[Analysis of the effect and safety of lumen reshaping after endovascular repair of Stanford B type aortic dissection at different intervention times].

Objective: To Compare the effects and safety of lumen reshaping after thoracic endovascular aortic repair (TEVAR) for Stanford B type aortic dissection (AD) at different intervention times. Methods: A retrospective analysis was conducted on the clinical data of 189 patients with Stanford type B aortic dissection treated with TEVAR at the Affiliated Hospital of Chengde Medical College from January 2016 to December 2020.Based on the time from onset to surgery, patients were divided into an early intervention group (≤14 days, n=127) and a delayed intervention group (>14 days, n=62).The diameters of the total aorta, true lumen and false lumen at different times and planes (S1 plane: at the bifurcation of the pulmonary artery; S2 plane: at the lower edge of the left atrium; S3 plane: at the upper edge of the celiac trunk) post-surgery were compared between the two groups, and the rate of change in diameters of true and false lumens across these planes was calculated. The patients were followed until December 1st, 2023, and the median follow-up time was 45(40, 49) months. The postoperative complications and survival of the two groups were compared. Results: The early intervention group comprised 86 men and 41 women, with an average age of (58.3±10.7) years. The delayed intervention group included 41 men and 21 women, with an average age of (58.5±9.2) years. Both groups had an operation success rate of 100%. Six months post-surgery, the early intervention group had an expansion rate of the true lumen diameter at planes S2 and S3 of 40.1%(25.5%, 56.1%) and 5.3%(-2.5%, 15.8%), respectively, which was superior to the delayed intervention group's 18.5%(10.6%, 39.8%) and 1.0%(-8.2%, 9.6%) (both P<0.05).The early intervention group had a reduction rate of the false lumen diameter at planes S1, S2, and S3 of -56.2%(-61.3%, -48.8%), -70.4%(-81.8%, -56.6%), and -5.4%(-17.4%, 0.1%), respectively, better than the delayed intervention group's -44.2%(-53.7%, -38.3%), -49.0%(-57.6%, -35.8%), and -3.1%(-6.7%, 1.8%) (all P<0.05).At plane S1, the true lumen diameter of patients in both groups showed an increasing trend over 36 months post-surgery, while the false lumen diameter showed a decreasing trend (both P<0.05).At plane S2, the true lumen diameter of patients in the early intervention group exhibited an increasing trend over 36 months post-surgery, and the false lumen diameter exhibited a decreasing trend (both P<0.05).At plane S3, the total aortic diameter of patients in the delayed intervention group showed a slight increasing trend over 36 months post-surgery (P<0.05).The overall survival time were 45.0 months (95%CI: 42.9-47.1) for patients in the early intervention group and 46.0 months (95%CI: 43.5-48.5) for those in the delayed intervention group, with no statistically significant difference observed (P>0.05).The incidence rates of complications such as aortic rupture, retrograde Type A dissection, new distal endograft dissection, endoleak, paraplegia, and others showed no statistically significant difference between the two groups (all P>0.05), with no cases of stent migration or deformation observed. Conclusion: Early intervention for Stanford type B aortic dissection provides a better aortic remodeling outcome than delayed intervention, with similar safety.

Posterior open wound healing in immediate implant placement using reactive soft tissue versus absorbable collagen sponge: a retrospective cohort study.

The soft and hard tissue healing of open wounds in immediate implant placement are yet to be explored. The aim of this study was to compare the clinical outcomes of open wound healing using reactive soft tissue (RST) and absorbable collagen sponge (ACS). Forty implants placed immediately in posterior sockets were included; autologous RST was used in 20 and ACS substitute was used in 20. Soft tissue healing was primarily assessed through a novel scoring system and the evaluation of gingival recession. The horizontal bone width (HBW) and interproximal marginal bone level (MBL) were measured on radiographs to observe the hard tissue healing. No significant difference in total soft tissue healing score was observed at 2 weeks postoperatively. Notably, the ACS group showed better tissue colour (P = 0.016) but worse fibrous repair (P = 0.043) scores than the RST group. Gingival recession levels were comparable in the two groups, both before tooth extraction and after placement of the restoration. Regarding hard tissue, HBW and MBL changes showed no intergroup differences. Within the limitations of this study, both RST and ACS seemed effective for open wound closure, achieving ideal soft and hard tissue healing in immediate implant placement.

Melatonin attenuates inflammation and cardiac dysfunction in myocardial infarction by regulating the miRNA-200b-3p/high mobility group box chromosomal protein 1 axis.

Melatonin confers protection against myocardial injury by reducing inflammation and inhibiting apoptosis. In the present study, we investigated whether melatonin regulates cardiomyocyte proliferation and improves cardiac function in rats with myocardial infarction (MI). Two MI models were established in vitro (H9c2 cells were cultured under hypoxia) and in vivo (the left anterior descending coronary artery of rats was surgically ligated). miR-200b-3p and high mobility group box 1 (HMGB1) levels were detected. Cell proliferation and apoptosis were analyzed in vitro, and cardiac function, inflammatory cytokines, and myocardial injury markers in vivo were tested. The experimental results reported that melatonin promoted proliferation and impaired apoptosis of H9c2 cells cultured in hypoxia. In vivo, melatonin improved cardiac function and inhibited the inflammation and myocardial injury of rats with MI. miR-200b-3p was downregulated and HMGB1 was upregulated in MI, while melatonin could upregulate miR-200b-3p and downregulate HMGB1. The HMGB1 was targeted by miR-200b-3p. Upregulating miR-200b-3p or downregulating HMGB1 could further promote the therapeutic effect of melatonin, and downregulating miR-200b-3p or upregulating HMGB1 could abolish the therapeutic effect of melatonin. In conclusion, melatonin alleviates inflammation and cardiac dysfunction after MI by regulating the miR-200b-3p/HMGB1 axis, offering a new therapeutic strategy for MI.

[Influencing factors of poor treatment adherence in uncontrolled asthma patients in China].

Objective: To evaluate the influencing factors of poor treatment adherence in patients with uncontrolled asthma in China. Methods: From April 2017 to April 2018, all asthma patients with uncontrolled asthma and poor compliance in 32 third-class hospitals in 28 provinces and cities of China mainland included in the "National Mobile Asthma Assessment and Management Project" were selected as the subjects. A total of 923 patients were enrolled in the study including 388 males and 535 females. By analyzing the baseline data of the patients at the initial visit when enrolled, the influencing factors of poor adherence of adult asthma was analyzed by inter-group comparison and χ2 test. Results: Poor compliance in asthma was related to the following factors: age from 59 to 68 years old, course of disease more than 20 years, low education level, non-local follow-up, having obstructive ventilation dysfunction and low awareness of the disease[P values were 0.026(t=1.20), 0.004(t=3.97), 0.001(t=4.92), 0.003(t=3.98), 0.032(t=1.22) and 0.001(t=4.99), respectively]. Totally, 243 patients (26.33%) answered all the questions about asthma correctly. Their medication adherence rating scale (MARS-A) scores were significantly higher than those who answered incompletely correctly (36.23±5.85 vs. 31.77±5.74, P=0.001). Conclusions: The adherence of adult asthma patients was affected by individual and external environment factors. Clinicians should choose individualized methods based on the characteristics of patients. Patient education should be strengthened to improve patients' awareness of the disease at the same time.

[Predictive value of serum Gal-13, GLP-1 and VEGF levels in adverse pregnancy outcomes of gestational diabetes mellitus].

To explore the application value of serum Gal-13, GLP-1 and VEGF in the prevention and guidance of adverse pregnancy outcomes in gestational diabetes (GDM). A retrospective study with case-control method was used to select 1 012 GDM patients from Haikou Maternal and Child Health Hospital from January 2019 to December 2022 as the study objects, and they were divided into poor pregnancy outcome group (n=342) and good pregnancy outcome group (n=670) according to whether they had adverse pregnancy outcomes. The medical records of 521 healthy women with normal glucose metabolism were selected as the control group. Serum Gal-13 and GLP-1 were detected by enzyme-linked immunosorbent assay and VEGF was determined by IAMMGE specific protein analyzer. After comparing the differences of the above factors among the three groups, multivariate logistic regression model was used to analyze the influencing factors of adverse pregnancy outcomes in GDM patients, and ROC curve was drawn to analyze the predictive value of serum Gal-13, GLP-1 and VEGF levels on adverse pregnancy outcomes in GDM patients. The results showed that Fasting blood glucose (FPG), glycosylated hemoglobin (HbA1c) and fasting insulin (FINS) in the adverse pregnancy outcome group were 5.92(4.98, 6.41) mmol/L, 5.32(4.96, 5.47)%, 62.56(49.21,99.50) pmol/L, VEGF was 495.47(389.14, 567.13) ng/L, TSH was 1.48(1.34, 1.58) mIU/L, right ventricular myocardial work index (Tei index) was 0.59(0.45, 0.67), 89 cases of elderly parturients; FPG was 4.45(4.16, 5.03) mmol/L, HbA1c was 5.04(4.86, 5.29)%, FINS was 57.41(46.90, 74.08) pmol/L, VEGF was 405.84(348.02, 462.68) ng/L, TSH was 1.42(1.25, 1.50) mIU/L, Tei index was 0.50(0.47, 0.64), there were 142 cases of old women. In the control group, FPG was 4.33(4.05, 4.75) mmol/L, HbA1c was 5.01(4.13, 5.18)%, FINS was 38.48(36.76, 41.72) pmol/L and VEGF was 302.45(283.14, 336.56) ng/L, TSH was 1.32(1.24, 1.47)mIU/L, Tei index was 0.48(0.39, 0.59), and there were 106 elderly parturiencies. The levels of FPG, HbA1c, FINS, VEGF, TSH and Tei index in the adverse pregnancy outcome group and the good pregnancy outcome group were higher than those in the control group, and the proportion of elderly parturients was higher than that in the control group, and the adverse pregnancy outcome group was higher than that in the good pregnancy outcome group. The differences were statistically significant (H=8.620, P<0.001, H=2.616, P=0.014, H=6.156, P<0.001, H=3.051, P<0.001, H=4.892, P=0.044, χ2=2.548, P=0.045). In the adverse pregnancy outcome group, Gal-13 was 15.27(8.35, 24.45)pg/ml, GLP-1 was 9.27(8.26, 12.35) pmol/L and FT4 was 11.59(9.67, 13.48) pmol/L. In the group with good pregnancy outcome, Gal-13 was 25.34(20.14, 29.73) pg/ml, GLP-1 was 12.38(10.25, 15.63) pmol/L and FT4 was 13.86(10.67, 15.10) pmol/L. In the control group, Gal-13 was 31.21(27.48, 34.45) pg/ml, GLP-1 was 11.34(10.40, 14.37) pmol/L and FT4 was 14.15(10.75, 15.43)pmol/L. The levels of Gal-13, GLP-1 and FT4 in the adverse pregnancy outcome group and the good pregnancy outcome group were significantly lower than those in the control group, and the adverse pregnancy outcome group was lower than that in the good pregnancy outcome group. The differences were statistically significant (H=6.458, P=0.011, H=8.445, P<0.001, H=5.694, P<0.001). The levels of Gal-13 and GLP-1 in normal blood glucose recovery group were higher than those in non-normal blood glucose recovery group, and the levels of VEGF were lower than those in non-normal blood glucose recovery group (P<0.05).In multivariate logistic regression analysis, Gal-13, GLP-1, VEGF, TSH, FT4 and Tei indexes were independent influencing factors for adverse pregnancy outcomes with GDM (P<0.05). ROC curve analysis showed that the AUC of Gal-13, GLP-1 and VEGF alone in predicting adverse pregnancy were 0.779, 0.761 and 0.615, respectively. The value of the combined diagnosis was the highest (AUC=0.912), the sensitivity was 90.1%, and the specificity was 80.0%. In conclusion, Gal-13, GLP-1 and VEGF may be independent influencing factors for adverse pregnancy outcomes in GDM patients, and the combined detection of the three may help to improve the auxiliary diagnostic efficacy for predicting adverse pregnancy outcomes.

Predicting the probability of malignant pathological type of kidney cancer based on mass size: A retrospective study.

BACKGROUND: Different degrees of malignancy of renal cell carcinoma (RCC) correspond to dissimilar therapies, and the prediction of malignancy of kidney cancer based on tumor size is still not fully studied. METHODS: We evaluated a total of 50,776 patients with T1-T2, N0, M0 RCC diagnosed between 2004 to 2015 based on the Surveillance, Epidemiology, and End Results database. Three and four fuhrman grade clear cell RCC, three and four fuhrman grade papillary RCC, collecting duct RCC, sarcomatoid differentiation RCC and unclassified RCC were classified as aggressive RCC. The other RCC was classified as indolent RCC. The probability of aggressive and indolent was estimated according to tumor size using a logistic regression model. Differences in survival between subgroups were assessed using the Kaplan-Meier method. RESULTS: There were 38,003 cases of indolent tumor and 12,773 cases of aggressive tumor totally. As tumor size increases, the predicted probability of an aggressive tumor also increases. Concretely, kidney cancers of 2cm, 3cm and 4cm were estimated to be 19.6%, 21.6% and 23.7% more likely to be aggressive. And for the same tumor size, clear cell RCC in men is more likely to be invasive relative to women and other kidney cancer pathology types. In addition, both the overall and tumor-specific survival are longer for indolent tumors than for aggressive tumors. CONCLUSION: We evaluated the degree of malignancy of different sizes RCC in a retrospective study. This result may be helpful in the choice of initial therapy strategies for kidney cancer patients.

[Gastric cancer-derived mesenchymal stem cells regulate the M2 polarization of macrophages within gastric cancer microenvironment via JAK2/STAT3 signaling pathway].

Objective: To investigate the role and mechanism of tumor-derived mesenchymal stem cells in regulating the M2 polarization of macrophages within gastric cancer microenvironment. Methods: Gastric cancer tissues and the adjacent non-cancerous tissues were collected from patients underwent gastric cancer resection in the First People's Hospital of Lianyungang during 2018. In our study, THP-1-differentiated macrophages were co-cultured with gastric cancer-derived mesenchymal stem cells (GC-MSCs). Then, the M2 subtype-related gene, the markers expressed on cell surface and the cytokine profile were analyzed by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR), flow cytometry and Luminex liquid chip, respectively. The key cytokines mediating the inducing effect of GC-MSCs on macrophage polarization into the M2 subtype were detected and screened by Luminex liquid chip, which were further confirmed by the neutralizing antibody test. The expressions of macrophage proteins involved in M2 polarization-related signaling pathways under the different co-culture conditions of GC-MSCs were detected by western blot. Results: In Mac+ GC-MSC-culture medium (CM) group, the expression levels of Ym-1 and Fizz-1 (1.53±0.32 and 13.22±1.05, respectively), which are markers for M2 subtype, were both significantly higher than those of Mac group (1.00±0.05 and 1.21±0.38, respectively, P<0.05). The level of iNOS in Mac+ GC-MSC-CM group (0.60±0.41) was significantly lower than that of Mac group (1.06±0.38, P=0.023). In Mac+ GC-MSC-Transwell (TW) group, the expression levels of Ym-1 and Fizz-1 (1.47±0.09 and 13.16±2.77, respectively) were both significantly higher than those of Mac group (1.00±0.05 and 1.21±0.38, respectively, P<0.05). The level of iNOS in Mac+ GC-MSC-CM group (0.56±0.03) was significantly lower than that of Mac group (1.06±0.38, P=0.026). The ratios of CD163(+) /CD204(+) cells in Mac+ GC-MSC-CM and Mac+ GC-MSC-TW groups (3.80% and 4.40%, respectively) were both remarkably higher than that of Mac group (0.60%, P<0.05). The expression levels of IL-10, IL-6, MCP-1 and VEGF in Mac+ GC-MSC-CM group were (592.60±87.52), (1 346.80±64.70), (11 256.00±29.03) and (1 463.90±66.67) pg/ml, respectively, which were significantly higher than those of Mac group [(41.03±2.59), (17.35±1.79), (5 213.30±523.71) and (267.12±12.06) pg/ml, respectively, P<0.05]. The levels of TNF-α, IP-10, RANTES and MIP-1α were (95.57±9.34), (410.48±40.68), (6 967.30±1.29) and (1 538.70±283.04) pg/ml, which were significantly lower than those of Mac group [(138.01±24.31, (1 298.60±310.50), (14 631.00±4.21) and (6 633.20±1.47) pg/ml, respectively, P<0.05]. The levels of IL-6 and IL-8 in GC-MSCs [(11 185.02±2.82) and (12 718.03±370.17) pg/ml, respectively] were both strikingly higher than those of MSCs from adjacent non-cancerous gastric cancer tissues [(270.71±59.38) and (106.04±32.84) pg/ml, repectively, P<0.05]. The ratios of CD86(+) cells in Mac+ IL-6-blocked-GC-MSC-CM and Mac+ IL-8-blocked-GC-MSC-CM groups (28.80% and 31.40%, respectively) were both higher than that of Mac+ GC-MSC-CM group (24.70%). Compared to Mac+ GC-MSC-CM group (13.70%), the ratios of CD204(+) cells in Mac+ IL-6-blocked-GC-MSC-CM and Mac+ IL-8-blocked-GC-MSC-CM groups (9.90% and 8.70%, separately) were reduced. The expression levels of p-JAK2 and p-STAT3, which are proteins of macrophage M2 polarization-related signaling pathway, in Mac+ GC-MSC-CM group (0.86±0.01 and 1.08±0.01, respectively) were significantly higher than those of Mac group (0.50±0.01 and 0.82±0.01, respectively, P<0.05). The expression levels of p-JAK2 in Mac+ IL-6-blocked-GC-MSC-CM group (0.47±0.02) were significantly lower those that of Mac+ GC-MSC-CM group (0.86±0.01, P<0.05). The expression levels of p-JAK2 and p-STAT3 in Mac+ IL-8-blocked-GC-MSC-CM group (0.50±0.01 and 0.85±0.01, respectively) were both significantly lower than those of Mac+ GC-MSC-CM group (0.86±0.01 and 1.08±0.01, P<0.05). The expression levels of p-JAK2 and p-STAT3 in Mac+ IL-6/IL-8-blocked-GC-MSC-CM group (0.37±0.01 and 0.65±0.01, respectively) were both significantly lower than those of Mac+ GC-MSC-CM group (0.86±0.01 and 1.08±0.01, P<0.05). Conclusion: GC-MSCs promote the activation of JAK2/STAT3 signaling pathway in macrophages via high secretions of IL-6 and IL-8, which subsequently induce the macrophage polarization into a pro-tumor M2 subtype within gastric cancer microenvironment.

Elastic criterion for shear-banding instability in amorphous solids.

In amorphous solids, plastic flow is prone to localization into shear bands via an avalanche of shear-transformation (ST) rearrangements of constituent atoms or particles. However, such banding instability still remains a lack of direct experimental evidence. Using a real 3D colloidal glass under shear as proof of principle, we study STs' avalanches into shear banding that is controlled by strain rates. We demonstrate that, accompanying the emergent shear banding, the elastic response fields of the system, typical of a quadrupole for shear and a centrosymmetry for dilatation, lose the Eshelby-type spatial symmetry; instead, a strong correlation appears preferentially along the banding direction. By quantifying the fields' spatial decay, we identify an elastic criterion for the shear-banding instability, that is, the strongly correlated length of dilatation is smaller than the full length of shear correlation. Specifically, ST-induced free volume has to be confined within the elastic shear domain of ST so that those STs can self-organize to trigger shear banding. This physical picture is directly visualized by tracing the real-space evolution of local dilatation and ST particles. The present work unites the two classical mechanisms: free volume and STs, for the fundamental understanding of shear banding in amorphous solids.

[Preparation of purified proteins from fresh Pheretima and their inhibitory effect against pulmonary fibrosis in mice].

OBJECTIVE: To develop a convenient method for rapid purification of fresh Pheretima proteins and assess the inhibitory effect of these proteins against pulmonary fibrosis. METHODS: The crude extract of fresh Pheretima was obtained by freeze-drying method and then purified by size exclusion chromatography. The composition of the purified proteins was analyzed by mass spectrometry. MRC-5 cells were treated with 5 ng/mL TGF-ß1 alone (model group) or in combination with SB431542 (2 µmol/L) or the purified proteins (13.125 µg/mL), and the cytotoxicity of purified proteins and their inhibitory effects on cell proliferation were detected with CCK8 assay. Flow cytometry was used to detect the changes in cell apoptosis, and the cellular expressions of α-SMA, Vimentin, E-cadherin, collagen I, Smad2/3 and P-Smad2/3 were detected using RT-PCR and Western blotting. In the animal experiment, adult male C57BL/6 mice were subjected to intratracheal instillation of bleomycin followed by treatment with the purified proteins (5 mg/mL) for 21 days, after which HE and Masson staining was used to observe the pathological changes in the lung tissue of the mice. RESULTS: We successfully obtained purified proteins from fresh Pheretima protein by size exclusion chromatography. Treatment with the purified proteins significantly inhibited TGF-ß1-induced proliferation of MRC-5 cells (P < 0.01), reduced the cellular expressions of α-SMA, Vimentin and collagen I (P < 0.001 or P < 0.01), increased the expression of E-cadherin (P < 0.01), and inhibited the expressions of Smad2/3 and P-Smad2/3 (P < 0.001 or P < 0.01). In male C57BL/6 mice models of bleomycin-induced pulmonary fibrosis, treatment with the purified proteins obviously reduced the number of inflammatory cells and fibrotic area in the lungs. CONCLUSION: The purified proteins from fresh Pheretima obtained by size exclusion chromatography can inhibit pulmonary fibrosis in mice by regulating the TGF-ß/ Smad pathway.

Genome-wide single nucleotide polymorphism array and whole-genome sequencing reveal the inbreeding progression of Banna minipig inbred line.

Inbred pigs are promising animal models for biomedical research and xenotransplantation. Established in 1980, the Banna minipig inbred (BMI) line originated from a sow and its own male offspring. It was selected from a small backcountry minority Lahu village, where records show that no other pig breed has ever been introduced. During the inbreeding process, we perfomed extreme inbreeding over 23 consecutive generations using full-sibling or parent-offspring mating. In order to investigate the inbreeding effects in BMI pigs across generations over the past 40 years, in this study we conducted a genome-wide SNP genotyping of the last 10 generations, representing generations 14-23. In total, we genotyped 57,746 SNPs, corresponding to an average decrease in heterozygosity rate of 0.0078 per generation. Furthermore, we were only able to identify 18,216 polymorphic loci with a MAF larger than 0.05, which is substantially lower than the values in previous reports on other pig breeds. In addition, we sequenced the genome of the first pig in the twenty-third generation (inbreeding coefficient 99.28%) to an average coverage of 12.4× to evaluate at the genome level the impact of advanced inbreeding. ROH analysis indicates that BMI pigs have longer ROHs than Wuzhishan and Duroc pigs. Those long ROH regions in BMI pigs are enriched for distinct functions compared with the highly polymorphic regions. Our study reveals a genome-wide allele diversity loss during the progress of inbreeding in BMI pigs and characterizes ROH and polymorphic regions as a result of inbreeding. Overall, our results indicate the successful establishment of the BMI line, which paves the way for further in-depth studies.

[Effect of histone deacetylase 2 and 4 activity on connective tissue disease associated pulmonary fibrosis in mice].

Objective: To investigate the effect of histone deacetylase (HDAC) activity on connective tissue diseases (CTD) associated pulmonary fibrosis (PF) in mice. Methods: A single tracheal administration of bleomycin induced PF in C57BL/6J male mice was performed to establish a PF model. The experimental mice were divided into three groups: bleomycin group (group B, n = 16) which was given bleomycin A2 physiological saline solution 2.5 µl/g body weight, saline group (Group C, n = 16) which was given physiological saline solution 2.5 µl/g body weight and no operation group (group N, n = 16). At 7, 14 and 21 days after administration, the animals were randomly killed and their specimens were collected. The activity of HDAC2 and HDAC4 was detected by colorimetry. Hematoxylin-eosin staining was used to evaluate pulmonary alveolitis and Masson staining for pulmonary fibrosis. The variance, correlation and binary variable correlation were analyzed. Results: The HDAC2 activity in lung tissue of mice in the bleomycin group was significantly higher than that in the no operation group (2.00±0.40 vs 1.00±0.23, P<0.05) and the saline group (2.00±0.40 vs 1.48±0.33, P<0.05). The HDAC2 activity in the bleomycin group was significantly higher than that in the no operation group (2.40±0.28 vs 1.00±0.23, P<0.01, 2.23±0.41 vs 1.00±0.23, P<0.01) and the saline group (2.40±0.28 vs 1.39±0.23, P<0.05, 2.23±0.41 vs 1.35±0.42, P<0.05). The change trend of HDAC2 activity between the bleomycin group and the saline group was different. There was no significant difference in HDAC4 activity in lung tissue of mice between the bleomycin group, the no operation group and the saline group. 14 days after tracheal administration, HDAC4 activity in the bleomycin group and the saline group were significantly higher than that in the no operation group (1.18±0.36 vs 1.00±0.12, P<0.01, 1.09±0.33 vs 1.00±0.12, P<0.01). HDAC2 activity in lung tissue of mice was positively correlated with pathological scores of alveolitis (r=0.428, P<0.01) and pulmonary fibrosis (r=0.508, P<0.01). HDAC4 activity in lung tissue of mice was positively correlated with the pathological scores of alveolitis (r=0.355, P<0.05) and pulmonary fibrosis (r=0.457, P<0.01). Binary linear regression analysis showed that HDAC2 activity had a stronger effect on the process of PF lesions than HDAC4 activity in lung tissue of mice. Conclusions: When pulmonary fibrosis occurred in mice, the activities of HDAC2 and 4 in pulmonary fibrosis were significantly increased. The activity of HDAC2 increased rapidly and lastingly, and the activity of HDAC4 fluctuated significantly and increased briefly. Changes in HDAC2 activity have stronger effects on alveolitis and fibrosis than HDAC4.

Chrysin induces osteogenic differentiation of human dental pulp stem cells.

OBJECTIVES: As an ideal cell source for tissue engineering and bone defect repair, dental pulp stem cells (DPSCs) have good osteogenic differentiation potential. Chrysin, a flavonoid extracted from oroxylum seeds, has been proven to promote bone formation of bone marrow stem cells. However, the effect of chrysin on osteogenic differentiation of DPSCs remains unclear. This study aimed to investigate the role of Chrysin in promoting osteogenic differentiation of DPSCs and in DPSC-based bone formation. MATERIAL AND METHODS: We investigated the effects of chrysin on DPSCs from patients by CCK-8 assay, Alizarin Red S staining, qPCR and Western blotting. The effects of chrysin on DPSC-based bone formation in a heterotopic osteogenesis model in nude mice and a rat calvarial defect model were also performed. Finally, we investigated the mechanism of chrysin-treated DPSCs by proteomics. RESULTS: Chrysin upregulated the expression of osteogenic proteins and induced osteogenic differentiation of DPSCs. Moreover, chrysin induced abundant ß-TCP-induced formation of mineralized bone tissue and promoted DPSC-based bone formation in a heterotopic osteogenesis model in nude mice and a rat calvarial defect model. Proteomics showed that upregulation of the Smad3 was closely related to osteogenic differentiation. Inhibiting of Smad3 activation by a Smad3 inhibitor could reverse the chrysin-mediated increases in the expression levels of osteogenic genes and osteogenic induction of DPSCs. CONCLUSIONS: Our study implies the intriguing potential of chrysin-treated DPSCs in bone regeneration and bone defect repair.

[The method of blood pressure evaluation among children and adolescents aged 7 to 17 years old in China].

The national health industry standard (WS/T 610-2018), 'the reference of screening for elevated blood pressure among children and adolescents aged 7-to 18-years-old', plays a significant role in the standardization of the blood pressure evaluation, the early detection of high blood pressure, and the early intervention of hypertension and other chronic non-communicable diseases among Chinese children and adolescents. This standard gives screening thresholds for blood pressure assessment of children and adolescents in different genders, ages, and heights. Given the complexity of applying this standard, it is error-prone and less efficient to evaluate blood pressure one by one or program this procedure. Therefore, this study provides a SPSS package based on the standard for researchers to download and use, combined with specific cases to guide the use of this package to evaluate the blood pressure of children and adolescents step by step, which could empower researchers to accurately and efficiently conduct blood pressure screening for children and adolescents in China.

MicroRNA-22 targets FMNL2 to inhibit melanoma progression via the regulation of the Wnt/ß-catenin signaling pathway and epithelial-mesenchymal transition.

OBJECTIVE: Melanoma is regarded as one common malignancy in skin cancers, and there is growing evidence that microRNAs (miRNAs) play a vital role in the oncogenesis of tumors. This study aimed to investigate the roles and mechanism of miR-22 in melanoma. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was utilized to detect the expressions of miR-22 and mRNA. The functions of miR-22 in melanoma cell proliferation, migration and invasion were investigated with functional assays, including MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) and transwell assay. Western blots were utilized to examine the protein expressions. Luciferase reporter analysis was conducted to confirm the interactions between formin-like 2 (FMNL2) and miR-22 in melanoma cells. FMNL2 expression levels in melanoma tissues were investigated by immunohistochemistry (IHC) assays. RESULTS: The qRT-PCR analysis demonstrated significant decreased miR-22 expressions in melanoma tissues. Decreased miR-22 in melanoma tissues were correlated with adverse clinicopathologic features and poor prognosis. Functional assays indicated that upregulation inhibited melanoma cell proliferation, invasion and migration capacities. Luciferase reporter assays showed that FMNL2 was targeted by miR-22 in melanoma cells. Western blots indicated that miR-22 exerted anti-tumor functions by regulating the Wnt/ß-catenin and epithelial-mesenchymal transition (EMT). CONCLUSIONS: Our findings showed that miR-22 served as a tumor suppressor in melanoma progression, implying that miR-22 may function as a novel therapeutic target and prognostic biomarker for melanoma treatments.

Resveratrol Promotes in vitro Differentiation of Osteoblastic MC3T3-E1 Cells via Potentiation of the Calcineurin/NFATc1 Signaling Pathway.

Resveratrol has been shown to stimulate differentiation of osteoblastic MC3T3-E1 cells in vitro; however, the mechanisms underlying the anabolic effect of resveratrol on osteoblasts remain largely unknown. Our study was aimed to investigate the molecular mechanism of resveratrol-induced differentiation of MC3T3-E1 cells. MC3T3-E1 cells were treated for 8 days with different concentrations of resveratrol (10-8-10-6 M) and 10-6 M cyclosporine A (CsA), a specific inhibitor of the calcineurin/NFAT pathway. According to the results of pilot studies of cell proliferation and alkaline phosphatase activity, 10-7 M concentration of resveratrol was used in subsequent experiments. The levels of mRNA expression of the osteosis-related genes CaN, NFATc1, and Runx2 were analyzed by real-time RT-PCR; the levels of the corresponding proteins were estimated by Western blot analysis. Resveratrol upregulated expression of the CaN, NFATc1, and Runx2 genes at both mRNA and protein levels compared to the control group (p < 0.05), while CsA reduced the effects of resveratrol (p < 0.05). Using immunohistochemical staining, we showed that resveratrol induced NFATc1 accumulation in the cell nuclei, and treatment with CsA inhibited resveratrol-mediated induction of NFATc1, suggesting that the calcineurin/NFATc1 signaling pathway plays an important role in the regulatory effect of resveratrol on osteoblasts.

Patient-centered care factors and access to care: a path analysis using the Andersen behavior model.

OBJECTIVES: Using the Andersen behavioral model, we examined the complex relationships among geographic access to care, financial disadvantage, patient-centered care factors, and access to care outcomes. STUDY DESIGN: This was a retrospective, cross-sectional study of the US civilian non-institutionalized population. METHODS: Our analytic sample included 15,787 US adults aged 18 years or older who had health insurance coverage for a full year in Medical Expenditure Panel Survey 2014-2015. Structural equation modeling was used to determine the associations among usual source of care, travel time to provider, financial disadvantage, patient-centered care factors (perceived interaction with health provider, shared decision-making, and value of health care), and access to care (perceived access to care and unmet need of health services). RESULTS: Our analysis showed that patient-centered care factors were associated with improved perceived access to care (ß = 0.03 to 0.56, P = .002) and reduced unmet needs of health care (ß = -0.03 to -0.17, P = .03 to < .001). Although longer travel time to provider and having financial disadvantage of paying medical bills had negative effects on access to care outcomes, these associations were mediated by patient-centered care quality factors. CONCLUSIONS: Our findings suggest that better patient-centered care factors are associated with enhanced patient access to care. Efforts that focus on improving patient experience could be an effective approach along with coverage expansion to enhance access to quality care.

[Endoscopic selective lateral neck dissection via a chest-breast approach for papillary thyroid carcinoma: preliminary experience in 20 cases].

Objective:To explore the feasibility of endoscopic selective lateral neck dissection(SLND) via a chest-breast approach.Method:We retrospectively reviewed 20 patients who underwent endoscopic total thyroidectomy along with SLND, between January 2017 and May 2018. Result: All the 20 patients underwent total thyroidectomy, central lymph nodes dissection and selective lateral lymph nodes dissection with endoscopic surgery via chest-breast approach. In this study, lymphatic leakage, transient voice hoarseness, internal jugular vein injury and external jugular vein injury were repectively found in one patient, and 4 patients suffered from transient parathyroid hypofunction, without other serious complications.Conclusion: Endoscopic lymph node dissection including levels Ⅱ,Ⅲ and Ⅳ is feasible. It has good cosmetic effect, and haven't serious adverse events.

[Seasonal distribution of patient hospitalization due to asthma exacerbation in 7 geographic areas in China].

Objective: To understand the seasonal distribution of patient hospitalization due to asthma exacerbation in 7 geographic areas in China. Methods: This was a retrospective study which involved patients hospitalized for asthma exacerbation in 29 hospitals throughout 7 geographic areas in the mainland of China (northeast, north, central, east, south, northwest and southwest). The numbers of asthmatic patients and total inpatients of the respiratory department of each hospital were recorded. The monthly ratio of asthmatic patients to the total inpatients in every area was calculated and compared. Results: During the study period, 6 480 patients were admitted for asthma exacerbation, accounting for 3.14% of all the 206 135 patients admitted to the respiratory departments in the 29 hospitals. The ratio of asthmatic patients to total inpatients in the northeast area (5.61%) was highest, and the ratio in east area was lowest (1.97%). Statistical analysis showed that the difference among different areas was significant (P<0.000 1). In most areas, both the number and proportion of hospitalized asthmatic patients peaked in spring (February-April) and autumn (September-October). In the northeast area, east area and south area, the peaks in spring were more obvious, while in the north area and southwest area, the peaks in autumn were more obvious. In the northwest area the peaks occurred in winter (December-January) and summer (June-August), respectively. The differences in hospitalization due to asthma among different months were significant in the northeast, north, and southwest areas (P<0.005). Conclusion: The number of patients hospitalized for asthma exacerbation fluctuated with season in different areas in China. In most areas, more asthmatic patients were admitted to hospitals in spring and autumn.

[A retrospective study of the mortality and death-related risk factors of patients hospitalized for asthma exacerbation in Chinese urban areas].

Objective: To study the mortality and death-related risk factors of patients hospitalized for asthma exacerbation in Chinese urban areas. Methods: A retrospective study was carried out in 29 hospitals of 29 provinces throughout mainland China. Patients hospitalized for asthma exacerbation during 2013-2014 in each hospital were included. For each patient, information about demography, admission time, comorbidities, severity of diseases, intense care unit (ICU) admission, use of mechanical ventilation and the outcome was obtained. The mortality of patients hospitalized for asthma exacerbation was calculated, and the basic information and causes of death of the patients who died were summarized. The death-related risk factors and numbers of comorbidities were compared between the patients who survived and those who died during hospitalization. Results: A total of 3 240 patients (median age 57.0) were included and among them 8 patients (median age 68.5) died. The mortality of patients hospitalized for asthma exacerbation was 0.25%. All the patients who died were admitted during the winter and spring. One patient died of acute myocardial infarction, one of cardiac shock, one of tension pneumothorax, one of sudden death, one of respiratory failure and three of unknown causes. The average number of comorbidities of patients who died was 1.10, larger than that of patients who survived (0.83) (P>0.05). More patients had diabetes, coronary artery diseases and hypertension as comorbidities in the patients who died (2/8) than those who survived[7.6% (246/3 232), 7.6% (246/3 232), 22.6% (731/3 232), respectively](all P>0.05). Conclusions: The in-hospital mortality of patients hospitalized for asthma exacerbation of China in this study is low. The patients who died are much older, and with more comorbidities, and a higher percentage of comorbidities such as diabetes, coronary artery diseases, and hypertension.