1.Analysis of Cumulative Live Birth Rate of Selective Single Embryo Transfer by Time-lapse Monitoring System and Conventional Morphological Assessment in IVF/ICSI-ET
Guihong CHENG ; Aiyan ZHENG ; Jie DING ; Qinyan ZOU ; Yongle XU ; Rui ZHU ; Fuxin WANG ; Huihua WU ; Hong LI ; Qingxia MENG
Journal of Practical Obstetrics and Gynecology 2024;40(2):130-135
		                        		
		                        			
		                        			Objective:To analyse the clinical significance of selective single embryo transfer by time-lapse mo-nitoring(TLM)or conventional morphology assessment(CMA)in vitro fertilization/intracytoplasmic sperm in-jection and embryo transfer(IVF/ICSI-ET),and to initially explore the predictive value of Raman spectral analy-sis of embryo culture medium for clinical pregnancy rate.Methods:The study is a prospective randomized con-trolled clinical trial.We assigned 139 patients treated with IVF/ICSI-ET in Reproductive and Genetics Center of Suzhou Municipal Hospital from April 2019 to July 2020,which were randomly assigned to either the CMA or the TLM group.We performed selective single-embryo transfer(fresh cycle and FET)after selecting the optimal em-bryos with TLM or CMA respectively.If the patient's first embryo transfer was unsuccessful,a second one would be performed to compare the differences in the cumulative live birth rate of embryo transfer and other pregnancy outcomes between the two groups.Meanwhile,we collected 15 μl of embryo culture medium at day 3 after IVF/ISCI fertilization for Raman spectroscopy analysis.Results:There were no differences in cumulative live birth,cu-mulative clinical pregnancy,cumulative premature birth,cumulative early spontaneous abortion,cumulative ectopic pregnancy and LGA or SGA between TLM and CMA groups(P>0.05).The Neonatal sex ratio in the TLM group was lower than that in the CMA group,but the difference was not significant(P>0.05).Raman spectros-copy analysis of embryo culture medium predicted the clinical pregnancy rate with 67.21%accuracy.Conclu-sions:In young women with a good ovarian reserve,the advantage of using TLM to evaluate embryos is not obvi-ous,so we should remain vigilant that embryo selection based on morphokinetic parameters may affect the sex ratio.Raman spectroscopic analysis of embryo culture medium is not yet able to effectively predict the planting ability of embryos.
		                        		
		                        		
		                        		
		                        	
2.Effect of ginseng polysaccharide on the expression of prostaglandin E2/6-keto-prostaglandin 1alpha in traumatic osteoarthritis model rats
Rui LI ; Guihong ZHANG ; Tao WANG ; Ping FAN
Chinese Journal of Tissue Engineering Research 2024;28(8):1235-1240
		                        		
		                        			
		                        			BACKGROUND:Ginseng extracts have been found to significantly improve osteoarthritis,but the therapeutic effects of ginseng polysaccharide extracts on osteoarthritis have not been reported. OBJECTIVE:To investigate the effect of ginseng polysaccharide on the expression of prostaglandin E2/6-keto-prostaglandin F1α in traumatic osteoarthritis model rats. METHODS:Sixty male Sprague-Dawley rats were selected and randomly divided into healthy group,model group,ginseng polysaccharide low-dose group,ginseng polysaccharide medium-dose group,ginseng polysaccharide high-dose group and dexamethasone group.Except for 10 rats in the healthy group,the other rats were taken to establish traumatic osteoarthritis models.The healthy group and model group were given 0.2 mL of normal saline intraperitoneally.The low-,medium-,and high-dose groups were intraperitoneally injected with 0.1,0.25,0.5 μg/mL ginseng polysaccharide,respectively.In the dexamethasone group,0.2mg/kg dexamethasone(0.2 mL)was injected intraperitoneally.Injections were given once every 3 days,for 4 consecutive weeks.Serum prostaglandin E2 and 6-keto-prostaglandin F1α levels were detected by ELISA.The bone and joint function of rats were assessed by the Mankin's score.Hematoxylin-eosin staining was used to observe the pathologic morphology of the knee joints of rats.Western blot and PCR were used to detect the protein and mRNA expression of tumor necrosis factor α and interleukin-1β,interleukin-10 in articular cartilage tissue,respectively. RESULTS AND CONCLUSION:Compared with the model group,serum prostaglandin E2 levels were decreased in the medium-dose group and dexamethasone group,while serum 6-keto-prostaglandin F1α levels were increased(P<0.05).Compared with the medium-dose group and dexamethasone group,the above-mentioned indicators were significantly improved in the high-dose group,and there was no significant difference between the medium-dose group and dexamethasone group(P>0.05).Compared with the model group,the Mankin's score was reduced in the medium-dose group and dexamethasone group(P<0.05),but there was no significant difference between the medium-dose group and dexamethasone group(P>0.05).Compared with the medium-dose group and dexamethasone group,the Mankin's score was significantly reduced in the high-dose group(P<0.05).The cartilage tissue layer of rats in the model and low-dose groups was significantly thinned,the cracks and chondrocytes deep into the bone layer were largely lost,the tide line was seriously broken and blurred,the collagen fibers in the synovial layer were increased and thickened,and a large number of chondrocytes were destroyed and arranged irregularly.These pathological changes were improved in the medium-dose group and dexamethasone group compared with the model group as well as improved in the high-dose group compared with the medium-dose group.Compared with the model group,the expression of tumor necrosis factor-α and interleukin-1β was reduced,while the expression of interleukin-10 was increased in the medium-dose group and dexamethasone group(P<0.05).These indicators in the joint were significantly improved in the high-dose group compared with the medium-dose group and dexamethasone group(P<0.05),but there was no significant difference between the medium-dose group and dexamethasone group(P>0.05).To conclude,ginseng polysaccharide can improve the inflammatory level and pathological morphology of traumatic osteoarthritis rats and reduce the Mankin's score.Its mechanism may be related to the regulation of prostaglandin E2/6-keto-prostaglandin F1α levels.
		                        		
		                        		
		                        		
		                        	
3.Embryo-fetal developmental toxicity and toxicokinetics of fluoropezil in New Zealand rabbits
Shanshan MAO ; Fang LI ; Guihong CAI ; Yunkai ZHU ; Xu XU ; Yanjun CUI ; Wen ZHOU ; Min CAO ; Li ZHOU
Chinese Journal of Pharmacology and Toxicology 2024;38(2):120-127
		                        		
		                        			
		                        			OBJECTIVE To study the effect of fluoropezil on embryo-fetal developmental toxicity and toxicokinetics in rabbits,and provide reference for clinical medication.METHODS According to the sequence of pregnancy,pregnant rabbits were divided into five groups:vehicle control group(1%hydroxy-propyl methylcellulose+1.5%polyethylene glycol 400 aqueous solution),positive control group(cyclo-phosphamide 18 mg·kg-1),and fluoropezil(3.6,9.0 and 22.5 mg·kg-1)groups.The vehicle control group and the fluoropezil groups were ig administrated on the 6th to 18th day of gestation(GD6-18)while the positive control group was ig given cyclophosphamide on GD6-20.The pregnant rabbits were sacri-ficed on GD28,and the embryo-fetal development was detected.Sex hormone levels of pregnant rabbits on GD5,GD18 and GD28 were detected by ELISA method.Blood samples with toxokinetics were collected for concomitant toxic generation at the first and last administration,and drug concentrations in fetal,placenta and amniotic fluid were detected with liquid chromatography tandem mass spectrometry(LC-MS/MS).RESULTS Fluoropezil 3.6,9.0 and 22.5 mg·kg-1 had no significant effect on body mass,mass gain,food consumption,pregnancy outcomes,fetal appearance,viscera,skeletal and physical growth and development of pregnant rabbits.Only on GD18 or GD28,the levels of follicle stimulating hormone,estra-diol and progesterone in each dose group fluctuated to some extent.The combined toxokinetics results indicated that fluoropezil could cross the placental barrier of the rabbits,but did not accumulate in preg-nant rabbits or fetuses.Fetal mass,crown-rump length and uterus mass in the cyclophosphamide group were lower than those in the vehicle control group.The appearance and bone of the cyclophos-phamide group were positive.CONCLUSION The no observed adverse effect level(NOAEL)of fluoro-pezil toxicity on rabbit embryo-fetal development is 22.5 mg·kg-1,which is 125 times of the effective dose.At the dosage level of 22.5 mg·kg-1,Cmax is 1093 μg·L-1,and AUC(0-24 h)6650 μg·h·L-1 on GD18.
		                        		
		                        		
		                        		
		                        	
4.Association of TSLP gene polymorphisms with Eos,IgE,and FeNO in 143 pediatric asthma cases
Zhumei LI ; Jing WU ; Guihong WU ; Wenjuan MENG ; Yali ZHANG ; Xiaoping ZHU
Immunological Journal 2024;40(4):375-382
		                        		
		                        			
		                        			To investigate the correlation of polymorphisms at the rs1837253 and rs3806933 loci of the thymic stromal lymphopoietin(TSLP)gene with asthma susceptibility and Eos,IgE,and FeNO levels in children.A total of 143 asthmatic children were selected as the study group,and 112 healthy children undergoing routine health examinations at the same hospital were chosen as the control group.The MassARRAY SNP genotyping technology was used to detect the genotypes at two loci,while serum IgE levels were determined by using the turbidimetric scattering method.The distribution differences in genotype and allele frequencies between the two groups were analyzed,along with the effects of different genotypes on Eos,IgE,and FeNO levels.There was no statistically significant difference in the distribution of rs1837253 allele and genotype frequencies as well as rs3806933 allele frequencies between the two groups(P>0.05).However,asthma group rs3806933 CT genotype frequency was higher than the control group,and CC genotype frequency was lower than the control group(P<0.05).Compared with the wild-type genotypes,children who carried rs1837253 CT+CC and rs3806933 CT,CT+TT genotypes had an increased risk of asthma(CT+CC vs TT:OR=2.737,95%CI:1.514-4.945;CT vs CC:OR=2.058,95%CI:1.194-3.543;CT+TT vs CC:OR=1.843,95%CI:1.109-3.062).There was an overall statistical difference in Eos counts among the three genotypes at the rs1837253 locus in the asthma group(P<0.05,correction for multiple comparisons P>0.05),but not in the control group(P>0.05).There were no statistically significant differences in Eos%,IgE,and FeNO levels among the genotypes at the two loci and no significant difference in Eos counts among genotypes at the rs3806933 loci(P>0.05).Taken together,polymorphisms at rs1837253 and rs3806933 loci in the promoter region of the TSLP gene are associated with asthma susceptibility in children.rs3806933 CT genotype may serve as a potential genetic marker for asthma,and rs1837253 CT+CC and rs3806933 CT+TT genotypes are risk factors for asthma in children;the rs1837253 locus polymorphism tended to affect blood Eos counts,while the two SNPs were not associated with Eos%,serum IgE,and FeNO levels.
		                        		
		                        		
		                        		
		                        	
5.Effects of sodium oligomannate combined with high-frequency repetitive transcranial magnetic stimulation on activity of daily living and intelligence level of patients with Alzheimer's disease
Junbo XIA ; Guihong JIAO ; Ning LI ; Yu WANG ; Yulong FENG ; Yanxia ZHU
Journal of Xinxiang Medical College 2024;41(8):755-761
		                        		
		                        			
		                        			Objective To explore the effects of sodium oligomannate combined with high-frequency repetitive transcranial magnetic stimulation on the activity of daily living and intelligence level of patients with Alzheimer's disease.Methods A total of 100 patients with Alzheimer's disease admitted to Henan Provincial Staff Hospital from September 2021 to September 2023 were selected as the research subjects.These patients were divided into an observation group and a control group according to the random number table method,with 50 patients in each group.Patients in the control group were given high-frequency repetitive transcranial magnetic stimulation,and patients in the observation group were given sodium oligomannate combined with high-fre-quency repetitive transcranial magnetic stimulation.Enzyme-linked immunosorbent assay was used to detect the levels of amyloid β-protein(Aβ)142,tumor necrosis factor-a(TNF-a)and interleukin-6(IL-6)in patients of the two groups before and after treatment.Chemiluminescence was used to detect the levels of neurotransmitters in patients of the two groups before and after treatment.The mental symptoms of patients in the two groups before and after treatment were evaluated by the behavioral pathology in Alzheimer's disease rating scale,the intelligence level of patients in the two groups before and after treatment was evaluated by the mini-mental state examination(MMSE)scale and the Montreal cognitive assessment(MoCA)scale,the activity of daily living of patients in the two groups before and after treatment was evaluated by Alzheimer's disease cooperative study-activity of daily living(ADCS-ADL),and the quality of life of patients in the two groups before and after treatment was evaluated by the quality of life-Alzheimer's disease scale.Results Before treatment,the two groups showed no significant difference in the levels of Aβ1-42,TNF-α and IL-6(P>0.05);after treatment,the levels of Aβ1-42,TNF-α and IL-6 in both groups were lower than those before treatment,and the levels of Aβ1-42,TNF-α and IL-6 in the observation group were lower than those in the control group(P<0.05).Before treatment,there were no statistically significant differences in the levels of 5-hydroxytryptamine(5-HT),acetylcholine(ACh),γ-aminobutyric acid(GABA),and Alzheimer-associated neuronal thread protein(AD7c-NTP)between the two groups(P>0.05);after treatment,the levels of 5-HT,ACh,and GABA in the two groups were higher than those before treatment,while the AD7c-NTP level was lower than that before treatment(P<0.05);after treatment,the levels of 5-HT,ACh,and GABA in the observation group were higher than those in the control group,while the AD7c-NTP level was lower than that in the control group(P<0.05).Before treatment,there were no significant differe-nces in the scores of paranoid and delusional ideas,hallucinations,behavioral disorders,aggressive behaviors,daily rhythm disorders,emotional disorders,anxiety and fear,and the total scores between the two groups(P>0.05);after treatment,the scores of paranoid and delusional ideas,hallucinations,behavioral disorders,aggressive behaviors,daily rhythm disorders,emotional disorders,anxiety and fear,and the total scores of patients in the two groups were lower than those before treatment,and the scores of paranoid and delusional ideas,hallucinations,behavioral disorders,aggressive behaviors,daily rhythm disorders,emotional disorders,anxiety and fear,and the total scores of patients in the observation group were lower than those in the control group(P<0.05).Before treatment,there were no significant differences in MMSE,MoCA and ADCS-ADL scores of patients between the two groups(P>0.05);after treatment,the MMSE,MoCA and ADCS-ADL scores of patientsin the two groups were higher than those before treatment,and the MMSE,MoCA and ADCS-ADL scores of patientsin the observation group were higher than those in the control group(P<0.05).Before treatment,there were no significant differences in the scores of physiological function,mental function,behavioral ability and interpersonal relationship,and the total scores of patients between the two groups(P>0.05).After treatment,the scores of physiological function,mental function,behavioral ability and interpersonal relationship,and the total scores of patients in the two groups were higher than those before treatment,and the scores of physiological function,mental function,behavioral ability and interpersonal relationship,and the total scores of patients in the observation group were higher than those in the control group(P<0.05).Conclusion Sodium oligomannate combined with high-frequency repetitive transcranial magnetic stimulation can improve the inflammatory state of patients with Alzheimer's disease,regulate neurotransmitter levels,alleviate psychiatric symptoms,enhance the intelligence level and the activity of daily living,and increase the quality of life.
		                        		
		                        		
		                        		
		                        	
6.Effect and Mechanism of Osthole on Proliferation and Apoptosis in Human Intrahepatic Cholangiocarcinoma HuCCT1 Cells
Dongjie DENG ; Li LI ; Chuting WANG ; Yi SUN ; Yan MENG ; Guihong WANG ; Guohua ZHENG ; Junjie HU
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(20):54-60
		                        		
		                        			
		                        			ObjectiveTo investigate the effect and mechanism of osthole on the proliferation and apoptosis in human intrahepatic cholangiocarcinoma HuCCT1 cells. MethodThe effect of 10, 20, 40, 80, and 120 μmol·L-1 osthole on the proliferation of HuCCT1 cells was detected by the cell counting kit-8 (CCK-8). A blank group, and low-, medium-, and high-dose osthole groups (16, 32, and 64 μmol·L-1) were set up. The effect of osthole on cell clone formation rate was detected by colony formation assay. The effect of osthole on cell cycle and apoptosis was detected by flow cytometry. The effect of osthole on cell apoptotic morphology was detected by Hoechst 33342 fluorescent staining. The effect of osthole on cell cycle protein cyclin B1, proliferating cell nuclear antigen (PCNA), cysteine-aspartic acid protease (Caspase)-9, Caspase-3, cleaved Caspase-9, cleaved Caspase-3, cleaved poly(ADP-ribose) polymerase (cleaved PARP), B-cell lymphoma-2 (Bcl-2), phosphorylated protein kinase B (p-Akt), phosphorylated mammalian target of rapamycin (p-mTOR), and phosphorylated ribosomal protein S6 (p-RPS6) was detected by Western blot. ResultThe cell viability in the osthole group(40,80,120 μmol·L-1) decreased (P<0.05,P<0.01), with the half maximal inhibitory concentration (IC50) of 63.8 μmol·L-1 as compared with that in the blank group. Compared with the blank group, the osthole groups(32,64 μmol·L-1)showed reduced clone formation rate (P<0.01), increased number of cells in the G2 phase (P<0.05,P<0.01), decreased number of cells, increased pyknosis and fragmentation, increased apoptosis rate (P<0.05,P<0.01), down-regulated expression of cyclin B1, PCNA, Bcl-2, Caspase-3, Caspase-9, p-Akt, p-mTOR, and p-RPS6 (P<0.05,P<0.01), and up-regulated expression of cleaved Caspase-3, cleaved Caspase-9, and cleaved PARP (P<0.05,P<0.01). ConclusionOsthole can inhibit the proliferation and promote the apoptosis of HuCCT1 cells, and its mechanism may be related to the Akt/mTOR signaling pathway. 
		                        		
		                        		
		                        		
		                        	
7.Development of adolescent health literacy evaluation scale under public health emergencies and its reliability and validity analysis in junior middle school students
Zhou WANG ; Tingye GAO ; Guangjian LI ; Jie ZHOU ; Yaping KONG ; Guihong FAN ; Qian BIAN ; Xing ZHANG ; Shijun ZHAO
Chinese Journal of Behavioral Medicine and Brain Science 2023;32(4):347-354
		                        		
		                        			
		                        			Objective:To develop and examine the reliability and validity of the adolescent health literacy evaluation scale under public health emergencies (AHLES-PHE) in junior middle school students.Methods:The initial version of AHLES-PHE was formed by combining the characteristics of public health emergencies and adolescent health literacy.The expert version of AHLES-PHE was formed by two rounds of Delphi expert consultation.Totally 1 729 adolescent students from three junior middle schools in Changzhou City were tested.The formal version of AHLES-PHE was formed through item analysis and factor analysis (structural validity). The content validity of the formal version of AHLES-PHE was evaluated by specialist analysis and sensibility analysis, and its correlation validity with the everyday health information literacy (EHIL) was tested.The internal consistency reliability, parity split-half coefficient and test-retest reliability were calculated.Results:(1)Item analysis: the correlation coefficient between the scores of each item and the total score of AHLES-PHE expert version was 0.420 to 0.722 ( P<0.01), and the CR of decision value was 10.140 to 66.980 ( P<0.01). (2)Validity analysis: the formal version of AHLES-PHE with 45 items and 8 factors was obtained by exploratory factor analysis.The 8 factors could explain 61.30% of the total variation.The fitting indexes of the confirmatory factor analysis model were χ2/ df=3.325, RMSEA=0.052, GFI=0.853, CFI=0.912, TLI=0.904, NFI=0.880.Sensibility analysis of the formal version of AHLES-PHE showed the Cronbach's α ranged from 0.957 to 0.958.The correlation coefficient between the total score of AHLES-PHE formal version and the total score of EHIL was 0.340 ( P<0.01). (3)Reliability analysis: the Cronbach's α coefficient and parity split-half coefficient of the formal version of AHLES-PHE were 0.958 and 0.975, respectively.The test-retest reliability of the formal version of AHLES-PHE was 0.753 ( P<0.01). Conclusion:The formal version of AHLES-PHE developed in this study has good reliability, structural validity and content validity, and the correlation validity with EHIL is common.This scale has a certain degree of applicability to the assessment of health literacy for junior middle school students under public health emergencies.
		                        		
		                        		
		                        		
		                        	
8.Reconstruction of thumb degloving injury with hallux nail flap combined with 3D printing: a report of 16 cases
Ziyun YU ; Chao LIU ; Wei DING ; Shiliang GENG ; Zhongcheng LI ; Chenglong XUE ; Guihong ZHANG ; Xuetao LIU
Chinese Journal of Microsurgery 2023;46(5):540-544
		                        		
		                        			
		                        			Objective:To explore the effect of hallux nail flap design assisted with 3D printing in reconstruction of thumb defect in degloving injury.Methods:From January 2020 to March 2022, 16 patients with thumb defect caused by degloving injury with intact digit flexor and extensor tendons were treated. The patients were 11 males and 5 females, aged 20 to 52 years old, with an average age of 31 years old. The injured patient's hands were firstly scanned by CT and the 3D models were created to map the profile of the tissues required for reconstruction. Photopolymer templates for the defects in thumb were then 3D printed. The printed templates were put on the great toes and accordingly the hallux nail flaps were designed and harvested. The degloving wound of thumb was repaired by the hallux nail flap. Donor sites were repaired with artificial dermis in 6 patients and with ilioinguinal flaps in 10 patients. The effect of surgery was observed at outpatient clinic during postoperative follow-up. The survival of the hallux nail flap and the recovery of the donor site were observed. Function recovery were evaluated according to the Evaluation Standard of Finger Replantation and Reconstruction of Hand Surgery Society of Chinese Medical Association.Results:All the harvested hallux nail flaps matched with the profiles of recipient sites. All the hallux nail flaps survived over 4 to 30 months of follow-up, in an average of 16 months. Appearance of all hallux nail flaps was similar to normal thumbs, with good fingerprint and nails. Sensation recovery were S 3-S 4, with TPD at 4-7 mm. According to the Evaluation Trial Standards of Upper Limb Partial Functional of Hand Surgery of Chinese Medical Association, 15 thumbs were excellent and 1 was good. Conclusion:Application of 3D printing assisted hallux nail flap transfer in reconstruction of defect of thumb in degloving injury can precisely design and harvest the required tissue and minimise a damage to the donor great toe. It improves the appearance of thumb as well as patient satisfaction. It is practical in reconstruction of the defect of thumb in degloving injury.
		                        		
		                        		
		                        		
		                        	
9.Research progress and future directions of adolescent health literacy evaluation tools
Chinese Journal of School Health 2022;43(12):1911-1914
		                        		
		                        			Abstract
		                        			Health literacy is closely related to the response to public health emergencies. This paper begins with health literacy evaluation tools in adults, then focuses on recent progress made in health literacy evaluation tools in adolescents from the perspective of public health emergencies. The development of adolescent health literacy evaluation tools, health education and health literacy from the perspective of public health emergencies should be greatly enhanced, helping adolescents to better respond to public health emergencies and maintain their physical and mental health.
		                        		
		                        		
		                        		
		                        	
10.Iodine nutrition levels of children aged 8 - 10 and pregnant women in Haikou City from 2016 to 2020
Yadie FU ; Guihong FANG ; Xiaozhen LI
Chinese Journal of Endemiology 2022;41(6):471-475
		                        		
		                        			
		                        			Objective:This study aims to provide scientific evidence for scientific iodine supplementation through monitoring the iodine nutrition status of children aged 8 - 10 and pregnant women in Haikou City.Methods:From 2016 to 2020, monitoring sites were selected in Longhua, Meilan, Qiongshan and Xiuying districts of Haikou City according to the requirements of the "Hainan Iodine Deficiency Disorders Monitoring Program". The iodine contents of drinking water, household edible salt and urinary iodine contents of children aged 8 - 10 and pregnant women were determined and analyzed.Results:The median iodine content of 388 drinking water samples was 5.60 μg/L, the median salt iodine content of 6 000 household edible salt samples was 25.70 mg/kg, the coverage rate of iodized salt was 98.65% (5 919/6 000), the qualified rate of iodized salt was 98.36% (5 822/5 919) and the consumption rate of qualified iodized salt was 97.03% (5 822/6 000). The median urinary iodine content of 4 000 children aged 8 - 10 was 181.68 μg/L and the median urinary iodine content of 2 000 pregnant women was 130.70 μg/L.Conclusions:The external environment of Haikou is iodine deficient. The iodine nutrition of children is generally in an appropriate state, and that of pregnant women is generally insufficient. While implementing the salt iodization policy, we should strengthen the monitoring of iodine nutrition among people and spreading iodine nutrition knowledge among residents, providing classified guidance and scientific iodine supplementation, so as to achieve the goal of continuous elimination of iodine deficiency disorders.
		                        		
		                        		
		                        		
		                        	
            

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