Referring to the rapid developed life science and the higher requirements for the approval of innovative Chinese drugs in recent years, this paper described systematically the discovery, research and development (R&D) approaches for the innovative Chinese drugs under the new situation from the following five aspects, i. e., active components discovered from TCMs, the discovery of effective fractions of TCMs and their formulae, the R&D of TCM innovative drugs based on famous classic prescriptions and famous Chinese patent drugs, and the transformation of clinical effective prescriptions, on the basis of analysing the advantages of innovative drugs derived from natural products based on TCM theories and the problems existed in current R&D of new TCM drugs. Moreover, five suggestions are also given for the rapid development of TCM innovative drugs in China. All these will provide reference for the R&D of TCM innovative drugs.
China ; Drug Discovery ; Drugs, Chinese Herbal ; chemistry ; isolation & purification ; pharmacology ; Humans ; Medicine, Chinese Traditional ; trends ; Research

Objective To investigate the effect on and mechansm by which prostaglandin E_1(PGE_1)protects liver functions after hepatectomy.Methods In this study,82 cases undergoing hepatectomy were divided randomly into control group with conventional therapy(41 cases),and PGE_1 treatment group(41 cases)treated with liposomal prostaglandin E_1 in addition to conventional therapy.Postoperative hospital days,urinary volume and abdominal drainage volume were observed.Pre-and postoperative liver functions were measured.Results Postoperative hospital days(median time 22 days)in PGE_1 treatment group were significantly shorter than those(median time 26 days)in control group.The postoperative levels of alanine transaminase,aspartic transaminase,total bilirubin and albumen in PGE_1 treatment group recovered to preoperative levels more quickly,than control group.Postoperative urinary volume in patients of PGE_1 treatment group was significantly more than that in control group,while abdominal drainage volume was markedly less,although there was no significant difference in prothrombin time between the two groups.Conclusion In patients undergoing hepatectomy,PGE_1 is very useful and safe to protect and improve hepatic function,decreasing the level of bilirubin,preventing ascites,formation shortening hospital days,without causing prolongation of prothrombin time remarkably.

Objective To study the regularity of occurrence and development in the elderly with AAA. Methods Twenty-seven elderly cases with abdominal aortic aneurysm(AAA) were analyzed and followed up with ultrasound for ten years. Results The AAA diameters were 2.5 ~6.6 cm,with the average in crease of(0.14 ? 0.01) cm/ year. Intraluminal thromi(ILT) were found in 63.0% of all the patients. ILT were found(3.9?2.0 ) years after the AAA diagnosis with the average in crease of(0.21 ? 0.05)cm / year. Conclusions The size of AAA in the elderly is slowly enlarged to varying degree with ageing. ILT are found in more than half of all the patients. A few cases of AAA are found ruptured and a few cases of ILT exfoliated.

Objective To study the relationship between extraocular muscle thickness and exophthalmos degree in patients with thyroid-associated ophthalmopathy (TAO),so as to provide a scientific basis for guiding clinical treatment.Methods Forty seven patients diagnosed with TAO from May 2005 to May 2011,in the 451 Hospital of the People's Liberation Army were chosen in this study,and divided into TAO group(23 cases) and treatment group (24 cases).Meanwhile,another 32 healthy people were selected as control.Extraocular rectus muscles (including the medial rectus muscle,lateral rectus muscle,superior rectus muscle and inferior rectus muscle) of all participants were measured with B-scan ultrasonography,and exophthalmos degree with Hertel exophthalmometer.Results The thicknesses of medial rectus in control group,TAO group and treatment group were (3.35 ± 0.25),(4.38 ± 0.85),(3.58± 0.52)mm,respectively; the thicknesses of lateral rectus muscle were (2.95 ± 0.61),(4.24 ± 0.75),(3.65 ± 0.42)mm,respectively; the thicknesses of superior rectus muscle were (3.15 ± 0.20),(4.65± 0.68),(4.01 ± 0.15)mm,respectively; the thicknesses of inferior rectus muscle were (3.17 ± 0.72),(4.75 ± 0.52),(3.71 ± 0.91)mm,respectively; the sums of binocular rectus thickness in these three groups were (21.95 ± 0.65),(28.02 ± 1.51),(22.95 ± 0.65)mm,respectively; the difference between the three groups was statistically significant(F=2.32,2.43,2.25,2.17,5.63,all P ＜ 0.05),and TAO group was significantly higher than that in the control group and in the treatment group(all P ＜ 0.05),while there was no statistically significant between the control group and the treatment group(all P ＞ 0.05).The eyes exophthalmos degree in TAO group and treatment group were (16.82 ± 2.46),(14.52 ± 1.83)mm,respectively.The sum of the rectus muscle thickness and eyes exophthalmos was positively correlated(r =0.65,0.58,all P ＜ 0.05).Conclusions Extraocular muscle thickness in patients with TAO is positively correlated with exophthalmos degree,and using B-scan ultrasonography to detect the changes is practical for clinical diagnosis and treatment.

Objective To evaluate the damage to the brochial plexus produced by pulsed radiofrequency (PRF)and radiofrequency thermocoagulation(RFTC).Methods Fifty-five male Wistar rats weighing 250-300 g were randomly divided into 3 groups:groupⅠPRF(n=25):groupⅡRFTC(n=25)and groupⅢnormal control(n=5).The animals were anesthetized with intraperitoneal chloral hydrate.The left brochial plexus was exposed and PRF or RFTC was applied to the left brochial plexus.The voltage and current of the minimal stimulation which elecited muscle twitching and the impedance before and after operation were recorded in group PRF and RFTC.The nerve function was scored according to Tarloo(0=flaccid paresis,5=normal gait)before and at 3d after operation.The animals were killed and the left brachial plexus was removed immediately and at 1, 7,14,30 d after operation(n=5 at each time point)for determination of histopathological changes using microscope.Results The impedance and Tarlov score were significantly decreased after operation as compared to the baseline values before operation in group RFTC and were also significantly lower than in group PRF. Microscopic examination showed that the myelinated nerve fibers exhibited Wallerian degeneration and axon regeneration and the cytochondria in cylindraxile were severely injured or disappeared in group RFTC.The myelinated nerve fibers and the cytochondria in cylindraxile were significantly less injured after operation in group PRF than in group RFTC and returned to normal at 7 d and 30 d respectively.Conclusion The injury to brachial plexus produced by PRF is slighter than that produced by RFTC.

Objective To investigate the effects of ulinastatin on the expression of neutrophil CD_(11b) and CD_(18) during orthotopic liver transplantation(OLT).Methods Forty patients with liver diseases,ASAⅢorⅣ, undergoing OLT were randomly divided into two groups.Ulinastatin group(n=20)received intravenous infusion of ulinastatin 3?10~5 IU in 100 ml normal saline after skin incision and repeated every 4 hours thereafter.Control group received same amount of normal saline instead(n=20).Blood samples were taken immediately before skin incision,120 min after skin incision,30 min of anhepatic phase,60 min of neohepatic phase and at the end of operation for measurement of CD_(11b) and CD_(18) expression of neutrophil by flow cytometry.Results CD_(11b)/CD_(18) expression was increased significantly in control group 60 min of neohepatic phase and at the end of operation compared to the level before skin incision,but in ulinastatin group there was no significant change in CD_(11b)/CD_(18) expression during the whole procedures(P＞0.05).CD_(11b)/CD_(18)expression was significantly lower 60 min of neohepatic phase and at the end of operation in ulinastatin group than in control group(P＜0.01).Conclusion Ulinastatin can inhibit the increase in CD_(11b)/CD_(18)expression during OLT,and be helpful for reducing the inflammatory response.

Objective:To observe the relationship between non -dipper heart rate and morbidity of coronary heart disease (CHD) in patients with hypertension .Methods :According to Holter monitored results ,a total of 130 pa‐tients with essential hypertension were divided into dipper heart rate group (n= 77 ) and non -dipper heart rate group (n=53) .Ambulatory blood pressure and dynamic ECG were monitored in two groups ,and CHD was diag‐nosed according to coronary angiography results .Ambulatory blood pressure ,ambulatory heart rate and incidence rate of CHD were compared and analyzed between two groups .Results:Compared with dipper heart rate group , there was significant reduction in daytime mean heart rate [ (73.45 ± 9.57) beats/min vs .(68.77 ± 12.61) beats/min] ,but significant rise in nighttime mean heart rate [ (61.30 ± 7.62) beats/min vs .(65.49 ± 12.97) beats/min] , P<0.05 both ;there were significant reductions in 24h mean diastolic blood pressure (DBP) [ (75.77 ± 10.91) mm‐Hg vs .(71.92 ± 9.30) mmHg] and daytime mean DBP [ (77.16 ± 11.11) mmHg vs .(72.81 ± 9.61) mmHg] , P<0.05 both in non -dipper heart rate group ,there were no significant difference in other blood pressure indexes be‐tween two groups (P>0.05);.Morbidity rate of CHD in non -dipper heart rate group was significantly higher than that of dipper heart rate group (71.70% vs .29.87% ,P=0.001) .Conclusion:Compared with dipper heart rate pa‐tients ,morbidity rate of CHD significantly rises in patients with hypertension and non -dipper heart rate .It may help to reduce occurrence of CHD by monitoring circadian changes of heart rate and recover circadian heart rate rhythm while treating hypertension .

Objective To investigate the relationship between retinal nerve fiber layer thickness and peripheral neuropathy in elderly patients with type 2 diabetes.Methods Clinical data of elderly patients with T2DM in Endocrinology Department in Beijing Hospital were retrospectively collected.Global and sectorial retinal nerve fiber layer(RNFL)thicknesses were measured by using optical coherence tomography(OCT),and never conduction velocity measurements were performed in all patients.Diabetic peripheral neuropathy was diagnosed by the criteria in diabetic neuropathies update(2010,American Diabetes Association).RNFL thickness was compared between diabetic nonperipheral neuropathy group (control group,n =30)and diabetic peripheral neuropathy group (DPN group,n=17)and between different sub-groups.Results The RNFL thicknesses of temporal,nasal,superior and inferior visual fields and the mean RNFL thickness were less in DPN group than in control group,among which there were significant differences in the RNFL thicknesses of superior,inferior visual fields and the mean RNFL thickness [(107.7±27.4)μm vs.(128.1±17.3)μm,(112.9 ±20.8)μm vs.(130.8±21.8)μm,(88.2±15.5)μm vs.(100.5± 11.3)μm,F=7.446,7.468,7.988,respectively,P=0.009,0.009 and 0.007].RNFL thickness was decreased along with the aggravation of DPN from the control group,the subclinical DPN group to the DPN group successively(all P＜ 0.05).Conclusions Retinal nerve fiber layer thickness is associated with diabetic peripheral neuropathy in elderly patients with type 2 diabetes,and the relationship is more significant in patients with serious DPN.

It is one of the main characters of malignant tumors that malignant tumor cells invade surrounding tissues and metastasize to distant tissues .Multiple factors are involved in this complicated dynamic process .Metastasis is the major factor influencing recurrence and prognosis .Therefore, it is important to explore the mechanism of invasion and metastasis for reducing recurrence rate and mortality of malignant tumors .Engulfment and cell mobility ( ELMO) family is one kind of conserved protein in evolutional process .It includes 3 members, ELMO1, ELMO2 and ELMO3.The members of ELMO family play an important role in cell phagocytosis and cell migration , and they also have close correlation with ma-lignant tumor cell invasion and metastasis .In this paper , we review the progress of the relationship between ELMO family and malignant tumor invasion and metastasis .

Objective To observe the effect of stageⅢdiabetic nephropathy(DN)treated by Qizhi Jiangtang capsule and explore its potential mechanism. Methods According to digital table method,the patients who conformed to the diagnostic criteria of stageⅢDN were randomly divided into two groups:an experiment group and a control group. All the patients in the two groups took elution treatment for 2 weeks,and then were treated with western basic therapy. The patients in the experiment group were administered orally with Qizhi Jiangtang capsule(2.5 g once, 3 times a day),while those in the control group treated with valsartan 80 mg,once a day. Urine microalbumin(mALB), mALB/urine creatinine(UCr),β2-microglobulin(β2-MG),α1-microglobulin(α1-MG)were observed in the two groups,endothelin-1(ET-1),nitric oxide(NO),thromboxane B2(TXB2),6-keto prostaglandin F1α(6-keto-PGF1α) were also determined. Serum creatinine(SCr),blood urea nitrogen(BUN),serum cystatin-C(Cys-C),retinol-binding protein(RBP),β2-MG were detected in the blood biochemistry automatic analyzer. These laboratory markers were inspected before treatment and at the 4th,8th and 12th week after treatment. Results Ninety-six patients in the experiment group and 95 patients in the control group were effectively included in the end. Before treatment,there were no statistic significant differences in urine mALB,mALB/UCr,β2-MG,α1-MG and blood ET-1,NO,TXB2, 6-keto-PGF1α between two groups(all P>0.05). Along with the prolongation of treatment,urine mALB,mALB/UCr,β2-MG,α1-MG and ET-1,TXB2 were significantly reduced,while NO,6-keto-PGF1α were significantly raised in the two groups after treatment,and the above changes in the experimental group were more obvious. There were statistic significant differences of mALB,mALB/UCr,β2-MG,α1-MG and TXB2,6-keto-PGF1αbetween two groups at the 12th week after treatment〔mALB(mg/L):36.6±9.2 vs. 78.6±16.5,mALB/UCr(mg/mmol):3.90±1.97 vs. 9.70±2.90,β2-MG(mg/L):0.25±0.10 vs. 0.40±0.12,α1-MG(mg/L):8.40±2.26 vs. 12.50±3.21,TXB2 (ng/L):75.8±18.7 vs. 94.7±21.7,6-keto-PGF1α(ng/L):73.4±15.2 vs. 65.2±11.5,P<0.05 or P<0.01〕. But there were no statistic significant differences of ET-1 and NO between experimental group and control group at the same time-points〔ET-1(ng/L):57.6±6.9 vs. 59.1±6.2,NO(μmol/L):68.9±11.6 vs. 65.4±10.7,both P>0.05〕. In each of the two groups,the comparisons of the levels of SCr,BUN before and after treatment,there was no statistical significant difference at any time point;the same comparisons between the two groups,there was also no statistic significant difference before treatment and at each of the same time-point after treatment(all P>0.05). The levels of Cys-C,RBP andβ2-MG of the control group after treatment had the tendency of decreasing,but no statistic significant differences were found(all P>0.05). The levels of Cys-C,RBP,β2-MG of the experimental group at the 12th week after treatment were significantly lower than those before treatment〔Cys-C(mg/L):0.72±0.07 vs. 0.89±0.12,RBP (mg/L):53.0±14.2 vs. 66.1±16.5,β2-MG(mg/L):1.86±0.71 vs. 2.79±0.82,all P<0.05〕. Conclusions Qizhi Jiangtang capsule can significantly reduce the levels of urine mALB and mALB/UCr of patients with stageⅢDN and stabilize their renal functions;its therapeutic effect is better then that of valsartan. Its mechanisms are related to the reduction of ET-1,elevation of NO,maintenance of dynamic equilibrium of thromboxane A2/prostacycline(TXA2/PGI2) and protection of vascular endothelial cells.