ObjectiveTo investigate whether Huanglian Jiedutang （HLJD） and its major active constituents （geniposide， baicalin， and berberine） can inhibit the inflammatory response of BV2 cells under lipopolysaccharide （LPS） stimulation via the high-mobility group protein B1 （HMGB1）/Toll-like receptor 4 （TLR4）/nuclear factor-κB （NF-κB） signaling pathway， and to explore differences in therapeutic efficacy among the three monomers， their combined formula， and HLJD under equal content ratios. MethodsBV2 microglial cells were used as the primary experimental model. Cell viability was assessed using the cell counting kit-8 （CCK-8） method to examine the effects of different concentrations of dimethyl sulfoxide （DMSO， 0.8%， 0.4%， 0.2%， 0.1%， and 0.05%） on cell viability. IncuCyte was employed to monitor the growth of cells under different concentrations of HLJD （200， 100， 50， 25， 12.5， 6.25 mg·L^-1）. Nitric oxide （NO） assay was used to screen the optimal HLJD concentration. High-performance liquid chromatography （HPLC） determined the content of geniposide， baicalin， and berberine in HLJD， and experimental groups were subsequently established according to the relative proportions of these constituents. CCK-8 assay evaluated cell viability under different treatments. Enzyme-linked immunosorbent assay （ELISA） measured levels of inflammatory factors （TNF-α， IL-1β， IL-6， IL-10） in the supernatant. Flow cytometry assessed the effects of treatments on M1-type polarization of BV2 cells. Western blot determined the expression levels of HMGB1， TLR4， and NF-κB-related proteins. ResultsCompared with the blank group， DMSO at concentrations ≤0.2% did not affect cell viability within 48 h. BV2 cell growth plateaued at 24 h after treatment with 200 mg·L^-1 HLJD. Under stimulation with 2 mg·L^-1 LPS， this concentration of HLJD effectively reduced NO release， and 6 h pre-treatment had a stronger inhibitory effect on NO than direct administration. HPLC results showed that 1 mg of HLJD freeze-dried powder contained approximately 24 μg of geniposide， 15 μg of baicalin， and 30 μg of berberine. Based on these ratios， experimental groups were blank， LPS （2 mg·L^-1）， HLJD （200 mg·L^-1）， monomer combination， geniposide （4.8 mg·L^-1）， baicalin （3 mg·L^-1）， and berberine （6 mg·L^-1）. The monomer combination group consisted of all three active constituents dissolved together. LPS and HLJD or its active constituents did not affect cell viability compared with the blank group. LPS significantly increased TNF-α， IL-1β， IL-6， and IL-10 in the supernatant （P<0.01）. HLJD and its active constituents significantly reduced pro-inflammatory factors TNF-α， IL-1β， and IL-6 （P<0.05， P<0.01） while upregulating anti-inflammatory IL-10 （P<0.01）， with the monomer combination showing the strongest effect （P<0.05， P<0.01）. Compared with the blank group， LPS significantly increased the proportion of CD80⁺CD86⁺ （M1-type） BV2 cells （P<0.01）. HLJD and its constituents partially inhibited M1 polarization （P<0.05， P<0.01）， with the monomer combination exhibiting the most pronounced effect （P<0.05， P<0.01）. Compared with the blank group， LPS upregulated HMGB1， TLR4， and NF-κB-related proteins （P<0.01）， whereas HLJD and its active constituents significantly reduced their expression （P<0.05， P<0.01）， with the monomer combination having the strongest regulatory effect （P<0.05， P<0.01）. ConclusionHLJD and its major active constituents （geniposide， baicalin， berberine） can inhibit LPS-induced inflammatory responses in BV2 cells. The combination of the three active constituents demonstrates the most potent anti-inflammatory effect， significantly attenuating M1-type polarization of BV2 cells via the HMGB1/TLR4/NF-κB signaling pathway.

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.

Currently,there are practical and technical difficulties in the construction of clinical ques-tions in the development of clinical practice guidelines.Clinicians or guideline developers seldom construct clin-ical questions based the actual case scenario,leading to some information loss between structured and actual clinical connotation.To overcome this challenge,we proposed a case-guided questions construction approach,and carried out case research and verification in the formulation of the guideline.We found that this method could more efficiently and scientifically assist the formulation of clinical questions,and provide reference for clinicians or guideline developers.

Currently, there are practical and technical difficulties in the construction of clinical questions in the development of clinical practice guidelines. Clinicians or guideline developers seldom construct clinical questions based the actual case scenario, leading to some information loss between structured and actual clinical connotation. To overcome this challenge, we proposed a case-guided questions construction approach, and carried out case research and verification in the formulation of the guideline. We found that this method could more efficiently and scientifically assist the formulation of clinical questions, and provide reference for clinicians or guideline developers.

The incidence of augmented renal clearance (ARC) in intensive care patients (ICU) is exceptionally high, and these patients are often co-morbid with infection. The occurrence of ARC will significantly increase the clearance rate of antibiotics, making it difficult for conventional doses to reach effective therapeutic concentrations and affect the patient's anti-infective treatment effect and prognosis. It can be seen that it is crucial to formulate a reasonable dosing regimen for ICU patients with ARC. Regrettably, few reports in China about the adjustment strategy of antibiotic dosing regimens for ARC patients. Therefore, this article reviews the domestic and foreign literature for reference to provide evidence for medical personnel to adjust the dose of antibacterial drugs for such patients.

Objective:To determine the clinical features of papillary thyroid microcarcinoma (PTMC) and the risk factors for central compartment lymph node (CCLN) metastasis in PTMC. Methods:Data of 1 401 patients with PTMC who were treated in Tianjin Medi-cal University Cancer Institute and Hospital between January 2014 and December 2014 were retrospectively analyzed. Chi-square test and multivariate Logistic regression analysis were used to study the risk factors. Results:With regard to clinicopathological features, the sex ratio is 1:3.4 in patients with PTMC. CCLN metastasis affected 427 (30.5%) of the total 1 401 patients. Age (χ2=14.587, P<0.01), sex (χ2=21.636, P<0.01), tumor multifocality (χ2=35.505, P<0.01), tumor size (χ2=58.868, P<0.01), tumor site (χ2=8.385, P<0.05), and extracapsular/extraglandular invasions (χ2=26.481, P<0.01) were significantly correlated with CCLN metastasis. For patients with a soli-tary primary tumor, tumor location in the lower third of the thyroid lobe was associated with a higher risk of CCLN metastasis (48.1%). The male gender, age<45 years, tumor size>6 mm, extracapsular spread, and tumor bilaterality were independently correlated with CCLN metastasis. Conclusion:A prophylactic neck dissection of the central compartment must be considered particularly in male PT-MC patients with age<45 years, tumor size>6 mm, extracapsular spread, and tumor bilaterality.

Objective To study the effects of percutaneous liver tumor injection combined with the clinical efficacy of transcatheter hepatic artery chemoembolization in the treatment of advanced liver cancer,and to provide ref-erence for clinical treatment.Methods 22 patients using percutaneous liver tumor injection combined with transcath-eter arterial chemoembolization for treatment were selected,with which 1 month follow-up after discharge.Situation of patients with percutaneous liver tumor injection and transcatheter hepatic artery chemoembolization was analyzed,and the changes of the patients in the following -up of survival time,tumor volume and clinical symptoms were also ana-lyzed.Results Among the patients of postoperative recheck after 6 weeks,6 cases were complete remission,there were partial remission in 8 cases,6 cases of stable,2 cases of progress.Follow up to 2013 December,the patients'sur-vival time was 17-82 months,the average survival time was (55.71 ±13.47)months.After treatment,4 cases of patients'tumor diameter reduced 1 -3cm,18 cases of tumor diameter reduced 3 -5cm,19 cases of liver area pain symptoms for more than half a year of remission,3 cases of liver area pain relief time less than half a year.During the follow -up period,12 patients died of multiple organ failure.Conclusion The development of percutaneous liver tumor injection combined with transcatheter hepatic arterial chemoembolization therapy can delay the development of the disease in patients with advanced HCC,and prolong the survival time.

Objective To evaluate the middle and short-term effects of integrative cognitive training on mild cognitive impairments(MCI).Methods All the participants with MCI aged over 70 years were selected from one sub-district of Putuo District,Shanghai and divided into cognitive intervention group (n=46) and control group (n=35).The integrative cognitive training was conducted in 24 sessions for 12 weeks.All subjects were assessed by Neuropsychological Test Battery for Elderly (NTBE) and by a questionnaire of Shanghai Health Survey for the Elderly (VER2006)at baseline,follow-up and one-year follow up phases.Results At baseline phase,semantic relations test in NTBE was better (t=2.13,P=0.037),verbal fluency test (vegetables) in NTBE was worse(t =-2.25,P=0.038) in intervention group than in control group,while there were no significant differences in scores of other neuropsychological tests between intervention group and control group(all P＞0.05).At follow up phase,16 subscales in reasoning test of NTBE were improved (t=-2.70,P=0.010)and 2 subscales were declined in cognitive intervention group(all P＜0.05).9 subscales in semantic relations test of NTBE (t=-2.27,P=0.013) were improved and 5 subscales were declined in control group (all P＜ 0.05).Comparison between groups at one year follow-up showed that 5 subscales in reasoning test of NTBE (F=16.80,P=0.000) were better in intervention group than in control group(all P＜0.05).General linear model (GLM) with repeated measures at three time points showed that 4 subscales in reasoning test of NTBE had a time-by group interaction (F=5.16,P=0.01).Conclusions Integrative cognitive training can improve cognitive function in patients with mild cognitive impairments,and the validity of reasoning ability can sustain one year.

Objective To evaluate clinical effects of integrated traditional Chinese and western medicine therapy for epilepsy after stroke. Methods Literatures about the treatment of epilepsy after stroke with the combination of traditional Chinese medicine and western medicine which come from the database such as CNKI, VIP, WanFang and Pubmed, were studied and all the randomized controlled trials on comparing therapeutic effects of treating epilepsy between combined treatment of TCM and western medicine and western medicine were enrolled. The Cochrane Collaboration's software RevMan 5 was used for meta-analysis. Results 7 articles were included in the study, there is homogeneity among these articles(P>0.05), The fixed effect model was used for the meta analysis. the combined results were OR=5.17, 95%CI(3.02, 8.82), the overall effect of test Z=6.01, P<0.01, the difference between the treatment group and the control groups was significant, that means the overall effect of the combination of traditional Chinese medicine and Western medicine treatment was better than western medicine treatment; Funnel plot graphic displayed asymmetrically, which indicated the literatures publication bias. Conclusion The current data indicate that the curative effect of TCM and west medicine combined treatment is better than pure western medicine therapy for epilepsy after stroke, but as the literature publication bias, clinical studies need more high quality large samples to prove this conclusion.