1.Production of GTKO pigs and kidney xenotransplantation from pigs to rhesus macaques
Yan WANG ; Yue CHANG ; Chang YANG ; Taiyun WEI ; Xiaoying HUO ; Bowei CHEN ; Jiaoxiang WANG ; Heng ZHAO ; Jianxiong GUO ; Hongfang ZHAO ; Xiong ZHANG ; Feiyan ZHU ; Wenmin CHENG ; Hongye ZHAO ; Kaixiang XU ; Ameen Jamal MUHAMMAD ; Zhendi WANG ; Hongjiang WEI
Organ Transplantation 2025;16(4):526-537
Objective To explore the construction of α-1,3-galactosyltransferase (GGTA1) gene-knockout (GTKO) Diannan miniature pigs and the kidney xenotransplantation from pigs to rhesus macaques, and to assess the effectiveness of GTKO pigs. Methods The GTKO Diannan miniature pigs were constructed using the CRISPR/Cas9 gene-editing system and somatic cell cloning technology. The phenotype of GTKO pigs was verified through polymerase chain reaction, Sanger sequencing and immunofluorescence staining. Flow cytometry was used to detect antigen-antibody (IgM) binding and complement-dependent cytotoxicity. Kidney xenotransplantation was performed from GTKO pigs to rhesus macaques. The humoral immunity, cellular immunity, coagulation and physiological indicators of the recipient monkeys were monitored. The function and pathological changes of the transplanted kidneys were analyzed using ultrasonography, hematoxylin-eosin staining, immunohistochemical staining and immunofluorescence staining. Results Single-guide RNA (sgRNA) targeting exon 4 of the GGTA1 gene in Diannan miniature pigs was designed. The pGL3-GGTA1-sgRNA1-GFP vector was transfected into fetal fibroblasts of Diannan miniature pigs. After puromycin selection, two cell clones, C59# and C89#, were identified as GGTA1 gene-knockout clones. These clones were expanded to form cell lines, which were used as donor cells for somatic cell nuclear transfer. The reconstructed embryos were transferred into the oviducts of trihybrid surrogate sows, resulting in 13 fetal pigs. Among them, fetuses F04 and F11 exhibited biallelic mutations in the GGTA1 gene, and F04 had a normal karyotype. Using this GTKO fetal pig for recloning and transferring the reconstructed embryos into the oviducts of trihybrid surrogate sows, seven surviving piglets were obtained, all of which did not express α-Gal epitope. The binding of IgM from the serum of rhesus monkey 20# to GTKO pig PBMC was reduced, and the survival rate of GTKO pig PBMC in the complement-dependent cytotoxicity assay was higher than that of wild-type pig. GTKO pig kidneys were harvested and perfused until completely white. After the left kidney of the recipient monkey was removed, the pig kidney was heterotopically transplanted. Following vascular anastomosis and blood flow restoration, the pig kidney rapidly turned pink without hyperacute rejection (HAR). Urine appeared in the ureter 6 minutes later, indicating successful kidney transplantation. The right kidney of the recipient was then removed. Seven days after transplantation, the transplanted kidney had good blood flow, the recipient monkey's serum creatinine level was stable, and serum potassium and cystatin C levels were effectively controlled, although they increased 10 days after transplantation. Seven days after transplantation, the levels of white blood cells, lymphocytes, monocytes and eosinophils in the recipient monkey increased, while platelet count and fibrinogen levels decreased. The activated partial thromboplastin time, thrombin time and prothrombin time remained relatively stable but later showed an upward trend. The recipient monkey survived for 10 days. At autopsy, the transplanted kidney was found to be congested, swollen and necrotic, with a small amount of IgG deposition in the renal tissue, and a large amount of IgM, complement C3c and C4d deposition, as well as CD68+ macrophage infiltration. Conclusions The kidneys of GTKO Diannan miniature pigs may maintain normal renal function for a certain period in rhesus macaques and effectively overcome HAR, confirming the effectiveness of GTKO pigs for xenotransplantation.
2.Plasma miRNA testing in the differential diagnosis of very early-stage hepatocellular carcinoma: a multicenter real-world study
Jie HU ; Ying XU ; Ao HUANG ; Lei YU ; Zheng WANG ; Xiaoying WANG ; Xinrong YANG ; Zhenbin DING ; Qinghai YE ; Yinghong SHI ; Shuangjian QIU ; Huichuan SUN ; Qiang GAO ; Jia FAN ; Jian ZHOU
Chinese Journal of Clinical Medicine 2025;32(3):350-354
Objective To explore the application of plasma 7 microRNA (miR7) testing in the differential diagnosis of very early-stage hepatocellular carcinoma (HCC). Methods This study is a multicenter real-world study. Patients with single hepatic lesion (maximum diameter≤2 cm) who underwent plasma miR7 testing at Zhongshan Hospital, Fudan University, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Anhui Provincial Hospital, and Peking University People’s Hospital between January 2019 and December 2024 were retrospectively enrolled. Patients were divided into very early-stage HCC group and non-HCC group, and the clinical pathological characteristics of the two groups were compared. The value of plasma miR7 levels, alpha-fetoprotein (AFP), and des-gamma-carboxy prothrombin (DCP) in the differential diagnosis of very early-stage HCC was evaluated using receiver operating characteristic (ROC) curves and area under the curve (AUC). In patients with both negative AFP and DCP (AFP<20 ng/mL, DCP<40 mAU/mL), the diagnostic value of plasma miR7 for very early-stage HCC was analyzed. Results A total of 64 528 patients from 4 hospitals underwent miR7 testing, and 1 682 were finally included, of which 1 073 were diagnosed with very early-stage HCC and 609 were diagnosed with non-HCC. The positive rate of miR7 in HCC patients was significantly higher than that in non-HCC patients (67.9% vs 24.3%, P<0.001). ROC curves showed that the AUCs for miR7, AFP, and DCP in distinguishing HCC patients from the non-HCC individuals were 0.718, 0.682, and 0.642, respectively. The sensitivities were 67.85%, 43.71%, and 44.45%, and the specificities were 75.70%, 92.78%, and 83.91%, respectively. The pairwise comparison of AUCs showed that the diagnostic efficacy of plasma miR7 detection was significantly better than that of AFP or DCP (P<0.05). Although its specificity was slightly lower than AFP and DCP, the sensitivity was significantly higher. Among patients negative for both AFP and DCP, miR7 maintained an AUC of 0.728 for diagnosing very early-stage HCC, with 67.82% sensitivity and 77.73% specificity. Conclusions Plasma miR7 testing is a potential molecular marker with high sensitivity and specificity for the differential diagnosis of small hepatic nodules. In patients with very early-stage HCC lacking effective molecular markers (negative for both AFP and DCP), miR7 can serve as a novel and effective molecular marker to assist diagnosis.
3.Exploring the mechanism and treatment principles of testicular radiation injury from the perspective of "the struggle between vital qi and pathogen" theory
Xiaoying CHEN ; An WANG ; Yifan YE ; Yan WANG ; Yuankai GAO ; Qing XU ; Shuran WANG ; Zhangdi ZHAO ; Sumin HU
Journal of Beijing University of Traditional Chinese Medicine 2025;48(3):379-385
Testicular radiation injury is a structural and functional abnormality of the testes caused directly or indirectly by radiation, which disrupts spermatogenesis and compromises male fertility. The development of effective preventive and therapeutic interventions is essential because of the high prevalence of this condition in clinical settings and its profound effect on patients′ reproductive health and overall well-being. The concept of "the struggle between vital qi and pathogen" is first seen in the Treatise on Cold Pathogenic Diseases. It denotes the dynamic struggle between vital and pathogenic qi. The occurrence, development, and sequelae of all diseases reflect this ongoing conflict. In this context, this study defines the "vital qi" of the testis as its capacity to generate and preserve the essence of reproduction and to resist damage. The pathogenic qi associated with testicular radiation injury is categorized into two types: ionizing poison and retaining evil. The pathogenesis of testicular radiation damage is delineated into three stages by integrating the characteristics of vital and pathogenic qi: the injury, adhesion, and recovery phases. Based on the theoretical framework advanced by this study, the therapeutic approach for testicular radiation injury should adhere to the fundamental principle of strengthening vital qi and eliminating pathogenic factors. Although the primary focus of treatment should be on strengthening vital qi, it should also be complemented by strategies to eliminate pathogenic influences. This paper aims to provide a novel perspective and strategic approach to the traditional Chinese medicine diagnosis, prevention, and treatment of testicular radiation injury. By elucidating the process of testicular radiation injury and its corresponding treatment principles, it seeks to offer valuable insights for clinical practice.
4.Associations between statins and all-cause mortality and cardiovascular events among peritoneal dialysis patients: A multi-center large-scale cohort study.
Shuang GAO ; Lei NAN ; Xinqiu LI ; Shaomei LI ; Huaying PEI ; Jinghong ZHAO ; Ying ZHANG ; Zibo XIONG ; Yumei LIAO ; Ying LI ; Qiongzhen LIN ; Wenbo HU ; Yulin LI ; Liping DUAN ; Zhaoxia ZHENG ; Gang FU ; Shanshan GUO ; Beiru ZHANG ; Rui YU ; Fuyun SUN ; Xiaoying MA ; Li HAO ; Guiling LIU ; Zhanzheng ZHAO ; Jing XIAO ; Yulan SHEN ; Yong ZHANG ; Xuanyi DU ; Tianrong JI ; Yingli YUE ; Shanshan CHEN ; Zhigang MA ; Yingping LI ; Li ZUO ; Huiping ZHAO ; Xianchao ZHANG ; Xuejian WANG ; Yirong LIU ; Xinying GAO ; Xiaoli CHEN ; Hongyi LI ; Shutong DU ; Cui ZHAO ; Zhonggao XU ; Li ZHANG ; Hongyu CHEN ; Li LI ; Lihua WANG ; Yan YAN ; Yingchun MA ; Yuanyuan WEI ; Jingwei ZHOU ; Yan LI ; Caili WANG ; Jie DONG
Chinese Medical Journal 2025;138(21):2856-2858
5.Study on the Innovative Development of Photon Counting CT from Patent and Clinical Research Perspectives.
Ping WANG ; Hao XU ; Xiaoying SUN ; Bochao ZHOU ; Zhanfeng XING
Chinese Journal of Medical Instrumentation 2025;49(4):389-395
This study analyzes the global patents development and clinical applications of photon counting CT (PCCT) technology in the past 20 years, including the trends of global patent application, the patent portfolio planning, key innovations and technological evolution of top medical device companies. The study utilizes patent retrievals in incoPat database, and then carries out patent navigation analysis. At the same time, with reports of clinical trials and research, the advantages and prospects of PCCT in clinical diagnosis are sorted out. With the rapid growth of the number of patent applications for PCCT, the technologies and clinical trials are becoming increasingly mature. It is expected that in the next few years, more PCCT products will be launched to the market, bringing a more accurate and safe diagnostic experience to radiologists and patients.
Patents as Topic
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Photons
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Tomography, X-Ray Computed
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Humans
6.Study on the effect of psychological flexibility intervention on cancer-related fatigue in lung cancer patients
Mengyuan XU ; Yingping XU ; Xiaoying SHEN
China Modern Doctor 2025;63(20):14-17,30
Objective To explore the effect of psychological flexibility based psychotherapy model on cancer-related fatigue in lung cancer patients.Methods A total of 60 lung cancer patients admitted to Zhejiang Cancer Hospital from March 2022 to December 2023 were selected as research subjects.They were divided into control group(n=30)and study group(n=30)by using a random number table method.Control group received routine psychological intervention,while study group was treated with a psychological flexibility-based therapy model in addition to the routine intervention.The scores of anxiety self-rating scales,depression self-rating scales,perceived burden,coping strategies,and cancer-related fatigue were compared between two groups.Results After intervention,the self-assessment scale scores of anxiety and depression,self-perceived burden and cancer-related fatigue in both groups decreased,and the reduction was more significant in study group(P<0.05).The coping style scores of both groups improved,and the improvement was more significant in study group(P<0.05).Conclusion Intervention with a psychological flexibility-based psychotherapy model in lung cancer patients can reduce negative emotions,self-perception burden and cancer-related fatigue,and improve patients' coping style.
7.Rehabilitation effects based on immersive virtual reality as a treatment for peripheral vestibular dysfunction:a Meta-analysis
Xiaoyi LIU ; Hong WANG ; Zhicong ZHOU ; Xu SUN ; Yiru WANG ; Ziwei TONG ; Xiaoying LIU
Chinese Journal of Nursing 2025;60(9):1140-1146
Objective To systematically evaluate the rehabilitation effect of immersive virtual reality technology for patients with peripheral vestibular dysfunction,and to provide theoretical basis and practical guidance for the design of efficient rehabilitation training programs.Methods PubMed,Embase,Cochrane Library,Web of Science,CINAHL,CNKI,Wanfang Database,VIP Database,and China Biomedical Literature Database were searched for randomized controlled trials on the intervention effect of immersive virtual reality technology in patients with peripheral vestibular dysfunction from inception to February 2025.RevMan5.4 software was used to perform meta-analysis of the literature that met the quality standards.Results A total of 10 papers with 491 patients with peripheral vestibular dysfunction were included.Meta-analysis showed that immersive virtual reality technology improved vertigo symptoms in patients with peripheral vestibular dysfunction compared with conventional vestibular rehabilitation care[SMD=-1.41,95%CI(-1.58,-0.70),P<0.001],and subgroup analysis showed that the frequency of intervention was<5 times/week[SMD=-1.31,95%CI=(-1.96,-0.66),P<0.001],single intervention duration<30 min[SMD=-1.45,95%CI=(-2.21,-0.70),P<0.001],and intervention period≤7 weeks[SMD=-1.49,95%CI(-2.04,-0.94),P<0.001]were more significant.Immersive virtual reality technology reduced the risk of falls[MD=4.66,95%CI(3.84,5.48),P<0.001],and improved anxiety and depression[SMD=2.65,95%CI(1.98,3.33),P<0.001].Conclusion Immer-sive virtual reality technology improves vertigo symptoms,reduces the risk of falls,and improves anxiety and depres-sion symptoms in patients with peripheral vestibular dysfunction,in which the intervention period of ≤7 weeks,<5 training sessions per week,and each training session of<30 min are better for improving vertigo symptoms in patients with peripheral vestibular dysfunction.
8.Clinical characteristics of 9 cases of Talaromyces marneffei infection and its early rapid diagnosis using third-generation nanopore sequencing technology
Chunyan ZHAO ; Chang SONG ; Aichun HUANG ; Chaoyan XU ; Xiaoying WEI ; Chunmei ZENG ; Qingdong ZHU
Chinese Journal of Nosocomiology 2025;35(15):2288-2292
OBJECTIVE To evaluate the potential of nanopore sequencing technology for rapid diagnosis of Talaro-myces marneffei(TM)infection.METHODS Nine patients with TM infection admitted to the Fourth People's Hospital of Nanning from May 13,2022 to Aug.3,2023 were retrospectively analyzed.Rapid diagnosis was con-ducted by nanopore sequencing technology,and a comprehensive analysis of their clinical characteristics and treat-ment processes was performed.RESULTS The 9 patients included in the study had infections in various sites such as the lungs,buttocks,blood and cervical lymph nodes.Comorbidities included AIDS,secondary pulmonary tuberculosis,non-tuberculous mycobacterial disease and adult-onset immune deficiency.Patients generally exhibited elevated C-reactive protein levels and erythrocyte sedimentation rates,along with increased neutrophil counts.Some patients had abnormal lymphocyte counts and CD4+/CD8+ratios.Microbiological tests showed positive cultures in 3 cases,positive smears in 2 cases and positive targeted detection in 6 cases.Nanopore sequencing detected various pathogens in the 9 patients.The treatment results indicated that 8 patients improved after medication,with 6 patients having medication regimens adjusted based on nanopore sequencing results.CONCLUSION Nanopore sequencing technology has shown potentials in the auxiliary diagnosis of TM infection,providing timely etiological diagnostic evidence for clinical practice.
9.Association between single nucleotide polymorphisms of CYP19A1 gene at rs700519 and rs4646 loci and risk of breast cancer
Xiaoying HE ; Sheng XU ; Ruijuan HENG ; Yong ZHOU ; Pan QI ; Yu SONG
Chinese Journal of Medical Genetics 2025;42(5):587-591
Objective:To assess the association of single nucleotide polymorphisms of rs700519 and rs4646 loci of cytochrome P450 19A1 ( CYP19A1) gene with risk of breast cancer. Methods:Two hundred patients with breast cancer treated at Xinxiang Central Hospital between January 2019 and January 2024 and 100 healthy individuals were enrolled as the study group and control group, respectively. The genotypes of the CYP19A1 gene at the rs700519 and rs4646 loci were determined by direct sequencing. The general data, distribution of CYP19A1 genotypes and alleles were compared between the two groups. This study has been approved by the Medical Ethics Committee of Xinxiang Central Hospital (Ethics No.2021-182). Results:No significant difference was found in age, body mass index, times of conception and proportion of menopause between the two groups ( P>0.05). The frequencies of AA genotype and A allele at the rs700519 locus, and the CC genotype and C allele at the rs4646 locus in the study group were significantly higher than those of the control group ( P<0.05). The frequencies of AA genotype at the rs700519 locus and CC genotype at the rs4646 locus in patients with breast cancer at stages Ⅲ-Ⅳ were significantly higher than those at stage Ⅰ-Ⅱ ( P<0.05). Conclusion:Polymorphisms of CYP19A1 gene at the rs700519 and rs4646 loci are associated with susceptibility of breast cancer. The AA and CC genotypes at the two loci may increase the risk for breast cancer.
10.Efficacy of different surgeries in the treatment of high myopia patients with moderately long axial length and macular hole retinal detachment
Bohan XU ; Xiaoying WEN ; Zhaohui GU
International Eye Science 2025;25(8):1330-1335
AIM: To compare the efficacy of simple autologous blood coverage with ILM flap tamponade combined with autologous blood coverage after pars plana vitrectomy(PPV)with internal limiting membrane(ILM)peeling in treating macular hole retinal detachment(MHRD)of high myopia patients with moderately long axial length.METHODS: This retrospective study enrolled 45 patients(45 eyes)with high myopia and MHRD, and axial lengths of 26-29 mm treated at our institution between January 1, 2020 and January 1, 2024. Patients were divided into two groups based on surgical technique: group A(24 eyes)underwent PPV with ILM peeling, ILM flap tamponade, autologous blood coverage, and silicone oil injection; group B(21 eyes)received PPV with ILM peeling followed by autologous blood coverage and silicone oil injection. Intraocular pressure, best-corrected visual acuity(BCVA), retinal reattachment and macular hole closure status were compared at 1 wk, 1, 3, and 6 mo postoperatively. Silicone oil removal was performed at 6 mo postoperatively, with additional 2-month follow-up.RESULTS:At 8-month postoperative follow-up, both groups achieved complete retinal reattachment. Macular hole closure rates showed no significant intergroup difference(88% vs 86%, P=0.860). Significant improvement in BCVA was observed in both groups compared to preoperative values, with the group B demonstrating better visual outcomes than the group A(P<0.001). Transient parafoveal subretinal fluid persistence was noted in 2 eyes of the group A(resolved spontaneously at 5 and 8 mo post-PPV, respectively), and 1 eye of the group B(resolved by 4 mo post-PPV). Serial optical coherence tomography(OCT)monitoring revealed no macular hole reopening, with complete subretinal fluid resolution confirmed in all cases at final follow-up.CONCLUSION:For high myopic MHRD patients with moderately long axial length, both surgical approaches effectively promote macular hole closure and retinal reattachment. However, the autologous blood coverage technique demonstrates better BCVA than the combined ILM tamponade.


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