Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

AIM:To evaluate the effects of intermittent exotropia(IXT)on the quality of life of children and their parents using the Chinese version of intermittent exotropia questionnaires(CIXTQ).METHODS: The scores of CIXTQ were collected from IXT children and the same number of age-matched control children in department of ophthalmology, Nanjing Children's Hospital from June 2020 to June 2021. They were the Chinese version of intermittent exotropia questionnaires scores(CIXTQ, for children to assess their health related quality of life), the parental proxy CIXTQ(pp-CIXTQ, for parents to assess children's life quality)scores and the parent CIXTQ(p-CIXTQ, for parents to assess their life quality)scores. To explore: 1)The differences in the CIXTQ, pp-CIXTQ and p-CIXTQ scores between IXT children and the normal children; 2)The relationship between the CIXTQ and pp-CIXTQ scores in IXT children; 3)The factors affecting the quality of life in children with IXT.RESULTS: A total of 156 patients with IXT and 156 age-matched normal children were included. CIXTQ scores in the children with IXT group was lower than that in the control group(t=-12.915, P<0.001). In IXT group, there was no difference observed in CIXTQ or pp-CIXTQ scores(t=-0.718, P=0.473). As suggested by item-level analysis, children in the IXT group were more concerned about how others think of them and their vision, whereas parents were more concerned about whether the child needs surgery, and whether the permanent damage of strabism caused to the eyes of their children and whether strabismus affects their social life.CONCLUSION: The CIXTQ performed better in distinguishing the children with IXT and those with normal condition, and it can accurately predict the impact of IXT on children, and benefit to make personalized treatment regimens.

OBJECTIVES: To investigate the effects of injury time, postmortem interval (PMI) and postmortem storage temperature on mRNA expression of glycoprotein non-metastatic melanoma protein B (Gpnmb), and to establish a linear regression model between Gpnmb mRNA expression and injury time, to provide aimed at providing potential indexes for injury time estimation. METHODS: Test group SD rats were anesthetized and subjected to blunt contusion and randomly divided into 0 h, 4 h, 8 h, 12 h, 16 h, 20 h and 24 h groups after injury, with 18 rats in each group. After cervical dislocation, 6 rats in each group were collected and stored at 0 ℃, 16 ℃ and 26 ℃, respectively. The muscle tissue samples of quadriceps femoris injury were collected at 0 h, 12 h and 24 h postmortem at the same temperature. The grouping method and treatment method of the rats in the validation group were the same as above. The expression of Gpnmb mRNA in rat skeletal muscle was detected by RT-qPCR. The Pearson correlation coefficient was used to evaluate the correlation between Gpnmb mRNA expression and injury time, PMI, and postmortem storage temperature. SPSS 25.0 software was used to construct a linear regression model, and the validation group data was used for the back-substitution test. RESULTS: The expression of Gpnmb mRNA continued to increase with the prolongation of injury time, and the expression level was highly correlated with injury time (P<0.05), but had little correlation with PMI and postmortem storage temperature (P>0.05). The linear regression equation between injury time (y) and Gpnmb mRNA relative expression (x) was y=0.611 x+4.489. The back-substitution test proved that the prediction of the model was accurate. CONCLUSIONS The expression of Gpnmb mRNA is almost not affected by the PMI and postmortem storage temperature, but is mainly related to the time of injury. Therefore, a linear regression model can be established to infer the time of injury.
Animals ; Rats ; Glycoproteins ; Linear Models ; Melanoma ; Membrane Glycoproteins/genetics* ; Postmortem Changes ; Rats, Sprague-Dawley ; RNA, Messenger/metabolism* ; Time Factors

Tanshinone Ⅱ_A( Tan Ⅱ_A),the liposoluble constituents of Salvia miltiorrhiza,can not only ameliorate the lipidic metabolism and decrease the concentration of lipid peroxidation,but also resist oxidation damage,scavenge free radicals and control inflammation,with a protective effect on prognosis after liver function impairment. Therefore,the studies on the exact mechanism of Tan Ⅱ_A in protecting the liver can provide important theoretical and experimental basis for the prevention and treatment effect of Tan Ⅱ_A for liver injury. In the present study,the protective effects and mechanism of Tan Ⅱ_A on 4-hydroxynonenal( 4-HNE)-induced liver injury were investigated in vitro. Normal liver tissues NCTC 1469 cells were used to induce hepatocytes oxidative damages by 4-HNE treatment. The protective effect of Tan Ⅱ_A on hepatocytes oxidative damages was detected by release amount of lactate dehydrogenase( LDH) analysis and hoechst staining. The protein expression changes of peroxisome proliferator-activated receptor α( PPARα) and peroxisome proliferator response element( PPRE) were analyzed by Western blot analysis in NCTC 1469 cells before and after Tan Ⅱ_A treatment. The gene expression changes of fatty aldehyde dehydrogenase( FALDH) were analyzed by Real-time polymerase chain reaction( PCR) analysis. The results showed that 4-HNE increased the release amount of LDH,lowered the cell viability of NCTC 1469 cells,and Tan Ⅱ_A reversed 4-HNE-induced hepatocyte damage. Western blot analysis and RT-PCR analysis results showed that 4-HNE decreased the expression of PPARα and FALDH and increased the expression of 4-HNE. However,the expression of PPARα and FALDH were increased significantly and the expression of 4-HNE was decreased obviously after Tan Ⅱ_A treatment. This study confirmed that the curative effect of Tan Ⅱ_A was obvious on hepatocytes damage,and the mechanism may be associated with activating PPARα and FALDH expression as well as scavenging 4-HNE.
Aldehyde Oxidoreductases ; metabolism ; Aldehydes ; Animals ; Cell Line ; Diterpenes, Abietane ; pharmacology ; Hepatocytes ; drug effects ; Lipid Peroxidation ; Mice ; Oxidative Stress ; PPAR alpha ; metabolism

Objective: To explore the effect and mechanism of Wuzi Yanzong Fang (WZ) on proliferation of spermatogonial stem cells in aging rats by regulating miR-let-7-Imp axis.Method: A total of 40 18-month-old male SD rats were randomly divided into aging model group, and low, middle and high-dose WZ groups, with 10 rats in each group. Ten 2-month old rats were used as young control group. Low, middle and high-dose WZ groups were given by gastric WZ 0.4, 0.8, 1.6 g·kg^-1 respectively. Young control group and aging model group were given normal saline for 4 months, which was suspended for 2 days every week. Rats were put to death after the final treatment with WZ, and then the testes were quickly removed from rats. The relative mRNA expression levels of miR-let-7 and Imp were detected by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). The expressions and localization of p-JAK2/JAK2, phosphate(p)-signal transduction and transcriptional activators3 (STAT3)/STAT3 signaling pathway proteins were detected by Western blot and immunofluorescence. The numbers of spermatogonial stem cells and the expression levels of proliferating cell nuclear antigen (PCNA) were detected by immunofluorescence. The testicular tissue morphology was observed using htoxylin eosin (HE) staining.Result: Compared with young control group, the expression levels of miR-let-7 mRNA were significantly increased, while the expression levels of Imp mRNA were decreased in the aging model group(P<0.01). Conversely, the expression levels of miR-let-7 mRNA were significantly decreased (P<0.05, P<0.01), while the mRNA expression levels of Imp mRNA were significantly increased after WZ treatment(P<0.05). The results of Western blotting and immunofluorescence showed that the expression levels of p-JAK2, p-STAT3 in aging model group were decreased significantly(P<0.01), while WZ significantly increased the expression levels of p-JAK2, p-STAT3(P<0.05, P<0.01). Immunofluorescence results showed that compared with young control group, the number of spermatogonial stem cells and PCNA expression decreased in aging model group. After WZ treatment, the number of spermatogonial stem cells was increased, whereas PCNA expression was up-regulated. HE showed that WZ significantly improved the testicular tissue structure of aging rats.Conclusion: WZ effectively promote the proliferation of spermatogonial stem cells by regulating miR-let-7-imp axis in testis.

Objective To observe the curative mechanism and effect of neurotoxicity injury induced by methamphetamine (MA) and the neuroprotective effects of gastrodin interfered. Whether the expression of astrocyte and proinflammatory cytokines has contributed to the effects of gastrodin.Methods 48 healthy male SD rats were randomly divided into three groups: control group (Daily intraperitoneal injection of saline for 8 weeks),MA group (A dose of 10 mg/kg MA was administered every day for four weeks,then given daily intraperitoneal injection with 10 mg/kg saline for 4 weeks) and gastrodin group (A dose of 10 mg/kg MA was administered every day for four weeks,then given daily intraperitoneal injection with 10 mg/kg gastrodin for 4weeks) . The behavioral changes of rats were measured by conditioned place preference ( CPP) and sterotyped behavior ( SB) induced by methamphetamine. Immunofluorescence staining was used to detect the expression of glial fibrillary acidic protein (GFAP) and NEUN in rat frontal cortex.The expression of IL－6 and TNF－α were detected by quantity RT－PCR and westrn bloting.Results Compa MA depndent 4 weeks group with control group, the scores of sterotyped behavior of MA depndent groups had signficantly increased (P＜0.01) . Comparing MA depndent 4 weeks group with MA depndent 4 weeks+gastrodin group, the scores of sterotyped behavior of MA dependent 4 weeks group had obviously decreaseed (P＜0.01) . Compared with the control group, the expression of GFAP of MA dependent 4 weeks group decreased and the expression of NEUN increased. Compared MA dependent 4 weeks group with control group, the expression of IL－ 6 and TNF－α increased (P＜0.01) . Compared MA dependent 4 weeks+gastrodian group with MA dependent 4 weeks group, the expression of TNF－α and IL－6 significantly reduced (P＜0.01) . Conclusion The neurological damage induced by methamphetamine might be related to the activation of astrocytes and the high expression of inflammatory cytokines including IL－6 and TNF－α. Gastrodin could abate the neurological injury of methamphetamine dependence via reducing the activation of astrocytes and decreasing the expression of IL－6 and TNF－α.

Objective To establish a rapid high performance liquid chromatography(HPLC)method for simultaneous determination of the concentration of total,free and reduced homocysteine (Hcy),glutathione(GSH),cysteine (Cys)and cys-teinylglycine (CysGly). Methods HPLC fluorescence detection method was established under the below conditions. The axci-tation and emission wavelengths was 330 nm and 380 nm respectively;the separation of thiols was achieved by using a C-18 column and the column temperature was 25 ℃;the mobile phase was gradient eluted with the three carboxyl ethyl phosphine (TCEP)as reducing agent and N-1- phenyl maleimide (NPM)as derivatization agent. The HPLC fluorescence detection meth-od was used to measure the thiol concentration in plasma of uraemia patients and healthy people. Results The linear range of total and free Hcy,GSH,Cys and CysGly were 1. 0 - 120. 0,2. 0 - 80. 0,10. 0 - 1500. 0 and 3. 0 - 240. 0 μmol·L - 1 respec-tively;the linear range of reduced Hcy,GSH,Cys and CysGly was 1. 25 - 50. 00,0. 10 - 8. 00,1. 25 - 50. 00 and 0. 01 -4. 00 μmol·L - 1 respectively. The intra-and inter-day ralative standard deviation were less than 5％;the recovery of this meth-od was 80. 1％ - 111. 7％ . The newly established HPLC fluorescence detection method was successfully applied to determine the total,free and reduced concentration of GSH,Cys,Hcy and CysGly in 34 uraemia patients and 32 healthy people. Conclu-sion A new HPLC fluorescence detection method for the determination of Hcy,GSH,Cys,and CysGly in plasma is developed and this method is accurate and reliable.

Objective To investigate current status of hemodialysis,and qualified status of dialysis water and dia-lysate in a city. Methods Status of hemodialysis in 36 medical institutions in a city which conducted blood purifica-tion programme was surveyed,dialysis water and dialysate were collected to perform microbial detection(including conventional and low temperature culture methods)and on-site ATP detection.Results 13.89% of equipments for water treatment were used less than 1 year,5.56% were used for more than 10 years. 77.78% of medical institu-tions didn't replace sand filtration which had been used for more than 1 year,the replacement time of 72.22% of fil-ter core was less than 3 months,2.78% of reverse water supply pipeline was used for more than 10 years.77.78%of medical institutions used finished A solution,72.22% used finished B solution,22.22% used centrally provided A solution,19.44% used centrally provided B solution,and 8.34% used self-made B solution. Routine microbial detection in 36 medical institutions were qualified,but 80.56% of detection results were"0" value for long period;ATP detection of on-site collected dialysis water and dialysate were all qualified. One specimen for microbial detec-tion under normal temperature exceeded the standard,2 reached the intervention value;4 specimens for microbial detection under low temperature exceeded the standard,6 reached the intervention value;qualified rates of 3 kinds of detection methods among different levels of medical institutions weren't significantly different(all P>0.05).Con-clusion The overall quality of hemodialysis water and dialysate in this city is good,the majority of medical institutions pay attention to the routine maintenance of water treatment equipment,detect the quality of hemodialysis water and dialysate regularly,but microbial detection technique needs to be improved,causes for abnormal results or intervention value of rou-tine detection needs to be analyzed and improved continuously.

To study the protective effect of Wuzi Yanzong recipe on testicular DNA damage and apoptosis in natural ageing rats, SPF grade 16-month-old SD male rats were randomly divided into three groups: ageing model group, low and high dose Wuzi Yanzong recipe groups (WZ, 1， 4 g·kg⁻¹). In addition, 2-month-old SD rats were used as adult control group (10 rats in each group). The ageing model group and the adult control group were fed with normal diet for 4 months. Wuzi Yanzong groups received medicated feed for 4 months. After fasting for 12 hours, the rats were sacrificed. Then testis tissues were taken and weighed to calculate the testis index. The change of testicular tissue morphology was observed by HE staining. Expression and localization of DNA damage-associated protein ATR were observed by immunofluorescence. The expressions of DNA damage-related proteins γ-H2AX, Chk1, p-p53 and apoptosis-related proteins Bcl-2 and Bax in testes were detected by Western blot. The apoptosis of testis tissue in rats was detected by using TUNEL. The results showed that as compared with the youth control group, the protein expression levels of γ-H2AX, Chk1, p-p53 and Bax were significantly increased while Bcl-2 protein expression level was significantly decreased intestis tissues of ageing model group. Wuzi Yanzong recipe significantly decreased protein expression levels of γ-H2AX, Chk1, p-p53 and Bax and increased Bcl-2 protein expression level as well as Bcl-2/Bax ratio. Immunofluorescence results showed that Wuzi Yanzong recipe could significantly decrease the ageing-induced ATR, increase in testis tissues. TUNEL results showed that Wuzi Yanzong recipe could significantly attenuate the germ cell apoptosis in testicular tissues. All the above results suggest that Wuzi Yanzong recipe could protect the germ cell in testicular tissues of natural ageing rates from DNA damage and apoptosis, and the mechanism may be associated with regulating p53 signaling pathway.

Objective: To investigate the effect of long-term deep slow-wave sleep deprivation on the gonad axis, sperm abnormality rate, and structure of the testis in male rats and possible mechanisms. Methods: A total of 30 specific pathogen-free male Wistar rats aged 5 weeks were randomly divided into slow-wave sleep deprivation group 1 (SD1 group) , slow-wave sleep and sleep time deprivation group 2 (SD2 group) , and control group, with 10 rats in each group. The flower pot method was used to establish a model of sleep deprivation. In addition to 12-hour sleep deprivation at night, the rats in the SD1 group were given interference once every 24 minutes, and those in the SD2 group were deprived of sleep for 8 minutes every 24 minutes; the rats in the control group were given 12-hour light illumination and then placed in dark environment for 12 hours. All rats were sacrificed by exsanguination from the femoral artery, and the testis, the epididymis, and blood were collected for analysis. Sperm abnormality rate and sperm motility rate were measured, and cauda epididymal sperm counting was performed. ELISA was used to measure the serum levels of testosterone (T) , follicle-stimulating hormone (FSH) , and luteinizing hormone (LH) . Results: Compared with the control group, the SD2 group had a significant increase in organ coefficient of the epididymis (P<0.05) and a significant reduction in sperm motility rate (P<0.05) . There were significant differences between the SD1 group and the SD2 group in the increase in sperm abnormality rate (P<0.05) and the reduction in cauda epididymal sperm count (P<0.05) . The levels of FSH and T tended to increase, and the level of LH tended to decrease. Pathological examination showed degeneration and vacuolization of a small amount of spermatogenic cells in the SD1 group; in the SD2 group, there were significant degeneration, edema, and vacuolization of most spermatogenic cells, some spermatogenic cells were observed in the lumen, and there were no sperms in the lumen. Conclusion Long-term deep slow-wave sleep deprivation impairs the structure of the testis, affects sperm motility rate and sex hormones, and increases the risk of sperm abnormality.