Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

OBJECTIVE To observe the effects of Xuesaitong soft capsule on the complement-inflammatory receptor system in patients with type 2 diabetic nephropathy. METHODS A total of 92 patients with type 2 diabetic nephropathy were divided into control group and observation group by random number table method ，with 46 cases in each group. Patients in the control group were given basic treatment programs （including low-salt and low-protein diet ，quitting smoking and alcohol ，appropriate exercise ， lowering blood pressure ，blood sugar and lipid ，etc.）. The patients in the observation group took Xuesaitong soft capsules orally on the basis of the treatment of the control group ，0.55 g each time ，3 times a day. The treatment course of both groups was 4 weeks. Compare the renal function of the two groups of patients [24 h urine protein quantification ，serum creatinine （Scr），blood urea nitrogen，glomerular filtration rate （GFR）]，fasting blood glucose ，glycosylated hemoglobin ，complement factors [C3，C5， complement factor H （CFH），C5b-9]，inflammatory factors [interleukin 1（IL-1），tumor necrosis factor α（TNF-α），IL-6，monocyte chemoattractant protein- 1（MCP-1）]，renal tubular injury markers [β2-microglobulin（β2-MG），retinol binding protein 4（RBP4）， neutrophil gelatinase associated lipocalin] levels；correlation between renal tubular damage and complement-inflammatory receptor system was analyzed in the observation group before and after treatment. RESULTS Compared with before treatment ，24 h urine protein quantity ，Scr，C3，IL-1，TNF-α，MCP-1，β2-MG and RBP 4 of 2 groups were reduced significantly after treatment ，while GFR and CFH were significantly increased ；except for C 3，the observation group was significantly better than the control group （P＜ 0.05）. C 5 of the observation group was significantly decreased after treatment and was significantly lower than the control group （P＜0.05）. There were no statistically significant 60979837。E-mail：shanght126@126.com differences in other indicators of the two groups before and after treatment and between groups （P＞0.05）. C 3，MCP-1 and TNF-α were significantly correlated with renal tubular com damage （P＜0.05），and esp ecially C 3. CONCLUSIONS Xuesaitong soft capsule can reduce renal tubular damage in patients with type 2 diabetic nephropathy and improve renal function by acting on the complement system and reducing inflammation.

OBJECTIVE: To quantify the relationship between cerebral blood flow velocity and peripheral blood pressure during hypotension period, aiming to predict the brain hypotension before symptomatic occurrence. METHODS: Twenty vasovagal syncope (VVS) patients who had a previous clinical history were selected in groups and 20 pair-matched control subjects underwent 70° tilt-up test. The subjects remained supine for 30 minutes before recordings when Doppler probes, electrodes and Finapres device were prepared. After continuous baseline recordings for 10 min, the subjects underwent head up tilt (HUT) test (70°), and were standing upright for 30 minutes or until syncope was imminent. For ethical reasons, the subjects were turned back to supine position immediately after SBP dropped to ≥20 mmHg, when their consciousness persisted. The point of syncope was synchronized for all the subjects by the point SBP reached the minima. Their beat-to-beat blood pressures (BP) were recorded continuously and bilateral middle cerebral artery (MCA) flow velocities were obtained with two 2 MHz Doppler probes from a transcranial Doppler ultrasonography (TCD) system. A nonlinear dynamic method--multimodal pressure flow (MMPF) analysis was introduced to access cerebral autoregulation during different time intervals. We introduced a new indicator--syncope index (SI), which was extracted from blood flow velocity (BFV) signal to evaluate the variation of cerebral vascular tension, and could reflect the deepness of dicrotic notch in BFV signal. RESULTS: Compared with the syncope index of the baseline value at the beginning of the tilt test, SI in VVS group showed significantly lower when the VVS occurred (0.16±0.10 vs.0.27±0.10,P<0.01),while there was no significant difference in syncope index between the control group at the end of the tilt test and the baseline value at the beginning of the tilt test. For those VVS patients, pulse index and resistance index had no significant change. Syncope index decreased significantly 3 minutes before the point of syncope (0.23±0.07 vs.0.29±0.07,P<0.01). CONCLUSION Dynamic regulation is exhausted when vasovagal syncope occurred. Tension decrease of small vessels could have some relationship with loss of the cerebral autoregulation capability. The proposed syncope index could be a useful parameter in predicting syncope of VVS patients since it decreased significantly up to 3 minutes earlier from the point of syncope.
Blood Pressure ; Heart Rate ; Humans ; Nonlinear Dynamics ; Syncope ; Syncope, Vasovagal ; Tilt-Table Test

Objective: To evaluate the prognostic significance of early phase full donor chimerism (FDC) after myeloablative allogeneic peripheral blood stem cell transplantation (allo-PBSCT). Methods: The clinical data of 72 hematological patients received myeloablative allo-PBSCT from Feb. 2016 to Jul. 2017 were analyzed retrospectively. The median age was 36.5 years (range 4-59), 44 were males and 28 females. Of the donors, there were 35 HLA matched sibling donors, 27 haploidentical donors and 10 unrelated donors. Polymerase chain reaction amplification of short tandem repeat sequence (PCR-STR) was used to detect donor cell chimerism (DC) rate of recipient bone marrow at one, two and three months after transplantation. Results: The median follow-up was 462 d (range: 47-805 d), 55 cases were still alive, and 45 cases were disease-free survival (DFS) at the end of follow-up. The 2-year overall survival (OS) and DFS were (68.9±7.7)% and (59.5±6.3)%, respectively. A number of 16 cases underwent relapses, with 2-year cumulative incidence of (24.1±5.3)%. The median time of recurrence was 157(32-374) d. Forty cases (55.6%) developed acute graft-versus-host diseases (aGVHD), with median time of 35.5 (13-90) d. Chronic GVHD (cGVHD) occurred in 23 patients (31.9%), with median time of 169 (94-475) d. Univariate analysis found the following factors were not related to OS, DFS or relapse rate (RR), including age, sex, blood type and sex of donor-recipient, occurrence of aGVHD and cGVHD. The OS and DFS in cases reached FDC and no FDC at two months after transplantation were (85.2±6.9)% vs (66.1±7.7)% (P=0.051) and (76.7±7.7)% vs (48.9±8.1)% (P=0.021), respectively. The RR rate in FDC group was lower than that in no FDC group [(16.6±6.8)% vs (30.4±7.8)%, P=0.187, respectively]. Conclusion: The present study confirmed the important value for predicting the prognosis with whether or not the patients reached FDC at the early phase after allo-PBSCT. The OS and DFS in cases with FDC at two months after transplantation were significantly higher than those of no FDC patients.
Adolescent ; Adult ; Child ; Child, Preschool ; Chimerism ; Female ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Middle Aged ; Peripheral Blood Stem Cell Transplantation ; Prognosis ; Retrospective Studies ; Young Adult

Aim To explore the effect of Cx43 over-expression on proliferation of C6 cells and its mechanisms by transfecting pCMV-Cx43cDNA plasmid into C6 cells.Methods pCMV-Cx43cDNA plasmid was transfected into C6 cells by liposome to up-regulate the expression of Cx43, and C6 cells with over-expression of Cx43 was stably cloned by using G418.Determination of cell doubling time and soft agar colony formation assay to detect the degree of cell proliferation.The cells were treated with ERK1/2 specific blocker PD98059(30 μmol·L-1) and p38MAPK specific blocker SB202190(10 μmol·L-1)respectively, the expression of Cx43, p-Cx43, p-ERK1/2 and p-p38MAPK of each group were detected by Western blot, and the activity of each group was detected by MTT Assay.Results pCMV-Cx43cDNA plasmid was transfected into C6 cells successfully.Cell lines with over-expression Cx43(C6-Cx43) or empty vector (C6-pCMV) were stably selected by using G418.Determination of cell doubling time and soft agar colony formation experiments showed that the proliferative rate and the colony number of C6-Cx43 group were significantly decreased, compared with that of C6 group and C6-pCMV group(P<0.01);ERK1/2, p38MAPK specific blockers were treated with each group,Western blot showed that the expression of Cx43 protein was increased(P<0.01), while p-Cx43 protein was decreased (P<0.05) in C6-Cx43+PD98059 group and C6-Cx43+SB202190 group,compared with that of C6-Cx43 group.Conclusion Cx43 may decrease the proliferation of glioma cells through ERK1/2, p38MAPK pathways.

Purpose To explore the correlation between the clinicopathological features and postoperative recurrence or metastasis of solid-pseudopapillary neoplasms of the pancreas (SPN).Method The clinicopathological characteristics of 73 SPNs were summarized,the patients' prognosis were followed up by telephone and then the correlation of clinicopathological characteristics and recurrence or metastasis was analyzed.Results 57 female patients and 16 male patients were included in this study.The age range was 7 to 68 years old with the average of 28 and median age of 27.The mean diameter of the tumors was 6.47 cm (range 0.31～ 14 cm).30 cases of tumors were located in the head of pancreas,9 in the body of pancreas,and 33 in the tail of pancreas.One case was a multiple lesion simultaneously located in the body and the tail.All patients were followed up by telephone for mean time 34.8 months with the range of 12 ～ 99 months.Necrosis,calcification,cholesterol crystal,foamy histiocytes,nuclear atypia,pancreatic parenchymal invasion,and perineural invasion had no statistical significance between non-recurrent/metastatic group and recurrent/metastatic group.However,there was significant difference for extra-pancreatic invasion,angiovascular invasion and Ki-67 proliferation index between non-recurrent/metastatic group and recurrent /metastatic group.Conclusion Extra-pancreatic invasion,angiovascular invasion and Ki-67 proliferation index ≥ 4％ have reference significance for predicting recurrence or metastasis of SPN.

Xin-Sheng-Hua granule (XSHG) is a popular remedy commonly used in clinic for the treatment of lochiostasis after delivery. To comparatively investigate the roles of herb pairs containing Angelicae Sinensis Radix (Danggui) upon the formula by evaluating the blood coagulation and hemorheology function in acute blood stasis rats, acute blood stasis rat model was established by ice water bath and subcutaneous injection of adrenaline. And the blood stasis mice were administrated intragastrically with different samples of the formula minus herb pairs containing Danggui and the whole formula (XSHG, SHD, DY, DC, DT, DH, DJ and DZ). The whole blood viscosity (WBV), plasma viscosity (PV), erythrocyte sedimentation rate (ESR) and haematocrit (HCT) were applied to evaluate the effects of the formula minus herb pairs containing Danggui on hemorheology of blood stasis rats. The thrombin time (TT), activated partial thromboplastin time (APTT), prothrombin time (PT), and plasma fibrinogen (FIB) were used to observe the effects of the formula minus herb pairs containing Danggui on blood coagulation function of blood stasis rats. Additionally, the maximum aggregation induced by adenosine diphosphate (ADP) was tested to observe the effect of different samples on platelet aggregation index of blood stasis rats.Afterwards, multi-attribute comprehensive index methods and principal component analysis were both applied to comprehensively assess the total effects of the formula minus herb pairs containing Danggui on promoting blood circulation and dissipating blood stasis. Compared with normal group, the hemorheological parameters and coagulation indexes of model group had statistical differences (P<0.01). Compared with model group, different samples (XSHG, SHD, DY, DC, DT, DH, DJ and DZ) could improve the blood hemorheology indexes, coagulation parameters and platelet aggregation in acute blood stasis rats. According to multi-attribute comprehensive index methods and the principal component analysis, the effects of promoting blood circulation by removing blood stasis became poor when excluding herb pairs containing Danggui from the formula, the sample DY and DC had the weakest effect of activating blood circulation and dissipating blood stasis, and the effect of sample DY was slightly poorer than DC. The orders of contribution of herb pairs containing Danggui on the formula were Danggui-Yimucao>Danggui-Chuanxiong>Danggui-Honghua>Danggui-Zhigancao>Danggui-Taoren>Danggui-Jiangtan. In conclusion, various herb pairs containing Danggui played different roles on the effects of improving the abnormality of hemorheology and coagulation function. And the herb pairs Danggui-Yimucao were particularly important for the formula, which was consistent with the characteristics of XSHG and the traditional effect of Yimucao. Moreover, it could lay foundation to further reveal the compatibility mechanism of XSHG.

BACKGROUNDRecrossing the compromised side branch (SB) with a balloon is sometimes technically challenging. The aim of this study was to evaluate whether in-stent anchoring (ISA) is safe and effective to facilitate SB balloon delivery for final kissing.

METHODSOne hundred and fifty-nine consecutive patients were included (166 bifurcation lesions) in this prospective, single-center registry. ISA was used as a bailout method after unsuccessful SB crossing using conventional techniques, including low-profile balloons. Technique success was defined as SB balloon delivery and final kissing.

RESULTSKissing-balloon delivery was successfully performed with conventional strategies in 149 of 166 lesions (89.8%). In the remaining 17 lesions (10.2%), recrossing of the main vessel stent strut was not successful; therefore, ISA was attempted. The balloon successfully crossed the stent struts, and final kissing was achieved in 15 of 17 lesions (88.2%). Total final kissing was achieved in 164 of 166 lesions (98.8%), with success rates of 100% in the single-stent group and 97.6% in the two-stent group. Two cases without balloon delivery had complex bifurcation lesions with severe calcification. There was no vessel dissection in the anchoring zone.

CONCLUSIONSISA is safe and effective for recrossing stent struts when conventional low-profile balloons have failed. However, large-scale trials are warranted for further evaluation.

Aged ; Angioplasty, Balloon, Coronary ; methods ; Coronary Angiography ; methods ; Coronary Artery Disease ; therapy ; Drug-Eluting Stents ; Female ; Humans ; Male ; Middle Aged ; Prospective Studies ; Registries ; Treatment Outcome

Objective: A novel and generally applicable approach was established for the interaction analysis on compatibility of Danshen-Honghua (Salviae Miltiorrhizae Radix and Carthami Flos) pair with different preparations and proportions when decocting together by using HPLC-PDA and fuzzy chemical identification strategy with poly-proportion design. Methods: A simple project was initially developed for the rapid identification and classification of four types of components in Danshen-Honghua based on the establishment of relevant component data base, recognition of the reference compound peaks, selection of the characteristics of ultraviolet spectrum, and formation of group networks. In this study, the accurate structures of the chemical components did not need to be determined, and only the constituents attributed to different groups were further considered for quantitative analysis. Results: A total of 47, 57, and 43 constituents from different preparations of Danshen-Honghua were classified into four kinds of chemical groups, and they were quantitatively analyzed furtherly according to semi-symmetric proportion design. The results showed that the preparation of methanol-water could significantly promote the dissolution of most salvianolic acids, chalcones, and flavonoids, while the contents of tanshinones in methanol were higher than others. The relative dissolution rate range of total optimization for the four types of components were from 5:1 to 5:2, and the highest proportion of the total relative dissolution were all 5:2. Conclusion: The most reasonable range may appear 5:1-5:2 for water preparation and be consistent with clinical ratio, which provides the reference for clinical application of Danshen-Honghua pair, and for modern research approach of herb pairs.

Objective: To evaluate the activating blood circulation and dissipating blood stasis effects of the compatibility between two effective parts (DT, DF, DST, and DF + DST) of Salvia miltiorrhiza. with different doses on rats with acute blood stasis. Methods: Acute blood stasis rat model was induced by sc injection of adrenaline and ice water bath. The blood stasis mice were ig administered with different effective parts of S. miltiorrhiza. The whole blood viscosity (WBV), plasma viscosity (PV), erythrocyte sedimentation rate (ESR), and haematocrit (HCT) were determined to observe the effects of two effective parts of Danshen on hemorheology of blood stasis rats. And the thrombin time (TT), prothrombin time (PT), activated partial thromboplastin time (APTT), and plasma fibrinogen (FIB) were tested to observe the effects of different effective parts of S. miltiorrhiza on blood coagulation function of blood stasis rats. In addition, the maximum aggregation induced by adenosine diphosphate (ADP) was tested to observe the effect of different active parts of S. miltiorrhiza on platelet aggregation index of blood stasis rats. Then principal component analysis (PCA) and multi-attribute comprehensive index methods were both used to comprehensively evaluate the total activating blood circulation and dissipating blood stasis effects of different effective parts of S. miltiorrhiza. Results: The hemorheological indexes and coagulation parameters of model group had the significant differences with normal group. Compared with model group, the effective parts of S. miltiorrhiza with different doses could improve the blood hemorheological indexes and coagulation parameters in acute blood stasis rats with dose-effect relation. Based on the PCA and multi-attribute comprehensive index methods, the group of high-dose DF + DST had the best effect of activating blood circulation and dissipating blood stasis effect in all medication administration teams. Under the condition of same dose of the effective parts of S. miltiorrhiza, the DF + DST could obviously improve the hemorheology and blood coagulation function in acute blood stasis rats. Conclusion: The combination of DF and DST has the better effects of activating blood circulation and dissipating blood stasis in comparison with those of single part. It could provide the scientific basis for more effective application of the compatibility between salvianolic acids and tanshinones in modern clinic medicine.