1. A new strategy for evaluating antitumor activity in vitro with time-dimensional characteristics of RTCA technology
Fang-Tong LIU ; Shu-Yan XING ; Jia YANG ; Guo-Ying ZHANG ; Rong RONG ; Xiao-Yun LIU ; Dong-Xue YE ; Yong YANG ; Xiao-Yun LIU ; Dong-Xue YE ; Rong RONG ; Yong YANG ; Xiao-Yun LIU ; Dong-Xue YE ; Yong YANG ; Xiao-Yun LIU ; Dong-Xue YE ; Yong YANG
Chinese Pharmacological Bulletin 2024;40(3):592-598
Aim To analyze the anti-A549 and HI299 lung ade-nocarcinoma activities via using examples of baicalin, astragalo-side, hesperidin and cisplatin based on real time cellular analysis (RTCA) technology, and to build a new strategy for EC50 e-valuation reflecting the time-dimensional characteristic. Methods Using RTCA Software Pro for data analysis and GraphPad Prism and Origin Pro plotting, the in vitro anti-A549 and H1299 lung adenocarcinoma activities of baicalin, astragaloside, hesperidin, and cisplatin were characterized using the endpoint method and time dimension, respectively. Results (X) There were significant differences in EC50 values of A549 and H1299 cells at 24 h and 48 h endpoint methods. (2) The correlation coefficient of the curve fitted with the four-parameter equation was > 0. 9, and the dynamic change of EC50 remained relatively stable (the linear fitting of EC50 at adjacent 4 points I slope 1^1) used to calculate the EC50 value within this time dimension. The EC50 of baicalin, astragaloside, hesperidin and cisplatin on A549 cells was 52. 97 ±1.75 плпо! • L~1(16~48 h) , 62.88 ± 2.91 ijunol • L"1 (32.25 -48 h) , 78.84 ±0.33 плпо1 • L"1 (21.5 -29.75 h), 13.57 ±1.54 плпо1 • L_1(27.5 -48 h), respectively; the EC50 of baicalin, astragaloside, hesperidin and cisplatin on H1299 cells was 43. 71 ± 1. 26 |лто1 • L_1 ( 19. 5 -48 h), 47.23 ±1. 19 |лто1 • L_1(14 -48 h) , 39.45 ±0.24 плпо1 • L"1 (12.75 -46.25 h), 25.97 ±4.76 плпо1 • L"1 (10. 25 -48 h) , respectively. The results showed that the time window for the anti-tumor effect of the test solution/drug was different. Conclusions Based on RTCA technology, it is more accurate and reasonable to select EC50 data that exhibit better fitting, stable changes, and time-dimensional characteristics for the evaluation of anti-tumor activity. In addition, this method of distinguishing different effective time of antitumor drugs can provide a reference for the timing of clinical combination drugs, and this approach will also provide a reference for further related studies.
2.Study on long-term toxicity of Tripterygium glycosides tablets based on type Ⅱ collagen-induced arthritis model rats
Tian-Xiang YE ; Ming-Zhu SHI ; Wei-Dong YANG ; Yan-Ming WEI ; Hui-Fang LI ; Sheng-Hui CHENG
The Chinese Journal of Clinical Pharmacology 2024;40(9):1296-1300
Objective To observe the multi-system toxicity of Tripterygium glycosides tablets in rats with type Ⅱ collagen-induced arthritis(CIA).Methods Healthy SD rats were randomly divided into normal group,model group and experimental group,with 10 rats in each group.In addition to the normal group,the other groups were established collagen-induced arthritis model.After the first immunization,the normal group and the model group were given an equal volume of 0.3%sodium carboxymethyl cellulose solution,and the experimental group was given 72 mg·kg-1·d-1 Tripterygium glycosides solution,once a day for 6 weeks.On the 42 nd day,the blood routine of each group was detected and the organ index was calculated.The levels of liver,kidney function and sex hormones in rats were detected by enzyme-linked immunosorbent assay.The histopathological changes of liver,kidney,ovary and testis were observed by hematoxylin-eosin(HE)staining.Results The testicular indexes of the normal group,the model group and the experimental group were(0.81±0.05)%,(0.97±0.06)%and(0.81±0.12)%;the estradiol contents were(63.90±16.19),(55.42±7.23)and(40.04±5.97)pg·mL-1;the testosterone contents were(1 290.96±257.94),(1 198.43±190.77)and(912.62±61.72)pg·mL-1,respectively.There were statistically significant differences in the above indexes between the model group and the experimental group(P<0.01,P<0.05).HE pathological results showed that Tripterygium glycosides tablets could cause abnormal histopathological changes of ovary and testis in CIA model rats.Conclusion Continuous administration of 8-fold clinical equivalent dose of Tripterygium glycosides tablets for 6 weeks can cause damage to the reproductive system of CIA rats.
3.Expert consensus on surgical treatment of oropharyngeal cancer
China Anti-Cancer Association Head and Neck Oncology Committee ; China Anti-Cancer Association Holistic Integrative Oral Cancer on Preventing and Screen-ing Committee ; Min RUAN ; Nannan HAN ; Changming AN ; Chao CHEN ; Chuanjun CHEN ; Minjun DONG ; Wei HAN ; Jinsong HOU ; Jun HOU ; Zhiquan HUANG ; Chao LI ; Siyi LI ; Bing LIU ; Fayu LIU ; Xiaozhi LV ; Zheng-Hua LV ; Guoxin REN ; Xiaofeng SHAN ; Zhengjun SHANG ; Shuyang SUN ; Tong JI ; Chuanzheng SUN ; Guowen SUN ; Hao TIAN ; Yuanyin WANG ; Yueping WANG ; Shuxin WEN ; Wei WU ; Jinhai YE ; Di YU ; Chunye ZHANG ; Kai ZHANG ; Ming ZHANG ; Sheng ZHANG ; Jiawei ZHENG ; Xuan ZHOU ; Yu ZHOU ; Guopei ZHU ; Ling ZHU ; Susheng MIAO ; Yue HE ; Jugao FANG ; Chenping ZHANG ; Zhiyuan ZHANG
Journal of Prevention and Treatment for Stomatological Diseases 2024;32(11):821-833
With the increasing proportion of human papilloma virus(HPV)infection in the pathogenic factors of oro-pharyngeal cancer,a series of changes have occurred in the surgical treatment.While the treatment mode has been im-proved,there are still many problems,including the inconsistency between diagnosis and treatment modes,the lack of popularization of reconstruction technology,the imperfect post-treatment rehabilitation system,and the lack of effective preventive measures.Especially in terms of treatment mode for early oropharyngeal cancer,there is no unified conclu-sion whether it is surgery alone or radiotherapy alone,and whether robotic minimally invasive surgery has better func-tional protection than radiotherapy.For advanced oropharyngeal cancer,there is greater controversy over the treatment mode.It is still unclear whether to adopt a non-surgical treatment mode of synchronous chemoradiotherapy or induction chemotherapy combined with synchronous chemoradiotherapy,or a treatment mode of surgery combined with postopera-tive chemoradiotherapy.In order to standardize the surgical treatment of oropharyngeal cancer in China and clarify the indications for surgical treatment of oropharyngeal cancer,this expert consensus,based on the characteristics and treat-ment status of oropharyngeal cancer in China and combined with the international latest theories and practices,forms consensus opinions in multiple aspects of preoperative evaluation,surgical indication determination,primary tumor re-section,neck lymph node dissection,postoperative defect repair,postoperative complication management prognosis and follow-up of oropharyngeal cancer patients.The key points include:① Before the treatment of oropharyngeal cancer,the expression of P16 protein should be detected to clarify HPV status;② Perform enhanced magnetic resonance imaging of the maxillofacial region before surgery to evaluate the invasion of oropharyngeal cancer and guide precise surgical resec-tion of oropharyngeal cancer.Evaluating mouth opening and airway status is crucial for surgical approach decisions and postoperative risk prediction;③ For oropharyngeal cancer patients who have to undergo major surgery and cannot eat for one to two months,it is recommended to undergo percutaneous endoscopic gastrostomy before surgery to effectively improve their nutritional intake during treatment;④ Early-stage oropharyngeal cancer patients may opt for either sur-gery alone or radiation therapy alone.For intermediate and advanced stages,HPV-related oropharyngeal cancer general-ly prioritizes radiation therapy,with concurrent chemotherapy considered based on tumor staging.Surgical treatment is recommended as the first choice for HPV unrelated oropharyngeal squamous cell carcinoma(including primary and re-current)and recurrent HPV related oropharyngeal squamous cell carcinoma after radiotherapy and chemotherapy;⑤ For primary exogenous T1-2 oropharyngeal cancer,direct surgery through the oral approach or da Vinci robotic sur-gery is preferred.For T3-4 patients with advanced oropharyngeal cancer,it is recommended to use temporary mandibu-lectomy approach and lateral pharyngotomy approach for surgery as appropriate;⑥ For cT1-2N0 oropharyngeal cancer patients with tumor invasion depth>3 mm and cT3-4N0 HPV unrelated oropharyngeal cancer patients,selective neck dissection of levels ⅠB to Ⅳ is recommended.For cN+HPV unrelated oropharyngeal cancer patients,therapeutic neck dissection in regions Ⅰ-Ⅴ is advised;⑦ If PET-CT scan at 12 or more weeks after completion of radiation shows intense FDG uptake in any node,or imaging suggests continuous enlargement of lymph nodes,the patient should undergo neck dissection;⑧ For patients with suspected extracapsular invasion preoperatively,lymph node dissection should include removal of surrounding muscle and adipose connective tissue;⑨ The reconstruction of oropharyngeal cancer defects should follow the principle of reconstruction steps,with priority given to adjacent flaps,followed by distal pedicled flaps,and finally free flaps.The anterolateral thigh flap with abundant tissue can be used as the preferred flap for large-scale postoperative defects.
4.MoS2 nanozyme attenuated inflammation-related endothelial cell injury by regulating mitochondrial dynamics and mitophagy
Dong-mei PAN ; Sun-kui KE ; Qian-hao YIN ; Pei-yan YANG ; Chao LI ; She-fang YE
Acta Pharmaceutica Sinica 2024;59(10):2791-2799
To explore the protective mechanisms of a novel molybdenum disulfide (MoS2) nanozyme in alleviating inflammation-related endothelial cell injury by regulating mitochondrial dynamic, flower like-MoS2 nanosheets were prepared by hydrothermal method, and its antioxidant enzyme-mimic activities were assessed
5.Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults (version 2024)
Qingde WANG ; Yuan HE ; Bohua CHEN ; Tongwei CHU ; Jinpeng DU ; Jian DONG ; Haoyu FENG ; Shunwu FAN ; Shiqing FENG ; Yanzheng GAO ; Zhong GUAN ; Hua GUO ; Yong HAI ; Lijun HE ; Dianming JIANG ; Jianyuan JIANG ; Bin LIN ; Bin LIU ; Baoge LIU ; Chunde LI ; Fang LI ; Feng LI ; Guohua LYU ; Li LI ; Qi LIAO ; Weishi LI ; Xiaoguang LIU ; Hongjian LIU ; Yong LIU ; Zhongjun LIU ; Shibao LU ; Yong QIU ; Limin RONG ; Yong SHEN ; Huiyong SHEN ; Jun SHU ; Yueming SONG ; Tiansheng SUN ; Yan WANG ; Zhe WANG ; Zheng WANG ; Hong XIA ; Guoyong YIN ; Jinglong YAN ; Wen YUAN ; Zhaoming YE ; Jie ZHAO ; Jianguo ZHANG ; Yue ZHU ; Yingjie ZHOU ; Zhongmin ZHANG ; Wei MEI ; Dingjun HAO ; Baorong HE
Chinese Journal of Trauma 2024;40(2):97-106
Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.
6.Performance of 99Tc m-PYP scintigraphy in differentiation of transthyretin-related cardiac amyloidosis and hypertrophic cardiomyopathy
Honghui GUO ; Xinlu ZHANG ; Xin XIANG ; Rongchen AN ; Zhihui FANG ; Qianchun YE ; Chuning DONG ; Xuan YIN ; Xiaowei MA ; Yunhua WANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2024;44(11):668-672
Objective:To investigate the efficacy of 99Tc m-pyrophosphate (PYP) SPECT imaging for the differential diagnosis of transthyretin-related cardiac amyloidosis (ATTR-CA) and hypertrophic cardiomyopathy (HCM). Methods:Data of patients who were definitively diagnosed with ATTR-CA (35 patients (28 males, 7 females); age 62.5(58.6, 64.3) years) or HCM (14 patients (13 males, 1 female); age 60.5(57.3, 68.7) years) by extracardiac biopsy and echocardiography in the Second Xiangya Hospital of Central South University between June 2020 and March 2023 were retrospectively analyzed. All patients underwent planar and SPECT imaging 1 h after injection of 370-720 MBq 99Tc m-PYP. Visual scoring was performed (0-1 was negative, 2-3 was positive), and heart-to-contralateral lung uptake ratio (H/CL) was calculated based on planar images. The χ2 test was used to compare the difference in visual scores between ATTR-CA and HCM groups, and the diagnostic efficacy of the visual score was calculated. The H/CL differences between ATTR and HCM groups were compared with Mann-Whitney U test, and the ROC curve was used to analyze the efficacy of H/CL for the differential diagnosis of ATTR-CA and HCM. Results:There were 34 patients with visual scores≥2 and 1 patient with visual score<2 in the ATTR-CA group, 6 patients with visual scores =2 and 8 patients with visual scores <2 in HCM group, and there were significant differences between the 2 groups ( χ2=16.20, P<0.001). The diagnostic sensitivity of the visual score was 97.1%(34/35), and the specificity was 8/14. The H/CL in the ATTR-CA group was significantly higher than that in the HCM group (2.08(1.97, 2.20) vs 1.26 (1.17, 1.35), z=-5.09, P<0.001). The ROC curve analysis suggested that the optimal cut-off value was 1.45 (AUC: 0.980, 95% CI: 0.946-1.000; P<0.001); the sensitivity of H/CL differential diagnosis between HCM and ATTR-CA was 97.1%(34/35), and the specificity was 14/14. Conclusion:99Tc m-PYP SPECT imaging is useful in differentiation of ATTR-CA and HCM, and the optimal cut-off value of H/CL for differential diagnosis of these 2 diseases is 1.45.
7.Time trend analysis of ischemic stroke mortality in Tengzhou City of Shandong Province from 2013 to 2021
Fang DONG ; Xinggui HAN ; Yuluan XU ; Hongyu ZHU ; Shujun YE ; Lin LIN ; Fuzhong SI ; Li CHENG
Chinese Journal of Cerebrovascular Diseases 2024;21(9):603-615
Objective Analyze the temporal trend of ischemic stroke(IS)mortality among the residents of Tengzhou City of Shandong Province during the period of hypertension control from 2013 to 2021.Methods On January 1,2013,Tengzhou City,Shandong Province,began its hypertension control program.The IS mortality rate was calculated using the mortality data from January 1,2013 to December 31,2021,and analyzed for its time trend among residents with different characteristics.The registered population was derived from the Public Security Bureau of Tengzhou City,Shandong Province,and the age and sex standardized mortality rate was calculated using the data of China's 7th population census in 2020.The Chi-square test was used to compare the differences in mortality rate,and Cochran-Armitage trend test was used to compare the time trend and age trend of mortality rate.Results The overall crude and standardized mortality rates of IS in Tengzhou showed a temporal trend from 2013 to 2021(Z values were 12.647,7.305,respectively;all P<0.001),and decreased by 23.77%and 30.99%(Z values were-7.393,-9.975,respectively;all P<0.001)respectively in 2021 compared with 2019.The crude mortality rate of IS in male increased by 13.27%in 2019 compared with 2017,while the crude and standardized mortality rate in female decreased by 16.39%and 19.49%in 2018 compared with 2017,respectively,with statistical significance(x2 values were 7.160,9.789,and 15.109,respectively;all P<0.05).Except the crude mortality rates in 2013 and 2015,the crude mortality rates and standardized mortality rates for males in other years were all higher than those for females,with statistically significant differences(x2 values:25.816-124.040,all P<0.001).The crude mortality rate for IS increased with age in all years(Z values:42.604-61.025,all P<0.001).The proportion of IS deaths among those aged≥65 was 85.85%.The overall crude mortality rates of the age group of male 45-54 years old showed a temporal trend from 2013 to 2021(Z=3.035,P<0.01),while females in the same age group did not show a temporal trend(P>0.05).The IS mortality rate in urban areas decreased from 62.61 per 100 000 in 2013 to 54.00 per 100 000 in 2021(Z=-2.097,P<0.05).The rural areas increased by 213.15%in 2019 compared with 2013 and decreased by 22.75%in 2021 compared with 2019(Z values were 19.074,-6.390,respectively;all P<0.001).Conclusions The IS mortality rate in Tengzhou City showed a decreasing trend in urban areas from 2013 to 2021,and a decreasing trend in rural areas after 2019.Compared to females,there is a trend of younger mortality among males in the age range of 45-54.Males and rural IS patients should be given special attention.
8.Mechanism of inflammatory microecological response to TAS2R14/SIgA/TSLP in regulating epithelial cell barrier in cold asthma rats through lung-gut axis by using Shegan Mahuang Decoction and bitter and purging Chinese herbs.
Ya-Mei YUAN ; Wei-Dong YE ; Yue CHENG ; Qiu-Hui LI ; Jia-Xin LIU ; Jia-le QIAO ; Kun WANG ; Xiang-Ming FANG
China Journal of Chinese Materia Medica 2024;49(24):6713-6723
This study aimed to investigate the mechanism by which Shegan Mahuang Decoction(SGMH) and its bitter Chinese herbs(BCHs) regulated the lung-gut axis through the bitter taste receptor 14(TAS2R14)/secretory immunoglobulin A(SIgA)/thymic stromal lymphopoietin(TSLP) to intervene in the epithelial cell barrier of cold asthma rats. Fifty SD rats were randomly divided into the following five groups: normal group, model group, dexamethasone group, SGMH group, and BCHs group. A 10% ovalbumin(OVA) solution was used to sensitize the rats via subcutaneous injection on both sides of the abdomen and groin, combined with 2% OVA atomization and cold(2-4 ℃) stimulation to induce a cold asthma model in rats. The SGMH, BCHs, and dexamethasone groups were given corresponding treatments by gavage and nebulization, while the normal and model groups received normal saline by gavage and nebulization. After the final stimulation, pathological changes in the lung and intestine tissues were observed using hematoxylin-eosin(HE) and periodic acid-Schiff(PAS) staining. Lung function was assessed by measuring the ratio of forced expiratory volume in the first second to forced vital capacity(FEV1/FVC), the ratio of the average flow rate at 25%-75% of forced vital capacity to foned vital capacity(FEV25%-75%/FVC), the peak expiratory flow(PEF), and pulmonary resistance(RL). The levels of IL-4, IL-5, IL-13, and TNF-α in serum, and sIgA in serum, intestinal, and bronchial mucosa were detected by enzyme-linked immunosorbent assay(ELISA). The expression of TAS2R14 protein in lung tissue was detected by Western blot(WB). The content of short-chain fatty acids(SCFAs) in rat feces was determined by gas chromatography-mass spectrometry(GC-MS). The effect of TAS2R14/TSLP on lipopolysaccharide(LPS)-induced inflammation in epithelial cells in the BCHs group was observed, and the expression of TAS2R14 and TSLP in cells was detected by WB. Compared with the normal group, the model group showed reduced water intake, diet, and body weight, increased infiltration of inflammatory cells in the lung and intestinal tissues, goblet cell hyperplasia, significantly decreased FEV1/FVC, FEV25%-75%/FVC, and PEF, and significantly increased RL. Moreover, serum levels of IL-4, IL-5, IL-13, and TNF-α were elevated, and sIgA levels in serum, intestine, and bronchial mucosa were significantly decreased. TAS2R14 expression in lung tissues was inhibited, and the content of acetic acid, propionic acid, and butyric acid in feces was significantly reduced. In the LPS group, TSLP expression increased, and TAS2R14 expression decreased. Compared with the model group, the general condition of rats in the SGMH and BCHs groups improved, with reduced infiltration of inflammatory cells and goblet cell hyperplasia in the lung and intestinal tissues. FEV1/FVC, FEV25%-75%/FVC, and PEF significantly increased, and RL significantly decreased. Serum levels of IL-4, IL-5, IL-13, and TNF-α decreased, while sIgA levels in serum, intestine, and bronchial mucosa significantly increased, and TAS2R14 expression was activated in lung and intestinal tissues. The content of acetic acid, propionic acid, and butyric acid in feces significantly increased. Compared with the model group, the BCHs group and the agonist group showed inhibited TSLP expression and increased TAS2R14 expression. The results showed that both SGMH and BCHs could reduce lung and intestinal inflammatory reactions, improve lung function, and regulate the content of intestinal SCFAs in asthmatic rats. There was no significant difference in TAS2R14 protein expression between the SGMH and BCHs groups, indicating that the clinical efficacy of BCHs may be related to the activation of the bitter receptor TAS2R14 and the regulation of immune inflammatory mediators in lung and intestinal epithelial cells.
Animals
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Drugs, Chinese Herbal/administration & dosage*
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Rats
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Rats, Sprague-Dawley
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Lung/metabolism*
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Asthma/metabolism*
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Cytokines/immunology*
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Male
;
Receptors, G-Protein-Coupled/immunology*
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Epithelial Cells/metabolism*
;
Thymic Stromal Lymphopoietin
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Immunoglobulin A, Secretory/genetics*
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Humans
;
Cold Temperature
9.Multiparametric ultrasound for the assessment of testicular lesions with negative tumoral markers.
Hui LIU ; Lin DONG ; Li-Hua XIANG ; Guang XU ; Jing WAN ; Yan FANG ; Shi-Si DING ; Ye JIN ; Li-Ping SUN ; Hui-Xiong XU
Asian Journal of Andrology 2023;25(1):50-57
The purpose of this study was to evaluate the diagnostic performance of multiparametric ultrasound (mpUS; grayscale US, color Doppler US, strain elastography, and contrast-enhanced US) in the assessment of testicular lesions with negative tumoral markers. MpUS imaging data, patient age, serum tumor markers, scrotal pain, cryptorchidism, and related clinical information were retrospectively collected for patients who underwent mpUS examination between January 2013 and December 2019. Histologic results or follow-up examinations were used as the reference standard. In total, 83 lesions from 79 patients were included in the analysis. Fifty-six patients were finally diagnosed with benign tumors, and 23 patients were ultimately diagnosed with malignant tumors. Chi-square tests or Fisher's exact tests were used to assess the difference between the two groups. Stepwise multivariate logistic regression analysis showed that lesion diameter (odds ratio [OR] = 1.072, P = 0.005), vascularization on color Doppler US (OR = 4.066, P = 0.001), and hyperenhancement during the early phase (OR = 6.465, P = 0.047) were significant independent risk factors for malignancy; however, when compared with neoplastic lesions, pain (OR = 0.136, P < 0.001), absence of vascularization on color Doppler US (OR = 1.680, P = 0.042), and nonenhancement during the late phase (OR = 3.461, P = 0.031) were strongly associated with nonneoplastic lesions. MpUS features are useful for differentiating testicular lesions with negative tumoral markers and improving the preoperative diagnosis, which may avoid inappropriate radical orchiectomy.
Male
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Humans
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Testicular Neoplasms/pathology*
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Biomarkers, Tumor
;
Retrospective Studies
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Contrast Media
;
Ultrasonography/methods*
10.Improvement effect of Shegan Mahuang Decoction on rats with cold-induced asthma based on TRPV1/NRF-1/mtTFA pathway.
Qiu-Hui LI ; Xiao-Xiao SHAN ; Xiao-Ying LIU ; Wei-Dong YE ; Ya-Mei YUAN ; Xun-Yan YIN ; Xiang-Ming FANG
China Journal of Chinese Materia Medica 2023;48(23):6414-6422
This study investigated the therapeutic effect of Shegan Mahuang Decoction(SGMHD) on cold-induced asthma in rats and explored its underlying mechanism. Seventy-two healthy male SD rats of specific pathogen free(SPF) grade were randomly divided into a blank group, a model group, a positive control group(dexamethasone, 0.4 mg·kg~(-1)), and low-, medium-, and high-dose SGMHD groups(3.2, 6.4, and 12.8 g·kg~(-1)). The blank group received saline, while the other groups were sensitized by intraperitoneal injection of ovalbumin(OVA) solution. Subsequently, the rats were placed in a cold chamber adjustable to 0-2 ℃, and OVA solution was ultrasonically nebulized to induce cold-induced asthma in rats. After three weeks of treatment, the general behaviors of rats were observed. Hematoxylin-eosin(HE) staining was used to evaluate pathological changes in lung tissues, periodic acid-Schiff(PAS) staining assessed mucin changes, and Masson staining was performed to examine collagen deposition. Enzyme-linked immunosorbent assay(ELISA) was used to measure the levels of the inflammatory factors interleukin-4(IL-4) and vascular endothelial growth factor(VEGF) in serum and bronchoalveolar lavage fluid(BALF). Real-time quantitative polymerase chain reaction(RT-PCR) was employed to assess the mRNA expression levels of transient receptor potential vanilloid subfamily member 1(TRPV1), nuclear respiratory factor 1(NRF-1), and mitochondrial transcription factor A(mtTFA) in lung tissues. Western blot was used to measure the protein expression levels of TRPV1, NRF-1, and mtTFA in lung tissues. Compared with the blank group, the model group exhibited signs of rapid respiration, increased frequency of defecation with looser stools, and disheveled and dull fur. Pathological results showed significant infiltration of inflammatory cells in lung tissues, narrowing of bronchial lumens, increased mucin secretion, and enhanced collagen deposition in the model group. Additionally, the levels of IL-4 and VEGF in serum and BALF were significantly elevated, and the mRNA and protein expression levels of TRPV1, NRF-1, and mtTFA in lung tissues were significantly increased. Compared with the model group, SGMHD improved the behaviors of rats, alleviated pathological changes in lung tissues, mucin production, and collagen deposition, significantly decreased the levels of IL-4 and VEGF in serum and BALF, and reduced the mRNA expression levels of TRPV1, NRF-1, and mtTFA in lung tissues, with the medium-dose SGMHD group showing the most significant effect. Moreover, the protein expression levels of TRPV1, NRF-1, and mtTFA in lung tissues were also reduced, with the medium-dose SGMHD group exhibiting the most significant effect. In conclusion, this study demonstrates that SGMHD can alleviate airway inflammation and inhibit airway remodeling in cold-induced asthma rats. These effects may be associated with the modulation of the TRPV1/NRF-1/mtTFA signaling pathway.
Rats
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Male
;
Animals
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Mice
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Interleukin-4/metabolism*
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Vascular Endothelial Growth Factor A/metabolism*
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Rats, Sprague-Dawley
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Asthma/genetics*
;
Lung
;
Bronchoalveolar Lavage Fluid
;
RNA, Messenger/metabolism*
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Collagen/metabolism*
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Mucins/therapeutic use*
;
Ovalbumin
;
Disease Models, Animal
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Mice, Inbred BALB C
;
TRPV Cation Channels/metabolism*
;
Drugs, Chinese Herbal


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