Tibetan medicine is an essential part of Chinese medicine and has unique theoretical experience and therapeutic advantages. According to the development principle of inheriting the essence, sticking to the truth, and keeping innovative, the supervision department should give clear and reasonable guidance considering the characteristics of Tibetan medicine, establish a standard system for quality control, clinical verification and evaluation, and accelerate the research and commercialization of new drugs. In view of the needs of drug supply-side reform and the current situation of Tibetan medicine and new pharmaceutical research, we ponder and provide suggestions on the confusion faced by the current supervision of Tibetan drug registration, hoping to contribute to the supervision strategy of Tibetan drug registration and the high-quality development of Tibetan medicine industry.
Tibet ; Medicine, Tibetan Traditional ; Quality Control ; Pharmaceutical Research ; Drug Industry

Objective: To explore the prognostic effects of mean corpuscular volume (MCV) in patients with myelodysplastic syndromes (MDS) . Methods: 321 newly diagnosed, untransfused primary MDS patients who administered from December 2009 to December 2017 were enrolled. The association of MCV with prognosis and several clinical features and genetic mutations were analyzed. Results: Patients were divided into MCV≤100 fl (n=148) and MCV>100 fl (n=173) cohorts. Median overall survival of patients with MCV≤100 fl was shorter than their counterparts (27 months vs 72 months, P<0.001) . In subgroup analysis, MCV≤100 fl patients had worse survivals in bone marrow blast <5% cohort (34 months vs not reached, P=0.002) , but not so in ≥5 % cohort (17 months vs 20 months, P=0.078) . MCV≤100 fl was still an independent adverse variable (HR=1.890, 95%CI 1.007-3.548, P=0.048) after adjusting for clinical and laboratory variables and mutation topography in bone marrow blasts<5% cohort. In bone marrow blasts<5% cohort, patients with MCV≤100 fl had higher hemoglobin levels [90 (42-153) g/L vs 78.5 (28-146) g/L, P=0.015].The proportions of Revised International Prognostic Scoring System (IPSS-R) high/very high risks and poor/very poor IPSS-R karyotypes were higher in MCV≤100 fl cohort (28.8% vs 10.8%, P=0.003; 24.7% vs 12.9%, P=0.049) . MCV≤100 fl cohort had more genetic mutations than those with MCV>100 fl though without significance (0.988 vs 0.769, P=0.064) . Mutated SF3B1 was less frequently in MCV≤100 fl cohort (4.7% vs 15.4%, P=0.018) . Conclusion: MCV≤100 fl was an independent adverse variable after adjusting for clinical and laboratory variables and mutation topography in MDS patients with bone marrow blasts<5%.
Bone Marrow ; Erythrocyte Indices ; Humans ; Karyotyping ; Myelodysplastic Syndromes ; Prognosis

Modified Da-chai-hu Decoction (MDD), a traditional Chinese medicinal formulation, which was empirically generated from Da-chai-hu decoction, has been utilized to treat severe acute pancreatitis (SAP) for decades. The aim of the present study was to explore its potential organprotective mechanism in SAP. In the present study, rat SAP model was induced by retrograde injection of 3.5% sodium taurocholate into the biliopancreatic duct, MDD (23.35 g/kg body weight, twelve times the clinical dose) were orally given at 2 h before and 10 h after injection. At 12 h after model induction, blood was taken from vena cava for analysis of amylase, diamine oxidase (DAO), pulmonary surfactant protein-A (SP-A), and C-reactive protein (CRP). Histopathological change of pancreas, ileum and lung was assayed by H&E staining, myeloperoxidase (MPO) activity were determinated using colorimetric assay, and the expressions of occludin and nuclear factor-κB (NF-κB) were detected by real-time RT-PCR and western blot, respectively. In addition, the tissue concentrations of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and monocyte chemoattractant protein-1 (MCP-1) were measured by enzyme-linked immunosorbent assay (ELISA). The results showed that in SAP rats, MDD significantly alleviated histopathological damage, depressed the MPO activity and the concentrations of TNF-α, IL-1β, and MCP-1 of pancreas, ileum and lung, and reduced the serum levels of amylase [(3283.4 ± 585.5) U·Lvs (5626.4 ± 795.1)U·L], DAO [(1100.1 ± 334.3) U·Lvs (1666.4 ± 525.3) U·L] and CRP [(7.6 ± 1.2) μg·mLvs (17.8 ± 3.8) μg·mL]. However, the serum SP-A concentration [(106.1 ± 16.6) pg·mLvs (90.1 ± 14.9) pg·mL] was elevated when treated SAP rats with MDD. Furthermore, MDD increased the occludin expression and reduced the NF-κB expression in pancreas, ileum and lung of SAP rats. Our findings suggested that MDD administration was an effective therapeutic approach for SAP treatment. It could up-regulate occludin expression to protect intercellular tight junction and down-regulate NF-κB expression to inhibit inflammatory reaction of pancreas, ileum and lung.

Objective: To evaluate clinical characteristics and prognosis of primary myelofibrosis (PMF) patients with thrombocytopenia in varied degrees. Methods: Clinical features and survival data of 1 305 Chinese patients with PMF were retrospectively analyzed. The prognostic value of thrombocytopenia in patients with PMF was evaluated. Results: 320 subjects (47%) presented severe thrombocytopenia (PLT<50×10(9)/L), 198 ones (15.2%) mild thrombocytopenia [PLT (50-99)×10(9)/L] and 787 ones (60.3%) without thrombocytopenia (PLT ≥ 100×10(9)/L). The more severe the thrombocytopenia, the higher the proportions of HGB<100 g/L, WBC<4×10(9)/L, circulating blasts ≥ 3%, abnormal karyotype and unfavourable cytogenetics (P<0.001, P<0.001, P=0.004, P<0.001 and P<0.001, respectively) were observed in this cohort of patients. The more severe the thrombocytopenia, the lower the proportion of JAK2V617F positive (P<0.001) was also noticed. Platelet count was positively correlated with splenomegaly, HGB and WBC (P<0.001, correlation coefficients were 0.131, 0.445 and 0.156, respectively). Platelet count was negative correlated with constitutional symptoms and circulating blasts (P=0.009, P=0.045, respectively; correlation coefficients were -0.096 and -0.056, respectively). The median survival of patients with severe thrombocytopenia, mild thrombocytopenia and without thrombocytopenia were 32, 67 and 89 months, respectively (P<0.001). Multivariate analysis identified thrombocytopenia in varied degrees (HR=1.693, 95%CI 1.320-2.173, P<0.001) and Dynamic Internation Prognostic Scoring System(DIPSS) prognostic model (HR=2.051, 95%CI 1.511-2.784, P<0.001) as independent risk factors for survival. Conclusion: PMF patients with severe thrombocytopenia frequently displayed anemia, leucopenia, circulating blasts and short survival, so active treatment measures should be taken especially in these patients.
Humans ; Primary Myelofibrosis ; Prognosis ; Retrospective Studies ; Thrombocytopenia

Objective: To explore the clinical implications and prognostic value of TP53 gene mutation and deletion in patients with myelodysplastic syndromes (MDS) . Methods: 112-gene targeted sequencing and interphase fluorescence in situ hybridization (FISH) were used to detect TP53 mutation and deletion in 584 patients with newly diagnosed primary MDS who were admitted from October 2009 to December 2017. The association of TP53 mutation and deletion with several clinical features and their prognostic significance were analyzed. Results: Alterations in TP53 were found in 42 (7.2%) cases. Of these, 31 (5.3%) cases showed TP53 mutation only, 8 (1.4%) cases in TP53 deletion only, 3 (0.5%) cases harboring both mutation and deletion. A total of 37 mutations were detected in 34 patients, most of them (94.6%) were located in the DNA binding domain (exon5-8) , the remaining 2 were located in exon 10 and splice site respectively. Patients with TP53 alterations harbored significantly more mutations than whom without alterations (z=-2.418, P=0.016) . The median age of patients with TP53 alterations was higher than their counterparts[60 (21-78) years old vs 52 (14-83) years old, z=-2.188, P=0.029]. TP53 alterations correlated with complex karyotype and International prognostic scoring system intermediate-2/high significantly (P<0.001) . Median overall survival of patients with TP53 alterations was shorter than the others[13 (95%CI 7.57-18.43) months vs not reached, χ(2)=12.342, P<0.001], while the significance was lost during complex karyotype adjusted analysis in multivariable model. Conclusion: TP53 mutation was more common than deletion in MDS patients. The majority of mutations were located in the DNA binding domain. TP53 alterations were strongly associated with complex karyotype and always coexisted with other gene mutations. TP53 alteration was no longer an independent prognostic factor when complex karyotype were occurred in MDS.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Genes, p53 ; Humans ; In Situ Hybridization, Fluorescence ; Middle Aged ; Mutation ; Myelodysplastic Syndromes/genetics* ; Prognosis ; Tumor Suppressor Protein p53 ; Young Adult

Objective To observe the anti-osteoporotic activity of representative phenolic glycosides (curculigoside, curculigine A, orcinol glucoside and orcinol rhamnoside) in Curculigo orchioides on osteoblasts in neonatal rat calvaria and on osteoclasts induced by myelomonocytes.Methods The proliferation of osteoblasts and osteoclasts were determined by MTT assay. The alkaline phosphatase (ALP) activity of osteoblasts and tartrate-resistant acid phosphatase (TRAP) of osteoclasts were detected by using p-PNPP-Na method. The mineralized nodule formation was determined by alizarin red-s (AR-S) staining. TRAP-positive multinucleated cells were counted through TRAP staining. The cytoskeleton of osteoblasts and F-actin ring of osteoclasts were labeled with rhodamine-conjugated phalloidin, and observed under confocal laser scanning microscope. The areas of osteoclastic bone resorption pit in co-culture of osteoblasts and osteoclasts were determined using computer image process. Results Curculigoside (10-9 mol/L and 10-8mol/L) significantly promoted the proliferation of osteoblasts and inhibited the TRAP activity of osteoclasts at the concentration of 10-7-10-5 mol/L (P<0.05). Curculigoside, orcinol glucoside and orcinol rhamnoside significantly decreased the number of osteoclasts (P<0.05). Curculigoside (10-10mol/L), curculigine A (10-9mol/L), orcinol glucoside (10-9mol/L) and orcinol rhamnoside (10-9mol/L) significantly increased the ALP activity and bone mineralized nodule formation of osteoblasts (P<0.01), reduced the injury of cytoskeleton of osteoblast induced by 1, 25-(OH)2-VD3, decreased the pit area formed by osteoclasts, and destroyed F-actin cytoskeleton structure and pseudopodia of osteoclasts. Conclusion Curculigoside, curculigine A, orcinol glucoside and orcinol rhamnoside, phenolic glycosides extracted from Curculigo orchioides, can promote osteoblastic bone formation and inhibit osteoclastic bone resorption, demonstrating a significant anti-osteoporotic activity.

Phytoestrogens, which can bind with estrogen receptor and produce estrogen-like effects, are a kind of nonsteroidal compound in plant. Phytoestrogens chemically include isoflavones, coumarins, lignans and other compounds. Phytoestrogens are selective estrogen receptor modulator, and have therapeutical effects on breast cancer, prostate cancer, cardiovascular disease, menopausal symptoms, osteoporosis and other disease, however, do not produce stimulatory hyperplasia effects on uterus, mammary glands and other tissues and organs with positive estrogen receptor. Long-term exposure or excessive use of phytoestrogens maybe affects male reproductive system and hematopoietic function of fetus. Some questions need to be further studied, such as evaluation criteria on biological activity, adverse effects, and action mechanism of phytoestrogen. This review covers plant sources, chemical structure, pharmacological activity and safety of phytoestrogens. It will provide a useful reference for intensive research and rational utilization the phytoestrogens.
Animals ; Humans ; Phytoestrogens ; chemistry ; pharmacology ; Phytotherapy ; Plant Extracts ; chemistry ; pharmacology ; Plants, Medicinal ; chemistry

THE causes of Cushing's syndrome are mainly divided into adrenocorticotropic hormone (ACTH) dependent and independent. ACTH dependent hypercortisolism represents excess ACTH se-creting by the pituitary or tumor outside the pituitary; and the latter one is also called as ectopic ACTH syndrome. Thorax is the most common location of causative lesions for ectopic ACTH syndrome, and the size of lesion is too small to be detected in some cases.1, 2 Cryptococcal pneumonia usually occurs in immunocompromised patients and excess cortisol production can theoretically produce a state of immunodeficiency. Development of cryptococcal pneumonia concomitant with Cushing syndrome (CS) was rare. Here, we report a case of pulmonary nodule in a patient with CS differentiated with ectopic ACTH-producing tumor. Cryptococcal pneumonia was diagnosed following lung resection.
ACTH Syndrome, Ectopic ; Cushing Syndrome ; Humans ; Positron-Emission Tomography ; Solitary Pulmonary Nodule ; Tomography, X-Ray Computed

OBJECTIVETo identify suitable hydroxyl polycyclic aromatic hydrocarbons (OH-PAHs) for co-evaluation of internal exposure level of PAHs by simultaneous determination of a variety of OH-PAHs in urine.

METHODSThe 24-h individual particulate matter and morning urine samples of 112 subjects were collected during June 2011. PAHs carried by individual particulate matter samples and OH-PAHs in urine samples were detected by gas chromatography-mass spectrometry.

RESULTSSeven OH-PAHs were detected in urine samples, among which 1-hydroxy-naphthalene (1-OHNap) concentration was the highest [(20.54 ± 28.94) µmol/mol Cr], while 1-hydroxy-pyrene (1-OHP) concentration was the lowest [(0.73 ± 0.63) µmol/mol Cr]. The concentrations of these seven OH-PAHs decreased in the following order: 1-hydroxy-naphthalene (1-OHNap) > 9-hydroxy-fluorene (9-OHFlu) > 2-hydroxy-naphthalene (2-OHNap) > 3-hydroxy-fluorene (3-OHFlu) > 2-hydroxy-fluorene (2-OHFlu) > 6-hydroxy-chrysene (6-OHChr) > 1-hydroxy-pyrene (1-OHP). The effects of gender and smoking upon the contents of OH-PAHs in urine samples were not significant. There was a good correlation between total hydroxy-naphthalene (ΣOHNap) and 1-OHNap (r = 0.948), and a good correlation was also showed between total hydroxy-fluorene (ΣOHFlu) and 9-OHFlu (r = 0.975). Naphthalene carried by atmospheric particulate matters demonstrated better correlation with 1-OHNap than 2-OHNap, while fluorene carried by atmospheric particulate matters showed better correlation with 9-OHFlu than 3-OHFlu and 2-OHFlu. The correlation coefficients of ΣOHNap, ΣOHFlu and 6-OHChr with 1-OHP were 0.427, 0.543 and 0.655, respectively, and the correlations were not strong.

CONCLUSIONIt cannot reflect internal exposure level of PAHs to use 1-OHP as the only biomarker, while 1-OHNap and 9-OHFlu can be well predictive of the exposure levels of corresponding total OH-PAHs, suggesting that simultaneous determination of 1-OHNap, 9-OHFlu and 1-OHP can be more accurate and comprehensive in evaluating the internal exposure level of PAHs.

Aged ; Air Pollutants ; analysis ; urine ; China ; Environmental Monitoring ; methods ; Female ; Humans ; Hydroxyl Radical ; analysis ; urine ; Male ; Middle Aged ; Polycyclic Aromatic Hydrocarbons ; analysis ; urine

OBJECTIVETo isolate and characterize the side population cells (SP cells) in the lung adenocarcinomas cell line A549.

METHODSThe protein expression of ABCG2 in human lung adenocarcinoma cell line A549 was detected by immunohistochemistry. SP and NSP cells in the cell line A549 were isolated by FACS, and their differentiation was analysed. ABCG2 expression in the two cell subsets was detected by RT-PCR. The cell growth curves, cell division indexes, cell cycles, plate clone formation tests, migration and invasion assays, chemotherapeutic susceptibility tests, tests of the intracellular drug levels, and the tumor cell implantation experiments on nude mice were applied to study the biological properties of the two cell subsets. The expression of ABCG2 in the transplanted tumor in nude mice was detected by immunohistochemistry and RT-PCR.

RESULTSThe positive rate of ABCG2 expression in the A549 cells by immunohistochemistry was 2.13%. SP and NSP cells were isolated by FACS. The SP cells could produce both SP and NSP cells, while NSP cells only produced NSP cells. SP cells expressed ABCG2, but NSP cells did not. The proliferation and migration abilities of the two cell subsets were similar, but the invasion and tumorigenic ability of SP cells was significantly higher than that of NSP cells. The susceptibilities to DDP and its intracellular levels of the two cell subsets were similar, but the susceptibilities to 5-FU, VP16, NVB and GEM and their intracellular levels of NSP cells were significantly higher than those of the SP cells.

CONCLUSIONSSP cells in the human lung adenocarcinomas cell line A549 is enriched with tumor stem cells. An effective way to get lung adenocarcinomas stem cells is to isolate SP cells by FACS.

ATP-Binding Cassette Transporters ; metabolism ; Adenocarcinoma ; pathology ; Animals ; Cell Cycle ; Cell Differentiation ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cell Transformation, Neoplastic ; metabolism ; Fluorouracil ; metabolism ; Humans ; Lung Neoplasms ; pathology ; Mice, Nude ; Neoplasm Proteins ; metabolism ; Neoplasm Transplantation ; Neoplastic Stem Cells ; drug effects ; Side-Population Cells