Cerebral organoids are three-dimensional nerve cultures induced by embryonic stem cells(ESCs)or induced pluripotent stem cells(iPSCs)that mimic the structure and function of human brain.With the continuous optimization of cerebral organoid culture technology and the combination with emerging technologies such as organ transplantation,gene editing and organoids-on-chip,complex brain tissue structures such as functional vascular structures and neural circuits have been produced,which provides new methods and ideas for studying human brain development and diseases.This article reviews the latest advances in brain organoid technology,describes its application in neurological diseases and advances in stroke modeling and transplantation treatment.

Post-stroke cognitive impairment(PSCI)is mainly manifested as learning and memory disorders.Highly enriched RNA m6A methylation modification in mammalian brain is involved in glial cell-mediated neuroinflammation.Given that neuroinflammation is the main mechanism for neural damage and spatial and memory impairment of PSCI,it is speculated that RNA m6A methylation modification can regulate the inflammatory response of glial cells after stroke to improve PSCI.This review summarizes and analyzes the role of RNA m6A methylation modification in the development of PSCI and analyzes its detailed mechanism of regulating glial cell-mediated inflammation,which will provide reference for researchers in this field.

BACKGROUND:Long non-coding RNAs(lncRNAs),as important regulators of the inflammatory response,are involved in the immune-inflammation-brain crosstalk mechanism after ischemic stroke and have the potential to become a therapeutic agent for neurological dysfunction after ischemic stroke. OBJECTIVE:To analyze and summarize the molecular mechanism of lncRNA acting on glial cells involved in the neuroimmuno-inflammatory cascade response after ischemic stroke and the associated signaling pathways,pointing out that lncRNAs have the potential to regulate inflammation after ischemic stroke. METHODS:PubMed was searched using the search terms of"ischemic stroke,long non-coding RNA,neuroinflammation,immune function,signal pathway,microglia,astrocytes,oligodendrocyte,mechanism,"and 63 relevant documents were finally included for review. RESULTS AND CONCLUSION:In the early stage of ischemic stroke,the death of nerve cells due to ischemia and hypoxia activates the innate immune response of the brain,promoting the secretion of inflammatory factors and inducing blood-brain barrier damage and a series of inflammatory cascades responses.As an important pathogenesis factor in ischemic stroke,the neuroimmuno-inflammatory cascade has been proved to seriously affect the prognosis of patients with ischemic stroke,and it needs to be suppressed promptly in the early stage.Neuroinflammation after ischemic stroke usually induces abnormal expression of a large number of lncRNAs that mediate a series of neuro-immune-inflammatory crosstalk mechanisms through regulating the polarization of microglia,astrocytes and oligodendrocytes to exert post-stroke neuroprotective effects.LncRNAs,as important regulatory factors of the inflammatory response,inhibit the neuroimmuno-inflammatory cascade response after ischemic stroke through regulating nuclear factor-κB,lncRNA-miRNA-mRNA axis,Rho-ROCK,MAPK,AKT,ERK and other signaling pathways to effectively improve neurological impairment after ischemic stroke.Most of experimental studies on the interaction between lncRNAs and ischemic stroke are based on a middle cerebral artery occlusion model or a cerebral ischemia-reperfusion injury model,but no clinical trials have been conducted.Therefore,it remains to be further explored about whether lncRNAs can be safely applied in clinical practice.At present,there are many therapeutic drugs for the treatment of ischemic stroke,but there are relatively few studies on the application of lncRNAs,exosomes and other transplantation technologies for the treatment of ischemic stroke using tissue engineering technology,which need to be further explored.lncRNA has become an important target for the treatment of ischemic stroke with its relative stability and high specificity.In future studies,more types of inflammatory lncRNAs that function under ischemic-hypoxia conditions should continue to be explored,in order to provide new research directions for the treatment of neuroinflammation after ischemic stroke.

Post-stroke cognitive impairment(PSCI)is a common complication after stroke,which significantly affects quality of life.However,the pathogenesis has not been fully explained.Increasing evidence has shown that the mechanism of programmed cell death(PCD)is related to PSCI,including apoptosis,necroptosis,pyroptosis,PANoptosis,parthanatos,and ferroptosis.Therefore,it is crucial to clearly understand the various mechanisms of PCD and their relationship with PSCI,and to elucidate the role of PCD in PSCI pathogenesis.The article reviews six PCD pathways related to PSCI,summarizes their mechanisms of action in PSCI,and elucidates the possible crosstalk among pathways to provide a basis for clinical targeting of regulatory factors in the PCD pathway for PSCI treatment.

Objective:To compare the application effect among Western Ontario and McMaster University Osteoarthritis Index (WOMAC) scale, Medical Outcomes Study 36-item Short Form (SF-36) scale and "Assessment for Therapeutic Efficacy on Kashin-Beck Disease" (WS/T 79-2011) standard in the evaluation of therapeutic effect of patients with Kashin-Beck disease, which could provide basis for the treatment evaluation of patients with Kashin-Beck disease.Methods:A total of 213 patients with Kashin-Beck disease in Gansu Province were investigated. WOMAC scale, SF-36 scale and standard of WS/T 79-2011 were used to analyze the quality of life of patients before and after treatment. The reliability, construct validity, content validity, discriminant validity of WOMAC and SF-36 scales were compared. Correlation between WOMAC, SF-36 scales and standard of WS/T 79-2011 were evaluated.Results:Both WOMAC and SF-36 scales had good construct validity and content validity (construct validity showed WOMAC and SF-36 scales contained 1 and 2 common factors, respectively; content validity showed WOMAC and SF-36 scales contained 3 and 8 common factors, respectively). The reliability and discriminant validity of WOMAC scale were better than those of SF-36 seale (reliability showed WOMAC reliability coefficient ≥0.934, the reliability coefficient of SF-36 scale was ranged from 0.386 to 0.999. Discriminant validity showed there were differences in 3 dimensions of the WOMAC scale before and after treatment, while there were differences in 6 out of 8 dimensions of the SF-36 scale). The correlation coefficients between WOMAC scale and standard of WS/T 79-2011 ranged from 0.175 to 0.437, the correlation coefficients between SF-36 scale and standard of WS/T 79-2011 ranged from - 0.434 to - 0.099 ( P < 0.05). Conclusion:The reliability, discriminant validity and correlation with the standard of WS/T 79-2011 of WOMAC scale are better than those of SF-36 scale in efficacy evaluation of patients with Kashin-Beck disease.

Objective:To further investigate the prevalence of tea-drinking-borne endemic fluorosis in Tianzhu Tibetan Autonomous County (referred to as Tianzhu) Gansu Province, to accurately master the information of patients with tea-drinking-borne endemic fluorosis, and to provide scientific basis for popularizing low fluoride brick tea and carrying out patient rescue and treatment.Methods:From 2019 to 2020, according to the "Investigation Plan of Tea-drinking-borne Endemic Fluorosis in Gansu Province in 2019", in the administrative villages with the habit of drinking and selling tea, drinking water samples of local residents were collected to detect the fluorine content of water in Tianzhu, 10 families were randomly selected in each village, basic situation of each family member and the drinking situation of tea were investigated, and tea samples were collected to determine the fluorine content. At the same time, all children aged 8 - 12 in the investigation village were examined for dental fluorosis; clinical examination of bone and joint symptoms and signs was conducted for permanent residents over the age of 25 in the investigation village (excluding 25 years old), X-ray examination of bone and joint was conducted for patients with clear clinical symptoms or signs of skeletal fluorosis, and urine samples were collected to detect urinary fluorine. Ion selective electrode method was used to detect fluorine in water, tea and urine, and dental fluorosis was diagnosed by "Diagnosis of Dental Fluorosis" (WS/T 208-2011), and the "Diagnostic criteria for Endemic Skeletal Fluorosis" (WS 192-2008) was used for the diagnosis of skeletal fluorosis.Results:A total of 161 water samples were collected, and the fluorine content in water was from 0.07 to 0.68 mg/L, which met the domestic drinking water standard ( < 1.0 mg/L). A total of 1 644 side-tea samples were collected, and the annual per capita consumption of side-tea of permanent residents over 16 years old was 1.05 kg. The average fluoride content of tea was 601.99 - 991.38 mg/kg. According to the detection results of tea fluorine, 16 administrative villages with an average daily intake of tea fluorine more than 3.5 mg/d were screened, the lowest intake was 4.91 mg/d in Tuta Village Danma Township, and the highest intake was 18.98 mg/d in Huashan Village Maozang Township. A total of 253 children aged 8 - 12 years old in 14 administrative villages were investigated. There were 3 cases of very mild dental fluorosis, 2 cases of mild dental fluorosis, and 1 case of moderate dental fluorosis. The overall prevalence of dental fluorosis was 4.74% (12/253). The clinical examination of bone and joint symptoms and signs was carried out for 3 100 permanent adults over the age of 25 (excluding the age of 25) in 15 administrative villages. The X-ray examination of bone and joint was carried out for 104 patients with definite clinical symptoms and/or signs of skeletal fluorosis. Six patients with skeletal fluorosis were diagnosed, including 3 mild and 3 severe, aged 56 - 76 years. The average urinary fluorine in the investigated villages was 0.73 - 4.74 mg/L (the number of investigated was 3 100). According to the determination and classification standards of tea-drinking-borne fluorosis area, Tuta Village Danma Township, Xiding Village Dahonggou Township and Daiqian Village Zhuaxixiulong Township were determined to be in the mild area of tea-drinking-borne endemic fluorosis, while Nannigou Village Zhuaxixiulong Township was in the moderate area of tea-drinking-borne endemic fluorosis.Conclusion:Tea-drinking-borne endemic fluorosis is prevalent in Tianzhu, Gansu Province, and targeted prevention methods and control measures need to be taken.

Objective:To master the epidemic trend of Kashin-Beck disease (KBD) in Gansu Province and provide a scientific basis for prevention and treatment of KBD.Methods:All children aged 7 - 12 or 16 years old were selected as the survey subjects in 37 KBD districts and counties in Gansu Province, clinical and X-ray monitoring results of KBD in children from 2004 to 2018 were collected to analyze the epidemic trend of the disease.Results:From 2004 to 2018, a total of 97 190 children were examined clinically and 94 180 X-ray films were taken in Gansu Province. Four hundred and twenty-eight clinical positive cases were detected, with a detection rate of 0.44%. There were 649 X-ray positive cases, and the detection rate was 0.69%. There were 435 metaphyseal positive cases, the detection rate was 0.46%. There were 214 positive cases of bone end, and the detection rate was 0.23%. The clinical positive rate was the highest (7.17%, 58/809) in 2004, followed by 2007 (4.60%, 51/1 109) and 2005 (4.48%, 187/4 173), and the positive rate in other years was less than 3%. The positive rate of X-ray was the highest (9.59%, 58/605) in 2004, followed by 2005 (5.10%, 213/4 173), 2008 (3.66%, 45/1 228) and 2006 (3.04%, 125/4 107), the positive rate of other years was less than 3%.Conclusions:The clinical positive rate and X-ray positive rate of KBD in children in Gansu Province are decreased rapidly and then maintain a low fluctuation. The effect of comprehensive prevention and control measures is remarkable.

Objective:To analyze the epidemic range of tea-drinking-borne endemic fluorosis in Gansu Province and accurately grasp the information of tea-drinking-borne endemic fluorosis patients, so as to provide basis for popularizing low fluorine brick tea and carrying out patient rescue and treatment.Methods:From 2019 to 2020, 12 counties (cities) in Gansu Province with a history of drinking brick tea were selected as the survey points according to the "Investigation Plan of Endemic Fluorosis of Tea Drinking Type in China in 2019" and the relevant information in Gansu Province. A cross-sectional survey was conducted in all villages with the habit of drinking brick tea (including the investigation of the fluoride content in drinking water, tea, the fluoride intake of the population, the dental fluorosis and urinary fluoride content of children aged 8 to 12, and the skeletal fluorosis and urinary fluoride content of adults), and the survey results were analyzed.Results:The survey covered 125 townships in 12 counties (cities), with 8 625 households in 860 villages. One thousand six hundred and seventy-two drinking water samples were collected, and the fluoride content in water ranged from 0.01 to 1.81 mg/L. Six villages with fluoride content > 1.0 mg/L were screened. A total of 3 664 tea samples were collected, the average fluorine content of brick tea was 481.33 mg/kg, and the fluorine content ranged from 31.88 to 1 643.40 mg/kg. There were 1 076 tea samples with fluorine content less than 300 mg/kg, and the qualified rate of fluorine content in brick tea was 29.37% (1 076/3 664). Among the 12 counties (cities), 92 townships and 496 villages were still drinking brick tea. The drinking rate of brick tea in villages was 57.67% (496/860), and the annual per capita consumption of brick tea was 1.21 kg. The average daily intake of tea fluoride in adults was 1.57 mg/d. In Maqu County, Aksai County, Tianzhu County and Sunan County, the daily intake of tea fluoride of adults in 31 villages of 13 townships was more than 3.5 mg, involving 5 272 households and 15 272 people. Sixty-five patients with dental fluorosis were found in the above 31 villages. The detection rate of dental fluorosis was 3.50% (65/1 856), mainly in very mild and mild cases. Urine samples were collected from 326 children. The median of urinary fluoride was 1.44 mg/L. The clinical investigation of skeletal fluorosis was carried out in 2 189 adults. X-ray examination of bones and joints was performed in 123 patients with definite clinical symptoms and/or signs of skeletal fluorosis. Seven cases of skeletal fluorosis were positive, the detection rate was 0.32% (7/2 189). Urine samples were collected from 83 adults. The median of urinary fluoride was 1.83 mg/L. Two villages with moderate disease were identified as Yehuwan Village in Anyuan Town of Tianzhu County and Nannigou Village in Zhuaxixiulong Town. Four villages in the mild diseased areas were identified as Daiqian Village in Zhuaxixiulong Town, Xiding Village in Dahonggou Town, Tuta Village in Danma Township of Tianzhu County and Annanba Village in Akeqi Township of Akesai County.Conclusion:Most of the endemic areas of tea-drinking-borne endemic fluorosis in Gansu Province have been under control, but the risk of tea fluoride exposure still exists in some areas, so it is urgent to take targeted prevention and control measures.

Objective:To comprehensively investigate the epidemic scope, geographic features and threatened population of tea drinking type endemic fluorosis in Gansu Province.Methods:From June 2019 to December 2020, according to the "2019 Investigation Plan on the Epidemic Situation of Tea Drinking Type Endemic Fluorosis" and the relevant information about the living habits of residents in cities (prefectures) in Gansu Province, 12 counties (cities) in 4 cities (prefectures) of Gannan, Wuwei, Jiuquan and Zhangye, which had the habit of drinking border-sale tea, were selected as the survey sites. The survey contents included temperature, altitude, the number of townships (towns), the number of administrative villages (residents' committees, referred to as villages), the total population under its jurisdiction, ethnic composition, production methods, drinking condition of border-sale tea, fluoride content of tea, etc. The fluoride content of tea was tested according to "The Fluoride Content of Brick Tea" (GB 19965-2005), and the evaluation of whether the fluoride content exceeded the standard (> 300 mg/kg) was carried out.Results:The annual average temperature of the survey sites ranged from 0.2 to 12.7 ℃, except for Zhouqu County, the annual average temperature of the other 11 counties (cities) was < 10 °C; the average altitude ranged from 1 200 to 4 874 m, and there were 6 counties (Maqu, Tianzhu, Subei, Sunan, Aksay and Luqu) with an altitude > 3 000 m. The total population of the 12 counties (cities) was 1 051 843, of which 492 597 (46.83%) were ethnic minorities who had the habit of drinking border-sale tea; among them, there were 474 620 Tibetans, 10 152 Yugurs, 4 660 Mongolians and 3 165 Kazaks. In 860 villages of 125 townships (towns), a survey was conducted on drinking condition of border-sale tea, and the survey rate was 79.48% (860/1 082); the drinking border-sale tea rates of villages and families were 57.67% (496/860) and 42.41% (3 658/8 625), respectively. From the perspective of production methods, the drinking border-sale tea rates of villages and families in the pastoral counties such as Aksay, Subei, Maqu, Luqu and Sunan, as well as in the semi-agricultural and semi-pastoral county of Tianzhu, were all > 95%. A total of 3 664 tea samples were tested, with an average fluoride content of 481.33 mg/kg. There were 2 588 tea samples with a fluoride content > 300 mg/kg, accounting for 70.63% (2 588/3 664).Conclusions:There are still a large number of populations who drink border-sale tea in Gansu Province, mainly distributes in the low-temperature and high-altitude pastoral counties such as Aksay, Subei, Maqu, Luqu and Sunan. The ethnic group most threatened by tea drinking type endemic fluorosis is Tibetans.

Objective:To analyze the results of polysomnography(PSG) in 523 children, and explore the sleep monitoring results and related influencing factors of obstructive sleep apnea hypopnea syndrome(OSAHS).Methods:The PSG monitoring results of children with OSAHS and non-OSAHS were analyzed for children aging from 0 to 16 years old, who were monitored at Sleep Medicine Center of Gansu Maternal and Child Health Hospital from January 2014 to December 2019.Results:A total of 523 children underwent PSG monitoring during the past 5 years.The male to female ratio was 1∶0.47, of which 66.9%(350/523)were children with OSAHS.The average proportion of rapid eye movement sleep was 1.95%(7.7/394). The height of non-OSAHS group was significantly higher than that of OSAHS group[(108.72±16.39)cm vs.(104.80±16.60)cm, P=0.016]. The incidence of OSAHS decreased with age( P=0.038). The apnea index, hypopnea index, apnea hypopnea index, obstructive apnea index, microarousal index, oxygen desaturation index, mean apnea time, and longest apnea time in the OSAHS group were higher than those in the non-OSAHS group( P<0.05). And the lowest oxygen saturation and the mean oxygen saturation during sleep were lower than those in the non-OSAHS group( P<0.05). Logistic regression analysis on the clinical data of OSAHS children showed that open mouth breathing and snoring at night had significant effects on children′s OSAHS, and the differences were statistically significant( P<0.05). Conclusion:PSG is of great significance for the diagnosis of OSAHS.The more severe the degree of OSAHS, the worse severe the night sleep hypoxemia.PSG should be recommended before taking any treatment for children with sleep disorders.