Objective To explore the roles of cytokines in the pathogenesis of hemorrhagic fever with renal syndrome(HFRS). Methods Double-antibody sandwich ELISA was used to determine serum interleukin (IL)-6, urine tumor necrosis factor (TNF), IL-6 and IL-8 levels in 56 patients with HFRS. Results Serum IL-6, urine TNF, IL-6 and IL-8 concentrations in HFRS patients were significantly higher than those in control group, respectively (P＜0.001). The concentrations increased at fever stage, then continued to increase during hypotension stage and peaked at oliguria stage. The concentrations of serum IL-6, urine TNF, IL-6 and IL-8 increased in accord with the severity of the disease and differed greatly among different types of the disease. Serum IL-6 had remarkable relationships with serum specific antibodies. It was positively related to serum β2-microglobulin (β2-MG), blood ureanitrogen (BUN) and creatinine (Cr). Significant positive relationships were also found both between urine IL-6 and TNF, and between IL-6 and IL-8 (r=0.5768, P＜0.05; r=0.3760, P＜0.01). Conclusion TNF, IL-6 and IL-8 activated during the course of the disease. IL-6 is associated with the immunopathological lesions caused by the hyperfunction of humoral immune response. IL-6, IL-8 and TNF are involved in the renal immune impairment. Determining them might, in certain extent, be used in predicting the prognosis and outcome of patients with HFRS.

Objective To determine the incidence of pregnancy complicated with heart disease and assess the current obstetric management principles of pregnancy complicated with heart disease. Methods 428 cases of pregnancy complicated with heart disease were reviewed.54 cases were sur- gically corrected heart disease.Results:The incidence of pregnancy complicated with heart dis- ease,during January,1973 to December,1982 and January,1983 to December,1992,were 1.2% (254/21 221) and 0.9% (174/18 726)respectively.The ratio of rheumatic heart disease and congenital heart disease were 4:1 and 1:2 in two periods.There were 37 cases of heart failure and 4 cases of ma- ternal deaths occured.No heart failure and maternal death occured in cases with surgically corrected heart disease.In the two periods,the cesarean section rate were 16.9%(43/254),and 33.3% (58/74) ,P

AIM: To evaluate the therapeutic effect and safety of Rhadiola Extract Injection for treatment of stable angina pectoris of coronary heart disease with cariac blood stasis syndrome. METHODS: Arandomized,double-blind,positive drug parallel controlled,multi-center clinical trial was adopted.414 patients with stable angna pectoris of coronary heart disease with cariac blood stasis syndrome were randomly chosen and divided into two groups: test group(n=308 cases) and control group(n=106 cases).The test group was treated with Rhadiola Extract Injection and the control group received Xiangdan Injection.Treatment course of each group was 10 days.(RESULTS:) The therapeutic effect and changes of electrocardiogram in the test group were better than that of the control group(P0.05).The test group had no obvious side-effects. CONCLUSION: Rhadiola Extract Injection is safe and effective in treating stable angina pectoris of coronary heart disease with cariac blood stasis syndrome.

Objective:To explore the correlation between ascending aortic elasticity and coronary blood flow reserve (CFR)in patients with hypertension.Methods:A total of 60 patients with essential hypertension were regarded as hypertension group,another 50 normotensive subjects were enrolled as normal control group during the same period. Ascending aortic dilation (D),stiffness (β)and CFR were measured and calculated by tissue Doppler ultrasound,then compared between two groups.Pearson correlation analysis was used to analyze the correlation amongβ,D and CFR.Results:Compared with normal control group,there were significant reductions in D [(3.59±0.30)10-6 cm2/d vs.(2.88±0.77)10-6 cm2/d]and CFR [(3.23±1.16)vs.(2.02±0.63)],and significant rise inβ[(3.54 ±1.52)vs.(5.46±1.98)]in hypertension group,P<0.05 or<0.01. Pearson correlation analysis indicated thatβwas significant inversely correlated with CFR (r=-0.413,P=0.005),while D was significant positively correla- ted with CFR (r=0.384,P=0.003 ).Conclusion:Reduced ascending aortic elasticity is significantly correlated with coronary blood flow reserve.

Objective To observe the relationship between expression of retinoic acid receptor-β (RAR-β) in esophageal squamous cell carcinoma (ESCC) and chemotherapy response. Methods Fifty-two cases advanced ESCC patients treated by DDP and 5-FU, DDP 80 mg/m2, divided into 5 days;5-FU 375 mg/m2, dl-5. Immunohistochemistry was used to exmine the expression of RAR-β in ESCC. Fifty cases normal esophageal tissue were used as controls. Results RAR-β immunoreactivity was recognizd in both cytoplasm and nucleus, RAR-β positive rate was lower in ESCC compared with normal tissue (61.5%vs 92% ,P ＜0. 05 ). The 52 cases ESCC patients were treated 228 chemotherapy cycles, the overall response rate (OR) was 71.2%. The OR in RAR-β positive patients was 84. 4% (27/32), significant higher than RAR-β negative patients 50. 0% ( 10/20 ) ( P ＜ 0. 05 ). The time-to-progression ( TTP ) for RAR-β positive patients was 5.9 months, the median survival period was 12. 1 months, 2 years survival rate was 56. 7%;whereas TTP for RAR-β negative patients was 2. 1 months, the median survival period was 5.8 months,2 years survival rate was 32. 9%. There was signifcant difference between the 2 groups ( P ＜ 0. 05 ) .Conclusion RAR-β protein expression by immunohistochemistry may be a useful indicator to predict the chemotherapy response and clinical outcome for ESCC, meanwhile it may be an avenue for target therapy.

Objective To analyze the preventive and therapeutic effects of a traditional Chinese medicine Taohe Chengqi decoction on a rat models of hepatic encephalopathy ( HE) induced by thioacetamide ( TAA) .Methods The rat model of HE was established by intraperitoneal injection of TAA,and the effects of Taohe Chengqi decoction were observed by neurobehavioral changes,neurological test,blood ammonia,serum biochemical indexes,and liver and brain pathological examination.Results The rat model of hepatic encephalopathy was successfully established.Low, medium and high dose Taohe Chengqi decoction markedly improved neuro-reflexes and liver and brain pathological damages, and significantly decreased the HE staging and serum biochemical indexes, and the results of high dose group was the best, similar to that of positive drug-treatment group.Conclusions Taohe Chengqi decoction exhibits promising preventive and therapeutic effects on the rat model of TAA-induced hepatic encephalopathy, and these results provide substantial experimetal evidence for its clinical application.

Objective To establish and validate a Nomogram model for predicting the overall survival(OS)of the patients with intrahepatic cholangiocarcinoma(ICC)based on domestic multicenter data,and screen the beneficiaries of adjuvant chemotherapy based on the prediction model.Methods From December 2011 to December 2017,the data of 278 patients with postoperative pathological diagnosis of ICC from 4 medical centers in our country were collected retrospectively COX regression model was used to screen the independent risk factors of OS and constructed a Nomogram model.This model was used to stratify the risk of OS for all patients and to screen the beneficiaries of adjuvant chemotherapy.Results A total of 278 patients were enrolled,and 23 cases(8.3%)received adjuvant chemotherapy.COX multivariate analysis showed that drinking history,ECOG score,method of hepatectomy,lymph node status,number of tumors,and tumor differentiation were independent risk factors for postoperative OS.The Nomogram model had a C-index of 0.690(95%CI:0.646-0.734)in the training cohort and 0.740(95%CI:0.863-0.617)in the validation cohort.According to risk stratification by Nomogram model,in the high-risk group there was a statistically significant difference in survival between adjuvant chemotherapy and non-adjuvant chemotherapy(P=0.033),whereas in the low-risk group,there was no significant difference in survival(P=0.59).Conclusions Nomogram model based on independent risk factors of OS demonstrated excellent predictive capability for survival and could be used to screen,and identify the patients with ICC who benefit from adjuvant chemotherapy.

Objective:To analyze the impact of lymph node dissection on textbook outcomes (TO) and the prognosis of intrahepatic cholangiocarcinoma (ICC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 376 ICC patients who underwent hepatectomy in 4 medical centers, including Mengchao Hepatobiliary Hospital of Fujian Medical University et al, from December 2011 to December 2017 were collected. There were 242 males and 134 females, aged 57(range, 48-63)years. According to the criteria of TO, patients were classified as two cate-gories, including patients achieving TO and not achieving TO. Measurement data with normal distri-bution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M(range) or M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were represented as absolute numbers, and comparison between groups was conducted using the chi-square test, Yates adjusted chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the non-parameter rank sum test. Univariate and multivariate analyses were conducted using the Logistic regression model. The Kaplan-Meier method was used to draw survival curve. Survival analysis was conducted using the Log-rank test. Results:(1) TO situations. Of the 376 ICC patients who underwent hepatectomy, 199 cases achieved TO, including 40 cases with lymph node dissection and 159 cases without lymph node dissection, 177 cases did not achieve TO, including 76 cases with lymph node dissection and 101 cases without lymph node dissection. (2) Influencing factors for TO after hepatectomy of ICC patients. Results of multivariate analysis showed that lymph node dissection, microvascular invasion, nerve invasion and the volume of intraoperative blood loss >800 mL were independent risk factors for achieving TO after hepatec-tomy of ICC patients ( odds ratio=2.22, 2.95, 3.58, 4.09,95% confidence interval as 1.34-3.69, 1.43-6.07, 1.40-9.17, 1.35-12.43, P<0.05). Of the 116 patients with lymph node dissection, 40 cases achieved TO, 103 cases achieved R 0 resection, 38 cases had postoperative complications, 67 cases had delayed hospital stay. The above indicators were 159, 255, 41, 65 of 260 patients without lymph node dissection. There were significant differences in the above indicators between patients with and without lymph node dissection ( χ2=22.90, 15.16, 13.95, 37.78, P<0.05). (3) Follow-up. All the 376 patients were followed up for 19(range, 1-74)months. Of 199 patients achieving TO, the 1-, 2-and 3-year survival rates of 40 patients with lymph node dissection were 54.0%, 36.6% and 26.1%, respectively, versus 67.7%, 42.7% and 34.4% of 159 patients without lymph node dissection, showing no significant difference between them ( χ2=1.89, P>0.05). Of 177 patients not achieving TO, the 1-, 2-and 3-year survival rates of 76 cases with lymph node dissection were 58.9%, 25.7% and 10.3%, respectively, versus 53.0%, 28.5% and 17.2% of 101 cases without lymph node dissection, showing no significant difference between them ( χ2=0.25, P>0.05). Conclusions:Lymph node dissec-tion, microvascular invasion, nerve invasion and the volume of intraoperative blood loss >800 mL are independent risk factors for achieving TO after hepatectomy of ICC patients. Lymph node dissec-tion may increase the postoperative complication rate, prolong the hospital stay and decrease the rate of achieving TO. However, it does not affect the prognosis of patients.

Since the first Drug Administration Law was issued in 1984， the drug regulation of China has undergone a forty- year process. During these four decades， China’s drug regulatory system has gradually transitioned from being extensive to refined， and the concept of supervision has become increasingly scientific. This paper first outlines the historical evolution of China’s drug regulatory laws and regulations since the founding of the People’s Republic of China， with a focus on the historical origins of the revision of the Drug Administration Law during 1984-2001. It also clarifies the new challenges faced by drug regulation as the industry innovates and develops， as well as the corresponding reform of the drug review and approval system. The paper summarizes the reform achievements of drug regulation. By studying and analyzing the challenges faced by drug regulation in terms of regulatory capacity， regulatory resources， and regulatory system in the context of internationalization of the industry， the paper proposes policy suggestions such as establishing a cross-regional regulatory system， reforming the review mechanism， strengthening the construction of the review team， and enhancing transparency in regulatory practices， with the aim of promoting the high-quality development of the pharmaceutical industry.

Fractures are frequently occurring diseases that endanger human health. Crucial to fracture healing is cartilage formation, which provides a bone-regeneration environment. Cartilage consists of both chondrocytes and extracellular matrix (ECM). The ECM of cartilage includes collagens and various types of proteoglycans (PGs), which play important roles in maintaining primary stability in fracture healing. The PG form of dentin matrix protein 1 (DMP1-PG) is involved in maintaining the health of articular cartilage and bone. Our previous data have shown that DMP1-PG is richly expressed in the cartilaginous calluses of fracture sites. However, the possible significant role of DMP1-PG in chondrogenesis and fracture healing is unknown. To further detect the potential role of DMP1-PG in fracture repair, we established a mouse fracture model by using a glycosylation site mutant DMP1 mouse (S89G-DMP1 mouse). Upon inspection, fewer cartilaginous calluses and down-regulated expression levels of chondrogenesis genes were observed in the fracture sites of S89G-DMP1 mice. Given the deficiency of DMP1-PG, the impaired IL-6/JAK/STAT signaling pathway was observed to affect the chondrogenesis of fracture healing. Overall, these results suggest that DMP1-PG is an indispensable proteoglycan in chondrogenesis during fracture healing.