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.Imaging features of severe unilateral transverse sinus and sigmoid sinus thromboses and efficacy and safety of intravascular interventional therapy in them
Tengfei LI ; Qi TIAN ; Shuailong SHI ; Jie YANG ; Ye WANG ; Zhen CHEN ; Yuncai RAN ; Baohong WEN ; Dong GUO ; Shaofeng SHUI ; Xinwei HAN ; Xiao LI ; Ji MA
Chinese Journal of Neuromedicine 2024;23(1):42-47
Objective:To summarize the imaging features of severe unilateral transverse sinus and sigmoid sinus thromboses, and evaluate the efficacy and safety of intravascular interventional therapy in them.Methods:Thirty-seven patients with severe unilateral transverse sinus and sigmoid sinus thromboses clinically mainly manifested as intracranial hypertension and accepted endovascular intervention in Department of Interventional Radiology, First Affiliated Hospital of Zhengzhou University from June 2012 to September 2022 were chosen; their clinical data were retrospectively analyzed and imaging features were summarized. Short-term efficacy was evaluated according to blood flow restoration degrees and pressure gradient reduction in the occlusive sinus and modified neurological symptoms before and after endovascular intervention. Hospitalized complications were observed; safety and long-term efficacy were evaluated according to postoperative clinical follow-up and imaging results 6-12 months after endovascular intervention.Results:(1) Preoperative brain MRI and (or) CT showed different degrees of swelling of the brain tissues, with the affected side as the target; mixed signals/density shadow could be seen in the blocked transverse sinus and sigmoid sinus; venous cerebral infarction or post-infarction cerebral hemorrhage could be combined in some patients. MRV, CTV and DSA showed poor or completely occluded transverse sinus and sigmoid sinus while normal in the contralateral side; obvious thrombus filling-defect was observed in the occluded venous sinus after mechanical thrombolysis. (2) Occlusive sinus blood flow was restored in all patients after endovascular intervention, and pressure gradient of the occlusive segment decreased from (16.6±3.3) mmHg before to (2.8±0.8) mmHg after endovascular intervention. Before discharge, clinical symptoms of all patients were significantly improved (modified Rankin scale [mRS] scores of 0 in 30 patients, 1 in 5 patients, 2 in 1 patient and 3 in 1 patient), and 2 patients had unilateral limb movement disorder (muscle strength grading III and IV, respectively). All patients received clinical follow-up for (9.6±3.0) months. At the last follow-up, neurological function obviously improved compared with that before endovascular intervention, without new neurosystem-related symptoms (mRS scores of 0 in 30 patients, 1 in 6, and 2 in 1 patient). In 34 patients received MRV or DSA follow-up, 28 had complete recanalization of occlusive sinus and 6 had partial recanalization, without obvious stenosis or recurrent occlusion.Conclusions:Severe unilateral transverse sinus and sigmoid sinus thrombosis can cause local intracranial venous blood stasis, and then cause "increased regional venous sinus pressure", which is manifested as unilateral brain tissue swelling and even venous cerebral infarction or post-infarction cerebral hemorrhage. Early diagnosis and endovascular intervention can obviously improve the prognosis of these patients, enjoying good safety.
3.Disease characteristics and costs of pediatric Mycoplasma Pneumoniae pneumonia hospitalization:a retrospective study at municipal hospitals from 2019 to 2023 in Shanghai
Ying-Wen WANG ; Feng WANG ; Li-Bo WANG ; Ai-Zhen LU ; Yi WANG ; Yong-Hao GUI ; Quan LU ; Yong YIN ; Jian-Hua ZHANG ; Ying-Zi YE ; Hong XU ; Bing SHEN ; Dan-Ping GU ; Xiao-Yan DONG ; Jia-Yu WANG ; Wen HE ; Xiao-Bo ZHANG
Fudan University Journal of Medical Sciences 2024;51(4):515-521
Objective To investigate disease characteristics and hospitalization costs of children with Mycoplasma Pneumoniae pneumonia(MPP)admitted to Shanghai municipal medical hospitals from 2019 to 2023.Methods Depending on the Shanghai Municipal Hospital Pediatric Alliance,we retrospectively investigated community acquired MPP pediatric patients hospitalized in 22 municipal hospitals with pediatric qualifications(including 4 children's hospitals)in Shanghai from Jan 2019 to Dec 2023.We collected the patients'diagnosis codes,gender,age,length of hospital stay,hospitalization costs,and whether they progressed to severe Mycoplasma pneumoniae pneumonia(SMPP).Results From 2019 to 2023,a total of 29 045 hospitalized children with MPP were treated,with 6 035 cases(20.8%)identified as SMPP in the 22 hospitals.Trend analysis revealed a rising trend with years in the proportion of SMPP patients(χ2trend=365.498,P<0.001).Among the 4 children's hospitals,there were 18 710 cases with MPP,including 4 078 cases(21.8%)of SMPP.The proportion of SMPP patients also showed an increasing trend with years(χ2trend=14.548,P<0.001),and the proportion in 2023(23.0%)was higher than that in previous years with statistical significance.There were statistical differences in the seasonal distribution of MPP cases between different years,with higher proportions in summer and autumn overall.The age distribution of hospitalized MPP children varied among different years,with school-age children accounting for the majority(56.8%)in 2023.There was no difference in the distribution of severe cases between different genders,but there were differences in the proportion of severe cases among different age groups in different years,with a gradual increase in severe cases among children aged 1 to 3 years(χ2trend=191.567,P<0.001).The average length of hospital stay for MPP during the epidemic was higher than that during non-epidemic periods,and there were statistically significant differences in the average length of hospital stay between different years(P<0.001).The individual hospitalization costs during the epidemic were higher than in other years,and there were statistically significant differences in individual hospitalization costs between different years(P<0.001).The total hospitalization costs were still higher in 2019 and 2023.The individual hospitalization costs for SMPP were higher than for non-SMPP cases.Conclusion MPP outbreaks occurred in Shanghai in 2019 and 2023,with the higher proportions in summer and autumn overall.Compared to previous years,the number of hospitalized MPP children in Shanghai was higher in 2023,with a higher proportion of SMPP cases,especially among children under 3 years old.The individual per capita hospitalization expenses for SMPP cases were higher than for non-SMPP cases.
4.Clinical characteristics and nutritional status of children with Crohn's disease and risk factors for malnutrition
Dong-Dan LI ; Xiao-Lin YE ; Mei-Chen WANG ; Hong-Mei HUANG ; Jie YAN ; Tian-Zhuo ZHANG ; Fei-Hong YU ; De-Xiu GUAN ; Wen-Li YANG ; Lu-Lu XIA ; Jie WU
Chinese Journal of Contemporary Pediatrics 2024;26(11):1194-1201
Objective To investigate the nutritional status of children with Crohn's Disease (CD) at diagnosis and its association with clinical characteristics. Methods A retrospective analysis was performed for the clinical data and nutritional status of 118 children with CD who were admitted to Beijing Children's Hospital,Capital Medical University,from January 2016 to January 2024. A multivariate logistic regression analysis was used to investigate the risk factors for malnutrition. Results A total of 118 children with CD were included,among whom there were 68 boys (57.6%) and 50 girls (42.4%),with a mean age of (11±4) years. Clinical symptoms mainly included recurrent abdominal pain (73.7%,87/118),diarrhea (37.3%,44/118),and hematochezia (32.2%,38/118),and 63.6% (75/118) of the children had weight loss at diagnosis. The incidence rate of malnutrition was 63.6% (75/118),and the children with moderate or severe malnutrition accounted for 67% (50/75). There were 50 children (42.4%) with emaciation,8 (6.8%) with growth retardation,and 9 (7.6%) with overweight or obesity. Measurement of nutritional indices showed a reduction in serum albumin in 83 children (70.3%),anemia in 74 children (62.7%),and a reduction in 25 hydroxyvitamin D in 15 children (60%,15/25). The children with malnutrition had significantly higher disease activity,proportion of children with intestinal stenosis,and erythrocyte sedimentation rate and a significant reduction in serum albumin (P<0.05). The multivariate logistic regression analysis showed that intestinal stenosis was an independent risk factor for malnutrition in children with CD (OR=4.416,P<0.05). Conclusions There is a high incidence rate of malnutrition in children with CD at diagnosis,which is associated with disease activity and disease behavior. The nutritional status of children with CD should be closely monitored.
5.High tibial osteotomy on varus knee osteoarthritis with medial meniscus posterior root injury
Chun-Jiu WANG ; Xiang-Dong TIAN ; Ye-Tong TAN ; Zhi-Peng XUE ; Wei ZHANG ; Xiao-Min LI ; Ang LIU
China Journal of Orthopaedics and Traumatology 2024;37(9):886-892
Objective To explore clinical effect of distal tibial tubercle-high tibial osteotomy(DTT-HTO)in treating knee osteoarthritis(KO A)with medial meniscus posterior root tear(MMPRT).Methods A retrospective analysis was performed on 21 patients with varus KOA with MMPRT from May 2020 to December 2021,including 3 males and 18 females,aged from 49 to 75 years old with an average of(63.81±6.56)years old,the courses of disease ranged from 0.5 to 18.0 years with an average of(5.9±4.2)years,and 4 patients with grade Ⅱ,14 patients with grade Ⅲ,and 3 patients with grade Ⅳ according to Kellgren-Lawrence;14 patients with type 1 and 7 patients with type 2 according to MMPRT damage classification.The distance of medi-al meniscusextrusion(MME)and weight-bearing line ratio(WBLR)of lower extremity were compared before and 12 months after operation.Visual analogue scale(V AS),Western Ontarioand and McMaster Universities(WOMAC)osteoarthritis index,and Lysholm knee score were used to evaluate knee pain and functional improvement before operation,1,6 and 12 months after operation,respectively.Results Twenty-one patients were followed up for 12 to 18 months with an average of(13.52±1.72)months.MME distance was improved from(4.99±1.05)mm before operation to(1.87±0.76)mm at 12 months after operation(P<0.05).WBLR was increased from(15.49±7.04)%before operation to(62.71±2.27)%at 12 months after operation(P<0.05).VAS was decreased from(7.00±1.14)before operation to(2.04±0.80),(0.90±0.62)and(0.61±0.50)at 1,6 and 12 months after operation.WOMAC were decreased from preoperative(147.90±9.88)to postoperative(103.43±8.52),(74.00±9.54)and(47.62±9.53)at 1,6 and 12 months,and the difference were statistically significant(P<0.05).Lysholm scores were increased from(46.04±7.34)before oepration to(63.19±8.93),(81.10±6.41)and(89.29±3.04)at 1,6 and 12 months after operation(P<0.05).Conclusion For the treatment of varus KOA with MMPRT,DTT-HTO could reduce medial meniscus pro-trusion distance,improve the ratio of lower limb force line,and effectively reduce knee pain and improve knee joint function.
6.Research progresses of endogenous vascular calcification inhibitor BMP-7
Xin ZHOU ; Lu XING ; Peng-Quan LI ; Dong ZHAO ; Hai-Qing CHU ; Chun-Xia HE ; Wei QIN ; Hui-Jin LI ; Jia FU ; Ye ZHANG ; Li XIAO ; Hui-Ling CAO
Chinese Pharmacological Bulletin 2024;40(7):1226-1230
Vascular calcification is a highly regulated process of ectopic calcification in cardiovascular system while no effective intervention can be clinically performed up to date.As vascular calcification undergoes a common regulatory mechanism within bone formation,bone morphogenetic protein 7(BMP-7)main-tains contractile phenotype of vascular smooth muscle cells and further inhibits vascular calcification via promoting the process of osteoblast differentiation,reducing ectopic calcification pressure by increasing bone formation and reducing bone resorption.This work systematically reviews the role of BMP-7 in vascular calcifi-cation and the possible mechanism,and their current clinical application as well.The current proceedings may help develope early diagnostic strategy and therapeutic treatment with BMP-7 as a new molecular marker and potential drug target.The expec-tation could achieve early prevention and intervention of vascular calcification and improve poor prognosis on patients.
7.Study on the machanism of Huannao Yicong Deoction targeting HAMP to regulate iron metabolism and improve cognitive impairment in AD model mice
Ning-Ning SUN ; Xiao-Ping HE ; Shan LIU ; Yan ZHAO ; Jian-Min ZHONG ; Ya-Xuan HAO ; Ye-Hua ZHANG ; Xian-Hui DONG
Chinese Pharmacological Bulletin 2024;40(7):1240-1248
Aim To explore the effects of Huannao Yicong decoction(HYD)on the learning and memory ability and brain iron metabolism in APP/PS1 mice and the correlation of HAMP knockout mice and APP/PS1 double transgenic model mice.Methods The ex-periment was divided into five groups,namely,HAMP-/-group(6-month HAMP gene knockout mice),APP/PS1 group(6-month APP/PS1-double-transgenic mice),HAMP-/-+HYD,APP/PS1+HYD,and negative control group(6-month C57BL/6J mice),with six mice in each group.The dose was ad-ministered(13.68 g·kg-1 weight),and the other groups received distilled water for gavage once a day for two months.After the administration of the drug,the mice in each group were tested for learning and memory in the Morris water maze;Biochemical detec-tion was performed to detect iron ion content in each mouse brain;Western blot and RT-qPCR were carried out to analyze hippocampal transferrin(TF),transfer-rin receptor1(TFR1),membrane iron transporter1(FPN1)divalent metal ion transporter 1(DMT1)and β-amyloid protein(Aβ)protein and mRNA expression levels in each group.Results Compared with the normal group,both HAMP-/-mice and APP/PS1 mice had reduced the learning and memory capacity,in-creased iron content in brain tissue,Aβ protein ex-pression increased in hippocampus of HAMP-/-group and APP/PS1 group mice(P<0.01),the protein and mRNA expression of TF,TFR1 and DMT1 increased in hippocampal tissues of HAMP-/-and APP/PS1 groups(P<0.01),and the FPN1 protein and mRNA expres-sion decreased(P<0.01).Compared with the HAMP-and APP/PS1 groups,respectively,HAMP-/-+HYD group and APP/PS1+HYD group had improved learning and memory ability,decreased iron content,decreased Aβ protein expression(P<0.01),decreased TF,TFR1,DMT1 protein and mR-NA expression(P<0.01),and increased expression of FPN1 protein and mRNA(P<0.01).Conclusions There is some association between HAMP-/-mice and APP/PS1 mice,HYD can improve the learning and memory ability of HAMP-/-and APP/PS1 mice and reduce the Aβ deposition.The mechanism may be related to the regulation of TF,TFR1,DMT1,FPN1 expression and improving brain iron overload.
8.Effects of GanoExtra combined with CTX on lung metastasis and immune function in mice
Shu LIAN ; Ting-Jian WU ; Jie CHEN ; Chun-Lian ZHONG ; Yu-Sheng LU ; Ye LI ; Chang-Hui WU ; Kun ZHANG ; Li JIA ; Xiao-Dong XIE
Chinese Pharmacological Bulletin 2024;40(7):1335-1342
Aim To investigate the enhanced efficacy and reduced toxicity of GanoExtra in combination with cyclophosphamide(CTX)on inhibiting lung metastasis and immune function in mice.Methods The CCK-8 method was used to verify the cytotoxic effects of Gano-Extra on MCF-7 and 4T1 tumor cells.In vivo experi-ment,a mouse model of lung metastasis of breast canc-er was established by injecting 4T1 tumor cells into the tail vein,which was divided into four groups including 4T1 model group,CTX group,GanoExtra group and GanoExtra+CTX group.The control group was set.After 21 days,the mice were euthanized under anes-thesia,and the body weight of the mice was recorded.Average lung index and spleen index were calculated.The mouse spleen lymphocyte transformation experi-ment was used to determine the activity of spleen cells.The NK cell activity assay was used to determine the activity of NK cells.Blood cells were determined in mouse blood samples.Flow cytometry was used to de-termine the levels of CD4+and CD8+T cells in blood samples.ELISA was used to measure the levels of TNF-α and IL-6 in serum.HE staining was used to ob-serve the pathological morphological changes in tumors and various tissues;and CFSE staining was used to de-termine the proliferative effect of GanoExtra on CD8+cells.Results In vitro GanoExtra at 50 mg·L-1 sig-nificantly inhibited the activity of MCF-7 and 4T1 tumor cells.In the breast cancer pulmonary metastasis model,compared with the model group,the spleen in-dex and blood WBCs content were significantly re-duced,while the activity of NK cells,spleen cells,and the proportion of RBCs,CD 3+and CD 8+T cells in the blood were significantly increased.At the end of the treatment,compared with the CTX group,the number of lung metastases and lung index of the Gano-Extra+CTX group were significantly reduced,and the levels of HGB,CD8+cells,IL-6,and TNF-α in the blood of mice were significantly increased.GanoExtra at 10 mg·L-1 significantly promoted the proliferation of CD8+T cells in vitro.Conclusions GanoExtra can enhance the inhibitory effect of CTX on tumor metasta-sis,alleviate adverse reactions such as splenomegaly and pulmonary enlargement caused by CTX,and have a health-promoting function of promoting the prolifera-tion of CD8+T cells to enhance the immune efficacy of the body.
9.Nomogram model based on multimodal ultrasound for predicting sentinel lymph node metastasis in patients with breast cancer
Xiao ZU ; Weilu DONG ; Ting CAI ; Qin ZHANG ; Chun ZHAO ; Ye QIANG ; Yiyun WU
Chinese Journal of Ultrasonography 2024;33(10):862-870
Objective:To analyze the multimodal ultrasound characteristics of primary breast cancer and sentinel lymph node (SLN) and to establish a nomogram model for predicting SLN metastasis in invasive breast cancer, thereby providing reference for precise clinical diagnosis and treatment.Methods:A total of 329 patients diagnosed with invasive breast cancer and admitted to the Affiliated Hospital of Nanjing University of Chinese Medicine from June 2018 to October 2023 were retrospectively enrolled. They were randomly divided into a training cohort ( n=230) and a validation cohort ( n=99) in a ratio of 7 to 3. In the training cohort, ultrasound findings and clinical parameters were analyzed, univariate and multivariate Logistic regression analyses were used to identify independent predictive factors for SLN metastasis, and a nomogram model was constructed based on these factors. The ROC curve, calibration curve, and decision curve analysis (DCA) were plotted between the training and validation cohorts to assess the discrimination, calibration, and clinical applicability of the nomogram model. Results:Regression analysis identified 3 independent risk factors for establishing the nomogram prediction model: ratio of the long diameter to the short diameter of SLN ( P=0.020), lymphatic contrast-enhanced ultrasound (LCEUS) enhancement pattern ( P<0.001) and intravenous contrast-enhanced ultrasound (ICEUS) enhancement mode ( P=0.002). The area under the curve (AUC) of the training cohort was 0.888, the accuracy was 0.865; the AUC of the validation cohort was 0.870, the accuracy was 0.859, demonstrating good predictive performance of the model in both cohorts. The calibration curve demonstrated that the nomogram has a strong concordance between predicted and actual probability. DCA demonstrated that the nomogram could increase net benefit within a certain probability threshold range. Conclusions:The nomogram based on ratio of the long diameter to the short diameter of SLN, LCEUS enhancement pattern and ICEUS enhancement mode can effectively predict SLN status in patients with invasive breast cancer, facilitating precise diagnosis and treatment.
10. Study on efficacy and regulation of inflammatory factors with oseltamivir phosphate by different time series of interventions in a murine model of influenza A H1N1 virus infection
Yu-Xiu HAN ; Liang-Xin ZHAO ; Yan-Liang LIU ; Qi-Hui SUN ; Rong RONG ; Xiao-Yun LIU ; Dong-Xue YE ; Yong YANG ; Rong RONG ; Xiao-Yun LIU ; Dong-Xue YE ; Yong YANG ; Xiao-Yun LIU ; Dong-Xue YE ; Yong YANG ; Qi-Hui SUN ; Xiao-Yun LIU ; Dong-Xue YE ; Yong YANG
Chinese Pharmacological Bulletin 2023;39(7):1339-1346
Aim To compare the effects of different time sequence interventions on virus infected mice by using oseltamivir (Tamiflu) as a "tool drug" in view of the current situation of the too early the administration time of antiviral in vivo experiment, so as to provide a basis for selecting a reasonable model intervention time point for antiviral drug research. Methods Balb/c mice were randomly divided into six groups. The virus infection model was established by intranasal infection with influenza virus (0.25 TCID50). Tamiflu-1 group and Tamiflu-2 group were administered orally on 1st and 4th day after exposure. The body mass, survival rate, organ index, viral load and inflammatory factor content were measured. Results Compared with the blank control group, the body weight of the mice in the model group decreased and the lung index increased significantly (P < 0.05). The expression levels of 13 inflammatory factors in model 2 group were significantly different ( P < 0.05). Compared with the model-1 group ,the lung index and spleen index of the Tamiflu-1 group decreased significantly (P < 0.05). Compared with the mode-2 group,the lung index in the Tamiflu-2 group was significantly lower (P <0.05) ,and the thy-mus index was significantly higher (P<0.05). The viral load was 0. 03 times that of the model-2 group. The expression levels of 13 inflammatory factors were significantly different (P < 0. 05). Conclusions The symptoms of the mice in Scheme 2 are more obvious and stable after exposure. After administration, the lung inflammation damage is alleviated. Considering the latency, drug intervention is in line with the drug indications when the model animals show symptoms. It will be more reasonable and accurate whether in the model evaluation or drug evaluation.

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