Objective To observe the therapeutic efficacy of Tiao Shen Tong Luo (regulating mind and unblocking collaterals) needling plus hyperbaric oxygen in treating leukoaraiosis (LA) coupled with mild cognitive impairment (MCI). Method Totally 112 patients with LA and MCI were randomized into a treatment group and a control group. In addition to the basic treatment, the treatment group was intervened by Tiao Shen Tong Luo needling plus hyperbaric oxygen, while the control group was given hyperbaric oxygen. The scales and event-related potential (P300) were evaluated and compared before and after the intervention. Result The scales scores and P300 were significantly changed in both groups after the treatment, and the therapeutic efficacy was higher in the treatment group than in the control group (P<0.05). Conclusion In addition to the basic treatment, Tiao Shen Tong Luo needling plus hyperbaric oxygen can produce a significant efficacy in treating LA couple with MCI.

Objective To elucidate the relationship between a 936C/T mutation at 3'-untranslated region of human vascular endothelial growth factor(VEGF) gene and diabetic peripheral neuropathy ( DPN ). Methods All subjects recruited in this study were assigned into DM (n = 92, diabetes without neuropathy, retinopathy or nephropathy), DPN (n = 102, diabetes with peripheral neuropathy only ), and healthy control (n = 120 ) groups,respectively. The gene polymorphism was determined by PCR-RFLP, as well as the other clinical parameters including serum VEGF by ELISA. Results The frequencies of both genotype CC and allele C were significantly higher in DPN group than those in either DM group(x2 = 5.578 and 5.614, P＜0. 05 ) or control group (x2 = 9. 406 and 9. 677, P＜0. 05 ). However, the frequencies of genotype(CT+TT) and allele T were significantly lower in DPN group than that in either DM group(x2 =5.578 and 5.614, P＜0. 05) and control group (x2=9.406 and 9.677, P＜0.05). The multivariate logistic regression analysis showed that the levels of HbA1c, total cholesterol, low-density lipoproteincholesterol( LDL-C ), and serum VEGF positively correlated with DPN, while the 936C/T polymorphism of VEGF gene negatively correlated with DPN(β= -1. 046, OR=0. 457, P=0. 006, 95% CI: 0. 166-0. 741 ). Conclusions Allele 936C of VEGF gene may serve as a genetic marker susceptible to DPN, while allele 936T may be a protective genetic marker of DPN.

[Summary] Glucose-dependent insulinotropic polypeptide ( GIP) is known to promote the release of insulin fromβcells, but this function suffers from a defect in obese patients. More and more evidences suggest that GIP is the bridge between a high-fat diet, obesity, insulin resistance, and type 2 diabetes. With the deepening of research in GIP in type 2 diabetes and obesity, GIP may provide new ideas for the treatment of type 2 diabetes and obesity.

Objective To observe the electroretinogram (ERG) photopic negative response (PhNR) of idiopathic macular hole (IMH) in stage 2 by vitrectomy with or without internal limiting membrane peeling (ILMP).Methods Twenty-three stage 2 IMH patients (23 eyes) were enrolled in this prospective study.All patients received the best corrected visual acuity (BCVA),optical coherence tomography and flash-ERG examinations.The patients were randomly divided into group A (11 eyes,vitrectomy) and B (12 eyes,vitrectomy with ILMP).There was no significant difference in BCVA (t=0.96,P=0.350),diameter of macular hole (MH) (t=3.21,P=0.580) and the PhNR amplitude (t=0.98,P=0.353) in group A and B.All patients underwent 25G vitrectomy,ILMP was carried out in group B.The follow-up time was 3 to 6 months,with the mean follow-up time of 4.3 months.BCVA,MH closure rate and PhNR amplitude in group A and B were analyzed before and after surgery.Results Three months after surgery,10 eyes (90.9％) gained MH closure but 1 eye (9.1％) failed in group A.In group B,12 eyes (100.0％) gained MH closure.There was no significant difference in MH closure rate between the two groups (P=0.462).The mean BCVA of group A and B was 0.69 ± 0.24 and 0.65 ± 0.22,there was no significant difference between the two groups (t=0.49,P=0.722).The amplitude of PhNR in group A was (36.647.4) μtV,which was lower than the pre-surgery PhNR,but the difference was not significant (t=0.73,P=0.472).The amplitude of PhNR in group B was (27.1 ± 12.4) μV,which was lower than that the presurgery PhNR,and the difference was significant (t =3.56,P =0.002).The difference of PhNR amplitude in group A and B was statistically significant (t=2.17,P=0.042).Conclusion Compared with non-ILMP,vitrectomy combined with ILMP will significantly reduce the PhNR amplitude ofIMH in stage 2.

Objective To elucidate cerebral cortical response to esophageal acid exposure in normal individuals by functional magnetic resonance imaging (fMRI) and the characteristics of activity. Methods Fifteen volunteers were received intraesophageal perfusion with either 0.9% of sodium chloride or acid (0.1 mmol/L HC1) solutions. The modified block-design model of fMRI scanning was performed simultaneously. All of 32 minutes were needed for resting (A, 8 minutes), 0.9% of sodium chloride perfusion (B,8 minutes), acid perfusion (C,8 minutes) and 0.9% of sodium chloride perfusion again (D,8 minutes). Each chunk was consisted of 160 scans and every scan contained 3 seconds. Six hundred and forty scans were collected in all. The clinical response to esophageal acid exposure was observed and the changes in the cerebral regions was statistically analyzed. Results After perfusion of 0.9% of sodium chloride or acid, 10 out of 15 volunteers had chemosensitive complaints, such as pain in pars laryngen pharyngis, heartburn and chest complaint. The initial active domains involved deutocerebrum, anterior part of callosal gyrus, left side of insula, two sides of amygdale and subiculum hippocampi, two outers of forehead cortex. The provoked regions of acid perfusion (C-A) and 0.9% of sodium chloride perfusion again (D-A) were as same as that of the activated domains by initial perfusion of 0.9% sodium chloride (B-A). The intensity and amplitude of most provoked regions increased gradually(D-A> B-A, P< 0.01). Conclusions The two different stimulations of saline and acid provoke similar cerebral regions that may act in the regulation of esophageal sensitivity. There are the evidences of the central mechanism of esophageal visceral hypersensitivity by acid perfusion.

Objective:To analyze risk factors for duration of small or medium-sized coronary artery aneurysms (CAA) in children with Kawasaki disease (KD) so as to provide clinical guidance for early and full course treatment.Methods:The clinical data of 68 children diagnosed with KD in the Department of Pediatrics, the First Affiliated Hospital of Xinxiang Medical University from January 2018 to January 2021 were retrospectively analyzed.According to duration of CAA, all cases were divided into 2 groups, duration of CAA ≥ 8 weeks group and duration of CAA <8 weeks group.Risk factors associated with CAA duration were screened using univariate analysis, and then independent risk factors for CAA duration in children with KD were analysed using multiple Logistic regression analysis. Results:A total of 68 cases were enrolled in this study.Among these cases, 45 cases (66.18%) were male and 23 cases (33.82%) were female.The onset age was from 3 months to 10 years old, and the median onset age was 1.59 (1.02-3.19). There were 31 cases in the group with CAA duration ≥8 weeks and 37 cases in the group with CAA duration <8 weeks.Univariate analysis showed that patients with the total fever course >10 days[45.16%(14/31 cases) vs.21.62%(8/37 cases)], time of treatment with intravenous immunoglobulin (IVIG)>10 days[54.84%(17/31 cases) vs.16.22%(6/37 cases)], platelet (PLT)>600×10 9/L[32.26%(10/31 cases) vs.10.81%(4/37 cases)], hypersensitive C-reactive protein (HsCRP) >100 mg/L[38.71%(12/31 cases) vs.13.51%(5/37 cases)] (all P<0.05 ) in the group with CAA duration ≥8 weeks were significantly more than those in the group with CAA duration <8 weeks.However, there were no significant differences in gender, age, type of KD, etiology evidence, hormone application, duration of fever before IVIG application, IVIG sensitivity, IVIG application way, urine leukocytes, white blood cells, hemoglobin, percent of neutrophilic granulocyte, erythrocyte sedimentation rate, glutamic-pyruvic transaminase between the 2 groups (all P>0.05). Multivariate Logistic regression analysis showed that the course of IVIG before application >10 days ( OR=6.589, 95% CI: 1.678-25.867, P=0.007)and HsCRP >100 mg/L ( OR=7.949, 95% CI: 1.947-32.461, P=0.004)were independent risk factors for predicting the duration of KD complicated with small and medium-sized CAA ≥8 weeks. Conclusions:The course of IVIG before application >10 days and HsCRP>100 mg/L are independent risk factors for KD complicated with small and medium-sized CAA lasting ≥8 weeks.

Objective:To investigate the effects of triptolide (TPL) and BET protein inhibitor JQ1 on proliferation inhibition and apoptosis induction of MLL-rearranged acute myeloid leukemia (AML) cell line MV4-11, and to explore their synergistic mechanisms.Methods:MV4-11 cells in logarithmic growth phase were treated with different concentrations (100, 200, 300, and 400 nmol/L) of JQ1, 4 nmol/L TPL or different concentrations of JQ1 combined with 4 nmol/L TPL for 48 h. Cell proliferation was detected by CCK-8 method, apoptosis was detected by flow cytometry (FCM), mitochondrial membrane potential was detected by JC-1 method, and expressions of mitochondrial apoptosis pathway-related proteins were detected by Western blot.Results:The 50% inhibitory concentration ( IC50) value of MV4-11 cells treated with JQ1 for 48 h was (283.9±10.7) nmol/L. However, 4 nmol/L TPL significantly enhanced the inhibitory effect of JQ1 on proliferation of MV4-11 cells, the IC50 value of MV4-11 cells treated with JQ1 combined with TPL was (148.1±2.6) nmol/L, and the difference was statistically significant ( t = 25.31, P = 0.029). The result of FCM assay showed that compared with the JQ1 alone group [(9.6±2.3)%, (12.6±1.4)%, (19.5±3.3)%, and (22.7±2.1)%], 4 nmol/L TPL combined with different concentrations (100, 200, 300, and 400 nmol/L) of JQ1 acted on MV4-11 cells for 48 h, the proportions of apoptotic cells were (16.4±1.9)%, (27.5±2.1)%, (32.9±3.6)%, and (35.5±3.0)%, respectively, the difference was statistically significant ( F = 9.25, P < 0.01). After treated with 4 nmol/L TPL and JQ1 for 12 h, the level of cell membrane potential in MV4-11 cells was significantly lower than that of JQ1 single agent group, and the difference was statistically significant ( P < 0.05). After treated by 4 nmol/L TPL combined with JQ1 for 24 h, the levels of anti-apoptotic proteins bcl-2 and Mcl-1 decreased, and the level of pro-apoptotic protein bax increased. Conclusion:TPL can significantly enhance the proliferation inhibition and apoptosis induction effects of BET protein inhibitor JQ1 on MLL-rearranged AML cells, and the mechanism may be related to enhancing the mitochondrial apoptosis pathway.

Objective · To compare the efficacy and prognostic factors of HCAG regimen with traditional IA regimen in the treatment of newly diagnosed elderly acute myeloid leukemia (AML) patients. Methods · Forty-one patients with AML (aged 55-71 years) were randomly divided into two groups (Group HCAG and Group IA) between 2014 and 2016 for induction and consolidation therapy. Multivariate analysis was applied to identify prognostic factors for relapse-free survival (RFS). Results · A total of 29 patients (70.7%) achieved complete remission (CR). The estimated 2-year overall survival (OS) was 66.8% in Group HCAG and 75.4% in Group IA (P=0.913). The estimated 2-year RFS was 61.8% in Group HCAG and 49.1% in Group IA (P=0.411). Age remained as the unfavorable prognostic factor, leading to significant differences in OS and RFS. In addition, RFS was influenced by cytogenetic/molecular risk stratification. Conclusion · Although HCAG seemed not to particularly benefit the group, the dose reduction of anthracyclines may be applied in elderly patients with comparable short-time outcome. Furthermore, the introduction of homoharringtonine resulted in an improvement of treatment response for more than 20% compared with CAG regimen.

Objective:To explore the effects of apatinib on the proliferation and apoptosis of FLT3-ITD mutant acute myeloid leukemia (AML) cells, and to explore the related mechanisms.Methods:The logarithmic growth phase FLT3-ITD mutant AML cell lines MV4-11 and MOLM-13 were treated with different concentration of apatinib for 48 hours. The cell proliferation was detected by CCK-8 method. Flow cytometry was performed to examine the effect of apatinib on apoptosis. The cell mitochondrial membrane potential changes were detected by JC-1. Then the expression changes of vascular endothelial growth factor receptor 2 (VEGFR2) pathway-related proteins were examined by Western blot.Results:Apatinib had proliferation inhibitory effects on both MV4-11 and MOLM-13 cells, and the half-maximal inhibitory concentration (IC 50) at 48 hours was (2.23±0.42) μmol/L and (4.08±2.62) μmol/L, respectively. After exposure to apatinib with increasing concentrations (10, 20, 30, and 40 μmol/L) for 48 h hours, the percentage of apoptotic cells was significantly increased in MV4-11 cells [(81.95±1.15)%, (88.80±0.23)%, (97.46±0.49)%, and (99.29±0.05)%] and MOLM13 cells [(47.30±0.87)%, (67.00±3.71)%, (82.60±2.89)%, and (98.06±5.34)%] in a dose-dependent manner, and the differences were statistically significant ( F = 6 915.0, P < 0.01; F = 5 385.0, P < 0.01). Detection of mitochondrial membrane potential by JC-1 method showed that after MV4-11 and MOLM-13 cells were treated by 10, 20, 30, and 40 μmol/L apatinib for 24 hours, the JC-1 aggregate/monomer mean fluorescence intensity (MFI) ratios were 0.45±0.06, 0.19±0.07, 0.12±0.03, 0.09±0.01, and 0.84±0.05, 0.66±0.13, 0.35±0.11, 0.27±0.02, which were different from the control group (0.67±0.15 and 0.97±0.42), and the differences were statistically significant ( F = 372.3, P < 0.05; F = 276.4, P < 0.05). Western blot was performed to detect different concentration of apatinib (2.5, 5.0 and 10.0 μmol/L) on the MV4-11 cells for 24 hours, the results showed that apatinib could down-regulate the phosphorylation of VEGFR2, Src and Stat3 in a dose-dependent manner. Conclusions:Apatinib can inhibit cell proliferation and induce apoptosis in AML with FLT3-ITD mutation. The possible mechanism is related to the down-regulation of phosphorylation of VEGFR2 and its downstream targets Src and Stat3.

ObjectiveBy starting with the combination of Os Draconis， Bupleuri Radix， and Ostreae Concha， the role of mineral medicine Os Draconis in the combination of the Bupleuri Radix-containing tri-herbal medicines was preliminarily explored from the perspective of supramolecular system formation. Method① The appearance and Tyndall phenomenon of single decoction of Os Draconis， Bupleuri Radix， and Ostreae Concha， as well as co-decoction of Bupleuri Radix-Os Draconis， Bupleuri Radix-Os Draconis-Ostreae Concha， and Bupleuri Radix-Ostreae Concha were observed， and the average particle size， dispersion coefficient， and Zeta potential of suspension particles in each decoction were determined. The micromorphology of supramolecular structures was observed by scanning electron microscope （SEM）. ② The pH of different compatibility systems， liquid viscosity coefficient， liquid surface tension， freeze-dried powder yield rate， and other physical properties were determined， and the interaction of different compatibility systems was detected by infrared absorption spectroscopy （FTIR） and UV-visible spectrophotometry （UV-Vis）. ③ The composition and content difference of different compatible systems were determined by high-performance liquid chromatography （HPLC） and ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry （UPLC-Q-TOF-MS）. ResultCompared with the single decoction， the co-decoction had more obvious turbidity and Tyndall phenomenon. The particles in the co-decoction suspension were smaller and more evenly distributed， and the Zeta potential was reduced， indicating a more stable system. Under SEM， Bupleuri Radix was irregularly lamellar， and Bupleuri Radix-Os Draconis and Bupleuri Radix-Os Draconis-Ostreae Concha were mainly spherical nanoparticles. Bupleuri Radix-Ostreae Concha was irregularly lamellar， with a small number of spherical nanoparticles. The pH of the single decoction of Bupleuri Radix and co-decoction increased， and the viscosity coefficient increased. The liquid surface tension decreased. The freeze-dried powder yield rate of the Bupleuri Radix-Os Draconis co-decoction was the highest， followed by Bupleuri Radix-Ostreae Concha decoction and Bupleuri Radix-Os Draconis-Ostreae Concha decoction， and the yield rate of Bupleuri Radix single decoction was the lowest. The main change of FTIR was the stretching vibration of -OH， and the co-decoction moved to the low-frequency direction obviously. UV-Vis showed that the maximum absorption occurred at 295.8 nm for all groups， and the absorption intensity was different （Bupleuri Radix-Os Draconis>Bupleuri Radix-Os Draconis-Ostreae Concha>Bupleuri Radix-Ostreae Concha>Bupleuri Radix）. The components of Bupleuri Radix were used as the indexes， and the content of methanol extract determined by HPLC was higher than that of water extract， and the components of Bupleuri Radix single decoction were mainly saikosaponin a （SSa） and saikosaponin c （SSc）， which were slightly higher after co-decoction compatibility. UPLC-Q-TOF-MS could identify 37 compounds in both single decoction and co-decoction. ConclusionThe combination of Bupleuri Radix， Os Draconis， and Ostreae Concha can form a smaller， more uniform， and stable nano-sized supramolecular system， which is conducive to the dissolution of the main components of Bupleuri Radix， and the Os Draconis contributes the most in this process.