1.Effects of Sishen Pills and its separated prescriptions on human intestinal flora based on in vitro fermentation model.
Jia-Yang XI ; Qi-Qi WANG ; Xue CHENG ; Hui XIA ; Lu CAO ; Yue-Hao XIE ; Tian-Xiang ZHU ; Ming-Zhu YIN
China Journal of Chinese Materia Medica 2025;50(11):3137-3146
Sishen Pills and its separated prescriptions are classic prescriptions of traditional Chinese medicine to treat intestinal diseases. In this study, a high-performance liquid chromatography-electrospray ionization tandem mass spectrometry(HPLC-ESI-MS/MS) technology was used to identify the components of Sishen Pills, Ershen Pills, and Wuweizi Powder. The positive and negative ion sources of electrospray ionization were simultaneously collected by mass spectrometry. A total of 11 effective components were detected in Sishen Pills, with four effective components detected in Ershen Pills and eight effective components detected in Wuweizi Powder, respectively. To explore the effects of Sishen Pills and its separated prescriptions on the human intestinal flora, an in vitro anaerobic fermentation model was established, and the human intestinal flora was incubated with Sishen Pills, Ershen Pills, and Wuweizi Powder in vitro. The 16S rDNA sequencing technology was used to analyze the changes in the intestinal flora. The results showed that compared with the control group, Sishen Pills, and its separated prescriptions could decrease the intestinal flora abundance and increase the Shannon index after fermentation. The abundance of Bifidobacterium was significantly increased in the Sishen Pills and Ershen Pills groups. However, the abundance of Lactobacillus, Weissella, and Pediococcus was significantly increased in the Wuweizi Powder group. After fermentation for 12 h, the pH of the fermentation solution of three kinds of liquids with feces gradually decreased and was lower than that of the control group. The decreasing amplitude in the Wuweizi Powder group was the most obvious. The single-bacteria fermentation experiments further confirmed that Sishen Pills and Wuweizi Powder had inhibitory effects on Escherichia coli, Staphylococcus aureus, and Enterococcus faecalis, and the antibacterial activity of Wuweizi Powder was stronger than that of Sishen Pills. Both Sishen Pills and Ershen Pills could promote the growth of Lactobacillus brevis, and Ershen Pills could promote the growth of Bifidobacterium adolescentis. This study provided a more sufficient theoretical basis for the clinical application of Sishen Pills and its separated prescriptions.
Humans
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Gastrointestinal Microbiome/drug effects*
;
Drugs, Chinese Herbal/chemistry*
;
Fermentation/drug effects*
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Bacteria/drug effects*
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Chromatography, High Pressure Liquid
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Tandem Mass Spectrometry
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Intestines/microbiology*
2.Effects of Prognostic Nutritional Index and Systemic Inflammatory Response Index on Short-Term Efficacy and Prognosis in Patients with Peripheral T-Cell Lymphoma.
Zi-Qing HUANG ; Yan-Hui LI ; Bin LYU ; Xue-Jiao GU ; Ming-Xi TIAN ; Xin-Yi LI ; Yan ZHANG ; Xiao-Qian LI ; Ying WANG ; Feng ZHU
Journal of Experimental Hematology 2025;33(5):1350-1357
OBJECTIVE:
To investigate the predictive value of the prognostic nutritional index (PNI) and systemic inflammatory response index (SIRI) for short-term efficacy and prognosis in newly treated patients with peripheral T-cell lymphoma (PTCL).
METHODS:
The general data, laboratory indicators, disease stage and other clinical data of 91 newly treated PTCL patients admitted to the Affiliated Hospital of Xuzhou Medical University from January 2015 to December 2023 were retrospectively analyzed. The optimal cutoff values for PNI and SIRI were determined using receiver operating characteristic (ROC) curves, and the patients were stratified into groups based on these cutoffs to compare clinical features and short-term efficacy between the different groups. Kaplan-Meier method was used to plot survival curves, and univariate and multivariate analyses were performed to identify the factors affecting overall survival (OS).
RESULTS:
The optimal cutoff values for PNI and SIRI were 45.30 and 1.74×109/L, respectively. Patients in different PNI groups showed statistically significant differences in age, Ann Arbor stage, lactate dehydrogenase (LDH) level, international prognostic index (IPI), prognostic index for PTCL-not otherwise specified (PIT), pathological subtypes, and complete response (CR) rate (P < 0.05). PTCL patients in different SIRI groups exhibited significant differences in Ann Arbor stage, LDH level, IPI score, PIT score, and CR rate (P < 0.05). Logistic regression analysis showed that age ≥60 years old (OR =2.750), Ann Arbor stage Ⅲ-Ⅳ (OR =5.200), IPI score ≥2 (OR =7.650), low PNI (OR =3.296), and high SIRI (OR =3.130) were independent risk factors affecting treatment efficacy in PTCL patients (P < 0.05). Cox proportional hazards regression model analysis showed that low PNI and elevated β2-microglobulin (β2-MG) levels were independent risk factors affecting OS (P < 0.05).
CONCLUSION
PNI and SIRI have certain application value in evaluating short-term efficacy and prognosis in patients with PTCL. Compared with SIRI, PNI demonstrates greater predictive value for patient prognosis.
Humans
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Prognosis
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Lymphoma, T-Cell, Peripheral/therapy*
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Retrospective Studies
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Nutrition Assessment
;
Male
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Female
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Middle Aged
;
ROC Curve
;
Inflammation
3.Analysis of HPV infection and genotype distribution among 1 658 male reproductive health outpatients
Nazhakaiti ABUDUKELIMU ; Jian-Hui LI ; Tian-Cheng ZHANG ; Xin WANG ; Zhi-Ming XU ; Qian-Xi ZHU
Fudan University Journal of Medical Sciences 2024;51(1):69-75
Objective To investigate the human papillomavirus(HPV)infection and genotype distribution characteristics among male reproductive health outpatients,and to compare the differences among different age groups of outpatients.Methods A total of 1 658 males,visited in the Affiliated Hospital of Shanghai Institute of Planned Parenthood Research from 2018 to 2022,were selected and 23 HPV genotypes were detected by PCR-reverse dot hybridization.Results Among the 1 658 subjects,the overall HPV infection rate was 22.50%.Single infection accounted for 66.76%,which was the main infection type.HPV infection among different age groups were statistically significant(P<0.001),with HPV infection of 16.83%,22.87%,34.63%,and 29.35%for 18-30,31-40,41-50,and≥51 years,respectively.The top 5 high risk HPV genotypes were HPV52(3.56%),HPV16(3.26%),HPV39(2.41%),HPV51(2.17%),HPV58(2.17%),and the top 1 low risk HPV genotype was HPV81(2.90%).The proportions of infected individuals in this study that could be completely covered by bivalent,quadrivalent,and nine-valent HPV vaccines were 7.77%,12.33%,and 26.27%,respectively.Conclusion The predominant infection type among male reproductive health outpatients was single infection type.HPV 52,16,39,51 and 58 were the most common high risk genotypes,while HPV 81 was the most common low risk genotype.Individuals aged 41-50 years had the highest HPV infection rate.
4.Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients (version 2024)
Yao LU ; Yang LI ; Leiying ZHANG ; Hao TANG ; Huidan JING ; Yaoli WANG ; Xiangzhi JIA ; Li BA ; Maohong BIAN ; Dan CAI ; Hui CAI ; Xiaohong CAI ; Zhanshan ZHA ; Bingyu CHEN ; Daqing CHEN ; Feng CHEN ; Guoan CHEN ; Haiming CHEN ; Jing CHEN ; Min CHEN ; Qing CHEN ; Shu CHEN ; Xi CHEN ; Jinfeng CHENG ; Xiaoling CHU ; Hongwang CUI ; Xin CUI ; Zhen DA ; Ying DAI ; Surong DENG ; Weiqun DONG ; Weimin FAN ; Ke FENG ; Danhui FU ; Yongshui FU ; Qi FU ; Xuemei FU ; Jia GAN ; Xinyu GAN ; Wei GAO ; Huaizheng GONG ; Rong GUI ; Geng GUO ; Ning HAN ; Yiwen HAO ; Wubing HE ; Qiang HONG ; Ruiqin HOU ; Wei HOU ; Jie HU ; Peiyang HU ; Xi HU ; Xiaoyu HU ; Guangbin HUANG ; Jie HUANG ; Xiangyan HUANG ; Yuanshuai HUANG ; Shouyong HUN ; Xuebing JIANG ; Ping JIN ; Dong LAI ; Aiping LE ; Hongmei LI ; Bijuan LI ; Cuiying LI ; Daihong LI ; Haihong LI ; He LI ; Hui LI ; Jianping LI ; Ning LI ; Xiying LI ; Xiangmin LI ; Xiaofei LI ; Xiaojuan LI ; Zhiqiang LI ; Zhongjun LI ; Zunyan LI ; Huaqin LIANG ; Xiaohua LIANG ; Dongfa LIAO ; Qun LIAO ; Yan LIAO ; Jiajin LIN ; Chunxia LIU ; Fenghua LIU ; Peixian LIU ; Tiemei LIU ; Xiaoxin LIU ; Zhiwei LIU ; Zhongdi LIU ; Hua LU ; Jianfeng LUAN ; Jianjun LUO ; Qun LUO ; Dingfeng LYU ; Qi LYU ; Xianping LYU ; Aijun MA ; Liqiang MA ; Shuxuan MA ; Xainjun MA ; Xiaogang MA ; Xiaoli MA ; Guoqing MAO ; Shijie MU ; Shaolin NIE ; Shujuan OUYANG ; Xilin OUYANG ; Chunqiu PAN ; Jian PAN ; Xiaohua PAN ; Lei PENG ; Tao PENG ; Baohua QIAN ; Shu QIAO ; Li QIN ; Ying REN ; Zhaoqi REN ; Ruiming RONG ; Changshan SU ; Mingwei SUN ; Wenwu SUN ; Zhenwei SUN ; Haiping TANG ; Xiaofeng TANG ; Changjiu TANG ; Cuihua TAO ; Zhibin TIAN ; Juan WANG ; Baoyan WANG ; Chunyan WANG ; Gefei WANG ; Haiyan WANG ; Hongjie WANG ; Peng WANG ; Pengli WANG ; Qiushi WANG ; Xiaoning WANG ; Xinhua WANG ; Xuefeng WANG ; Yong WANG ; Yongjun WANG ; Yuanjie WANG ; Zhihua WANG ; Shaojun WEI ; Yaming WEI ; Jianbo WEN ; Jun WEN ; Jiang WU ; Jufeng WU ; Aijun XIA ; Fei XIA ; Rong XIA ; Jue XIE ; Yanchao XING ; Yan XIONG ; Feng XU ; Yongzhu XU ; Yongan XU ; Yonghe YAN ; Beizhan YAN ; Jiang YANG ; Jiangcun YANG ; Jun YANG ; Xinwen YANG ; Yongyi YANG ; Chunyan YAO ; Mingliang YE ; Changlin YIN ; Ming YIN ; Wen YIN ; Lianling YU ; Shuhong YU ; Zebo YU ; Yigang YU ; Anyong YU ; Hong YUAN ; Yi YUAN ; Chan ZHANG ; Jinjun ZHANG ; Jun ZHANG ; Kai ZHANG ; Leibing ZHANG ; Quan ZHANG ; Rongjiang ZHANG ; Sanming ZHANG ; Shengji ZHANG ; Shuo ZHANG ; Wei ZHANG ; Weidong ZHANG ; Xi ZHANG ; Xingwen ZHANG ; Guixi ZHANG ; Xiaojun ZHANG ; Guoqing ZHAO ; Jianpeng ZHAO ; Shuming ZHAO ; Beibei ZHENG ; Shangen ZHENG ; Huayou ZHOU ; Jicheng ZHOU ; Lihong ZHOU ; Mou ZHOU ; Xiaoyu ZHOU ; Xuelian ZHOU ; Yuan ZHOU ; Zheng ZHOU ; Zuhuang ZHOU ; Haiyan ZHU ; Peiyuan ZHU ; Changju ZHU ; Lili ZHU ; Zhengguo WANG ; Jianxin JIANG ; Deqing WANG ; Jiongcai LAN ; Quanli WANG ; Yang YU ; Lianyang ZHANG ; Aiqing WEN
Chinese Journal of Trauma 2024;40(10):865-881
Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.
5.Effect comparison between improved 18F-PSMA-1007 PET-CT score and mpMRI PI-RADS score for diagnosis of prostate cancer
Lanlan BAO ; Ming ZHAO ; Rongrong TIAN ; Xi ZHANG ; Tong ZHAO ; Fengqin SHI
Cancer Research and Clinic 2024;36(9):670-677
Objective:To explore the diagnostic value of improved 18F-prostate specific membrane antigen (PSMA)-1007 PET-CT score (referred to as PSMA score) and multi parameter magnetic resonance imaging (mpMRI) prostate imaging reporting and data system (PI-RADS) score (referred to as PI-RADS score) for primary prostate cancer (PCa). Methods:A retrospective case series study was conducted. The imaging and clinical data of 134 suspected PCa patients underwent 18F-PSMA-1007 PET-CT and mpMRI examinations at Shanxi Province Cancer Hospital from July 2018 to May 2023 were collected. Pathological diagnosis showed 92 cases of PCa and 42 cases of benign prostatic lesions. The clinical and imaging parameters, as well as the distribution of patients with two scores, were compared between the two groups. The blind diagnosis of benign and malignant lesions was made based on the improved PSMA score (dividing 1 point into 1a and 1b points, 1b, 2 and 3 points were diagnosed as PCa), PI-RADS score (3, 4 and 5 points were diagnosed as PCa) and the combination of the two (diagnosed as PCa when either PSMA score ≥ 1b point or PI-RADS score ≥ 4 points was met). The indicators of the diagnostic efficiency of PSMA score, PI-RADS score and the combination of the two for PCa were calculated. Using pathological results as the gold standard, the receiver operating characteristic (ROC) curve of PSMA score, PI-RADS score and the combination of the two for diagnosing PCa was drawn, and the diagnostic efficiency of the 3 methods was analyzed. Results:The age, serum prostate-specific antigen, and maximum standard uptake value of PET-CT in the PCa group were higher than those in the benign prostatic lesion group, and the differences were statistically significant (all P < 0.05). The sensitivity, specificity, accuracy, false negative rate, false positive rate, positive predictive value, and negative predictive value of PSMA score for diagnosing PCa were 91.30% (84/92), 80.95% (34/42), 88.06% (118/134), 8.70% (8/92), 19.05% (8/42), 91.30% (84/92), and 80.95% (34/42), respectively; those of PI-RADS score were 93.48% (86/92), 61.90% (26/42), 83.58% (112/134), 61.90% (26/42), 38.10% (16/42), 84.31% (86/102), and 81.25% (26/32), respectively; those of the combination of the two were 97.83% (90/92), 88.10% (37/42), 94.78% (127/134), 2.17% (2/92), 11.90% (5/42), 94.74% (90/95), and 94.87% (37/39), respectively. The differences in specificity, accuracy, false negative rate, and false positive rate among the 3 methods were statistically significant (all P < 0.05). ROC curve analysis showed that the area under the curve of PSMA score, PI-RADS score and the combination of the two for diagnosing PCa were 0.930 (95% CI: 0.872-0.967), 0.935 (95% CI: 0.826-0.939) and 0.959 (95% CI: 0.910-0.986), respectively, and the differences between each two methods were statistically significant (all P < 0.05); the sensitivity of PSMA score, PI-RADS score and the combination of the two was 90.11%, 89.13% and 98.09%, and the specificity was 90.48%, 90.48% and 92.09%. Conclusions:Compared with the PI-RADS score, the improved PSMA score can improve the specificity and accuracy of PCa diagnosis, and decrease the false negative and false positive rates; the diagnostic efficiency of the combination of the two is superior.
6.Intelligent diagnostic model of keratoconus based on deep learning algorithm
Di-Hua AO ; Xi-Rui TIAN ; Ming-Xun MA ; Bo ZHANG ; Min CHEN ; Yan-Li PENG
International Eye Science 2023;23(2):299-304
AIM: To establish an intelligent diagnostic model of keratoconus for small-diameter corneas by data mining and analysis of patients' clinical data.METHODS: Diagnostic study. A total of 830 patients(830 eyes)were collected, including 338 male(338 eyes)and 492 female(492 eyes), with an average age of 14-36(23.19±5.71)years. Among them, 731 patients(731 eyes)had undergone corneal refractive surgery at Chongqing Nanping Aier Eye Hospital from January 2020 to March 2022, and 99 patients had a diagnosed keratoconus from January 2015 to March 2022. Corneal diameter ≤11.1 mm was measured by Pentacam in all patients. Two cornea specialists classified patients' data into normal corneas, suspect keratoconus, and keratoconus groups based on the Belin/Ambrósio enhanced ectasia display(BAD)system in Pentacam. The data of 665 patients were randomly selected as the training set and the other 165 patients as the validation set by computer random sampling method. Seven parametric corneal features were extracted by convolutional neural networks(CNN), and the models were built by Residual Network(ResNet), Vision Transformer(ViT), and CNN+Transformer, respectively. The diagnostic accuracy of models was verified by cross-entropy loss and cross-validation method. In addition, sensitivity and specificity were evaluated using receiver operating characteristic curve.RESULTS: The accuracy of ResNet, ViT, and CNN+Transfermer for the diagnosis of normal cornea and suspect keratoconus was 85.57%, 86.11%, and 86.54% respectively, and the area under the receiver operating characteristic curve(AUC)was 0.823, 0.830 and 0.842 respectively. The accuracy of models for the diagnosis of suspect keratoconus and keratoconus was 97.22%, 95.83%, and 98.61%, respectively, and the AUC was 0.951, 0.939, and 0.988 respectively.CONCLUSION: For corneas ≤11.1 mm in diameter, the data model established by CNN+Transformer has a high accuracy rate for classifying keratoconus, which provides real and effective guidance for early screening.
7.The Chinese herbal prescription JieZe-1 inhibits caspase-1-dependent pyroptosis induced by herpes simplex virus-2 infection in vitro.
Tong LIU ; Qing-Qing SHAO ; Wen-Jia WANG ; Tian-Li LIU ; Xi-Ming JIN ; Li-Jun XU ; Guang-Ying HUANG ; Zhuo CHEN
Journal of Integrative Medicine 2023;21(3):277-288
OBJECTIVE:
JieZe-1 (JZ-1), a Chinese herbal prescription, has an obvious effect on genital herpes, which is mainly caused by herpes simplex virus type 2 (HSV-2). Our study aimed to address whether HSV-2 induces pyroptosis of VK2/E6E7 cells and to investigate the anti-HSV-2 activity of JZ-1 and the effect of JZ-1 on caspase-1-dependent pyroptosis.
METHODS:
HSV-2-infected VK2/E6E7 cells and culture supernate were harvested at different time points after the infection. Cells were co-treated with HSV-2 and penciclovir (0.078125 mg/mL) or caspase-1 inhibitor VX-765 (24 h pretreatment with 100 μmol/L) or JZ-1 (0.078125-50 mg/mL). Cell counting kit-8 assay and viral load analysis were used to evaluate the antiviral activity of JZ-1. Inflammasome activation and pyroptosis of VK2/E6E7 cells were analyzed using microscopy, Hoechst 33342/propidium iodide staining, lactate dehydrogenase release assay, gene and protein expression, co-immunoprecipitation, immunofluorescence, and enzyme-linked immunosorbent assay.
RESULTS:
HSV-2 induced pyroptosis of VK2/E6E7 cells, with the most significant increase observed 24 h after the infection. JZ-1 effectively inhibited HSV-2 (the 50% inhibitory concentration = 1.709 mg/mL), with the 6.25 mg/mL dose showing the highest efficacy (95.76%). JZ-1 (6.25 mg/mL) suppressed pyroptosis of VK2/E6E7 cells. It downregulated the inflammasome activation and pyroptosis via inhibiting the expression of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (P < 0.001) and interferon-γ-inducible protein 16 (P < 0.001), and their interactions with apoptosis-associated speck-like protein containing a caspase recruitment domain, and reducing cleaved caspase-1 p20 (P < 0.01), gasdermin D-N (P < 0.01), interleukin (IL)-1β (P < 0.001), and IL-18 levels (P < 0.001).
CONCLUSION
JZ-1 exerts an excellent anti-HSV-2 effect in VK2/E6E7 cells, and it inhibits caspase-1-dependent pyroptosis induced by HSV-2 infection. These data enrich our understanding of the pathologic basis of HSV-2 infection and provide experimental evidence for the anti-HSV-2 activity of JZ-1. Please cite this article as: Liu T, Shao QQ, Wang WJ, Liu TL, Jin XM, Xu LJ, Huang GY, Chen Z. The Chinese herbal prescription JieZe-1 inhibits caspase-1-dependent pyroptosis induced by herpes simplex virus-2 infection in vitro. J Integr Med. 2023; 21(3): 277-288.
Caspase 1/metabolism*
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Inflammasomes/pharmacology*
;
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism*
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Pyroptosis
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Simplexvirus/metabolism*
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Drugs, Chinese Herbal/pharmacology*
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Herpes Simplex/drug therapy*
;
Humans
8. Construction and comparative study of ovariectomized mouse model
Shuo TIAN ; Ya-Gang SONG ; Ming BAI ; Ming-San MIAO ; Jun-Xi GE ; Lin GUO
Chinese Pharmacological Bulletin 2023;39(7):1392-1398
Aim To compare the effects of different methods on the preparation of ovariectomized mouse models. Methods The bilateral ovaries of mouse were completely removed by desmurgia and diathermocoagulation respectively. The effects of desmurgia and diathermocoagulation methods on ovariectomized mouse models were compared by detecting vaginal smears, organ indexes , biochemical indexes, Micro-CT was used to detect the mor-phological changes in femur tissue, and HE staining was used to observe the pathological changes in femur, uterus, thymus and spleen. Results Compared with the control group, the estrous cycle of mouse was disordered by desmurgia and diathermocoagulation, the indexes of uterus, spleen and thymus were reduced, the levels of BGP, BALP and E
9. Dorsal root ganglion receptor subtype P2X3R mediates postoperative-hyperalgesic priming in mice
Si-Jia ZHEN ; Bei ZHAO ; Bo-Xi ZHENG ; Shu-Xin TIAN ; Ting XU ; Ming-Hui WU ; Jun-Fan FANG ; Jun-Ying DU ; Chi XU ; Jian-Qiao FANG ; Yi LIANG ; Jie ZHOU ; Jian-Qiao FANG ; Yi LIANG
Chinese Pharmacological Bulletin 2023;39(7):1282-1288
Aim To investigate the differences in the role of different purinergic receptor subtypes at different sites in postoperative-hyperalgesic priming in mice. Methods A postoperative-hyperalgesic priming model was constructed by injecting PGE
10.Atezolizumab therapy in Chinese patients with locally advanced or metastatic solid tumors: An open-label, phase Ⅰ study.
Li ZHANG ; Ji Fang GONG ; Hong Ming PAN ; Yu Xian BAI ; Tian Shu LIU ; Ying CHENG ; Ya Chi CHEN ; Jia Ying HUANG ; Ting Ting XU ; Fei Jiao GE ; Wan Ling HSU ; Jia SHI ; Xi Chun HU ; Lin SHEN
Journal of Peking University(Health Sciences) 2022;54(5):971-980
OBJECTIVE:
To evaluate pharmacokinetics (PK), efficacy, and safety of atezolizumab (anti-PD-L1) in high interest cancers in China, including esophageal cancer (EC), gastric cancer (GC), hepatocellular carcinoma (HCC), nasopharyngeal cancer (NPC), and non-small cell lung can-cer (NSCLC).
METHODS:
This phase I, open-label study was conducted at 6 Chinese sites from August 4, 2016 to April 15, 2019. The patients were ≥18 years old with a histologically documented incurable or metastatic solid tumor that was advanced or recurrent and had progressed since the last anti-tumor the-rapy. The PK phase characterized PK and safety of atezolizumab following multiple-dose administration when atezolizumab was administered as a single agent. The extension phase studied safety and efficacy of atezolizumab, as monotherapy (EC, GC, HCC, NPC) and with chemotherapy (NSCLC).
RESULTS:
This study enrolled 120 patients (PK phase: n=20; extension phase: n=20/cohort). Fourty-two patients (42.0%) were PD-L1 positive in atezolizumab monotherapy group (100 patients), of the 9 patients (9.0%) with microsatellite instability-high (MSI-H) tumors. Atezolizumab clearance was 0.219 L/d, and steady state was reached after 6 to 9 weeks (2-3 cycles) of repeated dosing. Objective response rates (ORRs) in EC, GC, HCC, NPC, and NSCLC were 10.0%, 15.0%, 10.0%, 5.0%, and 40.0%, respectively. In the patients with PD-L1 positive tumors, ORR was 11.9% with atezolizumab and 46.2% with atezolizumab plus gemcitabine and cisplatin. Two GC patients achieved durable response after pseudo-progression. The most common treatment-related adverse events in the atezolizumab monotherapy group were fatigue, anemia, fever, and decreased white blood cell count. The most common treatment-related adverse events in the combination group were anemia, decreased white blood cell count, and decreased appetite. No new safety signals were identified.
CONCLUSION
Atezolizumab's PK, efficacy, and safety were similar in Chinese patients vs. global patients in previous studies.
Adolescent
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Antibodies, Monoclonal, Humanized
;
Antineoplastic Agents/therapeutic use*
;
Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
;
Carcinoma, Hepatocellular/drug therapy*
;
Cisplatin/therapeutic use*
;
Humans
;
Liver Neoplasms/drug therapy*
;
Lung Neoplasms/pathology*
;
Nasopharyngeal Neoplasms/drug therapy*

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