Chemotherapy is currently the mainstay of systemic management for triple-negative breast cancer (TNBC), but chemoresistance significantly impacts patient outcomes. Our research indicates that Doxorubicin (Dox)-resistant TNBC cells exhibit increased glycolysis and ATP generation compared to their parental cells, with this metabolic shift contributing to chemoresistance. We discovered that ALKBH3, an m¹A demethylase enzyme, is crucial in regulating the enhanced glycolysis in Dox-resistant TNBC cells. Knocking down ALKBH3 reduced ATP generation, glucose consumption, and lactate production, implicating its involvement in mediating glycolysis. Further investigation revealed that aldolase A (ALDOA), a key enzyme in glycolysis, is a downstream target of ALKBH3. ALKBH3 regulates ALDOA mRNA stability through m¹A demethylation at the 3'-untranslated region (3'UTR). This methylation negatively affects ALDOA mRNA stability by recruiting the YTHDF2/PAN2-PAN3 complex, leading to mRNA degradation. The ALKBH3/ALDOA axis promotes Dox resistance both in vitro and in vivo. Clinical analysis demonstrated that ALKBH3 and ALDOA are upregulated in breast cancer tissues, and higher expression of these proteins is associated with reduced overall survival in TNBC patients. Our study highlights the role of the ALKBH3/ALDOA axis in contributing to Dox resistance in TNBC cells through regulation of ALDOA mRNA stability and glycolysis.

A new wave of research has been inspired by the CRISPR-Cas system with respect to their application in genome editing. The CRISPR-Cas system can not only be applied in gene knockout and insertion, but also be used in base editing, transcriptional regulation and recombination of gene clusters. However, the low efficiency of homology-directed repair (HDR) limits its application. Unlike the CRISPR-Cas system, mobile genetic elements (MGE) can insert DNA fragments into cell chromosomes without the aid of HDR. Recently, it is reported that CRISPR-related transposable elements can guide targeted DNA insertion. Their transposition mechanisms and reprogramming abilities have brought novel opportunities to the development of this field. This review summarized the research progress and application development of natural CRISPR-related transposable elements in recent years, as well as the applications of fused dCas9-transposase. It proposed the application prospects and potential challenges of CRISPR-related transposable elements in the future, which provided a reference for the development direction of gene editing tools.
DNA Transposable Elements/genetics* ; Gene Editing ; CRISPR-Cas Systems/genetics*

Objective: To explore the effect of working memory intervention training on working memory and literacy of children with developmental dyslexia,so as to provide a preference for practice of the trianing of working memory among children with dyslexia. Methods: A total of 32 children with dyslexia of grade 3-5 in a primary school in Guiyang were randomly divided into two groups: the study group (n=16) and the control group (n=16),and the software of training exercises of working memory was applied to conduct interventional trainings of different durations to 2 gruops of children. Results: Through the intervention training of working memory, the scores of literacy and working memory tasks in the study group (2 217.88±252.32, 105.13±7.68) were significantly higher than those in the control group (1 907.69 ± 545.15, 96.50 ± 11.04) (t=2.06, 2.56, P<0.05). Conclusion The working memory ability of children with dyslexia can be improved by working memory intervention training for a certain period of time. The intervention effect is not only significant in the trained working memory task, but also can be extended to other untrained contents such as literacy.

Objective:To observe the dynamic changes of thyroid hormone levels and thyroid autoimmune antibodies in pregnant women in Xinjiang Uygur Autonomous Region during pregnancy, and to investigate the significance of repeated screening of thyroid function in different gestational ages.Methods:A retrospective study was carried out of pregnant women who completed thyroid function screening in Clinic, People's Hospital of Xinjiang Uygur Autonomous Region from January 2015 to December 2017, and the test results of thyroid stimulating hormone (TSH), free thyroxine (FT 4), free triiodothyronine (FT 3), thyroid peroxidase antibody (TPOAb), and anti-thyroglobulin antibody (TGAb) were collected and analyzed of their changes during pregnancy. Pregnant women were divided into 2 different gestational age groups by the age limit of 30, the changes of thyroid dysfunction rate with pregnancy were analyzed, and the clinical significance of repeated screening in different pregnancy stages was discussed. Results:Changes of thyroid-related indicators with pregnancy: first, second, and third trimesters were 404,725, and 767 cases, respectively; TSH level in the third trimester (2.76 mU/L) was significantly higher than those in the first and second trimesters (2.55, 2.36 mU/L, P < 0.05), there was no significant difference between the first trimester and the second trimester ( P > 0.05); the FT 4 and FT 3 levels decreased gradually with pregnancy ( P < 0.05); the positive rate of TPOAb was significantly higher in the first and second trimesters than that in the third trimester ( P < 0.05), there was no significant difference between the first trimester and the second trimester ( P > 0.05); the positive rate of TGAb decreased gradually with pregnancy ( P < 0.05). Comparison of abnormal rate of TSH in different gestational ages: the first, second, and third trimesters were 352, 664, 735 cases, respectively; the abnormal rate of TSH in the overall study was statistically significant at different stages of pregnancy (χ 2=31.627, P < 0.05), the first trimester was significantly higher those in the second and third trimesters ( P < 0.05). In pregnant women aged ≥30 years old, the abnormal rate of TSH in the first trimester was significantly higher than those in the second and third trimesters ( P < 0.05); in pregnant women aged < 30 years old, the abnormal rate of TSH in the first trimester was significantly higher than that in the third trimester ( P < 0.05). There were no significant differences in the abnormal rate of TSH in the first, second, and third trimesters between the < 30 years old group and ≥30 years old group ( P > 0.05). Comparison of abnormal rate of FT 4 in different gestational ages: there were no significant differences in the FT 4 abnormal rate among different pregnancy groups in the overall, < 30, ≥30 years old groups (P > 0.05). In early pregnancy, the abnormal rate of FT 4 in the ≥30 years old group was higher than that in the < 30 years old group ( P < 0.05); in second and third trimesters, there were no significant differences between the two age groups ( P > 0.05). Conclusions:Screening for thyroid function in the first trimester of pregnancy is important for women of different ages. Except for women with abnormal thyroid function who have not been treated during the first trimester, the rest may not need to be screened again. Pregnant women aged ≥30 years old may have a higher risk of thyroid dysfunction than those < 30 years old.

Objective To establish a reference range for specific thyroid function during pregnancy and to explore the influencing factors of hypothyroxinemia during pregnancy.Methods A retrospective analysis of 2 996 cases of thyroid function in the pregnant women who were with single pregnancy and without thyroid diseases and family history of those diseases.Results (1) Establish a unified reference range for specific thyroid function during pregnancy;the early,middle,and late trimesters thyrotropin (TSH) ranges were 0.02-6.39,0.16-6.23,0.64-6.59 mU/L,respectively,while free thyroxine (FT4) ranges were 11.32-23.00,9.39-18.92,8.54-16.73 pmol/L respectively.The specific reference ranges of Han and Uygur pregnant women were established separately.There was no difference in the detection rates of various thyroid diseases when using their respective reference ranges and the unified reference range of the hospital (P ＞ 0.05).(2) The detection rate of various thyroid diseases (except subclinical hyperthyroidism) of our subjects with China guideline reference range was significantly higher than the reference range with the hospital (P＜0.05).(3) The detection rates of hypothyroxinemia in all pregnant women with FT4 cut points of P2.5 and P5 were 4.3％ and 7.4％,respectively,of which the Han population was 4.3％ and 7.1％,respectively,and the Uygur population was 4.3％ and 7.9％,respectively.(4) Comparing the mean age,gestational age,median urine iodine,and thyroid antibody positive rate between the hypothyroxinemia group and the control group,only the mean age and gestational age were different (P＜0.05);Logistic binary regression analysis showed that age was the risk factor for hypothyroxinemia during pregnancy (OR =1.035,95％ CI 1.006-1.066,P ＜ 0.05).Conclusions The Han and Uygur pregnant women in this area both can use the thyroid reference range of our hospital during pregnancy.The establishment of thyroid reference range may avoid over-diagnosis of thyroid disease during pregnancy.Age is a possible influencing factor of hypothyroxinemia during pregnancy.

Objective:To compare the dissolution of compound fructus forsythiae, paracetamol and chlorphenamine maleate cap-sules from different manufacturers.Methods: The dissolution test was carried out by a basket method in 900 ml dissolution medium with the rotating speed at 100 r·min-1. The dissolution profiles of compound fructus forsythiae,paracetamol and chlorphenamine mal-eate capsules from different manufacturers in four dissolution media including hydrochloric acid solution, pH 4.5 acetate buffer solu-tion,water and pH 6.8 phosphate buffer solution were determined,and the dissolution curves were compared by a similar factor meth-od. Results:The cumulative dissolution of compound fructus forsythiae,paracetamol and chlorphenamine maleate capsules from seven manufacturers was all over 70% in 30 min in hydrochloric acid solution,while failed to dissolve well in pH 4.5 acetate buffer solution, water and pH 6.8 phosphate buffer solution. All the dissolution curves in the 4 dissolution media were different among the batches. Conclusion:The quality of compound fructus forsythiae,paracetamol and chlorphenamine maleate capsules from various manufacturers is much different. Promising dissolution should be guaranteed,at the same time,the stability needs to be improved.

Objective: Combining with national drug sampling program,to evaluate the current quality situation and problems of compound Yinqiao and paracetamol and chlorphenamine maleate capsules by testing and analyzing 78 batches of samples collected from the realm of drug production and circulation all over the country in 2015.Methods: As the current standard could not control the product quality, and combined the prescribed examination with exploratory research, the method of HPLC was used to determine the contents.GC and TLC was respectively used to identify peppermint oil and study on forsythin.Near infrared spectrum database was established by near-infrared spectroscopy (NIRS), which provided the basis for rapid testing.The results of the prescribed examination and exploratory research were statistically analyzed.Results: There were significant differences in the results of the prescribed examination and exploratory research.Conclusion: The results of exploratory research show that there are many defects in the statutory standards.The product quality of different manufactures was divers, and it is necessary to guide them to improve the preparation process and the quality.More exclusive, accurate and sensitive methods should be used to comprehensively control the quality.

Objective:To study the effect of combined acupuncture and rehabilitation training on early-stage Barthel index of ischemic stroke cases.Method:Fifty ischemic stroke cases were randomized into a treatment group of 24 cases and control group of 26 cases.In addition to routine internal treatment methods,rehabilitation training was applied to cases in the control group,and combined acupuncture and rehabilitation training were applied to cases in the treatment group.Warming and reinforcing manipulations were applied to Jianyu (LI 15),Quchi (LI 11),Hegu (LI 4),Yanglingquan (GB 34),Yinlingquan (SP 9),Zusanli (ST 36),and Sanyinjiao (SP 6),20 min of needle retaining for each point in one treatment.Then the scores of clinical neurological impairment and Barthel index of stroke cases were evaluated before the treatment and 3 weeks after respectively.Results:The significant progress and progress cases in the treatment group were 14 and 12 respectively,whereas that in the control group were 6 and 11 respectively,coupled with 7 cases of no progress.The therapeutic effect in the treatment is substantially better than the control group (P＜0.05).There was no significant difference (P＞0.05) in neurological impairment and scores of Barthel index of the two groups before the treatment,whereas significant difference (P＜0.05) after the treatment.The scores of neurological impairment in the treatment group were significantly reduced after the treatment (P＜0.05),and the scores of Barthel index were significantly increased (P＜0.05).Conclusion:Combined acupuncture and rehabilitation training can produce significantly better effect on early neurological impairment and Barthel index of stroke cases than rehabilitation training alone.

OBJECTIVE: To summarize the clinicopathologic feature and diagnostic and therapeutic experience of laryngeal contact granuloma. METHOD: A retrospective study was carried out among 18 cases with this disease through careful analysis on their clinical and pathological data. RESULT: All of 18 cases were male, aged 34 to 78 years,The most common symptoms were hoarseness. In general the granuloma located on the posterior of the larynx unilaterally. The histological appearances of the lesions were typical inflammatory granuloma. Little allotype cell were found in one histologic sample. Fifteen cases received surgical excision and the recurrence rate was 60% after operation. Recidivist received operation again,4 cases among these cases received antireflux therapy after operation but 3 cases recurrences again. Among those follow-up cases(3 cases), 1 case was self-cure and other 2 cases appeared no marked change during observation period. CONCLUSION Laryngeal contact granuloma predilected the middle-aged male. The localization and appearance of the granuloma is very characteristic. The correct diagnosis can be established by clinical examination alone, but the histological examination is necessary in order to avoid missed diagnosis. There is a high recurrence rate after operation and the effect of antireflux therapy need further research.
Adult ; Aged ; Granuloma, Laryngeal ; pathology ; surgery ; Humans ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Otorhinolaryngologic Surgical Procedures ; Retrospective Studies

Objective To find the effect and potential mechanism of ischemic postconditioning relief rCBF and VEGF expression during focal cerebral thrombosis.Methods The thrombotic focal cerebral ischemia was induced by photochemical reaction in tree shrews.The rCBF and VEGF expression in hippocampus CA1 area were detected,by laser-Doppler(LD) fowmeter and immunohistochemistry.Results rCBF reduces along with temporal lasting in cerebral thrombus,especially in 24 h;VEGF expression enhanced after cerebral ischemic,express of VEGF in 12 h is the most intensification(P0.05),mostly in 12 h(P