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*

The interaction of endophytes and host plant is an effective mean to regulate the growth and secondary metabolism of medicinal plants. Here we want to elucidate the effects and mechanism of Phoma herbarum D603 on the root development and tanshinone synthesis in root of Salvia miltiorrhiza by endophyte-plant coculture system. The mycelium of P. herbarum D603 was colonized in the root tissue space, and formed a stable symbiotic relationship with host plant. The in vitro activities analysis showed that the concentration of IAA produced by D603 can reach(6.45±0.23) μg·mL~(-1), and this strain had some abilities of phosphorus solubilization and siderophore production activities. The coculture experiment showed that strain D603 can significantly promote the synthesis and accumulation of tanshinones in the root of S. miltiorrhiza, in which after 8 weeks of treatment with D603, the content of tanshinone Ⅱ_A in the roots reached up to(1.42±0.59) mg·g~(-1). By the qRT-PCR analysis results, we found that D603 could improve the expression levels of some key genes(DXR, DXS, GGPP, HMGR, CPS) of tanshinone biosynthesis pathway in host plant S. miltiorrhiza, but the promoting effect mainly occurred in the early stage of the interaction, and the enzyme activity level decreased in varying degrees of the later stage. In summary, seed-associated endophyte P. herbarum D603 can promote the growth and root development of S. miltiorrhiza by producing hormones, promoting nutrient absorption and siderophore production, and promote the synthesis and accumulation of tanshinones by regulating the expression level of key genes in the synthetic pathway in S. miltiorrhiza.
Abietanes/biosynthesis* ; Ascomycota/growth & development* ; Endophytes/growth & development* ; Plant Roots/microbiology* ; Salvia miltiorrhiza/microbiology* ; Seeds/microbiology*

Child ; Cytomegalovirus Infections ; Haplotypes ; Hematopoietic Stem Cell Transplantation ; Humans

Objective·To evaluate the value of texture analysis in the discrimination of colorectal cancer (CRC) and ulcerative colitis (UC). Methods?·?The CT images of 61 CRC patients, 62 UC patients and 42 control objects were retrospectively analyzed. All the patients were pathologically proved and performed triphasic contrast-enhanced CT scan: non-enhanced phase (NP), the arterial phase (AP) and the enteric phase (EP). The region of interest was drawn along the abnormal bowel wall’s edge in each scan phase and texture features were generated by MaZda software. Based on 3 texture feature selection methods, the optimal subsets were generated and analyzed by 6 texture feature classification methods. The results were shown by misclassification rate (MCR). To compare the performance of texture-based classification and human visual classification, two radiologists with more than 10 years of gastrointestinal disease diagnostic experience analyzed the data. Results?·?The texture analysis based average MCR of differentiation between CRC and UC was (28.42±6.89)%, (28.19±4.07)%, (19.10±3.58)% in NP, AP, EP respectively. Compared with other texture feature classification methods, nonlinear discriminant analysis (NDA) was more accurate. In EP, NDA achieved an excellent classification result (MCR=12.61%). The average MCR between CRC and normally dilated bowel wall (NOR) was (13.33±7.21)%, (15.49±5.47)%, (6.74±3.02)%, while the average MCR between UC and NOR was (19.26±4.68)%, (20.04±6.63)%, (16.74±6.36)% in NP, AP and EP respectively. For visual classification between CRC and UC, the average MCR was (40.48±3.21)%, (35.71±1.60)%, (26.43±1.15)% in NP, AP, EP respectively. But the MCR of texture classification was lower than that of human vision classification, and computer texture classification had higher differential diagnosis rate. Conclusion?·?The CT-based texture analysis could be a feasible supplementary method to differentiate CRC from UC. NDA is more accurate than other classification methods, especially in EP.

Collection and rating of evidence,survey of patients' preference and value and economic evaluation of the Practice Guideline for Therapeutic Drug Monitoring of Voriconazole have been finished.The Guideline Consensus Panel reached consensus of the recommendations by 3 rounds Delphi and Grading of Recommendations Assessment,Development and Evaluation grid method.Consensus of 38 recommendations was reached,with a consensus percentage of 50.7％.Twenty seven recommendations were finalized and approved by the Guideline Steering Committee.Draft recommendations were generated.

In order to discover light quality's effects on growth, photosynthesis and effective components content of Panax notoginseng, a pot experiment using 7 light qualities (red, orange, yellow, green, cyan, violet, and blue) was conducted. The growth, photosynthesis and content change of effective components were measured during plant growth. The results showed that light qualities had significant effect on plant growth, red light increased the plant height, while cyan, yellow, violet, and blue lights promoted accumulation of biomass underground, blue and yellow lights increased the photosynthesis, cyan light increased accumulation of ginsenoside Rd, yellow and cyan lights increased total effective components of individual plant.
Light ; Panax notoginseng ; growth & development ; metabolism ; radiation effects ; Photosynthesis ; radiation effects ; Plant Extracts ; analysis ; metabolism

OBJECTIVETo develop a system for automatically controlling carotid sinus pressure in the study on baroreceptors.

METHODSThe preparation containing carotid sinus with parts of the connected vessels and carotid sinus nerve (CS-CSN) were isolated and perfused. A critical pressure controlling component (PRE-U, Hoerbiger, Deutschland) dictated by a computer was integrated into the system to clamp the intrasinus pressure. The pressure command and the relevant intrasinus pressure were compared to evaluate the validity of the pressure controlling system.

RESULTSA variety of sinus pressure-controlling patterns, including pulsation, ramp and step pressures, could be achieved accurately by using the system, and the pressure-dependent discharge activities of sinus nerve were confirmed.

CONCLUSIONThis system for clamping carotid sinus pressure could realize multiple pressure-controlling patterns and is a useful and flexible pressure controlling method that could applied in the study on mechano-electric transduction of baroreceptors.

Animals ; Blood Pressure ; Carotid Sinus ; innervation ; physiology ; Nerve Fibers ; physiology ; Pressoreceptors ; physiology ; Rabbits

Objective To construct the adeno-associated virus (AAV)vector of mouse carrying T-bet gene,which was applied to mouse model of asthma by nose,and to investigate the immunomodulatory effects of T-bet delivery on asthma.Methods Forty healthy Balb/c mice (aged 6-8 weeks) were randomly divided into 4 groups:control group (group A),asthma model group(group B),model/control recombinant adeno-associated virus carrying enhanced green fluorescent protein(rAAV-eGFP) intervention group (group C) and model/rAAV-T-bet virus intervention group(group D),with 10 mice in each group.In group B,group C,and group D,Balb/c mice were sensitized by intraperitoneal injection with OVA and challenged by nebulized OVA.In group C and group D,Balb/c mice were intervened with the isodose rAAV-eGFP and rAAV-T-bet,while in group B,the mice were intervened with the same amount of saline,both of them were dropped into the nasal cavity.Twenty-four hours after the last injection,the mice were sacrificed and the samples were obtained.The total cells in bronchoalveolar lavage fluid (BALF) were counted,and the types of cells were analyzed by Wright-Giemsa staining.The levels of interferon-γ (IFN-γ),IL-4 and IL-5 in BALF were determined by enzyme-linked immunosorbent assay.The expressions of T-bet,GATA-3 and Foxp3 protein in the lungs of asthmatic mice were detected with immunohistochemical technique.Results 1.The level of specific transcription factor T-bet in group B and group C were distinctly lower than that of group A (all P ＜ 0.05),while the level of GATA-3 was significantly higher than that of group A(all P ＜ 0.05).In group D,the expression of T-bet protein was stronger than that in group B and group C,however,the expression of GATA-3 decreased obviously (all P ＜ 0.05).The results of Foxp3 were similar to T-bet.2.In group D,the mice had suppressed levels of IL-4 [(158 ± 55) ng/L] and IL-5 [(68-± 22) ng/L] compared with those in group B and group C(all P ＜0.05).The level of IFN-γ[(113-±35) ng/L] increased compared with those in group B and group C (all P ＜ 0.05).At the same time,the number of total cells and eosinophil in BALF were both obviously lower than those of group B and group C (all P ＜ 0.05).Conclusions On the basis of building mouse model of asthma,intranasal administration of rAAV-T-bet can deliver T-bet gene to airway successfully and efficiently,and plays an immunomodulatory role in immune confusion of asthma.

Objective To study the feasibility of TNF-α promoting migration of rat mesenchymal stem cells (MSCs) to local damaged tissues. Methods The MSCs was exposed to TNF-α at different concentrations and the expression rate of surface adheslon molecules and specific markers as well as their adhesion to endothelial cells were detected.Based on the above steps,the MSCs stimulated with the optimal concentration of TNF-α were obtained and were injected intravenously to the rats whose hindlimbs experienced ischemia damage.The rats were executed for achieving the muscle samples in the ischemic area,which were made into frozen section to count the number of MSCs. Results ( 1 ) Twenty-four hours after the TNF-o stimulation,the expression of adhesion molecule (VCAM-1) of MSCs increased in a concentration-dependent manner,while the expression of adhesion molecules (ICAM-1,L-Selectin and VLA4) of MSCs showed no significant changes.Besides,the expression rate of specific markers of MSCs was also obscure.(2) Exposed to 10 ng/ml TNF-o,MSCs presented an obviously increased ability in adhesion to the endothelial cells.(3) MSCs stimulated with 10 ng/ml TNF-α showed a larger number in the ischemia-damaged tissue of rat hindlimbs than that in the control group. Conclusion TNF-α at concentration of 10 ng/ml is effective within a short term in increasing VCAM-1 expression in rat MSCs and promoting the adhesion of MSCs to endothelial cells without affecting their character.

OBJECTIVETo study the clinicopathologic features of uterine papillary serous carcinoma (UPSC) and the roles of adjuvant therapy.

METHODSSixty-one cases of UPSC with operation done and followed up for a period of 4 to 9 years were enrolled into the study. The histology of slides specimens were reviewed and immunohistochemical study was performed. The follow-up and survival data were analyzed.

RESULTSAll of the 61 patients were post-menopausal, with a median age of 68 years. The clinical presentations included abnormal vaginal bleeding, abdominal symptoms and abnormal Pap smears. The median size of the tumors was 7.5 cm (range=1.2 to 14.8 cm). There were 27.9% cases in FIGO stage I (8.2% in stage IA, 14.8% in stage IB and 4.9% in stage IC), 9.8% in stage II, 32.8% in stage III and 29.5% in FIGO stage IV. The histologic features were similar to those of the ovarian counterpart, with tumor cells containing the high-grade nuclei and arranged in complex papillae. Psammoma bodies were identified in 24.6% of the cases. Immunohistochemical study showed that the tumor cells demonstrated diffuse and strong nuclear staining for p53 and Ki-67. They were negative for estrogen receptor and progesterone receptor. Fifteen of the 61 cases (24.6%) showed no evidence of myometrial invasion. However, ten of the 15 cases had extrauterine disease, with peritoneal (6/15) and nodal (9/15) involvement. Tumors with deep myometrial invasion, lymphovascular permeation and nodal metastasis were associated with worse prognosis by univariate analysis. Fifty-six patients received adjuvant therapy. The number of patients receiving adjuvant chemotherapy alone, adjuvant radiotherapy alone and combined adjuvant chemotherapy/radiotherapy were 42, 24 and 10, respectively. The median survivals of the chemotherapy group and non-chemotherapy group (with or without radiotherapy) were 66.4 months and 32.8 months, respectively.

CONCLUSIONSUPSC has distinctive clinical and pathologic features. The tumor stage, lymph node status, lymphovascular permeation and depth of myometrial invasion were important prognostic factors. Adjuvant chemotherapy for stage III/IV tumors or recurrent UPSC may have survival benefit.

Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Carcinoma, Papillary ; drug therapy ; pathology ; radiotherapy ; surgery ; Chemotherapy, Adjuvant ; Cisplatin ; administration & dosage ; Cystadenocarcinoma, Serous ; drug therapy ; pathology ; radiotherapy ; surgery ; Female ; Follow-Up Studies ; Humans ; Lymphatic Metastasis ; Menopause ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Paclitaxel ; administration & dosage ; Radiotherapy, Adjuvant ; Survival Rate ; Uterine Neoplasms ; drug therapy ; pathology ; radiotherapy ; surgery