Objective To investigate the apoptosis of peripheral blood lymphocyte cells in patients with HAM/TSP and the roles of Fas/FasL system, TNF ? and Bcl 2 protein in occurrence and progression of HAM/TSP Methods The single cell gel electrophoresis (comet assay) was used to detect the apoptosis of lymphocyte cells in patients with HAM/TSP The presence of sFas, sFasL in the serum and cerebrospinal fluid (CSF) of patients with HAM/TSP was evaluated by using an enzyme linked immunosorbent assay (ELISA) The Fas, TNF ? and Bcl 2 protein expressions were quanlitatively determined by flow cytometry from 8 cases of HAM/TSP, and compared with the controls and other inflammatory neurological diseases (OIND) Results (1) The apoptotic ratio of lymphocyte cells in patients with HAM/TSP (13 63%?0 48%) was significantly increased as compared to the controls (1 63%?0 57%, P 0 05) Levels of sFas and sFasL in CSF from patients with HAM/TSP ((0 19?0 07) ng/ml and (0 24?0 08) ng/ml) were both significantly increased than those from OIND ((0 11?0 06) ng/ml and (0 01?0 01) ng/ml, P 0 05) or patients with OIND (34 84?9 63, P

Systemic Sclerosis(SSc) is a fibrotic disease characterized by immunological abnormalities,vascular injury and increased accumulation of extracellular matrix.The etiology has not been fully elucidated yet,so we need to establish a suitable animal model for research.This review is to introduce murine model of bleomycin-induced SSc,and summarize research works on the pathogenesis and treatment of SSc based on this model.

Objective: The reverse engineering technology was used to analyze the prescription and process of Good Sense Stay Awake®, the reference listed drug of caffeine tablets, in order to provide guidance for the development of generic caffeine tablets. Methods: Firstly, the prescription information of the reference listed drug was obtained by literature research. Then, quantitative analysis of the composition of the prescription was achieved by the high-performance liquid chromatography with a crystal refractive index detection and the gravimetric analysis method;the particle size of raw and auxiliary materials was analyzed by Raman imaging technology;the crystal habit and crystal form of active pharmaceutical ingredient(API)were characterized by the optical microscope and X-ray powder diffraction technology, respectively;the preparation process of reference listed drug was determined by disintegration method;and finally, the package material was identified by the morpholine reagent. Moreover, three batches of samples were pre-pared according to the determined prescription and process, and the quality was compared with the reference listed drug. Results: By the reverse engineering analysis of the reference listed drug, the prescription composition of the reference listed drug was determined to be composed of glucose, microcrystalline cellulose, pregelatinized starch, maltodextrin, magnesium stearate, colloidal silica and yellow lake, in which the glucose content was 32% and the microcrystalline cellulose content was <23%. The API crystal form of the reference listed drug was consistent with that of the self-made preparation. The average particle size of caffeine, microcrystalline cellulose, glucose, maltodextrin and pregelatinized starch was approximately 206, 112, 172 and 61 μm, respectively. The tablet preparation process was the direct compression method, and the packaging material was polyvinyl chloride aluminum foil. The quality of the three batches of home-made preparations was the same as that of the reference listed drug. Conclusion: Caffeine tablets with the same quality as Good Sense Stay Awake® were successfully prepared by reverse engineering of the reference listed drug, which provides a reference for the application of reverse engineering in the generic drug development and consistency evaluation.

There are two ways for marketing Over The Counter(OTC)drugs in the US: the OTC monographs and new drug application/simple application(NDA/ANDA) review procedures. New products that meet the final monograph can be marketed without FDA approval, but the reference preparations and standard preparations are not searchable in the FDA database, so the reference preparation cannot be determined for such products generally. For the convenience of finding out and confirming the US non-prescription generic reference preparation, this paper introduces the US OTC drug review procedure and inquiry method, taking the US OTC product caffeine tablet as an example to show how to determine the US OTC generic drug reference preparations, so as to provide a reference for the selection of reference preparations in the consistency evaluation of generic drugs in China.

The FDA approved a total of 37 new drugs in 2022, including 22 new molecular entities and 15 new biological products. This is the year with the lowest number of new drugs approved by the FDA since 2017. Among these approved drugs, 21 new drugs belong to the "first-in-class" category, accounting for 56% of the total approved drugs, which is the highest ratio in the past 10 years. Among the drugs approved in 2022, there are 5 small molecule kinase modulators, including the tyrosine kinase 2 (TYK2) allosteric inhibitor deucravacitinib, the first oral pyruvate kinase (PK) activator mitapivat, the Janus kinase 1 (JAK1) selective inhibitor abcrocitinib, the JAK2 selective inhibitor pacritinib and the broad-spectrum fibroblast growth factor receptor (FGFR) inhibitor futibatinib. This review briefly describes the discovery background, research and development process, synthesis routes and clinical efficacy and safety of small molecule kinase modulators approved by the FDA in 2022, hoping to provide ideas and methods for further research on kinase modulators.

Carcinoma, Papillary ; genetics ; Humans ; Mutation ; Proto-Oncogene Proteins B-raf ; genetics ; Thyroid Neoplasms ; genetics

BACKGROUND: Regeneration of type Ⅱ furcation defects of periodontal tissues is still a great clinical challenge. OBJECTIVE: To compare different densities of autologous bone marrow mesenchymal stem cells (auto-BMSCs) for repairing canine experimental class Ⅱ furcation defects of periodontal tissues. DESIGN: A randomized controlled trial. SETTING: Laboratory in Stomatological Hospital Affiliated to Fujian Medical University and Department of Animal Experiment in Fuzhou General Hospital. MATERIALS: Experiments were performed at the Laboratory in Stomatological Hospital Affiliated to Fujian Medical University and Department of Animal Experiment in Fuzhou General Hospital of Nanjing Military Area Command of Chinese PLA from July 2005 to September 2006. Six 18-month Beagle dogs were provided by Department of Animal Experiment in Fuzhou General Hospital of Nanjing Military Area Command of Chinese PLA. Animal intervention met animal ethical standards. Bio-Gide collagen membrane and BME-10X collagen membrane were used in the study.METHODS: Class Ⅱ furcation defects were induced surgically on the buccal side of canine mandibular second and third premolar (P2, P3) and first molar (M1). The ex vivo expanded auto-BMSCs from six 18-month Beagle dogs were seeded in BME-10X collagen membranes at cell density of 5×108 L-1，5×109 L-1，5×1010 L-1, and delivered into experimental class Ⅱ furcation defects, underneath a Bio-Gide membrane. Bio-Gide membrane alone was used as a control. The percentage of new cementum length and percentage of new alveolar bone area were measured on OLYPUS IX 71 inverted research microscope and OLYSIA BioAutoCell software in a computer.MAIN OUTCOME MEASURES: Each specimen was stained with hematoxylin and eosin. The lengths of new cementum and the area of new alveolar bone were calculated.RESULTS: The percentage of newly formed cementum length and the percentage of newly formed alveolar bone area were (51.5±5.6)% and (27.1±7.7)% in the control group,（84.8±8.9）% and（30.6±7.7）% in the 5×108 L-1 BMSCs group, (91.8±5.2)% and (68.3±11.4)% in the 5×109 L-1 BMSCs group and (88.8±7.2)% and (78.5±12.7)% in the 5×1010 L-1 BMSCs group. There were significant differences when comparing the BMSCs groups to the control group (P < 0.01), but there was no significant difference in each BMSCs group. There were significant differences in the percentage of newly formed alveolar bone when comparing the 5×109 L-1 and 5×1010 L-1 BMSCs groups to 5×108 L-1 BMSCs group and control group (P < 0.05), but there was no significantly difference between the first two groups, and neither was the later.CONCLUSION:Periodontal regeneration can be induced by BMSCs transplantation. The mechanism of regeneration is associated with inoculated density.

Objective To investigate the role of tissue factor in the occurrence and development of co agulation in acute vascular rejection of heart xenotransplantation. Methods An animal model for acute vascular rejection of heart xenotransplantation was es tablished by using rat as recipient and guinea pig as donor. The xenografts were removed at 4, 8, 12, 16, and 24 h after the operation for fibrin sedimentation by immunohistochemical technique to evaluate coagulation. Meanwhile, the express ion of tissue factor mRNA was detected at different time points by RT-PCR. Hear ts of normal guinea pigs were used as controls. Results Immunohistochemical examination showed that coagu lation developed at the 8 h when interstitial fibrin deposition and fibrinous th rombus appeared and aggravated with time. High expression of guinea pig tissue factor mRNA appeared at 4 h after the transplantation and then steadily d eclined and totally terminated at the 16 h. The expression of rat tissue factor mRNA appeared 16 h post operation and then kept steadily enhanced. Conclusions The tissue factor acts as an important role in the acute vascular rejection of h eart xenotransplantation. The high expression of donor tissue factor mRNA might be related to the trigger of coagulation and the high expression of the receptor ’s tissue factor may be related to the further development of coagulation.

Objective To study the apoptosis of peripheral blood lymphocyte cells in patients with HAM/TSP and the roles of Fas, TNF-? and Bcl-2 in occurrence and progression of HAM/TSP.Methods The single cell gel electrophoresis (comet assay) was used to detect the apoptosis of lymphocyte cells in 8 patients with HAM/TSP, 8 cases with other inflammatory neurologic diseases (OIND) and 8 healthy blood donors. The Fas, TNF-? and Bcl-2 protein expressions were quantitatively determined by flow cytometry from 8 cases of HAM/TSP.Results The apoptotic ratio of lymphocyte cells in patients with HAM/TSP significantly increased compared with the controls (P

Objective To evaluate clinical effects of single-dose intra-arterial infusion chemotherapy for the treatment of refractory bladder cancer after transurethral resection of bladder tumor (TURBt). Methods A retrospective analysis was made on clinical data of 12 cases of refractory bladder cancer treated by single-dose intra-arterial infusion chemotherapy after TURBt from November 1999 to June 2005. The bladder tumor was resected as thoroughly as possible. Postoperatively, a bilateral internal iliac arteriography was made by using the Seldinger technique. The tumor vessels and normal blood supply were identified through the intubation of the right femoral artery. Half dose of chemotherapeutics (epirubicin 25 mg) was infused into both internal iliac artery, then tumor vessels of bladder was selected and infused with peripheral embolization agent (a mix of fragmented gelatin sponge and cisplatin 200 mg). The embolization agent was used repeatedly until all tumor vessels were embolized. Intravesical instillation with epirubicin was carried out postoperatively, and cystoscopy was performed every 3 months after operation. Results After intra-arterial infusion chemotherapy, there were 12 cases of nausea and anepithymia, 3 cases of vomiting, and 2 cases of fever, all of which were symptomatically relieved with expectant treatment. Mild hip pain occurred in 6 cases and subsided in 3~5 days. Decreased erythrocyte and leucocyte were restored to normal levels in 2 weeks. Liver and renal functions did not present marked changes. Follow-up was conducted for 4~55 months (mean, 34 months). There were 1 case of recurrence at 32 postoperative month and 11 cases of progression free survival. Conclusions This technique lowers the recurrent rate of refractory bladder cancer and the incidence of side effects, being a new alternative for patients who are not willing to receive total cystectomy.