The innate immune sensor NLRP3 inflammasome overactivation is involved in the pathogenesis of ulcerative colitis. PGAM5 is a mitochondrial phosphatase involved in NLRP3 inflammasome activation in macrophages. However, the role of PGAM5 in ulcerative colitis and the mechanisms underlying PGAM5 regulating NLRP3 activity remain unknown. Here, we show that PGAM5 deficiency ameliorates dextran sodium sulfate (DSS)-induced colitis in mice via suppressing NLRP3 inflammasome activation. By combining APEX2-based proximity labeling focused on PGAM5 with quantitative proteomics, we identify NEK7 as the new binding partner of PGAM5 to promote NLRP3 inflammasome assembly and activation in a PGAM5 phosphatase activity-independent manner upon inflammasome induction. Interfering with PGAM5-NEK7 interaction by punicalagin inhibits the activation of the NLRP3 inflammasome in macrophages and ameliorates DSS-induced colitis in mice. Altogether, our data demonstrate the PGAM5-NEK7 interaction in macrophages for NLRP3 inflammasome activation and further provide a promising therapeutic strategy for ulcerative colitis by blocking the PGAM5-NEK7 interaction.

Although after the revascularization,heart blood vessel is unobstructed,the excessive use of surgical instruments can easily damage qi and blood,and disturb the mind;meanwhile,spleen and kidney are deficient.The combination of deficiency and excess in"qi,fire,dampness and stasis"leads to frequent chest pain after surgery.Qi and blood deficiency,heart spirit disturbance,and liver,spleen,and kidney qi disharmony are the symptom basis of chest pain after revascularization of coronary heart disease;liver qi stagna-tion,qi stagnation turning into fire,lack of heart-kidney interaction,yin deficiency and fire hyperactivity,heart qi deficiency,stasis obstructing the meridians,spleen and kidney yang deficiency,dampness accumulation turning into phlegm,and mixed"qi,fire,dampness and stasis"is the core pathogenesis of chest pain after revascularization of coronary heart disease.In clinical practice,it is necessary to distinguish the syndrome factors of qi,fire,dampness,and stasis and the deviation of the heart,liver,spleen,and kidney.From the perspective of the four dimensions of syndrome factors and viscera,the treatment ideas of clearing the heart and toni-fying the kidney,calming the mind,replenishing qi and activating blood circulation,removing stasis and unblocking collaterals,strengthening the spleen and warming the kidney,removing phlegm and relieving obstruction,soothing the liver and nourishing the liv-er,regulating qi and improving chest stuffiness are proposed,which provides a theoretical basis for the clinical diagnosis and treatment of chest pain after revascularization of coronary heart disease.

Arteriovenous malformations(AVMs)are a kind of high-flow vascular malformation.AVMs can be classified in many ways,including histo-embryological classification,hemodynamic classification,etc.At present,the two mainstream classification systems used to guide the embolization treatment of peripheral AVMs are proposed by Cho and Yakes respectively based on the angiographic morphology of the lesions.Interventional embolization is the first-line treatment for AVMs.Among the many embolization agents,absolute ethanol is a permanent liquid embolization agent.Absolute ethanol can directly destroy the vascular endothelial cells to achieve a good curative efficacy,therefore,it has been wildly used in the treatment of peripheral AVMs.Yakes classification combines the angiographic classification with absolute ethanol embolization therapy.During absolute ethanol treatment,close attention should be paid to the occurrence of complications such as elevated pulmonary artery pressure.Although there are challenges remaining in the treatment of AVMs,the rapid development of molecular genetics has made targeted drug adjunctive treatment for AVMs possible.Perhaps,the novel therapeutic mode of combination use of traditional therapy targeted drug may be able to make a breakthrough in the treatment of AVMs.

BACKGROUND:MXene nanoparticles have considerable application prospects as effective functional components of skin wound dressings due to their unique properties of conductivity,hydrophilicity,antibacterial activity,and biocompatibility. OBJECTIVE:To review the synthesis methods,functional properties,and application of MXene nanoparticles in skin injury repair. METHODS:"MXene,nanoparticles,nanomaterials,bioactive nanoparticles","wound dressing,wound dressing,wound repair materials","wound repair,wound healing,wound surface"were used as Chinese search terms to search Wanfang and CNKI databases."MXene,nanoparticles,nano-materials,bioactive nanoparticles","wound dressing,wound healing material","wound healing,wound repair,wound"were used as English search terms to search the PubMed database.Finally,88 articles were included for review analysis. RESULTS AND CONCLUSION:(1)MXene synthesis can be divided into two methods:bottom-up synthesis and top-down synthesis.The synthesized MXene can be further modified to enhance biocompatibility for better application in biomedicine.(2)MXene has a series of excellent properties such as hydrophilicity,antibacterial,photothermal properties,electrical conductivity,and good biocompatibility,all of which make it the basis for excellent skin repair materials.(3)At present,many scholars have developed new composite materials for wound dressings.Currently,these composite materials are based on MXene nanomaterials and make full use of its excellent characteristics as mentioned above,which play a role in local skin wound sterilization,drug delivery,and sustained release,active regulation of cytokines,and can integrate the advantages of other biologically active agents.It plays a better role in wound healing,especially in the treatment of complex chronic wounds.(4)Various composite materials such as MXene@PVA hydrogel and MXene@CH sponge developed based on various properties of MXene have shown good effects on improving tissue repair performance and repairing skin damage as drug carriers.It shows that MXenes nanoparticles are in the initial stage of development and have great prospects in the field of promoting skin repair.The characteristics and surface modification of MXenes nanoparticles have been well studied,but the molecular mechanism of dose-dependent biotoxicity is relatively incomplete.

ObjectiveTo observe the clinical efficacy and safety of Tinglu Yixin prescription in the treatment of patients with heart failure with preserved ejection fraction （HFpEF） combined with diabetes （syndromes of Qi and Yin deficiency and water retention and blood stasis） from taste-based compatibility and descending adverse Qi with bitter and pungent medicinals. MethodA total of 108 HFpEF patients with diabetes （syndromes of Qi and Yin deficiency and water retention and blood stasis） treated in the Nanjing Integrated Traditional Chinese and Western Medicine Hospital Affiliated to Nanjing University of Chinese Medicine from May 2022 to March 2023 were enrolled in this study and randomized into an observation group （54 patients） and a control group （54 patients）. Both groups received conventional Western medicine treatment according to the guide recommendations for chronic heart failure and diabetes， and the observation group additionally received Tinglu Yixin prescription. The treatment course for both groups was 12 weeks. The New York Heart Association （NYHA） grading of cardiac function， left ventricular end diastolic diameter （LVEDD）， left atrium diameter （LAD）， the ratio of early diastolic maximum mitral flow velocity （E） to early diastolic mitral annular motion velocity （e'） （E/e'）， N-terminal pro-B-type natriuretic peptide （NT-proBNP）， hemoglobin A1c （HbA1c）， 6-minute walking test （6MWT）， Minnesota Living with Heart Failure Questionnaire， traditional Chinese medicine （TCM） syndrome scores， and safety indicators were determined before and after treatment. ResultFinally， 104 patients were included for analysis， including 52 patients in the observation group and 52 patients in the control group. After treatment， 35 and 47 patients in the control and observation groups showed improved cardiac function， which indicated the total response rates of 67.3% and 90.4%， respectively. The total response rate regarding the cardiac function in the observation group was higher than that in the control group （χ²=2.754， P<0.05）. The observation group outperformed the control group in reducing LVEDD and LAD （P<0.05）， decreasing the E/e' ratio （P<0.05）， lowering the NT-proBNP and HbA1c levels （P<0.05）， and recovering the 6MWT and Minnesota quality of life score TCM syndrome scores （P<0.05）. None of the safety indicators in the two groups showed abnormal values before and after treatment， and no serious adverse reaction was observed. ConclusionTinglu Yixin prescription can improve the heart function， exercise tolerance， and quality of life， lower the HbA1c level， and alleviate the TCM syndrome in the patients with HFpEF combined with diabetes （syndrome of qi and yin deficiency and water stagnation and blood stasis）.

Vascular malformations, which mainly occur in the head and neck region, are a group of congenital disorders that cannot involute and dilate gradually as patients grow. Traditional therapeutic strategies for vascular malformations include laser therapy, sclerotherapy, interventional embolization, surgical resection, etc. However, for some cases with a relatively larger range of lesions, traditional therapeutic strategies might fall short of the goals. With the development of molecular genetics, gene mutations are currently recognized as the root cause of the occurrence of vascular malformations. The progression of vascular malformation lesions is further promoted by the activation of related pathways. Low-flow vascular malformations mainly involve activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway, whereas high-flow vascular malformations mainly involve activation of the rat sarcoma (RAS)/rapidly accelerated fibrosarcoma (RAF)/mitogen-activated protein kinase kinase (MAPKK)/extracellular-signal regulated protein kinase (ERK) pathway. Targeted drugs against relevant gene mutations and signaling pathways have also been applied in the treatment of vascular malformations, and previous studies have shown that the mTOR inhibitor rapamycin is effective and now widely used in the treatment of low-flow vascular malformations. The PI3K inhibitor alpelisib is also promising in the treatment of venous malformations, and the MAPKK inhibitor trametinib has shown good results in the treatment of arteriovenous malformations. Therefore, traditional therapies supplemented by targeted drugs may bring new breakthroughs to the treatment of vascular malformations.

Objective: To determine the association between anthropometric parameters and 20 meter shuttle run test (20 m SRT) score among children and adolescents. Methods: The convenient sampling method was conducted to select 3 192 primary and secondary school students in Baoan District, Shenzhen, based on the street school types school from April to May 2019. Height, weight, 20 m SRT score and general demographic indicators were assessed and collected. Individuals were divided into two groups based on the dose response correlation between different anthropometric parameters (the Z score of height, weight and BMI) and 20 m SRT score analyzed with the restricted cubic spline. The association between the Z score of height and 20 m SRT score was further analyzed using the Spearman correlation analysis. Logistic regression analysis was used to analyze separately the relationship different anthropometric parameters and 20 m SRT score. Results: The Z value of weight and 20 m SRT score showed a non linear dose response association ( P <0.01), the significant but weak linear correlation between the Z value of height and 20 m SRT score ( r=0.06, P <0.05). The prevalence rate on the low level of the Z value of 20 m SRT score in 3 192 children and adolescents was 44.7%, and the gender ( χ 2=14.02, P <0.01) and grade difference ( χ 2=93.28, P <0.01) were both statistically significant. There was no significant relationship between the Z value of height and 20 m SRT score grade among total population, different genders and different grades ( P > 0.05). Compared with the reference group on the Z value of weight ≤-0.23, individuals with the Z value of weight >-0.23 had the low level of 20 m SRT score ( OR =0.61, P <0.05). Compared with the reference group on the Z value of BMI ≤ 0.25, individuals with the Z value of weight >0.25 had the low level of 20 m SRT score ( OR =0.45, P <0.05). Stratified for gender and grade, the above significant relationship on the Z value of weight, Z value of BMI and 20 m SRT score were still observed ( P <0.01). Conclusions The higher height Z value shows on correlations with 20 m SRT score, but the positive association is found between weight and BMI Z value and the 20 m SRT score. The cardiopulmonary fitness improvement may be more effective among children and adolescents when tuking weight and BMI Z scores into consideration.

Objective: The aim of this study was to establish a comprehensive concise health index (CHI) for evaluating adolescents, so as to provide a basis for determining the overall health status of adolescents in China. Methods: On the basis of a literature review and consensus among core researchers, adolescent CHI indicators in the following five dimensions were assessed:physical growth, physical fitness, common diseases, mental health and behavioral health. A total of 24 experts used an analysis hierarcgy process (AHP) to calculate the indicators subjective weights. In addition, from October to December of 2021, two regions, A and B were selected to conduct empirical research, and the CRITIC method was used to calculate the objective weights of the indicators. Finally, the weight coefficients were determined through the AHP-CRITIC combination weight method, and comprehensive evaluation was performed with the TOPSIS method. Results: Across academic period and genders, the combined weighted coefficients of the health indicators were as follows:BMI, 0.081-0.095; waist circumference, 0.070-0.081; relative grip strength, 0.101-0.108; myopia, 0.110-0.128; dental caries, 0.055-0.070; psychological symptoms, 0.240-0.262; physical exercise, 0.085-0.115; screen time, 0.097-0.111; and sleep duration, 0.086-0.103. The health index of middle school students in city A (0.626±0.065) was significantly higher than that in city B(0.613±0.066)( t=6.34, P <0.01). Conclusion The comprehensive adolescent CHI evaluation method has good consistency and application value, and may serve as a reference for adolescent health monitoring.

ObjectiveTo observe the fine structure of the trunk kidney in zebrafish, and to identify its secreted exosomes. MethodsThe microstructure and ultrastructure of the trunk kidney in zebrafish were observed by light microscopy and electron microscopy, and the particle size of exosomes was detected by nanoparticle tracking analysis (NTA). ResultsThe trunk kidney was close and parallel to the spine in adult zebrafish. The nephron consisted of renal tubules and renal corpuscles. The renal tubules could be further divided into three types: proximal convoluted tubules, distal convoluted tubules, and cervical segments. The renal corpuscles were composed of glomerulus and renal capsules. The periodic acid-Schiff (PAS) staining results revealed that there were abundant glycogen granules in the proximal convoluted tubules, with brush-like outline in the apical surface of epithelial cells. Under transmission electron microscopy (TEM), there were exosomes distributed in the lumen of renal tubules, with numerous late endosomes and few number of multivesicular bodies (MVBs) in the cytoplasm of the epithelial cells concentrating on the apical side. Meanwhile, MVBs were also distributed in the apical regions of the renal tubules and the podocytes of the renal glomeruli. Immunohistochemical staining results showed that CD9, CD63 and TSG101 were strongly expressed in the lumen surface of the renal tubules, but weakly expressed in the corpuscles and lumen. NTA and TEM results showed that the exosomes isolated from zebrafish trunk kidney were saucer-like outline, and the particle size mode was 144.4 nm, which was consistent with the characteristics of morphological futures of exosome. ConclusionThe zebrafish somatic kidney has the typical structure of the mammalian kidney and is the urinary organ in the body. The renal tubules have the ability to secrete exosomes, and their formation is a process of releasing poly-vesicles to the free surface of epithelial cells into the extracellular space. This study laid a morphological foundation for further study of exosomes in urinary function in aquatic experimental animals as well as the development and application of related models.

Objective:To evaluate the clinical effect of embolization of congenital parotid arteriovenous fistula(AVF) using coils and absolute ethanol.Methods:From January 2015 to December 2019, 8 patients with congenital AVF in parotid region were admitted to the Department of Interventional Radiology Shanghai Ninth People’s Hospital. AVF was confirmed by angiography of common carotid artery and vertebral artery through femoral artery puncture with Seldinger technique. Using coaxial microcatheter to reach the fistula via artery or using direct percutaneous puncture to reach the dilated vein and introduced microcatheter to the fistula via puncture needle. Combined detachable coils with fiber coils, and used absolute ethanol to occlude the fistula. Then the outcome was evaluated.Results:There were 7 males and 1 female involved in this study. The average age was 28.5 years (3-58 years). All of the 8 patients were confirmed AVF in parotid region by angiography, five on the right and three on the left. The feeder artery was external carotid artery, and the outflow vein was external jugular vein. Among them, 6 patients used coaxial microcatheter to reach the fistula via artery, 2 patients used direct percutaneous puncture after failure via transarteral approach. All the 8 patients were treated with absolute ethanol, the total amount of which was 17.4 ml on average. After embolization, the external carotid angiography demonstrated that the fistula was completely occluded, the branches of the external carotid artery at the distal end of the fistula were normal, and there was no obvious reflux vein. After the operation, all the patients had no pulsation and tremor. The external jugular vein dilation disappeared in 4 patients. One patient had temporary facial paralysis on the same side of the operation area. The symptoms disappeared three days after treatment. This patient had undergone coils exposed three months after operation. After local debridement, the exposed coils were removed and the wound healed. The 8 patients were followed up for 6-12 months without recurrence.Conclusions:Embolization with coils combined with absolute ethanol is safe and affective treatment for congenital parotid AVF.