[Elesclomol-Cu Induces Cuproptosis in Human Acute Myeloid Leukemia Cells].

OBJECTIVE: To investigate the effects of elesclomol-Cu (ES-Cu) on the proliferation and cuproptosis of human acute myeloid leukemia (AML) cells. METHODS: The effects of ES-Cu on the proliferation of AML cells and the AML cells pre-treated with ammonium tetrathiomolybdate (TTM) were examined by CCK-8 assay. The Calcein/PI kit was used to detected the changes in activity and cytotoxicity of AML cells induced by ES-Cu. Flow cytometry and Cytation3 fully automated cell imaging multifunctional detection system were used to analyze DCFH-DA fluorescence intensity, so as to determine the level of reactive oxygen species (ROS). The GSH and GSSG detection kits were used to measure the intracellular GSH content. Western blot was used to detected the expression of cuproptosis-related proteins ATP7B, FDX1, DLAT and DPYD. RESULTS: ES-Cu inhibited the proliferation of Kasumi-1 and HL-60 cells in a concentration-dependent manner (r Kasumi-1=-0.99， r HL-60=-0.98). As the concentration of ES-Cu increased, the level of intracellular ROS also increased (P <0.01-0.001). TTM could significantly reverse the inhibitory effect of ES-Cu on cell proliferation and its promoting effect on ROS. With the increase of ES-Cu concentration, the content of GSH was decreased (r =-0.98), and Western blot showed that the protein expressions of ATP7B, FDX1, DLAT and DPYD were significantly reduced (P <0.05). CONCLUSION: ES-Cu can induce cuproptosis in AML cells, which provides a new idea for the treatment of AML.

Design and evaluate the performance of a mechanical system for the release of Harmonia axyridis adults.

Harmonia axyridis (H. axyridis) is the natural enemy of many aphid species. Traditional manual release of H. axyridis adults requires substantial manpower, and release efficiency is low. Automatic mechanical devices can improve the efficiency of delivery. Based on H. axyridis adults' morphological size, a prototype release system for H. axyridis was designed, which considered the adhesion characteristics of H. axyridis adults. According to the measured physical characteristics of H. axyridis adults, the structural parameters of the mechanical system for the release of the H. axyridis adults were determined. The relationship of the quantity of release, the impeller rotating speed, and the time for the release of H. axyridis adults were constructed. The mechanism can quantitatively adjust the number of H. axyridis adults to meet a certain H. axyridis-aphids ratio. Combining the image processing technology with the camera function of a mobile phone, the maximum cross-sectional area method was used to count the H. axyridis adults in the designated area. Results showed that the impeller rotating speed had a significant effect on the survival rate of the H. axyridis adults. When the airflow velocities were 29.5 m/s and 38.3 m/s, the survival rates of the H. axyridis adults were 93.8% and 94.5% at 4.2 rpm. The adhesion rate of the H. axyridis adults was 2.5%-4.6%. This work will provide technical support for the research of biological control.

The association between sarcopenia and incident of depressive symptoms: a prospective cohort study.

BACKGROUND: Epidemiological studies have shown that sarcopenia was associated with depression among older adults. However, most of these investigations used a cross-sectional design, limiting the ability to establish a causal relation, the present study examined whether sarcopenia was associated with incident depressive symptoms. METHODS: This is a prospective cohort study with participants from the Western China Health and Aging Trends (WCHAT) study. Participants could complete anthropometric measurements and questionnaires were included. The exposure was sarcopenia, defined according to the Asian Working Group for Sarcopenia in 2019, the outcome was depressive symptoms, evaluated by GDS-15. We excluded depression and depressive symptoms at baseline and calculated the risk of incident depressive symptoms during the follow-up year. RESULTS: A total of 2612 participants (mean age of 62.14 ± 8.08 years) were included, of which 493 with sarcopenia. 78 (15.82%) participants with sarcopenia had onset depressive symptoms within the next year. After multivariable adjustment, sarcopenia increased the risk of depressive symptoms (RR = 1.651, 95%CI = 1.087-2.507, P = 0.0187) in overall participants. Such relationship still exists in gender and sarcopenia severity subgroups. Low muscle mass increased the risk of depressive symptoms (RR = 1.600, 95%CI = 1.150-2.228, P = 0.0053), but low muscle strength had no effect (RR = 1.250, 95%CI = 0.946-1.653, P = 0.117). CONCLUSIONS: Sarcopenia is an independent risk factor for depressive symptoms, Precautions to early detect and targeted intervene for sarcopenia should continue to be employed in adult with sarcopenia to achieve early prevention for depression and reduce the incidence of adverse clinical outcomes.

Association between the triglyceride glucose index and low skeletal muscle mass: a cross-sectional study.

OBJECTIVES: Triglyceride glucose (TyG) represents a consistent surrogate biomarker and index of insulin resistance (IR), IR has also been linked to skeletal muscle mass loss (SMM-L). Here, we evaluated the association between SMM-L and the TyG index (TyGi). DESIGN: An analytical cross-sectional study. SETTING: Tertiary care hospitals. PARTICIPANTS: 36 275 participants who underwent health checks between 1 January 2013 and 31 December 2020. PRIMARY AND SECONDARY OUTCOME MEASURES: A bioelectrical impedance analysis was used to assess the body composition, SMM-L was defined as low ASMI (total limb lean mass/height2) and TyGi was calculated as ln(triglycerides (mg/dL)×fasting blood glucose (mg/dL)/2). RESULTS: A total of 36 275 subjects were included in the study, of which 58.46% were male, with a mean age of 43.74±12.33 years. The prevalence of low skeletal muscle mass (SMM) was 17.7% and the mean TyGi was 8.56±0.64. TyGi was found to be significantly correlated with low SMM in all subjects (OR 1.87, 95% CI 1.75 to 2.00, p<0.001), with higher correlations seen in younger subjects (OR 1.97, 95% CI 1.77 to 2.20, p<0.001), and remaining significant in middle age (OR 1.95, 95% CI 1.77 to 2.14, p<0.001), old age (OR 1.73, 95% CI 1.38 to 1.16, p<0.001), men (OR 1.60, 95% CI 1.46 to 1.76, p<0.001) and women (OR 2.59, 95% CI 2.39 to 2.87, p<0.001). CONCLUSIONS: These data demonstrated a significant independent interaction between TyGi and low SMM in all subjects regardless of sex and age subgroups in the general population.

Efficacy of ginseng-based Renshenguben oral solution for cancer-related fatigue among patients with advanced-stage hepatocellular carcinoma: A prospective multicenter cohort study.

BACKGROUND: Cancer-related fatigue (CRF) is a common and debilitating symptom experienced by patients with advanced-stage cancer, especially those undergoing antitumor therapy. This study aimed to evaluate the efficacy and safety of Renshenguben (RSGB) oral solution, a ginseng-based traditional Chinese medicine, in alleviating CRF in patients with advanced hepatocellular carcinoma (HCC) receiving antitumor treatment. METHODS: In this prospective, open-label, controlled, multicenter study, patients with advanced HCC at BCLC stage C and a brief fatigue inventory (BFI) score of ≥ 4 were enrolled. Participants were assigned to the RSGB group (RSGB, 10 mL twice daily) or the control group (with supportive care). Primary and secondary endpoints were the change in multidimensional fatigue inventory (MFI) score, and BFI and functional assessment of cancer therapy-hepatobiliary (FACT-Hep) scores at weeks 4 and 8 after enrollment. Adverse events (AEs) and toxicities were assessed. RESULTS: A total of 409 participants were enrolled, with 206 assigned to the RSGB group. At week 4, there was a trend towards improvement, but the differences were not statistically significant. At week 8, the RSGB group exhibited a significantly lower MFI score (P < 0.05) compared to the control group, indicating improved fatigue levels. Additionally, the RSGB group showed significantly greater decrease in BFI and FACT-Hep scores at week 8 (P < 0.05). Subgroup analyses among patients receiving various antitumor treatments showed similar results. Multivariate linear regression analyses revealed that the RSGB group experienced a significantly substantial decrease in MFI, BFI, and FACT-Hep scores at week 8. No serious drug-related AEs or toxicities were observed. CONCLUSIONS: RSGB oral solution effectively reduced CRF in patients with advanced HCC undergoing antitumor therapy over an eight-week period, with no discernible toxicities. These findings support the potential of RSGB oral solution as an adjunctive treatment for managing CRF in this patient population.

Effect of follicle-stimulating hormone and luteinizing hormone on apoptosis, autophagy, and the release and reception of some steroid hormones in yak granulosa cells through miR-23a/ASK1 axis.

Follicle-stimulating hormone (FSH), luteinizing hormone (LH), miR-23a, apoptosis signal-regulating kinase 1(ASK1)/c-Jun N-terminal kinase (JNK), autophagy and apoptosis play crucial roles in follicular development. However, their role in yak granulosa cells (GCs) remains unknown. Therefore, we examined the effect of miR-23a, ASK1, FSH, and LH on apoptosis, autophagy, and the release and reception of some steroid hormones in these cells. Our results showed that miR-23a overexpression significantly increased the abundance of Beclin1, the LC3II/I ratio, and the number of Ad-mRFP-GFP-LC3-labeled autophagosomes, and decreased p62 abundance. Additionally, Bax abundance and the number of terminal deoxynucleotidyl transferase deoxynucleotide triphosphate nick end labeling-positive cells were reduced, while Bcl2 expression was increased. Overexpression of miR-23a also significantly increased the abundance of estradiol receptor α (ER-α) and ß (ER-ß) and the concentrations of estradiol (E2), progesterone (P4) in yak GCs. Here, treating yak GCs with miR-23a decreased ASK1 expression, which regulates ASK1/JNK-mediated apoptosis, autophagy, E2 and P4 levels, and ER-α/ß abundance. In contrast, treatment of yak GCs with FSH (10 µg/mL) and LH (100 µg/mL) increased miR-23a abundance, regulating the subsequent effect on ASK1/JNK-mediated apoptosis, autophagy, ER-α/ß abundance, and E2 and P4 concentrations. In conclusion, miR-23a enhances autophagy in yak GCs, attenuates apoptosis, and increases ER-α/ß abundance and E2 and P4 concentrations by downregulating ASK1. Additionally, FSH and LH can regulate these effects of miR-23a by altering its expression. These results provide important insights that can inform the development of strategies to reduce abnormal follicular atresia and improve the reproductive rate of yaks.

Study on serum miR-185-5p in assessing the injury severity and prognosis of patients with traumatic brain injury.

Background: This study aims to explore whether serum miR-185-5p levels are related to the injury severity and prognosis of traumatic brain injury patients. Methods: Serum miR-185-5p level was quantified in 120 TBI patients. The Glasgow Coma Scale (GCS) was used to grade the damage, and the Glasgow Outcome Scale (GOS) was used to evaluate the prognosis 3 months after TBI. Pearson correlation analysis was performed to determine the relationship between serum miR-185-5p level and injury severity and prognosis, and the value of serum miR-185-5p level to assess injury severity and prognosis was evaluated by receiver operating characteristic (ROC) curve. Results: Serum miR-185-5p level in moderate and severe TBI patients was higher than in mild TBI patients, and serum miR-185-5p was closely related to GCS score and GOS score. Serum miR-185-5p level higher than 0.36 could distinguish patients with mild to moderate TBI injury, with 72.97% sensitivity and 97.62% specificity, while that higher than 0.43 had 46.34% sensitivity and 91.89% specificity to distinguish moderate to severe TBI patients. Moreover, serum miR-185-5p levels higher than 0.36, with a sensitivity of 96.30% and a specificity of 60.24%, distinguished the poor prognosis of TBI patients. Serum miR185-5p level was an independent predictor of poor prognosis in TBI patients after 3 months and was effective in discriminating adverse outcomes at 3 months. Conclusions: Serum miR-185-5p level was significantly correlated with 3-month injury and adverse prognosis in TBI patients, suggesting that serum miR-185-5p level may be a biomarker that provides supplementary prognostic information and can be used to identify the risk of adverse prognosis in TBI patients.

Chromosome-level Dinobdella ferox genome provided a molecular model for its specific parasitism.

BACKGROUND: Dinobdella ferox is the most frequently reported leech species parasitizing the mammalian nasal cavity. However, the molecular mechanism of this special parasitic behavior has remained largely unknown. METHODS: PacBio long-read sequencing, next-generation sequencing (NGS), and Hi-C sequencing were employed in this study to generate a novel genome of D. ferox, which was annotated with strong certainty using bioinformatics methods. The phylogenetic and genomic alterations of D. ferox were then studied extensively alongside the genomes of other closely related species. The obligatory parasitism mechanism of D. ferox was investigated using RNA-seq and proteomics data. RESULTS: PacBio long-read sequencing and NGS yielded an assembly of 228 Mb and contig N50 of 2.16 Mb. Along Hi-C sequencing, 96% of the sequences were anchored to nine linkage groups and a high-quality chromosome-level genome was generated. The completed genome included 19,242 protein-coding genes. For elucidating the molecular mechanism of nasal parasitism, transcriptome data were acquired from the digestive tract and front/rear ends of D. ferox. Examining secretory proteins in D. ferox saliva helped to identify intimate connections between these proteins and membrane proteins in nasal epithelial cells. These interacting proteins played important roles in extracellular matrix (ECM)-receptor interaction, tight junction, focal adhesion, and adherens junction. The interaction between D. ferox and mammalian nasal epithelial cells included three major steps of pattern recognition, mucin connection and breakdown, and repair of ECM. The remodeling of ECM between epithelial cells of the nasal mucosa and epithelial cells of D. ferox may produce a stable adhesion environment for parasitism. CONCLUSIONS: Our study represents the first-ever attempt to propose a molecular model for specific parasitism. This molecular model may serve as a practical reference for parasitism models of other species and a theoretical foundation for a molecular process of parasitism.

Spin in the abstracts of randomized controlled trials of nurse-led care: A cross-sectional study.

BACKGROUND: Nurse-led models of care had been reported as effective intervention approaches for improving health management and reducing hospitalizations of target patients in a number of studies. However, the reporting quality of studies in the field varied and there was a lack of literature evaluation. OBJECTIVE: The objective of the study was to assess the reporting quality and spin of abstracts of published randomized controlled trials which had statistically not significant primary outcomes. Moreover, potential factors associated with the presence of spin were also assessed. METHODS: Studies on nurse-led care were retrieved from PubMed from January 1st, 2017, to December 31st, 2021. Only randomized controlled trials with statistically not significant primary outcomes were included. Study screening and data extraction were carried out by two reviewers independently. The reporting quality of each abstract was evaluated by the Consolidated Standards of Reporting Trials statement, and spin strategies were analyzed using a pre-designed assessment form. Potential predictors for the presence of spin were analyzed by multivariate logistic regressions. RESULTS: The overall reporting quality of the included 75 randomized controlled trial abstracts was not satisfying, with a median score of 16-item Consolidated Standards of Reporting Trials statement at 6 (IQR 5, 8). Forty abstracts used at least one spin strategy in abstracts. Among them, 18 (45.0 %) used spin strategies in the result section and 39 (97.5 %) had spin in the conclusion section. The most common spin strategy identified in abstracts was focusing on statistically significant secondary outcomes (12/40, 30.0 %) in the result section and claiming benefit with no consideration of statistically not significant results for the primary outcomes (32/40, 80.0 %) in the conclusion section. Based on the definition, 29 (72.5 %) abstracts were assessed to have high level of spin in the conclusions of abstracts. By multivariate logistic regression analyses, it was found that only geographic origin (reference: studies from Asian countries, OR = 0.118, 95 % CI 0.027 to 0.511, P = 0.004) and the Consolidated Standards of Reporting Trials statement score (reference: lower score, OR = 0.625, 95 % CI 0.470 to 0.829, P = 0.001) were significantly associated with the presence of spin in abstracts. CONCLUSION: Among the randomized controlled trials with statistically not significant primary outcomes in the field of nurse-led care, the reporting quality of abstracts needs to be improved. Trials from Asian countries and with lower Consolidated Standards of Reporting Trials statement scores are more likely to present spin in abstracts. Findings reported in the result and conclusion sections of these abstracts need to be interpreted with caution.

AAV9-Tspyl2 gene therapy retards bleomycin-induced pulmonary fibrosis by modulating downstream TGF-ß signaling in mice.

Idiopathic pulmonary fibrosis (IPF) is a devastating fibrotic lung disease characterized by scarring and destruction of the lung architecture, with limited treatment options. Targeted gene therapy to restore cell division autoantigen-1 (CDA1) expression may be a potential treatment approach to delay the progression of pulmonary fibrosis (PF). Here, we focused on CDA1, which was significantly decreased in human IPF, in a mouse model of bleomycin (BLM)-induced PF, and in transforming growth factor (TGF-ß)-challenged lung fibroblasts. In vitro, CDA1 overexpression by lentivirus infection in human embryonic lung fibroblasts (HFL1 cells) inhibited the production of pro-fibrotic and pro-inflammatory cytokines, lung fibroblast-to-myofibroblast transition, and extracellular matrix protein expression induced by exogenous TGF-ß1 treatment, whereas CDA1 knockdown with small interfering RNA promoted this effect. CDA1 overexpression also inhibited cell proliferation and migration. In a mouse model of BLM-induced PF, we provided novel evidence that the intratracheal delivery of adeno-associated virus serotype 9 carrying the mouse Tspyl2 gene reduced lung tissue inflammation and fibrosis. Mechanistically, CDA1, as a transcription regulator, could repress the TGF-ß signal transduction in vivo and in vitro. In conclusion, our results show that Tspyl2 gene therapy plays an antifibrotic role by inhibiting the lung fibroblast-to-myofibroblast transition and downstream TGF-ß/Smad3 signaling transduction in BLM-induced PF in mice, suggesting that CDA1 is an appropriate and promising therapeutic target for PF.

Pregabalin induced balance disorder, asthenia, edema, and constipation in an elderly adult: A case report.

BACKGROUND: Pregabalin is widely used to treat neuropathic pain associated with postherpetic neuralgia. To our knowledge, this is the first report on simultaneously occurring dose-related adverse drug reactions (ADRs) of balance disorder, asthenia, peripheral edema, and constipation in an elderly patient after pregabalin. CASE SUMMARY: A 76-year-old female with a history of postherpetic neuralgia was prescribed pregabalin (300 mg daily). After taking pregabalin for 7 d, the patient developed balance disorder, weakness, peripheral pitting edema (2+), and constipation. On days 8-14, the pregabalin dose was reduced to 150 mg/d based on creatinine clearance. The patient's peripheral edema improved significantly with the disappearance of all other adverse symptoms. On day 15, the pregabalin dose was increased to 225 mg/d to relieve pain. Unfortunately, the symptoms mentioned earlier gradually reappeared after 1 wk of pregabalin treatment. However, the complaints were not as severe as when taking 300 mg/d pregabalin. The patient consulted her pharmacist by telephone and was advised to reduce the dose of pregabalin to 150 mg/d and add acetaminophen (0.5 g, q6h) to relieve pain. The patient's ADRs gradually improved over the following week. CONCLUSION: Older patients should be prescribed a lower initial dose of pregabalin. The dose should be titrated to the maximum tolerable dose to avoid dose-limiting ADR. Dose reduction and the addition of acetaminophen may help limit ADR and improve pain control.

Troglonectes canlinensis sp. nov. (Teleostei: Nemacheilidae), a New Troglomorphic Loach from Guangxi, China.

A new species of the genus Troglonectes is described based on specimens from a karst cave in Andong Town, Xincheng County, Liuzhou City, Guangxi, China. Troglonectes canlinensis sp. nov. can be distinguished from its congener species by the following combination of characteristics: eye degenerated into a black spot; whole body covered by scales, except for the head, throat, and abdomen; incomplete lateral line; forked caudal fin; 8-10 gill rakers on the first gill arch; 13-14 branched caudal fin rays; 8-9 branched dorsal fin rays; 5-6 anal fin rays; 9-10 pectoral fin rays; upper adipose keel depth mostly 1/2 of the caudal peduncle depth; and caudal fin forked.

The role of immunometabolism in macrophage polarization and its impact on acute lung injury/acute respiratory distress syndrome.

Lung macrophages constitute the first line of defense against airborne particles and microbes and are key to maintaining pulmonary immune homeostasis. There is increasing evidence suggesting that macrophages also participate in the pathogenesis of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), including the modulation of inflammatory responses and the repair of damaged lung tissues. The diversity of their functions may be attributed to their polarized states. Classically activated or inflammatory (M1) macrophages and alternatively activated or anti-inflammatory (M2) macrophages are the two main polarized macrophage phenotypes. The precise regulatory mechanism of macrophage polarization is a complex process that is not completely understood. A growing body of literature on immunometabolism has demonstrated the essential role of immunometabolism and its metabolic intermediates in macrophage polarization. In this review, we summarize macrophage polarization phenotypes, the role of immunometabolism, and its metabolic intermediates in macrophage polarization and ALI/ARDS, which may represent a new target and therapeutic direction.

Emerging roles of miRNAs in neuropathic pain: From new findings to novel mechanisms.

Neuropathic pain, which results from damage to the somatosensory nervous system, is a global clinical condition that affects many people. Neuropathic pain imposes significant economic and public health burdens and is often difficult to manage because the underlying mechanisms remain unclear. However, mounting evidence indicates a role for neurogenic inflammation and neuroinflammation in pain pattern development. There is increasing evidence that the activation of neurogenic inflammation and neuroinflammation in the nervous system contribute to neuropathic pain. Altered miRNA expression profiles might be involved in the pathogenesis of both inflammatory and neuropathic pain by regulating neuroinflammation, nerve regeneration, and abnormal ion channel expression. However, the lack of knowledge about miRNA target genes prevents a full understanding of the biological functions of miRNAs. At the same time, an extensive study on exosomal miRNA, a newly discovered role, has advanced our understanding of the pathophysiology of neuropathic pain in recent years. This section provides a comprehensive overview of the current understanding of miRNA research and discusses the potential mechanisms of miRNAs in neuropathic pain.

Preliminary identification of soil fungi for the degradation of polyurethane film.

Polyurethane (PU) is a versatile plastic that boasts high environmental resistance. The biodegradation of PU has become a hot topic of research aimed at finding ways to potentially solve PU pollutants. Identifying microorganisms capable of efficiently degrading PU plastics is pivotal for the development of a green recycling process for PU. This study aimed to isolate and characterize PU-degrading fungi from the soil of a waste transfer station in Luoyang, China. We isolated four different fungal strains from the soil. Among the isolates, the P2072 and P2073 strains were identified as Rhizopus oryzae (internal transcribed spacer identity, 99.66%) and Alternaria alternata (internal transcribed spacer identity, 99.81%), respectively, through microscopic, morphologic, as well as 18S rRNA sequencing. The degradation ability of strains P2072 and P2073 was analyzed through measurement of weight loss, and they exhibited a degradation rate of 2.7% and 3.3%, respectively, for the PU films after 2 months' growth in mineral salt medium (MSM) with PU films as the sole carbon source. In addition, the P2073 strain exhibited protease activity in the presence of PU. To our knowledge, R. oryzae has never been reported as a PU-degrading fungus. This study provides a new perspective on the biodegradation of PU.

Fra-1 induces apoptosis and neuroinflammation by targeting S100A8 to modulate TLR4 pathways in spinal cord ischemia/reperfusion injury.

Spinal cord ischemia/reperfusion injury (SCII) is a severe complication driven by apoptosis and neuroinflammation. An increase in the expression of c-Fos, a member of the AP-1 family, is known as a neuronal activation marker in SCII. The AP-1 family is composed of Jun, Fos, and is associated with the regulation of cytokines expression and apoptosis. Fra-1 is a member of the Fos family, however, the contribution of Fra-1 to SCII is still unclear. In our study, Fra-1 was highly upregulated especially in neurons and microglia and promoted apoptosis by changing the expression of Bax/Bcl-2 after SCII. Furthermore, we found that Fra-1 directly regulated the transcription expression of S100A8. We demonstrated that knockdown of Fra-1 alleviated S100A8 mediated neuronal apoptosis and inflammatory factor release, thus improved motor function after SCII. Interestingly, we showed that administration of TAK-242, the TLR4 inhibitor, to the ischemia/reperfusion (I/R) injury induced rats suppressed the activation of the ERK and NF-κB pathways, and further reduced Fra-1 expression. In conclusion, we found that Fra-1-targeted S100A8 was expressed the upstream of Fra-1, and the Fra-1/S100A8 interaction formed a feedback loop in the signaling pathways activated by SCII.

Reclassification of flat type sudden deafness / 中华耳鼻咽喉头颈外科杂志

Objective: To reclassify the flat type sudden deafness according to the types of audiogram shape, and to explore the correlation between different pattern of hearing loss and prognosis. Methods: All of 1 024 patients with unilateral sudden deafness (492 males and 532 females, aged from 19 to 65 years, with an average age of 41.2 years old) admitted to 33 hospitals nationwide from August 2007 to October 2011 were divided into four types according to Chinese Guideline of Sudden Deafness(2015): low-frequency, high-frequency, flat and total deafness. Then, 402 patients with flat type sudden deafness were further divided into ascending type, descending type and consistent type according to the audiogram shapes. First, we compared the clinical characteristics and prognosis among these three subtypes of flat deafness, then compared the clinical characteristics and prognosis between ascending flat deafness and low-frequency deafness, descending flat deafness and high-frequency deafness, consistent flat deafness and total deafness, explored the factors related to the prognosis of flat deafness. SPSS 21.0 software, ANOVA, χ2 test, t-test and Logistic regression were used to analyze the data. Results: The cure rates of flat ascending, flat descending and flat consistent sudden deafness groups were 70.7%, 17.1% and 34.0% respectively, with a statistically significant difference (χ2=33.984, P<0.001); However, there was no significant difference in age, sex and affected side (all P>0.05). The independent related factors for the recovery of flat type sudden deafness were as follows: whether there was dizziness [OR=0.459; 95% confidence interval (CI): 0.271-0.777], the type of audiogram shape (OR=0.721; 95%CI: 0.530-0.981), and days from onset to therapy (OR=0.903, 95%CI: 0.835-0.978), all of which had P values<0.05. There was no significant difference in the cure rates between ascending flat sudden deafness and low-frequency descending sudden deafness, descending flat sudden deafness and high-frequency descending sudden deafness (all P>0.05). The pure tone average(PTA) of flat consistent sudden deafness and total deafness were (69.1±18.9) and (101.7±17.7) dB HL, respectively, with a statistically significant difference (t=20.890, P<0.001), and the cure rates were 34.0% and 14.5%, respectively, with a statistically significant difference (χ2=29.012, P<0.001). Conclusion: According to the audiogram shape, the flat type sudden deafness can be further divided into ascending flat sudden deafness, descending flat sudden deafness and consistent flat sudden deafness, which can more effectively evaluate the prognosis. The cure rate of ascending flat sudden deafness is similar to that of low-frequency sudden deafness, and the prognosis is well; The cure rate of descending flat sudden deafness is similar to that of high-frequency descending sudden deafness, and the prognosis is poor. The cure rate of consistent flat sudden deafness is higher than that of total deafness. PTA plays an important role in the prognosis of consistent flat sudden deafness and total deafness. Total deafness can be regarded as a single type of sudden deafness.

Safety and efficacy of the early administration of levosimendan in patients with acute non-ST-segment elevation myocardial infarction and elevated NT-proBNP levels: An Early Management Strategy of Acute Heart Failure (EMS-AHF) / 中华内科杂志

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.

[Effect of Dihydroartemisinin and Arsenic Trioxide on Apoptosis of Acute Myeloid Leukemia Cells].

OBJECTIVE: To investigate the effect of dihydroartemisinin (DHA) combined with arsenic trioxide (ATO) on the viability and apoptosis of acute myeloid leukemia (AML) FLT3-ITD mutant cell line MOLM13 and its mechanism. METHODS: MOLM13 cells were treated with DHA or ATO alone or in combination. The viability of MOLM13 cells was detected by CCK-8 assay, cell proliferation was observed by colony formation assay, cell apoptosis and reactive oxygen species (ROS) level were measured by flow cytometry, and the expression levels of proteins related to apoptosis were detected by Western blot. RESULTS: Compared with the control group, treatment with DHA and ATO alone or in combination could inhibit cell proliferation, activate ROS formation, and finally induce cell apoptosis. DHA in combination with ATO produced a synergistic effect. Western blot analysis showed that DHA combined with ATO could significantly upregulate the level of c-PARP and activate apoptosis via inhibition of Mcl-1 and FLT3-ITD. CONCLUSION: DHA combined with ATO induces the apoptosis of FLT3-ITD AML cell line MOLM13 by inhibiting Mcl-1 pathway and activating FLT3-ITD protein degradation.