BACKGROUND:Nanocell vesicles possess functions such as re-epithelialization,antioxidation,anti-inflammation,and regulation of extracellular matrix remodeling.Meanwhile,apoptotic bodies have the immunomodulatory effects.Therefore,the combination of the two to form nanofusion vesicles can synergistically promote the healing of diabetic skin wounds.OBJECTIVE:To elucidate the impact of nanofusion vesicles on skin wound healing in a diabetic murine model.METHODS:(1)Material preparation and characterization:The primary bone marrow mesenchymal stem cells of C57BL/6J neonatal mice and the neutrophil apoptotic bodies of C57BL/6J mice were isolated and extracted.The nanofusion vesicles were prepared by micro-extrusion mechanism.(2)In vitro experiment:MTT assay was used to detect the proliferative effect of different concentrations of nanofusion vesicles on NIH-3T3 cells and human umbilical vein endothelial cells.Reactive oxygen species fluorescence probe was used to detect the antioxidant effect of nano-fusion vesicles on NIH-3T3 cells treated with hydrogen peroxide(H2O2).The inhibitory effect of nanofusion vesicles on RAW 264.7 macrophage inflammation induced by lipopolyside was detected by real-time quantitative RT-qPCR.(3)In vivo experiment:36 male C57BL/6J mice were employed to develop a murine model of diabetes mellitus.Following the successful induction of diabetes,two circular full-thickness wounds,each with a diameter of 6 mm,were created on either side of the diabetic mice's spine using a skin punch.The mice were divided into three groups by random number table method.The control group was injected with 0.1 mL of phosphate buffer solution.The nanovesicle group was injected with 0.1 mL nanovesicles(25 μg/mL).The nanofusion vesicle group was injected with 0.1 mL nanofusion(25 μg/mL)vesicles.After treatment for three consecutive days,the wound healing and histomorphological changes were observed.RESULTS AND CONCLUSION:(1)In vitro experiment:nanofusion vesicles,when administered at concentrations ranging from 0 to 100 μg/mL,exhibited no toxic effects and promoted the proliferation of NIH-3T3 and HUVEC cell lines.Notably,a concentration of 25 μg/mL nanofusion vesicle significantly enhanced the proliferation of NIH-3T3 cells.Furthermore,the survival rate of human umbilical vein endothelial cells was observed to increase in correlation with escalating concentrations of nanofusion vesicles.Nanofusion vesicles had a good antioxidant effect.In comparison to the H2O2 group,the fluorescence signal indicative of reactive oxygen species was progressively diminished in both the nanovesicle group and the nanofusion vesicle group.Furthermore,nanofusion vesicles possessed anti-inflammatory capabilities,effectively mitigating the inflammatory response in macrophages triggered by lipopolysaccharide stimulation.(2)In vivo experiment:Hematoxylin-eosin and Masson's trichrome staining revealed that in comparison to the control group,both the nanovesicle group and the nanofusion vesicle group exhibited a significant increase in granulation tissue formation and collagen fiber deposition within the wounds by day 6.Notably,the nanofusion vesicle group displayed the most pronounced effects.On day 12,the wound of nanofusion vesicle group was significantly reduced,and the healing rate was significantly faster than that of other groups(P＜0.01),and the effect of promoting wound healing was the most significant.Our findings demonstrated that nanofusion vesicles exhibited superior pro-cell proliferative,antioxidant,and anti-inflammatory properties,thereby exerting a beneficial effect on the promotion of skin wound healing in diabetic mouse models.

BACKGROUND:Nanocell vesicles possess functions such as re-epithelialization,antioxidation,anti-inflammation,and regulation of extracellular matrix remodeling.Meanwhile,apoptotic bodies have the immunomodulatory effects.Therefore,the combination of the two to form nanofusion vesicles can synergistically promote the healing of diabetic skin wounds.OBJECTIVE:To elucidate the impact of nanofusion vesicles on skin wound healing in a diabetic murine model.METHODS:(1)Material preparation and characterization:The primary bone marrow mesenchymal stem cells of C57BL/6J neonatal mice and the neutrophil apoptotic bodies of C57BL/6J mice were isolated and extracted.The nanofusion vesicles were prepared by micro-extrusion mechanism.(2)In vitro experiment:MTT assay was used to detect the proliferative effect of different concentrations of nanofusion vesicles on NIH-3T3 cells and human umbilical vein endothelial cells.Reactive oxygen species fluorescence probe was used to detect the antioxidant effect of nano-fusion vesicles on NIH-3T3 cells treated with hydrogen peroxide(H2O2).The inhibitory effect of nanofusion vesicles on RAW 264.7 macrophage inflammation induced by lipopolyside was detected by real-time quantitative RT-qPCR.(3)In vivo experiment:36 male C57BL/6J mice were employed to develop a murine model of diabetes mellitus.Following the successful induction of diabetes,two circular full-thickness wounds,each with a diameter of 6 mm,were created on either side of the diabetic mice's spine using a skin punch.The mice were divided into three groups by random number table method.The control group was injected with 0.1 mL of phosphate buffer solution.The nanovesicle group was injected with 0.1 mL nanovesicles(25 μg/mL).The nanofusion vesicle group was injected with 0.1 mL nanofusion(25 μg/mL)vesicles.After treatment for three consecutive days,the wound healing and histomorphological changes were observed.RESULTS AND CONCLUSION:(1)In vitro experiment:nanofusion vesicles,when administered at concentrations ranging from 0 to 100 μg/mL,exhibited no toxic effects and promoted the proliferation of NIH-3T3 and HUVEC cell lines.Notably,a concentration of 25 μg/mL nanofusion vesicle significantly enhanced the proliferation of NIH-3T3 cells.Furthermore,the survival rate of human umbilical vein endothelial cells was observed to increase in correlation with escalating concentrations of nanofusion vesicles.Nanofusion vesicles had a good antioxidant effect.In comparison to the H2O2 group,the fluorescence signal indicative of reactive oxygen species was progressively diminished in both the nanovesicle group and the nanofusion vesicle group.Furthermore,nanofusion vesicles possessed anti-inflammatory capabilities,effectively mitigating the inflammatory response in macrophages triggered by lipopolysaccharide stimulation.(2)In vivo experiment:Hematoxylin-eosin and Masson's trichrome staining revealed that in comparison to the control group,both the nanovesicle group and the nanofusion vesicle group exhibited a significant increase in granulation tissue formation and collagen fiber deposition within the wounds by day 6.Notably,the nanofusion vesicle group displayed the most pronounced effects.On day 12,the wound of nanofusion vesicle group was significantly reduced,and the healing rate was significantly faster than that of other groups(P＜0.01),and the effect of promoting wound healing was the most significant.Our findings demonstrated that nanofusion vesicles exhibited superior pro-cell proliferative,antioxidant,and anti-inflammatory properties,thereby exerting a beneficial effect on the promotion of skin wound healing in diabetic mouse models.

The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is higher among individuals with inflammatory bowel disease (IBD) than in the general population. Emerging evidence indicates that the development of MASLD in patients with IBD may occur independently of traditional metabolic risk factors, suggesting a unique pathophysiological mechanism distinct from conventional MASLD pathways. Bile acids (BAs), which act as critical signaling molecules in enterohepatic circulation, play an essential role in maintaining gastrointestinal homeostasis through bidirectional gut–liver axis communication. These molecules are increasingly recognized as pivotal regulators in the progression of both MASLD and IBD. While previous studies have characterized the dynamics of BA in blood or fecal samples under both conditions, a comprehensive understanding of their metabolic profiles and the associated interactions within the gut–liver axis is still lacking. This review synthesizes current evidence from studies employing BA metabolomics to investigate IBD and MASLD. By focusing on BA signatures, we summarize conserved alterations between these two conditions and their potential mechanisms of disease progression. Our review advances understanding of BA-mediated pathways in IBD and MASLD, providing a foundation for assessing their roles in contributing to the pathogenesis of MASLD in patients with IBD.

In order to explore the possible role and molecular mechanism of the combined action of leech and bear bile in liver and gallbladder diseases, this study first used network pharmacology methods to screen the components and targets of leech and bear bile, as well as the related target genes of liver and gallbladder diseases. The selected key genes were subjected to interaction network and GO/KEGG enrichment analysis. Then, using sodium oleate induced HepG2 cell lipid deposition model and DL-ethionine induced mouse fatty liver model, the activity of leech and bear bile alone and in combination in reducing liver fat was evaluated in vitro and in vivo, and the expression of key pathway related proteins suggested by network pharmacology was detected by Western blot. The results of network pharmacology analysis showed that the active ingredients of leech and bear bile have 295 intersecting targets with liver and gallbladder related diseases, involving more than 200 signaling pathways, including the PI3K/Akt signaling pathway and phospholipase D signaling pathway closely related to glucose and lipid metabolism. The results of in vitro validation experiments showed that both leech and bear bile, alone and in combination, can significantly inhibit the lipid deposition induced by sodium oleate in human liver cells, reduce the triacylglycerol level in cell culture supernatant, and inhibit the lipid content in liver cells. The observation results of Nile red staining confocal microscopy showed that the combination of leech and bear bile had better activity in reducing lipid deposition in liver cells compared to using them alone. In a mouse fatty liver model, the combination of leech and bear bile can better reduce elevated organ indices, blood lipids, and liver lipid levels, as well as lower the levels of serum liver injury biomarkers. The animals used in this experiment and related disposal meet the requirements of animal welfare. Before the experiment, it was reviewed and approved by IACUC, Institute of Materia Medica, Chinese Academy of Medical Sciences. The Western blot experiment results showed that the combination of leech and bear bile can significantly upregulate the expression levels of p-PI3K and p-Akt proteins, and increase the p-PI3K/PI3K and p-Akt/Akt ratios, which is consistent with the predicted results of network pharmacology. The combination of leech and bear bile has great potential for treating fatty liver disease, and activating the PI3K/Akt pathway may be one of the important mechanisms for reducing lipid deposition in liver cells.

Objective:This study aimed to examine the association between malnutrition diagnosed by the Global Leadership Initiative on Malnutrition(GLIM)criteria and clinical outcomes in surgical patients,as well as to assess its prognostic impact on postoperative adverse clinical outcomes.Methods:Electronic databases,including PubMed,Embase,Web of Science,CINAHL,Scopus,The Cochrane Library,Clinical Trials,CNKI,Wanfang Data Knowledge Service Platform,and the Chinese Biomedical Literature Database,were systematically searched.Relevant cohort studies utilizing GLIM criteria to preoperatively diagnose malnutrition in surgical inpatients were included.The exposed group comprised surgical patients diagnosed with preoperative malnutrition using GLIM criteria,while the control group consisted of surgically treated patients without malnutrition as per GLIM criteria.Literature quality was evaluated using the Newcastle-Ottawa Scale(NOS),and meta-analysis was performed using Review Manager 5.4 software.Results:Fourteen literatures were included,with a total sample size of 10,045 patients.Meta-analysis revealed that the malnourished group had a higher incidence of postoperative complications compared to the non-malnourished group[risk ratio(RR)=1.81,95%CI:1.66～1.98),P<0.00001].Additionally,the incidence of severe complications was significantly higher in GLIM-diagnosed malnourished patients.The malnourished group exhibited poorer overall survival[hazard ratio(HR)=1.90,95%CI:1.55～2.34,P<0.00001]and disease-free survival[HR=2.25,95%CI:1.02～4.93,P=0.04]compared to the non-malnourished group.Conclusion:GLIM-diagnosed malnutrition is significantly associated with adverse clinical outcomes in surgical patients,increasing postoperative complication rates and reducing overall and disease-free survival.The GLIM criteria demonstrate value in predicting adverse clinical outcomes in this population.Further high-quality studies are warranted to validate these findings.

Objective:To investigate the nutritional status of esophageal cancer patients and analyze the ability of the modified Patient-Generated Subjective Global Assessment(mPG-SGA)to evaluate nutritional status against the original PG-SGA standard.Method:We enrolled 479 patients newly diagnosed with esophageal cancer at a provincial tertiary hospital in Shenyang from August 2022 to April 2024.Blood samples were analyzed for nutritional indicators,and nutritional status was assessed using both PG-SGA and mPG-SGA.The nutritional assessment ability of mPG-SGA was evaluated using specificity,sensitivity,area under the curve(AUC),weighted kappa coefficient,and correlation analysis.Results:Among the 479 patients,the incidence of moderate-to-severe malnutrition was 74.9%(by PG-SGA)and 72.9%(by mPG-SGA).Using PG-SGA as the standard,mPG-SGA demonstrated sensitivities of 95.4%,100%,and 100%;specificities of 98.5%,92.3%,and 89.5%;and AUC values of 0.997,0.994,and 0.989(all P<0.001)for distinguishing mild vs.moderate-to-severe malnutrition,mild-to-moderate malnutrition,and moderate-to-severe malnutrition,respectively.The overall weighted Kappa coefficient between the scales was 0.898(P<0.001).Conclusion:Malnutrition is highly prevalent among esophageal cancer patients.The mPG-SGA shows strong accuracy and consistency with PG-SGA in assessing nutritional status.Given its simplicity and efficiency,mPG-SGA may become a primary nutritional assessment tool for this population,though further multicenter validation with larger samples is warranted.

T7 RNA polymerase (T7 RNAP) is one of the simplest known RNA polymerases. Its unique structural features make it a critical model for studying the mechanisms of RNA synthesis. This review systematically examines the static crystal structure of T7 RNAP, beginning with an in-depth examination of its characteristic “thumb”, “palm”, and “finger” domains, which form the classic “right-hand-like” architecture. By detailing these structural elements, this review establishes a foundation for understanding the overall organization of T7 RNAP. This review systematically maps the functional roles of secondary structural elements and their subdomains in transcriptional catalysis, progressively elucidating the fundamental relationships between structure and function. Further, the intrinsic flexibility of T7 RNAP and its applications in research are also discussed. Additionally, the review presents the structural diagrams of the enzyme at different stages of the transcription process, and through these diagrams, it provides a detailed description of the complete transcription process of T7 RNAP. By integrating structural dynamics and kinetics analyses, the review constructs a comprehensive framework that bridges static structure to dynamic processes. Despite its advantages, T7 RNAP has a notable limitation: it generates double-stranded RNA (dsRNA) as a byproduct. The presence of dsRNA not only compromises the purity of mRNA products but also elicits nonspecific immune responses, which pose significant challenges for biotechnological and therapeutic applications. The review provides a detailed exploration of the mechanisms underlying dsRNA formation during T7 RNAP catalysis, reviews current strategies to mitigate this issue, and highlights recent progress in the field. A key focus is the semi-rational design of T7 RNAP mutants engineered to minimize dsRNA generation and enhance catalytic performance. Beyond its role in transcription, T7 RNAP exhibits rapid development and extensive application in fields, including gene editing, biosensing, and mRNA vaccines. This review systematically examines the structure-function relationships of T7 RNAP, elucidates the mechanisms of dsRNA formation, and discusses engineering strategies to optimize its performance. It further explores the engineering optimization and functional expansion of T7 RNAP. Furthermore, this review also addresses the pressing issues that currently need resolution, discusses the major challenges in the practical application of T7 RNAP, and provides an outlook on potential future research directions. In summary, this review provides a comprehensive analysis of T7 RNAP, ranging from its structural architecture to cutting-edge applications. We systematically examine: (1) the characteristic right-hand domains (thumb, palm, fingers) that define its minimalistic structure; (2) the structure-function relationships underlying transcriptional catalysis; and (3) the dynamic transitions during the complete transcription cycle. While highlighting T7 RNAP’s versatility in gene editing, biosensing, and mRNA vaccine production, we critically address its major limitation—dsRNA byproduct formation—and evaluate engineering solutions including semi-rationally designed mutants. By synthesizing current knowledge and identifying key challenges, this work aims to provide novel insights for the development and application of T7 RNAP and to foster further thought and progress in related fields.

Objective:To investigate the efficacy and safety of different endovascular interventional treatments for extracranial carotid artery pseudoaneurysms.Method:The clinical data of 48 patients with extracranial carotid artery pseudoaneurysms treated with multiple endovascular procedures were retrospectively analyzed in the First Affiliated Hospital of Zhengzhou University from February 2012 to February 2024. The patients presented with a total of 48 extracranial carotid pseudoaneurysms, ranging in diameter from 2.5 to 34.2 mm [mean (12.0±9.6) mm]. The lesions were distributed as follows: 25 in the internal carotid artery, 16 in the external carotid artery and 7 in the common carotid artery. The selection of endovascular interventional techniques was tailored to individual cases according to the pseudoaneurysm size, anatomical location, morphological configuration, and specific features of the parent artery. Perioperative adverse events were monitored, and the efficacy of individualized endovascular interventional therapy was evaluated based on immediate postoperative and 6-month follow-up digital subtraction angiography (DSA) findings, including aneurysm occlusion and in-stent patency.Result:The treatment modalities included parent artery coiling occlusion ( n=16), overlapping braided carotid stent implantation ( n=3), covered stent placement ( n=23), combined implantation of covered stent and braided carotid stent implantation ( n=4) and flow-diverting stent implantation ( n=2) based on the characteristics of the pseudoaneurysms. Endovascular interventional procedures were successfully completed in 47 patients (technical success rate: 97.9%). Immediate postoperative DSA revealed residual pseudoaneurysm at the distal end of the stent in 1 case. Among the remaining cases, complete aneurysm obliteration or faint opacification was observed, with stent lumen patency confirmed in 31 cases and complete parent artery occlusion achieved in 16 cases. In one case involving a patient who underwent flow-diverting stent implantation, a pulsatile vascular murmur reappeared in the neck one week postoperatively. Follow-up DSA revealed stent migration into the aneurysm sac. After retrieval and removal of the displaced stent, combined implantation of a covered stent and a braided carotid artery stent was performed. Postoperative angiography confirmed complete aneurysm occlusion and patent parent artery blood flow. No severe perioperative adverse events (e.g., aneurysm rupture) were observed. During a postoperative follow-up period of 6.2-24.2 months, DSA at 6 months revealed mild in-stent or distal segment stenosis in 2 patients who underwent covered stent implantation. The remaining 46 patients exhibited complete aneurysm occlusion with no significant stenosis observed within the stent lumen. At the final follow-up, all patients demonstrated resolution or significant alleviation of clinical symptoms. Conclusion:Individualized endovascular interventional therapy demonstrates favorable safety and efficacy profiles in managing extracranial carotid artery pseudoaneurysms.

Objective To study the tongue manifestation of patients with different syndromes in non-small cell lung cancer(NSCLC)and the correlation between tongue characteristics of different syndromes and tumor markers and coagulation indicators.Methods Totally 497 patients with NSCLC were grouped according to syndrome differentiation,and the differences in tongue characteristics of different syndromes were compared.Bivariate correlation analysis was used to study the correlation between tongue characteristics and serum tumor markers and coagulation indicators in patients with NSCLC of different syndromes.Results Compared with healthy people of different syndromes,in TB-a,yin deficiency and phlegm-heat syndrome>healthy group>qi-yin deficiency syndrome>spleen deficiency and phlegm-dampness syndrome>lung stagnation and phlegm-stasis syndrome(P<0.001).In TB-L,healthy group>spleen deficiency and phlegm-dampness syndrome>qi-yin deficiency syndrome>lung stagnation and phlegm-stasis syndrome>yin deficiency and phlegm-heat syndrome(P<0.001).In TB-b,yin deficiency and phlegm-heat syndrome>qi-yin deficiency syndrome>spleen deficiency and phlegm-dampness syndrome>healthy group>lung stagnation and phlegm-stasis syndrome(P<0.001).Yin deficiency and phlegm-heat syndrome had the highest TB-a and the lowest Per-all.Spleen deficiency and phlegm-dampness syndrome had the highest TB-L and Per-all.Lung stagnation and phlegm-stasis syndrome had lower TB-b and TC-b than other groups,lower TB-a than the healthy group,and a high Per-all index(P<0.05).In terms of tumor markers,Per-all in spleen deficiency and phlegm-dampness syndrome was positively correlated with Ca199,Ca50 and Ca242(P<0.05).In terms of coagulation indicators,the tongue texture index of lung stagnation and phlegm-stasis syndrome had a high correlation with the coagulation indicator Fg(P<0.01).Conclusion Different TCM syndromes of NSCLC have their own typical tongue characteristics.Tongue manifestations of different syndromes are correlated with tumor markers and coagulation indicators,respectively,which can reflect changes in clinical status.

Objective:To investigate the ability to diagnose, treat and manage kidney disease in Shanghai community health service centers.Methods:This was a cross-sectional survey. An online questionnaire survey was conducted in November 2023 among 248 Shanghai community health service centers and 2 140 general practitioners in Shanghai. The main topics of the institutional research were the kidney disease-related inspection items that medical institutions could carry out, the kidney disease diagnosis and treatment drugs, the kidney disease grass-roots management training, the opening of kidney disease clinics and the establishment of kidney disease standard diagnosis and treatment records. The main topics of the survey of general practitioners were general information, standardized diagnosis and management measures of kidney disease, knowledge based on the diagnosis and treatment guidelines of chronic kidney disease, and difficulties in standardized management of kidney disease.Results:Among the laboratory examination items in Shanghai community health service centers, the rates of routine urine (99.60%, 247 centers), renal function (95.16%, 236 centers) and urinary microalbumin (89.11%, 229 centers) were high. Among the imaging examinations, B-ultrasound of urinary system had the highest rate (92.34%, 229 centers). The preparation rate of kidney disease drugs varied widely among the centers, and the preparation rate of Chinese drugs such as Jinshuibao, nephritis Kangfu tablet and Shenshuaining was more than 90%. Sixty-six (26.61%) community health service centers had established kidney disease clinics. The overall accuracy rate of community general practitioners was 63.81% (13 656/21 400), of which the accuracy rate for diagnosis and screening method, referral indication and emergency dialysis indication was more than 85%, but the accuracy rate for drug treatment and careful medication was low at 28.93% (1 238/4 280) and 33.22% (711/2 140), respectively. There was a willingness for Community general practitioners to provide all aspects of life guidance for patients with kidney disease, but for patients with end-stage renal disease replacement therapy, there was a preference for this to be provided by the appropriate specialist.Conclusions:The community health service centers in Shanghai has already had the basic conditions for the management of kidney disease in terms of basic examination and testing equipment, drugs, etc. The community general practitioners have a certain knowledge of kidney disease, and the drug treatment needs to be strengthened.