[Effects of Different Nutritional Scoring Systems on Prognosis of Elderly Patients with Multiple Myeloma].

OBJECTIVE: To analyze the prognostic nutritional index (PNI), controlling nutritional status (CONUT) and fibrinogen/albumin ratio (FAR) levels in elderly patients with multiple myeloma (MM) and their prognostic impact. METHODS: The clinical data of 74 elderly MM patients diagnosed in Gansu Provincial Hospital from January 2020 to July 2022 were retrospectively analyzed. The optimal cut-off values for PNI, CONUT score and FAR were obtained by receiver operating characteristic (ROC) curve, which were used for grouping patients. The correlation of above three indexes with clinical parameters such as sex, serum calcium (Ca), ß2-microglobulin (ß2-MG), serum creatinine (Cr) in elderly MM patients were analyzed. The survival rates of patients with different levels of each index were compared. Univariate and multivariate analysis of the impact of clinical indicators on the prognosis of patients were performed. RESULTS: The optimal cut-off values for PNI, CONUT score and FAR were 39.775, 3.5 and 0.175, respectively, according to which the patients were divided into high and low group. Statistical analysis showed that there were significant differences in albumin level among different groups (all P < 0.05). In addition, there was a significant difference in hemoglobin between high-PNI group and low-PNI group (P < 0.05), while in sex distribution between high-FAR and low-FAR group (P < 0.05). The survival rate of elderly MM patients with increased PNI, decreased CONUT score and FAR was higher (all P < 0.05). Univariate and multivariate analysis showed that ß2-MG, Cr, PNI, CONUT score and FAR were independent prognostic factors for elderly MM patients. CONCLUSION: PNI, CONUT score and FAR are related to some clinical indicators of elderly MM patients, and have an impact on the prognosis.

[Effects of Tomato Planting Years on Soil Physical and Chemical Properties and Microbial Communities].

Long-term continuous cropping of facility soils could influence soil properties; however, the differences in soil properties among different continuous cropping years are still not well understood. The objective of this study was to explore the effects of continuous cropping years of tomato on the physical and chemical properties and biological characteristics of facility soil. Conventional analysis, high-throughput sequencing, and other methods were used to examine the soil physicochemical properties, soil microbial community diversity, and enzyme activities in facility soil after continuous tomato cropping for 1-3 years, 5-7 years, and more than 10 years. As the continuous tomato cropping years increased, soil bulk density and pH decreased; soil maximal water holding capacity increased; and organic matter, total nitrogen, and total phosphorus accumulated. As continuous cropping years increased, the total salt and EC value decreased with continuous cropping for 5-7 years and increased from 5-7 years to more than 10 years continuous cropping and showed a trend of secondary soil salinization. There was a significant increase in alkaline phosphatase for 1-3 years to 5-7 years continuous tomato cropping. There were significant differences in fungal community abundance among different cropping years. The Simpson index and Shannon index of fungi showed a trend of increasing first and then decreasing with the extension of continuous cropping years and reached the maximum value at 5 years of continuous cropping. The Chao1 index decreased continuously following the cropping years. As continuous cropping years increased, Streptomyces became the dominant bacteria, and Aspergillus and Pseudaleuria became the dominant fungi. The key factors affected by continuous cropping years were available potassium and available nitrogen based on the redundancy analysis. The results of this study lay the foundation for future research on the influence of continuous cropping years on the health of facility soil.

[Microbial Diversity and Population Structure of Different Salinized Soil Types in Hebei Province].

The objective of this study was to explore the microbial diversity and community composition under saline soil and to screen the salt-tolerant microbial flora from salinization habitats. The soil from three different habitats(primary salinization, secondary salinization, and healthy soil) in Hebei Province were sampled. The convention method and high-throughput sequencing technology were used to examine the physicochemical properties and microorganism diversity. The soil chemical properties of the three habitats were significantly different. Compared with those of field soil, the soil OM, AP, AK, TS, and EC values of greenhouse soil and TS and EC values of coastal saline soil were significantly higher. However, other chemical indexes of coastal saline soil were significantly lower. The diversity index and abundance of soil bacteria in greenhouse soil were the highest, followed by those in field soil and coastal saline soil as the lowest. The diversity index and abundance of fungi in two saline habitats were significantly lower than that in field soil. The community structure of saline soil was analyzed at the phylum and genus levels. Chloroflexi and its genera and Ascomycota and its genera, such as Trichocladium and Fusarium, were the dominant microbial groups in saline soil. EC and TS were the main factors affecting microbial diversity and community composition. EC and TS were positively correlated with unclassified_A4b, unclassified_Chloroflexi, unclassified_α-Proteobacteria, Trichocladium, unclassified_Chaetomiaceae, Crassicarpon, Cephaliophora, and Sodiomyces. The results of this study lay the foundation for future research on screening microbial resources needed for saline soil remediation.

The electronic and optical properties of Cs2BX6 (B = Zr, Hf) perovskites with first-principle method.

The electronic structures and absorption properties of Cs2BX6 halide compounds are investigated with first principle calculation and exchange correlation functional of GGA-PBE. Pressure and halogen ion doping are employed to regulate band gap. All materials suffer transition from indirect to direct band gap semiconductors but with different phase transition pressure. Structural and band structure calculating results show that the value of phase transition pressure is mainly determined by the volume of octahedron. When the volume of vacancy octahedron is much less than B-ion octahedron, the lowest band point of B-d orbitals transforms to Γ point, then the indirect semiconductors transform into direct band gap semiconductors. Calculating results of optical absorption implied that the systems have obvious blue shift, which result in the optical properties reduced. Based on suitable band gap and higher absorption coefficient, Cs2ZrI4Br2 can be an ideal candidate for perovskites solar cells.

Deferoxamine in intracerebral hemorrhage: Systematic review and meta-analysis.

BACKGROUND: Intracerebral hemorrhage (ICH) is a stroke with a high morbidity and mortality rate. Deferoxamine (DFX) is thought to be effective in treating Intracerebral Hemorrhage. In our study, we performed a meta-analysis to evaluate the treatment effects of DFX. METHODS: We systematically searched PubMed, Embase, Web of Science, the Cochrane Central Register of Controlled Trials, and Chinese Biomedical Literature Database in Jan 2022 for studies on DFX for ICH patients. Outcome measures included relative hematoma volume, relative edema volume, good neurological functional outcome and adverse events. Odds risk (OR) and weighted mean difference (WMD) were used to evaluate clinical outcomes. RESULTS: After searching 636 articles, 4 RCTs, 2 NRCTs, and 1cohort study were included. We found that DFX was effective in hematoma absorption on day 7 after onset, but the difference was not significant on day 14. DFX could suppress edema expansion on days 3, 7, and 14 after onset. DFX did not contribute to better outcomes after 3 and 6 months when used the modified Rankin Scale and the Glasgow Outcome Scale to evaluate neurological prognosis. The pooled results showed no statistically significant difference in Serious adverse events between the experimental and control groups. CONCLUSIONS: DFX could limit edema expansion on days 3, 7, and 14 after commencement and facilitate hematoma absorption at week 1 without significantly increasing the risk of adverse events, but it did not improve neurological prognosis.

[Clinical Features and Prognosis of Patients with Castleman's Disease].

OBJECTIVE: To analyze the clinical features and prognosis of patients with Castleman's disease (CD) and improve the diagnosis and treatment of CD. METHODS: Clinical data of patients diagnosed with CD by pathological biopsy in Gansu Provincial Hospital from January 2009 to November 2020 were retrospectively analyzed. According to clinical classification, the patients were divided into two groups: UCD (unicentric CD) group (n=20) and MCD (multicentric CD) group (n=9). The clinical manifestations, laboratory examination, treatment regimens, pathological examination and follow-up data were statistically analyzed. RESULTS: There were no significant differences in average age and gender ratio between UCD group and MCD group. In UCD patients, 80.0% were hyaline vascular type, and 20.0% were plasma cell type. In MCD patients, 33.3% were hyaline vascular type, 55.6% were plasma cell type, and 11.1% were mixed type. There was significant difference in pathological classification between the two groups (P=0.039). The UCD patients usually presented asymptomatic single lymph node enlargement with mild clinical symptoms, while the MCD patients were characterized by multiple superficial and deep lymph node enlargement throughout the body. The incidences of asthenia, splenomegaly, serous effusion in MCD group were higher than those in UCD group (P<0.05). Meanwhile, the incidences of anemia, hypoproteinemia, increased ESR, elevated serum globulin and elevated ß2-microglobulin were significantly higher than those in UCD group too (P<0.05). There was no significant difference in the incidences of abnormal WBC, PLT and elevated LDH between the two groups (P>0.05). Among 20 patients with UCD, 13 cases reached complete remission (CR), 1 case achieved partial remission (PR). Among 9 patients with MCD, 3 cases received CR and 4 cases received PR. CONCLUSION: Patients with CD requires pathological examination for diagnosis. Patients with UCD show mild clinical symptoms, good surgical treatment effect and good prognosis. Patients with MCD have diversified clinical manifestations and relatively poor prognosis, and these patients require comprehensive treatment.

The Effect of Mesogenic Coronas on the Type and Anisotropy of Gold Nanoparticle Superlattices: When Can the Tail Wag the Dog?

The correlation between the size of nanoparticles, the structure and shape of mesogenic ligands and the ensuing assembly behaviour is not really understood. Closer inspection shows very surprising features. Here, 2- and 4-nm gold nanoparticles (NPs) were synthesized, and grafted with a forked ligand containing two rod-like mesogens in its branches: one cholesterol, the other with azobenzene. The 4-nm NPs also contained n-hexylthiol as co-ligand. They were found to form a FCC cubic superlattice, whereas the 2-nm NPs form hexagonal HCP with weak birefringence, hence with partially oriented ligands. The structures were compared with those of related systems containing a range of different azobenzene-to-cholesterol ratios, all giving body-centred tetragonal superlattices with various degrees of anisotropy. Geometric analysis is presented in terms of the asphericity of the NPs' surroundings, requirement for space-filling and structural anisotropy. Some general rules are derived to help design the soft corona around the NPs in order to obtain superlattices with the desired structure and anisotropy.

Progress in application of adult endogenous neurogenesis in brain injury repair / 生理学报

Persistent neurogenesis exists in the subventricular zone (SVZ) of the ventricles and the subgranular zone (SGZ) of the dentate gyrus of the hippocampus in the adult mammalian brain. Adult endogenous neurogenesis not only plays an important role in the normal brain function, but also has important significance in the repair and treatment of brain injury or brain diseases. This article reviews the process of adult endogenous neurogenesis and its application in the repair of traumatic brain injury (TBI) or ischemic stroke, and discusses the strategies of activating adult endogenous neurogenesis to repair brain injury and its practical significance in promoting functional recovery after brain injury.

Nanoscale Printing of Indium-Tin-Oxide by Femtosecond Laser Pulses.

For constructing optical and electrical micro-devices, the deposition/printing of materials with sub-1 µm precision and size (cross-section) is required. Crystalline c-ITO (indium tin oxide) nanostructures were patterned on glass with sufficient precision to form 20-50 nm gaps between individual disks or lines of ∼250 nm diameter or width. The absorbed energy density [J/cm3] followed a second-order dependence on pulse energy. This facilitated high-resolution and precise nanoscale laser-writing at a laser wavelength of 515 nm. Patterns for optical elements such as circular gratings and micro-disks were laser-printed using ITO as a resist. Unexposed amorphous a-ITO was chemically removed in aqueous 1% vol. HF solution. This use of a-ITO as a solid resist holds promise for metamaterial and micro-optical applications.

Activation of pyroptosis and ferroptosis is involved in radiation-induced intestinal injury in mice.

Radiation-induced intestinal injury (RIII) is one of the most common abdominal and pelvic radiation therapy complications. RIII seriously affects the treatment and prognosis of cancer patients, and there are no effective interventions. Radiation can cause intestinal tissue damage, inflammatory cell infiltration, and pro-inflammatory cytokine release. We established an RIII mouse model by subjecting C57BL/6 mice to abdominal irradiation. Our results show that both pyroptosis and ferroptosis play a key role in RIII. VX-765 and Ferrostatin-1 (Fer-1) can inhibit these two types of programmed cell death and ameliorate RIII, respectively. Activation of the nuclear factor-κB (NF-κB) signaling pathway exacerbates the chemotaxis of inflammatory cells. In the present study, we hypothesized that the activation of NF-κB signaling pathway plays an important role in intestinal inflammatory injury. We demonstrated that the nuclear expression levels of the NF-κB subunit p65 increased after irradiation treatment. Reduced release of inflammatory factors and intestinal tissue damage was observed after pretreatment with pyrrolidinedithiocarbamate ammonium (PDTC). Moreover, after PDTC treatment, the indicators related to pyroptosis and ferroptosis were reversed. Collectively, these results suggest that the activation of the intestinal NF-κB signaling pathway may be associated with pyroptosis, ferroptosis, and subsequent intestinal injury after irradiation.

Increased susceptibility of irradiated mice to Aspergillus fumigatus infection via NLRP3/GSDMD pathway in pulmonary bronchial epithelia.

BACKGROUND: Aspergillus fumigatus infection is difficult to diagnose clinically and can develop into invasive pulmonary aspergillosis, which has a high fatality rate. The incidence of Aspergillus fumigatus infection has increased die to widespread application of radiotherapy technology. However, knowledge regarding A. fumigatus infection following radiation exposure is limited, and the underlying mechanism remains unclear. In this study, we established a mouse model to explore the effect of radiation on A. fumigatus infection and the associated mechanisms. METHODS: In this study, a mouse model of A. fumigatus infection after radiation was established by irradiating with 5 Gy on the chest and instilling 5 × 107/ml Aspergillus fumigatus conidia into trachea after 24 h to explore the effect and study its function and mechanism. Mice were compared among the following groups: normal controls (CON), radiation only (RA), infection only (Af), and radiation + infection (RA + Af). Staining analyses were used to detect infection and damage in lung tissues. Changes in protein and mRNA levels of pyroptosis-related molecules were assessed by western blot analysis and quantitative reverse transcription polymerase chain reaction, respectively. Protein concentrations in the serum and alveolar lavage fluid were also measured. An immunofluorescence colocalization analysis was performed to confirm that NLRP3 inflammasomes activated pyroptosis. RESULTS: Radiation destroyed the pulmonary epithelial barrier and significantly increased the pulmonary fungal burden of A. fumigatus. The active end of caspase-1 and gasdermin D (GSDMD) were highly expressed even after infection. Release of interleukin-18 (IL-18) and interleukin-1ß (IL-1ß) provided further evidence of pyroptosis. NLRP3 knockout inhibited pyroptosis, which effectively attenuated damage to the pulmonary epithelial barrier and reduced the burden of A. fumigatus. CONCLUSIONS: Our findings indicated that the activation of NLRP3 inflammasomes following radiation exposure increased susceptibility to A. fumigatus infection. Due to pyroptosis in lung epithelial cells, it resulted in the destruction of the lung epithelial barrier and further damage to lung tissue. Moreover, we found that NLRP3 knockout effectively inhibited the pyroptosis and reducing susceptibility to A. fumigatus infection and further lung damage. Overall, our results suggest that NLRP3/GSDMD pathway mediated-pyroptosis in the lungs may be a key event in this process and provide new insights into the underlying mechanism of infection. Video abstract.

Self-assembly of Gold Nanoparticles into an Adjustable Plasmonic 3D Lattice using Janus-type Forked Mesogenic Ligands.

We report the formation of a 3D body-centred self-assembled superlattice of gold nanoparticles whose interparticle gap, and hence its plasmonic properties, are adjustable exclusively in the xy-plane. Thus, even though the particles are spherical, their anisotropic packing generates tailorable plasmonic dichroism. The gold nanoparticles are coated with forked ligands containing two mesogens: either two cholesterols ("twin"), one cholesterol and one azobenzene ("Janus"), or a mixture of the two. Beside the body-centered arrangement of gold nanoparticles, the structure also contains unusual two-dimensionally x-y dual undulated (eggbox-like) smectic-like layers of mesogens. Moreover, the presence of azobenzene mesogens allows the superlattice to be melted through UV-induced photo-isomerization; the process is reversible displaying low fatigue on repeated cycling.

CircNEIL3 mediates pyroptosis to influence lung adenocarcinoma radiotherapy by upregulating PIF1 through miR-1184 inhibition.

Circular RNAs (circRNAs) belong to an abundant category of non-coding RNAs that are stable and specific, and thus have great potential in cancer treatment. However, little is known about the role of circRNAs during radiotherapy in lung adenocarcinoma (LUAD). Here, we established the expression profiles of 1,875 dysregulated circRNAs in non-irradiated and irradiated A549 cells and identified circNEIL3 as a significantly downregulated circRNA in A549 cells treated with 0, 2, or 4 Gy of radiation, respectively. Functional assays demonstrated that circNEIL3 knockdown promoted radiation-induced cell pyroptosis, whereas circNEIL3 overexpression had the opposite effects. Importantly, the effects of circNEIL3 overexpression on inhibiting pyroptosis were reversed by PIF1 knockdown. Mechanistically, circNEIL3-mediated pyroptosis was achieved through directly binding to miR-1184 as a sponge, thereby releasing the inhibition of miR-1184 on PIF1, which ultimately induces DNA damage and triggers AIM2 inflammasome activation. In vivo, circNEIL3 knockdown significantly enhanced the efficacy of radiotherapy as evidenced by decreases in tumor volume and weight. Collectively, the circNEIL3/miR-1184/PIF1 axis that mediate pyroptosis induction may be a novel, promising therapeutic strategy for the clinical treatment of lung cancer.

miR-142a-3p Enhances FlaA N/C Protection Against Radiation-Mediated Intestinal Injury by Modulating the IRAK1/NF-κB Signaling Pathway.

PURPOSE: Our purpose was to investigate the role of recombinant protein flagellin A N/C (FlaA N/C) protein-mediated pyroptosis inhibition and related miRNA in radiation protection. METHODS AND MATERIALS: Mice received 10 Gy irradiation after FlaA N/C pretreatment, IRAK-1/4 Inhibitor I treatment, or pyrrolidine dithiocarbamate treatment. Human intestinal epithelial cells (HIEC) received 10 Gy irradiation after FlaA N/C pretreatment, overexpressed miR-142a-3p with miR-142a-3p mimics, or inhibited miR-142a-3p with miR-142a-3p inhibitor. Mouse & Rat miRNA OneArray determined the change in relevant miRNA after FlaA N/C pretreatment; real-time polymerase chain reaction detected IRAK1 and miR-142a-3p expression; a CCK-8 assay evaluated cell viability; LDH release analyzed cytotoxicity; caspase-1 activity assay, interleukin-1ß level, and flow cytometry analyzed pyroptosis in cells; hematoxylin-eosin staining evaluated the damage to intestinal tissue; CO-IP detected the inflammation activation; immunohistochemistry, Western blot analysis, and immunofluorescence analyzed activation of pyroptosis-related proteins and the activation of NF-kB signaling pathways; and luciferase reporter assay and fluorescence in situ hybridization detected the interaction between miR-142a-3p and IRAK1. RESULTS: FlaA N/C reduced radiation-induced pyroptosis in vivo and in vitro, and miR-142a-3p expression increased after FlaA N/C pretreatment. Upregulating the expression of miR-142a-3p inhibited radiation-induced pyroptosis in HIEC, and downregulating the expression of miR-142a-3p led to radiation-induced pyroptosis in HIEC after FlaA N/C pretreatment. IRAK1 was a direct target of miR-142a-3p and played an important role in radiation-induced pyroptosis in HIEC. Inhibiting IRAK1 reduced radiation-mediated pyroptosis in mice intestines. miR-142a-3p downregulated IRAK1 and suppressed the NF-kB pathway. Inhibiting the NF-kB signaling pathway can reduce radiation-mediated pyroptosis in mice intestines. CONCLUSIONS: Our findings indicated this new radioprotectant protein regulates miR-142a-3p, effectively inhibiting radiation-induced pyroptosis mediated by the IRAK1/NF-κB signaling pathway in intestinal cells.

Research progress on muscle spindle morphology / 生理学报

Muscle spindle is the key proprioceptor in skeletal muscles and plays important roles in many physiological activities, such as maintaining posture, regulating movement and controlling speed variation. It has significant clinical relevance and is emerging as a promising therapeutic target for the treatment of motor functional impairment and metabolic diseases. In this review, we summarized muscle spindle distribution and the mechanism of mechanical signal transmission, and reviewed the research progress on morphological and structural characteristics of muscle spindles.

Samotolisib Attenuates Acute Liver Injury Through Inhibiting Caspase-11-Mediated Pyroptosis Via Regulating E3 Ubiquitin Ligase Nedd4.

Acute liver injury (ALI) is associated with poor survival in patients with sepsis. During sepsis, the liver is the main site of bacterial endotoxin-induced inflammation. Lipopolysaccharide (LPS) promotes caspase-4/5/11 activation, leading to pyroptosis, a major sepsis driver. This study aimed to identify novel drugs that can control hepatocyte caspase-4/5/11 activation during sepsis. We performed LPS-induced caspase-11 activation and pyroptosis in RAW 264.7 cells and established an LPS-induced ALI mouse model. We identified samotolisib (ST), a novel dual phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) inhibitor, by screening a library of 441 pyroptosis compounds with known targets, which dose-dependently inhibited caspase-11 activation and N-terminal fragment of gasdermin D (GSDMD-NT) generation, reducing RAW 264.7 cell pyroptosis. In mice, ST preconditioning improved survival, attenuated LPS-induced serum alanine aminotransferase and aspartate aminotransferase activity, and inhibited severe liver inflammation and damage. Importantly, ST treatment activated Nedd4, which directly interacts with and mediates caspase-11 ubiquitination and degradation. This was largely abrogated by insulin-like growth factor 1. ST ameliorated LPS-induced hepatotoxicity by inhibiting caspase-11/GSDMD-NT pyroptosis signaling via regulating PI3K/AKT/mTOR/Nedd4 signaling. Hence, ST may play a key role in the prevention of liver injury in patients with sepsis.

AZD8055 ameliorates experimental autoimmune encephalomyelitis via the mTOR/ROS/NLRP3 pathway.

AIMS: Experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis (MS), is characterized by immune-mediated demyelination and neurodegeneration. NOD-like receptor protein 3 (NLRP3) inflammasome activation aggravates spinal cord inflammation in EAE. Autophagy is associated with alleviation of systemic inflammation, including that encountered in EAE. However, the effects of autophagy on NLRP3 in EAE are still unclear. Here, we evaluated the effects of the autophagy activator AZD8055 on EAE. METHODS: EAE model mice were established, histological examination was performed to assess the degree of inflammatory cell infiltration and demyelination. And the levels of autophagy and NLRP3-mediated pyroptosis in spinal cords were assessed. Western blotting and immunofluorescence analyses were performed to evaluate protein expression and localization. RESULTS: AZD8055 significantly enhanced autophagy in the spinal cords of EAE model mice, coupled with decreased abnormal clinical behavior scores and increased body weights. The degree of inflammatory cell infiltration and demyelination was mild in AZD8055-treated EAE model mice.Meanwhile, the pathway of ROS/NLRP3 was downregulated, and LC3 and NLRP3 were colocalized. CONCLUSIONS: AZD8055 ameliorated EAE through anti-inflammatory and anti-pyroptosis effects via the mammalian target of mTOR/ROS/NLRP3 pathway. These findings provide insights into the interactions between autophagy and pyroptosis and may facilitate the development of novel treatments for MS.

Left Ventricular Ejection Fraction and Cerebrospinal Fluid Biomarkers of Alzheimer's Disease Pathology in Cognitively Normal Older Adults: The CABLE Study.

BACKGROUND: Heart failure has been considered as a potential modifiable risk factor for cognitive impairment and dementia. Left ventricular ejection fraction (LVEF), an indicator of cardiac dysfunction, has also been associated with cognitive aging. However, the effect of LVEF on Alzheimer's disease (AD) pathology is still less known. OBJECTIVE: We aimed to investigate the associations of LVEF with cerebrospinal fluid (CSF) biomarkers for AD in cognitively normal elders. METHODS: A total of 423 cognitively normal individuals without heart failure were included from the Chinese Alzheimer's Biomarker and LifestylE (CABLE) study. Participants were divided into low LVEF group (50%≤LVEF < 60%) and high LVEF group (LVEF≥60%). The associations of LVEF with CSF AD biomarkers including CSF amyloid-ß 42 (Aß42), total-tau (t-tau), and phosphorylated tau (p-tau) were analyzed using multivariate linear regression models. RESULTS: Participants with low LVEF had higher levels of CSF t-tau (ß= -0.009, p = 0.006) and t-tau/Aß42 ratios (ß= -0.108, p = 0.026). Subgroup analyses showed that the associations only existed in female and middle-aged groups (< 65 years old). Besides, participants with low LVEF had higher levels of CSF p-tau (ß= -0.002, p = 0.043) in middle-aged group. CONCLUSION: In conclusion, our findings revealed the associations between LVEF and AD pathology, which may provide new insights into AD prevention through maintaining cardiac function.

[The Influence of Serum Homocysteine Level to the Prognosis of Newly Diagnosed Multiple Myeloma Patients and Analysis of Related Factors].

OBJECTIVE: To analyze the influence of serum homocysteine (Hcy) levels to the prognosis of newly diagnosed multiple myeloma (MM) patients, and to explore related factors affecting the prognosis of the patients. METHODS: The clinical pathological data of 180 newly diagnosed MM patients treated in our hospital from March 2013 to February 2015 were collected, and the patients were divided into high and low Hcy groups based on the median Hcy. The survival curves of the patients in the two groups were drawn to compare the differences of the survival; univariate and multivariate survival analysis was used to observe the influence of serum cysteine to the prognosis of newly diagnosed MM patients; the clinicopathological data of the patients with high and low Hcy in the two groups was compared, Pearson test was used to further analyzes the relationship between Hcy and different factors, and explores the related factors of Hcy affecting the prognosis of the patients. RESULTS: The median survival times of patients in the high and low Hcy groups were 32 (5-59) and 41 (7-71) months, respectively. The 3-year survival rate of the patients in high Hcy group was significantly lower than those in low Hcy group, and the difference shows statistically significant (P<0.05). The results of univariate survival analysis showed that the OS of newly diagnosed MM patients whom with advanced age, high bone disease grade, high-level bone marrow plasma cell count, LDH, C-reactive protein, Cr, ß2-MG, Hcy, low-level Hb, and ALB was significantly shortened (all P<0.05). The results of multivariate survival analysis showed that old age, high levels of bone marrow plasma cells, Cr, ß2-MG, low levels of Hb, and ALB were the independent risk factors shorting the overall survival (OS) time of newly diagnosed MM patients (all P<0.05), while Hcy showed no independent relation for the OS of patients (P>0.05). The Hb level of the patients in high Hcy group was significantly lower than those in low-Hcy group, while the LDH level was significantly higher than those in low Hcy group (all P<0.05). Pearson test results showed that serum Hcy and Hb showed negative correlation (r=-0.813, P<0.05), but it shows positive correlation with LDH (r=0.726, P<0.05). CONCLUSION: Serum Hcy level has a correlation trend with the survival of newly diagnosed MM, which is affected by factors such as Hb.

miR-324-3p reverses cisplatin resistance by inducing GPX4-mediated ferroptosis in lung adenocarcinoma cell line A549.

PURPOSE: MicroRNAs act as crucial regulators of a diverse range of biological processes, including chemoresistance. Our study aimed to investigate the effect of miR-324-3p on lung adenocarcinoma cell line A549 resistant to cis-diamminedichloroplatinum II (DDP, aka cisplatin). METHODS: The miR-324-3p expression levels in cisplatin-sensitive A549（A549） and cisplatin-resistant A549 (A549/DDP) cells were determined by qRT-PCR assay. Cell proliferation was determined with the commercial kit CCK-8 and colony formation assay, whereas cell death was analyzed using flow cytometry. The target gene of miR-324-3p was identified and validated with the luciferase reporter and western blot assays. The role of miR-324-3p in modulating cisplatin resistance was evaluated in vitro. RESULTS: The expression of miR-324-3p was found to be significantly downregulated in the A549/DDP cells. Conversely, miR-324-3p overexpression reversed cisplatin resistance in the cells. With regard to the possible mechanism underlying this phenomenon, we identified the glutathione peroxidase 4 (GPX4) gene as the direct target of miR-324-3p, where overexpression of the gene reversed the miR-324-3p effect of sensitizing the A549/DDP cells to cisplatin. Furthermore, the GPX4 inhibitor RSL3 could mimic the effect of miR-324-3p upregulation in increasing the sensitivity of the cisplatin-resistant cells to the drug. Significantly, miR-324-3p enhanced cisplatin-induced ferroptosis in the A549/DDP cells. CONCLUSION: Our findings revealed the role of the miR-324-3p-GPX4 signaling axis in A549/DDP cells and how the targeting of this axis could be a potential strategy for reversing cisplatin resistance in human non small cell lung cancer (NSCLC).