Objective To investigate the regulatory effect of suppressor of cytokine signaling 1 (SOCS1) on the proliferation and apoptosis of myelodysplastic syndrome (MDS) cells SKM-1 and its potential mechanisms. Methods SOCS1 was overexpressed in SKM-1 cells by transfection with exogenous SOCS1-overexpressing plasmid. Cell viability, cell cycle and apoptosis were analyzed with CCK-8 and flow cytometry assays, respectively. Western blot was used to evaluate the expression of proteins related to the Janus kinase 2/signal transducer and activator of transcription (JAK2/STAT) signaling pathway. Additionally, a NOD/SCID mouse model of MDS was established to record mouse body weight and survival time, assessing the impact of the SOCS1 gene on the growth of SKM-1 cells in vivo. Results Transfection of the SOCS1-overexpressing plasmid significantly increased the mRNA and protein expression levels of SOCS1 in the MDS cell line SKM-1. Overexpression of SOCS1 remarkably reduced cell viability, inhibited cell proliferation, and promoted apoptosis of SKM-1 cells, which also decreased the expression of phosphorylated-JAK2 (p-JAK2), phosphorylated-STAT3 (p-STAT3), and p-STAT5 proteins. Furthermore, in vivo experiment results showed that the body weight and survival time of mice in the SOCS1 overexpression group were significantly better than those in the MDS model group, and the number of CD45⁺ SKM-1 cells in the peripheral blood was significantly lower than that in the MDS model group, indicating that SOCS1 overexpression could inhibit the activity of SKM-1 cells in mice. Western blot results verified the protein expression level of SOCS1 in the bone marrow of mice in the SOCS1 overexpression group was significantly higher than that in the MDS model group, while the protein expression levels of p-JAK2, p-STAT3, and p-STAT5 were significantly lower than those in the MDS model group. Conclusion SOCS1 inhibits the proliferation of MDS cell line SKM-1 and promotes its apoptosis by negatively regulating the JAK2/STAT signaling pathway, making it a potential therapeutic target for myelodysplastic syndromes.
Animals ; Humans ; Mice ; Apoptosis ; Body Weight ; Bone Marrow/metabolism* ; Janus Kinase 2/metabolism* ; Mice, Inbred NOD ; Mice, SCID ; Myelodysplastic Syndromes/metabolism* ; Phosphorylation ; STAT3 Transcription Factor/metabolism* ; STAT5 Transcription Factor/metabolism* ; Suppressor of Cytokine Signaling 1 Protein/metabolism* ; Cell Proliferation

[摘 要] 目的：探讨miR-17-5p和含SET结构域蛋白2（SETD2）对骨髓增生异常综合征（MDS）SKM-1细胞增殖与凋亡的影响及其作用机制。方法：收集2019年3月至2021年5月衡水市人民医院就诊的35例MDS患者的骨髓标本（MDS组）、35例健康体检者的骨髓标本（对照组），以及MDS细胞系SKM-1。用qPCR法检测MDS骨髓和SKM-1细胞中miR-17-5p、SETD2 mRNA的表达水平。双荧光素酶报告基因实验验证miR-17-5p与SETD2的靶向关系。利用脂质体转染技术，分别将si-miR-NC、si-miR-17-5p、miR-NC、miR-17-5p mimic、pcDNA、pcDNA-SETD2、si-miR-17-5p+si-NC、si-miR-17-5p+si-SETD2等转染至SKM-1细胞，CCK-8法、流式细胞术检测细胞的增殖和凋亡水平，WB法检测细胞中SETD2、C-caspase-3、C-caspase-9的表达。结果：与对照组相比，MDS组骨髓中miR-17-5p表达水平显著升高、SETD2的mRNA和蛋白表达水平均显著降低（均P<0.01）。与si-miR-NC组相比，si-miR-17-5p组SKM-1细胞增殖能力显著降低、凋亡率显著升高，细胞中C-caspase-3和C-caspase-9表达显著升高（均P<0.01）。miR-17-5p明显抑制野生型SETD2细胞的荧光素酶活性（P<0.01），并负向调控SETD2的表达。过表达SETD2可显著抑制SKM-1细胞的增殖并促进细胞凋亡，同时干扰SETD2表达则可部分逆转干扰miR-17-5p对SKM-1细胞的增殖抑制和凋亡促进作用。结论：MDS骨髓中miR-17-5p呈高表达，干扰miR-17-5p可抑制SKM-1细胞增殖并促进细胞凋亡，其机制与miR-17-5p靶向负调控SETD2的表达有关。

【Objective】 To analyze the cure time from diagnosis to cure of coronavirus disease 2019(COVID-19). 【Methods】 Based on the time of admission, diagnosis, and discharge of cured cases announced by the provincial and municipal health committees, the average period from diagnosis to discharge was calculated. And based on the aggregate data including the cumulative number of diagnoses, the number of curedcases and the number of deaths and their proportional relationship, we calculated the cure time. 【Results】 The cure time curve of 580 COVID-19 patients had skewed distribution, with a skewness of 1.09, a mean cure time of (14.6±6.7) days, a median of 13 days, and a 95% confidence interval (6.9, 21.0). The average cure time calculated based on the relationship between the cumulative number of diagnoses, the number of cured cases and the number of deaths was (13.3±3.5)d, with a median of 13.5 d. The average value of the cure time calculated based on the proportion of cured cases to the number of endpoints was (14.2±4.2)d, with the median number of 14.5 d. Based on the calculation of the relationship between the cumulative number of diagnosed cases, the number of cured cases and the number of deaths, the median cure time of cases with COVID-19 in Wuhan, Hubei Province, and the whole country was 15 days, 15.5 days and 15 days, respectively. The mediancure time for COVID-19cases in Wuhan, Hubei, and the whole country was 14 days. 【Conclusion】 The median cure time of COVID-19 is 13-15.5 days. There is some variation at different time of the outbreak, but there is not much difference between different regions.

【Objective】 To investigate the death time of patients with coronavirus disease 2019 (COVID-19). 【Methods】 The death time was calculated and analyzed using individual data and aggregated data through the daily notification of the epidemic situation and the death cases published on the website of the Heath Commission of China and provinces. 【Results】 In the 153 patients who died of COVID-19, the shortest time from onset to death was 4 days and the longest time was 50 days with the mean±standard deviation of (16.7±9.2) days. The median was 14 days and the 95% confidence interval was 4.6-42.9. The shortest time from admission to death was 1 day and the longest time was 50 days with the mean ± standard deviation of (12.1±7.8) days. The median was 11 days and the 95% confidence interval was 2-32.8. The time curve from diagnosis to death was skewed. The death time from diagnosis to death was 0 to 48 days with the mean ± standard deviation of (11.1±8.9) days. The median was 9 days, the interquartile interval was 10.5 days, and the 95% confidence interval was 0-35.4. It took 3 days from onset to admission and 1 day from admission to diagnosis. Aggregated data showed that the time from diagnosis to death of COVID-19 patients in China, China (except Hubei Province), Hubei Province and Wuhan City was 8, 9, 6 and 6 days, respectively. 【Conclusion】 The time from diagnosis to death of COVID-19 patients varied significantly, with the median time of 6-9 days in different regions.

Objective:To detect serum levels of vitamin A (Vit A), vitamin D(Vit D)25-hydroxy vitamin D[25-(OH)D] and vitamin E(Vit E) in children aged 0-6 years in Tibetan Plateau of Garzi Prefecture, thus providing references for physical examinations and prevention of 4 key diseases (rickets, malnutrition anemia, pneumonia and diarrhea) in children in plateau areas by relevant government departments.Methods:A total of 2 122 children who participated in physical examination in 12 townships of Xiangcheng County and 14 townships of Daocheng County, Garzi Tibetan Autonomous Prefecture, Sichuan Province from April 2017 to April 2019 with 0-6 years old were recruited for surveying physical measurements and collection of venous blood.Serum Vit A and Vit E levels were detected by high performance liquid chromatography.Serum levels of 25-(OH)D were detected by high performance liquid chromatography tandem mass spectrometry.The relationship between Vit A, Vit E and 25-(OH)D levels with the gender, age, seasonal change and altitude was analyzed.Results:The serum Vit A level, subclinical Vit A deficiency rate and marginal vitamin A deficiency rate were(1.05±0.27) μmol/L, 8.15%(173/2 122 cases) and 45.99%(976/2 122 cases), respectively in 2 122 children with 0-6 years old.There were significant differences in the serum Vit A level, the subclinical Vit A deficiency rate and the marginal vitamin A deficiency rate in children with different ages, seasons and altitudes (all P<0.05). The serum level of 25-(OH)D and 25-(OH)D deficiency rate insufficient rate were (24.65±6.45) ng/L, 6.03%(128/2 122 cases) and 16.59%(352/2 122 cases), respectively.There were significant differences in the serum level of 25-(OH)D, 25-(OH)D deficiency rate and 25-(OH)D insufficient rate in children with different ages and seasons (all P<0.05). The mean serum Vit E level, Vit E deficiency rate and Vit E insufficient rate were (7.81±1.74) mg/L, 2.78%(59/2 122 cases) and 29.59%(628/2 122 cases), respectively.There were significant differences in serum Vit E level, Vit E deficiency rate and Vit E insufficient rate in children with different ages and seasons (all P<0.05). The mean serum levels of Vit A and Vit D remained the lowest before the age of 1 year, and their deficiencies at this age were the most significant.The mean serum level of Vit E remained the lowest in >1-2 years old, and its deficiency and insufficient at this age were the most significant.Vit A, D and E levels were significantly affected by seasonal changes, which were significantly higher in the summer than in the spring, autumn and winter.In addition, Vit A and 25-(OH)D were significantly affected by the altitude, which were the lowest above 4 km altitude. Conclusions:The overall serum levels of Vit A, 25-(OH) D and E in children with 0-6 years old in Tibetan Plateau areas of Ganzi Prefecture are lower than those in plain areas.Vit A, 25-(OH) D and Vit E levels significantly differed in the age, season and altitude, which are related to the lack of local resources, insufficient maternal nutrition during pregnancy and insufficient intake after birth, as well as temperature and light caused by changes in local seasons and altitude.Therefore, it is necessary to make reasonable supplements during pregnancy to prevent vitamin deficiency.

Objective To study the mechanism of the protective effect of α_(1A)-AR antagonist Tamsulosin (Tam) on renal ischemic injury in hepatorenal syndrome (HRS) rats. Methods HRS was induced in male Sprague-Dawley (SD) rats by intraperitoneal injection of D-(+)-galactosamine hydrochloride (GalN). Thirty-two HRS rats were divided into 3 groups randomly. Then surgical occlusions of the infrahepatic inferior vena cave (OIVC) were performed; Tam, an α_(1A)-AR antagonist, was administered daily before injection of GalN. During the operation, hemodynamic changes of the kidney and liver were measured by laser Doppler flowmetry (LDF). Serum samples were collected to measure serum levels of liver and renal function. At the same time, renal and liver samples were harvested and stained by HE and immunohistochemistry. Other parts of the sample were fixed with 2.5% glutaral to observe the cellular ultrastructure of renal and vascular endothelium by electron microscope. Results OIVC developed much severe ischemic injury in the kidney and liver of HRS rats. The renal cortex blood perfusion (RCBP) of HRS rats decreased rapidly after OIVC, and did not return to baseline after reflow. Pathological study showed severe injury of the liver and kidney. However, expressions of alpha-1 AR on renal artery and kidney were reduced in those rats that had received Tam before OIVC. Histological examination of the kidney also showed few abnormalities. Conclusion Marked increases of contractive response of renal artery of HRS rats induced by up-regulation of α_1-AR may be associated with a high risk of progression to acute renal failure in HRS rats after ischemia. Tamsulosin has a protective effect on renal ischemic injury through reducing α_(1A)-AR overexpression in HRS rats.

AIM: To observe the effect of Tongjingning Capsule (Radix Angelicae Sinensis, Rhizoma Chuanxiong, Rhizoma Cyperi, etc.) on reproductive organs of female immature mice and anti inflammatry analgesia. METHODS: Mouse uterus and ovaries were weighted. Mouse twisting numbers induced by acetic acid and mouse pain thresholds after heat stimulation were recorded. Swelling of mouse external ears, swelling of rat toes and rat granuloma were used for experiment models. RESULTS: Tongjingning Capsule significantly increased the weight of mouse uterus and ovaries. It could reduce mouse twisting numbers and prolong mouse pain thresholds after heat stimulation. It had inhibitory effects on swelling of mice's external ears resulted by dimethylbenzene, rat granuloma and swelling of rat toes resulted by egg white. CONCLUSION: Tongjingning Capsule can promote the growth of reproductive organs of female immature mice and ease pain and diminish inflammation.