Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with unclear etiology and limited treatment options. The median survival time for IPF patients is approximately 2-3 years and there is no effective intervention to treat IPF other than lung transplantation. As important components of lung tissue, endothelial cells (ECs) are associated with pulmonary diseases. However, the role of endothelial dysfunction in pulmonary fibrosis (PF) is incompletely understood. Sphingosine-1-phosphate receptor 1 (S1PR1) is a G protein-coupled receptor highly expressed in lung ECs. Its expression is markedly reduced in patients with IPF. Herein, we generated an endothelial-conditional S1pr1 knockout mouse model which exhibited inflammation and fibrosis with or without bleomycin (BLM) challenge. Selective activation of S1PR1 with an S1PR1 agonist, IMMH002, exerted a potent therapeutic effect in mice with bleomycin-induced fibrosis by protecting the integrity of the endothelial barrier. These results suggest that S1PR1 might be a promising drug target for IPF therapy.

Platelets are reprogrammed by cancer via a process called education, which favors cancer development. The transcriptional profile of tumor-educated platelets (TEPs) is skewed and therefore practicable for cancer detection. This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n = 3; Netherlands, n = 5; Poland, n = 1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, and early-stage ovarian cancer. However, these observations warrant prospective validations in a larger population before clinical utilities.
Humans ; Female ; Blood Platelets/pathology* ; Biomarkers, Tumor/genetics* ; Ovarian Neoplasms/pathology* ; China

Variations in the dynein axonemal heavy chain gene, dynein axonemal heavy chain 6 (DNAH6), lead to multiple morphological abnormalities of the flagella. Recent studies have reported that these deficiencies may result in sperm head deformation. However, whether DNAH6 is also involved in human acrosome biogenesis remains unknown. The purpose of this study was to investigate DNAH6 gene variants and their potential functions in the formation of defective sperm heads and flagella. Whole-exome sequencing was performed on a cohort of 375 patients with asthenoteratozoospermia from the First Affiliated Hospital of Anhui Medical University (Hefei, China). Hematoxylin and eosin staining, scanning electron microscopy, and transmission electron microscopy were performed to analyze the sperm morphology and ultrastructure. Immunofluorescence staining and Western blot analysis were conducted to examine the effects of genetic variants. We identified three novel deleterious variants in DNAH6 among three unrelated families. The absence of inner dynein arms and radial spokes was observed in the sperm of patients with DNAH6 variants. Additionally, deficiencies in the acrosome, abnormal chromatin compaction, and vacuole-containing sperm heads were observed in these patients with DNAH6 variants. The decreased levels of the component proteins in these defective structures were further confirmed in sperm from patients with DNAH6 variants using Western blot. After intracytoplasmic sperm injection (ICSI) treatment, the partner of one patient with a DNAH6 variant achieved successful pregnancy. Overall, novel variants in DNAH6 genes that contribute to defects in the sperm head and flagella were identified, and the findings indicated ICSI as an effective clinical treatment for such patients.

Objective To explore the relationship between self-reported chronic disease and smoking behavior among adult males in Jiangsu Province. Methods In 2007, 2010, and 2013 respectively, a multistage stratified cluster sampling method was used to select residents from 14 adult chronic diseases and their risk factor surveillance sites in Jiangsu Province to investigate the relationship between the prevalence of chronic diseases, smoking and smoking cessation behaviors among men aged 18 to 69 years. Results A total of 8 313 men aged 18 to 69 years had a self-reported prevalence of 1.5%, 1.1%, 1.5%, and 2.8% for cardiovascular and cerebrovascular diseases, malignancies, asthma, and chronic obstructive pulmonary disease (COPD), respectively.The self-reported prevalence of all four chronic diseases was higher in ex-smokers than in current smokers and non-smokers (all P<0.05).Multivariate analysis showed that the quit rate was of those suffering from cardiovascular and cerebrovascular diseases, malignancies, asthma, and COPD, respectively 3.356 times (95% CI: 1.966-5.728), 3.864 times (95% CI: 2.277-6.555), 2.103 times (95% CI: 1.321-3.345), and 2.586 times (95% CI: 1.872-3.573) higher, than those without. Conclusion Smoking cessation rates were significantly higher of those with chronic disease than those without, suggesting that illness would promote smoking cessation behaviors among smokers.

Two new polyketides, chinoketides A and B (1 – 2) with a known compound xylarphthalide A (3), were isolated from the solid medium of the endophytes from the leaves of the relic plant Distylium chinense with the “black-box” co-culture method, and the structures of two new compounds were elucidated by NMR, MS and CD spectra. And the absolute configurations of chinoketides A (1) and B (2) were determined as 2R,3R,8S and 5R,6S by calculating their ECD spectra to compare with the experimental CD spectra. Finally, the antimicrobial activities were evaluated to Erwinia carotovora sub sp. Carotovora (Jones) Bersey et al, and the results showed that compounds 1 – 3 displayed the antimicrobial activities with MIC value at 20.5, 30.4 and 10.2 µg/mL.
Coculture Techniques ; Endophytes ; Methods ; Pectobacterium carotovorum ; Plants ; Polyketides

BACKGROUND: It is of vital importance to fabricate an interface on the titanium implant surface which can promote early cell adhesion, proliferation, and differentiation, and exert better antibacterial effects with no cytotoxicity. OBJECTIVE: To prepare a TiN/Ag composite coating on the surface of pure titanium implant, and to explore its antibacterial properties and effects on MC3T3-E1 biobehaviors. METHODS: Acid etching blasting and multi-arc ion plating were adopted to prepare TiN/Ag composite coating on the smooth surface of pure titanium. Then, MC3T3-E1 cells that grew well were inoculated onto pure titanium plate, sandblasted and acid-etched titanium plate, and TiN/Ag-coated titanium plate. Twenty-four hours later, cell adhesion and viability were observed under confocal laser scanning microscope, and cell morphology was observed under scanning electron microscope. Cell counting kit-8 was used to detect cell proliferation and cytotoxicity at 24,48,72 hours after inoculation.In addition,Staphylococus aureus solution was dropped onto the smooth titanium plated, acid-etched and sandblasted titanium and TiN/Ag-coated titanium plate, and the growth of bacteria was observed by the laser confocal scanning microscope at 16 hours. RESULTS AND CONCLUSION: Under the confocal laser scanning microscope, spindle cells with bipolar or three poles were observed on the smooth titanium surface, and there was less F-actin and filopodia expression; cells on the TiN/Ag-coated titanium surface and sandblasted and acid-etched titanium surface were scattered with a large amount of interconnected filopodia that were fully stretched and adhered to the titanium surface, highly expressed F-actin was detected, and actin fibers were thickened. Under the scanning electron microscope, the cells on the smooth titanium surface were not fully adhered and stretched, and those on the TiN/Ag-coated titanium surface or the sandblasted and acid-etched titanium surface exhibited better adhesion and extension. Findings from the cell counting kit-8 showed that after 72 hours of inoculation,the cells on the smooth titanium surface grew well,with cytotoxicity level 1.In addition,Staphylococus aureus grew well on the smooth titanium surface under the confocal laser scanning microscope,while a large amount of Staphylococus aureus died on the TiN/Ag-coated titanium surface or on the sandblasted and acid-etched titanium surface. These findings indicated that TiN/Ag coating has good biocompatibility and antibacterial properties.

To study the triterpenoids from the roots of Rosa laevigata. The silica gel column chromatography was used to separate the chemical constituents from the roots of Rosa laevigata Michx. HPLC was used to analyze its purity, chemical and spectroscopy methods were used to determine their structures. 12 constituents were isolated and identified as(2R, 19R)methyl 2-acetyloxy-19- hydroxyl-3-oxo-urs-12-en-28-carboxylate(1), pomonic acid (2), 18, 19-seco, 2α, 3α-dihydroxy-19-oxo-urs-11, 13(18)-dien-28-oic acid(3), swinhoeic acid (4), myrianthic acid(5), 2α, 3β, 19α-trihydroxy-24-oxo-urs-12-en-oic acid (6), tormentic acid(7), arjunic acid (8), 1β-hydroxyeuscaphic acid(9), quadranoside Ⅷ (10), alpinoside(11), rubuside B (12). Compounds 1-4, 6, 9, 11-12 were obtained from this plant for the first time. Compounds 2-4, 6, 11-12 were obtained from the genus Rosa for the first time.

This study aimed to examine the optimal conditions of laser-induced interstitial thermotherapy (LITT) via a single-needle delivery system, and the ablation-related pathological and ultrasonic changes. Ultrasound (US)-guided LITT (EchoLaser system) was performed at the output power of 2-4 Wattage (W) for 1-10 min in ex vivo bovine liver. Based on the results of the ex vivo study, the output power of 3 and 4 W with different durations was applied to in vivo rabbit livers (n=24), and VX2 tumors implanted in the hind limbs of rabbits (n=24). The ablation area was histologically determined by hematoxylin-eosin (HE) staining. Traditional US and contrast enhanced ultrasound (CEUS) were used to evaluate the treatment outcomes. The results showed: (1) In the bovine liver, ablation disruption was grossly seen, including a strip-like ablation crater, a carbonization zone anteriorly along the fiber tip, and a surrounding gray-white coagulation zone. The coagulation area, 1.2 cm in length and 1.0 cm in width, was formed in the bovine liver subjected to the ablation at 3 W for 5 min and 4 W for 4 min, and it extended slightly with the ablation time. (2) In the rabbit liver, after LITT at 3 W for 3 min and more, the coagulation area with length greater than or equal to 1.2 cm, and width greater than or equal to 1.0 cm, was found. Similar coagulation area was seen in the implanted VX2 carcinoma at 3 W for 5 min. (3) Gross examination of the liver and carcinoma showed three distinct regions: ablation crater/carbonization, coagulation and congestion distributed from the center outwards. (4) Microscopy revealed four zones after LITT, including ablation crater/carbonization, coagulation, edema and congestion from the center outwards. A large area with coagulative necrosis was observed around a vessel in the peripheral area with edema and hyperemia. (5) The size of coagulation was consistent well to the CEUS findings. It was concluded that EchoLaser system at low power can produce a coagulation area larger than 1.0 cm×1.0 cm during a short time period. The real-time US imaging can be used to effectively guide and assess the treatment.
Animals ; Bone Neoplasms ; diagnostic imaging ; pathology ; therapy ; Cattle ; Hindlimb ; pathology ; Laser Therapy ; instrumentation ; methods ; Liver Diseases ; diagnostic imaging ; therapy ; Rabbits ; Treatment Outcome ; Ultrasonic Therapy ; instrumentation ; methods ; Ultrasonography

Objective To investigate the resistant mechanism of quinolones on multi-drug resistant Klebsiella caused pneumonia(MDR-KPN).Methods From August 2008 to May 2010,47 strains of MDR-KPN were collected from 6 hospitals in Hangzhou and Huzhou in Zhejiang province in China.Drug target genes to quinolones (gyrA,parC) and quinolone-resistance genes mediated by mobile genetic elements [qnrA,qnrB,qnrS,aac (6')-Ⅰ b-cr,qepA] were analyzed by PCR and verified by DNA sequencing.Results Positive results were found in 47 strains of MDR-KPN,43 strains (91.5％) of gyrA mutation,40 strains(85.1％) ofparC mutation,3 strains (6.4％) of qnrB2,1 strain (2.1％) ofqnrB 4,8 strains (17.0％) ofqnrS 1,5 strains (10.6％) of qnrS 4,2 strains (4.3％)of aac (6')-Ⅰ b-cr respectively.Moreover,5 novel variants of gyrA (GenBank accession number:JN811952,JN811953,JN811954,JN811955,JN811956),5 novel variants of parC (GenBank accession number:JN817432,JN817433,JN817434,JN817435,JN817436)were also identified.In addition,qnrS4 (GenBank accession number:JN836269) appeared to be the novel variants of qnrS.Conclusion Quinolone-resistance-determining region played a key role on the resistance to quinolones in this group of MDR-KPN,and quinolone-resistance genes mediated by mobile genetic elements [qnrB2,qnrB4,qnrS1,qnrS4,aac (6')-Ⅰ b-cr] showed positive in some parts of the strains.This was the first report on emergence of qnrS4 in the world.

Objective To explore the fluid control in patients with congestive heart failure,and discuss its effect on patients' thirsty,quality of life and prognosis.Methods Self-designed thirsty scale,Minnesota quality of life survey and telephone visit were used to collect 273 heart failure patients' data regarding fluid control,thirsty and quality of life before admission,during hospitalization and 3 months after discharge,and analyze the effect of fluid control on patients' quality of life and prognosis.Results Patients' rate of fluid control was 28.6％,97.4％ and 82.8％ before admission,during hospitalization and 3 months after discharge,and the difference was statistically significant (x2 =350.581,P ＜ 0.01).The thirsty score before admission,during hospitalization and 3 months after discharge was (2.45 ± 1.53),(3.30 ± 1.59),(1.98 ± 1.32) in patients with fluid control and (1.39 ± 0.88),(1.43 ± 1.13),(1.33 ± 0.83) in patients without fluid control,and the differences were statistically significant (t =5.734,4.268,3.762,respectively; P ＜ 0.05).Quality of life before hospitalization was (65.61 ± 19.40) in patients with fluid control,higher than that in patients without fluid control,and the difference was statistically significant (t =3.307,P ＜0.01).Quality of life after hospitalization was (30.55 ± 29.40) in patients with fluid control,and had no statistically significant difference from that in patients without fluid control (t =0.259,P ＞ 0.05).There was no statistically significant difference in cases of re -hospitalization and death due to heart failure between two groups (P ＞ 0.05).Conclusions Patients with heart failure have higher rate of fluid control during hospitalization and 3 months after discharge.Adherence to fluid control can increase patients' thirsty,but has no significant influence on their quality of life and prognosis.