Objective To investigate the therapeutic effects and mechanism of Compound Huangdai Tablets on nude mice with acute promyelocytic leukemia(APL).Methods An APL xenograft model was established in nude mice using NB4 cells.Successfully modeled mice were divided into a control group and low-and high-dose Compound Huangdai Tablets groups.The grouping intervention was as follow:the low-and high-dose Compound Huangdai Tablets groups were administered Compound Huangdai Tablets solution(suspended in 0.5％sodium carboxymethyl cellulose solution)by gavage at doses of 545 and 1 090 mg·kg-1,respectively,while the control group received an equal volume of normal saline.The administration was performed twice daily,with each dose being 0.2 mL,for a total duration of 25 days.The general condition,tumor volume,and tumor weight were observed.Reactive oxygen species(ROS)levels in tumor tissues were measured.Western Blot and immunohistochemistry(IHC)were used to detect the expression levels of key necroptosis molecules,including mixed lineage kinase domain-like protein(MLKL),receptor-interacting protein kinase 1(RIPK1),and receptor-interacting protein kinase 3(RIPK3).Results Mice in the Compound Huangdai Tablets groups showed no abnormal mental status,sudden weight loss,or feeding difficulties.There was no significant difference in body mass among the groups(P＞0.05).Compared with the control group,the high-dose Compound Huangdai Tablets group showed significantly reduced tumor volume and mass(P＜0.05),along with increased ROS levels in tumor tissues(P＜0.05).The expression levels of MLKL,RIPK1,and RIPK3 proteins in tumor tissues of the high-dose group were higher than those in the control group(P＜0.05).Conclusion Compound Huangdai Tablets promote necroptosis in nude mice with acute promyelocytic leukemia by activating MLKL protein.

Objective:To investigate the impact of excessive fluoride exposure on the expression profile of microRNA (miRNA) in mouse testes, and elucidate the reproductive toxicity mechanism of fluoride.Methods:A total of 24 8-week-old C57BL/6J male mice weighing (23 ± 1) g were randomly divided into a control group [0 mg/L sodium fluoride (NaF)] and a fluoride exposure group (50 mg/L NaF) using a random number table method, with 12 mice in each group. After 90 days of treatment, the mice were anesthetized and euthanized. Sperm samples were collected to assess their quantity, viability, and deformity rate. Additionally, testicular tissue was stained with hematoxylin-eosin (HE). RNA was extracted from testicular tissue, and high-throughput sequencing technology was employed to analyze the effect of fluoride on the expression profile of mouse testicular miRNA. Deferentially expressed miRNA was screened and its target genes were predicted, and functional annotation and pathway enrichment analysis were performed. Real-time fluorescence quantitative PCR (qRT-PCR) was used to verify the expression level of deferentially expressed miRNA.Results:Compared with the control group [number of sperm: (11.30 ± 2.52) × 10 6/ml; viability rate: (90.07 ± 4.34)%; deformity rate: (15.49 ± 3.25)%], the number of sperm of mice exposed to fluoride [(9.01 ± 2.25) × 10 6/ml] and the viability rate [(84.34 ± 4.21)%] decreased ( P = 0.041, 0.003), while deformity rate [(22.36 ± 6.51)%] increased ( P = 0.003). Furthermore, in the fluoride exposure group, the interstitial distance of testis increased, the number of sperm in the spermatogenic tubule decreased, and the cell arrangement was disordered. Through sequencing, 34 deferentially expressed miRNAs were identified in the testes of mice exposed to fluoride. According to qRT-PCR verification, compared with the control group, the expression levels of mmu-miR-29b-1-5p ( P < 0.001), mmu-miR-196a-5p ( P = 0.002), and mmu-miR-196b-5p ( P = 0.031) in the testes of mice exposed to fluoride were significantly increased, and the expression levels of mmu-let-7a-2-3p ( P < 0.001) and mmu-miR-466n-3p ( P = 0.018) were significantly decreased, consistent with the sequencing results. By KEGG enrichment of deferentially expressed miRNA target genes, it was found that fluoride exposure could change the axon guidance signal pathway, olfactory transduction pathway, neuroactive ligand-receptor interaction pathway, and lysosome signal pathway, etc., in mouse testes. Conclusions:Fluoride exposure may induce testicular injury by altering the expression profile of miRNA in the testes and by mediating the post-transcriptional regulatory signal pathway. Testicular miRNA may be a potential biomarker of fluoride reproductive toxicity, which may provide a new idea and perspective for exploring the mechanism of fluoride poisoning.

Objective:To investigate the hemodynamic characteristics of the lenticulostriate artery (LSA) in cerebral small vessel disease (CSVD) patients with recent small subcortical infarcts (RSSI) using 7.0 T two-dimensional phase-contrast MRI (2D PC-MRI).Methods:A total of 16 CSVD patients with deep RSSI and 18 age-and sex-matched healthy controls (HC group) meeting the inclusion criteria were prospectively recruited from July 2021 to June 2022 at Beijing Tiantan Hospital, Capital Medical University. All participants underwent 7.0 T 2D PC-MRI with imaging plane localized at the level of the basal ganglia. A self-developed software (Flow analyze V1.0) was used to analyze the hemodynamic status of bilateral LSAs. The hemodynamic parameters including the maximum velocity (V max), average velocity (V avg), pulsatility index (PI), and resistance index (RI) of LSAs were calculated and recorded. As for the CSVD cases, the symptomatic side was defined as the ipsilateral side to the RSSI (CSVD symptomatic-side group), and the contralateral side was defined as the asymptomatic side (CSVD asymptomatic-side group). ANOVA or Mann-Whitney U test was used to compare hemodynamic parameters among the three groups. Results:Significant differences in V max, V avg and PI were observed among the CSVD symptomatic-side group, CSVD asymptomatic-side group, and HC group ( F=5.22, P=0.006; F=3.47, P=0.033; F=4.37, P=0.014). Specifically, CSVD symptomatic-side group showed significantly reduced V max ( P=0.004) and V avg ( P=0.017), and increased PI ( P=0.007) compared to the HC group. The CSVD asymptomatic-side group showed decreased V max ( P=0.026) and increased PI ( P=0.039) compared to the HC group. Conclusions:Hemodynamic assessment based on 7.0 T 2D PC-MRI reveal that CSVD patients with RSSI decrease blood flow velocity and increase arterial PI of LSAs. These findings suggest potential corresponding hemodynamic mechanisms associated with CSVD with RSSI lesions.

Objective:To study the regulatory effect of miR-9 on the proliferation of breast cancer cells by targeting hexokinase 2 (HK2) .Methods:Breast cancer tissues and paracancer tissues were collected and the expression levels of miR-9 and HK2 were detected. MCF-7 cells were cultured and divided into blank control group, NC group, miR-9 group, NC-siRNA group and HK2-siRNA group. The cell viability, expression levels of HK2 and cleaved caspase-3 were detected, the targeted binding of miR-9 to HK2 was verifed.Results:the expression level of miR-9 in breast cancer was lower than that in paracancer tissue (0.52±0.08 vs 1.05±0.25, t=16.685, P<0.000) , and the expression level of HK2 was higher than that in paracancer tissue (0.73±0.14 vs 0.34±0.08, t=17.587, P<0.000) , and the expression level of miR-9 was negatively correlated with HK2; the OD490 level, the expression level of HK2 and the fluorescence activity of double luciferase reporter gene containing HK2 mRNA 3 'UTR in miR-9 group were lower than those in NC group (0.58±0.09 vs 1.04±0.21, 0.51±0.08 vs 1.18±0.24, 41.11±9.28 vs 148.28±29.59, t/P=4.027/0.007, 5.297/0.002, 6.912/0.001) , and the expression level of cleaved caspase-3 was higher than that in NC group (1.08±0.26 vs 0.42±0.09, t/P=4.797/0.003) . The OD490 level and the expression level of HK in HK-siRNA group were higher than that in NC-siRNA group, and the expression level of cleaved caspase-3 was higher than that of NC-siRNA group. Conclusion:miR-9 can inhibit the proliferation of breast cancer cells, and its mechanism may be related to the targeted inhibition of HK2 expression and the increase of downstream cleaved caspase-3 expression.

Objective To study the effect of maternal subclinical thyroid abnormalities [including subclinical hypothyroidism, hypothyroxinemia and positive anti-thyroid peroxidase antibody (TPOAb) with normal thyroid function] in women during 16-20 weeks of gestation on offspfing's intellectual development and motor function. Methods Sera from 1 268 women during 16-20 weeks of gestation (collected 2 years ago) were obtained and thyroid stimulating hormone (TSH), total thyroxine (TT4), free thyroxine (FT4) and TPOAb levels were measured. Pregnant specific thyroid function reference ranges were used to screen for subclinical hypothyroidism (18 cases), hypothyroxinemia (19 cases) and positive TPOAb (34 cases). From the same cohort, a total of 142 pregnant women who were euthyroid with negative TPOAb were selected as controls (a case: control ratio of 1 : 2). Intellectual and motor development score evaluations were performed in their children at 25-30 months of age. Results In the group of pregnant women with subclinical hypothyroidism, the offspring' s intelligence score was (109.89±13.81) points, which was 8.88 points lower than in the control group (P < 0.01). Similarly, the motor score of the offspring was (108.11±9.93) points, which was 9.98 points lower than in the control group (P < 0.01). In the pregnant women with hypothyroxinemia, the offspring's intelligence score was (112.32±15.10) points, 9.30 points lower than in the control group (P <0.01); the motor score was (112.21±12.26) points, 7.57 points lower than in the control group (P < 0.01). In the pregnant women with positive TPOAb and euthyroid function, the offspring's intelligence score was (112.70±20.64) points, 10.56 points lower than in the control group (P < 0.01); the motor score was (110.64±12.49) points, 9.03 points lower than in the control group (P < 0.01). Conclusion Maternal subclinical thyroid abnormality between 16-20 weeks of gestation adversely may affect offspring intellectual and motor development, suggesting the necessity for screening and treatment of maternal subclinical thyroid abnormality in the early stages of pregnancy.

Objective To explore the therapeutic efficacy of nanometer high-frequency square pulse light technology targeting kidney cancer.Methods Fifty BALB/c nude mice were vaccinated with human ACHN cell line and randomly divided into 1 control group and 4 therapeutic groups.The 4 therapeutic groups were cured with high-frequency square pulse light and nanometer high-frequency square pulse light.The treatment cycle was 4 weeks.The tumor growth condition and tumor-repres-sion change were observed and compared.Results The tumor volumes of the control group in-creased obviously,whereas the tumor volumes of the therapeutic groups decreased obviously or in-creased gently.The mean tumor volume and the tumor growth curve of the therapeutic groups were significantly lower than those of the control group(P＜0.05),but there was no significant difference between the therapeutic efficacy of the kidney cancer using high-frequency square pulse light and nanometer high-frequency square pulse light(P＞0.05).Synteresis of kidney carcinogenesis experiments results indicated that using high-frequency square pulse light and nanometer high-frequency square Dulse light could prevent the production and development of the kidney cancer(P＜0.05),but the svnteresis efficacy of the 2 methods had no obvious difference(P＞0.05).Conclusion Using highfrequency square pulse light and nanometer high-frequency square pulse light can cure the kidney cancer and,to some extent,prevent the production and development of kidney cancer.

Objective To investigate the effects of in situ venous arterialization on extensive artery obliterans occlusion of the lower extremity. Methods Lumbar sympathetic ganglionectomy and one stage in situ arterialization of the great saphemous vein were performed in 104 ischemic limbs of 88 patients with extensive arterial occlusion. Results Eighty-two of 104 limbs were followed-up from 6 months to over 6 years. The intermittent claudication, night pain improved in all cases, with satisfactory wound healing and no swelling of the lower limbs. Conclusions Arterial blood flow through venous conduit improves and reconstructs the blood circulation of the ischemic limbs.