OBJECTIVES: To compare the anti-inflammatory, antibacterial and analgesic effects of Yinqiao Powder (YQS) formulated granules and decoction. METHODS: We first evaluated the anti-inflammatory effects of the two dosage forms of YQS in a LPS-induced RAW 264.7 cell model using RT-qPCR and Western blotting. We further constructed zebrafish models of inflammation by copper sulfate exposure, caudal fin transection, or LPS and Poly (I:C) microinjection, and evaluated anti-inflammatory effects of YQS granules and decoction by examining neutrophil aggregation and HE staining findings. In a mouse model of acute lung injury (ALI) induced by intratracheal LPS instillation, the effects of YQS gavage at 10, 15, and 20 g/kg on lung pathologies were evaluated by calculating lung wet-dry weight ratio and using HE staining, ELISA and Western blotting. The microbroth dilution method was used to evaluate the antibacterial effect of YQS. Mouse pain models established by hot plate and intraperitoneal injection of glacial acetic acid were used to evaluate the analgesic effects of YQS at 10, 15, and 20 g/kg. RESULTS: Both YQS granules and decoction significantly reduced TNF-α, IL-6, and IL-1β expressions and p-STAT3 (Tyr 705) phosphorylation level in LPS-induced RAW 264.7 cells, and obviously inhibited neutrophil aggregation in the zebrafish models. In ALI mice, YQS granules and decoction effectively ameliorated lung injury, lowered lung wet-dry weight ratio, and reduced p-STAT3 (Tyr 705) expression and TNF-α and IL-6 levels. YQS produced obvious antibacterial effect at the doses of 15.63 and 31.25 mg/mL, and significantly reduced body torsion and increased pain threshold in the mouse pain models. CONCLUSIONS The two dosage forms of TQS have similar anti-inflammatory, antibacterial and analgesic effects with only differences in their inhibitory effect on TNF-α, IL-6 and IL-1β mRNA expressions in LPS-induced RAW 264.7 cells.
Animals ; Mice ; Drugs, Chinese Herbal/pharmacology* ; Anti-Inflammatory Agents/pharmacology* ; Analgesics/pharmacology* ; RAW 264.7 Cells ; Zebrafish ; Anti-Bacterial Agents/pharmacology* ; Powders ; Tumor Necrosis Factor-alpha/metabolism* ; Acute Lung Injury/drug therapy* ; Interleukin-6/metabolism* ; Lipopolysaccharides

OBJECTIVE To systematically review the efficacy and safety of ticagrelor versus clopidogrel in CYP2C19 loss-of-function carriers with mild ischemic stroke or transient ischemic attack(TIA). METHODS Databases such as PubMed, Embase, the Cochrane Library, CNKI, and Wanfang were systematically searched, and the search period was from database establishment to June 2022. Two reviewers independently screened literature, extracted data, and evaluated the methodological quality of the included studies. Meta-analysis was performed using RevMan 5.3 software. RESULTS A total of 2 studies with 7 087 patients were included. Compared with clopidogrel, ticagrelor reduced the incidence of stroke[RR=0.78, 95%CI(0.66−0.93), I2=0%, P=0.007] and vascular event[RR=0.78, 95%CI(0.66−0.91), I2=0%, P=0.002] in patients with mild ischemic stroke or TIA carrying the CYP2C19 loss-of-function allele. The incidence of any bleeding[HR=2.18, 95%CI(1.66−2.85)] and minor bleeding[HR=2.41, 95%CI (1.81−3.20)] in the ticagrelor-aspirin group was higher than that in the clopidogrel-aspirin group, and dyspnea (1.2% vs 0.2%, P<0.001) and arrhythmias(1.7% vs 0.8%, P=0.001) were more common in the ticagrelor-aspirin group than in the clopidogrel-aspirin group. There was no significant difference in the incidence of severe bleeding between the two groups. CONCLUSION Compared with clopidogrel, ticagrelor reduces the incidence of stroke and vascular events in patients with mild ischemic stroke or TIA carrying the CYP2C19 loss-of-function allele, and did not increase the risk of severe bleeding. However, the ticagrelor group had a higher incidence of minor bleeding, dyspnea and arrhythmias.

Objective To explore the molecular mechanism of lipopolysaccharide(LPS)on the contraction of pregnant uterine smooth muscle at tissue and cellular levels.Methods C57BL/6J mice at 16 days of gestation were randomly divided into control group and LPS group.The mice in LPS group were intraperitoneally injected with 20 μg in LPS solution to establish the model of preterm birth,and the mice in control group were intraperitone-ally injected with the same amount of normal saline.Isolated uterine muscle strips were used to detect changes in the contractile function of the tissue,as well as changes in the expression and function of the contraction key signa-ling molecule TWIK-related K+channel 1(TREK-1).Primary cultured pregnant mouse uterine smooth muscle cells were used to detect the expression of TREK-1 under the regulation of LPS.Results The contractility of mouse u-terine tissues was significantly enhanced by LPS,and the protein expression of TREK-1,a key signal for contrac-tion,was significantly reduced,and activation of TREK-1 resulted in a significant down-regulation of the enhanced contractility of mouse uterine tissues in the LPS group.However,there was no significant difference in the expres-sion of TREK-1 protein,which was highly expressed in the smooth muscle of pregnant mice,when LPS acted on the primary uterine smooth muscle cells of pregnant mice.Conclusion Uterine contractility is enhanced in pregnant mice uterine tissues by inhibiting TREK-1 expression and function in response to LPS,and it may be one of the mechanisms by which LPS induces preterm labor.However,the effect of LPS on TREK-1 on mouse pregnant uter-ine smooth muscle cells may be realized through intercellular signaling and not directly on uterine smooth muscle cells.This further suggests that the animal and histological experiments cannot be completely replaced by isolated cell experiments in the study of inflammatory preterm labor.

In recent years,with the gradual maturity of achievable remote collection of digital health technology,more and more clinical research have applied this technology to improve the quality of data collection and reduce the burden on subjects.However,its technological characteristics of detachment from the diagnostic and treatment environment and real-time transmission of sensitive information also pose corresponding risks to the protection of subjects'rights and interests and data standardization management,among which personal information protection and data control permissions are more prominent issues.Based on risk analysis and regulatory review,this paper explored the responsibilities of multiple parties,including the sponsors,researchers,clinical trial institutions,and ethics committee,as well as proposed five elements of special concern for ethical review,with a view to providing a reference for promoting the standardized development of digital health technology in clinical research.

Objective:To explore the genetic background for a patient with refractory myelodysplastic/myeloproliferative neoplasm (MDS/MPN) with co-morbid neutrophilia patient.Methods:A MDS/MPN patient who was admitted to the First Affiliated Hospital of Nanjing Medical University in May 2021 was selected as the study subject. RNA sequencing was carried out to identify fusion genes in his peripheral blood mononuclear cells. Fusion gene sequence was searched through transcriptome-wide analysis with a STAR-fusion procedure. The novel fusion genes were verified by quantitative real-time PCR and Sanger sequencing.Results:The patient, a 67-year-old male, had progressive thrombocytopenia. Based on the morphological and molecular examinations, he was diagnosed as MDS/MPN with co-morbid neutropenia, and was treated with demethylating agents and Bcl-2 inhibitors. Seventeen months after the diagnosis, he had progressed to AML. A novel fusion gene NCOR1: : GLYR1 was identified by RNA-sequencing in his peripheral blood sample, which was verified by quantitative real-time PCR and Sanger sequencing. The patient had attained morphological remission after a DCAG regimen (a combinatory chemotherapy of decitabine, cytarabine, aclarubicin and granulocyte colony-stimulating factors) plus Chidamide treatment. A significant decrease in the NCOR1: : GLYR1 expression was revealed by quantitative real-time PCR at post-chemotherapy evaluation. Conclusion:NCOR1: : GLYR1 gene is considered as the pathogenic factor for the MDS/MPN patient with neutropenia.

Objective To compare the anti-inflammatory,antitumor and anti-bacterial effects of the single extract(in granules)and the prepared drug in pieces of Forsythia Suspense(Lianqiao,a traditional Chinese herbal medicine).Methods In zebrafish embryo models of CuSO4 exposure,tail transection and LPS microinjection-induced inflammation,the anti-inflammatory effects of 10 μg/mL DEX,single extract of Forsythia Suspense,and the water extract of the prepared drug(400,600,and 800 μg/mL)were evaluated by observing neutrophil counts,RT-qPCR,HE staining and survival analysis.Zebrafish embryo models bearing different human tumor cell xenografts were used to assess the anti-tumor effect of the drugs in different dosage forms by fluorescence staining and HE staining.The microbroth dilution method was used to evaluate the antibacterial efficacy of the drugs.Results In the zebrafish embryo models of inflammation,both of the two dosage forms of Forsythia Suspense significantly inhibited neutrophil aggregation,reduced the mRNA expressions of TNF-α,IL-6,P38,Jnk,Erk and P65,and increased the survival rate of zebrafish.They both showed obvious inhibitory effects against xenografts of different human cancer cells including colon cancer cells(HCT116),pancreas adenocarcinoma cells(PANC-1),lung cancer cells(A549),liver cancer cells(Hep3B)and cervical carcinoma cells(Hela)in zebrafish embryos,and exhibited strong anti-bacterial effects at the concentration of 15.63 mg/mL.Conclusion The two dosage forms of Forsythia Suspense have similar anti-inflammatory,antitumor and antibacterial effects,but their effects for inhibiting IL-6,P65,and Jnk mRNA expressions and HCT116 cell proliferation differ significantly at low doses in zebrafish.

Objective:To establish an automated labeling method of 18F-AlF-1, 4, 7-triazocyclohexane-1, 4, 7-triacetic acid- D-Phe1-Tyr3-Thr8-octreotide (NOTATATE) and perform neuroendocrine tumor (NET) imaging. Methods:Based on the GE-FASTLab2 synthesis module, 18F-AlF-NOTATATE was automatically prepared by one-step chelation labeling with aluminum fluoride, and its labeling conditions were optimized. The product quality was analyzed. One patient (male, 47 years old) with lower rectal segment NET and one patient (female, 52 years old) with pancreatic NET underwent 18F-AlF-NOTATATE PET/CT imaging. Results:18F-AlF-NOTATATE was successfully prepared with a total synthesis time of 35 min. The optimized radiochemical yield was (23.8±3.1)% (without decay correction, n=3), the radioactivity was (4.63±0.68) GBq, and the radiochemical purity was >95%. The stability was good, and the product quality met the requirements. 18F-AlF-NOTATATE showed clear imaging in the patient with rectal segment NET, with SUV max of 13.3 and tumor/liver ratio of 3.3. Metastatic lesions in the liver, lymph nodes, and ribs showed high SUV max and tumor/liver ratios. The imaging of the pancreatic NET patient showed an abnormal increase in local radioactive uptake at the uncinate process of the pancreatic head, with SUV max of 5.6 and SUV max of 6.3 and the tumor/liver ratio of 2.3 after 2-hours imaging. Conclusions:Using the GE-FASTLab2 synthesis module, 18F-AlF-NOTATATE can be prepared with high activity. The preparation is simple, the method is stable, and the product has high radiochemical purity. 18F-AlF-NOTATATE exhibits good imaging performance in NET patients, providing valuable information for diagnosis, treatment, and prognosis evaluation.

Objective:To explore the clinical effectiveness of functional magnetic stimulation (FMS) of the sacral nerve root in the treatment of diabetic neurogenic bladder (DNB).Methods:A total of 134 DNB patients were divided into an observation group and a control group, each of 67. Both groups were given conventional drug therapy and bladder function training, while the observation group was additionally provided with sacral nerve root FMS for 4 weeks. The urine and urine flow dynamics of both groups were tested before and after the experiment.Results:After treatment the average daily volume of single urination had increased significantly in both groups and the average daily urinations and incidence of incontinence had decreased significantly. The observation group′s average single urination volume was then significantly greater than that of the control group. The observation group′s average daily urinations (8.87±1.42) and incontinence incidents (3.04±1.93) were then significantly fewer than the control group′s. After the treatment the detrusor pressure at maximum flow, bladder sense initial volition and residual urine volume of both groups had decreased significantly compared with before the treatment, while their average maximum flow rates had increased significantly. But the observation group′s averages were in all cases significantly better than those of the control group. The treatment′s total effectiveness rate among the observation group (88%) was significantly better than among the control group (72%).Conclusions:Supplementing routine bladder function training with FMS applied to the root of the sacral nerve can further promote the regaining of bladder function among DNB patients, improve their urinary flow dynamics and improve their quality of life. Such combination therapy is worthy of clinical promotion and application.

Objective:To investigate the effect of different timing of arterial -venous extracorporeal membrane oxygenation (VA-ECMO) on the prognosis of patients with acute myocardial infarction complicated with cardiogenic shock (AMICS).Methods:This study was a prospective cohort study. AMICS patients received VA-ECMO support primary percutaneous coronary intervention in Henan Provincial People's Hospital from May 2017 to July 2023 were divided into early VA-ECMO group and late VA-ECMO group. 64 AMICS patients who met the indications for VA-ECMO implantation, but did not revive VA-ECMO were included as control group. Demographic characteristics, coronary interventional (PCI) information and complications after VA-ECMO implantation were collected. The primary end points was 1-year survival, minor end point were in-hospital and perioperative death. Multivariate Logistic and Cox regression models were used to evaluate the effect of timing of VA-ECMO on prognosis of AMICS patients. Kaplan-Meier survival curve was used to analyze the 1-year survival outcome of the 3 groups.Results:A total of 143 AMICS patients were included, and materials of 136 patients entered in the final analysis, including 42 in the early VA-ECMO group, 34 in the late VA-ECMO group, and 60 in the non-VA-ECMO group. Compared with the late VA-ECMO group, the early VA-ECMO group had a higher ratio of PPCI after VA-ECMO, a longer D-to-B time, a shorter VA-ECMO support time, a higher success rate of VA-ECMO withdrawal, and a lower complication rate (all P<0.05). Compared with the early VA-ECMO group, the perioperative, in-hospital and 1-year mortality were significantly higher in Non-ECMO support (all P<0.05). There was no difference in perioperative and in-hospital mortality between the early VA-ECMO group and the late VA-ECMO group, but the 1-year mortality in the late VA-ECMO group was significantly higher ( P<0.05). Perioperative, in-hospital and 1-year mortality rates were lower in the late VA-ECMO group than in the no-VA-ECMO group, but the differences were not statistically significant. Multivariate Logistic and Cox regression analysis showed that after adjusting interference factors, early VA-ECMO was still a protective factor for in-hospital ( OR=0.244, P=0.015) and one year ( HR=0.308, P=0.001)mortality. Kaplan-Merier survival curve showed that compared with the late VA-ECMO group and the group without VA-ECMO, the early VA-ECMO group had the highest 1-year survival rate. Conclusion:Patients with AMICS may benefit more from early VA-ECMO than from late VA-ECMO support for PPCI.

Objective To compare the anti-inflammatory,antitumor and anti-bacterial effects of the single extract(in granules)and the prepared drug in pieces of Forsythia Suspense(Lianqiao,a traditional Chinese herbal medicine).Methods In zebrafish embryo models of CuSO4 exposure,tail transection and LPS microinjection-induced inflammation,the anti-inflammatory effects of 10 μg/mL DEX,single extract of Forsythia Suspense,and the water extract of the prepared drug(400,600,and 800 μg/mL)were evaluated by observing neutrophil counts,RT-qPCR,HE staining and survival analysis.Zebrafish embryo models bearing different human tumor cell xenografts were used to assess the anti-tumor effect of the drugs in different dosage forms by fluorescence staining and HE staining.The microbroth dilution method was used to evaluate the antibacterial efficacy of the drugs.Results In the zebrafish embryo models of inflammation,both of the two dosage forms of Forsythia Suspense significantly inhibited neutrophil aggregation,reduced the mRNA expressions of TNF-α,IL-6,P38,Jnk,Erk and P65,and increased the survival rate of zebrafish.They both showed obvious inhibitory effects against xenografts of different human cancer cells including colon cancer cells(HCT116),pancreas adenocarcinoma cells(PANC-1),lung cancer cells(A549),liver cancer cells(Hep3B)and cervical carcinoma cells(Hela)in zebrafish embryos,and exhibited strong anti-bacterial effects at the concentration of 15.63 mg/mL.Conclusion The two dosage forms of Forsythia Suspense have similar anti-inflammatory,antitumor and antibacterial effects,but their effects for inhibiting IL-6,P65,and Jnk mRNA expressions and HCT116 cell proliferation differ significantly at low doses in zebrafish.