1.Distribution characteristics of sIgE antibodies against four components of egg white in children with egg allergy
Yuanmin SUN ; Xin TAN ; Lisheng ZHENG ; Bei ZHANG ; Xiaohui YANG ; Yang YU ; Huiqiang LI
Chinese Journal of Clinical Laboratory Science 2024;42(1):1-5
Objective To investigate the distribution characteristics of serum sIgE antibodies against four allergenic protein components of egg white in children with egg allergy,and then clarify the clinical application value of single component-resolved diagnostics of egg allergy.Methods Serum samples from 197 children with egg allergy were collected.The levels of serum sIgE antibodies against four major allergenic protein components of egg white,including ovomucin,ovalbumin,ovotransferrin,and lysozyme,were detected by the light-excited chemiluminescence assay(LiCA),and the distribution characteristics of sIgE antibodies were analyzed.Results The positive rates of serum sIgE antibodies against ovalbumin,ovomucin,ovotransferrin,and lysozyme in 197 chlidren with egg allergy were 77.16%(152/197),70.56%(139/197),35.02%(69/197),and 18.27%(36/197),respectively.The positive rate of serum sIgE antibody against both ovomucin and ovalbumin was 30.45%.There was a weak correlation between the levels of sIgE antibodies against egg and the cumulative levels of sIgE antibodies against four allergenic protein components(r=0.266 8,P<0.05).There were signifi-cant individual differences in the levels of serum sIgE antibodies against four allergenic protein components of egg white in the children with egg allergy.Conclusion There is individual heterogeneity in the levels of serum sIgE antibodies against four components of egg white in the children with egg allergy.The detection of sIgE antibodies against egg white components can distinguish different forms of egg allergies,which is of great value for the accurate diagnosis and precise desensitization of children's egg allergy.
2.Progress and challenges in dengue vaccine development
Yiming SUN ; Huiqiang YANG ; Yonghong GE
Chinese Journal of Microbiology and Immunology 2024;44(7):635-640
Dengue fever, caused by of dengue virus (DENV) infection, is one of the most prevalent arboviral infections worldwide. It is estimated that approximately 390 million people are infected with DENV each year, of whom approximately 96 million will develop clinical symptoms and one in every twenty people may develop severe dengue leading to shock, internal bleeding and death. DENV includes four serotypes (1-4), each of which can cause various forms of disease. There is currently no specific treatment for dengue fever, and only two vaccines have been approved for use in some countries: CYD-TDV and TAK-003. CYD-TDV, which is suitable for people aged 9-45, can be affected by antibody-dependent enhancement (ADE), leading to more severe infections. Therefore, how to reduce or eliminate ADE becomes an important issue in current dengue vaccine research. In addition, the effects of DENV non-structural proteins on the immune system cannot be ignored. Currently, at least seven dengue vaccines are in various stages of development and clinical trials. This review will focus on three vaccine candidates that have made significant progress, and summarize the ways to avoid ADE the progress in the development of dengue vaccines using non-structural proteins as immunogens.
3.Efficacy and safety of mitoxantrone hydrochloride liposome injection in treatment of peripheral T-cell lymphomas: a multicenter, non-interventional, ambispective cohort, real-world study (MOMENT)
Huiqiang HUANG ; Zhiming LI ; Lihong LIU ; Liang HUANG ; Jie JIN ; Hongyan TONG ; Hui ZHOU ; Zengjun LI ; Zhenqian HUANG ; Wenbin QIAN ; Kaiyang DING ; Quande LIN ; Ming HOU ; Yunhong HUANG ; Jingbo WANG ; Pengcheng HE ; Xiuhua SUN ; Xiaobo WANG ; Zunmin ZHU ; Yao LIU ; Jinhai REN ; Huijing WU ; Liling ZHANG ; Hao ZHANG ; Liangquan GENG ; Jian GE ; Ou BAI ; Liping SU ; Guangxun GAO ; Xin LI ; Yanli YANG ; Yijian CHEN ; Aichun LIU ; Xin WANG ; Yi WANG ; Liqun ZOU ; Xiaobing HUANG ; Dongping HUANG ; Shujuan WEN ; Donglu ZHAO ; Jun MA
Journal of Leukemia & Lymphoma 2023;32(8):457-464
Objective:To evaluate the efficacy and safety of mitoxantrone hydrochloride liposome injection in the treatment of peripheral T-cell lymphoma (PTCL) in a real-world setting.Methods:This was a real-world ambispective cohort study (MOMENT study) (Chinese clinical trial registry number: ChiCTR2200062067). Clinical data were collected from 198 patients who received mitoxantrone hydrochloride liposome injection as monotherapy or combination therapy at 37 hospitals from January 2022 to January 2023, including 166 patients in the retrospective cohort and 32 patients in the prospective cohort; 10 patients in the treatment-na?ve group and 188 patients in the relapsed/refractory group. Clinical characteristics, efficacy and adverse events were summarized, and the overall survival (OS) and progression-free survival (PFS) were analyzed.Results:All 198 patients were treated with mitoxantrone hydrochloride liposome injection for a median of 3 cycles (range 1-7 cycles); 28 cases were treated with mitoxantrone hydrochloride liposome injection as monotherapy, and 170 cases were treated with the combination regimen. Among 188 relapsed/refractory patients, 45 cases (23.9%) were in complete remission (CR), 82 cases (43.6%) were in partial remission (PR), and 28 cases (14.9%) were in disease stabilization (SD), and 33 cases (17.6%) were in disease progression (PD), with an objective remission rate (ORR) of 67.6% (127/188). Among 10 treatment-na?ve patients, 4 cases (40.0%) were in CR, 5 cases (50.0%) were in PR, and 1 case (10.0%) was in PD, with an ORR of 90.0% (9/10). The median follow-up time was 2.9 months (95% CI 2.4-3.7 months), and the median PFS and OS of patients in relapsed/refractory and treatment-na?ve groups were not reached. In relapsed/refractory patients, the difference in ORR between patients with different number of treatment lines of mitoxantrone hydrochloride liposome injection [ORR of the second-line, the third-line and ≥the forth-line treatment was 74.4% (67/90), 73.9% (34/46) and 50.0% (26/52)] was statistically significant ( P = 0.008). Of the 198 PTCL patients, 182 cases (91.9%) experienced at least 1 time of treatment-related adverse events, and the incidence rate of ≥grade 3 adverse events was 66.7% (132/198), which was mainly characterized by hematologic adverse events. The ≥ grade 3 hematologic adverse events mainly included decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, and anemia; non-hematologic adverse events were mostly grade 1-2, mainly including pigmentation disorders and upper respiratory tract infection. Conclusions:The use of mitoxantrone hydrochloride liposome injection-containing regimen in the treatment of PTCL has definite efficacy and is well tolerated, and it is a new therapeutic option for PTCL patients.
4.The application value of GeneXpert MTB/RIF Ultra in the detection of special specimens of tuberculosis
WU Xia ; YANG Yuanli ; LI Aifang ; ZHENG Huiqiang ; TAN Xiaowen ; GUI Xiaoli ; KANG Lei ; ZHOU Yong ; YANG Han ; LEI Jing
China Tropical Medicine 2023;23(8):846-
Abstract: Objective To compare the diagnostic efficacy of the upgraded version of the GeneXpert automated fluorescent quantitative PCR system (GeneXpert MTB/RIF Ultra, GeneXpert Ultra) and the original version of the GeneXpert system (GeneXpert MTB/RIF, Xpert), real-time fluorescent quantitative nucleic acid detection (FQ-PCR), real-time fluorescent thermostatic amplification of Mycobacterium tuberculosis RNA (SAT-RNA), real-time fluorescent thermostatic amplification detection of DNA (thermostatic amplification method) and traditional BACTEC MGIT 960 liquid culture (culture method) for special specimens of tuberculosis, in order to analyze its application value in clinical detection. Methods Using prospective research methods, a total of 170 special specimens (including 47 pleural and ascites effusion samples, and 34 24-hour urinary sediment specimens, 49 tissue specimens and 40 fester specimens) were collected i'an Chest Hospital from January to September 2021. GeneXpert Ultra, Xpert, FQ-PCR, SAT-RNA, isothermal amplification, and traditional culture were used for detection. Clinical diagnosis was used as the standard, and sensitivity, specificity, positive predictive value, negative predictive value, coincidence rate, and Kappa value were compared among the methods. Results The sensitivities of GeneXpert Ultra, Xpert, FQ-PCR, SAT-RNA, isothermal amplification, and traditional culture were 65.18% (73/112), 49.11% (55/112), 37.50% (42/112), 19.64% (22/112), 8.04% (9/112), and 22.32% (25/112), respectively. The sensitivity of GeneXpert Ultra was higher than that of the other five methods, and the differences were statistically significant (χ2=66.25, 42.10, 28.89, 13.09, 4.92, 15.18, all P<0.05). GeneXpert Ultra result analysis showed that: 5.48%(4/73) cases had trace, that is, trace Mycobacterium tuberculosis load, 79.45% (58/73) cases were extremely low, 10.96% (8/73) cases were low, 2.74% (2/73) were medium, , and 1.36% (1/73) were high load. In 4 trace samples, the Xpert detection was negative for all. Of the 73 GeneXpert Ultra positive reports, 63 were rifampicin-sensitive, 6 were rifampicin-resistant, and 4 were rifampicin-resistant but of unclear resistance. Of the 55 Xpert positive reports, 45 were rifampicin-sensitive, 2 were rifampicin-resistant, and 8 were rifampicinresistant but of unclear resistance.. Conclusions The new generation of GeneXpert MTB/RIF Ultra has high sensitivity, specificity and drug resistance detection rate, and its advantage is even more apparent in the pathogenic diagnosis of special
specimens of tuberculosis. It can be used as one of the preferred methods in samples with low bacterial load.
5.Molecular pathogenesis of acetaminophen-induced liver injury and its treatment options.
Xiaopeng CAI ; Huiqiang CAI ; Jing WANG ; Qin YANG ; Jun GUAN ; Jingwen DENG ; Zhi CHEN
Journal of Zhejiang University. Science. B 2022;23(4):265-285
Acetaminophen, also known as N-acetyl-p-aminophenol (APAP), is commonly used as an antipyretic and analgesic agent. APAP overdose can induce hepatic toxicity, known as acetaminophen-induced liver injury (AILI). However, therapeutic doses of APAP can also induce AILI in patients with excessive alcohol intake or who are fasting. Hence, there is a need to understand the potential pathological mechanisms underlying AILI. In this review, we summarize three main mechanisms involved in the pathogenesis of AILI: hepatocyte necrosis, sterile inflammation, and hepatocyte regeneration. The relevant factors are elucidated and discussed. For instance, N-acetyl-p-benzoquinone imine (NAPQI) protein adducts trigger mitochondrial oxidative/nitrosative stress during hepatocyte necrosis, danger-associated molecular patterns (DAMPs) are released to elicit sterile inflammation, and certain growth factors contribute to liver regeneration. Finally, we describe the current potential treatment options for AILI patients and promising novel strategies available to researchers and pharmacists. This review provides a clearer understanding of AILI-related mechanisms to guide drug screening and selection for the clinical treatment of AILI patients in the future.
Acetaminophen/toxicity*
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Analgesics, Non-Narcotic/toxicity*
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Animals
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Chemical and Drug Induced Liver Injury/pathology*
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Chemical and Drug Induced Liver Injury, Chronic/pathology*
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Humans
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Inflammation/metabolism*
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Liver/pathology*
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Mice
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Mice, Inbred C57BL
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Necrosis/pathology*
6.Bendamustine monotherapy for Chinese patient treatment with relapsed or refractory B cell non-Hodgkin lymphoma: a phase Ⅱ, prospective, multicenter, single-arm study
Yan GAO ; Yu YANG ; Hong CEN ; Hong LIU ; Jinxiang FU ; Shunqing WANG ; Ru FENG ; Ding YU ; Xinyou ZHANG ; Zhuowen CHEN ; Yufu LI ; Huiqiang HUANG
Chinese Journal of Hematology 2022;43(11):934-939
Objective:To evaluate the efficacy and safety of bendamustine monotherapy in Chinese patients with relapsed/refractory (R/R) B cell non-Hodgkin lymphoma (B-NHL) .Methods:This prospective, multicenter, open label, single-arm, phase Ⅱ study investigated bendamustine’s efficacy and safety in Chinese patients with R/R B-NHL. A total of 78 patients with B-NHL in 11 hospitals in China from March 2012 to December 2016 were included, and their clinical characteristics, efficacy, and survival were analyzed.Results:The median age of all patients was 58 (range, 24-76) years old, and 69 (88.4% ) patients had stage Ⅲ/Ⅳ disease. 61 (78.2% ) patients were refractory to previous treatments. Patients received a median of 4 (range, 1-10) cycles of bendamustine treatment. The overall response rate was 61.5 (95% CI 49.8-72.3) % , the median response duration was 8.3 (95% CI 5.5-14.0) months, and the complete remission (CR) rate was 5.1 (95% CI 1.4-12.6) % . In the full analysis set, median progression-free survival (PFS) and median OS were 8.7 (95% CI 6.7-13.2) months and 25.5 months (95% CI 14.2 months to not reached) , respectively, after a median follow-up of 33.6 (95% CI 17.4-38.8) months. Lymphopenia (74.4% ) , neutropenia (52.6% ) , and leukopenia (39.7% ) , thrombocytopenia (29.5% ) and anemia (15.4% ) were the most common grade 3-4 hematologic adverse events (AE) . The most frequent non-hematologic AEs included nausea (43.6% ) , vomiting (33.3% ) , and anorexia (29.5% ) . Univariate and multivariate analysis showed that <4 cycles of bendamustine treatment was a poor prognostic factor for PFS ( P=0.003) , and failure to accept fludarabine containing regimen was a poor prognostic factor for OS ( P=0.009) . Conclusion:Bendamustine monotherapy has good efficacy and safety in the treatment of patient with R/R B-NHL.
7.Repurposing carrimycin as an antiviral agent against human coronaviruses, including the currently pandemic SARS-CoV-2.
Haiyan YAN ; Jing SUN ; Kun WANG ; Huiqiang WANG ; Shuo WU ; Linlin BAO ; Weiqing HE ; Dong WANG ; Airu ZHU ; Tian ZHANG ; Rongmei GAO ; Biao DONG ; Jianrui LI ; Lu YANG ; Ming ZHONG ; Qi LV ; Feifei QIN ; Zhen ZHUANG ; Xiaofang HUANG ; Xinyi YANG ; Yuhuan LI ; Yongsheng CHE ; Jiandong JIANG
Acta Pharmaceutica Sinica B 2021;11(9):2850-2858
COVID-19 pandemic caused by SARS-CoV-2 infection severely threatens global health and economic development. No effective antiviral drug is currently available to treat COVID-19 and any other human coronavirus infections. We report herein that a macrolide antibiotic, carrimycin, potently inhibited the cytopathic effects (CPE) and reduced the levels of viral protein and RNA in multiple cell types infected by human coronavirus 229E, OC43, and SARS-CoV-2. Time-of-addition and pseudotype virus infection studies indicated that carrimycin inhibited one or multiple post-entry replication events of human coronavirus infection. In support of this notion, metabolic labelling studies showed that carrimycin significantly inhibited the synthesis of viral RNA. Our studies thus strongly suggest that carrimycin is an antiviral agent against a broad-spectrum of human coronaviruses and its therapeutic efficacy to COVID-19 is currently under clinical investigation.
8.A feasibility study of posterior fixation and fusion for brucellar spondylitis
Shengsen YANG ; Long CHANG ; Cheng FAN ; Haifeng YUAN ; Yongdong QIAO ; Haoning ZHAO ; Huiqiang DING
Chinese Journal of Orthopaedics 2021;41(20):1447-1458
Objective:To investigate the difference between simple posterior interbody fixation and fusion and posterior interbody fixation combined with focus debridement and bone graft fusion for the treatment of mono- and bi-segmental lumbar brucella spondylitis.Methods:A total of 63 patients (42 males and 21 females), aged 50.9±8.18 years (range from 38 to 69 years) with mono- and bi-segmental lumbar brucella spondylitis who received surgical treatment from June 2014 to Feb 2018 were retrospectively analyzed. There were 44 cases of mono-segmental and 19 cases of bi-segmental. Thirty-one cases were treated with single posterior interbody fixation and fusion (PIFF group), and 32 caseswere treated with posterior interbody fixation combined with focus debridement and bone graft fusion (debridement group). The main observation indicators include operation time, intraoperative blood loss, postoperative hospital stay, postoperative medication time, Visual Analogue Scale(VAS), Oswestry Disability Index (ODI), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Frankel score and clinical efficacy.Results:All of 63 patients were followed up for 27.16±6.07 months (range 15 to 38 months). The operation time of mono-segmental patients of PIFF group was 105.86±16.66 min,the intraoperative blood loss was 295.00±55.11 ml, and the postoperative hospitalization was 4.45±1.53 days, which was significantly shorter than debridement group ( P<0.001), while the postoperative medication time was without significant difference between the two groups ( P>0.05). The opration time of bi-segmental patients of PIFF group was 150.33±26.29 min, the intraoperative blood loss was 242.05±50.56 ml, and the postoperative hospitalization was 4.56±1.50 days, which was significantly shorter than debridement group ( P<0.001), while the postoperative medication time was also without significant difference between the two groups. At the last follow-up time, the VAS scores and ODI values of mono- and bi-segments in PIFF group and debridement group were lower than those preoperation, but there was no significant difference between the two groups ( P>0.05). There was no significant difference in CRP between mono-segments of PIFF group and debridement group at the preoperation, 3 months after operation and the last follow-up time ( P>0.05). The CRP in mono-segments of PIFF group and debridement group decreased at 3 months after the operation compared with that preoperation, and the difference was statistically significant ( P<0.001). There was no significant difference in CRP between bi-segments of PIFF group and debridement group at 3 months after operation and the last follow-up time ( P>0.05). There was no significant difference in ESR between mono- and bi-segments of PIFF group and debridement group at 3 months after operation and the last follow-up time ( P>0.05). There was significant difference in ESR between mono- and bi-segments of PIFF group and debridement group at the preoperation, 3 months after operation and the last follow-up time. There was no statistical difference in the proportion of excellent postoperative clinical efficacy between the two groups. Complications were observed in two patients in PIFF group (6.5%, 2/31) compared with 8 patients in debridement group (25%, 8/32, χ2=4.057, P=0.044). Conclusion:On the basis of standardized anti-brucella drug therapy, simple posterior interbody fixation and fusion for the treatment of brucella spondylitis has a satisfactory surgical effect, and has the advantages of less surgical trauma, shorter time, earlier postoperative movement time and fewer complications.
9.Synthesis and biological evaluation of 68Ga-NODAGA-GE11
Huiqiang LI ; Zhifei ZHEN ; Weifeng ZHANG ; Shuguang LIAO ; Ang XUAN ; Chang FU ; Yang YOU ; Yongju GAO ; Junling XU
Chinese Journal of Nuclear Medicine and Molecular Imaging 2021;41(11):676-679
Objective:To prepare 68Ga-2-(4, 7-bis(carboxymethyl)-1, 4, 7-triazonan-1-yl)pentanedioic acid (NODAGA)-YHWYGYTPQNVI (GE11) and evaluate its feasibility of PET imaging for pancreatic cancer. Methods:GE11 peptide was conjugated with NODAGA and then labeled with 68Ga. The labeling yield, radiochemical purity, hydrophilicity, stability and specificity in vitro were determined. Human pancreatic cancer BxPC3 nude mice models ( n=9) were established. MicroPET imaging was then obtained after 30 and 90 min, and mice were sacrificed at 90 min to acquire the radioactivity distribution of main organs and tumors. Pair t test was used to analyze the data. Results:The labeling yield was (73.5±5.4)% and radiochemical purity was more than 98%. After incubation 120 min in mouse serum at 37 ℃, radiochemical purity was more than 92%. The uptake was specific in BxPC3 cell lines. MicroPET images showed that 68Ga-NODAGA-GE11 could accumulate quickly in tumor. Value of tumor uptake was significantly higher than that of normal pancreas at 90 min ((1.38±0.25) vs (0.49±0.07) %ID/g; t=12.67, P<0.05), and the radio-uptake of blood, muscle and bone was lower than that of tumor. Conclusions:68Ga-NODAGA-GE11 is easy to be prepared with high radiochemical purity and good stability, and can specifically target BxPC3 xenograft tumor. However, due to the high uptake in the kidneys and liver, the value of 68Ga-NODAGA-GE11 in PET imaging for pancreatic tumor needs further study.
10.Clinical features and treatment outcome of extranodal nasal-type NK/T-cell lymphoma of the extra-upper aerodigestive tract
Yuting ZHAO ; Ying WANG ; Shunan QI ; Yong YANG ; Xia HE ; Yujing ZHANG ; Huiqiang HUANG ; Liling ZHANG ; Gang WU ; Baolin QU ; Liting QIAN ; Xiaorong HOU ; Fuquan ZHANG ; Xueying QIAO ; Hua WANG ; Gaofeng LI ; Yuan ZHU ; Jianzhong CAO ; Junxin WU ; Tao WU ; Suyu ZHU ; Mei SHI ; Liming XU ; Zhiyong YUAN ; Hang SU ; Yuqin SONG ; Jun ZHU ; Yexiong LI
Chinese Journal of Oncology 2021;43(7):787-794
Objective:To investigate the clinical features and prognosis of extranodal nasal-type NK/T-cell lymphoma of the extra-upper aerodigestive tract (extra-UADT NKTCL).Methods:The clinical data of 159 patients with extra-UADT NKTCL from the China Lymphoma Collaborative Group (CLCG) database between November 2001 and December 2015 were retrospectively analyzed. Kaplan-Meier survival analysis and Log-rank test were used to evaluate the prognosis. The Cox regression model is used for multi-factor analysis.Results:Extra-UADT NKTCL commonly occurs in skin and soft tissues (106/159, 66.7%) and gastrointestinal tract (31/159, 19.5%). The incidences of elevated lactate dehydrogenase (LDH) and Ann Arbor Ⅲ~Ⅳ stage were 47.8% (76/159) and 64.2% (102/159), respectively. The 3-year overall survival (OS) and progression-free survival (PFS) rates were 43.6% and 27.9%, respectively. The corresponding OS rates of primary skin/soft tissue site and gastrointestinal tract site were 41.0% and 59.4% ( P=0.281), while the PFS rates were 24.8% and 48.3%, respectively ( P=0.109). Combined modality treatment improved the 3-year OS of all the patients (58.4% vs 33.9%, P=0.001) and 3-year PFS (40.7% vs 20.7%, P=0.008) when compared with chemotherapy alone. LDH elevation, Ann Arbor synthesising and ≥2 junction external bits were intrusive as independent risk factors for total survival ( P<0.05), LDH elevation and ≥2 junction outer bits were intrusive as independent risk factors for progressionless survival( P<0.05). The distant extranodal dissemination was the primary failure patterns. Conclusions:Extra-UADT NKTCL appears to have distinct clinical characteristics and poor outcome. Compared with chemotherapy alone, combined modality treatment may improve the prognosis of patients with extra-UADT NKTCL.

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