Accumulating evidence has demonstrated that nucleic acid-based therapies are promising for atherosclerosis. However, nearly all nucleic acid delivery systems developed for atherosclerosis necessitate injection, which results in rapid elimination and poor patient compliance. Consequently, oral delivery strategies capable of targeting atherosclerotic plaques are imperative for nucleic acid therapeutics. Herein we report the development of yeast-derived capsules (YCs) packaging an antisense oligonucleotide (AM33) targeting microRNA-33 (miR-33) for the oral treatment of atherosclerosis. YCs provide stability for AM33, preventing its premature release in the gastrointestinal tract. AM33-containing YCs, defined as YAM33, showed high transfection in macrophages, thus promoting cholesterol efflux and inhibiting foam cell formation by regulating the target genes/proteins of miR-33. Orally delivered YAM33 effectively accumulated within atherosclerotic plaques in ApoE ^-/- mice, primarily by transepithelial absorption via M cells in Peyer's patches and subsequent translocation via macrophages through the lymphatic system. Inhibition of miR-33 by oral YAM33 significantly delayed the progression of atherosclerosis. Moreover, oral treatment with YCs co-delivering AM33 and atorvastatin afforded significantly enhanced anti-atherosclerotic effects. Our findings suggest that yeast-based microcapsules represent an effective carrier for oral delivery of nucleic acids, either alone or in combination with existing drugs, offering a promising approach for precision therapy of atherosclerotic diseases.

Mycoplasma pneumoniae（MP）is a cell wall-deficient pathogen positioned between viruses and bacteria，possessing a small genome undergoing continuous reduction and primarily transmitted via droplets. MP infection typically manifests as an acute process，inducing a series of immune responses in the host. However，some pediatric patients experience prolonged or recurrent infections following acute episodes，suggesting incomplete clearance of MP by the host and the pathogen evasion from immune surveillance through specific mechanisms，leading to chronic infection. In recent years，increasing research has revealed the immune evasion strategies enabling MP's long-term survival within the host. This review summarizes recent domestic and international advances in studying immune evasion mechanisms during chronic MP infection，aiming to provide reference for clinical diagnosis and treatment.

Objective:To evaluate the effect of Bu-Zhong-Yi-Qi-Tang (BZYQT) combined with low molecular weight heparin (LMWH) on lower limb deep vein thrombosis (DVT) after fracture fixation in aged rabbits.Methods:Thirty-two elderly New Zealand rabbits of either sex, aged 36 months, weighing 3.5-4.0 kg, were divided into 4 groups ( n=8 each) using the random number table method: control group (C group), fracture fixation group (F group), low molecular weight heparin group (L group) and BZYQT combined with LMWH group (BL group). A model of fixation surgery for right femoral shaft fracture was established in anesthetized rabbits in F, L and BL groups. Starting from postoperative day 1, BL group received BZYQT at 3.6 ml/kg via gavage, F and L groups received normal saline at 3.6 ml/kg via gavage, L and BL groups received subcutaneous injection of LMWH at 200 IU/kg, and all the administrations were performed daily at 08: 00 for 7 consecutive days. On postoperative day 7, ultrasound examination was performed to assess lower limb DVT. Blood samples were collected from the marginal ear vein for determination of the serum concentrations of cortisol (COR), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and endothelin-1 (ET-1) by enzyme-linked immunosorbent assay. Femoral vein specimens were obtained under anesthesia for microscopic examination of the pathological changes of the femoral vein lumen and endothelial tissues (by HE staining) and of the morphology of vascular endothelial cells (by the transmission electron microscopy). Results:Compared with C group, the concentrations of serum COR, TNF-α, IL-6 and ET-1 were significantly increased in F, L and BL groups, and the incidence of lower limb DVT within 7 days after surgery was significantly increased in F and L groups ( P<0.05). Compared with F group, the incidence of lower limb DVT within 7 days after surgery was significantly decreased in L and BL groups, and the concentrations of serum COR, TNF-α, IL-6 and ET-1 were significantly decreased ( P<0.05), and the pathological damage was significantly reduced in BL group. Compared with L group, the incidence of lower limb DVT and concentration of IL-6 were significantly decreased ( P<0.05), and pathological damage was significantly alleviated in BL group. Conclusions:BZYQT combined with LMWH can prevent the occurrence of lower limb DVT after fracture fixation in aged rabbits.

Objective To study the current status of the randomized controlled trial(RCT)outcome indicators of acupuncture and moxibustion in the treatment of chronic fatigue syndrome(CFS);To provide guidance and references for clinical research and protocol design.Methods RCT of acupuncture and moxibustion for CFS were retrieved from CNKI,Wanfang Data,VIP,SinoMed,PubMed,Embase,Web of Science databases from January 1,2015 to December 9,2024.Through literature screening and data extraction,Excel 2019 was used to make a descriptive analysis of the basic characteristics,diagnostic criteria,intervention measures,classification of outcome indicators,use frequency and evaluation time points of the included studies.Origin2021 software was used to draw bubble charts for visual display.Results Totally 119 RCT were included,involving 8 445 subjects,5 diagnostic criteria of Western medicine,5 diagnostic criteria of TCM,and 6 outcome indicators,namely clinical symptoms/signs,symptoms/syndrome of TCM,physical and chemical examination,quality of life,safety evaluation,and patient satisfaction.A total of 58 outcome indicators were reported,with a cumulative frequency of 430 times.Conclusion The RCT of acupuncture and moxibustion treatment of CFS have some problems,such as incomplete baseline assessment,lack of sample size calculation basis,high risk of bias,ignorance of primary and secondary indicators in the selection of outcome indicators,numerous indicators selection and measurement points,lack of long-term follow-up,inconsistent evaluation criteria for TCM syndrome efficacy,and insufficient attention to health economics evaluation and safety outcome indicators.

Objective:To evaluate the effect of Bu-Zhong-Yi-Qi-Tang (BZYQT) combined with low molecular weight heparin (LMWH) on lower limb deep vein thrombosis (DVT) after fracture fixation in aged rabbits.Methods:Thirty-two elderly New Zealand rabbits of either sex, aged 36 months, weighing 3.5-4.0 kg, were divided into 4 groups ( n=8 each) using the random number table method: control group (C group), fracture fixation group (F group), low molecular weight heparin group (L group) and BZYQT combined with LMWH group (BL group). A model of fixation surgery for right femoral shaft fracture was established in anesthetized rabbits in F, L and BL groups. Starting from postoperative day 1, BL group received BZYQT at 3.6 ml/kg via gavage, F and L groups received normal saline at 3.6 ml/kg via gavage, L and BL groups received subcutaneous injection of LMWH at 200 IU/kg, and all the administrations were performed daily at 08: 00 for 7 consecutive days. On postoperative day 7, ultrasound examination was performed to assess lower limb DVT. Blood samples were collected from the marginal ear vein for determination of the serum concentrations of cortisol (COR), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and endothelin-1 (ET-1) by enzyme-linked immunosorbent assay. Femoral vein specimens were obtained under anesthesia for microscopic examination of the pathological changes of the femoral vein lumen and endothelial tissues (by HE staining) and of the morphology of vascular endothelial cells (by the transmission electron microscopy). Results:Compared with C group, the concentrations of serum COR, TNF-α, IL-6 and ET-1 were significantly increased in F, L and BL groups, and the incidence of lower limb DVT within 7 days after surgery was significantly increased in F and L groups ( P<0.05). Compared with F group, the incidence of lower limb DVT within 7 days after surgery was significantly decreased in L and BL groups, and the concentrations of serum COR, TNF-α, IL-6 and ET-1 were significantly decreased ( P<0.05), and the pathological damage was significantly reduced in BL group. Compared with L group, the incidence of lower limb DVT and concentration of IL-6 were significantly decreased ( P<0.05), and pathological damage was significantly alleviated in BL group. Conclusions:BZYQT combined with LMWH can prevent the occurrence of lower limb DVT after fracture fixation in aged rabbits.

Objective To study the current status of the randomized controlled trial(RCT)outcome indicators of acupuncture and moxibustion in the treatment of chronic fatigue syndrome(CFS);To provide guidance and references for clinical research and protocol design.Methods RCT of acupuncture and moxibustion for CFS were retrieved from CNKI,Wanfang Data,VIP,SinoMed,PubMed,Embase,Web of Science databases from January 1,2015 to December 9,2024.Through literature screening and data extraction,Excel 2019 was used to make a descriptive analysis of the basic characteristics,diagnostic criteria,intervention measures,classification of outcome indicators,use frequency and evaluation time points of the included studies.Origin2021 software was used to draw bubble charts for visual display.Results Totally 119 RCT were included,involving 8 445 subjects,5 diagnostic criteria of Western medicine,5 diagnostic criteria of TCM,and 6 outcome indicators,namely clinical symptoms/signs,symptoms/syndrome of TCM,physical and chemical examination,quality of life,safety evaluation,and patient satisfaction.A total of 58 outcome indicators were reported,with a cumulative frequency of 430 times.Conclusion The RCT of acupuncture and moxibustion treatment of CFS have some problems,such as incomplete baseline assessment,lack of sample size calculation basis,high risk of bias,ignorance of primary and secondary indicators in the selection of outcome indicators,numerous indicators selection and measurement points,lack of long-term follow-up,inconsistent evaluation criteria for TCM syndrome efficacy,and insufficient attention to health economics evaluation and safety outcome indicators.

Objective To observe the effect of Shenfu injection on lung injury caused by hemor-rhagic shock(HS)in rats and explore the related potential mechanism.Methods Thirty-six SPF healthy male SD rats,aged 16-17 weeks,weighing 400-600 g,were randomly divided into three groups:sham op-eration group(group SH),HS group(group HS),and Shenfu injection group(group SF),12 rats in each group.In group SH,only the right femoral vein and femoral artery were separated after anesthesia,and ve-nous catheterization was not performed.HS model was established in groups SF and HS.In group HS,liquid resuscitation was performed through an intravenous catheter,and the resuscitation fluid consisted of the auto-blood lost and the compound sodium chloride injection equivalent to 1.5 times the blood loss and 10 ml/kg normal saline.In group SF,the resuscitation fluid consisted of the lost autoblood and the compound sodium chloride injection equivalent to 1.5 times the blood loss and Shenfu injection 10 ml/kg.The whole perfusion time was about 60 minutes.Six rats in the three groups were randomly anesthetized 24 and 48 hours after op-eration.The wet/dry weight ratio(W/D)of lung tissues was detected.The concentrations of interleukin-6(IL-6),IL-17,IL-10,and transforming growth factor-β(TGF-β)were detected by ELISA,the mRNA ex-pression of retinoic acid-related orphan nuclear receptor γt(RORγt),transcription factor forkhead box pro-tein 3(Foxp3),and hypoxia-inducible factor-1α(HIF-1α)in lung tissues were detected by PCR.The pro-tein contents of RORγt,Foxp3,HIF-1α,aquaporin 1(AQP1),and AQP5 in lung tissue were detected by Western blot.Pathological changesunder HE staining light microscope and lung injury scores were observed.Results Compared with 24 hours after operation,W/D,the concentrations of IL-6 and IL-17,mRNA ex-pression and protein content of RORγt and HIF-1α,and lung injury score were significantly decreased(P＜0.05),the concentrations of IL-10,and TGF-β,Foxp3 mRNA expression and protein content,and AQP1 protein content were significantly increased in group SF 48 hours after operation(P＜0.05).Compared with group SH,W/D,the concentrations of IL-6,IL-17,IL-10,and TGF-β,mRNA expression and protein content of RORγt,Foxp 3,and HIF-1α,and lung injury score were significantly increased(P＜0.05),AQP1 and AQP5 protein contents were significantly decreased in groups HS and SF 24 and 48 hours after operation(P＜0.05),and alveolar structure was damaged under light microscope and alveolar interstitium was filled with a large amount of edematous fluid,during which a large number of inflammatory cells infiltra-ted.Compared with group HS,W/D,the concentrations of IL-6 and IL-17,mRNA expression and protein content of RORγt and HIF-1α,and lung injury score were significantly decreased(P＜0.05),the concen-trations of IL-10 and TGF-β,Foxp3 mRNA expression and protein content,AQP1 and AQP5 protein con-tents were significantly increased in group SF 24 and 48 hours after surgery(P＜0.05),and the alveolar structure was improved under light microscope,and edema was reduced,and the number of inflammatory cells was reduced.Conclusion Shenfu injection can regulate the balance between pro-inflammatory factors IL-6 and IL-17,and anti-inflammatory factors IL-10 and TGF-β,increase the protein content of AQP1 and AQP5 in lung tissue,and decrease the W/D and injury score in lung tissue,thus alleviating lung injury in HS rats.The mechanism may be related to the regulation of HIF-1α-RORγt/Foxp3 balance.

Objective:To summarize the best evidence for the prevention and nursing of peri-implant diseases in patients with dental implants.Methods:Guidelines, systematic reviews, evidence summaries, and expert consensus on prevention and nursing of peri-implant diseases in patients with dental implants were electronically retrieved on Guidelines International Network, Agency for Healthcare Research and Quality, Medlive, UpToDate, BMJ Best Practice, Cochrane Library, Web of Science, PubMed, China Biology Medicine disc, China National Knowledge Infrastructure and so on. The search period was from database establishment to June 1, 2023. Two researchers conducted a quality evaluation and extracted evidence from the included literature.Results:A total of 15 articles were included, including two guidelines, six expert consensus, and seven systematic reviews. Twenty pieces of evidence on the prevention and nursing of peri-implant diseases in patients with dental implants were summarized from five aspects: risk factor assessment, nursing measures, oral hygiene guidance, monitoring and follow-up, and health education.Conclusions:The best evidence for the prevention and nursing of peri-implant diseases in dental implant patients summarized is scientifically sound. Medical and nursing staff can apply evidence based on clinical context and patient wishes.

The nasal swab samples of swine influenza(SI)suspected pigs were collected and tested for H3 subtype swine influenza virus(SIV)positive by RT-qPCR.The positive samples were inoc-ulated into SPF chicken embryos for virus isolation.The full genome sequencing and sequence anal-ysis of the isolated H3N2 subtype SIV were conducted,and its pathogenicity was studied.The re-sults showed that a strain of SIV was successfully isolated and identified as H3N2 subtype by RT-PCR,named A/Swine/Yunnan/KM/06/2023(H3N2).The BLSAT results showed that the eight segments of SIV H3N2 KM had the highest homology with eight different strains of swine influ-enza or human influenza viruses,reaching 95.41％-97.49％.The HA and NA segments were de-rived from H3N2 subtype SIV,the NP segment was derived from H1N1 subtype human influenza virus,the M segment was derived from H1N2 subtype SIV,and all other segments were derived from H1N1 subtype SIV.The key receptor sites(190D,223V,226I,228S)of HA protein remained unchanged.The pathogenicity experiment results showed that infected piglets exhibited symptoms such as fever,sneezing,runny nose,the virus could be detoxified to the outside through the nasal cavity,and the lungs had different degrees of lesion.Immunohistochemistry(IHC)showed that the virus could replicate in the lungs.In conclusion,a strain of H3N2 subtype SIV was successfully iso-lated,and the genetic evolution,molecular characteristics and pathogenicity of the virus were stud-ied.It revealed that H3N2 subtype SIV is constantly evolving and had pathogenicity to piglets,pro-viding a reference for monitoring and preventing SIV epidemics in China,and provided a candidate strain for SI vaccine development.

Objective:To explore the value of circ_0054633 in early diagnosis and prognosis prediction of acute lung injury/acute respiratory distress syndrome (ALI/ARDS) in children with severe pneumonia.Methods:A retrospective case-control study was conducted on children with diagnosed severe pneumonia admitted to Tianjin Children's Hospital from July 1, 2022, to February 29, 2024. The clinical data was collected by electronic medical record system and clinical follow-up, including gender, age, lung injury prediction score (LIPS), pediatric critical illness score (PCIS), serum circ_0054633, interleukin-6 (IL-6), the indicators of the arterial blood-gas analysis, oxygenation index (PaO 2/FiO 2) within 24 hours of admission and the survival status of 28 days. According to whether ALI/ARDS occurred, they were divided into the ALI/ARDS group and the non-ALI/ARDS group. The differences of clinical data between the two groups were compared, and multivariate Logistic regression was used to analyze the risk factors for ALI/ARDS in children with severe pneumonia. The receiver operator characteristic curve (ROC curve) will be used to explore the early diagnostic value of ALI/ARDS in children with severe pneumonia. The patients of ALI/ARDS were divided into mild group, moderate group and severe group according to the level of PaO 2/FiO 2. The levels of serum circ_0054633 and IL-6 in various severity ALI/ARDS were compared. The differences of serum circ_0054633, IL-6 levels, PCIS score and LIPS score were compared between the two groups of ALI/ARDS patients according to different prognoses in 28 days, as well as the correlation between various risk factors and circ_0054633. Results:A total 74 children with severe pneumonia were included, with 34 cases in the ALI/ARDS group and 40 cases in the non-ALI/ARDS group. In ALI/ARDS group, there were 9 cases in the mild group, 15 cases in the moderate group and 10 cases in the severe group; while 12 cases died and 22 cases survived after 28 days. The serum circ_0054633, IL-6 level and LIPS score were higher in the ALI/ARDS group than the non-ALI/ARDS group, while the PCIS score was lower, and the two groups had significant difference. Multivariate Logistic regression analysis showed that circ_0054633 was independent predictors of ALI/ARDS in children with severe pneumonia [odds ratio ( OR) = 3.853, 95% confidence interval (95% CI) was 1.912-7.805, P = 0.017]. ROC curve analysis showed that the cut-off values for circ_0054633 in the diagnosis of ALI/ARDS were 3.955, sensitivity was 79.4%, specificity was 92.5%, area under the ROC curve (AUC) was 0.892. The serum circ_0054633 and IL-6 levels were higher in the children who died in 28 days than the children who were survived, while the PCIS score was lower, and the two groups had significant difference. Spearman correlation analysis showed that the level of circ_0054633 in children with ALI/ARDS was positively correlated with 28-day mortality and IL-6 ( r value was 0.675, 0.763, respectively, all P < 0.001), but negatively correlated with PCIS score ( r = -0.626, P < 0.001), while no significant correlation with LIPS score ( r = 0.389, P = 0.023). Conclusion:The level of serum circ_0054633 has a better value in early diagnosis and prognosis prediction of ALI/ARDS caused in children with severe pneumonia.