Objective:To investigate whether herb cake-insulated moxibustion affects the expression of cholesterol metabolism-related protein 3-hydroxy-3-methylglutaryl coenzyme A reductase(HMGR)and inhibits the development of atherosclerosis by regulating the exosomal miR-223 expression.Methods:Thirty-six male New Zealand rabbits were randomly assigned to a normal group,a model group,and an herb cake-insulated moxibustion group,with 12 rabbits in each group.The model and the herb cake-insulated moxibustion groups were fed a high-fat diet for 8 weeks to induce an atherosclerosis model.Following successful modeling,the herb cake-insulated moxibustion group was subjected to bundling and herb cake-insulated moxibustion intervention,while the other two groups were subjected only to bundling without moxibustion.After 8 weeks of intervention,hematoxylin-eosin(HE)staining was used to observe aortic morphology;the serum levels of total cholesterol(TC),triglyceride(TG),and low-density lipoprotein cholesterol(LDL-C)were detected using an automatic biochemical analyzer in each group.Exosome morphology was observed using the transmission electron microscope;Western blotting(WB)was used to detect the protein levels of serum exosomal CD63 and CD9 markers,as well as liver HMGR;additionally,real-time fluorescence quantitative polymerase chain reaction was used to quantify serum exosomal miR-223.Results:HE staining showed thickened aortic intima,lipid infiltration,foam cell aggregation,and structural damage to the arterial wall in the model group.Meanwhile,after modeling,the serum levels of LDL-C,TC,and TG increased significantly in the model and herb cake-insulated moxibustion groups compared to the normal group(P<0.05),suggesting successful atherosclerosis rabbit model preparation.The serum exosomes of rabbits in the model group exhibited a saucer-like or semi-concave spherical shape with diameters of 120-150 nm.WB detection results showed positive expression of the exosomal markers CD63 and CD9.After 8 weeks of intervention,the miR-223 level in the model group was significantly lower than that in the normal group(P<0.01).In contrast,the herb cake-insulated moxibustion group demonstrated significantly reduced serum levels of TC,TG,and LDL-C(P<0.05),increased miR-223 expression(P<0.01),and decreased relative liver HMGR protein expression(P<0.05)compared to the model group.Conclusion:Herb cake-insulated moxibustion may alleviate the progression of atherosclerosis by up-regulating exosomal miR-223 expression and down-regulating HMGR protein expression,thereby inhibiting cholesterol anabolic metabolism.

Objective To evaluate and summarise the best evidence on non-pharmacological preventive measures for lower limb lymphedema in patients with gynecologic malignancy so as to provide an evidence-based guidance for prevention of lower limb lymphedema.Methods Systematic searches were conducted from inception to 31th January,2024 on databases of UpToDate,BMJ Best Practice,the National Institute for Health and Care Excellence(NICE),the Oncology Nursing Society(ONS),Guidelines International Network(GIN),China Guideline Clearinghouse,Medlive,National Comprehensive Cancer Network(NCCN),Registered Nurses Association of Ontario(RNAO),American Society of Clinical Oncology(ASCO),European Society for Medical Oncology(ESMO),Cancer Australia(CA),National Lymphedema Network(NLN),Scottish Intercollegiate Guidelines Network(SIGN),Lymphedema Support Network(LSN),International Society of Lymphology(ISL),International Society of Nurses in Cancer Care,Lymphedema Association of Ontario,Lymphoedema United,Cochrane Library,Web of Science,PubMed,Scopus,OVID,Embase,CINAHL,VIP,Wangfang Data,CNKI and SinoMed for the relevant evidence in non-pharmacological preventive measures for lower limb lymphedema in patients with gynecological malignancy.Two researchers evaluated the quality of clinical decisions,expert consensus,systematic reviews and randomised controlled trials,while four investigators assessed the quality of the guidelines.Another two researchers performed data extraction and evidence summary.Results A total of 17 articles were included,comprising two clinical decisions,two guidelines,two systematic reviews,seven expert consensuses,one evidence summary,three randomised controlled trials.A total of 32 pieces of evidence were summarised across eight dimensions:prevention timing,evaluation element,general self-care,skin care,manual lymphatic drainage,compression therapy,exercise and health education.Conclusion This study provides an evidence-based guidance for prevention of lower limb lymphedema in patients with gynecological malignancy.Healthcare professionals should apply the best evidences based on the conditions,preferences,resource allocation,and other factors of the patients,to reduce limb lymphedema and improve the quality of life of the patients.

Objective To construct the K64 capsule depolymerase recombinant protein,Dep44,and investigate its potential application against carbapenem-resistant Klebsiella pneumoniae(CRKP)infections.Methods The de-polymerase-encoding phage vB_Kpn_HF1013(GenBank:PP803128)was isolated and genomically analyzed to screen for candidate depolymerases.The recombinant protein Dep44 was constructed and functionally verified for depolymerase activity.Dep44 sensitive range was validated and Dep44 antimicrobial activity was assessed by bio-film disruption and serum sterilization assays.Results The tail spike protein of phage vB_Kpn_HF1013 exhibited depolymerase activity and recombinant protein Dep44 specifically degraded K64 CRKP capsule.Biofilm eradication assays demonstrated that recombinant Dep44 at both 2 μg/mL and 10 μg/mL significantly disrupted bacterial bio-films relative to the control.Serum bactericidal assays showed that Dep44 exhibited synergistic activity with serum,dependent on the complement system,as Dep44 alone lacked bactericidal properties.Conclusion Dep44 effec-tively targets and degrades K64 CRKP capsule,disrupts biofilms,and enhances serum bactericidal activity,high-lighting its potential for managing K64 CRKP infections and clearing biofilms from medical devices.

Objective To evaluate and summarise the best evidence on non-pharmacological preventive measures for lower limb lymphedema in patients with gynecologic malignancy so as to provide an evidence-based guidance for prevention of lower limb lymphedema.Methods Systematic searches were conducted from inception to 31th January,2024 on databases of UpToDate,BMJ Best Practice,the National Institute for Health and Care Excellence(NICE),the Oncology Nursing Society(ONS),Guidelines International Network(GIN),China Guideline Clearinghouse,Medlive,National Comprehensive Cancer Network(NCCN),Registered Nurses Association of Ontario(RNAO),American Society of Clinical Oncology(ASCO),European Society for Medical Oncology(ESMO),Cancer Australia(CA),National Lymphedema Network(NLN),Scottish Intercollegiate Guidelines Network(SIGN),Lymphedema Support Network(LSN),International Society of Lymphology(ISL),International Society of Nurses in Cancer Care,Lymphedema Association of Ontario,Lymphoedema United,Cochrane Library,Web of Science,PubMed,Scopus,OVID,Embase,CINAHL,VIP,Wangfang Data,CNKI and SinoMed for the relevant evidence in non-pharmacological preventive measures for lower limb lymphedema in patients with gynecological malignancy.Two researchers evaluated the quality of clinical decisions,expert consensus,systematic reviews and randomised controlled trials,while four investigators assessed the quality of the guidelines.Another two researchers performed data extraction and evidence summary.Results A total of 17 articles were included,comprising two clinical decisions,two guidelines,two systematic reviews,seven expert consensuses,one evidence summary,three randomised controlled trials.A total of 32 pieces of evidence were summarised across eight dimensions:prevention timing,evaluation element,general self-care,skin care,manual lymphatic drainage,compression therapy,exercise and health education.Conclusion This study provides an evidence-based guidance for prevention of lower limb lymphedema in patients with gynecological malignancy.Healthcare professionals should apply the best evidences based on the conditions,preferences,resource allocation,and other factors of the patients,to reduce limb lymphedema and improve the quality of life of the patients.

Objective To construct the K64 capsule depolymerase recombinant protein,Dep44,and investigate its potential application against carbapenem-resistant Klebsiella pneumoniae(CRKP)infections.Methods The de-polymerase-encoding phage vB_Kpn_HF1013(GenBank:PP803128)was isolated and genomically analyzed to screen for candidate depolymerases.The recombinant protein Dep44 was constructed and functionally verified for depolymerase activity.Dep44 sensitive range was validated and Dep44 antimicrobial activity was assessed by bio-film disruption and serum sterilization assays.Results The tail spike protein of phage vB_Kpn_HF1013 exhibited depolymerase activity and recombinant protein Dep44 specifically degraded K64 CRKP capsule.Biofilm eradication assays demonstrated that recombinant Dep44 at both 2 μg/mL and 10 μg/mL significantly disrupted bacterial bio-films relative to the control.Serum bactericidal assays showed that Dep44 exhibited synergistic activity with serum,dependent on the complement system,as Dep44 alone lacked bactericidal properties.Conclusion Dep44 effec-tively targets and degrades K64 CRKP capsule,disrupts biofilms,and enhances serum bactericidal activity,high-lighting its potential for managing K64 CRKP infections and clearing biofilms from medical devices.

Objective:To investigate whether herb cake-insulated moxibustion affects the expression of cholesterol metabolism-related protein 3-hydroxy-3-methylglutaryl coenzyme A reductase(HMGR)and inhibits the development of atherosclerosis by regulating the exosomal miR-223 expression.Methods:Thirty-six male New Zealand rabbits were randomly assigned to a normal group,a model group,and an herb cake-insulated moxibustion group,with 12 rabbits in each group.The model and the herb cake-insulated moxibustion groups were fed a high-fat diet for 8 weeks to induce an atherosclerosis model.Following successful modeling,the herb cake-insulated moxibustion group was subjected to bundling and herb cake-insulated moxibustion intervention,while the other two groups were subjected only to bundling without moxibustion.After 8 weeks of intervention,hematoxylin-eosin(HE)staining was used to observe aortic morphology;the serum levels of total cholesterol(TC),triglyceride(TG),and low-density lipoprotein cholesterol(LDL-C)were detected using an automatic biochemical analyzer in each group.Exosome morphology was observed using the transmission electron microscope;Western blotting(WB)was used to detect the protein levels of serum exosomal CD63 and CD9 markers,as well as liver HMGR;additionally,real-time fluorescence quantitative polymerase chain reaction was used to quantify serum exosomal miR-223.Results:HE staining showed thickened aortic intima,lipid infiltration,foam cell aggregation,and structural damage to the arterial wall in the model group.Meanwhile,after modeling,the serum levels of LDL-C,TC,and TG increased significantly in the model and herb cake-insulated moxibustion groups compared to the normal group(P<0.05),suggesting successful atherosclerosis rabbit model preparation.The serum exosomes of rabbits in the model group exhibited a saucer-like or semi-concave spherical shape with diameters of 120-150 nm.WB detection results showed positive expression of the exosomal markers CD63 and CD9.After 8 weeks of intervention,the miR-223 level in the model group was significantly lower than that in the normal group(P<0.01).In contrast,the herb cake-insulated moxibustion group demonstrated significantly reduced serum levels of TC,TG,and LDL-C(P<0.05),increased miR-223 expression(P<0.01),and decreased relative liver HMGR protein expression(P<0.05)compared to the model group.Conclusion:Herb cake-insulated moxibustion may alleviate the progression of atherosclerosis by up-regulating exosomal miR-223 expression and down-regulating HMGR protein expression,thereby inhibiting cholesterol anabolic metabolism.

Background: Neuroblastoma (NB) is a malignant pediatric tumor requiring new therapies. Accumulating evidence has confirmed that micro RNAs play critical roles in NB metastasis. Dihydroartemisinin (DHA) is capable of inhibiting the growth of NB cells. The primary objective of the current investigation was to characterize a newly discovered microRNA, miR-32-5p, in terms of the functional role, underlying mechanism of action, and potential synergistic therapeutic impact in the context of NB metastasis. Materials and methods: Real-time quantitative polymerase chain reaction and Western blotting were employed to assess the expression levels of miR-32-5p and its target, vacuolar protein sorting 4B (VPS4B). Furthermore, Transwell assay was utilized to evaluate in vitro cell migration and invasion, whereas a metastasis xenograft model was established in nude mice via caudal vein injections. Results: Gene Expression Omnibus database and real-time quantitative polymerase chain reaction analysis showed that miR-32-5p was downregulated in human NB samples and NB cell lines, in comparison with the normal tissue and cell lines. Inhibiting miR-32-5p induced the migration and invasion of NB cells, whereas overexpression of miR-32-5p prevented the migration and invasion in NB cell lines. Furthermore, VPS4B was identified as the direct target of miR-32-5p and the miR-32-5p reduction associated with NB metastasis upregulated the expression of VPS4B. Conversely, overexpression of VPS4B reversed the suppressive effects ofmiR-32-5p onNB cells. Moreover, miR-32-5p increased the sensitivity to DHA both in NB cells and in the metastasis xenograft model of nude mice. Conclusions: The downregulation of miR-32-5p in NB regulates NB metastasis by targeting VPS4B. Moreover, miR-32-5b can improve the sensitivity of DHA in the xenograft mouse model. Our findings have important implications for the combined application of miR-32-5p and DHA in the treatment of NB.

Objective To investigate and assess the risk signals of adverse drug events(ADEs)associated with the post-marketing 4 long-acting anticholinergic antagonists(LAMA),including adionium bromide,glycopyrronium bromide,umeonium bromide,and tiotropium bromide,to provide references for clinically safe prescribing practices.Methods Four LAMA drugs-related ADE records were selected by searching the FAERS database from the first quarter of 2004 to the first quarter of 2024 and standardizing the drug name of adionium bromide,glycopyrronium bromide,umeonium bromide,and tiotropium bromide,with the primary suspected drug as a restriction.Potential ADE signals were mined using the reporting odds ratio(ROR)method,medicines and healthcare products regulatory agency(MHRA)method and Bayesian confidence propagation neural network(BCPNN)method,and Medical Dictionary for Drug Regulatory Activities 26.1 was used to classify the results systematically.Results A total of 80 680 reports of four LAMA drugs-related ADE were collected,including 4 287 reports for aclidinium bromide,3 584 reports for glycopyrronium bromide,3 084 reports for umeclidinium bromide and 69 725 reports for iotropium bromide.The reports predominantly involved female patients(47 725 cases,59.15％)over male patients(27 525 cases,34.11％).The United States emerged as the principal reporting country,with consumers,pharmacists,and physicians as the primary reporters.Serious ADE outcomes included life-threatening conditions,hospitalizations,disabilities,deaths.A total of 902 signals were identified,mainly affecting 27 systems or organs.Specifically,aclidinium bromide(180 signals),glycopyrronium bromide(210 signals),umeclidinium bromide(142 signals),and tiotropium bromide(370 signals)exhibited signals predominantly in the respiratory,thoracic and mediastinal disorders,investigations,injury,poisoning and procedural complications,eye and organ diseases cgastrointestinal disorders.Conclusion When using LAMA drugs for respiratory conditions,clinicians should implement preventive measures to monitor respiratory diseases,thoracic and mediastinal diseases,eye and organ changes and various laboratory examination indicators,to reduce the risk of medication.

Objective To investigate the effect of evodiamine(EVO)on retinal injury in diabetic rats by regulating the cyclic adenosine monophosphate(cAMP)/protein kinase A(PKA)signaling pathway.Methods Totally 96 Sprague-Dawley rats(192 eyes)were divided into the negative control(NC)group,Model group,low-dose EVO(EVO-L)group,medium-dose EVO(EVO-M)group,high-dose EVO(EVO-H)group,calcium dobesilate(CD)group,SQ22536 group and EVO-H+SQ22536 group,with 12 rats in each group.Rats in the NC group were intraperitoneally injected with physiological saline instead of streptozotocin,and diabetic retinopathy models were established in all other groups.After successful mod-eling,the drug was administered once a day for 4 weeks.The blood glucose level of rats in each group was measured by blood glucose meter;HE staining was applied to detect the pathological changes of the retina of rats;TUNEL staining was adopted to detect the apoptosis of ganglion cells in the retina of rats;the levels of superoxide dismutase(SOD),malondial-dehyde(MDA),tumor necrosis factor-α(TNF-α),interleukin(IL)-6 and cAMP in the retina of rats were detected;West-em blot was used to detect the protein expressions of Bcl-2 associated X protein(Bax),P53 and phosphorylated protein ki-nase A(p-PKA)in the retina of rats.Results Compared with the NC group,the pathological injury of the retina in the Model group was more serious;the blood glucose,apoptosis rate of retinal ganglion cells,MDA,TNF-α,IL-6,Bax and P53 protein expressions increased,and the SOD,cAMP and p-PKA/PKA protein expression decreased,with statistically significant differences(all P＜0.05).Compared with the Model group,the pathological injury of the retina was relieved,the blood glucose,apoptosis rate of retinal ganglion cells,MDA,TNF-α,IL-6,Bax and P53 protein expressions decreased,and the SOD,cAMP and p-PKA/PKA protein expression increased in the EVO-L group,EVO-M group,EVO-H group and CD group,with statistically significant differences(all P＜0.05).Compared with the Model group,the retinal tissue of the SQ22536 group was severely damaged,the blood glucose,apoptosis rate of retinal ganglion cells,MDA,TNF-α,IL-6,Bax and P53 protein expressions increased,and the SOD,cAMP,p-PKA/PKA protein expression decreased,with statistically significant differences(all P＜0.05).Compared with the EVO-H group,the EVO-H+SQ22536 group showed more serious pathological injury of retinal tissue,increased blood glucose,apoptosis rate of retinal ganglion cells,MDA,TNF-α,IL-6,Bax and P53 protein expressions,and decreased SOD,cAMP and p-PKA/PKA protein expression,and the differences were statistically significant(all P＜0.05).Conclusion EVO may alleviate retinal injury in diabetic rats by activating the cAMP/PKA signaling pathway.

【Objective】 To construct and validate a risk prediction model for cognitive impairment after stroke based on demographic, clinical, and neuroimaging characteristics. 【Methods】 Through the medical record system, we collected all data of the patients. We finished cognitive function testing three months after the indexed stroke. The Mini-Mental State Examination Scale score≤26 was defined as cognitive dysfunction. Optimal subset regression analysis was used to screen variables, Logistic regression analysis was used to construct a predictive model for cognitive impairment, and C-index, calibration chart and clinical decision curve analyses were used to evaluate the discrimination, consistency, and clinical availability of the model. And nomograms were used to express the performance of the model. 【Results】 Seven variables were selected: cognitive function before stroke, age, years of education, National Institutes of Health Stroke Scale score at admission, history of ischemic heart disease, the number of old lacunar infarct lesions, and medial temporal lobe atrophy scale. The prediction model had a C-index of 0.845 (95% CI: 0.805-0.885). The clinical decision curve showed that the model had a positive net benefit when the threshold probability was 9.0%-90.0%. 【Conclusion】 The predictive model of cognitive impairment in stroke patients has good predictive efficiency and provides an effective assessment tool for screening high-risk cases of cognitive impairment in patients with stroke of various subtypes.