OBJECTIVE: To explore the clinical characteristics and prognostic factors of patients with extranasal NK/T-cell lymphoma (NKTCL). METHODS: The clinical data of 138 patients with NKTCL diagnosed in 10 medical centers of Huaihai Lymphoma Working Group from June 2015 to April 2021 were collected and analyzed retrospectively. The differences in clinicopathological characteristics of patients with different involvement and efficacy of pegaspargase regimen were compared, as well as perform survival analysis. RESULTS: A total of 138 extranasal NKTCL patients were included, with a median age of 46 years, and the ratio of males to females was approximately 2∶1. There were 39 patients with gastrointestinal involvement, 32 patients with oropharyngeal involvement, 17 patients with skin involvement, 11 patients with lymph node involvement, 11 patients with orbital involvement, and 28 patients with other parts involvement. Patients with skin involvement had a higher proportion of advanced disease and a lower proportion of CD56 positive rate compared to those with oropharyngeal involvement. Among the patients with gastrointestinal involvement, the survival rate of patients who received pegaspargase regimen was significantly higher than those who were treated without pegaspargase (P < 0.01). Multivariate analysis showed that serum creatinine was an independent prognostic factor for patients with skin involvement ( HR =1.027, 95%CI : 1.001-1.054, P =0.040), ECOG PS and EBV DNA were independent prognostic factors for patients with gastrointestinal involvement ( HR =2.635, 95%CI : 1.096-6.338, P =0.030; HR =4.772, 95% CI : 1.092-20.854, P =0.038), and ECOG PS and CA stage were independent prognostic factors for patients with oropharyngeal involvement ( HR =13.875, 95%CI : 2.517-76.496, P =0.002; HR =20.261, 95%CI : 2.466-166.470, P =0.005). CONCLUSION The clinicopathological characteristics of extranasal NKTCL patients with different sites of involvement are vary, and effective individualized treatment need to be further explored.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Asparaginase/therapeutic use* ; Lymphoma, Extranodal NK-T-Cell/pathology* ; Prognosis ; Retrospective Studies ; Survival Rate ; Polyethylene Glycols

Alzheimer's disease (AD) is a common neurodegenerative disorder among the elderly, and BuChE has emerged as a potential therapeutic target. In this study, we reported the development of compound 8e, a selective reversible BuChE inhibitor (eqBuChE IC₅₀ = 0.049 μmol/L, huBuChE IC₅₀ = 0.066 μmol/L), identified through extensive virtual screening and lead optimization. Compound 8e demonstrated favorable blood-brain barrier permeability, good drug-likeness property and pronounced neuroprotective efficacy. Additionally, 8e exhibited significant therapeutic effects in zebrafish AD models and scopolamine-induced cognitive impairments in mice. Further, 8e significantly improved cognitive function in APP/PS1 transgenic mice. Proteomics analysis demonstrated that 8e markedly elevated the expression levels of very low-density lipoprotein receptor (VLDLR), offering valuable insights into its potential modulation of the Reelin-mediated signaling pathway. Thus, compound 8e emerges as a novel and potent BuChE inhibitor for the treatment of AD, with significant implications for further exploration into its mechanisms of action and therapeutic applications.

The PA-PB1 interface of the influenza polymerase is an attractive site for antiviral drug design. In this study, we designed and synthesized a mini-library of indazole-containing compounds based on rational structure-based design to target the PB1-binding interface on PA. Biological evaluation of these compounds through a viral yield reduction assay revealed that compounds 27 and 31 both had a low micromolar range of the half maximal effective concentration (EC₅₀) values against A/WSN/33 (H1N1) (8.03 μmol/L for 27; 14.6 μmol/L for 31), while the most potent candidate 24 had an EC₅₀ value of 690 nM. Compound 24 was effective against different influenza strains including a pandemic H1N1 strain and an influenza B strain. Mechanistic studies confirmed that compound 24 bound PA with a K _d which equals to 1.88 μmol/L and disrupted the binding of PB1 to PA. The compound also decreased the lung viral titre in mice. In summary, we have identified a potent anti-influenza candidate with potency comparable to existing drugs and is effective against different viral strains. The therapeutic options for influenza infection have been limited by the occurrence of antiviral resistance, owing to the high mutation rate of viral proteins targeted by available drugs. To alleviate the public health burden of this issue, novel anti-influenza drugs are desired. In this study, we present our discovery of a novel class of indazole-containing compounds which exhibited favourable potency against both influenza A and B viruses. The EC₅₀ of the most potent compounds were within low micromolar to nanomolar concentrations. Furthermore, we show that the mouse lung viral titre decreased due to treatment with compound 24. Thus our findings identify promising candidates for further development of anti-influenza drugs suitable for clinical use.

The increasing number of TCM standards brings challenges to the practice of standards development,revision and comprehensive management.Therefore,empowering standards with digital technology has significant strategic significance.This article proposed a modeling method for inter standard relationships based on entity-relation model by deeply mining and interpreting the information of TCM standard titles,constructed a relationship model containing 7 relationship patterns,and demonstrated the application scenarios of the model using standard retrieval as an example,with the purpose to provide support for machine reading and using standards,improving the efficiency of TCM standard retrieval,mastering target standard related resources,and promoting the digital transformation of TCM standards.

China has become the world's second largest consumer market for cosmetics. The rapid development of the cosmetics industry requires that its regulatory management and standard and regulation also need to keep pace with the times and constantly improve. This paper compares domestic and foreign standards for skin sensitisation test, skin phototoxicity test and skin photoallergy test, and analysis the specific problems of the current standards and make recommendations.

OBJECTIVE To explore the intracellular expression changes of p38 and Erk1/2 under three phototoxic conditions, compare three detection methods, and further investigate their molecular mechanisms. METHODS The methods involved using three testing approaches to assess the phototoxicity of chlorpromazine(CPZ) and tiaprofenic acid(TA). Subsequently, whole-cell lysates from the biological samples used in the three testing methods were collected, and the changes in the expression levels of intracellular p38 and Erk1/2 were evaluated using Western blotting. RESULTS All three testing methods accurately identified CPZ and TA as phototoxic compounds. In the 3T3 NRU phototoxicity assay, compared to the control group, the expression of p38 significantly increased under phototoxic doses of TA and CPZ(P<0.05), a phenomenon not observed in other testing methods. In phototoxicity assays using guinea pig and artificial skin models, similar expression pattern changes were observed for p38 and Erk1/2. CONCLUSION p38 and Erk1/2 have obvious dose dependence and high sensitivity in the 3T3 NRU phototoxicity test, and can be considered as potential molecular markers for evaluating the phototoxicity of 3T3 NRU. However, they have not been feasible in guinea pig tests and EpiKutis artificial skin tests. Guinea pigs and EpiKutis artificial skin exhibit more similar changes in p38 and Erk1/2 expression, suggesting that the EpiKutis artificial skin model test method may be a better alternative to animal testing than the 3T3 NRU method.

Objective:To provide evidence-based recommendations for the prevention and management of lower limb ischemia in veno-arterial extracorporeal membrane oxygenation (VA-ECMO) patients during treatment according to search, evaluate, and summarize the best evidence on the prevention and management of lower limb ischemia in patients with VA-ECMO.Methods:Based on the PIPOST framework (population, intervention, professional, outcome, setting, and type of evidence), an evidence-based question was formulated. A systematic search was conducted according to the "6S" evidence pyramid model in both domestic and international databases, as well as professional association websites, for all evidence related to the prevention and management of lower limb ischemia in VA-ECMO patients (aged ≥18 years). The types of evidence included clinical decisions, guidelines, expert consensus, systematic reviews, evidence summaries, and original studies. The search was conducted from the construction of the databases to February 2024. Two researchers independently conducted a literature quality evaluation, extracted and summarized evidence from the studies that met the quality criteria.Results:A total of 13 articles were included, consisting of 3 clinical decisions, 3 guidelines, 3 expert consensus, 3 systematic reviews, and 1 randomized controlled trial. A total of 18 pieces of evidence in 7 dimensions were summarized, including risk factors of VA-ECMO lower limb ischemia, evaluation before catheterization, evaluation and monitoring during treatment, prevention of lower limb ischemia, treatment of lower limb ischemia, management of distal perfusion catheter (DPC), and monitoring after VA-ECMO weaning.Conclusion:This evidence summary provides evidence-based recommendations for the prevention and management of lower limb ischemia in VA-ECMO patients, aiming to assist clinical healthcare professionals in developing tailored strategies for the prevention and management of lower limb ischemia based on during VA-ECMO support.

Objective:To explore the clinical efficacy and cardiovascular protective effect of sodium-glucose co-transporter 2 inhibitor(SGLT-2i)on patients with type 2 diabetic nephropathy(T2DN).Methods:A total of 376 T2DN patients admitted in our Department of Endocrinology and Department of Cardiology from January 2018 to December 2021 were selected.According to therapeutic program,they were divided into control group(n=177,re-ceived routine treatment program)and SGLT-2i group(n=199,received SGLT-2i based on routine treatment program),both groups were continuously treated for 1 year.Blood glucose,blood pressure,blood lipids,uric acid,body mass index,renal function-related indexes and the occurrence of major adverse cardiovascular events were compared between the two groups after 12 months,as well as the adverse drug reactions.Results:After 12-month treatment,compared with control group,there were significant reductions in levels of blood pressure,fasting blood glucose(FBG),glycosylated hemoglobin A1e(HbA1c),urinary albumin/creatinine ratio(UACR),creatinine(Cr),blood urea nitrogen(BUN),total cholesterol(TC),triglyceride(TG),low density lipoprotein cholesterol(LDL-C)and uric acid(UA),and significant rise in estimated glomerular filtration rate(eGFR),levels of high density lipoprotein cholesterol(HDL-C),albumin(Alb)and alanine aminotransferase(ALT)in SGLT-2i group(P＜0.05 or＜0.01).Incidence rates of acute myocardial infarction(1.51％vs.6.21％)and heart failure caused-readmission(2.51％vs.6.78％)in SGLT-2i group were significantly lower than those of control group,and inci-dence rate of urinary system infection(8.54％vs.1.69％)was significantly higher than that of control group(P＜0.05 all).Conclusion:SGLT-2i can not only effectively control blood glucose,but also reduce body weight and blood pressure,improve blood lipids,reduce uric acid,improve renal hyperfiltration,reduce urinary protein and possess unique cardiovascular benefits,but risk of urinary system infection calls for attention.

Background: Inflammation following stroke is associated with poor outcomes, and the anti-inflammatory effects of neural stem cells (NSCs) have been reported. However, the direct immunomodulatory effects of NSCs in hemorrhagic stroke remain unclear. In the present study, we investigated the anti-inflammatory mechanism of direct co-culture with NSCs on RAW 264.7 cells stimulated by hemolysate. Methods: RAW 264.7 cells were stimulated with the hemolysate for 4 hours to induce hemorrhagic inflammation in vitro. Regarding direct co-culture, RAW 264.7 cells were cultured with HB1.F3 cells for 24 hours in normal medium and stimulated with hemolysate for 4 hours. Inflammatory cell signaling molecules, including cycloxygenase-2 (COX-2), interleukin-1β (IL-1β), and extracellular signal-regulated kinase (ERK), as well as tumor necrosis factor-α (TNF-α), were evaluated. Results: After stimulation with the hemolysate, levels of the inflammatory markers COX-2, IL-1β, and TNF-α were increased in RAW264.7 cells. Inflammatory marker production was reduced in the group subjected to direct co-culture with HB1.F3 in comparison to that in the RAW264.7 group stimulated by the hemolysate. In addition, direct co-culture with HB1.F3 significantly suppressed the phosphorylation of ERK 1/2 in hemolysate-stimulated RAW 264.7 cells. Moreover, treatment of the ERK inhibitor (U0126) suppressed the expression levels of inflammatory markers in hemolysate-stimulated RAW246.7 cells. Conclusion These results demonstrate that direct co-culture with HB1.F3 suppresses inflammation by attenuating the ERK pathway. These findings suggest that direct NSC treatment modulates the inflammatory response in hemorrhagic stroke.

Background::Oral anti-coagulants (OAC) are the intervention for the prevention of stroke, which consistently improve clinical outcomes and survival among patients with atrial fibrillation (AF). The main purpose of this study is to identify problems in OAC utilization among hospitalized patients with AF in China.Methods::Using data from the Improving Care for Cardiovascular Disease in China-Atrial Fibrillation (CCC-AF) registry, guideline-recommended OAC use in eligible patients was assessed.Results::A total of 52,530 patients with non-valvular AF were enrolled from February 2015 to December 2019, of whom 38,203 were at a high risk of stroke, 9717 were at a moderate risk, and 4610 were at a low risk. On admission, only 20.0% (6075/30,420) of patients with a diagnosed AF and a high risk of stroke were taking OAC. The use of pre-hospital OAC on admission was associated with a lower risk of new-onset ischemic stroke/transient ischemic attack among the diagnosed AF population (adjusted odds ratio: 0.54, 95% confidence interval: 0.43–0.68; P <0.001). At discharge, the prescription rate of OAC was 45.2% (16,757/37,087) in eligible patients with high stroke risk and 60.7% (2778/4578) in eligible patients with low stroke risk. OAC utilization in patients with high stroke risk on admission or at discharge both increased largely over time (all P <0.001). Multivariate analysis showed that OAC utilization at discharge was positively associated with in-hospital rhythm control strategies, including catheter ablation (adjusted odds ratio [OR] 11.63, 95% confidence interval [CI] 10.04–13.47; P <0.001), electronic cardioversion (adjusted OR 2.41, 95% CI 1.65–3.51; P <0.001), and anti-arrhythmic drug use (adjusted OR 1.45, 95% CI 1.38–1.53; P <0.001). Conclusions::In hospitals participated in the CCC-AF project, >70% of AF patients were at a high risk of stroke. Although poor performance on guideline-recommended OAC use was found in this study, over time the CCC-AF project has made progress in stroke prevention in the Chinese AF population.Registration::ClinicalTrials.gov, NCT02309398.