Recent studies have indicated that the expression of ubiquitin-specific protease 51 (USP51), a novel deubiquitinating enzyme (DUB) that mediates protein degradation as part of the ubiquitin‒proteasome system (UPS), is associated with tumor progression and therapeutic resistance in multiple malignancies. However, the underlying mechanisms and signaling networks involved in USP51-mediated regulation of malignant phenotypes remain largely unknown. The present study provides evidence of USP51's functions as the prominent DUB in chemoresistant triple-negative breast cancer (TNBC) cells. At the molecular level, ectopic expression of USP51 stabilized the 78 kDa Glucose-Regulated Protein (GRP78) protein through deubiquitination, thereby increasing its expression and localization on the cell surface. Furthermore, the upregulation of cell surface GRP78 increased the activity of ATP binding cassette subfamily B member 1 (ABCB1), the main efflux pump of doxorubicin (DOX), ultimately decreasing its accumulation in TNBC cells and promoting the development of drug resistance both in vitro and in vivo. Clinically, we found significant correlations among USP51, GRP78, and ABCB1 expression in TNBC patients with chemoresistance. Elevated USP51, GRP78, and ABCB1 levels were also strongly associated with a poor patient prognosis. Importantly, we revealed an alternative intervention for specific pharmacological targeting of USP51 for TNBC cell chemosensitization. In conclusion, these findings collectively indicate that the USP51/GRP78/ABCB1 network is a key contributor to the malignant progression and chemotherapeutic resistance of TNBC cells, underscoring the pivotal role of USP51 as a novel therapeutic target for cancer management.

Acetaminophen (APAP) is the primary cause of drug-induced acute liver failure. Ovarian tumor deubiquitinase 6A (OTUD6A), a recently discovered deubiquitinase of the OTU family, has been primarily studied in tumor contexts. However, its role in APAP-induced liver injury (AILI) remains unclear. Therefore, this study aimed to investigate the involvement of OTUD6A in the pathogenesis of AILI. Our findings demonstrated a substantial upregulation of OTUD6A in both the liver tissue and isolated hepatocytes of mice following APAP stimulation. OTUD6A knockout exacerbated APAP-induced inflammation, hepatocyte necrosis, and liver injury, whereas OTUD6A overexpression alleviated these pathologies. Mechanistically, OTUD6A directly interacted with the enhancer of zeste homolog 2 (EZH2) and selectively removed K48-linked polyubiquitin chains from EZH2, enhancing its stability. This resulted in increased protein levels of EZH2 and H3K27me3, as well as reduced endoplasmic reticulum (ER) stress and cell death in hepatocytes. Collectively, our research uncovers a novel role for OTUD6A in mitigating APAP-induced liver injury by promoting EZH2 stabilization.

Objective We aimed to observe the differences in the effects of different acupuncture technique on the endometrium of mice with simple endometrial hyperplasia model and to explore the potential mechanisms. Methods According to the random number tables,32 female C57BL/6J mice were divided into a blank control group,a model group,a quick needle group and a retaining needle group,with 8 mice in each group. A mouse model of simple endometrial hyperplasia was established using bilateral ovariectomy combined with estrogen loading. In the quick needle group,mice were punctured at the bilateral for "Yinbai"(SP1) points and withdrawn immediately,with the treatmeat performed once every other day for a total of 12 times. In the retaining needle group,mice were punctured at the bilateral "Yinbai"(SP1) points and the needles were retained for 15 min each time,with the treatment also performed once every other day for a total of 12 times. After the intervention,samples were collected. HE staining was used to observe morphological changes in the mouse uterine tissue;ELISA was used to detect serum estradiol level;flow cytometry was used to detect the ratio of M1 and M2 macrophages(M1/M2) and immunohistochemical method was used to measure the expression of CD86 and CD206 in uterine tissue;and Western blotting was used to detect the expression of interleukin-13 (IL-13) and interferon-γ(IFN-γ) in uterine tissue. Results The endometrium of mice in the model group showed simple hyperplasia. Compared with the blank control group,the endometrium of the model group was thickened (P<0.01);the level of estradiol in the serum was increased (P<0.01);M1/M2 in uterine tissues was decreased (P<0.01),the expression of CD86 was decreased (P<0.01),and the positive expression of CD206 was increased (P<0.01);and the level of IFN-γ protein expression in uterine tissues was decreased (P<0.01),and the expression of IL-13 protein was increased (P<0.01). Compared with the model group,the endometrial thicknesses of the quick needle group and the retaining needle group were reduced (P<0.05),the levels of estradiol in serum were reduced (P<0.05),M1/M2 in uterine tissues increased (P<0.01),and the reduction of CD206 positive expression,and IL-13 protein expression reduced (P<0.01);the level of CD86 positive expression,IFN-γ protein expression increased (P<0.01). Compared with the quick needle group,IL-13 protein expression increased in the retaining needle group (P<0.01).Conclusion Both quick needle and retaining needle may be through the regulation of the expression of IFN-γ and IL-13,thus prompting the polarization of macrophages from M2 to M1 type,inhibiting the pro-cell proliferative ability and tissue repair ability of M2 type macrophages,thus reducing the degree of endometrial hyperplasia,and the quick needle group was superior to the retaining needle group in regulating the expression of IL-13.

Objective:To evaluate the clinical efficacy of acupuncture in the treatment of anxiety state in patients with primary insomnia(PI). Methods:Randomized controlled trials of acupuncture treatment for PI patients with an anxiety state in Web of Science,Cochrane Library,PubMed,Excerpta Medica Database(EMBASE),China National Knowledge Infrastructure(CNKI),Wanfang Data Knowledge Service Platform(Wanfang),and Chongqing VIP Database(VIP)were retrieved by computer.The retrieval time was from each database's inception to December 30,2022.Data extraction and evaluation were performed for the included studies.The Cochrane risk of bias assessment tool was used to assess the risk of bias in each article.Meta-analysis of valid data was performed using the RevMan 5.4 software.If the outcome indicator was a categorical variable,relative risk(RR)was used as the effect size.If it was a continuous variable,mean difference(MD)was used to calculate the effect size.Each effect size was expressed as a 95%confidence interval(CI).P<0.05 was considered to indicate a statistically significant difference. Results:A total of 18 studies were included,comprising a total of 1198 patients.The findings of the meta-analysis showed that electroacupuncture had a significant advantage in improving the Hamilton anxiety scale(HAMA)score than benzodiazepines[MD=-1.61,95%CI(-2.17,-1.06),P<0.001].Acupuncture was superior to sham acupuncture[MD=-14.90,95%CI(-20.39,-9.41),P<0.001]and benzodiazepines[MD=-3.39,95%CI(-4.67,-2.12),P<0.001]in reducing the self-rating anxiety scale(SAS)score.Acupuncture was superior to sham acupuncture in reducing the insomnia severity index(ISI)score[MD=-5.61,95%CI(-6.63,-4.89),P<0.001].Acupuncture was superior to benzodiazepines[MD=0.84,95%CI(-1.42,-0.25),P=0.005]and sham acupuncture[MD=-8.39,95%CI(-8.39,-7.86),P<0.001]in improving the Pittsburgh sleep quality index(PSQI)score.Acupuncture had a better effective rate than benzodiazepines[RR=1.16,95%CI(1.08,1.25),P<0.001]and sham acupuncture[RR=8.94,95%CI(4.63,17.25),P<0.001]in treating PI. Conclusion:Acupuncture or electroacupuncture has certain therapeutic advantages over benzodiazepines and sham acupuncture in the treatment of anxiety in PI patients.However,more high-quality randomized controlled trials are needed for further verification.

This study was aimed at comparing performance differences among three metagenomic sequencing platforms,MGISEQ-2000,Illumina NextSeq 2000,and Ion GeneStudio S5 Plus,to optimize the sequencing process for trace samples.The three sequencing platforms were used to perform high-throughput sequencing on DNA standards and simulated samples.Through analysis of the quality of raw data and microbial detection capabilities,systematic differences among platforms were compared.The sequencing results were optimized for trace samples by incorporation of exogenous nucleic acids during the li-brary preparation process.In terms of data output per batch and base quality,MGISEQ-2000 surpassed the other two plat-forms.Illumina NextSeq 2000 had the lowest proportion of duplicate reads,whereas Ion GeneStudio S5 Plus had the highest proportion,and significant differences were observed across platforms(P＜0.001).In sequencing uniformity,MGISEQ-2000 and Illumina NextSeq 2000 were superior to Ion GeneStudio S5 Plus.MGISEQ-2000 provided a substantial advantage in microbial detection capability(P＜0.001),but the advantage diminished with decreasing bacterial fluid concentration.Ion GeneStudio S5 Plus had the shortest duration for single-batch sequencing.Moreo-ver,for trace samples with DNA content ≤0.05 ng,the experi-mental group(with added exogenous nucleic acids)achieved a higher number of reads than the control group(without exogenous nucleic acids),with a 11.09±8.03 fold increase.In conclu-sion,the different sequencing platforms each had advantages and disadvantages,thus allowing researchers to choose the appro-priate platform according to specific needs.Furthermore,the addition of exogenous nucleic acids improved the microorganism detection efficiency,and provided better support for subsequent diagnosis and evaluation of results.

Objective:To explore the clinical correlation and prognostic value of the Albumin-Bilirubin(ALBI)score in children with secondary hemophagocytic syndrome(sHLH).Methods:A retrospective analysis was conducted on the data of children's sHLH cases clearly diagnosed in the Affiliated Hospital of Zunyi Medical University from January 2012 to March 2023.Survival analysis was conducted according to the ALBI classification.Spearman correlation analysis was conducted between the ALBI score and clinical indicators.The Receiver Operating Characteristic(ROC)curve was used to evaluate the ALBI score,select the best cutoff value,and evaluate the accuracy of prognostic prediction value.Kaplan-Meier method was used to draw the survival curve.Log-rank method was used to compare the differences of survival curve between groups.Cox regression was used for prognostic analysis and restricted cubic spline curves used to calculate the relationship between ALBI scores and the risk of death in children with sHLH.Results:A total of 128 children with sHLH were included in this study,with a median age of 38(13.25,84)months.There were 70 males(54.69％)and 58 females(45.31％).The survival analysis results of ALBI grading showed that the survival rate of HLH patients with ALBI grade 3 was significantly lower than those with ALBI grades 1 and 2.Spearman correlation analysis results showed that ALBI score was positively correlated with splenomegaly,respiratory failure,disseminated intravascular coagulation(DIC),pulmonary hemorrhage,gastrointestinal hemorrhage,central nervous system involvement,ALT,AST,TG,LDH,PT,APTT,and SF(the correlation coefficients are:r=0.181,0.362,0.332,0.221,0.351,0.347,0.391,0.563,0.180,0.448,0.483,0.37,0.356),and was negatively correlated with HB,PLT,and FIB(the correlation coefficients are:r=-0.321,-0.316,-0.423),but was not significantly correlated with EBV infection,fungal infection,hepatomegaly,and ANC(P＞0.05).Using the ROC curve,the cutoff value of ALBI was-1.76.Single factor Cox regression analysis results showed that HB＜90 g/L,ALT ≥ 80 U/L,AST≥200 U/L,LDH ≥1 000 U/L,PT ≥20 s,APTT≥40 s,FIB＜1.5 g/L,ALBI ≥-1.76,combined pulmonary hemorrhage,DIC,central nervous system involvement,gastrointestinal bleeding,and not using blood purification may be the prognostic risk factors for children with sHLH(P＜0.05).Multivariate Cox regression results showed that FIB＜1.5 g/L(HR=2.119,95％CI:1.028-4.368),ALBI≥-1.76(HR=2.452,95％CI:1.233-4.875),and central nervous system involvement(HR=4.674,95％CI:2.486-8.789)were independent risk factors affecting prognosis,while blood purification(HR=0.306,95％CI:0.153-0.612)was an independent protective factor for prognosis.The application of restricted cubic splines shows that the risk of death increases with the increase of ALBI score.The area under the ROC curve(AUC)of the ALBI score for predicting the risk of 1-week,2-week,4-week,and overall mortality were 0.825,0.807,0.700,and 0.693,respectively,indicating good predictive performance for early mortality risk.According to subgroup analysis results of clinical manifestations,compared with the ALBI＜-1.76 group,ALBI≥-1.76 was associated with age ≤2 years,EBV infection,HLH-1994/2004 treatment,concomitant respiratory failure,and ANC≤1.0 × 109/L,HB＜90 g/L,PLT＜100 × 109/L,TG≥3.0 mmol/L,LDH ≥ 1 000 U/L,APTT≥40 s,and FIB＜1.5 g/L(P＜0.05).Conclusion:The ALBI score is related to the clinical characteristics and laboratory indicators of sHLH,and can be used as a beneficial indicator for assessing the prognostic risk of sHLH in children.It has good accuracy and clinical application value in predicting the prognosis of sHLH in children.

Objective: To understand the distribution of tobacco retailer within 100 meters outside middle schools in Wuhan City and its impact on smoking behavior of middle school students, so as to provide basis and feasible suggestions for the development of tobacco control policy for adolescents. Methods: From February to May 2023, a multi stage stratified cluster random sampling method was used to select 20 middle schools from 4 districts in Wuhan City. To investigate the distribution of tobacco retailer within 100 metres outside the school and the sale of tobacco to minors. A total of 4 882 students were surveyed using the core questions of the 2021 Chinese Adolescent Tobacco Prevalence Questionnaire. Fisher exact probability test, Chi square test and Chi square trend test were used for statistical analysis. Results: Nearly 70.00% of middle schools had tobacco retailer within 100 metres, with an average of (1.10±0.97) per middle school. The awareness rate (100.00%) and labeling rate (87.50%) of licensed tobacco retailer were higher than those of non licensed tobacco retailer (33.33%, 16.67%) ( P <0.05). The rates of tried smoking, current smoking and buying cigarettes within 30 days were 7.13%, 1.99% and 2.54%, respectively. The rates of students who tried smoking ( 8.58 %), current smoking (2.29%) and buying cigarettes within 30 days (2.85%) in schools with tobacco retailer within 100 metres were higher than those in schools without tobacco retailer (3.79%, 1.28%, 1.83%)( χ 2=35.80, 5.37, 4.37 , P <0.05). And as the grade increased, the rates of tried smoking, current smoking and buying cigarettes among middle school students all showed an upward trend ( χ 2 trend =66.20, 36.10, 16.17, P <0.05). Conclusions Middle school students in Wuhan City have high tobacco availability. The findings suggest that school ban should be extended from 50 meters to 100 meters, and the regulatory authorities must strictly prohibit selling tobacco products to minors at tobacco retailer.

Dynamic tracking analysis of monoclonal antibodies (mAbs) biotransformation in vivo is crucial, as certain modifications could inactivate the protein and reduce drug efficacy. However, a particular challenge (i.e. immune recognition deficiencies) in biotransformation studies may arise when modifications occur at the paratope recognized by the antigen. To address this limitation, a multi-epitope affinity technology utilizing the metal organic framework (MOF)@Au@peptide@aptamer composite material was proposed and developed by simultaneously immobilizing complementarity determining region (CDR) mimotope peptide (HH24) and non-CDR mimotope aptamer (CH1S-6T) onto the surface of MOF@Au nanocomposite. Comparative studies demonstrated that MOF@Au@peptide@aptamer exhibited significantly enhanced enrichment capabilities for trastuzumab variants in comparison to mono-epitope affinity technology. Moreover, the higher deamidation ratio for LC-Asn-30 and isomerization ratio for HC-Asn-55 can only be monitored by the novel bioanalytical platform based on MOF@Au@peptide@aptamer and liquid chromatography-quadrupole time of flight-mass spectrometry (LC-QTOF-MS). Therefore, multi-epitope affinity technology could effectively overcome the biases of traditional affinity materials for key sites modification analysis of mAb. Particularly, the novel bioanalytical platform can be successfully used for the tracking analysis of trastuzumab modifications in different biological fluids. Compared to the spiked phosphate buffer (PB) model, faster modification trends were monitored in the spiked serum and patients' sera due to the catalytic effect of plasma proteins and relevant proteases. Differences in peptide modification levels of trastuzumab in patients' sera were also monitored. In summary, the novel bioanalytical platform based on the multi-epitope affinity technology holds great potentials for in vivo biotransformation analysis of mAb, contributing to improved understanding and paving the way for future research and clinical applications.

Objective: To observe the immediate effect of small-angle Tui-Pushing and An-Pressing anti-rotation bone-setting manipulation in improving the correction of braces for adolescent idiopathic scoliosis. Methods: A total of 50 cases of adolescent idiopathic scoliosis were selected and given brace correction first. The whole spine anteroposterior and lateral radiographs were taken, the Cobb angle was measured, and the visual analog scale (VAS) score of pain caused by brace wearing was recorded. After removal of the brace, small-angle Tui-Pushing and An-Pressing anti-rotation bone-setting manipulation was performed once. After treatment, the same brace was put on again to take a whole spine anteroposterior radiograph, the Cobb angle was measured, and the VAS score was recorded. The changes in Cobb angle and VAS score after manipulation were compared, and the immediate efficacy was evaluated. Results: After the manipulation, the Cobb angle was significantly smaller than that before treatment (P<0.01) and the VAS score was significantly lower than that before treatment (P<0.01). Conclusion: Small-angle Tui-Pushing and An-Pressing anti-rotation bone-setting manipulation can improve the immediate efficacy of brace in treating adolescent idiopathic scoliosis and relieve the pain caused by brace wearing at the same time.