ObjectiveTo explore the clinical safety of Feilike Mixture （FLK） in the real world. MethodsThe safety of all children who received FLK from 29 institutions in 12 provinces between January 21，2021 and December 25，2021 was evaluated through prospective centralized surveillance and a nested case control study. ResultsA total of 3 035 juveniles were included. There were 29 research centers involved，which are distributed across 12 provinces，including one traditional Chinese medicine （TCM） hospital and 28 general hospitals. The average age among the juveniles was （4.77±3.56） years old，and the average weight was （21.81±12.97） kg. Among them，119 cases （3.92%） of juveniles had a history of allergies. Acute bronchitis was the main diagnosis for juveniles，with 1 656 cases （54.46%）. FLK was first used in 2 016 cases （66.43%），and 142 juvenile patients had special dosages，accounting for 4.68%. Among them，92 adverse drug reactions （ADRs） occurred，including 73 cases of gastrointestinal system disorders，10 cases of metabolic and nutritional disorders，eight cases of skin and subcutaneous tissue diseases，two cases of vascular and lymphatic disorders，and one case of systemic diseases and various reactions at the administration site. The manifestations of ADRs were mainly diarrhea，stool discoloration，and vomiting，and no serious ADRs occurred. The results of multi-factor analysis indicated that special dosages （the use of FLK）［odds ratio （OR） of 2.642， 95% confidence interval （CI） of 1.105-6.323］，combined administration： spleen aminopeptide （OR of 4.978， 95%CI of 1.200-20.655），and reason for combined administration： anti-infection （OR of 1.814， 95%CI of 1.071-3.075） were the risk factors for ADRs caused by FLK. Conclusion92 ADRs occurred among 3 035 juveniles using FLK. The incidence of ADRs caused by FLK was 3.03%，and the severity was mainly mild or moderate. Generally，the prognosis was favorable after symptomatic treatment such as drug withdrawal or dosage reduction，suggesting that FLK has good clinical safety.

Transcranial temporal interference stimulation (tTIS) is a novel non-invasive transcranial electrical stimulation technique that achieves deep brain stimulation through multiple electrodes applying electric fields of different frequencies. Current studies on the mechanism of tTIS effects are primarily based on rodents, but experimental outcomes are often significantly influenced by electrode configurations. To enhance the performance of tTIS within the limited cranial space of rodents, we proposed various electrode configurations for tTIS and conducted finite element simulations using a realistic mouse model. Results demonstrated that ventral-dorsal, four-channel bipolar, and two-channel configurations performed best in terms of focality, diffusion of activated brain regions, and scalp impact, respectively. Compared to traditional transcranial direct current stimulation (tDCS), these configurations improved by 94.83%, 50.59%, and 3 514.58% in the respective evaluation metrics. This study provides a reference for selecting electrode configurations in future tTIS research on rodents.
Animals ; Transcranial Direct Current Stimulation/instrumentation* ; Electrodes ; Mice ; Computer Simulation ; Finite Element Analysis ; Brain/physiology*

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

OBJECTIVES: To explore the correlation of ELFN1 expression level with prognosis of colorectal cancer and its regulatory role in colorectal cancer cell proliferation and metastasis. METHODS: We analyzed the expression levels of ELFN1 across 33 cancer types using publicly available databases and identified differential genes related to ELFN1 in colorectal cancer. Gene function annotation and enrichment analysis were used to identify the involved signaling pathways. Logistic analysis, Kaplan-Meier analysis and Cox regression analysis were performed to evaluate the correlation between ELFN1 expression and clinicopathological parameters and survival of colorectal cancer patients. qPCR and Western blotting were used to validate the expression levels of ELFN1 in different colorectal cancer cell lines and tissues, and Transwell and EDU experiments were carried out to assess the effect of ELFN1 knockdown on biological behaviors of SW480 cells. RESULTS: ELFN1 was highly expressed in 14 cancers, and its expression was significantly higher in colon cancer tissues than in adjacent tissues. A high expression of ELFN1 mRNA was associated with a poorer overall survival of colorectal cancer patients. Cox regression analysis indicated that ELFN1 expression was an independent prognostic factor for overall survival of the patients. ELFN1 was significantly enriched in tumor metastasis and proliferation and participated in several tumor signaling pathways. The colon cancer cell lines showed significantly higher expression levels of ELFN1 than normal cells, ELFN1 knockdown obviously inhibited proliferation and migration of SW480 cells in vitro. CONCLUSIONS ELFN1 is overexpressed in colorectal cancer and is associated with poor clinical prognosis of the patients. A high ELFN1 expression is associated with malignant phenotypes of colorectal cancer and promotes cancer cell proliferation and metastasis, suggesting its potential as a prognostic biomarker for colorectal cancer.
Humans ; Colorectal Neoplasms/diagnosis* ; Cell Proliferation ; Prognosis ; Cell Line, Tumor ; Biomarkers, Tumor/metabolism* ; Neoplasm Metastasis ; Gene Expression Regulation, Neoplastic ; Nerve Tissue Proteins/metabolism* ; Female ; Male

Objective:To evaluate the efficacy and safety of transepithelial photorefractive keratectomy (Trans-PRK) combined with accelerated corneal cross-linking (CXL) for refractive error in patients with thin or irregular corneas, excluding keratoconus.Methods:An observational case series study was performed.Fifty-five right eyes of 55 myopic patients diagnosed with thin or irregular corneas, who underwent Trans-PRK combined with prophylactic CXL surgery, were included at Baotou Chaoju Eye Ophthalmic Hospital from August 2017 to July 2018.Uncorrected distance visual acuity (UDVA) of the operated eye was measured using international standard visual acuity charts, and refractive diopters were measured by computer and comprehensive refraction before surgery and at 1 week, 1, 3, 6, and 12 months after surgery.Corneal morphology was assessed with the Pentacam anterior segment analyzer before surgery and at 3, 6, and 12 months after surgery.Intraocular pressure (IOP) was measured with a non-contact tonometer before surgery and at 1, 3, 6, and 12 months after surgery.The incidence of postoperative complications was recorded.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Baotou Chaoju Ophthalmic Hospital (No.btcj-u-1). Written informed consent was obtained from each subject.Results:Preoperative, 1-week, 1-, 3-, 6-, and 12-month postoperative UDVA (LogMAR) were 0.52(0.55, 0.78), 0.22(0.12, 0.17), 0.10(0.04, 0.07), 0.00(-0.04, -0.16), -0.08(-0.05, -0.03) and -0.08(-0.06, -0.04), respectively, showing a statistically significant overall difference ( Z=249.44, P<0.001). UDVA at each postoperative time point was improved compared to preoperative, and UDVA at 3, 6, and 12 months postoperatively was significantly improved compared to 1 week and 1 month postoperatively (all at P<0.001). The spherical diopter at each postoperative time point decreased significantly compared to preoperative, with the spherical diopter at 1, 3, 6, and 12 months postoperatively being lower than that at 1 week postoperatively, and the 12-month postoperative spherical diopter being lower than that at 3 and 6 months postoperatively, showing statistically significant differences (all at P<0.001). The cylindrical degree at 1, 3, 6, and 12 months postoperatively was lower than that at preoperative and 1 week postoperatively, with statistically significant differences (all at P<0.05). After the operation, the spherical equivalent of the operated eye gradually decreased with time, tending toward emmetropia.The spherical equivalent at each postoperative time point decreased compared to preoperative, with the spherical equivalent at 1, 3, 6, and 12 months postoperatively being lower than that at 1 week postoperatively, and the spherical equivalent at 12 months postoperatively being lower than that at 3 and 6 months postoperatively, showing statistically significant differences (all at P<0.001). The corneal K1 and K2 values at 3, 6, and 12 months postoperatively were significantly lower than preoperatively (all at P<0.001), and the corneal K1 and K2 values at 3 months postoperatively tended to stabilize.The IOP of the operated eye at 3, 6, and 12 months postoperatively was significantly lower than preoperatively, and the IOP at 6 and 12 months postoperatively was lower than that at 1 and 3 months postoperatively, with statistically significant differences (all at P<0.001). One eye developed grade 0.5 corneal haze at 1 week postoperatively, which spontaneously resolved to transparency at 1 month postoperatively. Conclusions:Trans-PRK combined with accelerated CXL has good efficacy, stability and safety for refractive error patients with thin or irregular corneas, except for keratoconus.

Objective:To explore the role of conducting a"thematic morning report"based on post-competency in the standardized residents training in hospital in the Intensive Care Unit(ICU).Methods:A total of 60 resident training physicians who participated in the standardized residents training in hospital in the ICU of this hospital from January 2020 to December 2022 were included,and randomly divided into an observation group and a control group,with 30 in each group.The observation group adopted an interactive teaching method of themed morning report based on post-competency,while the control group adopted the traditional teaching method.The assessment results of clinical theoretical knowledge and operational skills of the two groups of resident training physicians under different teaching methods were compared.The 360°assessment method was used to record the multi-directional evaluation of patients or their families,nurses,colleagues,and teaching teachers on the post-competence of resident training physicians(self-learning ability,team collaboration ability,effective communication ability,and learning interest).Results:The assessment scores of clinical theoretical knowledge and practical skills in the observation group after teaching were higher than those in the control group,with statistically significant differences(theoretical assessment:t=2.101,P＜0.05;practical assessment:t=9.647,P＜0.05).The post-competence scores of nurses,colleagues,and teaching teachers on resident training physicians in the observation group were higher than those in the control group after one-month regular training,and the differences were statistically significant(nurses'evaluation of self-learning ability:t=3.182,P=0.002,team collaboration ability:t=3.978,P＜0.05,effective communication ability:t=2.180,P=0.0335,learning interest:t=3.884,P＜0.05;colleagues'evaluation of self-learning ability:t=2.888,P=0.005,team cooperation ability:t=6.816,P＜0.05,effective communication ability:t=3.833,P＜0.05,learning interest:t=4.086,P＜ 0.05;teaching teacher's evaluation of self-learning ability:t=3.429,P=0.001,team cooperation ability:t=3.086,P=0.003,effective communication ability:t=3.493,P=0.001,learning interest:t=3.126,P=0.003).There was a statistically significant difference in the satisfaction scores of patients or their familymembers towards the two groups of resident training physicians(t=3.126,P=0.003).Conclusion:The use of the interactive teaching method of thematic morning report based on post-competency in the standardized residents training in hospital in the ICU can not only improve the theoretical practice and case analysis test scores of resident training physicians,but also improve the post-competence and the satisfaction of patients and their families.

Objective To evaluate 99mTc-HYNIC-TOC somatostatin receptor and 131 I-MIBG imaging in clinical diag-nostic of pheochromocytoma and paraganglioma(PPGL).Methods This was a retrospective study.359 PPGL pa-tients diagnosed by pathology microscopy were included.The diagnostic sensitivity and influencing factors on 99mTc-HYNIC-TOC somatostatin receptor and 131 I-MIBG imaging were analyzed.Results The positive rate of 99mTc-HYN-IC-TOC somatostatin receptor scintigraphy was 57.7%(184/319)and 131I-MIBG imaging was 83.2%(232/279).The positive rates of 99m Tc-HYNIC-TOC somatostatin receptor imaging in the adrenal glands,retroperitoneum,head and neck,heart and mediastinum,pelvis and bladder were 53.3%,62.5%,95.0%,66.7%,50.0%and 11.0%respec-tively and the positive rates of 131I-MIBG imaging were 86.7%,88.5%,45.4%,50.0%,75.0%and 33.3%respec-tively.The positive rate of the two imaging did not showed difference among patients with different genetic back-grounds(SDH,VHL,RET mutations).The median maximum diameter of tumors was 4.4(3.0,6.1)cm.and the diag-nostic sensitivity of somatostatin receptor imaging and 131 I-MIBG imaging for larger tumors(≥4.4 cm)was signifi-cantly higher than those for the smaller tumor group(＜4.4 cm)(64.0%vs.51.3%;92.3%vs.74.1%)(P＜0.01).Tumors in 19 patients(5.3%)failed to uptake neither imaging method.Conclusions This is the largest PPGL cohort in China concerning 99m Tc-HYNIC-TOC somatostatin receptor imaging and 131 I-MIBG imaging.The sensitivity of 131 I-MIBG imaging is higher than that of 99m Tc-HYNIC-TOC somatostatin receptor imaging,but for some tumors,such as head and neck paraganglioma,the latter has obvious advantages.These two imagings technol-ogies are complementary and the choice of them should depend the individual situation of patients.

The current production of Chinese herbal decoction pieces faces several issues including strong subjectivity,unstable quality,low production efficiency,and a lack of intelligent systems.In order to expedite the intelligent transformation and upgrading of Chinese medicine processing,this paper delves deeply into the problems and challenges encountered in establishing a digital and intel-ligent production model for Chinese herbal pieces.Addressing the slow progress in fundamental research on traditional Chinese medi-cine processing mechanisms,the absence of online digital quality characterization techniques,the low level of production equipment in-telligence,and the lack of evaluation standards for high-quality decoction pieces,this paper proposes a"New Quality Productive Forces"formation approach driven by technological innovation.Through interdisciplinary integration methods,the paper explores the mechanisms of Chinese medicine processing in depth,clarifies the correlation between the processing procedures and the"medicinal properties-quality"relationship,and employs bionic sensing and artificial intelligence to achieve a holistic quality characterization of decoction pieces.Additionally,the use of cloud-edge collaborative big data systems is proposed to enhance intelligent upgrades of the production lines.The paper also aims to establish a high-quality decoction piece evaluation system integrating"physical-chemical-bio-logical"multimodal data fusion.This approach aims to steer the Chinese medicine processing towards becoming more efficient,precise,and sustainable,thereby promoting high-quality sustainable development of the Chinese herbal decoction industry and providing both theoretical and practical support for the modernization of traditional Chinese medicine.

OBJECTIVE To explore the detoxification mechanism of Terminalia chebula Retz(TCR)soup-processed Euphorbia fischeriana Steud.(EFS)based on LC-MS and simulation processing.METHODS The changes of chemical composition of TCR soup-processed EFS,and dichloromethane extracts of crude EFS after simulation processing with TCR soup were analyzed by LC-MS.Mice were orally administered with alcoholic extracts of crude EFS,alcoholic extracts of water-processed EFS,alcoholic extracts of TCR soup,alcoholic extracts of TCR soup-processed EFS,dichloromethane extracts of crude EFS,dichloromethane extracts of TCR soup-processed EFS,and dichloromethane extracts of crude EFS after simulation processing with TCR soup,respectively.Toxicity changes in TCR soup-processed EFS and dichloromethane extracts of crude EFS after simulation processing with TCR soup were evalu-ated by fecal water contents,release levels of TNF-α and IL-1β,and intestinal pathology.RESULTS A total of 115 and 53 com-pounds were identified in EFS and TCR soup,respectively.The contents of 58 and 12 compounds significantly decreased and signifi-cantly increased respectively in EFS after processing with TCR soup.Compared to the blank control group,the fecal water contents and the release levels of TNF-α and IL-1β significantly increased in both the crude and water-processed EFS groups(P<0.01),and no-table intestinal injury was observed.Compared to the crude EFS group,the fecal water contents and the release levels of TNF-α and IL-1β significantly decreased in both the TCR soup group and the TCR soup-processed EFS group(P<0.01),and repaired intestinal injury was observed.After simulation processing for the dichloromethane extracts of crude EFS with TCR soup,the ion intensity change rates for diterpenoids and tannin phenolic acid compounds ranged from-6.75%to 8.09%and 66.06%to 100.00%,respectively.The ion intensity change rates of diterpenoids in the dichloromethane extracts of TCR soup-processed EFS ranged from-9.92%to 54.72%with almost no tannin phenolic acid compounds.Compared to the blank control group,the fecal water contents and the release levels of TNF-α and IL-1β significantly increased in both the dichloromethane extracts of crude and TCR soup-processed EFS groups(P<0.01),and severe intestinal injury was observed.Compared to the dichloromethane extracts of crude EFS group,the fecal water contents and the release levels of TNF-α and IL-1β significantly decreased in the group of the dichloromethane extracts of crude EFS after simulation processing with TCR soup(P<0.01),with no apparent intestinal injury.CONCLUSION TCR soup pro-cessing can alleviate the intestinal toxicity of EFS.The detoxification mechanism may involve the introduction of a large number of tan-nin phenolic acid compounds in TCR soup during the processing of EFS,which plays a pharmacological antagonistic role in the animal body.