Antisense oligonucleotides are a type of gene therapy that targets mRNA and inhibits gene expression. They have been applied in the treatment of various diseases, but there are still problems with poor enzyme stability and high dosage in vivo, due to the shortage of appropriate delivery system. Insulin-like growth factor 1 receptor (IGF1R) is a cell surface receptor with tyrosine kinase activity. Its expression is abnormal in a variety of malignant tumors. It mediates the malignant proliferation, migration and invasion of tumor cells through a variety of ways. In this study, an antisense oligonucleotide (ASO, N04) targeting IGF1R mRNA was designed and chemically modified (PS, 2'-OMOE), then neutral cytidine lipid DNCA and cystine backbone cationic lipid CLD (Mix) were used to encapsulate ASOs. The particle size, polymer dispersity index and ζ potential of the formulations were 151 nm, 0.18 and -3.9 mV. The nanoparticles entered liver cancer cells (HepG-2, Huh-7), silenced target mRNA, arrested cell cycle in S phase, promoted apoptosis, and inhibited the proliferation efficiently. These results indicate that Mix/N04_MOE5 has great potential in tumor treatment, which provides a basis for further research on novel agents against hepatocellular carcinoma.

Aim To design and synthesize a series of phenylacetamide derivatives with different substituted phenylacetic acid as raw materials,and to investigate the protective effects of the compound on the damage of pancreatic β cells induced by palmitate acid(PA).Methods Min6 cells were cultured and divided into B blank control group,PA treatment group and PA+compounds group.The viability of Min6 cells was de-tected by CCK-8.The protein expressions of TXNIP and NLRP3 were observed by Western blot.MDA con-tent and SOD activity were detected by MDA and SOD kit.The insulin secretion of Min6 islet cells was meas-ured with insulin ELISA kit.Results A total of 10 phenylacetamide derivatives were designed and synthe-sized.Their structures were confirmed by 1H NMR and ESI-MS.Pharmacological activity study showed that most of the compounds had protective effects on islet βcells,among which LY-6 and LY-8 had stronger pro-tective effects than PA model group,with the cell via-bility of 61.4％,and LY-6 had the highest cell activi-ty,reaching to 104.9％.Compared with PA group,the protein expression of TXNIP and NLRP3 decreased in LY-6 and LY-8 groups,MDA content decreased and SOD activity increased,and insulin secretion of Min6 cell increased.Conclusions LY-6 and LY-8 inhibit TXNIP expression and decrease the activation of NL-RP3 inflammasome,and decrease the production of MDA and increase SOD activity,and thus reducing is-let β cells apoptosis and increasing insulin secretion.Therefore,the compound LY-6 could serve as a poten-tial anti-diabetic new chemical entity.

In order to quickly deploy and carry out emergency diagnosis and treatment of gynecological diseases,a portable mobile folding cabin for gynecological diagnosis and treatment in emergency treatment scenarios was developed.The cabin folding cabin was mainly composed of two parts:the folding cabin structure and the folding heated gynecological examination bed.The cabin body was folded and retracted by means of lightweight plate and hinging;the folding bed was designed to realize the emergency diagnosis and treatment of gynecological diseases through the folding of the bed body and key components,the heating system and the disposable antibacterial bed sheet.The portable mobile gynecological diagnosis and treatment folding cabin and supporting examination folding bed can meet the requirements of gynecological disease diagnosis and treatment,meet the design requirements of"integration of storage,transportation,exhibition,collection and transportation",solve the problem that the examination bed can be heated and prevent cross-infection,and at the same time,it can realize the rapid deployment of gynecological diagnosis and treatment activities,which supplements the vacancy of portable mobile equipment required for gynecological diagnosis and treatment in emergency treatment scenarios.

OBJECTIVE: To investigate the anti-coronavirus potential and the corresponding mechanisms of the two ingredients of Reduning Injection: quercetin and luteolin. METHODS: A pseudovirus system was designed to test the efficacy of quercetin and luteolin to inhibit SARS-CoV-2 infection and the corresponding cellular toxicity. Luteolin was tested for its activities against the pseudoviruses of SARS-CoV-2 and its variants. Virtual screening was performed to predict the binding sites by Autodock Vina 1.1.230 and PyMol. To validate docking results, surface plasmon resonance (SPR) was used to measure the binding affinity of the compounds with various proteins of the coronaviruses. Quercetin and luteolin were further tested for their inhibitory effects on other coronaviruses by indirect immunofluorescence assay on rhabdomyosarcoma cells infected with HCoV-OC43. RESULTS: The inhibition of SARS-CoV-2 pseudovirus by luteolin and quercetin were strongly dose-dependent, with concentration for 50% of maximal effect (EC₅₀) of 8.817 and 52.98 µmol/L, respectively. Their cytotoxicity to BHK21-hACE2 were 177.6 and 405.1 µmol/L, respectively. In addition, luetolin significantly blocked the entry of 4 pseudoviruses of SARS-CoV-2 variants, with EC₅₀ lower than 7 µmol/L. Virtual screening and SPR confirmed that luteolin binds to the S-proteins and quercetin binds to the active center of the 3CLpro, PLpro, and helicase proteins. Quercetin and luteolin showed over 99% inhibition against HCoV-OC43. CONCLUSIONS The mechanisms were revealed of quercetin and luteolin inhibiting the infection of SARS-CoV-2 and its variants. Reduning Injection is a promising drug for COVID-19.
Humans ; SARS-CoV-2 ; COVID-19 ; Luteolin ; Quercetin

A variety of full 2ʹ-F/OMe-modified siRNAs were designed and synthesized, and the activity against hepatocellular carcinoma Huh-7 and HepG2 cells was evaluated. K&A DNA/RNA H-8 synthesizer was used to synthesize siRNAs, and neutral cytidinyl lipid DNCA mixed with cationic lipid CLD were used to transfect siRNA. By RT-qPCR and CCK-8 assay, the target gene silence and the proliferation of Huh-7 and HepG2 cells were detected. The siRNAs loading into Ago2 protein was detected by RNA-binding protein immunoprecipitation. Drug uptake and cell apoptosis were detected by flow cytometry, and the expression of PLK1 protein was detected by Western blot. Partial full 2ʹ-F/OMe modified siRNAs, especial siPLK1A3, increased the uptake of Huh-7 cells, enhanced their binding to Ago2 and gene silencing activity, down-regulated PLK1 protein, as well as induced more Huh-7 cell apoptosis and proliferation inhibition activity. It provides important data for the development of novel siRNA modification patterns and anti-HCC formulations.

OBJECTIVE: Clinical characteristics and outcome in COVID-19 with brucellosis patients has not been well demonstrated, we tried to analyze clinical outcome in local and literature COVID-19 cases with brucellosis before and after recovery. METHODS: We retrospectively collected hospitalization data of comorbid patients and prospectively followed up after discharge in Heilongjiang Infectious Disease Hospital from January 15, 2020 to April 29, 2022. Demographics, epidemiological, clinical symptoms, radiological and laboratory data, treatment medicines and outcomes, and follow up were analyzed, and findings of a systematic review were demonstrated. RESULTS: A total of four COVID-19 with brucellosis patients were included. One patient had active brucellosis before covid and 3 patients had nonactive brucellosis before brucellosis. The median age was 54.5 years, and all were males (100.0%). Two cases (50.0%) were moderate, and one was mild and asymptomatic, respectively. Three cases (75.0%) had at least one comorbidity (brucellosis excluded). All 4 patients were found in COVID-19 nucleic acid screening. Case C and D had only headache and fever on admission, respectively. Four cases were treated with Traditional Chinese medicine, western medicines for three cases, no adverse reaction occurred during hospitalization. All patients were cured and discharged. Moreover, one case (25.0%) had still active brucellosis without re-positive COVID-19, and other three cases (75.0%) have no symptoms of discomfort except one case fell fatigue and anxious during the follow-up period after recovery. Conducting the literature review, two similar cases have been reported in two case reports, and were both recovered, whereas, no data of follow up after recovery. CONCLUSION These cases indicate that COVID-19 patients with brucellosis had favorable outcome before and after recovery. More clinical studies should be conducted to confirm our findings.
Female ; Humans ; Male ; Middle Aged ; Brucellosis ; COVID-19 ; Retrospective Studies ; SARS-CoV-2 ; Treatment Outcome ; Case Reports as Topic

Objective:To analyze and compare the association between different obesity-related indices and vitamin D deficiency in middle-aged and elderly population dwelled in Lanzhou city.Methods:From May, 2011 to September, 2012, middle-aged and elderly individuals with complete baseline data were included via randomly cluster sampling from 3 communities in Lanzhou. The subjects were divided into 4 subgroups by vitamin D levels and various obesity-related indices were compared across subgroups with the same gender. The relationship between the obesity-related indices and the severity of vitamin D deficiency was analyzed using Spearman correlation analysis, and the effects of different obesity-related indices on the severity of vitamin D deficiency was analyzed using multivariate logistic regression analysis.Results:A total of 9 437 residents were included. The overall prevalence of vitamin D deficiency was 97.7%. Compared with the group with lower vitamin D level, participants in the group with higher vitamin D level showed evidently lower body mass index (BMI), waist circumference (WC), lipid accumulation product (LAP), visceral adiposity index (VAI) and triglyceride/ high density lipoprotein cholesterol (TG/HDL-C) ratio in the total population and females, while only WC, LAP, VAI and TG/HDL-C in the males (all P<0.05). Spearman correlation analysis showed that BMI, WC, LAP, VAI and TG/HDL-C were positively correlated with the severity of vitamin D deficiency in the total population and the females, while only LAP, VAI and TG/HDL-C in the males (all P<0.05) . Multivariate logistic regression analysis showed that higher levels of these obesity related indices were correlated with more severe vitamin D deficiency in the total population and the females, while only higher LAP, VAI and TG/HDL-C in the males (all P<0.05). The effects of higher LAP was the most prominant in the total population ,the females and the males. Conclusion:Various obesity phenotypes are closely related to vitamin D deficiency in middle-aged and elderly women, while only visceral obesity and abnormal lipid metabolism are related to vitamin D deficiency in middle-aged and elderly men, with LAP being the most important influencing factor.

Objective: To investigate the feasibility and safety of extracorporeal membrane oxygenation (ECMO)-supported percutaneous coronary intervention (PCI) in chronic coronary total occlusion (CTO) patients with reduced left ventricular ejection fraction (LVEF). Methods: The CTO patients with LVEF≤35% and undergoing CTO-PCI assisted by ECMO in the General Hospital of Northern Theater Command from December 2018 to March 2022 were enrolled in this study. The post-procedure complications, changes of LVEF from pre-procedure to post-procedure during hospitalization, and the incidence of all-cause mortality and changes of LVEF after discharge were assessed. Results: A total of 17 patients aged (59.4±11.8) years were included. There were 14 males. The pre-procedure LVEF of these patients were (29.00±4.08)%. Coronary angiography results showed that there were 29 CTO lesions in these 17 patients. There was 1 in left main coronary artery, 7 in left anterior descending artery, 11 in left circumflex artery, and 10 in right coronary artery. ECMO was implanted in all patients before procedure. Among 25 CTO lesions attempted to cross, 24 CTO were successfully implanted with stents. All patients underwent successful PCI for at least one CTO lesion. The number of drug-eluting stents implantation per patient were 4.6±1.3. After procedure, there were 8 patients with hemoglobin decreased>20 g/L, and 1 patient with ECMO-access-site related bleeding. The LVEF value at a median duration of 2.5 (2.0-5.5) days after procedure significantly increased to (38.73±7.01)% (P<0.001 vs. baseline). There were no in-hospital deaths. Patients were followed up for 360 (120, 394) days after discharge, 3 patients died (3/17). The LVEF value was (41.80±7.32)% at 155 (100, 308) days after discharge, which was significantly higher than the baseline value (P<0.001). Conclusion: The results of present study demonstrate that it is feasible, efficient and safe to perform ECMO)-supported CTO-PCI in CTO patients with reduced LVEF.
Male ; Humans ; Stroke Volume ; Ventricular Function, Left ; Extracorporeal Membrane Oxygenation ; Percutaneous Coronary Intervention ; Heart ; Vascular Diseases

Objective: To investigate the feasibility and safety of extracorporeal membrane oxygenation (ECMO)-supported percutaneous coronary intervention (PCI) in chronic coronary total occlusion (CTO) patients with reduced left ventricular ejection fraction (LVEF). Methods: The CTO patients with LVEF≤35% and undergoing CTO-PCI assisted by ECMO in the General Hospital of Northern Theater Command from December 2018 to March 2022 were enrolled in this study. The post-procedure complications, changes of LVEF from pre-procedure to post-procedure during hospitalization, and the incidence of all-cause mortality and changes of LVEF after discharge were assessed. Results: A total of 17 patients aged (59.4±11.8) years were included. There were 14 males. The pre-procedure LVEF of these patients were (29.00±4.08)%. Coronary angiography results showed that there were 29 CTO lesions in these 17 patients. There was 1 in left main coronary artery, 7 in left anterior descending artery, 11 in left circumflex artery, and 10 in right coronary artery. ECMO was implanted in all patients before procedure. Among 25 CTO lesions attempted to cross, 24 CTO were successfully implanted with stents. All patients underwent successful PCI for at least one CTO lesion. The number of drug-eluting stents implantation per patient were 4.6±1.3. After procedure, there were 8 patients with hemoglobin decreased>20 g/L, and 1 patient with ECMO-access-site related bleeding. The LVEF value at a median duration of 2.5 (2.0-5.5) days after procedure significantly increased to (38.73±7.01)% (P<0.001 vs. baseline). There were no in-hospital deaths. Patients were followed up for 360 (120, 394) days after discharge, 3 patients died (3/17). The LVEF value was (41.80±7.32)% at 155 (100, 308) days after discharge, which was significantly higher than the baseline value (P<0.001). Conclusion: The results of present study demonstrate that it is feasible, efficient and safe to perform ECMO)-supported CTO-PCI in CTO patients with reduced LVEF.
Male ; Humans ; Stroke Volume ; Ventricular Function, Left ; Extracorporeal Membrane Oxygenation ; Percutaneous Coronary Intervention ; Heart ; Vascular Diseases

The purpose of this study was to investigate the effect of isorhyncophylline on hippocampal endogenous metabolites in spontaneously hypertensive rats (SHR) by ¹H NMR metabolomics and molecular docking. Twelve SHR were randomly divided into a model group and a treatment group. Six Wistar-Kyoto rats were selected as a control group. The rats in the treatment group were administered isorhyncophylline (0.3 mg·kg^-1) while the rats in the other two groups were treated with the same amount of sterilized saline solution. Animal experiment was authorized by the Ethics Committee of Shandong University of Traditional Chinese Medicine (No. SDUTCM20210721002). Hippocampal tissues were removed after administration for 8 weeks and assayed by ¹H NMR based metabolomics technology combined with a pattern recognition method to find characteristic metabolites, and the metabolic targets were retrieved from the Kyoto Encyclopedia of Genes and Genomes database. Molecular docking technology was used to evaluate binding of isorhyncophylline to the core targets. The results of a principal components analysis (PCA) and partial least squares discriminant analysis (PLS-DA) showed a clear cluster of samples among three groups. There were seven differentially altered metabolites, and glucose metabolism and glutamate metabolism were the principal related pathways. Molecular docking indicated that isorhyncophylline had good binding properties with nine key candidate target proteins. According to the above research results, isorhyncophylline can influence energy metabolism and glutamate metabolism in the hippocampus.