Metabolic dysfunction-associated fatty liver disease (MAFLD), characterized by fatty acid overload, secondary chronic inflammation, and fibrosis, has become the most prevalent chronic liver disease globally. While no effective pharmacotherapy exists for MAFLD, mitigating inflammatory responses represents a promising approach to preventing the progression from steatosis to severe steatohepatitis. The NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, which detects endogenous danger and stress signals, has emerged as a significant target for inflammatory disease treatment, as transcriptional inactivation of its components demonstrates the therapeutic potential for MAFLD. Natural products targeting NLRP3 inflammasome activation have shown promising efficacy in MAFLD therapy. This review synthesizes the current understanding of NLRP3 inflammasome activation and therapeutic targets for NLRP3 homeostasis. Additionally, natural products reported to inhibit NLRP3 inflammasome for MAFLD improvement are categorized according to their mechanisms of action. The review also addresses limitations and future directions regarding natural products targeting NLRP3 inflammasome in MAFLD treatment. Enhanced understanding of NLRP3 inflammasome activation mechanisms in MAFLD and the identification of novel natural products supported by mechanistic research will significantly advance MAFLD treatment.
Humans ; NLR Family, Pyrin Domain-Containing 3 Protein/immunology* ; Inflammasomes/metabolism* ; Biological Products/therapeutic use* ; Animals ; Fatty Liver/immunology*

Objective:To evaluate the efficacy and safety of Rituximab (RTX) combined with short-term use of glucocorticoids in the treatment of the initial episode of steroid-sensitive nephrotic syndrome (SSNS).Methods:A retrospective case summary.A total of 30 children with SSNS treated in the Department of Intrarenal Rheumatism and Immunology, Xuzhou Children′s Hospital from December 2021 to March 2023, were enrolled in this study.They were given a standard dose of RTX (375 mg/m 2) and glucocorticoids for a short term.The patients were followed up for 1 year, and the general condition, changes in CD19 + B lymphocytes expression after RTX treatment, the relapse rate, the median relapse-free survival and adverse reactions of RTX were recorded.Kaplan-Meier method was used to analyze the relapse-free survival time. Results:CD19 + B lymphocytes were depleted 2 weeks after RTX treatment, and the median time required for CD19 + B lymphocytes reconstitution was 5 months after RTX treatment.The 1-year relapse-free rate was 90.00%, and the median relapse-free survival was 11 months.The glucocorticoid discontinuation rate was 93.33% in 3 months after RTX treatment, and 100% in 6 and 12 months after RTX treatment.Adverse reactions included infusion reactions in 7 cases (23.33%), neutropenia/leukopenia in 5 cases (16.67%), hypoimmunoglobulinemia in 10 cases (33.33%), infections in 4 cases.One case was complicated with severe influenza A virus infection after CD19 + B lymphocytes reconstruction. Conclusions:A standard dose of RTX can significantly reduce the relapse frequency, maintain long-term remission of proteinuria, and reduce the dose of glucocorticoids in patients at the initial episode of SSNS.Thus, it is worthy of clinical promotion.

Objective:To evaluate the efficacy and safety of Rituximab (RTX) combined with short-term use of glucocorticoids in the treatment of the initial episode of steroid-sensitive nephrotic syndrome (SSNS).Methods:A retrospective case summary.A total of 30 children with SSNS treated in the Department of Intrarenal Rheumatism and Immunology, Xuzhou Children′s Hospital from December 2021 to March 2023, were enrolled in this study.They were given a standard dose of RTX (375 mg/m 2) and glucocorticoids for a short term.The patients were followed up for 1 year, and the general condition, changes in CD19 + B lymphocytes expression after RTX treatment, the relapse rate, the median relapse-free survival and adverse reactions of RTX were recorded.Kaplan-Meier method was used to analyze the relapse-free survival time. Results:CD19 + B lymphocytes were depleted 2 weeks after RTX treatment, and the median time required for CD19 + B lymphocytes reconstitution was 5 months after RTX treatment.The 1-year relapse-free rate was 90.00%, and the median relapse-free survival was 11 months.The glucocorticoid discontinuation rate was 93.33% in 3 months after RTX treatment, and 100% in 6 and 12 months after RTX treatment.Adverse reactions included infusion reactions in 7 cases (23.33%), neutropenia/leukopenia in 5 cases (16.67%), hypoimmunoglobulinemia in 10 cases (33.33%), infections in 4 cases.One case was complicated with severe influenza A virus infection after CD19 + B lymphocytes reconstruction. Conclusions:A standard dose of RTX can significantly reduce the relapse frequency, maintain long-term remission of proteinuria, and reduce the dose of glucocorticoids in patients at the initial episode of SSNS.Thus, it is worthy of clinical promotion.

Hepatitis E virus(HEV)is one of the most common pathogens in acute viral hepatitis.There are at least eight distinct genotypes of HEV.Only humans can contract HEV genotypes 1 and 2,but zoonotic viruses like genotypes 3 and 4 are mostly spread by eating undercooked or in-fected pork in some affluent nations.As a result,boars,both domestic and wild,are typically regar-ded as primary hosts of HEV.Nevertheless,during the past few years,a growing body of research has demonstrated that a number of other wild ruminant animals,such as wild deer and goats,are also susceptible to HEV infection.Determining their participation in the epidemiological cycle of hepatitis E thus requires an understanding of the risk variables that influence the transmission be-tween wild ruminants and humans.With an emphasis on published serological and molecular re-search,this review offers a broad summary of the body of knowledge currently available on the epi-demiology of HEV in wild ruminants.It addresses potential risk factors that could impact the spread of HEV among animals as well as their potential to serve as a source of infectious zoonotic illnesses.It presents an overview of the most recent developments in the epidemiology of HEV in wild ruminants and offers a framework for HEV prevention and management based on science.

To identify the intestinal roundworms of Eclectus roratus and Psittacula alexandri from the Guangdong region by morphological analysis and molecular biology techniques,and to amplify the mitochondrial genome of parrot roundworms using PCR,as well as to carry out phylogenetic analyses based on the sequences of their mitochondrial genes.The results showed that the parrot roundworms identified in this identification belongs to Ascaridia.nymphii and its mitochondrial genome consists of 12 protein coding genes,22 tRNA genes,2 ribosomal RNA genes and two non-coding regions.Phylogenetic analyses showed that A.nymphii identified in this study is located in the same evolutionary branch as the previously reported Ascaridia sp.,is closely related and con-stitutes a separate clade of avian ascarids with pigeon roundworms and chicken roundworms.This study provides important data for the classification,molecular epidemiology and population genetic evolution of parrot roundworms.

Objective To explore the molecular mechanism of curcurin in the treatment of Osteoarthritic(OA)based on ferroptosis gene through bioinformatics.Methods Through Gene Expression Omnibus(GEO)retrieval,high-throughput sequencing data of curcumin in the treatment of osteoarthritis were downloaded.Principal component analysis was used to investigate the changes of principal components before and after curcumin treatment.limma algorithm was used to investigate the transcriptome changes before and after curcumin treatment.The change of signal pathway before and after curcumin treatment was investigated by gene ontology enrichment algorithm.GeneMANIA online tool was used to construct protein-protein interaction network and screen hub genes.The effect of curcumin therapy on hub gene expression was verified in vitro by fluorescence quantitative PCR.Results After curcumin treatment,the transcriptome expression and signaling pathway activity of chondrocytes were significantly changed(P＜0.05).Protein-protein interaction network showed that GCLC,HMOX1,FTL,FTH1 and SLC7A11 were ferroptosis hub genes.The results of ferrous ion fluorescence probe detection and intracellular Reactive oxygen species(ROS)detection showed that IL-1βsignificantly induced inflammation and increased the accumulation of Fe2+and ROS in chondrocytes compared with the control group.Curcumin treatment significantly alleviated IL-1(3-induced inflammation.The contents of Fe2+and ROS in chondrocytes were significantly decreased.The results of quantitative PCR and western blot showed that curcumin treatment significantly changed the expression level of hub gene(P＜0.05).Conclusion Curcumin may affect the ferroptosis process of chondrocytes by mediating up-regulation of GCLC and SLC7A11 genes and down-regulation of HMOX1,FTL and FTH1 genes,so as to have therapeutic effect on osteoarthritis.

Objective To investigate the effect of mechanical stretch on the proliferation and differen-tiation of skeletal satellite cells in mice,and explore its mechanism.Methods The research was divid-ed into two parts.In the first part,all mice were not given osteogenic or adipogenic induction,and randomly divided into a control group,a mechanical stretch(MS)group,a solvent control group[Di-methyl sulfoxide(DMSO)+mechanical stretch],a Notch inhibitor(KY-02111)+mechanical stretch group and a Wnt inhibitor(FLI-06)+mechanical stretch group,with the aim to evaluate cell prolifera-tion and migration,and the effect of mechanical stretch on the Wnt and Notch signaling pathway.In the second part,all mice were randomly divided into 6 groups:a control group,an induced differentia-tion(ID)group,an induced differentiation+mechanical stretch(IDMS)group,an induced differentia-tion+DMSO+mechanical stretch(IDDMS)group,an induced differentiation+Notch inhibitor(KY-02111)+mechanical stretch(IDNMS)group,and an induced differentiation+Wnt inhibitor(FLI-06)+mechanical stretch(IDWMS)group.All groups except the control group were induced differenti-ation using osteoblastic or adipogenic medium,and the IDMS group was applied tensile stress to the cell basement membrane,with the IDDMS and IDNMS groups given DMSO and KY-02111 or FLI-06 with a final concentration of 5 μM into the culture medium,respectively.On the 7th and 14th days af-ter culture,cell proliferation was detected using CCK-8,while on the 14th day after culture,cell mi-gration was observed using the streak method.Alkaline phosphatase and oil red staining were per-formed on all cells.Moreover,the mRNA expression of osteogenic[alkaline phosphatase(ALP)and Runt-related transcription factor(Runx)-2]and adipogenic[fatty acid-binding protein(FABP)4 and li-poprteinlipase(LPL)]differentiation marker genes were quantitatively detected by using the real-time PCR.Meanwhile,while the expression of c-Myc and Cyclin B(CCNB)1 proteins was measured using Western blotting.Results Cell proliferation increased significantly in MS group compared with the con-trol group(P<0.01),while that of IDMMS and IDNMS groups decreased significantly compared with MS group.As to cell migration,MS group was significantly better than the control group(P<0.01),while there was a significant decrease in both IDMMS and IDNMS groups compared with MS group(P<0.01).According to ALP and oil red staining,a significant increase in ALP activity and lipid droplet secretion was observed in skeletal muscle satellite cells of ID groups compared with the control group,with the increase in IDMMS and IDNMS groups significantly greater than MS group.More-over,the results of real-time PCR showed that the expression of ALP and Runx-2mRNA in the osteo-genic induction group and the FABP4 and LPL mRNA in the adipogenic induction group increased sig-nificantly compared with the control group(P<0.05),with a significant decrease in the above measure-ments of IDMS group compared with ID group,but a significant increase in IDMMS and IDNMS groups compared with IDMS group(P<0.01).Meanwhile,according to Western blotting,the expres-sion of c-Myc and CCNB1proteins increased significantly in the skeletal muscle satellite cells of MS group compared with the control group(P<0.01),while that of IDMMS and IDNMS groups decreased significantly compared with MS group(P<0.01).Conclusion Mechanical stretch can promote the prolif-eration and migration of skeletal satellite cells in mice,but inhibit osteogenic and adipogenic differenti-ation.Its mechanism is related to the activation of Wnt and Notch signal pathways.

Objective To explore the molecular mechanism of curcurin in the treatment of Osteoarthritic(OA)based on ferroptosis gene through bioinformatics.Methods Through Gene Expression Omnibus(GEO)retrieval,high-throughput sequencing data of curcumin in the treatment of osteoarthritis were downloaded.Principal component analysis was used to investigate the changes of principal components before and after curcumin treatment.limma algorithm was used to investigate the transcriptome changes before and after curcumin treatment.The change of signal pathway before and after curcumin treatment was investigated by gene ontology enrichment algorithm.GeneMANIA online tool was used to construct protein-protein interaction network and screen hub genes.The effect of curcumin therapy on hub gene expression was verified in vitro by fluorescence quantitative PCR.Results After curcumin treatment,the transcriptome expression and signaling pathway activity of chondrocytes were significantly changed(P＜0.05).Protein-protein interaction network showed that GCLC,HMOX1,FTL,FTH1 and SLC7A11 were ferroptosis hub genes.The results of ferrous ion fluorescence probe detection and intracellular Reactive oxygen species(ROS)detection showed that IL-1βsignificantly induced inflammation and increased the accumulation of Fe2+and ROS in chondrocytes compared with the control group.Curcumin treatment significantly alleviated IL-1(3-induced inflammation.The contents of Fe2+and ROS in chondrocytes were significantly decreased.The results of quantitative PCR and western blot showed that curcumin treatment significantly changed the expression level of hub gene(P＜0.05).Conclusion Curcumin may affect the ferroptosis process of chondrocytes by mediating up-regulation of GCLC and SLC7A11 genes and down-regulation of HMOX1,FTL and FTH1 genes,so as to have therapeutic effect on osteoarthritis.

Objective:To investigate the effect of optimizing perioperative measures on reducing postoperative gastric emptying disorder in gastrointestinal reconstruction after pancreaticoduodenectomy.Methods:The clinical data of 146 patients who underwent pancreaticoduodenectomy from Jan 2019 to Dec 2020 at the Department of Hepatobiliary and Pancreatic Surgery,the First Affiliated Hospital ,Anhui Medical University were analyzed retrospectively. Among them, 78 cases underwent traditional Billroth Ⅱ gastrojejunal anastomosis for gastrointestinal reconstruction, and 68 cases in the improvement group took optimization measures. The time to first postoperative flatus, time to oral intake, postoperative hospital stay and complications were observed.Results:The operation time in the control group was (351.4±71.6) min, less than that in the improved group (368.8±97.6) min, while the time [(9.9±6.5)d vs. (7.6±6.0)d] to first oral take and postoperative hospital stay [(20.7±8.6)d vs. (17.9±7.0)d] were significantly longer than those in the improved group. The incidence of postoperative gastric emptying disorder (19.2% vs. 7.4%) was significantly higher than that in the improved group ( P<0.05). There was no significant difference in postoperative time to first flatus and postoperative gastrointestinal bleeding between the two groups (all P>0.05). Conclusions:The measures of optimizing gastrointestinal reconstruction in the perioperative period of pancreaticoduodenectomy have obvious advantages in reducing gastric emptying disorder, promoting the recovery of gastrointestinal function and shortening the length of hospital stay.

Objective: To observe the clinical application effect of modified small incision double eyelid surgery and its effect on the incidence of complications after operation. Methods: From June 2016 to December 2018, 86 patients who underwent double eyelid surgery in department of ophthalmology of Wenzhou Heping Plastic Hospital were divided into two groups by random number table method, with 43 cases in each group.The control group was treated with traditional catgut embedding double eyelid operation, while the observation group was treated with modified small incision double eyelid operation.The patients' satisfaction, total incidence of complications, self-confidence score and self-image evaluation score were counted and compared between the two groups. Results: After follow-up, 40 patients in the observation group were satisfied with the operation effect, and satisfaction rate was 93.02%.Thirty-five patients in the control group were satisfied with the operation effect at the same time, and the satisfaction rate was 81.40%.The satisfaction rate in the observation group was significantly higher than that in the control group (Z=-5.349, P<0.05). After 12 months of follow-up, the incidence rates of swelling, scar and pain in the observation group were 2.33%, 4.65% and 6.98%, respectively, which were lower than those in the control group (9.30%, 13.95% and 16.28%), the differences were statistically significant (χ²=4.435, 5.127, 4.208, all P<0.05). Before operation, the scores of self-confidence and self-image evaluation in the two groups were (3.85±0.33)points, (3.38±0.42)points, and (3.88±0.32)points, (3.40±0.45)points, the differences were no significant differences (t=0.141, 0.137, all P>0.05). After 12 months of follow-up, the self-confidence score[(9.43±0.28)points] and self-image evaluation score[(9.64±0.32)points] of the observation group were higher than those of the control group [(8.24±0.26)points and (8.55±0.35)points], the differences were statistically significant (t=1.342, 1.331, all P<0.05). Conclusion The modified small incision double eyelid surgery in double eyelid surgery achieves better application effect and lower incidence of long-term complications.It is worthy of popularizing.