1.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.
2.Pressure-induced differentiation of rabbit retinal stem cells into retinal ganglion cells
Min DAI ; Zefeng KANG ; Zhulin HU ; Yan LI
Chinese Journal of Experimental Ophthalmology 2022;40(12):1134-1140
Objective:To investigate the effect of pressure on the differentiation of rabbit retinal stem cells (RSCs) co-cultured with retinal ganglion cells (RGCs).Methods:SPF grade New Zealand rabbits on the day 22 of gestation were selected, and embryos were removed to obtain retinal ciliary margin pigment epithelial tissue and culture primary RSCs.Six SPF grade newborn New Zealand rabbits were selected, and retinal neuroepithelial layer tissues were isolated to culture primary RGCs.Rabbit RSCs cultured in vitro were identified by immunofluorescence staining of nestin antibody, bromodeoxyuridine (BrdU) cell proliferation assay kit, RSCs spontaneously differentiated cells immunofluorescence detection and flow cytometry.RGCs were identified through immunofluorescence staining of Brn3b antibody and Thy1.1 antibody.A co-culture system of RGCs and RSCs cultured in the upper and lower layers of a transwelll plate respectively was constructed.The mRNA and protein expression levels of nestin and Thy1.1 in RSCs and differentiated cells under pressures of 0, 20, 40, 60, 80 mmHg (1 mmHg=0.133 kPa) were detected by real-time fluorescence quantitative PCR and Western blot.The feeding and use of laboratory animals were in accordance with the Regulations on the Administration of Laboratory Animals promulgated by the State Science and Technology Commission.The study protocol was approved by the Ethics Committee of Yunnan University Affiliated Hospital (No.KPRC-IACUC17008). Results:RSCs cultured in vitro were nestin-positive.The percentage of BrdU-positive isolated RSCs was (92.26±3.28)%.Some cells differentiated from RSCs were Brn3b-positive, accounting for (13.00±3.06)%, and some were GS-positive, accounting for (31.60±3.67)%.RGCs cultured in vitro were Brn3b- and Thy1.1-positive.There were statistically significant differences in the relative mRNA and protein expressions of nestin and Thy1.1 between RSCs and differentiated cells under different pressures (mRNA: F=127.600, 137.400; both at P<0.01; protein: F=82.480, 158.700; both at P<0.001). The relative mRNA and protein expressions of nestin were significantly reduced in RSCs, and relative mRNA and protein expressions of Thy1.1 were significantly increased in differentiated cells at 20, 40, 60 and 80 mmHg in comparison with 0 mmHg (all at P<0.05). When the pressure was 40 mmHg, the relative mRNA and protein expressions of nestin were lowest in RSCs, and the relative mRNA and protein expressions of Thy1.1 in differentiated cells were highest. Conclusions:Within a certain range, pressure can promote the differentiation of RSCs co-cultured with RGCs into ganglion-like cells, and excessive pressure can inhibit the differentiation of RSCs.
3.Multimodal imaging characteristics of combined hamartoma of retina and retinal pigment epithelium
Juan ZHANG ; Xiaoyan CUI ; Juanjuan LI ; Hua LI ; Zhulin HU ; Yinyan MA ; Xiaofan ZHANG
Chinese Journal of Experimental Ophthalmology 2022;40(3):235-240
Objective:To observe the multimodal imaging characteristics of combined hamartoma of the retina and retinal pigment epithelium (CHRRPE).Methods:A cross-sectional study was conducted.Sixteen eyes of 16 patients with CHRRPE were enrolled in Second People's Hospital of Yunnan Province from March 2013 to July 2019.Fundus color photography, fundus autofluorescence (FAF), fluorescein fundus angiography (FFA), indocyanine green angiography (ICGA), optical coherence tomography (OCT), optical coherence tomography angiography (OCTA) and multicolor imaging were performed in all patients.The multimodal imaging characteristics were analyzed.This study protocol adhered to the Declaration of Helsinki and was approved by an Ethics Committee of Second People's Hospital of Yunnan Province (No.20130106). Written informed consent was obtained from patients or their guardians prior to any medical examination.Results:Tumors were located in the posterior optic disc, and translucent glial lesions with unclear borders and slight elevations were observed.The surface of the lesions was attached by different degrees of fibroproliferative membrane, and the adjacent vessels were twisted and dilated.The tumors presented flat bulging green reflexes on the retina at the posterior pole by multicolor imaging, and OCT image showed thickened optic disc and retina near the optic disc, structural disorder, high reflectance of the surface, and low reflectance of the deep retina below the periretinal membrane.OCTA showed irregular blood flow signals, and the signal of retinal blood vessels was twisted and dilated.FAF showed that the autofluorescence intensity of tumors was weakened to different degrees.Early lesions presented different degrees of blocked fluorescence in FFA.Deformed and tortuous blood vessels were found in the eyes, and telangiectasia showing needle-like punctate strong fluorescence leakage was observed in severe eyes by FFA.ICGA showed no abnormal choroidal vessels.Conclusions:The main imaging features of CHRRPE include abnormal retinal blood vessels in the tumor area and fibrous proliferative membranes on the surface in color image; OCT shows that the retina and the retinal pigment epithelium are involved, and the retina in the tumor is thickened with disordered structure; high reflection OCTA shows irregular internal blood flow signals inside the tumor; FFA examination shows fluorescence obscuration and obviously tortuous retinal blood vessels.Multimodal imaging examinations are helpful for the diagnosis of CHRRPE.
4.Establishment of orthotopic colorectal cancer model by colonoscopy with submucosal injection in living mice
Zhengchun WU ; Lingxiang WANG ; Xiongying MIAO ; Zhulin YANG ; Kang CHEN ; Kunpeng WANG ; Wenhao CHEN ; Zijian ZHANG ; Kai DENG ; Junjiao HU ; Xibin YANG ; Yu WEN ; Li XIONG
International Journal of Biomedical Engineering 2018;41(3):250-256
Objective To set up a living mice colonoscopy platform to establish an orthotopic model of colorectal cancer in mice under direct vision,and to observe its biological behavior such as metastasis.Methods Eighteen-week-old male C57/BL mice were anesthetized,and the intestinal lumen of the mice was examined by a self-developed living mice colonoscopy and Olympus URF-P5 ureteroscopy,respectively.The imaging effects of the two methods were compared.Human colon cancer HT-29 cells were injected into the colonic mucosa of BALB/c-nu mice under direct vision.The colonoscopy was performed on the 3rd,7th and 15th day after the injection to observe the tumor formation in the intestinal lumen.The mice were sacrificed when the body weight decreased significantly or cachexia appeared,and then the abdominal cavity was examined including the tumor formation and metastasis.Results The self-developed living mice colonoscopy platform can provide clear vision of enteric cavity,and no mice died in the colonoscopy examination.In vivo subcutaneous injection of HT-29 cells in mice was performed with a perforation rate of 15%,a mortality rate of 33.3%,a tumor formation rate of 62.5%,an abdominal metastasis rate of 60%,a liver metastasis rate of 25%,and an abdominal wall transfer rate of 25%.Conclusion The self-developed mice colonoscopy platform can be used for the study of colorectum in living mice.The imaging effect is no less than that of Olympus URF-P5 ureteroscopy.In addition,an orthotopic colorectal cancer model can be established by this platform combing with submucosal injection technology.
5.The treatment effect of intraocular lens ciliary sulcus implantation combined with posterior capsular incarceration of intraocular lens on children with traumatic cataract
Tingting WAN ; Hong ZHANG ; Zhulin HU
Chinese Journal of Experimental Ophthalmology 2018;36(6):454-458
Objective To compare the treatment effect of intraocular lens ciliary sulcus implantation combined with posterior capsular incarceration of intraocular lens and simple intraocular lens ciliary sulcus implantation.Methods We retrospectively analyzed 60 eyes of 60 children with traumatic cataract from June 2012 to June 2015 in the Second People's Hospital of Yunnan Province,including 44 males and 16 females and the average age ranged from 1 to 14 years.The patients were divided into two groups according to the situation of posterior capsular,30 eyes of 30 children for each group.The patients in combined surgery group were performed intraocular lens ciliary sulcus implantation combined with posterior capsular incarceration of intraocular lens,and the patients in simple surgery group were performed simple intraocular lens ciliary sulcus implantation.The follow-up time ranged from 1 month to 6 months.The best corrected visual acuity(BCVA),grade of optic axis turbid,dislocation of intraocular lens,postoperative complications and surgical duration were compared between the two groups.Results The BCVA after surgery was significantly different from that before surgery in both groups (combined surgery group:x2 =7.548,P< 0.05;simple surgery group:x2 =5.579,P<0.05).The postoperative turbidity of central axis area and BCVA were not significantly different between the 2 groups (x2 =0.362,P>0.05).The dislocation degree of intraocular lens and proportion of postoperative complications were lower in the combined surgery group than those in the simple surgery group (x2 =9.858,P<0.05;x2 =7.200,P<0.05).The duration of surgery was not significantly different between the 2 groups (x2 =0.658,P > 0.05).Conclusions Posterior capsular incarceration of intraocular lens has fewer complications,lower dislocation degree of intraocular lens and more effective for children with traumatic cataract than intraocular lens ciliary sulcus implantation.
6.Stimulating effects of conjunctival sac implants after eye enucleation on orbital bone tissue in rabbits
Xiaoying LIU ; Zhulin HU ; Jianshu KANG ; Hong ZHANG
Chinese Journal of Experimental Ophthalmology 2018;36(10):761-766
Objective To investigate the stimulating effects of conjunctival sac implants following eye enucleation on orbital bone tissue in rabbits model.Methods Eighty 1-month-old New Zealand rabbits were randomly divided into normal control group,only eyeball enucleation group,2-week interval group and 4-week interval group.The right eyeballs were enucleated in the rabbits in the only eyeball enucleation group,2-week interval group and 4-week interval group,and conjunctival sac implants were placed intraoperatively.Then a larger implant was replaced in a 2-week interval or 4-week interval in different groups,respectively.Spiral CT scan was used to evaluate the orbital bone development with aging.The peripheral blood of 3 ml was collected in the rabbits for the detection of osteocalcin and alkaline phosphatase using osteocalcin test kit (N-MID Osteocalcin) and alkaline phosphatase assay kit (NPP substrate-AMP buffer method),respectively.The animals were sacrificed at 3 months after operation for the histopathological examination of orbital bone tissue.Results The operation was successful in all the rabbits and no infection occurred after operation.The variance of orbital bone CT value was obvious in all the rabbits.The intercalated osteocalcin concentration was (48.55 ± 7.99),(59.80 ± 2.96),(57.94 ± 5.20) and (55.96 ± 3.22) μg/L and the alkaline phosphatase concentration was (284.66± 132.69),(232.96±54.39),(232.40± 118.23),(284.20± 130.41) μg/L in the normal control group,only eyeball enucleation group,2-week interval group and 4-week interval group,respectively,showing insignificant differences among the four groups (F =2.710,0.281,both at P > 0.05).Similar pathological findings were in the 2-week interval group and 4-week interval group,such as no obvious orbital bone malformations,weak bone absorption and few bone osteoclasts under the optical microscope.Varying degrees of orbital deformities and bone tissue absorption were found in the only eyeball enucleation group.No orbital bone developing abnormality was seen in the normal control group and the left eyes in various groups under the optical microscope.Conclusions Compared with the only eyeball enucleated eyes,the orbital bone tissue has a well developed process in conjunctiva sac implant eyes following eyeball enucleation.Conjunctiva sac implant is an effective method to stimulate orbital growth and orbital volume increasing.
7.Changes of Th1/Th2 inflammatory factors in the aqueous humor of tree shrews with fusarium solani keratitis
Yan LI ; Lihong LI ; Hai LIU ; Zhichao SHENG ; Jie MIN ; Zhulin HU
Recent Advances in Ophthalmology 2017;37(9):824-827
Objective To observe the changes of Th1 / Th2 inflammatory factors in the aqueous humor of tree shrews with fusarium solani keratitis,as well as to explore the relationship between Thl / Th2 inflammatory factors and inflammatory response in fusarium solani keratitis.Methods Forty healthy tree shrews were randomly divided into experimental group(n =30) and control group (n =10).Fusarium solani was inoculated into sabina culture medium and cultured at 26 ℃ for 7 days,and then the fungal suspension was collected and the density of spores was adjusted to 10 × 109 CFU · mL-1.In the experimental group,50 μL fungal spore suspension was injected into the center of the cornea stroma,while the control group received the same amount of saline.Next the levels of cytokines including interleukin (IL)-1 β,IL-6,IL-4 and IL-10 were analyzed by flow cytometry on day 3,day 7,day 14 after successful modeling,and the changes in types of infiltrating cells were observed by histopathological examination.Results The expression level of IL-1 β and IL-6 (Th1 type cytokines) was the highest on day 7,and the difference was statistically significant at each time point when compared with the control group (all P < 0.05).The expression level of IL-10 (Th2 type cytokines) was the highest on day 14,and the difference was statistically significant at each time point when compared with the control group (all P < 0.05).The difference in IL-4 expression was statistically significant on day 7 (P < 0.05).In addition,histopathological examination showed that the number of infiltration cell reached its peak on day 7,mainly neutrophils,and fungal hyphae were observed to be parallel to the matrix fibers at each time point.Conclusion The proinflammatory cytokines IL-1β and IL-6 and the anti-inflammatory cytokines IL-10 may play an important role in the molecular mechanism of inflammatory response of fusarium solani keratitis in tree shrews.
8.Establishment of a tree shrew model of Fusarium keratitis
Yan LI ; Jiejie DAI ; Xiaomei SUN ; Hai LIU ; Zhulin HU
Acta Laboratorium Animalis Scientia Sinica 2017;25(4):420-424
Objective To establish a tree shrew model of Fusarium solani keractitis by injecting Fusarium solani conidia into the corneal stroma.Methods Fusarium solani was inoculated into Sabouraud culture medium and incubated at 26℃ for 7 days.Fungal suspension was collected and the number of spores was adjusted to 1 × 1010 CFU /mL on the blood cell count plate.Forty healthy tree shrews were randomly divided into experimental group (n=30) and control group (n=10).In the experimental group, 50 μL of fungal spore suspension was injected into the cornea center with a 29G needle, and 50 μL saline was injected in the control group.The models were evaluated by anterior segment photography, in vivo confocal microscopy, histopathology, and corneal tissue culture.Results The fungal infiltration, the degree of edema of corneal epithelial and endothelial cells, and the number of mycelium were positively correlated with time.The number of infiltrating inflammatory cells, mainly, neutrophils, reached a peak on the 7th day after modeling.The mycelial growth was parallel to the stromal fibers.After the successful establishment of the model, the corneal tissue culture showed the growth of Fusarium solani.The successful rate of modeling was 86%.Conclusions The tree shrew model of Fusarium solani keratitis is established by injecting spores of Fusarium solani into the cornea.
9.Comparison of the corneal endothelial cells of rhesus monkeys and tree shrews
Min WU ; Na LI ; Xiaomei SUN ; Zhulin HU
Acta Laboratorium Animalis Scientia Sinica 2016;24(2):164-168
Objective To analyze and compare the characteristics and differences of corneal endothelial cells of rhesus monkey and tree shrew eyes.Methods Corneal endothelial cells of 6 healthy rhesus monkeys (12 eyes) and 20 healthy tree shrews (40 eyes) were measured using a non-contact SP3000P specular microscope.Eight parameters were de-termined and compared with relevant parameters of human eyes reported in the literature, including minimum cell area (Smin), maximum cell area (Smax), average cell area (Savg), standard deviation of cell area (SD), coefficient of variabili-ty ( CV) , cell density ( CD) , hexagonality percentage ( HG%) and central corneal thickness ( CCT) .Results The ima-ging and measurement of all parameters could be completed in a short time both in rhesus monkeys and tree shrews.The time spent in the two kinds of animals was not significantly different.The CCT was ( 449.2 ±12.8 ) μm and ( 262.4 ± 24.6) μm, Smin was (120.4 ±26.3) S/μm2 and (153.2 ±42.9) S/μm2 , Smax was (705.0 ±130.8) S/μm2 and (468.7 ±109.3) S/μm2 , Savg was (351.1 ±26.1) and (295.4 ±18.9) S/μm2 , SSD was (113.1 ±27.4) and (75.9 ±27.3) S/μm2, CV was (31.9 ±6.0) and (25.3 ±8.3), CD was (2874.2 ±203.8) p/cell· mm-2 and (3399.3 ±224.7) p/cell· mm-2 , and the HG% was (58.6 ±9.1) and (94.0 ±9.7) in the rhesus monkeys andt tree shrews, respectively. The differences of all the above parameters between rhesus monkeys and tree shrews were statistically significant ( P<0.05 for all) .The cornea of tree shrews was significantly thinner than that of rhesus monkeys.The area and coefficient of varia-bility of tree shrews were smaller to those of rhesus monkeys, while the cell density and hexagonality percentage were higher than those of rhesus monkeys.Compared with human eyes, the CCT, CV and HG%in rhesus monkeys were highly simi-lar, while the CD was lower than that of human eyes.The CCT in tree shrew was only 60%of the rhesus monkey eyes and 50%of human eyes, while the CD and Savg were similar to that of human eyes in the 10-20 years old group.Conclu-sions The morphology and parameters of corneal endothelial cells in rhesus monkeys and tree shrews are significantly dif-ferent.There are similarities and differences among the human, rhesus monkey and tree shrew corneal endothelial cells. Both rhesus monkeys and tree shrews are appropriate experimental animals feasible for researches on human corneal endo-thelial diseases.
10.Meta-analysis of Xiyanping Combined with Ribavirin in the Treatment of Herpangina in Children
Baotao LIAN ; Zhulin WU ; Zezhang LI ; Jiacheng CHEN ; Xiaoying HU
China Pharmacy 2016;27(3):337-340
OBJECTIVE:To systematically review the efficacy and safety of Xiyanping injection versus Ribavirin injection in the treatment of herpangina in children,and provide evidence-based reference for clinical treatment. METHODS:Retrieved from PubMed,Cochrane Library,EMBase,VIP Database,CJFD,Wanfang Database and CBM,randomized controlled trials (RCT) about efficacy and safety of Xiyanping injection versus Ribavirin injection in the treatment of herpangina in children were collected. Meta-analysis was performed by using Rev Man 5.3 software after data extracting and quality evaluating by modified Jadad. RE-SULTS:Totally 14 RCTs were enrolled,involving 1 939 patients. Results of Meta-analysis showed total effective rate [OR=4.69, 95%CI(3.36,6.55),P<0.001],fever clearance time [MD=-1.36,95% CI(-1.60,-1.12),P<0.001],herpes regression time [MD=-1.34,95%CI(-1.61,-1.06),P<0.001],hospitalization time [MD=-1.88,95% CI(-3.68,-0.07),P=0.04] and sali-vation disappearance time [MD=-1.07,95% CI(-1.30,-0.84),P<0.001] of Xiyanping injection were significantly better than Ribavirin injection,there were statistically significant differences. And there was no significant difference in the incidence of ad-verse reactions [OR=0.56,95% CI(0.31,1.03),P=0.06]. CONCLUSIONS:The efficacy of Xiyanping injection is better than Rib-avirin injection in the treatment of herpangina in children,with similar safety.

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