Objective To investigate the protective effect and underlying mechanism of human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-Exo) on renal ischemia-reperfusion injury (IRI). Methods hucMSC-Exos were isolated and characterized. A mouse renal IRI model was established and the animals were divided into Sham, IRI, IRI+hucMSC-Exo, IRI+hucMSC-Exo+JY-2 and Sham+JY-2 groups. Serum creatinine (Scr) and blood urea nitrogen (BUN) were measured. Hematoxylin-eosin (HE) staining was used to evaluate renal histopathology. Enzyme-linked immune absorbent assay was performed to determine serum interleukin (IL)-1β and IL-18 levels. Western blotting was used to detect the expression of activating transcription factor 3 (ATF3), Toll-like receptor 4 (TLR4), nuclear factor (NF)-κB, NOD-like receptor protein 3 (NLRP3), cysteineyl aspartate specific proteinase (Caspase)-1 p20 and Gasdermin D(GSDMD). Real-time fluorescent quantitative polymerase chain reaction was employed to measure ATF3, TLR4 and NF-κB messenger RNA (mRNA). Immunohistochemistry was conducted to examine NLRP3, Caspase-1 p20 and GSDMD. An in vitro hypoxia/reoxygenation (H/R) model was established in HK-2 cells and divided into Control, H/R, H/R+hucMSC-Exo, H/R+hucMSC-Exo+JY-2 and Control+JY-2 groups. Western blotting was used to detect the expression of ATF3, TLR4 and NF-κB. Real-time fluorescent quantitative polymerase chain reaction was used to measure NLRP3, GSDMD and Caspase-1 mRNA. Results HucMSC-Exos were successfully isolated and identified. Compared with the Sham group, the IRI group exhibited elevated Scr and BUN, higher tubular injury scores, increased protein expression levels of ATF3, TLR4, NF-κB p65, NLRP3, Caspase-1 p20 and GSDMD, and raised mRNA expression levels of ATF3, TLR4, NF-κB. Compared with the IRI group, the IRI+hucMSC-Exo group showed decreased Scr and BUN, lower tubular injury scores, up-regulated ATF3 protein and mRNA, down-regulated TLR4, NF-κB p65, NLRP3, Caspase-1 p20 and GSDMD protein, and declined TLR4 and NF-κB mRNA. Compared with the IRI+hucMSC-Exo group, the IRI+hucMSC-Exo+JY-2 group exhibited increased Scr and BUN levels, elevated renal tubular injury scores, decreased ATF3 protein expression levels, elevated protein expression levels of TLR4, NF-κB p65, NLRP3, Caspase-1 p20, and GSDMD, decreased ATF3 mRNA expression levels, and elevated mRNA expression levels of TLR4 and NF-κB. (all P < 0.05). Compared with the Control group, the expression levels of ATF3, TLR4 and NF-κB p65 proteins were increased in the H/R group, and the expression levels of NLRP3, Caspase-1 and GSDMD mRNA were increased. Compared with the H/R group, the expression level of ATF3 protein was increased, the expression levels of TLR4 and NF-κB p65 proteins were decreased, and the expression levels of NLRP3, Caspase-1 and GSDMD mRNA were decreased in the H/R+hucMSC-Exo group. Compared with the H/R+hucMSC-Exo group, the expression level of ATF3 protein was decreased, the expression levels of TLR4 and NF-κB p65 proteins were increased, and the expression levels of NLRP3, Caspase-1 and GSDMD mRNA were increased in the H/R+hucMSC-Exo+JY-2 group (all P < 0.05). Conclusions HucMSC-Exos alleviate renal IRI by up-regulating ATF3, thereby negatively regulating the TLR4/NF-κB signaling pathway and subsequently inhibiting pyroptosis.

Objective:To investigate the current prevalence and control status of coal-burning-borne endemic fluorosis in key areas of the disease in Zhenxiong County of Yunnan Province, thereby providing scientific basis for formulating subsequent prevention strategies and measures.Methods:From October to November 2023, a simple random sampling method was used to conduct a survey in three key townships (towns) in Zhenxiong County, Chishuiyuan Town, Yanyuan Town, and Linkou Yi and Miao Ethnic Township. Three administrative villages were selected from each township (town) as survey sites, and dental fluorosis examination on children aged 8 - 12 years who were born and lived in the local area was conducted. Thirty households were selected from each survey site, the use of household stoves and the formation of related healthy living behaviors were investigated. At the same time, a survey was conducted among primary school students and housewives to investigate their knowledge of coal-burning-borne endemic fluorosis prevention and control. The control and elimination of endemic areas were evaluated according to the "Assessment Protocol for Control and Elimination of Key Endemic Diseases (2019 Edition)".Results:A total of 1 172 children were examined, and the detection rate of dental fluorosis was 7.76% (91/1 172), with a dental fluorosis index of 0.11. A total of 295 households were investigated, and the qualified improved stoves rate and the correct use rate of qualified improved stoves were 95.59% (282/295) and 100% (282/282), respectively. The correct drying rate of edible corn and chili peppers was 79.66% (235/295). The awareness rates of coal-burning-borne endemic fluorosis prevention and control knowledge among housewives and primary school students were 46.69% (409/876) and 82.49% (440.5/534), respectively. Among the 9 villages investigated, two villages had met the criteria for eliminating endemic disease areas, two villages had met the criteria for controlling endemic disease areas, and the remaining 5 villages were uncontrolled.Conclusions:After implementing the comprehensive prevention and control measures mainly based on changing stoves, coal-burning-borne endemic fluorosis condition in Zhenxiong County has been effectively controlled, but there is still a significant gap between the elimination goals of some endemic fluorosis areas. Therefore, it is necessary to continue to strengthen prevention and control measures and promote health education.

The blood products industry in China,the United States,the European Union and Japan are at different stages of development,with very different laws,regulations and regulatory systems.This paper uses methods such as literature review,policy comparison,and case study.By analyzing and comparing the blood product regulatory policies in various countries,it is found that compared with the United States,the European Union and Japan,China has differences in several areas,including plasma quarantine period,plasma fractionation processes and intermediate products,segmented production of blood products,and import management policies.It is suggested that we should learn from foreign regulatory experiences,and explore the establishment of blood product regulatory policies suitable for China's national conditions.Recommendations include optimizing China's source plasma quarantine period and blood product production process management policies,promoting multiple sites and segmented production of blood products,and establishing flexible blood product import and export management systems.These measures aim to provide references for promoting the development of the blood product industry and improving the accessibility of medications for the public.

Blood products are biological products derived from human plasma for use in clinical treatment.As such,they inherently carry the risk of blood-bome viral contamination,which has garnered significant attention from regulatory agencies worldwide regarding the viral safety of these products.This article compares and discusses the differences in domestic and international regulations on viral safety for blood products,focusing on aspects such as raw material selection and viral testing.Additionally,the article explores further impactful measures for viral safety control,namely,viral reduction during the manufacturing process and strategies to prevent cross-contamination.Moreover,we propose corresponding recommendations for China's regulatory framework to further enhance the viral safety of blood products in the country.

BACKGROUND:Molecular stability and biocompatibility of hemerythrin surpass those of human and mammalian hemoglobin,making it a potential candidate for a safer and more effective erythrocyte substitute after modification.OBJECTIVE:To prepare multi-modified hemerythrin nanoparticles,characterize them,and test their performance in vitro.METHODS:The hemerythrin of Sipunculus sphenodontus was separated and purified by tangential flow ultrafiltration.The intramolecular cross-linking was completed by genipin.The nanoparticles were encapsulated by dopamine,and passivated by polyethylene glycol to obtain multi-modified hemerythrin nanoparticles.The physicochemical properties of the nanoparticles were characterized.Hemerythrin nanoparticles,hemerythrin,and hemoglobin oxygen carrier HBOC-201 with different mass concentrations(0,0.25,0.5,1.0,and 2.0 mg/mL)were incubated with macrophages for 6 and 24 hours,and with endothelial cells for 24 hours.The cell survival rate was detected by CCK-8 assay.The levels of nitric oxide and vascular cell adhesion factor 1 in the culture medium of endothelial cells were detected by ELISA.RESULTS AND CONCLUSION:(1)Under electron microscopy,hemerythrin nanoparticles were ellipsoidal,with a dense outer membrane and a relatively uniform internal texture.The particle size was(150.12±1.67)nm;the dispersion index was 0.21±0.03;the Zeta potential was(-24.54±2.61)mV;the half-saturated oxygen partial pressure was(0.97±0.15)kPa,and the Hill coefficient was 1.49±0.16.(2)After incubation for 6 hours,within the mass concentration range of≤1.0 mg/mL,the survival rates of macrophages in the hemerythrin nanoparticle group,the hemerythrin group,and the HBOC-201 group were all above 85%.At a mass concentration of 2.0 mg/mL,only the survival rate of macrophages in the hemerythrin nanoparticle group was above 80%.After incubation for 24 hours,the survival rates of macrophages in the three groups were all lower than 80%,among which the survival rate of macrophages in the hemerythrin nanoparticle group was higher than that in the hemerythrin group and the HBOC-201 group(P<0.05).(3)With the increase of drug concentration,the survival rate of vascular endothelial cells in the three groups decreased.At 1.0 mg/mL or 2.0 mg/mL mass concentration,the survival rate of cells in the hemerythrin nanoparticle group was higher than that in the hemerythrin group and HBOC-201 group(P<0.05).At the same mass concentration,the nitric oxide level in the hemerythrin nanoparticle group was higher than that in the hemerythrin group and HBOC-201 group(P<0.05).In the range of 0.25-2.0 mg/mL mass concentration,the vascular cell adhesion factor 1 level in the hemerythrin nanoparticle group was lower than that in the hemerythrin group and HBOC-201 group(P<0.05).(4)The results showed that the hemerythrin nanoparticles modified with intramolecular cross-linking and polydopamine/polyethylene glycol had good oxygen-carrying activity in vitro,better anti-phagocytic performance,and less cytotoxicity.

BACKGROUND:Molecular stability and biocompatibility of hemerythrin surpass those of human and mammalian hemoglobin,making it a potential candidate for a safer and more effective erythrocyte substitute after modification.OBJECTIVE:To prepare multi-modified hemerythrin nanoparticles,characterize them,and test their performance in vitro.METHODS:The hemerythrin of Sipunculus sphenodontus was separated and purified by tangential flow ultrafiltration.The intramolecular cross-linking was completed by genipin.The nanoparticles were encapsulated by dopamine,and passivated by polyethylene glycol to obtain multi-modified hemerythrin nanoparticles.The physicochemical properties of the nanoparticles were characterized.Hemerythrin nanoparticles,hemerythrin,and hemoglobin oxygen carrier HBOC-201 with different mass concentrations(0,0.25,0.5,1.0,and 2.0 mg/mL)were incubated with macrophages for 6 and 24 hours,and with endothelial cells for 24 hours.The cell survival rate was detected by CCK-8 assay.The levels of nitric oxide and vascular cell adhesion factor 1 in the culture medium of endothelial cells were detected by ELISA.RESULTS AND CONCLUSION:(1)Under electron microscopy,hemerythrin nanoparticles were ellipsoidal,with a dense outer membrane and a relatively uniform internal texture.The particle size was(150.12±1.67)nm;the dispersion index was 0.21±0.03;the Zeta potential was(-24.54±2.61)mV;the half-saturated oxygen partial pressure was(0.97±0.15)kPa,and the Hill coefficient was 1.49±0.16.(2)After incubation for 6 hours,within the mass concentration range of≤1.0 mg/mL,the survival rates of macrophages in the hemerythrin nanoparticle group,the hemerythrin group,and the HBOC-201 group were all above 85%.At a mass concentration of 2.0 mg/mL,only the survival rate of macrophages in the hemerythrin nanoparticle group was above 80%.After incubation for 24 hours,the survival rates of macrophages in the three groups were all lower than 80%,among which the survival rate of macrophages in the hemerythrin nanoparticle group was higher than that in the hemerythrin group and the HBOC-201 group(P<0.05).(3)With the increase of drug concentration,the survival rate of vascular endothelial cells in the three groups decreased.At 1.0 mg/mL or 2.0 mg/mL mass concentration,the survival rate of cells in the hemerythrin nanoparticle group was higher than that in the hemerythrin group and HBOC-201 group(P<0.05).At the same mass concentration,the nitric oxide level in the hemerythrin nanoparticle group was higher than that in the hemerythrin group and HBOC-201 group(P<0.05).In the range of 0.25-2.0 mg/mL mass concentration,the vascular cell adhesion factor 1 level in the hemerythrin nanoparticle group was lower than that in the hemerythrin group and HBOC-201 group(P<0.05).(4)The results showed that the hemerythrin nanoparticles modified with intramolecular cross-linking and polydopamine/polyethylene glycol had good oxygen-carrying activity in vitro,better anti-phagocytic performance,and less cytotoxicity.

This study identified the types and pathogen carrying status of fleas on the surface of sheep in some areas of southern Xinjiang,and analyzed the genetic evolution differences with respect to related pathogens.The aim was to provide a reference for the local prevention and control of fleas and insect borne infectious diseases.A total of 1 586 fleas were collected from agricultural and pas-toral areas of Tumushuke City and Hotan Prefecture.Flea species were identified on the basis of morphology and the Pulex irritans mi-tochondrial COII gene.Flea DNA was extracted,and PCR was conducted to amplify the Bartonella gltA gene;Arsenophonus,Ana-plasma,Ehrlichia,and Wolbachia 16S rRNA genes;RickettsiaOmpA,17kDa,16S rRNA genes,and Yersinia pestis 16S rDNA gene.The amplified products were sequenced,and the homology of the genes of the three detected pathogens(gltA gene of Bartonella,16S rRNA gene of Wolbachia,and Anaplasma phagocytophilum)with respect to known corresponding genes of the same pathogen in Gen-Bank was analyzed.Phylogenetic trees were constructed with the adjacency method in MEGA 11.0.According to morphological and mo-lecular biology identification results,all fleas collected in this study were Pulex irritans.PCR indicated that the target gene fragments had been added to the mitochondrial COII,BartonellagltA,Wolbachia,and autophagosomal 16S rRNA genes of human fleas,all of which were consistent with the expected fragment sizes.Target bands were not amplified from Ehrlichia,Arsenophonus,spotted fever group Rickettsia,and Yersinia pestis.According to homology and genetic evolution analysis of human flea mitochondrial COII and the corresponding genes of the above-described pathogens,the COX2 gene(ON455234.1)of human fleas in Tumushuke city and Iran ob-tained in this study showed the highest homology(99.84%).The COII gene(NC_063709.1)of human fleas in Hetan City and Hunan region showed the highest homology(100%).Our findings further confirmed that the flea species was Pulex irritans.The PCR amplifi-cation results indicated that the collected Pulex irritans carried multiple pathogens,among which Bartonella and Wolbachia had the highest infection rates,and the infection rate with Anaplasma phagocytophilum was relatively low.This study is the first to discover flea species on the surface of sheep in some areas of southern Xinjiang.Our findings preliminarily confirmed that Bartonella,Wolba-chia,and Anaplasma phagocytophilum are the main Pulex irritans pathogens.

The blood products industry in China,the United States,the European Union and Japan are at different stages of development,with very different laws,regulations and regulatory systems.This paper uses methods such as literature review,policy comparison,and case study.By analyzing and comparing the blood product regulatory policies in various countries,it is found that compared with the United States,the European Union and Japan,China has differences in several areas,including plasma quarantine period,plasma fractionation processes and intermediate products,segmented production of blood products,and import management policies.It is suggested that we should learn from foreign regulatory experiences,and explore the establishment of blood product regulatory policies suitable for China's national conditions.Recommendations include optimizing China's source plasma quarantine period and blood product production process management policies,promoting multiple sites and segmented production of blood products,and establishing flexible blood product import and export management systems.These measures aim to provide references for promoting the development of the blood product industry and improving the accessibility of medications for the public.

Blood products are biological products derived from human plasma for use in clinical treatment.As such,they inherently carry the risk of blood-bome viral contamination,which has garnered significant attention from regulatory agencies worldwide regarding the viral safety of these products.This article compares and discusses the differences in domestic and international regulations on viral safety for blood products,focusing on aspects such as raw material selection and viral testing.Additionally,the article explores further impactful measures for viral safety control,namely,viral reduction during the manufacturing process and strategies to prevent cross-contamination.Moreover,we propose corresponding recommendations for China's regulatory framework to further enhance the viral safety of blood products in the country.

Objective:To summarize the surgical strategies and to evaluate the clinical outcomes of up-per urinary tract reconstruction in patients with stone-related ureteral strictures.Methods:This retro-spective study included 71 patients diagnosed with ureteral strictures secondary to urinary stones who un-derwent upper urinary tract reconstructive surgery at Peking University First Hospital between March 2014 and November 2023.Patient data were collected,including demographic characteristics,clinical presen-tation,laboratory results,imaging findings,surgical procedures,and follow-up outcomes.Ureteral stric-tures were classified according to anatomical location into upper,middle,lower,or multiple segments.Surgical procedures were carried out depending on the stricture characteristics.Surgical success was de-fined as resolution or improvement of clinical symptoms,radiographic improvement or stabilization of hy-dronephrosis,and maintenance of normal and stable renal function.Results:Among the 71 patients,36(50.7％)had strictures in the upper ureter,9(12.7％)in the middle ureter,15(21.1％)in the lower ureter,and 11(15.5％)had multifocal ureteral strictures.The median stricture length was 5.0 cm(interquartile range:3.0-15.0 cm).Surgical approach selection was individualized based on the location and extent of the stricture.For upper ureteral strictures,the most frequently employed techniques were oral mucosal graft ureteroplasty(13/36,36.1％)and appendiceal flap ureteroplasty(8/36,22.2％).Other options included ureteroureterostomy and ileal ureter replacement for longer or more complex strictures.In middle ureteral strictures,treatment was stratified by length:balloon dilation(1/9,11.1％)and ureteroureterostomy(1/9,11.1％)were applied in shorter strictures,while oral mucosal graft ureteroplasty(3/9,33.3％)and ileal ureter replacement(4/9,44.4％)were reserved for longer segments.For lower ureteral strictures,ureteral reimplantation into the bladder was the most common approach(10/15,66.7％),often combined with a psoas hitch or Boari flap when necessary.All the patients with multiple segmental strictures underwent ileal ureter replacement due to the extensive nature of the disease.The median follow-up period was 14.2 months(range:6.1-107.1 months).During follow-up,69 of 71 patients(97.2％)achieved surgical success.Conclusion:Stone-related ure-teral strictures present with considerable heterogeneity in terms of anatomical location,length,and com-plexity.Careful preoperative evaluation and individualized surgical planning are critical to successful re-construction.With appropriate selection of surgical methods,favorable long-term clinical outcomes can be achieved in the majority of patients.