Objective:To explore the role of NK cells in allogeneic hematopoietic stem cell micro-transplantation(MST)in the treatment of patients with acute myeloid leukemia(AML).Methods:Data from 93 AML patients treated with MST at our center from 2013-2018 were retrospectively analyzed.The induction regimen was anthracycline and cytarabine combined with peripheral blood stem cells transplantation mobilization by granulocyte colony stimulating factor(GPBSC),followed by 2-4 courses of intensive treatment with medium to high doses of cytarabine combined with GPBSC after achieving complete remission(CR).The therapeutic effects of one and two courses of MST induction therapy on 42 patients who did not reach CR before transplantation were evaluated.Cox proportional hazards regression analysis was used to analyze the impact of donor NK cell dose and KIR genotype,including KIR ligand mismatch,2DS1,haplotype,and HLA-Cw ligands on survival prognosis of patients.Results:Forty-two patients received MST induction therapy,and the CR rate was 57.1％after 1 course and 73.7％after 2 courses.Multivariate analysis showed that,medium and high doses of NK cells was significantly associated with improved disease-free survival(DFS)of patients(HR=0.27,P=0.005;HR=0.21,P=0.001),and high doses of NK cells was significantly associated with improved overall survival(OS)of patients(HR=0.15,P=0.000).Donor 2DS1 positive significantly increases OS of patients(HR=0.25,P=0.011).For high-risk patients under 60 years old,patients of the donor-recipient KIR ligand mismatch group had longer DFS compared to the nonmismatch group(P=0.036);donor 2DS1 positive significantly prolonged OS of patients(P=0.009).Conclusion:NK cell dose,KIR ligand mismatch and 2DS1 influence the therapeutic effect of MST,improve the survival of AML patients.

Jichuanjian，a famous classical formula with definite clinical efficacy in Jingyue Quanshu （《景岳全书》） by ZHANG Jing-yue in the Ming Dynasty， was included in the Catalogue of Ancient Famous Classical Formulas （The First Batch） published by the National Administration of Traditional Chinese Medicine（TCM） in 2018．By means of bibliometrics，43 relevant ancient book data were collected，including 26 ancient books of TCM. The historical origin and development，main indications and symptoms，composition and prescription，dosage，processing，and decoction and administration methods of Jichuanjian were systematically summarized to provide literature support for the development and clinical application of famous classic formulas. It was found that the main symptoms of Jichuanjian were expanded in the past dynasties from deficiency constipation， postpartum constipation， and qi stagnation recorded in the original formula to additional dryness accumulation， blood stasis， Yin constipation， infantile constipation， and lung（intestine）diseases induced by eye diseases. The applicable population of Jichuanjian was extended to children in addition to puerpera and adults，and the disease scope was extended to pediatrics， ophthalmology， and otorhinolaryngology in addition to internal medicine，gynecology and obstetrics．Although Jichuanjian was modified by doctors in the past dynasties，the compatibility of Angelicae Sinensis Radix，Achyranthis Bidentatae Radix，Cistanches Herba，Alismatis Rhizoma，Cimicifugae Rhizoma and Aurantii Fructus has been constant. The decoction and administration methods basically remained unchanged， i.e.， water decoction and administration before meals. Meanwhile， doctors in the Qing Dynasty made a lot of general comments on this formula with little controversy．

Wulingsan， a classic prescription first recorded in the Treatise on Cold Damage （Shang Han Lun） by ZHANG Zhong-jing for patients with water retention syndrome due to the disturbance of Qi transformation in bladder， has often been modified by ancient and modern doctors for the treatment of renal diseases. It produced satisfactory outcomes without inducing adverse reactions. The databases including China National Knowledge Infrastructure （CNKI）， Wanfang Data Knowledge Service Platform， and PubMed were searched for articles concerning the clinical application and pharmacological mechanism of Wulingsan in the treatment of renal diseases published by domestic and foreign scholars in recent years. The summary of the included articles revealed that Wulingsan has been widely employed for the treatment of renal edema， diabetic nephropathy， acute and chronic glomerulonephritis， nephrotic syndrome， renal insufficiency， abnormal urination， etc.， and the resulting outcomes were satisfactory. Wulingsan alone or in combination with western medicine yielded better clinical outcomes than the western medicine alone. In the exploration of its pharmacological mechanism， there existed some individual reports by Korean scholars， while Chinese scholars tended to work as a team. After years of research， each team has found that Wulingsan was superior to Wulingsan decoction in excreting water， which might be related to the absence of massive low-polarity and volatile components in the decoction that were responsible for regulating the expression of aquaporins （AQP） in kidney of saline-loaded rats. Wulingsan regulates the endocrine state of rats with kidney yang deficiency， inhibits the reabsorption of water， increases the activity of Na⁺-K⁺-ATPase， and reduces the expression of AQP 1， AQP 2， AQP 3， and AQP 4. Besides， it bi-directionally regulates the human water metabolism， which is achieved via the dual-directional regulation of purinergic P2X3 receptor expression on bladder detrusor. The efficacy of Wulingsan in treating chronic renal failure is attributed to its protection against the damaged renal tissue，structure and fanction. Hence， this paper summarized the research progress of Wulingsan in the treatment of renal diseases in recent years， aiming to provide a reference for the clinical and basic exploration of Wulingsan against renal diseases in the future.

The inheritance of traditional clinical value of famous classical formulae is an important direction for the development of traditional Chinese medicine industry.Compared with the previous research and development of new drugs, the management requirement of " material reference" was introduced into the famous classical formulae research, which is used as the reference of process optimization and quality control.The characteristics of compound preparation of famous classical formulae are also reflected in the core concept of " quality inheritance of classics" in the road of industrial development.How to implement the above requirements and concepts into product development and industrial production? There are many specific common problems to be solved in practical research.How to effectively establish the " material reference" of famous classical formulae of different dosage forms? How to use " material reference" to guide the process optimization of compound preparation of famous classical formulae? How to determine the daily dose of famous classical formulae? How to take effective measures in the selection of raw material to reduce quality fluctuation range? This paper discusses the key issues such as production process and quality evaluation from the following aspects.Firstly, the management regulations and research and development guidelines are analyzed, and the specific implementation methods are given.Then, the possible problems in the Requirements for Declaration Documents (Draft for Opinions) are pointed out, and relevant suggestions are given.Finally, based on the research experience of standard decoction and famous classical formulae in the laboratory, an example is given to provide reference for the development of compound preparation of famous classical formulae.

BACKGROUND: Investigation on epidemiologic features of knee osteoarthritis in many areas of China has been much reported. However, multicenter studies with large samples have been rarely reported. The published papers cannot give a good description about the epidemiologic features of knee osteoarthritis. OBJECTIVE: To evaluate the epidemiologic features of knee osteoarthritis in the patients aged over 40 years in China. METHODS: Meta-analysis was used to evaluate the data extracted from papers published 2001-2016 on the epidemiology of knee osteoarthritis in the middle-aged and elderly in China. The prevalence rate of knee osteoarthritis in the patients over 40 years of age was summarized, with every 10 years as group, and then analyzed on Stata 12.0 software. RESULTS AND CONCLUSION: Twenty-six articles were included, involving 42 199 people aged more than 40 years old. The total prevalence rate of knee osteoarthritis at the age above 40 years old in China was 17.0% (95% CI:16.7%-17.4%),the prevalence rate was 12.3% in male and 22.2% in female(P<0.05).Noticeably,the prevalence rate increased with age.The total prevalence rate in northern China was 16.1%(95% CI:15.6%-16.6%),12.2% in male and 21.4% in female;the total prevalence in southern China was 18.0%(95%CI:17.5%-18.5%), 12.3% in male and 23.1% in female. There was no significant difference in the prevalence rate between northern and southern China(P>0.05).The total prevalence rate in rural China was 23.6%(95%CI:16.7%-30.4%),with 15.4% in male and 28.1% in female;and the total prevalence in urban China was 20.0%(95% CI:16.2%-23.9%),with 13.7% in male and 24.3% in female. There was no significant difference in the prevalence rate between rural and urban China (P > 0.05). These results suggest that knee osteoarthritis in China is a common disease, characterized by increased prevalence with age, relatively significant difference between male and female, but no difference between northern and southern China as well as between rural and urban China. It is of great significance to timely propagate and perform interventional strategies for prevention and treatment of knee osteoarthritis in China.

Objective: Analysis of the molecular characteristics of eosinophilia. Methods: Targeting sequence to 24 patients with chronic eosinophilic leukemia (CEL) with rearrangement of PDGFRA, PDGFRB, or FGFR1 and 62 patients with hyper-eosinophilic syndrome (HES). Mutation annotation and analysis of amino acid mutation using authoritative databases to speculate on possible pathogenic mutation. Results: Thirty-seven kinds of clonal variant were detected from 17 patients with CEL, no recurrent mutation site and hot spot region were found. No pathogenic mutation was detected in 19 patients with PDGFRA rearrangement, but pathogenic mutations of ASXL1, RUNX1 and NRAS were detected from 2 patients with FGFR1 rearrangement who progressed to acute myeloid leukemia and 1 patient with PDGFRB rearrangement who progressed to T lymphoblastic lymphoma, respectively. One hundred and two kinds of clonal abnormalities were detected in 49 patients with HES. The main hot spot mutation regions included: CEBPA Exon1, TET2 Exon3, ASXL1 Exon12, IDH1 Y208C, and FGFR3 L164V. CRRLF2 P224L and PDGFRB R370C point mutations were detected separately in 2 patients with HES who treated with imatinib monotherapy and achieved hematologic remission. Conclusion: The pathogenesis of CEL with PDGFRA, PDGFRB or FGFR1 rearrangement is usually single, and the progression of the disease may involve other driver mutation. A variety of genes with hot mutation regions may be involved in the pathogenesis of HES, and some mutation sites are sensitive to tyrosine kinase inhibitors.
Chronic Disease ; Humans ; Hypereosinophilic Syndrome ; Imatinib Mesylate ; Leukemia ; Receptor, Platelet-Derived Growth Factor alpha ; Receptor, Platelet-Derived Growth Factor beta

Dilated cardiomyopathy (DCM) is the most frequent pattern of non-ischemic cardiomyopathy with poor prognosis and high mortality.Studies in recent years found that non-coding small RNA molecules (miRNA) were closely related to the clinical course of DCM.The present article made a review on the expression pattern of miRNA and development of DCM study.

To study the influence of astragaloside on mRNA expression of PI3K/Akt/mTOR signal transduction in anemia model mice induced by chemotherapy, 48 male BALB/c mice which were 6-7 week old were picked as the research objects and randomly divided into four groups, blank group, model group, astragaloside group and astragaloside IV group. Each group was 12 mice. Chemotherapy anemia model was established by cyclophosphamide. The mice were drawn blood from eyeball after 14 days treatment. The QPCR was used to test the mRNA concentrations of Akt, PI3K, BCL-xl, bad, FoxO, mTOR, PTEN in mouse spleen. In comparison of blank group, astragaloside group and astragaloside IV group,the erythrocyte counting and values of Hb in model group were significantly lower (P<0.05). The volumes mRNA of Akt,PI3K,BCL-xl,bad,mTOR were lower in blank group, compared with other groups (P<0.05 or P<0.01). The similar trend in astragaloside IV group except PI3K, comparing with blank group (P<0.05 or P<0.01). The contents of these five genes were no significant differentiations between astragaloside group and blank group. The statistics were obvious between astragaloside group and astragaloside IV group (P<0.05 or P<0.01). The concentrations of FoxO, PTEN were higher in model group,compared with blank group and astragaloside group (P<0.05 or P<0.01), but no difference with astragaloside IV group. Comparing with blank group, the volumes of these two genes were increased in astragaloside IV group (P<0.05), FoxO was higher in astragaloside group (P<0.05), but PTEN was not significant. There was no the same as astragaloside group and Astragaloside IV group. Therefore, astragaloside could increase the contents of Akt, PI3K, BCL-xl, bad, mTOR (P<0.01), decrease the concentrations of FoxO, PTEN (P<0.05). The changes in cyclophosphamide-induced anemia were highly significant by astragaloside. It could be related to the mRNA expression of PI3K/Akt/mTOR Signal Transduction.

OBJECTIVETo assess the efficacy and safety of the Osbon ErecAid Vacuum Therapy System in the treatment of erectile dysfunction (ED) that fails to respond to PDE-5i.

METHODSThis study included 70 cases of ED not responding to the medication of PDE-5i. The patients were aged 25 -66 (38.9 +/- 9.1) years. Under our direction, the patients used the Osbon ErecAid Vacuum Therapy System for a month to increase blood oxygenation to the corpora cavernosa, and then employed the vacuum constriction device (VCD) to maintain penile erection for sexual intercourse. We compared their IIEF-5 scores and their and their partners' sexual satisfaction before and 3 months after treatment, and evaluated the safety and effect of the vacuum therapy.

RESULTSThe mean IIEF-5 scores of the patients were significantly increased from 10.2 +/- 4.0 before treatment to 13.3 +/- 4.7 at 3 months after the vacuum therapy (P < 0.05). The rate of therapeutic effectiveness was 77.1% (54/70), and the rates of sexual satisfaction of the patients and their partners were 64.3% (45/70) and 65.7% (46/70),

CONCLUSIONVacuum therapy for ED that does not respond to PDE-5i can significantly improve the patients' erectile function as well as their and their partners'sexual satisfaction, and therefore deserves clinical application.

Adult ; Aged ; Erectile Dysfunction ; drug therapy ; therapy ; Humans ; Male ; Middle Aged ; Penis ; Phosphodiesterase 5 Inhibitors ; therapeutic use ; Treatment Failure ; Treatment Outcome ; Vacuum

S-phase kinase-associated protein 2 (Skp2), which plays a role in cell cycle regulation, is commonly overexpressed in a variety of human cancers and associated with poor prognosis. However, its role in nasopharyngeal carcinoma (NPC) is not well understood. In this study, we examined the clinical significance of Skp2, with a particular emphasis on overall survival (OS) and disease-free survival (DFS), in NPC cases in South China, where NPC is an epidemic. Additionally, we explored the function of Skp2 in maintaining a cancer stem cell-like phenotype in NPC cell lines. Skp2 expression was assessed for 127 NPC patients using tissue microarrays and immunohistochemistry and analyzed together with clinicopathologic features, OS, and DFS. Skp2 expression was detectable, or positive, in 75.6% of patients. Although there was no correlation between Skp2 and any clinicopathologic factor, Skp2 expression significantly portended inferior OS (P = 0.013) and DFS (P = 0.012). In the multivariate model, Skp2 expression remained significantly predictive of poor OS [P = 0.009, risk ratio (RR) = 4.06] and DFS (P = 0.008, RR = 3.56), and this was also true for clinical stage (P = 0.012 and RR=3.201 for OS; P = 0.002 and RR=1.94 for DFS) and sex (P = 0.016 and RR=0.31 for OS; P = 0.006 and RR = 0.27 for DFS). After Skp2 knockdown, a colony formation assay was used to evaluate the self-renewal property of stem-like cells in the NPC cell lines CNE-1 and CNE-2. The colony formation efficiency in CNE-1 and CNE-2 cells was decreased. In Skp2-transfected CNE-1 and CNE-2 cells, side population (SP) proportion was increased as detected by flow cytometry. Skp2 is an independent prognostic marker for OS and DFS in NPC. Skp2 may play a role in maintaining the cancer stem cell-like phenotype of NPC cell lines.
Adolescent ; Adult ; Aged ; Carcinoma ; Cell Line, Tumor ; China ; Disease-Free Survival ; Female ; Follow-Up Studies ; Gene Knockdown Techniques ; Humans ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; genetics ; metabolism ; pathology ; Neoplasm Staging ; Neoplastic Stem Cells ; pathology ; RNA, Small Interfering ; genetics ; S-Phase Kinase-Associated Proteins ; genetics ; metabolism ; Sex Factors ; Survival Rate ; Tissue Array Analysis ; Transfection ; Young Adult