1.Species-level Microbiota of Biting Midges and Ticks from Poyang Lake
Jian GONG ; Fei Fei WANG ; Qing Yang LIU ; Ji PU ; Zhi Ling DONG ; Hui Si ZHANG ; Zhou Zhen HUANG ; Yuan Yu HUANG ; Ben Ya LI ; Xin Cai YANG ; Meihui Yuan TAO ; Jun Li ZHAO ; Dong JIN ; Yun Li LIU ; Jing YANG ; Shan LU
Biomedical and Environmental Sciences 2024;37(3):266-277,中插1-中插3
Objective The purpose of this study was to investigate the bacterial communities of biting midges and ticks collected from three sites in the Poyang Lake area,namely,Qunlu Practice Base,Peach Blossom Garden,and Huangtong Animal Husbandry,and whether vectors carry any bacterial pathogens that may cause diseases to humans,to provide scientific basis for prospective pathogen discovery and disease prevention and control. Methods Using a metataxonomics approach in concert with full-length 16S rRNA gene sequencing and operational phylogenetic unit(OPU)analysis,we characterized the species-level microbial community structure of two important vector species,biting midges and ticks,including 33 arthropod samples comprising 3,885 individuals,collected around Poyang Lake. Results A total of 662 OPUs were classified in biting midges,including 195 known species and 373 potentially new species,and 618 OPUs were classified in ticks,including 217 known species and 326 potentially new species.Surprisingly,OPUs with potentially pathogenicity were detected in both arthropod vectors,with 66 known species of biting midges reported to carry potential pathogens,including Asaia lannensis and Rickettsia bellii,compared to 50 in ticks,such as Acinetobacter lwoffii and Staphylococcus sciuri.We found that Proteobacteria was the most dominant group in both midges and ticks.Furthermore,the outcomes demonstrated that the microbiota of midges and ticks tend to be governed by a few highly abundant bacteria.Pantoea sp7 was predominant in biting midges,while Coxiella sp1 was enriched in ticks.Meanwhile,Coxiella spp.,which may be essential for the survival of Haemaphysalis longicornis Neumann,were detected in all tick samples.The identification of dominant species and pathogens of biting midges and ticks in this study serves to broaden our knowledge associated to microbes of arthropod vectors. Conclusion Biting midges and ticks carry large numbers of known and potentially novel bacteria,and carry a wide range of potentially pathogenic bacteria,which may pose a risk of infection to humans and animals.The microbial communities of midges and ticks tend to be dominated by a few highly abundant bacteria.
2.Diagnostic concordance and influencing factors of quantitative flow fraction and fractional flow reserve
Rui-Tao ZHANG ; Peng-Xin XIE ; Zhen-Yu TIAN ; Lin MI ; Ji-Sheng ZHOU ; Ben-Zhen WU ; Li-Yun HE ; Li-Jun GUO
Chinese Journal of Interventional Cardiology 2024;32(9):481-488
Objective This study aimed to explore the diagnostic concordance of fractional flow reserve(FFR)and quantitative flow ratio(QFR)and the characteristics affecting this concordance.Methods Patients with non-acute myocardial infarction admitted to the Department of Cardiology,Peking University Third Hospital between January 2019 and December 2021 were enrolled.The patients were divided into four groups:FFR+/QFR+and FFR-/QFR-,FFR+/QFR-and FFR-/QFR+with FFR or QFR≤0.80 as positive and>0.80 as negative.Using FFR as the gold standard,the diagnostic value of QFR was analyzed,and differences in clinical features and pathological characteristics among the groups were compared.Results A total of 236 patients were included.The mean age was(64.48±9.63)years,and 67.8%were male.All patients had 30%-70%coronary stenosis.The consistency rate of QFR and FFR was 78.0%(n=184),and the Person correlation coefficient was 0.557(P<0.001).Among FFR+patients,the minimum lumen diameter was larger[(1.56±0.34)mm vs.(1.39±0.31)mm,P=0.019],lesion length was shorter[(21.37±11.73)mm vs.(36.86±18.09)mm,P<0.001],and coronary angiography-based index of microcirculartory resistance(AMR)was higher[(277.50±28.87)mmHg·s/m vs.(178.02±49.13)mmHg·s/m,P<0.001]in the disconcordance group.Multivariate regression analysis suggested that AMR[OR 0.93,95%CI 0.88-0.99,P=0.030]and lesion length[OR 1.27,95%CI 1.01-1.60,P=0.045]were independent predictors of disconcordance.In the FFR-group,the lesion length was longer[(33.08±16.05)mm vs.(21.40±13.36)mm,P=0.020],and AMR[(169.66±24.01)mmHg·s/m vs.(265.95±44.78)mmHg·s/m,P<0.001]and low-density lipoprotein-C[1.57(1.10,1.97)mmol/L vs.2.15(1.79,2.74)mmol/L,P=0.031]were lower in the disconcordance group.No statistically significant variables were identified by multivariate regression.Conclusions QFR had high diagnostic value compared with FFR.In the FFR+group,AMR and lesion length may have affected the diagnostic consistency of QFR and FFR.The study provided more evidence for the clinical application of QFR.
3.Progress in understanding of the effects of Listeria monocytogenes infection on maternal pregnancy in humans and ruminants
Kang-Li LI ; Ben LIU ; Wei-Hua ZHOU
Chinese Journal of Zoonoses 2024;40(7):656-661
Listeria monocytogenes(LM)is a parthenogenetic intracellular parasitic Gram-positive short bacillus that causes listeriosis in humans and animals.LM is considered one of the four major food pathogens in the world.Infection susceptibility during pregnancy is due to pregnancy-associated immunodeficiency and LM's tropism toward reproductive organs.LM infection in pregnancy is strongly associated with miscarriage,preterm labor,and neonatal complications.This article describes events related to LM infection in pregnancy in China and other countries;discusses recent advances in the diagnosis and treatment of listeriosis in detail;and focuses on the obstetric outcomes of LM infection in pregnancy.The aim of this article is to provide a reference for the future prevention and control of LM infection in pregnancy in humans and ruminants,as well as to support food safety.
4.Neoadjuvant chemotherapy in the treatment of locally advanced olfactory neuroblastoma in 25 cases.
Yan SUN ; Shu Rong ZHANG ; Ming Jie WANG ; Qian HUANG ; Shun Jiu CUI ; Ben Tao YANG ; E QIU ; Cheng LI ; Bing ZHOU
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2023;58(5):425-430
Objective: To evaluate the efficacy of neoadjuvant chemotherapy (NACT) in the treatment of locally advanced olfactory neuroblastoma (ONB), and to explore the factors related to the efficacy of NACT. Methods: A total of 25 patients with ONB who underwent NACT in Beijing TongRen Hospital from April 2017 to July 2022 were retrospectively analyzed. There were 16 males and 9 females, with an average age of 44.9 years (ranged 26-72 years). There were 22 cases of Kadish stage C and 3 cases of stage D. After multiple disciplinary team(MDT) discussion, all patients were treated sequentially with NACT-surgery-radiotherapy. Among them, 17 cases were treated with taxol, cis-platinum and etoposide (TEP), 4 cases with taxol, nedaplatin and ifosfamide (TPI), 3 cases with TP, while 1 case with EP. SPSS 25.0 software was used for statistical analysis, and survival analyses were calculated based on the Kaplan-Meier method. Results: The overall response rate of NACT was 32% (8/25). Subsequently, 21 patients underwent extended endoscopic surgery and 4 patients underwent combined cranial-nasal approach. Three patients with stage D disease underwent cervical lymph node dissection. All patients received postoperative radiotherapy. The mean follow-up time was 44.2 months (ranged 6-67 months). The 5-year overall survival rate was 100.0%, and the 5-year disease-free survival rates was 94.4%. Before NACT, Ki-67 index was 60% (50%, 90%), while Ki-67 index was 20% (3%, 30%) after chemotherapy [M (Q1, Q3)]. The change of Ki-67 before and after NACT was statistically significant (Z=-24.24, P<0.05). The effects of age, gender, history of surgery, Hyams grade, Ki-67 index and chemotherapy regimen to NACT were analyzed. Ki-67 index≥25% and high Hyams grade were related to the efficacy of NACT (all P<0.05). Conclusions: NACT could reduce Ki-67 index in ONBs. High Ki-67 index and Hyams grade are clinical indicators sensitive to the efficacy of NACT. NACT-surgery-radiotherapy is effective for patients with locally advanced ONB.
Male
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Female
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Humans
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Adult
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Middle Aged
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Aged
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Neoadjuvant Therapy/methods*
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Retrospective Studies
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Esthesioneuroblastoma, Olfactory/etiology*
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Ki-67 Antigen
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Paclitaxel
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Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
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Nasal Cavity
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Nose Neoplasms/therapy*
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Neoplasm Staging
5.Clinical treatment outcomes and their changes in extremely preterm twins: a multicenter retrospective study in Guangdong Province, China.
Bi-Jun SHI ; Ying LI ; Fan WU ; Zhou-Shan FENG ; Qi-Liang CUI ; Chuan-Zhong YANG ; Xiao-Tong YE ; Yi-Heng DAI ; Wei-Yi LIANG ; Xiu-Zhen YE ; Jing MO ; Lu DING ; Ben-Qing WU ; Hong-Xiang CHEN ; Chi-Wang LI ; Zhe ZHANG ; Xiao RONG ; Wei SHEN ; Wei-Min HUANG ; Bing-Yan YANG ; Jun-Feng LYU ; Hui-Wen HUANG ; Le-Ying HUO ; Hong-Ping RAO ; Wen-Kang YAN ; Xue-Jun REN ; Yong YANG ; Fang-Fang WANG ; Dong LIU ; Shi-Guang DIAO ; Xiao-Yan LIU ; Qiong MENG ; Yu WANG ; Bin WANG ; Li-Juan ZHANG ; Yu-Ge HUANG ; Dang AO ; Wei-Zhong LI ; Jie-Ling CHEN ; Yan-Ling CHEN ; Wei LI ; Zhi-Feng CHEN ; Yue-Qin DING ; Xiao-Yu LI ; Yue-Fang HUANG ; Ni-Yang LIN ; Yang-Fan CAI ; Sha-Sha HAN ; Ya JIN ; Guo-Sheng LIU ; Zhong-He WAN ; Yi BAN ; Bo BAI ; Guang-Hong LI ; Yue-Xiu YAN
Chinese Journal of Contemporary Pediatrics 2022;24(1):33-40
OBJECTIVES:
To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China.
METHODS:
A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups.
RESULTS:
Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05).
CONCLUSIONS
There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.
Bronchopulmonary Dysplasia/epidemiology*
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Female
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Gestational Age
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Humans
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Infant
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Infant, Extremely Premature
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Infant, Newborn
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Pregnancy
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Respiratory Distress Syndrome, Newborn/epidemiology*
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Retrospective Studies
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Treatment Outcome
6.Comparison of the efficacy of IA and HAD induction regimens in the treatment of patients with newly diagnosed acute myeloid leukemia: a single-center study.
Cong Xiao ZHANG ; Shao Wei QIU ; Ben Fa GONG ; Xiao Yuan GONG ; Yan LI ; Yun Tao LIU ; Qiu Yun FANG ; Guang Ji ZHANG ; Kai Qi LIU ; Chun Lin ZHOU ; Shu Ning WEI ; Dong LIN ; Bing Cheng LIU ; Ying WANG ; Ying Chang MI ; Hui WEI ; Jian Xiang WANG
Chinese Journal of Hematology 2022;43(5):383-387
Objective: To compare the efficacy of two induction regimens, namely, idarubicin combined with cytarabine (IA) versus the combination of homoharringtonine, daunorubicin, and cytarabine (HAD) , in adult patients with newly diagnosed de novo acute myeloid leukemia (AML) . Methods: From May 2014 to November 2019, 199 patients diagnosed with AML receiving either the IA or HAD regimens were assessed for overall survival (OS) , relapse-free survival (RFS) , as well as the CR rate and the MRD negative rate after induction therapy. The differences in prognosis between the two induction therapy groups was assessed according to factors, including age, white blood cell (WBC) count, NPM1 mutation, FLT3-ITD mutation, 2017 ELN risk stratification, CR(1) transplantation, and the use of high-dose cytarabine during consolidation therapy, etc. Results: Among the 199 patients, there were 104 males and 95 females, with a median age of 37 (15-61) years. Ninety patients received the IA regimen, and 109 received the HAD regimen. Comparing the efficacy of the IA and HAD regimens, the CR rates after the first induction therapy were 71.1% and 63.3%, respectively (P=0.245) , and the MRD negative rates after the first induction therapy were 53.3% and 48.6%, respectively (P=0.509) . One patient in the IA group and two in the HAD group died within 60 days after induction. The two-year OS was 61.5% and 70.6%, respectively (P=0.835) , and the two-year RFS was 51.6% and 57.8%, respectively (P=0.291) . There were no statistically significant differences between the two groups. Multivariate analysis showed that the ELN risk stratification was an independent risk factor in both induction groups; CR(1) HSCT was an independent prognostic factor for OS and RFS in the IA patients and for RFS in the HAD patients but not for OS in the HAD patients. Age, WBC level, NPM1 mutation, and FLT3-ITD mutation had no independent prognostic significance. Conclusion: The IA and HAD regimens were both effective induction regimens for AML patients.
Adolescent
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Adult
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Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
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Cytarabine/therapeutic use*
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Daunorubicin/therapeutic use*
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Female
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Homoharringtonine/therapeutic use*
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Humans
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Induction Chemotherapy
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Leukemia, Myeloid, Acute/genetics*
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Male
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Middle Aged
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Nuclear Proteins
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Prognosis
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Remission Induction
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Retrospective Studies
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Young Adult
7.Efficacy and safety of IAC regimen for relapse/refractory acute myeloid leukemia: a prospective randomized controlled study.
Chun Hong LI ; Shu Ning WEI ; Shao Wei QIU ; Ben Fa GONG ; Xiao Yuan GONG ; Yan LI ; Yun Tao LIU ; Qiu Yun FANG ; Guang Ji ZHANG ; Kai Qi LIU ; Chun Lin ZHOU ; Dong LIN ; Bing Cheng LIU ; Ying WANG ; Ying Chang MI ; Hui WEI ; Jian Xiang WANG
Chinese Journal of Hematology 2022;43(4):287-292
Objective: To evaluate the efficacy and toxicity profiles of idarubicin, cytarabine, and cyclophosphamide (IAC) in relapse/refractory acute myeloid leukemia (AML) . Methods: This study was a prospective, randomized controlled clinical trial with the registration number NCT02937662. The patients were randomly divided into two groups. The experimental group was treated with an IAC regimen, and the regimen of the control group was selected by doctors according to medication experience. After salvage chemotherapy, allogeneic hematopoietic stem cell transplantation (allo-HSCT) was conducted as far as possible according to the situation of the patients. We aimed to observe the efficacy, safety, and toxicity of the IAC regimen in relapse/refractory AML and to explore which is the better regimen. Results: Forty-two patients were enrolled in the clinical trial, with a median age of 36 years (IAC group, 22 cases and control groups, 20 cases) . ①The objective response rate was 71.4% in the IAC group and 40.0% in the control group (P=0.062) ; the complete remission (CR) rate was 66.7% in the IAC group and 40.0% in the control group (P=0.121) . The median follow-up time of surviving patients was 10.5 (range:1.7-32.8) months; the median overall survival (OS) was 14.1 (range: 0.6-49.1) months in the IAC group and 9.9 (range: 2.0-53.8) months in the control group (P=0.305) . The 1-year OS was 54.5% (95%CI 33.7%-75.3%) in the IAC group and 48.2% (95%CI 25.9%-70.5%) in the control group (P=0.305) , with no significant difference between these two regimens. ②The main hematologic adverse events (AEs) were anemia, thrombocytopenia, and neutropenia. The incidence of grade 3-4 hematologic AEs in the two groups was 100% (22/22) in the IAC group and 95% (19/20) in the control group. The median time of neutropenia after chemotherapy in the IAC group and control group was 20 (IQR: 8-30) and 14 (IQR: 5-50) days, respectively (P=0.023) . ③The CR rate of the early relapse (relapse within 12 months) group was 46.7% and that of the late relapse (relapse after 12 months) group was 72.7% (P=0.17) . The median OS time of early recurrence was 9.9 (range:1.7-53.8) months, and that of late recurrence patients was 19.3 (range: 0.6-40.8) months (P=0.420) , with no significant differences between the two groups. The 1-year OS rates were 45.3% (95%CI 27.2%-63.3%) and 66.7% (95%CI 40.0%-93.4%) , respectively (P=0.420) . Survival analysis showed that the 1-year OS rates of the hematopoietic stem cell transplantation group and non-hematopoietic stem cell transplantation group were 87.5% (95%CI 71.2%-100%) and 6.3% (95%CI 5.7%-18.3%) , respectively. The OS rate of the hematopoietic stem cell transplantation group was significantly higher than that of the non-hematopoietic stem cell transplantation group (P<0.001) . Conclusion: The IAC regimen is a well-tolerated and effective regimen in relapsed/refractory AML; this regimen had similar efficacy and safety with the regimen selected according to the doctor's experience for treating relapsed/refractory AML. For relapsed/refractory patients with AML, allogeneic hematopoietic stem cell transplantation should be attempted as soon as possible to achieve long-term survival.
Adult
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Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
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Cyclophosphamide/therapeutic use*
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Cytarabine/therapeutic use*
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Hematopoietic Stem Cell Transplantation
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Humans
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Idarubicin/therapeutic use*
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Leukemia, Myeloid, Acute/drug therapy*
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Neutropenia
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Prospective Studies
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Recurrence
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Retrospective Studies
8.Diagnostic efficacy of indirect haemagglutination assay for detection of Schistosoma japonicum infections among boatmen and fishermen in the Dongting Lake region.
Zhong Qiu MEI ; Ting ZENG ; Xin Ting CAI ; Ben Jiao HU ; Sheng Ming LI ; Jie ZHOU ; Tie Wu JIA
Chinese Journal of Schistosomiasis Control 2022;34(3):300-306
OBJECTIVE:
To evaluate the diagnostic efficacy of indirect haemagglutination assay (IHA) for detection of Schistosoma japonicum infections among boatmen and fishermen in Dongting Lake region, so as to provide insights into improving the schistosomiasis surveillance program among boatmen and fishermen.
METHODS:
The boatmen and fishermen were detected for S. japonicum infections using IHA and Kato-Katz technique or miracidium hatching test nylon gauze simultaneously at schistosomiasis testing sites in the anchor sites for boatmen and fishermen in the Dongting Lake region during the period from 2014 to 2016, and using IHA for serological screening followed by parasitological testing of seropositives during the period from 2017 to 2019. The sensitivity and specificity of IHA were evaluated for detection of S. japonicum infections among boatmen and fishermen, with the 2014-2016 parasitological testing results as a gold standard. In addition, the seroprevalence of S. japonicum infections was compared among boatmen and fishermen with different characteristics and among years.
RESULTS:
A total of 306 schistosomiasis testing sites were assigned for boatmen and fishermen, and a total of 143 360 person-time boatmen and fishermen were tested for S. japonicum infections in the Dongting Lake region from 2014 to 2019. The sensitivity and specificity of IHA were 69.9%, 97.3% and 96.1% (χ2 = 74.6, P < 0.05), and 70.9%, 74.5% and 71.9% for detection of S. japonicum infections from 2014 to 2016 (χ2 = 29.4, P < 0.05), respectively. The seroprevalence of S. japonicum infections reduced from 30.3% in 2014 to 1.8% in 2019 among boatmen and fishermen, appearing an overall tendency towards a decline (Z = 1 552.4, P < 0.05). In addition, male, individuals at ages of 45 to 60 years, full-time boatmen and fishermen were more likely to be seropositive for S. japonicum infections (all P values < 0.05).
CONCLUSIONS
The seroprevalence of S. japonicum infections appeared a tendency towards a decline among boatmen and fishermen in the Dongting Lake region year by year from 2014 to 2019. IHA presented a high efficacy for screening of S. japonicum infections among boatmen and fishermen in the Dongting Lake region.
Animals
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China/epidemiology*
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Hemagglutination
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Humans
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Lakes
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Male
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Middle Aged
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Prevalence
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Schistosoma japonicum
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Schistosomiasis/epidemiology*
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Schistosomiasis japonica/prevention & control*
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Seroepidemiologic Studies
9.Efficacy and safety study of Chinese botulinum toxin A 100U in patients with overactive bladder: a prospective, multicenter, double-blind and randomized controlled trial
Limin LIAO ; Huiling CONG ; Zhihui XU ; Enhui LI ; Zhiliang WENG ; Haihong JIANG ; Ben LIU ; Xiao HUANG ; Shujie XIA ; Wei WEN ; Juan WU ; Guowei SHI ; Yang WANG ; Peijun LI ; Yang YU ; Zujun FANG ; Jie ZHENG ; Ye TIAN ; Haodong SHANG ; Hanzhong LI ; Zhongming HUANG ; Liqun ZHOU ; Yunxiang XIAO ; Yaoguang ZHANG ; Jianlong WANG ; Xiaodong ZHANG ; Peng ZHANG ; Dongwen WANG ; Xuhui ZHANG ; Keji XIE ; Bin WANG ; Lulin MA ; Xiaojun TIAN ; Lijun CHEN ; Jinkai DONG
Chinese Journal of Urology 2021;42(6):414-422
Objective:To assess the efficacy and safety of 100 units of botulinum toxin A (BTX-A) intradetrusor injection in patients with overactive bladder.Methods:From April 2016 to December 2018, 17 tertiary hospitals were selected to participate in this prospective, multicenter, randomized, double-blind, placebo-controlled study. Two phases of study were conducted: the primary phase and the extended phase. This study enrolled patients aged 18 to 75 years who had been inadequately managed by anticholinergic therapy (insufficient efficacy or intolerable side effects) and had spontaneous voiding with overactive bladder. Exclusion criteria included patients with severe cardiac, renal and hepatic disorders, patients with previous botulinum toxin treatment for 6 months or allergic to BTX-A, patients with urinary tract infections, patients with urinary stones, urinary tract tumors, diabetes mellitus, and bleeding tendency. Eligible patients were randomly assigned to BTX-A group and placebo control group in a ratio of 2∶1. Two groups of patients received 20 intradetrusor injections of BTX-A 100U or placebo at the depth of the submucosal muscle layer respectively under cystoscope, including 5 injections at the base of the bladder, 3 injections to the bladder triangle, 5 injections each to the left and right walls and 2 injections to the top, sparing the bladder neck. As a placebo control group, patients received same volume of placebo containing no BTX-A and only adjuvant freeze-dried preparations for injection with the same method. A combination of gelatin, sucrose, and dextran served as adjuvants. Average micturition times per 24 hours, urinary incontinence (UI) episodes per day, average micturition volume per day, OAB symptom score(OABSS), and quality of life (QOL) score were recorded at baseline and the 2nd, 6th and 12th week after treatment. The primary efficacy endpoint was the change from baseline in the average micturition times per 24 hours at the 6th week after treatment. The secondary efficacy endpoints included the change from baseline in the average micturition times per 24 hours at 2nd and 12th week, as well as the change from baseline in the OABSS, QOL score, average frequency of urgency and UI episodes per day, urgency score, average micturition volume per day at 2nd, 6th and 12th week after treatment. Patients were followed for 12 weeks to assess adverse events (AEs). After assessed at week 12, if the micturition times has decreased less than 50% compared to baseline and the patient is willing to receive retreatment, then patients could enter the extended trial phase. In that phase, patients in both groups were injected with 100 units BTX-A from 12th week onwards and then followed up the same indicators for 12 weeks.Results:216 patients were enrolled in this trial (144 cases in the BTX-A group and 72 cases in the placebo control group). Baseline characteristics such as age (47.75±14.20 in the BTX-A group and 46.39±15.55 in the control group), sex (25 male/117 female in the BTX-A group and 10/61 in the control group), and disease duration (0.51 years in the BTX-A group and 0.60 years in the control group) were balanced between the two groups( P>0.05). A marked reduction from baseline in average micturition times per 24 hours was observed in all treatment groups at the 6th week and the reduction of the two groups was statistically different ( P<0.001 and P=0.008 respectively). Compared with the baseline, the average micturition times per 24 hours at the 6th week decreased from baseline by 2.40(0.70, 4.60)times for the BTX-A group and 0.70(-1.00, 3.30) times for the placebo control group respectively, and the difference between the two groups was considered to be statistically significant ( P=0.003). The change rates of average micturition times per 24 hours from baseline at the 6th week of the two groups were (16±22)% and (8±25)% respectively, and the difference between the two groups was statistically significant ( P=0.014). Compared with the baseline, the average micturition times per 24 hours at 2nd and 12th week decreased by 2.00(0.00, 4.00)and 3.30(0.60, 5.03)for the BTX-A group, 1.00(-1.00, 3.00)and 1.70(-1.45, 3.85)for the placebo control group respectively. The difference between two groups was considered to be statistically significant ( P=0.038 and P=0.012); the changes of average urgency times per day for the BTX-A group and the control group at the 2nd, 6th and 12th week were 2.00(0.00, 4.30)and 2.40(0.30, 5.00), 3.00(0.30, 5.70)and 0.70(-1.30, 2.70), 0.70(-1.30, 3.00) and 1.35(-1.15, 3.50), respectively. There were significant differences between two groups at the 2nd, 6th and 12th week, ( P=0.010, P=0.003 and P=0.025, respectively). The OABSS of the BTX-A group and the control group at the 6th week decreased by 1.00(0.00, 4.00)and 0.50(-1.00, 2.00) compared with the baseline, and the difference between the two groups was statistically significant ( P=0.003). 47 cases of BTX-A group and 34 cases of placebo control group entered the extended trial phase, and 40 and 28 cases completed the extended trial phase, respectively. The average micturition volume per 24 hours changed by -16.60(-41.60, -0.60)ml and -6.40(-22.40, 13.30)ml, (-35.67±54.41)ml and(-1.76±48.69)ml, (-36.14±41.51)ml and (-9.28±44.59)ml, (-35.85±43.35)ml and(-10.41±40.29)ml for two groups at the 12th, 14th, 18th and 24th week, and the difference between two groups was statistically significant at each follow-up time ( P=0.01, 0.006, 0.012 and 0.016, respectively). There was no significant difference in other parameters( P>0.05). However, adverse reactions after intradetrusor injection included increased residual urine volume (27 in the BTX-A group and 3 in the control group), dysuria (21 in the BTX-A group and 6 in the control group), urinary infection (19 in the BTX-A group and 6 in the control group), bladder neck obstruction (3 in the BTX-A group and 0 in the control group), hematuria (3 in the BTX-A group and 1 in the control group), elevated alanine aminotransferase (3 in the BTX-A group and 0 in the control group), etc. During the follow-up period, there was no significant difference in the other adverse events between two groups except the increase of residual urine volume( P<0.05). In the primary trial phase, among the 27 cases with increased residual urine volume in BTA group, only 1 case (3.70%) with PVR more than 300 ml; the PVR of 3 patients in the placebo group was less than 100 ml. The increase of residual urine volume caused by the injection could be improved or disappeared with the passage of time. Conclusions:Intradetrusor injection of Chinese BTX-A improved the average micturition times per 24 hours, the average daily urgent micturition times, OABSS, and average micturition volume per time, and reduced the adverse effects in patients with overactive bladder.Chinese BTX-A at dose of 100U demonstrated durable efficacy and safety in the management of overactive bladder.
10. Study on rat small intestinal absorption characteristics of gallic acid based on single-pass perfusion model
Zhen-Zhen CHENG ; Ben-Hong ZHOU ; Shan JIANG ; Dan JIN ; Zhen-Zhen CHENG ; Ben-Hong ZHOU ; Kuang-Yu LI
Chinese Pharmacological Bulletin 2021;37(5):669-673
Aim To investigate the absorption characteristics of gallic acid in the intestine, and to provide a theoretical basis for improving the bioavailability of tannins. Methods Single-pass intestinal perfusion (SPIP) model was used for rat in situ and HPLC to determine the concentration of gallic acid. The absorption rate constant Ka and effective apparent permeability coefficient Peff of gallic acid in each intestinal segment were calculated. The effects of different intestinal segments, drug concentrations, pH value, P-glycoprotein (P-gp), and multidrug resistance protein2 (MRP2) on intestinal absorption were assessed. Results The absorption rate constant (Ka) of gallic acid decreased following the sequence of jejunum > duodenum > ileum ≈ colon. With the increase of drug concentration, there was no significant difference in the absorption of gallic acid. The acidic environment (pH 5. 5) was conducive to the absorption of gallic acid. After the addition of P-gp and MRP2 inhibitors, the absorption of gallic acid was significantly different from that without P-gp and MRP2 inhibitors (P < 0. 05). Conclusions Gallic acid can be well absorbed in the intestine of rats, and is best absorbed in jejunum. The absorption mechanism is determined to be passive diffusion. The gallic acid absorption process is affected by the efflux of P-gp and MRP2, which may be the P-gp and MRP2 substrates.

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