BACKGROUND:Rev-erbα is involved in the regulation of inflammation,but pharmacological activation of Rev-erbα increases the risk for cardiovascular diseases.To reduce the relevant risk,an exploration on SR9009,a Rev-erbα agonist,combined with other drugs to relieve inflammation in skeletal myoblasts was conducted,laying the theoretical foundation for the treatment of inflammation-associated skeletal muscle atrophy. OBJECTIVE:To investigate the relationship of SR9009,indolepropionic acid and nuclear factor-κB signaling pathways in lipopolysaccharide-induced C2C12 myoblasts. METHODS:(1)C2C12 myoblasts were induced to differentiate in the presence of lipopolysaccharide(1 μg/mL).RNA-seq and KEGG pathway analysis were used to study signaling pathways.(2)C2C12 myoblast viability was assessed using the cell counting kit-8 assay to determine optimal concentrations of indolepropionic acid.Subsequently,cells were categorized into control group,lipopolysaccharide(1 μg/mL)group,SR9009(10 μmol/L)+lipopolysaccharide group,indolepropionic acid(80μmol/L)+lipopolysaccharide group,and SR9009+indolepropionic acid+lipopolysaccharide group.ELISA was employed to measure protein expression levels of interleukin-6 in the cultured supernatant.Real-time quantitative PCR were employed to measure mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.Western blot assay were employed to measure protein expression levels of NF-κB p65 and p-NF-κB p65.(3)After Rev-erbα was knocked down by siRNA,knockdown efficiency was assessed by RT-qPCR.And mRNA levels of interleukin-6 and tumor necrosis factor α were also measured. RESULTS AND CONCLUSION:Compared with the blank control group,lipopolysaccharide time-dependently inhibited myofibroblast fusion to form myotubes,the mRNA expression levels of interleukin-6 and tumor necrosis factor α were elevated,and the level of interleukin-6 in the cell supernatant was significantly increased.The results of KEGG pathway showed that the nuclear factor-κB signaling pathway was activated by lipopolysaccharide.Indolepropionic acid exhibited significant suppression of C2C12 myoblasts viability when its concentration exceeded 80 μmol/L.Indolepropionic acid and SR9009 inhibited the activation of NF-κB signaling pathway,thereby played an anti-inflammatory role,and suppressed the mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.Compared with the lipopolysaccharide group,the ratio of p-NF-κB p65/NF-κB p65 protein expression were downregulated.SR9009 combined with indolepropionic acid notably reduced lipopolysaccharide-induced inflammation,further downregulated the mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.The ratio of p-NF-κB p65/NF-κB p65 protein expression was significantly lower than that in the SR9009+lipopolysaccharide group or indolepropionic acid+lipopolysaccharide group.Rev-erbα increases time-dependently with lipopolysaccharide induction.The knockdown efficiency of Rev-erbα by siRNA reached over 58%,and lipopolysaccharide was added after Rev-erbα was successfully knocked down.Compared with the lipopolysaccharide group,the mRNA expression levels of interleukin-6 and tumor necrosis factor α were significantly up-regulated.These results conclude that Rev-erbα may act as a promising pharmacological target to reduce inflammation.SR9009 targeted activation of Rev-erbα combined with indolepropionic acid significantly inhibits the nuclear factor-κB signaling pathway and attenuates the inflammatory response of C2C12 myofibroblasts.Moreover,the combined anti-inflammatory effect is superior to that of the intervention alone.

Matrine has various pharmacological effects,including antitumor,anti-inflammatory,and antibacterial effects,which is an adjuvant drug widely used in clinical cancer chemotherapy.However,due to the fact that matrine is both an active and toxic component of Chinese materia medica,its clinical safety is particularly important.This article reviewed the research progress in the pharmacological effects of matrine from the aspects of anti-inflammatory,anticancer,antibacterial and antiviral,cardiovascular protection,neuroprotection,liver and kidney protection,and detoxification.It also summarized its toxicity and clinical application research,aiming to provide reference for the rational use of matrine.

Objective:To investigate the protective effect of lactoferrin(Lf) on lung injury in mice exposed to irradiation.Methods:C57BL/6 J mice were randomly divided into control group, 15 Gy irradiation group (IR group) and lactoferrin combined 15 Gy irradiation group (Lf+ IR group), with 5 mice in each group. The mice in the Lf+ 15 Gy group drank lactoferrin solution (10 mg/ml) from 3 days before irradiation and contained the whole experiments. Then, single chest 15 Gyirradiation was performed both in the IR and Lf+ IR groups. The body weight and other characteristics were monitored during the experiment. The mice were killed at day 14 after irradiation. The lung histopathology was observed by HE staining. Serum inflammatory cytokine such as HMGB1, TNF-α, IL-1β and IL-6 was determined by ELISA method . The expression of inflammatory related protein in lung tissue including HMGB1, TLR4, MyD88 and NF-κB were performed by immune histochemistry and Western blot method.Results:Compared with the control group, lung weight was significantly increased ( t=3.20, P<0.05), pulmonary hyperemia and inflammatory cell infiltration was observed in the IR group. Exposure also significantly increased serum level of TNF-α[(291.80±5.49) vs.(332.25±22.18)pg/ml]( t=3.07, P<0.05), up-regulated the expression of inflammatory related protein in lung tissue ( t=4.04, 4.78, 3.77, 6.14, P<0.05). Lactoferrin intervention (Lf+ IR group) significantly decreased lung weight ( t=2.18, P<0.05), alleviated histopathologic changes, decrease serum levels of HMGB1, TNF-α and IL-1β ( t=4.67, 2.97, 3.49, P<0.05). On the other hand, lactoferrin intervention decreased the positive cell number of HMGB1 and NF-κB, and down-regulated the protein expression of HMGB1, TLR4, MyD88 and NF-κB in lung tissues, with significant difference with the IR group ( t=8.06, 9.80, 3.07, 5.56, P<0.05). Conclusions:Lactoferrin plays the protective effect of radiation-induced lung injury through the downregulation of inflammatory response, such as HMGB1/TLR4/MyD88/NF-κB signaling pathway.

Objective:To investigate and analyze the current situation, screening, clinical characteristics, prevention and treatment of bleeding esophageal varices in cirrhotic patients with portal hypertension in Tibet region.Methods:Clinical data of cirrhotic patients with portal hypertension through March 2017 to February 2020 from Tibet region were collected and analyzed retrospectively.Results:511 cases with liver cirrhosis were included in the study, of which 185 cases (36.20%) had compensated cirrhosis and 326 cases (63.80%) had decompensated cirrhosis. Further analysis of the etiological data of liver cirrhosis showed that 306 cases (59.88%) were of chronic hepatitis B, 113 cases (22.11%) of alcoholic liver disease, and 68 cases (13.31%) of chronic hepatitis B combined with alcoholic liver disease. Among patients with compensated liver cirrhosis, 48 cases (25.95%) underwent endoscopic examination of which 33 diagnosed as high-risk variceal bleeding. However, none of these 33 cases had received non-selective β-blocker therapy, and only four patients had received endoscopic variceal banding therapy. Among patients with decompensated liver cirrhosis, 83 cases (25.46%) had a history of upper gastrointestinal bleeding, 297 cases (91.10%) had ascites, 23 cases (7.05%) had hepatic encephalopathy, and 3 cases (0.92%) had hepatorenal syndrome. Among the patients with a history of upper gastrointestinal bleeding, 42 cases (50.60%) had received secondary preventive treatment for bleeding esophageal varices, including 39 cases of endoscopic treatment, 1 case of endoscopic combined drug treatment, 3 cases of interventional treatment, and 2 cases of surgical treatment.Conclusion:Chronic hepatitis B and alcoholic liver diseases are the main causes of liver cirrhosis in Tibet region. Moreover, this region lacks screening, prevention and treatment for bleeding esophageal varices in cirrhotic patients with portal hypertension. Therefore, it is necessary to increase the screening of high-risk groups to prevent and improve the first-time bleeding, and promote multidisciplinary team to prevent and treat re-bleeding.

Objective To assess the clinical efficacy of perforators positioning technique in anterolateral thigh perforator sub lobe flap transplantation for reconstructing soft tissue defects of forearm or hand.Methods A retrospective case series study was performed to analyze 24 patients with forearm and hand soft tissue defects admitted from January 2013 to August 2017.There were 18 males and six females,aged 31-68 years (mean,52.3 years).The wound defect areas ranged from 11 cm × 10 cm to 18 cm× 14 cm.The anterolateral thigh sub lobe perforator flaps were used for repair.CT angiography (CTA) combined with color Doppler ultrasound (CDS) was used to determine the perforator position before operation.After the appropriate thigh side was selected according to the perforator position and the wound area,the lobed flaps were designed to ensure all the flaps for the stage I suture after the length was converted into width.All patients obtained stage Ⅱ repair,and the repair time was 5-29 days,with an average of 13 days.The accuracy of perforation positioning was observed during operation (the error was not more than 1 cm for accurate positioning).The flap survival and complications were recorded within 2 weeks after operation.Follow-up was performed using the seven indicators of flap function to evaluate the efficacy.Results The positioning accuracy rate was 99％.One case was seen necrosis about 2 cm at the proximal end of flap.Two cases had arterial crisis after flap operation and survived after active exploration.In two nonunion cases because of wound infection around the flap,one case was healed after dressing change,and another case was healed after debridement.The donor site of the flap obtained stage Ⅰ direct suture,and one case was seen obvious scar hyperplasia at the donor site.Flaps were made thinner in two patients with hand defects at the later stage.All 24 patients were followed up for 7-33 months,with an average of 18.3 months.According to the seven indexes of the flap function,the results were excellent in seven cases,good in 13,fair in three,and poor in onee,with an excellent and good rate of 83％.The flaps appeared soft with good color at the last follow-up.Conclusions In the treatment of soft tissue defects of forearm or hand using anterolateral thigh flap,conversion from length to width and direct suture of donor site can cover the wound well and reduce complications.Perforators positioning technique can facilitate precise preoperative planning and intraoperative accurate cutting.

Objective To evaluate the validity of stroke volume variation (SVV) for predicting fluid responsiveness in different grades of intra-abdominal pressure (IAP).Methods Forty pigs were involved in the study.Hypovolemia was made by blood withdraw of 30% of estimated blood volume from each animal via carotid artery.All the pigs were randomized into four groups namly 0 mm Hg (L0), 15 mm Hg (L15), 25 mm Hg (L25) and 35 mm Hg (L35).Nitrogen was inflated slowly till IAP to 0, 15, 25 and 35 mm Hg.Fluid loading was performed with 500 ml hydroxyethyl starch within 30 minutes.Hemodynamic parameters were evaluated by the thermodilution technique of pulse induced continuous cardiac output (PiCCO).SVV and stroke volume (SV) were measured before and after fluid loading.Results In groups L0 and L15, SVV was positive correlated with changes in SV (r=0.888, 0.942, respectively, P<0.05).In groups L25 and L35, there were poor correlations between SVV and changes in SV(r=0.068,-0.114, respectively).Conclusion When IAP was slightly increased up to 15 mm Hg, SVV remains an effectiveness index to predict fluid responsiveness index, however it failed to assess fluid responsiveness effectively when IAP is further raised up to 25 mm Hg or more.

Objective To investigate the regularity and predictors of weight loss during concurrent chemo-radiotherapy for nasopharyngeal carcinoma patients. Methods A retrospective study was carried out on 82 patients with nasopharyngeal carcinoma ,with average age of 45 years ,who received concurrent chemoradiotherapy at the Affiliated Cancer Hospital of Guangzhou Medical University. Paired t-test was used to analyze the weight loss pattern during chemoradiotherapy. The Spearman′s rank correlation analysis was used to investigate the correlation between high weight loss(HWL)and the clinical factors. Results The paired t-test showed that the weight of the patients decreased continuously every week during chemoradiotherapy(P < 0.05),and the value dropped most significantly during the 4th week. Among these 82 patients,32 were determined as HWL(weight loss > 10%). Spearman′s rank correlation analysis showed that HWL was associated with older age,female,higher T and TNM stage,3D-CRT technology,the higher dose of radiotherapy in nasopharynx and in neck lymph node,and decreases of leukopenia and hemoglobin over degree Ⅱ(P<0.05). Conlousions Weight may decrease continuously every week during chemoradiotherapy for nasopharyngeal carcinoma patients. Age,gender,T stage,TNM stage,radio-therapy dose,and leukopenia and hemoglobin decreases may be predictors for weight loss degree during concurrent chemoradiotherapy for nasopharyngeal carcinoma patients.

Objective To study the effects of fluid loading during fluid resuscitation on hemodynamics and cerebral perfusion(CPP)under different levels of intra-abdominal pressure(IAP).Methods Forty swine were employed in the study.Hypovolemia was made by blood withdrawal of 30% of estimated blood volume from each animal through the carotid artery line.All swine were randomized(random number) into four groups, namely IAPL0, IAPL15, IAPL25 and IAPL35.Then N2 gas was used to inflate in the abdomen slowly for elevating the IAP to 0,15, 25 and 35 mmHg.Fluid loading were performed with 500 mL hydroxyethyl starch within 30 minutes.Hemodynamic variables were evaluated by PiCCO.Heart rate (HR),mean arterial pressure(MAP), central venous pressure(CVP), cardiac output(CO), global end-diastolic volume index(GEDVI) and stroke volume index(SVI)were measured 30 minutes before fluid loading and 30 minutes after fluid loading.After placement of intracranial pressure optical fiber probe in the ventricle connected to intracranial pressure monitor for continuous monitoring of ICP changes, cerebral perfusion pressure (CPP) could be calculated.Results (1)HR decrease, MAP increased, SVI, CI and GEDVI significantly increased after fluid loading in all four groups (IAPL0,IAPL15,IAPL25 and IAPL35)(P<0.05),and there were not significant changes in CVP and EVLWI(P>0.05).SVRI decreased significantly in group IAPL15,IAPL25 and IAPL35 respectively(P<0.05).(2) ICP increased significantly in group IAPL15, IAPL25 and IAPL35(P<0.05), and CPP increased significantly in group IAPL25 and IAPL35(P<0.05) while CPP only slightly increased in group IAPL15(P>0.05).Conclusion When combined with intra-abdominal hypertension,fluid loading could improve the circulation of swine due to increase in CO and improve CPP.

[Objective] Based on the combination of teaching in the scientific scenario of PBL teaching mode improving the status of implementation of standardized teaching.[Methods]Firstly,domestic science teaching methods summary review and classification details of the traditional teaching methods,problem-centered teaching methods,teaching scenarios and situational approach combining four kinds of PBL teaching content as well as the first three inadequate teaching methods.And analysis showed that this method can promote standardization within science teaching implemented.[Results] The combination of PBL teaching scenarios for students can play an active role,while teachers also have some pedagogical implications.[Conclusion]The combination of PBL teaching scenario of higher professional level of teachers,innovation and professionalism requirements,etc.,in the teaching process,also requires teachers to have a certain ability to manage the classroom and modern teaching philosophy to fully mobilize students active learning.

Objective:To observe influence of mitochondrial manganese superoxide dismutase (MnSOD ) on vascular alkaline phosphatase (ALP) activity ,transcription factor :Runx2 and Osterix expression levels in MnSOD‐Tg mice model of vascular calcification .Methods :A total of 20 wild type (WT) mice were selected as WT group and 20 Mn‐SOD‐Tg mice were enrolled as MnSOD‐Tg group ,then mice model of vascular calcification was established .Vascu‐lar ALP activity ,expression levels of transcription factor Runx2 and Osterix were compared and analyzed between two groups .Results:After successful model establishment ,compared with WT group ,there were significant reduc‐tions in ALP activity [ (75.89 ± 4.17) vs .(61.32 ± 3.12)] , expression levels of transcription factor Runx2 [ (0.928 ± 0.016) vs .(0.694 ± 0.007)] and Osterix [ (0.472 ± 0.036) vs .(0.257 ± 0.013)] in MnSOD‐Tg group , P<0.01 all .Conclusion:Manganese superoxide dismutase may be improving atherosclerosis via reducing activity of vascular alkaline phosphatase ,expression levels of transcription factor Runx2 and Osterix .