1.Human umbilical cord mesenchymal stem cell-derived exosomes attenuate renal ischemia-reperfusion injury by up-regulating ATF3 to inhibit the TLR4/NF-κB pathway
Xingyu* WAN ; Yujia LIU ; Ruiyan WANG ; Hao WANG ; Yi ZHAO ; Lu GUO ; Zhihua YANG ; Xinghua LÜ
Organ Transplantation 2026;17(2):275-286
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.
2.Comparison of Domestic and International Regulations on Blood Products and Insights
Hongbo PAN ; Yingying LIU ; Pei MAO ; Michael WENDT ; Wei ZHANG ; Zhihua YUE ; Zhigang ZHAO
Herald of Medicine 2025;44(8):1250-1256
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.
3.Differences in Domestic and International Supervision of Blood Products Virus Safety and Related Recommendations
Peng WU ; Denis KLOCHKOV ; Jens REHBEIN ; Christoph ZUERCHER ; Connie BROUMIS ; Eleonora WIDMER ; Wei ZHANG ; Zhihua YUE ; Zhigang ZHAO
Herald of Medicine 2025;44(8):1265-1271
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.
4.Research progress on postoperative quality of life in adult patients with ureteropelvic junction obstruction
Zhihua LI ; Man ZHANG ; Xiang WANG ; Han ZHAO ; Qiang ZHANG ; Xinfei LI ; Kunlin YANG ; Xuesong LI
International Journal of Surgery 2025;52(10):657-661
Ureteropelvic junction obstruction, as a common urological disorder, not only affects the renal function of patients, but also seriously reduces their quality of life. Pyeloplasty, as the first-line therapy for ureteral stricture at present, is a key approach to eliminating hydronephrosis and improving renal function. The quality of life of postoperative patients, as an important criterion for measuring the therapeutic effect, has also attracted increasing attention. Therefore, this article reviews the evaluation tools, research status and influencing factors of the postoperative quality of life of ureteropelvic junction obstruction patients, aiming to provide a reference for the formulation of relevant nursing intervention measures in clinical practice.
5.Digital design and manufacturing method of double constrained split guide for orthodontic miniscrew implantation.
Xin DU ; Aonan WEN ; Zixiang GAO ; Zhihua LI ; Sheng ZHANG ; Yong WANG ; Yijiao ZHAO
West China Journal of Stomatology 2025;43(4):603-612
This study explored a novel digital design and fabrication method for a double constrained split orthodontic miniscrew guide to improve the accuracy and safety of clinical miniscrew implantation and reduce related complications. A patient requiring miniscrew implantation was selected, and data were acquired using cone beam computed tomography (CBCT) and intraoral optical scanning. For the construction of a double constrained split guide including a screw-hole guide and an insertion rod guide, different types of software such as Mimics 24.0, Geomagic wrap 2021, and Materialise magics 21.0 were utilized for 3D reconstruction, model integration, and guide design. The guide was then fabricated via laser metal 3D printing. Model and intraoral try-in results demonstrated that the guide fitted well and was stable. Postoperative CBCT verified that the final miniscrew implantation site was consistent with the preoperative design, and no related complications occurred. This double constrained split orthodontic miniscrew guide provides a precise and safe digital solution for clinical miniscrew implantation.
Humans
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Bone Screws
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Cone-Beam Computed Tomography
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Printing, Three-Dimensional
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Orthodontic Anchorage Procedures/instrumentation*
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Imaging, Three-Dimensional
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Computer-Aided Design
6.Detection and genetic evolution analysis of pathogens borne by Pulex irritans in selected areas of Xinjiang
Xinxin HAN ; Jing ZHAO ; Xuefeng LIU ; Yitao LI ; Tingting WU ; Junang DAI ; Mengyang YAN ; Zhihua SUN ; Hui ZHANG
Chinese Journal of Zoonoses 2025;41(8):852-858
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.
7.Current situation and prevention and control of coal-burning-borne endemic fluorosis in key areas of the disease in Zhenxiong County, Yunnan Province
Kailian HUANG ; Anwei WANG ; Zhihua ZHAO ; Yujie LI ; Jiaguo LI ; Changyan PENG ; Tingting QIAN
Chinese Journal of Endemiology 2025;44(8):647-651
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.
8.The relationship between SII,RDW and 25(OH)D levels and frailty index in elderly patients with type 2 diabetes mellitus
Zhihua ZHOU ; Qian WANG ; Nan YANG ; Xiaoying WANG ; Hong GONG ; Meng GUO ; Jieqiong ZHAO
International Journal of Laboratory Medicine 2025;46(13):1626-1630
Objective To explore the relationship between systemic immune-inflammation index(SII),red blood cell distribution width(RDW),25-hydroxy-vitamin-D[25(OH)D]levels and frailty index in elderly pa-tients with type 2 diabetes mellitus(T2DM).Methods A total of 197 elderly patients with T2DM admitted to the hospital from March 2023 to March 2024 were collected as the research subjects.The patients were divided into the frailty group(106 cases)and the non-frailty group(91 cases)according to the scores of the clinical frailty scale.The clinical data and the levels of SII,RDW and 25(OH)D of the two groups were compared.Pearson correlation analysis was used to analyze the correlations between the levels of SII,RDW and 25(OH)D and the frailty index of elderly patients with T2DM.Logistic regression was used to analyze the influencing factors of frailty in elderly patients with T2DM.Results Compared with the non-frailty group,the proportion of women,the history of falls within 1 year,and the age of the frailty group increased,while the body mass in-dex and the proportion of men decreased,and the differences were statistically significant(P<0.05).The SII and RDW levels in the non-frailty group were lower than those in the frailty group,and the 25(OH)D level was higher than that in the frailty group,and the differences were statistically significant(P<0.05).Pearson correlation analysis showed that SII and RDW levels were positively correlated with frailty index,and 25(OH)D level was negatively correlated with frailty index in elderly T2DM patients(P<0.05).Logistic regression analysis showed that female,age ≥ 74.25 years old,SII≥ 938.36,RDW≥ 15.19%,and 25(OH)D≥48.42 nmol/L were independent risk factors for frailty in elderly T2DM patients(P<0.05).Conclusion The levels of SII,RDW and 25(OH)D in elderly patients with T2DM are related to the frailty index.
9.Clinical efficacy of minimally invasive coronary artery bypass grafting via left intercostal small incision for multivessel coronary artery disease: A retrospective cohort study
Zeyuan ZHAO ; Zhihua WANG ; Sheng WANG ; Xianjie CHEN ; Zhao LI ; Guoqing LU ; Zhenchang QI ; Zhaoyun CHENG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(10):1455-1461
Objective To investigate the early clinical efficacy of minimally invasive cardiac surgery coronary artery bypass grafting (MICS CABG) via left intercostal small incision for multivessel coronary artery disease. Methods The patients who received off-pump CABG in the Central China Fuwai Hospital of Zhengzhou University from June 2021 to June 2023 were enrolled. Patients were divided into two groups according to the operative technique used, including a traditional midline sternotomy group and a left intercostal small incision group. The clinical data of the two groups were compared. Results A total of 143 patients were enrolled, including 70 patients in the traditional midline sternotomy group and 73 patients in the left intercostal small incision group. The age of the patients in the left intercostal small incision group and the traditional midline sternotomy group was (63.8±8.0) years and (63.0±7.8) years, respectively; the proportions of males were 69.9% and 74.3%, respectively. The differences were not statistically significant (all P>0.05). All patients in the two groups successfully completed the operation, and no patients in the left intercostal small incision group were converted to thoracotomy. The patients in the left intercostal small incision group showed less postoperative drainage within postoperative 24 hours [(239.4±177.7) mL vs. (338.0±151.9) mL, P<0.001], lower perioperative blood transfusion rate [32.9% (24/73) vs. 51.4% (36/70), P=0.028], higher postoperative myoglobin level within postoperative 24 hours [366.1 (247.9, 513.0) ng/mL vs. 220.8 (147.2, 314.9) ng/mL, P<0.001], shorter intensive care unit stay [45.5 (31.5, 67.5) h vs. 68.0 (46.0, 78.5) h, P=0.001] and postoperative hospital stay [(10.8±4.0) d vs. (13.1±5.3) d, P=0.028] compared to the traditional midline sternotomy group. There was no significant difference in the incidence of major adverse cardiac and cerebrovascular event between the two groups [2.7% (2/73) vs. 2.9% (2/70), P=1.000]. Conclusion Compared to the full median sternotomy, MICS CABG leads to a good clinical result with smaller trauma, faster overall recovery, and less perioperative blood transfusion.
10.Complete transcatheter versus surgical aortic valve replacement for aortic valve stenosis with coronary artery disease: A propensity score matching study
Zhihua WANG ; Zeyuan ZHAO ; Junlong HU ; Yaojue SONG ; Chenyi CUI ; Jiahui LI ; Jianchao LI ; Zhaoyun CHENG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(12):1708-1715
Objective To compare and analyze the early- to mid-term outcomes of transcatheter aortic valve replacement (TAVR) combined with percutaneous coronary intervention (PCI) versus surgical aortic valve replacement (SAVR) combined with coronary artery bypass grafting (CABG) for the treatment of significant aortic stenosis (AS) and coronary artery disease (CAD). Methods The data of patients with significant AS and CAD who underwent surgical treatment at Central China Fuwai Hospital of Zhengzhou University from January 2018 to July 2023 were collected. These patients were divided into a TAVR+PCI group and a SAVR+CABG group according to the operation method. Propensity score matching (PSM) was used to select patients with close clinical baseline characteristics, and the early- to mid-term outcomes of the two groups were compared. Results A total of 272 patients were enrolled, including 208 males and 64 females, with a mean age of (64.16±8.24) years. There were 47 patients in the TAVR+PCI group and 225 patients in the SAVR+CABG group. After 1 : 1 PSM, 32 pairs were selected. There was no statistical difference in baseline data between the two groups (P>0.05). Compared with the SAVR+CABG group, the TAVR+PCI group had significantly shorter operative time, mechanical ventilation time, ICU stay, postoperative hospital stay, and less intraoperative bleeding, and significantly lower postoperative transfusion and complete revascularization rates (P<0.05). The differences in the rates of postoperative in-hospital death, myocardial infarction, stroke, or other complications between the two groups were not statistically significant (P>0.05), and the differences in the rates of moderate-to-severe perivalvular leakage, death, or readmission in the mid-term follow-up were not statistically significant (P>0.05). Conclusion In patients with significant AS and CAD, the early- and mid-term rates of death and complications are similar between those treated with TAVR+PCI and SAVR+CABG, and TAVR+PCI is a safe alternative to SAVR+CABG.

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