Objective To investigate the dynamics of NK cells and Treg cells,as well as their potential prognostic significance in relation to TKI discontinuation among patients diagnosed with chronic myeloid leukemia(CML).Methods In this study,a total of 200 patients diagnosed with CML were randomly selected and divided into two groups:the discontinuation group(n=100)and the non-discontinuation group(n=100).Within the discontinuation group,patients were further categorized into a recurrence subgroup(n=41)and a non-recurrence subgroup(n=59).Clinical data and follow-up information of these patients were retrospectively analyzed.Logistic regression analysis was performed to investigate the impact of various variables on patient outcomes following drug discontinuation,as well as to explore independent factors influencing recurrence in these individuals.Receiver operating characteristic(ROC)curve analysis was employed to assess the predictive value of NK cells and Treg cells for TKI discontinuation outcomes.A significance level of P<0.05 was considered statistically significant.Results The proportion of patients treated with interferon in the discontinuation group was significantly higher than that in the non-discontinuation group(P<0.05).Moreover,the former group exhibited a significantly higher number of NK cells(P<0.05)and Treg cells(P<0.01)compared to the latter group.Compared to the recurrence group,there was a significant increase in the proportion of patients using interferon in the non-recurrence group(P<0.05),along with longer durations of TKI treatment and deep molecular response(DMR)duration(P<0.05).The number of NK cells and Treg cells in the non-recurrence group was significantly higher than that in the recurrence group(P<0.01).Logistic regression analysis found that the use of interferon(OR=1.25,95%CI:1.11～2.03,P<0.001),duration of DMR(OR=1.16,95%CI:1.08～1.92,P<0.05),NK cells(OR=1.64,95%CI:1.14～2.28,P<0.01),and Treg cells(OR=1.83,95%CI:1.15～2.42,P<0.01)were all influencing factors for the recurrence of patients after drug discontinuation.The results of ROC curve analysis showed that the AUC of NK cells combined with Treg cells for predicting the recurrence of TKI after discontinuation was 0.892(95%CI:0.857～0.927,P<0.001).Conclusion The frequencies of NK cells and Treg cells were significantly elevated in patients who remained recurrence-free following TKI discontinuation,highlighting the potential predictive value of combined NK cell and Treg cell analysis for drug cessation in CML patients.

The mechanism of acupuncture in treating primary dysmenorrhea(PD)in rats was reviewed.The research on the mechanism of acupuncture in the treatment of PD involves endocrine,nervous,immune,metabolic and other aspects.However,the basic research did not actively pay attention to the clinical problems encountered in the treatment of PD by acupuncture and moxibustion,including the rule of point selection and the correlation mechanism between acupoints and uterus in the treatment of PD by acupuncture and moxibustion,the key technical parameters of the treatment of PD by acupuncture and moxibustion and the rule of the action of acupuncture and moxibustion.The basic research of acupuncture treatment of primary dysmenorrhea should pay attention to translational medicine.

Chemotherapy is one of the important methods to treat cancer, and the emergence of multidrug resistance (MDR) is one major cause for the failure of cancer chemotherapy. Almost all anti-tumor drugs develop drug resistance over a period of time of application in cancer patients, reducing their effects on killing cancer cells. Chemoresistance can lead to a rapid recurrence of cancers and ultimately patient death. MDR may be induced by multiple mechanisms, which are associated with a complex process of multiple genes, factors, pathways, and multiple steps, and today the MDR-associated mechanisms are largely unknown. In this paper, from the aspects of protein-protein interactions, alternative splicing (AS) in pre-mRNA, non-coding RNA (ncRNA) mediation, genome mutations, variance in cell functions, and influence from the tumor microenvironment, we summarize the molecular mechanisms associated with MDR in cancers. In the end, prospects for the exploration of antitumor drugs that can reverse MDR are briefly discussed from the angle of drug systems with improved targeting properties, biocompatibility, availability, and other advantages.

Objective To investigate the neuroprotective effect of methylene blue on diabetic retinopathy in rats. Methods Thirty SD rats were randomly divided into blank, control and experimental groups. The control and experimental groups were induced with diabetes by streptozotocin (STZ) intraperitoneal injection. After 6 weeks of successful modeling, the experimental group received intravitreal injection of methylene blue at a dose of [0.2 mg/(kg.d)], while the control group received an equal amount of dimethyl sulfoxide (DMSO) intravitreal injection, both continuously injected for 7 days. ELISA was used to detect the levels of retinal superoxide dismutase (SOD), 8-iso-prostaglandin F2alpha (iPF2α) and interleukin-1β (IL-1β) in rats. Western blot analysis was used to detect the expression of retinal extracellular signal-regulated kinase 1/2 phosphorylation (p-ERK1/2) and phosphorylated protein kinase B (p-AKT), and PAS staining was used to detect retinal morphological changes. Results Compared with the blank group rats, the retinal SOD activity in the control and experimental group rats was significantly reduced. iPF2α, IL-1β and p-ERK1/2 level increased, while p-AKT level decreased. Compared with the control group, the SOD activity of the experimental group rats increased. iPF2α and IL-1β level went down, while p-ERK1/2 and p-AKT level went up significantly. The overall thickness of the retinal layer and the number of retinal ganglion cells were significantly reduced. Conclusion Methylene blue improves diabetic retinopathy in rats by reducing retinal oxidative stress and enhancing ERK1/2 and AKT phosphorylation.
Rats ; Animals ; Diabetic Retinopathy/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Mitogen-Activated Protein Kinase 3/metabolism* ; Interleukin-1beta/metabolism* ; Methylene Blue/pharmacology* ; Phosphorylation ; Rats, Sprague-Dawley ; MAP Kinase Signaling System ; Diabetes Mellitus, Experimental/drug therapy* ; Superoxide Dismutase/metabolism*

Objective To investigate the clinical features and related risk factors of osteoporosis (OP) and osteoporotic fracture (OPF) in patients with rheumatoid arthritis (RA).Methods Two hundred and seventytwo in-patients with RA between 2010-2011 were surveyed,X-ray was detected for the diagnosis of fracture.Bone mineral density(BMD) of proximal femur and lumbar vertebrae (L2-4) in 203 patients were measured by dual energy X-ray absorptio-metry (DEXA),and the radiographic changes in both hands of 169 RA patients were assessed by Sharp scoring system.All the clinical and laboratory factors of RA were recorded in detail by rheumatologists.The results of 120 normal people were used as controls.T-test,Mann-whitney test,x2 test and Logistic regression were used for statistical analysis.Results ① Compared to the normal group,the BMDs of RA patients at each measured location were significantly lower (P＜0.01),the OP incidence was 32.0％ (65/203),which was significantly higher than that of the normal group,which was 15.0％ (18/120) (x2=11.442,P=0.001).There were 33 cases of OPF among all 272 RA patients,and the occurrence rate was 12.1％.BMDs of the femur in RA with OPF were lower than those in RA without OPF (P＜0.01).② Incidence of OP in RA with glucoco-rticoid was 42.2％(46/109),which was higher than that in RA without glucocorticoid (20.2％,18/89) (x2=10.818,P=0.001).Compared with RA without glucocorticoid,the incidence of OPF in RA with glucocorticoid elevated evidently [7.2％ (9/125) vs 17.5％ (24/137)] (x2=6.321,P=0.012).③ Logistic regression (back-ward LR method) analysis found that the risk factors for OP in RA patients were age [OR=1.050,P=0.001,95％CI(1.020,1.080)],HAQ [OR=1.966,P=0.031,95％CI (1.064,3.631)],and glucocorticoid average daily dosage [OR=1.075,P=0.031,95％CI (1.007,1.148)].The risk factors for OPF in RA patients were age [OR=1.041,P=0.046,95％CI (1.001,1.084)] and OP [OR=3.484,P=0.016,95％CI (1.258,9.646)].Conclusion RA patients have higher incidence of OP and OPF than general population.The incidence of OP and OPF are closely correlated with age,diseases activity,local bone erosion and the use of glucocorticosteroid.

Objective To observe the effect of carboprost tromethamine(hemabate) combined with modified patch suture in placenta previa postpartum hemorrhage.Methods 62 patients with placenta previa were divided into the control group (3 0 cases) and treatment group (3 2 cases).The control group was treated with hemabate,and the treatment group was treated with hemabate combined with modified patch suture.The two groups of intraoperative,postpartum 2 hours,24 hours postpartum were compared in bleeding volume and hemoglobin changes.Results The intraoperative bleeding volume [(321.9 ± 67.8) ml vs (435.9 ± 83.3) ml] and 2h,24h postpartum bleeding volume [(417.7±68.0)ml vs (539.6 ±70.4)ml and (485.3 ±68.5)ml vs (621.0±81.3)ml]of the treatment group were significant less than that of the control group(t =5.926,6.938,7.133,all P ＜ 0.05).Significant difference in changes of hemoglobin level was also observed between the two groups,though postpartum level was not significantly reduced in the treatment group compared with the control group [(5.0 ± 6.5) g/L vs (-4.0 ± 6.8) g/L] (t =-3.662,P ＜ 0.05).Conclusion Hemabate combined with modified patch suture can be more effective in the prevention of postpartum haemorrhage in placenta previa.

Objective To investigate the value of tumor necrosis factor (TNF)-α receptor gene,TNFRSF1A+36A/G(rs767455) and-383A/C(rs2234649),TNFRSF1B+196T/G(rs1061622) single nucleotide polymorphism (SNP) for the susceptibility to ankylosing spondylitis (AS) and the relationship between SNP and AS.T test,Chi-square test,and ANOVA were used for statististical analysis.Methods Two hundred and fifteen patients who had definite diagnosis of AS and 216 healthy blood donors were involved in this study.SNPs of TNF-α receptor gene:TNFRSF1A +36A/G(rs767455),-383A/C(rs2234649) and TNFRSF1B+196T/G (rs1061622) were detected with the ligase detection reaction (LDR-PCR) method.Results ① Distribution frequencies of A alleles(86.8％,91.5％) and G alleles (13.2％,8.5％) of TNFRSF1A(rs767455) in AS and controls were significantly different with each other (x2=4.627,P=0.0315),while the distribution frequency in group of homozygotes (AA or GG genotype) in AS and controls were 74.6％(150/201) and 83.9％(177/211),the frequencies in group of heterozygotes (AG) were 25.4％ (51/201) and 16.1％(34/211)(x2=5.390,P=0.020).Frequency of alleles and the genotypes of TNFRSF1A (rs2234649) and TNFRSF1B (rs1061622) between AS and control group were similar(P＞0.05).It also demonstrated that TNF-αreceptor gene haplotype (rs1061622T-rs2234649A-rs767455G) carriers apparently increased the susceptibility to AS (11.5％ vs 6.9％)(OR:1.753,95％CI:1.078～2.852,P=0.022).② Analysis of variance found that the duration of morning stiffness (F=3.168,P=0.044) and peripheral joint tenderness counts (F=4.598,P=0.011) among the three genotype groups of TNFRSF1B (rs1061622) in patient with AS were evidently differed with each other.Bath AS functional index (BASFI) among different genotype groups of TNFRSF1A (rs2234649) in AS had remarkable diversity (F=5.783,P=0.004).None of above indicators among groups of different genotypes of TNFRSF1A (rs767455) in AS were uniform (P＞0.05).③ Forty-four patients were treated with TNF-α antagonist (entanercept),25 mg,subcutaneous injection,twice weekly for 3 months,then followed with Sulfaslazine (SASP) 2.0 g/d and Celecoxib 0.4 g/d for another 9 months.ASAS20 was the primary endpoint for the evaluation of therapeutic effect at the visit of 3 month and 12 month.No associations were found between SNP and short or long term outcome of treatment with TNF-α antagonist in AS (P＞0.05).Conclusion TNFRSF1A (rs767455) SNP correlates with susceptibility to AS in Anhui Han local patients.Carriers of TNF-α receptor gene haplotype (rs1061622T-rs2234649A-rs767455G) may increase the susceptibility to AS.SNP of TNFRSF1B (rs1061622) is associated with disease activity in AS,while SNP of TNFRSF1A(rs2234649)relates to functional index of the disease.There is no association between SNP of TNFRSF1A / TNFRSF1B and short or long term outcome of treatment with TNF-α antagonist in AS.

Objective To investigate the relationship between the general osteoporosis and local bone erosion in patients with rheumatoid arthritis (RA).Methods Bone mineral density (BMD) of femur (femur neck,Ward area,greater trochanter) and lumbar spine 2-4 (L2-4) by dual energy X-ray absorptiometry was measured in 120 patients with RA and 120 normal controls.All the clinical and laboratory factors of RA were recorded in details,and the radiographic changes in both hands of 76 RA patients were assessed by Sharp'method.Statistical anylysis was carried out by using t test and x2 test.Results ① Compared with normal controls,the BMD of total femur,L2,L3,L4 and L2-4 decreased significantly (P＜0.01),while there was no significant differences in the BMD of femur neck,Ward area and greater trochanter between the two groups (P＞0.05).② The incidence of osteoporosis in RA (34.2％) was higher than that in normal controls (15.0％)(x2=11.889,P=0.001).③ Patients with osteoporosis had elder age,higher scores of HAQ,higher scores of space narrowing and bone erosion of joint by X-ray' Sharp method than those of patients without osteoporosis.There were no significant differences in the changes of other clinical and laboratory parameters between the two groups(P＞0.05).④ BMD of total femur,femur neck,Ward area,greater trochanter,L2,L3,L4 correlated with Sharp scores in RA and had shown a negative correlations(P＜0.05).Logistic regression analysis showed that age(OR=1.069,P=0.012,95％CI:1.015-1.125) and Sharp scores(OR=1.022,P=0.003,95％CI:1.007-1.037) were risk factors for osteoporosis in RA patients,but treating with DMARD (OR=0.172,P=0.041,95％CI:0.032-0.930) was a protective factor for osteoporosis in patients with RA.Conclusion The BMD decreases significantly and correlates with age and local bone erosion in patients with RA,while the incidence of osteoporsis increases remarkably.

Aim To investigate the transcytosis mechanism of chlorogenic acid(CGA)by using Caco-2 and MDCK(Madin Darby canine kidney) monolayers models.Method ① Caco-2 and MDCK cell models:Caco-2 cell(105 cells/cm2) and MDCK cell(5?104 cells/cm2) were inoculated in Millicell-CM culture plate inserts,and the TEER of cell monolayer were detected to make sure the models are available for experiments.② Permeating experiments: to measure the value of OD of CGA and calculate the cumulative amount.Result CGA could be Absorbed and secreted on two monolayer models.Verapamil could inhibit the secretion at lower concentration of CGA on MDCK monolayer model.P-pg could partly act on the secretion of CGA on Caco-2 and MDCK cell models.Conclusion CGA can secrete and Absorb at the same time across Caco-2 and MDCK cell monolayers,P-pg partly involving in the secretion of CGA.