1.Evaluation of Animal Models with Diminished Ovarian Reserve Based on Clinical Disease and Syndrome Characteristics of Traditional Chinese Medicine and Western Medicine
Mingyue YU ; Ling TANG ; Xiaohui SUN ; Jingjing ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(9):240-248
ObjectiveWith the development of society and the increasing demand for pregnancy at an advanced age, diminished ovarian reserve (DOR) has attracted wider attention. This disease affects the normal menstruation of women and poses a threat to their mental health. Current research on DOR is still in the initial stage, and advancing research progress in DOR necessitates the construction of effective and clinically relevant animal models. Building on existing literature and integrating the diagnosis criteria of DOR in traditional Chinese medicine (TCM) and Western medicine, this study summarized, analyzed, and evaluated existing models, providing a reference for optimizing DOR animal models. MethodsA retrospective analysis of literature on DOR-related animal models was conducted, and the diagnostic criteria of DOR in TCM and Western medicine were sorted out. By means of evaluation methods of animal models, the clinical relevance of each model to TCM and Western medicine was assessed. ResultsDOR animal models included those based on natural factors, iatrogenic factors, immune factors, metabolic factors, and environmental factors. Among them, the model based on iatrogenic factors, especially models induced by Tripterygium wilfordii preparations, cyclophosphamide, and cisplatin, had a high degree of relevance to both Western medical diseases and TCM syndromes and was confirmed as the optimal modeling method for studying DOR at present. ConclusionThe existing DOR modeling methods mostly have a high degree of clinical relevance to Western medical diseases, while the number of DOR animal models with clear TCM syndromes is very limited. TCM plays an indispensable role in exploring DOR treatment methods. Therefore, the development of DOR animal models related to TCM syndromes should be strengthened, further exploring the potential of TCM and providing strong theoretical support for the application of TCM in DOR treatment.
2.Establishment of Psoriasis Rat Model with Spleen Deficiency and Dampness Obstruction Syndrome Induced by External Dampness Factors
Yating ZHANG ; Haojie SU ; Fanlu LIU ; Panyu ZHOU ; Qing WANG ; Junhong ZHANG ; Jingjing WU ; Ling HAN
Journal of Traditional Chinese Medicine 2025;66(13):1369-1377
ObjectiveTo construct a rat model of psoriasis with spleen deficiency and dampness obstruction syndrome (external dampness type), and evaluate the macroscopic manifestations and microscopic indicators of the model. MethodsTwenty-two SD rats were divided into normal group (n=3), common psoriasis group (n=5), spleen deficiency and dampness obstruction syndrome (external dampness type) group (n=7), and psoriasis with spleen deficiency and dampness obstruction syndrome (external dampness type) group (n=7). The spleen deficiency and dampness obstruction syndrome (external dampness type) rat model was established through 32-week exposure to an artificially simulated high-humidity environment, while the common psoriasis model was developed via 7-day topical application of imiquimod cream, and these two approaches were combined to construct a composite model of psoriasis with spleen deficiency and dampness obstruction syndrome (external dampness type). Rats in the normal group were housed under normal humidity conditions. The general state, tongue manifestation of rats were observed to evaluate the macroscopic syndrome manifestations; the microscopic syndrome manifestations of rats were evaluated through adipose tissue and liver tissue changes; the severity of psoriasis in rats was evaluated through skin pathological changes, psoriasis area and severity index (PASI), proliferating cell nuclear antigen (PCNA) expression and spleen tissue changes; changes in rat CD4+ interferon-γ+ cells (CD4+IFN-γ+ cells), CD4+ tumour necrosis factor-α+ cells (CD4+ TNF-α+ cells), and forkhead framing protein P3+ regulatory T cells (CD3+CD4+FoxP3+ Treg cells) were detected by flow cytometry. ResultsMacroscopically, both the spleen deficiency and dampness obstruction syndrome (external dampness type) group and psoriasis with spleen deficiency and dampness obstruction syndrome (external dampness type) group exhibited manifestations of spleen deficiency and dampness obstruction, including lethargy, huddling behavior, dull and disheveled fur, as well as soft or loose stools and perianal soiling in some individuals; both these two groups displayed enlarged tongue, swollen, and moist tongue texture, accompanied by slippery tongue surface. Microscopically, compared to the common psoriasis group, the psoriasis with spleen deficiency and dampness obstruction syndrome (external dampness type) group showed increased epididymal fat index (P<0.05); compared to the normal group and spleen deficiency and dampness obstruction syndrome (external dampness type) group, the psoriasis with spleen deficiency and dampness obstruction syndrome (external dampness type) group demonstrated significantly elevated spleen mass (P<0.05), while hepatic gross morphology and HE staining revealed no significant histopathological changes across all groups. Dorsal skin lesions were markedly exacerbated in the psoriasis with spleen deficiency and dampness obstruction syndrome (external dampness type) group when compared to those in common psoriasis group. Both the common psoriasis group and psoriasis with spleen deficiency and dampness obstruction syndrome (external dampness type) group exhibited significantly higher erythema scores, scaling scores, infiltration scores, PASI total scores, and proportions of CD3+CD4+FoxP3+Treg cells compared to the normal group and spleen deficiency and dampness obstruction syndrome (external dampness type) group (P<0.05), with pronounced PCNA-positive expression observed in the epidermal basal layer and dermis; the psoriasis with spleen deficiency and dampness obstruction syndrome (external dampness type) group displayed significantly increased proportions of CD4+TNF-α+cells compared to the spleen deficiency and dampness obstruction syndrome (external dampness type) group (P<0.05); whereas no significant differences were detected in CD4+IFN-γ+cell proportions among groups (P>0.05). ConclusionThe rat model of psoriasis with spleen deficiency and dampness obstruction syndrome (external dampness type) can be successfully constructed by artificially simulating a high-humidity environment combined with imiquimod induction.
3.Real-world efficacy and safety of azvudine in hospitalized older patients with COVID-19 during the omicron wave in China: A retrospective cohort study.
Yuanchao ZHU ; Fei ZHAO ; Yubing ZHU ; Xingang LI ; Deshi DONG ; Bolin ZHU ; Jianchun LI ; Xin HU ; Zinan ZHAO ; Wenfeng XU ; Yang JV ; Dandan WANG ; Yingming ZHENG ; Yiwen DONG ; Lu LI ; Shilei YANG ; Zhiyuan TENG ; Ling LU ; Jingwei ZHU ; Linzhe DU ; Yunxin LIU ; Lechuan JIA ; Qiujv ZHANG ; Hui MA ; Ana ZHAO ; Hongliu JIANG ; Xin XU ; Jinli WANG ; Xuping QIAN ; Wei ZHANG ; Tingting ZHENG ; Chunxia YANG ; Xuguang CHEN ; Kun LIU ; Huanhuan JIANG ; Dongxiang QU ; Jia SONG ; Hua CHENG ; Wenfang SUN ; Hanqiu ZHAN ; Xiao LI ; Yafeng WANG ; Aixia WANG ; Li LIU ; Lihua YANG ; Nan ZHANG ; Shumin CHEN ; Jingjing MA ; Wei LIU ; Xiaoxiang DU ; Meiqin ZHENG ; Liyan WAN ; Guangqing DU ; Hangmei LIU ; Pengfei JIN
Acta Pharmaceutica Sinica B 2025;15(1):123-132
Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T NANC), time to symptom improvement (T SI), and time of hospital stay (T HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.
4.A Systematic Evaluation Study of a Mouse Model of Psoriasis with Pattern of Spleen Deficiency and Dampness Obstruction
Fanlu LIU ; Haojie SU ; Panyu ZHOU ; Yating ZHANG ; Qing WANG ; Yue SUN ; Hongyu YUE ; Jingjing WU ; Jianan WEI ; Ling HAN
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(10):1470-1482
Objective To construct a mouse model of psoriasis with spleen deficiency and dampness obstruction pattern and evaluate the model from multiple dimensions and directions,expects to provide research support for the study of traditional Chinese medicine (TCM) treatment of psoriasis with spleen deficiency and dampness obstruction pattern. Methods A mouse model of spleen deficiency and dampness obstruction pattern was established by feeding a high-fat diet,a mouse model of psoriasis vulgaris was established by externally applying imiquimod ointment,and a mouse model of psoriasis with spleen deficiency and dampness obstruction pattern was constructed by combining the above two models. Indications of spleen deficiency and dampness obstruction pattern were evaluated by comparing the body mass,food intake and water intake of mice in each group. The severity of psoriasis in mice was evaluated by comparing the area of skin lesions,PASI score,the value of transdermal water loss (TEWL),and histopathological morphological changes of skin under HE staining in each group. Flow cytometry was used to detect the expression in various cell types to evaluate the degree of inflammatory response of psoriasis in mice. Observation of adiposity index,changes in the histopathological morphology of liver tissue under HE staining,changes in the mRNA expression levels of related factors in liver tissue and adipose tissue of epididymis of mice detected by RT-qPCR,and changes of ABCA1 protein expression level of skin detected by Western Blot were used to evaluate the lipid metabolism disorders in mice. Results Compared with the mice in the psoriasis vulgaris model group,the mice in the model of psoriasis with pattern of spleen deficiency and dampness obstruction had significantly higher body mass (P<0.001),significantly lower food intake (P<0.005),and the symptoms of pattern of spleen deficiency and dampness obstruction such as greasy fur,mental fatigue,etc. appeared. The TWEL were significantly increased(P<0.001),and the PASI scores also significantly increased(P<0.001). HE results were found psoriasis-like manifestations including hypertrophy of the spinous layer and clubbed hyperplasia. The expression of CD11bhighLy6G+neutrophil subpopulation,CD11binLy6Chigh monocyte subpopulation,CD11binCD11chigh classical dendritic cell subpopulation,F4/80-CD11c+dendritic cell subpopulation was significantly increased (P<0.001). HE staining suggested that the cellular morphology of liver showed obvious vacuolated degeneration,and the index of subcutaneous white adiposity and epididymal adiposity index were both significantly increased (P<0.005). The mRNA levels of FABP4 and CD36 in liver tissue were significantly elevated(P<0.005,P<0.001),while the mRNA expression levels of ABCA1 and PPARγ in epididymal fat tissue were decreased (P<0.05,P<0.01). ABCA1 protein level in skin increased(P>0.05). Conclusion The mouse model of psoriasis with spleen deficiency and dampness obstruction pattern can be used as a reliable animal model for combining disease and pattern,which can provide a reference for further exploration of TCM in the treatment of psoriasis with spleen deficiency and dampness obstruction pattern.
5.The developmental changes in the expression of Rap1B and the effect of mo-nocular form deprivation during the critical period on its expression in the mouse superior colliculus
Changlin LUAN ; Ying LING ; Jingjing YE ; Xuefeng SHI
Recent Advances in Ophthalmology 2024;44(7):522-525
Objective To explore the developmental changes in the expression of Rap1B and the effect of monocular form deprivation(MD)during the critical period of visual development on the expression of Rap1B in the mouse superior colliculus(SC).Methods Forty-five SPF-grade healthy male C57BL/6J mice were used in this experimental study.Ex-periment 1:To study the developmental changes of Rap1B expression in the mouse SC,the experimental mice were divided into three groups:the pre-critical period group[postnatal day 18(P18)],the critical period group(P32),and the adult group(P60).The expression levels of Rap1B gene and protein in the left and right SC of mice in each group were detected by quantitative polymerase chain reaction(qPCR)and Western blot,respectively.Experiment 2:To study the effect of MD on the expression levels of Rap1B gene and protein in the SC,the experimental mice were divided into two groups:the right eye MD group(MD models of the right eyes were established at P28 and detected at P32)and the normal control group(NC group,P32).The expression levels of Rap1B gene and protein in the left and right SC of mice in each group were measured by qPCR and Western blot,respectively.Results The expression levels of Rap1B gene and protein were low in the left and right SC of mice in the pre-critical period group;compared with the pre-critical period group,the ex-pression levels of Rap1B gene and protein in the critical period group significantly increased(both P<0.05);compared with the critical period group,the expression levels of Rap1B gene and protein in the adult group significantly decreased(both P<0.05).Mice in the right eye MD group showed significantly higher expression levels of Rap1B gene and protein in the left SC(both P<0.05),while significantly lower expression levels of Rap1B gene and protein in the right SC(both P<0.05)compared to mice in the NC group.Conclusion The developmental trend of Rap1B gene expression in the mouse SC is consistent with the critical period of visual development,and Rap1B may be involved in the regulatory effect of MD during the critical period on the development of SC.
6.HLA-B*5801 gene polymorphisms detection in prediction of severe drug eruption associated allopurinol:a rapid health technology assessment
Jinjin CAO ; Ya LING ; Jie ZHANG ; Jingjing ZHANG ; Jianguo ZHU ; Xiufang CAO
Chinese Journal of Pharmacoepidemiology 2024;33(9):1044-1053
Objective To evaluate the accuracy,sensitivity,specificity and economy of HLA-B*5801 gene polymorphisms detection in predicting allopurinol-related severe drug eruption before receiving allopurinol treatment using rapid health technology assessment(rHTA),to provide clinicians and policymakers with an efficient and convenient evidence-based basis.Methods PubMed,Cochrane Library,Web of Science,Embase,WanFang Data,CNKI databases and the official website of health technology assessment(HTA)agency were electronically searched to collect HTA reports,systematic reviews/Meta-analyses and pharmacoeconomic literature on the HLA-B*5801 gene polymorphisms detection from inception to December 31,2023.Two reviewers independently screened studies,extracted data,assessed the included studies'quality,and analyzed and summarised the results.Results A total of 16 literature were included,of which 5 systematic reviews/Meta-analyses and 11 pharmacoeconomic studies.The results showed that the HLA-B*5801 gene mutation rate was significantly higher in patients presenting with severe drug eruption than in the allopurinol-tolerant group(P<0.05).Two studies reported the sensitivity and specificity of the HLA-B*5801 gene polymorphisms assay for predicting severe drug eruption,the sensitivity of 0.78,0.93,and specificity of 0.96,0.89,respectively.The economic study showed that HLA-B*5801 gene polymorphisms detection before allopurinol treatment was cost-effective in Chinese Han,Korean,Thai populations,but not in British,American(Caucasian or Hispanic),Singaporean and Malaysian populations.Conclusion HLA-B*5801 gene polymorphisms detection before allopurinol treatment and guiding drug use according to the screening results in Chinese Han population can reduce the risk of severe drug eruption and treatment costs.
7.Risk factors and distribution characteristics for skip metastasis in papillary thyroid carcinoma
Changjiao YAN ; Meiling HUANG ; Jingjing XIAO ; Rui LING
Chinese Journal of General Surgery 2024;39(7):544-549
Objective:To investigate the risk factors and distribution characteristics for skip lateral lymph node metastasis in patients of papillary thyroid carcinoma (PTC).Methods:Clinical data of 720 PTC patients with postoperative pathologically confirmed lymph node metastasis in the lateral cervical region at Xijing Hospital of Air Force Military Medical University from Jan 2014 to Dec 2021 were retrospectively analyzed. According to whether there is skip metastasis in the lymph nodes of the patients, patients were divided into skip metastasis group (92 cases) and non-skip metastasis group (628 cases).Results:The rate of lymph node skip metastasis in PTC in this study was 12.7% (92/720). Women ( OR=1.890, 95% CI:1.118-3.198, P=0.018), age ≥55 years ( OR=2.508, 95% CI:1.412-4.454, P=0.002), tumor involving the upper pole ( OR=1.919, 95% CI:1.220-3.018, P=0.005), and unilateral glandular lobe lesions ( OR=1.926, 95% CI:1.153-3.214, P=0.012) were independent risk factors for lymph node skip metastasis. Skip metastasis is most likely to occur in region Ⅲ, followed by region Ⅵ, Ⅱ and Ⅴ. Larger cancer tended to have more than one jumping metastases in regions Ⅲ and Ⅳ ( P=0.001, 0.016). Conclusion:In female PTC patients, age≥55 years , tumors involving upper pole, and unilateral lesions,are all the hazardous factor for skip metastasis in the lateral neck region.
8.Research progress of matrix metalloproteinase-28 in pulmonary disease
Ling TAN ; Xue MA ; Jingjing WANG ; Fengfeng LEI
The Journal of Practical Medicine 2024;40(20):2949-2953
Matrix metalloproteinase-28(MMP-28)is widely expressed in vertebrates and plays diverse biological roles,participating in the regulation of various pathophysiological processes in the body.Increased expression of MMP-28 has been observed in chronic obstructive pulmonary disease,pulmonary fibrosis,and other lung diseases.Studies have demonstrated that MMP-28 promotes chronic inflammation and tissue remodeling by regulating macrophage recruitment and M2 polarization,and is involved in the pathogenesis of lung diseases by promoting cell proliferation and epithelial-mesenchymal transition.This article provides a review of the relationship between the basic characteristics of MMP-28 and pulmonary diseases.
9.Clinical characteristics and prognostic factors of breast cancer patients with tumor deposits in the ipsilateral axillary region
Jingjing XIAO ; Meiling HUANG ; Changjiao YAN ; Rui LING ; Hongliang WEI
Chinese Journal of Oncology 2024;46(2):146-154
Objective:To investigate the clinicopathologic features and prognostic factors of breast cancer patients with tumor deposits in the ipsilateral axillary region.Methods:We retrospectively analyzed the clinicopathologic data and follow-up results of 155 patients with breast cancer diagnosed for the first time and complicated with tumor deposits in the ipsilateral axillary region in the Department of Thyroid-Breast-Vascular Surgery of Xijing Hospital from January 2008 to September 2018. Kaplan-Meier method was used for survival analysis. Log rank test was used for the univariate analysis of prognostic factors, and Cox regression was used for multivariate analysis.Results:The median disease free survival (DFS), median distant metastasis free survival (DMFS), and median overall survival (OS) of the 155 patients were 52.0 months, 66.6 months, and 102.2 months, respectively. The 5-year and 10-year DFS rates were 45.7% and 23.1%, the 5-year and 10-year DMFS rates were 56.9% and 28.9%, and the 5-year and 10-year OS rates were 79.3% and 46.0%, respectively. Multivariate Cox regression analysis showed that family tumor history ( HR=0.362, 95% CI: 0.140-0.937), clinical T stage (T3: HR=3.508, 95% CI: 1.380-8.918; T4: HR=2.220, 95% CI: 1.076-4.580), estrogen/progesterone receptor status ( HR=0.476, 95% CI: 0.261-0.866), number of tumor deposits ( HR=1.965, 95% CI:1.104-3.500) and neoadjuvant chemotherapy ( HR=1.961, 95% CI: 1.032-3.725) were independent influencing factors for DFS. Molecular subtype [human epidermal growth factor receptor-2(HER-2) positive and hormone receptor negative: HR=7.862, 95% CI: 3.189-19.379], number of tumor deposits ( HR=2.155, 95% CI: 1.103-4.212), neoadjuvant chemotherapy ( HR=5.002, 95% CI: 2.300-10.880) and radiotherapy ( HR=2.316, 95% CI: 1.005-5.341) were independent influencing factors of DMFS. Histological grade ( HR=4.362, 95% CI: 1.932-9.849), estrogen/progesterone receptor expression ( HR=0.399, 95% CI: 0.168-0.945), HER-2 expression ( HR=2.535, 95% CI: 1.114-5.768) and neoadjuvant chemotherapy ( HR=4.080, 95% CI: 1.679-9.913) were independent influencing factors of OS. Conclusions:The presence of tumor deposits weakens the influence of axillary lymph node status and distant metastases on the prognosis of breast cancer patients. Therefore, a clinicopathological staging system taking into account tumor deposits should be developed. Since the number of tumor deposits affects the risk of recurrence and metastasis of breast cancer patients, we recommend that the number of tumor deposits should be reported in detail in the pathological report after breast cancer surgery.
10.Clinical characteristics and prognostic factors of breast cancer patients with tumor deposits in the ipsilateral axillary region
Jingjing XIAO ; Meiling HUANG ; Changjiao YAN ; Rui LING ; Hongliang WEI
Chinese Journal of Oncology 2024;46(2):146-154
Objective:To investigate the clinicopathologic features and prognostic factors of breast cancer patients with tumor deposits in the ipsilateral axillary region.Methods:We retrospectively analyzed the clinicopathologic data and follow-up results of 155 patients with breast cancer diagnosed for the first time and complicated with tumor deposits in the ipsilateral axillary region in the Department of Thyroid-Breast-Vascular Surgery of Xijing Hospital from January 2008 to September 2018. Kaplan-Meier method was used for survival analysis. Log rank test was used for the univariate analysis of prognostic factors, and Cox regression was used for multivariate analysis.Results:The median disease free survival (DFS), median distant metastasis free survival (DMFS), and median overall survival (OS) of the 155 patients were 52.0 months, 66.6 months, and 102.2 months, respectively. The 5-year and 10-year DFS rates were 45.7% and 23.1%, the 5-year and 10-year DMFS rates were 56.9% and 28.9%, and the 5-year and 10-year OS rates were 79.3% and 46.0%, respectively. Multivariate Cox regression analysis showed that family tumor history ( HR=0.362, 95% CI: 0.140-0.937), clinical T stage (T3: HR=3.508, 95% CI: 1.380-8.918; T4: HR=2.220, 95% CI: 1.076-4.580), estrogen/progesterone receptor status ( HR=0.476, 95% CI: 0.261-0.866), number of tumor deposits ( HR=1.965, 95% CI:1.104-3.500) and neoadjuvant chemotherapy ( HR=1.961, 95% CI: 1.032-3.725) were independent influencing factors for DFS. Molecular subtype [human epidermal growth factor receptor-2(HER-2) positive and hormone receptor negative: HR=7.862, 95% CI: 3.189-19.379], number of tumor deposits ( HR=2.155, 95% CI: 1.103-4.212), neoadjuvant chemotherapy ( HR=5.002, 95% CI: 2.300-10.880) and radiotherapy ( HR=2.316, 95% CI: 1.005-5.341) were independent influencing factors of DMFS. Histological grade ( HR=4.362, 95% CI: 1.932-9.849), estrogen/progesterone receptor expression ( HR=0.399, 95% CI: 0.168-0.945), HER-2 expression ( HR=2.535, 95% CI: 1.114-5.768) and neoadjuvant chemotherapy ( HR=4.080, 95% CI: 1.679-9.913) were independent influencing factors of OS. Conclusions:The presence of tumor deposits weakens the influence of axillary lymph node status and distant metastases on the prognosis of breast cancer patients. Therefore, a clinicopathological staging system taking into account tumor deposits should be developed. Since the number of tumor deposits affects the risk of recurrence and metastasis of breast cancer patients, we recommend that the number of tumor deposits should be reported in detail in the pathological report after breast cancer surgery.

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