Effects of HMGB1/TLR4 on secretion IL-10 and VEGF in human jaw bone-marrow mesenchymal stem cells

Abstract Objective: We aimed to investigate the regulatory effects of HMGB1/TLR4 signaling pathway on the expression of IL-10 and VEGF in human bone marrow mesenchymal stem cells. Methodology: Human JBMSCs were isolated and cultured. Then, HMGB1 was added into the JBMSCs culture medium, and the protein and mRNA expression levels of IL-10 and VEGF were assessed. Moreover, cells were pretreated with a specific TLR4 inhibitor (TAK-242), and the expression changes of IL-10 and VEGF were compared. Results: Compared with the control group, exposure to HMGB1 in human JBMSCs up-regulated TLR4, IL-10, and VEGF secretion at both protein and mRNA levels (P<0. 05). In addition, the increased expression of IL-10 and VEGF could be restrained in TAK-242 group compared with the HMGB1 group (P<0.05). Conclusions: The results indicated that HMGB1 activate TLR4 signaling pathway in Human JBMSCs, which plays a regulatory role in cytokines expression.

Knockdown of ACC1 promotes migration of esophageal cancer cell / 中华肿瘤杂志

Objective: To investigate the effect of acetyl-CoA carboxylase 1 (ACC1) knockdown on the migration of esophageal squamous cell carcinoma (ESCC) KYSE-450 cell and underlying mechanism. Methods: Lentiviral transfection was conducted to establish sh-NC control cell and ACC1 knocking down cell (sh-ACC1). Human siRNA HSP27 and control were transfected by Lipo2000 to get si-HSP27 and si-NC. The selective acetyltransferase P300/CBP inhibitor C646 was used to inhibit histone acetylation and DMSO was used as vehicle control. Transwell assay was performed to detect cell migration. The expression of HSP27 mRNA was examined by reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) and the expressions of ACC1, H3K9ac, HSP27 and epithelial-mesenchymal transition-related proteins E-cadherin and Vimentin were detected by western blot. Results: The expression level of ACC1 in sh-NC group was higher than that in sh-ACC1 group (P<0.01). The number of cell migration in sh-NC group was (159.00±24.38), lower than (361.80±26.81) in sh-ACC1 group (P<0.01). The protein expression levels of E-cadherin and Vimentin in sh-NC group were statistically significant compared with sh-AAC1 group (P<0.05). The migrated cell number in sh-NC+ si-NC group was (189.20±16.02), lower than (371.60±38.40) in sh-ACC1+ si-NC group (P<0.01). The migrated cell number in sh-NC+ si-NC group was higher than that in sh-NC+ si-HSP27 group (152.40±24.30, P<0.01), and the migrated cell number in sh-ACC1+ si-NC group was higher than that in sh-ACC1+ si-HSP27 group (P<0.01). The protein expression levels of E-cadherin and Vimentin in sh-NC+ si-NC group were significantly different from those in sh-ACC1+ si-NC and sh-NC+ si-HSP27 groups (P<0.01). The protein expression levels of E-cadherin and Vimentin in sh-ACC1+ si-NC group were significantly different from those in sh-ACC1+ si-HSP27 group (P<0.01). After 24 h treatment with C646 at 20 μmmo/L, the migrated cell number in sh-NC+ DMSO group was (190.80±11.95), lower than (395.80±17.10) in sh-ACC1+ DMSO group (P<0.01). The migrated cell number in sh-NC+ DMSO group was lower than that in sh-NC+ C646 group (256.20±23.32, P<0.01). The migrated cell number in sh-ACC1+ DMSO group was higher than that in sh-ACC1+ C646 group (87.80±11.23, P<0.01). The protein expressions of H3K9ac, HSP27, E-cadherin and Vimentin in sh-NC+ DMSO group were significantly different from those in sh-ACC1+ DMSO group and sh-NC+ C646 group (P<0.01). The protein expression levels of H3K9ac, HSP27, E-cadherin and Vimentin in sh-ACC1+ DMSO group were significantly different from those in sh-ACC1+ C646 group (P<0.01). Conclusion: Knockdown of ACC1 promotes the migration of KYSE-450 cell by up-regulating HSP27 and increasing histone acetylation.

Construction of NKG2D CAR-NK92 cells and its killing effect on multiple myeloma cells / 细胞与分子免疫学杂志

Objective This study aims to construct and identify the chimeric antigen receptor NK92 (CAR-NK92) cells targeting NKG2D ligand (NKG2DL) (secreting IL-15Ra-IL-15) and verify the killing activity of NKG2D CAR-NK92 cells against multiple myeloma cells. Methods The extracellular segment of NKG2D was employed to connect 4-1BB and CD3Z, as well as IL-15Ra-IL-15 sequence to obtain a CAR expression framework. The lentivirus was packaged and transduced into NK92 cells to obtain NKG2D CAR-NK92 cells. The proliferation of NKG2D CAR-NK92 cells was detected by CCK-8 assay, IL-15Ra secretion was detected by ELISA and killing efficiency was detected by lactate dehydrogenase (LDH) assay. The molecular markers of NKp30, NKp44, NKp46, the ratio of apoptotic cell population, CD107a, and the secretion level of granzyme B and perforin were detected using flow cytometry. In addition, the cytotoxic mechanism of NKG2D CAR-NK92 cells on the tumor was verified by measuring the degranulation ability. Moreover, after NKG2D antibody inhibited effector cells and histamine inhibited tumor cells, LDH assay was utilized to detect the effect on cell-killing efficiency. Finally, the multiple myeloma tumor xenograft model was constructed to verify its anti-tumor activity in vivo. Results Lentiviral transduction significantly increased NKG2D expression in NK92 cells. Compared with NK92 cells, the proliferation ability of NKG2D CAR-NK92 cells was weaker. The early apoptotic cell population of NKG2D CAR-NK92 cells was less, and NKG2D CAR-NK92 cells had stronger cytotoxicity to multiple myeloma cells. Additionally, IL-15Ra secretion could be detected in its culture supernatant. NKp44 protein expression in NKG2D CAR-NK92 cells was clearly increased, demonstrating an enhanced activation level. Inhibition test revealed that the cytotoxicity of CAR-NK92 cells to MHC-I chain-related protein A (MICA) and MICB-positive tumor cells was more dependent on the interaction between NKG2D CAR and NKG2DL. After stimulating NKG2D CAR-NK92 cells with tumor cells, granzyme B and perforin expression increased, and NK cells obviously upregulated CD107α. Furthermore, multiple myeloma tumor xenograft model revealed that the tumors of mice treated with NKG2D CAR-NK92 cells were significantly reduced, and the cell therapy did not sensibly affect the weight of the mice. Conclusion A type of CAR-NK92 cell targeting NKG2DL (secreting IL-15Ra-IL-15) is successfully constructed, indicating the effective killing of multiple myeloid cells.

SWOT analysis of HIV control strategy in key areas of Zhejiang Province / 预防医学

Objective @#To analyze the problems in the AIDS control strategy in key areas of Zhejiang Province, so as to provide insights into the improvement of the control strategy.@*Methods @#The AIDS control data were collected from 10 key counties (districts) in Zhejiang Province, and the AIDS control strategy was comprehensively evaluated using a SWOT analysis.@*Results @#The strengths of the AIDS control strategy in key counties (districts) of Zhejiang Province included distinct working objectives, well-organized leadership, and effective control measures, the weaknesses included large number of HIV-infected cases, high burden of disease, difficulty in management of AIDS transmission and insufficient AIDS control capability, and the opportunities included the AIDS control in key counties (districts) conforming to the current status of AIDS control, strong support of innovative strategies and technical support from professional teams, while the threats included insufficient working mechanisms for AIDS control, the gap between the effectiveness of AIDS control and the target goal and unverified scientific evidence of the control strategy. Supported policies should be fully used, working mechanisms need to be improved, control strategies need to be innovated, and assessments need to be implemented for AIDS control in key counties (districts). @*Conclusions @#There are both opportunities and challenges for AIDS control in key counties (districts) of Zhejiang Province. Optimization of the working mechanisms, promotion of precision interventions, and search for repeatable control strategy in other disease-affected regions are required for AIDS control.

Effect of thermophilic bacterium HB27 manganese superoxide dismutase in a rat model of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) / 亚洲男科学杂志(英文版)

We investigated the therapeutic effects of superoxide dismutase (SOD) from thermophilic bacterium HB27 on chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and its underlying mechanisms. A Sprague-Dawley rat model of CP/CPPS was prepared and then administered saline or Thermus thermophilic (Tt)-SOD intragastrically for 4 weeks. Prostate inflammation and fibrosis were analyzed by hematoxylin and eosin staining, and Masson staining. Alanine transaminase (ALT), aspartate transaminase (AST), serum creatinine (CR), and blood urea nitrogen (BUN) levels were assayed for all animals. Enzyme-linked immunosorbent assays (ELISA) were performed to analyze serum cytokine concentrations and tissue levels of malondialdehyde, nitric oxide, SOD, catalase, and glutathione peroxidase. Reactive oxygen species levels were detected using dichlorofluorescein diacetate. The messenger ribonucleic acid (mRNA) expression of tissue cytokines was analyzed by reverse transcription polymerase chain reaction (RT-PCR), and infiltrating inflammatory cells were examined using immunohistochemistry. Nuclear factor-κB (NF-κB) P65, P38, and inhibitor of nuclear factor-κBα (I-κBα) protein levels were determined using western blot. Tt-SOD significantly improved histopathological changes in CP/CPPS, reduced inflammatory cell infiltration and fibrosis, increased pain threshold, and reduced the prostate index. Tt-SOD treatment showed no significant effect on ALT, AST, CR, or BUN levels. Furthermore, Tt-SOD reduced inflammatory cytokine expression in prostate tissue and increased antioxidant capacity. This anti-inflammatory activity correlated with decreases in the abundance of cluster of differentiation 3 (CD3), cluster of differentiation 45 (CD45), and macrophage inflammatory protein 1α (MIP1α) cells. Tt-SOD alleviated inflammation and oxidative stress by reducing NF-κB P65 and P38 protein levels and increasing I-κBα protein levels. These findings support Tt-SOD as a potential drug for CP/CPPS.

Impact of bicuspid aortic valve or tricuspid aortic valve on hemodynamics and left ventricular reverse remodeling in patients after transcatheter aortic valve replacement / 中华心血管病杂志

Objective: To compare the impact of bicuspid aortic valve (BAV) or tricuspid aortic valve (TAV) on hemodynamics and left ventricular reverse remodeling after transcatheter aortic valve replacement (TAVR). Methods: We retrospectively analyzed the clinical data of patients who underwent TAVR in our hospital from January 2019 to March 2021. Patients were divided into BAV group and TAV group according to aortic contrast-enhanced CT. Each patient was followed up by N-terminal pro B-type natriuretic peptide (NT-proBNP) and echocardiography at four time points, namely before TAVR, 24 hours, 1 month and 6 months after TAVR. Echocardiographic data, including mean pressure gradient (MPG), aortic valve area (AVA), left ventricular ejection fraction (LVEF), left ventricle mass (LVM) and LV mass index (LVMi) were evaluated. Results: A total of 41 patients were included. The age was (75.0±8.6) years, and male patients accounted for 53.7%. There were 19 BAV patients and 22 TAV patients in this cohort. All patients undergoing TAVR using a self-expandable prosthesis Venus-A valve. MPG was (54.16±21.22) mmHg(1 mmHg=0.133 kPa) before TAVR, (21.11±9.04) mmHg at 24 hours after TAVR, (18.84±7.37) mmHg at 1 month after TAVR, (17.68±6.04) mmHg at 6 months after TAVR in BAV group. LVEF was (50.42±13.30)% before TAVR, (53.84±10.59)% at 24 hours after TAVR, (55.68±8.71)% at 1 month after TAVR and (57.42±7.78)% at 6 months after TAVR in BAV group. MPG and LVEF substantially improved at each time point after operation, and the difference was statistically significant (all P<0.05) in BAV group. MPG in TAV group improved at each time point after operation, and the difference was statistically significant (all P<0.05). LVMi was (164.13±49.53), (156.37±39.11), (146.65±38.84) and (134.13±39.83) g/m2 at the 4 time points and the value was significantly reduced at 1 and 6 months post TAVR compared to preoperative level(both P<0.05). LVEF in the TAV group remained unchanged at 24 hours after operation, but it was improved at 1 month and 6 months after operation, and the difference was statistically significant (all P<0.05). LVMi in TAV group substantially improved at each time point after operation, and the difference was statistically significant (all P<0.05). NT-proBNP in both two groups improved after operation, at 1 month and 6 months after operation, and the difference was statistically significant (all P<0.05). MPG in TAV group improved better than in BAV group during the postoperative follow-up (24 hours after TAVR: (11.68±5.09) mmHg vs. (21.11±9.04) mmHg, P<0.001, 1 month after TAVR: (10.82±3.71) mmHg vs. (18.84±7.37) mmHg, P<0.001, 6 months after TAVR: (12.36±4.42) mmHg vs. (17.68±6.04) mmHg, P=0.003). There was no significant difference in NT-proBNP between BAV group and TAV group at each time point after operation (all P>0.05). There was no significant difference in paravalvular regurgitation and second prosthesis implantation between the two groups (all P>0.05). Conclusions: AS patients with BAV or TAV experience hemodynamic improvement and obvious left ventricular reverse remodeling after TAVR, and the therapeutic effects of TAVR are similar between BAV and TAV AS patients in the short-term post TAVR.

The construction of comprehensive stroke prevention and control system requires attention to the precise policies of young stroke / 中华预防医学杂志

Youth is the core force of social and economic development, once the occurrence of youth stroke will place a heavy burden on society and family. However, the prevention and control of stroke in China is mainly aimed at middle-aged and elderly patients, the part of young stroke is relatively easy to be ignored. This article focuses on the characteristics, research progress, prevention and control status of young stroke, pointing out the importance of centering on the prevention and treatment of young stroke. At the same time, it hopes that the industry can concentrate on the prevention and treatment of young stroke, making precise policies in the future, and developing secondary prevention guidelines for the causes or risk factors of young stroke, so as to improve comprehensive stroke prevention and control system. On this basis, the health level of the whole population will be improved, and the life expectancy of residents will be extended, thus promoting the realization of the strategic goal of "Healthy China 2030".

The disease burden of degenerative mitral valve disease in the Chinese population from 1990 to 2019 / 中华心血管病杂志

Objective: To explore the trend of disease burden of degenerative mitral valve disease (DMVD) in the Chinese population from 1990 to 2019. Methods: Based on the 2019 Global Burden of Disease database (GBD 2019), the number of patients, the number of new cases, the number of deaths, the disability-adjusted life years (DALY) as well as the prevalence, incidence and death rate, DALY rate and their age-standardized rates were used to analyze the trend of the burden of DMVD in the Chinese population from 1990 to 2019. Results: In 2019, the number of patients, the number of new cases, and the number of deaths with DMVD in China were 461.2, 27.0 and 0.129 ten thousand, respectively, which increased by 209.0%, 199.1% and 13.2% when compared with 1990. In 2019, the age-standardized prevalence, incidence and death rate were 228.1/100 000, 12.7/100 000 and 0.075/100 000, respectively. Compared with 1990, the change of the age-standardized prevalence, incidence and death rate were 32.6%, 42.8% and -54.1%, respectively. In addition, the 2019 data also showed that the age-standardized prevalence and incidence were higher in females than in males (the age-standardized prevalence was 190.1 (181.5-198.9)/100 000 for males and 262.0 (250.3-273.9)/100 000 for females); the age-standardized incidence was 10.5 (10.0-11.0)/100 000 for males and 14.9 (14.3-15.6)/100 000 for females. The age group with the largest number of DMVD patients was 65 to 69 years old, and the highest incidence was 60 to 64 years old. From 1990 to 2019, DALY caused by DMVD showed an upward trend in China, from 46 439 person-years in 1990 to 69 402 person-years in 2019, with an increase of 49.4%. While the age-standardized DALY rate continued to decline, from 5.5/100 000 in 1990 to 3.8/100 000 in 2019, with a drop of 30.8%. The DALY and the age-standardized DALY rate of females were always higher than that of males in different years. Conclusion: From 1990 to 2019, DALY and the age-standardized prevalence and incidence of DMVD in China shows an increasing trend, and the disease burden caused by DMVD is severe in China.

Research progress in the prevention and treatment of diabetic retinopathy based on retinal neurovascular unit damage and its coupling imbalance / 国际眼科杂志(Guoji Yanke Zazhi)

Diabetic retinopathy(DR), one of the common complications of diabetes, is a major cause of blindness. Traditionally, DR has been considered primarily a microvascular disease, and as research has progressed, it is now believed that disruption of the neuro-glia-vascular unit(NVU)and imbalance in its coupling mechanisms(coupling)play a key role in the early onset of DR. Understanding the cellular and molecular basis of NVU and how diabetes alters normal cellular communication and disrupts the cellular environment is important for the early prevention and treatment of DR. This paper summarizes the retinal NVU and its involvement in the molecular mechanism of DR pathogenesis, DR treatment based on retinal NVU repair, and discusses the future prospects and problems of DR.

circ_0091579/miR-330-3p/RNF126 axis affects the proliferation, invasion and apoptosis of colorectal cancer LoVo cells / 中国肿瘤生物治疗杂志

@#目的：探讨环状 RNA circ_0091579 作为分子海绵吸附 miR-330-3p 介导环指蛋白 126（ring finger protein 126， RNF126）对结直肠癌（colorectal cancer，CRC）细胞增殖、凋亡、侵袭的影响。方法：选取 2019 年 2 月至 2020 年 5 月在大理大学 第一附属医院行手术治疗的 60 例 CRC 患者的癌组织和癌旁组织。构建 circ_0091579、miR-330-3p 的过表达或敲减的 CRC LoVo 细胞，qPCR 检测 CRC 组织和细胞中 circ_0091579、miR-330-3p 和 RNF126 的表达；MTT、Transwell、流式细胞术分别检测 细胞的增殖、侵袭、凋亡情况；生物信息学方法预测 circ_0091579 和 miR-330-3p、miR-330-3p 和 RNF126 的靶向关系并用双荧光 素酶报告实验和 RNA 免疫沉淀实验验证。结果：CRC 组织和多种细胞（HCT116、SW620、CW-2、LoVo 细胞）中，circ_0091579 和 RNF126 均高表达、miR-330-3p 均低表达（均 P<0.05）。敲减 circ_0091579 可以抑制 LoVo 细胞的增殖、侵袭而促进其凋亡 （均 P<0.05），但该影响在加入 miR-330-3p 后被逆转；过表达 miR-330-3p 使 LoVo 细胞增殖和侵袭能力减弱但凋亡程度加强 （均 P<0.05），该影响在加入 RNF126 后被抵消。circ_0091579、miR-330-3p 和 RNF126 之间存在靶向作用关系。结论：circ_0091579 通过 miR-330-3p/RNF126 轴促进 LoVo 细胞增殖、迁移和侵袭而抑制其凋亡。

Study on Improvement Effect and Mechanism of MEBO on LPS-induced Injury of Rat Skin Fibroblasts / 中国药房

OBJECTIVE：To study the improvement effect and mechanism of MEBO on lipopolysaccharide （LPS）-induced injury of rat skin fibroblasts. METHODS ：Skin fibroblasts of rats were divided into control group ，LPS group （5 μg/mL）， Kangfuxin solution group （positive control ，5 μg/mL LPS+1.25％ Kangfuxin solution ）and MEBO group （5 μg/mL LPS+0.6 mg/mL MEBO），with 6 wells in each group. Inflammatory injury cell model was induced by LPS （except for control group ）. After a certain period of cultivation ，the cell survival rate and cell migration rate were detected in each group. The contents of TNF-α and IL-6 in cell supernatant was detected. The localization and fluorescence intensity of IL- 6 protein were detected. The protein expression of PTEN ，p-p65，TNF-α，IL-6，PI3K and Akt in the fibroblasts were also determined. RESULTS ：Compared with control group ，survival rate of the fibroblasts was increased significantly in LPS group ，while cell migration was decreased significantly；the contents of TNF-α and IL-6 in cell supernatant as well as relative protein expression of PTEN ，p-p65，TNF-α， IL-6 and PI 3K were increased significantly （P＜0.05 or P＜0.01）；IL-6 protein mainly expressed in the cytoplasm ，and the fluorescence intensity was enhanced. Compared with LPS group ，survival rate of the fibroblasts was decreased significantly in Kangfuxin solution group and MEBO group ，while migration rate was increased significantly ；the contents of TNF-α and IL-6， relative protein expression of PTEN ，p-p65，TNF-α，IL-6（except for Kangfuxin solution group ），PI3K and Akt （except for Kangfuxin solution group ） were decreased significantly （P＜0.05 or P＜0.01），while fluorescence intensity of IL- 6 protein decreased；relative protein expression of TNF-α，IL-6，PI3K and Akt in MEBO group were significantly lower than Kangfuxin solution group （P＜0.05 or P＜0.01）. CONCLUSIONS ：MEBO can inhibit the proliferation of LPS-induced skin fibroblasts ， reduce the level of inflammatory factors and the intensity of inflammatory reaction ， which may be related to the jiang- down-regulation of PTEN/NF-κB，PI3K/Akt signaling pathway.

Application of single incision plus one port laparoscopic surgery in radical right hemicolon cancer surgery / 中华胃肠外科杂志

Objective: To investigate the feasibility and advantages of the SILS+1 technique in the radical right hemicolectomy, by comparing the short-term efficacy, postoperative recovery of intestinal function, and stress and inflammatory response of patients with right-sided colon cancer undergoing the conventional 5-hole laparoscopic technique or the single incision plus one port laparoscopic surgery (SILS+1). Methods: A retrospective cohort study was performed. Thirty-five patients with right-sided colon cancer undergoing SILS+1 surgery at Department of Gastrointestinal Surgery of Fujian Cancer Hospital from January 2018 to September 2020 were enrolled in the SILS+1 group. Then a total of 44 patients who underwent completely 5-hole laparoscopic right hemicolectomy at the same time were selected as the conventional laparoscopic surgery (CLS) group. The intraoperative observation indexes (operative time, intraoperative blood loss, and incision length) and postoperative observation indexes (time to ambulation after surgery, time to flatus, pain score in the first 3 days after surgery, hospitalization days, number of lymph node dissections, postoperative complication morbidity, and postoperative total protein, albumin and C-reaction protein) were compared between the two groups. Results: There was no conversion to laparotomy or laparoscopic-assisted surgery in both groups. All the patients successfully completed radical right hemicolectomy under total laparoscopy. There were no statistically significant differences in gender, age, body mass index or tumor stage between the two groups (all P>0.05). Compared with the CLS group, the SILS+1 group had shorter incision length [(5.1±0.6) cm vs. (8.5±4.1) cm, t=4.124, P=0.012], shorter time to the first ambulation (median: 27.6 h vs. 49.3 h, Z=4.386, P=0.026), and shorter time to the first flatus (median:42.8 h vs. 63.2 h, Z=13.086, P=0.012), lower postoperative pain score [postoperative 1-d: 2.0 ± 1.1 vs. 3.6 ± 0.9; postoperative 2-d: 1.4 ± 0.2 vs. 2.9±1.4; postoperative 3-d: 1.1 ± 0.1 vs. 2.3±0.3, F=49.128, P=0.003), shorter postoperative hospital stay [(9.1 ± 2.7) d vs. (11.2 ± 2.2) d, t=3.267,P=0.001], which were all statistically significant (all P<0.05). On the second day after surgery, as compared to CLS group, SILS+1 group had higher total protein level [(59.7±18.2) g/L vs. (43.0±12.3) g/L, t=2.214, P=0.003], higher albumin level [(33.6±7.3) g/L vs. (23.7±5.4) g/L, t=5.845, P<0.001], but lower C-reactive protein level [(16.3 ± 3.1) g/L vs. (63.3 ± 4.5) g/L, t=4.961, P<0.001], which were all statistically significant. There were no significant differences in the operative time, intraoperative blood loss, number of harvested lymph node, number of metastatic lymph node, and postoperative complication morbidity (all P>0.05). Conclusions: The SILS+1 technique has good operability and potential for popularization. Under the premise of radical resection, this technology not only reduces incision number and postoperative physical pain, but also speeds up postoperative recovery and shortens hospital stay.

In vivo study of liposome-modified polyetheretherketone implant on bacteriostasis and osseointegration / 北京大学学报(医学版)

OBJECTIVE@#To develop dexamethasone plus minocycline-loaded liposomes (Dex/Mino liposomes) and apply them to improve bioinert polyetheretherketone (PEEK) surface, which could prevent post-operative bacterial contamination, enhance ossification for physiologic osseointegration, and finally reduce implant failure rates.@*METHODS@#Dex/Mino liposomes were covalently grafted onto the PEEK surface using polydopamine (pDA) coating as a medium. Confocal laser scanning microscopy was used to confirm the binding of fluorescently labeled liposomes onto the PEEK substrate, and a microplate reader was used to semiquantitatively measure the average fluorescence intensity of fluorescently labeled liposome-decorated PEEK surfaces. Moreover, the mouse subcutaneous infection model and the beagle femur implantation model were respectively conducted to verify the bioactivity of Dex/Mino liposome-modified PEEK in vivo, by means of micro computed tomography (micro-CT) and hematoxylin and eosin (HE) staining analysis.@*RESULTS@#The qualitative and quantitative results of fluorescently labeled liposomes showed that, the red fluorescence intensity of the PEEK-pDA-lipo group was stronger than that of the PEEK-NF-lipo group (P < 0.05); the liposomes were successfully and uniformly decorated on the PEEK surfaces due to the pDA coating. After mouse subcutaneous implantation of PEEKs for 24 hours, HE staining results showed that the number of inflammatory cells in the PEEK-Dex/Mino lipo group were lower than that in the inert PEEK group (P < 0.05), indicating a lower degree of infection in the test group. These results suggested that the Mino released from the liposome-functionalized surface provided an effective bacteriostasis in vivo. After beagle femoral implantation of PEEK for 8 weeks, micro-CT results showed that the PEEK-Dex/Mino lipo group newly formed more continuous bone when compared with the inert PEEK group; HE staining results showed that more new bones were formed in the PEEK-Dex/Mino lipo group than in the inert PEEK group, which were firmly bonded to the functionalized PEEK surface and extended along the PEEK interface. These results suggested that the Dex released from the liposome-functionalized surface induced effective bone regeneration in vivo.@*CONCLUSION@#Dex/Mino liposome modification enhanced the bioactivity of inert PEEK, the functionalized PEEK with enhanced antibacterial and osseointegrative capacity has great potential as an orthopedic/dental implant material for clinical application.

Forsythiae Fructus inhibits melanoma growth through activating MAPKs/Nrf2/HO-1 signaling and modulating glycerophospholipid metabolism / 中国药理学与毒理学杂志

OBJECTIVE Forsythiae Fructus (Lianqiao) is a typical heat-clearing and detoxicating traditional Chinese medicine (TCM) herb, which has been traditionally used for treating cancer according to TCM theory. However, the under?lying mechanism has not been fully explained. METHODS In this study, we investigated the antitumor effect of Forsyth?iae Fructus aqueous extract (FAE) on B16-F10 melanoma. RESULTS FAE strongly inhibited the tumor growth and metastasis formation in B16-F10 melanoma transplanted mice. The survival time of tumor-bearing mice was also signifi?cantly prolonged by FAE. The levels of ROS, MDA, TNF-α and IL-6 decreased, while GSH increased in the FAE treat?ment group, indicating FAE possesses strong anti-oxidative and anti-inflammatory activity. Western blotting analysis demonstrated that antioxidant proteins Nrf2 and HO-1, tumor suppressors P53 and p-PTEN, and the MAPK pathways in tumor tissues were upregulated by FAE treatment. Serum metabolomics analysis further uncovered that 17 metabolites mostly involving in glycerophospholipid metabolism were correlated with the antitumor effect of FAE. Notably, several lysophosphatidylcholines (LysoPCs) significantly decreased in tumor model group, while FAE treatment restored the changes of these phospholipids to about normal condition. LysoPC acyltransferase 1 (LPCAT1) and autotaxin (ATX) highly expressed in melanoma and markedly downregulated by FAE were believed to be responsible for this modulation. CONCLUSION FAE exhibites strong antitumor activity against B16-F10 melanoma through activating MAPKs/Nrf2/HO-1 mediated anti-oxidation and anti-inflammation and modulating glycerophospholipid metabolism via downregulating LPCAT1 and ATX. Besides, it is suggested that serum LysoPCs could be potential biomarkers for the diagnosis and prog?nosis of melanoma.

Molecular epidemiology of Listeria monocytogenes isolated from ready-to-eat food in 2017 in China / 中华预防医学杂志

To analyze the molecular characteristics of strains from ready-to eat food in China. A total of 239 strains isolated from ready-to-eat food in 2017, all strains underwent whole-genome sequencing (WGS) , and comparisons uncovered population structure derived from lineages, clonal complex, serogroups, antimicrobial susceptibility and virulence, which were inferred in silico from the WGS data. Core genome multilocus sequence typing was used to subtype isolates. All strains were categorized into three different lineages, lineage Ⅱ was the predominant types in food, and IIa was the main serogroups. CC8, CC101 and CC87 were the first three prevalent CCs among 23 detected CCs, accounting for 49.4%. Only 4.6% (11 isolates) of tested strains harbored antibiotic resistance genes, which were mostly trimethoprim genes (7 isolates, 2.9%). All strains were positive for LIPI-1, and only a part of strains harbored LIPI-3 and LIPI-4, accounting for 13.8% (33 isolates) and 14.2% (34 isolates), respectively. ST619 carried both LIPI-3 and LIPI-4. 51.5% (123 isolates) of strains carried SSI-1, and all CC121 strains harbored SSI-2. Different lineages, serogroups and CCs can be separated obviously through cgMLST analysis, and 24 sublineages were highly concordant with CCs. Ⅱa was the main serogroups in ready-to-eat food isolates in China; CC8, CC101 and CC87 were the prevalent CCs, and CC87 isolates was hypervirulent isolates, cgMLST method can be adopted for prospective foodborne disease surveillance and outbreaks detection.

Comparison of short-term and long-term outcomes between thoracoscopic pneumonectomy and open pneumonectomy for non-small cell lung cancer: a study based on propensity score matching / 中华外科杂志

To compare the short-term and long-term results of thoracoscopic and open pneumonectomy for non-small cell lung cancer. The clinical data of patients with non-small cell lung cancer who underwent pneumonectomy in the Department of Thoracic Surgery, Qingdao University Hospital from January 2008 to December 2016 were collected. Totally 142 patients (55 in the thoracoscopic group and 87 in the open group) were included in the study. A total of 29 pairs of patients were successfully matched by propensity score matching (PSM). Perioperative outcomes and overall survival were compared between the two groups using test, χ(2) test, Kaplan-Meier curve and Log-rank test, respectively. Camparion with open group, the thoracoscopic group had longer operative time ((209.7±70.2) minutes . (171.3±43.5) minutes, 2.50, 0.02), more mediastinal lymph node dissection ((): 17(9) . 11(10), =388, 0.02) and shorter postoperative hospital stay (7.0(3.5) . 9.0(3.0), =285, 0.03). There was no significant difference in estimated blood loss, postoperative drainage time, dissected lymph node number, dissected lymph node station and perioperative complications. After PSM, there were no signifificant differences found in 3-year survival (71.4% . 48.1%, 0.10) and 3-year disease-free survival (67.4% . 47.2%, 0.13) between the two groups. Thoracoscopic pneumonectomy is safe and feasible for the treatment of non-small cell lung cancer with more mediastinal lymph node dissection and accelerating recovery, and equivalent long-term prognosis when compared with open approach.

High salt-induced weakness of anti-oxidative function of natriuretic peptide receptor-C and podocyte damage in the kidneys of Dahl rats / 中华医学杂志(英文版)

BACKGROUND@#Atrial natriuretic peptide (ANP) and its natriuretic peptide receptors A (NPR-A) and C (NPR-C) are involved in the regulation of physiological and pathophysiological process of blood pressure. The present study aimed to determine the role of NPR-C in the development of salt-sensitive hypertension.@*METHODS@#The Dahl salt-sensitive (DS) and salt-resistant (DR) rats were used in this study. Animals were matched according to their age and weight, and then placed on either a high-salt (HS, 8%) or a normal-salt (NS, 0.4%) diet for 6 weeks randomly using random number table. The systolic blood pressure (SBP), plasmatic sodium concentration (PLNa), urinary sodium excretion (UVNa), and serum creatinine concentration (Scr) were measured. The concentration of ANP in blood and tissues (heart and kidney) was detected by enzyme-linked immunosorbent assay. The expression of ANP, NPR-A, and NPR-C in kidney was evaluated with western blot analysis. Regarding renal redox state, the concentration changes in malondialdehyde (MDA), lipofuscin, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox), and nitric oxide synthase (NOS) in kidney were detected by a spectrophotometric method. The kidney damage was evaluated using pathological techniques and the succinodehydrogenase (SDHase) examination. Furthermore, after an intra-peritoneal injection of C-atrial natriuretic peptide (ANP)4-23 (C-ANP4-23), an NPR-C receptor agonist, the SBP, biochemical values in blood and urine, and renal redox state were evaluated. The paired Student's t test and analysis of variance followed by the Bonferroni test were performed for statistical analyses of the comparisons between two groups and multiple groups, respectively.@*RESULTS@#The baseline SBP in all groups was within the normal range. At the end of the 6-week experiment, HS diet significantly increased the SBP in DS rats from 116.63 ± 2.90 mmHg to 162.25 ± 2.15 mmHg (t = -10.213, P  0.05). The significant increase of PLNa, UVNa, and Scr related to an HS diet was found in both DS and DR rats (all P < 0.05). However, significant changes in the concentration (t = -21.915, P < 0.001) and expression of renal ANP (t = -3.566, P = 0.016) and the expression of renal NPR-C (t = 5.864, P = 0.002) were only observed in DS hypertensive rats. The significantly higher desmin immunochemical staining score (t = -5.715, P = 0.005) and mitochondrial injury score (t = -6.325, P = 0.003) accompanied by the lower SDHase concentration (t = 3.972, P = 0.017) revealed mitochondrial pathologic abnormalities in podocytes in DS rats with an HS diet. The distinct increases of MDA (t = -4.685, P = 0.009), lipofuscin (t = -8.195, P = 0.001), and Nox (t = -12.733, P < 0.001) but not NOS (t = -0.328, P = 0.764) in kidneys were also found in DS hypertensive rats. C-ANP4-23 treatment significantly decreased the SBP induced by HS in DS rats (P < 0.05), which was still higher than NS groups with the vehicle or C-ANP4-23 treatment (P < 0.05). Moreover, the HS-induced increase of MDA, lipofuscin, Nox concentrations, and Nox4 expression in DS rats was significantly attenuated by C-ANP4-23 treatment as compared with those with HS diet and vehicle injection (all P < 0.05).@*CONCLUSIONS@#The results indicated that the renal NPR-C might be involved in the salt-sensitive hypertension through the damage of mitochondria in podocytes and the reduction of the anti-oxidative function. Hence, C-ANP4-23 might serve as a therapeutic agent in treating salt-sensitive hypertension.

Value of Head and Neck CT Angiography in the Clinical Evaluation of Intraoperative Bleeding Volume of Carotid Body Tumours / 中国医学科学院学报

To investigate the value of head and neck CT angiography(CTA)in the evaluation of intraoperative hemorrhage of carotid body tumours. Head and neck CTA images of 36 patients with carotid body tumours confirmed by pathology were retrospectively analyzed.Patients were divided into two groups based on the intraoperative bleeding volume:<500 ml and≥500 ml groups.The patient's age,sex,Shamblin classification,size of the lesion,number of blood supply arteries,course of the disease,plain scan,and enhanced CT value between two groups were compared and analyzed.Logistics regression equation was established based on the CTA parameters with significant differences between the two intraoperative bleeding volume groups,and combined parameter was acquired.The receiver operating characteristic curve was established based on CTA single and combined parameters. The bleeding volume during the operation of carotid body tumors was significantly correlated with the age of patients(=0.019),the maximum diameter of tumours on axial images(=0.003),the maximum upper and lower diameters(=0.004),Shamblin classification(=0.012),and number of blood supply arteries(<0.001).The area under the receiver operating characteristic curve of the number of feeding arteries,the maximum diameter of axial images,maximum upper and lower diameters,Shamblin classification,and combined parameters were 0.865,0.781,0.806,0.766,and 0.927,respectively.When the optimal critical value was 0.408,the Youden index was 0.794,and the corresponding accuracy,sensitivity,and specificity were 0.919,0.909,and 0.923,respectively. Preoperative head and neck CTA can be used to evaluate the intraoperative blood loss.Combined parameters has the best diagnostic performance compared with single parameters.

Advances on research of physical environment affecting stem cell differentiation in ligament tissue engineering / 中国骨伤

Ligament tissue engineering is currently a novel approach to the treatment of ligament injury, which can replace the deficiency of autografts. Ligament tissue engineering consists of four basic elements:seed cells, nanoscaffolds, growth factors, and mechanical stimulation. At present, the main problem in ligament tissue engineering is how to control seed cells to ligament cells more controllly. The study found that each physical property of the natural bio ligament and mechanical stimulation (uniaxial stretching) plays an important role in the differentiation of stem cells into ligament cells. Therefore, the design of nanofiber scaffolds must consider the elastic modulus of the material and the material. Structure(material arrangement, porosity and diameter, etc.), elastic modulus and material structure in different ranges will guide cells to differentiate into different lineages. Considering that the ligament is the main force-bearing tissue of the human body, mechanical stimulation is also essential for stem cell differentiation, especially uniaxial stretching, which best meets the stress of the ligament in the body. A large number of studies have found the frequency and amplitude of stretching. And time will also lead the cells to differentiate in different directions. RhoA/ROCK plays a regulatory role in cytoskeletal remodeling and cell differentiation. It is also found that RhoA/ROCK protein participates in the process of nanofiber arrangement and uniaxial stretching to guide stem cells to differentiate into ligament cells, specifically how to influence stem cell differentiation. It is not clear at present that understanding the effects of physical properties on stem cell differentiation and understanding the mechanism of action of RhoA/ROCK protein will provide a new theoretical basis for further optimization of ligament tissue engineering.

Exploration into the simplex reinforcing-reducing manipulation of acupuncture / 中国针灸

Four controversial types of simplex reinforcing-reducing manipulation of acupuncture and their possible meanings were summarized to explore several key elements of reinforcing-reducing manipulation of acupuncture, in addition, the simplex reinforcing-reducing manipulation of acupuncture was classified by single factor. It is concluded that the definition of simplex reinforcing-reducing manipulation of acupuncture should try not to include other non-manipulative elements. According to single factor, it can be divided into: needle-oriented reinforcing-reducing manipulation, twisting reinforcing-reducing manipulation, lifting and interpolating reinforcing-reducing manipulation, fast and slow reinforcing-reducing manipulation, breathing reinforcing-reducing manipulation, opening and closing reinforcing-reducing manipulation. In addition, after considering the effect and principle of number reinforcing-reducing manipulation, it can be considered.