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 make a preliminary application of the assessment system for cancer pain management and find insuffi-ciency in the clinical practice of cancer pain diagnosis and treatment. Methods:Data from 41 doctor questionnaires, 43 nurse question-naires, 50 patient questionnaires, and 12 ward questionnaires from the tumor departments of 3 hospitals were analyzed, and the insuffi-ciency in cancer pain management was determined. The wards in the tumor and non-tumor departments related to oncology were as-sessed using rank test, and differences between the 2 wards were investigated. Results:The average scores of doctor, nurse, and wards were 85.41±5.93, 88.46±5.09 and 83.75±3.11, respectively, whereas patient score was 68.67±7.14. To further analyze the patient subsys-tem by converting into a hundred-mark system, the effectiveness and safety scores for the pain management was 81.69±7.71. However, patients' opinion score on pain treatment was only 55.78±11.37. The score of tumor departments was 82.22±2.03, whereas related non-tumor departments had a score of 39.27 ± 3.58. Wilcoxon W value was at 120.0 with P<0.01 after rank test. Conclusion:Education on patients' opinion on cancer pain management should be promoted in the tumor wards, and continuous education on cancer pain diagno-sis and treatment is needed in the non-tumor departments relative to oncology.

The high performance liquid chromatography-fluorescence micelle assay (HPLC-FMA) method for the content determination of polysorbate 80 in monoclonal antibody drugs was validated to study its applicability and transferability between various laboratories, and the feasibility to be included in the Chinese Pharmacopoeia. Both J.T. Baker and Nanjing Well-sourced polysorbate 80 was used in the collaborative validation of polysorbate 80 content analysis in seven different laboratories. The results show that when the protein concentration was no more than 20 mg·mL^-1 and the concentration of polysorbate 80 ranged from 0.05 to 0.5 mg·mL^-1, the method had good specificity. The recovery rates of the spiked samples ranged from 92.20% to 117.70% for J.T.Baker and from 93.90% to 117.20% for Nanjing Well. The intra-laboratory precision (%RSD) was less than 4.30% for J.T. Baker, and less than 2.60% for Nanjing Well, while the overall precision was less than 5.45% for J.T. Baker, and less than 6.70% for Nanjing Well. The linear correlation coefficient was more than 0.98 for J.T. Baker and more than 0.99 for Nanjing Well. The results of the collaborative validation prove that the HPLC-FMA method has good accuracy, precision, linearity, and specificity, and could be used for release control analysis of polysorbate 80 content in monoclonal antibodies across different laboratories.

A new steroidal ester, beta-rosaterol palmitate (1) along with ten known compounds, uvaol(2), 3-epi-ursolic acid (3), 2alpha, 3beta, 24-trihydroxyolean-12-en-28-oic acid (4), 2alpha, 3alpha, 24-trihydroxyurs-12-en-28-oic acid (5), 2alpha, 3alpha, 24-trihydroxyolean-12-en-28-oic acid (6), 2alpha, 3alpha, 24-trihydroxyolean-12-en-28-oic acid-28-O-beta-D-glucopyranosyl ester (7), (Z)-9-hexadecenoic acid (8), octacosyl alcohol (9), beta-sitosterol (10) and beta-daucosterol (11), has been isolated from the stems and leaves of Vitex trifolia. Their structures were elucidated using a combination of 1D and 2D NMR techniques (COSY, HMQC, and HMBC)and HR-ESI-MS analyses. Compounds 2-7 were isolated from this plant for the first time.
Drugs, Chinese Herbal ; chemistry ; isolation & purification ; Magnetic Resonance Spectroscopy ; Molecular Structure ; Spectrometry, Mass, Electrospray Ionization ; Vitex ; chemistry

Objective To evaluate early and dynamic changes of the left ventricular systolic function of patients with septic shock by two-dimensional speckle tracking imaging (2D-STI), and to provide guidance for treatment and prognosis.Methods Fifty-eight septic shock patients admitted to intensive care unit (ICU) of Subei People's Hospital from January 2016 to April 2017 were enrolled. The septic shock patients were given early fluid resuscitation. The left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left ventricular ejection fraction (LVEF), early diastolic mitral flow velocity/early diastolic mitral annular peak velocity (E/Em) were obtained by conventional echocardiography, and the left ventricular global longitudinal strain (GLS), global circumferential strain (GCS), global radial strain (GRS) were obtained by 2D-STI before fluid resuscitation and 1, 3, 7, 14 days after fluid resuscitation. According to the 28-day survival, the septic shock patients were divided into survival group (38 cases) and death group (20 cases). Thirty normal subjects with age and sex matched were selected as control group.Results① Compared with control group, heart rate (HR) and LVESV were increased [HR (bpm): 92.71±12.51 vs. 73.07±5.52, LVESV (mL): 42.50±7.89 vs. 38.73±4.23, bothP < 0.05], while LVEF, GLS, GCS were decreased [LVEF: 0.57±0.06 vs. 0.61±0.03, GLS: (-17.72±1.35)% vs. (-22.07±1.95)%, GCS: (-17.08±1.49)% vs. (-22.98±1.97)%] in septic shock group (allP < 0.01). ② Compared with the data before fluid resuscitation, heart rate was declined (bpm: 87.83±11.50vs. 92.71±12.51,P < 0.01), while LVEDV and LVEF were increased [LVEDV (mL): 102.32±9.23 vs. 99.24±8.86, LVEF: 0.59±0.05 vs. 0.56±0.06] in patients of the septic shock after fluid resuscitation (allP <0.01). ③ With the extension of treatment time, HR, LVEDV, LVESV, E/Em were increased gradually, and LVEF, GLS, GCS, GRS were decreased gradually in dead patients. In septic shock patients, compared with survival group, GCS was significantly different on day 1 [(-15.98±1.41)% vs. (-17.66±1.22)%,P < 0.05], HR, LVEDV, LVESV, GLS were significantly different on the 3rd day [HR (bpm): 104.60±10.94 vs. 88.71±5.06, LVEDV (mL): 109.69±10.00 vs. 103.99±5.74, LVESV (mL): 47.78±7.21 vs. 42.29±5.13, GLS: (-14.44±0.92)% vs. (-16.36±1.00)%, allP < 0.05], LVEF, GRS were significantly different on the 7th day [LVEF: 0.47±0.07 vs. 0.58±0.04, GRS: (28.27±3.23)% vs. (31.48±3.12)%, bothP < 0.05], and E/Em was significantly different on the 14th day (12.81±1.56 vs. 10.61±1.27) in dead group (P < 0.05).Conclusions Our study demonstrates myocardial dysfunction at the early phase in septic shock patients, and 2D-STI GCS can be more sensitive than the conventional echocardiography to determine prognosis. 2D-STI GCS, GLS, GRS were not volume-load dependent parameter. Low levels of GLS, GCS might suggest a poor prognosis.

OBJECTIVETo search for an optimum method for testicular prothesis implantation in the treatment of testis loss.

METHODSWe retrospectively analyzed the surgical methods and outcomes of 53 cases of terminal prostate cancer and 4 cases of unilateral testicular torsion treated by implantation of testicular prothesis with the polypropylene mesh.

RESULTSThe 57 male patients all received testicular prothesis with the polypropylene mesh. All the patients were satisfied with the appearance and size of the scrotum after surgery. No scrotal hematoma, prosthesis infection, or autoimmune disease occurred postoperatively.

CONCLUSIONTestis loss is not a rare condition clinically, for the treatment of which surgical implantation of testicular prothesis with the polypropylene mesh can achieve both a fine tissue compatibility and a desirable scrotal appearance.

Humans ; Male ; Polypropylenes ; Prostatic Neoplasms ; surgery ; Prostheses and Implants ; Retrospective Studies ; Scrotum ; Spermatic Cord Torsion ; surgery ; Surgical Mesh ; Testis

OBJECTIVETo evaluate biomechanical properties in different methods of internal fixation combined with distal tibiofibular syndesmosis injury, in order to provide a theoretical basis for clinical choice.

METHODSSix lower limbs specimens were collected and divided into 5 groups, including normal group, distal tibiofibular syndesmosis injury (injury group), 3 cortexes group, 4 cortexes group and hook-plate fixation group. Neutral position, plantar flexion position (30°), dorsiflexion (20°) supination external rotation position of foot movement were simulated on universal materials tester. Strength, stiffness and stability of ankle joint in 4 kinds of motion conditions were measured.

RESULTSThere was significant differences in strength and stiffness of ankle joint between injury group and normal group in 4 different kinds of motion conditions (P<0.05). Strength and stiffness of ankle joint in 3 cortexes group, 4 cortexes group and hook-plate fixation group were improved obviously in 4 different kinds of motion conditions, and biomechanical indexes were recovered normally or better than normal group. Stiffness of the three fixation groups were better than normal group,but there was no significant differences among three groups (P > 0.05), while stiffness of hook-plate fixation group was closed to normal group.

CONCLUSIONFor distal tibiofibular syndesmosis injury, 1 screw with 3 cortexes, 4 cortexes and hook-plate had a positive impact on strength, stiffness and stability of distal tibiofibular syndesmosis injury stress,and could restore the normal stabllity of ankle joint after reconstruction. While fixing by screw fixation would limit the rototary motion of ankle joint,ankle mortise could not adapt to changes of talus bone, thus induces screw breakage and traumatic arthritis. Hook-plate fixation is more suitable than 3 cortexes or 4 cortexes fixation for bilmechanical properties,and its' stress is more balance and can reduce postoperative complcations.

Ankle Injuries ; physiopathology ; surgery ; Biomechanical Phenomena ; Fibula ; injuries ; surgery ; Fracture Fixation, Internal ; methods ; Humans ; Joint Instability ; physiopathology ; prevention & control ; Reconstructive Surgical Procedures ; methods ; Tibia ; injuries ; surgery

Objective To study the effect of spontaneous subarachnoid hemorrhage (SAH)on transient receptor potential melastatin 4 (TRPM4)channel activity. Methods Seventeen SD rats of clean grade were selected. They were randomly divided into either a SAH (n = 10)or a sham operation group (n = 7) according to the random number table. At day 5 after SAH modeling,the cerebral arteries were harvested and the cerebral arterial smooth muscle cells were isolated using enzymatic digestion method. Western blot was used to detect TRPM4 expression and translocation rate. Patch-clamp techniques were used to study the maximum current intensity of the TRPM4 single channel in cerebral arterial smooth muscle cells. Results The fluorescent-stained TRPM4 were observed in cerebral arterial smooth muscle cells in the 2 groups of rats. The relative quantities of TRPM4 in the total protein of the sham operation group and the SAH group were 24 ± 3% and 32 ± 4% respectively. There was significant difference between the 2 groups (t = 4. 47,P < 0. 01). The translocation rates of TRPM4 in the sham operation group and the SAH group were 44. 0 ± 1. 9% and 60. 1 ± 2. 3% respectively,and the SAH group was higher than the sham operation group (χ2 = 4. 48,P < 0. 05). When the clamping voltages were - 100 mV,- 80 mV,- 60 mV,and - 40 mV,the maximum current intensity of TRPM4 single channel of the sham operation group was more than that of the SAH group. There were significant differences between the 2 groups (- 1. 90 ± 0. 10 mV vs. - 2. 23 ± 0. 08 mV,- 1. 68 ± 0. 12 mV vs. - 1. 99 ± 0. 12 mV,- 0. 89 ± 0. 09 mV vs. - 1. 24 ± 0. 09 mV,and - 0. 69 ± 0. 12 mV vs. - 0. 92 ± 0. 11 mV;all P < 0. 01). When the clamping voltages were - 20,0,20,40,60,80,and 100 mV,there was no significant difference in the maximum current intensity of TRPM4 single channel between the 2 groups (all P > 0. 05). Conclusion SAH has the induced effect for TRPM4 activity.

Objective To evaluate the efficacy and safety of dorsal ligament reconstruction in treatment of old dorsal dislocation of distal radioulnar joint.Methods Seven patients with old dorsal dislocation of distal radioulnar joint were treated with dorsal ligament reconstruction using the palmaris longus tendon from March 2005 to May 2012 in our institute,including 4 males and 3 females with a mean age of 37 years.All patients had a history of wrist injury for more than 3 months and were diagnosed as isolated dislocation of distal radioulnar joint without fractures.During the operation a bone tunnel was made at dorsal ulnar side of radius near the ulnar notch,which was parallelized to long axial of ulna,two holes were drilled from dorsal to palmarulnaris side through the extensor carpi ulnaris sulcus of the ulna.The palmaris longus tendon was harvested and the strip of the tendon was penetrated through the radial hole.After the tips being crossed,put them through the holes of ulna,reduct the distal radioulnar joint by supinating the forearm,the strip of the tendon was sutured after being tightened,the reversed back the free end of the tendon to reconstruct the sheath of extensor carpi ulnaris tendon.Postoperatively,the upper extremity were kept in a long arm plaster in the position of elbow flexion 90° and forearm supination for 3 weeks,then the below elbow cast was replaced for another 3 weeks.Results Patients were followed-up for 1 year and 8 months 4 years and 2 months with the average of 2 years and 9 months.The rotation of wrist was improved and the handgrip strength was increased significantly.A functional evaluation was performed using the modified Mayo wrist scoring system.All patients had better wrists scores postoperatively (mean,93) compared to preoperatively (mean,68).All patients satisfied with the final result.Conclusion Dorsal ligament reconstruction should be a promise surgical modality for the old dorsal dislocation of distal radioulnar joint.

Objective To investigate the effect of arterial and venous subarachnoid hemorrhage ( SAH)on voltage-dependent calcium channel( VDCC)currents of cerebral artery smooth muscle cells and the relationship between the concentration of oxyhemoglobin( OxyHb)in arterial and venous blood and cerebral blood flow. Methods Thirty-six clean grade rats were colleted. A rat SAH model was induced by injection of autologous arterial or venous blood in suprasellar cistern using assisted stereotaxic apparatus. The rats were divided into three groups:an arterial SAH( n=14 ),a venous SAH( n=13 ),and a sham operation( n=9 )group. The arterial and venous OxyHb concentrations were measured. Three days after SAH modeling,a patch clamp was used to detect the relative surface area of the cerebral artery smooth muscle cells,resting potential,and VDCC currents in rats. A fluorescent microsphere method was used to quantitatively analyze cerebral blood flow(CBF). Results (1)Arterial SAH OxyHb concentration (127 ± 4 g/L)was significantly higher than venous SAH OxyHb concentration(54 ± 6 g/L),and that of the sham operation group was 50 ± 5 g/L. The differences were statistically significant among the 3 groups( P<0. 01).(2)The maximum current of VDCC of the arterial SAH group(3. 22 ± 0. 31 pA)was significantly higher than that of the venous SAH group(2. 19 ± 0. 27 pA)and the sham operation group(2. 18 ± 0. 29 pA). The differences were statistically significant among the 3 groups( P<0. 01 ). The VDCC currents of the arterial SAH group were consisted of L- and R-currents,while the currents of the venous SAH group were only consisted of L-VDCC.(3)The cerebral blood flow of the arterial SAH group(0. 83 ± 0. 14 mL/[g·min])was significantly higher than that of the venous SAH group(1. 28 ± 0. 28 mL/[g·min])and the sham operation group(1. 35 ± 0. 19 mL/[g·min]). The differences were statistically significant(P<0. 01). Conclusions The changing effect of arterial SAH on the expression and function of the cerebral artery smooth muscle cells are greater than that of the venous SAH. This difference may be associated with the concentration and composition of vasospasm factors of OxyHb in arterial and venous blood.