Background:The burden of Crohn's disease(CD)is rising globally,and the efficacy and safety of ustekinumab(UST)in treatment of CD need to be further verified.Aims:To assess the short-term efficacy and safety of UST in CD patients.Methods:A single-center retrospective observational study was conducted in the First Affiliated Hospital of Kunming Medical University.The clinical data of CD patients treated with UST from January 2020 to December 2023 were analyzed retrospectively.The clinical activity and endoscopic severity of the disease were assessed using Crohn's disease activity index(CDAI)and simple endoscopic score for Crohn's disease(SES-CD),respectively.The primary outcomes were clinical response(CDAI score decreased≥70 points,or CDAI score decreased<70 points but the total score<150)and clinical remission(CDAI score<150),while the secondary outcomes included endoscopic response(SES-CD decreased≥50%),endoscopic remission(SES-CD≤2),changes of inflammatory and nutritional indicators,and the adverse events.Results:Twenty-seven CD patients were included,of which,16 were males,and 11 were females,with median disease duration of 3.00 years.After treatment with UST,the median CDAI score decreased from 213.00(178.83,302.98)at baseline to 129.83(89.67,151.33)at week 16/20 and 95.07(67.45,178.34)at week 32(all P<0.017).The clinical response rate and remission rate at week 16/20 were 92.6%and 70.4%,respectively,and those at week 32 were 95.5%and 72.7%,respectively.When patients were stratified as biologic na?ve and exposure,or as with and without dose optimization,no significant differences were found in clinical response and remission rates among various subgroups.Seventeen patients reviewed endoscopy at week 16/20,the SES-CD decreased significantly from baseline(5.47±4.53 vs.9.88±4.58,P<0.05),with the endoscopic response rate and remission rate of 35.3%and 23.5%,respectively.C-reactive protein decreased significantly from baseline at week 16/20 and week 32 of treatment(all P<0.017),while the platelet count,hemoglobin,albumin and body mass index only showed insignificant improving trends.No serious adverse events were observed during the medication period.Conclusions:UST can improve the clinical symptoms,endoscopic manifestations,and systemic inflammation effectively in CD patients in short-term follow-up,and represents a good safety profile.

Objective To compare the sedative effect and safety of remimazolam and midazolam in synchronous electrical cardioversion in patients with atrial fibrillation.Methods Thirty-two patients with at-rial fibrillation receiving synchronous electrical cardioversion from January 2021 to December 2022 were en-rolled,22 males and 10 females,aged 18-80 years,BMI 20-30 kg/m2,ASA physical status Ⅱ or Ⅲ.The patients were randomly divided into two groups using random number table method:remimazolam group and midazolam group,16 patients in each group.The remimazolam group was sedated with 0.2 mg/kg of intra-venous remimazolam,and the midazolam group was sedated with 0.025 mg/kg of midazolam intravenously,and the drug injection time in both groups was 1 min.The anesthesia onset time,awakening time,and ori-entation recovery time were recorded.SBP,DBP,and SpO2 were recorded before anesthesia induction(T,),when the eyelash reflex was absent(T2),after the completion of electrical cardioversion(T3),and at the time of awakening(T4).Neurobehavioral cognitive state examination(NCSE)was performed 5 mi-nutes after the patients were awake,including language ability,structural ability,memory,calculation abil-ity and reasoning ability,and the pass rate of each ability test was calculated.The occurrence of adverse re-actions during surgery(body movement,apnea)and within 12 hours after surgery(nausea,vomiting,and chest pain)was recorded.Results Compared with the midazolam group,the anesthesia onset time,awak-ening time,and orientation recovery time in the remimazolam group were significantly shortened(P＜0.05).There was no significant difference in SBP,DBP,and Sp02 between the two groups at different time points.Compared with the midazolam group,the pass rate of the reasoning ability test was higher in the remimazolam group 5 minutes after awakening(P＜0.05).There was no significant difference in the inci-dence of adverse reactions between the two groups.Conclusion Compared with midazolam,remimazolam has faster onset of sedation,faster awakening,faster recovery of orientation in synchronous electrical cardio-version of atrial fibrillation,and faster recovery of reasoning ability in NCSE after synchronous electrical car-dioversion.

Objective: To investigate the effect of activation of the stimulator of interferon genes(STING) pathway on macrophage polarization function and its role in T-cell response. Methods: Mouse macrophage RAW264.7 cells were used.STING signaling related proteins in RAW264.7 macrophage treated with STING agonist diABZI were analyzed by Western blot,including TANK-binding kinase-1(TBK1),interferon regulatory factor-3(IRF3),STING,p-TBK1,p-IRF3,p-STING.The polarization of macrophage RAW264.7 cells treated with diABZI was analyzed by flow cytometry.Co-culture of diABZI-treated RAW264.7 macrophage and T cells was applied to evaluate the change of T cell response. Results: STING signaling related proteins were upregulated in macrophage RAW264.7 cells treated with diABZI for 3 hours.The expression of CD86 was upregulated on the surface of macrophages after 12 hours of diABZI treatment,and the CD86/CD206 ratio was elevated,which presented the M1 polarization phenotype.When coculturing diABZI-treated macrophage RAW264.7 cells with T cells,the cytokine secretion ability of T cells including CD4+T and CD8+T cells was enhanced and the expression of CD107a in CD8+T cells was upregulated. Conclusion STING signaling induces M1 polarization of macrophages which enhance the function of T cells,especially CD8+T cell immune response.

Background:The burden of Crohn's disease(CD)is rising globally,and the efficacy and safety of ustekinumab(UST)in treatment of CD need to be further verified.Aims:To assess the short-term efficacy and safety of UST in CD patients.Methods:A single-center retrospective observational study was conducted in the First Affiliated Hospital of Kunming Medical University.The clinical data of CD patients treated with UST from January 2020 to December 2023 were analyzed retrospectively.The clinical activity and endoscopic severity of the disease were assessed using Crohn's disease activity index(CDAI)and simple endoscopic score for Crohn's disease(SES-CD),respectively.The primary outcomes were clinical response(CDAI score decreased≥70 points,or CDAI score decreased<70 points but the total score<150)and clinical remission(CDAI score<150),while the secondary outcomes included endoscopic response(SES-CD decreased≥50%),endoscopic remission(SES-CD≤2),changes of inflammatory and nutritional indicators,and the adverse events.Results:Twenty-seven CD patients were included,of which,16 were males,and 11 were females,with median disease duration of 3.00 years.After treatment with UST,the median CDAI score decreased from 213.00(178.83,302.98)at baseline to 129.83(89.67,151.33)at week 16/20 and 95.07(67.45,178.34)at week 32(all P<0.017).The clinical response rate and remission rate at week 16/20 were 92.6%and 70.4%,respectively,and those at week 32 were 95.5%and 72.7%,respectively.When patients were stratified as biologic na?ve and exposure,or as with and without dose optimization,no significant differences were found in clinical response and remission rates among various subgroups.Seventeen patients reviewed endoscopy at week 16/20,the SES-CD decreased significantly from baseline(5.47±4.53 vs.9.88±4.58,P<0.05),with the endoscopic response rate and remission rate of 35.3%and 23.5%,respectively.C-reactive protein decreased significantly from baseline at week 16/20 and week 32 of treatment(all P<0.017),while the platelet count,hemoglobin,albumin and body mass index only showed insignificant improving trends.No serious adverse events were observed during the medication period.Conclusions:UST can improve the clinical symptoms,endoscopic manifestations,and systemic inflammation effectively in CD patients in short-term follow-up,and represents a good safety profile.

Objective: To construct the mmu-miR-155 eukaryotic overexpression vector pmR-155 and to investigate its effect on HBV replication and expression of PTEN in vivo. Methods: The mmu-mir-146a precursor gene fragment pre-mmu-mir-146a was amplified by PCR, then connected to the pmR-mCherry plasmid vector after double enzyme digestion, the accuracy of recombinant vector was verified by colony PCR、double enzyme digestion and sequencing; then the recombinant vector was transfected HBV transgene mice(Experimental Group)with hydrodynamics-based injection via vena caudalis, and pmR-mCherry plasmid、PBS were respectively transfected into the mice as Empty plasmid Group、Blank Group. The concentration of IFN-γ in the serum was detected by ELISA. The expression of SOCS1、PTEN mRNA in the liver was detected by qPCR at 30d post-transfectioned. The Western blot was performed to detect the changes in SOCS1、PTEN、HBX in the liver tissue at 30 d post-transfectioned. The results were analyzed with Student’s t-test, or one-way analysis of variance and the least significant difference test. Results: the colony PCR、double enzyme digestion and sequencing verified that the gene was inserted into the pmR-mCherry vector. Compared with Blank Group, the expression of miR-155 in the Experimental Group was significantly increased(t = 8.90, P < 0.01); the concentration of IFN-γ in the Experimental Group was significantly increased(F = 26.58, P < 0.01); the mRNA(F_{SOCS1 mRNA} = 19.72, P < 0.01; F_{PTEN mRNA} = 7.38, P < 0.05) and protein(F_SOCS1 = 50.30, P < 0.01; F_PTEN = 129.00, P < 0.01) expression of COCS1、PTEN was significantly decreased in the Experimental group and the protein of HBX was also significantly(F_HBX = 77.97, P < 0.01). Conclusion The pmR-155 eukaryotic overexpression vector is successfully constructed, this recombinant vector can express miR-155 stably; miR-155 can down-regulate cocs1、PTEN gene expression and up-regulate the expression of IFN-γ, it can inhibit the replication of HBV and a potential targets to treating hepatocellular carcinoma.

Objective To translate and revise the Atrial Fibrillation-Quality of Life -18 (AF-QoL-18),and to test its reliability and validity. Methods The Chinese version of AF-QoL-18 was developed through the process of translation, back- translation, cultural adaptation, and preliminary experiment. A total of 187 atrial fibrillation (AF) patients in eight hospitals in Jiangsu province were investigated using the Chinese version to test the reliability and validity. Results Exploratory factor analysis identified three factors, including physiological, psychological and sexual dimensions, which could explain 65.055%of the total variance. The content validity index was 0.969. The Cronbach α coefficient was 0.915 and the retest reliability was 0.948 for the total scale. Conclusions The Chinese version AF-QoL-18 has proved to be reliable and valid.It can be used to measure the quality of life of AF patients in China.

Objective To construct the has-miR 146a eukaryotic overexpression vector pmR 146a and to explore its effect on the expression of c-Myc gene in HepG2.2.15 cells.Methods The has-miR-146a precursor gene fragment pre-has-miR-146a was amplified by PCR,then connected to the pmR-mCherry plasmid vector after double enzyme digestion,the accuracy of recombinant vector was verified by colony PCR,double enzyme digestion and sequencing;then the recombinant vector was transfected into HepG2.2.15 cells as the experimental group,meanwhile the empty vector group (transfecting pmR-mCherry empty plasmid group) and blank group(transfecting reagent lip2000+PBS),then the fluorescent protein expression amount was observed under the fluorescence microscopy at 24,48 h;the expression of has miR-146a was evaluated by qPCR;at 24,48 h after transfection,the expression levels of c-Myc gene mRNA were detected by qPCR,and the c-Myc protein expression level after 48 h was detected by Western blot.Results The colony PCR,double enzyme digestion and sequencing verified that the pre-has-miR-146a gene fragment was inserted into the pmR-mCherry vector;at 24,48 h after transfection in the experimental group and empty vector group,intracellular strong fluorescence was seen by fluorescent microscope,the transfection efficiency was at 50％-60％ contrasting without fluorescence;the has-miR-146a expression level in the experimental group was significantly higher than that in the empty vector group and blank group (P＜0.01);the c-Myc mRNA expression at 24,48 h after tranfection was significantly lower than that in the empty vector group and blank group (P＜0.05);the protein expression amount at 48 h after transfection was lower than that in the empty vector group and blank group (P＜0.01).Conclusion The pmR-146a eukaryotic overexpression vector is successfully constructed,this recombinant vector can express miR-146a stably;miR-146a can down-regulate c-Myc cancer gene expression,which can serve as one of potential targets for treating hepatocellular carcinoma.

Objective To construct the miRNA‐21 eukaryotic overexpression vector pmR‐21 and to explore its regulation effect on the expression of c‐myc gene in HepG2 .2 .15 cells .Methods The miRNA‐21 precursor gene fragment pre‐miRNA‐21 was amplified by PCR ,then connected to the pmR‐mCherry plasmid vector after double enzyme digestion ,the accuracy of the recombi‐nant vector was verified by double enzyme digestion and sequencing ;then the recombinant vector was transfected into HepG2 .2 .15 cells ,the fluorescent protein expression was observed under the fluorescence microscopy at 24 h and the transfection efficiency was detected by flow cytometry ;the expression of miRNA‐21 was evaluated by real‐time quantitative PCR;at 72 h after transfection ,the expression levels of c‐myc gene were detected by RT‐PCR and Western blot ;CCK‐8 was used to detect the cell proliferation in each group .Results The double enzyme digestion and Western blot verified that the target gene fragment was inserted into the pmR‐mCherry vector;at 24 h after transfection ,intracellular strong fluorescence was seen ,the transfection efficiency was higher than 50% ;miRNA‐21 expression level of the pmR‐21 recombinant vector group was significantly increased;c‐myc gene expression was increased in the pmR‐21 recombinant vector group at 72 h after transfection ,the cell proliferation in the pmR‐21 recombinant group was faster than that in the control group(P<0 .05) .Conclusion The pmR‐21 eukaryotic overexpression vector is successfully con‐structed ,this recombinant vector can express miRNA‐21 stably ;miRNA‐21 can up‐regulate c‐myc gene expression ,c‐myc gene is one of miR‐21′s targets for playing a cancer‐promoting action .

Cardiomyopathies ; etiology ; Humans ; Polymyositis ; complications

Objective To evaluate the effect of intra-aortic balloon pumping(IABP)in treating serious coronary heart disease. MethodsA retrospective analysis was performed on 19 patients who suffered from serious coronary heart disease and accepted IABP therapy,the differences of mean arterial pressure before and after treatment were compared.In order to compare the in-hospital mortality,the patients were divided into 2 groups:6 of 19 patients accepted single IABP therapy,13 of 19 patients attempted IABP and revascularization(thrombolytic/percutaneous coronary intervention/coronary artery bypass graft)therapy. ResultsBedside success rate of IABP operation was 100%without complication.Effective rate was 89.5%(17/19),2 patients who were irreversible phase of cardiogenic shock,were an ineffective treatment.The patient's mean arterial pressure increased from(52.1 ± 18.4)mm Hg to(78.3 20.8)mm Hg after using IA BP for 30 minutes(P＜0.01).The in-hospital mortality was significantly lower in patients received revascularization therapy in addition to IABP compared with patients who had IABP support alone 7.7% vs 83.3%(P＜0.01). ConclusionIABP in treating serious coronary heart disease was safe and effective.IABP treatment before irreversible phase of shock and revascularization therapy following IABP are the key to decrease in-hospital mortality.