OBJECTIVEThe pathophysiology of beta-thalassemia is the imbalance of the alpha and non-alpha globin chain which leads to a series of clinical symptoms of hemolytic anemia. Scientists continuously try to explore gene-activated drugs to increase the level of non-alpha globin chain or decrease the level of alpha globin chain in the treatment of beta-thalassemia. To probe into the effects on globin-gene expression of meisoindigo (Me) in cultured erythroid cells derived from peripheral blood, so as to provide the theoretical basis for applying Me in the treatment of beta-thalassemia.

METHODSBy using the two-step liquid culture of erythroid progenitor cells and reverse transcription polymerase chain reaction (RT-PCR), and by using alpha mRNA as an inner control, the level of gamma mRNA and beta mRNA in cultured erythroid cells derived from peripheral blood of 11 patients with severe beta-thalassemia and 6 normal volunteers were measured under the effect of different concentration (2.5 micro mol/L, 5 micro mol/L and 10 micro mol/L) of Me.

RESULTS(1) No statistic significance was found in the ratio of beta/alpha mRNA by Me in cultured cells from both normal individuals and beta-thalassemia. (2) Me can significantly increase the ratio of gamma/alpha mRNA and (beta + gamma)/alpha mRNA (that is non-alpha/alpha mRNA) in cultured cells from normal individuals and beta-thalassemia. The ratio of gamma/alpha mRNA was increased 0.31 - 0.45 times and the ratio of non-alpha mRNA/alpha mRNA increased 0.21 - 0.32 times in Me induced cells from normal individuals. No significant result was observed among the different concentrations of Me (2.5 micro mol/L, 5 micro mol/L and 10 micro mol/L) in normal individuals. With the increasing of Me concentrations, the ratios of gamma/alpha mRNA and alpha/alpha mRNA were increased in cultured cells from beta-thalassemia. The ratio of gamma/alpha mRNA was increased 0.33 - 1.17 times and the ratio of non-alpha/alpha mRNA increased 0.25 - 0.89 times in Me induced cells from beta-thalassemia. There was no significant difference between the concentrations of 2.5 micro mol/L and 5 micro mol/L concentration in beta-thalassemia. However, there was significant difference between the concentrations of 10 micro mol/L and the concentrations of 2.5 micro mol/L and 5 micro mol/L in beta-thalassemia. (3) The increase of the ratio of gamma/alpha mRNA and non-alpha/alpha mRNA in beta-thalassemia was higher than that in normal individual with induction by Me with a higher concentration (10 micro mol/L).

CONCLUSIONMe can raise the ratio of gamma/alpha mRNA and non-alpha/alpha mRNA in cultured erythroid cells derived from peripheral blood of both normal individual and beta-thalassemia in the level of transcription, which can improve the imbalance of the alpha and non-alpha globin chain. So Me has a latent value in the therapy of beta-thalassemia.

Cells, Cultured ; Child ; Child, Preschool ; Erythroid Precursor Cells ; drug effects ; metabolism ; Female ; Gene Expression ; drug effects ; Globins ; genetics ; Humans ; Indoles ; pharmacology ; Infant ; Male ; RNA, Messenger ; drug effects ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction

Objective To investigate clinical effect of tendons pulling,poking and kneading for the treatment of external humeral epicondylitis.Metods From January 2018 to December 2021,a multicenter randomized controlled study was per-formed to collect 192 patients with external humeral epicondylitis in Wangjing Hospital,Beijing Dianli Hospital,and Beijing Fengsheng Osteotraumatology Hospital,respectively,and they were divided into treatment group and control group by random number table method.There were 96 patients in treatment group,including 36 males and 60 females,aged from 28 to 60 years old with an average of(41.20±5.50)years old;the course of disease ranged from 1 to 14 days with an average of(5.24±1.35)days;they were treated once every other day for 2 weeks.There were 96 patients in control group,including 33 males and 63 females,aged from 26 to 60 years old with an average of(43.35±7.75)years old;the course of disease ranged from 1 to 14 days with an average of(5.86±1.48)days;they were treated with topical voltaalin combined with elbow joint fixation for 2 weeks.Visual analogue scale(VAS)and Hospital for Surgery Scoring System(HSS)elbow pronation and supination angles,wrist metacarpal flexion and dorsal extension angles,elbow tenderness between two groups were compared before treatment and at 1,3,5,7,11 and 13 days after treatment;Hospital for Surgery Scoring System 2(HSS2)was compared before treatment and the final treatment.Results All patients were followed up for 10 to 14 days with an average of(12±1.6)days.VAS between treatment group and control group before treatment were 6.83±1.36 and 6.79±1.58,respectively,and decreased to 1.49±1.09 and 2.11±1.81 after the final treatment.VAS of treatment group were significantly lower than those of control group at 1,3,5,7,9,11 and 13 days after treatment(P＜0.05).HSS between two groups were 61.73±11.00 and 36.47±12.45 before treatment,respectively,and increased to 94.42±5.9 and 91.44±9.11 at the final treatment.HSS of treatment group were signifi-cantly higher than those of control group at 1,3,5,7,9,11 and 13 days after treatment(P＜0.05).On the 5th day after treat-ment,the external and internal rotation angles of elbow in treatment group were(66.41±12.69)° and(66.35±13.54)°,while those in control group were(62.08±16.03)° and(61.77±16.35)°.On the 7th day after treatment,the external and internal ro-tation angles of elbow were(69.79±12.64)° and(70.02±13.55)° in treatment group,and(65.28±15.86)° and(65.09± 16.67)° in control group.Elbow joint motion in treatment group was higher than that in control group(P＜0.05).On the 5th day after treatment,angles of wrist dorsiflexion and palm flexion were(39.43±15.94)°and(46.68±11.10)° in treatment group,and(38.51±18.49)° and(44.27±13.58)° in control group.On the 7th day after treatment,angles of wrist dorsiflexion and palm flexion were(42.52±16.50)° and(49.23±10.96)° in treatment group,and(41.18±20.09)° and(46.64±14.63)° in control group.The motion of wrist joint in treatment group was higher than that in control group(P＜0.05).On the 13th day after treatment,HSS2 in treatment group 93.61±6.32 were higher than those in control group 92.06±7.94(P＜0.05).There was no significant difference in elbow tenderness between two groups at each time point(P＞0.05).Conclusion Voltaren external treatment combined with elbow fixation and tendons pulling,poking and kneading could effectively improve symptoms of exter-nal humeral epicondylitis.Compared with voltaren external treatment,tendons pulling,poking and kneading has advantages of longer analgesic time and better elbow function recovery.

BACKGROUNDSpinocerebellar ataxia type 3 (SCA3) is the most common subtype of SCA worldwide, and runs a slowly progressive and unremitting disease course. There is currently no curable treatment available. Growing evidence has suggested that nerve growth factor (NGF) may have therapeutic effects in neurodegenerative diseases, and possibly also in SCA3. The objective of this study was to test the efficacy of NGF in SCA3 patients.

METHODSWe performed an open-label prospective study in genetically confirmed adult (>18 years old) SCA3 patients. NGF was administered by intramuscular injection (18 μg once daily) for 28 days consecutively. All the patients were evaluated at baseline and 2 and 4 weeks after treatment using the Chinese version of the scale for assessment and rating of ataxia (SARA).

RESULTSTwenty-one SCA3 patients (10 men and 11 women, mean age 39.14 ± 7.81 years, mean disease duration 4.14 ± 1.90 years, mean CAG repeats number 77.57 ± 2.27) were enrolled. After 28 days of NGF treatment, the mean total SARA score decreased significantly from a baseline of 8.48 ± 2.40 to 6.30 ± 1.87 (P < 0.001). Subsections SARA scores also showed significant improvements in stance (P = 0.003), speech (P = 0.023), finger chase (P = 0.015), fast alternating hand movements (P = 0.009), and heel-shin slide (P = 0.001).

CONCLUSIONSOur preliminary data suggest that NGF may be effective in treating patients with SCA3.

Adult ; Animals ; Female ; Humans ; Injections, Intramuscular ; Machado-Joseph Disease ; drug therapy ; Male ; Mice ; Middle Aged ; Nerve Growth Factor ; administration & dosage ; therapeutic use ; Prospective Studies