BACKGROUND:Repetitive trans-spinal magnetic stimulation(rTSMS)can inhibit inflammatory responses following spinal cord injury.rTSMS applies magnetic field stimulation to the spinal cord region to modulate neuronal excitability and synaptic transmission,thereby promoting plasticity and repair of the nervous system. OBJECTIVE:To observe the effects of rTSMS on the Toll-like receptor 4(TLR4)/nuclear factor(NF)-κB/NLRP3 signaling pathway after spinal cord injury and explore its mechanism in promoting motor function recovery. METHODS:Male C57BL/6J mice,SPF grade,were randomly divided into sham surgery group,spinal cord injury group,and rTSMS group.The latter two groups of mice were anesthetized and the T9 vertebral plate was removed using rongeur forceps to expose the spinal cord,and the spinal cord was clamped using a small aneurysm clip for 20 seconds to establish the spinal cord injury model.Mice in the rTSMS group underwent a 21-day rTSMS intervention starting on day 1 after spinal cord injury.The stimulation lasted 10 minutes per day,5 days per week with an interval of 2 days.Basso Mouse Scale scores were used to assess motor function recovery in mice after spinal cord injury at 1,3,7,14,and 21 days after spinal cord injury.Western blot was employed to detect the expression of AQP4,apoptotic factors Bax,Bcl-2,CL-Caspase-3,inflammatory factors tumor necrosis factor-α,interferon-γ,interleukin-6,interleukin-4,and the TLR4/NF-κB/NLRP3 signaling pathway related proteins in the injured spinal cord.Oxidative stress assay kit was used to measure the activity of superoxide dismutase,glutathione peroxidase,and malondialdehyde content at the site of spinal cord injury.Immunofluorescence staining was performed to detect the expression of neuronal nuclei(NeuN). RESULTS AND CONCLUSION:The Basso Mouse Scale score in the rTSMS group was significantly higher than that in the spinal cord injury group(P<0.05).Compared with the spinal cord injury group,the rTSMS group showed a reduction in spinal cord water content.The expression of AQP4 protein,malondialdehyde content,and expression of Bax,Bcl-2,CL-Caspase-3,tumor necrosis factor-α,interferon-γ,interleukin-6,and TLR4/NF-κB/NLRP3 signaling pathway related proteins were all decreased in the rTSMS group,while the activities of superoxide dismutase and glutathione peroxidase,as well as the expression of Bcl-2,interleukin-4,and NeuN,were all increased(P<0.05).These results suggest that rTSMS downregulates the expression of proteins related to the TLR4/NF-κB/NLRP3 signaling pathway,alleviating symptoms after spinal cord injury such as spinal cord edema,oxidative stress,apoptosis,and inflammation,exerting neuroprotective effects,and thereby promoting the recovery of hindlimb motor function after spinal cord injury.

Huntington's disease(HD)is an autosomal dominant neurodegenerative disease,with the main symptoms including chorea-like involuntary movements,psychiatric behavioral abnormalities,and cognitive impairment,which severely affect the lives of patients and consume extensive social and medical resources.Various experimental animal models of HD have been successfully established,to further our understanding of the pathological mechanisms and to explore treatment method of HD.This review outlines the establishment and application of various animal models,ranging from Caenorhabditis elegans,Drosophila melanogaster and zebrafish to mice,rats and miniature pigs,and analyzes the characteristics and advantages of the different models.By reviewing the different animal models and their relevant evaluation indicators,this article emphasizes the importance of utilizing a combination of multiple animal models to promote a deeper understanding of the disease mechanisms and develop effective treatment strategies.

There are many difficulties in digital medical teaching, including new course content, multiple key and difficult points, wide knowledge coverage, large knowledge structure span, high requirements for teachers, and few shared resources for online teaching during the epidemic. This research aims to give full play to the advantages of our team in the field of digital medicine, and promote the construction of network resources of this course and its extensive development in more universities through the exploratory and research on the course construction and teaching mode of the Digital Medicine MOOC (massive open online course). The questionnaire study found that the satisfaction score of the average satisfaction score of MOOC teaching in terms of students' pre-class preview, quick grasp of knowledge points in class and after-class review reached more than 90 points, and the score of improving students' learning initiative was (88.10±10.87) points. It can be seen that the use of MOOC teaching mode can significantly help students to preview before class, master knowledge points in class and review after class, and improve students' initiative in learning. The research suggests that the production of Digital Medicine MOOC should keep the consistency and individuality of all knowledge points under the framework of digital medical knowledge; teachers should focus on the explanation of basic knowledge points and deepen in further step integrated with frontiers of this field; it’s suggested to make a separate MOOC on frontier knowledge and application explanation, so as to cope with the outdated courseware content caused by the development and update of this subject.

Evidence-based Practice Guideline of Medication Therapy of High-dose Methotrexate in China was published in the British Journal of Clinical Pharmacology in February 2022. The guideline followed the latest definition of clinical practice guideline and the methodology specification for the guideline development of WHO. The Grading of Recommendations Assessment ， Development，and Evaluation （GRADE）approach was applied to rate the quality of evidence and determine the strength of recommendations. Finally ，this guideline presents 28 recommendations covering the whole process of clinical medication of high-dose methotrexate ，involving evaluation prior to administration （liver and renal function ，pleural effusion and ascites ， comedication，genetic testing ），pre-treatment and routine dosing regimen （pretreatment of hydration and alkalization ，urine alkalization，routine dosing regimen ），therapeutic drug monitoring （necessity，method，timing，target concentration ），leucovorin rescue（rescue timing ，rescue regimen ，rescue dose optimization ），and management of toxicities （liver and kidney function monitoring，supportive treatment ，blood purification treatment ）. This article aims to summarize and interpret the recommendations of this guideline ，so as to promote the better promotion and implementation of this guideline and provide comprehensive technical support and suggestions for whole-course individualized administration of high-dose methotrexate in China.

OBJECTIVE: To assess the predictors and outcomes of acute kidney injury (AKI) among patients with coronavirus disease 2019 (COVID-19). OBJECTIVE: This retrospective observational study was conducted among patients with a confirmed diagnosis of COVID-19 admitted to Hankou Hospital between January, 5 and March 8, 2020. We evaluated the association of AKI with the demographic and biochemical parameters and clinical outcomes of the patients using univariate regression analysis. OBJECTIVE: Atotal of 287 COVID-19 patients, including 55 with AKI and 232 without AKI, were included in the analysis. Compared with the patients without AKI, the patients with AKI were older, predominantly male, and were more likely to have hypoxia and pre-existing hypertension and cerebrovascular diseases. The patients with AKI also had higher levels of white blood cells, D-dimer, aspartate aminotransferase, total bilirubin, creatine kinase, lactate dehydrogenase, procalcitonin, C-reactive protein, a higher prevalence of hyperkalemia, lower lymphocyte counts, and higher chest computed tomographic scores. The incidence of stage 1 AKI was 14.3% and that of stage 2 or 3 AKI was 4.9%. The patients with AKI had much higher mortality rate than those without AKI. OBJECTIVE AKI is an important complication of COVID-19. An older age, a male gender, multiple pre- existing comorbidities, lymphopenia, increased infection indicators, elevated D-dimer, and impaired heart and liver functions are all potential risk factors ofAKI. COVID- 19 patients with AKI that progresses into stages 2 or 3 AKI have a high mortality rate. Prevention of AKI and monitoring kidney function is critical in the care of COVID-19 patients.
Acute Kidney Injury/epidemiology* ; Aged ; COVID-19 ; China/epidemiology* ; Humans ; Male ; Retrospective Studies ; SARS-CoV-2

Objective:To investigate the key mechanism of transforming growth factor-β (TGF-β) inducing the expression of interleukin-17D (IL-17D) in lung cancer-associated fibroblast (CAF) and promoting the recruitment of myeloid-derived suppressor cells (MDSCs).Methods:C57BL/6 mice were established for B16 lung melanoma metastasis model (tumor model group), and control group was set up, 6 mice in each group. Flow cytometry (FACS) was used to detect the lung CAF and the changes of its ability to secrete IL-17D and the proportion of MDSCs in tumor mice. The changes of TGF-β level in lung tumor were examined by ELISA and quantitative real-time PCR (RT-qPCR). Lung fibroblasts were screened by FACS, and the effects of TGF-β on the secretion of IL-17D, C-C motif chemokine ligand (CCL)2 and CCL7 in fibroblasts were detected by RT-PCR. The migration of MDSCs under the condition of TGF-β stimulating fibroblasts was detected by Transwell.Results:The proportion of CAF (CD45 -CD326 -CD31 -) in the tumor model group was higher than that in the control group [(28.02±2.23)% vs. (7.35±2.14)%, t=9.956, P<0.001]. The ability of CAF to secrete IL-17D in the tumor model group was significantly higher than that in the control group [(38.27±2.93)% vs. (19.04±3.16)%, t=5.995, P=0.001]. The proportion of MDSCs in the tumor model group was significantly higher than that in the control group [(12.93±1.27)% vs. (8.21±1.40)%, t=4.804, P=0.009]. Compared with the control group, the protein and transcription levels of TGF-β in lung of the tumor model group were significantly increased [(1 685.07±135.61) ng/L vs. (1 047.98±68.50) ng/L, t=5.051, P=0.002; 2.17±0.03 vs. 1.00±0.05, t=51.237, P<0.001]. In vitro, lung fibroblasts were stimulated with different concentrations of TGF-β (0, 5 and 10 μg/L) for 24 hours, the relative expressions of IL-17D mRNA secreted by stimulated fibroblasts were 0.42±0.01, 0.67±0.01 and 0.84±0.04 respectively, the relative expressions of CCL2 mRNA in each group were 0.89±0.08, 1.08±0.04, 1.19±0.01 and CCL7 were 0.53±0.05, 0.65±0.04, 0.74±0.03 respectively. With the increase of TGF-β concentration, the expression levels of IL-17D, CCL2 and CCL7 in fibroblasts were significantly increased ( F=57.384, P<0.001; F=15.802, P=0.004; F=14.544, P=0.005). In addition, compared with the control group (0 μg/L TGF-β), fibroblasts treated with 10 μg/L TGF-β for 24 hours could promote the migration of MDSCs in spleen of tumor mice [(9.59±0.21)% vs. (2.14±0.24)%, t=6.585, P<0.001]. Conclusion:TGF-β can induce high expression of IL-17D in lung CAF, which is an important factor in promoting the expressions of CCL2 and CCL7 and the migration of MDSCs in tumor microenvironment.

OBJECTIVE：To prepar e Breviscapine gastric adhesive tablets ，to optimize the formulation and to evaluate the quality. METHODS ：HPMC K 100M and carbomer 934P were used as bioadhesives and skeleton materials ，and lactose was used as filler，and magnesium stearate was used as glidant and lubricant to prepare Breviscapine gastric adhesive tablets by direct powder pressing method. The comprehensive scores of scores of accumulative release rate of Breviscapine gastric adhesive tablets in pH 6.8 PBS at 2，6，12 h（Q2 h，Q6 h，Q12 h，with scutellarin meter ，by HPLC method ）and in vitro adhesion force of gastric tissue were evaluated by weighting method. Taking this scores as indexes，L9（34）orthogonal test design was used to optimize the amount of HPMC K 100M，carbomer 934P and lactose in Breviscapine gastric adhesive tablets and validation tests were conducted. The properties，identification，weight difference ，fragility，release and the content of scutellarin of the gastric adhesive tablets were determined. RESULTS ：The optimal prescription of Breviscapine gastric adhesive tablets were 42％ breviscapine，10％ HPMC K100M，3％ carbomer 934P and 45％ lactose. The verification test results show that the Q2 h，Q6 h，Q12 h of 3 batches of Breviscapine gastric adhesive tablets were 20.36％，48.55％，and 87.00％ ；the average in vitro adhesion force of gastric tissue was 31.36 g/cm2；the average comprehensive score was 70.23（RSD＝1.84％，n＝3）. The gastric adhesive tablets were light yellow，tasteless or slightly salty ；the peak time was consistent with that of scutellarin control ；its weight difference were ±6％， the fragility was 0.54％，and the Q12 h was 83.51％（RSD＝2.14％，n＝6）. The content of scutellarin was 288.47 mg/g（RSD＝ 0.70％，n＝3）. CONCLUSIONS ：Breviscapine gastric adhesive tablets is prepared successfully ，and its quality evaluation conforms to the requirements of Chinese Pharmacopoeia （2015 edition）.

Salvianolic acid A (SalA) is an effective compound extracted from traditional Chinese medicine Bunge. The Forkhead box O3a (FOXO3a) signaling pathway plays crucial roles in the modulation of ischemia-induced cell apoptosis. However, no information about the regulatory effect of SalA on FoxO3a is available. To explore the anti-cerebral ischemia effect and clarify the therapeutic mechanism of SalA, SH-SY5Y cells and Sprague-Dawley rats were applied, which were exposed to oxygen glucose deprivation/reoxygenation (OGD/R) and middle cerebral artery occlusion/reperfusion (MCAO/R) injuries, respectively. The involved pathway was identified using the specific inhibitor LY294002. Results showed that SalA concentration-dependently inhibited OGD/R injury triggered cell viability loss. SalA reduced cerebral infarction, lowered brain edema, improved neurological function, and inhibited neuron apoptosis in MCAO/R rats, which were attenuated by the treatment of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) specific inhibitor LY294002. SalA time- and concentration-dependently upregulated the phosphorylation levels of protein kinase B (AKT) and its downstream protein FOXO3a. Moreover, the nuclear translocation of FOXO3a was inhibited by SalA both and , which was also reversed by LY294002. The above results indicated that SalA fought against ischemia/reperfusion damage at least partially the AKT/FOXO3a/BIM pathway.

Objective To study the gastrointestinal absorption process of three letrozole polymorphs in rats, and evaluate the different pharmacokinetics parameters of different polymorphs. Methods A total of 18 SD rats were given the different letrozole polymorphs. Then the high-performance liquid chromatographic method was used for the determination of plasma concentration of letrozole in these SD rats.Finally the pharmacokinetic parameters among the different polymorphs were calculated. Results Cmax of letrozole crystal form I, crystal form II and crystal form III were (9.247± 4.612) ,(23.387± 9.049) and (15.682±1.589) mg·L-1, respectively, and AUC0→t were(198.115±47.014) ,(476.641±125.467) and (271.817±41.068) mg·L-1·h,respectively. Conclusion The different crystal forms of letrozole result in different plasma concentration in SD rats. Crystal form II may be its preponderant polymorphs which deserves further research and development.

Objective To study the mangiferin absorption process of mangiferin polymorphs in SD rats thus to find out the optimal crystal form and explore the factors that may affect the clinical effects of mangiferin. Methods Each rat was given one of three crystal forms of mangiferin. Plasma concentration of mangiferin were determined by HPLC-MS method. After liquidliquid extraction by ethyl acetate, the chromatographic separation was carried out on an Agilent ZORBAX SB-C18 (2.1 mm× 100 mm,3.5 μm) with a mobile phase consisting of methanol-0.1％ formic acid aqueous solution (30:70) . Mass spectrometry were performed in positive ion mode. Ion mass-to-charge ratio was set at 445 and 447 for mangiferin and, cefuroxime sodium (internal standard) respectivel for quantitive analysis. Results The main pharmacokinetic parameters of mangiferin form II, Ⅴ, Ⅵ were as follows: AUC(0-24 h) were (1323. 27 ± 218. 07) ,(1974. 34 ± 469. 24) ,(1737. 79 ± 623. 06) ng · mL-1 · h, respectively; Cmax were (321.92±85.18) ,(455.83±277.07) ,(319.92±86.07) μg·L-1, respectively; tmax were (0.70±0.45) , (0.50±0.32) ,(0.50± 0.34) h, respectively; t1/2z were (2.78± 1.72) ,(5.29± 2.67) ,(5.31± 2.82) h, respectively. Conclusion The main pharmacokinetic parameters of mangiferin polymorphs in plasma of rats are different, and mangiferin form Ⅴ has the hightest AUC(0-24 h) and Cmax.