Objective To observe the effect of pirfenidone on myocardial fibrosis in rats and inves-tigate its underlying mechanism.Methods Twenty-four SD rats were randomly divided into sham-operation group,model group,low-and high-dose pirfenidone groups,with 6 rats in each group.Rat model of myocardial fibrosis was established by injecting isoprenaline into the tail vein,while normal saline was given to the sham operation group.Pirfenidone of 150 and 300 mg/(kg·d)were infused gastrically to the rats of low-and high-dose pirfenidone groups after modeling.Mas-son staining was used to observe the severity of myocardial fibrosis,immunohistochemical assay was employed to detect the expression of Collagen-1,NOD-like receptor thermal protein domain associated protein 3(NLRP3)inflammasome,cysteinyl aspartate-specific protease-1(Caspase-1),and Western blotting was performed to detect the protein levels of Collogen-1 and atrial desmo-plakin D(gasdermin D,GSDMD).Results The model group showed obvious myocardial fibrosis,and elevated expression of Collogen-1,NLRP3,Caspase-1 and GSDMD when compared with the sham operation group(P＜0.05).Low-and high-dose pirfenidone treatment resulted in signifi-cantly reduced myocardial fibrosis and reduced expression of Collogen-1,NLRP3,Caspase-1 and GSDMD[(8.14±1.40)％,(6.56±0.75)％vs(22.15±2.57)％,P＜0.05;0.14±0.03 vs 0.33±0.05,0.42±0.13,P＜0.05;(10.34±1.40)％,(10.33±3.40)％vs(23.22±1.99)％,P＜0.05;(15.67±0.56)％,(17.33±0.78)％vs(22.87±1.92)％,P＜0.05;0.43±0.06,0.46±0.11 vs 0.65±0.03,P＜0.05].Conclusion Pirfenidone inhibits cardiomyocyte pyroptosis and attenuates myocar-dial fibrosis through the NLRP3/Caspase-1/GSDMD signaling axis.

Ketosis is an energy metabolism disorder occurring frequently in periparturient dairy cows,primarily attributed to elevated non-esterified fatty acid(NEFA)levels resulting from nega-tive energy balance(NEB).Excessive NEFA will be incompletely oxidated into large amounts of ketone bodies or be re-esterified and deposit in the liver as a consequence of hepatic limited oxida-tive capacity,ultimately leading to ketosis and fatty liver.Hypoxic microenvironments are com-monly found during the progression of various liver diseases.Hypoxia inducible factor-2 alpha(HIF-2 alpha)has been identified as a crucial regulator of lipid metabolism.However,it is still un-clear the association between HIF-2α and disrupted lipid metabolism in the livers of in ketotic cows.This study aims to investigate the effect of high concentrations of NEFA on HIF-2α expres-sion and cellular oxygen homeostasis through bovine liver tissue and primary hepatocytes.In vivo,hepatic triglyceride(TAG)content was assessed to determine the extent of hepatic lipid accumula-tion,and HIF-2α protein and mRNA levels were analyzed by immunohistochemistry staining,Western blot and qRT-PCR assay in liver tissue samples from dairy cows;in vitro,bovine primary hepatocytes were treated with different concentrations of NEFA.Oil Red O staining and TAG con-tent assay were performed to determine hepatocellular steatosis extent,and immunofluorescence staining.Western blot,and qRT-PCR were performed to analyze HIF-2α expression,in addition,lu-minescent oxygen sensor[Ru(dpp)3]Cl2 was added to indicate intracellular oxygen levels.These results showed a significant increase in TAG content and elevated HIF-2α expression in the liver tissue of ketotic cows,and high concentrations of NEFA induced lipid accumulation,upregulation of HIF-2α expression,and intracellular hypoxia in bovine primary hepatocytes.These findings sug-gested that HIF-2α was significantly"activated"in the liver of ketotic cows and high concentration of NEFA-induced bovine primary hepatocytes,and that high concentrations of NEFA induced in-tracellular hypoxia in vitro.This study provides a potential molecular target for further investiga-tion of the mechanism underlying hepatic lipid metabolism disorders in ketotic cows.

Objective To establish a mouse model of H1N1 influenza wind-heat syndrome by combining climate intervention with influenza virus nasal drops.Methods Seventy-two BALB/c mice were divided randomly into nine groups:a Control group,wind-heat(FR)groups(FR-3Day,FR-5Day),and Model groups(1LD-3Day,2LD-3Day,3LD-3Day,1LD-5Day,2LD-5Day,2LD-5Day,3LD-5Day)(n=8 mice per group).Mice in the Control group were housed in a normal environment,while mice in the FR and Model groups were kept in wind-heat conditions for 7 d.Mice in the Model groups received nasal PR8 influenza virus infection on the 8th day,and mice in the Control and FR heat groups received equal amounts of physiological saline nasal drops.After virus challenge,each group was housed in a normal environment and samples were taken on days 3 and 5.The appearance of the mice was observed and recorded and the lung index,routine blood parameters,lung tissue pathology,serum interleukin(IL)-6 levels,and virus titers were detected in each group based on their behavioral status,stools,and body temperature.Results After 7 d of wind-heat intervention,mice in the FR groups showed no significant abnormalities in terms of appearance,stools,body temperature,routine blood parameters,or lung tissue pathology compared with the Control group.The appearance,lung index,red blood cell count,hemoglobin,hematocrit,pathological result,and body temperature in the Model groups worsened progressively with increasing time and toxin dosage,while the neutrophil percentage,lymphocyte percentage,virus titer,and serum IL-6 levels peaked on day 3 after viral attack,for the same viral dose,and then decreased slightly on day 5.Conclusions PR8 nasal drops and 7 d of wind-heat climate intervention can be used to establish a mouse model of influenza wind-heat syndrome.

Objective To observe the effect of pirfenidone on myocardial fibrosis in rats and inves-tigate its underlying mechanism.Methods Twenty-four SD rats were randomly divided into sham-operation group,model group,low-and high-dose pirfenidone groups,with 6 rats in each group.Rat model of myocardial fibrosis was established by injecting isoprenaline into the tail vein,while normal saline was given to the sham operation group.Pirfenidone of 150 and 300 mg/(kg·d)were infused gastrically to the rats of low-and high-dose pirfenidone groups after modeling.Mas-son staining was used to observe the severity of myocardial fibrosis,immunohistochemical assay was employed to detect the expression of Collagen-1,NOD-like receptor thermal protein domain associated protein 3(NLRP3)inflammasome,cysteinyl aspartate-specific protease-1(Caspase-1),and Western blotting was performed to detect the protein levels of Collogen-1 and atrial desmo-plakin D(gasdermin D,GSDMD).Results The model group showed obvious myocardial fibrosis,and elevated expression of Collogen-1,NLRP3,Caspase-1 and GSDMD when compared with the sham operation group(P＜0.05).Low-and high-dose pirfenidone treatment resulted in signifi-cantly reduced myocardial fibrosis and reduced expression of Collogen-1,NLRP3,Caspase-1 and GSDMD[(8.14±1.40)％,(6.56±0.75)％vs(22.15±2.57)％,P＜0.05;0.14±0.03 vs 0.33±0.05,0.42±0.13,P＜0.05;(10.34±1.40)％,(10.33±3.40)％vs(23.22±1.99)％,P＜0.05;(15.67±0.56)％,(17.33±0.78)％vs(22.87±1.92)％,P＜0.05;0.43±0.06,0.46±0.11 vs 0.65±0.03,P＜0.05].Conclusion Pirfenidone inhibits cardiomyocyte pyroptosis and attenuates myocar-dial fibrosis through the NLRP3/Caspase-1/GSDMD signaling axis.

Ketosis is an energy metabolism disorder occurring frequently in periparturient dairy cows,primarily attributed to elevated non-esterified fatty acid(NEFA)levels resulting from nega-tive energy balance(NEB).Excessive NEFA will be incompletely oxidated into large amounts of ketone bodies or be re-esterified and deposit in the liver as a consequence of hepatic limited oxida-tive capacity,ultimately leading to ketosis and fatty liver.Hypoxic microenvironments are com-monly found during the progression of various liver diseases.Hypoxia inducible factor-2 alpha(HIF-2 alpha)has been identified as a crucial regulator of lipid metabolism.However,it is still un-clear the association between HIF-2α and disrupted lipid metabolism in the livers of in ketotic cows.This study aims to investigate the effect of high concentrations of NEFA on HIF-2α expres-sion and cellular oxygen homeostasis through bovine liver tissue and primary hepatocytes.In vivo,hepatic triglyceride(TAG)content was assessed to determine the extent of hepatic lipid accumula-tion,and HIF-2α protein and mRNA levels were analyzed by immunohistochemistry staining,Western blot and qRT-PCR assay in liver tissue samples from dairy cows;in vitro,bovine primary hepatocytes were treated with different concentrations of NEFA.Oil Red O staining and TAG con-tent assay were performed to determine hepatocellular steatosis extent,and immunofluorescence staining.Western blot,and qRT-PCR were performed to analyze HIF-2α expression,in addition,lu-minescent oxygen sensor[Ru(dpp)3]Cl2 was added to indicate intracellular oxygen levels.These results showed a significant increase in TAG content and elevated HIF-2α expression in the liver tissue of ketotic cows,and high concentrations of NEFA induced lipid accumulation,upregulation of HIF-2α expression,and intracellular hypoxia in bovine primary hepatocytes.These findings sug-gested that HIF-2α was significantly"activated"in the liver of ketotic cows and high concentration of NEFA-induced bovine primary hepatocytes,and that high concentrations of NEFA induced in-tracellular hypoxia in vitro.This study provides a potential molecular target for further investiga-tion of the mechanism underlying hepatic lipid metabolism disorders in ketotic cows.

Objective To establish a mouse model of H1N1 influenza wind-heat syndrome by combining climate intervention with influenza virus nasal drops.Methods Seventy-two BALB/c mice were divided randomly into nine groups:a Control group,wind-heat(FR)groups(FR-3Day,FR-5Day),and Model groups(1LD-3Day,2LD-3Day,3LD-3Day,1LD-5Day,2LD-5Day,2LD-5Day,3LD-5Day)(n=8 mice per group).Mice in the Control group were housed in a normal environment,while mice in the FR and Model groups were kept in wind-heat conditions for 7 d.Mice in the Model groups received nasal PR8 influenza virus infection on the 8th day,and mice in the Control and FR heat groups received equal amounts of physiological saline nasal drops.After virus challenge,each group was housed in a normal environment and samples were taken on days 3 and 5.The appearance of the mice was observed and recorded and the lung index,routine blood parameters,lung tissue pathology,serum interleukin(IL)-6 levels,and virus titers were detected in each group based on their behavioral status,stools,and body temperature.Results After 7 d of wind-heat intervention,mice in the FR groups showed no significant abnormalities in terms of appearance,stools,body temperature,routine blood parameters,or lung tissue pathology compared with the Control group.The appearance,lung index,red blood cell count,hemoglobin,hematocrit,pathological result,and body temperature in the Model groups worsened progressively with increasing time and toxin dosage,while the neutrophil percentage,lymphocyte percentage,virus titer,and serum IL-6 levels peaked on day 3 after viral attack,for the same viral dose,and then decreased slightly on day 5.Conclusions PR8 nasal drops and 7 d of wind-heat climate intervention can be used to establish a mouse model of influenza wind-heat syndrome.

In recent years,the"One Hospital with Multiple Campuses"model has emerged in major public hospitals across China,providing intrinsic impetus and vitality for the expansion and balanced distribution of high-quality medical re-sources.This paper analyzed the current situation and challenges of the multiple campuses development in public hospitals within China,adopting a problem-oriented approach to explore optimized path to a unified management system.The aim was to establish a collaborative management model across campuses based predicated on the homogenization of systems,management,supervi-sion,professionals,and performance.Taking the Third Affiliated Hospital of Sun Yat-sen University as a case in this study,the paper reviewed and summarized management strategies and practical experience from the aspects of management model,resource allocation,information-orientation,homogenized management,and cultural development.Additionally,the article suggested to u-tilize 5G technology to empower homogenization across campuses.In this way,the hospital's overall operational efficiency can be improved,optimize resource allocation optimized,homogenized medical services ensured,and core competitiveness enhanced.These efforts will provide a reference for the high-quality development of multi-campus public hospitals.

Objective To study the role of microRNA(miR)-483-3p in reducing myocardial fibrosis in rats,and explore the relationship between its mechanism and autophagy.Methods A total of 24 male SD rats were randomly divided into sham operation group,model group,blank transfec-tion group and high expression group,with 6 rats in each group.The blank transfection group and the high-expression group were pretreated with a single injection of adeno-associated virus(AAV)-blank transfection and AAV-miR-483-3p(5×1011 vg)in the tail vein,respectively.In 14 d later,the sham group was injected with 2.5 ml/(kg·d)normal saline for 14 d,and rat model of myocardial fibrosis was established by 2 mg/ml isoproterenol[2.5 ml/(kg·d)]injection through tail vein for 14 consecutive days.Myocardial pathological damage,severity of myocardial fibrosis,and expression levels of collagen-Ⅰ,microtubule-associated protein light chain 3(LC3),autoph-agy-related protein 5(Atg5)and autophagy degradation substrate(P62)in cardiomyocytes were evaluated and measured.Results Compared with the sham operation group,the model group had obviously larger myocardial fibrosis area,higher positive expression of Collagen-Ⅰ,and increased protein levels of Atg5 and LC3-Ⅱ/LC3-Ⅰ,and decreased expression level of P62 protein(P＜0.05).The myocardial fibrosis area,positive expression of Collagen-Ⅰ,the expression levels of Atg5 and LC3-Ⅱ/LC3-Ⅰ protein[(13.64±1.51)％vs(27.47±1.55)％,(13.48±3.07)％vs(30.91±2.45)％,0.98±0.17 vs 1.24±0.28,0.66±0.05 vs 1.26±0.09,P＜0.05]were significant-ly decreased,and the expression level of P62 was notably increased(0.91±0.11 vs 0.74±0.06,P＜0.05)in the high expression group than the model group.Conclusion MiR-483-3p attenuates myocardial fibrosis in rats,and the mechanism may be related to the inhibition of cardiomyocyte autophagy.

Objective:To analyze the morphological changes and features of meibomian gland in patients with meibomian gland cyst under in vivo confocal microscope (IVCM). Methods:A cross-sectional study was performed.A total of 34 patients (34 eyes) with meibomian gland cysts and 18 control subjects (18 eyes) in the outpatient department without meibomian gland cysts treated in Shantou International Eye Center from September 2018 to April 2019 were included into the meibomian gland cyst group and control group accordingly.All the subjects underwent routine ophthalmologic examination and IVCM examination.IVCM test indicators included the opening area of meibomian gland, the longest diameter and the shortest diameter of meibomian gland opening, the morphology of glandular tube and acinus adjacent to the meibomian gland opening.The measurement indexes of the meibomian gland cyst group and the control group were compared and analyzed.This study followed the Declaration of Helsinki and was approved by the Ethics Committee of Joint Shantou International Eye Center of Shantou University and The Chinese University of Hong Kong (No.EC20171103[6]-P01). Written informed consent was obtained from each patient before examination.Results:The opening of the meibomian glands of the 34 subjects in the meibomian gland cyst group were all enlarged irregularly with smooth boundaries, and emboli in the openings were observed in 70.59% (24/34) of patients.The longest diameter, the shortest diameter and the area of meibomian gland openings were (148.12±70.16)μm, (114.77±52.38)μm and 9 239.11(5 506.96, 24 111.36)μm 2 in the meibomian gland cyst group, respectively, while (59.35±16.78)μm, (41.98±11.77)μm and 2 094.19 (1 432.28, 2 945.65)μm 2 in the control group, respectively.Compared with the control group, the longest diameter and shortest diameter in the meibomian cyst group were longer, and the area of meibomian gland openings in the meibomian cyst group was larger, and the differences were statistically significant (all at P<0.01). Adjacent to the opening, there was cystic dilation of glandular tube containing accumulated secretion of different characteristics detected in the 61.76% (21/34) of patients in the meibomian gland cyst group, and the dilated glandular tubes were with flat edges.The boundaries between the dilated glandular tubes and surrounding acini were clear. Conclusions:In vivo confocal microscope can detect the morphological changes of meibomian glands in patients with meibomian gland cyst, including enlarged opening with embolus, cystic dilation of glandular tube with clear boundary and accumulated secretion.

Enrichment of trace bioactive constituents and metabolites from complex biological samples is chal-lenging. This study presented a one-pot synthesis of magnetic polydopamine nanoparticles (Fe3O4@-SiO2@PDA NPs) with multiple recognition sites for the magnetic dispersive solid-phase extraction (MDSPE) of ginsenosides from rat plasma treated with white ginseng. The extracted ginsenosides were characterized by combining an ultra-high-performance liquid chromatography coupled to a high-resolution mass spectrometry with supplemental UNIFI libraries. Response surface methodology was statistically used to optimize the extraction procedure of the ginsenosides. The reusability of Fe3O4@-SiO2@PDA NPs was also examined and the results showed that the recovery rate exceeded 80％ after recycling 6 times. Furthermore, the proposed method showed greater enrichment efficiency and could rapidly determine and characterize 23 ginsenoside prototypes and metabolites from plasma. In com-parison, conventional methanol method can only detect 8 ginsenosides from the same plasma samples. The proposed approach can provide methodological reference for the trace determination and charac-terization of different bioactive ingredients and metabolites of traditional Chinese medicines and food.