[Objective] To explore the predictive value of HALP score for prognosis in patients with multiple myeloma (MM). [Methods] A retrospective analysis was conducted on laboratory indicators and related clinical data of newly diagnosed multiple myeloma (NDMM) patients, treated at the Affiliated Hospital of North Sichuan Medical College from January 2016 to October 2023, prior to their first treatment. The HALP score was calculated, and the optimal cutoff value for HALP was determined using X-tile software. Survival analysis was performed using Kaplan-Meier curves for high HALP and low HALP groups. Univariate and multivariate analyses were conducted using the Cox regression model, and a forest plot was generated using Graphpad Prism to illustrate factors that may impact patient prognosis. The predictive ability of HALP score combined with β2-microglobulin and ECOG score for prognosis in MM patients was evaluated using receiver operating characteristic curve (ROC) analysis. [Results] A total of 203 MM patients were included, with the optimal cutoff value for HALP score being 29.15 (P<0.05). Among them, 101 patients were in the low HALP score group, and 102 patients were in the high HALP score group. The results of univariate and multivariate analysis using the Cox regression model showed that a HALP score <29.15 was an independent risk factor for progression-free survival (PFS) and overall survival (OS) (P<0.05). ROC curve analysis indicated that the combination of HALP score with β2-microglobulin and ECOG score had a higher predictive value for prognosis in MM patients compared to using HALP score alone. [Conclusion] The HALP score is closely related to the prognosis of patients with NDMM. A low HALP score indicates a poorer prognosis, while the combination of HALP score with β2-microglobulin and ECOG score provides a higher predictive value when assessed together.

OBJECTIVE: To observe the efficacy and safety of 21-day venetoclax (VEN) plus azacitidine (AZA) (21-day VA) in newly diagnosed unfit acute myeloid leukemia (AML) patients in the real-world. METHODS: The clinical data of patients with unfit-AML who received 21-day VA regimen from December 2020 to July 2024 in our center and completed at least 1 cycle of therapeutic effect assessment was retrospectively collected to analyze the safety, efficacy and its influencing factors. RESULTS: A total of 59 patients were enrolled in our study, with a median age of 67(48-87) years old. After 1 cycle of therapy, the composite complete remission (cCR) rate was 74.5%, 54.2% of cases were negative for minimal residual disease (MRD). Among them, the MRD negative rate of patients with NPM1 mutation was significantly higher than that of patients without NPM1 mutation ( P =0.032). The median follow-up of patients was 19(2-38) months, the best cCR and MRD negative rates were 78% and 64.4%, respectively, the median overall survival (OS) time was 12 months, and the median progression free survival (PFS) time was 5 months. Multivariate Cox regression analysis showed less than 4 cycles of VA chemotherapy were independent risk factor for PFS and OS ( P < 0.05). After achieving remission, anemia and thrombocytopenia improved with the increase of the number of chemotherapy cycle. CONCLUSION In real-world, 21-day VA regimen still shows significant efficacy in the treatment of newly diagnosed unfit-AML, without adversely affecting remission rate and MRD negative rate of the first cycle.
Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Aged ; Middle Aged ; Bridged Bicyclo Compounds, Heterocyclic/therapeutic use* ; Sulfonamides/therapeutic use* ; Azacitidine/therapeutic use* ; Aged, 80 and over ; Male ; Female ; Retrospective Studies ; Nucleophosmin ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Remission Induction ; Mutation ; Treatment Outcome

OBJECTIVE To observe the short-term efficacy and safety of venetoclax combined with homoharringtonine and cytarabine in the treatment of acute myeloid leukemia （AML）. METHODS The data of 40 newly diagnosed AML patients admitted to our hospital from October 2022 to November 2023 were retrospectively collected and divided into observation group and control group according to treatment plan， with 20 cases in each group. The patients in the control group were given Daunorubicin hydrochloride for injection+Cytarabine for injection， and the patients in the observation group were given Venetoclax tablets+ Homoharringtonine injection+Cytarabine for injection. The patients in both groups were given relevant medicine， with 28 days as one cycle. The short-term efficacy， negative rate of minimal residual disease （MRD）， duration of granulocyte deficiency， duration of platelet （PLT） ＜20×109 L－1， transfusion volume of suspended red blood cells and platelet， and the occurrence of adverse drug reactions were evaluated in both groups after 1 cycle of induction chemotherapy. RESULTS The complete remission or complete remission with incomplete hematologic recovery （CR/CRi） rate in the observation group was significantly higher than control group （P＜0.05）， and the negative rate of MRD in the observation group was also significantly higher than control group （P＜0.05）. However， in low-， medium- and high-risk patients， there was no statistical significance in CR/CRi rates between the two groups （P＞0.05）. There were no significant differences in the duration of agranulocytosis， the duration of PLT ＜20×109 L－1， the amount of suspended red blood cell transfusion， the amount of platelet transfusion， the incidence of hematologic toxicity and the incidence of non-hematologic toxicity between 2 groups （P＞0.05）. CONCLUSIONS Venetoclax combined with homoharringtonine and cytarabine show good short-term efficacy and safety in the treatment of AML.

[Objective]To explore how hyperthyroidism induces ventricular remodeling via activating β-catenin/FoxO1 in rat cardiomyocytes.[Methods]Hyperthyroidism-induced ventricular remodeling rat models were established by intraperitoneal injection of levothyroxine(T4)at 0.1 mg/kg for 30 days.β-catenin inhibitor MSAB(14 mg/kg)was admin-istrated for 30 days.We used western blot to detect the expression of myocardial hypertrophy marker ANP,β-catenin and FoxO1;immunofluorescence to examine the expression and intracellular distribution of β-catenin and FoxO1.Hyperthy-roidism-induced cardiomyocyte hypertrophy rat models were established by treatment of triiodothyronine(T3)into cul-tured primary neonatal rat cardiomyocytes for 24 hours.β-catenin siRNA(30 nmol/L)was used to down-regulate β-catenin expression in cardiomyocytes.Western blot and immunofluorescence were used to analyze the effects of β-catenin inhibition on the hyperthyroidism-induced cardiomyocyte hypertrophy.[Results]Following Wnt/β-catenin activation,β-catenin was found increased nuclear expression,to bind to the nuclear transcriptional factors and regulate the gene ex-pression.β-catenin nuclear expression was significantly increased in the hyperthyroidism-induced ventricular remodeling rats,but no change was found in the expression of typical transcriptional factor TCF7l2.Our results revealed that inhibiting β-catenin by MSAB attenuated the hyperthyroidism-induced rat ventricular remodeling.Further analysis indicated that β-catenin/FoxO1 expression was significantly increased in hyperthyroidism-induced myocardial hypertrophy which could be attenuated by suppressing β-catenin/FoxO1 in cardiomyocytes.[Conclusions]β-catenin/FoxO1 is activated in hyperthy-roidism-induced myocardial hypertrophy and β-catenin/FoxO1 inhibition attenuates hyperthyroidism-induced cardiomyo-cyte hypertrophy.

Objective To investigate the prognostic evaluation value of the HALP score composed of hemoglobin,albumin,lymphocytes and platelets before chemotherapy in the patients with diffuse large B-cell lymphoma(DLBCL).Methods The clinical data and laboratory indicators before chemotherapy in the pa-tients with DLBCL newly diagnosed in this hospital from January 2015 to October 2022 were retrospectively analyzed.The optimal cut-off value of HALP was calculated by X-tile software.The patients were grouped ac-cording to the optimal cutoff value,the Chi-square test was used to analyze the difference in the constituent ra-tio of clinical characteristics among different HALP score groups,the survival curves of the progression-free survival(PFS)time and overall survival(OS)time among the groups with different scores were drawn by u-sing the Kaplan-Meier method,the Cox univariate and multivariate analysis regression model was adopted to analyze the prognostic influencing factors in DLBCL patients,and the predictive ability of HALP score for PFS time and OS time in DLBCL patients was evaluated by using the receiver operating characteristic(ROC)curve.Results A total of 132 patients with DLBCL were included,the optimal cutoff value of HALP score was 21.23 points.There were 54 cases in the low HALP score group and 78 cases in the high HALP score group.The low HALP score group was correlated with the later clinical stage,higher IPI and NCCN-IPI scores,higher LDH level and lower overall response rate(ORR)(P＜0.05).Compared to the high HALP score group,the PFS time and OS time in the low HALP score group were shorter(P＜0.05).The Cox uni-variate and multivariate regression model analysis results indicated that the HALP score≤21.23 points was an independent risk factor affecting the PFS time(HR=1.811,P=0.031).The ROC curve results suggested that the combination of HALP score combined with IPI score or NCCN-IPI score had higher predictive value for PFS time and OS time in DLBCL patients compared to use IPI or NCCN-IPI alone.Conclusion The HALP score is correlated with the prognosis of DLBCL patients,and could early identify the high-risk DLBCL patients with poor prognosis.The HALP score,IPI score and NCCN-IPI score combined evaluation has higher predictive value.

Prior to clinical application,reliability of percutaneous ventricular assist devices(pVAD)requires to be tested systematically.Currently,there's a lack of dedicated reliability testing equipment and methodologies for pVAD.Considering the structural and functional aspects of percutaneous ventricular assist devices,this study conducts research on pVAD reliability test engineering.Test setups,clinical conditions,failure modes,effects analysis,and evaluation models have been investigated.A highly feasible methodological approach for percutaneous ventricular assist device reliability assessment has been formed.This study offers valuable insights into standardizing their reliability evaluation in clinical settings.

Objective To analyze the correlation between the multiple evaluation indicators in the early stage and the cure time(needed time from treatment to cure)of the patients with facial neuritis treated by ac-upuncture combined with medication,and to optimize the subjective and objective indicators enable predicting the cure time of facial neuritis in early stage.Methods All patients were treated by acupuncture and medica-tion combination.The research subjects were 64 patients with facial neuritis from the outpatient of cupuncture and moxibustion department of this hospital.The correlation between the grade of facial nerve paralysis,sur-face electromyography related data,scores of self-made symptom scoring scale,Sunnybrook Facial Grading System(SFGS)score,Facial Disability Index-Physical(FDIP)score,Facial Disability Index-Social(FDIS)score on 7 d of onset with the cure time was analyzed.Results The cure time was positively correlated with the grade of facial nerve paralysis and FDIS score on 7 d of onset(P＜0.01),amd negatively correlated with the scores of self-made symptom scoring scale,FDIP score,SFGS score and the affected side to healthy ratio of CMAP amplitude of buccal temporal branch of facial nerve(P＜0.01 or P＜0.05);the cure time had no sig-nificant correlation with the ratio of affected side and healthy side of CMAP amplitude in zygomatic branch of facial nerve,the ratio of affected side and healthy side of CMAP latent period of temporal branch,buccal branch and zygomatic branch of facial nerve and F wave output rate(P＞0.05).Conclusion In the early stage subjective indicators of the acupuncture combined with medication for treating facial neuritis,grade of facial nerve paralysis,self-made symptom scoring scale,scores of self-made symptom scoring scale,FDIP and FDIS scores and the ratio of affected side to healthy side of CMAP amplitude of the buccal branch,temporal branch of the facial nerve in sEMG in the objective indicators could be used to predict the cure time,better guide the treatment and have more effective and accurate comunication with the patients.

Objective To investigate the mechanism of action of the long non-coding RNA(lncRNA)taurine up-regulating factor 1(TUG1)with high glucose(HG)-induced cellular pyroptosisin microglial cell.Methods Mouse BV2 cells were cultured and divided into normal control(NC),HG,lentiviral empty vector(sh-Con),TUG1 lentiviral gene silencing vector(sh-TUG1),HG+sh-Con and HG+sh-TUG1 group.RT-PCR was used to detect the expression and transfection efficiency of TUG1 mRNA.Nucleotide-binding oligomerized structural domain-like receptor protein 3(NLRP3),cysteoaspartate protease-1(Caspase-1),and ghrelin D(GSDMD),IL-18,IL-1β mRNA and protein expression were detected by RT-PCR and Western blot.Results TUG1 mRNA expression was higher in HG group than in NC group(P＜0.05).After transfection,a lot of green fluorescence appeared in sh-TUG1 and sh-Con group,while no green fluorescence was observed in NC group.The expression of TUG1 mRNA was lower in sh-TUG1 group than in NC group(P＜0.05).Accordingly,the recombinant lentivirus successfully infected BV2 cell.The expressions of the mRNA and protein of NLRP3,Caspase-1,GSDMD,IL-18 and L-1β were higher in HG,HG+sh-Con groups than in NC group(P＜0.05).The expressions of the mRNA and protein of NLRP3,Caspase-1,GSDMD and IL-18 and L-1β were lower in HG+shTUG1 group than in HG,HG+sh-Con groups(P＜0.05).Conclusions TUG1 is involved in high glucose induced pyroptosis in microglia and leads to inflammatory response.Silencing TUG1 can inhibit the pathological reaction.

The hyperacute stage of myocardial infarction refers to a period of time within 30 minutes after the occurrence of myocardial infarction, when the symptoms are not obvious and the diagnosis is difficult, and the related pathophysiological mechanism has received less attention. In this study, proteomics was used to investigate the pathological changes in the early hyperacute phase of myocardial infarction, aiming to provide experimental evidence for pathological mechanism of myocardial infarction hyperacute stage. Meanwhile, the intervention effect and related mechanism of salvianolate injection were discussed based on heat shock protein B6 (HSPB6), aiming to benefit the clinical rational use of salvianolate injection. The protein expression changes before and after myocardial infarction model establishment were detected by label-free proteomics via mass spectrometry and analyzed by bioinformatics method. Then the binding effect of salvianolate injection on the commonly differential protein HSPB6 was evaluated by molecular docking technology, which was finally verified by animal experiments. All animal experimental protocols were approved by the Ethics Committee of Xiyuan Hosptial (2022XLC041). The results of this study showed that a total of 2 166 proteins were quantified by lable-free proteomics, of which 194 shared differential proteins were involved in myocardial injury and body regulation in the hyperacute phase of myocardial infarction, mainly involving molecular functions such as protein homodimerization activity, oxygen binding and transport, and serine endopeptidase inhibitor activity. Among them, HSPB6 protein is involved in the regulation of myocardial function. Molecular docking results indicated that magnesium salvianolate acetate, which is the main component of salvianolate injection, had the lowest binding energy with HSPB6 protein: -14.53 kcal·mol^-1. Animal experiments showed that compared with the Sham group, the model group had significantly lower ejection fraction (EF) and fractional shortening (FS) (P < 0.001), cardiac blood perfusion decreased significantly (P < 0.001). There were obvious pathological changes such as myocardial fiber disorder, cardiomyocyte edema and interstitial small blood vessel congestion; the injury of cardiac function of rats in the administration group was attenuated, and the FS of rats in the low-dose group was significantly improved (P < 0.05), the pathological injury of myocardial tissue was markedly mitigated, and the expression of HSPB6 protein was up-regulated to varying degrees (P < 0.01, P < 0.001). In conclusion, salvianolate injection could be able to improve the cardiac function and pathological morphology of rats in the early hyperacute stage of myocardial infarction, and its mechanism may be related to the promotion of expression of HSPB6.

Humans ; COVID-19 ; Pandemics ; SARS-CoV-2 ; Anxiety ; Brain ; Depression