1.Standardization Challenges in Outcome Evaluation Systems of Animal Experiments and Considerations for Core Outcome Set Construction Strategies
Qingyong ZHENG ; Yongjia ZHOU ; Tengfei LI ; Jianguo XU ; Chen TIAN ; Hui LIU ; Min TIAN ; Ziyu ZHOU ; Caihua XU ; Yating CUI ; Junfei WANG ; Jinhui TIAN
Laboratory Animal and Comparative Medicine 2026;46(1):138-148
Animal experimentation constitutes a critical link between basic research and clinical application, making its research quality and translational efficiency paramount. Although considerable progress has been made in standardizing operational procedures and ethical guidelines, the standardization of outcome evaluation systems has significantly lagged, creating a key bottleneck that constrains the quality of biomedical research and evidence synthesis. This deficiency is manifested by pronounced heterogeneity in outcome selection across similar studies, incomplete methodological reporting, and disparate criteria for result interpretation, which severely impairs the comparability of findings and the evidence integration. To cope with this challenge, this paper systematically introduces a mature methodological tool from clinical research–the core outcome set (COS)–and explores its construction strategies and application potential in the field of animal experimentation. Given the extensive diversity of animal experiments, a pragmatic strategy of "focusing on key areas, implementing phased pilots, and promoting gradual expansion" should be adopted. This approach prioritizes the development of domain-specific COS for disease areas characterized by high research volume, urgent translational needs, and well-established animal models. A multi-source integration pathway for COS development is detailed, comprising systematic literature searches, methodological appraisals, and expert consensus, with the feasibility of leveraging artificial intelligence (AI) to enhance efficiency also being examined. The development and promotion of such COS are not intended to restrict scientific exploration; rather, they aim to establish a new, tiered evaluation paradigm consisting of "core outcomes" (mandatory), "recommended outcomes" (encouraged), and "exploratory outcomes" (optional). This framework is expected not only to enhance research quality through standardization and to adhere to the "3R" principles but also to accelerate the accumulation of high-quality evidence. This, in turn, provides a solid foundation for higher-level evidence synthesis, ultimately facilitating the effective translation of basic research findings into clinical practice and providing an essential methodological framework for scientific advancement in relevant disciplines.
2.Analysis of Clinical and Genetic Characteristics of SELENON-Related Myopathy
Xiaohong HUANG ; Min QIAN ; Lin CHEN ; Liying CUI ; Yi DAI
JOURNAL OF RARE DISEASES 2026;5(2):200-206
To summarize the clinical characteristics and genetic mutation spectrum of patients with SELENON-related myopathy(SELENON-RM), in order to improve awareness among physicians. A total of 12 patients from independent families with genetically confirmed SELENON-RM at Peking Union Medical College Hospital between January 2016 and December 2025 were retrospectively included. Clinical data were collected, and their clinical and genetic features were analyzed. The mean age at presentation was(16.7±9.7) years(range: 6-35 years), with males accounting for 66.7%(8/12). Patients presented with delayed motor development since early childhood, followed by a relatively stable disease course without significant progression over several years. Among 10 patients tested for serum creatine kinase, 4 had normal levels and 6 showed elevated levels. Electromyography performed in 9 patients indicated myogenic damage in both upper and lower limbs. Muscle biopsy in 6 patients revealed myopathic changes, including variation in muscle fiber size and fiber-type disproportion with predominance of type Ⅰ fibers. Pulmonary function tests in 5 patients demonstrated restrictive ventilatory defects. Overnight polysomnography in 6 patients revealed severe nocturnal hypoxemia. Genetic analysis showed that among the 12 patients, 9 patients had compound heterozygous mutations in the Patients with SELENON-RM usually develop symptoms in early life, presenting with motor developmental delay, scoliosis or rigid spine, and frequently with occult but significant respiratory involvement. Patients in this study appear to predominantly carry compound heterozygous variants, and exons 1 and 11 of the
3.From Bedside to Molecular Diagnosis-Multidisciplinary Treatment of a Rare Case of Autoinflammatory Disease Presenting with Skin Induration and Limb Weakness
Hanhui FU ; Wenjun WANG ; Yaping LIU ; Hui YOU ; Tao WANG ; Wen ZHANG ; Xuejun ZENG ; Liying CUI ; Huijuan ZHU ; Xiuli ZHAO ; Min SHEN ; Yicheng ZHU
JOURNAL OF RARE DISEASES 2026;5(2):207-213
This article reports a rare case of autoinflammatory disease presenting initially with skin induration and swelling after trauma as the initial manifestation, followed by progressive limb weakness. The patient was a middle-aged female who developed skin induration and swelling after trauma, which gradually progressed to limb weakness, dysarthria and bilateral facial paralysis, accompanied by livedo reticularis of the lower extremities, diffuse skin induration of the limbs, and beaded subcutaneous nodules in the right upper limb. The patient had a susceptibility to infection since childhood and a history of chronic livedo reticularis. Skin pathological examination revealed panniculitis. A comprehensive etiological screening for special infections and autoimmune diseases was completed with an unremarkable results, and whole-exome sequencing showed no abnormal findings. Following a multidisciplinary discussion combined with RNA sequencing results, the patient was diagnosed with an autoinflammatory disease, with a suspected type Ⅰ interferonopathy. Treatment with tofacitinib resulted in gradual improvement of clinical symptoms. This case highlights the importance of detailed medical history collection, systematic physical examination and multidisciplinary collaborative diagnosis and treatment, and underscores the pivotal role of molecular diagnosis in the confirmation of rare diseases. It can provide a reference for the clinical diagnosis and management of similar rare cases.
4.Differences in deltamethrin resistance and kdr gene mutation in Culex tritaeniorhynchus population in and outside the Yellow Sea wetland
Xiao-er ZHANG ; Zhi-ming WU ; Ye TIAN ; Qian CUI ; Yu-qian JI ; Huan WANG ; Shu-juan YANG ; Yi-chao ZHAO ; Yu WANG ; Hua-yu YIN ; Yu DING ; Guo-jin YAN ; Min-sen ZHAO ; Shou-gang ZHANG ; Bing-dong SONG ; Hong-na CHEN ; Jian GAO ; Wei-fang YANG ; Yu-fu ZHANG ; Hui LIU ; Hong-liang CHU
Acta Parasitologica et Medica Entomologica Sinica 2026;33(2):101-107
Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.
5.Epidemiological investigation of a cluster of rural severe fever with thrombocytopenia syndrome cases and tick ecological monitoring results in Zibo City
Jun DU ; Ai-min FENG ; Bao-qiang CUI ; Tao SUN ; Yi-chuan YANG ; Yan-dong WANG
Acta Parasitologica et Medica Entomologica Sinica 2026;33(2):128-133
Objective To understand the epidemiological characteristics of a clustered outbreak of severe fever with thrombocytopenia syndrome(SFTS)as well as the ecological tick monitoring results for Zibo City, and to provide a scientific basis for formulating prevention and control strategies. Methods A case definition was cited before epidemic investigations were performed. Epidemiological investigations were performed on the index cases and their close contacts. Blood samples were collected from cases and close contacts, and quantitative real-time RT-PCR was used to detect SFTS virus(SFTSV)nucleic acid sequences. A retrospective cohort study was conducted to analyze risk factors and develop prevention and control strategies. Results This clustered outbreak involved two index cases and six close contacts with no deaths. Case A exhibited symptom onset on July 26. SFTS was confirmed on August 2. Case B exhibited symptom onset on August 1, and SFTS was confirmed on August 3. Patient B reported a recent history of tick bites. In both index cases, the incubation period for SFTS was inferred to be 7-12 days. The time interval from symptom onset to clinical diagnosis in the two cases ranged from 2-8 days, with an average period of 5 days. SFTSV nucleic acid test result were positive for both patients, whereas all six close contacts tested negative. All captured ticks tested negative for SFTSV using quantitative real-time RT-PCR. The densities of parasitic and free-living ticks in the emergency monitoring area around the cases were 12.60 and 4.65 ticks/(flag·100 m). In 2024, the average parasitic tick index and free-living tick density index were 4.21 and 2.43 ticks/(flag ·100 m)in Yiyuan County, respectively. Conclusions No evidence of human-to-human transmission was found in the assessed SFTS clusters. The infections were likely acquired through tick bites during fieldwork, and the risk of a subsequent outbreak spreading was low.
6.The prevalence of skeletal fluorosis and the management and treatment of patients in endemic fluorosis areas of Shaanxi Province in 2023
Min YANG ; Xiaoqian LI ; Qiongjie DING ; Binbin CHEN ; Panhong ZHANG ; Ping CHEN ; Chengbao CUI ; Zhongxue FAN ; Rong ZHOU
Chinese Journal of Endemiology 2025;44(8):684-688
Objective:To investigate the prevalence of skeletal fluorosis and the management and treatment of patients in endemic fluorosis areas of Shaanxi Province.Methods:From March to November 2023, in accordance with the requirements of the "2023 Monitoring Plan for Endemic Fluorosis in Shaanxi Province", the implementation of prevention and control measures of endemic fluorosis in Shaanxi Province was investigated. The data of patients with skeletal fluorosis from January to December 2023 were downloaded from Shaanxi Province Endemic Disease Control Information Management Platform, and the epidemiological characteristics were analyzed. At the same time, the management and treatment of patients with skeletal fluorosis in endemic fluorosis areas of Shaanxi Province were carried out in accordance with the requirements of the "Shaanxi Province Endemic Disease Patient Management Service Specification".Results:In 2023, there were 10 drinking water-borne endemic fluorosis cities in Shaanxi Province, involving 3 715 endemic villages, including 3 650 water improvement villages with a water-improving rate of 98.25%. There were 2 coal-burning-borne endemic fluorosis cities in Shaanxi Province, involving 641 746 households in 1 414 endemic villages. Among them, 641 617 households had changed their furnaces and stoves, with a furnace and stove change rate of 99.98%. There were 37 462 patients with skeletal fluorosis in the province, with 35 792 from drinking water-borne endemic fluorosis areas and 1 670 from coal-burning-borne endemic fluorosis areas. The condition was mainly mild and moderate (94.12%, 35 258/37 462), with females accounting for 55.13% (20 654/37 462). The education level was mainly primary school and illiteracy (83.64%, 31 333/37 462), and the occupation was mainly farmers (99.29%, 37 196/37 462). A total of 37 116 patients with skeletal fluorosis were followed up and managed, with a management rate of 99.08% (37 116/37 462). A total of 35 756 patients were managed in a standardized manner, and the standardized management rate was 96.34% (35 756/37 116). A total of 30 649 patients with skeletal fluorosis were actually treated, with a treatment rate of 84.27% (30 649/36 370) and a total effective rate of 98.08% (30 062/30 649).Conclusion:In 2023, the prevalence of skeletal fluorosis in endemic fluorosis areas of Shaanxi Province is mainly mild and moderate, with a wide coverage of community management and a high level of treatment efficiency.
7.Whole genome sequencing and analysis of multidrug resistant ST314 Salmonella Kentucky from a broiler slaughterhouse
Jia-rui LI ; Rui-yuan SUN ; Pei-jie HE ; Hao-tian LIU ; Ru-yi KUANG ; Jing XIA ; Min CUI ; Yong HUANG ; Li-kou ZOU ; Xin-feng HAN
Chinese Journal of Zoonoses 2025;41(5):537-543
This study investigated the potential pathogenicity and genetic characteristics of ST314 Salmonella Kentucky(S.Ken-tucky)isolates from a broiler slaughterhouse.Antimicrobial susceptibility testing and whole-genome sequencing(WGS)were used to determine antimicrobial resistance,virulence factors,and the presence of antimicrobial resistance genes(ARGs)and mobile genetic elements(MGEs)among the isolates.The three multidrug resistant(MDR)isolates exhibited high resistance to multiple antimicrobial agents.The F4-2S strain exhibited resistance to 14 drugs across seven categories,whereas the F4T strain showed resistance to 13 drugs in the same number of categories.In contrast,the Y23 strain was resistant to nine drugs in six categories.Notably,F4-2S dem-onstrated high homology with F4T:both possessed 13 ARGs distributed across nine categories,in addition to a wide range of virulence factors,including secretion systems and effector proteins.The presence of IncR and IncX1 plasmids significantly enhanced both the antimicrobial resistance and pathogenicity of the isolates.The genome map of Y23 revealed a chromosome alongside two plasmids.The chromosome containedonly one resistance gene but several virulence factors,including the type III secretion system(T3SS),which is crucial for bacterial invasion.The plasmid pY23-1 contained eight types of 19 ARGs.Comparative analysis indicated that pY23-1 ex-hibited high homology with pZ1323SSL0055 and pSAL-045,all of which contained multiple ARGs,thus suggesting critical roles of these genes in the evolution of bacterial resistance.In conclusion,ST314 S.Kentucky demonstrated a complex mechanism of resis-tance coupled with significant pathogenic potential.The ARGs and MGEs in the plasmid contributed to the emergence and dissemina-tion of antimicrobial resistance.The multiple virulence factors present in the chromosome may be key factors driving the increasing virulence of ST314 S.Kentucky.
8.Genetic evolution characteristics and their influence on disease transmission in sandflies in various environments in China
Lei CUI ; Ya-qi HE ; Zheng-bin ZHOU ; Yuan FANG ; Zhong-qiu LI ; Yuan-yuan LI ; Li-min YANG ; Yi ZHANG
Chinese Journal of Zoonoses 2025;41(5):501-507
This study analyzed the genetic evolutionary characteristics of sandflies and their effects on the spread of kala-azar in various environments in endemic provinces in China,to provide a scientific basis for kala-azar disease prevention and control.Sand-flies were collected in kala-azar endemic areas such as southern Xinjiang,the large hilly areas of southern Gansu,the northern Sich-uan and Taihang Mountains,and surrounding small hills.The cytochrome c oxidase subunit I and cytochrome b gene fragments of mito-chondrial DNA were amplified to identify sandfly species.The COI and Cytb gene sequences of sandflies from southern Xinjiang and Si-chuan recorded in NCBI were also collected.The intraspecific and interspecific genetic differences of sandflies were calculated in MEGA11.0,and a phylogenetic tree was constructed through the neighbor-joining method,for analysis of the genetic and evolutionary characteristics of sandfly populations and their effects on disease transmission.A total of 155 sandflies were collected from nine sam-pling sites in seven provinces of China;the species included Phlebotomus chinensis,Phlebotomus wui,and Sergentomyia squamirostris.Five sandfly species belonging to two genera were collected:P.chinensis,P.wui,and Phlebotomus alexandri in the genus Phleboto-mus,and S.squamirostris in the genus Sergentomyia.Genetic evolution analysis based on COI and Cytb gene sequences indicated intra-specific genetic distances of 0-0.062 and 0-0.056,respectively,and interspecific genetic distances of 0.126-0.176 and 0.110-0.171,respectively.The phylogenetic tree indicated that P.wui,P.alexandri,Phlebotomus longiductus,and S.squamirostris clus-tered into one branch.The sequences of P.chinensis in the large and small hilly areas clustered into two geographical clades.In the small hilly areas,the sequences of P.chinensis aggregates showed small genetic differences,the pathogen infection was consistent,and the cases showed an epidemic spread trend.Large genetic differences at the molecular level were observed among sandflies in dif-ferent ecological regions,thus indicating key effects on leishmaniasis transmission.On the basis of these findings,prevention and con-trol strategies should be adapted to local conditions,and precise and effective prevention and control measures should be formulated according to the genetic evolution characteristics of sandflies in different regions,to better control the transmission of Kala-azar.
9.Research progress of bone morphogenetic protein signaling pathway in central nervous system
Yin-gying GAN ; Min HU ; Shuya CUI ; Zhi CHAI ; Huijie FAN
The Journal of Practical Medicine 2025;41(1):141-145
Bone morphogenetic proteins are a large subclass of the transforming growth factor β family,and Their signaling pathways are mainly classified into two kinds based on whether they depend on Smad protein to mediate or not.BMP signaling pathways are involved in regulating cell proliferation and differentiation,as well as the formation and development of multiple tissues and organs.Recent studies have shown that BMP signaling path-ways mainly promote the differentiation and growth of neurons and astrocytes,and are closely related to the my-elination of oligodendrocytes.In addition,BMP signaling pathways also play an important role in the occurrence of central nervous system diseases,such as spinal cord injuries,multiple sclerosis,neural tube defects,and Parkin-son's disease.This article reviews the BMP signaling pathways'composition,transduction mechanism and their role in the central nervous system and related diseases,in order to provide more potential ideas for basic research and clinical treatment of central nervous system diseases.
10.Whole genome sequencing and analysis of multidrug resistant ST314 Salmonella Kentucky from a broiler slaughterhouse
Jia-rui LI ; Rui-yuan SUN ; Pei-jie HE ; Hao-tian LIU ; Ru-yi KUANG ; Jing XIA ; Min CUI ; Yong HUANG ; Li-kou ZOU ; Xin-feng HAN
Chinese Journal of Zoonoses 2025;41(5):537-543
This study investigated the potential pathogenicity and genetic characteristics of ST314 Salmonella Kentucky(S.Ken-tucky)isolates from a broiler slaughterhouse.Antimicrobial susceptibility testing and whole-genome sequencing(WGS)were used to determine antimicrobial resistance,virulence factors,and the presence of antimicrobial resistance genes(ARGs)and mobile genetic elements(MGEs)among the isolates.The three multidrug resistant(MDR)isolates exhibited high resistance to multiple antimicrobial agents.The F4-2S strain exhibited resistance to 14 drugs across seven categories,whereas the F4T strain showed resistance to 13 drugs in the same number of categories.In contrast,the Y23 strain was resistant to nine drugs in six categories.Notably,F4-2S dem-onstrated high homology with F4T:both possessed 13 ARGs distributed across nine categories,in addition to a wide range of virulence factors,including secretion systems and effector proteins.The presence of IncR and IncX1 plasmids significantly enhanced both the antimicrobial resistance and pathogenicity of the isolates.The genome map of Y23 revealed a chromosome alongside two plasmids.The chromosome containedonly one resistance gene but several virulence factors,including the type III secretion system(T3SS),which is crucial for bacterial invasion.The plasmid pY23-1 contained eight types of 19 ARGs.Comparative analysis indicated that pY23-1 ex-hibited high homology with pZ1323SSL0055 and pSAL-045,all of which contained multiple ARGs,thus suggesting critical roles of these genes in the evolution of bacterial resistance.In conclusion,ST314 S.Kentucky demonstrated a complex mechanism of resis-tance coupled with significant pathogenic potential.The ARGs and MGEs in the plasmid contributed to the emergence and dissemina-tion of antimicrobial resistance.The multiple virulence factors present in the chromosome may be key factors driving the increasing virulence of ST314 S.Kentucky.


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