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.Evidence-based study on postoperative chemotherapy guidelines/consensuses for ovarian epithelial tumor
Xiandan LUO ; Yanli LU ; Yihang WU ; Yanxiang GUO ; Xiaoyi YAN ; Yongchao HUO ; Hui YAN ; Zhenjiang YANG ; Hongliang ZHANG
China Pharmacy 2025;36(18):2328-2333
OBJECTIVE To systematically evaluate the methodological quality of the postoperative chemotherapy guidelines/ consensuses for ovarian epithelial tumor. METHODS A search was conducted across databases including PubMed, Embase, Web of Science, CBM, VIP, Chinese Medical Journal Data, Wanfang Data, and CNKI, as well as the official websites of GIN, NICE, Medlive, AHRQ, CSCO, ASCO, and NCCN. The search period was from the establishment of the databases/websites to March 10, 2025. The quality of the included guidelines/consensus was evaluated by using the AGREE-Ⅱ tool. RESULTS A total of 16 guidelines/consensuses were included. The domain scores of AGREE-Ⅱ evaluation were as follows: scope and purpose of 85.07%, participants of 47.92%, rigor of development of 57.49%, clarity of presentation of 88.02%, applicability of 8.20%, and independence of 53.39%. Among them, 14 were recommended at grade B and 2 were recommended at grade C. The subgroup analysis by different countries/regions and different types of studies showed that the scores for participants, rigor of development, and independence of the guidelines/consensuses in China were significantly lower than foreign countries (P<0.05); the scores for participants and rigor of development of the guidelines were significantly higher than consensuses (P<0.05). The guideline/ consensus recommendation results indicated that grade B guidelines/consensus recommend platinum-based combination chemotherapy as the preferred adjuvant chemotherapy regimen for stage Ⅰ high-grade serous carcinoma patients;platinum-based combination chemotherapy±bevacizumab was recommended as the preferred adjuvant chemotherapy regimen for stage Ⅱ-Ⅳ high- grade serous carcinoma patients and for platinum-sensitive recurrent high-grade serous carcinoma patients; non-platinum single- agent chemotherapy±bevacizumab was recommended as the preferred chemotherapy regimen for platinum-resistant recurrent high- grade serous carcinoma patients. CONCLUSIONS The overall quality of postoperative chemotherapy guidelines/consensuses for ovarian epithelial tumor is not high. The methodological quality of guidelines/consensuses in China is still lagging behind that of foreign countries. The recommendations differ from those in foreign countries. It is recommended to improve the aspects of participants, rigor of development, and independence, to recommend treatment plans based on the different stages of ovarian cancer, and develop guidelines/consensuses that align with China’s national conditions.
3.Efficiency of chairside case-based learning in the prosthodontic clinic
Jingyi HUO ; Chunlan GUO ; Xinyuan ZHANG ; Pengyue YOU ; Xiaomin WU ; Kuo WAN ; Haitao DONG
Basic & Clinical Medicine 2025;45(9):1253-1257
Objective To evaluate the application of modified chairside case-based learning(CBL)in the teaching of dental residents in the prosthodontic clinic.Methods Dental residents in Peking Union Medical College Hospital from September 2022 to September 2024 were enrolled.Traditional CBL was conducted in control group.Modified chairside CBL was conducted in test group.The scores of department rotation examination and questionnaire results were analyzed with t-test statistical analysis.Results The score of"patient reception"in test group was significantly higher than control group(P<0.05).24 valid questionnaires were collected in two groups each.The rate of approval in test group was significantly higher than control group in the following items of questionnaire,including"reduce learning pressure or burden""improve the capacity of doctor-patient communication""improve the capacity of literature review""improve the capacity of group cooperation"(P<0.05).Conclusions Modified chairside CBL has showed good teaching effects in improving the capacity of patient reception,doctor-patient communication,literature review,group cooperation,and meanwhile reduced learning pressure or burden.
4.Exploring the need for head simulation teaching of stomatology in the eight-year medical doctor program of clinical medicine
Pengyue YOU ; Jiayi LI ; Chunlan GUO ; Xinyuan ZHANG ; Jingyi HUO ; Kuo WAN ; Haitao DONG
Basic & Clinical Medicine 2025;45(11):1528-1531
Objective To explore the need and evaluate the effectiveness for head-simulator in the teaching of sto-matology within the eight-year program of clinical medicine.Methods Questionnaire survey was conducted among the students from 2017 cohort of the eight-year program of clinical medicine at Peking Union Medical College.The survey results were statistically analyzed and described.Results Totally 87.9%of the students believed that incor-porating head-simulator into the clinical practice course of stomatology were necessary,and 93.9%expressed will-ingness to join the training.Most students preferred to practice peri-odontal scaling and cavity preparation for caries during the simulated training sessions.The majority of students considered two or four class hours of simulated head teaching to be reasonable.The pilot head simulation training was successfully implemented;75.0%of the students acknowledged clear teaching and convincible demonstrations.All the trainees agreed that the head simulation course helped them better understand stomatology knowledge,stimulated their interest in learning and expressed a desire for increased head simulation sessions during clinical practice course of stomatology.Additionally,87.5%of the students preferred head simulation training course to be applied in classic clinical clerkships.Conclusions There is strong demand among students of eight-year program of clinical medicine for incorporating head-simulator into the education of stomatology.The pilot simulation training received positive evaluations.Further exploration is needed to optimize specific scheduling and content arrangement.
5.Economic burden due to hospital-associated infections in children with acute leukemia during transplantation
Yi XU ; Yu ZHANG ; Peng XU ; Xuan GUO ; Binghao BIAN ; Jingyi LYU ; Dongdong HUO
Chinese Journal of Nosocomiology 2025;35(21):3238-3242
OBJECTIVE To investigate the incidence of hospital-associated infections among the children with acute leukemia and analyze the economic burden so as to provide scientific bases for formulating the hospital infec-tion management strategies.METHODS A total of 140 children with acute leukemia who were hospitalized in pedi-atric hematology department of the First Affiliated Hospital of Shandong First Medical University and underwent hematopoietic stem cell transplantation from Jan.1,2018 to Jun.30,2024 were recruited as the research subjects.The clinical data,incidence of infections and cost data were collected.The infection group and the non-infection group were matched in a 1∶1 ratio by propensity score matching method.The length of hospital stay and costs of medical items were compared between the infection group and the non-infection group.The economic burden due to the hospital-associated infections was estimated.RESULTS Of the 140 children,59 had hospital-as-sociated infections,with the incidence of infections 42.14%.A total of 125 children who conformed to the inclu-sion and exclusion criteria were included in the study,among whom 53 pairs were matched successfully by propen-sity score matching method.The median hospitalization cost was 230,125.79 yuan in the infection group after the matching,189,880.90 yuan in the non-infection group,and there was significant difference between the two groups(Z=-2.038,P=0.042).The direct economic burden due to the hospital-associated infections in the chil-dren with acute leukemia was 40,244.89 yuan.The median costs of western medicine,self-pay and antibiotics were increased most remarkably among all the costs of medical items(all P<0.05).CONCLUSION The targeted surveillance of hospital-associated infections and early warning of suspected cases are the major strategies to reduce the incidence of infections and relieve the economic burden.
6.Economic burden due to hospital-associated infections in children with acute leukemia during transplantation
Yi XU ; Yu ZHANG ; Peng XU ; Xuan GUO ; Binghao BIAN ; Jingyi LYU ; Dongdong HUO
Chinese Journal of Nosocomiology 2025;35(21):3238-3242
OBJECTIVE To investigate the incidence of hospital-associated infections among the children with acute leukemia and analyze the economic burden so as to provide scientific bases for formulating the hospital infec-tion management strategies.METHODS A total of 140 children with acute leukemia who were hospitalized in pedi-atric hematology department of the First Affiliated Hospital of Shandong First Medical University and underwent hematopoietic stem cell transplantation from Jan.1,2018 to Jun.30,2024 were recruited as the research subjects.The clinical data,incidence of infections and cost data were collected.The infection group and the non-infection group were matched in a 1∶1 ratio by propensity score matching method.The length of hospital stay and costs of medical items were compared between the infection group and the non-infection group.The economic burden due to the hospital-associated infections was estimated.RESULTS Of the 140 children,59 had hospital-as-sociated infections,with the incidence of infections 42.14%.A total of 125 children who conformed to the inclu-sion and exclusion criteria were included in the study,among whom 53 pairs were matched successfully by propen-sity score matching method.The median hospitalization cost was 230,125.79 yuan in the infection group after the matching,189,880.90 yuan in the non-infection group,and there was significant difference between the two groups(Z=-2.038,P=0.042).The direct economic burden due to the hospital-associated infections in the chil-dren with acute leukemia was 40,244.89 yuan.The median costs of western medicine,self-pay and antibiotics were increased most remarkably among all the costs of medical items(all P<0.05).CONCLUSION The targeted surveillance of hospital-associated infections and early warning of suspected cases are the major strategies to reduce the incidence of infections and relieve the economic burden.
7.Effects of acute sleep deprivation on behavior and synaptic biomarker expression in rats
Shibin ZHANG ; Lu WANG ; Chu WANG ; Pengcheng GUO ; Xusheng YAN ; Dongsheng HUO ; Zhanjun YANG ; Yanguo WANG ; Jianxin JIA
Chinese Journal of Comparative Medicine 2024;34(5):55-64
Objective To investigate the effects of acute sleep deprivation on the behavior and synaptic protein expression of rats.Methods Seventy healthy male Wistar rats were randomly divided into seven groups,a Control group and sleep deprivation groups(24,48,72,96,120 and 144 hours).The sleep deprivation rat model was established by the modified multiplatform water environment sleep deprivation method.Spatial learning and memory were assessed by the Morris water maze.Anxiety was assessed by the open field test.The morphology and quantity of hippocampal neurons were observed by Nissl staining.Western blot and Real-time PCR were used to determine the expression of synaptophysin(SYN),post-synaptic density protein-95(PSD-95),and brain-derived neurotrophic factor(BDNF)in rats.Results Compared with the Control group,the numbers of standing and modification were significantly increased by prolongation of the sleep deprivation time(P<0.05).The escape latency and path length were significantly increased in 120 and 144 h groups(P<0.05),whereas the number of platform crossings and the percentage of the target quadrant time were significantly decreased(P<0.01)and negatively correlated to the sleep deprivation time.The expression levels of BDNF,SYN,and PSD-95 were significantly decreased with the prolongation of sleep deprivation time(P<0.01).Conclusions With the increase in sleep deprivation time,cognitive dysfunction and anxiety gradually deteriorated,which may be related to decreases in the expression of synaptic biomarkers.
8.Research progress on breed characteristics and germplasm resources itilization of Zi goose
Mingdong HUO ; Jiaqiang DONG ; Ping LI ; Wenkai GUO ; Zhifeng CHEN ; Zhigang MA ; Nian-Dong WEI ; Yue ZOU ; Hong ZHANG ; Zhiqiang WANG ; Haotian YANG ; Caihong HAO ; Mingzhe LYU ; Yuxiang HUANG
Chinese Journal of Veterinary Science 2024;44(11):2496-2501
Zi goose is a small local variety with high fecundity,good meat quality,roughage resist-ance,strong adaptability and excellent down quality.It is an excellent female parent for cross breeding among varieties.With the rapid development of goose industry,the variety of Zi goose has not been well protected,the variety is hybrid and degraded seriously,and the number of pure Zi goose is decreasing day by day.This paper reviewed the research progress on the breeding distribu-tion and preservation status of Zi goose and the variety characteristics of Zi goose,in order to pro-vide reference for the research,protection and utilization of germplasm resources of Zi goose and the stable development of goose industry.
9.Clinical Efficacy of Chailian Lvping Granules on Post-Stroke Anxiety and Their Effect on Serum Neurotransmitter and Oxidative Stress
Jiang-Tao HUO ; Jin-Jin CAI ; Hui LIANG ; Gong-Bing GUO ; Xiao-Qiao ZHANG ; Lin LUO
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(9):2239-2245
Objective To investigate the clinical efficacy of Chailian Lvping Granules(mainly composed of Bupleuri Radix,Coptidis Rhizoma,Paeoniae Radix Alba,Angelicae Sinensis Radix,Salviae Miltiorrhizae Radix et Rhizoma,Citri Sarcodactylis Fructus,and Ziziphi Spinosae Semen)in treating post-stroke anxiety and to observe their effect on serum neurotransmitters and oxidative stress.Methods A total of 104 patients with post-stroke anxiety of liver-qi stagnation and heart-fire exuberance type were randomly divided into an observation group and a control group,52 cases in each group.The control group was treated with conventional western medicine of Paroxetine,and the observation group was treated with Chailian Lvping Granules on the basis of treatment for the control group.The course of treatment lasted for eight weeks.The two groups were observed in the changes of Hospital Anxiety and Depression Scale(HADS)score,Hamilton Anxiety Scale(HAMA)score,serum neurotransmitter parameters of brain-derived neurotrophic factor(BDNF),dopamine(DA),5-hydroxytryptamine(5-HT)and norepinephrine(NE),and oxidative stress indicators of malondialdehyde(MDA),superoxide dismutase(SOD),and glutathione peroxidase(GSH-Px)before and after treatment.Moreover,the clinical efficacy and total incidence of adverse reactions were compared between the two groups.Results(1)After eight weeks of treatment,the total effective rate of the observation group was 94.23%(49/52),and that of the control group was 76.92%(40/52).The intergroup comparison(tested by chi-square test)showed that the curative effect of the observation group was significantly superior to that of the control group(P<0.05).(2)After treatment,the HADS score and HAMA score for the axienty degree in the two groups were decreased compared with those before treatment(P<0.05),and the decrease of HADS score and HAMA score in the observation group was significantly superior to that in the control group(P<0.01).(3)After treatment,the serum level of neurotransmitter BDNF in the two groups was increased while the serum levels of DA,5-HT and NE were decreased compared with those before treatment(P<0.05).The increase of serum BDNF level and the decrease of serum DA,5-HT and NE levels in the observation group were significantly superior to those in the control group(P<0.01).(4)After treatment,the serum level of oxidative stress indicator MDA in the two groups was decreased while the serum levels of SOD and GSH-Px were increased compared with those before treatment(P<0.05).The decrease of serum MDA level and the increase of serum SOD and GSH-Px levels in the observation group were significantly superior to those in the control group(P<0.05 or P<0.01).(5)The total incidence of adverse reactions in the observation group was 5.77%(3/52),and that in the control group was 9.62%(5/52).There was no significant difference between the two groups(P>0.05).Conclusion On the basis of conventional western medicine treatment,Chailian Lvping Granules exert certain effect in the treatment of patients with post-stroke anxiety of liver-qi stagnation and heart-fire exuberance type.The combined therapy is effective and safe on alleviating the anxiety symptoms of patients,decreasing the degree of neurological impairment and stress response level,and has few adverse reactions.
10.Expert Consensus on Clinical Diseases Responding Specifically to Traditional Chinese Medicine:Fibromyalgia Syndrome
Juan JIAO ; Jinyang TANG ; Xiujuan HOU ; Mengtao LI ; Dongfeng LIANG ; Yuhua WANG ; Weixia JING ; Guangtao LI ; Qin ZHANG ; Yongfeng ZHANG ; Guangyu LI ; Qian WANG ; Yang YANG ; Jin HUO ; Mei MO ; Jihua GUO ; Xiaoxiao ZHANG ; Quan JIANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(1):216-222
Fibromyalgia syndrome (FMS) is a refractory, chronic non-articular rheumatic disease characterized by widespread pain throughout the body, for which there are no satisfactory therapeutic drugs or options. There are rich Chinese medical therapies, and some non-drug therapies, such as acupuncture, Tai Chi, and Ba-Duan-Jin, have shown satisfactory efficacy and safety and definite advantages of simultaneously adjusting mind and body. FMS is taken as a disease responding specifically to traditional Chinese medicine (TCM) by the National Administration of Traditional Chinese Medicine in 2018. In order to clarify the research progress in FMS and the clinical advantages of TCM/integrated Chinese and Western medicine, the China Academy of Chinese Medicine organized a seminar for nearly 20 experts in Chinese and Western medicine, including rheumatology, psychology, acupuncture and moxibustion, and encephalopathy, with the topic of difficulties in clinical diagnosis and treatment of FMS and advantages of TCM and Western medicine. The recommendations were reached on the difficulties in early diagnosis and solutions of FMS, mitigation of common non-specific symptoms, preferential analgesic therapy, TCM pathogenesis and treatment advantages, and direction of treatment with integrated Chinese and Western medicine. FMS is currently facing the triple dilemma of low early correct diagnosis, poor patient participation, and unsatisfactory benefit from pure Western medicine treatment. To solve the above problems, this paper suggests that rheumatologists should serve as the main diagnostic force of this disease, and they should improve patient participation in treatment decision-making, implement exercise therapy, and fully utilize the holistic and multidimensional features of TCM, which is effective in alleviating pain, improving mood, and decreasing adverse events. In addition, it is suggested that FMS treatment should rely on both TCM and Western medicine and adopt multidisciplinary joint treatment, which is expected to improve the standard of diagnosis and treatment of FMS in China.

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