Long-term Complete Remission of Decitabine-Primed Tandem CD19/CD22 CAR-T Therapy with PD-1 and BTK Inhibitors Maintenance in a Refractory Primary Central Nervous System Lymphoma Patient / Journal of the Korean Cancer Association, 대한암학회지

Primary central nervous system lymphoma (PCNSL) is a rare and aggressive non-Hodgkin’s lymphoma that affects the brain, eyes, cerebrospinal fluid, or spinal cord without systemic involvement. The outcome of patients with PCNSL is worse compared to patients with systemic diffuse large B-cell lymphoma. Given potential mortality associated with severe immune effector cell-associated neurotoxicity syndrome (ICANS), patients with PCNSL have been excluded from most clinical trials involving chimeric antigen receptor T-cell (CAR-T) therapy initially. Here, we report for the first time to apply decitabine-primed tandem CD19/CD22 dual-targeted CAR-T therapy with programmed cell death-1 (PD-1) and Bruton’s tyrosine kinase (BTK) inhibitors maintenance in one patient with multiline-resistant refractory PCNSL and the patient has maintained complete remission (CR) for a 35-month follow-up period. This case represents the first successful treatment of multiline resistant refractory PCNSL with long-term CR and without inducing ICANS under tandem CD19/CD22 bispecific CAR-T therapy followed by maintenance therapy with PD-1 and BTK inhibitors. This study shows tremendous potential in the treatment of PCNSL and offers a look toward ongoing clinical studies.

Preparation of a recombinant tumor-targeting ribosome inactivating protein luffin-α-NGR and evaluation of its antitumor activity / 生物工程学报

Loofah seeds ribosome inactivating protein luffin-α was fused with a tumor-targeting peptide NGR to create a recombinant protein, and its inhibitory activity on tumor cells and angiogenesis were assessed. luffin-α-NGR fusion gene was obtained by PCR amplification. The fusion gene was ligated with pGEX-6p-1 vector to create a recombinant plasmid pGEX-6p-1/luffin-α-NGR. The plasmid was transformed into E. coli BL21, and the target protein was isolated and purified by GST affinity chromatography. The luffin-α-NGR fusion gene with a full length of 849 bp was successfully obtained, and the optimal soluble expression of the target protein was achieved under the conditions of 16 ℃, 0.5 mmol/L IPTG after 16 h induction. SDS-PAGE and Western blotting confirmed the recombinant protein has an expected molecular weight of 56.6 kDa. Subsequently, the recombinant protein was de-tagged by precision protease digestion. The inhibitory effects of the recombinant protein on liver tumor cells HepG2 and breast cancer cells MDA-MB-231 were significantly stronger than that of luffin-α. The Transwell and CAM experiment proved that the recombinant protein luffin-α-NGR also had a significant inhibitory effect on tumor cells migration and neovascularization. The inhibitory activity on tumor cells and angiogenesis of the recombinant luffin-α-NGR protein lays a foundation for the development of subsequent recombinant tumor-targeting drugs.

China experts' consensus on preventive and interceptive orthodontic treatments of malocclusions of children / 华西口腔医学杂志

Malocclusion is one of the three most common oral diseases reported by World Health Organization(WHO). In China, its incidence rate is rising. Malocclusion seriously affects the dental and maxillofacial function, facial appearance and growth development of nearly 260 million children in China, and what is more, it affects their physical and mental health development. Malocclusion occurrence is related to genetic and environmental factors. Early treatment of malocclusion can create a good dental and maxillofacial development environment, correct abnormal growth and control the adverse effects of abnormal genetic factors. It can effectively reduce the prevalence of children's malocclusion and enhance their physical and mental health. This is an urgent need from the economic perspective of our society, so it has great practical and social significance. Experts from the project group "standard diagnose and treatment protocols for early orthodontic intervention of malocclusions of children" which initiated by China National Health Institute of Hospital Administration wrote the "China Experts' Consensus on Preventive and Interceptive Orthodontic Treatments of Malocclusions of Children", which aims to guide and popularize the clinical practice, improve the clinical theory and practice level, and accelerate the disciplinary development of early treatment of children's malocclusion in China. The consensus elaborates the harmfulness of malocclusion and the necessity of early treatment, and brings up the principles and fundamental contents. Based on the law of dental and maxillofacial development, this paper puts forward the guiding suggestions of preventive and interceptive treatments in different stages of dental development ranging from fetus to early permanent dentition. It is a systematic project to promote and standardize the early treatment of malocclusion. Through scientific and comprehensive stratified clinical practice and professional training, the clinical system of early treatment of malocclusion in China will eventually be perfected, so as to comprehensively care for children's dental and maxillofacial health, and improve their oral and physical health in China.

Optimization of noni callus induction and establishment of callus suspension system / 生物工程学报

The aim of the study was to obtain the secondary metabolites in the stem segment of noni and to establish genetic transformation system. The stem segments (no axillary buds) of noni were used as explants to induce the callus, and then to establish the cell suspension system. The factors affecting callus induction and cell suspension were studied. The results showed that the optimal culture medium for induction was MS with 1.0 mg/L 6-Benzylaminopurine (6-BA) and 0.1 mg/L 2,4-dichlorophenoxyacetic acid (2,4-D), and the optimum culture medium for suspension was MS with 1.0 mg/L 6-BA and 0.1 mg/L 2,4-D, 3% sucrose and the pH of 5.85, with the initial inoculation amount of 37.5 g/L, and the speed of 110 r/min and 25±2 °C applying darkness culture. The suspension cells grew well and showed the maximum growth rate. The growth curve of the suspension cells from the stem segment of noni was in "S-typed" trend, and it should be transformed to the fresh medium between 12 and 20 d. During the culture, the pH of the culture medium decreased and then slowly increased, and the optimum pH for the suspension cells culture of callus from noni's stem segments was 4.5-5.0. In this study, the stable cell suspension system of the stem segment of noni was successfully established.

Time series observation on microstructure development of mandibular bone under different occlusal force in rats / 实用口腔医学杂志

Objective: To study the microstructure development of mandibular bone in rats on timing sequence and under different occlusal force. Methods: 63 male SD rats aged 23 days were randomly divided into three groups (n = 7): Baseline group, soft-diet (SD) group and hard-diet (HD) group. 7 rats were killed at week 0, 2, 4, 6 and 8 respectively after feeding the food with different hardness.Micro-CT was used to reconstruct and analysis microstructure of the region of interest in mandible of the rats. Results: Compared with HD group, bone volume/total volume (BV/TV) and trabecular thickness (Tb. Th) decreased significantly after 4 th week (P ＜ 0. 05), the bone surface/bone volume (BS/BV) and trabecular separation (Tb. Sp) increased significantly during the 4 th to the 6 th week (P ＜0. 05) . Conclusion: In the process of mandibular development in rats, reduction of occlusal force may lead to reduction of bone mass, and the changes of microstructure are closely related to the time of intervention.

Efficay and safety analysis of bronchoscopic interventional therapy in 33 children with severe refractory pneumonia / 中华实用儿科临床杂志

Objective To evaluate the efficacy and safety of the application of bronchoscopic interventional intervention in children with severe refractory pneumonia.Methods The study was based on case analysis of subjects diagnosed with severe refractory pneumonia and hence receiving bronchoscopic interventional therapy.The standards of clinical efficacy were set against clinical symptoms,microscopic manifestations and chest CT.Thirty-three children in Guiyang Children's Hospital were selected as subjects during a time span from January 2015 to March 2017.Results Mucous hyperemia,swelling and secretion were observed in all the 33 subjects,among whom 100.0％ (33/33 cases) were observed with tmucosal atrophy and longitudinal plica,63.6％ (21/33 cases) with mucosalerosion,36.4％ (12/33 cases) with proliferation of granulation tissue,27.2％ (9/33 cases) with plastic secretion plug,18.2％ (6/33 cases) with spiny change of fish bone,18.2％ (6/33 cases) with tracheobronchia stenosis,15.2％ (5/35 cases) with tracheobronchial malacia,15.2％ (5/35 cases) with tracheobronchial atresia and 9.1％ (3/33 cases) with subglottic stenosis.All the 33 cases received different bronchoscopic pulmonary interventional therapy strategies accordingly.Nine subjects with plastic bronchitis secretion plug were treated with bronchoalveolar lavage and repeated clamping by tracheal foing;5 subjects with occult foreign body were treated with argon plasma coagulation,basket-shaped foreign body forceps,cryotherapy or laser cutting;1 case with subglottic stenosis,5 cases with tracheobronchial malacia and 6 cases with tracheobronchial stenosis were treated with balloon dilatation;2 cases with subglottic stenosis and 5 cases with tracheobronchial atresia received the combined therapy.As a result,27 cases out of the 33 subjects were evaluated as complete resgonse and the rest were evaluated as partial response.In some cases,transient complications were observed during or after operation,which were well-handled and displeased.No serious complications were observed.Conclusion Based on a comprehensive understanding of the indications,contraindications and operation points of different bronchoscopic intervention modes,the strictly application of bronchoscopic interventional therapy accordingly in children with severe refractory pneumonia was proved to be effective and highly safe.

Study of histology in accellular dermal matrix after being transplanted in vivo over time / 实用医学杂志

Objective To demonstrate the histology in acellular dermal matrix(ADM)after being transplanted in vivo over time. Methods Forty male SD rats were recruited for the experiment. Subcutaneous implantation of an 1 cm × 1 cm ADM was given in the left sides on the back of the rat for the experimental group, while only dissection and suturing were performed in right side of the back for the control group. All the animals will be sacrificed at appointed time after operation, Five ADM samples were harvested in each time point. The content and proportion of collagen type were examined with HE staining, Picrosirius staining, Masson′s trichrome staining, and Immunohistochemical staining (targets: pan macrophage, M1 macrophage and M2 macrophage). Results All rats survived after operative without any complications. Significant differences of thickness were not observed at the end of 5 months; HE scores suggested that ADM increased in cell infiltration scores in 2 weeks before the plateau , vascularity also showed a similar trend; Collagen trichrome staining showed a substantial increase in density of collagen bundles with time. The comparison of the proportion of collagen among days showed significant differences (P < 0.05). Immunohistochemical staining of M1 and M2 showed that macrophages had distinct polarization profiles in materials. Furthermore, the comparison of M1 vs M2 response associated with different materials showed significant differences in all time points (P < 0.05). Conclusions The chemically cross-linked ADM could keep long time in the body; ADM significantly stimulated proinflammatory of M2 differentiation from M1 in constructive remodeling.

Determination of Residual Solvents in Faeces Bombycis Extract by GC / 中国药师

Objective:To establish a method for the determination of solvent residues in faeces bombycis extract by GC .Meth-ods: A GC-headspace injection method was adopted to detect the residual organic solvents in the extract of faeces bombycis .A DB-5MS (30 m ×0.25 mm ×0.25 μm) quartz capillary column was used as the chromatographic column;nitrogen was used as the carrier gas at a flow rate of 0.6 ml· min-1;the injector temperature was 200℃;the detector was a flame ionization detector( FID) with the temperature of 250℃;the temperature program included two phases:the initial temperature was set at 40℃for 10 min, and then risen to 200℃at a rate of 5℃· min-1 and maintained for 5 min;the equilibrium temperature of headspace was 95℃;the equilibrium time was 30 min;the capillary temperature was 110℃;the injection ring temperature was 125℃.Results:The linear range of acetone , 2, 3-dimethylpentane, 3-methylhexane, heptane, 2,2-dimethylhexane, p-xylene, m-xylene, O-xylene and 2,4,6-collidine was 101-3 034μg· ml-1 , 100-2 995 μg· ml-1 , 107-3 197 μg· ml-1 , 101-3 019 μg· ml-1 , 99-2 962 μg· ml-1 , 45-1 358 μg· ml-1 , 44-1 325μg· ml-1, 47-1 411 μg· ml-1 and 104-3 130 μg· ml-1, respectively, and the average r was all above 0.992.The recovery of the method met the requirement , and the blank solvent showed no interference .Eight samples were all accordance with the requirements after the examination .Conclusion:The headspace injection method for the determination of residual organic solvents in the extract of faeces bombycis is simple and reliable .

The function of the bridging epithelium in the development of lip and palate / 实用口腔医学杂志

Objective:To explore the function of the bridging epithelium between maxillary process and nasal process in the devel-opment of lip and palate.Methods:The fertilized white leghorn chick eggs incubated to the appropriate Hamburger and Hamilton(H-H)stages were examined by tissue histologic studies,scanning electron microscopy observation,BrdU assay and TUNEL assay re-spectively.Results:At H-H stage 24,the epithelia between maxillary,lateral nasal and globular process were juxtaposed.At H-H stage 26-27,string-like filopodia appeared and the bridging epithelium formed,then in the bridging epithelium cell proliferation was decreased and the apoptotic cells appeared.At H-H stage 28,the apoptosis of the bridging epithelium cells increased,the full fusion of the processes was completed.Conclusion:The occurrence of bridging epithelium between maxillary process and nasal process plays an important role in the development of lip and palate.

Anti-inflammation,Analgesia and Ulcer Healing Promotion of Zhenbing Koukuining Tablets / 中国药师

Objective:To investigate the anti-inflammation,analgesia and ulcer healing promotion of Zhenbing Koukuining tab-lets. Methods:The anti-inflammatin,analgesia and ulcer healing promotion of the preparation was respectively observed in the croton oil-induced auricular edema in mice,acetic acid-induced writhing in mice and acetic acid-induced oral ulcer in golden hamsters. Re-sults:The tablets could obviously alleviate the auricular edema(P<0. 01)and reduce the writhing times in mice(P<0. 05),and nar-row the oral ulcer(P<0. 01 or P<0. 05)and inhibit the inflammation reaction in golden hamsters. Conclusion:Zhenbing Koukuining tablets have anti-inflammatory,analgesia and ulcer healing promotion effects.

Endoscopic sphincterotomy vs open surgery in the treatment of common bile duct stones / 中华普通外科杂志

Objective To compare the value of ERCP plus EST and laparotomy in the treatment of common bile duct stones.Methods 56 cases of common bile duct stones were treated with ERCP and EST in our hospital from June 2012 to June 2013 (endoscopy group),78 cases were treated with laparotomy and common bile duct exploration (laparotomy group).The two groups were compared on success rate of stone removal,operation time,intraoperative bleeding volume,incidence of infection and pancreatitis and hyperamylasemia,common bile duct stone recurrence rate,hospital stays,hospital costs.Results Operation time,intraoperative bleeding volume and infection rate in endoscopic group was lower than the laparotomy group,the incidence of hyperamylasemia,hospital costs in the endoscopic group was higher than laparotomy group.The success rate of stone removal and the recurrence rate of common bile duct stone in the endoscopic group was lower than the laparotomy group,incidence of pancreatitis in the endoscopic group was higher than the laparotomy group,though the differences were not statistically significant.Conclusions ERCP and EST is a time saving procedure fast relieving the bile duct obstruction,less traumative,spelling lower infection rate,less hospital stays,though causing higher incidence of hyperamylasemia and hospital costs.