Search

Li-Zhi Chen,1,2,&ast; Han-Shu Li,1,2,&ast; Gao-Wei Han,1,2,&ast; Yong Su,1,3 Tian-Zhu Lu,1– 3 Hong-Hui Xie,1,3 Xiao-Chang Gong,1,3 Jin-Gao Li,1,3 Yun Xiao1,3 1NHC Key Laboratory of Personalized Diagnosis and Treatment of Nasopharyngeal Carcinoma, Jiangxi Clinical Research Center for Cancer, Jiangxi Cancer Hospital, The Second Affiliated Hospital of Nanchang Medical College, Nanchang, Jiangxi, 330029, People’s Republic of China, Nanchang, Jiangxi, 330029, People’s Republic of China; 2Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330029, People’s Republic of China; 3Department of Radiation Oncology, Jiangxi Clinical Research Center for Cancer, Jiangxi Cancer Hospital, The Second Affiliated Hospital of Nanchang Medical College, Nanchang, Jiangxi, 330029, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jin-Gao Li; Yun Xiao, Department of Radiation Oncology, Jiangxi Clinical Research Center for Cancer, Jiangxi Cancer Hospital, The Second Affiliated Hospital of Nanchang Medical College, 519 East Beijing Road, Nanchang, Jiangxi, 330029, People’s Republic of China, Tel +86-791-88313632, Fax +86-791-8321742, Email lijingao@hotmail.com; 813898920@qq.comPurpose: This study aimed to assess the prognostic and predictive value of a circulating hematological signature (CHS) and to develop a CHS-based nomogram for predicting prognosis and guiding individualized chemotherapy in non-metastatic nasopharyngeal carcinoma (NPC) patients.Patients and Methods: NPC patients were recruited between January 2014 and December 2017 at the Jiangxi Cancer Hospital. The CHS was constructed based on a series of hematological indicators. The nomogram was developed by CHS and clinical factors.Results: A total of 779 patients were included. Three biomarkers were selected by least absolute shrinkage and selection operator regression, including prognostic nutritional index, albumin-to-fibrinogen ratio, and prealbumin-to-fibrinogen ratio, were used to construct the CHS. The patients in the low-CHS group had better 5-year DMFS and OS than those in the high-CHS group in the training (DMFS: 85.0% vs 56.6%, p< 0.001; OS: 90.3% vs 65.4%, p< 0.001) and validation cohorts (DMFS: 92.3% vs 43.6%, p< 0.001; OS: 92.1% vs 65.5%, p< 0.001). The nomogram_CHS showed better performance than clinical stage in predicting distant metastasis (concordance index: 0.728 vs 0.646). In the low-TRS (total risk scores) group, the patients received RT alone, CCRT and IC plus CCRT had similar 5-year DMFS and OS (p> 0.05). In the middle-TRS group, the patients received RT alone had worse 5-year DMFS (58.7% vs 80.8% vs 90.8%, p=0.002) and OS (75.0% vs 94.1% vs 95.0%, p=0.001) than those received CCRT or IC plus CCRT. In the high-TRS group, the patients received RT alone and CCRT had worse 5-year DMFS (18.6% vs 31.3% vs 81.5%, p< 0.001) and OS (26.9% vs 53.2% vs 88.8%, p< 0.001) than those received IC plus CCRT.Conclusion: The developed nomogram_CHS had satisfactory prognostic accuracy in NPC patients and may individualize risk estimation to facilitate the identification of suitable IC candidates.Keywords: nasopharyngeal carcinoma, circulating hematological signature, induction chemotherapy, distant metastasis-free survival, overall survival

Enzyme immobilization is an effective strategy for achieving efficient and sustainable enzyme catalysis. As a kind of promising enzyme-loading materials, the systematic research on zirconium based metal organic frameworks (Zr-MOFs) about immobilization performance at molecular level is still in its initial stage. In this work, UiO-66 was functionalized with various groups (-H, -NH 2 , -COOH, -OH, -2OH) for the immobilization of cytochrome c (Cyt c) and antioxidant enzyme catalase (CAT). Then the effects of surface-functionalized UiO-66 derivatives on the loading efficiency, enzyme stability and catalysis kinetics were systematically investigated. In addition, the affinity constants of Cyt c and CAT towards UiO-66-series MOFs carriers were also compared. The results have shown that hydroxyl group functionalized UiO-66 represents the highest enzyme loading capacity, enhanced activity and improved stability for Cyt c and CAT possibly due to high surface area and suitable microenvironments as well as enhanced affinity towards the enzymes provided by the introduction of a single hydroxyl group. Our research would foresee immense potential of MOFs in engineering biocatalysts., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Anthrax bacillus is a very dangerous zoonotic pathogen that seriously endangers public health. Rapid and accurate qualitative and quantitative detection of its biomarkers, 2,6-dipicolinic acid (DPA), is crucial for the prevention and treatment of this pathogenic bacterium. In this work, a novel Cd-based MOF (TTCA-Cd) has been synthesized from a polycarboxylate ligand, [1,1':2',1″-terphenyl]-4,4',4″,5'-tetracarboxylic acid (H 4 TTCA), and further doped with Tb(III), forming a dual-emission lanthanide-functionalized MOF hybrid (TTCA-Cd@Tb). TTCA-Cd@Tb can be developed as a high-performance ratiometric fluorescent sensor toward DPA with a very low detection limit of 7.14 nM and high selectivity in a wide detection range of 0-200 μM, demonstrating a big advancement and providing a new option for the detection of DPA.

Objective: Ciprofol (also known as cipepofol and HSK3486), is a compound similar to propofol in chemical structure and hypnotic effect. Herein we evaluated the efficacy and safety of ciprofol for sedation in outpatient gynecological procedures., Methods: This phase III multicenter randomized trial with a non-inferiority design was conducted in nine tertiary hospitals. We enrolled 135 women aged 18-65 years who were scheduled for ambulatory gynecological procedures. Patients were randomly assigned to receive either ciprofol (0.4 mg/kg for induction and 0.2 mg/kg for maintenance) or propofol (2.0 mg/kg for induction and 1.0 mg/kg for maintenance) sedation in a 2:1 ratio. Patients and investigators for data collection and outcome assessment were blinded to study group assignments. The primary outcome was the success rate of sedation, defined as completion of procedure without remedial anesthetics. The non-inferiority margin was set at -8%. Secondary outcomes included time to successful induction, time to full awake, time to meet discharge criteria, and satisfaction with sedation assessed by patients and doctors. We also monitored occurrence of adverse events and injection pain., Results: A total of 135 patients were enrolled; 134 patients (90 patients received ciprofol sedation and 44 patients propofol sedation) were included in final intention-to-treat analysis. The success rates were both 100% in the two groups (rate difference, 0.0%; 95% CI, -4.1 to 8.0%), i.e., ciprofol was non-inferior to propofol. When compared with propofol sedation, patients given ciprofol required more time to reach successful induction (median difference [MD], 2 s; 95% CI, 1 to 7; p < 0.001), and required more time to reach full awake (MD, 2.3 min; 95% CI, 1.4 to 3.1; p < 0.001) and discharge criteria (MD, 2.3 min; 95% CI, 1.5 to 3.2; p < 0.001). Fewer patients in the ciprofol group were dissatisfied with sedation (relative risk, 0.21; 95% CI, 0.06 to 0.77; p = 0.024). Patients given ciprofol sedation had lower incidences of treat-emergent adverse events (34.4% [31/90] vs. 79.5% [35/44]; p < 0.001) and injection pain (6.7% [6/90] vs. 61.4% [27/44]; p < 0.001)., Conclusion: Ciprofol for sedation in ambulatory gynecological procedures was non-inferior to propofol, with less adverse events and injection pain., Clinical Trial Registration: ClinicalTrials.gov, identifier NCT04958746., Competing Interests: The authors declare that this study received funding from Haisco Pharmaceutical Group Co., Ltd. The funder had the following involvement in the study: data collection, analysis and draft writing., (Copyright © 2024 Xu, Yang, Zeng, Zou, Ren, Xia, Xie, Yu, Xu, Chen and Wang.)

Food safety is a common concern among people, and the development of high-performance food freshness detection technology is crucial, but is still highly challenging. Fluorescent sensing based on metal organic frameworks is a promising technology to tackle this issue. In this work, three UiO-66 type Zirconium organic frameworks (ZrOFs) which are functionalized with varying numbers of hydroxyl groups to alter the energy levels, and partial replacement of Zirconium(IV) by Terbium(III) ions to introduce additional emitting centers, were explored as probes for the sensing of Histamine (His). With one hydroxyl group introduced, UiO-66-OH@Tb can be developed as ratiometric fluorescent probe with improved sensing performance, showing a wide detection range of 0 to 120 mg/L, and a low detection limit of 0.13 mg/L. UiO-66-OH@Tb can also be fabricated into composite film to function as visual sensing material of His. This work can provide instructions for the development of other fluorescent sensors., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objectives: Inadequate cytotrophoblast migration and invasion are speculated to result in preeclampsia, which is a pro-inflammatory condition. Sodium dichloroacetate (DCA) exerts anti-inflammatory actions. Thus,we sought to investigate the effect of DCA on the migration function of the lipopolysaccharide (LPS)-stimulated human-trophoblast-derived cell line (HTR-8/SVneo)., Materials and Methods: HTR-8/SVneo cells were treated with LPS to suppress cell migration. Cell migration was examined by both scratch wound healing assay and transwell migration assay. Western blotting was used to analyze the expression levels of toll-like receptor-4 (TLR4), nuclear factor-κB (NF-κB), TNF-α, IL-1β, and IL-6 in the cells., Results: DCA reversed LPS-induced inhibition of migration in HTR-8/SVneo cells. Furthermore, DCA significantly suppressed LPS-induced activation of TLR4, phosphorylation of NF-κB (p65), translocation of p65 into the nucleus, and the production of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6). Treatment with inhibitors of TLR4 signal transduction (CLI095 or MD2-TLR-4-IN-1) reduced LPS-induced overexpression of pro-inflammatory cytokines, and a synergistic effect was found between TLR4 inhibitors and DCA in HTR-8/SVneo cells., Conclusion: DCA improved trophoblast cell migration function by suppressing LPS-induced inflammation, at least in part, via the TLR4/NF-κB signaling pathway. This result indicates that DCA might be a potential therapeutic candidate for human pregnancy-related complications associated with trophoblast disorder., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest.

Energetic materials (EMs) have been widely employed in both military and civilian areas for nearly two centuries. The introduction of high-energy azide anions to assemble energetic metal-organic frameworks (EMOFs) is an efficient strategy to enhance energetic properties. However, azido-based EMOFs always suffer low stabilities to external mechanical stimulation. Herein, we employed an in situ hydrothermal reaction as a technique to refine azide anions with a neutral triazole-cyano-based ligand TrzAt (TrzAt = 2-(1 H -1,2,4-triazol-1-yl)acetonitrile) to yield two tetrazole-based EMOFs, namely, [ZnBr(trmetz)] n 1 and [Cd(trmetz) 2 ] n 2 (Htrmetz = 5-(1,2,4-triazol-1-ylmethyl)-1 H -tetrazole). Compound 1 features a closely packed 2D layered network, while compound 2 exhibits a 3D architecture. With azide anions inlaid into a nitrogen-rich and chelating ligand in the EMOFs, compounds 1 and 2 present remarkable decomposition temperatures ( T dec ≥ 300 °C), low impact sensitivities (IS ≥ 32 J) and low friction sensitivities (FS ≥ 324 N). The calculated heat of detonation (Δ H det ) values of 1 and 2 are 3.496 and 4.112 kJ g -1 , respectively. In particular, the Δ H det value of 2 is higher than that of traditional secondary explosives such as 2,4,6-trinitrotoluene (TNT, Δ H det = 3.720 kJ g -1 ). These results indicate that EMOFs 1 and 2 may serve as potential replacements for traditional secondary explosives. This work provides a simple and effective strategy to obtain two EMOFs with satisfactory energy densities and reliable stabilities through an in situ hydrothermal technique for desensitization of azide anions.

Objective: To explore the value of artificial intelligence (AI) in improving the detection rate of traumatic rib fractures by radiologist residents and the consistency among different readers., Methods: Chest CT images of 393 patients with acute trauma from China-Japan Union Hospital of Jilin University (hospital 02) and Shanghai Ninth People' s Hospital (hospital 03) were collected in this research. The consensus achieved by three radiology experts was regarded as the reference standard. All the images assigned to three hospitals: Peking University First Hospital (hospital 01), hospital 02 and hospital 03, and were then randomly divided into two groups (group A and group B: group A included 197 patients, and group B included 196 patients). Each group was read by one radiologist resident from each hospital for rib fracture detection. Each case was read twice by the same radiologist, with and without the assistance of the AI ["radiologist-only" reading and "radiologist + AI" reading]. The detection rates of different types of rib fractures (displaced fractures and occult fractures) were compared between "radiologist-only" reading and "radiologist + AI" reading. The consistencies of different radiologists with different reading methods were evaluated., Results: The detection rates of displaced rib fractures and occult rib fractures by "radiologist + AI" reading were significantly higher than those read by "radiologist-only" reading (94.56% vs . 78.40%, 76.60% vs . 49.42%, P < 0.001). For "radiologist-only reading", the Kappa coefficients of the radiologists between hospital 01 and hospital 03 were slightly greater than 0.4 (indicating moderate consistency), the coefficients of the radiologists between hospital 01/hospital 02 and hospital 02/hospital 03 were less than 0.4 (indicating poor consistency). The Phi coefficients of the radiologists among different hospitals were all less than 0.6 (indicating moderate correlation). With "radiologist + AI" reading, the Kappa and Phi coefficient among the radiologists in dif-ferent hospitals were greater than or equal to 0.6 (indicating good consistency and correlation)., Conclusion: AI software can be used to automatically detect suspected rib fracture lesions, which helps to improve the detection rate of fracture lesions and the consistency among different readers.

Ethnopharmacological Relevance: Inadequate trophoblasts migration and invasion is considered as an initial event resulting in preeclampsia, which is closely related to oxidative stress. Berberine hydrochloride (BBR), extracted from the traditional medicinal plant Coptis chinensis Franch., exerts a diversity of pharmacological effects, and the crude drug has been widely taken by most Chinese women to treat nausea and vomit during pregnancy. But there is no research regarding its effects on trophoblast cell function., Aim of the Study: This study aimed to investigate the effect of BBR on human-trophoblast-derived cell line (HTR-8/SVneo) migration ability and its mechanism., Materials and Methods: Cell viability was detected by CCK-8 assay. The effect of BBR on cells migration function was examined by scratch wound healing assay and transwell migration assay. Intracellular nitric oxide (NO), superoxide (O 2 - ) and peroxynitrite (ONOO - ) levels were measured by flow cytometry. The expression levels of inducible NO synthase (iNOS), eNOS, p-eNOS, MnSOD, CuZnSOD, Rac1, NOX1, TLR4, nuclear factor-κB (NF-κB), p-NFκB, pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) in cells were analyzed by Western blotting. Uric acid sodium salt (UA), the scavenger of ONOO - , PEG-SOD (a specific superoxide scavenger), L-NAME (a NOS inhibitor) and antioxidants (Vit E and DFO) were further used to characterize the pathway of BBR action., Results: 5 μM BBR decreased both the migration distance and the number of migrated cells without affecting cells viability in HTR-8/SVneo cells after 24 h treatment. BBR could increase the level of NO in HTR-8/SVneo cells, and the over-production of NO might be attributable to iNOS, but not eNOS. BBR could increase intracellular O 2 - levels, and the over-production of O 2 - is closely related with Rac1 in HTR-8/SVneo cells. The excessive production of NO and O 2 - further react to form ONOO - , and the increased ONOO - level induced by BBR was blunted by UA. Moreover, UA improved the impaired migration function caused by BBR in HTR-8/SVneo cells. The depressed migration function stimulated by BBR in HTR-8/SVneo cells was diminished by PEG-SOD and L-NAME. Furthermore, BBR increased the expression of IL-6 in HTR-8/SVneo cells, and antioxidants (Vit E and DFO) could decrease the expression of IL-6 and iNOS induced by BBR., Conclusions: BBR inhibits the cell migration ability through increasing inducible NO synthase and peroxynitrite in HTR-8/SVneo cells, indicating that BBR and traditional Chinese medicines containing a high proportion of BBR should be used with caution in pregnant women., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Er-xian Decoction (EXD) is a well-known prescription widely used to prevent and treat climacteric syndrome and osteoporosis in China. BK channel positively affects osteoblast bone formation in vitro. However, it is still unclear whether the effect of EXD on promoting osteoblasts osteogenic differentiation is related to BK channel., Aim of the Study: The study is aimed at determining whether the EXD-containing serum promotes the proliferation of osteoblasts and their differentiation through BK channel., Materials and Methods: The chemical compounds of EXD were analyzed by UPLC-Q-TOF/MS. An osteogenic induction medium (OM) was used to induce MC3T3-E1 cells' osteogenic differentiation. The effects of EXD-containing serum and tetraethylammonium (TEA) on the proliferation activity of Mc3t3-e1 cells were detected by CCK-8 assay. ALP activity was determined by an alkaline phosphatase kit. The protein expression (BMP2, OPG, and COL1) was analyzed by Western blot, and the mRNA expression (Runx2, OPG, and BMP2) was assessed by real-time PCR. Alizarin red was used to stain the mineralized region of osteoblasts. In addition, we analyzed the relationship between BK channel and its downstream PTEN/Akt/Foxo1 signaling pathway., Results: 72 compounds were identified by UPLC-Q-TOF/MS analysis in EXD. Mangiferin, ferulic acid, berberine, and icariin were main active components of EXD. EXD-containing serum could enhance the cell viability of MC3T3-E1 cells by decreasing the expression of BKα protein. EXD-containing serum increased ALP activity and calcium nodule formation of Mc3t3-e1 cells, promoted the protein expression of BKα, COL1, BMP2, OPG, and the mRNA expression of RUNX2, OPG, and BMP2, however, these effects can be reversed after adding TEA. In addition, EXD-containing serum could upregulate phosphorylation of Akt and Foxo1 in osteogenic-induced Mc3t3-e1 cells, and lower the expression of PTEN. And these effects of EXD-containing serum could be reduced by TEA., Conclusions: The effect of EXD-containing serum on promoting cell proliferation and osteogenic differentiation of Mc3t3-e1 cells might be linked to the regulation of BK channel., Competing Interests: Declaration of competing interest All the authors have no competing interests., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Two zero-dimensional inorganic-organic hybrids, namely, [C 4 mim][Cd(TCDPPA) 3 ] ( 1 ) and [C 4 mpy][Cd(TCDPPA) 3 ] ( 2 ), where (TCDPPA) - = 2,2,2-trichloro- N -(di(pyrrolidin-1-yl)phosphoryl)acetamide, (C 4 mim) + = 1-butyl-3-methylimidazolium, and (C 4 mpy) + = 1-butyl-4-methylpyridinium, have been synthesized via metathesis reactions and characterized systematically. These ionic cadmium-containing inorganic-organic hybrid compounds are assembled from a bulky organic cation and a complex anion constructed from the chelation of three TCDPPA ligands to one cadmium ion. These compounds possess wide band gaps and emit in the deep-blue region intensely with a quantum yield as high as 34.04%. The success of this work provides a new method for the design and fabrication of high-efficiency blue-emitting materials.

The design and synthesis of energetic materials (EMs) with high energy and reliable stabilities has attracted much attention in the field of EMs. In this work, we employed a strategy of the coordination polymerization of mild dicyanamide ions (DCA - ), two isomeric ligands 1-methyl-5-aminotetrazole (1-MAT) and 2-methyl-5-aminotetrazole (2-MAT) to construct energetic coordination polymers (ECPs). Four new ECPs {[Co(DCA) 2 (1-MAT) 2 ]·H 2 O} n 1, [Cu(DCA) 2 (1-MAT)] n 2, [Cd(DCA) 2 (1-MAT) 2 ] n 3 and [Cd(DCA) 2 (2-MAT) 2 ] n 4 were successfully synthesized through solvent evaporation routes. Compounds 1 and 4 display 1D chains, while 2 and 3 exhibit 2D-layered structures. Compounds 1-3 with the 1-MAT ligand all exhibit reliable thermal stabilities (> 200 °C). The calculated heats of detonation (Δ H det ) of 1-3 are all higher than 1.4 kJ g -1 , which are higher than traditional explosive TNT (1.22 kJ g -1 ) and the reported ECP AgMtta (HMtta = 5-methyl-1 H -tetrazole, Δ H det = 1.32 kJ g -1 ). Furthermore, sensitivity testing demonstrates that 1-4 features low mechanical sensitivity to external mechanical action in contrast with the extremely sensitive azide-based ECPs [Cu 3 (2-MAT) 2 (N 3 ) 6 ] n . In addition, compound 2 shows hypergolic properties via an 'oxidizer-fuel' drop experiment, demonstrating its application prospects in the field of propellants. This work details an approach of synthesizing multipurpose ECPs with reliable stabilities by introducing mild dicyanamide anions into nitrogen-rich skeletons.

It is of great clinical significance to develop potential novel strategies to prevent diabetic cardiovascular complications. Endothelial progenitor cell (EPC) dysfunction is a key contributor to diabetic vascular complications. In the present study we evaluated whether low-dose nifedipine could rescue impaired EPC-mediated angiogenesis and prevent cardiovascular complications in diabetic mice. Diabetes was induced in mice by five consecutive injections of streptozotocin (STZ, 60 mg·kg -1 ·d -1 , i.p.). Diabetic mice were treated with low-dose nifedipine (1.5 mg·kg -1 ·d -1 , i.g.) for six weeks. Then, circulating EPCs in the peripheral blood were quantified, and bone marrow-derived EPCs (BM-EPCs) were prepared. We showed that administration of low-dose nifedipine significantly increased circulating EPCs, improved BM-EPCs function, promoted angiogenesis, and reduced the cerebral ischemic injury in diabetic mice. Furthermore, we found that low-dose nifedipine significantly increased endothelial nitric oxide synthase (eNOS) expression and intracellular NO levels, and decreased the levels of intracellular O 2 .- and thrombospondin-1/2 (TSP-1/2, a potent angiogenesis inhibitor) in BM-EPCs of diabetic mice. In cultured BM-EPCs, co-treatment with nifedipine (0.1, 1 μM) dose-dependently protected against high-glucose-induced impairment of migration, and suppressed high-glucose-induced TSP-1 secretion and superoxide overproduction. In mice with middle cerebral artery occlusion, intravenous injection of diabetic BM-EPCs treated with nifedipine displayed a greater ability to promote local angiogenesis and reduce cerebral ischemic injury compared to injection of diabetic BM-EPCs treated with vehicle, and the donor-derived BM-EPCs homed to the recipient ischemic brain. In conclusion, low-dose nifedipine can enhance EPCs' angiogenic potential and protect against cerebral ischemic injury in diabetic mice. It is implied that chronic treatment with low-dose nifedipine may be a safe and economic manner to prevent ischemic diseases (including stroke) in diabetes., (© 2022. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

The overuse of tetracyclines (TCs) in livestock breeding may cause a series of health and environmental problems. It is necessary to develop more accurate, convenient, and rapid sensing methods toward TCs, but it is still very challenging. In this work, three isostructural zirconium organic frameworks (Zr-MOFs) have been investigated as probes for the fluorescent sensing of TCs in water. By varying the functional group at the central benzene core, their sensing performances toward TCs can be modified. Under optimized conditions, the limit of detection can be as low as 0.08 nM in a wide detection range of 0-147 μM with high sensitivity and selectivity. These Zr-MOFs can also be applied in the detection of TCs in real pork samples with satisfying reliabilities and correctness. This work provides a new method for the design and optimization of fluorescent sensors toward TCs.

Respiratory syncytial virus (RSV) infection can deteriorate asthma by inducing persistent airway inflammation. Increasing evidence elucidated that pyroptosis plays a pivotal role in asthma. Conciliatory anti-allergic decoction (CAD) exhibits an anti-inflammatory effect in ovalbumin (OVA)-induced asthma; however, the effects and mechanisms of CAD in RSV-infected asthmatic mice have not yet been elucidated. The RSV-infected asthmatic mice model and lipopolysaccharide (LPS)-induced 16HBE cell pyroptosis model were established, respectively. Pulmonary function, ELISA, and histopathologic analysis were performed to assess the airway inflammation and remodeling in mice with CAD treatment. Furthermore, ultra-performance liquid chromatography-quadrupole time-of-flight/mass spectrometry (UPLC-Q-TOF/MS) was conducted to identify the chemical compounds of high-dose CAD (30 g/kg). Cell viability and apoptosis of 16HBE cells were assessed by CCK-8 and flow cytometry assays, respectively. Finally, the expression levels of apoptosis-, pyroptosis-, and TLR3/NLRP3/NF- κ B/IRF3 signaling-related genes were measured with qRT-PCR or western blotting, respectively. Pulmonary function tests showed that CAD significantly ameliorated respiratory dysfunction, airway hyperresponsiveness, inflammation cell recruitment in BALF, pulmonary inflammation, collagen deposition, and cell death in lung tissues. CAD significantly decreased the content of TNF- α , IL-13, IL-4, IL-1 β and IL-5 in the bronchoalveolar lavage fluid (BALF), IL-17, IL-6, and OVA-specific IgE in serum and increased serum IFN- γ in asthma mice. The results of UPLC-Q-TOF/MS showed that high-dose CAD had 88 kinds of chemical components. In vitro, CAD-contained serum significantly suppressed LPS-induced 16HBE cell apoptosis. Additionally, CAD and CAD-contained serum attenuated the up-regulated expressions of Bax, Cleaved caspase-3, NLRP3, ASC, Cleaved caspase-1, GSDMD-N, IL-18, IL-1 β , TLR3, p-P65, p-I κ B α , and IRF3 but increased Bcl-1 and GSDMD levels in the asthma mice and LPS-induced 16HBE cells, respectively. These results illustrated that CAD may have a potential role in improving airway inflammation and pyroptosis through inhibition of the TLR3/NLRP3/NF- κ B/IRF3 signaling pathway., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2022 Ya-qin Chen et al.)

Air pollution adversely affects skin, leading to skin inflammation and premature skin aging. Plant derived antioxidant compounds have been considered to be promising in discovery of effective agents for the protection of skin from the damage by air pollutants. Our previous studies demonstrated that Averrhoa carambola fruit (known as star fruit) is rich in flavonoid C-glycosides with unique structures and potent antioxidant activity. Thus, the star fruit extract (SFE) and main flavonoid C-glycoside components, carambolasides I, J, and P (1-3), carambolaflavone B (4), and isovitexin 2″-O-α-L-rhamnoside (5), were investigated for the activity against air pollutant stress in human epidermis. As a result, SFE and compounds 1-5 exhibited significant inhibitory activity against protein carbonylation in oxidative-stressed stratum corneum with the best activity being shown by compound 3. SFE and compounds 2-5 were also active against engine exhaust-induced protein carbonylation in stratum corneum. When further evaluated, SFE and compound 3 significantly inhibited gene expression of the key inflammation mediators IL-1α and COX-2 in PM-stressed keratinocytes. The results indicated that SFE and the flavonoid C-glycosides are potentially effective against air pollutant-induced skin inflammation and premature aging., (© 2022. The Author(s).)

It is of great clinical significance to develop potential novel strategies to prevent cardio-cerebrovascular complications in patients with hyperlipidemia. Vascular Endothelial integrity and function play a key role in the prevention of cardio-cerebrovascular diseases. Endothelial progenitor cells (EPCs) can home to sites of ischemic injury and promote endothelial regeneration and neovascularization. Hypercholesterolemia impairs the function of EPC. The present study attempted to identify the effect of piperlongumine on EPCs' angiogenic potential and cerebral ischemic injury in high-fat diet-fed (HFD-fed) mice. Here, we showed that treatment with low-does piperlongumine (0.25 mg/kg/day) for 8 weeks significantly improved EPCs function and reduced the cerebral ischemic injury (both infarct volumes and neurobehavioral outcomes) in HFD-fed mice. In addition, low-dose piperlongumine administration increased intracellular NO level and reduced intracellular O 2 - level in EPCs of HFD-fed mice. Moreover, incubation with piperlongumine (1.0 μM, 24 h) reduced thrombospondin-1/2 (TSP-1/2, a potent angiogenesis inhibitor) expression levels in EPCs from HFD-fed mice, increased the therapeutic effect of EPC from HFD-fed mice on cerebral ischemic injury reduction and angiogenesis promotion in HFD-fed mice, and the donor derived EPCs homed to the recipient ischemic brain. In conclusion, low-dose piperlongumine can enhance EPCs' angiogenic potential and protect against cerebral ischemic injury in HFD-fed mice. It is implied that treatment with low-dose piperlongumine might be a potential option to prevent ischemic diseases (including stroke) in patients with hyperlipidemia, and priming with piperlongumine might be a feasible way to improve the efficacy of EPC-based therapy for ischemic diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Dong, Peng, Zhang, Jiang, Yang, He, Tao, Zhang, Chen and Xie.)

Background: Perioperative neurocognitive disorders (PND) are a series of severe complications in the perioperative and anesthetic periods with a decline in memory, execution ability, and information processing speed as the primary clinical manifestation. This study aimed to evaluate the impact of edaravone (EDA) on PND and peripheral blood C-X-C motif chemokine ligand 13 (CXCL13) levels in elderly patients with hip replacement., Methods: A total of 160 elderly patients undergoing hip arthroplasty in Affiliated Dongguan People's Hospital of Southern Medical University (from March 2016 to March 2018) were randomly and double-blindly categorized into an EDA group and a control group (CON). Group EDA was administered intravenously EDA 30 min before surgery, and group CON was administered intravenously saline. The cognitive function of the two groups was evaluated 1-day before the operation and at 1 and 12 months after surgery, and the incidence of post-operative delirium was tested on days 1, 3, and 7 after surgery using the Chinese version of the confusion assessment method. Serum CXCL13 and interleukin (IL)-6 concentrations were measured before anesthesia, during surgery (30 min after skin incision), and on days 1, 3, and 7 after surgery. The continuous variables in accordance with normal distribution were tested using the Student's t test, the continuous variables without normal distribution using the Mann-Whitney U test, and categorical variables by the χ2 test or Fisher exact test., Results: The incidence of post-operative delirium within 7 days after surgery was significantly higher in group CON than that in group EDA (31.3% vs. 15.0%, t = -5.6, P < 0.001). The modified telephone interview for cognitive status and activities of daily life scores were significantly higher in the group EDA than those in the group CON at 1 month (39.63 ± 4.35 vs. 33.63 ± 5.81, t = -2.13, P < 0.05 and 74.3 ± 12.6 vs. 61.2 ± 13.1, t = -1.69, P < 0.05) and 12 months (40.13 ± 5.93 vs. 34.13 ± 5.36, t = -3.37, P < 0.05 and 79.6 ± 11.7 vs. 65.6 ± 16.6, t = -2.08, P < 0.05) after surgery; and the incidence of neurocognitive dysfunction was significantly lower in the group EDA than that in the group CON (P < 0.05). Serum CXCL13 and IL-6 concentrations were significantly lower in the group EDA than those in the group CON during and after surgery (P < 0.05)., Conclusion: EDA can significantly reduce the serum concentrations of CXCL13 and IL-6 and improve the PND of patients., (Copyright © 2021 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Introduction: Subchromosomal deletions and duplications could currently be detected by noninvasive preliminary screening (NIPS). However, NIPS is a screening test that requires further diagnosis. Here we report a fetus with an autosomal abnormality revealed by NIPS and conventional karyotype combined with copy number variations sequencing (CNV-seq) confirmed the fetus with an unbalanced translocation., Patient Concern: This was the fourth pregnancy of a 30-year-old woman who underwent 2 spontaneous abortions and gave birth to a child with a normal phenotype. The woman and her husband were healthy and nonconsanguineous. NIPS indicated a repeat of about 19-Mb fragment at the region of 16q22.1-q22.4 at 17-week gestation., Diagnoses: The combination of traditional karyotype and CNV-seq could better locate the abnormal chromosomal region and further identify the source of fetal chromosomal abnormalities. Simultaneously, we evaluated the fetal morphology by ultrasound examination. The karyotype of the fetus was 46,XX,der(7)t(7;16)(p22;q23) and CNV-seq results showed an approximately 20.96-Mb duplication in 16q22.1-q24.3 (69200001-90160000) and an approximately 3.86-Mb deletion in 7p22.3-p22.2 (40001-3900000). Prenatal ultrasound revealed the fetal micrognathia. The paternal karyotype was 46,XY, t (7;16) (p22;q23), while the maternal was normal. The fetus inherited an abnormal chromosome 7 from its father., Interventions: No treatment for the fetus., Outcomes: Pregnancy was terminated., Conclusions: To our knowledge, the occurrence of de novo partial trisomy 16q (16q22.1-qter) and partial monosomy 7p (7p22.2-pter) has not previously been reported up to now. Here, we present the perinatal findings of such a case and a review of the literatures. CNV-seq combined with karyotype is a useful tool for chromosomal abnormalities indicated by NIPS., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

The rat osteoarthritis model was replicated by injection of sodium iodoacetate into the knee joint cavity, and the effects of Gancao Fuzi Decoction on rat osteoarthritis and the proteome of articular cartilage were investigated. Sixty SD rats weighing 230-250 g were randomly divided into normal group, model group, glucosamine sulfate group, and Gancao Fuzi Decoction high, medium and low dose groups. Osteoarthritis model was induced by intra-articular injection of sodium iodoacetate(3 mg on each leg) in all groups except the normal group. After modeling, each administration group was given intragastric administration for 1 month. During the administration period, joint pain test and joint width measurement were performed every week to observe the autonomous behavior of rats. Enzyme linked immunosorbent assay(ELISA) method was used to detect the contents of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), matrix metalloproteinase-3(MMP-3), and matrix metalloproteinase tissue inhibitor(TIMP-1) in rat joint lavage fluid. Hematoxylin-eosin(HE) staining was used to observe bone and joint morphology. Nano-LC-LTQ-Orbitrap system was used to detect arti-cular cartilage proteins. The results showed that, compared with the model group, Gancao Fuzi Decoction could significantly improve joint pain and joint swelling in osteoarthritis rats, significantly reduce the contents of TNF-α, IL-1β and MMP-3 in the joint cavity la-vage fluid, increase the content of TIMP-1, and relieve inflammatory diseases such as enlarged joint space, rough cartilage edge, different thickness of cartilage layer, and disordered arrangement of chondrocytes. After comparing the proteins between the groups, 273 differential proteins were screened out. KEGG analysis found that the above differential proteins involved 43 signaling pathways such as systemic lupus erythematosus, among which 11 signaling pathways were related to osteoarthritis. The above results indicated that Gancao Fuzi Decoction had a preventive effect on osteoarthritis, and its mechanism of action may be accomplished by regulating the protein expression of osteoarthritis-related signal pathways.

Sisal (Agave sisalana Perrine) is an important hard fiber crop that is widely planted in Guangxi, Guangdong, Hainan, Yunnan, and Fujian provinces, China. In July 2019, a new leaf disease of sisal with a disease incident of about 36% was found in Guangxi (Fig.1a~d). The oval or circular black lesions were 2.3 cm to 15.9 cm in length and 1.6 cm to 5.5 cm in width on both sides of the diseased leaves. The central part of the lesions was slightly hollow. The lesions continuously enlarged and ultimately penetrated the leaves. Reddish brown and dark mucus was secreted from the lesions. The junction of lesions and healthy parts was reddish brown to yellow. The diseased leaf fiber and mesophyll tissues were reddish brown and necrotic. Fresh leaf yield was reduced about 30% by the disease, and fiber quality was significantly compromised every year in Guangxi. Six kinds of fungi distinguished by their morphology, size and color of the colonies were isolated from diseased leaf tissues of 60 sisal plants sampled from five different farms in Guangxi. Isolate JMHB1 was isolated at a rate of 95.67%. The isolate JMHB1 was initially white with dense and hairy aerial mycelium, gradually turning dark grey to olive green on PDA (Fig. 2). Conidia, arthrospores, and chlamydospores were observed on PDA in culture (Fig. 3). The conidia formed arthric chains, disarticulating, cylindrical-truncate, oblong-obtuse to doliiform, colorless and transparent, zero- to one-septate, and averaging 4.4 to 13.8 µm × 2.2 to 5.6 µm (n=100). Arthrospores were short columnar, pigmented and transparent, single or formed arthric chains, averaging 5.5 to 17.9 µm × 2.1 to 3.5 µm (n=100). Chlamydospores were dark brown, round or oval, averaging 4.5 to 9.6 µm × 4.5 to 8.6 µm (n=100). Pathogenicity testing was conducted by inoculating 3-year-old healthy sisal plants with PDA plugs (5 × 5 mm) on which the fungus had grown for 5 days. Nine healthy plants were wounded on the leaves with a sterile needle, and mycelial plugs were placed on the wounds, covered with sterile moist cotton, and wrapped with parafilm. Nine control plants were wounded and treated with PDA plugs as the negative control. The test was repeated three times. All treated plants were kept in a greenhouse at ~28 ℃ and 40% RH. After 5 days, only leaves inoculated with isolate JMHB1 showed lesions similar to symptoms observed in the field (Fig.1e~f). The fungus was re-isolated from all nine diseased plants, and no symptoms were observed on the leaves of control plants. Molecular identification of the fungus was made by PCR amplification of the internal transcribed spacer (ITS) region of rDNA, EF1-α gene and β-tubulin gene using primers ITS1/ITS4 (White et al. 1990), EFl-728F/EF1-986R (Carbone and Kohn 1999), TUB2Fd/TUB4Rd (Aveskamp et al. 2009) respectively. The ITS (MT705646), EF1-α (MT733516) and β-tubulin (MT773603) sequences of JMHB1 were similar to the ITS (AY819727), EF1-α (EU144063) and β-tubulin (KF531800) sequences of the epitype of Neoscytalidium dimidiatum (CBS 499.66) with 100%, 99.65% and 99.02% identity, respectively. Based on pathogenicity testing, morphological characteristics, and molecular identification, the pathogen of sisal causing black spot was identified as N. dimidiatum (Penz.) Crous & Slippers (Crous et al. 2006). To our knowledge, this is the first report of black spot caused by N. dimidiatum on sisal in China. Sisal is the main economic crop in arid and semi-arid areas that is widely planted in several provinces of southern China. The serious occurrence of the disease caused by N. dimidiatum has greatly affected the development of sisal industry and local economic income in China. Identification of the pathogen of the disease is of great significance to guide disease control, increase farmers' income and promote the development of sisal industry. References: Aveskamp, M. M., et al. 2009. Mycologia, 101: 363. https://doi.org/10.3852/08-199. Carbone, I., and Kohn, L. M. 1999. Mycologia, 91:553. https://doi.org/10.1080/00275514.1999. 12061051. Crous, P. W., et al. 2006. Stud. Mycol. 55:235. https://doi.org/10.3114/sim.55.1.235. White, T. J., et al. 1990. PCR Protocols: A Guide to Methods and Applications. Academic Press, San Diego, Page 315. doi.org/10.1002/mrd.1080280418. Supplemental photographs: Fig. 1 Symptoms of sisal black spot disease a, b, c, d showed symptoms in the field, e and f were symptoms after inoculating Neoscytalidium dimidiatum JMHB1. a, c, and e were the front of the lesions, b, d, and f were the back of the lesions. Fig. 2 Primary colony (a) and old colony (b) of Neoscytalidium dimidiatum JMHB1 Fig. 3 Arthrospores (a), conidia and chlamydospores (b) of Neoscytalidium dimidiatum JMHB1.

Objective: To investigate the diagnosis and treatment for enterocutaneous fistula (ECF) in China, and to explore the prognostic factors of ECF. Methods: A multi-center cross-sectional study was conducted based on the Registration System of Chinese Gastrointestinal Fistula and Intra-Abdominal Infections to collect the clinical data of ECF patients from 54 medical centers in 22 provinces/municipalities from January 1, 2018 to December 31, 2018. The clinical data included patient gender, age, length of hospital stay, intensive care unit (ICU) admission, underlying diseases, primary diseases, direct causes of ECF, location and type of ECF, complications, treatment and outcomes. All medical records were carefully filled in by the attending physicians, and then re-examined by more than two specialists. The diagnosis of ECF was based on the clinical manifestations, laboratory/imaging findings and intraoperative exploration. Results: A total of 1521 patients with ECF were enrolled, including 1099 males and 422 females, with a median age of 55 years. The top three primary diseases of ECF were malignant tumors in 626 cases (41.2%, including 540 gastrointestinal tumors, accounting for 86.3% of malignant tumors), gastrointestinal ulcers and perforations in 202 cases (13.3%), and trauma in 157 cases (10.3%). The direct causes of ECF were mainly surgical operation in 1194 cases (78.5%), followed by trauma in 156 (10.3%), spontaneous fistula due to Crohn ' s disease in 92 (6.0%), radiation intestinal injury in 41 (2.7%), severe pancreatitis in 20 (1.3%), endoscopic treatment in 13 (0.9%) and 5 cases (0.3%) of unknown reasons. All the patients were divided into three groups: 1350 cases (88.7%) with simple ECF, 150 (9.9%) with multiple ECF, and 21 (1.4%) with combined internal fistula. Among the patients with simple ECF, 438 cases (28.8%) were jejuno - ileal fistula, 313 (20.6%) colon fistula, 170 (11.2%) rectal fistula, 111 (7.3%) duodenal fistula, 76 (5.0%) ileocecal fistula, 65 (4.3%) ileocolic anastomotic fistula, 55 (3.6%) duodenal stump fistula, 36 (2.4%) gastrointestinal anastomotic fistula, 36 (2.4%) esophagogastric/esophagojejunal anastomotic fistula, 29 (1.9%) gastric fistula and 21 (1.4%) cholangiopancreatiointestinal. Among all the simple ECF patients, 991 were tubular fistula and 359 were labial fistula. A total of 1146 patients finished the treatment, of whom 1061 (92.6%) were healed (586 by surgery and 475 self-healing) and 85 (7.4%) died. A total of 1043 patients (91.0%) received nutritional support therapy, and 77 (6.7%) received fistuloclysis. Infectious source control procedures were applied to 1042 patients, including 711 (62.0%) with active lavage and drainage and 331 (28.9%) with passive drainage. Among them, 841 patients (73.4%) underwent minimally invasive procedures of infectious source control (replacement of drainage tube through sinus tract, puncture drainage, etc.), 201 (17.5%) underwent laparotomy drainage, while 104 (9.1%) did not undergo any drainage measures. A total of 610 patients (53.2%) received definitive operation, 24 patients died within postoperative 30-day with mortality of 3.9% (24/610), 69 (11.3%) developed surgical site infection (SSI), and 24 (3.9%) had a relapse of fistula. The highest cure rate was achieved in ileocecal fistula (100%), followed by rectal fistula (96.2%, 128/133) and duodenal stump fistula (95.7%,44/46). The highest mortality was found in combined internal fistula (3/12) and no death in ileocecal fistula. Univariate prognostic analysis showed that primary diseases as Crohn's disease (χ(2)=6.570, P =0.010) and appendicitis/appendiceal abscess ( P =0.012), intestinal fistula combining with internal fistula (χ(2)=5.460, P =0.019), multiple ECF (χ(2)=7.135, P =0.008), esophagogastric / esophagojejunal anastomotic fistula (χ(2)=9.501, P =0.002), ECF at ileocecal junction ( P =0.012), non-drainage/passive drainage before the diagnosis of intestinal fistula (χ(2)=9.688, P =0.008), non-drainage/passive drainage after the diagnosis of intestinal fistula (χ(2)=9.711, P =0.008), complicating with multiple organ dysfunction syndrome (MODS) (χ(2)=179.699, P <0.001), sepsis (χ(2)=211.851, P <0.001), hemorrhage (χ(2)=85.300, P <0.001), pulmonary infection (χ(2)=60.096, P <0.001), catheter-associated infection (χ(2)=10.617, P =0.001) and malnutrition (χ(2)=21.199, P <0.001) were associated with mortality. Multivariate prognostic analysis cofirmed that sepsis (OR=7.103, 95%CI:3.694-13.657, P <0.001), complicating with MODS (OR=5.018, 95%CI:2.170-11.604, P <0.001), and hemorrhage (OR=4.703, 95%CI: 2.300-9.618, P <0.001) were independent risk factors of the death for ECF patients. Meanwhile, active lavage and drainage after the definite ECF diagnosis was the protective factor (OR=0.223, 95%CI: 0.067-0.745, P =0.015). Conclusions: The overall mortality of ECF is still high. Surgical operation is the most common cause of ECF. Complications e.g. sepsis, MODS, hemorrhage, and catheter-associated infection, are the main causes of death. Active lavage and drainage is important to improve the prognosis of ECF.

Background: The effectiveness of multiband mucosectomy (MBM) for early esophageal cancer and precancerous lesions is still in uncertainty. We aimed to evaluate the efficacy and safety of this procedure and to compare it with cap-assisted endoscopic resection (EMR-cap)., Methods: A systematic search of both English and Chinese databases was performed from inception to April 30, 2019. Complete resection rate, local recurrence rate, and procedure time were considered the primary outcome measures. Prevalence of complications was considered the secondary outcome measure. All data analyses were performed using Review Manager Software., Results: Two randomized controlled trials (RCTs) and 3 non-RCTs were included in the final meta-analysis. When compared with the EMR-cap technique, MBM had a similar complete resection rate [odds ratio (OR)=2.09, 95% confidence interval (CI): 0.78-5.60, P=0.14], a similar local recurrence rate (OR=0.50, 95% CI: 0.09-2.67, P=0.42), a shorter resection time (mean difference: -9.08, 95% CI: -13.86 to -4.30, P=0.0002), a shorter procedure time (mean difference: -13.36, 95% CI: -17.85 to -8.86, P<0.00001), a lower bleeding rate (OR=0.45, 95% CI: 0.24-0.83, P=0.01), a similar perforation rate (OR=0.55, 95% CI: 0.15-2.06, P=0.37), and a similar stricture rate (OR=0.77, 95% CI: 0.10-5.84, P=0.80). The results of non-RCTs were consistent with those of RCTs., Conclusions: MBM is similar to EMR-cap in terms of efficacy and safety for endoscopic resection of early cancer and precancerous lesions of the esophagus. However, MBM is less time-consuming.

Objective: The objective of this study is to investigate the risk factors and distribution features for level IB metastasis in nasopharyngeal carcinoma (NPC) and provide clinical evidence for defining the indications and clinical target volume (CTV) of prophylactic level IB irradiation., Methods: We retrospectively analyzed 798 patients with newly-diagnosed, non-metastatic and histologically confirmed NPC underwent intensity-modulated radiation therapy (IMRT). Two sides of neck in each patient have been analyzed separately. The correlations of level IB metastasis and the clinical risk factors were analyzed with Chi-square test and logistic regression model. The risk score model (RSM) of level IB metastasis was calculated by totaling up the scores of each independent variable. We divided level IB into three areas, including anterolateral space of submandibular glands, medial space of the submandibular glands and submandibular glands., Results: Maximal axial diameter (MAD) of level IIA nodes >20mm or extra capsular spread (ES) of level IIA nodes, anterior half of nasal cavity involvement and submandibular gland involvement/compression were independently significantly risk factors for level IB lymph nodes (LNs) metastasis at diagnosis. Two groups based on RSM were obtained: low risk (total score=0-2.5); high risk (4-8.5). The incidence of IB LNs metastasis at diagnosis of the two groups were 0.9% and 6.3%, respectively (P<0.001). The cervical lymph nodes of level IB were distributed in the anterolateral space of submandibular glands. There was no positive/negative LNs inside or medial space of the submandibular glands., Conclusion: Level IB LNs metastasis is associated with MAD of level IIA nodes >20mm or ES of level IIA nodes, anterior half of nasal cavity involvement and submandibular gland involvement/compression in NPC patients. Omission of level IB irradiation may be feasible for patients with low-risk IB LNs metastasis at diagnosis. The submandibular gland should not be included in level IB., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: MicroRNAs (miRNAs) have emerged as the critical modulators of the tumorigenesis and tumor progression., Methods: The levels of miR-663 in ovarian cancer cell lines and clinical tissues were detected using qRT-PCR assays. The Transwell invasion and wound healing assay were conducted to assess the roles of miR-663 in the migration and invasion of ovarian cancer cell in vitro. Rescue assays were carried out to confirm the contribution of tumor suppressor candidate 2 (TUSC2) in the aggressiveness of cancer cell which was regulated by miR-663., Results: The levels of miR-663 were up-regulated in ovarian cancer tissues in comparison with the corresponding normal tissues. Up-regulation of miR-663 increased the proliferation, colony formation, migration and invasion of ovarian cancer SKOV3 cell. Additional, over-expression of miR-663 increased the tumor growth of SKOV3 in xenograft model. Bioinformatics analysis and luciferase reporter assay identified that miR-663 decreased the level of TUSC2 via binding to the 3'-UTR of TUSC2 gene. Finally, the expression of TUSC2 was inversely associated with the level of miR-663 in ovarian carcinoma tissue and over-expression of TUSC2 inhibited the migration and invasion abilities of SKOV3 that was promoted by miR-663., Conclusion: Altogether, these results indicate that miR-663 acts as a potential tumor-promoting miRNA through targeting TUSC2 in ovarian cancer.

There is a pressing need for new approaches to prevent stroke. Endothelial progenitor cells (EPCs) promote vascular repair and revascularization in the ischemic brain. The present study sought to evaluate whether preventive delivery of EPCs could prevent or protect against stroke. Stroke-prone spontaneously hypertensive rats (SHR-SP) received a single injection of EPCs, and their survival time was monitored. In addition, at 28 and/or 42 days after a single injection of EPCs, SHR-SP and mice were subjected to cerebral ischemia, and cerebral ischemic injury, local angiogenesis and in vivo EPC integration were determined. Other experiments examined the effects of EPC conditioned medium, and the distribution of donor EPCs taken from GFP transgenic mice. It was found that EPC-pretreated SHR-SP showed longer lifespans than untreated controls. A single preventive injection of EPCs could produce persistent protective effects against cerebral ischemic injury (lasting at least 42 days), and promote local angiogenesis in the ischemic brain, in two types of animals (SHR-SP and normotensive mice). EPCs of donor origin could be detected in the recipient peripheral blood, and integrated into the recipient ischemic brains. Furthermore, it was suggested that mouse EPCs might exert paracrine effects on cerebral ischemic injury in addition to their direct angiogenic effects. In conclusion, a single preventive injection of EPCs prolonged the lifespan of SHR-SP, and protected against cerebral ischemic injury for at least 7 weeks. It is implied that EPC injection might be a promising candidate for a preventive role in patients at high risk for stroke., (© 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

To investigate the effect of Er-xian decoction on ovariectomy induced-learning and memory disability in rats based on the differences in hippocampus proteomic expression, the female rats were ovariectomized for perimenopausal status and then randomly divided into 3 groups, namely sham group, control group and Er-xian decoction group. The rats in sham group and control group were given normal saline by gavage everyday, the rats in Er-xian decoction group were given 12 g·kg⁻¹ of Er-xian decoction by gavage once a day. After treatment for 90 day, all of the animals were tested by Morris water maze, and all of the samples were collected for testing. The hippocampus proteins were detected by Nano-LC-LTQ-Orbitrap system, and identified by Protein Discovery software. The intensity of differential proteins were quantitated by SIEVE software，and the biological functions of protein were analyzed by DIVAD database. The results showed that Er-xian decoction could significantly improve the abilities of learning and memory. Compared with control group， 216 differential proteins with a consistent variation trend with the sham group were found in the Er-xian decoction group. And they mainly concentrated in calcium signaling pathway, Rab3A and Rab14 were key genes with the highest functional classification enrichment score in the gene group. Er-xian decoction could significantly improve the abilities of learning and memory in perimenopausal model rats. The invention effect of Er-xian decoction may be correlated with the calcium signaling pathway and Ras-related protein Rab-3A, and Ras-related protein Rab-14., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

The transcription factor Forkhead box protein M1 (FOXM1) plays critical roles in cancer development and progression, including human hepatocellular carcinoma (HCC). However, the regulatory role and underlying mechanisms of FOXM1 is still limited. Here, we found that the high level expression of FOXM1 and CCNB1 is closely associated with poor prognosis in HCC patients. And FOXM1 and CCNB1 were overexpressed concomitantly in liver tumor tissues. Knockdown of FOXM1 significantly inhibited the expression levels of CCNB1 in HCC cell lines at both the mRNA and protein levels. Mechanistic studies revealed that FOXM1 binds directly to the promoter region of CCNB1 and regulates the expression levels of the CCNB1 gene in the transcriptional level. Furthermore, the loss of functional and rescue experiments showed that CCNB1 is essential for FOXM1-driven proliferation in HCC cells. In the present study, our results partially explained the dysregulated expression of FOXM1 play an important role in proliferation of human hepatocellular carcinoma cells via transcriptional activation of CCNB1 expression. And it also highlights a FOXM1/CCNB1 axis could be a potential target for the treatment of HCCs., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To study the effect of Erxian Decoction (EXD) on oligospermia (OS) induced by cyclophosphamide in mice., Methods: Eighty 6-week-old male Kunming mice were randomly divided into five groups of equal number, normal control, OS model control, and low-, medium- and high-dose EXD, the former two groups treated intragastrically with normal saline and the latter three with EXD at 3, 6 and 12 g per kg of the body weight qd for 30 days. From the 21st day of administration, the mice of the normal control group were injected intraperitoneally with saline and those of the other four groups with cyclophosphamide at 80 mg per kg of the body weight qd for 5 consecutive days. At 24 hours after the last gavage, the bilateral epididymides of the mice were collected and sperm suspension prepared for determination of the sperm count and motility, and the bilateral testes were harvested for histomorphological observation and measurement of the concentrations of superoxide dismutase (SOD), malondialdehyde (MAD) and glutathione (GSH) in the testis tissue., Results: Compared with the normal controls, the mice of the OS model control group showed significant decreases in epididymal sperm concentration (［9.31 ± 1.32］ vs ［3.32 ± 1.13］×107/ml, P <0.01) and motility (［44.75 ± 8.12］% vs ［25.95 ± 11.41］， P<0.01) and the concentrations of SOD (［37.27 ± 0.99］ vs ［14.23 ± 1.99］ U/mg prot, P <0.01) and GSH (［101.55 ± 8.74］ vs ［58.77 ± 8.93］ μmol/L, P <0.01) but an obvious increase in the MDA level (［2.21 ± 0.65］ vs ［2.61 ± 0.15］ nmol/mg prot, P <0.05) in the testis tissue. In comparison with the OS model controls, the mice treated with low-, medium- and high-dose EXD exhibited significantly increased epididymal sperm concentration (［8.34 ± 2.59］, ［8.59 ± 1.10］ and ［8.41 ± 1.47］×107/ml) (P <0.01) and motility (［36.04 ± 12.33］%, ［38.87 ± 13.13］% and ［41.90 ± 8.09］%) (P <0.01) and concentrations of SOD (［22.99 ± 1.11］, ［20.82 ± 1.81］ and ［21.33 ± 1.66］ U/mg prot) (P <0.01) and GSH (［104.74 ± 2.47］, ［98.61 ± 12.98］ and ［108.89 ± 5.85］ μmol/L) (P <0.01) but decreased level of MDA (P <0.05)., Conclusions: Erxian Decoction can improve cyclophosphamide-induced reduction of sperm concentration and motility, which might be associated with its abilities of resisting oxidation and reducing oxidative stress injury.

An efficient Rh III -catalyzed direct C2-alkenylation of indoles using readily available potassium vinyltrifluoroborate under mild conditions has been developed. This protocol features wide substrate scope and excellent functional group compatibility, enabling a facile access to diverse terminal vinylindoles in moderate to good yields. Furthermore, the C2-alkenylated indole can be easily transformed into 9H-carbazole through a ring-closing metathesis/aromatization cascade., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: To investigate the effects and mechanism of yes-associated protein 1 (YAP1) on thyroid carcinoma cells., Materials and Methods: Quantitative Real-time PCR (qRT-PCR) and Western blot assay were used to detect the expression of YAP1 in normal thyroid cells (HT-ori3) and four types of thyroid carcinoma cells: FTC-133, IHH-4, TPC-1 and NPA. The cell lines with the highest expression of YAP1 were selected as the experimental materials. qRT-PCR and Western blot assay were used to detect the interference effect of si-YAP1. The cell proliferation and the effect on the PI3K-Akt signal pathway were examined by MTT and Western blot., Results: The expression of YAP1 significantly increased in the thyroid carcinoma cell line compared with normal thyroid cells, among which the expression of YAP1 in TPC-1 was the highest. Quantitative PCR and Western blot results showed significant interference effects. The MTT assay indicated that YAP1 interference suppressed the proliferation of cells and the expression of p-Akt., Conclusions: The interference of YAP1 can inhibit the growth of thyroid cancer cells, and its mechanism may be associated with the PI3K-Akt signaling pathway.

Ethnopharmacological Relevance: Banxia (BX) is the dried tuber of Pinellia ternata (Thunb.) Breit., a commonly prescribed Chinese medicinal herb for the treatment of cough, phlegm, and vomiting in pregnant women. However, raw BX has been demonstrated to exert toxic effects on reproduction and the precise and comprehensive mechanisms remain elusive., Aim of the Study: We applied an iTRAQ (isobaric tags for relative and absolute quantitation, iTRAQ)-based proteomic method to explore the mechanisms of raw BX-induced fetal toxicity in mice., Materials and Methods: The mice were separated into two groups, control mice and BX-treated mice. From gestation days 6-8, the control group was treated with normal saline and the BX group was exposed to BX suspension (2.275g/kg/day). Gastrulae were obtained and analyzed using the quantitative proteomic approach of iTRAQ coupled to liquid chromatography-tandem mass spectrometry (LC-MS/MS). A multi-omics data analysis tool, OmicsBean (http://www.omicsbean.cn), was employed to conduct bioinformatic analysis of differentially abundant proteins (DAPs). Quantitative real-time PCR (qRT-PCR) and western blotting methods were applied to detect the protein expression levels and validate the quality of the proteomics., Results: A total of 1245 proteins were identified with < 1% false discovery rate (FDR) and 583 protein abundance changes were confidently assessed. Moreover, 153 proteins identified in BX-treated samples showed significant differences in abundance. Bioinformatics analysis showed that the functions of 37 DAPs were predominantly related to nervous system development. The expression levels of the selected proteins for quantification by qRT-PCR or western blotting were consistent with the results in iTRAQ-labeled proteomics data., Conclusion: The results suggested that oral administration of BX in mice may cause fetal abnormality of the nervous system. The findings may be helpful to elucidate the underlying mechanisms of BX-induced embryotoxicity., (Copyright © 2017 Elsevier B.V. All rights reserved.)

We measured the interleukin-34 (IL-34) level in sera from patients with systemic lupus erythematosus (SLE) and discoid lupus erythematosus (DLE) using an enzyme-linked immunosorbent assay (ELISA). Blood tests, including assays to determine C-reactive protein (CRP), complement (C) 3, C4, immunoglobulin (Ig) A, IgG, IgM, anti-double-stranded DNA antibody (Anti-dsDNA Ab) and hemoglobin (Hb) levels and white blood cell (WBC) and platelet (PLT) counts, were performed using standard methods. Lupus nephritis (LN) was diagnosed according to the American College of Rheumatology (ACR) renal criteria. The SLE disease activity was scored using the SLE Disease Activity Index (SLEDAI). Among the 110 SLE cases, IL-34 could be detected in 79 cases (71.8%). IL-34 was barely detected in the control group. The serum level of IL-34 was significantly higher in the SLE group. No change was observed in the serum IL-34 concentration in the SLE patients regardless of LN status. Correlations were observed between the serum IL-34 level and the disease activity parameters. The SLE patients with detectable IL-34 levels had higher SLEDAI and IgG concentrations and lower C3 and Hb levels than patients with undetectable IL-34 levels. Therefore, IL-34 could be a potential disease activity marker for SLE.

Eight compounds were isolated from the seeds of Holarrhena antidysenterica Wall.ex A.DC. On the basis of physico-chemical properties and spectroscopic data, holarrhenanan (1) was identified as a new compound, compounds 2-3 were isolated from H. antidysenterica for the first time, and five known compounds were also obtained. Inhibitory effects of some compounds and extracts to the intestinal peristalsis were evaluated. Results showed that the extracts and compounds 4, 6 exhibited remarkable inhibitory effects with tension inhibition rate of 32.77, 32.77% and amplitude inhibition rate of 59.51, 55.98%, respectively on the vitro rabbit intestinal peristalsis.

Background/aims: Chronic cold exposure may increase energy expenditure and contribute to counteracting obesity, an important risk factor for cerebrocardiovascular diseases. This study sought to evaluate whether preventive cold acclimation before ischemia onset might be a promising option for preventing cerebral ischemic injury., Methods: After a 14-day cold acclimation period, young and aged mice were subjected to permanent cerebral ischemia, and histological analyses and behavioral tests were performed. Mouse endothelial progenitor cells (EPCs) were isolated, their function and number were determined, and the effects of EPC transplantation on cerebral ischemic injury were investigated., Results: Preventive cold acclimation before ischemia onset increased EPC function, promoted ischemic brain angiogenesis, protected against cerebral ischemic injury, and improved long-term stroke outcomes in young mice. In addition, transplanted EPCs from cold-exposed mice had a greater ability to reduce cerebral ischemic injury and promote local angiogenesis compared to those from control mice, and EPCs from donor animals could integrate into the recipient ischemic murine brain. Furthermore, transplanted EPCs might exert paracrine effects on cerebral ischemic injury, which could be improved by preventive cold acclimation. Moreover, preventive cold acclimation could also enhance EPC function, promote local angiogenesis, and protect against cerebral ischemic injury in aged mice., Conclusions: Preventive cold acclimation before ischemia onset improved long-term stroke outcomes in mice at least in part via promoting the reparative function of EPC. Our findings imply that a variable indoor environment with frequent cold exposure might benefit individuals at high risk for stroke., (© 2018 The Author(s). Published by S. Karger AG, Basel.)

Objective: To explore molecular and genetic mechanism of 3 cases of para-Bombay blood group., Methods: The bood samples of proband and family members were selected to identify their blood groups with conventional serologic methods, and salivary components carrying the ABH antigens were detected. The coding regions of FUT1 as well as exon 6 and 7 of the ABO gene were amplified using polymerase chain reaction(PCR), and the FUT1 gene was directly sequenced., Results: All the 3 cases of proband were confirmed as para-Bombay blood group. Direct sequencing revealed h new2 (nt328G→A) and h1(nt 547 ΔAG) in FUT1 gene of the proband 1, and FUT1 genotype was h1/h new2. However, the genotypes of his parents were H/h1 and H/h new2, which were non-Bombay individuals. The FUT1 genotypes of proband 2 and 3 were h1h2 (nt 547 ΔAG) and h1h2 (nt 880 ΔTT), respectively., Conclusion: The technology of molecular biology can be used to detect the base deletion mutations in FUT1 gene, which contributes to the analysis of molecular and genetic mechanism of para-Bombay blood group.

Subtherapeutic antibiotics have been widely used in agriculture since the 1950s, which can be accumulated in human body through various approaches and may have long-term consequences. However, there is limited information about the link between chronic subtherapeutic antibiotic exposure and the outcome of ischemic brain injury. Here we showed that long-term treatment with subtherapeutic chlortetracycline, penicillin or vancomycin, which were widely used in agriculture approved by US Food and Drug Administration (FDA), could impair EPC functions, reduce ischemic brain angiogenesis and aggravate cerebral ischemic injury and long-term stroke outcomes in mice. In addition, transplantated EPCs from chronic antibiotic-treated mice showed a lower therapeutic effect on cerebral ischemic injury reduction and local angiogenesis promotion compared to those from control mice, and EPCs from the donor animals could integrate into the recipient ischemic brain in mice. Furthermore, transplanted EPCs might exert paracrine effects on cerebral ischemic injury reduction in mice, which could be impaired by chronic antibiotic exposure. In conclusion, chronic subtherapeutic antibiotic exposure aggravated cerebral ischemic injury in mice, which might be partly attributed to the impairment of both EPC-mediated angiogenesis and EPCs' paracrine effects. These findings reveal a previously unrecognized impact of chronic subtherapeutic antibiotic exposure on ischemic injury., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

Trisomy 8 in myelodysplastic syndrome (MDS) plays an important role in concurrent intestinal Behçet's disease (BD) pathogenesis. Here, we reported a case of intestinal BD combined with MDS involving trisomy 8. A 48-year-old woman who has had a 20-year history of recurrent oral ulcer, perineal ulcer and iris, was diagnosed as MDS with trisomy 8 four years ago. She developed high fever and acute abdominal pain. Multiple ulcerative perforations in ileum and colon were found by endoscopy, meeting the criteria for intestinal BD. The patient was successfully treated with immunomodulatory drugs.

Elevated homocysteine levels are known to be a risk factor for congenital cardiac septal defects (CCSDs), but the mechanism underlying this effect is unknown. The genetic variants that were significantly associated with circulating homocysteine concentrations have been systematically identified through the genome-wide association studies of one-carbon core metabolites. To examine the role of the genome-wide significant homocysteine related variants in the occurrence of CCSDs, we investigated the association between these variants and CCSDs in Han Chinese populations. Five variants of the genome-wide significant homocysteine-related genes were selected for analysis in two stages of case-controlled studies with a total of 904 CCSD patients and 997 controls. SYT9 expression was detected in human cardiovascular tissue using qRT-PCR. The intronic variant rs11041321 of the SYT9 gene was associated with an increased risk of developing CCSDs in both the separate and combined case-controlled studies. Combined samples from the two stage cohorts had a significant elevation in CCSD risk for the T allele (OR = 1.43, P = 2.6 × 10 -6 ), CT genotype and TT genotype (CT: OR = 1.30, TT: OR = 2.21; P = 1 × 10 -4 ) compared with the wild-type C allele and CC genotype, respectively. The risky T allele carriers exhibited decreased SYT9 mRNA expression, compared with wild-type C allele carriers. The intronic SYT9 variant rs11041321, which exhibits a significant genome-wide association with circulating homocysteine, was associated with the occurrence of CCSDs. This finding helps to characterize the unexpected role of SYT9 in homocysteine metabolism and the development of CCSDs, which further highlighted the interplay of diet, genetics, and human birth defects. © 2017 IUBMB Life, 69(9):700-705, 2017., (© 2017 International Union of Biochemistry and Molecular Biology.)

The aim of the present study was to investigate the effects of epigallocatechin-3-gallate (EGCG) on the apoptosis of the human MCF-7 cancer cell line and the underlying mechanism. MCF-7 cells were divided into the control group and EGCG groups. The proliferation of MCF-7 cells in the two groups was determined using MTT and apoptosis was examined using flow cytometry. Western blot analysis and qRT-PCR were used to analyze P53 and Bcl-2 expression levels. The silencing effect of specific siRNA was evaluated using RT-PCR and western blot analysis. P53 and Bcl-2 expression levels were determined using western blot analysis in the si-P53, EGCG and EGCG-combined si-P53 groups. EGCG inhibited the proliferation of MCF-7 cells in a concentration-dependent manner and IC 50 was 37.681 mol/l. The apoptotic rates were 1.37 and 5.83% (t=8.9, p=0.0124) in the blank control and treatment groups after treatment with 30 µmol/l EGCG. The RT-qPCR and western blot results demonstrated that the effect of siRNA interference was evident. The expression of P53 in the EGCG-combined si-P53 group was higher than that of the si-P53 group, but lower than the EGCG group. The Bcl-2 expression level in the EGCG-combined si-P53 group was lower than that of the si-P53 group and higher than that of the EGCG group. In conclusion, EGCG suppressed the proliferation of human MCF-7 breast cancer cells and promoted apoptosis. In addition, the underlying mechanism may be related to the P53/Bcl-2 signaling pathway.

This experiment was mainly aimed to investigate the effect of Er-xian decoction on osteoporosis and the femur proteomics in ovariectomized rats with osteoporosis. The female SD rats were randomly divided into sham operation group, model group, Alendronate group (1 mg•kg⁻¹), Er-xian decoction group (in dose of 8 g•kg⁻¹) according to their weight. The rats in sham operation group and model group were gavaged with normal saline; the rats in Alendronate group were gavaged with the Alendronate at the dose of 1 mg•kg⁻¹ and the rats in Er-xian decoction group were gavaged with Er-xian decoction at the dose of 8 g•kg⁻¹, once a day for continuous 90 days. Then the femoral bone mineral density (BMD) was detected. The femoral bone proteins were detected by NanoLC-LTQ-Orbitrap system, identified by Protein Discovery software, and the intensity of differentially expressed proteins were quantitated by SIEVE software. The results showed that Er-xian decoction could significantly improve femoral BMD in ovariectomized rats. As compared with model group, 41 differentially expressed proteins whose variation trend was consistent with the sham operation group, were found in Er-xian decoction group, mainly including biological oxidation related protein, signal transduction pathway related protein, proteins involved in aliphatic acid metabolism, cytoskeleton related protein, proteins involved in energy metabolism, and proteins involved in glucose metabolism etc. The osteoporosis could be prevented and cured by Er-xian decoction. The differentially expressed proteins such as carbonic anhydrase 2 and integrin β1 may be the action targets for Er-xian decoction., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

Objective: To explore the protective role of basic fibroblast growth factor (bFGF) on attenuating hydrogen peroxide-induced injury in cultured rat myoblasts., Methods: Cultured rat myoblasts at growth phase were randomly divided into four groups ( n =6):control group (control), bFGF group (bFGF), model group(H 2 O 2 ) and the treatment group (bFGF + H 2 O 2 ). Model group was treated with 100 μ mol/L hydrogen peroxide for 4h. B-cell lymphoma-2 (Bcl-2) positive particles were detected by immunohistochemistry; Reactive oxygen species (ROS) and expression for Bcl-2 associated X protein (Bax), Bcl-2 and Cytochrome C (Cyt. C) fluorescence were observed under the invented microscope; Cyt. C and Poly ADP-ribose polymerase(PARP)protein were assessed by Western blot., Results: Compared with control group, the myoblats in the model group showed low expression of Bcl-2 positive particles, accompanied by high expression of ROS level and Cyt. C fuorescence ( P < 0.05); Compared with model group, bFGF enhanced Bcl-2 activity of the myoblasts, and significantly downregulated Cyt. C and PARP expression ( P < 0.05)., Conclusions: bFGF could attenuate oxidative injury of rat myoblasts induced by hydrogen peroxide, which mechanism might be related to enhanced Bcl-2 and reduced ROS, Cyt. C levels.

Objective: As a class of cholesterol-lowering drugs, statins have been reported to cause unexpected decrease in blood pressure (BP). However, most studies in this issue were subject to inadequate study design or very small sample size. The present study was designed to examine the BP-lowering effect of various statins., Methods: Here we retrieved 5.9 million clinical reports submitted to FDA Adverse Event Reporting System (FAERS) from 2004 to 2015. Meta-analysis was performed to estimate the overall reporting odds ratio (ROR) of hypotension adverse events concurrent with various statins (i.e., atorvastatin, simvastatin, and rosuvastatin)., Results: Comparing the reporting rate of hypotension event between statins and other drugs found that atorvastatin (pooled ROR = 1.26, adjusted p-value = 8.60 × 10 -4 ) and simvastatin (pooled ROR = 1.94, adjusted p-value = 4.16 × 10 -45 ) were significantly associated with reduction in BP. On the other hand, the association between rosuvastatin and hypotension was observed to be nonsignificant (adjusted p-value = 0.65)., Conclusion: To our knowledge, this is the first pooled analysis on large-scale data of adverse events to identify the BP-lowering effect of statins. The results will contribute to the development of novel statin-based antihypertensive therapies. In addition, the differential effects of individual statins can warrant subsequent research on the underlying mechanisms of BP control.

Genetic diversity of 23 Lasiodiplodia theobromae isolates on Morus alba and 6 isolates on Agave sisalana in Guangxi province, China, was studied by using random amplified polymorphic DNA and inter-simple sequence repeat molecular markers. Results of two molecular markers showed that the average percentage of polymorphic loci of all isolates was more than 93%. Both dendrograms of two molecular markers showed obvious relationship between groups and the geographical locations where those strains were collected, among which, the 23 isolates on M. alba were divided into 4 populations and the 6 isolates on A. sisalana were separated as a independent population. The average genetic identity and genetic distance of 5 populations were 0.7215, 0.3284 and 0.7915, 0.2347, respectively, which indicated that the genetic identity was high and the genetic distance was short in the 5 populations. Average value of the gene diversity index ( H ) and the Shannon's information index ( I ) of 29 isolates were significantly higher than 5 populations which showed that genetic diversity of those isolates was richer than the populations and the degree of genetic differentiation of the isolates was higher. The Gst and Nm of 29 isolates were 0.4411, 0.6335 and 0.4756, 0.5513, respectively, which showed that the genetic diversity was rich in those isolates.

Ultrasmall black phosphorus quantum dots (BPQDs) serve as the near-infrared light absorber and charge transfer layer in the photocathode of a bifacial n-type dye sensitized solar cell. Wideband light absorption and ≈20% enhancement in the light-to-electron efficiency are accomplished due to the fast carrier transfer and complementary light absorption by the BPQDs demonstrating that BP has large potential in photovoltaics., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Ethnopharmacological Relevance: Banxia (BX) is the root of Pinellia ternata (Thunb.) Berit. Its processed products, such as Jiang Banxia (JBX), have been clinically used in traditional Chinese medicine to treat vomiting, coughing, and inflammation. However, data for their safety for pregnant women are contradictory and confusing., Aim of the Study: To further explore the safety of BX, an ultra-performance liquid chromatography coupled with liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) metabolomics approach was used to evaluate the metabolic perturbation in pregnant rats caused by BX and JBX., Materials and Methods: Placenta and amniotic fluid samples were collected from control Sprague-Dawley pregnant rats and exposed to BX suspension and JBX decoction (1.434g/kg/day). Samples were analyzed using LC-MS and GC-MS. The acquired MS data of above samples were further subjected to multivariate data analysis, and the significantly altered metabolites were identified. The associated pathways were constructed using MetaboAnalyst 3.0., Results: The weight and histopathology of the placenta from each group of rats had no definite difference. However, we found 20 differential endogenous metabolites that changed significantly in the placenta and amniotic fluid samples. The alterations of identified metabolites indicated a perturbation in glycerophospholipid metabolism, amino acid metabolism, and carbohydrate metabolism in pregnant rats exposed to BX and JBX., Conclusion: In summary, this work suggested that oral administration of BX and JBX may induce disturbances in the intermediary metabolism in pregnant rats. This work contributes to further understanding the safety of BX and its processed products., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Objective: To observe the expressions of tumor necrosis factor alpha (TNF-α), matrix metalloproteinase 2 (MMP-2) and collagen in local skin tissue of pressure ulcer of rats, and to explore the possible mechanism of the pathogenesis of pressure ulcer., Methods: Forty male SD rats were divided into normal control group, 3 d compression group, 5 d compression group, 7 d compression group, and 9 d compression group according to the random number table, with 8 rats in each group. The rats in normal control group did not receive any treatment, whereas the rats in the latter 4 groups were established the deep tissue injury model (3 d compression group) and pressure ulcer model (the other 3 groups) on the gracilis muscle on both hind limbs using a way of cycle compression of ischemia-reperfusion magnet. The rats in 3 d compression group received only three cycles of compression, while the compressed skin of the rats in 5 d compression group, 7 d compression group, and 9 d compression group were cut through and received pressure to 5, 7 and 9 cycles after three cycles of compression, respectively. The rats in 3 d compression group were sacrificed immediately after receiving compression for 3 d (the rats in normal control group were sacrificed at the same time), and the rats in the other 3 groups were respectively sacrificed after receiving compression for 5, 7, and 9 d, and the skin tissue on the central part of gracilis muscle on both hind limbs were harvested. The morphology of the skin tissue was observed with HE staining. The expression of collagen fiber was observed with Masson staining. The expressions of collagen type Ⅳ and MMP-2 were detected by immunohistochemical method. The expressions of TNF-α and phosphorylated NF kappa B (NF-κB) were determined by Western blotting. Data were processed with one-way analysis of variance and LSD test., Results: (1) In normal control group, the skin tissue of rats was stratified squamous epithelium, with the clear skin structure, and there was no obvious infiltration of inflammatory cells. In 3 d compression group, the skin layers of rats were clear, with quite a few fibroblasts, and the inflammatory cells began to infiltrate. In 5 d compression group, 7 d compression group, and 9 d compression group, the epidermis of rats thickened, with the number of fibroblasts reduced, and the infiltration of inflammatory cells enhanced with the compressed time prolonging. (2) In normal control group, the collagen fibers in skin tissue of rats were arranged in order, with rich content. In 3 d compression group, the collagen fibers in skin tissue of rats were arranged orderly, with high expression level, which was similar to that in normal control group (P>0.05). In 5 d compression group and 7 d compression group, the collagen fibers in skin tissue of rats were arranged in disorder, with the expression level gradually reduced, which were significantly lower than that in normal control group (with P values below 0.01). In 9 d compression group, the expression of collagen fiber in skin tissue of rats was a little higher than that in 7 d compression group, but it was still significantly lower than that in normal control group (P<0.01). (3) The expressions of collagen type Ⅳ in skin tissue of rats in normal control group, 3 d compression group, 5 d compression group, 7 d compression group, and 9 d compression group were respectively 11.0±2.8, 9.0±1.7, 8.3±2.8, 5.1±1.8, and 5.4±1.2. The expression of collagen type Ⅳ in skin tissue of rats in 3 d compression group was similar to that in normal control group (P>0.05). The expressions of collagen type Ⅳ in skin tissue of rats in 5 d compression group, 7 d compression group, and 9 d compression group were significantly lower than that in normal control group (P<0.05 or P<0.01). The expression of MMP-2 in skin tissue of rats in 3 d compression group was similar to that in normal control group (P>0.05). The expressions of MMP-2 in skin tissue of rats in 5 d compression group, 7 d compression group, and 9 d compression group were significantly higher than that in normal control group (P<0.05 or P<0.01). (4) The expression of TNF-α in skin tissue of rats in normal control group was 0.48±0.11, and the expressions of TNF-α in skin tissue of rats in 3 d compression group, 5 d compression group, 7 d compression group, and 9 d compression group were respectively 0.84±0.08, 1.13±0.19, 1.34±0.16, and 1.52±0.23, which were all significantly higher than that in normal control group (with P values below 0.01). The expressions of phosphorylated NF-κB in skin tissue of rats in 3 d compression group and 9 d compression group were similar to that in normal control group (with P values above 0.05), and the expressions of phosphorylated NF-κB in skin tissue of rats in 5 d compression group and 7 d compression group were significantly higher than that in normal control group (P<0.05 or P<0.01)., Conclusions: The high expression of MMP-2 and reduction of collagen induced by inflammatory reaction mediated by the high expression of TNF-α in local skin tissue of pressure ulcer of rats may be one of the important reasons for the formation of pressure ulcer.

Pressure ulcer is a complex and significant health problem in long-term bedridden patients, and there is currently no effective treatment or efficient prevention method. Furthermore, the molecular mechanisms and pathogenesis contributing to the deep injury of pressure ulcers are unclear. The aim of the study was to explore the role of endoplasmic reticulum (ER) stress and Akt/GSK3β signaling in pressure ulcers. A model of pressure-induced deep tissue injury in adult Sprague-Dawley rats was established. Rats were treated with 2-h compression and subsequent 0.5-h release for various cycles. After recovery, the tissue in the compressed regions was collected for further analysis. The compressed muscle tissues showed clear cellular degenerative features. First, the expression levels of ER stress proteins GRP78, CHOP, and caspase-12 were generally increased compared to those in the control. Phosphorylated Akt and phosphorylated GSK3β were upregulated in the beginning of muscle compression, and immediately significantly decreased at the initiation of ischemia-reperfusion injury in compressed muscles tissue. These data show that ER stress may be involved in the underlying mechanisms of cell degeneration after pressure ulcers and that the Akt/GSK3β signal pathway may play an important role in deep tissue injury induced by pressure and ischemia/reperfusion.