ObjectiveTo explore the potential mechanism by which Huangqi Baijiang Yiren decoction （HBY） repairs the intestinal mucosal injury in the rat model of ulcerative colitis （UC） via the miR-21/suppressor of cytokine signaling 1 （SOCS1）/Janus kinase 1 （JAK1）/signal transducer and activator of transcription 6 （STAT6） signaling pathway. MethodsSixty SPF-grade male SD rats were randomly assigned into six groups： blank， model， low-dose （3.68 g·kg^-1） HBY， medium-dose （7.35 g·kg^-1） HBY， high-dose （14.5 g·kg^-1） HBY， and mesalazine （0.035 g·kg^-1）， with 10 rats in each group. The rat model of UC was established in other groups except the blank group by 3% dextran sulfate sodium solution. The rats were administrated with corresponding drugs once a day for 7 consecutive days since the 3th day after modeling. The histopathological changes of the colon were observed by hematoxylin-eosin staining， and the Robarts histopathology index （RHI） was scored. Enzyme-linked immunosorbent assay was employed to measure the levels of pro-inflammatory cytokines ［interleukin （IL）-6， IL-18， IL-1β， and tumor necrosis factor-α （TNF-α）］ in the serum. Real-time PCR was employed to determine the mRNA levels of miR-21， SOCS1， JAK1， and STAT6 in the colon tissue. Western blot was employed to determine the protein levels of SOCS1， JAK1， phosphorylated （p）-JAK1， STAT6， p-STAT6， Occludin， and Claudin-1 in the colon tissue. ResultsCompared with the blank group， the model group showed an increase in disease activity index （DAI） （P<0.01）， shortening of colon length （P<0.01）， severe histopathological damage in the colon tissue， and an increase in RHI， rises in serum levels of IL-6， IL-1β， IL-18， and TNF-α （P<0.01）， up-regulation in mRNA levels of miR-21， JAK1， and STAT6 and protein levels of p-JAK1 and p-STAT6 （P<0.01）， and down-regulation in mRNA and protein levels of SOCS1 and protein levels of Occludin and Claudin-1 （P<0.01）. The treatment with HBY reduced the DAI （P<0.01）， alleviated colon shortening and histopathological damage in the colon tissue， decreased the RHI （P<0.01）， lowered the serum levels of IL-6， IL-1β， IL-18， and TNF-α （P<0.01）， down-regulated the mRNA levels of miR-21， JAK1， and STAT6 （P<0.05， P<0.01）， up-regulated the mRNA level of SOCS1 （P<0.05）， up-regulated the protein levels of SOCS1， Occludin， and Claudin-1 （P<0.05， P<0.01）， and down-regulated the protein levels of p-JAK1 and p-STAT6 （P<0.05， P<0.01）. ConclusionHBY may modulate the miR-21/SOCS1/JAK1/STAT6 signaling pathway to suppress inflammatory responses and restore the intestinal mucosal barrier in UC rats.

AIM:This study aimed to observe the analgesic effects of Hegu acupoint catgut embedding in a rat model of labor and investigate its influence on biomarkers such as calcitonin gene-related peptide(CGRP)signals at the Hegu acupoint.METHODS:Thirty-six pregnant rats were randomly divided into three groups:control group,Hegu acu-puncture group,and Hegu catgut embedding group.Pain threshold changes were assessed using the tail immersion test and paw withdrawal thermal latency at four time points:pre-induction,before the onset of labor,at the onset of labor,and at the mid-stage of labor.Tissue samples from the Hegu acupoint were collected at the mid-stage of labor to detect the ex-pression of CGRP,substance P(SP),and mast cells using immunofluorescence.The concentrations of ATP and ade-nosine were measured using ELISA.RESULTS:Before labor induction,there was no significant difference in tail immer-sion test and paw withdrawal thermal latency among the three groups(P>0.05).Before the onset of labor,both the acu-puncture and catgut embedding groups exhibited significantly higher tail-flick times and paw withdrawal latencies com-pared to the control group(P<0.05).At labor initiation and mid-labor,the catgut embedding group had significantly higher tail-flick times and paw withdrawal latencies compared to both the control and acupuncture groups(P<0.05).During mid-labor,the expression of CGRP,SP,mast cells,ATP,and adenosine concentrations in the catgut embedding group was significantly higher than that in the control and acupuncture groups(P<0.05),with co-expression of CGRP,SP,and mast cells observed.CONCLUSION:Hegu acupoint catgut embedding effectively alleviates labor pain,and its mechanism may involve increased local expression of CGRP and SP,promoting mast cell degranulation,and increasing ATP release and its conversion to adenosine.

Precancerous lesions of gastric cancer is a key stage in the development of gastric cancer.The reprogramming of glucose metabolism is a prominent feature of precancerous lesions of gastric cancer.Hypoxic microenvironment and hypoxia-inducible factors are important factors influencing the occurrence of glucose metabolic reprogramming.This article summarized the relationship between hypoxic microenvironment and the reprogramming of glucose metabolism in precancerous lesions of gastric cancer,and concluded the relevant research on TCM compounds and effective components to improve hypoxic microenvironment and further regulate glycolysis for the treatment of this disease.It was concluded that the mechanism may be the inhibition of angiogenesis,regulation of signaling pathways and key proteins of glycolysis,expression of multiple enzymes,reduction of lactate secretion,inhibition of cell malignant proliferation and invasion.It explored the mechanism of Chinese materia medica in improving hypoxic microenvironment and regulating glycolysis,so as to provide reference for the prevention and treatment of precancerous lesions of gastric cancer.

Objective:To investigate the effects of intravenous thrombolysis combined with Xingnaojing injection on hemodynamic indexes and neurological function in patients with cerebral infarction. Methods:A total of 142 patients with cerebral infarction who were treated in Xing An Meng Hospital from April 2020 to May 2021 were included in this study. They were randomly divided into a control group ( n = 71, intravenous thrombolysis) and a Xingnaojing injection group ( n = 71, intravenous thrombolysis + Xingnaojing injection). Intracranial arterial hemodynamic indexes, National Institutes of Health Stroke Scale score, Fugl-Meyer Assessment Scale score, serum inflammatory factors, oxidative stress indexes, brain injury markers, and the incidence of adverse reactions were compared between the two groups. Results:After treatment, serum levels of interleukin-1β, interleukin-6, and tumor necrosis factor-α were significantly lower in the Xingnaojing injection group than the control group [interleukin-1β: (4.05 ± 0.83) ng/L vs. (6.85 ± 1.02) ng/L, interleukin-6: (43.61 ± 5.14) ng/L vs. (60.31 ± 7.04) ng/L, tumor necrosis factor-α: (35.93 ± 4.25) ng/L vs. (20.93 ± 3.11) ng/L, t = 17.94, 16.14, 15.37, all P < 0.001]. After treatment, the mean blood flow velocities of the anterior cerebral artery, middle cerebral artery, and posterior cerebral artery in the Xingnaojing injection group were significantly higher than those in the control group [anterior cerebral artery: (49.36 ± 5.28) cm/s vs. (41.15 ± 5.12) cm/s, middle cerebral artery: (61.27 ± 7.02) cm/s vs. (50.19 ± 6.08) cm/s, posterior cerebral artery: (44.92 ± 5.63) cm/s vs. (37.26 ± 4.93) cm/s, t = 9.40, 10.05, 8.62, all P < 0.001]. After treatment, the National Institutes of Health Stroke Scale score and Fugl-Meyer Assessment Scale score in the Xingnaojing injection group were superior to those in the control group [National Institutes of Health Stroke Scale score: (10.36 ± 1.52) points vs. (14.62 ± 2.05) points, Fugl-Meyer Assessment Scale score: (76.19 ± 8.08) points vs. (65.28 ± 7.14) points, t = 14.06, 8.52, both P < 0.05]. After treatment, the serum level of malondialdehyde in the Xingnaojing injection group was significantly higher than that in the control group [(6.35 ± 1.02) μmol/L vs. (10.05 ± 1.63) μmol/L), t = 16.21, P < 0.001]. The serum level of superoxide dismutase in the Xingnaojing injection group was significantly lower than that in the control group [(114.31 ± 13.69) U/L vs. (92.25 ± 10.16) U/L), t = 10.90, P < 0.001]. Serum levels of neuron-specific enolase and S100β in the Xingnaojing injection group were significantly lower than those in the control group [neuron-specific enolase: (24.01 ± 3.24) IU/L vs. (30.31 ± 4.02) IU/L, S100β: (0.73 ± 0.17) ng/L vs. (1.13 ± 0.22) ng/L, t = 10.28, 12.12, both P < 0.001). There was a significant difference in the incidence of adverse reactions between the two groups ( P > 0.05). Conclusion:Intravenous thrombolysis combined with Xingnaojing injection for the treatment of cerebral infarction can improve intracranial hemodynamics, reduce the inflammatory response and oxidative stress, and alleviate brain tissue injury. The combined therapy is beneficial to protect the neurological function of patients with cerebral infarction and is highly safe.

Chronic myeloid leukemia (CML) is a malignant tumor formed by clonal proliferation of bone marrow hematopoietic stem cells. With the improvement of disease awareness and the introduction of new drugs, more than 90% of CML patients can achieve long-term survival. However, a few patients still show drug resistance. This article reviews the mechanism of drug resistance in CML patients treated with tyrosine kinase inhibitor (TKI) and the characteristics of ABL kinase region mutation.

Objective:To investigate the clinical characteristics and prognosis of acute myeloid leukemia (AML) patients with positive TLS-ERG fusion gene.Methods:The clinical data of 9 AML patients with positive TLS-ERG fusion gene in the First Hospital of Jilin University from June 2013 to August 2020 were retrospectively analyzed, and the relevant literature was reviewed.Results:Among 9 patients with positive TLS-ERG fusion gene, there were 5 males and 4 females, with a median age of 16 years old (6-40 years old). Five patients received chemotherapy alone, 3 patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT), and 1 patient did not receive systematic treatment. Among 8 patients with systematic treatment, 1 patient had complete remission after the first induction chemotherapy and 5 patients had complete remission after induction therapy. The median overall survival time of 5 patients with chemotherapy alone was 1.5 months (1-11 months), of which 3 patients did not respond to the first course of treatment and died of infection, and 2 patients died after relapse. The median overall survival time of 3 patients with allo-HSCT was 16 months (13-17 months), of which 2 patients died after relapse and 1 patient had sustained molecular complete remission by the end of follow-up.Conclusions:AML with positive TLS-ERG fusion gene has low incidence rate and poor induction efficacy. Hematopoietic stem cell transplantation may partially improve the survival prognosis of patients, but it cannot overcome the adverse effect of positive TLS-ERG fusion gene on prognosis.

OBJECTIVES: To explore the effect of resveratrol (Res) on Kawasaki disease (KD)-induced myocardial injury and to evaluate its effect on apoptosis and autophagy. METHODS: Forty-eight juvenile male Sprague Dawley rats were randomly divided into a control group, a Res group, a lactobacillus casei cell wall extract (LCWE)-induced Kawasaki disease group (KD group), and a LCWE-induced Kawasaki disease + Res treatment group (Res+KD group). The control group was intraperitoneally injected with saline. The Res group was intraperitoneally injected with resveratrol (100 mg/kg). The KD group was intraperitoneally injected with 0.5 mL LCWE (1 mg/mL). The Res+KD group was intraperitoneally injected with 0.5 mL LCWE (1 mg/mL) and resveratrol (100 mg/kg). After 4 weeks, the left ventricular ejection fraction (LVEF) and short axis shortening rate (LVFS) were detected by echocardiography. The apoptotic rate was detected by terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) staining. The levels of B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), microtubule-associated protein 1 light chain 3β (LC3B), Beclin-1, autophagy related 5 (Atg5) and sequestosome-1 (p62) were detected by Western blotting. The formation of autophagosome was observed under transmission electron microscope. RESULTS: There was no significant difference in the above-mentioned indexes between the control group and the Res group (all CONCLUSIONS Res can attenuate the KD-induced myocardial injury via inhibiting the apoptosis and autophagy.
Animals ; Apoptosis ; Autophagy ; Male ; Mucocutaneous Lymph Node Syndrome/drug therapy* ; Rats ; Rats, Sprague-Dawley ; Resveratrol/therapeutic use* ; Stroke Volume ; Ventricular Function, Left

Objective: To investigate the current status and real performance of the detection of RUNX1-RUNX1T1 fusion transcript levels and WT1 transcript levels in China through interlaboratory comparison. Methods: Peking University People’s Hospital (PKUPH) prepared the samples for comparison. That is, the fresh RUNX1-RUNX1T1 positive (+) bone morrow nucleated cells were serially diluted with RUNX1-RUNX1T1 negative (-) nucleated cells from different patients. Totally 23 sets with 14 different samples per set were prepared. TRIzol reagent was added in each tube and thoroughly mixed with cells for homogenization. Each laboratory simultaneously tested RUNX1-RUNX1T1 and WT1 transcript levels of one set of samples by real-time quantitative PCR method. All transcript levels were reported as the percentage of RUNX1-RUNX1T1 or WT1 transcript copies/ABL copies. Spearman correlation coefficient between the reported transcript levels of each participated laboratory and those of PKUPH was calculated. Results: ①RUNX1-RUNX1T1 comparison: 9 samples were (+) and 5 were (-) , the false negative and positive rates of the 20 participated laboratories were 0 (0/180) and 5% (5/100) , respectively. The reported transcript levels of all 9 positive samples were different among laboratories. The median reported transcript levels of 9 positive samples were from 0.060% to 176.7%, which covered 3.5-log. The ratios of each sample’s highest to the lowest reported transcript levels were from 5.5 to 12.3 (one result which obviously deviated from other laboratories’ results was not included) , 85% (17/20) of the laboratories had correlation coefficient ≥0.98. ②WT1 comparison: The median reported transcript levels of all 14 samples were from 0.17% to 67.6%, which covered 2.6-log. The ratios of each sample’s highest to the lowest reported transcript levels were from 5.3-13.7, 62% (13/21) of the laboratories had correlation coefficient ≥0.98. ③ The relative relationship of the reported RUNX1-RUNX1T1 transcript levels between the participants and PKUPH was not always consistent with that of WT1 transcript levels. Both RUNX1-RUNX1T1 and WT1 transcript levels from 2 and 7 laboratories were individually lower than and higher than those of PKUPH, whereas for the rest 11 laboratories, one transcript level was higher than and the other was lower than that of PKUPH. Conclusion The reported RUNX1-RUNX1T1 and WT1 transcript levels were different among laboratories for the same sample. Most of the participated laboratories reported highly consistent result with that of PKUPH. The relationship between laboratories of the different transcript levels may not be the same.

Objective To evaluate the role of the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)or Janus kinase(JAK)/signal transducer and activator of transcription 3(STAT-3)signaling pathways in reduction of myocardial ischemia-reperfusion(I/R)injury by combination of limb ischemic and morphine postconditioning in rats.Methods Eighty SPF healthy male Sprague-Dawley rats,aged 8 weeks,weighing 280-320 g,were used in the study.Myocardial I/R was induced by occlusion of the left anterior descending branch of the coronary artery for 30 min followed by 120 min reperfusion.The rats were divided into 8 groups(n=10 each)using a random number table:I/R group,limb ischemic postconditioning group(LIP group),morphine postconditioning group(group MP),combination of limb ischemic and morphine postconditioning group(LIP+MP group)and signaling pathway blocker groups(I/Rb group,LIPb group,MPb group,LIP+MPb group).In I/R,LIP,MP and LIP+MP groups,the animals were sacrificed at the end of reperfusion,and myocardial specimens in ischemic and non-ischemic regions were obtained for determination of phosphorylated STAT-3(p-STAT-3),STAT-3,phosphorylated Akt(p-Akt)and Akt expression(by Western blot)and STAT-3 and Akt mRNA expression(by polymerase chain reaction).In I/Rb,LIPb,MPb and LIP+MPb groups,PI3K/Akt signaling pathway blocker LY294002 0.3 mg/kg was intravenously injected in 5 rats of each group,and JAK/STAT-3 signaling pathway blocker AG490 5 mg/kg was intravenously injected in the other 5 rats of each group.The animals were sacrificed at the end of reperfusion,and myocardial specimens in the ischemic region were obtained for determination of myocardial infarct size.Results Compared with I/R group,the p-STAT-3/STAT-3 ratio in LIP,MP and LIP+MP groups and p-Akt/Akt ratio in LIP+MP group were significantly increased,and the expression of STAT-3 and Akt mRNA was up-regulated in LIP+MP group(P<0.05).Compared with LIP and MP groups,the p-STAT-3/STAT-3 and p-Akt/Akt ratios were significantly increased,and the expression of STAT-3 and Akt mRNA was up-regulated in LIP+MP group(P<0.05).There was no significant difference in myocardial infarct size between the four groups when PI3K inhibitor LY294002 was applied(P>0.05).When JAK2 inhibitor AG490 was applied,the myocardial infarct size was significantly smaller in LIP+MPb group than in I/Rb,LIPb and MPb groups(P<0.05),and there was no significant difference in myocardial infarct size between I/Rb,LIPb and MPb groups(P>0.05).Conclusion Combination of limb ischemic and morphine postconditioning can enhance the activation of PI3K/Akt or JAK/STAT-3 signaling pathways,and the cardioprotection is dependent on the integrity of the PI3K/Akt signaling pathway and partially dependent on the integrity of the JAK/STAT-3 signaling pathway when applied in combination in rats.

Objective:To study the inductive effect of recombinant MUC1-MBP fusion protein combined with R848 on the immune activity of T cells in the mice,and to provide experimental basis for searching the suitable adjuvants of recombinant MUC1-MBP fusion protein.Methods:A total of 21 C57BL/6 mice were randomly divided into control group(treat with normal saline),MUC1-MBP+R848 group (treated with MUC1-MBP+R848),and MUC1-MBP+baillus calmette guerin(BCG) group(treated with MUC1-MBP+BCG)(n=7).After immunized for 4-7 d,the spleen tissue was taken and the spleen indexes of the mice in various groups were measured;the stimmulus index(SI) of the mice was detected by lymphocyte proliferation response;the levels of tumor necrosis factor-γ(TNF-γ) and interleukin-4(IL-4) were detected by ELISA method;the proprotions of T lymphocyte subsets in spleen cells were analyzed by flow cytometry.Results:Compared with control group,the spleen indexes,SI,and TNF-γ levels of the mice in MUC1-MBP+ R848 and MUC1-MBP+BCG groups were significantly increased (P<0.05 or P<0.01);the indexes metioned above of the mice in MUC1-MBP+ R848 were higher than those in MUC1-MBP+BCG group;the IL-4 levels had no significant difference(P>0.05).Compared with control group,the proprotions of CD3+T,CD4+T,and CD8+ T cells of the mice in MUC1-MBP+ R848 group and MUC1-MBP+BCG group were significantly increased(P<0.05 or P<0.01).Conclusion:Both MUC1-MBP fusion protein combined with R848 and BCG can induce the Th1 type of immune activity in the mice,and R848 is the potential candidate adjuvant for MUC1-MBP.