Impact of COVID-19 pandemic on depression incidence and healthcare service use among patients with depression: an interrupted time-series analysis from a 9-year population-based study.

BACKGROUND: Most studies on the impact of the COVID-19 pandemic on depression burden focused on the earlier pandemic phase specific to lockdowns, but the longer-term impact of the pandemic is less well-studied. In this population-based cohort study, we examined the short-term and long-term impacts of COVID-19 on depression incidence and healthcare service use among patients with depression. METHODS: Using the territory-wide electronic medical records in Hong Kong, we identified all patients aged ≥ 10 years with new diagnoses of depression from 2014 to 2022. We performed an interrupted time-series (ITS) analysis to examine changes in incidence of medically attended depression before and during the pandemic. We then divided all patients into nine cohorts based on year of depression incidence and studied their initial and ongoing service use patterns until the end of 2022. We applied generalized linear modeling to compare the rates of healthcare service use in the year of diagnosis between patients newly diagnosed before and during the pandemic. A separate ITS analysis explored the pandemic impact on the ongoing service use among prevalent patients with depression. RESULTS: We found an immediate increase in depression incidence (RR = 1.21, 95% CI: 1.10-1.33, p < 0.001) in the population after the pandemic began with non-significant slope change, suggesting a sustained effect until the end of 2022. Subgroup analysis showed that the increases in incidence were significant among adults and the older population, but not adolescents. Depression patients newly diagnosed during the pandemic used 11% fewer resources than the pre-pandemic patients in the first diagnosis year. Pre-existing depression patients also had an immediate decrease of 16% in overall all-cause service use since the pandemic, with a positive slope change indicating a gradual rebound over a 3-year period. CONCLUSIONS: During the pandemic, service provision for depression was suboptimal in the face of increased demand generated by the increasing depression incidence during the COVID-19 pandemic. Our findings indicate the need to improve mental health resource planning preparedness for future public health crises.

Global trends in melanoma burden: A comprehensive analysis from the Global Burden of Disease Study, 1990-2021.

BACKGROUND: Melanoma, a significant global health concern, has shown evolving epidemiologic trends. Accurate estimation of melanoma's burden is essential for public health strategies and interventions. OBJECTIVES: This study aims to estimate the incidence, mortality, and disability-adjusted life years for melanoma, stratified by region, gender, and age group, from 1990 to 2021. METHODS: Using data from the Global Burden of Disease 2021, we analyzed melanoma incidence, mortality rates, and disability-adjusted life years in 204 countries from 1990 to 2021. These metrics were age-standardized and stratified by age, sex, Socio-Demographic Index, region, and country. The estimated annual percentage change was calculated to track temporal trends. RESULTS: Our study shows a substantial global increase in melanoma incidence, with significant disparities between genders and age groups. Higher Socio-Demographic Index regions had increased incidence rates, while global mortality declined, likely due to improved detection and treatment. LIMITATIONS: The reliance on estimates and models may introduce bias due to variability in disease definitions, diagnostic criteria, and data collection methods. CONCLUSION: This study underscores the dynamic nature of melanoma's burden and the need for targeted, age-specific, and gender-specific interventions. Continued research is essential to address the growing challenges posed by melanoma.

Effects of Tannic Acid Supplementation of a High-Carbohydrate Diet on the Growth, Serum Biochemical Parameters, Antioxidant Capacity, Digestive Enzyme Activity, and Liver and Intestinal Health of Largemouth Bass, Micropterus salmoides.

We investigated the effects of dietary tannic acid (TA) supplementation of a high-carbohydrate diet on growth, feed utilization, whole-body proximate composition, serum biochemical indicators, antioxidant capacity, digestive enzyme activity, and liver and intestinal health of juvenile largemouth bass, Micropterus salmoides (initial mean weight: 8.08 ± 0.08 g). Five diets were prepared, including a positive control (dietary carbohydrate level, 16%, LC0), a negative control (dietary carbohydrate level, 21%, HC0), and three TA-supplementation diets based on the negative control diet with TA addition at 200, 400, and 800 mg/kg, respectively. After 8 weeks of feeding, the results showed that compared with the LC0 diet, 400-800 mg/kg dietary TA significantly improved the survival rate of largemouth bass (P < 0.05) while significantly reducing its weight-gain rate and specific growth rate (P < 0.05). Compared with the HC0 diet, 400 mg/kg dietary TA significantly increased serum catalase activity (P < 0.05), and significantly decreased serum malondialdehyde, liver glycogen, lightness (L ∗), and yellowness (b ∗) (P < 0.05). Moreover, compared with the HC0 diet, 200-400 mg/kg dietary TA effectively improved the vacuolation of hepatocytes caused by the high-carbohydrate diet and reduced the occurrence of intestinal epithelial cell vacuolation and necrosis. In turn, 800 mg/kg dietary TA significantly inhibited protease activity in the pyloric caecum and intestine (P < 0.05). In conclusion, dietary supplementation with TA inhibited protease activity, which resulted in decreased growth performance in largemouth bass. However, it was also found that 200-400 mg/kg TA enhanced the antioxidant capacity of largemouth bass in the case of the high-carbohydrate diet, reduced liver glycogen levels, and improved liver and intestinal health. Finally, it should be noted that, when the dietary TA level exceeded 800 mg/kg, TA appeared to play a pro-oxidation role in the liver, which may cause oxidative stress in the liver.

Polystyrene microplastics enhanced copper-induced acute immunotoxicity in red swamp crayfish (Procambarus clarkii).

Microplastic pollution has attracted a lot of attention in recent years. Not only can it be ingested by animals, but it can easily become a carrier of other pollutants, forming a composite pollutant with potentially toxic effects on organisms. We investigated the effect of Cu on the accumulation of polystyrene microplastics (PS) in the gills of Procambarus clarkii and whether PS exacerbated the immune toxicity of Cu to P. clarkii were exposed to Cu, PS and PS+Cu for 48 h, the accumulation of PS in gill and hepatopancreas immune and antioxidant indices were analyzed. The objective was to investigate the toxic effects of Ps and Cu compound pollutants on P. clarkii and whether the accumulated pollutants would cause food safety problems. The results showed that microplastic particles adhered to each other and aggregated in the PS+Cu group, and the number of microplastic particles in gill in the PS+Cu group was significantly lower than that in the PS group. Compared with the other two treatment groups, SOD, CAT, GPx activities and MDA content increased significantly in the PS+Cu group and were relatively delayed. At 12 h, 24 h, 36 h and 48 h, the SOD mRNA expression levels in the PS+Cu group were all significantly lower than those in the Cu group (P < 0.05). At 24 h and 48 h, CAT mRNA expression in the PS+Cu group was significantly higher than that in the Cu group (P < 0.05). Crustin 4 mRNA expressions in the PS+Cu group was significantly higher than that in the Cu group at 12 h and 36 h (P < 0.05). The results demonstrate that the PS and Cu compound reduced the accumulation of microplastic particles in the gill. PS particles delayed Cu entry into P. clarkii for a short time (12 h) and reduced the toxic effect, but with the increase of exposure time (24 h and 48 h), the toxic effect of PS and Cu complexes on P. clarkii increases, and the large accumulation of PS and Cu complexes may cause food safety problems.

Synthetic High-Density Lipoprotein-Based Nanomedicine to Silence SOCS1 in Tumor Microenvironment and Trigger Antitumor Immunity against Glioma.

Immunotherapies have shed light on the treatment of many cancers, but have not improved the outcomes of glioma (GBM). Here, we demonstrated that suppressor of cytokine signaling 1 (SOCS1) was associated with the GBM-associated immunosuppression and developed a multifunctional nanomedicine, which silenced SOCS1 in the tumor microenvironment (TME) of GBM and triggered strong antitumor immunity against GBM. Synthetic high-density lipoprotein (sHDL) was selected as the nanocarrier and a peptide was used to facilitate the blood-brain-barrier (BBB) penetration. The nanocarrier was loaded with a small interfering RNA (siRNA), a peptide, and an adjuvant to trigger antitumor immunity. The nanomedicine concentrated on the TME in vivo, further promoting dendritic cell maturation and T cell proliferation, triggering strong cytotoxic T lymphocyte responses, and inhibiting tumor growth. Our work provides an alternative strategy to simultaneously target and modulate the TME in GBM patients and points to an avenue for enhancing the efficacy of immunotherapeutics.

Predictive factors of nonfatal self-harm among community-dwelling older adults assessed for support services.

BACKGROUND: Older adults receiving support services are a population at risk for self-harm due to physical illness and functional impairment, which are known risk factors. This study aims to investigate the relative importance of predictive factors of nonfatal self-harm among older adults assessed for support services in New Zealand. METHODS: interRAI-Home Care (HC) national data of older adults (aged ≥ 60) were linked to mortality and hospital discharge data between January 1, 2012 and December 31, 2016. We calculated the crude incidence of self-harm per 100,000 person-years, and gender and age-adjusted standardized incidence ratios (SIRs). The Fine and Gray competing risk regression model was fitted to estimate the hazard ratio (HR; 95% CIs) of self-harm associated with various demographic, psychosocial, clinical factors, and summary scales. RESULTS: A total of 93,501 older adults were included. At the end of the follow-up period, 251 (0.27%) people had at least one episode of nonfatal self-harm and 36,333 (38.86%) people died. The overall incidence of nonfatal self-harm was 160.39 (95% CI, 141.36-181.06) per 100,000 person-years and SIR was 5.12 (95% CI, 4.51-5.78), with the highest incidence in the first year of follow-up. Depression diagnosis (HR, 3.02, 2.26-4.03), at-risk alcohol use (2.38, 1.30-4.35), and bipolar disorder (2.18, 1.25-3.80) were the most significant risk factors. Protective effects were found with cancer (0.57, 0.36-0.89) and severe level of functional impairment measured by Activities of Daily Living (ADL) Hierarchy Scale (0.56, 0.35-0.89). CONCLUSION: Psychiatric factors are the most significant predictors for nonfatal self-harm among older adults receiving support services. Our results can be used to inform healthcare professionals for timely identification of people at high risk of self-harm and the development of more efficient and targeted prevention strategies, with specific attention to individuals with depression or depressive symptoms, particularly in the first year of follow-up.

Once-per-week selinexor, bortezomib, and dexamethasone versus twice-per-week bortezomib and dexamethasone in patients with multiple myeloma (BOSTON): a randomised, open-label, phase 3 trial.

BACKGROUND: Selinexor combined with dexamethasone has shown activity in patients with heavily pre-treated multiple myeloma. In a phase 1b/2 study, the combination of oral selinexor with bortezomib (a proteasome inhibitor) and dexamethasone induced high response rates with low rates of peripheral neuropathy, the main dose-limiting toxicity of bortezomib. We aimed to evaluate the clinical benefit of weekly selinexor, bortezomib, and dexamethasone versus standard bortezomib and dexamethasone in patients with previously treated multiple myeloma. METHODS: This phase 3, randomised, open-label trial was done at 123 sites in 21 countries. Patients aged 18 years or older, who had multiple myeloma, and who had previously been treated with one to three lines of therapy, including proteasome inhibitors, were randomly allocated (1:1) to receive selinexor (100 mg once per week), bortezomib (1·3 mg/m2 once per week), and dexamethasone (20 mg twice per week), or bortezomib (1·3 mg/m2 twice per week for the first 24 weeks and once per week thereafter) and dexamethasone (20 mg four times per week for the first 24 weeks and twice per week thereafter). Randomisation was done using interactive response technology and stratified by previous proteasome inhibitor therapy, lines of treatment, and multiple myeloma stage. The primary endpoint was progression-free survival in the intention-to-treat population. Patients who received at least one dose of study treatment were included in the safety population. This trial is registered at ClinicalTrials.gov, NCT03110562. The trial is ongoing, with 55 patients remaining on randomised therapy as of Feb 20, 2020. FINDINGS: Of 457 patients screened for eligibility, 402 were randomly allocated-195 (49%) to the selinexor, bortezomib, and dexamethasone group and 207 (51%) to the bortezomib and dexamethasone group-and the first dose of study medication was given between June 6, 2017, and Feb 5, 2019. Median follow-up durations were 13·2 months [IQR 6·2-19·8] for the selinexor, bortezomib, and dexamethasone group and 16·5 months [9·4-19·8] for the bortezomib and dexamethasone group. Median progression-free survival was 13·93 months (95% CI 11·73-not evaluable) with selinexor, bortezomib, and dexamethasone and 9·46 months (8·11-10·78) with bortezomib and dexamethasone (hazard ratio 0·70 [95% CI 0·53-0·93], p=0·0075). The most frequent grade 3-4 adverse events were thrombocytopenia (77 [39%] of 195 patients in the selinexor, bortezomib, and dexamethasone group vs 35 [17%] of 204 in the bortezomib and dexamethasone group), fatigue (26 [13%] vs two [1%]), anaemia (31 [16%] vs 20 [10%]), and pneumonia (22 [11%] vs 22 [11%]). Peripheral neuropathy of grade 2 or above was less frequent with selinexor, bortezomib, and dexamethasone (41 [21%] patients) than with bortezomib and dexamethasone (70 [34%] patients; odds ratio 0·50 [95% CI 0·32-0·79], p=0·0013). 47 (24%) patients in the selinexor, bortezomib, and dexamethasone group and 62 (30%) in the bortezomib and dexamethasone group died. INTERPRETATION: A once-per-week regimen of selinexor, bortezomib, and dexamethasone is a novel, effective, and convenient treatment option for patients with multiple myeloma who have received one to three previous lines of therapy. FUNDING: Karyopharm Therapeutics.

Effect of age and frailty on the efficacy and tolerability of once-weekly selinexor, bortezomib, and dexamethasone in previously treated multiple myeloma.

Elderly and frail patients with multiple myeloma (MM) are more vulnerable to the toxicity of combination therapies, often resulting in treatment modifications and suboptimal outcomes. The phase 3 BOSTON study showed that once-weekly selinexor and bortezomib with low-dose dexamethasone (XVd) improved PFS and ORR compared with standard twice-weekly bortezomib and moderate-dose dexamethasone (Vd) in patients with previously treated MM. This is a retrospective subgroup analysis of the multicenter, prospective, randomized BOSTON trial. Post hoc analyses were performed to compare XVd versus Vd safety and efficacy according to age and frailty status (<65 and ≥65 years, nonfrail and frail). Patients ≥65 years with XVd had higher ORR (OR 1.77, p = .024), ≥VGPR (OR, 1.68, p = .027), PFS (HR 0.55, p = .002), and improved OS (HR 0.63, p = .030), compared with Vd. In frail patients, XVd was associated with a trend towards better PFS (HR 0.69, p = .08) and OS (HR 0.62, p = .062). Significant improvements were also observed in patients <65 (ORR and TTNT) and nonfrail patients (PFS, ORR, ≥VGPR, and TTNT). Patients treated with XVd had a lower incidence of grade ≥ 2 peripheral neuropathy in ≥65 year-old (22% vs. 37%; p = .0060) and frail patients (15% vs. 44%; p = .0002). Grade ≥3 TEAEs were not observed more often in older compared to younger patients, nor in frail compared to nonfrail patients. XVd is safe and effective in patients <65 and ≥65 and in nonfrail and frail patients with previously treated MM.

Selinexor, bortezomib, and dexamethasone versus bortezomib and dexamethasone in previously treated multiple myeloma: Outcomes by cytogenetic risk.

In the phase 3 BOSTON study, patients with multiple myeloma (MM) after 1-3 prior regimens were randomized to once-weekly selinexor (an oral inhibitor of exportin 1 [XPO1]) plus bortezomib-dexamethasone (XVd) or twice-weekly bortezomib-dexamethasone (Vd). Compared with Vd, XVd was associated with significant improvements in median progression-free survival (PFS), overall response rate (ORR), and lower rates of peripheral neuropathy, with trends in overall survival (OS) favoring XVd. In BOSTON, 141 (35.1%) patients had MM with high-risk (presence of del[17p], t[4;14], t[14;16], or ≥4 copies of amp1q21) cytogenetics (XVd, n = 70; Vd, n = 71), and 261 (64.9%) exhibited standard-risk cytogenetics (XVd, n = 125; Vd, n = 136). Among patients with high-risk MM, median PFS was 12.91 months for XVd and 8.61 months for Vd (HR, 0.73 [95% CI, (0.4673, 1.1406)], p = 0.082), and ORRs were 78.6% and 57.7%, respectively (OR 2.68; p = 0.004). In the standard-risk subgroup, median PFS was 16.62 months for XVd and 9.46 months for Vd (HR 0.61; p = 0.004), and ORRs were 75.2% and 64.7%, respectively (OR 1.65; p = 0.033). The safety profiles of XVd and Vd in both subgroups were consistent with the overall population. These data suggest that selinexor can confer benefits to patients with MM regardless of cytogenetic risk. ClinicalTrials.gov identifier: NCT03110562.

Identifying COVID-19 cases in outpatient settings.

Case identification is an ongoing issue for the COVID-19 epidemic, in particular for outpatient care where physicians must decide which patients to prioritise for further testing. This paper reports tools to classify patients based on symptom profiles based on 236 severe acute respiratory syndrome coronavirus 2 positive cases and 564 controls, accounting for the time course of illness using generalised multivariate logistic regression. Significant symptoms included abdominal pain, cough, diarrhoea, fever, headache, muscle ache, runny nose, sore throat, temperature between 37.5 and 37.9 °C and temperature above 38 °C, but their importance varied by day of illness at assessment. With a high percentile threshold for specificity at 0.95, the baseline model had reasonable sensitivity at 0.67. To further evaluate accuracy of model predictions, leave-one-out cross-validation confirmed high classification accuracy with an area under the receiver operating characteristic curve of 0.92. For the baseline model, sensitivity decreased to 0.56. External validation datasets reported similar result. Our study provides a tool to discern COVID-19 patients from controls using symptoms and day from illness onset with good predictive performance. It could be considered as a framework to complement laboratory testing in order to differentiate COVID-19 from other patients presenting with acute symptoms in outpatient care.

Bearing Fault Diagnosis Based on Energy Spectrum Statistics and Modified Mayfly Optimization Algorithm.

This study proposes a novel resonance demodulation frequency band selection method named the initial center frequency-guided filter (ICFGF) to diagnose the bearing fault. The proposed technology has a better performance on resisting the interference from the random impulses. More explicitly, the ICFGF can be summarized as two steps. In the first step, a variance statistic index is applied to evaluate the energy spectrum distribution, which can adaptively determine the center frequency of the fault impulse and suppress the interference from random impulse effectively. In the second step, a modified mayfly optimization algorithm (MMA) is applied to search the optimal resonance demodulation frequency band based on the center frequency from the first step, which has faster convergence. Finally, the filtered signal is processed by the squared envelope spectrum technology. Results of the proposed method for signals from an outer fault bearing and a ball fault bearing indicate that the ICFGF works well to extract bearing fault feature. Furthermore, compared with some other methods, including fast kurtogram, ensemble empirical mode decomposition, and conditional variance-based selector technology, the ICFGF can extract the fault characteristic more accurately.

A Novel Ternary Vector System United with Morphogenic Genes Enhances CRISPR/Cas Delivery in Maize.

The lack of efficient delivery methods is a major barrier to clustered regularly interspaced short palindromic repeats/CRISPR-associated protein (CRISPR/Cas)-mediated genome editing in many plant species. Combinations of morphogenic regulator (MR) genes and ternary vector systems are promising solutions to this problem. In this study, we first demonstrated that MR vectors greatly enhance maize (Zea mays) transformation. We then tested a CRISPR/Cas9 MR vector in maize and found that the MR and CRISPR/Cas9 modules have no negative influence on each other. Finally, we developed a novel ternary vector system to integrate the MR and CRISPR/Cas modules. Our ternary vector system is composed of new pGreen-like binary vectors, here named pGreen3, and a pVS1-based virulence helper plasmid, which also functions as a replication helper for the pGreen3 vectors in Agrobacterium tumefaciens The pGreen3 vectors were derived from the plasmid pRK2 and display advantages over pGreen2 vectors regarding both compatibility and stability. We demonstrated that the union of our ternary vector system with MR gene modules has additive effects in enhancing maize transformation and that this enhancement is especially evident in the transformation of recalcitrant maize inbred lines. Collectively, our ternary vector system-based tools provide a user-friendly solution to the low efficiency of CRISPR/Cas delivery in maize and represent a basic platform for developing efficient delivery tools to use in other plant species recalcitrant to transformation.

MPC1 deletion is associated with poor prognosis and temozolomide resistance in glioblastoma.

OBJECT: Mitochondrial pyruvate carrier (MPC) proteins MPC1 and MPC2 form a transporter complex to control rate-limiting pyruvate transportation through the inner mitochondrial membrane. MPC1 plays a crucial role in the tumor metabolite and biosynthesis process. However, the role of MPC1 in glioblastoma (GBM) is unknown. METHODS: The Cancer Genome Atlas (TCGA) data set, which included 631 cases of GBM with genomic and clinical data, was obtained from the UCSC Xena browser. The clinical data set contained demographic, survival rate, and histological and pathological information. The association between MPC1 gene copy number segments and GBM patient overall survival was analyzed by Kaplan-Meier survival analysis, which was performed using the R2 web-based platform to identify the best cut-off. GraphPad Prism 7 was used to compare the differences in MPC1 gene copy number segments between various groups and subtypes. RESULTS: A total of 631 patients with glioblastoma (mean age 57.78 ± 14.36 years, 59% of males) were examined in this study, including 438 cases with MPC1 intact (MPC1 copy number segments > - 0.1, 69.4%) and 157 cases with MPC1 deletion (24.9%) tumors. Among the four GBM subtypes, the proneural group had the highest MPC1 copy number segments and GBM patients diagnosed with proneural subtype showed the best outcome. The expression of MPC1 transcripts was different in the TCGA-GBM dataset compared with the GTEx dataset. MPC1 copy number segments showed a significant correlation with MGMT copy number segments (r = 0.1322, p = 0.0012). MGMT gene expression level in MPC1 intact tumors was significantly lower than that in MPC1 deletion tumors (p = 0.0003). Significant relevancy was observed between better OS and the MPC1 intact group compared with the MPC1 deletion group (p = 0.020). Moreover, patients with MPC1 deletion tumors treated with temozolomide (TMZ) had worse survival than patients with MPC1 intact tumors (p = 0.027). CONCLUSIONS: Our results suggest a role of decreased MPC1 copy number segments in reducing overall survival in glioblastoma. MPC1 deletion is associated with poor response to TMZ chemotherapy in GBM.

Telbivudine can safely reduce mother-to-child transmission in chronic hepatitis B women after 12 weeks of gestation.

BACKGROUND: To evaluate the efficacy and safety of telbivudine in chronic hepatitis B women during the second and third trimesters of pregnancy. METHODS: The week 12-34 of pregnant women were screened in this prospective non-intervention study, with HBV DNA > 106 IU/mL and alanine aminotransferase > 50 IU/L. The patients were received telbivudine treatment as a treatment group or without antiviral treatment as a control group. All infants were received recombinant hepatitis B vaccine 10 µg within 12 h of birth, at week 4 and week 24, immunoglobulin G within 12 h of birth and were detected HBV markers at the range from 7 to 12 months after delivery. RESULTS: A total of 241 patients were finally enrolled, 139 patients in telbivudine group and 102 patients in control group. HBsAg negative rate of infants was 99.3% (135/136) in telbivudine group and was 91.9% (91/99) in control group after 7 months (P = 0.005), respectively. The incidence of undetectable HBV DNA levels (47.5%) was significantly lower in telbivudine-treated mothers than that in the controls (0%), and 75.5% patients alanine aminotransferase returned to normal in telbivudine group, and 51% in control group at delivery (P < 0.001), respectively. CONCLUSIONS: Telbivudine can safely reduce mother-to-child transmission in chronic hepatitis B women after 12 weeks of gestation.

Cardioprotective mechanisms of salvianic acid A sodium in rats with myocardial infarction based on proteome and transcriptome analysis.

Ischemic heart diseases (IHDs) cause great morbidity and mortality worldwide, necessitating effective treatment. Salvianic acid A sodium (SAAS) is an active compound derived from the well-known herbal medicine Danshen, which has been widely used for clinical treatment of cardiovascular diseases in China. This study aimed to confirm the cardioprotective effects of SAAS in rats with myocardial infarction and to investigate the underlying molecular mechanisms based on proteome and transcriptome profiling of myocardial tissue. The results showed that SAAS effectively protected against myocardial injury and improved cardiac function. The differentially expressed proteins and genes included important structural molecules, receptors, transcription factors, and cofactors. Functional enrichment analysis indicated that SAAS participated in the regulation of actin cytoskeleton, phagosome, focal adhesion, tight junction, apoptosis, MAPK signaling, and Wnt signaling pathways, which are closely related to cardiovascular diseases. SAAS may exert its cardioprotective effect by targeting multiple pathways at both the proteome and transcriptome levels. This study has provided not only new insights into the pathogenesis of myocardial infarction but also a road map of the cardioprotective molecular mechanisms of SAAS, which may provide pharmacological evidence to aid in its clinical application.

Effects of Different 980-nm Diode Laser Parameters in Hepatectomy.

BACKGROUND AND OBJECTIVE: Despite the successful application of laser in animal experiments and clinics, the adjustment of laser parameters during surgery is still unclear. This study aimed to investigate the effect of different 980-nm diode laser parameters in hepatectomy. This could provide a clear protocol for using 980-nm diode laser in hepatectomy. STUDY DESIGN/MATERIALS AND METHODS: In total, 48 Sprague-Dawley rats were used to explore the effects of different 980-nm diode laser parameters in hepatectomy, by setting different parameter combinations. The rats were randomly divided into eight groups, including the continuous wave group and quasi-continuous wave group. The effects were assessed in terms of liver resection speed, extent of intraoperative bleeding, and thermal damage. RESULTS: In the quasi-continuous wave group, there was a significant difference in resection speed at the different laser parameters (P < 0.001); however, there was no significant difference in intraoperative bleeding and thermal damage. In the continuous wave group, there was a significant difference in resection speed, intraoperative bleeding, and thermal damage at different parameters. CONCLUSION: The study showed that the average power determined hemostasis efficiency and thermal damage, and peak power determined the liver resection speed, whereas the pulse width and repetition frequency are not independent factors. When using 980-nm diode laser in hepatectomy, the average power should be decreased to prove hemostasis efficiency in delicate operations, and the peak power should be decreased to accelerate the procedure without worsening thermal damage. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Initial Impairment and Recovery of Vision-Related Functioning in Participants With Acute Optic Neuritis From the RENEW Trial of Opicinumab.

BACKGROUND: Leucine-rich repeat and immunoglobulin domain-containing Nogo receptor-interacting protein 1 (LINGO-1) is a key suppressor of oligodendrocyte differentiation and axonal remyelination and regeneration. This analysis evaluated the potential benefit of opicinumab, a human monoclonal antibody against LINGO-1, vs placebo on exploratory clinical endpoints of patient-reported vision-related functioning and high-contrast visual acuity (HCVA) in RENEW participants with acute optic neuritis (AON). METHODS: Participants were randomized to 100 mg/kg opicinumab intravenous or placebo every 4 weeks (6 infusions). Assessments were conducted in the per-protocol (PP) population and included: 25-item National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25), 10-item Neuro-Ophthalmic Supplement (NOS-10), and HCVA. RESULTS: The opicinumab group (n = 33) had worse mean (SD) baseline patient-reported vision-related functioning scores vs placebo (n = 36): NEI-VFQ-25 composite, 75.5 (17.6) vs 79.0 (16.6); NOS-10 composite, 63.6 (19.8) vs 69.8 (21.2), respectively. By Week 24, the placebo and opicinumab groups experienced substantial mean improvements from baseline (NEI-VFQ-25 composite, 15.17 vs 13.51 [difference (95% CI): -1.66 (-5.11 to 1.78)]; NOS-10 composite, 17.40 vs 16.04 [difference (95% CI): -1.35 (-7.38 to 4.67)]). Between-treatment differences in mean change from baseline were not significantly different at any time point. Analysis of covariance-adjusted mean recovery from baseline in HCVA at Week 24 for the affected eyes was 11.8 and 8.7 letters for placebo and opicinumab, respectively (P = 0.202). CONCLUSIONS: Most participants in the RENEW PP population demonstrated substantial recovery from baseline in patient-reported vision-related functioning and HCVA, regardless of treatment and structural damage. Average scores after recovery remained lower than those of published disease-free control groups. These results provide important information on visual function recovery in patients with AON, as measured by NEI-VFQ-25 and NOS-10.

Establishment and characterization of a cell line HCS1220 from human liver metastasis of colon cancer.

BACKGROUND: To establish one primary cell line of human liver metastasis of colon cancer. METHODS: HCS1220 cell line was derived from one liver metastasis of colon cancer patient's resected tumor sample. The characterization of the cell line was defined by karyotype analysis, short tandem repeat (STR) analysis and mycoplasma contamination. Subcutaneous injection 1 × 106 cells to four BALB/c nude mice, the viable tumors were developed and diagnosed (H&E staining). The expression of biomarkers CK20 and CDX2 for colon cancer were determined by immunocytochemistry assay. RESULTS: HCS1220 cell line can grow stably and continuously passage. During the grow process, the contact loss in the growth process and superimposed growth, which could be defined as proliferation of malignant tumor. Chromosome analysis revealed the cells derived from human female. The cells were not contaminated by mycoplasma. By immunohistochemistry, the cell line was proven to express the biomarkers of colon cancer CK20 and CDX2, while a-fetoprotein, hep-1 and glypican-3 were stained negative, which demonstrated that the HCS1220 cell line originating from the intestinal tissue. CONCLUSIONS: HCS1220 cell line has the characteristics of primary human liver metastasis of colon cancer. The results of STR have genetically showed that cell line is original, which can provided cell materials for research in vitro and can also help for establishing the mechanism model of liver metastasis of colon cancer and preparing, screening and evaluating anti-tumor drugs.

Outcome of children with newly diagnosed acute lymphoblastic leukemia treated with CCLG-ALL 2008: The first nation-wide prospective multicenter study in China.

Acute lymphoblastic leukemia (ALL) is the most common malignancy among children. The trial Chinese Children Leukemia Group (CCLG)-ALL 2008 was a prospective clinical trial designed to improve treatment outcome of childhood ALL through the first nation-wide collaborative study in China. Totally 2231 patients were recruited from ten tertiary hospitals in eight cities. The patients were stratified according to clinical-biological characteristics and early treatment response. Standard risk (SR) and intermediate risk (IR) groups were treated with a modified BFM based protocol, and there was 25%-50% dose reduction during intensification phases in the SR group. Patients in high risk (HR) group received a more intensive maintenance treatment. Minimal residual disease (MRD) monitoring with treatment adjustment was performed in two hospitals (the MRD group). Complete remission (CR) was achieved in 2100 patients (94.1%). At five years, the estimate for overall survival (OS) and event-free survival (EFS) of the whole group was 85.3% and 79.9%, respectively. The cumulative incidence of relapse (CIR) was 15.3% at five years. The OS, EFS and CIR for the SR group were 91.5%, 87.9%, and 9.7%, respectively. The outcome of the MRD group is better than the non-MRD group (5y-EFS: 82.4% vs 78.3%, P = .038; 5y-CIR: 10.7% vs 18.0%, P < .001). Our results demonstrated that the large-scale multicenter trial for pediatric ALL was feasible in China. Dose reduction in the SR group could achieve high EFS. MRD-based risk stratification might improve the treatment outcome for childhood ALL.

An Efficient ISAR Imaging of Targets with Complex Motions Based on a Quasi-Time-Frequency Analysis Bilinear Coherent Algorithm.

The inverse synthetic aperture radar (ISAR) imaging for targets with complex motions has always been a challenging task due to the time-varying Doppler parameter, especially at the low signal-to-noise ratio (SNR) condition. In this paper, an efficient ISAR imaging algorithm for maneuvering targets based on a noise-resistance bilinear coherent integration is developed without the parameter estimation. First, the received signals of the ISAR in a range bin are modelled as a multicomponent quadratic frequency-modulated (QFM) signal after the translational motion compensation. Second, a novel quasi-time-frequency representation noise-resistance bilinear Radon-cubic phase function (CPF)-Fourier transform (RCFT) is proposed, which is based on the coherent integration of the energy of auto-terms along the slope line trajectory. In doing so, the RCFT also effectively suppresses the cross-terms and spurious peaks interference at no expense of the time-frequency resolution loss. Third, the cross-range positions of target's scatters in ISAR image are obtained via a simple maximization projection from the RCFT result to the Doppler centroid axis, and the final high-resolution ISAR image is thus produced by regrouping all the range-Doppler frequency centroids. Compared with the existing time-frequency analysis-based and parameter estimation-based ISAR imaging algorithms, the proposed method presents the following features: (1) Better cross-term interference suppression at no time-frequency resolution loss; (2) computationally efficient without estimating the parameters of each scatters; (3) higher signal processing gain because of 2-D coherent integration realization and its bilinear function feature. The simulation results are provided to demonstrate the performance of the proposed method.