Ethyl Lithospermate Reduces Lipopolysaccharide-Induced Inflammation through Inhibiting NF-κB and STAT3 Pathways in RAW 264.7 Cells and Zebrafish / 中国结合医学杂志

OBJECTIVE@#To explore the anti-inflammatory effects of ethyl lithospermate in lipopolysaccharide (LPS)-stimulated RAW 264.7 murine-derived macrophages and zebrafish, and its underlying mechanisms.@*METHODS@#3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazoliumbromide (MTT) assays were performed to investigate the toxicity of ethyl lithospermate at different concentrations (12.5-100 µ mol/L) in RAW 264.7 cells. The cells were stimulated with LPS (100 ng/mL) for 12 h to establish an inflammation model in vitro, the production of pro-inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor α (TNF-α) were assessed by enzyme linked immunosorbent assay (ELISA). Western blot was used to ascertain the protein expressions of signal transducer and activator of transcription 3 (STAT3), nuclear factor kappa B (NF-κB) p65, phospho-STAT3 (p-STAT3, Tyr705), inhibitor of NF-κB (IκB) α, and phospho-I κB α (p-IκB α, Ser32), and confocal imaging was used to identify the nuclear translocation of NF-κB p65 and p-STAT3 (Tyr705). Additionally, the yolk sacs of zebrafish (3 days post fertilization) were injected with 2 nL LPS (0.5 mg/mL) to induce an inflammation model in vivo. Survival analysis, hematoxylin-eosin (HE) staining, observation of neutrophil migration, and quantitative real-time polymerase chain reaction (qRT-PCR) were used to further study the anti-inflammatory effects of ethyl lithospermate and its probable mechanisms in vivo.@*RESULTS@#The non-toxic concentrations of ethyl lithospermate have been found to range from 12.5 to 100 µ mol/L. Ethyl lithospermate inhibited the release of IL-6 and TNF-α(P<0.05 or P<0.01), decreased IκBα degradation and phosphorylation (P<0.05) as well as the nuclear translocation of NF-κB p65 and p-STAT3 (Tyr705) in LPS-induced RAW 264.7 cells (P<0.01). Ethyl lithospermate also decreased inflammatory cells infiltration and neutrophil migration while increasing the survival rate of LPS-stimulated zebrafish (P<0.05 or P<0.01). In addition, ethyl lithospermate also inhibited the mRNA expression levels of of IL-6, TNF-α, IκBα, STAT3, and NF-κB in LPS-stimulated zebrafish (P<0.01).@*CONCLUSION@#Ethyl lithospermate exerts anti-Inflammatory effected by inhibiting the NF-κB and STAT3 signal pathways in RAW 264.7 macrophages and zebrafish.

Analysis on echocardiographic data of fetal heart defects at high altitude in Yunnan province and surrounding high altitude areas / 中华心血管病杂志

Objective: To explore the current situation of fetal heart defects in Yunnan Province and surrounding high altitude areas and the social factors affecting pregnancy outcome. Methods: This is a retrospective study. Pregnant woman who underwent fetal echocardiography and diagnosed as fetal cardiac defects in Yunnan Fuwai Cardiovascular Hospital from June 2017 to January 2021 were included. According to the clinical prognostic risk scoring system and grading criteria of fetal cardiac birth defects, the cases were divided into grade Ⅰ to Ⅳ. The disease distribution and proportion of each prognostic grade, pregnancy outcomes were analyzed and compared. The cases were divided into continued pregnancy group and terminated pregnancy group according to pregnancy outcome. The social factors that may affect the selection of pregnancy outcomes were analyzed by multivariate logistic regression analysis. Results: A total of 4 929 fetal echocardiography examination data were collected, and 4 464 cases (90.57%) were from Yunnan Province and surrounding high altitude areas. 2 166 cases of heart defects were finally analyzed, including 998 cases of congenital heart disease (CHD), 93 cases of cardiac tumors, cardiomyopathy and arrhythmia, 1 075 cases of foramen ovale, ductus arteriosus abnormalities and normal variations. The pregnant women were (29.2±5.0) years old with (25.6±3.8) gestational weeks. The number of cases with prognostic grade from Ⅰ to Ⅳ was 1 037 (47.88%), 620 (28.62%), 314 (14.50%), and 44 (2.03%), respectively. And 151 cases (6.97%) were not classified. The cases of normal variation and thin aortic arch development accounted for 42.66% (924/2 166), 5.22% (113/2 166), respectively. The top 3 diseases of grade Ⅱ were ventricular septal defect, coarctation of aorta and mild-moderate pulmonary stenosis, respectively, and their distribution was 11.63% (252/2 166), 3.92% (85/2 166) and 2.35% (51/2 166) respectively in all cases of heart defects, and 25.25% (252/998), 8.52% (85/998) and 5.11% (51/998) respectively in cases of CHD. Among the cases rated as grade Ⅲ and Ⅳ, most of them were complicated congenital heart disease, and the disease types are scattered. The more common cases in grade Ⅲ were complete transposition of great arteries (accounting for 2.40% (52/2 166) of all cases with heart defects, 5.21% (52/998) of all cases with CHD) and pulmonary artery occlusion (type Ⅰ to Ⅲ) with ventricular septal defect (accounting for 2.17% (47/2 166) of all cases with heart defects, and 4.71% (47/998) of all cases with CHD). In grade Ⅳ, single ventricle (0.74% (16/2 166) of all cases with heart defects, 1.60% (16/998) of all cases with CHD) and left ventricular dysplasia syndrome (0.65% (14/2 166) of all cases with heart defects, 1.40% (14/998) of all cases with CHD) are more common. A total of 1 084 cases were successfully followed up, and 675 cases were born, 392 cases were terminated, spontaneous abortion occurred in 17 cases. The proportion of terminated pregnancy cases was significantly increased from grade Ⅰ to Ⅳ, accounting for 5.24% (21/401), 27.78% (70/252), 89.54% (214/239) and 95.56% (43/45), respectively. Among the terminated pregnancy cases, those with grade Ⅲ accounted for the highest proportion (54.59% (214/392)). The distribution of terminated pregnancy cases was mainly complex congenital malformations or diseases with very poor prognosis (pregnancy outcome grade Ⅲ and Ⅳ), and proportion of terminated pregnancy with pregnancy outcome grade Ⅰ and Ⅱ cases (normal variation or good prognosis) accounted for 5.36% (21/392) and 17.86% (70/392), respectively. The results of multivariate logistic regression analysis showed that pregnant women with low education (high school and below: OR=2.73, 95%CI 1.26-5.93, P<0.001; illiteracy: OR=3.27, 95%CI 1.29-7.10, P<0.001) and low family income (Annual income<100 000 yuan: OR=2.47, 95%CI 1.69-5.12, P<0.001) were more likely to choose termination of pregnancy in case of fetal heart defect. Conclusion: In Yunnan province and the surrounding high altitude areas, the disease distribution of fetal heart defect is mainly simple or low-risk disease, but the complex malformation, especially the disease with poor pregnancy outcome, accounts for a relative high proportion. Pregnancy termination also occurs in some cases with good pregnancy outcome. The education level and family income of pregnant women may affect their choice of pregnancy outcome in case of fetal heart defect.

Clinical application of Flow-through bridge anterolateral thigh flap in repair of complex calf soft tissue defects / 中国修复重建外科杂志

OBJECTIVE@#To investigate the effectiveness of Flow-through bridge anterolateral thigh flap transplantation in the treatment of complex calf soft tissue defects.@*METHODS@#The clinical data of the patients with complicated calf soft tissue defects, who were treated with Flow-through bridge anterolateral thigh flap (study group, 23 cases) or bridge anterolateral thigh flap (control group, 23 cases) between January 2008 and January 2022, were retrospectively analyzed. All complex calf soft tissue defects in the two groups were caused by trauma or osteomyelitis, and there was only one major blood vessel in the calf or no blood vessel anastomosed with the grafted skin flap. There was no significant difference between the two groups in general data such as gender, age, etiology, size of leg soft tissue defect, and time from injury to operation ( P>0.05). The lower extremity functional scale (LEFS) was used to evaluate the sufferred lower extremity function of the both groups after operation, and the peripheral blood circulation score of the healthy side was evaluated according to the Chinese Medical Association Hand Surgery Society's functional evaluation standard for replantation of amputated limbs. Weber's quantitative method was used to detect static 2-point discrimination (S2PD) to evaluate peripheral sensation of the healthy side, and the popliteal artery flow velocity, toenail capillary filling time, foot temperature, toe blood oxygen saturation of the healthy side, and the incidence of complications were compared between the two groups.@*RESULTS@#No vascular or nerve injury occurred during operation. All flaps survived, and 1 case of partial flap necrosis occurred in both groups, which healed after free skin grafting. All patients were followed up 6 months to 8 years, with a median time of 26 months. The function of the sufferred limb of the two groups recovered satisfactorily, the blood supply of the flap was good, the texture was soft, and the appearance was fair. The incision in the donor site healed well with a linear scar, and the color of the skin graft area was similar. Only a rectangular scar could be seen in the skin donor area where have a satisfactory appearance. The blood supply of the distal limb of the healthy limb was good, and there was no obvious abnormality in color and skin temperature, and the blood supply of the limb was normal during activity. The popliteal artery flow velocity in the study group was significantly faster than that in the control group at 1 month after the pedicle was cut, and the foot temperature, toe blood oxygen saturation, S2PD, toenail capillary filling time, and peripheral blood circulation score were significantly better than those in the control group ( P<0.05). There were 8 cases of cold feet and 2 cases of numbness on the healthy side in the control group, while only 3 cases of cold feet occurred in the study group. The incidence of complications in the study group (13.04%) was significantly lower than that in the control group (43.47%) ( χ 2=3.860, P=0.049). There was no significant difference in LEFS score between the two groups at 6 months after operation ( P>0.05).@*CONCLUSION@#Flow-through bridge anterolateral thigh flap can reduce postoperative complications of healthy feet and reduce the impact of surgery on blood supply and sensation of healthy feet. It is an effective method for repairing complex calf soft tissue defects.

Clinical efficacy of liver transplantation for intrahepatic cholangiocarcinoma: a multicenter study / 中华消化外科杂志

Objective:To investigate the clinical efficacy of liver transplantation for intra-hepatic cholangiocarcinoma.Methods:The retrospective cohort study was conducted. The clinico-pathological data of 22 patients with intrahepatic cholangiocarcinoma who underwent liver trans-plantation in the 5 medical centers, including First Hospital of Jilin University, et al, from September 2005 to December 2021 were collected. There were 18 males and 4 females, aged 57(range, 38?71)years. Observing indicators: (1) clinicopathological characteristics of patients with intrahepatic cholangiocarcinoma; (2) follow-up; (3) prognosis. Measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers or percentages. The Kaplan-Meier method was used to draw survival curves. The Log-Rank test was used for survival analysis. Results:(1) Clinicopathological characteristics of patients with intrahepatic cholangio-carcinoma. Of the 22 patients, 20 cases were diagnosed as intrahepatic cholangiocarcinoma before liver transplantation, 7 cases had viral hepatitis type B, 1 case had primary sclerosing cholangitis, 7 cases had tumor treatment before liver transplantation, 7 cases, 6 cases and 9 cases were classified as grade A, grade B and grade C of the Child-Pugh classification, 16 cases had preoperative CA19-9 >40 U/mL, 14 cases had single tumor, 11 cases with tumor located at right lobe of liver, 6 cases with tumor located at both left and right lobe of liver, 5 cases with tumor located at left lobe of liver, 9 cases with tumor vascular invasion. All 22 patients were diagnosed as moderate-poor differentiated tumor. There were 9 cases with liver cirrhosis, 4 cases with tumor lymph node metastasis, 10 cases with tumor burden within Milan criteria. The tumor diameter of 22 patients was 4.5(range, 1.5?8.0)cm. (2) Follow-up. All 22 patients were followed up for 15(range, 3?207)months. Of the 22 patients, 9 cases had tumor recurrence and 8 cases died. (3) Prognosis. The 1-year overall survival rate and 1-year disease-free survival rate of the 22 patients was 72.73% and 68.18%, respectively. Results of subgroup analysis showed there were significant differences in overall survival and disease-free survival between the 10 patients with tumor burden within Milan criteria and the 12 patients with tumor burden beyond Milan criteria who underwent liver transplantation ( hazard ratio=0.13, 0.26, 95% confidence interval as 0.03?0.53, 0.08?0.82, P<0.05). Results of further analysis of the 12 patients with tumor burden beyond Milan criteria showed there were significant differences in overall survival and disease-free survival between the 5 patients with preoperative tumor down-staging treatment and the 7 patients without preoperative tumor down-staging treatment ( hazard ratio=0.18, 0.14, 95% confidence interval as 0.04?0.76, 0.04?0.58, P<0.05). Conclusions:Intrahepatic cholangiocarcinoma patients with tumor burden within Milan criteria have a better prognosis than patients with tumor burden beyond Milan criteria after liver transplantation. For patients with tumor burden beyond Milan criteria, active tumor down-staging treatment before liver transplantation can improve the prognosis.

Effect of chronic restraint stress on the phenotypic transition of hippocampal astrocytes and depression-like behavior in mice / 解剖学报

Objective To explore the effect of chronic restraint stress (CRS) on the phenotypic transition of hippocampal astrocytes and depression-like behavior in mice. Methods Forty eight male C57BL/6 mice were randomly divided into control groups (control), model groups (CRS) and fluoxetine(FLX) drug intervention groups (CRS+FLX), 16 for each group. The mice of the CRS group were subjected to 3 weeks chronic restraint stress. The mice of CRS + FLX group were treated with fluoxetine by intraperitoneal injection 30 minutes before restraint stress from the day 8 to day 21.

Dexmedetomidine improving complete Freund's adjuvant-induced anxiety-like and depression-like behaviour by promoting the expression of brain-derived neurotrophic factor-tyrosin kinase receptor B in mice hippocampus / 解剖学报

Objective To study the effect of dexmedetomidine (DEX), an α2- adrenoceptor agonist, on the pain-related anxiety-like and depression-like behaviour induced by complete Freund' s adjuvant (CFA) injection and its possible regulatory mechanism. Methods Thirty-six ICR female mice were randomly divided into normal saline (NS) group, CFA group and DEX + CFA group, n = 12 for each group. Chronic inflammatory pain model was established by subcutaneous injection of 10 μl CFA into the right hind limb of mice. DEX + CFA group mice were injected intraperitoneally with 0.025 mg/kg DEX 30 minutes before nociceptive behavior test, and once a day for 7 days. Von-frey fiber was used to evaluate the threshold of mechanical pain in mice, n = 12 for each group. The anxiety-like behavior of mice were detected by open field test, n = 12 for each group. Sucrose preference, tail suspension test and forced swimming test were used to detected the depression-like behavior of mice, n = 12 for each group. The expression of adrenergic receptor β2 (ADRB2), Brain-derived neurotrophic factor (BDNF), tyrosine kinase B receptor (TrkB), and glutamate receptors 1 (GluR1) and GluR2 were detected by Western blotting, n = 8 for each group. Immunohistochemical staining was used to detect the expression of recombinant doublecortin(DCX), which is a marker of newborn neurons in the hippocampus, n = 4 for each group. Results Compared with the NS group, the mechanical threshold of mice on the 1st, 3rd and 7th day after CFA injection decreased significantly (P 0.05). Compared with the NS group, the time spent in the inner ares (P<0.01), number of entering the central grid area (P<0.01) and distance travelled in the inner area (P<0.01) of CFA group mice reduced significantly, while the time (P<0.01), numbers (P < 0.05) and distance (P < 0.05) of DEX + CFA group mice entering the central grid area enhanced significantly. The result of depression-like behavior tests showed that the sucrose preference percentage (P < 0.05) reduced significantly in CFA group when compared with NS group, and the immobility time increased significantly in tail suspension test (P<0.01) and forced swimming test (P< 0.001) in CFA mice when compared with NS group, while DEX intervention could significantly increase the sucrose preference scores (P<0.05) and decreased the immobility time in tail suspension test (P<0.05) and forced swimming test (P<0.05). The result of Western blotting showed that compared with the NS group, the levels of ADRB2 (P<0.0010), BDNF (P < 0.001), TrkB (P < 0.01), GluR1 (P < 0.001) and GluR2 (P < 0.001) in the hippocampus of CFA group were significantly decreased, while DEX intervention could significantly increase the expression of ADRB2 (P<0.05), BDNF (P < 0.001), TrkB (P < 0.001), GluR1 (P < 0.001) and GluR2 (P < 0.001). Immunohistochemical result showed that compared with the NS group, the average absorbance (AA) of DCX decreased significantly in hippocampus of CFA group (P<0.05), but increased significantly in DEX+CFA group (P < 0.05). Conclusion Dexmedetomidine may promote hippocampal neurogenesis through upregulated the expression of BDNF-TrkB, thus improving CFA-induced anxiety-like and depression-like behaviors in mice.

Effects of chronic restraint stress on the expression of N6-methyladenosine and related enzymes in the hippocampus of mice / 解剖学报

Objective To investigate the effect of chronic restraint stress on the expression of N6-methyladenosine (m6A)and related enzymes in the hippocampus of mice. Methods Twenty C57BL/6J male mice were randomly divided into control group and chronic restraint stress (CRS) group, the model group was given for 3 weeks chronic restraint stress to establish a mouse anxiety model. Open field test and elevated plus maze test were used to detect anxiety-like behavior; Immunohistochemistry and m6A RNA methylation assay were used to detect the expression changes of mouse hippocampal m6A; Western blotting and Real-time PCR were used to analyze hippocampal m6A related enzymes expression. Results 1.The behavioral results showed that, compared with the control group, the CRS group showed significantly reduced time spent in the center of the open field(P<0.01), the CRS group showed significantly reduced exploration time in the open arm of elevated plus maze (P<0.0001); 2. Immunohistochemical results showed that, compared with the control group, the hippocampal m6A content in the CRS group reduced significantly (P < 0.001); The results of the m6A RNA methylation assay showed that, compared with the control group, the CRS group showed significantly reduced amount of hippocampal m6A(P<0.05); 3. Real-time PCR results showed that the expression of hippocampal demethylase anaplastic lymphoma kinase B(AlkB) homolog 5(ALKBH5) (P<0.001) and fat mass and obestity associated protein(FTO) (P< 0.05) in the CRS group significantly up-regulated, the expression of methylase Wilms' tumour 1-associating protein (WTAP) (P<0.05) was significantly down-regulated compared with the control group; The expression of m6A methylation binding protein YTH domaincontaining family protein 3 (YTHDF3) (P < 0.05) and YTH domaincontaining protein 2 (YTHDC2) (P < 0.01) was significantly up-regulated. Western blotting result showed that, compared with the control group, the mouse hippocampal demethylase ALKBH5 (P < 0.05) and FTO (P < 0.05) expression in the CRS group significantly up-regulated, the expression of WTAP (P<0.01) was significantly down-regulated; m6A methylation binding protein YTHDF3 (P<0.01) and YTHDC2 (P<0.05) were significantly up-regulated. Conclusion In the anxiety model induced by chronic restraint stress, the expression of m6A in the hippocampus of mice is down-regulated. The mechanism may be related to the up-regulation of the m6A demethylase ALKBH5 and FTO or the down-regulation of the methylase WTAP.

Diagnosis and individualized drug therapy for the rejection with hyperglycemia after liver Transplantation / 中国临床药理学与治疗学

AIM: To establish individualized drug therapy strategy for patients with rejection and hyperglycemia after liver transplantation. METHODS: Clinical pharmacist collaborated with the surgeons and participated in the diagnosis and treatment of rejection and hyperglycemia after liver transplantation. Taking together liver function, therapeutic drug monitoring, drug-drug interactions between tacrolimus and wuzhi capsule, individualized drug therapy was adapted to improve the prognosis. RESULTS: The patient recovered well and survived in good health till now. CONCLUSION: It is highly suggested that clinical pharmacists actively involved in treatment of more severe and difficult-to-treat disease and design the individualized dosing regimens. This will largely contribute in reduced adverse drug reaction, improved safety and effectiveness in drug use as well as the quality of life in the "post-transplantation era".

Identification of Complex and Combined Antibody Consisted of Anti-c, Anti-E, Anti-Jka and Anti-Fya / 中国实验血液学杂志

OBJECTIVE@#To investigate the role of multiple serological methods in the identification of complex antibodies.@*METHODS@#The blood group antigens were detected by saline and microcolumn agglutination methods. The saline method was used to screen and identify IgM-type antibodies in the patient's serum, while the polybrene, anti-globulin, microcolumn agglutination, enzymic and absorption-elution methods were used to screen and identify IgG-type antibodies.@*RESULTS@#The patient was B/CCDee/Jk(a-b+)/Fy(a-b+) blood type. The serum reacted with panel cells, and the reaction presented anti-E pattern in the saline medium. It was fully positive in the microcolumn agglutination card, except 2 negative ones after using papain to treat the panel cells. Referring to the pattern table, it was concluded that there existed anti-c, anti-E, and anti-Jka antibodies, and one antibody corresponding to an antigen that was easily destroyed by papain. The red blood cells with specific phenotype were selected for absorption-elution to identify IgG-type anti-c, anti-E, anti-Jka and anti-Fya antibodies.@*CONCLUSION@#It is confirmed that IgM-type anti-E, and IgG-type anti-c, anti-E, anti-Jka and anti-Fya antibodies exist in the patient's serum by multiple serological methods.

The mediating role of emotion regulation strategies between symptoms and anxiety problems in children with attention deficit hyperactivity disorder / 中国当代儿科杂志

OBJECTIVES@#To study the mediating role of emotion regulation strategies between symptoms and anxiety problems in children with attention deficit hyperactivity disorder (ADHD).@*METHODS@#Convenience cluster sampling was performed to select 435 eligible children with ADHD from 10 211 students in 10 elementary schools in Kashgar of Xinjiang Uygur Autonomous Region. SNAP-IV Assessment Scale, Emotion Regulation Questionnaire for Children and Adolescents, and Conners Parent Symptoms Questionnaire were used to obtain relevant information. The Spearman correlation analysis and the moderated mediation method were used for data analysis.@*RESULTS@#For the children with ADHD, the score of cognitive reappraisal was negatively correlated with the scores of symptoms and anxiety problems (rs=-0.254 and -0.270 respectively, P<0.001), and the score of symptoms was positively correlated with the score of anxiety problems (rs=0.329, P<0.001). The analysis of mediating effect showed that cognitive reappraisal played a partial mediating role between symptoms and anxiety problems, with a 95% confidence interval of 0.008-0.027, and the mediating effect accounted for 16.10% of the total effect. In addition, sex played a regulatory role in this mediation model (P<0.001).@*CONCLUSIONS@#Cognitive reappraisal plays a mediating role between symptoms and anxiety problems in children with ADHD, while sex regulates the relationship of symptoms with cognitive reappraisal and anxiety problems in these children.

Effect of curcumin on renal fibrosis induced by acute respiratory distress syndrome in rats / 中华急诊医学杂志

Objective:To investigate the effect of curcumin on renal fibrosis in lipopolysaccharide (LPS) induced acute respiratory distress syndrome (ARDS) in adult SD rats.Methods:Twenty-four male SD rats were randomly (random number) divided into four groups: control group, ARDS group, low dose group, and high dose group ( n=6 per group). In the control group, the rats were given atomization intratracheal of standard saline 2 mL/kg; in the ARDS group, low-dose group, and high-dose group, the rats were given atomization intratracheal of 4 mg/kg LPS; in the low-dose group, the rats were given curcumin 100 mg/d by the oral administration, and in the high-dose group, the rats were given curcumin or 200 mg/d respectively. After seven days, the rats were sacrificed. The superoxide dismutase (SOD) activity and the content of malondialdehyde (MDA) and glutathione (GSH) in renal tissue were detected by colorimetric assay. Nuclear factor kappa-B p65 (NF-κB p65) and transforming growth factor-β1 (TGF-β1) were detected by Western blot. The expression of interleukin-6 (IL-6) mRNA, proline hydroxylase 3 (PHD3) mRNA, vascular endothelial growth factor (VEGF) mRNA and erythropoietin receptor (EPOR) mRNA were detected by quantitative real-time PCR (qRT-PCR). HE staining and Masson staining were used to assess pathological damage. One-way analysis of variance was used for comparison among multiple groups and SNK method was used for comparison between two groups. Results:Compared with the control group, the SOD activity and GSH content in the ARDS group, low-dose group, and high-dose group were significantly decreased (all P<0.05); the protein expression levels of MDA, NF-κB p65, and TGF-β1 were increased significantly, and IL-6 mRNA, PHD3 mRNA, VEGF mRNA, and EPOR mRNA were significantly upregulated (all P<0.05). HE staining showed inflammatory cell infiltration, and fibrogenesis in kidney tissue, and Masson staining showed deposition of collangen-like substance. Compared with the ARDS group, SOD activity and GSH content were increased, while the protein expression of NF-κB p65 and TGF-β1, IL-6 mRNA, PHD3 mRNA, VEGF mRNA, and EPOR mRNA were decreased significantly in the low-dose group and high-dose group (all P<0.05). Curcumin therapy reduced inflammatory cellular infiltration, and the deposition of collagen-like substance in kidney tissue. Compared with the low-dose group, SOD activity and GSH content were increased in the high-dose group (all P<0.05), and the protein expression of NF-κB p65 and TGF-β1, IL-6 mRNA, PHD3 mRNA, VEGF mRNA, and EPOR mRNA were decreased significantly in the high-dose group (all P<0.05). The high-dose group exhibited a significant reduction in edema, and a decrease of the deposition of collagen-like substance in kidney tissue. Conclusions:Curcumin can inhibit the development of renal fibrosis induced by acute respiratory distress syndrome in rats, and its mechanism may be related to inhibiting the expression of inflammatory factors and enhancing hypoxia tolerance.

Repair of complex soft tissue defect in calf by ALTF with a cross-limb bridged "Y" shape vascular anastomosis: a report of 33 cases / 中华显微外科杂志

Objective:To explore the clinical effect of ALTF transfer with cross-limb bridged "Y" shape vascular anastomosis in repair of complex soft tissue defects in calf.Methods:From August 2010 to September 2020, 33 patients(23 males and 10 females) with complex traumatic soft tissue defects in calf were treated. Preoperative angiography and intraoperative exploration confirmed that there was only 1 main vessel remained in the affected calf or the wound surface and the vessel could not be anastomosed with the vascular pedicle of the ALTF. The size of flap were 16 cm × 8 cm to 25 cm × 18 cm. Two patients received bilobed ALTFs. A "Y" shape anastomosis between the artery of ALTF vascular pedicle and the posterior tibial artery of the contralateral lower limbs was made in all 33 patients to establish the blood supply to the transferred free ALTF. The "Y" shape cross-limb bridged blood vessels at the proximal end of the vascular pedicle artery of the flap were embedded at both ends of the cut-off superior ankle posterior tibial artery of the contralateral lower limb. The vein of the flap was anastomosed with the saphenous vein that associates with the posterior tibial artery. The surface of the suspended blood vessel "bridge" was wrapped with a free skin craft, and the lower limbs were fixed in a straight and parallel position with an external fixation frame. The perfused area of the flap was directly sutured or covered with a free skin craft. The vascular bridge was kept for 3 to 6 weeks before being separated. Outpatient follow-up after discharge.Results:All the patients were entered the postoperative follow-up was 13 months to 7 years, in an average of 25 months. Among the 33 flaps, 31 survived completely, except 1 had necrosis and the other 1 had partial necrosis at the distal end of the flap. The flaps received good blood supply, hence with soft texture and satisfactory appearance. Doppler or DSA was performed after the surgery on the posterior tibial artery of the healthy limb, and the vascular pulsation and patency were found normal. Donor sites for the free skin graft healed well.Conclusion:The ALTF transfer with cross-limb bridged "Y" vascular anastomosis is one of the effective techniques and it was employed in the repair of complex defects of calf soft tissue. It solved the tissue that there was only 1 main vessel or even without a suitable vessel could be anastomosed with the pedicle of the flap.

Effect and mechanism of bromodomain-containing protein 4 inhibitor JQl on formaldehyde solution induced inflammatory pain in mice / 解剖学报

Objective To explore the expression and role of bromodomain-containing protein 4(BRD4) in spinal cord of mice which suffered inflammatory pain induced by formaldelryde solution. Methods Thirty-two ICR mice were randomly divided into normal saline group and formaldehyde injection 5 minutes, 30 minutes and 60 minutes groups, with 8 mice in each group. The expression of BRD4 protein and mRNA in spinal cord of mice in each group were detected by Western blotting (n = 4/group) and Real-time PCR (n = 4/group); 66 mice were randomly divided into formaldelryde injection group, vehicle (DMSO) plus formaldelryde injection group and 6. 25, 12. 5, 25 and 50 mg/kg JQl injection plus formaldelryde solution group, with 11 mice in each group. The effect of BRD4 inhibitor JQl on spontaneous pain in each group was observed (n= 11/group); Immunohistochemistry (n= 3/group), Real-time PCR (n = 4/group) or Western blotting (n= 4/group) were used to detect the effects of 25 mg/kg JQ1 on the expression of c-fos and glutamate receptor 2 (GluR2) in the spinal cord of model mice. Results The result showed that levels of BRD4 protein (P<0. 01) and mRNA in spinal cord increased significantly 30 min and 60 min after formaldehyde solution injection (P<0. 05). The behavioral test showed that both 25 mg/kg and 50 mg/kg JQf administration could reduce the second phase spontaneous pain compared with the solvent (DMSO) group (P < 0 . 05). Furthennore, immunohistochemistry and Real-time PCR result showed that 25 mg/kg JQf injection could significantly reduce positive numbers (P<0. 01) and high mRNA expression of c-fos in mouse spinal cord induced by formaldehyde solution (P < 0 . 05), and the Western blotting result showed that 25 mg/kg JQf administration could significantly reduce the expression of glutamate receptor GluR2 (P < 0. OOf). Conclusion BRD4 may play an important role in the induction of central sensitization of inflammatory pain, and JQf may alleviate inflammatory pain behavior by inhibiting the formation of central sensitization of pain.

Sequential treatment of initially diagnosed systemic multiple metastases advanced prostate cancer / 中华泌尿外科杂志

sequential treatment of advanced prostate cancer is a current research hotspot. One patient with advanced prostate cancer with multiple metastases at initial diagnosis in our institution was sequentially treated with endocrine, abiraterone, polymerase inhibitor, and enzalutamide with an overall survival of 35 months.

Localization of Melanoma-associated Antigen MAGEA1 and Identification of Its Interacting Proteins / 中国生物化学与分子生物学报

Melanoma associated antigen family A1 (MAGEA1) is expressed in germ cells and tumors of various histological origins, but its mechanism is still unclear. In this study, the eukaryotic recombinant MAGEA1 expression plasmids with Flag or GFP tags were constructed and transfected into HeLa and HEK293T cells. Western blotting, immunocytochemistry, co-immunoprecipitation, nuclear protein and cytoplasmic protein separation, and mitochondrial isolation were used to detect the expression and location of MAGEA1 and its interaction with other proteins in cells. The results of immunocytochemistry (ICC) and Western blotting showed that the overexpressed MAGEA1 was mainly localized in the cytoplasm and partially co-localized with mitochondria. Co-immunoprecipitation experiments verified the interactions between MAGEA1 and TRIM31, SNW1, HDAC1, and found that MAGEA1 may mainly interact with HDAC1 in the cytoplasm. The studies above indicate that MAGEA1 may be involved in different cellular biological processes and co-localize with mitochondria. It interacts with TRIM31, SNW1 and HDAC1, while MAGEA1 may mainly interact with HDAC1 in the cytoplasm. We propose that it may be involved in protein ubiquitination and the Notch signaling pathway. The results of this study laid an experimental foundation for the subsequent in-depth study of the mechanism of MAGEA1.

Relationship between complete Freund ' s adjuvant-induced chronic pain-induced negative emotions and morphological changes of hippocampal microglia / 解剖学报

Objective To investigate the alteration of mood and hippocampal microglia morphology in a mouse model of chronic inflammatory pain induced by complete Freund' s adjuvant (CFA). Methods Thirty-two male ICR mice were randomly divided into two groups, including normal saline control group (NS) and CFA model group (CFA). The pain model was established by right hindpaw intraplantar CFA injection. The change of mechanical pain threshold after CFA injection was measured by von Frey fiber needle, the locomotor activity and anxiety-like behavior were determined by open field test (OFT), the depression-like behavior was determined by sucrose preference test (SPT) and forced swimming test (FST). The expression of microglia marker ionized calcium binding adaptor molecule-1 (IBA-1) in the hippocampus was determined by immunohistochemistry and its morphological change was analyzed by Sholl analysis. Results Compared with the NS group, the mechanical pain threshold of CFA group decreased significantly (P<0.01). The behavior result showed that the CFA group showed remarkably reduced time in the inner area (P<0.01) compared with the NS group in the open field test; In the sucrose preference test, the percentage of sucrose preference (P<0.01) of CFA mice decreased significantly compared with the NS mice, while the immobility time of CFA mice (P<0.01) increased significantly in the forced swimming test compared with the NS mice. The immunohistochemistry showed that the number of microglia in the dentate gyrus (DG) of CFA mice increased significantly compared with the NS mice. The Sholl analysis result showed that compared with the NS mice, the number of intersections of microglia in hippocampal DG decreased significantly in CFA mice. Conclusion Our finding indicates that the negative emotions in CFA-induced chronic inflammatory pain may be related to the morphological changes of hippocampal microglia in the mice.

Heat-Clearing Chinese Medicines in Lipopolysaccharide-Induced Inflammation / 中国结合医学杂志

Lipopolysaccharide (LPS)-induced inflammation causes massive threatening diseases, such as sepsis, acute lung injury and multiple organ dysfunction syndrome. Efficient treatment to prevent inflammation is crucial in LPS-induced inflammatory diseases. Heat-clearing Chinese medicines (CMs) have been used to ameliorate LPS-induced inflammation in China for centuries. Heat-clearing CMs regulate inflammatory pathways, thereby inhibiting the release of inflammatory factors. This review aimed to introduce promising heat-clearing CMs countering LPS-induced inflammation in the last 5 years, exploring the underlying molecular mechanisms.

Two Novel Mutations at the CD36 Gene Splicing Sites and Their Molecular Basis for the CD36 Deficiency / 中国实验血液学杂志

OBJECTIVE@#To study two novel CD36 gene mutations at the CD36 splicing sites found in Guangxi population, as well as the molecular basis and population incidence of them.@*METHODS@#DNA sequencing and cDNA clonal sequencing were used to detect CD36 exon sequence and the protein coding region sequence of CD36 mRNA for 2 CD36 deficient individuals (HHC and WGM) found in Guangxi population. Eukaryotic expression cell lines were established for the discovery of CD36 mRNA abnormal transcripts and Western blot assay was used to verify the effect of abnormal CD36 mRNA transcripts on CD36 expression. A DNA PCR-SSP genotyping method was established for the two CD36 novel mutations, and the population distribution was investigated among 110 CD36 deficient individuals in Guangxi region and 296 random individuals in Guangxi population.@*RESULTS@#Novel mutation of c.430 -1G>C was found at the CD36 splicing site in HHC and WGM individuals, and novel mutation of c.1006 +2T>G at the CD36 splicing site was also found in the WGM individual. CD36 cDNA clonal sequencing showed that CD36 c.430 -1G>C could lead to the production of the two CD36 mRNA transcript variants: c.429_430ins［430-17_430-2;C］(p.Ala144fsTer1) and c.430_609del(p.Ala144_Pro203del)(GenBank:HM 217023.1); and CD36 c.1006 +2T>G could lead to the production of CD36 mRNA transcript variant of c.819_1006 del (p.Ser274GlufsTer16) (GenBank: HM217025.1). It was verified that all the three transcript variants could lead to CD36 deficiency by establishment of eukaryotic expression cell lines and Western blot assay. A study of the population incidence of two novel CD36 splicing site mutations found showed that in 110 CD36 deficient individuals and in 296 random individuals in Guangxi region, the mutation rate of CD36 c.430 -1G>C was 10.91% (12/110) and 1.35% (4/296), respectively, while CD36 c.1006 +2T>G was 2.73% (3/110) and 0 (0/296), respectively.@*CONCLUSION@#This study identifies two novel CD36 mutations at CD36 splicing site, and preliminary clarified their molecular basis for the CD36 deficiency and the distribution characteristics in Guangxi population as well. It provides an experimental and theoretical basis for studying the molecular mechanism and characteristics of CD36 deficiency in Chinese population.

Real-time assessments of liver quality in cold ischemia injury based on the technique of laser scanning confocal microscope / 中华器官移植杂志

Objective To assess the quality of donor liver allografts by employing laser scanning confocal microscope (LSCM ) and clinical liver function tests .Methods Sprague-Dawley rats were used for establishing cold ischemia models of liver allografts .According to different timepoints of cold ischemia ,four groups of CIT1h ,CIT6h ,CIT12h and CIT24h were designated .At the end of cold ischemia time (CIT) of each group , perfusion and preservation fluids were collected and fluoresceins perfused . After LSCM examinations ,tissue samples were harvested for HE examination .Finally a comparison was made between LSCM results and hematoxylin & eosin (HE) examinations .Also some relevant clinical parameters were detected in preserving and flushing fluids .Results Both LSCM examination and pathological examination indicated that the quality of liver allografts decreased significantly with the elapsing of time . Only the difference of LDH was statistically significant (P<0 .001) .Conclusions LSCM may be used for evaluating the ex vivo qualities of liver allografts .Simple handling and time efficiency re great advantages of LSCM .As compared with alanine transaminase (ALT ) and aspartate transaminase (AST ) ,LDH is a better indicator reflecting the quality of liver allografts .

Willingness analyses on volunteers to perform on-site rescue for patients with apnea and cardiac arrest:comparison of results before and after cardiopulmonary resuscitation training / 中国中西医结合急救杂志

Objective To evaluate the impact of cardiopulmonary resuscitation (CPR) training on the willingness to perform on-site rescue for patients with apnea and cardiac arrest. Methods Through questionnaire survey, the analyses on the differences in the results of evaluating various indicators in CPR Willingness Questionnaire in 364 willingness (including 14 recurrent training personnel) of Yunnan Emergency Center from January 2017 to June 2018 before and after CPR training were carried out in order to observe the impact of training on willingness CPR willingness. Results A total of 364 questionnaires were distributed and 364 valid questionnaires were recovered, with a recovery rate of 100%. Compared with those before the CPR training, the analyses of the contents of the questionnaire showed that the proportions of following 6 types of volunteer who were reluctant to implement CPR on site begore training were significantly lower after CPR training [no confidence in their own operational skills: 20.3% (74/364) vs. 83.2% (303/364), being impossible to identify the patients requiring CPR: 25.5% (93/364) vs. 87.1% (317/364), fear of mouth-to-mouth artificial respiration to contract infectious diseases: 30.2% (110/364) vs. 82.4% (300/364), worried about chest compressions leading to bone fractures: 23.3% (85/364) vs. 86.8% (316/364), worried about the inaccurate positioning of chest compressions: 12.4% (45/364) vs. 82.4% (300/364) and fear of taking legal responsibility: 14.3% (52/364) vs. 89.8% (327/364)], and the differences were statistically significant (all P < 0.05); after training, the following 3 kinds of proportions of carrying out CPR were much higher than those before training [volunteers were willing to implement CPR on site for strangers: 83.2% (303/364) vs. 54.9% (200/364), volunteers were willing to implement CPR on site for friends, colleagues, classmates and other acquaintances: 83.5% (304/364) vs. 58.2% (212/364), volunteers were willing to implement CPR on site for family members: 84.6% (308/364) vs. 61.8% (225/364)], the differences being statistically significant (all P < 0.05). Conclusion CPR training for volunteers can improve their willingness to perform on-site rescue for patients with apnea and cardiac arrest, but there are still partial barriers of CPR willingness for strangers.