1.Targeted inhibition of Gus-expressing Enterococcus faecalis to promote intestinal stem cell and epithelial renovation contributes to the relief of irinotecan chemotoxicity by dehydrodiisoeugenol.
Ruiyang GAO ; Bei YUE ; Cheng LV ; Xiaolong GENG ; Zhilun YU ; Hao WANG ; Beibei ZHANG ; Fangbin AI ; Ziyi WANG ; Donghui LIU ; Zhengtao WANG ; Kaixian CHEN ; Wei DOU
Acta Pharmaceutica Sinica B 2024;14(12):5286-5304
Irinotecan (CPT11) chemotherapy-induced diarrhea affects a substantial cancer population due to β-glucuronidase (Gus) converting 10-O-glucuronyl-7-ethyl-10-hydroxycamptothecin (SN38G) to toxic 7-ethyl-10-hydroxycamptothecin (SN38). Existing interventions primarily address inflammation and Gus enzyme inhibition, neglecting epithelial repair and Gus-expressing bacteria. Herein, we discovered that dehydrodiisoeugenol (DDIE), isolated from nutmeg, alleviates CPT11-induced intestinal mucositis alongside a synergistic antitumor effect with CPT11 by improving weight loss, colon shortening, epithelial barrier dysfunction, goblet cells and intestinal stem cells (ISCs) loss, and wound-healing. The anti-mucositis effect of DDIE is gut microbiota-dependent. Analysis of microbiome profiling data from clinical patients and CPT11-induced mucositis mice reveals a strong correlation between CPT11 chemotoxicity and Gus-expressing bacteria, particularly Enterococcus faecalis (E. faecalis). DDIE counters CPT11-induced augmentation of E. faecalis, leading to decreased intestinal Gus and SN38 levels. The Partial Least Squares Path Model (PLS-PM) algorithm initially links E. faecalis to dysregulated epithelial renovation. This is further validated in a 3D intestinal organoid model, in which both SN38 and E. faecalis hinder the formation and differentiation of organoids. Interestingly, colonization of E. faecalis exacerbates CPT11-induced mucositis and disturbs epithelial differentiation. Our study unveils a microbiota-driven, epithelial reconstruction-mediated action of DDIE against mucositis, proposing the 'Gus bacteria-host-irinotecan axis' as a promising target for mitigating CPT11 chemotoxicity.
2.Construction of AQHI based on joint effects of multi-pollutants in 5 provinces of China
Jinghua GAO ; Chunliang ZHOU ; Jianxiong HU ; Ruilin MENG ; Maigeng ZHOU ; Zhulin HOU ; Yize XIAO ; Min YU ; Biao HUANG ; Xiaojun XU ; Tao LIU ; Weiwei GONG ; Donghui JIN ; Mingfang QIN ; Peng YIN ; Yiqing XU ; Guanhao HE ; Xianbo WU ; Weilin ZENG ; Wenjun MA
Journal of Environmental and Occupational Medicine 2023;40(3):281-288
Background Air pollution is a major public health concern. Air Quality Health Index (AQHI) is a very important air quality risk communication tool. However, AQHI is usually constructed by single-pollutant model, which has obvious disadvantages. Objective To construct an AQHI based on the joint effects of multiple air pollutants (J-AQHI), and to provide a scientific tool for health risk warning and risk communication of air pollution. Methods Data on non-accidental deaths in Yunnan, Guangdong, Hunan, Zhejiang, and Jilin provinces from January 1, 2013 to December 31, 2018 were obtained from the corresponding provincial disease surveillance points systems (DSPS), including date of death, age, gender, and cause of death. Daily meteorological (temperature and relative humidity) and air pollution data (SO2, NO2, CO, PM2.5, PM10, and maximum 8 h O3 concentrations) at the same period were respectively derived from China Meteorological Data Sharing Service System and National Urban Air Quality Real-time Publishing Platform. Lasso regression was first applied to select air pollutants, then a time-stratified case-crossover design was applied. Each case was matched to 3 or 4 control days which were selected on the same days of the week in the same calendar month. Then a distributed lag nonlinear model (DLNM) was used to estimate the exposure-response relationship between selected air pollutants and mortality, which was used to construct the AQHI. Finally, AQHI was classified into four levels according to the air pollutant guidance limit values from World Health Organization Global Air Quality Guidelines (AQG 2021), and the excess risks (ERs) were calculated to compare the AQHI based on single-pollutant model and the J-AQHI based on multi-pollutant model. Results PM2.5, NO2, SO2, and O3 were selected by Lasso regression to establish DLNM model. The ERs for an interquartile range (IQR) increase and 95% confidence intervals (CI) for PM2.5, NO2, SO2 and O3 were 0.71% (0.34%–1.09%), 2.46% (1.78%–3.15%), 1.25% (0.9%–1.6%), and 0.27% (−0.11%–0.65%) respectively. The distribution of J-AQHI was right-skewed, and it was divided into four levels, with ranges of 0-1 for low risk, 2-3 for moderate risk, 4-5 for high health risk, and ≥6 for severe risk, and the corresponding proportions were 11.25%, 64.61%, 19.33%, and 4.81%, respectively. The ER (95%CI) of mortality risk increased by 3.61% (2.93–4.29) for each IQR increase of the multi-pollutant based J-AQHI , while it was 3.39% (2.68–4.11) for the single-pollutant based AQHI . Conclusion The J-AQHI generated by multi-pollutant model demonstrates the actual exposure health risk of air pollution in the population and provides new ideas for further improvement of AQHI calculation methods.
3.Design and practice of general population cohort study in northeastern China
Hehua ZHANG ; Qing CHANG ; Qijun WU ; Yang XIA ; Shanyan GAO ; Yixiao ZHANG ; Yuan YUAN ; Jing JIANG ; Hongbin QIU ; Jing LI ; Chunming LU ; Chao JI ; Xin XU ; Donghui HUANG ; Huixu DAI ; Zhiying ZHAO ; Xing LI ; Xiaoying LI ; Xiaosong QIN ; Caigang LIU ; Xiaoyu MA ; Xinrui XU ; Da YAO ; Huixin YU ; Yuhong ZHAO
Chinese Journal of Epidemiology 2023;44(1):21-27
In 2016, a national one million general population cohort project was set up in China for the first time in "Precision Medicine Research" Key Project, National Key Research and Development Program of China, which consists of general population cohorts in seven areas in China. As one of the seven major areas in China, northeastern China has unique climate and specific dietary patterns, and population aging is serious in this area. And the burden of chronic and non-communicable diseases ranks tops in China. Therefore, it is of great significance to establish a large general population cohort in northeastern China to explore the area specific exposure factors related to pathogenesis and prognosis of chronic and non-communicable diseases, develop new prevention strategies to reduce the burden of the diseases and improve the population health in northeastern China. In July 2018, the general population cohort study in northeastern China was launched, the study includes questionnaire survey, health examination and blood, urine and stool sample collection and detection in recruited participants. By now, the cohort has covered all age groups, and the baseline data of 115 414 persons have been collected. This paper summarizes the design and practice of the general population cohort study in northeastern China to provide reference for related research in China.
4.Clinical efficacy and optimal dose of apatinib combined with chemotherapy in patients with advanced non-small cell lung cancer
Shile GAO ; Donghui LU ; Meiqin LIU ; Xingjun XU ; Huan MA ; Yu ZHANG
Journal of International Oncology 2022;49(3):140-145
Objective:To explore the clinical efficacy of different doses of apatinib combined with chemotherapy in patients with advanced non-small cell lung cancer (NSCLC) and the adverse reactions.Methods:A total of 69 patients with NSCLC diagnosed in the No. 901 Hospital of the Chinese People′s Liberation Army Joint Logistics Support Force were selected from January 2018 to June 2020, and were divided into chemotherapy alone group (docetaxel+ cisplatin was used), apatinib group A [apatinib (0.25 g)+ docetaxel+ cisplatin was used] and apatinib group B [apatinib (0.50 g)+ docetaxel+ cisplatin was used] according to random number table method, with 23 cases in each group. The objective response rate (ORR), disease control rate (DCR), median overall survival (OS), median progression-free survival (PFS), and incidences of adverse reactions were compared between the three groups of patients.Results:One patients in the apatinib group B withdrew from the study due to acute myocardial infarction. After 4 cycless of treatment, the ORR of the patients in the chemotherapy alone group, apatinib group A and apatinib group B were 17.39% (4/23), 47.83% (11/23) and 54.55% (12/22) respectively, with a statistically significant difference ( χ2=7.41, P=0.024). The ORR of the apatinib group B was higher than that of the chemotherapy alone group, with a statistically significant difference ( χ2=6.77, P=0.009). There were no statistically significant differences in ORR between the apatinib group A and chemotherapy alone group, the apatinib group A and apatinib group B ( χ2=4.85, P=0.028; χ2=0.20, P=0.652). The DCR of the patients in the three groups were 47.83% (11/23), 78.26% (18/23) and 86.36% (19/22) respectively, with a statistically significant difference ( χ2=9.03, P=0.011). The DCR of the apatinib group B was higher than that of the chemotherapy alone group, with a statistically significant difference ( χ2=7.52, P=0.006). There were no statistically significant differences in DCR between the apatinib group A and the chemotherapy alone group, the apatinib group A and apatinib group B ( χ2=4.57, P=0.033; χ2=0.51, P=0.477). The median OS of the patients in the three groups were 6.8, 9.2 and 9.9 months respectively, with a statistically significant different ( χ2=8.91, P=0.022). Compared with the chemotherapy alone group, the median OS of the apatinib group A and apatinib group B were significantly prolonged, with statistically significant differences ( χ2=7.25, P=0.036; χ2=8.60, P=0.029). Compared with the apatinib group A, the median OS of the apatinib group B was prolonged, but there was no statistically significant different ( χ2=1.54, P=0.201). The median PFS of the patients in the three groups were 5.2, 7.7 and 8.2 months respectively, with a statistically significant different ( χ2=8.79, P=0.026). Compared with the chemotherapy alone group, the median PFS of the apatinib group A and apatinib group B were significantly prolonged, with statistically significant differences ( χ2=7.01, P=0.039; χ2=8.36, P=0.031). Compared with the apatinib A group, the median PFS of the apatinib group B was prolonged, but there was no statistically significant different ( χ2=1.68, P=0.186). There were statistically significant differences in the incidences of fatigue [34.78% (8/23) vs. 65.22% (15/23) vs. 72.73% (16/22), χ2=7.50, P=0.024], hypertension [4.35% (1/23) vs. 34.78% (8/23) vs. 68.18% (15/22), χ2=20.07, P<0.001], hand-foot syndrome [4.35% (1/23) vs. 43.48% (10/23) vs. 72.73% (16/22), χ2=22.28, P<0.001] and oral mucositis [8.70% (2/23) vs. 39.13% (9/23) vs. 72.73% (16/22), χ2=19.26, P<0.001] among the three groups. Compared with the chemotherapy alone group, the incidences of hypertension and hand-foot syndrome in the apatinib group A and the incidences of fatigue, hypertension, hand-foot syndrome and oral mucositis in the apatinib group B were increased, with statistically significant differences ( χ2=6.77, P=0.009; χ2=9.68, P=0.002; χ2=6.51, P=0.011; χ2=20.00, P<0.001; χ2=22.37, P<0.001; χ2=19.21, P<0.001). Conclusion:Apatinib (0.50 g) combined with chemotherapy has better short-term efficacy than chemotherapy alone in advanced NSCLC. Apatinib (0.25 g) and apatinib (0.50 g) can prolong the survival of patients, but increasing the treatment dose can not achieve longer survival benefit.
5.Evaluation of the short-term efficacy and safety of bevacizumab combined with doxorubicin liposomes in the treatment of patients with platinum-resistant recurrent epithelial ovarian cancer
LIU Meiqin ; LU Donghui ; GAO Shile ; XU Xingjun ; ZHANG Yu
Chinese Journal of Cancer Biotherapy 2021;28(8):818-823
[摘 要] 目的:探讨贝伐珠单抗联合多柔比星脂质体治疗铂类耐药复发性卵巢上皮性癌患者的近期疗效和不良反应,并随访生存情况。方法:选取中国人民解放军联勤保障部队第九〇一医院2018年1月至2019年12月收治的76例铂类耐药复发性卵巢上皮性癌患者,采用数字随机分组法分为对照组38例、观察组38例,对照组给予多柔比星脂质体单药化疗4个周期,观察组给予贝伐珠单抗联合多柔比星脂质体化疗4个周期,观察两组患者治疗后近期疗效和不良反应,以及血清肿瘤标志物人附睾蛋白4(human epididymis protein 4,HE4)、糖类抗原125(carbohydrate antigen 125,CA125)变化,并随访总生存期(OS)和无疾病进展生存期(PFS)。结果:对照组患者客观有效率(ORR)为40.54%、疾病控制率(DCR)为67.57%,观察组患者ORR为69.44%、DCR为88.89%,观察组ORR和DCR显著高于对照组(均P<0.05)。治疗后观察组患者血清HE4和CA125分别为(142.67±46.81)pmol/L、(31.79±11.65)U/L,显著低于对照组患者的(219.33±75.67)pmol/L、(57.05±17.85)U/L(均P<0.05)。两组患者的胃肠反应、骨髓抑制、肝肾功能损伤、心脏毒性、过敏反应、血栓栓塞和出血等不良反应相比较差异无统计学意义(均P>0.05);观察组患者高血压发生率显著高于对照组(P<0.05),但可控、可耐受。观察组患者中位OS 和中位PFS分别分别为17.2个月和10.9个月,显著长于对照组患者的14.1个月和7.8个月(均P<0.05)。结论:对于铂类耐药复发性卵巢上皮性癌患者,贝伐珠单抗联合多柔比星脂质体近期疗效可靠、安全性好、不良反应可耐受,值得临床推广。
6.Effect of modified oral strong suction device on reducing sandblasting dust pollution
Donghui GAO ; Wenzhou XU ; Kexin WANG ; Jingying WANG
Chinese Journal of Modern Nursing 2021;27(18):2510-2512
Objective:To compare the suction effect of modified and conventional strong suction devices on sand blasting dust during sand blasting cleaning.Methods:A pre-experiment was carried out using an oral bionic head mold containing 28 standard teeth to compare the dust suction effect of the modified and conventional strong suction devices under different conditions. Using the convenient sampling method, a total of 186 patients who underwent sandblasting treatment in Department of Periodontology in Hospital of Stomatology of Jilin University were selected from February to April 2019, and they were divided into the experimental group and the control group. The experimental group used a modified strong suction device, while the control group used a clinical routine strong suction device. The comfort and VAS scores of patients in the two groups during the sandblasting treatment were compared.Results:Under the conditions of 1/3 and 2/3 of the amount of blasting, 5 and 10 minutes of blasting time and 15 cm and 30 cm of sandblasting powder collection distance, the dust reduction effect of the experimental group was better than that of the control group, and the differences were statistically significant ( P<0.05) . The comfort score of the experimental group was higher than that of the control group and the VAS score of the experimental group was lower than that of the control group, and the differences were statistically significant ( P<0.05) . Conclusions:The modified strong suction device can control the spread of dust from pollution sources and improve the consulting room environment, thereby reducing the occupational hazards of medical staff, reducing the stimulating inducement of people with low immunity and improving the comfort of patients and the quality of nursing.
7.Effects of posterior internal fixation combined with transpedicular bone grafting on osteoporotic thoracolumbar fractures in elderly patients
Zhicheng ZHOU ; Donghui YANG ; Zhiren ZHANG ; Shan GAO ; Guoxin XU
Chinese Journal of Geriatrics 2020;39(8):936-940
Objective:To investigate the effects of posterior internal fixation combined with transpedicular bone grafting in elderly patients with osteoporotic thoracolumbar fractures.Methods:Clinical data of 92 elderly patients with osteoporotic thoracolumbar fractures were retrospectively analyzed.According to the operation method, patients were divided into the control group(n=38)and the observation group(n=54). The control group received the conventional posterior approach and short-segment transpedicular fixation, and the observation group underwent transpedicular fusion in addition to the treatment the control group received.Surgery quality metrics, clinical effects and postoperative recovery were compared between the two groups.Results:The operation time and bleeding volume were higher in the observation group than in the control group( P<0.05). The bone fusion rate was higher and the failure rate of internal fixation was lower in the observation group than in the control group(96.3% vs.78.9%, 3.7% vs.15.8%, χ2=6.929 and 4.103, all P<0.05). The Japanese Orthopaedic Association score(JOA score)increased in both groups after operation( Ftime=47.628, P<0.05). The increase of the JOA score( Finteraction=4.477, P<0.05)and the overall JOA score( Fgroup=5.638, P<0.05)were greater in the observation group than in the control group.The Oswestry Disability Index(ODI)index in both groups decreased with time( Ftime=72.581, P<0.05). The decrease of the ODI index( Finteraction=7.421, P<0.05)and the overall ODI( Fgroup=9.276, P<0.05)were higher in the observation group than in the control group.The visual analogue scale(VAS)score in both groups decreased with time( Ftime=93.157, P<0.05). The decreases of the VAS score( Finteraction=9.473, P<0.05)and the overall VAS( Fgroup=13.272, P<0.05)score were greater in the observation group than in the control group.The Frankel nerve function grade was better in the observation group than in the control group 12 months after operation( z=2.123, P<0.05). Conclusions:Posterior internal fixation combined with transpedicular bone grafting can help improve nerve function, reduce postoperative pain, and has a high bone fusion rate and a low failure rate of internal fixation.
8.Observation of short-term clinical efficacy and adverse reactions with stereotactic radiotherapy in locally recurrent non-small cell lung cancer
Xiuli XU ; Zongtao HU ; Donghui LU ; Shile GAO
Chinese Journal of Radiation Oncology 2019;28(7):495-498
Objective To investigate the short-term clinical efficacy and adverse reactions of stereotactic radiotherapy (SRT) in the treatment of locally recurrent non-small cell lung cancer (NSCLC).Methods Clinical data of 120 cases of recurrent NSCLC after radiotherapy admitted to our hospital from October 2009 to October 2015 were retrospectively analyzed.SRT was adopted for further radiotherapy.The prescription dose was 50% dose curve surrounding the target area.The total dose was 40-50 Gy,with a single dose of 4-5 Gy for 8-12 times.The chest CT was re-examined every 2 months after radiotherapy.The short-term clinical efficacy and adverse reactions were evaluated.The changes of Karnofsky performance score (KPS) and quality of life (QOL) were recorded before and after radiotherapy.Results One patient terminated the radiotherapy due to grade 3 acute radiation-induced pneumonia,25 patients (21.0%) obtained complete remission (CR),61 cases (51.3%) of partial remission (PR),19 cases (16.0%) of stable disease (SD),14 cases (11.8%) of progress disease (PD),86 cases (72.3%) of objective remission rate (CR+PR),and 105 cases (88.2%) of disease control (CR+PR+SD),respectively.Thirty-one patients experienced radiation-induced pneumonia,23 cases of radiation-induced myelosuppression and 1 case of acute radiation-induced heart injury.All these adverse reactions were mitigated after symptomatic treatment.The KPS was significantly increased from 68.16±15.22 before SRT to 78.39± 11.50 after SRT (P<0.05).The QOL was considerably elevated from 27.58±5.37 prior to SRT to 38.16±8.39 following SRT (P<0.01).Conclusion SRT is an efficacious and safe treatment of locally recurrent NSCLC,which yields controllable and tolerable adverse reactions and enhances the QOL of patients.
9.Short term efficacy and toxicity of apatinib and docetaxel combined with cisplatin chemotherapy for advanced gastric cancer
GAO Shile ; LU Donghui ; LIU Meiqin ; WANG Chong ; WEI Lei ; XU Peng ; LIU Yan ; TANG Zhengzhong ; HU Zongtao
Chinese Journal of Cancer Biotherapy 2018;25(11):1131-1134
Objective: : To observe the short-term efficacy and toxicity of apatinib monotherapy as well as docetaxel plus cisplatin in advanced gastric cancer. Method: : According to inclusion and exclusion criteria, 108 patients with advanced gastric cancer in the 105th Hospital of PLA were selected. According to random table grouping method, there were 54 cases in group A and 54 cases in group B. Patients in group A received continuous oral administration of apatinib alone, while group B received docetaxel plus cisplatin chemotherapy, with 3 weeks as a cycle and 4 cycles for a course. The efficacy and side effects were evaluated 3 months later. Results: : In groupA, there were 4 cases of CR, 25 cases of PR, 18 cases of SD and 7 cases of PD; the ORR was 53.7% and DCR was 87%. In group B, there were 2 cases of CR, 19 cases of PR, 21 cases of SD and 12 cases of PD; the ORR was 38.9% and DCR was 77.8%. The ORR and DCR in group A were significantly better than those in group B (P<0.05). The main adverse reactions were gastrointestinal reaction, myelosuppression, hypertension and hand-foot syndrome, all of which were grade 1 to 2; The incidence of bone marrow suppression and gastrointestinal reaction in group A was lower than that in group B (P<0.05), while the incidence of hand-foot syndrome and hypertension in group B was lower than that in group A (P<0.01). Conclusion: :The short-term efficacy of targeted therapy of apatinib alone was better than that of docetaxel combined with cisplatin chemotherapy, and the toxicity and side effects of both regimens were controllable;Apatinib can be used as the primary regimen for the treatment of advanced gastric cancer.
10. The efficacy of ansa cervicalis anterior root for unilateral recurrent laryngeal nerve injury
Yingna GAO ; Shicai CHEN ; Donghui CHEN ; Meng LI ; Wei WANG ; Fei LIU ; Minhui ZHU ; Hongliang ZHENG
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2018;53(9):655-660
Objective:
To discuss the long-term efficacy of laryngeal reinnervation using the anterior root of the ansa cervicalis in the treatment of unilateral vocal fold paralysis (UVFP) caused by thyroid surgery.
Method:
From January 2010 to January 2016, a total of 39 UVFP patients who underwent ansa cervicalis anterior root-to-recurrent laryngeal nerve (RLN) anastomosis and who had suffered nerve disfunction for 6 to 24 months were enrolled as UVFP group.Another 39 age and gender matched normal subjects served as control group. Videostroboscopy, vocal function assessment (acoustic analysis, perceptual evaluation and maximum phonation time), and laryngeal electromyography were performed preoperatively and postoperatively for assessing surgery efficacy. Paired sample

Result Analysis
Print
Save
E-mail