Objective:To investigate the effect of tripartite motif-containing protein 59 (TRIM59) on glucose metabolism in macrophages and its role in regulating hypoxia-inducible factor-1α (HIF-1α)/IL-10 axis in macrophages under inflammatory conditions.Methods:The differentially expressed genes between macrophages with high expression of TRIM59 and control cells transfected with empty TRIM59 plasmid were analyzed by GO and KEGG. The expression of HIF-1α by RAW264.7 macrophages with high expression of TRIM59 was detected at different time points after lipopolysaccharide (LPS) stimulation by RT-qPCR and Western blot. Bone marrow was isolated from TRIM59-cKO and TRIM59 flox/flox mice and induced to differentiate into bone marrow-derived macrophages (BMDMs). These BMDMs were stimulated with LPS and the supernatants of cell culture were collected at 3, 6, 12 and 24 h after stimulation to detect IL-10 level by ELISA. In addition, mouse models of cecal ligation and puncture (CLP) were established, and bronchoalveolar lavage fluid (BALF) samples were collected at the same time points to detect IL-10 level by ELISA. Histopathological changes in lung tissues were observed after HE staining. Results:There was a significant change in glucose metabolism-related genes in macrophages with high expression of TRIM59, and the content of lactic acid increased significantly. Compared with the control group, the expression of HIF-1α at mRNA level in BMDMs from TRIM59-cKO mice decreased after LPS stimulation ( P<0.05); the level of IL-10 increased at 3 h and 24 h in the TRIM59-cKO group, but there was no significant difference in IL-10 level at 6 h or 12 h between the two groups. In the TRIM59-cKO mouse model of CLP, the levels of IL-10 in the BALF samples increased with time, but decreased at 24 h. The level of IL-10 was higher in the TRIM59-cKO mouse model group than that in the control group at each time point ( P<0.05 or P<0.01). Conclusions:TRIM59 can inhibit inflammation and lung injury by decreasing HIF-1α-mediated lactate secretion and IL-10 expression in macrophages. This study provides a new idea for developing novel anti-sepsis drugs based on TRIM59.

Neuropathic pain(NP) has similar phenotypes but different sequential neuroinflammatory mechanisms in the pathological process. It is of great significance to inhibit the initiation of neuroinflammation, which has become a new direction of NP treatment and drug development in recent years. Mongolian drug Naru-3 is clinically effective in the treatment of trigeminal neuralgia, sciatica, and other NPs in a short time, but its pharmacodynamic characteristics and mechanism of analgesia are still unclear. In this study, a spinal nerve ligation(SNL) model simulating clinical peripheral nerve injury was established and the efficacy and mechanism of Naru-3 in the treatment of NPs was discussed by means of behavioral detection, side effect evaluation, network analysis, and experimental verification. Pharmacodynamic results showed that Naru-3 increased the basic pain sensitivity threshold(mechanical hyperalgesia and thermal radiation hyperalgesia) in the initiation of SNL in animals and relieved spontaneous pain, however, there was no significant effect on the basic pain sensitivity threshold and motor coordination function of normal animals under physiological and pathological conditions. Meanwhile, the results of primary screening of target tissues showed that Naru-3 inhibited the second phase of injury-induced nociceptive response of formalin test in mice and reduced the expression of inflammatory factors in the spinal cord. Network analysis discovered that Naru-3 had synergy in the treatment of NP, and its mechanism was associated with core targets such as matrix metalloproteinase-9(MMP9) and interleukin-1β(IL-1β). The experiment further took the dorsal root ganglion(DRG) and the stage of patho-logical spinal cord as the research objects, focusing on the core targets of inducing microglial neuroinflammation. By means of Western blot, immunofluorescence, agonists, antagonists, behavior, etc., the mechanism of Naru-3 in exerting NP analgesia may be related to the negative regulation of the MMP9/IL-1β signaling pathway-mediated microglia p38/IL-1β inflammatory loop in the activation phase. The relevant research enriches the biological connotation of Naru-3 in the treatment of NP and provides references for clinical rational drug use.
Rats ; Mice ; Animals ; Matrix Metalloproteinase 9/metabolism* ; Rats, Sprague-Dawley ; Neuroinflammatory Diseases ; Interleukin-1beta/metabolism* ; Spinal Cord/metabolism* ; Signal Transduction ; Hyperalgesia/metabolism* ; Neuralgia/metabolism*

The Baimai Ointment with the effect of relaxing sinew and activating collaterals demonstrates a definite effect on Baimai disease with pain, spasm, stiffness and other symptoms, while the pharmacodynamic characteristics and mechanism of this agent remain unclear. In this study, a rat model of chronic compression of L4 dorsal root ganglion(CCD) was established by lumbar disc herniation, and the efficacy and mechanism of Baimai Ointment in the treatment of CCD were preliminarily explored by behavioral tests, side effect evaluation, network analysis, antagonist and molecular biology verification. The pharmacodynamic experiment indicated that Baimai Ointment significantly improved the pain thresholds(mechanical pain, thermal pain, and cold pain) and gait behavior of CCD model rats without causing tolerance or obvious toxic and side effects. Baimai Ointment inhibited the second-phase nociceptive response of mice in the formalin test, increased the hot plate threshold of normal mice, and down-regulated the expression of inflammatory cytokines in the spinal cord. Network analysis showed that Baimai Ointment had synergistic effect in the treatment of CCD and was related to descending inhibition/facilitation system and neuroinflammation. Furthermore, behavioral tests, Western blot, and immunofluorescence assay revealed that the pain-relieving effect of Baimai Ointment on CCD may be related to the regulation of the interaction between neuroactive ligand and receptors(neuroligands) such as CHRNA7, ADRA2A, and ADRB2, and the down-regulation of the expression of NOS2/pERK/PI3K, the core regulatory element of HIF-1 signaling pathway in spinal microglia. The findings preliminarily reveal the mechanism of relaxing sinew and activating collaterals of Baimai Ointment in the treatment of Baimai disease, providing a reference for the rational drug use and further research of this agent.
Rats ; Mice ; Animals ; Chronic Pain/metabolism* ; Rats, Sprague-Dawley ; Ganglia, Spinal/metabolism* ; Ligands ; Signal Transduction ; Hyperalgesia/metabolism* ; Drugs, Chinese Herbal

The animal models used in the experimental research of Traditional Chinese Medicine (TCM) to prevent and treat T2DM are mainly spontaneous and induced. The experimental research of TCM in the prevention and treatment of type 2 diabetes can be divided into Chinese medicine compound, Chinese medicine and its extract, Chinese medicine monomer. The mechanism is mainly through regulating intestinal flora, increasing insulin content, lowering blood sugar, lowering blood lipids, improving glucose tolerance, and improving gluconeogenesis, antioxidant, inhibit cell apoptosis, etc. play the role of preventing and treating T2DM in multiple links and multiple targets.

By reviewing the 2015 edition of Chinese Pharmacopoeia, the author collected 37 neutral blood-activating and stasis-removing traditional Chinese medicines. And by retrieving literatures on relevant material basis and pharmacological effects on CNKI, the author organized and summarized their chemical composition and pharmacological effects. Neutral blood-activating and stasis-removing traditional Chinese medicines are rich in chemical components, such as flavonoids, steroids and sugars. At the same time, it has a variety of pharmacological effects, including anti-platelet aggregation and anti-thrombotic mechanism, anti-atherosclerosis, inhibition of ischemia-perfusion injury, anti-tumor, anti-fibrosis, liver protection, anti-inflammatory analgesia, blood pressure reduction and immune regulation. It is widely used in the treatment of liver fibrosis, cardiovascular disease, liver cancer, uterine cancer, hypertension, hyperlipidemia and other diseases. Nowadays, as people has paid increasing attention to neutral herbs, studies on traditional Chinese medicines for activating blood circulation and removing blood stasis have been further deepened, which provides a better development prospect for neutral blood-activating and stasis-removing traditional Chinese medicines. From the perspective of medicinal properties, the authors systematically collected and summarized the pharmacological effects and material basis of neutral blood-activating and stasis-removing traditional Chinese medicines. This article provides theoretical guidance for the clinical application of neutral blood-activating and stasis-removing traditional Chinese medicines and new medicine research ideas for neutral blood-activating and stasis-removing traditional Chinese medicines.

Objective:To analyze the characteristics of malaria epidemic situation before and after malaria elimination in Qiandongnan Prefecture, and to provide the basis for establishment of effective strategies and measures to consolidate the achievements of malaria prevention and control.Methods:The data of malaria cases in 16 counties (cities) of Qiandongnan Prefecture from 2005 to 2018 were collected, and descriptive epidemiological method was used to analyze the infection rate of Plasmodium among local residents and floating population before (2005-2011) and after (2012-2018) elimination of malaria, and the characteristics of population distribution, seasonal distribution, species of Plasmodium and types of malaria vectors were analyzed. Results:Before elimination of malaria, total of 1 412 cases of malaria were reported, among those cases, 1 361 cases were local cases, accounting for 96.39% of the total cases. After elimination of malaria, total of 17 cases were reported, all of them were imported cases. After comparison of malaria cases before and after the elimination, the proportion of people aged from 18 to 60 was 70.54% (996/1 412) before the elimination, all 17 imported cases were 18-60 years old after the elimination, and the proportion of children/students decreased from 24.65% (348/1 412) before the elimination to 0 after the elimination. The peak incidence of malaria cases before the elimination was from June to October, and cases occurred every month. After the elimination, the imported cases were sporadic. Plasmodium vivax was the main species of Plasmodium before the elimination (98.58%, 1 392/1 412), and Plasmodium falciparum was mainly imported after the elimination (70.59%, 12/17). Before and after the elimination, Anopheles sinensis, the malaria vector, was the dominant population, but no distribution of Anopheles minimus and Anopheles anthropophagus was found after 2015. Conclusions:After the elimination of malaria in Qiandongnan Prefecture, there is a risk of local malaria cases caused by imported cases. It is suggested that local authorities should focus on the treatment of suspected malaria cases and vector surveillance of overseas returnees in the future.

Objective: To summarize and discuss the characteristics of endoscopic approach to manage the middle ear cholesteatoma, and to evaluate the operative safety and outcomes based on the data from the multicenter study. Methods: The data of 242 cases diagnosed with the middle ear cholesteatoma and received operation through endoscopic approach between June 2016 and June 2017 in six tertiary hospitals in China were analyzed in this work. There were 130 males and 112 females, with the age ranging from 3 to 72 years old. We evaluated the strategy about how to manage the cholesteatoma, discussed the detailed techniques about how to remove the cholesteatoma and to improve the efficiency under endoscopic visualization. Meanwhile, the recurrence rate and residual rate of cholesteatoma as well as the complications in endoscopic approach were summarized. Results: A total of 158 cases were operated in exclusively endoscopic transcanal approach, 72 cases operated in combined approach, and 12 cases operated majorly under microscope and minorly under endoscope. 219 cases were operated in one stage surgery, 23 cases received second look. In the second look, 3 cases were detected with residual cholesteatomas. Among them, 2 cases were found by MRI-DWI examination after the first-stage operation. With endoscopic examination after operation, 17 cases showed retracted pocket recurrence (7%,17/242). With introduction of endoscope in cholesteatoma, 153 cases were achieved canal wall-up operation (63%, 153/242). The complications in endoscopic approach included chord tympani never injury in 27 cases, skin injury of ear canal in 11 cases, tinnitus in 13 cases, vertigo in 7 cases, external ear canal stenosis in 1 case. Conclusions Using otoendoscope in cholesteatoma surgery would help keeping the normal structures of middle ear as much as possible, benefit to remove the hiding pathologies, help reducing residual cholesteatoma and lowering the rate of canal wall-down operation as well. This study showed good safety of otoendoscopic cholesteatoma surgery, however, strict evaluation of indication and quite good surgical techniques and skills are necessary for avoiding unexpected complication.

OBJECTIVE: To evaluate the efficacy and safety of Tongxiening Granules (, TXNG) in the treatment of irritable bowel syndrome with predominant diarrhea (IBS-D). METHODS: A randomized, double-blind, double-dummy, and positive parallel controlled clinical trial was conducted from October 2014 to March 2016. Totally 342 patients from 13 clinical centers were enrolled and randomly assigned (at the ratio of 1:1) to a treatment group (171 cases) and a control group (171 cases) by a random coding table. The patients in the treatment group were administered orally with TXNG (5 g per time) combined with pinaverium bromide Tablet simulator (50 mg per time), 3 times per day. The patients in the control group were given TXNG simulator (5 g per time) combined with pinaverium bromide Tablets (50 mg per time), 3 times per day. The treatment course lasted for 6 weeks. The improvement of Irritable Bowel Syndrome Symptom Severity Score (IBS-SSS) was used to evaluate the primary outcome. Secondary outcomes included adequate relief (AR) rate, Irritable Bowel Syndrome-Quality of Life Questionnaire (IBS-QOL), Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), and the recurrence rate at follow-ups. Safety indices including the adverse events (AEs) and related laboratory tests were evaluated. RESULTS: Primary outcome: IBS-SSS at baseline, weeks 2, 4, 6 showed no statistical significance in both full analysis set (FAS) and per protocol set (PPS, P>0.05). After 6 weeks of treatment, the total effective rate of IBS-SSS scores in the treatment group (147/171,86.0%) was higher than the control group (143/171, 83.6%) by FAS (P>0.05). In regard to secondary outcomes, after 6-week treatment, there was no significant difference in AR rate, total score of IBS-QOL, improvement of HAMD and HAMA total scores between the two groups (P>0.05). The recurrence rate at 8-week follow-up was 12.35% (10/18) in treatment group and 15.79% (12/76) in control group, respectively (P>0.05). A total of 21 AEs occurred in 15 cases, of which 11 occurred in 8 cases in the treatment group and 10 AEs in 7 cases in the control group. The incidence of AEs had no statistical significance between the two goups (P>0.05). CONCLUSION Tongxiening Granules could relieve the symptoms of patients with IBS-D and the treatment effect was comparable to pinaverium bromide. (No. ChiCTR-IPR-15006415).

Objective To evaluate the analytical performance of four lipoprotein associated phospholipase A2(Lp-PLA2)activity reagents on Beckman AU5800 automatic biochemical analyzer. Methods The remaining serum samples of 214 patients and 140 apparently healthy individuals were collected from March to July 2017 in Peking Union Medical College Hospital.These samples were used for method comparison and reference interval evaluation.According to the guidelines of EP15-A,EP6-A,EP-17 and EP7-P from Clinical and Laboratory Standards Institute(CLSI)standards,the precision, linearity, sensitivity and common interferences(e.g free bilirubin, conjunct bilirubin, hemoglobin and chyle)were assessed.According to EP9-A2,method comparisons of differents regents(Evermed,DiaSys,Hengxiao and Zhongyuan were labeled as A,B,C and D,respectively)were conducted and the differences were estimated at medical decision levels(328U/L,391U/L and 485U/L).Results The precision of four reagents were acceptable.The repeatability(CV%)of A to D were 0.5%-1.7%, 0.7%-3.0%, 0.9%-2.0% and 0.5%-3.3%,respectively.The reproducibility(CV%)were 0.7%-2.9%, 1.4%-3.2%, 1.3%-1.9%and 0.8%-4.1%,respectively.Both of those achievedlaboratory defined quality objective(<5%).The linearity of A to D were 44 -1 992 U/L,39 -1 798 U/L,13 -540 U/L and 75-1 717U/L,respectively.The regression coefficient R2 was between 0.997 and 1.000, and the correlation coefficient(r)was between 0.998 and 1.000.The interference of chyle were acceptable among these four reagents andmet the manufacturer′s requirementsor clinical needs.In a low level of Lp-PLA2,bilirubin had an obvious interferenceonreagent C;B and C were negatively affected when the hemoglobin was 4.5 g/L; and D was positively affected when the hemoglobin was 2.45 g/L.The regression coefficients R2 of A,C,D compared with B were between 0.978 and 0.995,and the correlation coefficients(r)were between 0.989 and 0.998. The expected differences at medical decision levels ranged from -240 U/L to 113 U/L.For A to D,the Lp-PLA2 activity results of 131(93.6%), 140(100%), 82(58.6%), and 128(91.4%)cases were analysed within the manufacturer′s claimed reference intervals.Conclusion The precision and linearity of the four Lp-PLA2 activity detection reagents used in automatic biochemical analyzer are good, but the anti-interference ability needs to be improved.

Objective To evaluate the effect of personnel activities and air purifiers on airborne microorganisms and particulate matter in bronchoscopy room.Methods According to whether there was personal activity and air purifier in the bronchoscopy room,the experiment was divided into four groups:dynamic non-purification group,dynamic purification group,static non-purification group,and static purification group,indoor air samples were collected and analyzed at five different time points (0,0.5,1,2,4 h),microorganisms in the air were collected by planktonic method,then cultured and counted,concentration of particulate matter was determined by DT-9881M laser dust particle counter,variance analysis of factorial design was used for statistical analysis.Results Colony count/concentration of airborne bacteria,fungi,total microorganisms (bacteria + fungi),PM2.5,and PM2.5-10.0 in dynamic non purification group were (113.53 ± 7.78) CFU/m3,(89.67 ± 7.17) CFU/m3,(203.20 ± 10.92) CFU/m3,(86 557.20 ±4 158.29) counts/m3,and (659.69 ± 38.91) counts/m3 respectively,in static non-purification group were (84.33 ± 3.65) CFU/m3,(65.00 ± 2.65)CFU/m3,(149.33 ± 4.98) CFU/m3,(45 812.64 ±1 279.61) counts/m3,and (189.15 ± 4.64) counts/m3 respectively,in dynamic purification group were (84.80 ±8.08) CFU/m3,(90.40 ± 5.50) CFU/m3,(175.20 ± 9.22) CFU/m3,(49 336.38 ± 2 039.16) counts/m3,and (218.36 ± 7.02) counts/m3 respectively,in static purification group were (67.80 ± 5.63) CFU/m3,(38.27 ± 3.70)CFU/m3,(106.07 ± 6.76) CFU/m3,(29 772.53 ± 2 212.93) counts/m3,and (124.80 ± 7.16) counts/m3 respectively.Colony count/concentration of airborne bacteria,total microorganisms,PM2.5,and PM2.s 10.0 in dynamic group were all higher than those in static group,non-purification group were higher than purification group(both P ＜0.05),colony count of fungi in dynamic non-purification group was higher than static non-purification group,in static purification group was lower than static non-purification group(both P＜0.05),there was no significant difference between dynamic purification group and dynamic non-purification group (P =0.936).Conclusion Personal activities can increase colony count/concentration of microorganisms and particulate matter in bronchoscopy room,air purifier can reduce the bacteria,total microbial count,and particulate matter in the air of bronchoscopy room.