1.Clinical analysis of assisted reproductive technology assisted pregnancy outcome in female patients with thyroid cancer after surgery
Xiang YAO ; Wenjuan XU ; Jianye WANG ; Qun GAO ; Gang ZHAO ; Ping ZHOU
Acta Universitatis Medicinalis Anhui 2026;61(1):151-155
ObjectiveTo evaluate the pregnancy outcomes of assisted reproductive technology (ART) in women with a history of thyroid cancer who retained fertility intentions after completing cancer treatment. MethodsA retrospective analysis was performed on 61 patients with a history of thyroid cancer who underwent in vitro fertilization/intracytoplasmic sperm microinjection and embryo transfer (IVF/ICSI-ET). These patients were included as the case group. A total of 122 non-cancer patients who received ART during the same period were selected as the control group using 1∶2 matching based on age and oocyte retrieval time. Baseline characteristics, outcomes of the first ART cycle, and cumulative pregnancy outcomes were compared between the two groups. ResultsThere was no significant difference in the basic data, the total amount of gonadotropin (Gn) and the days of use between the case group and the control group (P>0.05). However, the case group had significantly fewer retrieved oocytes, mature oocytes (MII), lower fertilization and cleavage rates, and fewer transferable and high-quality embryos, as well as fewer embryos transferred during the first cycle (P < 0.05). However, there was no significant difference in the rate of first embryo implantation and first clinical pregnancy between the two groups (P>0.05). In the analysis of cumulative outcomes, the two groups did not show statistically significant differences in the cumulative pregnancy rate, clinical pregnancy rate per transfer cycle, the number of oocyte retrieval cycles required per live birth, the number of embryo transfer cycles required per live birth, and the number of embryos used for each live birth (P>0.05). However, the cumulative live birth rate was significantly lower in the case group compared to the control group (P=0.005). ConclusionAfter treatment for thyroid cancer, when ART is used to help pregnant women, the pregnancy outcome is comparable to that of women without tumors. Individualized reproductive management and timely fertility preservation strategies are recommended to optimize reproductive outcomes in this population.
2.Effect and Mechanism of Liangyi Paste on Hepatic Lipid Deposition in Naturally Aged Mice with High-fat Diet via Cuproptosis/Oxidative Stress Pathway
Meiling ZHANG ; Yuanguang DONG ; Xiaofei SUN ; Jiaxin WANG ; Yu LIU ; Jingxuan ZHU ; Qun WANG ; Nan SONG ; Guoyuan SUI ; Lianqun JIA
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(9):91-99
ObjectiveTaking the cuproptosis/oxidative stress pathway as the entry point, this study investigated the effect and mechanism of Liangyi Paste on hepatic lipid deposition in naturally aged mice fed with a high-fat diet. MethodsAfter adaptive feeding, 80 ten-week-old male C57BL/6 mice were used. Thirty of them were randomly divided into three groups (10 mice per group): The 12-month-old control group (12MCON), the 15-month-old control group (15MCON), and the 15-month-old group with a high-fat diet (15MHFD). The 12MCON and 15MCON groups were continuously fed a standard diet, while the 15MHFD group started receiving a high-fat diet at 12 months of age. Tissue samples were collected at the corresponding time points for each group. The remaining 50 mice were randomly divided into five groups (10 mice per group): the 20-month-old control group (20MCON), the model group, and the low-, medium-, and high-dose Liangyi Paste groups (2.91 , 5.82 , 11.64 g·kg-1·d-1, respectively). The 20MCON group was continuously fed a standard diet, while the other groups started receiving a high-fat diet at 15 months of age. At 18 months of age, the Liangyi Paste groups were administered the corresponding doses of Liangyi Paste by gavage, while the 20MCON and model groups were given an equal volume of saline by gavage. After 8 weeks of continuous gavage (when the mice reached 20 months of age), tissue samples were collected. Hepatic TG levels were measured using assay kits; liver histology and lipid deposition were observed via hematoxylin-eosin (HE) and oil red O staining; reactive oxygen species (ROS) were detected by enzyme-linked immunosorbent assay (ELISA); Cu2+, superoxide dismutase (SOD), and malondialdehyde (MDA) levels were measured by colorimetry; mRNA and protein expression of genes related to cuproptosis and oxidative stress pathways were analyzed by Real-time polymerase chain reaction(Real-time PCR) and Wes automated protein expression system. ResultsCompared with 12MCON, the 15MCON group showed significantly increased hepatic TG, Cu2+, ROS, and MDA levels (P<0.01), decreased SOD (P<0.01), hepatocyte swelling, and disordered arrangement. The mRNA and protein levels of ferredoxin 1 (FDX1), dihydrolipoamide S-acetyltransferase (DLAT), heat shock protein 70 (HSP70), dihydrolipoamide dehydrogenase (DLD), pyruvate dehydrogenase E1 subunit-β (PDHB), nuclear factor erythroid 2-related factor 2 (Nrf2), and peroxisome proliferator-activated receptor γ (PPARγ) were significantly elevated (P<0.05, P<0.01). Compared with 15MCON group, the 15MHFD and 20MCON groups exhibited further increases in TG, Cu2+, ROS, and MDA (P<0.01), reduced SOD (P<0.01), and aggravated hepatocyte swelling and disorder. There were increased lipid droplets with mild vacuolization in the 15MHFD group, and no significant lipid deposition was observed in the 20MCON group. FDX1, DLAT, HSP70, DLD, PDHB, Nrf2, and PPARγ mRNA and protein levels were significantly increased (P<0.05, P<0.01). Compared with 20MCON group, the model group demonstrated markedly elevated TG, Cu2+, ROS, and MDA (P<0.01), reduced SOD (P<0.01), severe hepatic steatosis, and upregulated expression of FDX1, DLAT, HSP70, DLD, PDHB, Nrf2, and PPARγ mRNA and proteins (P<0.05, P<0.01). All abnormalities were significantly reversed after Liangyi Paste treatment. ConclusionLiangyi paste can ameliorate hepatic lipid deposition in naturally aged mice with a high-fat diet by modulating the cuproptosis/oxidative stress pathway.
3.Nomogram based on multimodal MRI radiomics for discriminating molecular subtypes of HER-2-negative breast cancer
Qun WANG ; Hongli PAN ; Xiaohu LI ; Yongqiang YU ; Yunwen YAN ; Weishu HOU
Acta Universitatis Medicinalis Anhui 2026;61(4):715-723
ObjectiveTo explore the value of a multimodal MRI-based radiomics nomogram for differentiating human epidermal growth factor receptor-2 (HER-2) negative breast cancer molecular subtypes.MethodsA retrospective analysis was conducted on 190 patients with HER-2 negative breast cancer who underwent multimodal MRI examination, and the patients were divided into two molecular subtype groups: a HER-2 low expression group (n=108) and a HER-2 zero expression group (n=82). The cases were randomly stratified and sampled at a ratio of 7∶3 and divided into a training set of 133 cases and a testing set of 57 cases. The clinical and radiological features of the patients were collected, the radiomics features based on T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), and dynamic contrast-enhanced (DCE)-MRI were extracted, and the clinical-radiological model, unimodal radiomics model, multimodal radiomics model, and combined model were constructed respectively. Then the nomogram combined multimodal radiomics signature (radsocre) with clinical-radiological features was used to construct a visualized predictive model, and the area under the curve (AUC) was used to compare the effectiveness of different models in distinguishing HER-2 low expression and zero expression subtypes.ResultsA significant difference in radscore was demonstrated between the HER-2 low and HER-2 zero expression groups in both the training (P<0.000 1) and testing sets (P<0.01). The AUC of the multimodal radiomics model in the training set and the testing set were 0.914 and 0.836, respectively, which was superior to any unimodal radiomics model. The nomogram demonstrated great diagnostic efficacy (AUC=0.930 in training set; AUC=0.865 in testing set).ConclusionA multimodal MRI-based nomogram incorporating radsocre and clinical-radiological features can accurately distinguish the subtypes of HER-2 negative breast cancer.
4.Molecular Mechanism of Gypenoside L Inducing Ovarian Cancer Cell Apoptosis by Regulating NUF2 and Influencing Magnesium Homeostasis
Yang HONG ; Di ZHANG ; Yuanguang DONG ; Jiaxin WANG ; Lu PAN ; Lijiang ZHOU ; Mingdian YUAN ; Qun WANG ; Nan SONG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(13):155-165
ObjectiveThis paper aims to investigate the role of NDC80 kinetochore complex component (NUF2) and magnesium homeostasis in ovarian cancer cell apoptosis, as well as the regulatory mechanism of gypenoside L (Gyp-L) on NUF2 and magnesium homeostasis. MethodsOvarian cancer OVCAR3 cells were divided into a blank control group, a low-concentration Gyp-L group (50 µmol·L-1), a high-concentration Gyp-L group (100 µmol·L-1), and a cisplatin (15 µmol·L-1) group. The migration, proliferation, and apoptosis capabilities of OVCAR3 cells were evaluated through cell scratch assays, clonal experiments, and terminal-deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL) staining. Differentially expressed genes of ovarian cancer were screened by using the Gene Expression Omnibus (GEO) database. The interaction relationships of differentially expressed genes and proteins were analyzed via the Search Tool for Recurring Instances of Neighbouring Genes (STRING) database. The prognostic survival analysis was performed by using the Tumor Immune Estimation Resource (TIMER) database, and the differential expression levels of genes were validated with the Gene Expression Profiling Interactive Analysis (GEPIA) database. The mRNA expression levels of NUF2, magnesium homeostasis-related indicators, such as magnesium transporter 1 (MAGT1), non-imprinted in Prader-Willi/Angelman syndrome 1 (NIPA1), NIPA-like domain containing 1 (NIPAL1), as well as apoptosis-related indicators B cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax) in OVCAR3 cells, were detected by real-time quantitative polymerase chain reaction (Real-time PCR). The protein expression levels of NUF2, MAGT1, NIPA1, NIPAL1, Bcl-2, and Bax in OVCAR3 cells were quantitatively analyzed by ProteinSimple WES. A model of overexpression of NUF2 was constructed, and Gyp-L intervention was performed. The molecular mechanism by which Gyp-L induces ovarian cancer cell apoptosis by regulating NUF2 and influencing magnesium homeostasis was quantitatively analyzed and detected through cell cloning, TUNEL staining, Real-time PCR, and ProteinSimple WES. Finally, the Mg2+ content and protein synthesis efficiency were detected by immunofluorescence. ResultsGyp-L significantly inhibited the migration and proliferation capabilities of OVCAR3 cells and promoted their apoptosis (P<0.05). Overexpression of NUF2 markedly increased the expression levels of MAGT1, NIPA1, NIPAL1, and Bcl-2, while reducing the expression level of Bax (P<0.05). It also significantly elevated intracellular Mg2+ content and protein synthesis efficiency and simultaneously inhibited apoptosis (P<0.05). Gyp-L could reverse the magnesium homeostasis imbalance and apoptosis inhibition caused by the overexpression of NUF2, downregulating the expression levels of NUF2, MAGT1, NIPA1, NIPAL1, and Bcl-2 (P<0.05), while upregulating the expression level of Bax (P<0.05). ConclusionGyp-L can inhibit the occurrence of ovarian cancer, and its mechanism may involve inhibiting the expression of NUF2 to maintain magnesium homeostasis and inducing apoptosis of ovarian cancer cells.
5.Nomogram based on DCE-MRI radiomics combined with clinical-radiological features in predicting hormone receptor status in breast cancer with low Her-2 expression
Weishu Hou ; Hongli Pan ; Qun Wang ; Xiaohu Li ; Yunwen Yan ; Yongqiang Yu
Acta Universitatis Medicinalis Anhui 2025;60(9):1745-1754
Objective:
To explore the value of nomogram based on DCE-MRI radiomics combined with clinical-ra- diological features in predicting HR status in breast cancer with Her-2 low expression.
Methods:
A total of 198 pa- tients of Her-2 low expression breast cancer who underwent standardized breast MRI in our hospital from January 2019 to February 2025 were retrospectively analyzed.Patients were divided into HR ( + ) group ( n = 137) and HR ( -) group ( n = 61) .The cases were divided into a training set ( 138 cases) and a testing set ( 60 cases) in a 7 ∶ 3 ratio.Clinical-radiological model was based on clinical and traditional radiological features,radiomics model was based on DCE-MRI,and combined model was constructed,respectively.The nomogram was drawn,and re- ceiver operating characteristic curve was used to compare the performance of different models in predicting HR sta- tus.
Results:
The DCE-MRI radiomics score ( Radscore) between the HR ( + ) group and the HR ( -) group showed statistical differences in both the training and testing sets ( both P<0. 001) .The AUC of the clinical-radio- logical model based on lesion mobility,Ki67,TIC type,enhancement pattern and maximum diameter for predicting HR status in the training set and testing set were 0. 643 and 0. 616,respectively.The AUC of the DEC-MRI ra- diomics model in the training set and testing set were 0. 897 and 0. 860,respectively.The nomogram drawn by combining clinical-radiological features and Radscore showed better predictive performance in both the training set ( AUC = 0. 913) and testing set ( AUC = 0. 898) than the clinical-radiological model ( all P<0. 05) .
Conclusion
The nomogram combined by DCE-MRI radiomics and clinical-radiological features can effectively predict HR sta-tus of breast cancer with low Her-2 expression,which is helpful to the building of individualized treatment plan for breast cancer patients.
6.Trends in incidence and mortality of prostate cancer in Ningbo City from 2011 to 2023
ZHANG Qun ; WANG Yong ; CHEN Jieping ; BAO Kaifang ; FENG Yueyi ; Wang Xiaoli
Journal of Preventive Medicine 2025;37(1):46-50
Objective:
To analyze the trends in incidence and mortality of prostate cancer in Ningbo City, Zhejiang Province, so as to provide insights into the prevention and control of prostate cancer.
Methods:
Data of the incidence and mortality of prostate cancer in Ningbo City from 2011 to 2023 were collected through Ningbo Chronic Disease Collaborative Management System. The incidence and mortality of prostate cancer were calculated and standardized by the data from the sixth national population census in 2010 and the Segi's world standard population in 1960. The trends in incidence and mortality of prostate cancer were evaluated using average annual percent change (AAPC).
Results:
A total of 15 411 cases of prostate cancer were reported in Ningbo City from 2011 to 2023, and the crude incidence, Chinese-standardized incidence and world-standardized incidence were 39.62/105, 22.18/105 and 16.49/105, respectively, showing upward trends (AAPC=14.782%, 10.390% and 10.608%, all P<0.05). The Chinese-standardized incidence of prostate cancer was higher in urban areas than in rural areas, and both showed upward trends (25.14/105 vs. 19.44/105; AAPC=9.057% and 14.272%, both P<0.05). The crude incidence of prostate cancer in the groups aged 50-<60 years, 60-<70 years, 70-<80 years and ≥80 years showed upward trends (AAPC=11.657%, 14.031%, 10.734% and 5.300%, all P<0.05). A total of 3 739 deaths were reported, and the crude mortality, Chinese-standardized mortality and world-standardized mortality were 9.66/105, 5.23/105 and 3.71/105, respectively, showing upward trends (AAPC=8.458%, 3.620% and 3.602%, all P<0.05). The Chinese-standardized mortality of prostate cancer was higher in urban areas than in rural areas, and both showed upward trends (5.35/105 vs. 5.13/105; AAPC=3.183% and 3.962%, both P<0.05). The crude mortality of prostate cancer the groups ageds ≥80 years showed an upward trend (AAPC=7.482%, P<0.05).
Conclusions
From 2011 to 2023, the incidence and mortality of prostate cancer in Ningbo City showed upward trends. Special attention should be paid to urban residents, and prostate cancer screening should be strengthened among males aged 50 years and older.
7.Modified Ditan Tang Regulates Biorhythm-related Genes in Rat Model of Non-alcoholic Fatty Liver Disease
Zhiwen PANG ; Yu LIU ; Nan SONG ; Jie WANG ; Jingxuan ZHU ; Zhen HUA ; Yupeng PEI ; Qun WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(6):115-124
ObjectiveTo investigate the effects of modified Ditan tang on genes related to the transcription-translation feedback loop (TTFL) of biorhythm in the rat model of non-alcoholic fatty liver disease (NAFLD) and its mechanism for prevention and treatment of NAFLD. MethodsSixty-five healthy SPF male SD rats were randomly assigned into blank (n=20), model (n=15), and low-, medium-, and high-dose (2.68, 5.36, and 10.72 g·kg-1·d-1, respectively) modified Ditan tang (n=10) groups. Other groups except the blank group were fed a high-fat diet for 12 weeks. The modified Ditan tang groups were treated with the decoction at corresponding doses by gavage, and the blank and model groups were treated with an equal volume of normal saline from the 9th week for 4 weeks. The levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) in the serum were measured by an automatic biochemical analyzer. TG and non-esterified fatty acid (NEFA) assay kits were used to measure the levels of TG and NEFA in the liver. The pathological changes in the hypothalamus and liver were observed by hematoxylin-eosin staining, and the lipid deposition in the liver was observed by oil red O staining. The levels of brain-muscle ARNT-like protein 1 (BMAL1/ARNTL) in the hypothalamus and liver were determined by immunohistochemical staining. The mRNA and protein levels of BMAL1, circadian locomotor output cycles kaput (CLOCK), period circadian clock 2 (PER2), and cryptochrome1 (Cry1) in the hypothalamus and liver were determined by Real-time PCR and Western blot, respectively. ResultsCompared with the blank group, the model group showed elevated levels of TG, TC, LDL-C, AST, and ALT (P<0.01) and a lowered level of HDL-C (P<0.05) in the serum, elevated levels of TG and NEFA in the liver (P<0.01), pyknosis and deep staining of hypothalamic neuron cells, and a large number of vacuoles in the brain area. In addition, the model group showed lipid deposition in the liver, up-regulated mRNA and protein levels of CLOCK and BMAL1 (P<0.01), and down-regulated mRNA and protein levels of Cry1 and PER2 (P<0.01) in the hypothalamus and liver. Compared with the model group, all the three modified Ditan tang groups showed lowered levels of TG, TC, LDL-C, ALT, and AST (P<0.05, P<0.01) and an elevated level of HDL-C (P<0.05) in the serum, and lowered levels of TG and NEFA (P<0.05, P<0.01) in the liver. Furthermore, the three groups showed alleviated pyknosis and deep staining of hypothalamic neuron cells, reduced lipid deposition in the liver, down-regulated mRNA and protein levels of CLOCK and BMAL1 (P<0.05, P<0.01), and up-regulated mRNA and protein levels of Cry1 and PER2 (P<0.05, P<0.01) in the hypothalamus and liver. ConclusionModified Ditan tang can reduce lipid deposition in the liver and regulate the expression of CLOCK, BMAL1, Cry1, and PER2 in the TTFL of NAFLD rats.
8.Prevalence of latent tuberculosis infection among freshmen in middle schools and their willingness of preventive treatment in Yunyan District of Guiyang
PENG Xiaowei, ZHANG Jiangping, LUO Peng, CHEN Siyin, XU Mengqun, WANG Qun
Chinese Journal of School Health 2025;46(1):129-133
Objective:
To investigate the status of latent tuberculosis infection(LTBI)among freshmen in middle schools and their willingness of preventive treatment in Yunyan District of Guiyang, so as to provide a reference for the prevention and control of tuberculosis in schools.
Methods:
The tuberculin skin test (TST) and X-ray scans were used to screen the TB infection of 13 915 freshmen in middle schools in Yunyan District of Guiyang in 2023, and a questionnaire survey on the willingness of accepting tuberculosis preventive treatment was conducted to LTBI patients. The χ 2 test and Fisher exact probability was conducted for the comparison of the rates among the groups.
Results:
Among the freshmen screened, the detection rate of LTBI was 3.29%. There were statistically significant difference in LTBI rates among freshmen of different genders (boys:2.87%, girls:3.81%), age groups (12-15 years old:3.31%, 16-17 years old:3.92%, 18-20 years old:1.91%), and school stages (junior high school:3.52%, ordinary high school:5.96%, vocational high school:2.29%)( χ 2=9.59, 13.08, 54.30, P <0.01). A total of 356 LTBI freshmen completed questionnaire survey,and 299(83.99%) were willing to accept tuberculosis preventive treatment, but the actual number of LIBI freshman who underwent preventive treatment was zero. Those LTBI who had received Bacille Calmette Guérin(BCG) vaccine(86.97%) was higher in the reporting rates of being willing to accept preventive treatment than that of LTBI who had not received BCG vaccine( 75.79 %),the differences were statistically significant( χ 2=6.48, P <0.05). The main reasons for refusing preventive treatment was worry about adverse drug reactions(80.70%), social acceptance and the support of social institutions were needed most(85.96%).
Conclusions
The LTBI rate among freshmen in Yunyan District of GuiYang is higher. Although the freshmen with LTBI have a higher willingness to accept preventive treatment, however, no one has undergone preventive treatment. Corresponding measures need to be taken for improving the preventive treatment rate of LIBI freshmen.
9.Comprehensive Application of AHP-CRITIC Hybrid Weighting Method, Grey Correlation Analysis and BP-ANN in Optimization of Extraction Process of Qizhi Prescription
Qun LAN ; Yi CHENG ; Zian LI ; Bingyu WU ; Jinyu WANG ; Dewen LIU ; Yan TONG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(8):176-186
ObjectiveBased on analytic hierarchy process(AHP)-criteria importance through intercriteria correlation(CRITIC) hybrid weighting method, grey relational analysis and backpropagation artificial neural network(BP-ANN), to optimize the water extraction process of Qizhi prescription, so as to provide an experimental basis for optimization of the preparation process of this prescription and the establishment of quality standards. MethodsL9(34) orthogonal test was employed, and the AHP-CRITIC hybrid weighting method was utilized to determine the weight coefficients of the quality fractions of various components, including astragaloside Ⅳ, polygalaxanthone Ⅲ, calycosin-7-O-β-D-glucoside, tenuifolin, and 3,6′-disinapoylsucrose, as well as the dry extract yield. The comprehensive score of each factor level combination in the orthogonal test were calculated as evaluation indicator to select the optimal extraction process parameters. The effects of extraction times, extraction time, and solvent dosage on the aqueous extraction process of the formula were investigated through intuitive analysis, variance analysis, and grey relational analysis. Meanwhile, a BP-ANN model was established to reverse-predict the optimal extraction process parameters of Qizhi prescription, and the optimized process parameters were validated. ResultsThe weight coefficients of the five index components(astragaloside Ⅳ, tenuifolin, calycosin-7-O-β-D-glucoside, polygalaxanthone Ⅲ, and 3,6′-disinapoylsucrose) and dry extract yield were 25.7%, 20.82%, 16.41%, 12.45%, 15.96% and 8.67%, respectively. The optimized extraction process parameters were extracted 3 times with 8, 6, 6 times the amount of water, each time for 1 h. The network prediction results of BP-ANN test samples were consistent with the orthogonal test results, and the mean square error(MSE) of the predicted and measured values of the network was <1%. The water extraction process of Qizhi prescription analyzed and predicted by relevant mathematical models was stable and feasible, which could effectively improve the extraction efficiency of the active ingredients of Astragali Radix and Polygalae Radix, and the average comprehensive score of the validation test was 90.85 with the relative standard deviation(RSD) of 1.55%. ConclusionThis study establishes a water extraction process for compound Qizhi granules, and the optimized extraction process can effectively improve the extraction efficiency of active ingredients, which provides useful references for the optimization of preparation process and the establishment of quality standards for other clinical experience formulas.
10.Characterization and features of dampness-heat obstruction syndrome in rats with knee osteoarthritis based on "disease-syndrome-symptom" combination research strategy.
Li-Li WANG ; Teng-Teng XU ; Xiao-Xiao WANG ; Qun LI ; Li-Ting XU ; Wei-Heng CHEN ; Chun-Fang LIU ; Na LIN
China Journal of Chinese Materia Medica 2025;50(7):1861-1871
A combination of the "disease-syndrome-symptom" approach was used to study the syndrome characterization and features of dampness-heat obstruction syndrome in papain-induced knee osteoarthritis(KOA) model rats during the disease process. Forty-eight male SD rats were randomly divided into sham and model groups. The KOA model was established by injecting a mixture of papain and L-cysteine into the joint cavity on days 1, 3, and 5. During the 8 weeks following model establishment, the rats were assessed weekly for the plantar mechanical pain threshold, knee joint diameter, local skin temperature of the knee joint, weight-bearing difference between the two hind feet, and the modified Lequesne MG score of the knee joint. Samples were collected at 1, 2, 4, 6, and 8 weeks after model establishment to observe the gross lesions in cartilage and synovium. Histopathological changes in joint tissues were examined using hematoxylin-eosin, Masson's trichrome, and Senna red O-solid green staining. ELISA and immunohistochemical analysis were performed to detect the levels of interleukin(IL)-1β, IL-6, tumor necrosis factor(TNF)-α, prostaglandin E2(PGE2), and the expression of aquaporins(AQP) 1 and 3 in serum and synovium. The results showed that the ink score of articular cartilage in the model group significantly increased from 4 to 8 weeks, the cartilage Mankin's score and the percentage of Masson-positive area in cartilage increased significantly from 1 to 8 weeks. The percentage of red-stained area for cartilage proteoglycans decreased significantly from 1 to 8 weeks. The synovitis score from 1 to 6 weeks and the percentage of blue-stained collagen fibers in the synovium from 1 to 8 weeks increased significantly, with statistically significant differences compared to the sham group. The mechanical pain threshold in the model group significantly decreased from 1 to 8 weeks, the knee joint diameter significantly increased from 1 to 6 weeks, and the local skin temperature of the knee joint, the weight-bearing difference between the two hind feet, and the modified Lequesne MG score from 1 to 5 weeks significantly increased, all with statistically significant differences compared to the sham group. The levels of IL-1β, IL-6, TNF-α, and PGE2 in serum and synovium of the model group significantly increased from 1 to 6 weeks. Serum TNF-α and PGE2, and synovial IL-1β, also significantly increased at 8 weeks. The levels of cartilage AQP1 and AQP3 significantly increased from 1 to 4 weeks, while synovial AQP1 and AQP3 increased significantly from 1 to 6 weeks, with all differences statistically significant compared to the sham group. In conclusion, papain-induced KOA rats exhibited pathological changes, including articular cartilage degeneration and synovial inflammation, within 1 week of induction. The KOA rats showed characteristics of dampness-heat obstruction syndrome, such as joint pain, swelling, elevated skin temperature, and decreased function, as well as increased inflammatory factors and AQP1、AQP3 in serum and joint tissues within 5 to 6 weeks of disease onset. These results provide an experimental model for studying the syndromes of KOA with dampness-heat obstruction syndrome.
Animals
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Male
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Rats, Sprague-Dawley
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Rats
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Osteoarthritis, Knee/physiopathology*
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Disease Models, Animal
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Humans
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Interleukin-1beta/metabolism*
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Interleukin-6/metabolism*
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Tumor Necrosis Factor-alpha/metabolism*
;
Knee Joint/pathology*


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