Live birth of chimeric monkey with high contribution from embryonic stem cells.

A formal demonstration that mammalian pluripotent stem cells possess preimplantation embryonic cell-like (naive) pluripotency is the generation of chimeric animals through early embryo complementation with homologous cells. Whereas such naive pluripotency has been well demonstrated in rodents, poor chimerism has been achieved in other species including non-human primates due to the inability of the donor cells to match the developmental state of the host embryos. Here, we have systematically tested various culture conditions for establishing monkey naive embryonic stem cells and optimized the procedures for chimeric embryo culture. This approach generated an aborted fetus and a live chimeric monkey with high donor cell contribution. A stringent characterization pipeline demonstrated that donor cells efficiently (up to 90%) incorporated into various tissues (including the gonads and placenta) of the chimeric monkeys. Our results have major implications for the study of primate naive pluripotency and genetic engineering of non-human primates.

The zinc finger protein Miz1 suppresses liver tumorigenesis by restricting hepatocyte-driven macrophage activation and inflammation.

Chronic inflammation plays a central role in hepatocellular carcinoma (HCC), but the contribution of hepatocytes to tumor-associated inflammation is not clear. Here, we report that the zinc finger transcription factor Miz1 restricted hepatocyte-driven inflammation to suppress HCC, independently of its transcriptional activity. Miz1 was downregulated in HCC mouse models and a substantial fraction of HCC patients. Hepatocyte-specific Miz1 deletion in mice generated a distinct sub-group of hepatocytes that produced pro-inflammatory cytokines and chemokines, which skewed the polarization of the tumor-infiltrating macrophages toward pro-inflammatory phenotypes to promote HCC. Mechanistically, Miz1 sequestrated the oncoprotein metadherin (MTDH), preventing MTDH from promoting transcription factor nuclear factor κB (NF-κB) activation. A distinct sub-group of pro-inflammatory cytokine-producing hepatocytes was also seen in a subset of HCC patients. In addition, Miz1 expression inversely correated with disease recurrence and poor prognosis in HCC patients. Our findings identify Miz1 as a tumor suppressor that prevents hepatocytes from driving inflammation in HCC.

Associations of the circulating levels of cytokines with the risk of myeloproliferative neoplasms: a bidirectional mendelian-randomization study.

OBJECTIVE: In the pathogenesis of myeloproliferative neoplasms (MPN), inflammation plays an important role. However, it is unclear whether there is a causal link between inflammation and MPNs. We used a bidirectional, two-sample Mendelian randomization (MR) approach to investigate the causal relationship between systemic inflammatory cytokines and myeloproliferative neoplasms. METHODS: A genome-wide association study (GWAS) of 8293 European participants identified genetic instrumental variables for circulating cytokines and growth factors. Summary statistics of MPN were obtained from a GWAS including 1086 cases and 407,155 controls of European ancestry. The inverse-variance-weighted method was mainly used to compute odds ratios (OR) and 95% confidence intervals (Cl). RESULTS: Our results showed that higher Interleukin-2 receptor, alpha subunit (IL-2rα) levels, and higher Interferon gamma-induced protein 10 (IP-10) levels were associated with an increased risk of MPN (OR = 1.36,95%CI = 1.03-1.81, P = 0.032; OR = 1.55,95%CI = 1.09-2.22, P = 0.015; respectively).In addition, Genetically predicted MPN promotes expression of the inflammatory cytokines interleukin-10 (IL-10) (BETA = 0.033, 95% CI = 0.003 ~ 0.064, P = 0.032) and monokine induced by interferon-gamma (MIG) (BETA = 0.052, 95% CI = 0.002-0.102, P = 0.043) and, on activation, normal T cells express and secrete RANTES (BETA = 0.055, 95% CI = 0.0090.1, P = 0.018). CONCLUSION: Our findings suggest that cytokines are essential to the pathophysiology of MPN. More research is required if these biomarkers can be used to prevent and treat MPN.

Directional region-based feature point matching algorithm based on SURF.

Feature point matching is one of the fundamental tasks in binocular vision. It directly affects the accuracy and quality of 3D reconstruction. This study proposes a directional region-based feature point matching algorithm based on the SURF algorithm to improve the accuracy of feature point matching. First, same-name points are selected as the matching reference points in the left and right images. Then, the SURF algorithm is used to extract feature points and construct the SURF feature point descriptors. During the matching process, the location relationship between the query feature point and the reference point in the left image is directed to determine the corresponding matching region in the right image. Then, the matching is completed within this region based on Euclidean distance. Finally, the grid-based motion statistics algorithm is used to eliminate mismatches. Experimental results show that the proposed algorithm can substantially improve the matching accuracy and the number of valid matched points, particularly in the presence of a large amount of noise and interference. It also exhibits good robustness and stability.

Exosome miRNA-203 promotes M1 macrophage polarization and inhibits prostate cancer tumor progression.

Prostate cancer (PCa) is a prevalent malignant neoplasm affecting the male reproductive system globally. However, the diagnostic and therapeutic approaches fall short of meeting the demands posed by PCa. Poor expression of miRNA-203 (miR-203) within PCa tissues and cells implies its potential utility as a diagnostic indicator for PCa. Exosomes (Exo), membranous vesicles released by various cells, are rich reservoirs of miRNAs. However, the presence of miR-203 presents within Exo derived from PCa cells remains unclarified. In this study, Exo was isolated from urine specimens collected from clinical PCa patients and LNCaP cells to detect miR-203 expression. Meanwhile, the impact of overexpressed miR-203 on M0 macrophages (mø) was analyzed. Subsequently, alterations in the proliferative, migratory, and invasive capacities of LNCaP cells were examined within a co-culture system featuring elevated miR-203 levels in both macrophages and LNCaP cells. Furthermore, the repercussions of miR-203 upregulation or inhibition were explored in a murine PCa tumor model. The results revealed that Exo manifested a circular or elliptical morphology, encapsulating a phospholipid bilayer approximately 100 nm in diameter. Notably, Exo readily infiltrated, with both Exo and miR-203-overexpressing Exo prompting macrophage polarization toward the M1 subtype. In the co-culture system, miR-203 exhibited pronounced suppression of LNCaP cell proliferation, migration, and invasion, while concurrently fostering apoptosis as compared with the LNCaP group (Control). In vivo experiments further disclosed that miR-203 greatly inhibited the growth of PCa tumors in nude mice. Markedly heightened expression of M1 macrophage markers such as IL-1ß, IL-6, IL-12, CXCL9, and CXCL10 was observed within the tumor microenvironment following miR-203 intervention, as opposed to the model group. However, the introduction of miR-203 antagomir led to a reversal in tumor growth trends. This investigation indicates the presence of miR-203 within the urine of PCa patients and Exo originating from cells, and that miR-203 exerted antitumor effect by facilitating M1 macrophage polarization. Our study furnishes valuable insights into the potential applicability of miR-203 as a diagnostic biomarker and therapeutic target for PCa.

Orelabrutinib for the treatment of relapsed or refractory marginal zone lymphoma: A phase 2, multicenter, open-label study.

Marginal zone lymphoma (MZL) is an indolent type of non-Hodgkin lymphoma that develops through pathological B cell receptor signaling. Orelabrutinib, a new-generation oral small molecule Bruton's tyrosine kinase inhibitor, was evaluated in relapsed/refractory (r/r) MZL patients. Previously treated r/r MZL patients received orelabrutinib 150 mg once daily in a phase 2, multicenter, single-arm study conducted in China. The primary endpoint was overall response rate (ORR) assessed by an Independent Review Committee (IRC) based on the Lugano 2014 classification. Other efficacy, safety, and pharmacokinetic profiles were evaluated as secondary outcome measures. A total of 111 patients were enrolled, of which 90 patients had MZL confirmed by central pathology review, who were mainly with extra-nodal MZL of mucosa-associated lymphoid tissue (MALT, 46.7%) and nodal MZL (35.6%). The majority had late-stage disease, with stage IV accounting for 75.6%. After a median follow-up duration of 24.3 months, the IRC-assessed ORR was 58.9% (95% confidence interval [CI], 48.0-69.2), with rates of complete response and partial response being 11.1% and 47.8%, respectively. The IRC-assessed median duration of response was 34.3 months, and the IRC-assessed median progression-free survival (PFS) was not reached with a 12-month PFS rate of 82.8% (95% CI, 72.6-89.5). The rate of overall survival at 12 months was 91.0% (95% CI, 82.8-95.4). Common all-grade treatment-related adverse events (TRAEs) included anemia (27.9%), neutrophil count decrease (23.4%), white blood cell count decrease (18.0%), platelet count decrease (17.1%), blood present in urine (16.2%), rash (14.4%), and upper respiratory tract infection (10.8%). Thirty-four patients (30.6%) experienced grade 3 or higher TRAEs. Serious TRAEs occurred in 18 patients (16.2%), of which pneumonia (5.4%) was the most common. Seven patients (6.3%) discontinued orelabrutinib due to TRAEs. Orelabrutinib demonstrated high response rates with durable disease remission and was well tolerated in Chinese patients with r/r MZL.

Iron chelation of hetrombopag in aplastic anemia: a post hoc analysis of a phase II study.

Hetrombopag is the only CFDA-approved thrombopoietin (TPO) receptor agonist for severe aplastic anemia (SAA) in China. Its chemical structure has an iron chelation domain. To explore the iron chelation effect of hetrombopag, we performed a post hoc analysis of the phase II clinical trial (NCT03557099). Thirty-five immunosuppressive therapy (IST)-refractory SAA patients were enrolled in the study, and the longitudinal changes of serum ferritin (SF) were assessed. At 18 weeks post-hetrombopag initiation, 51.4% of patients showed decreased SF levels by a median of 49.0 (18.1-95.5) % from baseline (median ΔSF decrease value, 917.2 ng/ml, range from 104.0 to 7030.0 ng/ml). A decrease in SF was found in 75.0% of hematologic responders and 31.6% of non-responders. Among the 24 patients with iron overload, 12 had decreased SF levels by up to 51% of the baseline. Patients with normal SF levels also showed decreased SF levels, and iron deficiency occurred in two patients. In conclusion, hetrombopag showed a powerful and rapid iron chelation effect.

Zinc in cereal grains: Concentration, distribution, speciation, bioavailability, and barriers to transport from roots to grains in wheat.

Zinc (Zn) is an essential micro-nutrient for humans, and Zn deficiency is of global concern. In addition to inherited and pathological Zn deficiencies, insufficient dietary intake is leading cause, especially in those consuming cereal grains as a stable food, in which Zn concentration and bioavailability are relatively low. To improve Zn levels in the human body, it is important to understand the accumulation and bioavailability of Zn in cereal grains. In recent years, knowledge on the molecular mechanisms underlying Zn uptake, transport, homeostasis, and deposition within cereal crops has been accumulating, paving the way for a more targeted approach to improving the nutrient status of crop plants. In this paper, we briefly review existing studies on the distribution and transport pathways of Zn in major small-grained cereals, using wheat as a case study. The findings confirm that Zn transport in plants is a complex physiological process mainly governed by Zn transporters and metal chelators. This work reviews studies on Zn uptake, transport, and deposition in wheat plants, summarizes the possible barriers impairing Zn deposition in wheat grains, and describes strategies for increasing Zn concentration in wheat grains.

Reduction in daily ambient PM2.5 pollution and potential life gain by attaining WHO air quality guidelines in Tehran.

BACKGROUND: Fine particulate matter pollution (PM2.5) is widely considered to be a top-ranked risk factor for premature mortality and years of life lost (YLL). However, evidence regarding the effect of daily air quality improvement on life expectancy is scarce, especially in the Middle East such as Iran. This study aimed to investigate the potential benefits in life expectancy at concentrations meeting the daily PM2.5 standards during 2012-2016 in Tehran, Iran. METHODS: We collected daily non-accidental mortality and data on air pollutants and weather conditions from Tehran, Iran, 2012-2016. A quasi-Poisson or Gaussian time-series regression was employed to fit the associations between ambient PM2.5 and mortality or YLL. Potential gains in life expectancy (PGLE) and attributable fraction (AF) were estimated by assuming that daily PM2.5 concentrations attained the World Health Organization air quality guidelines (WHO AQG) 2005 (25 µg/m3) and 2021 (15 µg/m3). RESULTS: During the study period, a total of 221,231 non-accidental deaths were recorded in Tehran, resulting in 3.6 million YLL. The mean concentration of ambient PM2.5 was 34.7 µg/m3 (standard deviation: 15.3 µg/m3). For a 10-µg/m3 rise in 4-day moving average (lag 03-day) in PM2.5 concentration, non-accidental mortality and YLL increased by 1.12% (95% confidence interval: 0.60, 1.65) and 20.73 (7.08, 34.39) person years, respectively. A relatively higher effect was observed in males and young adults aged 18-64 years. We estimated that 39830 [AF = 1.1%] and 74284 [AF = 2.1%] YLL could potentially be avoided if daily PM2.5 concentrations attained the WHO AQG 2005 and 2021, respectively, which corresponded to potential gains in life expectancy of 0.18 (0.06, 0.30) and 0.34 (0.11, 0.56) years for each deceased person. PM2.5-associated PGLE estimates were largely robust when performing sensitivity analyses. CONCLUSIONS: Our findings indicated that short-term exposure to PM2.5 is associated with increased non-accidental YLL and mortality. Prolonged life expectancy could be achieved if the particulate matter air pollution level were kept under a stricter standard.

Genetic and immune changes in Tibetan high-altitude populations contribute to biological adaptation to hypoxia.

BACKGROUND: Tibetans have lived at very high altitudes for thousands of years, and have a distinctive suite of physiological traits that enable them to tolerate environmental hypoxia. Expanding awareness and knowledge of the differences in hematology, hypoxia-associated genes, immune system of people living at different altitudes and from different ethnic groups may provide evidence for the prevention of mountain sickness. METHOD: Ninety-five Han people at mid-altitude, ninety-five Tibetan people at high-altitude and ninety-eight Han people at high-altitude were recruited. Red blood cell parameters, immune cells, the contents of cytokines, hypoxia-associated gene single nucleotide polymorphisms (SNPs) were measured. RESULTS: The values of Hematocrit (HCT), Mean cell volume (MCV) and Mean cell hemoglobin (MCH) in red blood cell, immune cell CD19+ B cell number, the levels of cytokines Erb-B2 receptor tyrosine kinase 3 (ErbB3) and Tumor necrosis factor receptor II (TNF-RII) and the levels of hypoxia-associated factors Hypoxia inducible factor-1α (HIF-1α), Hypoxia inducible factor-2α (HIF-2α) and HIF prolyl 4-hydroxylase 2 (PHD2) were decreased, while the frequencies of SNPs in twenty-six Endothelial PAS domain protein 1 (EPAS1) and Egl-9 family hypoxia inducible factor 1 (EGLN1) were increased in Tibetan people at high-altitude compared with that of Han peoples at high-altitude. Furthermore, compared with mid-altitude individuals, high-altitude individuals showed lower blood cell parameters including Hemoglobin concentration (HGB), HCT, MCV and MCH, higher Mean cell hemoglobin concentration (MCHC), lower immune cells including CD19+ B cells, CD4+ T cells and CD4/CD8 ratio, higher immune cells containing CD8+ T cells and CD16/56NK cells, decreased Growth regulated oncogene alpha (GROa), Macrophage inflammatory protein 1 beta (MIP-1b), Interleukin-8 (IL-8), and increased Thrombomodulin, downregulated hypoxia-associated factors including HIF1α, HIF2α and PHD2, and higher frequency of EGLN1 rs2275279. CONCLUSIONS: These results indicated that biological adaption to hypoxia at high altitude might have been mediated by changes in immune cells, cytokines, and hypoxia-associated genes during the evolutionary history of Tibetan populations. Furthermore, different responses to high altitude were observed in different ethnic groups, which may provide a useful knowledge to improve the protection of high-altitude populations from mountain sickness.

Risk stratification and outcomes of intracranial hemorrhage in patients with immune thrombocytopenia under 60 years of age.

Intracranial hemorrhage (ICH) is a devastating complication of immune thrombocytopenia (ITP). However, information on ICH in ITP patients under the age of 60 years is limited, and no predictive tools are available in clinical practice. A total of 93 adult patients with ITP who developed ICH before 60 years of age were retrospectively identified from 2005 to 2019 by 27 centers in China. For each case, 2 controls matched by the time of ITP diagnosis and the duration of ITP were provided by the same center. Multivariate analysis identified head trauma (OR = 3.216, 95%CI 1.296-7.979, P =.012), a platelet count ≤ 15,000/µL at the time of ITP diagnosis (OR = 1.679, 95%CI 1.044-2.698, P =.032) and severe/life-threatening bleeding (severe bleeding vs. mild bleeding, OR = 1.910, 95%CI 1.088-3.353, P =.024; life-threatening bleeding vs. mild bleeding, OR = 2.620, 95%CI 1.360-5.051, P =.004) as independent risk factors for ICH. Intraparenchymal hemorrhage (OR = 5.191, 95%CI 1.717-15.692, P =.004) and a history of severe bleeding (OR = 4.322, 95%CI 1.532-12.198, P =.006) were associated with the 30-day outcome of ICH. These findings may facilitate ICH risk stratification and outcome prediction in patients with ITP.

miR-499a inhibits the proliferation and apoptosis of prostate cancer via targeting UBE2V2.

BACKGROUND: Prostate cancer is one of the malignant tumors of the urinary system and ranks second among the fatal cancers in men. And with age, the incidence of prostate cancer will increase linearly. METHODS: In this study, we measured the expression of Ubiquitin Conjugating Enzyme E2 V2 (UBE2V2) in prostate cancer tissues and cell lines by WB and explored the effect of UBE2V2 on the proliferation characteristics of prostate cancer by MTT and colony formation test. RESULTS: In our research, we found that the UBE2V2 protein level in prostate cancer cell lines was significantly higher than the UBE2V2 protein level in normal prostate cells, and the mRNA expression level did not change significantly compared with normal prostate tissue cells. At the same time, we found that miR-499a combined with UBE2V2 inhibited the expression of UBE2V2 in prostate cancer cells. CONCLUSIONS: In conclusion, our results indicate that miR-499a inhibits the proliferation of human prostate cancer cells by targeting UBE2V2, which will provide a potential target for the treatment of prostate cancer.

ATBdiscrimination: An in Silico Tool for Identification of Active Tuberculosis Disease Based on Routine Blood Test and T-SPOT.TB Detection Results.

Tuberculosis remains one of the deadliest infectious diseases worldwide. Only 5-15% of people infected with Mycobacterium tuberculosis develop active TB disease (ATB), while others remain latently infected (LTBI) during their lifetime, which has a completely different clinical treatment schedule. However, most current clinical diagnostic methods are based on the immune response of M. tuberculosis infections and cannot distinguish ATB from LTBIs. Thus, the rapid diagnosis of active or latent tuberculosis infections remains a serious challenge for clinicians. In this work, based on the test data of a total of 478 patients, 36 blood biochemical data were specially included with T-SPOT.TB detection results which are all from routine clinical practice as commercially available. Then a discrimination method to detect ATB infections was successfully developed based on these data by the random forest algorithm. This method presents a robust classification performance with AUC as 0.9256 and 0.8731 for the cross-validation set and the external validation set, respectively. This work suggests an innovative strategy for identification of ATB disease from a single drop of blood with advantages of being timely, efficient, and economical. It also provides valuable information for the comprehensive understanding of TB with deep associations between TB infection and routine blood test data. The web server of this identification method, called ATBdiscrimination, is now available online at http://lishuyan.lzu.edu.cn/ATB/ATBdiscrimination.html .

Development of a High-Sensitivity Optical Accelerometer for Low-Frequency Vibration Measurement.

Low-frequency vibration is a harmful factor that affects the accuracy of micro/nano-measuring machines. Low-frequency vibration cannot be completely eliminated by passive control methods, such as the use of air-floating platforms. Therefore, low-frequency vibrations must be measured before being actively suppressed. In this study, the design of a low-cost high-sensitivity optical accelerometer is proposed. This optical accelerometer mainly comprises three components: a seismic mass, a leaf spring, and a sensing component based on a four-quadrant photodetector (QPD). When a vibration is detected, the seismic mass moves up and down due to the effect of inertia, and the leaf spring exhibits a corresponding elastic deformation, which is amplified by using an optical lever and measured by the QPD. Then, the acceleration can be calculated. The resonant frequencies and elastic coefficients of various seismic structures are simulated to attain the optimal detection of low-frequency, low-amplitude vibration. The accelerometer is calibrated using a homemade vibration calibration system, and the calibration experimental results demonstrate that the sensitivity of the optical accelerometer is 1.74 V (m·s-2)-1, the measurement range of the accelerometer is 0.003⁻7.29 m·s-2, and the operating frequencies range of 0.4⁻12 Hz. The standard deviation from ten measurements is under 7.9 × 10-4 m·s-2. The efficacy of the optical accelerometer in measuring low-frequency, low-amplitude dynamic responses is verified.

[Procalcitonin impact analysis, respiratory function and blood gas analysis on Xiaoqinglong decoction combined with non-invasive ventilation in treatment of AECOPD patients].

To observe the effect of Xiaoqinglong decoction combined with noninvasive ventilation on procalcitonin (PCT), blood gas analysis and respiratory functions in acute exacerbation of chronic obstructive pulmonary disease in the elderly (AECOPD), and investigate its correlation and clinical significance. Eighty-four elderly AECOPD patients with respiratory failure in our hospital from January 2015 to October 2017, were randomly divided into control group and observation group, 42 cases in each group. The control group received western medicine combined with noninvasive ventilator therapy, and the patients in observation group additionally received Xiaoqinglong decoction on the basis of the treatment in control group. Both groups were treated for 2 weeks. The clinical effects of two groups were observed and their PCT, blood gas analysis outcomes [arterial oxygen partial pressure (PaO2), arterial partial pressure of carbon dioxide (PaCO2), respiratory function, forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), FEV1/FVC], TCM syndrome score and other indexes and adverse reactions were compared before and after treatment. The total efficiency was 95.24% (40/42) in observation group, higher than 76.19% (32/42) in control group, with statistically significant difference (P<0.05). There were no statistically significant differences in PCT, PaO2, PaCO2, FVC, FEV1/FVC, FEV1, and TCM syndrome scores between two groups before treatment. But after treatment, PCT and PaCO2 levels in the observation group were lower and PaO2, FVC, FEV1/FVC, FEV1 levels was higher than those in the control group (P<0.05); TCM syndrome scores were lower than those in the control group (P<0.05); both groups had no obvious adverse reactions. The results showed that Xiaoqinglong decoction combined with noninvasive ventilator could significantly reduce the procalcitonin level, effectively improve the respiratory function and blood gas analysis indexes, and significantly reduce the clinical symptoms in AECOPD patients, so it is worthy of promotion.

Prognostic Significance of Monocytes and Monocytic Myeloid-Derived Suppressor Cells in Diffuse Large B-Cell Lymphoma Treated with R-CHOP.

BACKGROUND/AIMS: To evaluate the prognostic significance of monocytes and monocytic myeloid-derived suppressor cells (M-MDSCs) for patients with diffuse large B-cell lymphoma (DLBCL) under R-CHOP chemotherapy. METHODS: Flow cytometry (FCM) was applied to measure M-MDSCs (CD14+ HLA-DRlow/- M-MDSCs). RESULTS: Analysis of 144 patients with DLBCL under R-CHOP treatment showed that the 5-year overall survival rate was 61.09% (95% CI: 43.72%-72.56%) and the average survival time of patients with monocytes (%) ≥ 8% was shorter than those with monocytes (%) < 8% (P = 0.0036). Further stratified analysis suggested that the average survival time of patients with monocytes (%) ≥ 8% was shorter than patients with monocytes (%) < 8% in the moderate outcome group (R-IPI = 1, 2) (P = 0.0168) and in the poorest outcome group (R-IPI > 2) (P = 0.0397), meanwhile, there was no significant difference in survival of patients with monocytes (%) ≥ 8% compared to patients with monocytes (%) < 8% in the best outcome group (R-IPI = 0) (P = 0.3106). Both of monocytes (%) and M-MDSCs were decreased in different R-IPI groups after 4-course of R-CHOP chemotherapy (P < 0.05). CONCLUSION: Our results indicated that monocytes (%) and M-MDSCs combined with R-IPI may be a simple and efficient immunological index to evaluate prognosis.

Therapeutic outcomes of canal wall up mastoidectomy in combination with Type I tympanoplasty in otitis media.

OBJECTIVE: To evaluate the therapeutic effects in terms of disease clearance and hearing improvement of canal wall up mastoidectomy in combination with Type I tympanoplasty in otitis media. METHODS: A total of 78 patients (81 ears) with otitis media were treated by canal wall up mastoidectomy in combination with Type I tympanoplasty. The postoperative tympanic membrane morphology, average of pure-tone hearing thresholds and average air-bone gap were used as the indices for evaluating therapeutic effects. RESULTS: The patients were followed up for two years in average. All the tympanic membranes recovered, with the ear canals being dry. There were five cases (5 ears) of tympanic membrane retraction and one case of otitis media recurrence. Hearing was effectively recovered by 76.54% (62/81) after surgery. CONCLUSION: Combining canal wall up mastoidectomy with Type I tympanoplasty can treat otitis media safely and effectively due to high postoperative dry ear canal rate, satisfactory reconstruction of hearing and maintenance of ear morphology.

Efficacy of porcine antihuman lymphocyte immunoglobulin compared to rabbit antithymocyte immunoglobulin as a first-line treatment against acquired severe aplastic anemia.

Immunosuppressive therapy (IST) with antithymocyte immunoglobulin (ATG) or antilymphocyte immunoglobulin (ALG) and cyclosporine A (CsA) is the treatment of choice against severe aplastic anemia (SAA) worldwide. However, a comparison of the efficacy of porcine ALG (pALG) and rabbit ATG (rATG) as a first-line treatment for acquired SAA has not been reported. In the present study, we retrospectively analyzed SAA patients treated with either pALG (n = 43) or rATG (n = 32) and compared their hematologic responses and survivals. There were no significant differences in overall response (OR) rates between pALG and rATG groups at 3 months (OR 41.86 versus 40.62% (P = 0.914), 6 months (OR 66.67 versus 61.29% (P = 0.635), 9 months (OR 69.05 versus 61.29% (P = 0.490), or 12 months (OR 69.05 versus 64.51% (P = 0.684), respectively. The OR rates in patients with SAA or very severe aplastic anemia (vSAA) in both groups were similar after a 12-month treatment (pALG 74.07 versus 60.00%, P = 0.550; rATG 70.00 versus 54.55%, P = 0.640). Patients who experienced <30-day interval between diagnosis and treatment displayed higher OR rates (at 12 months) than those with intervals ≥30 days (pALG 83.33 versus 50.00%, P = 0.021; rATG 87.50 versus 40.00%, P = 0.006). There were no significant differences in 2-year overall survival (OS) between pALG (87.4 ± 6.2%) and rATG (83.2 ± 7.8%) (P = 0.493). Infection was the major cause of death in both groups. In summary, pALG + CsA showed similar efficacy as rATG + CsA, as a first-line treatment for acquired SAA.

Association between the hearing aid and mental health outcomes in people with hearing impairment: A case-control study among 28 European countries.

BACKGROUND: Hearing loss affects over 1.5 billion individuals globally, with significant implications for mental health. This study investigates the association between hearing aid use and mental health outcomes, by particularly focusing on depression and unmet mental health needs (UMHN), across a diverse international sample. METHODS: Utilizing data from the third wave of the European Health Interview Survey (EHIS), this study involved 17,660 participants with hearing impairment from 28 countries. The study examined the association between hearing aid use and mental health outcomes, including the likelihood of moderate and severe depression and UMHN due to lack of contact with general practitioners (GPs) and mental health specialists. Logistic regression models, adjusted for socio-demographic characteristics, health risk behaviours, and other relevant variables, were employed. Inverse probability weights were used to mitigate potential selection bias. RESULTS: Hearing aid usage was associated with significantly lower likelihoods of moderate depression (Odds Ratio [OR] = 0.58, 95%CI = [0.54, 0.63]) and severe depression (OR = 0.61, 95%CI = [0.55, 0.69]), compared to non-usage. Hearing aid usage was also associated with reduced UMHN due to lack of GP contact for moderate (OR = 0.82, 95%CI = [0.75, 0.89]) and severe depression (OR = 0.75, 95%CI = [0.59, 0.95]). The depression risk reductions were greater among females and higher-educated subgroups but lower in individuals aged ≥65 years. Income level and rurality also impacted UMHN due to the lack of GP contact. No associations were found between hearing aids and UMHN due to the lack of mental health specialist contact. CONCLUSIONS: Hearing aid adoption showed protective associations against mood disorders and lowered unmet primary mental healthcare needs. Tailoring intervention strategies to vulnerable sociodemographic profiles could optimize mental health benefits among those with hearing loss. Integrating hearing health services within mental healthcare delivery frameworks is vital amidst the rising global burden.

Lycorine attenuated proliferation and induced apoptosis on imatinib-resistant K562 cell by inhibiting autophagy.

BACKGROUND: Tyrosine kinase inhibitor (TKI) resistance is a significant factor exacerbating the burden on chronic myeloid leukemia (CML) patients and impacting clinical efficacy. The main goal is to offer new insights into overcoming drug resistance in treating CML. METHODS: Imatinib (IM) resistant K562/IM cells were generated using gradient induction. Responses to IM, lycorine, and autophagy modulators were assessed using CCK-8. Protein expression of Beclin-1, Atg5, LC3, Caspase-3, P62, Bax, Bcl-2, and P-gp was detected using Western blot. Lycorine-induced apoptosis and cell cycle changes were evaluated through flow cytometry, while autophagy alterations were detected using monodansylcadaverine (MDC) staining. In the K562/IM mice model, non-obese diabetic severe combined immunodeficent (NOD-SCID) mice were subcutaneously inoculated with K562/IM cells. After 17 days of lycorine injection, assessments included tumor size, hematoxylin-eosin (HE) staining, and Ki67 expression. RESULTS: After 72 h of IM treatment, K562/IM cells showed a 55.86-fold increase in drug resistance compared to K562 cells. Lycorine treatment for 24 h inhibited cell proliferation and induced G0/G1 phase cell cycle arrest and apoptosis in both K562 and K562/IM cells. MDC staining indicated reduced autophagy in K562/IM cells, mitigated by lycorine. In vivo experiments demonstrated reduced tumor size and Ki67 proliferation index in the lycorine treatment group (K562+L, K562/IM+L) compared to the control group, particularly in the drug-resistant group. However, no significant change in Ki67 was observed in the K562 group after lycorine treatment. CONCLUSION: In summary, K562/IM cells displayed heightened autophagy levels compared to K562 cells. Lycorine effectively impeded the proliferation of K562/IM cells through diverse mechanisms, including reduced autophagy, enhanced apoptosis, and induced cell cycle arrest.