Purpose This study aims to analyze genetic mutations in patients with BCR ∷ABL negative myelopro-liferative neoplasms(MPN)and to explore their relationship with clinical features.Methods We retrospectively ana-lyzed the clinical data of 208 patients diagnosed with BCR ∷ABL negative MPN,which included 34 patients with poly-cythemia vera(PV),33 with essential thrombocytopenia(ET),and 141 with primary myelofibrosis(PMF).Mutations in driver genes were assessed in all patients.A total of 72 patients underwent next-generation sequencing(NGS)with 69-gene panel,and the relationship between gene mutations and clinical features were analyzed.Results Among the 208 MPN patients,at least one driver gene mutation(JAK2,CALR,MPL)was detected in 96.15％(200/208)of the patients.Only 0.48％(1/208)of the patients exhibited both JAK2 and CALR driver mutations.We analyzed the clinical data of 136 patients with only driver gene mutations to compare the relationship between the most common JAK2 mutations(identified in 110 patients)and clinical outcomes.The JAK2 mutation group demonstrated higher white blood cell(WBC)counts and lower platelet(PLT)counts compared to the group without JAK2 mutations.173 muta-tions in 40 genes were detected in 72 patients,per capita carried(2.40±1.40)mutations.TET2,ASXL1,and TP53 are the most prevalent non-driver gene mutations,with 44.4％(32/72)of patients exhibiting at least one mutation in these three genes.In comparison to patients without detected mutations in TET2,ASXL1,and TP53,those with muta-tions in these genes demonstrated lower hemoglobin(HGB)levels,a higher incidence of splenomegaly,and more se-vere bone marrow fibrosis.High-molecular risk category(HMR)mutations were detected in 22.22％(16/72)of the patients,and patients with HMR exhibited lower hemoglobin(HGB)levels,lower PLT counts,a higher likelihood of peripheral blood primitive cell percentage ≥ 1％,a greater incidence of splenomegaly,and more severe myelofibrosis.Mutations in the ASXL1 gene were exclusively observed in patients with PMF.Among the PMF patients with ASXL1 mutations(12 patients),there was a higher likelihood of having a peripheral blood primitive cell percentage of ≥1％,as well as a more severe degree of myelofibrosis.Conclusion Approximately 97％of patients with myeloproliferative neoplasms(MPN)exhibit positivity for driver genes,with a notably high mutation rate of the JAK2 gene.Each sub-group of MPN is characterized by distinct gene mutation patterns.Notably,ASXL1 mutations are exclusive to patients with primary myelofibrosis(PMF).Furthermore,PMF patients harboring ASXL1 mutations tend to demonstrate more pronounced bone marrow fibrosis and a greater proportion of blast cells in peripheral blood.

Purpose This study aims to analyze genetic mutations in patients with BCR ∷ABL negative myelopro-liferative neoplasms(MPN)and to explore their relationship with clinical features.Methods We retrospectively ana-lyzed the clinical data of 208 patients diagnosed with BCR ∷ABL negative MPN,which included 34 patients with poly-cythemia vera(PV),33 with essential thrombocytopenia(ET),and 141 with primary myelofibrosis(PMF).Mutations in driver genes were assessed in all patients.A total of 72 patients underwent next-generation sequencing(NGS)with 69-gene panel,and the relationship between gene mutations and clinical features were analyzed.Results Among the 208 MPN patients,at least one driver gene mutation(JAK2,CALR,MPL)was detected in 96.15％(200/208)of the patients.Only 0.48％(1/208)of the patients exhibited both JAK2 and CALR driver mutations.We analyzed the clinical data of 136 patients with only driver gene mutations to compare the relationship between the most common JAK2 mutations(identified in 110 patients)and clinical outcomes.The JAK2 mutation group demonstrated higher white blood cell(WBC)counts and lower platelet(PLT)counts compared to the group without JAK2 mutations.173 muta-tions in 40 genes were detected in 72 patients,per capita carried(2.40±1.40)mutations.TET2,ASXL1,and TP53 are the most prevalent non-driver gene mutations,with 44.4％(32/72)of patients exhibiting at least one mutation in these three genes.In comparison to patients without detected mutations in TET2,ASXL1,and TP53,those with muta-tions in these genes demonstrated lower hemoglobin(HGB)levels,a higher incidence of splenomegaly,and more se-vere bone marrow fibrosis.High-molecular risk category(HMR)mutations were detected in 22.22％(16/72)of the patients,and patients with HMR exhibited lower hemoglobin(HGB)levels,lower PLT counts,a higher likelihood of peripheral blood primitive cell percentage ≥ 1％,a greater incidence of splenomegaly,and more severe myelofibrosis.Mutations in the ASXL1 gene were exclusively observed in patients with PMF.Among the PMF patients with ASXL1 mutations(12 patients),there was a higher likelihood of having a peripheral blood primitive cell percentage of ≥1％,as well as a more severe degree of myelofibrosis.Conclusion Approximately 97％of patients with myeloproliferative neoplasms(MPN)exhibit positivity for driver genes,with a notably high mutation rate of the JAK2 gene.Each sub-group of MPN is characterized by distinct gene mutation patterns.Notably,ASXL1 mutations are exclusive to patients with primary myelofibrosis(PMF).Furthermore,PMF patients harboring ASXL1 mutations tend to demonstrate more pronounced bone marrow fibrosis and a greater proportion of blast cells in peripheral blood.

Objective To analyze the epidemiological characteristics and epidemic situation of children with Kashin-Beck disease (KBD) in China,and provide the basis for formulating prevention and control measures. Methods Fixed-point monitoring,moving-point monitoring,and full coverage of monitoring were promoted successively from 1990 to 2023. Some children (7-12 years old) underwent clinical and right-hand X-ray examinations every year. According to the KBD diagnosis criteria,clinical and X-ray assessments were used to confirm the diagnosis. Results In 1990,the national KBD detectable rate was 21.01％. X-ray detection decreased to below 10％ in 2003 and below 5％ in 2007. Between 2010 and 2018,the prevalence of KBD in children was less than 0.4％,which fluctuated at a low level,and has decreased to 0％ since 2019. Spatial epidemiological analysis indicated a spatial clustering of adult patients prevalence rate in the KBD areas. Conclusion The evaluation results of the elimination of KBD in China over the last 5 years showed that all villages in the monitored areas have reached the elimination standard. While the adult KBD patients still need for policy consideration and care.

Objective:To investigate the dynamic prevalence of Kashin-Beck disease (KBD) in 2020, and to provide the basis for assessment of KBD control and elimination.Methods:According to the "Kashin-Beck Disease Monitoring Plan (2019 Edition)", collection of basic information of endemic areas and children KBD examination were executed in all endemic areas from every endemic county (city, district, banner) of 13 endemic provinces. All children aged 7 - 12 years in endemic areas underwent clinical examination, X-ray examination was performed for clinically positive children. According to the criteria of "Diagnosis of Kashin-Beck Disease" (WS/T 207-2010), KBD cases were diagnosed by both clinical examination and X-ray check.Results:In monitoring of 827 986 children of 7 - 12 years old, a total of 703 children with similar clinical signs of KBD were suspected positive cases. X-ray results showed that 703 children were normal, with no X-ray positive change, they were not children KBD cases.Conclusions:In 2020, no cases of Kashin-Beck disease are detected in children nationwide, and the condition of Kashin-Beck disease in children nationwide continues to be at a level of elimination.

Objective:To investigate the effects of glucosamine sulfate, chondroitin sulfate and diacerein on liver function in patients with Kashin-Beck disease.Methods:According to the criteria of "Diagnosis of Kashin-Beck Disease" (WS/T 207-2010), 333 cases of Kashin-Beck disease were selected from the disease severely affected areas, and randomly divided into 3 groups according to the matching principle of age, gender and disease grading: glucosamine sulfate group (group A, 118 cases), chondroitin sulfate group (group B, 99 cases) and diacerein group (group C, 116 cases), and the patients in each group were treated for 180 days. Fasting venous blood samples were collected from the patients in the three groups at 0, 90 and 180 days after treatment. Serum was separated. The biochemical analyzer was used to determine the serum levels of albumin (ALB), alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), direct bilirubin (DBIL), glutamyl transpeptidase (GGT), total bilirubin (TBIL), and total protein (TP) of the three groups of patients.Results:There was no difference in the expression levels of 8 liver function indexes between the groups on day 0 of treatment ( P > 0.05). After 90 days of treatment, the expression level of GGT in group B was higher than that in group A ( P < 0.05); compared with 0 day of treatment, ALB levels of groups A, B and C were all decreased, ALP and TBIL levels increased ( P < 0.05), the abnormal expression rate of ALB index decreased in all the three groups ( P < 0.001), the abnormal expression rate of TBIL index in group A was decreased ( P = 0.006). After 180 days of treatment, ALB level of group B was higher than that of group A, ALP level of group B was higher than that of groups A and C, and AST level of group B was higher than that of group C ( P < 0.05); compared with 90 days of treatment, ALB levels of groups A, B and C were all increased, ALP, ALT and AST levels of groups A and C were decreased, GGT levels of groups B and C were decreased ( P < 0.05); compared with 0 day of treatment, the abnormal expression rate of ALB index increased in all the three groups at 180 days of treatment ( P < 0.001), and the abnormal expression rate of ALP index decreased in group C ( P = 0.031). Conclusion:The liver function indicators ALB, ALP and TBIL should be monitored when taking the three oral drugs for a short time, especially the GGT, ALP and AST indicators when taking chondroitin sulfate for a long time.

Objective:To explore whether the limit of "before the equal-diameter period" is reasonable in the current criteria for "Diagnosis of Kashin-Beck Disease" (WS/T 207-2010) in children, and to provide basic data and technical support for revision of the criteria for "Diagnosis of Kashin-Beck Disease" (WS/T 207-2010).Methods:In 2018, the historical Kashin-Beck disease (KBD) areas in Heilongjiang Province were selected as the investigation sites. The right-hand X-ray films of all children aged 7-12 years old were taken. According to the different X-ray manifestations of the growth and development of the phalangeal epiphysis, they were divided into five periods: before the equal-diameter period, equal-diameter period, ultra-diameter period, pre-closure period and closure period. Firstly, after stratifying by basic data such as age and gender, the data were standardized and analyzed. Secondly, the detection rates of metaphysis-epiphysis (CRME) in each period were calculated and compared. Finally, based on the mean value of the detection rate of metaphyseal change in Linkou and Fuyu counties of Heilongjiang Province in 1990, the rates of expected detection and missed diagnosis of metaphyseal changes of KBD among investigated children were calculated and compared under the limitation of before the equal-diameter period, before the ultra-diameter period or age range reduction.Results:A total of 5 019 children were investigated. The proportion of children before the equal-diameter period was 53.94% (2 707/5 019), and that of before the ultra-diameter period was 77.92% (3 911/5 019). The results showed that the equal-diameter period mainly appeared in 7-10 years old, and showed a decreasing trend with the increase of age (χ 2trend = 390.10, P<0.05); the ultra-diameter period mainly occurred in 10-12 years old, showing a decreasing trend with the increase of age (χ 2trend = 65.39, P < 0.05); the pre-closure period mainly occurred in 10-12 years old, with an increasing trend with the increase of age (χ 2trend = 51.86, P<0.05); the closure period mainly occurred in 11-12 years old and increased with age (χ 2trend = 7.58, P<0.05). The CRME of children in ultra-diameter period was 14.78% (158/1 069), however CRME did not occur in children with equal-diameter period. Among children before equal-diameter period, before ultar-diameter period and aged 7-10 years old, the expected detection rates of metaphyseal changes of KBD were 5.90%, 8.53% and 7.42%, respectively. The expected missed diagnosis rates of metaphyseal changes of KBD were 5.06%, 2.45% and 3.52%, respectively. Conclusion:In order to improve the rate of expected detection and lower the rate of missed diagnosis of metaphyseal changes of KBD, children in "equal-diameter period" should be included in X-ray diagnosis and disease monitoring of KBD.

Objective:To master the status of Kashin-Beck disease (KBD) in 2019, to provide the basis for assessment of KBD control and elimination.Methods:Data of endemic areas basic information collection and children KBD examination were executed in all endemic villages from every endemic county (city, district, banner) of 13 endemic provinces. All children aged 7 - 12 years in endemic villages underwent clinical examination, and X-ray examination was performed for clinically positive children. When both the clinical examination and X-ray reexamination were positive, the diagnosis was KBD.Results:In monitoring of 823 365 7 - 12 years old children, a total of 3 057 children with similar clinical signs of KBD were suspected positive cases. The results of X-ray reexamination showed that the X-ray manifestations of 3 057 children were normal, and no X-ray positive changes were found, that is, there was no case of KBD in children. A total of 16 559 endemic villages in 13 endemic provinces were monitored, and all reached the criteria for KBD elimination. Surveillance of all endemic villages was completed except Tibet Autonomous Region, the KBD elimination rates of endemic villages were 100.00% in 12 endemic provinces and 99.01% (16 559/16 725) in all 13 endemic provinces.Conclusions:No children KBD case is detected in 2019, children KBD stays at its eliminating level throughout the country. And 100.00% endemic villages meet the criteria for KBD elimination in the remaining 12 endemic provinces except Tibet Autonomous Region.

As the main pollutant of food crops, T-2 toxin has toxic effects on human and animal digestive system, nervous system, reproductive development and so on. In Kashin-Beck disease related areas in China, the etiological substance of Kashin-Beck disease is the abnormal accumulation of T-2 toxin in the grain produced in the endemic area. The prevention and treatment of Kashin-Beck disease has achieved remarkable results through the comprehensive prevention and control measures, such as changing the production and life style, grain exchange, etc., but there are still pathogenic factors in the external environment of the disease area. In this paper, the metabolic kinetics of T-2 toxin is reviewed, and the physicochemical properties, distribution in the body, metabolic kinetics, biotransformation and damage of T-2 toxin and its metabolites to various organs are described, so as to provide new thinking for the study on the effects of T-2 toxin on various organs of the body.

Objective:To investigate the oral medication treatment of adult patients with Kashin-Beck disease(KBD) in China, so as to provide theoretical basis for medication screening of KBD and to provide scientific guidance for clinical treatment of KBD.Methods:Based on the "Endemic Disease Prevention and Control Project of Special Funds for Local Public Health Subsidized by the Central Government" and "Major Public Health Service Endemic Disease Prevention and Control Project", the treatment information of adult patients with KBD in 11 provinces (autonomous regions, referred to as provinces) in China from 2006 to 2017 was collected, and the treatment coverage of adult patients with KBD in different years and regions was analyzed, and the curative effect of patients with different severity was evaluated.Results:From 2006 to 2017, the number of provinces participating in the treatment project was from 2 to 11. The actual total number of people treated in China was 68 061, with a completion rate of 78.10% (68 061/87 149); the annual number of people treated increased linearly; the overall clinical symptom remission rates of adult patients with KBD in all regions reached more than 50%, and the overall treatment effect showed an upward trend year by year; compared with patients with grade Ⅲ, after oral medication, the remission rates of clinical symptoms in patients with gradeⅠandⅡ were higher (the average remission rate of clinical symptoms was 84.13% for gradeⅠ, 80.71% for grade Ⅱ and 72.11% for grade Ⅲ, P < 0.05). Conclusions:Oral medication treatment can effectively alleviate the clinical symptoms of most adult patients with KBD of grade Ⅰ and Ⅱ. Patients of grade Ⅲ should be considered treating with oral medication combined with other treatment methods. A considerable number of patients are still ineffective in taking drugs at this stage, and it is urgent to carry out the screening, research and development of specific medications for KBD.

Objective:To observe and compare the therapeutic effects of glucosamine sulfate (GS) and diacerein (DCN) on adult Kashin-Beck disease (KBD).Methods:A clinical randomized controlled trial was conducted in the historical severe KBD areas Fanrong Township, Fulu Town, Long'anqiao Town, Lianghe Town, Shaowen Township of Heilongjiang Province, and 240 patients were selected according to the criteria of "Diagnosis of Kashin-Beck Disease" (WS/T 207-2010), then divided into GS and DCN groups (gender, age, and KBD condition balanced) via the random number table method, with 120 patients in each group. Followed up once a month to investigate the patient's medication and clinical symptoms, and distributed drugs for the next stage. Fasting blood samples and urine samples were collected before, during, and at the end of treatment (0, 90, and 180 days). Enzyme-linked immunosorbent assay (ELISA) was used to detect the serum interleukin (IL)-1β level and urine pyridinol (PYD) level. Visual analog scale (VAS) scores, evaluation of affected joints, self-evaluated efficacy, and evaluation of adverse reactions were carried out through questionnaires. Joint dysfunction scores and medications efficacy determination were performed according to the "Judgment of Kaschin-Beck Disease Treatment Effect" (WS/T 79-2011).Results:Expression of cytokines related to cartilage metabolism: after 180 days of treatment, serum IL-1β levels, urine PYD levels in GS group and urine PYD levels in DCN group were lower than those in the same group at 0 day of treatment ( Z = - 2.332, - 5.420, - 5.204, P < 0.05). VAS scores: after 90 days of treatment, the pain, stiffness scores of patients in GS group and the pain, stiffness, and function scores in DCN group were lower than those in the same group at 0 day of treatment ( Z = - 2.612, - 2.359, - 3.637, - 2.881, - 2.238, P < 0.05); after 180 days of treatment, the pain, stiffness and function scores of patients in GS and DCN groups were significantly lower than those of the same group at 0 day of treatment ( Z = - 6.738, - 9.530, - 7.781, - 5.428, - 3.761, - 3.587, P < 0.01). Evaluation of affected joints: after 90 and 180 days of treatment, except for pain of weather changes in DCN group, the scores of symptomatic joints in the two groups were lower than those at 0 day of treatment ( P < 0.05). Efficacy self-evaluation: after 180 days of treatment, the self-evaluated efficacy ratio of DCN group was higher than that of GS group and the same group after 90 days of treatment (χ 2 = 4.165, 4.022, P < 0.05). Evaluation of adverse reactions: after 90 and 180 days of treatment, the main adverse reactions of patients in GS and DCN groups were gastrointestinal symptoms. Joint dysfunction scores: after 90 days of treatment, the sum of the effective rate and the markedly effective rate of GS group was higher than that of DCN group (χ 2 = 4.993 , P < 0.05); while after the 180 days of treatment, there was no significant difference between the two groups (χ 2 = 0.417 , P > 0.05). Conclusions:Both GS and DCN have a certain therapeutic effect on adult KBD and can improve clinical symptoms. The GS takes effect quickly, and long-term use can protect cartilage from inflammatory factors to a certain extent.