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

italic>Panax quinquefolium L. is a valuable Chinese herbal medicine with a large market demand. It has a complex chemical composition and numerous biological activities. At present, research on P. quinquefolium is focused on its underground parts, with especial interest in its saponins. There are few studies on non-saponins and the aboveground parts of Panax quinquefolium. Current quality standards are based on the saponin contents, which does not address the other benefits of Panax quinquefolium. This paper summarizes progress on the chemical components, pharmacological effects, quality evaluation, and product development of P. quinquefolium in recent years, and provides references for its further R&D and comprehensive utilization.

A high-throughput three-dimensional (3D) hepatocyte culture model is constructed in this study. It is capable of replicating the 3D in vivo environment and offers the advantages of high throughput, enhanced reproducibility, low cost, and simplified operation, rendering a valuable tool for hepatotoxicity screening of traditional Chinese medicine (TCM). First, we constructed the 3D high throughput liver chip model using collagen hydrogel. The precision and its difference with traditional cell culture plates were assessed using acetaminophen, Tripterygium hypoglaucum, and Qili San as the references. The feasibility of this model was also investigated by comparing the hepatotoxicity among four batches of T. hypoglaucum and Qili San. The methodology verification shows that the 3D hepatocyte model is better than traditional two-dimensional (2D) cell culture model in precision and feasibility. Subsequently, we compared the hepatotoxicity of different samples over a period of three or seven days and found that the hepatotoxicity of TCM extracts increased over time. Finally, we compared the hepatotoxicity of T. hypoglaucum and its compound formula Kunxian capsule under equivalent concentration. The results showed that the compound Kunxian capsule could significantly reduce hepatotoxicity of T. hypoglaucum. Generally, we constructed a high-throughput, robust 3D liver-on-a-chip model with the potential of rapid assessing TCM-induced liver toxicity.

Objective To quantitatively assess the cardiopulmonary exercise function of spinal cord injury (SCI) patients and observe the effect of aerobic exercise on cardiopulmonary function, motor function and activities of daily living. Methods From December, 2014 to June, 2016, 34 incomplete SCI patients (ASIA C and D) and 23 healthy controls received cardiopulmonary exercise test (CPET). SCI pa-tients were randomly divided into conventional rehabilitation group (n=17) and aerobic exercise group (n=17). The aerobic exercise group received aerobic exercise for four weeks. They were assessed with CPET, motor and sensory function, walking index for spinal cord injury II (WISCI II) and spinal cord independence measure (SCIM) before and four weeks after training. Results Oxygen uptake (VO2)peak, anaerobic threshold (AT), metabolic equivalent of energy (METpeak), VO2/heart rate (HR)peak, respiratory exchange rate (RER)peak, minute ventilation (VE)peak, work rate (WR)peak and systolic blood pressure (SBP)peak were lower in the patients than in the controls (t>2.714, P<0.05). VO2peak、AT、METpeak、VO2/HRpeak、WRpeak increased in the aerobic exercise group after training (t>2.431, P<0.05). METpeak and WRpeak improved in the conventional rehabilitation group after training (t>3.282, P<0.01). The scores of motor in ASIA and SCIM improved in both groups after training (t>2.985, P<0.05). Conclusion The cardiopulmonary function decreased in incomplete SCI patients, which could be improved by moderate intensity aerobic exercise.

AIM:To explore a novel method to isolate human nucleus pulposus mesenchymal stem cells (hNP-MSCs) in vitro and to identify their biological characteristics.METHODS:The explant culture method was employed to isolate hNP-MSCs from nucleus pulposus tissue obtained by percutaneous endoscopic lumbar discectomy (PELD).The isolated cells were passaged for purification and cultured in vitro followed by morphological observation.The cell proliferation ability was detected by CCK-8 assay.Growth curves of the cells were drawn and surface antigens were detected by flow cytometry.The cells at the 3rd~6th passages were induced for adipogenic, osteogenic and chondrogenic differentiation, and examined by oil red O staining, alizarin red staining and Alcian blue staining.RESULTS:The cells with self-renewal were obtained from nucleus pulposus tissue obtained by PELD.The results of flow cytometry analysis revealed that the cells were positive for CD29, CD44, CD90, CD73 and CD105, but negative for CD34 and CD45.The proliferative capacity was consistent with the growth characteristics of MSCs and multilineage differentiation potential was identified.CONCLUSION:A novel method to efficiently isolate and culture hNP-MSCs,PELD combined with explant culture method,was established, which would promote the study of regenerative medicine based on hNP-MSCs.

Objective To investigate the relationship between the human papillomavirus (HPV) and esophageal carcinoma in Baoding City of Hebei Province. Methods We detected HPV DNA in 42 formalin-fixed and paraffin-embedded tissues from surgically resected esophageal carcinomas from Baoding City of Hebei Province, by PCR with the general primer set of GP5 +/6 + for HPV L1 gene and type-specific primer sets for HPV16 and 18 as well. Results 37 from 42 esophageal carcinoma samples were HPV positive and the rate was 88.1% . Among the samples detected, 19 were HPV16 E6 positive and rate was 45.2%, eight were HPV18 E6 positive and rate was 19.0%. Conclusion The high rate of HPV in the esophageal carcinoma samples suggested that HPV plays an etiologic role in the development of esophageal cancer in Baoding City of Hebei Province.

OBJECTIVETo study the clinical characteristics, treatment and prognosis 24 cases of carcinoma in pleomorphic adenoma in salivary gland.

METHODSThe clinical data of 24 patients with carcinoma in pleomorphic adenoma treated in our hospital from September 1974 to July 1995 were analyzed.

RESULTSThe overall 5-year survival rate was 66.7%. The five-year survival rates of patients with carcinoma in pleomorphic adenoma in the major and minor salivary glands were 63.6% and 2/2, respectively.

CONCLUSIONOperation is the optimal treatment and extensive resection at the initial operation is suggested. For lumps in the submaxillary gland, preventive neck dissection should be considered. Postoperative radiotherapy can not improve the local-control rate.

Adenoma, Pleomorphic ; diagnosis ; mortality ; therapy ; Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Metastasis ; Neoplasm Recurrence, Local ; Prognosis ; Salivary Gland Neoplasms ; mortality ; pathology ; therapy ; Survival Rate

OBJECTIVETo construct a lentiviral vector of repressor element-1/neuron-restrictive silencer element (RE-1/NRSE) double-stranded RNA (dsRNA).

METHODSThe RE-1/NRSE cDNA containing both sense and antisense oligo DNA fragments of the targeting sequence was synthesized and cloned into the pGC-LV vector. The obtained lentiviral vector containing RE-1/NRSE dsRNA was confirmed by PCR and sequencing. A total of 293T cells were cotransfected with lentiviral vector of L-smNRSE/RE-1, pHelper 1.0, and pHelper 2.0. The titer of virus was measured based on the expression level of green fluorescent protein. The transfection efficiency of green fluorescent protein into rat mesenchymal stem cells was calculated.

RESULTSPCR and DNA sequencing demonstrated that the constructed lentivirus vector of L-smNRSE/RE-1 produced RE-1/NRSE dsRNA.The titer of the concentrated virus was 4x108 TU/m1. The virus was stably transfected into rat mesenchymal stem cells, and the infection efficiency reached 100% when the multiplicity of infection was 80.

CONCLUSIONThe lentivirus vector of RE-1/NRSE dsRNA is successfully constructed.

Animals ; Bone Marrow Cells ; Cells, Cultured ; Genetic Vectors ; Lentivirus ; genetics ; Mesenchymal Stromal Cells ; Plasmids ; genetics ; RNA, Double-Stranded ; genetics ; Rats ; Repressor Proteins ; genetics ; Silencer Elements, Transcriptional ; genetics ; Transfection

It was recently discovered that a subset of osteoblasts functions as a key component of the hematopoietic stem cells (HSC) niche in vivo, controlling HSC self-renewal and multi-lineage differentiation. Disruption of Smad4 gene specifically in osteoblasts leads to a remarkable decrease of osteoblast number and endosteal surface area. In order to elucidate if the osteoblast loss has any effect on hematopoietic activity, the bone marrow (BM) and extramedullary hematopoiesis in the osteoblast-specific Smad4 knockout mice were systematically analyzed, the proportions of mature hematocytes in BM, liver and spleen were detected by flow cytometry, the hematopoietic progenitor number in different stages was measured by colong-forming assay, CFU-S and analysis of LSK cells. The results indicated that the conditional mutant mice demonstrated normal BM hematopoiesis without sign of extramedullary hematopoiesis. Furthermore, the proportion of hematopoietic progenitor cells was normal, while cell number/body weight of the conditional knockout mice increased. It is concluded that hematopoiesis is normally maintained in osteoblast-specific Smad4 knockout mice, and osteoblast loss does not of necessity result in the decrease in BM hematopoiesis.
Animals ; Bone Marrow Cells ; cytology ; Hematopoiesis ; Hematopoietic Stem Cells ; cytology ; physiology ; Mice ; Mice, Knockout ; Osteoblasts ; cytology ; physiology ; Smad4 Protein ; genetics