submandibular region and underwent neck dissection again; no recurrence or metastasis occurred in the remaining cases. Conclusion: The V-Y advancement flap with facial artery perforator can be used to repair medium, large or complex midface skin defects, with a high survival rate, and the operation method is safe and reliable.

Intravenous tranexamic acid significantly improved visualization and shortened the operation time in microscopic middle ear surgery: a randomized controlled trial.

BACKGROUND: The microscopic middle ear surgery involves a limited operating space and numerous important anatomical structures in which good visualization is crucial, as even a small amount of bleeding can greatly affect the clarity of surgical field. This study aims to investigate whether intravenous 1gram of tranexamic acid can improve surgical visualization and further shorten the operation time in microscopic middle ear surgery. METHODS: This study is a prospective, randomized, double-blind, controlled trial conducted from December 2021 to December 2022, enrolling patients who were scheduled for microscopic modified radical mastoidectomy due to chronic otitis media. In addition to standard techniques to optimize the surgical field, participants were randomized into the TXA (tranexamic acid) group (1gram diluted to 20 mL normal saline) and the control group (20 mL normal saline). The primary outcome was assessed based on the clarity of the surgical field using the Modena Bleeding Score. Secondary outcomes included operation time, the surgeon satisfaction with the visual clarity, postoperative 24-hour coagulation parameters, and the incidence of adverse events. Student's t test, Chi-square test and ANOVA of repeated measures were used for statistical analyses. RESULTS: A total of 28 patients were enrolled in each group using a 1:1 randomized allocation with similar demographic characteristics, including 24 male and 32 female individuals, and the mean age is 45.6±11.9 years. The surgical visualization in the TXA group was significantly better than that of the control group (2.29±0.46 vs. 2.89±0.31, P<0.001) as assessed by the Modena Bleeding Score. Furthermore, the TXA group demonstrated a shorter operation time compared to the control group (88.61±10.9 vs. 105.2±15.9, P<0.001) and higher surgeon satisfaction with surgical field (7.82±0.55 vs. 6.50±0.64, P<0.001). No statistically significant differences were found in postoperative coagulation parameters in the two groups. No TXA-related adverse events or complications occurred during the 12-month follow-up. CONCLUSION: Intravenous 1gram of TXA can further significantly improve the visual clarity in the microscopic middle ear surgery and shorten the operation time based on other standard measures implemented.

Evaluation of brain iron deposition in different cerebral arteries of acute ischaemic stroke patients using quantitative susceptibility mapping.

AIM: To investigate differences in iron deposition between infarct and normal cerebral arterial regions in acute ischaemic stroke (AIS) patients using quantitative susceptibility mapping (QSM). MATERIALS AND METHODS: Forty healthy controls and 40 AIS patients were recruited, and their QSM images were obtained. There were seven regions of interest (ROIs) in AIS patients, including the infarct regions of responsible arteries (R1), the non-infarct regions of responsible arteries (R2), the contralateral symmetrical sites of lesions (R3), and the non-responsible cerebral arterial regions (R4, R5, R6, R7). For the healthy controls, the cerebral arterial regions corresponding to the AIS patient group were selected as ROIs. The differences in corresponding ROI susceptibilities between AIS patients and healthy controls and the differences in susceptibilities between infarcted and non-infarct regions in AIS patients were compared. RESULTS: The susceptibilities of infarct regions in AIS patients were significantly higher than those in healthy controls (p<0.0001). There was no significant difference in non-infarct regions between the two groups (p>0.05). The susceptibility of the infarct regions in AIS patients was significantly higher than those of the non-infarct region of responsible artery and non-responsible cerebral arterial regions (p<0.01). CONCLUSIONS: Abnormal iron deposition detected by QSM in the infarct regions of AIS patients may not affect iron levels in the non-infarct regions of responsible arteries and normal cerebral arteries, which may open the door for potential new diagnostic and treatment strategies.

Association of healthy sleep patterns with risk of mortality and life expectancy at age of 30 years: a population-based cohort study.

BACKGROUND: The importance of sleep on cardiovascular health has been increasingly acknowledged. However, the effect of combined sleep behaviors on life expectancy remains understudied. AIM: To investigate the association between sleep patterns with total and cause-specific mortality and life expectancy, using a nationally representative sample of US adults. DESIGN: Population-based cohort study. METHODS: This cohort study included 172 321 adults aged 18 years or older in the National Health Interview Survey (2013-18) with linkage to the National Death Index records up to 31 December 2019. The life expectancy at the age of 30 years by the number of low-risk sleep scores was estimated using a flexible parametric survival model. RESULTS: During a median follow-up of 4.3 years, of the 172 321 adults (50.9% women; mean [SE] age, 46.98 [0.10] years), 8681 individuals died. The adjusted hazard ratios (95% confidence intervals [CI]) of participants with five vs. 0-1 low-risk sleep factors for all-cause, cardiovascular, and cancer mortality were 0.70 (0.63-0.77), 0.79 (0.67-0.93) and 0.81 (0.66-0.98), respectively. Nearly 8% (population attributable fraction 7.9%, 95% CI: 5.5-10.4) of mortality in this cohort could be attributed to suboptimal sleep patterns. When compared to those with 0-1 low-risk sleep factors, life expectancy at the age of 30 years for individuals with all five low-risk sleep factors was 4.7 (95% CI: 2.7-6.7) years greater for men and 2.4 (95% CI: 0.4-4.4) years greater for women. CONCLUSIONS: Our findings suggest that greater adherence to a low-risk sleep pattern may lead to significant gains in life expectancy among US adults.

[Analysis of disease burden of lung cancer attributable to chromium in Chinese population from 1990 to 2019].

Objective: To analyze the disease burden and change trend of lung cancer attributable to chromium in Chinese population from 1990 to 2019, and to provide reference for the formulation of health policies and strategies of disease prevention and control. Methods: In October 2022, using the data and findings of the burden of disease, injury and risk factor published in the Global Burden of Disease Study 2019 (GBD 2019), the burden of lung cancer and its changes caused by occupational hexavalent chromium exposure in Chinese population from 1990 to 2019 were analyzed according to year and gender. The average age structure of the world population was used as the standard population to calculate standardized indicators, and then compared with the global population. Results: The incidence number, death number, disability adjusted life years (DALY) of lung cancer attributable to chromium in Chinese population of 2019 were 833 cases, 790 cases and 22118 person years, respectively. Compared with 1990 (257 cases, 277 cases, 8631 person years), the increase was 224.1%, 185.2%, 156.3%, higher than the global level (101.0%, 134.2%, 117.2%). The standardized morbidity, mortality and DALY rates of lung cancer attributable to chromium in Chinese population of 2019 were 0.059/100000, 0.056/100000 and 1.555/100000, which respectively increased by 169.7%, 137.4%, 113.3% in comparison with that of 1990 (0.022/100000, 0.023/100000 and 0.729/100000). The average annual percent changes were 18.8%, 15.1% and 13.5%, which were higher than the global level (5.7%, 8.4% and 7.0%). In 2019, the DALY caused by chromium-related lung cancer in the Chinese population accounted for 0.0058% (22118/382205568) of the all-cause disease burden in the Chinese population, and 51.8% (22118/42718) of the global population. In 2019, the disease burden of lung cancer attributable to chromium was higher in males than in females, the number of incidence, death and DALY were 576 cases (69.1%), 525 cases (66.5%) and 14717 person years (66.5%), respectively. Conclusion: In 2019, the proportion of disease burden caused by lung cancer attributable to chromium in the Chinese population is low, but it accounts for a high proportion of the global population burden of lung cancer attributable to chromium, and the standardized incidence, mortality and DALY rates show an increasing trend year by year from 1990 to 2019.

Causal association between aspirin use and risk of endometrioid carcinoma: a Mendelian randomization study.

OBJECTIVE: The aim of the study was to investigate the causal relationship between aspirin use and the risk of endometrial endometrioid cancer (EEC) using two-sample Mendelian randomization (TSMR) and multivariable Mendelian randomization (MVMR) study. MATERIALS AND METHODS: A TSMR analysis was conducted to estimate the potential causal relationship between aspirin use and the risk of EEC using genome-wide data from Genome-wide association study (GWAS). The causal association between aspirin use and EEC was further analyzed by MVMR analysis after adjusting for various factors such as obesity, hypertension, diabetes, and infertility. The single nucleotide polymorphism (SNP) data associated with aspirin use and EEC was obtained from the GWAS catalog database. RESULTS: A total of six SNPs were included as instrumental variables in TSMR, which showed that taking aspirin reduced the risk of EEC [OR = 0.02, 95% CI = 0-0.28, p = 0.005, inverse variance weighted (IVW) method]. Besides, the results of the weighted median (WME) method, weighted mode, and simple mode were consistent with the results shown by the IVW method. After further using the MVMR method, the causal association of aspirin use and prevention of EEC onset remained significant after adjusting for the effects of obesity, hypertension, and diabetes (OR = 0.076, 95% CI = 0.007-0.793, p = 0.031). Sensitivity analyses, including heterogeneity, horizontal multiplicity, and leave-one-out tests, showed the reliability of the instrumental variables, proving that the results were reliable and not significantly biased. CONCLUSIONS: Taking aspirin can reduce the risk of EEC morbidity, and it is expected to be of great significance for the early prevention and treatment of endometrial cancer by exploring the biological mechanism of aspirin on endometrioid cancer at a deeper level.

[GPR109A partly mediates inhibitory effects of ß-hydroxybutyric acid on lung adenocarcinoma cell proliferation, migration and invasion].

OBJECTIVE: To explore the mechanism that mediates the inhibitory effects of ß-hydroxybutyrate (BHB) on lung adenocarcinoma cells. METHODS: A549 and LLC cell lines treated with 5 or 10 mmol/L BHB were examined for changes in cell viability, proliferation, migration, and invasion using CCK-8 assay, EdU staining, scratch assay, and Transwell assay. The differential expression of GPR109A in lung adenocarcinoma and normal lung tissue was analyzed using GEPIA database. GPR109A expressions in BHB-treated lung adenocarcinoma cells were determined using RT-PCR and Western blotting. The changes in IC50 of BHB were examined in A549 and LLC cells with GPR109A knockdown. The effect of BHB administered via gavage for 21 days on tumor growth was evaluated in nude mouse and Balb/c mouse models bearing xenografts derived A549 and LLC cells with or without GPR109A knockdown. RESULTS: Treatment with BHB concentration-dependently repressed the viability, proliferation, migration and invasion of A549 and LLC cells. GPR109A expression was significantly decreased in lung adenocarcinoma tissues and A549 and LLC cell lines (P<0.05). Loss of function experiments showed that the inhibitory effects of BHB on A549 and LLC cells were partly mediated by GPR109A, and in the tumor-bearing mouse models, BHB significantly inhibited tumor growth partly by regulating GPR109A expression (P<0.05). CONCLUSION: BHB can repress the malignant behaviors of A549 and LLC cells and inhibit tumor growth in mice, and these effects are mediated partly by regulating GPR109A expression.

The effect of small molecule inhibitor NSC348884 on nucleophosmin 1-mutated acute myeloid leukemia cells.

OBJECTIVE: Nucleophosmin 1 (NPM1) is a common shuttling protein. Mutation in the NPM1 gene is the most frequent gene alteration in acute myeloid leukemia (AML). This study aims to explore the inhibitory effects of small molecule NSC348884 on wild-type and NPM1-mutated AML cells. MATERIALS AND METHODS: Immunofluorescence was used to determine the intracellular localization of NPM1 protein in wild-type (OCI-AML2) and NPM1-mutated (OCI-AML3) AML cell lines. The oligomerization state of NPM1 was assessed by Western blot analysis, and the inhibitory effect of NSC348884 on the proliferation of AML cells was evaluated by Cell-counting kit-8 (CCK-8). Flow cytometry was used to detect the proapoptotic effect of NSC348884 on AML cells. RESULTS: Western blot results showed a significant reduction in the levels of the oligomeric NPM1 protein after the treatment with NSC348884. NSC348884 had an inhibitory effect on the proliferation of both wild-type and NPM1-mutant AML cells. The inhibitory effect on OCI-AML3 cells was stronger, compared to OCI-AML2 cells. Flow cytometry showed that NSC348884 could significantly induce AML cell apoptosis and had a stronger proapoptotic effect on OCI-AML3 cells. CONCLUSIONS: NSC348884 had inhibitory and proapoptotic effects on both wild-type and NPM1-mutated AML cells. The effect of NSC348884 on AML cells, carrying NPM1 mutation was significantly stronger.

[Guizhi Fuling Capsule inhibits migration and induces apoptosis of human ovarian cancer cells by regulating the NF-κB signaling pathway].

OBJECTIVE: To study the inhibitory effect of Guizhi Fuling Capsule (GFC) on migration of human ovarian cancer cells and explore the possible mechanism. METHODS: Sixty Wistar rats were randomized into 4 groups for daily gavage of saline or 4, 8, or 16 g/kg GFC suspension for 5 days to prepare blank and low-, medium- and high-dose GFC-medicated sera. Cisplatinresistant ovarian cancer SKOV3/DDP cells were treated with these sera with nuclear factor-κB (NF-κB) inhibitor SN50 as the positive control, and the changes in migration ability and apoptosis of the cells were examined using scratch assay and flow cytometry, respectively; the changes in the mRNA and protein expressions of CDH1, CDH2, caspase 3 and NF- κB were detected using RT-qPCR and Western blotting. ATAC-seq was used to analyze the changes in expressions of CDH1, CDH2, caspase 3 and NF-κB genes in the open chromatin. RESULTS: Treatment with GFC-medicated sera dose-dependently inhibited the migration (P < 0.05), increased apoptosis (P < 0.01), inhibited CDH2 and NF-κB mRNA expression (P < 0.05), and enhanced caspase 3 and CDH1 mRNA expressions (P < 0.01) in SKOV3/DDP cells. The effects of high-dose GFC-medicated serum were comparable to those of SN50 (P>0.05), but its effect for enhancing DH1 protein expression was weaker than that of SN50 (P < 0.01). GFC-medicated sera significantly lowered the expressions of NF-κB and CDH2 and increased CDH1 expression in the open chromatin without obviously affecting caspase 3 expression. CONCLUSION: GFC- medicated sera inhibits the migration ability of SKOV3/DDP cells possibly by promoting cell apoptosis and caspase 3 and CDH1 expressions, inhibiting CDH2 and NF-κB expressions, and regulating the expressions of NF-κB, CDH2 and CDH1 in the open chromatin.

Application of lung ultrasound in monitoring bronchopulmonary dysplasia and pulmonary arterial pressure in preterm infants.

OBJECTIVE: The aim of this study was to evaluate the application value of lung ultrasound in monitoring bronchopulmonary dysplasia (BPD) and pulmonary artery pressure in premature infants. PATIENTS AND METHODS: A total of 98 preterm infants diagnosed with BPD in the Fourth Hospital in Shijiazhuang were recruited, and their disease severity was classified as mild (n=32), moderate (n=33), or severe BPD (n=33) based on gestational age and oxygen concentration. Lung ultrasonography of the children was performed. The correlation between lung ventilation scores and disease severity was statistically analyzed, and the discrete optimization results were documented. The pulmonary hypertension indexes of the three groups of children were compared. RESULTS: Aberrant alterations of the pleural line were observed in all included children, and the B-line rose as the disease progressed. The duration of invasive ventilation, medication, and hospital stay increased with disease exacerbation (p<0.05). The three groups significantly differed in terms of ultrasound pulmonary ventilation scores and clinical severity (p<0.05). Only mild BDP was identified by lung ultrasound on the first day of birth (T1), and severe BDP was detectable during the first and second week (T2-T3) as well as the third and fourth week (T4-T5). Severe BPD was associated with significantly higher levels of pulmonary hypertension indices vs. mild and moderate BPD (p<0.05). CONCLUSIONS: Pulmonary ultrasonography demonstrates great potential to predict pulmonary hypertension in children and assesses the disease severity. Pulmonary ultrasound allows for dynamical real-time observation of the pulmonary lesions in children with pulmonary hypertension, thereby revealing the severity of pulmonary hypertension in premature children.

[Value of autocrine motility factors in the prediction of the disease progression of PBC- associated hepatocellular carcinoma].

Objective: To clarify the value of autocrine motility factor (ATX) in predicting the disease progression of primary biliary cholangitis (PBC)-associated hepatocellular carcinoma (HCC). Methods: A prospective cohort of 179 newly diagnosed autoimmune liver disease (PBC) patients admitted to the Department of Hepatology at the Fifth Medical Center of the People's Liberation Army General Hospital from January 2016 to January 2018 was selected. All PBC patients received ursodeoxycholic acid (UDCA) treatment and were followed up.The endpoint of the follow-up was the occurrence of primary liver cancer. The relationship between ATX and the clinical characteristics of patients and its significance in predicting disease progression and HCC were analyzed. Results: The peripheral blood ATX level was significantly higher in PBC patients than that of alcoholic cirrhosis (t = 3.278, P = 0.001) and healthy controls (t = 6.594, P < 0.001), but there was no significant difference in ATX levels compared with patients with non-PBC- associated HCC (t = -0.240, P = 0.811). The expression of ATX in liver tissue of PBC patients was significantly higher than that of healthy individuals (Z = -3.633, P < 0.001) and patients with alcoholic cirrhosis (Z = -3.283, P < 0.001), while the expression of ATX in the advanced stage was significantly higher than that in early-stage PBC patients (Z = -2.018, P = 0.034). There was a significant difference in baseline ATX levels between PBC patients without HCC and PBC patients with HCC (228.451 ± 124.093 ng/ml vs. 301.583 ± 100.512 ng/ml, t = 2.339, P = 0.021). Multivariate logistic regression analysis showed that ATX was an independent predictor of PBC progression to HCC (OR = 1.245, 95%CI 1.097-1.413). The baseline peripheral blood ATX level in predicting AUROC of PBC-associated HCC was 0.714, 95%CI 0.597-0.857 and the sensitivity and specificity were 84.6%, and 59.0%, respectively. The optimal cutoff value for predicting serum ATX levels in the occurrence of HCC was 235.254 ng/ml. Conclusion: Patients with PBC have significantly higher levels of ATX expression in their peripheral blood and liver tissue, which can be utilized to assess treatment effectiveness and predict disease progression.

[Clinical characteristics of 111 cases with mucopolysaccharidosis â £A].

Objective: To analyze the clinical characteristics of patients with Mucopolysaccharidosis ⅣA (MPS ⅣA). Methods: A retrospective study was conducted on 111 patients with MPS ⅣA in Xinhua Hospital of Shanghai Jiao Tong University School of Medcine from December 2008 to August 2020, confirmed by enzyme activity and genetic testing. General situation, clinical manifestations and enzyme activity test results were analyzed. According to the clinical manifestations, it can be divided into severe, intermediate and mild group. The independent sample t test was used to compare the birth body length and weight of children with that of normal boys and girls, and group comparisons of enzyme activities were evaluated by median test. Results: One hundred and eleven unrelated patients, 69 males and 42 females, were classified into 3 subtypes: severe (n=85), intermediate (n=14), and mild (n=12). The age at symptom onset were 1.6 (1.0, 3.0) years, and at diagnosis were 4.3 (2.8, 7.8) years. Skeletal manifestations were observed in all patients and consisted mainly of pectus carinatum (96/111, 86.5%), motor dysfunction (78/111, 70.3%), spinal deformity (71/111, 64.0%), growth retardation (64/111, 57.7%), joint laxity (63/111, 56.8%) and genu valgum (62/111, 55.9%). Eighty-eight patients (88/111, 79.3%) with MPS ⅣA were also along with non-skeletal manifestations, mainly including snoring (38/111, 34.2%), coarse faces (34/111, 30.6%), and visual impairment (26/111, 23.4%). The most common skeletal manifestation was pectus carinatum (79 cases), and non-skeletal manifestation was snoring (30 cases) and coarse faces (30 cases) in severe patients, pectus carinatum (13 cases) and snoring (5 cases) in intermediate type, motor dysfunction (11 cases) and snoring (3 cases) and visual impairment (3 cases) in mild patients. The height and weight of severe patients began to fall below -2 s at 2-<5 years and 5-<7 years, respectively. At the age of 10-<15 years, the standard deviation score of the height of severe patients reached (-6.2±1.6) s in males and (-6.4±1.2) s in females, and the score of weight got (-3.0±1.1) s in males and (-3.5±0.5) s in females. The height of intermediate patients began to fall below -2 s at the age of 7-<10 years, and the standard deviation score of height were -4.6 s and -3.6 s in 2 males, and -4.6 s and -3.8 s in 2 females at the age of 10-<15 years. The weight remained within -2 s in 72.0% (18/25) of intermediate patients compared to age-matched healthy children. In the mild patients with MPS ⅣA, the mean standard deviation score of height and weight was within -2 s. The enzyme activities of mild patients (2.02 (1.05, 8.20) nmol/(17 h·mg)) were both significantly higher than that of intermediate (0.57 (0.47, 0.94) nmol/(17 h·mg)) and severe (0.22 (0, 0.59) nmol/(17 h·mg)) patients (Z=9.91, 13.98, P=0.005, 0.001), and the enzyme activity of intermediate patients was significantly higher than that of severe patients (Z=8.56, P=0.010). Conclusions: The clinical manifestations of MPS ⅣA are charactered by pectus carinatum, motor function impairment, spinal deformity and growth retardation. The clinical characteristics, growth rate and enzyme activity differ among the 3 subtypes of MPS ⅣA.

[A meta-analysis of risk factors for multidrug-resistant tuberculosis in China].

Objective: To explore the main risk factors of multidrug-resistant tuberculosis (MDR-TB) in China and to provide evidence-based evidence for MDR-TB preventon and control. Methods: All relevant literatures were searched in thedatabases, such as Pubmed, Web of Science and CNKI, Wanfang, VIP and SinoMed from 2000 to 2021. Quality evaluation and data extraction were carried out, and then a meta-analysis was performed using Stata 16.0 software. Results: A total of 59 literatures (36 cross-sectional and 23 case-control) including 75 793 participants were included in this study, and meta-analysis results showed age (OR=1.27, 95%CI: 1.05-1.54), education level (OR=1.29, 95%CI: 1.02-1.65), positive sputum smear (OR=2.56, 95%CI: 1.09-6.04), pulmonary cavity (OR=1.99, 95%CI: 1.57-2.52), course of disease (OR=4.25, 95%CI: 1.95-9.30), history of tuberculosis treatment (OR=6.42,95%CI:5.40-7.63), treatment interruption (OR=2.81, 95%CI: 1.50-5.29), irregular medication (OR=5.02, 95%CI: 2.95-8.54), adverse drug reactions (OR=4.27, 95%CI: 2.22-8.19), combined chronic obstructive pulmonary disease (COPD) (OR=2.21, 95%CI: 1.45-3.37), tuberculosis exposure history (OR=1.99, 95%CI: 1.36-2.91), smoking history (OR=1.35, 95%CI: 1.09-1.66) and floating population (OR=1.60, 95%CI: 1.04-2.44) were associated with the occurrence of MDR-TB. Conclusions: The high risk groups were farmer, low education level, pulmonary cavity, long course of disease, history of tuberculosis treatment, treatment interruption, irregular medication, adverse drug reaction, co-COPD, contact history of tuberculosis, smoking history, rural residence, and floating population. We should pay attention to high-risk groups, strengthen management and take effective measures such as early screening, knowledge education on tuberculosis, standardized and personalized treatment and whole-course supervision.

[hsa_circ_0000231 affects the progression of tongue squamous cell carcinoma by activating Wnt/ß-catenin signaling pathway].

Objective: To explore the action mechanism of hsa_circ_0000231 in the occurrence and development of tongue squamous cell carcinoma (TSCC). Methods: Tissue samples of 60 TSCC patients were examined. The patients, including 32 males and 28 females, aged from 36 to 84 years old, underwent surgery in the Affiliated Hospital of Nantong University and Affiliated Tumor Hospital of Nantong University from December 2014 to December 2017. Saliva samples were obtained from healthy volunteers (5 males and 5 females, aged from 40 to 75 years old) and 10 TSCC patients. The TSCC cell lines (CAL-27, Tca-8113 and HN-4) were used. The expression levels of hsa_circ_0000231 in 60 pairs of freshly matched TSCC and para-carcinoma tissue samples, 10 pairs of saliva samples and 3 TSCC cell lines were detected by quantitative real-time polymerase chain reaction (qRT-PCR). hsa_circ_0000231 gene interference and lentiviral transfection were constructed, hsa_circ_0000231 in TSCC cell lines CAL-27 and Tca-8113 was knocked down, and the expressions of hsa_circ_0000231 in hsa_circ_0000231 interference group (sh-circ) and no-load lentivirus group (negative control) were tested with qRT-PCR. Cells with the highest knock-down efficiency were selected for CCK-8 test, colony formation assay, transwell invasion assay and scratch assay. The expressions of EMT-related proteins including E-cadherin, snail protein, N-cadherin and vimentin and proteins related to Wnt/ß-catenin signaling pathway including ß-catenin, C-myc, Bcl-2, MMP-9 and Cyclin D1 were measured by western blot. After TSCC cells in the interference group were co-cultured with Wnt/ß-catenin pathway activator LiCl, the expressions of above proteins were re-measured by western blot. TSCC cells in interference group and control group were subcutaneously injected into nude mice to compare the effect of hsa_circ_0000231 knockdown on the growths of the tumors grafted subcutaneously in the nude mice. Statistical analysis software 25.0 was used for data analysis, and t-test or chi-square test was used for comparison between groups. Results: hsa_circ_0000231 was highly expressed in the tissue and saliva samples of TSCC patients and cell lines CAL-27, Tca-8113 and HN-4, but lowly expressed in paired para-carcinoma tissues, saliva samples of healthy people and normal human oral keratinocytes (all P<0.05). Log-rank univariate analysis showed that hsa_circ_0000231 expression level, tumor differentiation degree and T stage were related to the survival of TSCC patients (all P<0.05). Multivariate Cox risk regression model analysis suggested that hsa_circ_0000231 expression level (χ2=5.77,P=0.016) and T stage (χ2=5.27,P=0.029) were independent factors for the poor prognosis of TSCC patients. Western blot showed the expressions of snail protein, N-cadherin and vimentin were down-regulated, but E-cadherin was up-regulated in interference group compared with control group. In interference group, the expressions of ß-catenin, C-myc, Bcl-2, MMP-9 and CyclinD1 were down-regulated, which were reversed after TSCC cells were co-cultured with LiCl. The knockdown of hsa_circ_0000231 reduced the proliferation, invasion and metastasis abilities of CAL-27 and Tca-8113 cells, which were reversed after TSCC cells were co-cultured with LiCl. The growth rate and volume of the tumors grafted subcutaneously in interference group using LiCl were greater than those in negative control group. Conclusion: hsa_circ_0000231 is an independent prognostic factor of TSCC. Highly expressed hsa_circ_0000231 can promote the proliferation, invasion and metastasis of TSCC cells.

[Investigation on dust pollution and pneumoconiosis incidence in a steel enterprise].

Objective: To analyze the change trend of underground dust concentration, the incidence and survival status of pneumoconiosis patients, and provide reference for improving the working environment of dust-exposed workers and the prevention and treatment of pneumoconiosis patients in the future. Methods: In February 2020, a retrospective investigation was conducted on the dust data of underground mining operations in a steel enterprise in Jiangsu Province from 1991 to 2019, and the case data of patients diagnosed with pneumoconiosis from 1956 to 2019 were collected. The time trends of the number of pneumoconiosis patients and dust concentration, the stage of pneumoconiosis and survival status of patients were analyzed. Results: From 1956 to 2019, a total of 241 patients with pneumoconiosis were diagnosed in the steel enterprise. From 1991 to 2019, the annual average dust concentration in the mine showed a downward trend as a whole. Compared with the transportation platform (14.28%, 1447/10132) , the average dust concentration exceeding rate of the mining platform (43.68%, 8415/19263) was significantly higher (χ(2)=2674.84, P<0.01) . The average age of pneumoconiosis patients was (73.54±10.42) years old, and the average working age of dust exposure was (21.41±8.68) years, of which 85 cases (35.27%) survived and 156 cases (64.73%) died. The main type of pneumoconiosis was silicosis (90.46%, 218/241) , and the main stage of pneumoconiosis was the stage I (96.68%, 233/241) ; The higher the stage of pneumoconiosis, the younger the diagnosis age (P<0.01) . The average survival time of patients was (27.264±1.982) years, and the median survival time was 28 years. The cumulative survival rates of patients with pneumoconiosis in different diagnosis time periods were significantly different (χ(2)=35.57, P<0.01) . Conclusion: The improved dust-proof measures have a significant effect on reducing the concentration of underground dust. We need to focus on the dust control of underground mining platforms and the treatment of patients with stage Ⅲ pneumoconiosis.

[Toxic effects of long-term pesticides exposure and key gene discovery].

Objective: Bioinformatics methods were used to mine differentially expressed genes (DEGs) and enriched signal pathways induced by chronic pesticide exposure, and explore its potential pathogenic mechanisms and key genes. Methods: In July 2021, high-throughput gene expression profile data related to pesticide toxicity was downloaded from Gene Expression Omnibus (GEO) database to obtain DEGs. The samples were from American male farm workers who had been exposed to pesticides for a long time and other industry workers. The functional enrichment analysis of GO, KEGG and Geme Set Enrichment Analysis (GSEA) were performed by R package clusterProfiler. STRING, Cytoscape and other tools were applied to construct and visualize the protein interaction network. With the help of MCODE and Cytohubba plugins, gene function modules were obtained, and hub gene was screened out. Results: 189 DEGs were screened from GSE30335 dataset, including 101 up-regulated genes and 88 down-regulated genes. The results of GO, KEGG and GSEA were mainly enriched in biological functions such as regulation of neuron projection development, regulation of locomotion, ribosomal protein synthesis, and pathways related to complex nervous system diseases such as Parkinson's disease. And the comprehensive screening showed that KLF1 was the hub gene of pesticide exposure, with a fold change of 0.456 (t=-3.82, P=0.021) . Conclusion: Long term exposure to pesticides results in the differential expression of multiple genes in the exposed population, which may be involved in the pathological changes of nervous system by down regulating KLF1 and related biological pathways.

pH Sensitive Erythrocyte-Derived Membrane for Acute Systemic Retention and Increased Infectivity of Coated Oncolytic Vaccinia Virus.

Oncolytic viruses have emerged as a promising modality in cancer treatment given their high synergy with highly efficient immune checkpoint inhibitors. However, their potency is limited by their rapid in vivo clearance. To overcome this, we coated oncolytic vaccinia viruses (oVV) with erythrocyte-derived membranes (EDMs), hypothesizing that they would not only remain in systemic circulation for longer as erythrocytes would when administered intravenously, but also respond to environmental pH cues due to their membrane surface sialic acid residues. For this, we developed a model based on DLVO theory to show that the acidic moieties on the surface of EDM confers it the ability to respond to pH-based stimuli. We corroborate our modeling results through in vitro cell culture models and show that EDM-coated oVV infects cancer cells faster under acidic conditions akin to the tumor microenvironment. When EDM-coated oVVs were intravenously injected into wild-type mice, they exhibited prolonged circulation at higher concentrations when compared to the unprocessed oVV. Furthermore, when EDM-coated oVV was directly injected into xenografted tumors, we observed that they were suppressed earlier than the tumors that received regular oVV, suggesting that the EDM coating does not hinder oVV infectivity. Overall, we found that EDM was able to serve as a multi-functional encapsulant that allowed the payload to remain in circulation at higher concentrations when administered intravenously while simultaneously exhibiting pH-responsive properties.

EPIGENETIC FACTORS OF SERUM URIC ACID LEVEL AND RELATED GENE POLYMORPHISMS IN SHENYANG, CHINA.

Background: The purpose of this study was to explore the influencing factors of serum uric acid (SUA) level and related gene polymorphisms in the healthy population. Methods: A total of 346 healthy individuals screened from different areas in Shenyang City and 195 patients with high SUA levels were included. Results: The levels of TC (total cholesterol), HDL-C (high-density lipoprotein cholesterol), LDL-C (low-density lipoprotein cholesterol), TG (triglycerides), GLU (blood glucose) ALT (alanine aminotransferase), TBA (total bile acid), TBIL (total bilirubin), CR (creatinine) and CYSC (Cystatin C) were statistically different between the healthy and hyperuricemia population (P<0.05). However, there was no statistical difference in the UA level between the two groups (P>0.05). After adjusting for UA, TC, HDL-C, LDL-C, GLU, TBIL and CYSC, the additive and recessive models of rs2231142 were statistically significant in females (P<0.05). For males, haplotypes of A-C-A-A-G-G, A-C-G-C-G-G and A-T-G-A-A-G had significant difference between the healthy and hyperuricemia population (P<0.05). For females, the haplotypes of A-C-G-C-G-G and A-T-A-C-A-T had significant differences (P<0.05). Conclusion: The distributions of SLC2A9 (solute carrier family 2 and facilitated glucose transporter member 9), ABCG2 (ATP-binding cassette G2), GCKR (glucokinase regulatory protein), KCNQ1, IGFIR (Insulin-like growth factor-I receptor) and VEGFR (Vascular Endothelial Growth Factor Receptor) were balanced in the population in Shenyang City. The haplotypes of A-C-A-A-G-G, A-C-G-C-G-G and A-T-G-A-A-G were the influencing factors of high SUA in the population in Shenyang City.

[Clinical characteristics of 272 437 patients with different histopathological subtypes of primary esophageal malignant tumors].

Objective: To characterize the histopathological subtypes and their clinicopathological parameters of gender and onset age by common, rare and sparse primary esophageal malignant tumors (PEMT). Methods: A total of 272 437 patients with PEMT were enrolled in this study, and all of the patients were received radical surgery. The clinicopathological information of the patients was obtained from the database established by the State Key Laboratory of Esophageal Cancer Prevention & Treatment from September 1973 to December 2020, which included the clinical treatment, pathological diagnosis and follow-up information of esophagus and gastric cardia cancers. All patients were diagnosed and classified by the criteria of esophageal tumor histopathological diagnosis and classification (2019) of the World Health Organization (WHO). The esophageal tumors, which were not included in the WHO classification, were analyzed separately according to the postoperative pathological diagnosis. The χ2 test was performed by the SPSS 25.0 software on count data, and the test standard α=0.05. Results: A total of 32 histopathological types were identified in the enrolled PEMT patients, of which 10 subtypes were not included in the WHO classification. According to the frequency, PEMT were divided into common (esophageal squamous cell carcinoma, ESCC, accounting for 97.1%), rare (esophageal adenocarcinoma, EAC, accounting for 2.3%) and sparse (mainly esophageal small cell carcinoma, malignant melanoma, etc., accounting for 0.6%). All the common, rare, and sparse types occurred predominantly in male patients, and the gender difference of rare type was most significant (EAC, male∶ female, 2.67∶1), followed with common type (ESCC, male∶ female, 1.78∶1) and sparse type (male∶ female, 1.71∶1). The common type (ESCC) mainly occurred in the middle thoracic segment (65.2%), while the rare type (EAC) mainly occurred in the lower thoracic segment (56.8%). Among the sparse type, malignant melanoma and malignant fibrous histiocytoma were both predominantly located in the lower thoracic segment (51.7%, 66.7%), and the others were mainly in the middle thoracic segment. Conclusion: ESCC is the most common type among the 32 histopathological types of PEMT, followed by EAC as the rare type, and esophageal small cell carcinoma and malignant melanoma as the major sparse type, and all of which are mainly occur in male patients. The common type of ESCC mainly occur in the middle thoracic segment, while the rare type of EAC mainly in the lower thoracic segment. The mainly sparse type of malignant melanoma and malignant fibrous histiocytoma predominately occur in the lower thoracic segment, and the remaining sparse types mainly occur in the middle thoracic segment.