Objective:To explore the clinical characteristics,molecular characteristics,treatment and prognosis of pediatric Philadelphia chromosome-like acute lymphoblastic leukemia(Ph-like ALL)with a therapeutic target.Methods:A total of 27 patients of Ph-like ALL with targeted drug target were initially diagnosed in Children's Hospital of Soochow University from December 2017 to June 2021.The data of age,gender,white blood cell(WBC)count at initial diagnosis,genetic characteristics,molecular biological changes,chemotherapy regimen,different targeted drugs were given,and minimal residual disease(MRD)on day 19,MRD on day 46,whether hematopoietic stem cell transplantation(HSCT)were retrospective analyed,and the clinical characteristics and treatment effect were summarized.Survival analysis was performed by Kaplan-Meier method.Results:The intensity of chemotherapy was adjusted according to the MRD level during induced remission therapy in 27 patients,10 patients were treated with targeted drugs during treatment,and 3 patients were bridged with HSCT,1 patient died and 2 patients survived.Among the 24 patients who did not receive HSCT,1 patient developed relapse,and achieved complete remission(CR)after treatment with chimeric antigen receptors T cells(CAR-T).The 3-year overall survival,3-year relapse-free survival and 3-year event-free survival rate of 27 patients were(95.5±4.4)％,(95.0±4.9)％and(90.7±6.3)％respectively.Conclusion:Risk stratification chemotherapy based on MRD monitoring can improve the prognosis of Ph-like ALL in children,combined with targeted drugs can achieve complete remission as soon as possible in children whose chemotherapy response is poor,and sequential CAR-T and HSCT can significantly improve the therapeutic effect of Ph-like ALL in children whose MRD is continuously positive during induced remission therapy.

Objective:To investigate the effects of the serine/threonine kinase family member 1(PIM1)gene on the proliferation and apoptosis of acute myeloid leukemia(AML)U937 cells,and the regulation effect on Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)pathway.Methods:Bone marrow mononuclear cells from newly diagnosed adult AML patients and patients with iron deficiency anemia were collected and PIM1 mRNA expression was detected by RT-qPCR.AML cell line U937 cells were divided into U937 group(U937 cells were cultured normally),Si-PIM1 group(U937 cells were transfected with low expression adenovirus vector containing PIM1 mRNA),Si-NC group(U937 cells were transfected with low expression adenovirus vector without PIM1 mRNA),coumermycin A1(CoA1)group(JAK2 activator CoA1 was added to U937 cells at a concentration of 20 μ mol/L),and Si-PIM1+CoA1 group(U937 cells were transfected with adenoviral vector containing low expression of PIM1 mRNA and added with CoA1 at a concentration of 20 μ mol/L).After culture for 24 h,the expressions of PIM1 mRNA and protein,JAK2/STAT3 pathway,cell cycle and apoptosis-related proteins in U937 cells were detected by RT-qPCR and Western blot,the cell proliferation activity was detected by MTT assay,and flow cytometry was used to detect cell cycle changes and apoptosis rate.Results:The PIM1 mRNA expression level in bone marrow mononuclear cells in AML patients was higher than that in patients with iron deficiency anemia(P＜0.05).Compared with U937 group,PIM1 mRNA and protein,phosphorylated JAK2(p-JAK2)/JAK2,phosphorylated STAT3(p-STAT3)/STAT3,Cyclin D1,cyclin-dependent kinase 2(CDK2)protein,cell proliferation activity,S phase and G2/M phase proportions were decreased in Si-PIM1 group(all P＜0.05),while p27,Caspase-3 protein,G0/G,phase proportion and apoptosis rate were increased(all P＜0.05).However,the changes of above indicators in CoA1 group were just opposite to those in Si-PIM1 group,indicating that CoA1 could reverse the effect of Si-PIM1 on U937 cells.There were no significant differences in above indexes of U937 cells between U937 group,Si-PIM1+CoA1 group and Si-NC group(P＞0.05).Conclusion:Knockdown of PIM1 gene expression can inhibit U937 cell proliferation and promote apoptosis,in order to alleviate ALM process,which may be related to the inhibition of JAK2/STAT3 pathway activation.

AIM To analyze the constituents absorbed into blood and brain from Zhishe Tongluo Capsules.METHODS Sixteen rats were randomly assigned into four groups and given intragastric administration(3.1 g/kg),after which the cerebral ischemia-reperfusion injury(MACO)model was established,the blood and brain tissues were collected,and UHPLC-Q Exactive Focus MS/MS was adopted in the identification of prototype constituents.RESULTS Total 70 constituents were identified,20 of which were found in the blood,mainly including flavonoids,tanshinones and Ligusticum chuanxiong phthalides,and 7 of them could enter the brain through blood-brain barrier.Compared with the normal administration group,the MACO administration group demonstrated added constituents absorbed into blood containing 3-hydroxybenzoic acid,calycosin-7-glucoside,curcumenol,senkyunolide B,dihydrotanshinone I and cryptotanshinone;removed constituents absorbed into brain containing puerarin,elemicin,sedanolide,and added those containing salvianolic acid A,senkyunolide I,dihydrotanshinone I in the left brain tissues(infarcted side).CONCLUSION The constituents absorbed into blood and brain from Zhishe Tongluo Capsules,along with the enhanced absorptions of phthalides,quinones and phenols in MACO rats in vivo may be the active substances for treating cerebral infarction.

Objective: To investigate the association between gestational diabetes mellitus (GDM) and preterm birth subtypes. Methods: Based on the cohort of pregnant women in Anqing Prefectural Hospital, the pregnant women who received prenatal screening in the first or second trimesters were recruited into baseline cohorts; and followed up for them was conducted until delivery, and the information about their pregnancy status and outcomes were obtained through electronic medical record system and questionnaire surveys. The log-binomial regression model was used to explore the association between GDM and preterm birth [iatrogenic preterm birth, spontaneous preterm birth (preterm premature rupture of membranes and preterm labor)]. For multiple confounding factors, the propensity score correction model was used to compute the adjusted association. Results: Among the 2 031 pregnant women with a singleton delivery, the incidence of GDM and preterm birth were 10.0% (204 cases) and 4.4% (90 cases) respectively. The proportions of iatrogenic preterm birth and spontaneous preterm birth in the GDM group (n=204) were 1.5% and 5.9% respectively, while the proportions in non-GDM group (n=1 827) were 0.9% and 3.2% respectively, and the difference in the proportion of spontaneous preterm birth between the two groups was significant (P=0.048). Subtypes of spontaneous preterm were further analyzed, and the results showed that the proportions of preterm premature rupture of membranes and preterm labor in the GDM group were 4.9% and 1.0% respectively, while the proportions in the non-GDM group were 2.1% and 1.1% respectively. It showed that the risk of preterm premature rupture of membranes in GDM pregnant women was 2.34 times (aRR=2.34, 95%CI: 1.16-4.69) higher than that in non-GDM pregnant women. Conclusions: Our results showed that GDM might increase the risk of preterm premature rupture of membranes. No significant increase in the proportion of preterm labor in pregnant women with GDM was found.
Infant, Newborn ; Female ; Pregnancy ; Humans ; Premature Birth ; Diabetes, Gestational ; Obstetric Labor, Premature ; Hospitals ; Iatrogenic Disease

Objective: To investigate the application value of computed tomography (CT) examination of lymph node short diameter in evaluating cardia-left gastric lymph node metastasis in thoracic esophageal squamous cell carcinoma (ESCC). Methods: A total of 477 patients with primary thoracic ESCC who underwent surgical treatment in the Affiliated Cancer Hospital of Zhengzhou University from January 2013 to December 2017 were collected. All of them underwent McKeown esophagectomy plus complete two-field or three-field lymph node dissection. Picture archiving and communication system were used to measure the largest cardia-left gastric lymph node short diameter in preoperative CT images. The postoperative pathological diagnosis results of cardia-left gastric lymph node were used as the gold standard. Receiver operating characteristic (ROC) curve was used to evaluate the efficacy of CT lymph node short diameter in detecting the metastasis of cardia-left gastric lymph node in thoracic ESCC, and determine the optimal cut-off value. Results: The median short diameter of the largest cardia-left gastric lymph node was 4.1 mm in 477 patients, and the largest cardia-left gastric lymph node short diameter was less than 3 mm in 155 cases (32.5%). Sixty-eight patients had cardia-left gastric lymph node metastases, of which 38 had paracardial node metastases and 41 had left gastric node metastases. The lymph node ratios of paracardial node and left gastric node were 4.0% (60/1 511) and 3.3% (62/1 887), respectively. ROC curve analysis showed that the area under the curve of CT lymph node short diameter for evaluating cardia-left gastric lymph node metastasis was 0.941 (95% CI: 0.904-0.977; P<0.05). The optimal cut-off value of CT examination of the cardia-left gastric lymph node short diameter was 6 mm, and the corresponding sensitivity, specificity and accuracy were 85.3%, 91.7%, and 90.8%, respectively. Conclusion: CT examination of lymph node short diameter can be a good evaluation of cardia-left gastric lymph node metastasis in thoracic ESCC, and the optimal cut-off value is 6 mm.
Humans ; Esophageal Squamous Cell Carcinoma/pathology* ; Cardia/surgery* ; Esophageal Neoplasms/pathology* ; Lymphatic Metastasis/pathology* ; Lymph Nodes/pathology* ; Lymph Node Excision ; Tomography, X-Ray Computed/methods* ; Esophagectomy/methods* ; Retrospective Studies

Objective: To investigate the application value of computed tomography (CT) examination of lymph node short diameter in evaluating cardia-left gastric lymph node metastasis in thoracic esophageal squamous cell carcinoma (ESCC). Methods: A total of 477 patients with primary thoracic ESCC who underwent surgical treatment in the Affiliated Cancer Hospital of Zhengzhou University from January 2013 to December 2017 were collected. All of them underwent McKeown esophagectomy plus complete two-field or three-field lymph node dissection. Picture archiving and communication system were used to measure the largest cardia-left gastric lymph node short diameter in preoperative CT images. The postoperative pathological diagnosis results of cardia-left gastric lymph node were used as the gold standard. Receiver operating characteristic (ROC) curve was used to evaluate the efficacy of CT lymph node short diameter in detecting the metastasis of cardia-left gastric lymph node in thoracic ESCC, and determine the optimal cut-off value. Results: The median short diameter of the largest cardia-left gastric lymph node was 4.1 mm in 477 patients, and the largest cardia-left gastric lymph node short diameter was less than 3 mm in 155 cases (32.5%). Sixty-eight patients had cardia-left gastric lymph node metastases, of which 38 had paracardial node metastases and 41 had left gastric node metastases. The lymph node ratios of paracardial node and left gastric node were 4.0% (60/1 511) and 3.3% (62/1 887), respectively. ROC curve analysis showed that the area under the curve of CT lymph node short diameter for evaluating cardia-left gastric lymph node metastasis was 0.941 (95% CI: 0.904-0.977; P<0.05). The optimal cut-off value of CT examination of the cardia-left gastric lymph node short diameter was 6 mm, and the corresponding sensitivity, specificity and accuracy were 85.3%, 91.7%, and 90.8%, respectively. Conclusion: CT examination of lymph node short diameter can be a good evaluation of cardia-left gastric lymph node metastasis in thoracic ESCC, and the optimal cut-off value is 6 mm.
Humans ; Esophageal Squamous Cell Carcinoma/pathology* ; Cardia/surgery* ; Esophageal Neoplasms/pathology* ; Lymphatic Metastasis/pathology* ; Lymph Nodes/pathology* ; Lymph Node Excision ; Tomography, X-Ray Computed/methods* ; Esophagectomy/methods* ; Retrospective Studies

This study aimed to investigate the anti-inflammatory effect of astragaloside Ⅳ in mice with ulcerative colitis(UC) and its effect on the percentage of peripheral blood T helper(Th17) cells. Following the establishment of UC mouse model with 2% sodium dextran sulfate(DSS), mice in the positive control group and low-and high-dose astragaloside Ⅳ groups were treated with corresponding drugs by gavage. Disease activity index(DAI) was calculated, and serum interleukin-17(IL-17), tumor necrosis factor-α(TNF-α), and transforming growth factor-β(TGF-β) levels were assayed by ELISA. The pathological changes in colon tissue were observed by HE staining, and Th17/regulatory T cells(Treg) ratio in the peripheral blood was determined by flow cytometry. Western blot was conducted for detecting the relative protein expression levels of forkhead box protein P3(Foxp3) and retinoic acid-related orphan nuclear receptor γT(ROR-γt). The findings demonstrated that in normal mice, the colonic structure was intact. The goblet cells were not reduced and the glands were neatly arranged, with no mucosal erosion, bleeding, or positive cell infiltration. In the model group, the colonic mucosal structure was seriously damaged, manifested as disordered arrangement or missing of glands, vascular dilatation, congestion, and massive inflammatory cell infiltration. The pathological injury of colon tissue was alleviated to varying degrees in drug treatment groups. Compared with the normal group, the model group exhibited elevated percentage of Th17 cells, increased IL-17 and TNF-α content, up-regulated relative ROR-γt protein expression, lowered TGF-β, reduced percentage of Treg cells, and down-regulated relative Foxp3 protein expression. The comparison with the model group showed that DAI score, pathological score, percentage of Th17 cells, IL-17 and TNF-α content, and relative ROR-γt protein expression in the positive control group, low-dose astragaloside Ⅳ group, and high-dose astragaloside Ⅳ group were decreased, while TGF-β content, percentage of Treg cells, and relative Foxp3 protein expression were increased. The DAI score, pathological score, percentage of Th17 cells, IL-17 and TNF-α content, and relative ROR-γt protein expression in the low-dose astragaloside Ⅳ group were higher than those in the positive control group, whereas the content of TGF-β, percentage of Treg cells, and relative Foxp3 protein expression were lower. DAI score, pathological score, percentage of Th17 cells, IL-17 and TNF-α content, relative ROR-γt protein expression in the high-dose astragaloside Ⅳ group declined in contrast to those in the low-dose astragaloside Ⅳ group, while the TGF-β content, percentage of Treg cells, and relative Foxp3 protein expression rose. There was no significant difference between the positive control group and the high-dose astragaloside Ⅳ group. Astragaloside Ⅳ is able to inhibit inflammatory response and diminish the percentage of Th17 cells in mice with UC.
Animals ; Colitis, Ulcerative/metabolism* ; Mice ; Saponins/pharmacology* ; T-Lymphocytes, Regulatory ; Th17 Cells ; Triterpenes/pharmacology*

The present study designed and prepared near-infrared responsive sinomenine hydrochloride(SIN) reservoir microneedles and evaluated the feasibility of this type of microneedles in increasing the drug loading and transdermal absorption by characterizing their mechanical properties and in vitro release characteristics.SIN was selected as the model drug, and methoxy poly(ethylene glycol) poly(caprolactone)(mPEG-PCL) copolymers and indocyanine green(ICG) were employed as amphiphilic block copolymers and light inductor to prepare near-infrared responsive nanoparticles.Based on the preparation principle of bubble microneedles, near-infrared responsive SIN reservoir microneedles were designed and prepared.The features of the near-infrared responsive SIN reservoir microneedles were characterized by measuring the morphology, length, mechanical properties, and skin penetration of microneedles.Meanwhile, the drug release performance of reservoir microneedles was evaluated by in vitro release assay.The results showed that the prepared SIN microneedles were conical, with an exposed tip height of about 650 μm.Each needle could load about 0.5 mg of drugs per square centi-meter, and this type of microneedle showed good mechanical properties and performance in skin penetration.The results of the in vitro release assay showed that the 24 h cumulative release per unit area and release rate of the microneedle were 825.61 μg·cm~(-2) and 74.3%, respectively, which indicated that its release kinetics was in line with the first-order kinetic model.This study preliminarily proved that the reservoir microneedle could effectively increase the drug loading with good mechanical properties and release perfor-mance.
Drug Delivery Systems/methods* ; Drug Liberation ; Indocyanine Green ; Morphinans ; Needles ; Polyethylene Glycols

OBJECTIVE: To investigate the effect of baicalein on polymicrobial sepsis-induced immune dysfunction and organ injury. METHODS: A sepsis model was induced in Sprague-Dawley rats via caecal ligation and puncture (CLP). Specific pathogen free rats were randomly divided into a sham group, CLP group and CLP + baicalein (Bai) group (n=16 each). Rats in the CLP + Bai group were intravenously injected with baicalein (20 mg/kg) at 1 and 10 h after CLP. Survival rate, bacterial load, and organ damage were assessed. Then each group was evaluated at 6, 12, and 24 h to investigate the effect of baicalein on immune cells and inflammatory cytokines in septic rats. RESULTS: Baicalein treatment significantly improved the survival of septic rats, decreased the bacterial burden, and moderated tissue damage (spleen, liver, and lung), as observed by haematoxylin and eosin staining. Septic rats treated with baicalein had strikingly increased proportions of CD3⁺CD4⁺ T cells and ratios of CD4⁺/CD8⁺ T cells in the peripheral blood and spleen (all P<0.05). Moreover, baicalein treatment decreased the apoptotic rate of whole white blood cells and spleen cells at 24 h after surgery (P<0.05). Baicalein significantly reduced the levels of tumor necrosis factor α and interleukin-6 (IL-6) and increased IL-10, and the expression levels of galectin 9 were also raised in the spleen (P<0.01). CONCLUSION Baicalein may be an effective immunomodulator that attenuates overwhelming inflammatory responses in severe abdominal sepsis.
Animals ; CD8-Positive T-Lymphocytes ; Flavanones ; Inflammation/drug therapy* ; Rats ; Rats, Sprague-Dawley ; Sepsis/drug therapy*

OBJECTIVE: To evaluate whether the efficacy of Getong Tongluo Capsule (, GTC, consisted of total flavone of Radix Puerariae) on improving patients' quality of life and lowering blood pressure are superior to the extract of Ginkgo biloba (EGB) for patients with convalescent-phase ischemic stroke and primary hypertension. METHODS: This randomized, positive-drug- and placebo-controlled, double-blind trial was conducted from September 2015 to October 2017. Totally 477 eligible patients from 18 hospitals in China were randomly assigned in a 2:1:1 ratio to the following interventions, twice a day for 12 weeks: (1) GTC 250 mg plus EGB-matching placebo 40 mg (237 cases, GTC group), (2) EGB 40 mg plus GTC-matching placebo 250 mg (120 cases, EGB group) or (3) GTC-matching placebo 250 mg plus EGB-matching placebo 40 mg (120 cases, placebo group). Moreover, all patients were orally administered aspirin enteric-coated tablets 100 mg, once a day for 12 weeks. The primary outcome was the Barthel Index (BI). The secondary outcomes included the control rate of blood pressure and National Institutes of Health Stroke Scale (NIHSS) scores. The incidence and severity of adverse events (AEs) were calculated and assessed. RESULTS: The BI relative independence rates, the clinical recovery rates of NIHSS, and the total effective rates of NIHSS in the GTC and EGB groups were significantly higher than the placebo group at 12 weeks after treatment (P<0.05), and no statistical significance was found between the GTC and EGB groups (P>0.05). The control rate of blood pressure in the GTC group was significantly higher than the EGB and placebo groups at 12, 18 and 24 weeks after treatment (P<0.01). There were no statistically significant differences in the incidences of AEs, adverse drug reactions, or serious AEs among the 3 groups (P>0.05). CONCLUSION GTC exhibited significant efficacy in improving patients' quality of life as well as neurological function and controlling hypertension. (Registration No. ChiCTR1800016667).