OBJECTIVE To study the improvement effect and mechanism of Tripterygium wilfordii multiglucoside （TWM） on nephrotic syndrome in rats. METHODS The nephrotic syndrome model was established by intravenous injection of adriamycin via the tail vein. The modeling rats were randomly divided into the model group （distilled water）， prednisone group （10 mg/kg）， and TWM high- and low-dose groups （10 and 5 mg/kg， respectively）. Additionally， blank group （distilled water） without model induction was established. Each group consisted of 9 rats. Rats in each group were administered the corresponding drugs or distilled water by gavage， once a day， for 6 consecutive weeks. The histopathological morphology of kidney tissues in rats was observed； the levels of 24-hour urinary protein （24 h-UTP） and serum biochemical indicators [albumin （ALB）， blood urea nitrogen （BUN）， serum creatinine （SCr）， cholesterol （CHOL）， and triglyceride （TG）] in rats were determined； the levels of oxidative stress indicators [superoxide dismutase （SOD）， malondialdehyde （MDA）] in kidney tissue of rats were determined； expressions of hypoxia-inducible factor-1α （HIF-1α）/microRNA-155-5p （miR-155-5p）/nuclear factor erythriod 2- related factor 2 （Nrf2） signaling pathway-related mRNA and protein in the renal tissues of rats were detected. RESULTS Compared with the blank group， the rats in the model group exhibited disordered renal tissue structure， with a small amount of glomerular necrosis and edema of the renal tubular epithelial cells. 24 h-UTP， serum levels of SCr， BUN， CHOL and TG， MDA content， mRNA and protein expressions of HIF-1α and Keap1 as well as the expression of miR-155-5p in renal tissues were increased significantly （ P ＜0.05）. Serum level of ALB， SOD level in renal tissue as well as mRNA and protein expressions of Nrf2 were decreased significantly （ P ＜0.05）. Compared with the model group， TWM high-dose and low-dose groups exhibited significant improvements in renal injury， with notable reversals in the levels of the above quantitative indicators （ P ＜0.05）. CONCLUSIONS TWM can alleviate oxidative stress-induced damage and thereby improve nephrotic syndrome in rats by regulating the HIF-1α/miR-155-5p/Nrf2 signaling pathway.

Plant-derived extracellular vesicles (PDEVs) are nanoscale extracellular vesicles secreted by plant cells, characterized by a lipid bilayer structure. These vesicles carry a variety of bioactive molecules, including proteins, nucleic acids, and lipids, and play essential roles in intercellular communication and physiological regulation in plants. Compared to animal-derived extracellular vesicles, PDEVs offer several advantages, such as a broad range of sources, high biocompatibility, low immunogenicity, and low production costs. Furthermore, PDEVs have demonstrated remarkable potential as natural nanocarriers for drug delivery, due to their ability to efficiently traverse biological barriers, such as the blood-brain barrier, making them promising candidates for drug delivery systems. This review systematically elaborates on the complex composition of PDEVs, which consists of lipids, proteins, and nucleic acids, the typical structural characteristics of their lipid bilayers ranging from 30 to 150 nm, and their versatile loading capabilities as drug carriers, efficiently encapsulating various types of therapeutic agents such as hydrophilic small molecules, hydrophobic drugs, nucleic acids, and proteins. We systematically summarize the recent advancements in strategies for enhancing the loading efficiency of PDEVs, which include methods such as co-incubation, ultrasound-assisted loading, electroporation, freeze-thaw cycles, and microfluidic technology. These techniques are evaluated based on their underlying principles, suitable drug types, and their respective advantages. In addition to loading strategies, we focus on the engineered approaches to achieve targeted delivery using PDEVs, such as genetic engineering modifications, chemical ligand conjugation, membrane fusion technology, and polyethylene glycol (PEG) modification. We discuss the mechanisms of these strategies in enhancing targeting efficiency, prolonging in vivo circulation time, and improving therapeutic efficacy. Further, this review highlights the application of PDEVs in various disease models, including tumor, skin inflammation, metabolic disorders, and neurodegenerative diseases, showcasing their therapeutic potential as multifunctional delivery platforms. The ability of PDEVs to encapsulate diverse therapeutic agents and target specific tissues or cells opens up new avenues for the treatment of complex diseases, offering advantages over conventional drug delivery systems. However, despite the promising applications of PDEVs, several challenges remain in their development and clinical translation. These challenges include variability in source materials, standardization of preparation processes, quality control, scalability of production, and the need for clinical validation. To overcome these obstacles, the integration of advanced technologies such as artificial intelligence-assisted design and multi-omics analysis is proposed as a way to facilitate the precise development of PDEVs. These emerging technologies hold the potential to further enhance the precision and effectiveness of plant-based drug delivery systems, ultimately advancing the field of precision medicine. In conclusion, the use of PDEVs as a platform for drug delivery represents a promising area of research with the potential to revolutionize therapeutic strategies. Their ability to encapsulate and deliver a wide variety of bioactive molecules, along with their inherent advantages in biocompatibility and versatility, makes them a valuable tool in the development of more efficient and targeted therapeutic interventions. Continued research and innovation in this field will pave the way for the clinical implementation of PDEVs in the treatment of various diseases, offering new hope for more effective and sustainable therapeutic options.

To investigate the transcriptionally regulatory mechanism of the senp8 promoter in yellow cat-fish(Pelteobagrus fulvidraco);this study used P.fulvidraco as the research subject.Dual-luciferase re-porter assay and electrophoretic mobility shift assay were employed to analyze the functional activity of the promoter;coupled with in vivo experiments.The results indicated that the 2 045 bp senp8 promoter se-quence contained key transcription factor binding sites such as SP1;TATA-Box;CCAAT-Box;SREBP1;PPARα;and PPARγ.The binding sites of SREBP1(-901/-910 bp);PPARα(-1 291/-1 308 bp);and PPARγ(-1 292/-1 306 bp)in the senp8 promoter positively regulate its activity;and oleic acid or palmitic acid promote this binding.Furthermore;high-fat feeding promoted the expression of the senp8 gene and its protein in the liver of P.fulvidraco;oleic acid or palmitic acid treatment significantly en-hanced the activity of the senp8 promoter;and this enhancement could be achieved through the regulatory effects of SREBP1;PPARα;and PPARγ response elements.Additionally;high-fat feeding influenced the mRNA and protein expression levels of genes related to deSUMOylation modification in the liver of P.fulvidraco.This study provides new insights into the relationship between deSUMOylation modification and the regulation of lipid metabolism in the vertebrates.

Objective:To investigate the association of the interaction and combined effect of renal function and body mass index (BMI) with the risk for all-cause death in patients with type 2 diabetes mellitus (T2DM) in communities of Jiangsu Province.Methods:The study subjects were from the Comprehensive Research Project of Diabetes Prevention and Control conducted in Jiangsu from December 2013 to January 2014, and follow up was conducted for them until September 30, 2023. A total of 20 025 subjects were included in the study. Cox proportional hazards regression model was used to analyze the association of renal function with risk for death in T2DM patients, and the association of interaction between renal function and BMI and their combined effect with all-cause death risk in T2DM patients.Results:In the follow up for 198 370 person-years, a total of 4 459 deaths were recorded. Cox proportional hazards regression model analysis showed that renal dysfunction was associated with 71% risk of all-cause mortality in all T2DM patients [hazard ratio ( HR) =1.71, 95% CI: 1.59-1.84], as well as in all BMI subgroups. Likelihood ratio test indicated an interaction between renal function and BMI (interaction for P=0.030). Compared with patients with normal renal function and normal BMI, those with normal renal function and over weight or obesity had a lower risk of all-cause mortality, and those with renal dysfunction and low weight had the highest risk for death ( HR=2.78, 95% CI: 1.87-4.14). Conclusions:There is association of interaction between renal function and BMI with all-cause mortality in T2DM patients. T2DM patients with renal dysfunction and low body weight had significant higher risk for death.

Objective:To investigate the clinicopathological characteristics and molecular variants of chromophobe renal cell carcinoma with small cell components/neuroendocrine-like features (ChRCC-SC/ND-L).Methods:There were 7 cases of ChRCC-SC/ND-L diagnosed by light microscopy and immunohistochemical staining were collected from the Affiliated Hospital of Qingdao University (5 cases) and 971 Hospital of the People′s Liberation Army Navy (2 cases) between January 2010 and December 2023. The clinical data, histological characteristics, and immunohistochemical staining results of the patients were summarized. Among them, 4 cases underwent whole exome sequencing.Results:Among the 7 cases, 5 cases were male and 2 cases were female. The mean age was 53 (43,58)years,with a range of 36 to 76 years. Gross examination showed that the mean maximum tumor diameter was 7.9 (6.0,9.0) cm,with a range of 5.5 to 13.0 cm. The tumors were nodular, well-defined, gray, red or yellow in color with a solid cut surface, except for 1 case with cystic and solid on cut surface. One case showed visible necrosis, and 1 case invaded the renal pelvis and sinus. Microscopically, the tumors had clear boundaries. Typical ChRCC components (5 cases of classical type, 2 cases of eosinophilic type) were found in all cases, accompanied by varying amounts of small cell components (5%-90%). The two components were mixed in 6 cases or directly adjacent to each other in 1 case. The small cell components were arranged in clusters, dense acinar and nest-like structures, beam-like, fence-like, chrysanthemum-shaped clusters, and ribbon-like patterns. Three cases exhibited patchy necrosis. Intravascular tumor thrombus was found in 1 case. Immunohistochemically, EMA was expressed consistently in the small cell and typical ChRCC components (7/7); whilst both CK7 and CD117 were negative in 1 case with typical ChRCC component (6/7). Small cell components in 3 cases were positive for CD56, whereas all 7 cases were negative for CgA, Syn, and INSM1. The Ki-67 proliferation index was less than 1% in both components. Whole exome sequencing revealed that the 4 cases exhibited different genetic aberrations including 1 case with multiple chromosomal deletions, while 2 cases showed amplification of chromosome 12 and deletion of chromosome 11, respectively. The 7 cases were followed up for 25 to 172 months. Except for 1 patient that died with unknown causes 25 months after surgery, the remaining 6 cases were still alive (average 103.8 months, median 101 months).Conclusions:ChRCC-SC/ND-L is a very rare subtype of ChRCC. The small cell component does not represent true neuroendocrine differentiation and might indicate a morphological heterogeneity of the tumor. The presence of typical chromophobe cell carcinoma components is helpful for the diagnosis of ChRCC-SC/ND-L and they do not have consistent molecular characteristics. ChRCC-SC/ND-L has a good prognosis and the small cell components/neuroendocrine-like components might not have a significant impact on the outcome of patients with the tumor.

To investigate the transcriptionally regulatory mechanism of the senp8 promoter in yellow cat-fish(Pelteobagrus fulvidraco);this study used P.fulvidraco as the research subject.Dual-luciferase re-porter assay and electrophoretic mobility shift assay were employed to analyze the functional activity of the promoter;coupled with in vivo experiments.The results indicated that the 2 045 bp senp8 promoter se-quence contained key transcription factor binding sites such as SP1;TATA-Box;CCAAT-Box;SREBP1;PPARα;and PPARγ.The binding sites of SREBP1(-901/-910 bp);PPARα(-1 291/-1 308 bp);and PPARγ(-1 292/-1 306 bp)in the senp8 promoter positively regulate its activity;and oleic acid or palmitic acid promote this binding.Furthermore;high-fat feeding promoted the expression of the senp8 gene and its protein in the liver of P.fulvidraco;oleic acid or palmitic acid treatment significantly en-hanced the activity of the senp8 promoter;and this enhancement could be achieved through the regulatory effects of SREBP1;PPARα;and PPARγ response elements.Additionally;high-fat feeding influenced the mRNA and protein expression levels of genes related to deSUMOylation modification in the liver of P.fulvidraco.This study provides new insights into the relationship between deSUMOylation modification and the regulation of lipid metabolism in the vertebrates.

To understand the background of Escherichia coli(E.coli)carried by artificially bred sika deer and the biological characteristics of the isolated strains,such as drug resistance and pathogenicity,in April 2024,we collected 184 fresh deer fecal samples from four deer farms in Luxiang Township,Shuangyang District,Changchun City,Jilin Province,for isolation and cultivation of E.coli.The isolates were tested for drug resistance and biochemical identification with a BD PhoenixTM-100 Automated Microbiology System.The virulence genes were detected with PCR,and the strains were molecularly typed with ERIC-PCR.A total of 165 E.coli strains were isolated from 184 samples of deer feces,with an isolation rate of 89.67%.Twenty strains had a drug resistance phenotype,and the drug resistance rate was 12.12%;these strains included 15 strains of multi-drug resistant bacteria and 11 strains of ESBL-producing bacteria.Virulence gene detection indicated that the sika deer isolates carried multiple diarrhea-associated virulence genes,such as EAST-1(12.12%),eae(1.21%),stx1(7.88%),stx2(7.27%),and STa(1.82%).ERIC-PCR demonstrated that the isolates showed high polymorphism.The ESBL-producing E.coli carried by sika deer are likely to spread drug resistance in the community and livestock population.Some isolates carried multiple diarrhea-associated virulence genes,thus posing a human transmission risk.Therefore,monitoring of drug resistance and virulence genes must be strengthened,and antibiotics must be used reasonably during the breeding process to avoid excessive use and misuse.

To understand the background of Escherichia coli(E.coli)carried by artificially bred sika deer and the biological characteristics of the isolated strains,such as drug resistance and pathogenicity,in April 2024,we collected 184 fresh deer fecal samples from four deer farms in Luxiang Township,Shuangyang District,Changchun City,Jilin Province,for isolation and cultivation of E.coli.The isolates were tested for drug resistance and biochemical identification with a BD PhoenixTM-100 Automated Microbiology System.The virulence genes were detected with PCR,and the strains were molecularly typed with ERIC-PCR.A total of 165 E.coli strains were isolated from 184 samples of deer feces,with an isolation rate of 89.67%.Twenty strains had a drug resistance phenotype,and the drug resistance rate was 12.12%;these strains included 15 strains of multi-drug resistant bacteria and 11 strains of ESBL-producing bacteria.Virulence gene detection indicated that the sika deer isolates carried multiple diarrhea-associated virulence genes,such as EAST-1(12.12%),eae(1.21%),stx1(7.88%),stx2(7.27%),and STa(1.82%).ERIC-PCR demonstrated that the isolates showed high polymorphism.The ESBL-producing E.coli carried by sika deer are likely to spread drug resistance in the community and livestock population.Some isolates carried multiple diarrhea-associated virulence genes,thus posing a human transmission risk.Therefore,monitoring of drug resistance and virulence genes must be strengthened,and antibiotics must be used reasonably during the breeding process to avoid excessive use and misuse.

Objective:To investigate the clinicopathological characteristics and molecular variants of chromophobe renal cell carcinoma with small cell components/neuroendocrine-like features (ChRCC-SC/ND-L).Methods:There were 7 cases of ChRCC-SC/ND-L diagnosed by light microscopy and immunohistochemical staining were collected from the Affiliated Hospital of Qingdao University (5 cases) and 971 Hospital of the People′s Liberation Army Navy (2 cases) between January 2010 and December 2023. The clinical data, histological characteristics, and immunohistochemical staining results of the patients were summarized. Among them, 4 cases underwent whole exome sequencing.Results:Among the 7 cases, 5 cases were male and 2 cases were female. The mean age was 53 (43,58)years,with a range of 36 to 76 years. Gross examination showed that the mean maximum tumor diameter was 7.9 (6.0,9.0) cm,with a range of 5.5 to 13.0 cm. The tumors were nodular, well-defined, gray, red or yellow in color with a solid cut surface, except for 1 case with cystic and solid on cut surface. One case showed visible necrosis, and 1 case invaded the renal pelvis and sinus. Microscopically, the tumors had clear boundaries. Typical ChRCC components (5 cases of classical type, 2 cases of eosinophilic type) were found in all cases, accompanied by varying amounts of small cell components (5%-90%). The two components were mixed in 6 cases or directly adjacent to each other in 1 case. The small cell components were arranged in clusters, dense acinar and nest-like structures, beam-like, fence-like, chrysanthemum-shaped clusters, and ribbon-like patterns. Three cases exhibited patchy necrosis. Intravascular tumor thrombus was found in 1 case. Immunohistochemically, EMA was expressed consistently in the small cell and typical ChRCC components (7/7); whilst both CK7 and CD117 were negative in 1 case with typical ChRCC component (6/7). Small cell components in 3 cases were positive for CD56, whereas all 7 cases were negative for CgA, Syn, and INSM1. The Ki-67 proliferation index was less than 1% in both components. Whole exome sequencing revealed that the 4 cases exhibited different genetic aberrations including 1 case with multiple chromosomal deletions, while 2 cases showed amplification of chromosome 12 and deletion of chromosome 11, respectively. The 7 cases were followed up for 25 to 172 months. Except for 1 patient that died with unknown causes 25 months after surgery, the remaining 6 cases were still alive (average 103.8 months, median 101 months).Conclusions:ChRCC-SC/ND-L is a very rare subtype of ChRCC. The small cell component does not represent true neuroendocrine differentiation and might indicate a morphological heterogeneity of the tumor. The presence of typical chromophobe cell carcinoma components is helpful for the diagnosis of ChRCC-SC/ND-L and they do not have consistent molecular characteristics. ChRCC-SC/ND-L has a good prognosis and the small cell components/neuroendocrine-like components might not have a significant impact on the outcome of patients with the tumor.

Objective:To investigate the association of the interaction and combined effect of renal function and body mass index (BMI) with the risk for all-cause death in patients with type 2 diabetes mellitus (T2DM) in communities of Jiangsu Province.Methods:The study subjects were from the Comprehensive Research Project of Diabetes Prevention and Control conducted in Jiangsu from December 2013 to January 2014, and follow up was conducted for them until September 30, 2023. A total of 20 025 subjects were included in the study. Cox proportional hazards regression model was used to analyze the association of renal function with risk for death in T2DM patients, and the association of interaction between renal function and BMI and their combined effect with all-cause death risk in T2DM patients.Results:In the follow up for 198 370 person-years, a total of 4 459 deaths were recorded. Cox proportional hazards regression model analysis showed that renal dysfunction was associated with 71% risk of all-cause mortality in all T2DM patients [hazard ratio ( HR) =1.71, 95% CI: 1.59-1.84], as well as in all BMI subgroups. Likelihood ratio test indicated an interaction between renal function and BMI (interaction for P=0.030). Compared with patients with normal renal function and normal BMI, those with normal renal function and over weight or obesity had a lower risk of all-cause mortality, and those with renal dysfunction and low weight had the highest risk for death ( HR=2.78, 95% CI: 1.87-4.14). Conclusions:There is association of interaction between renal function and BMI with all-cause mortality in T2DM patients. T2DM patients with renal dysfunction and low body weight had significant higher risk for death.