AIM:To investigate the effect of circular RNA MYO9A-006(circMYO9A_006)on hypertrophic phenotype of cardiomyocytes and the underlying mechanism.METHODS:The effect of adenovirus-mediated overexpres-sion of circMYO9A_006 on the expression of hypertrophy-related proteins,including β-myosin heavy chain(β-MHC),skeletal muscle actin alpha 1(ACTA1)and atrial natriuretic peptide(ANP),was evaluated in neonatal mouse ventricular cardiomyocytes(NMVCs).Moreover,a neonatal rat ventricular cardiomyocyte(NRVC)model of phenylephrine(PE)-in-duced hypertrophy was established.The effect of circMYO9A_006 overexpression on NRVC size was ascertained using Phalloidin-iFluor 647 staining method.Dual-luciferase reporter assay was employed to measure the activity of potential in-ternal ribosome entry sites(IRES)in circMYO9A_006.The translation and intracellular location of the circMYO9A_006-translated protein,MYO9A-208aa,were verified using Western blot.To investigate the role of MYO9A-208aa in the ef-fect of circMYO9A_006 on the cardiomyocyte hypertrophic phenotype,we prepared and used the following adenoviruses:the recombinant circMYO9A_006-ORF adenovirus to express MYO9A-208aa,the recombinant circMYO9A_006-ATG-mut adenovirus that does not express MYO9A-208aa,the recombinant circMYO9A_006 adenovirus,and the adenovirus vector control.These were then employed to infect NRVCs.RESULTS:Successful adenovirus-mediated overexpression of circMYO9A_006 was observed in NMVCs.The increased expression of circMYO9A_006 notably reduced the expres-sion of hypertrophy-related proteins in NMVCs(P<0.01).Concurrently,overexpression of circMYO9A_006 substantially reduced the expression of hypertrophy-associated proteins and diminished the size of PE-induced NRVCs(P<0.05).Dual-luciferase reporter assay identified the activity of 2 IRES in circMYO9A_006.Western blot results indicated that circ-MYO9A_006 could produce the MYO9A-208aa protein with an anticipated molecular weight of 28 kD in NRVCs,primari-ly found in the cytoplasm.Elevated expression of both circMYO9A_006 and MYO9A-208aa consistently reduced the ex-pression of hypertrophy-associated proteins(P<0.01),and counteracted the enlarged size of PE-induced NRVCs(P<0.05).However,increased expression of circMYO9A_006-ATG-mut did not counteract the PE-induced hypertrophic phe-notype of NRVCs.CONCLUSION:circMYO9A_006 attenuates the hypertrophic phenotype of cardiomyocytes by synthe-sizing the MYO9A-208aa protein.

A subset of patients with non-alcoholic fatty liver disease(NAFLD)can progress to nonalcoholic steatohepatitis(NASH).When NASH reaches a fibrosis degree of F≥2 and a NAS score of≥4,this stage of NASH is referred to as fibrotic NASH,which is a key focus in clinical drug trials.Currently,liver biopsy is the gold standard for assessing the histological changes of the liver,but its clinical application is limited by its invasiveness,and therefore,it is of particular importance to develop noninvasive detection methods for fibrotic NASH.This article summarizes the recent research achievements in novel noninvasive diagnostic methods for fibrotic NASH and elaborates on these new diagnostic methods for predicting fibrotic NASH in terms of current status,challenges faced,and prospects for future development.

Objective:To investigate the prevalence and potential classification of symptoms after total knee arthroplasty (TKA) in patients with knee osteoarthritis (KOA), and to analyze the differences in demographic characteristics and surgical data, compare the different potential subgroups, in order to provide a basis for clinical symptom management plans.Methods:This study was a multicenter cross-sectional survey. Through convenience sampling, patients with KOA undergoing TKA in the orthopaedic wards of four tertiary hospitals in Urumqi were selected as the study from November 2023 to February 2024. The study subjects were surveyed using a general information questionnaire, the Visual Analogue Scale (VAS) for pain, the Hospital Anxiety and Depression Scale (HADS), and the Pitts Burgh Sleep Quality Index (PSQI), and the degree of postoperative joint swelling and size of ecchymosis were measured. Latent class analysis was performed using Mplus 8.3 software, and Logistic regression analysis was conducted using SPSS 26.0 software to explore the influencing factors of the latent classes.Results:Totally 337 effective questionnaires were collected, and the recovery rate was 94.7% (337/356), and the age distribution ranged from 47 to 85 (65.19 ± 6.99) years old, with 90 (26.7%) males and 247 (73.3%) females. There were 92.3% (311/337) of TKA patients with postoperative symptom cluster. The symptom cluster of patients with TKA were identified as 3 classes. They were named as "high level pain-psychological disorder group"(12.5%, 39/311), "high bruises-moderate psychological disorders group"(25.4%, 79/311) and "low symptom burden group" (62.1%, 193/311). The results of the unordered multi-class logistic regression analysis showed that age 45-59 years ( OR = 2.367), body mass index 24.0-27.9 kg/m 2 ( OR = 0.207), living with children/parents ( OR = 6.473), and this being the second joint surgery ( OR = 0.040) were the factors influencing the "high level pain-psychological disorders group" (all P<0.05). The factors influencing the "high bruises-moderate psychological disorders group" were living with children/parents ( OR = 4.023), comorbid chronic diseases ( OR = 1.979, 3.842), and intraoperative blood loss ≤100 ml ( OR = 2.342) (all P<0.05). Conclusions:The postoperative symptom cluster of TKA patients have a relatively high incidence, and there is heterogeneity within the symptom cluster, so nurses need to identify at-risk patients early according to the characteristics of different categories and give interventions.

Objective To retrospectively analyze the safety and efficacy data of envafolimab-containing treatment regimens for digestive adenocarcinoma in the real world.Methods Treatment information of 35 patients with digestive adenocarcinoma who received envafolimab-containing regimens at Shanxi Provincial Cancer Hospital from December 2021 to July 2023 was retrospectively collected.Data were analyzed using IBM SPSS Statistics 27.Descriptive statistics were used to present quantitative data as mean±standard deviation or median,and qualitative data as frequency and percentage.Survival status was analyzed using the Kaplan-Meier(KM)method,and graphs were created using GraphPad Prism 9.5.1.Results Among 108 patients,35 met the inclusion criteria.Twenty-four(68.6％)experienced grade 1-3 adverse events(AEs),with no grade 4 or 5 AEs.The incidence rate of immune-related AEs was 31.4％.The median time to overall AE occurrence was 4.8 months.Twenty-three of the 35 patients underwent at least one efficacy evaluation,with 5 achieving partial response(PR)and 15 achieving stable disease(SD).No patients achieved complete response(CR).The objective response rate(ORR)was 21.7％,and the disease control rate(DCR)was 87.0％.Among the six patients with deficient mismatch repair/microsatellite instability-high(dMMR/MSI-H)lesions,the ORR was 50％,and the DCR was 100％.Among the 17 patients with proficient mismatch repair/microsatellite stable(pMMR/MSS)lesions,the ORR was 11.8％,and the DCR was 82.4％.Conclusion Envafolimab-containing regimens demonstrate good safety and favorable efficacy in the real-world treatment of digestive adenocarcinoma.

Objective To investigate the current status of off-label drug use(OLDU)management in tertiary hospitals of Guizhou province and to provide baseline evidence for developing a unified administration regulation for OLDU in Guizhou province.Methods In line with the relevant policies and regulations,a questionnaire including basic information about the person filling out the form,basic information about the hospitals,and information about OLDU was developed.The questionnaire was sent to 84 tertiary hospitals in Guizhou province through the Wenjuanxing.Results A total of 84 questionnaires were distributed and recovered,with a response rate of 100.00%.Of the 84 hospitals,77 had OLDU,of which 68(88.31%)had established a management system for OLDU.Among the 77 hospitals with OLDU,65(84.42%),42(54.55%),58(75.32%),36(46.75%),15(19.48%),and 21(27.27%)hospitals respectively,required approval from the Committee on Drug Administration and Pharmacotherapy before OLDU,restricted the qualifications of doctors prescribing OLDU,required informed consent from patients or their families before OLDU,recorded the matters and reasons in the medical records of patients treated with OLDU,followed up patients in their files and evaluated the reasonableness of the OLDU,and carried out special reviews for OLDU.Only 30(38.96%)hospitals have set up a catalogue of OLDUs,and 58(75.32%)hospitals have urgent needs to set up a unified provincial catalogue of OLDUs.Conclusion The pharmacy administration level of OLDU in tertiary hospitals of Guizhou province is relatively low,so there is an urgent need to establish a unified OLDU management system and medication catalog.

Objective To evaluate the effect of Internet-based psychosocial intervention for primary caregivers of patients with terminal stage cancer.Methods The relevant randomized controlled trials of Internet-based psychosocial intervention for primary caregivers of patients with terminal stage cancer were systematically searched from 10 databases,such as Chinese Biomedical Literature Database,CNKI,PubMed,Embase and CINAHL and etc.The search period was from the establishment to December 18,2023,and 2 investigators screened the literature according to inclusion and exclusion criteria and extracted data.Cochrane Manual 5.1.0 was used to assess the quality of the literature.Meta-analysis was performed using Revman 5.4 software.Results A total of 9 pieces of the literature including 592 primary caregivers were included.Meta-analysis showed that Internet-based psychosocial intervention reduced the level of anxiety and depression for primary caregivers of patients with terminal stage cancer[MD=-1.64,95％CI(-2.68,-0.59),P=0.002]and the burden of care[SMD=-0.39,95％CI(-0.60,-0.18),P＜0.001],and improved quality of life[SMD=0.25,95％CI(0.01,0.48),P=0.040];further research is needed to explore the effect of reducing the level of distress[MD=-0.88,95％CI(-1.91,0.16),P=0.100].Conclusion The Internet-based psychosocial intervention is effective in improving the anxiety,depression and the burden of care of the primary caregivers of patients with terminal stage cancer,and it can improve the quality of life;further research is needed to explore the level of distress reduction.

Objective To analyze the heat-clearing and anti-inflammatory mechanism of Xiaoyan Tuire Granules by network pharmacology,and to determine the 8 main active components of Xiaoyan Tuire Granules by ultra-high performance liquid chromatography-mass spectrometry(UPLC-MS/MS).Methods SwissTargetPrediction database was used to screen the target of components absorbed in the blood of Xiaoyan Tuire Granules.The main target of disease was obtained by CTD database,and the protein-protein interaction(PPI)was analyzed by String platform.GO and KEGG enrichment analysis were conducted using the DAVID database,followed by the construction of the components-targets-pathways network using Cytoscape software.Finally,the molecular docking verification of the key compound-target was conducted.The main active components in Xiaoyan Tuire Granules,including indirubin,isoliquiritigenin,liquiritigenin,glycyrrhizinic acid,liquiritin,esculetin,caffeic acid and chlorogenic acid,were determined by UPLC-MS/MS method.Analysis was performed on a WATERS ACQUITY UPLC? BEH C18 column(2.1 mm×100 mm,1.7 μm)with gradient elution of 0.1%formate in acetonitrile(A)-0.1%formate-5 mmol·L-1 ammonium formate(B),and the determination was carried out in multiple reaction monitoring(MRM)mode.Results Sixteen potential active components,such as indirubin,esculetin,and caffeic acid were identified by network pharmacology and molecular docking,and 10 core targets including transcription factor AP-1(JUN),adhesive connexin β1(CTNNB1)and cysteine aspartic protease-3(CASP3)were predicted.The pathway enrichment analysis revealed that heat-clearing and anti-inflammatory effects of Xiaoyan Tuire Granules were mainly related to signaling pathways such as interleukin-17(IL-17)and hypoxia-induced cause-1(HIF-1).Molecular docking experiments showed that its main active components docked well with core targets.The results of content determination exhibited that all components had good linear relationship within certain concentration range(r＞0.999),good precision,repeatability,and stability.The contents of 8 components in 16 batches of samples were 0.94-3.41,0.99-5.61,0.80-5.84,85.48-141.11,4.30-10.09,152.35-271.80,11.31-26.94,1.99-5.58 μg·g-1,respectively.The contents of indirubin,isoliquiritigenin,liquiritigenin,liquiritin,and chlorogenic acid in Xiaoyan Tuire Granules from two manufacturers were significantly different.Conclusion This study preliminarily revealed the mechanism of Xiaoyan Tuire Granules,which exerted heat-clearing and anti-inflammatory effects through multiple components,targets and pathways.A method for the determination of multiple components in Xiaoyan Tuire Granules was established.This study may provide a reference for its pharmacological research and quality control.

We investigated correlation between the level of miR-16 expression and the severity of Staphylococcus aureus sepsis,and further explored its potentially clinical significance.Blood samples were collected from 32 patients,including each 8 cases of septic shock,severe sepsis and general sepsis,as well as 8 cases of healthy volunteers.Blood samples from 24 cases of healthy subjects with different ages were measured,and additionally 8 cases of blood samples from gram negative bacteria sepsis were also determined in current study as a control.Trizol solution for the whole blood lysis was added into blood samples,and followed by the extraction of microRNA.The expression levels of miR-16 in different groups were measured by fluorescence quantitative PCR,in which 2-Delta Ct method was used.SPSS software (version 13.0) was used to analyze the statistical differences between the groups,and further analyze the correlation between miR-16 value and the corresponding CRP and PCT values.Results showed that the expression level of miR-16 was negatively correlated with the severity of Staphylococcus aureus sepsis.There were statistically significant differences in experimental groups when compared with the control (P＜0.001),and there was also a statistically significant difference between each experimental group (P＜0.01).We found that the expression level of miR-16 was negatively correlated with CRP and PCT,the correlation coefficients were-0.561 and-0.769 respectively,and trend analysis showed that there was a significantly negative correlation.A significantly negative correlation was found between the miR-16 expression level and severity of sepsis,suggesting that miR-16 may serve as a biomarker for the severity of Staphylococcus aureus sepsis.

Objective To investigate the effects of labeling Schwann cells with different concentrations of SPIO, and to investigate the feasibility of in vitro MR imaging. Methods The C57BL/6 mices'Schwann cells were isolated, purified, and then 0.5 × 106, 1.0 × 106, 5.0 × 106 cells were labeled with 25.0 μg/ml, 50.0 μg/ml SPIO. Prussian blue stain and transmission electron microscope (TEM) were performed for showing intracellular iron. The signal intensity of cells were evaluated by 3.0 MRI with different sequences in vitro. Results Different cell population (0.5 × 106, 1.0 × 106,5.0 × 106) were cultured with different concentration SPIO about 24 hours. Dyeing degree of labeling cells stained by Prussion blue gradually deepened from 25.0 μg/ml to 50.0 μg/ml. Transmission electron microscope indicated that iron particles accumulated inendosomes/lysosomes. The MR signal intensity of labeling cells were inversely correlated with the concentration of SPIO groups in T2WI and GRE/30° imaging in vitro. Conclusion Schwann cells could be labeled effectively with SPIO, and MRI could be used to monitor these labeled cells in vitro.

In this paper,the low rate of commercial of biomedical engineering scientific achievements transfer in military universities was discussed in detail.The main problems were analyzed.The commercial strategies of biomedical engineering scientific achievements transfer inmilitary universities were propound.