1.Exosomes Treat Ischemic Stroke by Regulation of Ferroptosis Through the NRF2/SLC7A11/GPX4 Pathway in Mice
Yingtao XU ; Mengmeng WANG ; Ping LIN ; Haitao CHI ; Yi WANG ; Ying BAI
Laboratory Animal and Comparative Medicine 2026;46(1):20-31
ObjectiveA middle cerebral artery occlusion (MCAO) mouse model is established by electrocoagulation of the middle cerebral artery. The study examines the mechanism by which exosomes (EXO) derived from human amniotic mesenchymal stem cells (hAMSCs) improve ischemic stroke and regulate neural ferroptosis-related injury. MethodsThirty-two SPF-grade male C57BL/6J mice aged 6 - 8 weeks were randomly divided into four groups (n=8 per group): sham group (Sham), model group (MCAO), MCAO plus normal saline group (MCAO+NaCl), and MCAO plus exosome group (MCAO+EXO). The mouse MCAO model was established by electrocoagulation of the middle cerebral artery. Mice in the Sham group underwent exposure of the middle cerebral artery without electrocoagulation. Twenty-four hours before MCAO induction, mice in the MCAO+EXO group received a tail vein injection of 100 μL of exosomes derived from the culture supernatant of hAMSCs at a concentration of 9.5×1011 particles/mL. Mice in the MCAO+NaCl group were injected with an equal volume of normal saline via the tail vein. Twenty-four hours after model establishment, neurological deficits were evaluated using the Longa neurological deficit scoring system. Cerebral infarct volume was assessed by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Hematoxylin and eosin (HE) staining was performed to evaluate morphological changes of neurons in the ischemic brain regions. The contents of ferrous iron (Fe2+), malondialdehyde (MDA), total glutathione (total GSH), oxidized glutathione (GSSG), and reduced glutathione (GSH) in the infarct core and peri-infarct regions were determined using microcolorimetric assays to evaluate differences among groups. The mRNA expression levels of ferroptosis-related factors, including nuclear factor erythroid 2-related factor 2 (NRF2), solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4) in the infarct core and peri-infarct regions were measured by real-time quantitative PCR. Protein expression levels of NRF2, SLC7A11, and GPX4 in the infarct and peri-infarct regions of each group were analyzed by Western blotting. ResultsCompared with the MCAO group, the Longa neurological deficit score was significantly reduced in the MCAO+EXO group (P<0.01). Prominent cerebral infarction was observed in the MCAO group, whereas the infarct volume ratio was markedly decreased in the MCAO+EXO group compared with the MCAO group (P<0.001). Histopathological analysis revealed that mice in the MCAO group exhibited obvious neuronal damage, including cytoplasmic vacuolar degeneration, nuclear pyknosis and fragmentation, unclear nuclear structure, and disorganized neuronal arrangement, compared with the Sham group. In contrast, neurons in the MCAO+EXO group showed relatively preserved morphology, with intact cellular structures and large, regular nuclei located centrally within the cells. Biochemical analysis demonstrated that Fe2+ and MDA levels in the infarct core and peri-infarct regions were significantly increased in the MCAO group compared with the Sham group (P<0.001). These levels were significantly reduced in the MCAO+EXO group compared with the MCAO group (P<0.01). In addition, total glutathione (total GSH), oxidized glutathione (GSSG), and reduced glutathione (GSH) levels were markedly decreased in the MCAO group relative to the Sham group (P<0.01). Compared with the MCAO group, the MCAO+EXO group exhibited significantly increased levels of total GSH and GSH (P<0.001), while no significant change was observed in GSSG levels (P>0.05). Furthermore, both mRNA and protein expression levels of nuclear factor erythroid 2-related factor 2 (NRF2), solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4) were significantly downregulated in the MCAO group compared with the Sham group (P<0.01, P<0.001). In contrast, both mRNA and protein expression levels of NRF2, SLC7A11, and GPX4 were significantly upregulated in the MCAO+EXO group compared with the MCAO group (P<0.05). ConclusionIn the mouse MCAO model, tail vein injection of exosomes derived from hAMSCs can improve motor function, reduce infarct area, protect neuronal cell morphology, and reduce the degree of nerve injury. Exosomes may exert a protective effect by activating the NRF2/SLC7A11/GPX4 pathway and reducing ferroptosis in neuronal cells of MCAO model mice.
2.Prevalence of thyroid nodules and its association with metabolic syndrome in physical examination population of Mianyang Region
Yanlin PU ; Haitao XU ; Fang HE ; Jianrong SU ; Huiying ZHAO ; Yaozhou JIA ; Li LIU
Journal of Public Health and Preventive Medicine 2026;37(3):151-154
Objective To investigate the prevalence of thyroid nodules in the physical examination population in Mianyang region and analyze its association with metabolic syndrome. Methods A retrospective study was conducted on 9 978 individuals who underwent health examinations at our hospital from January 2024 to May 2025. Thyroid examinations were performed using color Doppler ultrasound to analyze the prevalence of thyroid nodules in this population. Clinical data of all subjects were collected, and logistic regression analysis was employed to assess the association between metabolic syndrome and the risk of thyroid nodule development. Results The prevalence of thyroid nodules in the physical examination population of Mianyang region was 17.98% (1 794/9 978). The logistic regression results showed that after adjusting for gender, age, BMI, occupation, consumption of non-iodized salt, staying up late, daily sleep duration, anxiety, and depression, metabolic syndrome (OR=6.593, 95% CI: 3.961-10.975) was associated with thyroid nodules (P<0.05). Conclusion The prevalence of thyroid nodules among the physical examination population in the Mianyang area is 17.98%, and metabolic syndrome remains associated with the risk of thyroid nodules after effectively controlling for confounding factors.
3.A case report of giant neurofibromatosis of maxillofacial, neck and chest was treated by multidisciplinary cooperation.
Shuzhen CHEN ; Leifeng LIU ; Haitao QIU ; Jun YAO ; Qizhu CHEN ; Mei XU
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2025;39(4):376-378
Neurofibromatosis Type 1 (NF1) is an autosomal dominant hereditary neurological disorder. One of the typical manifestations of NF1 is neurofibroma, which can develop gradually over time. When the volume exceeds 100 cm², it is referred to as giant neurofibroma, representing a tumor-like proliferation of Schwann cells within the nerve fiber sheath. The Department of Otolaryngology at the Affiliated Hospital of Guangdong Medical University received a rare case involving a patient with giant neurofibromatosis affecting the maxillofacial region, neck, and chest. The patient underwent successful surgical treatment with the collaboration of various medical disciplines.
Humans
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Head and Neck Neoplasms/surgery*
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Neck
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Neurofibromatoses
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Neurofibromatosis 1/surgery*
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Thoracic Neoplasms/surgery*
4.A case of young adult with neck lymphoma presenting with recurrent syncope as the initial symptom and literature review.
Xin XU ; Jun YAO ; Leifeng LIU ; Haitao QIU ; Feng JIANG ; Mei XU
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2025;39(7):667-673
Recurrent syncopal episodes associated with head and neck lymphoma are rarely reported. Through a typical case study, this article analyzes the clinical features of patients with neck lymphoma presenting with syncope as the initial symptom, aiming to improve understanding of this type of disease. By reviewing the clinical data of this patient with neck masses admitted for recurrent syncope in June 2023 and integrating findings with relevant literature, the clinical characteristics of this patient population is presented. The first symptoms of lymphoma presenting as syncope are relatively rare and often lead to misdiagnosis. Diagnosis is mainly based on pathological and immunohistochemical analysis.
Humans
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Head and Neck Neoplasms/diagnosis*
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Lymphoma/diagnosis*
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Recurrence
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Syncope/etiology*
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Young Adult
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Diagnostic Errors
5.Gut microbiota-derived tryptophan metabolites regulated by Wuji Wan to attenuate colitis through AhR signaling activation.
Wanghui JING ; Sijing DONG ; Yinyue XU ; Jingjing LIU ; Jiawei REN ; Xue LIU ; Min ZHU ; Menggai ZHANG ; Hehe SHI ; Na LI ; Peng XIA ; Haitao LU ; Sicen WANG
Acta Pharmaceutica Sinica B 2025;15(1):205-223
Disruption of the intestinal mucosal barrier caused by gut dysbiosis and metabolic imbalance is the underlying pathology of inflammatory bowel disease (IBD). Traditional Chinese medicine Wuji Wan (WJW) is commonly used to treat digestive system disorders and showed therapeutic potential for IBD. In this interdisciplinary study, we aim to investigate the pharmacological effects of WJW against experimental colitis by combining functional metabolomics and gut-microbiota sequencing techniques. Treatment with WJW altered the profile of the intestinal microbiota and notably increased the abundance of Lactobacillus, thereby facilitating the conversion of tryptophan into indole-3-acetic acid (IAA) and indoleacrylic acid (IA). These indole derivatives activated the aryl hydrocarbon receptor (AhR) pathway, which reduced colonic inflammation and restored the expression of intestinal barrier proteins. Interestingly, the beneficial effects of WJW on gut barrier function improvement and tryptophan metabolism were disappeared in the absence of gut microbiota. Finally, pre-treatment with the AhR antagonist CH-223191 confirmed the essential role of IAA-mediated AhR activation in the therapeutic effects of WJW. Overall, WJW enhanced intestinal barrier function and reduced colonic inflammation in a murine colitis model by modulating Lactobacillus-IAA-AhR signaling pathway. This study provides novel insights into colitis pathogenesis and presents an effective therapeutic and preventive approach against IBD.
6.Current status and prospects of botulinum toxin type-A combined with platelet-rich plasma injection
Siqing WANG ; Ningjie CHEN ; Haitao WANG ; Qingpeng XU ; Doudou CHAI ; Shuang YAN
Chinese Journal of Medical Aesthetics and Cosmetology 2025;31(5):451-456
In recent years, botulinum toxin type-A (BTX-A) combined with cosmetic injections and radiofrequency lasers have been widely implemented to achieve better tissue repair. Among these therapies, platelet-rich plasma (PRP), rich in growth factors, has demonstrated notable efficacy in promoting tissue regeneration and repair. However, there is some controversy regarding the combined use of these two biomaterials in the treatment of various diseases. This review summarizes the current status of their combined application in peripheral neuropathic pain, seborrheic alopecia, and facial rejuvenation, also analyzes the advantages, interactions, and influencing factors of the combined application. Although the effectiveness and safety of PRP combined with BTX-A injection therapy in many of the above diseases are relatively high, the conclusion should still be carried out in the future multi-center, large-sample clinical studies to improve the credibility and representativeness of the results.
7.Research progress on the resistance mechanism of anti-angiogenesis targeted drugs in the treatment of colorectal cancer
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(2):193-199
Colorectal cancer(CRC)is one of the most common malignancies worldwide,although anti-angiogenic targeted agents such as bevacizum-ab have shown significant efficacy in the treatment of metastatic CRC,however,the emergence of drug resistance is still a key obstacle affecting the suc-cess rate of treatment and survival of patients.This article reviews the progress of anti-angiogenesis targeted drugs in the treatment of CRC,the mecha-nism of drug resistance and how to solve the prob-lem of drug resistance.
8.Comparison of efficacy and safety of crisaborole ointment 2% versus pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children: a multicenter, randomized, controlled clinical trial
Xing XIAO ; Shan WANG ; Huan YANG ; Hong SHU ; Yanping GUO ; Jinping CHEN ; Yao LU ; Qinfeng LI ; Yuan LIANG ; Mutong ZHAO ; Xiaoyan LUO ; Limin MIAO ; Rui XU ; Xuemei LI ; Sha LAI ; Jianhong LI ; Zhen LUO ; Lu YU ; Lu XING ; Meitan WANG ; Xiaoli LI ; Haitao XU ; Ping LI ; Hua WANG ; Lin MA
Chinese Journal of Dermatology 2025;58(5):425-430
Objective:To compare the efficacy and safety of crisaborole ointment 2% versus pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children aged 2 years or older.Methods:A multicenter, randomized, open-label, controlled clinical trial was conducted. A total of 120 pediatric patients aged 2 - 17 years with mild to moderate atopic dermatitis were enrolled from departments of dermatology of 8 hospitals in China between March 2022 and February 2023. The participants were randomly assigned in a 1∶1 ratio to the crisaborole group and the pimecrolimus group, and received the treatment with crisaborole ointment 2% and pimecrolimus cream 1% respectively, twice a day for 4 weeks. Visits were scheduled at baseline/on day 1, as well as on days 8, 15, and 29. The primary efficacy outcome was the percentage of patients achieving the Investigator's Static Global Assessment (ISGA) success (defined as clear [0] or almost clear [1] on the ISGA scale, combined with ≥ 2‐grade improvement from baseline) on day 29. The secondary efficacy outcomes included changes in the Eczema Area and Severity Index (EASI) total scores from baseline to day 29, percentages of patients achieving ISGA improvement (defined as clear [0] or almost clear [1] on the ISGA scale), as well as changes in the Peak Pruritus Numerical Rating Scale (NRS) scores, Dermatology Life Quality Index (DLQI) /Infants' Dermatology Life Quality Index (IDLQI) /Children's Dermatology Life Quality Index (CDLQI) scores, and in the Dermatitis Family Impact (DFI) scores. Drug safety was evaluated according to the incidence of adverse events. Categorical data were compared using the chi-square test. Since measurement data did not follow a normal distribution, the rank sum test was used for comparisons of measurement data between groups.Results:A total of 106 children with mild to moderate atopic dermatitis were included in the per-protocol analysis set, with 52 in the crisaborole group (26 males and 26 females) and 54 in the pimecrolimus group (27 males and 27 females). There were no significant differences in age, disease duration, ISGA and EASI scores at baseline between the two groups (all P > 0.05). On day 29, 22 patients (42.31%) in the crisaborole group and 25 (46.30%) in the pimecrolimus group achieved ISGA success, with no significant difference between the two groups ( χ2 = 0.17, P = 0.68) ; 35 patients (67.31%) in the crisaborole group and 45 (83.33%) in the pimecrolimus group achieved ISGA improvement, also with no significant difference between the two groups ( χ2 = 3.68, P = 0.06) ; additionally, there were no significant differences in the EASI, pruritus NRS, DLQI/IDLQI/CDLQI, or DFI scores between the two groups (all P > 0.05). Adverse reactions to the two topical agents were mainly local reactions such as mild to moderate pain, itching, or worsening of itching, and no obvious systemic adverse reactions occurred. The incidence of drug-related adverse reactions was 46.15% (24 cases) in the crisaborole group and 37.04% (20 cases) in the pimecrolimus group, with no significant difference between the two groups ( χ2 = 0.91, P = 0.34) . Conclusion:The efficacy of crisaborole ointment 2% was comparable to that of pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children aged ≥ 2 years, and it yielded early and rapid improvement in the quality of life of patients and their families, with good safety and tolerability profiles.
9.Efficacy of a baby smoothing and special caring cream in reducing the recurrence of atopic dermatitis in infancy: a randomized controlled trial
Qisa WANG ; Wenling ZHAO ; Xiufeng HAN ; Huanyue MA ; Haitao SHI ; Lin MA ; Zhe XU
Chinese Journal of Dermatology 2025;58(10):975-979
Objective:To investigate the clinical efficacy and safety of a baby smoothing and special caring cream in reducing the recurrence of atopic dermatitis (AD) in infancy.Methods:A randomized controlled trial was conducted. Children with moderate AD (with overall investigator's global assessment [IGA] scores of 3 - < 4) were enrolled from Shunyi Maternal and Children′s Hospital of Beijing Children′s Hospital from April 2021 to June 2024. During the induction period, all children were topically treated with 0.1% hydrocortisone butyrate cream twice daily on the lesional skin, as well as with a baby smoothing and special caring cream at least twice daily throughout the body; at the 2-week visit, patients with an IGA score of ≤ 1 point entered the maintenance phase, while those with an IGA score of > 1 point continued the treatment for another 2 weeks; at the 4-week visit, patients with an IGA score of ≤ 1 point entered the maintenance phase, while those still with an IGA score of > 1 point were withdrawn from the study, and received conventional treatment. Patients who entered the maintenance period were randomly divided into the test group and the control group in a 1∶1 ratio using a random number table. In the test group, the hydrocortisone butyrate cream was discontinued, while the baby smoothing and special caring cream was continued twice daily for 8 consecutive weeks; in the control group, both the hydrocortisone butyrate cream and the baby smoothing and special caring cream were discontinued. IGA and Scoring AD (SCORAD) scores were assessed by clinicians at weeks 4 and 8 in the maintenance phase, while the patient-oriented eczema measure (POEM) score was evaluated weekly by patients' parents. The Kaplan-Meier survival analysis and Breslow test were used to compare recurrence rates in the two groups (the primary efficacy outcome), and a generalized estimating equation model was used to evaluate the changes in IGA, SCORAD, and POEM scores in the two groups (the secondary efficacy outcomes). Adverse reactions were monitored throughout the study to evaluate safety.Results:A total of 68 children with moderate AD aged from 3 months to 2 years were included. There were 38 females and 30 males, aged 11.72 ± 6.03 months. Fifty-two patients entered the maintenance phase; 2 were lost to follow-up, and 50 were included in the per-protocol set, with 28 in the test group and 22 in the control group. The recurrence rate during the maintenance phase was 7.14% (2/28) in the test group and 31.82% (7/22) in the control group, showing a significant difference between the two groups ( χ 2 = 5.08, P = 0.032). At weeks 4 and 8 in the maintenance phase, the IGA scores were significantly lower in the test group than in the control group (Wald χ 2 = 5.06, P = 0.024), whereas the SCORAD scores showed no significant differences between the two groups (Wald χ 2 = 2.92, P = 0.087). During weeks 1 - 8 in the maintenance phase, the POEM scores showed no significant differences between the two groups or over time (both P > 0.05), while the two groups showed different change trends in POEM scores over time (Wald χ 2interaction = 55.37, Pinteraction < 0.001). Throughout the entire study period, no adverse reactions were observed among all 68 subjects. Conclusion:With a high safety profile, the baby smoothing and special caring cream could reduce the recurrence rate during the maintenance phase, showing promise as an adjuvant therapy for the maintenance treatment of AD in infancy, and is worthy of clinical application.
10.Safety Analysis of Pembrolizumab in the General Population and Elderly Based on the FAERS Database
Yuxi ZHANG ; Ao XU ; Yan WANG ; Haitao CHEN ; Xiaoting XU ; Li CHEN
Herald of Medicine 2025;44(9):1448-1455
Objective To explore and analyze the adverse drug event(ADE)signals associated with pembrolizumab and to provide a reference for the real-world safety of drug use on elderly patients.Methods ADE reports of pembrolizumab in the general population and elderly population were collected from the FDA Adverse Event Reporting System(FAERS)for the period between January 1st,2019,and June 30th,2024.Multiple signal detection methods(ROR,PRR,MHRA)were employed for data mining.Classification and statistical analysis were performed using the System Organ Class(SOC)and Preferred Term(PT)from the MedDRA(Version 27.1)dictionary.Results A total of 966 signals were identified in the general population,spanning 24 SOCs,while 593 signals were detected in the elderly population,spanning 23 SOCs.Comparative visualization analysis of critical PTs under four major SOCs revealed no significant abnormal signals in elderly patients.Conclusion A comprehensive and multidimensional analysis of the ADE data from the FAERS database indicates that pembrolizumab appears to be relatively safe for use in elderly patients.


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