Objective: To observe the changes of PD-1 expression, mRNA level and cytotoxic activity of CD19 CAR-T cells during the culture process of CAR-T cells. Methods: The peripheral blood T cells of 6 lymphoma patients with high expression of PD-1 and 6 healthy volunteers were the source of CAR-T cells. The expression of PD-1 was analyzed by flow cytometry. The mRNA level of PD-1 was analyzed by PCR. The cell proliferation was analyzed by CCK-8 assay. The cytotoxicity was analyzed by LDH assay. Results: ①The transfection efficiency of high PD-1 expression T cells and healthy volunteer T cells were as the same (P>0.05) . ②The cell proliferation capacity of CD19 CAR-T cells from high PD-1 expression T cells or healthy volunteer T cells, with or without PD-1 inhibitor were as the same (P>0.05) . ③The cytotoxicity to lymphoma cells of high PD-1 expression T cells and CAR-T cells were lower than that of these two T cells combined with PD-1 inhibitor and the CAR-T cells from healthy volunteer T cells (P<0.001) . There was no difference of the cytotoxicity between the CAR-T cells from high PD-1 expression T cells combined with PD-1 inhibitor and the CAR-T cells from healthy volunteer (P>0.05) . ④There was no difference of the expression of PD-1 in all CAR-T cell groups during the culture process (P>0.05) . There was no difference of mRNA level of PD-1 in all groups during the culture process (P>0.05) . ⑤The PD-1 expression of CAR-T cells increased by the time of culture after contacting with lymphoma cells (P<0.001) . The PD-1 inhibitors could antagonize this effect. There was no difference of mRNA level of PD-1 in all groups after contacting with lymphoma cells (P>0.05) . Conclusion The PD-1 expression of CAR-T cells from high PD-1 expression T cells increased by the time of culture after contacting with lymphoma cells. However, the mRNA level of PD-1 of all groups did not change, even if PD-1 inhibitor was applied.

Objective: To observe the changes of PD-1 expression, mRNA level and cytotoxic activity of CD19 CAR-T cells during the culture process of CAR-T cells. Methods: The peripheral blood T cells of 6 lymphoma patients with high expression of PD-1 and 6 healthy volunteers were the source of CAR-T cells. The expression of PD-1 was analyzed by flow cytometry. The mRNA level of PD-1 was analyzed by PCR. The cell proliferation was analyzed by CCK-8 assay. The cytotoxicity was analyzed by LDH assay. Results: ①The transfection efficiency of high PD-1 expression T cells and healthy volunteer T cells were as the same (P>0.05) . ②The cell proliferation capacity of CD19 CAR-T cells from high PD-1 expression T cells or healthy volunteer T cells, with or without PD-1 inhibitor were as the same (P>0.05) . ③The cytotoxicity to lymphoma cells of high PD-1 expression T cells and CAR-T cells were lower than that of these two T cells combined with PD-1 inhibitor and the CAR-T cells from healthy volunteer T cells (P<0.001) . There was no difference of the cytotoxicity between the CAR-T cells from high PD-1 expression T cells combined with PD-1 inhibitor and the CAR-T cells from healthy volunteer (P>0.05) . ④There was no difference of the expression of PD-1 in all CAR-T cell groups during the culture process (P>0.05) . There was no difference of mRNA level of PD-1 in all groups during the culture process (P>0.05) . ⑤The PD-1 expression of CAR-T cells increased by the time of culture after contacting with lymphoma cells (P<0.001) . The PD-1 inhibitors could antagonize this effect. There was no difference of mRNA level of PD-1 in all groups after contacting with lymphoma cells (P>0.05) . Conclusion: The PD-1 expression of CAR-T cells from high PD-1 expression T cells increased by the time of culture after contacting with lymphoma cells. However, the mRNA level of PD-1 of all groups did not change, even if PD-1 inhibitor was applied.
Antigens, CD19 ; Humans ; Programmed Cell Death 1 Receptor/genetics* ; RNA, Messenger ; Receptors, Antigen, T-Cell ; T-Lymphocytes

OBJECTIVETo assess the influence of polymorphisms of methylenetetrahydrofolate reductase (MTHFR) gene on response to antidepressant treatment.

METHODSTwo hundred and eight one Chinese Han patients have received single antidepressant drugs for at least 6 weeks, among whom 275 were followed up for 8 weeks. Hamilton depression scale 17 (HAMD-17) was used to evaluate the severity of depressive symptoms and therapeutic effects. Single nucleotide polymorphisms (SNPs) of the MTHFR gene were determined using gene chips. Associations of single loci and haplotypes with response to treatment were analyzed using an Unphased 3.0.13 software.

RESULTSNo significant differences in gender, age, year of education, family history, episode times, and antidepressant agents were found between responders and non-responders (all P U+003E 0.05), while the baseline scores of HAMD-17 was significantly different(t=2.891, P=0.004). There was also no significant difference between age, years of education, family history, baseline scores of HAMD-17 and antidepressant agents between remitters and non-remitters (both P U+003E 0.05), while proportion of male patients was significantly higher in non-remission group than remission group (t=2.381, P=0.018), and episode times in non-remission group was significantly higher (t=-1.983, P=0.049). Single locus association analysis has found no significant association between SNPs rs1801131 and rs1801133 in the MTHFR gene with antidepressant response (P U+003E 0.05). On the other hand, haplotype A-C of MTHFR gene (rs1801131 and rs1801133) was significantly associated with antidepressant response in total group (U+03C7 2=11.39, P=0.0007), male subgroup (U+03C7 2=8.767, P=0.003) and serotonin noradrenaline reuptake inhibitors (SNRIs) subgroup (U+03C7 2=10.51, P=0.001).

CONCLUSIONParticular haplotype of MTHFR gene may be related with antidepressant effect, in which the haplotype (rs1801131, rs1801133) A-C type may be associated with better antidepressant efficacy, particularly in males and patients receiving SNRIs drugs.

Adult ; Alleles ; Antidepressive Agents ; therapeutic use ; Depressive Disorder, Major ; drug therapy ; genetics ; Female ; Haplotypes ; Humans ; Male ; Methylenetetrahydrofolate Reductase (NADPH2) ; genetics ; Middle Aged ; Polymorphism, Single Nucleotide ; Serotonin Uptake Inhibitors ; therapeutic use ; Sex Factors ; Treatment Outcome ; Young Adult

Objective:To study the clinical features of neonatal hyperthyroidism.Methods:From September 2013 to September 2020, clinical data of neonates with hyperthyroidism admitted to the neonatal intense care unit of our hospital were retrospectively collected and analyzed.Results:A total of 7 neonates were included. The average gestation age was (35.8±2.3) weeks with 5 cases had GA<37 weeks. The median age of diagnostic was 16 d (7~18 d). The common clinical manifestations included tachycardia, irritability, low-grade fever, hyperhidrosis, bulimia, poor weight gain, diarrhea and jaundice. The levels of serum free triiodothyronine (FT 3) and thyroxine (FT 4) were elevated in all 7 cases and thyroid stimulating hormone (TSH) were decreased. The Doppler ultrasound of thyroid gland in two neonates revealed enlarged thyroid gland with abundant blood flow. All 7 mothers had hyperthyroidism with 4 mothers provided the history of hyperthyroidism and the other 3 were also confirmed after their infants were diagnosed. All 7 infants were treated with anti-thyroid drugs (ATD) and 2 were additionally given β-blockers to control heart rate. The median ATD duration was 40 d (7~58 d). 2 cases (both preterm infants) had slight decrease in FT 4 during medication. FT 4 of all 7 cases returned to normal before TSH. Conclusions:Neonatal hyperthyroidism has various and nonspecific clinical manifestations. Early diagnosis and timely treatment are important to prevent short-term and long-term adverse outcomes. Whether their mothers provide definite history of thyroid disorder or not, the thyroid function of the suspected neonates should be carefully monitored.

Parkinsonism is a clinical syndrome caused by many reasons, mainly manifested as bradykinesia, stiffness, static tremor and postural instability. Common disease development patterns include occult onset, gradual development, and little natural remission. However, clinically there are some Parkinsonism that will improve, naturally alleviate or "cure", called reversible parkinsonism (RP). By searching the relevant literature, RP was classified into 12 different types: drugs induced, poisoning induced, infection induced, intracranial vascular induced, structural encephalopathy related, changes in intracranial pressure related, imbalance of internal environment induced, visceral diseases related, alcohol withdrawal related, surgery related, immunization and radiotherapy induced RP. This article aims to provide clinicians with more ideas for the clinical diagnosis and treatment of parkinsonism, so as to promote clinicians to make reasonable identification and diagnosis and treatment of parkinsonism as soon as possible.

OBJECTIVETo express the recombinant D protein in prokaryotic expression system solubly and make preparation for producing D-carrier conjugate vaccine next step.

METHODSThe hpd gene fragment removed of signal peptide from genomic DNA of Hib CMCC was inserted into pET43. 1a. The recombinant plasmid was transformed to competent E. coli BL21 (DE3) for expression under induction of IPTG. The expressed recombination protein was precipitated with ammonium sulfate, purified by DEAE anion exchange column chromatography and identified for reactogenicity by Western Blot.

RESULTSThe expressed recombination protein, in a soluble form, constained about 50% of total somatic protein and showed specific reaction with the HIB antisera after preliminary purification.

CONCLUSIONThe D protein recombined expression plasmid was constructed successfully and expressed D protein in prokaryotic cells in a solube form.

Bacterial Proteins ; genetics ; Blotting, Western ; Carrier Proteins ; genetics ; Escherichia coli ; genetics ; Haemophilus influenzae type b ; genetics ; Immunoglobulin D ; genetics ; Lipoproteins ; genetics ; Plasmids ; Recombinant Proteins ; biosynthesis ; Solubility

OBJECTIVETo explore the safety and efficacy of cochlear implantation among elderly patients with severe to profound hearing loss.

METHODSEight pre-elderly and elderly patients with an medium age of 58 years who suffered from bilateral severe to profound sensorineural hearing loss received cochlear implantation between November 2008 and November 2009. The patients' tolerance to implant surgery and the occurrence of complications were observed. Three months after switch-on, aided threshold and speech performance were measured.

RESULTSThe surgery was uneventful in all cases with normal intraoperative neural response telemetry elicited. Three months after switch-on, average aided threshold across speech frequencies was 35 - 50 dB HL measured in sound field with warble tone. The results of speech audiometry showed large variation between individuals. Some patients achieved good performance in monosyllable recognition test, disyllables threshold test and sentences recognition test under both bubble noise and quiet conditions.

CONCLUSIONSPre-elderly and elderly patients can endure a state of general anesthesia for cochlear surgery without complications. Cochlear implant can provide reconstruction of speech recognition capabilities for elderly patients suffering from severe to profound hearing loss. Cochlear implantation can improve the quality of life of elderly patients with hearing loss.

Aged ; Cochlear Implantation ; Cochlear Implants ; Female ; Hearing Loss ; rehabilitation ; Humans ; Male ; Middle Aged ; Treatment Outcome

OBJECTIVES: To analyze the relationship between the suicide method and the sex, age, education background and cause of suicide to provide reference for the forensic identification of suicide. METHODS: After scene investigation, external body examination, autopsy and case investigation, 124 identified suicide cases which happened in recent three years in Wuhua district in Kunming were collected. Analytical methods as chi-square test and descriptive statistics were performed by SPSS 22.0. RESULTS: In all the suicide cases, male to female ratio was 1.53∶1. The suicide methods were mainly fatal fall, hanging and drowning. The ratio of local to non-native residents was 1∶1. The suicide rate in the people with primary school or junior middle school education level was highest. The group of >10-50 years tended to choose fatal fall suicide and people over 60 years were more likely to choose hanging. People with different academic background tended to choose fatal fall suicide. The suicide methods as fatal fall and hanging were chosen because of mental and physical diseases and economic problems, while the suicides with emotional problems were more likely to choose fatal fall and poisoning. CONCLUSIONS Suicide belongs to a kind of complex cases. For the cases of suspected suicide, complete exploration and overall consideration should be done to determine the nature of cases based on comprehensive analysis of all the influence factors.
Adolescent ; Adult ; Age Distribution ; Aged ; Autopsy ; Cause of Death ; Child ; China/epidemiology* ; Drowning/psychology* ; Female ; Humans ; Incidence ; Male ; Mental Disorders/psychology* ; Middle Aged ; Sex Distribution ; Suicide/statistics & numerical data* ; Young Adult

Kudzu plants in the subfamily sphenoideae of Leguminosae are commonly used herbs in China, Japan, Korea, India and Thailand, with a long history of medicinal use. They are recorded in Chinese Pharmacopoeia, Japanese Pharmacopeia, Korea Pharmacopeia, Ayurveda Pharmacopoeia of India and Flora of Thailand. There are 15-20 species of Pueraria in the world, including 7 species and 2 varieties in China. At present, there are 6 species with medicinal value, such as Pueraria lobata and P. thomsonii. The main chemical components of the genus are isoflavones, flavonoids, terpenes, steroids, coumarins, puerarin glycosides and benzopyrans. A total of 240 compounds have been isolated and identified from this genus, and their pharmacological effects mainly include improvement of the cardiovascular system, antioxidant, hypoglycemic, antipyretic, anti-inflammatory, anti-alcoholic and estrogen-like effects. In this study, chemical constituents and pharmacological activities of Pueraria at home and abroad were systematically summarized, in order to provide references for the material basis, quality control and further development of Pueraria genus.
China ; Isoflavones/pharmacology* ; Japan ; Plant Roots ; Pueraria ; Republic of Korea ; Thailand

Objective: To investigate the efficacy and predictors of autologous hematopoietic stem cell transplantation (auto-HSCT) in the treatment of T lymphoblastic lymphoma (T-LBL) . Methods: 41 patients with T-LBL who underwent auto-HSCT from April 2006 to July 2017 in the Department of Hematology, the First Affiliated Hospital of Soochow University and the Department of Lymphoma, Peking University Cancer Hospital were analyzed retrospectively. Results: ①Among 41 patients, there were 30 males and 11 females with median age of 24 (11-53) years old. According to the Ann Arbor staging, 33 (80.5%) patients were in stage Ⅲ/Ⅳ. 12 (29.3%) patients have mediastinal involvement, and 20 (48.8%) patients have bone marrow (BM) involvement. Before transplantation, there were 26 (63.4%) patients who achieved first complete remission (CR(1)) , the other 15 (36.6%) patients were in the non-CR(1) group, and there were 29 (70.7%) patients in the low-intermediate risk group (IPI<3 scores) , the other 12 (34.1%) patients were in the middle-high risk group (IPI≥3 scores) . ②The median follow-up was 29 (3-98) months. The 3-year overall survival (OS) and progression-free survival (PFS) for 41 patients were (64.3±8.2) % and (66.0±7.8) %, respectively. 3-year cumulative recurrence rate (CIR) was (30.7±7.4) %, and 3-year non-recurring mortality (NRM) was (4.8±4.6) %. ③The 3-year OS of the CR(1) group and the non-CR(1) group were (83.4±7.6) % and (38.9±12.9) % (P=0.010) , and the 3-year PFS of two groups were (83.8±7.4) % and (40.0±12.6) % (P=0.006) , respectively. The 3-year CIR of these two groups were (16.2±7.4) % and (53.3±12.9) % (P=0.015) , and the 3-year NRM were 0 and (14.3±13.2) % (P=0.157) , respectively. ④The 3-year OS of the IPI low-intermediate risk group and the high-intermediate risk group were (76.9±8.4) % and (35.7±15.2) % (P=0.014) and the 3-year PFS were (77.4±8.2) % and (40.0±14.6) (P=0.011) , respectively. The 3-year CIR of these two groups were (18.1±7.3) % and (60.0±14.6) % (P=0.006) , and the 3-year NRM were (5.6±5.4) % and 0 (P=0.683) , respectively. The OS and PFS of patients with low-intermediate risk group were significantly higher than the other group. Conclusion: Auto-HSCT could improve the survival of T-LBL. Pre-transplant status and IPI score are important predictors for survival T-LBL patients with auto-HSCT.
Adolescent ; Adult ; Child ; Disease-Free Survival ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy* ; Prognosis ; Retrospective Studies ; T-Lymphocytes ; Transplantation, Autologous ; Treatment Outcome ; Young Adult