Mevalonate improves anti-PD-1/PD-L1 efficacy by stabilizing CD274 mRNA

Mevalonate metabolism plays an important role in regulating tumor growth and progression; however, its role in immune evasion and immune checkpoint modulation remains unclear. Here, we found that non-small cell lung cancer (NSCLC) patients with higher plasma mevalonate response better to anti-PD-(L)1 therapy, as indicated by prolonged progression-free survival and overall survival. Plasma mevalonate levels were positively correlated with programmed death ligand-1 (PD-L1) expression in tumor tissues. In NSCLC cell lines and patient-derived cells, supplementation of mevalonate significantly up-regulated the expression of PD-L1, whereas deprivation of mevalonate reduced PD-L1 expression. Mevalonate increased CD274 mRNA level but did not affect CD274 transcription. Further, we confirmed that mevalonate improved CD274 mRNA stability. Mevalonate promoted the affinity of the AU-rich element-binding protein HuR to the 3'-UTR regions of CD274 mRNA and thereby stabilized CD274 mRNA. By in vivo study, we further confirmed that mevalonate addition enhanced the anti-tumor effect of anti-PD-L1, increased the infiltration of CD8+ T cells, and improved cytotoxic function of T cells. Collectively, our findings discovered plasma mevalonate levels positively correlated with the therapeutic efficacy of anti-PD-(L)1 antibody, and provided the evidence that mevalonate supplementation could be an immunosensitizer in NSCLC.

The impact of lipids on the cancer-immunity cycle and strategies for modulating lipid metabolism to improve cancer immunotherapy

Lipids have been found to modulate tumor biology, including proliferation, survival, and metastasis. With the new understanding of tumor immune escape that has developed in recent years, the influence of lipids on the cancer-immunity cycle has also been gradually discovered. First, regarding antigen presentation, cholesterol prevents tumor antigens from being identified by antigen presenting cells. Fatty acids reduce the expression of major histocompatibility complex class I and costimulatory factors in dendritic cells, impairing antigen presentation to T cells. Prostaglandin E2 (PGE2) reduce the accumulation of tumor-infiltrating dendritic cells. Regarding T-cell priming and activation, cholesterol destroys the structure of the T-cell receptor and reduces immunodetection. In contrast, cholesterol also promotes T-cell receptor clustering and relative signal transduction. PGE2 represses T-cell proliferation. Finally, regarding T-cell killing of cancer cells, PGE2 and cholesterol weaken granule-dependent cytotoxicity. Moreover, fatty acids, cholesterol, and PGE2 can improve the activity of immunosuppressive cells, increase the expression of immune checkpoints and promote the secretion of immunosuppressive cytokines. Given the regulatory role of lipids in the cancer-immunity cycle, drugs that modulate fatty acids, cholesterol and PGE2 have been envisioned as effective way in restoring antitumor immunity and synergizing with immunotherapy. These strategies have been studied in both preclinical and clinical studies.

Analysis of incidence and clinical characteristics of osteonecrosis of femoral head in patients with systemic lupus erythematosus treated with glucocorticoid: A descriptive study based on a prospective cohort / 中国修复重建外科杂志

OBJECTIVE@#To describe the disease characteristics of osteonecrosis of the femoral head (ONFH) in patients with systemic lupus erythematosus (SLE) who experiencing prolonged glucocorticoid (GC) exposure.@*METHODS@#Between January 2016 and June 2019, 449 SLE patients meeting the criteria were recruited from multiple centers. Hip MRI examinations were performed during screening and regular follow-up to determine the occurrence of ONFH. The cohort was divided into ONFH and non-ONFH groups, and the differences in demographic baseline characteristics, general clinical characteristics, GC medication information, combined medication, and hip clinical features were compared and comprehensively described.@*RESULTS@#The age at SLE diagnosis was 29.8 (23.2, 40.9) years, with 93.1% (418 cases) being female. The duration of GC exposure was 5.3 (2.0, 10.5) years, and the cumulative incidence of SLE-ONFH was 9.1%. Significant differences ( P<0.05) between ONFH and non-ONFH groups were observed in the following clinical characteristics: ① Demographic baseline characteristics: ONFH group had a higher proportion of patients with body mass index (BMI)<20 kg/m 2 compared to non-ONFH group. ② General clinical characteristics: ONFH group showed a higher proportion of patients with cutaneous and renal manifestations, positive antiphospholipid antibodies (aPLs) and anticardiolipin antibodies, severe SLE patients [baseline SLE Disease Activity Index 2000 (SLEDAI-2K) score ≥15], and secondary hypertension. Fasting blood glucose in ONFH group was also higher. ③ GC medication information: ONFH group had higher initial intravenous GC exposure rates, duration, cumulative doses, higher cumulative GC doses in the first month and the first 3 months, higher average daily doses in the first 3 months, and higher proportions of average daily doses ≥15.0 mg/d and ≥30.0 mg/d, as well as higher full-course average daily doses and proportion of full-course daily doses ≥30.0 mg/d compared to non-ONFH group. ④ Combined medications: ONFH group had a significantly higher rate of antiplatelet drug use than non-ONFH group. ⑤ Hip clinical features: ONFH group had a higher proportion of hip discomfort or pain and a higher incidence of hip joint effusion before MRI screening than non-ONFH group.@*CONCLUSION@#The incidence of ONFH after GC exposure in China's SLE population remains high (9.1%), with short-term (first 3 months), medium-to-high dose (average daily dose ≥15 mg/d) GC being closely associated with ONFH. Severe SLE, low BMI, certain clinical phenotypes, positive aPLs, and secondary hypertension may also be related to ONFH.

Application research of multiple intelligences theory combined with the ADDIE model in surgical clinical practice teaching / 中华医学教育探索杂志

Objective:To explore the effect of multiple intelligences theory combined with the analysis, design, development, implementation, and evaluation (ADDIE) model in surgical clinical practice teaching.Methods:A total of 100 residents trained in Department of Gastrointestinal Surgery of Heping Hospital Affiliated to Changzhi Medical College from July 2019 to April 2020 were randomly divided into the control group ( n=50) and the observation group ( n=50). The control group used the ADDIE model, and the observation group adopted the multiple intelligences theory combined with the ADDIE model. The teaching assessment of the two groups was compared, and the core competence, critical thinking ability, self-evaluation, and teaching satisfaction of the two groups were evaluated. SPSS 22.0 was used for Chi-square test and t-test. Results:The scores of basic knowledges of gastrointestinal surgery, surgical clinical thinking and case analysis, routine skills and operations, and the total scores in the observation group were higher than those in the control group ( P<0.05). The scores of professional knowledge and skills, patient safety and rights, scientific research and academic ability, professional ethics, teamwork, personal and professional development ability in the observation group were higher than those in the control group ( P<0.05). While, there was no significant difference in the mastering of knowledge between the two groups ( P>0.05). The four dimensions of learning interest, self-learning ability, innovation ability, and clinical thinking establishment in the observation group were higher than those in the control group ( P<0.05). Conclusion:Multiple intelligences theory combined with ADDIE model in surgical clinical practice teaching can improve the teaching assessment results, significantly enhance the core competence, stimulate the learning interest, cultivate the self-learning ability and innovation ability of residents, and help them to establish clinical thinking ability.

The diagnostic value of ultrasound-guided transperineal systematic prostate biopsy and cognitive fusion multi-parameter magnetic resonance imaging transperineal suspicious targeted biopsy in the prostate cancer in different serum prostate specific antigen levels / 中华超声影像学杂志

Objective:To evaluate the value of ultrasound-guided transperineal systematic prostate biopsy(SPB)and cognitive fusion multi-parameter magnetic resonance imaging(mpMRI) suspicious transperineal targeted biopsy(CFTB) in the prostate cancer with different serum prostate specific antigen(PSA) levels.Methods:A retrospective analyses were performed in 527 patients with suspected prostate cancer who underwent ultrasound-guided SPB from January 2018 to December 2019 in Shanghai Jiaotong University Affiliated 6th People′s Hospital. According to the PSA levels, they were divided into group A(PSA 4-10 μg/L) and group B(PSA>10 μg/L). All the patients underwent ultrasound-guided SPB, 376 patients with suspicious mpMRI had two additional targeted biopsies. The detection rates of ultrasound-guided SPB and CFTB in prostate cancer were tested by χ 2 test. Compared with pathological results, the sensitivity, specificity, accuracy of two methods were calculated and tested by χ 2 test, and a P<0.05 was defined as statistically significant difference. Results:Prostate cancer was detected in 319 of 527 patients(60.5%). One hundred and three cases of 198 patients in group A were diagnosed as prostate cancer, with an overall detection rate was 52.0%. Among them, ultrasound-guided SPB detected 72 cases of prostate cancer, the detection rate was 36.4%, sensitivity was 67.9%, specificity was 17.7%, accuracy was 26.5%, the detection rate, sensitivity, specificity and accuracy of CFTB were 39.9%, 75.6%, 91.6% and 88.8%, respectively. In this group, there were no statistically significant differences in the detection rate and sensitivity of the two methods in the diagnosis of prostate cancer (χ 2=0.525, 0.005, both P>0.05), and the differences in specificity and accuracy were statistically significant (χ 2=108.340, 79.829, respectively, both P<0.05). Two hundred and sixteen cases of 329 patients in group B were diagnosed as prostate cancer, with an overall detection rate was 65.7%. Among them, 160 cases of perineal prostate cancer were detected by ultrasound-guided SPB, with the detection rate was 48.6%, sensitivity was 78.2%, specificity was 37.6% and accuracy was 49.5%. A total of 189 cases of prostate cancer detected by CFTB, the detection rate was 57.4%, the sensitivity was 89.3%, the specificity was 90.6%, and the accuracy was 90.2%. All the differences were statistically significant in group B(χ 2=5.131, 4.391, 61.339, 38.982, all P<0.05). Conclusions:When PSA is greater than 10 μg/L, CFTB has a higher diagnostic efficiency than SPB.When PSA is 4-10 μg/L, there are no significant differences between the two methods in the detection rate and sensitivity of prostate cancer.

Current Advance in Targeted Treatment and Immunotherapy for BRAF-mutant Advanced Non-small Cell Lung Cancer / 中国肺癌杂志

With the development of precision medicine, therapies of targeting driver genes have significantly prolonged survival in advanced non-small cell lung cancer (NSCLC) patients. Among them, BRAF gene mutation is relatively rare, and the traditional regimen follows the treatment plan of NSCLC without driver gene mutation, which is far from meeting the clinical needs. In recent years, targeted therapy for NSCLC patients with BRAF V600E mutations has shown good efficacy when we are still exploring the better targeted therapies for other BRAF-mutated subtypes. Immunotherapy also showed positive antitumor activity in V600E and non-V600E subtypes of BRAF-mutated NSCLC. This article reviewed the progress of immunological and targeted therapy for patients with BRAF-mutated NSCLC.
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Cancer incidence and mortality in Pearl River Delta Area, 2009-2013 / 中华肿瘤杂志

Objective@#To estimate the incidence, mortality and characteristics of cancer in Pearl River Delta Area of Guangdong Province between 2009-2013.@*Methods@#Based on five population-based cancer registration data from Guangzhou, Shenzhen, Zhongshan, Jiangmen and Sihui spanning from 2009 to 2013, along with those corresponding population data, the incidence and mortality rates were estimated by gender and age groups. Chinese standard population derived from the 2000 Population Census and Segi′s standard population were used for age-standardized incidence and mortality rates.@*Results@#Between 2009 and 2013, the crude cancer incidence rate was 262.50/100 000, 274.76/100 000 in male and 249.49/100 000 in female. After adjusting for Chinese and Segi′s standard population, the age-standardized incidence rates were 225.63/100 000 and 219.88/100 000, respectively. The crude mortality rate was 175.51/100 000, 222.92/100 000 in male and 127.46/100 000 in female, respectively. After adjusting for Chinese and Segi′s standard population, the age-standardized mortality rates were 116.02 /100 000 and 114.31/100 000, respectively. The incidence rates were at low levels in the population less than 40 years old, thereafter went up rapidly with age especially in male, and then reached the peak in the population aged 80 and above. As with incidence, the mortality rates kept at low levels in the population before their 50 s and then rose up steadily with age until peaking in the 85+ age group. The most common cancers were female breast cancer, lung cancer, colorectal cancer, liver cancer and nasopharyngeal cancer with descending incidence rate. Lung cancer, liver cancer, colorectal cancer, female breast cancer and nasopharyngeal cancer were the top five cancer-attributable causes of death.@*Conclusions@#Currently, Pearl River Delta Area were faced with huge cancer burden. Lung cancer, colorectal cancer, nasopharyngeal cancer, female breast cancer and male liver cancer are predominant cancers and more efforts should be made to fight against them.

Experimental study on increasing the volume of radiofrequency ablation of canine benign prostatic hyperplasia by low frequency ultrasound irradiation / 中华医学超声杂志（电子版）

Objective To evaluate the effect of low frequency ultrasound on the volume of the radiofrequency ablation lesion in canine hyperplasia prostate tissue.Methods A total of 9 experimental dogs were divided into three groups(3 in each group).Radiofrequency ablation was performed on the canine prostates.Low-frequency ultrasound was performed before the ablation of the experimental group.Radiofrequency ablation or low-frequency ultrasound was performed only in the control groups.Then all experiment animals underwent routine rectal examination,contrast-enhanced ultrasonography and MRI.The volume of prostate ablation lesions in enhanced magnetic resonance imaging was compared between the low-frequency ultrasound irradiation plus radiofrequency ablation group and the control group with radiofrequency ablation only.Statistical analysis was performed using the t-test to compare the differences between groups.Results Contrast enhanced ultrasonography(CEUS)performed immediately after low-frequency ultrasound irradiation showed that the time to peak of intra-prostatic contrast agent shortened,the maximum intensity decreased compared with those before irradiation [(28.55±10.88)s vs(14.81±5.15)s,t=2.796,P=0.0189],and the contrast agent duration increased [(2046.56±424.66)dB s vs(1454.82±458.12)dB s],the difference was statistically significant(t=2.32,P=0.0427).CEUS and MRI can accurately evaluate the size of the prostate radiofrequency ablation.The ablation volume of the experimental group after ablation was(1.27 ± 0.21)cm3in the experimental group,while the volume of the ablation group in the control group was(0.73±0.18)cm3,and the difference was statistically significant(t=3.382,P=0.0277); however,the other group which were only exposed to low-frequency ultrasound did not show lesions.Conclusion Low frequency ultrasound irradiation can effectively block the blood flow in proliferative prostatic tissue,and combined with radiofrequency ablation can effectively increase the volume of ablation.

Blood perfusion disruption and reperfusion after low-frequency ultrasound combing microbubbles on prostate cancer xenografts in nude mice / 中华超声影像学杂志

Objective To explore the duration of blood blocking effect and recovery process induced by low-frequency ultrasound combining microbubbles (USMB) on prostate cancer xenografts.Methods A total of 88 nude mice undergoing USMB was studied.Contrast enhanced ultrasound,Hemotoxylin and eosin staining,and modified Martius-Sarlet-Blue staining were used to compared the average peak intensity(API),time to peak intensity(TP) and histological alteration before and after treatment.Results Immediately after the treatment,the tumor contrast perfusion completely disappeared,API dropped from 68.63±5.25 to 18.01±2.73 (P0.05).From post-3 hours after treatment ,the tumor perfusion began a process of perfusion recovery,and showed nodular or large patch of heterogeneous enhancement.API at 3 hours after treatment was 51.99±6.20 (P0.05,vs pre-treatment).Histological examinations showed that,immediately after treatment,microvessels severely dilated,ruptured and intravascular and extravascular thrombi formed.At 30 minutes,1-hour and 2-hour after treatment,extravascular thrombi and hematomas gradually disappeared.From 3-hour after treatment,vessel dilation was lessened,and intravascular thrombi gradually shrank.At 12-hour after treatment,microvessels had almost fully recovered as pre-treatment.Conclusions USMB could block blood perfusion of prostate cancer xenografts in nude mice for 2 hours.The blood reperfusion is probably mainly caused by thrombolysis in microvessels.

Clinical study on microwave ablation combined with concurrent chemotherapy in treatment of locally advanced pancreatic cancer / 肿瘤研究与临床

Objective To investigate the clinical efficacy and safety of microwave ablation combined with concurrent chemotherapy in treatment of locally advanced pancreatic cancer. Methods Thirty-one patients with locally advanced pancreatic cancer with between August 2013 and April 2016 were divided into two groups according to the different treatments: 15 patients in the control group were treated with gemcitabine monotherapy; 16 patients in the combination group were treated with the same regimen as control group 1-2 weeks after the microwave ablation. The efficacy and side effects of the two groups were compared by chi-square test. Results The effective rates in the combination group and control group were 25.0%(4/16) and 13.3%(2/15), the difference between the two groups was not significant (χ 2=1.034, P=0.247); the local control rates were 68.8%(11/16) and 26.7%(4/15), the difference between the two groups was statistically significant (χ2=6.579, P=0.012). The pain relief rates in the combination group and control group were 87.5%(14/16) and 26.7%(4/15) (χ2=8.146, P=0.004). The 3-, 6-, 9- and 12-month survival rates in the combination group and control group were 100.0%vs. 100.0%(P=1.000), 68.8%vs. 40.0%(P=0.097),56.3%vs.20.0%(P=0.033),50.0%vs.13.3%(P=0.021).In the combination group,9 cases (56.3%)occurred postablation syndrome,the serum amylase of 7 cases(43.8%)increased 1d after ablation,1 case (6.3%) occurred pancreatic fistula. The intraoperative and perioperative death did not occur. The main complications of the two groups were myelosuppression, gastrointestinal reactions and so on. Conclusions Microwave ablation combined with concurrent chemotherapy has a synergistic effect in treatment of locally advanced pancreatic cancer. In disease control rate, pain relief rate and survival of patients, microwave ablation combined with concurrent chemotherapy is better than chemotherapy alone, but the adverse reactions are similar.

Clinical study on microwave ablation combined with concurrent chemotherapy in treatment of locally advanced pancreatic cancer / 肿瘤研究与临床

Objective To investigate the clinical efficacy and safety of microwave ablation combined with concurrent chemotherapy in treatment of locally advanced pancreatic cancer. Methods Thirty-one patients with locally advanced pancreatic cancer with between August 2013 and April 2016 were divided into two groups according to the different treatments: 15 patients in the control group were treated with gemcitabine monotherapy; 16 patients in the combination group were treated with the same regimen as control group 1-2 weeks after the microwave ablation. The efficacy and side effects of the two groups were compared by chi-square test. Results The effective rates in the combination group and control group were 25.0%(4/16) and 13.3%(2/15), the difference between the two groups was not significant (χ 2=1.034, P=0.247); the local control rates were 68.8%(11/16) and 26.7%(4/15), the difference between the two groups was statistically significant (χ2=6.579, P=0.012). The pain relief rates in the combination group and control group were 87.5%(14/16) and 26.7%(4/15) (χ2=8.146, P=0.004). The 3-, 6-, 9- and 12-month survival rates in the combination group and control group were 100.0%vs. 100.0%(P=1.000), 68.8%vs. 40.0%(P=0.097),56.3%vs.20.0%(P=0.033),50.0%vs.13.3%(P=0.021).In the combination group,9 cases (56.3%)occurred postablation syndrome,the serum amylase of 7 cases(43.8%)increased 1d after ablation,1 case (6.3%) occurred pancreatic fistula. The intraoperative and perioperative death did not occur. The main complications of the two groups were myelosuppression, gastrointestinal reactions and so on. Conclusions Microwave ablation combined with concurrent chemotherapy has a synergistic effect in treatment of locally advanced pancreatic cancer. In disease control rate, pain relief rate and survival of patients, microwave ablation combined with concurrent chemotherapy is better than chemotherapy alone, but the adverse reactions are similar.

The predictive value of modified version Essen stroke risk score for recurrent cerebral infarction / 中国医师进修杂志

Objective To explore the predictive value of modified version Essen stroke risk score (ESRS) for recurrent cerebral infarction in 1 year. Methods Factors ofcerebrovascular stenosisand≥ 2 lesions in diffusion weighted imaging (DWI) which reflected large vascular stenosis and unstable plaques to the ESRS were added, and the 2 factors of other cardiovascular diseases and“peripheral vascular disease”which were difficult to operate clinically and had a lower incidence compared with the European and American people were got rid of. Thus, the total score of the modified version ESRS was still 9 scores. The risk of recurrent cerebral infarction in 1 year in 263 patients with cerebral infarction were evaluated by ESRS and modified version ESRS, and the predictive value was evaluated by area under receiver-operating characteristics (ROC) curve. Results The incidence of recurrent cerebral infarction in 1 year in 263 patients with cerebral infarction was 15.59% (41/263). There were statistical differences in the incidences of recurrent cerebral infarction in 1 year for different risk stratification patients by 2 methods (P<0.01). Multiple factor Logistic regression analysis results showed that thecerebrovascular stenosisand≥2 lesions in DWIwere the independent risk factors in predicting recurrent cerebral infarction in 1 year (OR=12.48 and 18.72, 95%CI 5.083-30.641 and 7.718-43.242, P=0.000 and 0.000). The area under ROC of predicting recurrent cerebral infarction in 1 year by ESRS and modified version ESRS was 0.68 (95% CI 0.58- 0.79) and 0.70 (95% CI 0.60-0.79), and there was statistical difference (P<0.01). Conclusions The predictive value of modified version ESRS in recurrent cerebral infarction in 1 year is higher than that of ESRS, and it is an effective method.

Retrograde endovascular angioplasty and conventional anterograde endovascular angioplasty for the treatment of below-the-knee arterial occlusion diseases：a comparative study / 介入放射学杂志

Objective To compare the clinical efficacy of transdorsal-to-plantar (TDP) or transplantar-to-dorsal (TPD) retrograde endovascular angioplasty in treating below-the-knee arterial occlusion diseases, and to compare it with conventional anterograde endovascular angioplasty. Methods A total of 96 patients with below-the-knee arterial occlusion diseases (112 diseased lower extremities in total), who were admitted to authors’ hospital during the period from Oct. 2009 to July 2011 to receive conventional anterograde endovascular angioplasty, were enrolled in this study. The clinical data were retrospectively analyzed. Among the 112 diseased lower extremities, conventional anterograde endovascular angioplasty failed in 27, and TDP or TPD retrograde endovascular angioplasty had to be carried out. A total of 71 patients (85 diseased lower limbs) were successfully treated with conventional anterograde endovascular angioplasty (routine group), while 20 patients (22 diseased lower limbs) were successfully treated with retrograde endovascular angioplasty (retrograde group). The preoperative ankle-brachial index(ABI), the coronary angiography-based thrombolysis in myocardial infarction (TIMI) flow score, the dorsal or plantar arterial pulse score, the postoperative limb salvage rate and target vessel patency rate were calculated, and the results were compared between the two groups. Results The technical success rate in the retrograde group and the routine group was 75.9% and 74.0%respectively (P>0.05). Preoperative ABI value of the retrograde group and the routine group was 0.55± 0.21 and 0.56±0.14 respectively, after the treatment which increased to 0.93±0.19 and 0.89±0.18 respectively (P>0.05). Preoperative TIMI score of the retrograde group and the routine group was 0.1 ±0.5 and 0.8 ±0.8 respectively, which significantly increased to 2.5±0.6 and 1.8±0.8 respectively (P0.05). Twenty-four months after endovascular angioplasty Kaplan-Meier analysis indicated that the limb salvage rate of the retrograde group and the routine group was 95.5%and 96.5%respectively (P>0.05). Conclusion Compared with conventional anterograde endovascular angioplasty for the treatment of below-the-knee arterial occlusion diseases, retrograde endovascular angioplasty via TDP or TPD path can immediately improve the blood flow with obvious improvement of ABI score, primary target vessel patency rate as well as the limb salvage rate. Therefore, retrograde endovascular angioplasty should be regarded as an effective supplementary technique when anterograde angioplasty fails.

Effects of Shenfu injection intervention based on early goal-directed therapy on organ function and prognosis in patients with septic shock / 中国中西医结合急救杂志

Objective To approach the effect of Shenfu injection (SFI) and conventional early goal-directed therapy (EGDT) on organ functions and outcomes of septic shock patients. Methods Eighty-four cases conformed to the criteria for the diagnosis of septic shock admitted to Department of Critical Care Medicine of Xuzhou Central Hospital were randomly divided into conventional treatment group (42 cases), and SFI treatment group (42 cases). Conventional treatment was given in the two groups;in SFI treatment group, SFI 100 mL was additionally given by trace continuous intravenous pump 20 mL/h, twice daily for 7 days. Before and after treatment for 1, 6, 12, 24, 48, 72 hours, the levels of hemodynamic status, lactic acid and dosage of vasoactive drugs used, organ function, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score, sequential organ failure assessment (SOFA) score, the time of weaning from ventilator, the length of stay in intensive care unit (ICU), time without organ failure and 28-day mortality rate were observed. Results Compared with those before treatment, after treatment in the two groups, the mean arterial pressure (MAP), cardiac index (CI) and systemic vascular resistance index (SVRI) were increased, while the levels of heart rate (HR) and lactate were decreased (all P0.05). Compared with that before treatment, in the conventional treatment group after treatment for 1 and 3 days, gamma glutamyl transpeptidase (GGT) was increased, on the 5th day it began to decrease, reaching its minimum on the 7th day (U/L:26.75±16.74 vs. 46.96±25.85);while in SFI treatment group, GGT was increased after treatment for 1 day, on 3rd day it began to decrease, reaching its lowest level on the 7th day (U/L:22.41±17.87 vs. 51.23±27.74);aspartate aminotransferase (AST), total bilirubin (TBil), oxygenation index (PaO2/FiO2) were increased after the treatment for 1, 3, 5, 7 days, and blood urea nitrogen (BUN), creatinine (Cr) were decreased at different time points after treatment. In the conventional treatment group, the precursor protein (PA) was decreased after treatment for 1, 3, 5 days, on the 7th day it was increased (mg/L:134.20±63.44 vs. 115.70±45.96);while in SFI treatment group, after the treatment for 1 days and 3 days, it was decreased, on the 5th day it was increased, reaching its highest level on the 7th day (mg/L:145.40±59.75 vs. 108.20±54.34). Compared with those before treatment, after treatment for 1, 3, 5, 7 days, APACHEⅡscore and SOFA score were decreased in the two groups, but there was no statistically significant difference in APACHEⅡscore between the two groups, in SFI treatment group after treatment for 3 days, SOFA score was significantly lower than that of the conventional treatment group (6.31±3.86 vs. 7.14±4.03, P0.05). Conclusion The combined use of SFI and EGDT can improve hemodynamics, reduce damage to vital organs, and shorten the times for ventilation and stay in ICU in septic shock patients.

Effects of Reduning injection on activity of hepatic microsomal CYP450 isozymes in rats / 中国中药杂志

To research the influence of Reduning injection on the activity and mRNA expression of cytochrome P450 (CYP450) system in rat liver microsomes. Rat liver microsomes were prepared after a seven-days continuous administration of Reduning injection. An HPLC-MS method was applied to determine the specific metabolites of CYP450 probe substrates in rat liver microsomal incubations. The activity of CYP450 isozymes were represented by the formation of metabolites. The Real-time quantitative polymerase chain reaction (Q-PCR) was applied to determine the mRNA expression levels of CYP450. Reduning injection significantly reduced the activity of CYP2B1, 2C12, 2C13 (P < 0.01), but did not affect CYPlA2; low dose and high dose of Reduning injection had an inhibition trend on the activity of CYP2D2, but did not statistically differ from control group; low dose of Reduning injection significantly induced the activity of CYP3A1 (P < 0.01), high dose of Reduning injection had an induce trend on the activity of CYP3A1, but did not statistically differ from control. At the mRNA level, low and high dose of Reduning injection had an induce trend on the expression of CYP1A2, 2C11, 2D1, 2E1, 3A1, but did not statistically differ from control. Reduning injection significantly induced the activity of CYP2B1. Reduning injection significantly induced the activity of CYP3A1 in mRNA expression and enzyme activity levels, which may result adverse drug reaction after being combined with macrolides antibiotics. Reduning injection significantly reduced the activity of CYP2B1, 2C12, 2C13, 2D2 in enzyme activity levels, when combined with other drugs, it should be fully taken into account of the possible drug-drug interaction in order to avoid adverse side effects.

Retrograde endovascular angioplasty and conventional anterograde endovascular angioplasty for the treatment of below-the-knee arterial occlusion diseases：a comparative study / 介入放射学杂志

Objective To compare the clinical efficacy of transdorsal-to-plantar (TDP) or transplantar-to-dorsal (TPD) retrograde endovascular angioplasty in treating below-the-knee arterial occlusion diseases, and to compare it with conventional anterograde endovascular angioplasty. Methods A total of 96 patients with below-the-knee arterial occlusion diseases (112 diseased lower extremities in total), who were admitted to authors’ hospital during the period from Oct. 2009 to July 2011 to receive conventional anterograde endovascular angioplasty, were enrolled in this study. The clinical data were retrospectively analyzed. Among the 112 diseased lower extremities, conventional anterograde endovascular angioplasty failed in 27, and TDP or TPD retrograde endovascular angioplasty had to be carried out. A total of 71 patients (85 diseased lower limbs) were successfully treated with conventional anterograde endovascular angioplasty (routine group), while 20 patients (22 diseased lower limbs) were successfully treated with retrograde endovascular angioplasty (retrograde group). The preoperative ankle-brachial index(ABI), the coronary angiography-based thrombolysis in myocardial infarction (TIMI) flow score, the dorsal or plantar arterial pulse score, the postoperative limb salvage rate and target vessel patency rate were calculated, and the results were compared between the two groups. Results The technical success rate in the retrograde group and the routine group was 75.9% and 74.0%respectively (P>0.05). Preoperative ABI value of the retrograde group and the routine group was 0.55± 0.21 and 0.56±0.14 respectively, after the treatment which increased to 0.93±0.19 and 0.89±0.18 respectively (P>0.05). Preoperative TIMI score of the retrograde group and the routine group was 0.1 ±0.5 and 0.8 ±0.8 respectively, which significantly increased to 2.5±0.6 and 1.8±0.8 respectively (P0.05). Twenty-four months after endovascular angioplasty Kaplan-Meier analysis indicated that the limb salvage rate of the retrograde group and the routine group was 95.5%and 96.5%respectively (P>0.05). Conclusion Compared with conventional anterograde endovascular angioplasty for the treatment of below-the-knee arterial occlusion diseases, retrograde endovascular angioplasty via TDP or TPD path can immediately improve the blood flow with obvious improvement of ABI score, primary target vessel patency rate as well as the limb salvage rate. Therefore, retrograde endovascular angioplasty should be regarded as an effective supplementary technique when anterograde angioplasty fails.

Impact of air temperature on years of life lost among residents in Guangzhou and Zhuhai:a ;time-series study / 中华流行病学杂志

Objective To evaluate the impacts of air temperature on years of life lost(YLL) among the residents in Guangzhou and Zhuhai,Guangdong province. Methods Daily mortality and meteorology data in Guangzhou and Zhuhai were collected,and distributed lag non-linear model (DLNM)was used to evaluate the cumulative and delayed effects of daily air temperature on YLL of total non-accident mortality. The accumulative effect of air temperature on mortality under the extreme high temperature(0-1 days)and extreme low temperature(0-13 days)situation in Guangzhou and Zhuhai were analyzed respectively. Results The average YLL was 1 928.0 in Guangzhou and 202.5 in Zhuhai. The exposure-response functions seemed to be non-linear. The hot effect seemed to be acute and reached the peak at the same day,while the cold effect reached the peak at 5th days and lasted for about two weeks. Low temperature had stronger gross effect than high temperature had. The cold effect among males was greater than that among females in Guangzhou. The hot/cold effect on YLL was greater in people aged ≥65 years than in people aged <65 years and in people suffering from respiratory disease than in people suffering from cardiovascular disease in both Guangzhou and Zhuhai. Conclusion The effects of high and low temperatures on YLL were obvious,and the impact of low temperature was greater. The elderly and people suffering from respiratory disease or cardiovascular disease are the vulnerable populations.

Impact of air temperature on years of life lost among residents in Guangzhou and Zhuhai:a ;time-series study / 中华流行病学杂志

Objective To evaluate the impacts of air temperature on years of life lost(YLL) among the residents in Guangzhou and Zhuhai,Guangdong province. Methods Daily mortality and meteorology data in Guangzhou and Zhuhai were collected,and distributed lag non-linear model (DLNM)was used to evaluate the cumulative and delayed effects of daily air temperature on YLL of total non-accident mortality. The accumulative effect of air temperature on mortality under the extreme high temperature(0-1 days)and extreme low temperature(0-13 days)situation in Guangzhou and Zhuhai were analyzed respectively. Results The average YLL was 1 928.0 in Guangzhou and 202.5 in Zhuhai. The exposure-response functions seemed to be non-linear. The hot effect seemed to be acute and reached the peak at the same day,while the cold effect reached the peak at 5th days and lasted for about two weeks. Low temperature had stronger gross effect than high temperature had. The cold effect among males was greater than that among females in Guangzhou. The hot/cold effect on YLL was greater in people aged ≥65 years than in people aged <65 years and in people suffering from respiratory disease than in people suffering from cardiovascular disease in both Guangzhou and Zhuhai. Conclusion The effects of high and low temperatures on YLL were obvious,and the impact of low temperature was greater. The elderly and people suffering from respiratory disease or cardiovascular disease are the vulnerable populations.

Impact of air temperature on years of life lost among residents in Guangzhou and Zhuhai: a time-series study / 中华流行病学杂志

<p><b>OBJECTIVE</b>To evaluate the impacts of air temperature on years of life lost (YLL) among the residents in Guangzhou and Zhuhai, Guangdong province.</p><p><b>METHODS</b>Daily mortality and meteorology data in Guangzhou and Zhuhai were collected, and distributed lag non-linear model (DLNM) was used to evaluate the cumulative and delayed effects of daily air temperature on YLL of total non-accident mortality. The accumulative effect of air temperature on mortality under the extreme high temperature (0-1 days) and extreme low temperature (0-13 days) situation in Guangzhou and Zhuhai were analyzed respectively.</p><p><b>RESULTS</b>The average YLL was 1 928.0 in Guangzhou and 202.5 in Zhuhai. The exposure-response functions seemed to be non-linear. The hot effect seemed to be acute and reached the peak at the same day, while the cold effect reached the peak at 5(th) days and lasted for about two weeks. Low temperature had stronger gross effect than high temperature had. The cold effect among males was greater than that among females in Guangzhou. The hot/cold effect on YLL was greater in people aged ≥ 65 years than in people aged < 65 years and in people suffering from respiratory disease than in people suffering from cardiovascular disease in both Guangzhou and Zhuhai.</p><p><b>CONCLUSION</b>The effects of high and low temperatures on YLL were obvious, and the impact of low temperature was greater. The elderly and people suffering from respiratory disease or cardiovascular disease are the vulnerable populations.</p>

MRI for assessment of iron overload in patients with hematologic disease / 中华血液学杂志

<p><b>OBJECTIVE</b>Compare the characteristics of magnetic resonance imaging（MRI）liver T2*, cardiac T2* and serum ferritin on the assessment of iron overload.</p><p><b>METHODS</b>A total of sixty-nine patients from November 2011 to June 2014 were enrolled in this study. Their cardiac and liver iron concentration levels were measured through MRI examination, with other clinical data were collected to perform statistical analysis.</p><p><b>RESULTS</b>The correlation between liver T2* and adjusted serum ferritin（ASF） was statistically significant（P=0.003）. However, no significant correlation was found between cardiac T2* and liver T2*, ASF, respectively. According to the statistical analysis of the 69 cases, it is found that the number of iron overload cases diagnosed by liver T2* was 62 and 20 cases were severe iron overload （32.26%）; the number of iron overload cases diagnosed by ASF was 47 and 14 cases were severe iron overload（29.79%）, while the number of iron overload cases diagnosed by cardiac T2* was only 25 and no severe iron overload cases.</p><p><b>CONCLUSION</b>Since SF was affected by other factors, it cannot reflect the level of iron overload in human body objectively. Now, liver T2* has become the gold standard for assessment of iron overload because of its good reliability and repeatability. However, cardiac T2* cannot correctly be used as assessment for iron overload, and it is only a method of evaluating the level of cardiac iron deposition.</p>