This review paper presents the current research progress, challenges and future development on microelectrode array of retinal prosthesis, including epi-retinal and sub-retinal implants.
Microelectrodes ; Prosthesis Design ; Visual Prosthesis

AIMTo study the chemical composition of Tripterygirm wilfordii Hook. f.

METHODSColunm chromatography was used to separate the chemical constituents. UV, IR, MS, HRMS, 1HNMR, 13CNMR (COM and OFR), 1H-1H COSY, 1H-13C COSY, NOESY and COLOC spectra were used to determine the structures of the isolated constituents.

RESULTSTwo sesquiterpene alkaloids were isolated and their structures were elucidated as wilforgine and wilfordlongine on the basis of spectral evidence.

CONCLUSIONWilfordclonine is a new sesquiterpene alkaloid.

Lactones ; chemistry ; isolation & purification ; Molecular Structure ; Plant Roots ; chemistry ; Plants, Medicinal ; chemistry ; Pyridines ; chemistry ; isolation & purification ; Tripterygium ; chemistry

Objective: To investigate the efficacy and safety of CD19 chimeric antigen receptor T (CAR-T) lymphocytes for the treatment of B cell lymphoma. Methods: A total of 22 patients with B-cell lymphoma from February 1, 2017 to July 1, 2018 were reviewed to evaluate the efficacy and adverse reactions of CD19 CAR-T. Results: Of 22 patients with B-cell lymphoma received CD19 CAR-T cells, the median dose of CAR-T cells was 7.2 (2.0-12.0) ×10⁶/kg. Nine of 12 cases of relapse refractory patients were overall response. Complete remission (CR) occurred in 2 of 12 patients, partial remission (PR) in 7 of 12 patients. The overall response in minor residual disease positive (MRD) group was 8 of 10 patients. CD19 CAR-T cells proliferated in vivo and were detectable in the blood of patients. The peak timepoints of CAR-T cells proliferated in the relapsed refractory and MRD positive groups were 12 (5-19) and 4.5 (1-12) days after treatment respectively, and among peripheral blood cells, CAR-T cells accounted for 10.10% (3.55%-24.74%) and 4.02% (2.23%-28.60%) of T lymphocytes respectively. The MRD positive patients achieved sustained remissions during a median follow-up of 8 months (rang 3-18 months) . None of all the patients relapsed during a median follow-up time of 10 months (3-18 months) . However, 7 PR responders of the relapsed refractory patients maintained a good condition for 1.5-6.0 months. One patient bridged to hematopoietic stem cell transplantation, another one sustained remission for 12 months. Cytokine-release syndrome (CRS) occurred in 14 patients with grade 1-2 CRS in MRD positive group and grade 3 CRS in relapsed refractory group. Conclusions CAR-T cell therapy not only played a role in the rescue treatment of relapsed and refractory patients, but also produced a surprising effect in the consolidation and maintenance of B-cell lymphoma. CD19 CAR-T cells might be more effective in the treatment of MRD positive B-cell lymphoma patients than in the refractory or relapsed cases. High response rate was observed with fewer adverse reactions.

Isotemporal substitution model is a powerful tool to explore the real association between physical behavior and health outcomes, which has the potential of the application in large-scale cohort study. This paper systematically introduces the principle of isotemporal substitution model and its implementation method in specific analysis to provide analytical ideas for the epidemiological research related to physical behavior in China. The baseline data of Regional Ethic Cohort Study in Northwest China conducted in Shaanxi province were used to analyze the relationship between physical behavior and cardiovascular disease with single-factor model, partition model and isotemporal substitution model. The advantages and disadvantages of different models were compared, and the advantages of isotemporal substitution model in quantifying physical activity health risk were introduced. Isotemporal substitution model could qualify physical behavior and health outcomes, which has wide application value in epidemiological research.
Humans ; Cohort Studies ; Epidemiologic Studies ; Cardiovascular Diseases ; China/epidemiology*

Objective: To investigate the efficacy and safety of CD19 chimeric antigen receptor T (CAR-T) lymphocytes for the treatment of B cell lymphoma. Methods: A total of 22 patients with B-cell lymphoma from February 1, 2017 to July 1, 2018 were reviewed to evaluate the efficacy and adverse reactions of CD19 CAR-T. Results: Of 22 patients with B-cell lymphoma received CD19 CAR-T cells, the median dose of CAR-T cells was 7.2 (2.0-12.0) ×10⁶/kg. Nine of 12 cases of relapse refractory patients were overall response. Complete remission (CR) occurred in 2 of 12 patients, partial remission (PR) in 7 of 12 patients. The overall response in minor residual disease positive (MRD) group was 8 of 10 patients. CD19 CAR-T cells proliferated in vivo and were detectable in the blood of patients. The peak timepoints of CAR-T cells proliferated in the relapsed refractory and MRD positive groups were 12 (5-19) and 4.5 (1-12) days after treatment respectively, and among peripheral blood cells, CAR-T cells accounted for 10.10% (3.55%-24.74%) and 4.02% (2.23%-28.60%) of T lymphocytes respectively. The MRD positive patients achieved sustained remissions during a median follow-up of 8 months (rang 3-18 months) . None of all the patients relapsed during a median follow-up time of 10 months (3-18 months) . However, 7 PR responders of the relapsed refractory patients maintained a good condition for 1.5-6.0 months. One patient bridged to hematopoietic stem cell transplantation, another one sustained remission for 12 months. Cytokine-release syndrome (CRS) occurred in 14 patients with grade 1-2 CRS in MRD positive group and grade 3 CRS in relapsed refractory group. Conclusions: CAR-T cell therapy not only played a role in the rescue treatment of relapsed and refractory patients, but also produced a surprising effect in the consolidation and maintenance of B-cell lymphoma. CD19 CAR-T cells might be more effective in the treatment of MRD positive B-cell lymphoma patients than in the refractory or relapsed cases. High response rate was observed with fewer adverse reactions.
Antigens, CD19 ; Humans ; Lymphoma, B-Cell ; Neoplasm Recurrence, Local ; Receptors, Antigen, T-Cell ; Receptors, Chimeric Antigen ; T-Lymphocytes

OBJECTIVETo investigate the effects of oral administration of low-dose propranolol on heart rate variability (HRV), acceleration capacity (AC), deceleration capacity (DC), and cardiac conduction in the treatment of infantile hemangioma.

METHODSA total of 118 infants with hemangioma (≤1 year) were enrolled, and 24-hour ambulatory electrocardiography was performed before oral administration of low-dose propranolol and after one month of administration. The changes in time-domain indices [standard deviation of all normal sinus RR intervals (SDNN), standard deviation of all mean 5-minute RR intervals (SDANN), root mean squared successive difference (RMSSD), and percentage of successive normal sinus RR intervals >50 ms (PNN50)] and frequency-domain indices [low frequency (LF) and high frequency (HF)] for HRV, AC, and DC were observed, as well as abnormalities in cardiac conduction and other aspects after administration of propranolol.

RESULTSAfter administration of propranolol, the infants had significantly increased SDNN, RMSSD, LF, HF, and PNN50 (P<0.01), and significantly reduced AC, mean heart rate (HR) and minimum HR (P<0.01). The 24-hour ambulatory electrocardiographic findings showed a nonsignificantly higher abnormal rate after administration of propranolol.

CONCLUSIONSIn the treatment of infantile hemangioma, propranolol can inhibit the activity of sympathetic nerve and block cardiac conduction, but without any serious adverse effect.

Administration, Oral ; Electrocardiography ; drug effects ; Female ; Heart Rate ; drug effects ; Hemangioma ; drug therapy ; physiopathology ; Humans ; Infant ; Male ; Propranolol ; pharmacology ; therapeutic use

Objective:To establish autoverification rules for coagulation tests in multicenter cooperative units, in order to reduce workload for manual review of suspected results and shorten turnaround time (TAT) of test reports, while ensure the accuracy of results.Methods:A total of 14 394 blood samples were collected from fourteen hospitals during December 2019 to March 2020. These samples included: Rules Establishment Group 11 230 cases, including 1 182 cases for Delta check rules; Rules Validation Group 3 164 cases, including 487cases for Delta check; Clinical Application Trial Group 77 269 cases. Samples were analyzed for coagulation tests using Sysmex CS series automatic coagulation analyzers, and the clinical information, instrument parameters, test results, clinical diagnosis, medication history of anticoagulant and other relative results such as HCT, TG, TBIL, DBIL were summarized; on the basis of historical data, the 2.5 and 97.5 percentile of all data arranged from low to high were initially accumulated; on the basis of clinical suggestions, critical values and specific drug use as well as relative guidelines, autoverification rules and limits were established.The rules were then input into middleware, in which Stage I/Stage II validation was done. Positive coincidence, negative coincidence, false negative, false positive, autoverification pass rate, passing accuracy (coincidence of autoverification and manual verification) were calculated. Autoverification rules underwent trial application in coagulation results reports.Results:(1) The autoverification algorisms involve 33 rules regarding PT/INR, APTT, FBG, D-dimer, FDP,Delta check, reaction curve and sample abnormalities; (2)Autoverification Establishment Group showed autoverification pass rate was 68.42% (7 684/11 230), the false negative rate was 0%(0/11230), coincidence of autoverification and manual verification was 98.51%(11 063/11 230), in which positive coincidence and negative coincidence were respectively 30.09% (3 379/11 230) and 68.42%(7 684/11 230); Autoverification Validation Group showed autoverification pass rate was 60.37%(1 910/3 164), the false negative rate was 0%(0/11 230), coincidence of autoverification and manual verification was 97.79%(3 094/3 164), in which positive coincidence and negative coincidence were respectively 37.42%(1 184/3 164) and 60.37%(1 910/3 164); (3) Trialed implementation of these autoverification rules on 77 269 coagulation samples showed that the average TAT shortened by 8.5 min-83.1 min.Conclusions:This study established 33 autoverification rules in coagulation tests. Validation showedthese rules could ensure test quality while shortening TAT and lighten manual workload.

Objective To explore the expression characteristics of cytochrome P450(CYP)candidate genes(CYP6M3, CYP6Y1,CYP6P5,CYP4H14,CYP4G17,CYP12F16)in Anopheles sinensis.Methods The samples were collected from dif-ferent developmental stages(eggs,larvae,pupae and adult mosquitoes(females and males)),and different tissues(salivary glands,malpighian tubes,midguts,ovaries,and fat bodies)of An.sinensis and the female adult mosquitoes exposed by differ-ent insecticide doses(0,1.25,3.75,6.25,12.5μg/bottle)and time points(0,5,15,30,60 minutes),then the total RNA was extracted. Quantitative reverse transcription PCR(qPCR)assay was used to analyze the relative expressions of six CYP genes in An.sinensis at different developmental stages,tissues and different insecticide exposure doses and time.Results The expressions of CYP6M3 and CYP6Y1 in the male adult mosquitoes were the highest,the expression of CYP6M3 gene in the males was 35.1 times higher than that in the females,the expression of CYP6Y1 in the males was 61.4 times higher than that in the females;the expression level of CYP4H14 in the larvae was the lowest,the expression of CYP4H14 in the females was 22.5 times higher than that in the fourth instar larvae.The expressions of candidate CYP genes in different tissues of An.sinensis were significantly different,the expression of CYP6M3 in the malpighian tubule was 38.9 times higher than that in the ovary,the ex-pression of CYP6Y1 in the fatbody was 9.1 times higher than that in the ovary,the expression of CYP4G17 was 4.6 times higher than that in the ovary,and the expression of CYP12F16 was 4.4 times higher thanthat in the ovary.The exposure to different in-secticide doses and time showed some induction effects in the expressions of candidate CYP genes,which affected the expres-sions of candidate CYP genes in An.sinensis.Conclusion The expression of candidate CYP genes varies significantly in differ-ent developmental stages and various tissues of An.sinensis,and exposure to deltamethrin at various doses and time points af-fects CYP genes expression in An.sinensis.

OBJECTIVETo establish a MDS mouse model with iron overload and to study the effect of iron overload on MDS.

METHODSThe exogenous mutant gene RUNX1-S291fs was inserted into the mice bone marrow mononuclear cell's genome in mice by retrovirus and transplanted into C57BL/6 mice irradiated by Co γ-ray. After 8 weeks,intraperitoneal injection of iron was performed to establish an MDS mouse model with iron overload. After 24 weeks of transplantation, the peripheral blood, bone marrow, femur, liver and spleen of mice were taken, then the morphological characteristics of peripheral blood and bone marrow cells were observed by Wright's staining; the liver, spleen and bone marrow were stained with Prussian blue to observe the iron deposition. The surface antigens of bone marrow cells were detected by flow cytometry. Bone marrow mononuclear cells and spleen tissue proteins were detected by Western blot to confirm the transfection of RUNX1-S291fs gene and expression of protein. The blood routine and transplanted cell chimeric rate of mice were monitored periodically.

RESULTSCompared with the empty plasmid control mice, levels of leukocyte and hemoglobin as well as platelet were decreased in RUNX1-S291fs mutant mice; the peripheral blood cells and bone marrow cells showed pathological hematopoiesis; the liver and spleen enlarged significantly; the tissue structure of femur, liver and spleen was abnormal; the expression of bone marrow cell surface antigens was abnormal. Bone marrow cells and spleen tissue expressed the RUNX1-S291fs protein. Compared with the controlled mice injected with normal saline, iron deposition occurred in the bone marrow, liver and spleen stained with Prussian blue in the mice injected with iron agent.

CONCLUSIONMice engineered to carry exogenous mutant gene RUNX1-S291fs and injected with iron showed pathologic features of MDS and iron overload, resulting in establishing MDS iron overloaded mouse model successfully, which lays a foundation for studying the effect of iron overload on MDS.

Animals ; Bone Marrow ; Disease Models, Animal ; Iron Overload ; Mice ; Mice, Inbred C57BL ; Spleen

Objective To analyze the results of samples testing of Jiangsu Provincial Malaria Diagnostic Reference Laboratory in 2017, so as to provide the evidence for improving the malaria diagnostic performance in this province. Methods The samples of reported malaria cases in Jiangsu were collected by the provincial reference laboratory (PRL) in 2017. The microscopy and nucleic acid test were performed to confirm the infection of Plasmodium species of each case, while Plasmodium antigen tests (rapid diagnostic test, RDT) were performed as well. The detection results were analyzed among different areas and different species. Results Totally 242 malaria cases were reported and the samples were collected by PRL in 2017. A total of 239 cases were confirmed Plasmodium infections, including 163 cases of Plasmodium falciparum infection, 21 cases of P. vivax infection, 11 cases of P. malariae infection, 43 cases of P. ovale infection, and 1 case of P. falciparum and P. ovale mixed-infection. The diagnostic coincidence rates of reported malaria case in 13 prefectures with districts were all > 80%, and the total coincidence rate was 88.8%. The species diagnostic coincidence rates of P. falciparum, P. vivax, P. malariae, and P. ovale were 98.8%, 57.1%, 63.6%, and 81.4% respectively, and the detection rates by RDT to those four species infections were 95.7%, 85.0%, 63.6% and 79.1% respectively. Conclusions In 2017, the malaria diagnostic quality of medical technicians is generally high in Jiangsu Province. However, the diagnostic capacity is slightly different among different regions, and the ability to identify non- P. falciparum parasites remains to be improved. RDT is not ideal for the detection of non-P. falciparum infection. In the current stage of malaria elimination, the malaria diagnostic capacity of technicians in all the sectors should be strengthened and maintained.