Objective:To explore the influence of Shenhong Tongluo Granules in the lipid levels,atherosclerosis plaques and apoptosis in the plaques of atherosclerotic apolipoprotein E (ApoE)-knokout mice,and to clarify the mechanism of Shenhong Tongluo Granules in anti-atherosclerosis.Methods:Forty SPF male mice aged six-week old were randomly divided into normal control group,model group,low dose of traditional chinese medicine (TCM) group and high dose of TCM group (n=10)after fed adaptively for 1 week.The mice in normal control group were fed with normal diet continuously, the mice in other three groups were fed with high fat diet to establish atherosclerosis model,and then the mice in low and high doses of TCM groups were respectively given Shenhong Tongluo Granules (5.06 and 10.12 g·kg-1 · d-1 )by gavage for 6 weeks. The levels of serum total cholesterol (TC),triglycerides (TG),low density lipoprotein cholesterol (LDL-C)and high density lipoprotein cholesterol (HDL-C)of the mice in various groups were measured after the eyeball blood was collected.The aortic arch tissue was separated,and the morphotogy and the areas of atherosclerotic plaques were observed and calculated by HE staining;the apoptosis in plaques of the mice was evaluated by TUNEL method, and the apoptosis index was calculated. The expressions of apoptosis-assoicated gene Bcl-2 and Bax protein were measured by immunohistochemical staining.Results:The serum level of TG in low dose of TCM group was lower than that in model group (P <0.05);the serum levels of HDL-C in low and high doses of TCM groups were lower than that in model group (P <0.05 or P <0.01);the serum levels of TG and HDL-C in high dose of TCM group was higher than that in low dose of TCM group (P <0.05).The areas of atherosclerotic plaques of the mice in low and high doses of TCM groups were significantly smaller than that in model group (P <0.01).The apoptosis index of mice in low and high doses of TCM groups were significantly lower than that in model group (P <0.01);the expression levels of Bcl-2 protein in atherosclerosis plaques of the mice in low and high doses of TCM groups were lower than that in model group,while the expression levels of Bax were significantly higher than that in model group (P <0.05 or P <0.01).Conclusion:Shenhong Tongluo Granules could effectively reduce the serum lipid level of ApoE-/-mice,meanwhile it could inhibit apoptosis by regulating the expressions of Bcl-2 and Bax protein,and then inhibit the progression of atherosclerotic plaques.

Objective:To summarize the age, gender difference, cause, location, time, treatment and prognosis of femoral intertrochanteric fracture complicated with pseudoaneurysm, and analyze the influence of different treatment methods on the occurrence of femoral intertrochanteric fracture complicated with pseudoaneurysm.Methods:Using the method of systematic literature review, a total of 76 literatures were retrieved from multiple databases at home and abroad, and 45 literatures were screened out through the second screening of title, abstract and full text. The patients with intertrochanteric fracture complicated with pseudoaneurysm were selected as the research objects, and the duplicate cases were deleted; the age, gender, onset age, etiology, location, treatment and prognosis of the disease were retrospectively analyzed.Results:A total of 54 cases of femoral intertrochanteric fracture related pseudoaneurysms were selected from 45 literatures, including 25 males and 27 females, and 2 cases had no gender; aged from 43 to 94 years old, and 4 cases were younger than 60 years old, 6 between 61 and 70, 17 between 71 and 80, and 25 between 81 and 90. Forty-five cases occurred in deep femoral artery, 3 cases in superficial femoral artery, 1 case in superior gluteal artery, 1 case of medial circumflex artery, 1 case of lateral circumflex femoral artery, 1 case of femoral artery, and 2 cases of unknown location. The occurrence time of pseudoaneurysm: 17 cases within 1 week after fracture, 8 cases from 1 week to 3 weeks, 19 cases from 3 weeks to 3 months, 2 cases more than 3 months, and 8 cases unknown. The causes of pseudoaneurysm: among the 54 patients, 41 cases had definite causes, including 21 cases of vascular injury caused by fracture block; 20 cases of iatrogenic injury, of which the incidence of direct injury of blood vessels by screw or drill was the highest, accounting for 55% (11/20). Twenty-two cases were treated with vascular embolization, 10 cases with surgical sutures, 8 cases with surgical ligation, 4 cases with resection of pseudoaneurysm, 5 cases with covered stent, and 4 cases with thrombin injection. There were 42 cases who had follow-up data, and no recurrence and other complications were found during the follow-up period.Conclusion:The peak age of femoral intertrochanteric fracture complicated with pseudoaneurysm was 71-90 years old. The incidence of femoral intertrochanteric fracture complicated with pseudoaneurysm was more often within 1 week after fracture and 3 weeks to 3 months after fracture, due to fracture fragments and iatrogenic vascular injury caused by the location of the profundus femoris artery. Treatment options include vascular embolization, surgical ligation, suture or resection of pseudoaneurysm, covered stent and thrombin injection, and the prognosis is generally good.

OBJECTIVE To identify the role of mixed lineage kinase domain like protein(MLKL)in cerebral small vessel disease(CSVD)and explore the underlying mechanism.METHODS Transient bilateral common carotid artery occlusion(tBCCAO)was used to establish a mouse model of CSVD.Immunofluorescence staining and Western blotting were used to observe the expres-sions of RIPK3/MLKL signaling molecules in brain tissues at 7,14 and 28 d after tBCCAO.Open field test,rotarod test,Y-maze and novel object recognition test were used to observe the effect of MLKL knockout on cognitive func-tion after tBCCAO.Blood-brain barrier(BBB)disruption was observed by sodium fluorescein permeability test and the expressions of tight junction proteins.Immunoflu-orescence staining and Western blotting were used to detect the expression of microglia marker Iba-1,astro-cyte marker GFAP,and NLRP3/Caspase-1 signaling mol-ecules in the hippocampus of CSVD mice.ELISA was used to detect the level of inflammatory factors(TNF-α,IL-1β,IL-18)in hippocampus.RESULTS The expres-sions of RIPK3/MLKL signaling molecules increased in cortex and hippocampus after tBCCAO,especially on day 14.The expression of pMLKL mainly increased in neurons,glia cells and endothelial cells in CSVD mice.MLKL knockout improved the cognitive functions such as motor learning,spatial learning and working memory,and object recognition ability in CSVD mice.MLKL knock-out alleviated the leakage of sodium fluorescein and attenuated the down-regulation of tight junction proteins at 1 d and 14 d after tBCCAO.At 14 d after tBCCAO,MLKL knock out inhibited the activations of microglia and astrocytes,attenuated the expressions of NLRP3/cas-pase-1 molecules,and decreased the levels of inflamma-tory factors in the hippocampus of mice.CONCLUSION Genetic inhibition of MLKL exerts protective effects against cognitive impairment by ameliorating BBB dam-age and neuroinflammation in a mouse cerebral small vessel disease model.

OBJECTIVETo investigate α-toxin-induced apoptosis of umbilical vein endothelial cells and explore its role in vertical infection of Staphylococcus aureus L-form.

METHODSHUV-EC-C cells exposed to different concentrations (0, 10, 30, 90, and 270 ng/ml) of α-toxin for different time lengths (0, 2, 4, 6, and 8 h) were examined for apoptosis using flow cytometry with Annexin V-PI staining. The levels of tumor necrosis factor-α (TNF-α) and the activities of, caspase-3 and caspase-8 in the cell culture were detected by ELISA and colorimetric method, respectively. α-Toxin-induced cell apoptosis was also analyzed in HUV-EC-C cells treated with a neutralizing antibody of TNF-α or with the inhibitory peptides of caspase-3 (zDEVD-FMK) and caspase-8 (zIETD-fmk).

RESULTSα-Toxin induced apoptosis of HUV-EC-C cells in a dose- and time-dependent manner and caused significantly enhanced expression of TNF-α and the activation of both caspase-3 and caspase-8. Inhibition of TNF-α with its neutralizing antibody and the inhibitory peptides of caspase-3 or -8 all significantly decreased α-toxin-induced cell apoptosis, and the caspase-3 inhibitor completely blocked α-toxin-induced cell apoptosis.

CONCLUSIONα-Toxin-induced apoptosis is partially mediated by the extrinsic cell death pathway of TNF-α and caspase-8 and plays an important role in the vertical infection of S. aureus L-form to affect fetal growth and development.

Apoptosis ; Bacterial Toxins ; toxicity ; Caspase 3 ; metabolism ; Caspase 8 ; metabolism ; Cells, Cultured ; Human Umbilical Vein Endothelial Cells ; cytology ; Humans ; L Forms ; Staphylococcal Infections ; Staphylococcus aureus ; Tumor Necrosis Factor-alpha ; metabolism

Objective: To evaluate the treatment of complex acetabular fractures involving the posterior column by anterograde lag screws via the ilioinguinal approach. Methods: A retrospective study was conducted of the 8 patients with complex acetabular fracture involving the posterior column who had been treated at Department of Orthopaedics, The Second Affiliated Hospital to Inner Mongolia Medical University from January 2017 to June 2018. They were 5 males and 3 females, aged from 35 to 62 years (average, 43.5 years). According to the Letournel-Judet classification, 3 cases were T-shaped fractures, 4 anterior column plus posterior hemitransverse fractures and one both column fracture. The interval from injury to operation averaged 8 days (from 7 to 17 days). The anterior acetabulum was fixated by a reconstruction plate and the posterior column by antegrade lag screws, all through the ilioinguinal approach. The quality of fracture reduction, fracture union time, function of the affected hip and complications were recorded. Results: By the Matta imaging criteria, the quality of fracture reduction was rated as excellent in 7 cases and as fine in one. Intraoperative major hemorrhage or injury to sciatic nerve occurred in none of the patients. This cohort obtained an average follow-up of 8 months (from 6 to 18 months). All fractures united well after an average of 10 weeks (from 8 to 12 weeks). The function of affected hip evaluated by the improved Merle d’Aubigne & Postel criteria at the last follow-up was excellent in 7 cases and fine in one. Follow-ups revealed no incidence of deep vein thrombosis or heterotopic ossification. Conclusions For patients with complex acetabular fracture involving the posterior column, internal fixation of the anterior acetabulum with a reconstruction plate through the ilioinguinal approach and fixation of the posterior column with antegrade lag screws also through the ilioinguinal approach can result in fine therapeutic effects, because complications like ectopic ossification and sciatic nerve injury related to the Kocher-Langenbeck approach can be prevented. This treatment is particularly suitable for the patients whose condition of the soft tissues at the posterior pelvis is poor.

Objective:To investigate the effect of mechano-growth factor（MGF）on osteoclast activity and its mechanism.Methods:The RAW264.7 precursor osteoclast cell line was cultured with 25 ng/ml macrophage-colony stimulating factor（M-CSF）and 30 ng/ml receptor activator of NF-κB ligand（RANKL），and identified by tartrate resistant acid phosphatase（TRAP）staining after 7 days of culture. Western blot anslysis was used to determine the effect of 45 ng/ml MGF on the phosphoinositide-3-kinase/protein kinase B（PI3K/AKT）signaling pathway in separated osteoclasts，including levels of AKT，phosphorylation（p）-AKT，lactation mammalian target of rapamycin（mTOR），p-mTOR and TRAP at 0，4，8 and 12 hours. Real-time fluorescence quantitative PCR was used to expressions of TRAP in osteoclasts at 0，4，8 and 12 hours. The PI3K/Akt phosphorylation inhibitor LY294002（20 μmol/L）combined with MGF（45 ng/ml）was used to act on osteoclasts，and expression levels of Akt，p-Akt，mTOR，p-mTOR and TRAP were detected by Western blot at 0，4，8 and 12 hours.Results:After culturing RAW264.7 cells with M-CSF and RANKL for 7 days，a large number of osteoclasts with positive TRAP staining can be obtained. Western blot analysis showed expression levels of Akt and mTOR did not change significantly over time（ P>0.05），expression levels of p-Akt and p-mTOR increased continuously from（2.18±0.34）pg/ml and（0.83±0.10）pg/ml at 0 hour to（3.86±0.36）pg/ml and（1.56±0.19）pg/ml at 12 hours（ P<0.05），and expression level of TRAP decreased significantly over time，from（5.66±0.47）pg/ml at 0 hour to（3.76±0.38）pg/ml at 12 hours（ P<0.05）. Real-time fluorescence quantitative PCR analysis of expression of TRAP in osteoclasts showed that MGF inhibited the expression of TRAP in osteoclasts，which decreased from 1.02±0.06 at 0 hour to 0.53±0.11 at 12 hours（ P<0.05）. After acting LY294002 combined with MGF on osteoclasts，Western blot analysis showed expression levels of Akt and mTOR did not change significantly over time（ P>0.05），expression levels of p-AKT and p-mTOR decreased significantly from（3.28±0.18）pg/ml and（3.29±0.22）pg/ml at 0 hour to（2.06±0.34）pg/ml and（2.04±0.20）pg/ml at 12 hours（ P<0.05），and expression level of TRAP had no significant difference over time（ P>0.05）. Conclusions:MGF inhibits osteoclast activity by inhibiting the expression of TRAP in osteoclasts through PI3K/Akt signaling pathway. LY294002 inhibits the expression of PI3K/Akt signaling pathway in osteoclasts，further verifying the mechanism of MGF inhibiting osteoclast activity，and this finding puts forward new ideas for clinical prevention and treatment of osteoporosis.

Background Long-term exposure to free silica particles will lead to fibrosis of lung tissue, and abnormal expression of microRNA (miRNA) may affect the occurrence and process of fibrosis. Objective To observed possible intervention effect of miR-204-3p overexpression adenovirus on silicosis fibrosis induced by silica dust using a silicosis rat model via non-exposed intratracheal instillation. Methods Forty SD rats were randomly divided into four groups: control group, silicosis model group, miRNA-NC group, and miR-204-3p intervention group. Under ether anesthesia, rats in the silicosis model group, miRNA-NC group, and miR-204-3p intervention group were injected with 1 mL (50 mg·mL⁻¹) of free silica dust suspension into the trachea, while the control group was injected with the same volume of normal saline. After 30 d of dust exposure, the miR-204-3p intervention group was injected with rno-mir-204 adenovirus vector to overexpress miR-204-3p, and the miRNA-NC group was given empty virus vector. After 30 d of normal feeding, the animals were sacrificed by chloral hydrate anesthesia, and the lung tissue was taken for subsequent experiments. The relative expression level of miR-204-3p in lung tissue of rats in each group was detected by real-time fluorescence quantitative PCR (RT-qPCR). HE staining, Masson staining, and Sirius red staining were used for pathological observation. Immunohistochemistry was used to detect the expression of Fibronectin and Collagen I in lung tissue of rats in each group. RT-qPCR was used to detect the relative gene expression levels of fibrosis markers Fibronectin, Vimentin, Collagen I, and Collagen III in lung tissue of rats in each group. Western blot was used to detect the protein expression levels of fibrosis markers Fibronectin, Vimentin, Collagen I, and Collagen III in lung tissue of rats in each group. Results The anatomical features of lung tissue in the control group were pink lung tissue with soft texture and smooth surface, while those in the silicosis model were grayish white tissue with hard texture and scars and grayish white silicon nodules on the surface. Compared with the silicosis model group, the color of lung tissue in the miR-204-3p intervention group became ruddy, the surface was smooth, and the texture became soft. The staining results showed that the alveolar wall of the control group was thin, there were a small number of capillaries in the alveoli, and the alveolar structure was clear and complete. In the silicosis model group, the alveolar wall became thicker, the pulmonary septum was partially broken, the alveolar structure was defective, and a large amount of collagen fibers were deposited. The alveolar structure of the miR-204-3p intervention group was relatively clear and there was a small amount of collagen fiber deposition. RT-qPCR results showed that compared with the control group, the relative expression levels of miR-204-3p in lung tissue of the silicosis model group and the miRNA-NC group were decreased (P<0.05), and the relative expression level of miR-204-3p in lung tissue of the miR-204-3p intervention group was increased (P＜0.05). The results of immunohistochemistry showed that compared with the control group, the expression levels of Fibronectin and Collagen I in lung tissue of the silicosis model group were increased (P＜0.05). Compared with the silicosis model group, the relative expression levels of Fibronectin and Collagen I in lung tissue of the rats in the miR-204-3p intervention group were significantly decreased (P<0.05). The results of RT-qPCR and Western blot showed that compared with the control group, the relative protein and gene expression levels of fibrosis factors Fibronectin, Vimentin, Collagen I, and Collagen III in lung tissue of the silicosis model group increased (P＜0.05). Compared with the silicosis model group, the relative gene and protein expression levels of fibrosis factors Fibronectin, Vimentin, Collagen I, and Collagen III in lung tissue of rats in the miR-204-3p intervention group were decreased (P＜0.05). Conclusion Silica dust can cause lung fibrosis in rats, and overexpression of miR-204-3P in vivo can reduce silicosis fibrosis in rats caused by silica dust.

Objective: To analyze the prognostic factors on multidisciplinary team patients for diagnosis, and treatment of hepatocellular carcinoma. Methods: This retrospective study enrolled 132 HBsAg positive patients with HCC. MDT diagnostic approach was conducted at our hospital between 1 January 2015 and 31 December 2015, and all patients were followed up to 31 December 2017. Groups were arranged according to variables such as Barcelona stage, MDT compliance, and multidisciplinary combination therapy. TTP and OS were statistically analyzed. Results: The survival of the MDT compliance group was better than the non-compliance group. The difference in survival curves was statistically significant (χ² = 4.062, P < 0.05). The 1- and 2-year survival rates of the former group were 72.0%, 60.9%, and the latter was 64.3%, 40.3%. The survival of the combined treatment group was better than the non-combination group. The survival curves of the two groups were statistically significant (χ² = 9.502, P < 0.05), and they were independent influencing factors of survival (HR = 0.451, 95% CI, 0.210-0.968). The 1- and 2-year survival rates of the former group were 82.2% and 75.4%, and the latter was 63.1% and 44.6%. The median survival time of the follow-up group was 29.4 months, and the non-compliance and the uncombined group were 17.0 months. The difference was statistically significant (χ² = 13.336, P < 0.001). The median tumor progression time was 15.7 months in the combination group and 10.1 months in the non-compliance group (χ² = 7.263, P < 0.05). Conclusion An advanced MDT compliance with implementation of multidisciplinary combination therapy may help to improve the prognosis of MDT patients with liver cancer.

OBJECTIVE: To investigate the correlation of hemoglobin (Hb) level with prognosis of elderly patients diagnosed as sepsis. METHODS: A retrospective cohort study was conducted. Information on the cases of elderly patients with sepsis in the Medical Information Mart for Intensive Care-IV (MIMIC-IV), including basic information, blood pressure, routine blood test results [the Hb level of a patient was defined as his/her maximum Hb level from 6 hours before admission to intensive care unit (ICU) and 24 hours after admission to ICU], blood biochemical indexes, coagulation function, vital signs, severity score and outcome indicators were extracted. The curves of Hb level vs. 28-day mortality risk were developed by using the restricted cubic spline model based on the Cox regression analysis. The patients were divided into four groups (Hb < 100 g/L, 100 g/L ≤ Hb < 130 g/L, 130 g/L ≤ Hb < 150 g/L, Hb ≥ 150 g/L groups) based on these curves. The outcome indicators of patients in each group were analyzed, and the 28-day Kaplan-Meier survival curve was drawn. Logistic regression model and Cox regression model were used to analyze the relationship between Hb level and 28-day mortality risk in different groups. RESULTS: A total of 7 473 elderly patients with sepsis were included. There was a "U" curve relationship between Hb levels within 24 hours after ICU admission and the risk of 28-day mortality in patients with sepsis. The patients with 100 g/L ≤ Hb < 130 g/L had a lower risk of 28-day mortality. When Hb level was less than 100 g/L, the risk of death decreased gradually with the increase of Hb level. When Hb level was ≥ 130 g/L, the risk of death gradually increased with the increase of Hb level. Multivariate Logistic regression analysis revealed that the mortality risks of patients with Hb < 100 g/L [odds ratio (OR) = 1.44, 95% confidence interval (95%CI) was 1.23-1.70, P < 0.001] and Hb ≥ 150 g/L (OR = 1.77, 95%CI was 1.26-2.49, P = 0.001) increased significantly in the model involving all confounding factors; the mortality risks of patients with 130 g/L ≤ Hb < 150 g/L increased, while the difference was not statistically significant (OR = 1.21, 95%CI was 0.99-1.48, P = 0.057). The multivariate Cox regression analysis suggested that the mortality risks of patients with Hb < 100 g/L [hazard ratio (HR) = 1.27, 95%CI was 1.12-1.44, P < 0.001] and Hb ≥ 150 g/L (HR = 1.49, 95%CI was 1.16-1.93, P = 0.002) increased significantly in the model involving all confounding factors; the mortality risks of patients with 130 g/L ≤ Hb < 150 g/L increased, while the difference was not statistically significant (HR = 1.17, 95%CI was 0.99-1.37, P = 0.053). Kaplan-Meier survival curve showed that the 28-day survival rate of elderly septic patients in 100 g/L ≤ Hb < 130 g/L group was significantly higher than that in Hb < 100 g/L, 130 g/L ≤ Hb < 150 g/L and Hb ≥ 150 g/L groups (85.26% vs. 77.33%, 79.81%, 74.33%; Log-Rank test: χ² = 71.850, P < 0.001). CONCLUSIONS Elderly patients with sepsis exhibited low mortality risk if their 100 g/L ≤ Hb < 130 g/L within 24 hours after admission to ICU, and both higher and lower Hb levels led to increased mortality risks.
Humans ; Male ; Female ; Aged ; Retrospective Studies ; Sepsis/diagnosis* ; Critical Care ; Intensive Care Units ; Prognosis ; Hemoglobins ; ROC Curve

OBJECTIVE: To analyze the incidence and risk factors of benign liver space-occupying mass in patients with chronic hepatitis B (CHB) and the ultrasound features that differentiate these masses from small hepatocellular carcinoma. METHODS: We retrospectively analyzed the color Doppler and clinical data of 17 721 patients with CHB treated in the Hepatology Unit of Nanfang Hospital between January, 2016 and December, 2017. The data were compared with those of 21629 healthy control subjects undergoing routine physical examination in the Center of Heath Management of Nanfang Hospital during the same period. RESULTS: Compared with the control subjects, the patients with CHB had significantly higher incidences of hepatic cysts (11.8% 8.7%, < 0.05), hepatic hemangioma (8.2% 1.6%, < 0.05) and hepatic cirrhosis nodules (20.6% 2.4%, < 0.05). The incidences of hepatic cysts and cirrhosis nodules increased with age and was significantly higher in male than in female patients ( < 0.001). The highest incidence of hepatic hemangioma was found in CHB patients aged 30-49 years without a gender difference (>0.05). Sonographically, the benign liver masses commonly showed homogeneous echo within the lesion with clear boundaries and regular shape. Hepatic hemangioma was distinctively hyperechoic in 83.32% (1579/1895) of the patients, while small hepatocellular carcinoma presented with weaker peripheral and internal blood flow signals with a lower flow velocity in the arteries and a higher flow velocity in the portal vein. Liver cirrhosis nodules mostly showed a mixture of strong and weak echoes (79.60%; 7637/9595) without blood flow signal within or around the nodule; an increased volume of the nodule accompanied by heterogeneous echoes within the nodule indicated an increased probability of malignant lesion. Hepatic cysts often displayed no echo within the lesion, but the echo could be enhanced posteriorly. CONCLUSIONS The patients with CHB are at a significantly higher risk of developing hepatic cysts, hepatic hemangiomas and hepatic cirrhosis nodules than the control population, and an older age and the male gender are associated with a higher incidence of hepatic cysts or cirrhosis. The differences in the sonographic and hemodynamic features can help to differentiate hepatic benign mass from malignant lesions, and kinetic changes in sonography can be used to monitor potential malignant transformation of the cirrhotic lesions.