1.Effect of Acupuncture at Neiguan (PC6) on Improving Autism by Promoting Myelination Through The METTL14/m⁶A/PTEN Axis Based on “Xuanfu-Suiqiao” Theory
Wei-Li DANG ; Lü-Yuan LIANG ; Yu-Xin LI ; Zhi-Yao LI ; Sai-Dan LIU ; Jia-Lei CAO ; Rong-Ze MA ; Yun-Kai WANG ; Xiao-Qing YANG ; Bing-Qi WEI ; Bing-Xiang MA
Progress in Biochemistry and Biophysics 2026;53(5):1165-1177
ObjectiveTo clarify whether METTL14 mediates the core role of acupuncture at Neiguan (PC6) in promoting myelination and improving behavior in young autistic rats through gene intervention technology. MethodsThe ASD model was established by intraperitoneal injection of valproic acid (VPA) in pregnant rats. Male offspring were intracerebroventricularly injected with adenovirus-packaged METTL14 shRNA (sh-METTL14) or its control (sh-NC) on postnatal day 1, with a model group set as well. Subsequently, the juvenile rats were divided into model group, acupuncture group, acupuncture+sh-NC group, and acupuncture+sh-METTL14 group. The acupuncture group received acupuncture at Neiguan (PC6) from postnatal day 7, once daily for 21 consecutive days. Neurobehavioral changes were evaluated by behavioral tests; METTL14 knockdown efficiency and the expression of METTL14, METTL3, and PTEN were detected by quantitative real-time PCR (qRT-PCR) and Western blot (WB); PTEN m6A levels were measured by RNA immunoprecipitation-qPCR (RIP-qPCR); myelin ultrastructure, expression of myelin basic protein (MBP) and neurofascin 155 (NF155), and dendritic spine density were observed using transmission electron microscopy (TEM), enzyme-linked immunosorbent assay (ELISA), immunofluorescence, qRT-PCR, and primary neuron culture. ResultsBehaviorally, knockdown of METTL14 significantly counteracted the beneficial effects of acupuncture in improving self-grooming, open field exploration, three-chamber social interaction, and Morris water maze learning and memory (P<0.05, P<0.01). Compared with the acupuncture+sh-NC group, the acupuncture+sh-METTL14 group showed significantly decreased mRNA and protein expression of hippocampal METTL14 (P<0.01), and the upregulating effects of acupuncture on METTL3 and PTEN expression were reversed (P<0.01). Meanwhile, knockdown of METTL14 significantly inhibited the acupuncture-induced increase in PTEN m6A levels (P<0.01). Morphologically, knockdown of METTL14 attenuated the improvement of myelin structure by acupuncture, reversed the downregulation of MBP and upregulation of NF155 induced by acupuncture, and blocked the increase in dendritic spine density (P<0.05, P<0.01). ConclusionMETTL14 is a key molecule mediating the therapeutic effect of acupuncture at Neiguan. Acupuncture at Neiguan upregulates METTL14, thereby enhancing m6A methylation modification of PTEN mRNA to stabilize its expression, ultimately promoting myelin development and improving behavioral symptoms in ASD juvenile rats. This preliminarily reveals the modern biological connotation of “opening Xuanfu and dredging myelin”.
2.Effect of Acupuncture at Neiguan (PC6) on Improving Autism by Promoting Myelination Through The METTL14/m⁶A/PTEN Axis Based on “Xuanfu-Suiqiao” Theory
Wei-Li DANG ; Lü-Yuan LIANG ; Yu-Xin LI ; Zhi-Yao LI ; Sai-Dan LIU ; Jia-Lei CAO ; Rong-Ze MA ; Yun-Kai WANG ; Xiao-Qing YANG ; Bing-Qi WEI ; Bing-Xiang MA
Progress in Biochemistry and Biophysics 2026;53(5):1165-1177
ObjectiveTo clarify whether METTL14 mediates the core role of acupuncture at Neiguan (PC6) in promoting myelination and improving behavior in young autistic rats through gene intervention technology. MethodsThe ASD model was established by intraperitoneal injection of valproic acid (VPA) in pregnant rats. Male offspring were intracerebroventricularly injected with adenovirus-packaged METTL14 shRNA (sh-METTL14) or its control (sh-NC) on postnatal day 1, with a model group set as well. Subsequently, the juvenile rats were divided into model group, acupuncture group, acupuncture+sh-NC group, and acupuncture+sh-METTL14 group. The acupuncture group received acupuncture at Neiguan (PC6) from postnatal day 7, once daily for 21 consecutive days. Neurobehavioral changes were evaluated by behavioral tests; METTL14 knockdown efficiency and the expression of METTL14, METTL3, and PTEN were detected by quantitative real-time PCR (qRT-PCR) and Western blot (WB); PTEN m6A levels were measured by RNA immunoprecipitation-qPCR (RIP-qPCR); myelin ultrastructure, expression of myelin basic protein (MBP) and neurofascin 155 (NF155), and dendritic spine density were observed using transmission electron microscopy (TEM), enzyme-linked immunosorbent assay (ELISA), immunofluorescence, qRT-PCR, and primary neuron culture. ResultsBehaviorally, knockdown of METTL14 significantly counteracted the beneficial effects of acupuncture in improving self-grooming, open field exploration, three-chamber social interaction, and Morris water maze learning and memory (P<0.05, P<0.01). Compared with the acupuncture+sh-NC group, the acupuncture+sh-METTL14 group showed significantly decreased mRNA and protein expression of hippocampal METTL14 (P<0.01), and the upregulating effects of acupuncture on METTL3 and PTEN expression were reversed (P<0.01). Meanwhile, knockdown of METTL14 significantly inhibited the acupuncture-induced increase in PTEN m6A levels (P<0.01). Morphologically, knockdown of METTL14 attenuated the improvement of myelin structure by acupuncture, reversed the downregulation of MBP and upregulation of NF155 induced by acupuncture, and blocked the increase in dendritic spine density (P<0.05, P<0.01). ConclusionMETTL14 is a key molecule mediating the therapeutic effect of acupuncture at Neiguan. Acupuncture at Neiguan upregulates METTL14, thereby enhancing m6A methylation modification of PTEN mRNA to stabilize its expression, ultimately promoting myelin development and improving behavioral symptoms in ASD juvenile rats. This preliminarily reveals the modern biological connotation of “opening Xuanfu and dredging myelin”.
3.Guideline for the prevention of intraoperative acquired pressure injury in paraplegic patients with spinal cord injury (version 2025)
Aijun XU ; Shuixia LI ; Bo CHEN ; Mengyuan YE ; Lejiao LANG ; Ning NING ; Lin ZHANG ; Changqing LIU ; Zhonglan CHEN ; Weihu MA ; Weishi LI ; Xiaoning WANG ; Dongmei BIAN ; Jiancheng ZENG ; Xin WANG ; Yuan GAO ; Yaping CHEN ; Jiali CHEN ; Yun HAN ; Xiuting LI ; Yang ZHOU ; Xiaojing SU ; Qiong ZHANG ; Tianwen HUANG ; Ping ZHANG ; Hua LIN ; Xingling XIAO ; Ruifeng XU ; Fanghui DONG ; Bing HAN ; Luo FAN ; Yanling PEI ; Suyun LI ; Xiaoju TAN ; Rongchen GUO ; Yefang ZOU ; Xiaoyun HAN ; Junqin DING ; Yi WANG ; Shuhua DENG ; Jinli GUO ; Yinhua LIANG ; Yuan CEN ; Xiaoqin LIU ; Junru CHEN ; Haiyang YU ; Lunlan LI ; Ying REN ; Yunxia LI ; Jianli LU ; Ying YING ; Lan WEI ; Yin WANG ; Qinhong XU ; Yanqin ZHANG ; Yang LYU ; Shijun ZHANG ; Sui WENJIE ; Sanlian HU ; Shuhong YANG ; Guoqing LI ; Jingjing AN ; Baorong HE ; Leling FENG
Chinese Journal of Trauma 2025;41(6):530-541
Paraplegia caused by spinal cord injury is a serious neurological complication, for which surgery is currently the main treatment method. Due to different surgical approaches, patients are usually expected to maintain a passive prone position for a long time or switch between the supine and prone positions. Affected by multiple factors such as neurogenic sensory disorders, pathological changes in muscle tone and operative duration, the risk of intraoperative acquired pressure injury (IAPI) is significantly increased. Current clinical prevention strategies for IAPI in these patients predominantly focus on localized pressure relief during positioning, lacking systematic, standardized comprehensive prevention protocols or evidence-based guidelines. To address it, Department of Nursing, Orthopedics Branch, China International Exchange and Promotive Association for Medical and Health Care, Spinal Trauma Professional Committee, Orthopedics Branch, Chinese Medical Doctor Association, Nursing Group of Spine and Spinal Cord Professional Committee of Chinese Association of Rehabilitation Medicine organized experts in relevant fields to formulate Guideline for the prevention of intraoperative acquired pressure injury in paraplegic patients with spinal cord injury ( version 2025), based on evidence-based medical evidence and latest research results and clinical practice at home and abroad. Eleven recommendations were put forward from the aspects of preoperative risk assessment, intraoperative prevention strategies, postoperative handover and monitoring, and supportive mechanisms for IAPI prevention, aiming to standardize the prevention measures and management strategies of IAPI in paraplegic patients with spinal cord injury and accelerate the recovery of patients and improve the therapeutic effect.
4.Identifying risk factors for acute graft-versus-host disease in patients with acute myeloid leukemia undergoing haploidentical hematopoietic stem cell transplantation
Dan FENG ; Wei LIANG ; Jiaxin CAO ; Yigeng CAO ; Xin CHEN ; Cuicui LIU ; Rongli ZHANG ; Weihua ZHAI ; Jialin WEI ; Qiaoling MA ; Donglin YANG ; Yi HE ; Sizhou FENG ; Mingzhe HAN ; Aiming PANG ; Hongtao WANG ; Jiaxi ZHOU ; Erlie JIANG
Chinese Journal of Hematology 2025;46(10):914-920
Objective:To identify the risk factors for acute graft-versus-host disease (aGVHD) in patients with acute myeloid leukemia (AML) undergoing haploidentical hematopoietic stem cell transplantation (HID-HSCT) .Methods:A total of 141 AML patients who underwent HID-HSCT at the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences, from January 2020 to July 2021 were included. The cumulative incidence of aGVHD was analyzed using the Fine-Gray competing risk model, with relapse and death as competing events, to compare differences between groups. Potential risk factors were evaluated by univariable and multivariable Cox proportional hazards regression analyses to determine their independent effects on aGVHD.Results:Among the 141 patients, 86 (61.0%) were male and 55 (39.0%) were female, with a median age at transplantation of 34 years. Within 100 days post-transplant, 59 patients developed grade Ⅱ-Ⅳ aGVHD, whereas 86 patients experienced no or grade Ⅰ aGVHD (the grade 0-Ⅰ aGVHD group) . Survival analysis showed that the 3-year overall survival was 68.7% (95% CI: 57.7%-81.9%) in the grade Ⅱ-Ⅳ aGVHD group, compared with 78.8% (95% CI: 70.4%-88.3%) in the grade 0 - Ⅰ aGVHD group, with the difference not being statistically significant ( P=0.190) . Univariable analysis identified donor age ( P=0.020, HR=1.020, 95% CI: 1.000-1.040) and the female donor-male recipient sex combination ( P=0.033, HR=1.980, 95% CI: 1.160-3.380) as risk factors for grade Ⅱ-Ⅳ aGVHD. Multivariable analysis confirmed that donor age ( P=0.005, HR=1.026, 95% CI: 1.008-1.047) and the female donor-male recipient sex combination ( P=0.002, HR=2.339, 95% CI: 1.354-4.037) were independent risk factors for aGVHD. Patients receiving grafts from donors aged >45 years had a significantly higher 100-day cumulative incidence of grade Ⅱ-Ⅳ aGVHD compared with those receiving grafts from donors ≤45 years [54.7% (95% CI: 42.3%-67.0%) vs 31.6% (95% CI: 21.0%-42.1%) , P=0.006]. Similarly, patients with the female donor-male recipient sex combination had a higher 100-day cumulative incidence of grade Ⅱ-Ⅳ aGVHD than those with other sex combinations [56.8% (95% CI: 40.4%-73.1%) vs 36.9% (95% CI: 27.5%-46.3%) , P=0.015]. Conclusion:Older donor age and the female donor-male recipient sex combination remain independent risk factors for aGVHD in patients with AML undergoing HID-HSCT.
5.Validity of an enhanced nutrition management model for all pregnant women in reducing the incidence of macrosomia
Shengnan LIANG ; Wei ZHENG ; Xiaoxin WANG ; Wei SONG ; Cuimei GUO ; Xin YAN ; Guanghui LI
Chinese Journal of Health Management 2025;19(6):434-439
Objective:To analyze the validity of an enhanced nutrition management model for all pregnant women in reducing the incidence of macrosomia.Methods:This retrospective cohort study utilized data from the Beijing Birth Cohort database established by Beijing Obstetrics and Gynecology Hospital, Capital Medical University. A total of 73 193 pregnant women who underwent regular prenatal examinations and delivered at the hospital between January 2018 and December 2023 were consecutively included. From 2018 to 2020, all participants received nutrition education, and high-risk pregnancies predisposed to macrosomia were referred to nutrition clinics for further follow-up. From 2021 to 2023, obstetricians participated in nutritional assessments and gestational weight gain guidance, with repeated nutrition evaluations and education provided during early, mid, and late pregnancy. A multidisciplinary team (obstetrics and nutrition departments) collaborated to implement an enhanced nutrition management model for all pregnant women. General data, parity, gestational age at delivery, neonatal birth weight, and clinical information were collected. Annual incidences of macrosomia and low birth weight were calculated. Chi-square tests and variance analysis were used to analyzed yearly changes in macrosomia rates and evaluate the impact of the two-phase management strategies on macrosomia incidence, thereby to explore the validity of an enhanced nutrition management model for all pregnant women in reducing the incidence of macrosomia.Results:The number of deliveries included annually from 2018 to 2023 was 14 578, 15 413, 11 496, 11 146, 10 396, and 10 164, respectively. Maternal pre-pregnancy body mass indices in 2022 to 2023 were higher than those in 2018 to 2021 [(22.26±3.50) and (22.23±3.65) vs (21.87±3.27), (21.82±3.31), (21.86±3.34) and (21.94±3.39) kg/m2, respectively (all P<0.05)]. Neonatal birth weights in 2021 to 2022 were lower than those in 2018 to 2020 [(3 271±514) and (3 270±513) vs (3 323±504), (3 314±500), and (3 315±510) g], and the birth weight in 2023 was further reduced compared to that in 2018 to 2022 [(3 236±506) vs (3 323±504), (3 314±500), (3 315±510), (3 271±514) and (3 270±513) g] (all P<0.05). The incidence of macrosomia in 2021 to 2022 was lower than those in 2018 to 2020 (5.55%, 5.75% vs 6.97%, 6.68%, 6.67%), and the incidence in 2023 further decreased compared to those in 2018 to 2022 (4.16% vs 6.97%, 6.68%, 6.67%, 5.55%, 5.75%) (all P<0.05). Conclusion:The enhanced nutrition management model for all pregnant women effectively reduces the incidence of macrosomia, demonstrating significant clinical value for widespread implementation.
6.Guideline for Adult Weight Management in China
Weiqing WANG ; Qin WAN ; Jianhua MA ; Guang WANG ; Yufan WANG ; Guixia WANG ; Yongquan SHI ; Tingjun YE ; Xiaoguang SHI ; Jian KUANG ; Bo FENG ; Xiuyan FENG ; Guang NING ; Yiming MU ; Hongyu KUANG ; Xiaoping XING ; Chunli PIAO ; Xingbo CHENG ; Zhifeng CHENG ; Yufang BI ; Yan BI ; Wenshan LYU ; Dalong ZHU ; Cuiyan ZHU ; Wei ZHU ; Fei HUA ; Fei XIANG ; Shuang YAN ; Zilin SUN ; Yadong SUN ; Liqin SUN ; Luying SUN ; Li YAN ; Yanbing LI ; Hong LI ; Shu LI ; Ling LI ; Yiming LI ; Chenzhong LI ; Hua YANG ; Jinkui YANG ; Ling YANG ; Ying YANG ; Tao YANG ; Xiao YANG ; Xinhua XIAO ; Dan WU ; Jinsong KUANG ; Lanjie HE ; Wei GU ; Jie SHEN ; Yongfeng SONG ; Qiao ZHANG ; Hong ZHANG ; Yuwei ZHANG ; Junqing ZHANG ; Xianfeng ZHANG ; Miao ZHANG ; Yifei ZHANG ; Yingli LU ; Hong CHEN ; Li CHEN ; Bing CHEN ; Shihong CHEN ; Guiyan CHEN ; Haibing CHEN ; Lei CHEN ; Yanyan CHEN ; Genben CHEN ; Yikun ZHOU ; Xianghai ZHOU ; Qiang ZHOU ; Jiaqiang ZHOU ; Hongting ZHENG ; Zhongyan SHAN ; Jiajun ZHAO ; Dong ZHAO ; Ji HU ; Jiang HU ; Xinguo HOU ; Bimin SHI ; Tianpei HONG ; Mingxia YUAN ; Weibo XIA ; Xuejiang GU ; Yong XU ; Shuguang PANG ; Tianshu GAO ; Zuhua GAO ; Xiaohui GUO ; Hongyi CAO ; Mingfeng CAO ; Xiaopei CAO ; Jing MA ; Bin LU ; Zhen LIANG ; Jun LIANG ; Min LONG ; Yongde PENG ; Jin LU ; Hongyun LU ; Yan LU ; Chunping ZENG ; Binhong WEN ; Xueyong LOU ; Qingbo GUAN ; Lin LIAO ; Xin LIAO ; Ping XIONG ; Yaoming XUE
Chinese Journal of Endocrinology and Metabolism 2025;41(11):891-907
Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.
7.Primary intraosseous synovial sarcoma:a case report and literature review
Wen ZHAO ; Wei-Jun QIAN ; Li LI ; Yan-Min WANG ; Peng-Hui SU ; Chao-Xin ZHANG ; Liang XU ; Tie-Cheng WU ; Jun-Qi LIU ; Ya-Jun WANG
Medical Journal of Chinese People's Liberation Army 2025;50(11):1419-1425
Objective To report a case of tibial synovial sarcoma and review relevant literature to enhance understanding of this disease.Methods The clinical data of a patient with tibial synovial sarcoma treated at Kaifeng Central Hospital were retrospectively analyzed.A literature search was conducted in domestic and international databases,including China National Knowledge Infrastructure(CNKI),Wanfang Data,PubMed,Web of Science,and Embase,up to July 2024.Relevant literature was comprehensively reviewed to summarize the imaging and pathological characteristics,treatment,and prognosis of synovial sarcoma.Results A 29-year-old female patient was admitted with left lower extremity pain.X-ray examination revealed a proximal tibia space-occupying lesion suggestive of malignancy,and a mid-tibial space-occupying lesion considered benign.Contrast-enhanced computed tomography(CT)and plain magnetic resonance imaging(MRI)of the proximal tibial lesion also suggested malignancy.Ultrasound-guided biopsy of the proximal tibial tumor revealed a poorly differentiated malignant tumor.Immunohistochemistry results indicated monophasic synovial sarcoma,requiring genetic testing for definitive diagnosis.The patient underwent wide resection of the proximal left tibial malignancy with tumor-type artificial joint replacement,combined with curettage and bone cement filling for the left mid-tibial lesion under anesthesia.Postoperative pathology of space-occupying lesions in the proximal tibia confirmed monophasic synovial sarcoma,and fluorescence in situ hybridization(FISH)demonstrated a rupture of the synovial sarcoma translocation gene(SYT)(i.e.,SS18 positive).There was no recurrence or metastasis found in the patient during the reexamination 6 months after postoperative chemotherapy.As of July 2024,15 cases of genetically confirmed primary intraosseous synovial sarcoma have been reported internationally.Symptoms included pain and swelling,with a medical history of 1-2 years.The X-ray and CT findings showed osteolytic destruction with bone cortical discontinuity.In 13 cases,the intraosseous masses extended to the extraosseous area;in 2 cases,punctate calcifications were detected within the masses.Plain MRI scan showed iso-signal or hypo-signal on T1WI and hyper-signal,iso-signal,and hypo-signal on fat-suppressed T2WI,and enhanced MRI scan demonstrated heterogeneous enhancement.Pathological examination showed spindle-shaped cells under microscopy.Immunohistochemistry results showed positive epithelial membrane antigen(EMA),broad-spectrum cytokeratin(AE1/AE3),Ewing's sarcoma marker(CD99),and transducin-like enhancer of Split 1(TLE1).Twelve patients underwent surgical treatment;6 patients received adjuvant chemotherapy after surgery,of whom 4 developed local recurrence or distant metastasis at initial diagnosis,and 3 died during follow-up.Among the 6 patients who did not receive adjuvant chemotherapy,3 suffered from recurrence or distant metastasis.Conclusions Primary intraosseous synovial sarcoma is a rare malignant tumor with non-specific clinical manifestations.Imaging features typically include osteolytic destruction and intraosseous masses extending extraosseously,suggesting an intraosseous origin.Pathology and immunohistochemistry aid diagnosis,but definitive confirmation relies on further genetic testing.At present,the main treatment regimens for synovial sarcoma involve comprehensive therapies such as surgery and adjuvant chemotherapy,and the prognosis of patients is poor.
8.Differentiation of bone marrow mesenchymal stem cells into cardiomyocytes induced by rehmannia glutinosa polysaccharide combined with basic fibroblast growth factor
Wei-Hong LIANG ; Hui-Ying YANG ; Xin-Ru XU ; Hao-Dan SUN ; Yang LÜ ; Hai-Ping WANG
Acta Anatomica Sinica 2025;56(6):681-687
Objective To explore the effects of pretreatment with rehmannia glutinosa polysaccharide(RGP)and basic fibroblast growth factor(FGF-2)alone or in combination on the differentiation of bone marrow mesenchymal stem cells(BMSCs)into cardiomyoid cells and the related mechanisms.Methods BMSCs pretreated with FGF-2 and RGP alone or in combination were cultured for 1,2,and 4 weeks.The expression levels of NKx2.5 and GATA-4 were detected by Real-time PCR.BMSCs pretreated with FGF-2 or RGP alone and PI3K/Akt signaling pathway inhibitor LY294002 were used to detect the expression levels of myocardial specific proteins and related pathway proteins by Western blotting.Results Compared with the blank control group,pretreatment with FGF-2 or RGP alone increased the expression rate of myocardial specific markers,and the effect of combined pretreatment with FGF-2 and RGP was more obvious(P<0.05).Compared with pretreatment with FGF-2 or RGP alone,pretreatment with LY294002 combined with FGF-2 or RGP significantly down-regulated the expression of cardiac-specific proteins in BMSCs and inhibited the phosphorylation of Akt(P<0.05).Conclusion Both FGF-2 and RGP can induce BMSCs to differentiate into cardiomyocyte-like cells by regulating PI3K/Akt signaling pathway,and the combination of FGF-2 and RGP has a better inductive effect.
9.IL-17A collaborating with TGF-β1 in regulating benign tracheal stenosis after tracheal injury in experimental dogs
Chun ZHAO ; Yunfeng DENG ; Wei SU ; Hongyan DAI ; Lusheng LIANG ; Xueguang CAI ; Song XU ; Jun WANG ; Xin YANG ; Junren ZENG
Journal of Interventional Radiology 2025;34(5):487-492
Objective To discuss the effect of interleukin-17A(IL-17A)and transforming growth factor-β1(TGF-β1)on the benign tracheal stenosis after tracheal injury in experimental dogs.Methods The trachea stenosis model of healthy Beagle dogs was established by burning the middle part of trachea with electric snare under bronchoscopy guidance.A total of 21 dogs were divided into normal group(n=3,receiving normal feeding),molding group(n=12,after airway modeling every 3 dogs were sacrificed each week for 4 weeks),IL-17A suppression group(n=3,receiving Secukinumab after airway modeling),and IL-17A inhibitor+TGF-β1 inhibitor group(n=3,receiving Secukinumab and SB43154 after airway modeling).Bronchoscopy and CT scan were performed once a week,and the stenosis degree was calculated.RT-qPCR,immunohistochemistry,and HE staining of the obtained tracheal tissues were performed.Results Within 1-4 weeks after molding,in module-making dogs the degree of stenosis of the injured trachea gradually increased,and the expressions of ECM-related proteins,TGF-β1 and IL-17A were up-regulated.After treatment with IL-17A inhibitors,the inflammatory infiltration and granulation tissue hyperplasia were reduced and the early tracheal stenosis was improved(P<0.05).The combination use of IL-17A inhibitor and TGF-β1 inhibitor had a better remission effect(P<0.05).Conclusion IL-17A and TGF-β1 may synergistically affect the formation of tracheal stenosis.
10.Construction of A Mouse Model of Liver Cancer Resistant to PD-1 Monoclonal Antibody and Analysis of Its Metabolic Changes
Xin-ru NIU ; Xia WANG ; Zhi-ting SHU ; Zi-lan XU ; Xiao-li QIU ; Wei DAI ; Liang-qian ZHANG ; Xiang-liang DENG
Progress in Modern Biomedicine 2025;25(12):1931-1941,1954
Objective:To establish a mouse model of liver cancer resistant to PD-1 monoclonal antibody and analyze the changes in its metabolomics to explore the potential mechanism of drug resistance.Methods:BALB/c mice were randomly divided into control and treatment groups after being loaded with tumor,and a normal group was additionally set up.The normal and control groups were injected with saline,and the treatment group was injected with PD-1 monoclonal antibody,after which the mice in the treatment group were screened for drug resistant and response groups.Observed the drug-resistant situation,body mass,tumor growth and survival rate of mice in each group,calculate the spleen index.The pathological features of tumor tissues were observed by HE staining method.Serum metabolites were detected by non-targeted metabolomics.Finally,a bivariate Pearson correlation analysis was conducted between the differential serum metabolites and tumor size.Results:The tumor-bearing mouse model with PD-1 monoclonal antibody resistance was successfully established,and the drug resistance rate of the mice was 50%.Compared with the normal and response groups,mice in the resistant group showed an increase in body weight,a significant increase in tumor volume,a decrease in survival rate,and a significant increase in splenic index.There was less lymphocyte infiltration in the tumor tissue.Metabolomics analysis showed that the serum levels of glutamic acid and aspartic acid increased and malic acid decreased in the resistant mice compared with the response group,and these changes were closely related to the arginine biosynthesis pathway.Conclusions:The tumor-bearing mouse model with PD-1 monoclonal antibody resistance was successfully established.The changes in its peripheral serum metabolomics mainly involve arginine metabolism and the related changes of aspartate,malate and glutamate.

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