OBJECTIVE: To explore the short-term efficacy and adverse reactions of orelabrutinib combined with high-dose methotrexate (HD-MTX) in the first-line treatment of elderly high-risk primary central nervous system lymphoma (PCNSL), as well as the survival of patients. METHODS: Twenty-five elderly patients with high-risk primary central nervous system diffuse large B-cell lymphoma admitted to Fujian Provincial Hospital from June 2016 to June 2022 were enrolled in this study, and complete clinical data from all patients were collected retrospectively, and the cut-off for follow-up was December 2022. 15 patients had received temmozolomide combined with HD-MTX regimen for at least four cycles, sequential lenalidomide maintenance therapy, while 10 patients had received orelabrutinib combined with HD-MTX regimen for at least four cycles, sequential orelabrutinib maintenance therapy. The short-term efficacy and adverse reactions of the two groups of patients after treatment were observed. Kaplan-Meier was used to analyze the progression-free survival (PFS) and time to progression (TTP). RESULTS: The objective response rate (ORR) and 2-year median FPS of orelabrutinib combined with HD-MTX regimen group were similar to the temozolomide combined with HD-MTX regimen group (ORR: 100% vs 66.7%; 2-year median PFS: 16 months vs 15 months, P>0.05). The 2-year median TTP of the orelabrutinib+HD-MTX regimen group was better than that of the temozolomide+HD-MTX regimen group (not reached vs 12 months, P<0.05). There were no significant differences in adverse reactions such as gastrointestinal reactions, bone marrow suppression, liver and kidney damage, cardiotoxicity, pneumonia and bleeding between these two groups (P>0.05). CONCLUSION For elderly patients with high-risk PCNSL, orelabrutinib combined with HD-MTX has reliable short-term efficacy, good safety, and tolerable adverse reactions, which is worthy of clinical promotion.
Humans ; Aged ; Methotrexate/adverse effects* ; Retrospective Studies ; Temozolomide/therapeutic use* ; Central Nervous System Neoplasms/drug therapy* ; Antineoplastic Combined Chemotherapy Protocols ; Lymphoma, Large B-Cell, Diffuse/drug therapy* ; Central Nervous System

OBJECTIVE: To analyze clinical response of the Rituximab-based chemotherapy and prognostic features in patients with primary gastric diffuse large B-cell lymphoma (PGDLBCL). METHODS: From June 2008 to December 2020, the data of 53 PGDLBCL patients were analyzed retrospectively. RESULTS: The median age was 46(25-77) years old in 53 patients including 35 males and 18 females. Stomachache is the most common symptom. The diagnosis were confirmed in 47 patients by endoscopic biopsy and 6 patients by surgery. Twenty-six patients had Ⅰ/Ⅱ1 stage (Lugano staging system) disease and 27 cases had II2/IV stage disease. All patients were treated with chemotherapy, including RCHOP (25/53) and R-DA-EPOCH (28/53). Complete remission rate was 79.2%（42/53）. The 3-year and 5-year overall survival (OS) rates were 77.4% and 69.8%. Univariate analysis showed that lactate dehydrogenase(LDH), Lugano stage and lesion size affected OS. Multivariate Cox regression analysis revealed that IPI score and Lugano stage were independent prognosis risk factors affecting OS. The patients in the R-DA-EPOCH group presented better survival outcomes than those in the RCHOP group with late stage (P_5-year OS=0.035). CONCLUSION Rituximab in combination with chemotherapy is the backbone of therapy for PGDLBCL. IPI score and Lugano stage are independent prognosis risk factors affecting OS of PGDLBCL. R-DA-EPOCH can be superior to R-CHOP as a first-line regimen in PGDLBCL patients with late stage.
Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Cyclophosphamide/therapeutic use* ; Disease-Free Survival ; Doxorubicin/therapeutic use* ; Female ; Humans ; L-Lactate Dehydrogenase ; Lymphoma, Large B-Cell, Diffuse/pathology* ; Male ; Middle Aged ; Prednisone/therapeutic use* ; Prognosis ; Retrospective Studies ; Rituximab/therapeutic use* ; Vincristine/therapeutic use*

OBJECTIVE: To reveal the effect and mechanism of Jiaotai Pill (, JTP) on insomniac rats. METHODS: The insomniac model was established by intraperitoneal injection of p-chlorophenylalanine (PCPA). In behavioral experiments, rats were divided into control, insomniac model, JTP [3.3 g/(kg•d)], and diazepam [4 mg/(kg•d)] groups. The treatment effect of JTP was evaluated by weight measurement (increasement of body weight), open field test (number of crossings) and forced swimming test (immobility time). A high performance liquid chromatography-electrochemical detection (HPLC-ECD) method was built to determine the concentration of monoamine transmitters in hypothalamus and peripheral organs from normal, model, JTP, citalopram [30 mg/(kg•d)], maprotiline [40 mg/(kg•d)] and bupropion [40 mg/(kg•d)] groups. Expressions of serotonin transporter (SERT), dopamine transporter (DAT), and norepinephrine transporter (NET) were analyzed by quantitative polymerase chain reaction (qPCR) and Western blot in normal, model and JTP groups. A high performance liquid chromatography-electrospray ionization mass spectrometry (HPLC-ESI-MS/MS) method was established to determine the pharmacokinetics, urine cumulative excretion of metformin in vivo, and tissue slice uptake in vitro, which were applied to assess the activity of organic cation transporters (OCTs) in hypothalamus and peripheral organs. RESULTS: Compared with the insomniac model group, the body weight and spontaneous locomotor were increased, and the immobility time was decreased after treatment with JTP (P<0.01). Both serotonin and dopamine contents in hypothalamus and peripheral organs were increased (P<0.01). The norepinephrine content was increased in peripheral organs and decreased in hypothalamus (P<0.05 or P<0.01). At the same time, SERT, DAT, OCT1, OCT2, and OCT3 were down-regulated in hypothalamus and peripheral organs (P<0.05). NET was down-regulated in peripheral organs and up-regulated in hypothalamus (P<0.05 or P<0.01). Moreover, the activity of OCTs in hypothalamus and peripheral organs was inhibited (P<0.05). CONCLUSION JTP alleviates insomnia through regulation of monoaminergic system and OCTs in hypothalamus and peripheral organs.

Objective To study the reliability and validity of the Chinese version of the Lymphedema Quality of Life Questionnaire (LYMQOL) in lymphedema patients. Methods LYMQOL was translated into Chinese. The Chinese version of the LYMQOL was distributed with the official Wechat account "Lymphedema Channel" to lymphedema patients who were recruited from October 28
China ; Humans ; Lymphedema ; Quality of Life ; Reproducibility of Results ; Surveys and Questionnaires

OBJECTIVE: To explore the appropriate procedures for preparing extracellular microvesicles (MV) derived from human mesenchymal stem cells (MSC). METHODS: Human MSCs from umbilical cords were cultured in a serum-free medium and maintained in a basal medium for 72 hours after the cell confluence reached to 80%. The supernatants of cultured cells were collected and MVs were enriched. MVs were identified by flow cytometry and electron microscopy. The total protein amount in MVs was used as a parameter for the content of MVs. The supernatants were adjusted to different pH values, and the output of MVs was detected. The supernatants were also collected for enriching the MV and detecting the protein content of MV after the cells were maintained in the basic medium for different time. RESULTS: Flow cytometric analysis showed that the MVs expressed CD9, CD63 and CD81, morphologically presented round under an electron microscope and the diameter of MV was around 100 nm. After enrichment of MV, the protein content of MVs in the supernatants was 416.8±128.1, 255.4±77.9 and 142.8±46.4 μg per 10 MSC，respectively at pH of supernatant 3, 7 and 9 (P＜0.05). The protein content of the supernatants per 10 MSC was 173.6±44.5, 262.4±49.6 and 364.2±37.8 μg respectively after starvation culture for 48, 72 and 96 hrs (P＜0.05). CONCLUSION MVs can be readily collected after MSCs were starved for 96 hours, and the pH of the supernatants is adjusted at 3.0.
Cell-Derived Microparticles ; Cells, Cultured ; Flow Cytometry ; Humans ; Mesenchymal Stem Cells ; Umbilical Cord

Multiple sclerosis (MS) is a chronic inflammatory disease, mainly due to the activation of the T cells, which makes oxidative stress reaction in brain and leads to demyelination finally. Kelch-like ECH-associated protein-1 (Keap1)-nuclear factor erythroid 2-related factor-2 (Nrf2)/antioxidant responsive element (ARE) signal pathway is one of the most important endogenous antioxidant pathways, which promotes the expression of detoxification enzymes and antioxidant protein to eliminate oxygen free radicals and balance intracellular redox system. Activation of the Keap1-Nrf2/ARE may delay the progression of MS by drugs or rehabilitation.

The randomized controlled trials about modified Sangbaipi Decoction in the treatment of acute exacerbation of chronic obstructive pulmonary disease( AECOPD) patients were collected from 7 databases( PubMed,CNKI,et al) from the establishment to December 5,2018. All the studies searched were strictly evaluated. Literatures were independently screened by two researchers according to the inclusion and exclusion criteria,and the methodological quality of included studies was evaluated. To systematically review the efficacy of modified Sangbaipi Decoction in treating AECOPD,the Meta-analysis and trial sequential analysis were conducted by using Stata/SE 14. 0 and TSA 0. 9. 5. 10 Beta,respectively. A total of 25 RCTs involving 1 784 patients were included. According to the results of Meta-analysis,compared with the control groups,the trial group had a higher clinical efficacy in AECOPD patients( RR =1. 18,95%CI[1. 13,1. 22],P = 0),improved pulmonary functions including forced expiratory volume in one second( FEV1,WMD =0. 44,95%CI[0. 01,0. 87],P = 0. 046),and the forced vital capacity( FVC,WMD = 0. 42,95%CI[0. 07,0. 22],P = 0),but no statistical significance in the percentage of forced expiratory volume in one second( FEV1%,P = 0. 067) and the first seconds breathing volume percentage of forced vital capacity( FEV1/FVC,P = 0. 238); it improved the arterial oxygen partial pressure( PaO2,SMD =0. 85,95%CI[0. 41,1. 30],P = 0) and decreased the arterial partial pressure of carbon dioxide( PaCO2,SMD =-0. 94,95% CI[-1. 70,-0. 18],P= 0. 016); and in terms of inflammatory markers,it improved the white blood cell count( WBC,WMD=-0. 94,95%CI[-1. 17,-0. 70],P = 0). The trial sequential analysis showed that the studies included with the improvement of clinical efficacy had passed the conventional and TSA threshold,so as to further confirm the evidence. According to the findings,in addition to conventional Western medicine treatment,modified Sangbaipi Decoction could improve the efficiency in treating acute exacerbation patients with chronic obstructive pulmonary disease,increase PaO2,and decrease PaCO2,with a high safety but no effect on pulmonary function. However,restricted by the low quality of studies included,this conclusion shall be further verified by more high-quality clinical trials.
Arterial Pressure ; Drugs, Chinese Herbal ; therapeutic use ; Forced Expiratory Volume ; Humans ; Lung ; Partial Pressure ; Pulmonary Disease, Chronic Obstructive ; drug therapy ; Randomized Controlled Trials as Topic ; Vital Capacity

Objective To evaluate the effectiveness and safety of modified scleral tunnel for the prevention of Ahmed valve tube exposure in Ahmed valve implantation for refractory glaucoma.Methods A retrospective study was conducted in 72 patients with Ahmed glaucoma valve implantation for refractory glaucoma.All the patients were divided into unmodified and modified scleral tunnel group.In the unmodified scleral tunnel group,38 patients (38 eyes) underwent traditional scleral tunnel in Ahmed valve implantation,while in the modified scleral tunnel group,34 patients (34 eyes) received modified scleral tunnel in the procedures.The changes in intraocular pressure and visual acuity after operation were observed,and the incidence of drainage tube exposure and other complications were compared between the two methods after Ahmed valve implantation.The patients were followed up for 6 to 36 months with an average of 18 months.Results The intraocular pressure was (16.30 ±5.73) mmHg (1kPa =7.5 mmHg) in the unmodified scleral tunnel group and (15.80 ± 6.12)mmHg in the modified scleral tunnel group,with no significant difference between the two groups (P ＞ 0.05),but there was significant difference with the preoperative data (48.4 ± 5.79) mmHg (P ＜ 0.01).During the follow-up,conjunctival tube exposure was seen in 3 eyes (7.9％) in the unmodified scleral tunnel group,whereas there was no tube exposure in the modified scleral tunnel group.Conclusion The modified scleral tunnel is capable to prevent conjunctival tube exposure in patients with refractory glaucoma,which is more efficient and safe than traditional scleral tunnel in Ahmed glaucoma valve implantation.

OBJECTIVETo study the effect of the DA-EPOCH chemotherapy combined with G-CSF and the CTX therapy with G-CSF on mobilizing and collecting the peripheral blood hematopoietic stem cells and the later hematopoietic recovery.

METHODSForty patients accepted mobilization and collection of peripheral blood stem cells(PBSC) after treated by CTX+G-CSF and DA-EPOCH+G-CSF therapy respectively, and were treated by auto-transfusion after BEAM pre-regimen. The mobilization efficacy, adverse effects and hematopoietic recovery after autologous transplantation were analyzed retrospectively.

RESULTSDuring the CTX+G-CSF mobilization, only one patient achieved the white blood cell(WBC) at 0.8×10/L, while the others were with the lowest WBC level above 2.0×10/L. The platelet counts were all normal with the exception of 3 cases at 80×10/L. The median percentage of CD34cells in one period of collection was 0.99(0.35-1.30)%. The median MNC was (3.80±2.05)×10. The cumulative total of mononuclear cell was (5.84±2.48)×10/kg, and the median CD34cell count was 3.84(3.91-6.5)×10/kg. During the DA-EPOCH+G-CSF mobilization, the peripheral WBC count of patients were decreased to the lowest level at (0.2-1.4)×10/L. The platelet counts were all above 40×10/L except for 1 case in which the platelet count was reduced to 8×10/L. The median percentage of CD34cells in one period of collection was 0.85(0.34-1.2)%. The median MNC was (3.68±1.56)×10. The cumulative total of mononuclear cells was (6.01±2.26)×10/kg, and the median CD34cell count was 4.44(2.7-7.10)×10/kg. There were no statistical differences between the 2 groups in the median percentage of CD34cells, the median MNC, the cumulative total of mononuclear cells and the median CD34cell counts (P>0.05). The average acquired time for granulocyte engraftment was 10.00(9.00-11.00) days, and for platelet engraftment was 12.50(11.00-17.25) days, with no statistical difference(P>0.05). No death occurred during the process of transplantation.

CONCLUSIONDA-EPOCH therapy combined with G-CSF can effectively mobilize the peripheral blood hematopoietic stem cells in NHL patients with higher safety and lower price, and proves to be worth recommending in clinical use.

OBJECTIVETo establish the normal reference ranges of transabdominal ultrasound measurements of the posterior fossa structure in fetuses at 11 to 13⁺⁶ gestational weeks and explore their clinical value in screening open spina bifida (OSB).

METHODSBetween January, 2013 and September, 541 randomly selected normal fetuses underwent nuchal translucency at the gestational age 11 to 13⁺⁶ weeks. The parameters of the posterior fossa were measured in mid-sagittal view of the fetal face and the axial view of the transverse cerebellum insonated through the anterior fontanel by transabdominal ultrasound to establish the normal reference ranges. The measurements were obtained from 3 fetuses with OSB for comparison with the reference ranges.

RESULTSIn normal fetuses, the parameters of the posterior fossa measured in the two views showed no significant differences (P>0.05). Two high echogenic lines were observed in normal fetuses, as compared with one in fetuses with OSB representing the posterior border of the brain stem and the anterior border of the fourth ventricle. The line between the posterior border of the fourth ventricle and the anterior border of the cisterna magna was not displayed in fetuses with OSB. The anteroposterior diameters of the brain stem, the fourth ventricle, and cisterna magna all increased in positive correlation with the crown-lump length in normal fetuses. In the 3 OSB fetuses, the anteroposterior diameter of the brain stem exceeded the 95th percentile and the anteroposterior diameter of fourth ventrical-cisterner magena was below the 5th percentile of the reference range for CRL; the brain stem to fourth ventrical-cisterner magena anteroposterior diameter ratio was increased to above 1.

CONCLUSIONThe established normal reference ranges of the parameters of fetal posterior fossa may provide assistance in early OSB detection. The absence of the posterior border of the fourth ventricle and the anterior border of the cisterna magna and a brainstem to fourth ventrical-cisterner magena anteroposterior diameter ratio greater than 1 can be indicative of OSB at 11 to 13⁺⁶ gestational weeks.

Brain Stem ; Cerebellum ; Cisterna Magna ; Cranial Fossa, Posterior ; Female ; Fourth Ventricle ; Gestational Age ; Humans ; Nuchal Translucency Measurement ; Pregnancy ; Pregnancy Trimester, First ; Reference Values ; Spina Bifida Cystica ; diagnostic imaging ; Ultrasonography, Prenatal