In order to explore the dose-response patterns of Gancao (Radix Glycyrrhizae) in Shanghan Lun (Treatise on Febrile Diseases), all prescriptions containing Gancao in Shanghan Lun were analyzed by frequency and hierarchical clustering analysis. The doses of Gancao used in Shanghan Lun ranged from six zhu (Chinese unit, and one zhu is equal to 0.65 g) to four liang (Chinese unit, and one liang is equal to 15.625 g). Doses of one, two, three or four liang were commonly used. One liang Gancao as juvantia was usually matched with Mahuang (Herba Ephedrae), Xingren (Semen Armeniacae) and Guizhi (Ramulus Cinnamomi) for restricting the excessive diaphoresis of Mahuang. Two liang Gancao was often matched with some couple drugs, such as Guizhi and Shaoyao (Radix Paeoniae), Shigao (Gypsum Fibrosum) and Zhimu (Rhizoma Anemarrhenae), Fuzi (Radix Aconiti Lateralis) and Ganjiang (Rhizoma Zingiberis), for warming yang to supplement qi, nourishing yin, detoxifying Fuzi, and preventing qi impairment from heat evil. Three liang Gancao was mainly matched with Banxia (Rhizoma Pinelliae) or Renshen (Radix Ginseng) for treating middle energizer emesis. Four liang Gancao was matched with Ganjiang or tonifying herbs for invigorating vital qi and relieving spasm in deficiency syndromes with contraction, palpitation or diarrhea. Gancao is used for treating many syndromes in Shanghan Lun. It is frequently used to treat excess or heat syndromes with one or two liang in a dose and deficiency or cold syndromes with three or four liang in a dose.

Objective To investigate mobilization of the bone-marrow-derived stem cell (BMSC) into peripheral blood by granulocyte-colony stimulating factor (G-CSF) to accelerate the renal regeneration.Methods Six-week-old transgenic C57BL/6J mice labeled with green fluorescent protein (GFP) as bone marrow donors and C57BL/6 mice without fluorescence label as recipients ( n =20 ) of bone marrow transplantation were used.All recipients received lethal dose of 8.5 Gy total body γ-ray irradiation with 137 Cs before bone marrow transplantation,and the transplantation of bone marrow mononuclear cells 2 × 105 by retrobulbar injection was done two hours later after irradiation. Bone marrow reconstruction after transplantation was proved by flow cytometry five weeks after transplantation.Six weeks after the bone marrow reconstruction completed,left renal pedicles of all mice were cross-clasped for 30 minutes followed by reperfusion to establish the animal model of ischemia-reperfusion injury.Mice were divided into two groups:( 1 ) Saline control group ( n =10),saline 0.2 ml/day was injected subcutaneously into chimeric mice from 3 days before to 4 days after operation ; (2) G-CSF mobilization group (n =10),chimeric mice were injected subcutanously with recombinant human G-CSF,200μg/kg/day,once a day from three days before surgery for a week.On the 1st day after mobilization,the percentage of stem cell in non-erythroid cells of peripheral blood was detected by using flow cytometry.One week after ischemia,the homing of BMSC to kidney was identified by flow cytometory.Renal tissue sections were stained with Hemotoxylin and Eosin staining method for pathological study,and the degree of renal tubular injury was analyzed by semiquantitative method of Vyacheslav.Four weeks after ischemia,the differences in degree of renal regeneration between the two groups by analysis the numbers of vascular endothelial cells in the kidney.Results After G-CSF mobilization,the percentage of stem cells with Sca-1 +,c-Kit +,CD29 and CD34 + antigen in peripheral blood in G-CSF mobilization group were higher than those in control group.One week after ischemia,mice of mobilization group showed higher percentage of Sca-1 +,c-Kit + and CD34 + bone marrow derived stem cells in tbe kidney compared to control group (P ＜0.05).One week after ischemia,the tubular epithelial damage score of mobilization group was lower significantly than that of the control group (P ＜ 0.05 ) studied by Hemotoxylin and Eosin staining. Four weeks after ischemia,mice of G-CSF mobilization group showed more CD31 positive cells in the kidney compared to control group (P ＜ 0.05 ).Conclusions G-CSF can effectively mediate the mobilization of bone marrow derived stem cells to peripheral blood and homing to kidney.G-CSF mobilization can accelerate renal regeneration and alleviate the degree of renal histopathological changes after ischemia.

Transient receptor potential (TRP) superfamily is a superfamily of cation channels that can be divided into seven subfamilies. TRPM2 is the second member of the TRPM subfamily, which includes eight members, namely TRPM1-8. TRPM2 is widely expressed in excitable and non-excitable cells, where it forms a Ca(2+)-permeable cation channel and performs diverse cellular functions. TRPM2 channels are activated by ADP-ribose (ADPR), Ca(2+), H2O2 and other reactive oxygen species (ROS). It is established that TRPM2 serves as a cellular sensor for oxidative stress, mediating oxidative stress-induced [Ca(2+)]i increase and contributing to pathological processes in many cell types. Accumulating evidence has indicated that TRPM2 is a potential therapeutic target for oxidative stress-related diseases. This review will highlight recent progress in this field.
Adenosine Diphosphate Ribose ; metabolism ; Calcium ; physiology ; Calcium Channels ; physiology ; Humans ; Hydrogen Peroxide ; metabolism ; Oxidative Stress ; Reactive Oxygen Species ; metabolism ; TRPM Cation Channels ; physiology

Objective To investigate the effect of flipped classroom based on WeChat and mi-crolecture in medical chemistry experiment course in the context of "internet". Methods The classes were randomly divided into 2 groups, experimental group (flipped classroom teaching, n=97) and the control group (traditional teaching, n=98). Comparison of the chemistry experiment test results were performed with the use of t test between the two teaching groups at the end of the semester to evaluate the experimental teaching method. All statistical processing and analyses were performed with SPSS software (version 12.0). Results The chemistry experiment test score of the experimental group was higher than that of the control group [(77.84±8.22) vs. (73.43±10.14), t=3.341, P=0.008), and the difference was statistically significant. The results of the questionnaire showed that the students in the experimental group generally consider that flipped classroom teaching is better than the traditional teaching in terms of the cultivation of comprehen-sive quality and the teaching effect. Conclusion In the context of "internet", flipped classroom teaching with WeChat microlecture can better mobilize the enthusiasm of students to learn and participate in medical chemistry experiment course, which has been welcomed by students and further suggest good application prospects.

Objective: To investigate the effect and the mechanism of Astragalus membranaceus (Huangqi in Chinese, HQ) extract on the intestinal absorption of six alkaloids of Aconitum carmichaelii (Fuzi in Chinese, FZ) in rats with spleen deficiency and provide novel insights into the application of HQ on modulating intestinal barrier. Methods: Four-week-old male Sprague-Dawley rats were fed with Xiaochengqi Decoction to induce the spleen deficiency model for 40 d. Single-pass intestinal perfusion model were used to study the effects of HQ extract on the absorption of alkaloids. Protein expression and mRNA levels of MRP2 and BCRP and tight junction proteins (TJ, including Claudin-1, Occludin and ZO-1) were measured using Western blot and real-time PCR, respectively. The location and expression of TJ protein was also investigated by the immunofluorescence method. Results: Compared with the normal group, the protein expression of MRP2, BCRP and TJ proteins in the model group were significantly down-regulated. After oral administration of HQ, the alkaloid absorption in intestinal villi was inhibited, MRP2, BCRP and TJ proteins were up-regulated, the green fluorescence staining of Claudin-1, Occludin, and ZO-1 was enhanced, and a thick layer of mucus was deposited on the surface of the epithelium of the intestinal cavity. Conclusion: HQ as an intestinal barrier modulator improves the physiological changes of the intestinal environment of spleen deficiency to reduce the absorption of toxic components, leading to a decrease in the absorption of drug-like molecules.

Objective: To analyze the clinical effects of arthroscopic autologous bone grafting and percutaneous fixation in treating scaphoid nonunion. Methods: From May 2013 to August 2017, a total of 25 cases of patients including 20 males and 5 females with unilateral scaphoid fractures and nonunion were reviewed, with mean age of 35.80±2.41 years (18-65 years). The duration from injury to treatment was averaged 11.70±1.90 months (5-18 months). All of the cases sustained waist and proximal end fractures. X-ray and CT scan showed sclerosis and bone resorption without any callus at the fracture sites. However, there were no serious deformities and wrist arthritis. The patients suffered pain and weakness at the radial side of the wrist. The type of the fractures were Slade-Geissler's III-VI, including grade III 4 cases, grade IV 13 cases, grade V 7 cases and grade VI 1 case. The patients were treated with arthroscopic debridement of the sclerotic bone, autologous bone grafting, percutaneous screw (9 cases) or K-wires fixation (16 cases) and immobilization by plaster for 3 weeks after operation, followed by functional rehabilitation training. Bone union was assessed by serial plain radiographs and CT scan regularly. The functional effects were evaluated by comparing the modified Mayo wrist score with the visual analogue scale (VAS) for pain, range of motion (ROM) and the grip strength, which were measured before operation and at 18 months after operation. Results: All cases were followed up. Bone union was achieved in all of 25 nonunion. The average radiological union duration was 10.24±2.10 weeks (6-20 weeks). The average VAS score decreased from 6.75±1.10 preoperatively to 1.33±0.21. The mean ROM of wrist was improved to 168.48°±12.41° (92.90% of that of the normal side), compared to that of 135.24°±17.47° preoperatively (79.80% of that of the normal side). The mean grip strength showed improvement from an average of 35.68±3.81 kg (80.46% of that of normal side) preoperatively to 48.75±4.42 kg (90.65% of that of normal side). The average modified Mayo wrist score improved from 61.52±6.32 preoperatively to 85.88±8.37. Conclusion Arthroscopic autologous bone grafting with percutaneous cannulated screw and K-wires fixation is an effective and minimally invasive treatment for scaphoid nonunion, which could protect the blood supply of the fracture sites, decrease the surgical complications, promote bone healing and lead to a faster recovery.

The CD19-targeting bispecific T-cell engager blinatumomab has shown remarkable efficacy in patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia. However, several studies showed that blinatumomab has a short plasma half-life due to its low molecular weight, and thus its clinical use is limited. Furthermore, multiple trials have shown that approximately 30% of blinatumomab-relapsed cases are characterized by CD19 negative leukemic cells. Here, we design and characterize two novel antibodies, A-319 and A-2019. Blinatumomab and A-319 are CD3/CD19 bispecific antibodies with different molecular sizes and structures, and A-2019 is a novel CD3/CD19/CD20 trispecific antibody with an additional anti-CD20 function. Our in vitro, ex vivo, and in vivo experiments demonstrated that A-319 and A-2019 are potent antitumor agents and capable of recruiting CD3 positive T cells, enhancing T-cell function, mediating B-cell depletion, and eventually inhibiting tumor growth in Raji xenograft models. The two molecules are complementary in terms of efficacy and specificity profile. The activity of A-319 demonstrated superior to that of A-2019, whereas A-2019 has an additional capability to target CD20 in cells missing CD19, suggesting its potential function against CD19 weak or negative CD20 positive leukemic cells.
Antigens, CD19/therapeutic use* ; Antineoplastic Agents/pharmacology* ; Humans ; Immunotherapy ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; T-Lymphocytes