BACKGROUND:Flap transplantation technique is a commonly used surgical procedure for the treatment of severe tissue defects,but postoperative flap necrosis is easily triggered by ischemia-reperfusion injury.Therefore,it is still an important research topic to improve the survival rate of transplanted flaps. OBJECTIVE:To review the pathogenesis and latest treatment progress of flap ischemia-reperfusion injury. METHODS:CNKI,WanFang Database and PubMed database were searched for relevant literature published from 2014 to 2024.The search terms used were"flap,ischemia-reperfusion injury,inflammatory response,oxidative stress,Ca2+overload,apoptosis,mesenchymal stem cells,platelet-rich plasma,signaling pathways,shock wave,pretreatment"in Chinese and English.After elimination of irrelevant literature,poor quality and obsolete literature,77 documents were finally included for review. RESULTS AND CONCLUSION:Flap ischemia/reperfusion injury may be related to pathological factors such as inflammatory response,oxidative stress response,Ca2+overload,and apoptosis,which can cause apoptosis of vascular endothelial cells,vascular damage and microcirculation disorders in the flap,and eventually lead to flap necrosis.Studies have found that mesenchymal stem cell transplantation,platelet-rich plasma,signaling pathway modulators,shock waves,and pretreatment can alleviate flap ischemia/reperfusion injuries from different aspects and to varying degrees,and reduce the necrosis rate and necrosis area of the grafted flap.Although there are many therapeutic methods for skin flap ischemia/reperfusion injury,a unified and effective therapeutic method has not yet been developed in the clinic,and the advantages and disadvantages of various therapeutic methods have not yet been compared.Most of the studies remain in the stage of animal experiments,rarely involving clinical observations.Therefore,a lot of research is required in the future to gradually move from animal experiments to the clinic in order to better serve the clinic.

ObjectivesTo investigate the molecular epidemiological characteristics of HIV-1 infection among men who had sex with men (MSM) in Taizhou City, Zhejiang Province, and to provide a scientific reference for acquired immune deficiency syndrome prevention and control efforts. MethodsThe research subjects were all newly reported MSM population in Taizhou City from 2020 to 2023. Blood samples without antiviral therapy were collected. The HIV-1 pol gene was amplified and sequenced, and the sequences were submitted to the Stanford University drug resistance database to identify the mutation sites and drug resistance. MEGA 11.0 software was used to analyze the nucleic acid sequences, construct phylogenetic tree, and calculate genetic distance of gene sequences. The molecular transmission network diagram of HIV-1 was constructed using Cytoscape_v3.10.1, and the influencing factors of network entry were analyzed by logistic regression. ResultsA total of 363 newly reported HIV-infected MSM patients were included, with a median age [M (P₂₅, P₇₅)] of 34 (26,47) years old. The majority had an educational level of junior high school or below (55.65%). A total of eight subtypes were found, mainly CRF07_BC and CRF01_AE. The primary drug resistance rate was 10.47% (38/363). The optimal molecular network gene distance was 0.019, with a network access rate of 42.70% (155/363), and a total of 47 molecular clusters were formed. Multivariate logistic analyses showed that compared with the CRF01_AE subtype, the clustering risk of CRF07_BC subtype was higher (OR=1.916, 95%CI: 1.191‒3.109), cases with drug resistance had a higher risk of cluster formation than those without drug resistance (OR=2.011, 95%CI: 1.006‒4.080), and recent infected patients had a lower risk of entering the largest molecular cluster than long-term infected patients (OR=0.376, 95%CI: 0.137‒0.928). ConclusionThe newly diagnosed infections among the MSM population are active in Taizhou City, Zhejiang Province, with a high level of primary drug resistance. Individuals carrying drug-resistant strains are more likely to cluster. Drug resistance monitoring should be strengthened to prevent further spread of drug-resistant strains in the network.

Mitochondrial DNA (mtDNA) acts as a damage-associated molecular pattern to activate the stimulator of interferon genes (STING) signaling in macrophages, promoting tissue inflammation. However, its role in acute myocardial infarction (AMI) remains unclear. Macrophage-specific Sting1 knockout mice were used to validate STING's pathological role in AMI. Cardiac and liver mtDNA were used to activate macrophages in co-culture systems with cardiomyocytes to assess fibrosis and hypertrophy. Panaxatriol saponin (PTS) was tested for its ability to block mtDNA-driven macrophage activation and subsequent cardiomyocyte damage. STING-PTS binding ability was analyzed. AMI rats received PTS to evaluate its effects on myocardial inflammation and ventricular remodeling. In vivo, macrophage-specific Sting1 knockout reduced myocardial inflammation and injury after AMI. In vitro, mtDNA-activated macrophages induced cardiomyocyte fibrosis and hypertrophy through STING signaling. PTS suppressed mtDNA-driven macrophage activation by directly binding STING, thereby blocking inflammatory cascades. In AMI rats, PTS treatment attenuated acute inflammation and reversed ventricular remodeling. These findings establish the mtDNA-STING axis in macrophages as a critical driver of post-AMI inflammation and identify pharmacological STING inhibition with PTS as a promising therapeutic strategy. The study bridges genetic validation with translational applications, highlighting macrophage STING as a novel target for ischemic heart disease management.

Tongue squamous cell carcinoma (TSCC) is a prevalent malignancy that afflicts the head and neck area and presents a high incidence of metastasis and invasion. Accurate diagnosis and effective treatment are essential for enhancing the quality of life and the survival rates of TSCC patients. The current treatment modalities for TSCC frequently suffer from a lack of specificity and efficacy. Nanoparticles with diagnostic and photothermal therapeutic properties may offer a new approach for the targeted therapy of TSCC. However, inadequate accumulation of photosensitizers at the tumor site diminishes the efficacy of photothermal therapy (PTT). This study modified gold nanodots (AuNDs) with the TSCC-targeting peptide HN-1 to improve the selectivity and therapeutic effects of PTT. The Au-HN-1 nanosystem effectively targeted the TSCC cells and was rapidly delivered to the tumor tissues compared to the AuNDs. The enhanced accumulation of photosensitizing agents at tumor sites achieved significant PTT effects in a mouse model of TSCC. Moreover, owing to its stable long-term fluorescence and high X-ray attenuation coefficient, the Au-HN-1 nanosystem can be used for fluorescence and computed tomography imaging of TSCC, rendering it useful for early tumor detection and accurate delineation of surgical margins. In conclusion, Au-HN-1 represents a promising nanomedicine for imaging-based diagnosis and targeted PTT of TSCC.
Tongue Neoplasms/diagnostic imaging* ; Carcinoma, Squamous Cell/diagnostic imaging* ; Animals ; Gold/chemistry* ; Mice ; Photothermal Therapy/methods* ; Tomography, X-Ray Computed ; Photosensitizing Agents ; Metal Nanoparticles ; Humans ; Cell Line, Tumor

AIM:To investigate the effects of Xiaozhong-Zhitong mixture(XZZT)on M2 polarization and Toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)/nuclear factor-κB(NF-κB)signaling pathway in mouse microglia(BV2 cells).METHODS:The BV2 cells were divided into 5 groups:blank group,model group[lipo-polysaccharide(LPS)+hypoxia],TAK-242(resatorvid,a TLR4 inhibitor)group(LPS+hypoxia+TAK-242),XZZT group(LPS+hypoxia+XZZT),and TAK-242+XZZT group(LPS+hypoxia+TAK-242+XZZT).Flow cytometry was used to detect early apoptosis and cell cycle of BV2 cells,and immunofluorescence staining was employed to detect the positive expres-sion of M1-type marker inducible nitric oxide synthase(iNOS)and M2-type marker CD206.Western blot was utilized to detect the expression of TLR4/MyD88/NF-κB signaling pathway-related proteins,including TLR4,MyD88,NF-κB p65,phosphorylated p65(p-p65),phosphorylated transforming growth factor-β-activated kinase 1(p-TAK1),and phosphory-lated IκB kinase α/β(p-IKKα/β).RT-qPCR was used to detect the mRNA expression of interleukin-1β(IL-1β),IL-10,tumor necrosis factor-α(TNF-α),TLR4,MyD88,and NF-κB p65.RESULTS:Compared with model group,the rate of early apoptosis was significantly decreased in XZZT group(P<0.01),the percentage of cells arrested in the S phase was significantly increased(P<0.01),and the protein levels of TLR4,MyD88,NF-κB p65,p-IKKα/β,p-p65,and p-TAK1 were significantly decreased(P<0.05 or P<0.01).Additionally,IL-1β,TNF-α,TLR4,MyD88 and NF-κB p65 mRNA expression levels were significantly decreased(P<0.05 or P<0.01),while IL-10 mRNA expression was significantly in-creased(P<0.05).Compared with TAK-242 group,the average percentage of iNOS positive area was significantly de-creased,while CD206 was significantly increased in TAK-242+XZZT group(P<0.01).CONCLUSION:The XZZT has the effect of inducing M2 polarization of mouse microglia,and the mechanism may be linked to the inhibition of TLR4/MyD88/NF-κB signaling pathway.

Objective To investigate the role and mechanism of NLRP3/Caspase-1/IL-1 β inflammasome pathway in the formation of aortic dissection in mice.Methods Fifty male C57BL/6 mice(3 weeks old,body weight 10～13 g)were divided into control group(n =10,normal diet),β-aminopropionitrile(BAPN)group[n =20,drink water containing 1 g/(kg·d)BAPN],and BAPN+MCC950 group[n=20,drink water containing 1 g/(kg·d)BAPN and intraperitoneal injection of 20 mg/(kg·d)NLRP3 inhibitor,MCC950]by random sampling.Water intake,body weight,incidence of aortic dissection and aortic dissection-related mortality were recorded.The inflammatory infiltration in the aorta was observed with HE staining,elastic fiber breakage was observed by elastic Van Gieson(EVG)staining,average fluorescence intensity of NLRP3,IL-1β,α-SMA and OPN was detected by immunofluorescence assay,and protein expression levels of NLRP3,Caspase-1,ASC,IL-1β,α-SMA and OPN were measured with Western blotting.Results No aortic dissection or death was observed in the control group.The BAPN group had an incidence of aortic dissection of 80％,aortic dissection-related mortality of 35％,and obvious broken elastic fibers and inflammatory infiltrate in the aortic wall,and increased expression levels of NLRP3,Caspase-1,ASC and IL-1 β,decreased contractile α-SMA and increased synthetic protein OPN when compared with the control group(P<0.05).While MCC950 treatment decreased the incidence of aortic dissection(80％vs 35％,P=0.004)and aortic dissection-related mortality(35％vs 15％,P=0.144),alleviated the broken elastic fibers and inflammatory infiltrate in the aortic wall,and down-regulated the expression of NLRP3,Caspase-1,ASC and IL-1β,enhanced contractile α-SMA and decreased the synthetic protein when compared with the BAPN group(P<0.05).Conclusion The occurrence of aortic dissection in mice is associated with activation of NLRP3/Caspase-1/IL-1 β inflammasome pathway.NLRP3 inhibitor,MCC950,can reduce the occurrence of aortic dissection and show a protective effect on blood vessels.

Objective:To investigate the relationship between the visceral adiposity index(VAI) and cognitive decline.Methods:A cross-sectional study was conducted.Between October 2020 and March 2023, 483 elderly residents living in communities in Hefei were recruited and divided into four groups based on VAI scores, Q1(VAI ≤ 1.14), Q2(VAI>1.15 and ≤1.85), Q3(VAI>1.86 and ≤2.81) and Q4(VAI>2.82).General cognitive function was assessed by(MMSE)and(MoCA).Attention and working memory were tested by forward and backward digit span tasks.Logistic regression was utilized to analyze the relationship between different VAI scores and insulin resistance.The correlation between different VAI scores and cognitive function domains was analyzed by partial correlation.Results:The values of BMI, fasting plasma glucose, fasting insulin, HbA1c, high-sensitivity C-reactive protein, HOMA-IR and HOMA-β increased with increasing VAI scores(all P<0.01).VAI was significantly correlated with insulin sensitivity after adjusting for confounding factors including sex.The risk of insulin resistance in Q4 was 7.40 times that in Q1( OR=7.40, 95% CI: 4.30-12.74, P<0.05).In addition, the correlation coefficients between VAI and forward digital span and between VAI and backward digital span were -0.116 and -0.105, respectively(both P<0.05), but there was no correlation between VAI and MMSE or MoCA. Conclusions:VAI is closely related to insulin resistance and also associated with early cognitive decline in elderly people with visceral obesity.

Objective:This study aims to explore the prevalence of hepatitis E virus (HEV) infection in patients and the screening value of serological indicators for HEV infection patients.Methods:Retrospective analysis was conducted on 97 440 cases of anti-HEV IgM and IgG simultaneously tested in two Beijing hospitals from January 1, 2018 to August 31, 2023. Among them, there were 61 005 males and 36 435 females, with an average age of 51.65±13.05 years old. According to the positivity of anti HEV specific antibodies, they were divided into anti-HEV IgM positive group (3 588 cases), anti-HEV IgG positive group (18 083 cases), and anti-HEV antibody negative group (78 892 cases). Results of HEV RNA, liver function, AFP, PIVKA-Ⅱ and PT were collected, and their basic clinical information were recorded. The prevalence of HEV infection in patients, as well as the relationship between the positivity of anti-HEV specific antibodies and the patient′s age group, HEV RNA, and clinical characteristics were analyzed.Results:Among 97 440 patients who tested anti-HEV IgM and IgG simultaneously, the positivity rate of anti-HEV IgM was 3.68% (3 588/97 440), and was 18.56% for anti-HEV IgG (18 083/97 440). The overall positivity rates of anti-HEV IgM in two Beijing hospitals from 2018 to 2023 were 2.51%, 2.53%, 3.02%, 4.59%, 5.72%, and 4.26% ( χ2=1 401.73, P<0.001), while the positivity rates of anti-HEV IgG were 12.56%, 12.32%, 12.85%, 22.65%, 27.42%, and 26.66% ( χ2=1 058.29, P<0.001). These rates showed a gradual increase until 2023 when a decline was observed. The positivity rates of anti-HEV IgM (2.28%, 3.60%, 4.47%) ( χ2=89.62, P<0.001) and IgG (4.71%, 17.86%, 25.94%) ( χ2=2 017.32, P<0.001) increased with age in patients who aged 1-30, >30-60, and over 60 years old. The age and ALB values of patients in the anti-HEV IgM positive group were lower than the IgG-positive group, while the proportion of males, TBIL, ALT, AFP and PT values were higher than the IgG-positive group, and the differences were statistically significance ( P<0.05). Furthermore, patients in both the anti-HEV IgM and IgG positive groups had higher age, male proportion, TBIL, ALT, AFP, PIVKA-Ⅱ, and PT values than the anti-HEV negative group. Additionally, both groups had lower ALB values than the anti-HEV negative group, all of which were statistically significant ( P<0.05). 2 162 HEV infected patients were grouped based on HEV RNA positivity. The proportion of anti-HEV IgM single positive, IgG single positive, IgM+IgG double positive, and antibody negative patients in the HEV RNA positive group were 5.42% (18/332), 3.62% (12/332), 90.36% (300/332), and 0.60% (2/332), respectively. Among them, the proportion of anti-HEV IgM+IgG double positive patients in the HEV RNA positive group was higher than that in the HEV RNA negative group ( χ2=302.87, P<0.001), while the proportion of anti-HEV IgG single positive ( χ2=174.36, P<0.001) and anti-HEV antibody negative patients ( χ2=59.28, P<0.001) were lower than that in the HEV RNA negative group, both of which were statistically significant ( P<0.001). In addition, the positive rates of HEV RNA in anti-HEV IgM positive, IgG positive, and antibody negative patients were 29.23% (318/1 088), 17.59% (312/1 774), and 0.65% (2/306), respectively. Conclusion:The HEV infection rate among patients declined in 2023. HEV infection is age-related, with older individuals being more susceptible. Abnormal liver function and jaundice were commonly observed during HEV infection. It is crucial to note that the absence of anti-HEV specific antibodies cannot rule out HEV infection; therefore, additional testing for HEV RNA and/or HEV Ag is necessary for accurate diagnosis.

BACKGROUND:In recent years,it has been found that some traditional Chinese medicine monomers can alleviate oxidative stress and apoptosis of the skin flap,promote vascular regeneration of the skin flap and prevent skin flap necrosis by activating autophagy. OBJECTIVE:To review the research progress of traditional Chinese medicine monomer regulating autophagy in preventing flap necrosis. METHODS:The Chinese and English key words were"traditional Chinese medicine(TCM),autophagy,skin flaps".The first author searched the relevant articles published in CNKI and PubMed databases from January 2010 to October 2022.A total of 196 articles were retrieved in the preliminary screening and then screened according to the inclusion and exclusion criteria.The quality assessment was conducted by reading the literature titles and abstracts.Finally,55 articles were summarized. RESULTS AND CONCLUSION:(1)The regulation of autophagy is mediated by AMPK/mTOR,PI3K/AKT and other signaling pathways.Activation of autophagy can alleviate the oxidative stress and apoptosis of the flap,promote the regeneration of blood vessels in the flap,and prevent flap necrosis.(2)Terpenoids(Betulinic acid,Andrographolide,Notoginseng Triterpenes,Catalpa),phenolic compounds(Resveratrol,Curcumin,Gastrodin),phenolic acids(Salvianolic acid B)and steroid compounds(Pseudoginsenoside F11)in traditional Chinese medicine monomers can alleviate oxidative stress and apoptosis of skin flap by regulating related signaling pathways to activate autophagy,promote skin flap angiogenesis and promote skin flap survival.(3)Studying the research progress of traditional Chinese medicine monomer to prevent flap necrosis by regulating autophagy can provide a reference and theoretical basis for traditional Chinese medicine to prevent flap necrosis and promote flap healing in the clinic.

BACKGROUND:Mesenchymal stem cells have great potential in the treatment of ischemia-reperfusion injury of skin flaps.However,their defects and the decline of their role in the treatment of ischemia-reperfusion injury of skin flaps restrict their wide application. OBJECTIVE:To review the strategies for improving the treatment of ischemia-reperfusion injury of skin flaps with mesenchymal stem cells,and provide a reference for its further theoretical research and clinical application. METHODS:Relevant documents included in CNKI,WanFang and PubMed were searched.The Chinese and English search terms were"mesenchymal stem cell,ischemia-reperfusion adjustment of skin flap,mesenchymal stem cells,stem cells,skin flap,ischemia-reperfusion injury,pretreatment,gene modification,biomaterial packaging,joint application".The relevant documents since 2007 were retrieved,and the documents with little relationship between the research content and the article theme,poor quality and outdated content were eliminated through reading the article,and finally 75 documents were included for summary. RESULTS AND CONCLUSION:(1)Mesenchymal stem cells can inhibit inflammatory reactions,resist oxidative stress and induce angiogenesis,which has great potential in the treatment of skin flap ischemia-reperfusion injury.(2)Although mesenchymal stem cells have shown great potential in the treatment of skin flap ischemia-reperfusion injury,their shortcomings in treatment have limited their widespread clinical application.Through pre-treatment(cytokines,hypoxia,drugs,and other pre-treatment mesenchymal stem cells),gene-modified mesenchymal stem cells,biomaterial encapsulation of mesenchymal stem cells,as well as the combined use of mesenchymal stem cells and other drugs or therapeutic methods,can not only overcome the shortcomings of mesenchymal stem cells in treatment,but also improve their therapeutic effectiveness in skin flap ischemia-reperfusion injury.(3)Therefore,further improving the effectiveness of mesenchymal stem cells in treating skin flap ischemia-reperfusion injury and exploring its therapeutic potential are of great significance for the research of mesenchymal stem cells and the treatment of skin flap ischemia-reperfusion injury.