AIMTo investigate the pharmacokinetics of mycophenolic acid (MPA), an active metabolite of mycophenolate mofetil (MMF) in Chinese adult liver transplant patients.

METHODSThirty-eight liver transplant patients (male 30, female 8) receiving MMF 1.0 g, twice daily in accordance with the recommended regimen were included in this study. Plasma MPA concentrations were measured by high performance liquid chromatography at 0.5, 1, 1.5, 2, 4, 6, 8, 10 and 12 h after the administration of a single dose. Pharmacokinetic parameters were calculated with 3P97 software.

RESULTSThe plasma MPA concentration-time curve was characterized with an early sharp peak reached at 0.5 - 6.0 h after oral administration. And in some patients there was a small second peak due to enterohepatic circulation of mycophenolic acid glucuronide (MPAG), which underwent deglucuronidation and re-absorption as MPA at 4 to 12 h postdose. The mean peak plasma concentration (C(max)) and area under concentration-time curve (AUC(0-12 h)) were (12 +/- 7) microg x mL(-1) and (44 +/- 16) microg x h x mL(-1), respectively. However, a large variability of pharmacokinetic parameters existed in these patients.

CONCLUSIONIn view of the inter-individual variability of MMF pharmacokinetics, plasma MPA concentration should be monitored routinely after MMF administration for individual patient.

Adult ; Aged ; Area Under Curve ; Female ; Humans ; Immunosuppressive Agents ; pharmacokinetics ; Liver Transplantation ; Male ; Middle Aged ; Mycophenolic Acid ; analogs & derivatives ; pharmacokinetics

OBJECTIVETo investigate the potentiality of herpes simplex virus thymidine kinase transduced endothelial progenitor cells (EPC-TK) as angiogenesis-targeting vector in the glioma treatment in vitro and in vivo.

METHODSEPC-TK were mixed with human umbilical vein endothelial cells (HUVECs), U87 or U251 cells at various ratios for ganciclovir (GCV) treatment. The bystander effect was observed by counting the survival cells using MTT assay, and the apoptotic cells were determined by annexin-V and propidium iodide (PI) staining. EPC-TK, EPCs, or phosphate buffered saline (PBS) were injected into the nude mice model of glioma xenograft by tail vein, for the EPC-TK group, EPC group, and PBS group, respectively. And then the changes of tumor volume and tumor vasculature were observed.

RESULTSGCV killed most EPC-TK and reduced the number of other viable cells in a cell:cell ratio-dependent and time-dependent manner. EPC-TK obviously inhibited tumor growth. The tumor volumes on day 21 were 1741.20+/- 576.10 mm(3), 3275.52 +/- 710.86 mm(3) and 3033.09+/-1134.86 mm(3) in the EPC-TK, EPC and PBS group, respectively. EPC-TK also displayed a significant effect on the inhibition of tumor angiogenesis.

CONCLUSIONEPC-TK can exert a potent antiglioma effect via inhibiting angiogenesis.

Angiogenesis Inhibitors ; pharmacology ; Animals ; Antiviral Agents ; pharmacology ; Bystander Effect ; Cell Transformation, Viral ; physiology ; Endothelial Cells ; virology ; Endothelium ; Genetic Vectors ; Glioma ; therapy ; Humans ; Mice ; Mice, Nude ; Simplexvirus ; enzymology ; genetics ; Thymidine Kinase ; genetics ; Transduction, Genetic ; Transfection ; Xenograft Model Antitumor Assays

OBJECTIVETo investigate the effects of procyanidins on proliferation and apoptosis of a hormone-dependent prostate cancer cell line LNCaP in vitro.

METHODSLNCaP cells were cultured in the presence of procyanidin (at 100, 200 and 300 microg/ml, respectively). After 24, 48 and 72 h of culture, the morphological changes of LNCaP cells were examined, and the inhibition of cell proliferation was measured by MTT assay and cell apoptosis evaluated by flow cytometry.

RESULTSAfter procyanidins treatment, some LNCaP cells presented characteristic morphological changes. Procyanidins inhibited the growth of LNCaP cells in a concentration- and time-dependent manner. Flow cytometry analysis showed that procyanidins induced apoptosis of LNCaP cells and the percentage of apoptotic cells increased with the concentration of procyanidins administered and also the elongation of treatment time.

CONCLUSIONProcyanidins inhibit the proliferation and promote the apoptosis of prostate cancer cells.

Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Humans ; Male ; Proanthocyanidins ; pharmacology ; Prostatic Neoplasms ; drug therapy

OBJECTIVETo observe the changes in the activity of dendritic cells (DCs) after carcino-embryonic antigen (CEA) gene transfection mediated by recombinant adeno-associated virus type2 (rAAV) and tumor cell lysate.

METHODSImmature DCs isolated from peripheral blood monocytes of HLA-A11-positive healthy volunteers were infected with the rAAV carrying CEA gene or loaded with tumor cell lysate. The surface markers of the DCs such as CD40, CD 1alpha, and CD86 were analyzed by flow cytometry. Interleukin-12 (IL-12) in the supernatants of DCs and interferon-gamma (IFN-gamma) released by the cytotoxic T lymphocytes (CTLs) were determined by ELISA detection kit. The specific killing activity of CTL against LoVo cells was assessed by MTT assay.

RESULTSThe DCs following antigen loading with the two methods both highly expressed CD40, CD86 and IL-12, and induced specific CTL that specifically recognized and killed LoVo cells, but the killing effect resulting from rAAV infection of the DCs was much better than that induced by tumor cell lysate loading.

CONCLUSIONBoth methods of antigen loading can induce mature DCs from peripheral blood monocyte cells, but rAAV infection of the DCs can be more effective than tumor cells lysate loading. DCs infected with rAAV may have the potential to serve as an adjuvant immunotherapy for patients with colorectal carcinoma.

B7-2 Antigen ; metabolism ; CD40 Antigens ; metabolism ; Cancer Vaccines ; biosynthesis ; immunology ; Carcinoembryonic Antigen ; genetics ; Cell Line, Tumor ; Colorectal Neoplasms ; therapy ; Dendritic Cells ; immunology ; metabolism ; Dependovirus ; genetics ; Genetic Vectors ; Humans ; Interleukin-12 ; metabolism ; Transfection

Objective To study the effects of Jianpi Xiaoai Prescription on cell cycle and apoptosis of human colon cancer HCT116 cells and related factors of Wnt/β-catenin signaling pathway; To investigate its mechanisms of anti-metastasis and recurrence of colorectal cancer. Methods The logarithmic growth phase HCT116 cells were divided into blank group, saline group, 5-Fu group, and Jianpi Xiaoai Prescription low-, medium-, and high-dose groups. After intervention for 48 h, the cells were harvested, and the cell cycle and apoptosis were detected by flow cytometry. The protein expression of β-catenin in the nucleus was detected by Western blot, and the expression of c-myc and cyclinD1 mRNA was detected by PCR. Results Compared with the blank group and saline group, the ratio of HCT116 cells apoptosis of Jianpi Xiaoai Prescription low-, medium-, and high-dose groups increased; the proportion of cells in phase G1 increased and the proportion of S cells decreased; the expression of β-catenin protein in the nucleus and the expression of c-myc,cyclinD1 mRNA decreased,especially in the Jianpi Xiaoai Prescription high-dose group,with statistical significance(P<0.05,P<0.01).Conclusion Jianpi Xiaoai Prescription can promote apoptosis of human colon cancer HCT116 cells and block the cell cycle, and its mechanism may be related to regulating Wnt/β-catenin signaling pathway.

Objective: To assess the risk of public health emergencies in Zhejiang Province, March 2021. Methods: An expert counsel was conducted to assess the risk of coronavirus disease 2019 ( COVID-19 ) , enteritis due to norovirus, chicken pox and influenza by professionals in Zhejiang CDC, based on the information from infectious disease and public health emergency surveillance in Zhejiang Province, domestic health administrative departments, World Health Organization, and European CDC. Results: In March 2021, the risk of imported COVID-19 epidemic will be high in Zhejiang Province, and the possibility of local spread could not be ruled out. The possibility of a large-scale outbreak of enteritis due to norovirus and a small-scale outbreak of chickenpox in schools and kindergartens could not be ruled out after the new term begins. An increased risk of influenza epidemic is predicted in collective units such as schools and kindergartens, yet the risk of a large-scale one will be low. Conclusion High attention should be paid to COVID-19 and enteritis due to norovirus, and general attention should be paid to chicken pox and influenza outbreak.

BACKGROUND:High ankle sprain is easily missed and leads to ankle dysfunction.Arthroscopy can detect hidden high ankle sprain.Suture-button elastic fixation can restore the biomechanical stability of the distal tibiofibular syndesmosis. OBJECTIVE:To explore the clinical efficacy of Suture-button elastic fixation for high ankle sprain under ankle arthroscopy. METHODS:A retrospective analysis was performed on 40 cases of high ankle sprain patients treated with Suture-button elastic fixation under ankle arthroscopy from August 2019 to August 2021 in the Department of Foot and Ankle Surgery,Wuhan Fourth Hospital.All patients underwent Suture-button elastic fixation.The American Orthopedic Foot and Ankle Society function score,Visual Analog Scale pain score,ankle range of motion,preoperative imaging data,and arthroscopic tibiofibular syndesmosis separation degree were recorded.Meislin criteria were used to evaluate the curative effect and postoperative complications were recorded. RESULTS AND CONCLUSION:(1)40 patients were followed up for 16-48 months after operation.(2)At the last follow-up,American Orthopedic Foot and Ankle Society score was(88.95±6.64 points).Visual Analog Scale score was(1.78±1.23 points).Ankle dorsiflexion range of motion was(33.50±5.79 degrees).Ankle plantarflexion range of motion was(34.50±5.97 degrees).There were statistically significant differences before and after surgery(P<0.05).(3)There was a low positive correlation between the radiographic separation index and the degree of arthroscopic separation(r=0.612,P<0.01).(4)The curative effect was evaluated by Meislin standard,with an excellent and good rate of 95%(38/40).Postoperative ankle joint pain was relieved,and ankle joint activities were significantly improved.(5)During the follow-up period,all patients had no nerve injury or incision infection.In 1 patient,the internal fixation was removed due to skin irritation and squatting sensation after operation.(6)It is concluded that Suture-button elastic fixation for high ankle sprain is effective under ankle arthroscopy in restoring ankle function and maintaining joint stability without the need for secondary removal,and it is worth clinical application.

Chinese medicine processing is a kind of traditional pharmaceutical technology,which can reduce toxicity,enhance the curative effect,change the properties and facilitate dispensing preparations in clinical use.The technology of detoxification is a great pioneering work for the safe application of toxic Chinese medicine,which can reduce the side effects of certain drugs,ensure the clinical safe use and expand the scope of clinical application through processing.In this paper,we searched the toxic Chinese medicine and the processing technology in ancient literatures of TCM,and then we summarized and analyzed their lat-est studies at home and abroad.Thus,we make a summary of toxic Chinese medicine including its classification,site of action,the toxic components,detoxification and its clinical application.Meanwhile,we proposed an opinion that toxic Chinese medi-cines with the same processing technology had common detoxification rules.Therefore,we hope this work will provide new perspectives for the research on the processing of toxic Chinese medicine and the mechanism of detoxification.

Objective To investigate the changes and clinical significance of NOD like receptor protein 3(NLRP3)in-flammasomes and related factors in patients with spinal fractures complicated with acute spinal cord injury(SCI).Methods Eighty-six spinal fracture patients complicated with acute SCI admitted to hospital from June 2019 to March 2022 were selected as SCI group,There were 48 males and 38 females,with an average age of(43.48±6.58)years old.And 100 healthy volunteers who underwent physical examination during the same time were selected as control group,including 56 males patients and 44 females patients,with an average age of(45.13±6.43)years old.Peripheral blood mononuclear cell(PBMC)were collected,and the mRNA expressions of NLRP3 and Caspase-1 were detected.Serum was collected and the levels of interleukin(IL)-1β,IL-18 were detected.According to Frankel's grade,the SCI group was divided into complete injury patients and incomplete injury patients,and according to the Japanese Orthopedic Society(JOA)grade,the SCI group was divided into good prognosis group and poor prognosis group.The difference of NLRP3,Caspase-1,IL-1β,IL-18 among groups were compared,the influ-encing factors for poor prognosis in SCI patients was analyzed by Logistic regression.Results The mRNA expression levels of NLRP3(1.41±0.33)and Caspase-1(1.44±0.35)in PBMC and the levels of IL-1β(45.34±13.22)pg·ml-1,IL-18(40.95±8.77)pg·ml-1 in serum of SCI group were higher than those of the control group[(1.00±0.19),(1.00±0.16),(16.58±4.24)pg·ml-1,(12.57±3.68)pg·ml-1](P＜0.05).The mRNA expression levels of NLRP3(1.63±0.34)and Caspase-1(1.67±0.27)in PBMC and the levels of IL-1β(51.09±11.10)pg·ml-1,IL-18(47.65±7.93)pg·ml-1 in serum of patients with complete injury in the SCI group were higher than those of patients with incomplete injury[(1.31±0.27),(1.34±0.33),(42.85±13.36)pg·ml-1,(38.05±7.48)pg·ml-1](P＜0.05).The mRNA expression levels of NLRP3(1.66±0.31)and Caspase-1(1.72±0.31)in PBMC and the levels of IL-1β(51.21±11.31)pg·ml-1,IL-18(45.70±7.25)pg·ml-1 in serum,the proportion of complete injury(21 patients),and the proportion of spinal cord edema or bleeding of patients(15 patients)with poor prognosis in the SCI group were higher than those of patients with good prognosis[(1.28±0.26),(1.37±0.36),(42.79±13.25)pg·ml-1、(38.90±8.63)pg·ml-1,5、20 cases](P＜0.05).Complete injury and the mRNA expression of NLRP3 in PBMC were the influencing fac-tors for poor prognosis in the SCI group(P＜0.05).Conclusion The activation of NLRP3 inflammasomes in patients with spinal fractures complicated with acute SCI is associated with worsening injury and poor prognosis,and NLRP3 expression can serve as a marker for evaluating prognosis.

OBJECTIVETo investigate the effect of Lishi No.5 formula on the growth of human neuroblastoma cell line SY5Y and find out the most effective drug dose.

METHODSY5Y cells were administrated by Lishi No.5 formula in different concentration. MTT metabolic rate was measured as the cell survival rate, then the dose-effect curve was made. LDH leakage rate, axonal length and area of cell body were used as the indicators.

RESULTIn 0.125-0.75 g x L(-1) Lishi No. 5 formula could increase the cell survival rate and MTT metabolic rate, decreased LDH leakage rate, and enhance axonal length and area of cell body, compared with control group.

CONCLUSIONLishi No.5 formula has the neurotrophic effect and can induce the survival of neuron.

Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cell Survival ; drug effects ; Dose-Response Relationship, Drug ; Drug Combinations ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Humans ; L-Lactate Dehydrogenase ; metabolism ; Neuroblastoma ; metabolism ; pathology ; Plants, Medicinal ; chemistry