A repeating fast radio burst associated with a persistent radio source.

The dispersive sweep of fast radio bursts (FRBs) has been used to probe the ionized baryon content of the intergalactic medium1, which is assumed to dominate the total extragalactic dispersion. Although the host-galaxy contributions to the dispersion measure appear to be small for most FRBs2, in at least one case there is evidence for an extreme magneto-ionic local environment3,4 and a compact persistent radio source5. Here we report the detection and localization of the repeating FRB 20190520B, which is co-located with a compact, persistent radio source and associated with a dwarf host galaxy of high specific-star-formation rate at a redshift of 0.241 ± 0.001. The estimated host-galaxy dispersion measure of approximately [Formula: see text] parsecs per cubic centimetre, which is nearly an order of magnitude higher than the average of FRB host galaxies2,6, far exceeds the dispersion-measure contribution of the intergalactic medium. Caution is thus warranted in inferring redshifts for FRBs without accurate host-galaxy identifications.

A fast radio burst source at a complex magnetized site in a barred galaxy.

Fast radio bursts (FRBs) are highly dispersed, millisecond-duration radio bursts1-3. Recent observations of a Galactic FRB4-8 suggest that at least some FRBs originate from magnetars, but the origin of cosmological FRBs is still not settled. Here we report the detection of 1,863 bursts in 82 h over 54 days from the repeating source FRB 20201124A (ref. 9). These observations show irregular short-time variation of the Faraday rotation measure (RM), which scrutinizes the density-weighted line-of-sight magnetic field strength, of individual bursts during the first 36 days, followed by a constant RM. We detected circular polarization in more than half of the burst sample, including one burst reaching a high fractional circular polarization of 75%. Oscillations in fractional linear and circular polarizations, as well as polarization angle as a function of wavelength, were detected. All of these features provide evidence for a complicated, dynamically evolving, magnetized immediate environment within about an astronomical unit (AU; Earth-Sun distance) of the source. Our optical observations of its Milky-Way-sized, metal-rich host galaxy10-12 show a barred spiral, with the FRB source residing in a low-stellar-density interarm region at an intermediate galactocentric distance. This environment is inconsistent with a young magnetar engine formed during an extreme explosion of a massive star that resulted in a long gamma-ray burst or superluminous supernova.

A bimodal burst energy distribution of a repeating fast radio burst source.

The event rate, energy distribution and time-domain behaviour of repeating fast radio bursts (FRBs) contain essential information regarding their physical nature and central engine, which are as yet unknown1,2. As the first precisely localized source, FRB 121102 (refs. 3-5) has been extensively observed and shows non-Poisson clustering of bursts over time and a power-law energy distribution6-8. However, the extent of the energy distribution towards the fainter end was not known. Here we report the detection of 1,652 independent bursts with a peak burst rate of 122 h-1, in 59.5 hours spanning 47 days. A peak in the isotropic equivalent energy distribution is found to be approximately 4.8 × 1037 erg at 1.25 GHz, below which the detection of bursts is suppressed. The burst energy distribution is bimodal, and well characterized by a combination of a log-normal function and a generalized Cauchy function. The large number of bursts in hour-long spans allows sensitive periodicity searches between 1 ms and 1,000 s. The non-detection of any periodicity or quasi-periodicity poses challenges for models involving a single rotating compact object. The high burst rate also implies that FRBs must be generated with a high radiative efficiency, disfavouring emission mechanisms with large energy requirements or contrived triggering conditions.

No pulsed radio emission during a bursting phase of a Galactic magnetar.

Fast radio bursts (FRBs) are millisecond-duration radio transients of unknown physical origin observed at extragalactic distances1-3. It has long been speculated that magnetars are the engine powering repeating bursts from FRB sources4-13, but no convincing evidence has been collected so far14. Recently, the Galactic magnetar SRG 1935+2154 entered an active phase by emitting intense soft γ-ray bursts15. One FRB-like event with two peaks (FRB 200428) and a luminosity slightly lower than the faintest extragalactic FRBs was detected from the source, in association with a soft γ-ray/hard-X-ray flare18-21. Here we report an eight-hour targeted radio observational campaign comprising four sessions and assisted by multi-wavelength (optical and hard-X-ray) data. During the third session, 29 soft-γ-ray repeater (SGR) bursts were detected in γ-ray energies. Throughout the observing period, we detected no single dispersed pulsed emission coincident with the arrivals of SGR bursts, but unfortunately we were not observing when the FRB was detected. The non-detection places a fluence upper limit that is eight orders of magnitude lower than the fluence of FRB 200428. Our results suggest that FRB-SGR burst associations are rare. FRBs may be highly relativistic and geometrically beamed, or FRB-like events associated with SGR bursts may have narrow spectra and characteristic frequencies outside the observed band. It is also possible that the physical conditions required to achieve coherent radiation in SGR bursts are difficult to satisfy, and that only under extreme conditions could an FRB be associated with an SGR burst.

[Efficacy and safety of different nerve block methods for the treatment of pudendal neuralgia].

Objective: To identify efficacy and safety of pudendal nerve block in tubing through the third posterior sacral foramen for the treatment of pudendal neuralgia (PN). Methods: A retrospective study with 222 PN patients was conducted in the Department of Pain Management of Beijing Tsinghua Changgung Hospital from January 2020 to April 2023. These patients were divided into two groups based on their treatment methods: pudendal nerve block in tubing through the third posterior sacral foramen (observation group, n=101) and ultrasound-guided pudendal nerve block (control group, n=121). Primary outcome measure was the 90-day postoperative pain relief rate. Secondary outcome measures included visual analog scale (VAS) at 1, 7, 14, 30 and 90 d after surgery, the incidence of tramadol uses after surgery, postoperative self-rating anxiety scale (SAS) scores and the incidence of adverse events. Factors that influenced pain relief within 90 days after surgery were analyzed by using binary logistic regression analysis. Results: Observation group included 34 males and 67 females, aged (49.8±16.0) years old. Control group included 38 males and 83 females, aged (43.7±14.0) years old. The 90-day postoperative pain relief rate of the observation group patients was 38.6% (39/101), which was higher than the 24.0% (29/121) of the control group patients (P=0.018). Both the observation group and the control group showed an interaction effect of time and group after treatment for VAS scores (both P<0.05). In intra-group comparison, the VAS scores at 1, 7, 14, 30 and 90 d after treatment in both groups were lower than those before treatment (all P<0.05). In inter-group comparison, the differences of the VAS scores were not statistically significant in the observation group compared with those in the control group at 1, 7, 14, 30 and 90 d after surgery (all P>0.05). The SAS score of the observation group at 90 d after surgery was 51.5±6.2, which was lower than the 53.4±5.8 of the control group (P=0.022). There was no statistically significant difference in the incidence of postoperative tramadol uses and adverse events between the two groups (both P>0.05). Pudendal nerve block in tubing through the third posterior sacral foramen was a protective factor for pain postoperative relief in PN patients at 90 d after surgery (OR=1.92, 95%CI: 1.05-3.48, P=0.033). Conclusion: Pudendal nerve block in tubing through the third posterior sacral foramen is a safe and effective minimally invasive treatment. It has a higher postoperative pain relief rate within 90 d after surgery, without increasing the uses of postoperative rescue analgesics and the incidence of adverse events.

[Clinical research progress in non-invasive positive pressure ventilation in 2023].

Non-invasive positive pressure ventilation (NPPV) is a widely used method of providing respiratory support in a variety of clinical settings, including emergency departments, general wards, and intensive care units. The relevant research articles on NPPV published between 1st October 2022 and 30th September 2023 were retrieved from Medline and reviewed. In the management of acute respiratory failure (ARF) associated with COVID-19, studies have highlighted the significant influence of regional economic status on the choice of respiratory support strategies. It has been observed that NPPV is more suitable for patients with mild to moderate acute respiratory distress syndrome (ARDS) than for those with severe ARDS, as the latter group has an increased risk of delayed intubation. In addition, patients with severe dyspnea tended to benefit more from NPPV compared with high flow nasal cannula (HFNC) and conventional oxygen therapy, with a reduced risk of self-induced lung injury. For non-COVID-19-related ARF, research shows no significant differences in mortality and intubation rates between HFNC and NPPV in patients with hypercapnic ARF. The updated HACOR score and ROX score have been validated to have a high predictive value for clinical outcomes in patients receiving NPPV for hypoxemic ARF. With regard to weaning from invasive mechanical ventilation, immediate application of NPPV after extubation showed a lower mortality rate compared to continued invasive weaning. Moreover, NPPV with active humidification significantly decreased the reintubation rate within 7 days after extubation compared with HFNC. The choice between using NPPV and HFNC should be based on the specific etiology of the patient's condition. The potential effect of noninvasive high-frequency oscillatory ventilation on CO2 clearance was also investigated.

[Cardio-metabolic risk and adverse pregnancy outcomes in the first trimester: findings from the Shenzhen birth cohort study].

Objective: To investigate the relationship between cardio-metabolic abnormalities in the first trimester and adverse pregnancy outcomes (APO). Methods: This cohort study recruited singleton pregnancies in the first trimester (6-13+6 weeks of gestation) from Shenzhen Maternal and Child Health Care Hospital between January 1, 2021, and October 31, 2022. Cardiometabolic markers, including body mass index (BMI), blood pressure, fasting plasma glucose (FPG), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG), were recorded during the first trimester. Incidence of APO, including gestational hypertension, preeclampsia, gestational diabetes mellitus, preterm birth, fetal growth restriction, small for gestational age infant, and placental abruption, was documented. Cardiovascular metabolic abnormalities in the first trimester were defined as meeting one or more of the following criteria: elevated BMI (BMI≥24 kg/m²), elevated TG (TG≥1.7 mmol/L), decreased HDL-C (HDL-C<1.0 mmol/L), elevated blood pressure (systolic pressure≥130 mmHg (1 mmHg=0.133 kPa) and/or diastolic pressure≥85 mmHg), elevated FPG (FPG≥5.6 mmol/L). Enrolled women were categorized into abnormal cardio-metabolic and normal cardio-metabolic groups. Poisson regression was employed to analyze the association between cardio-metabolic abnormalities in the first trimester and APO. Results: The study included 14 197 pregnant women with an age of (32.0±4.1) years. There were 8 139 women in the normal cardio-metabolic group and 6 058 women in the abnormal cardio-metabolic group. Women with cardio-metabolic disorders in the first trimester had a younger gestational age and higher incidence rates of preterm birth, gestational hypertension, preeclampsia, and gestational diabetes mellitus (all P<0.05). In multivariable Poisson regression, elevated BMI (RR=1.22, 95%CI 1.15-1.29), elevated FPG (RR=1.59, 95%CI 1.38-1.82), elevated TG (RR=1.22, 95%CI 1.13-1.31), and elevated blood pressure (RR=1.50, 95%CI 1.39-1.63) were independent risk factors for APO, while decreased HDL-C (RR=0.93, 95%CI 0.70-1.23) was not. Elevated blood pressure (RR=5.57, 95%CI 4.58-6.78), elevated BMI (RR=1.71, 95%CI 1.40-2.09), and elevated TG (RR=1.38, 95%CI 1.10-1.74) had the greatest impact on the risk of developing preeclampsia. Elevated FPG (RR=1.70, 95%CI 1.45-1.99) had the greatest impact on the risk of gestational diabetes. Conclusions: Elevated blood pressure, BMI, TG and FPG in the first trimester are closely related to APO.

[Clinical update in non-invasive positive pressure ventilation for respiratory failure in 2022].

In this article, we searched the research literatures related to clinical investigation of non-invasive positive pressure ventilation (NPPV) in acute respiratory failure(ARF)/chronic respiratory failure(CRF) between 1st October 2021 and 30th September 2022 through Medline, and reviewed the important advances. Three prospective randomized controlled studies related to the efficacy and safety of NPPV and/or high-flow nasal cannula oxygen therapy (HFNC) on patients with COVID-19 with ARF were reported, showing that NPPV (including continuous positive airway pressure and bilevel positive airway pressure) was able to reduce the intubation rate, but the efficacy of HFNC was contradictory. In addition, progress has been made in outcome prediction models for ARF treated with NPPV, NPPV-related cardiac arrest, and the impact of human-machine interface on NPPV treatment outcomes. The effects of NPPV as preoxygenation method before intubation was reported to be able to reduce severe desaturation during intubation, especially in obese population. The use of NPPV in extubated patients resulting in reduced reintubation rate was also studied. With regard to long-term home application of NPPV, five indicators of successful initiation were proposed, but the success rate was low in clinical practice. Some reports showed that psychological support could improve the adherence to NPPV. The results of these studies contributed to the rational selection and optimal application of NPPV in clinical practice.

First-in-human phase 1 study of the anti-TIGIT antibody vibostolimab as monotherapy or with pembrolizumab for advanced solid tumors, including non-small-cell lung cancer☆.

BACKGROUND: In this first-in-human phase 1 study (NCT02964013; MK-7684-001), we investigated the safety and efficacy of the anti-TIGIT (T cell immunoglobulin and ITIM domain) antibody vibostolimab as monotherapy or in combination with pembrolizumab. PATIENTS AND METHODS: Part A enrolled patients with advanced solid tumors, and part B enrolled patients with non-small-cell lung cancer (NSCLC). Patients received vibostolimab 2.1-700 mg alone or with pembrolizumab 200 mg in part A and vibostolimab 200 mg alone or with pembrolizumab 200 mg in part B. Primary endpoints were safety and tolerability. Secondary endpoints included pharmacokinetics and objective response rate (ORR) per RECIST v1.1. RESULTS: Part A enrolled 76 patients (monotherapy, 34; combination therapy, 42). No dose-limiting toxicities were reported. Across doses, 56% of patients receiving monotherapy and 62% receiving combination therapy had treatment-related adverse events (TRAEs); grade 3-4 TRAEs occurred in 9% and 17% of patients, respectively. The most common TRAEs were fatigue (15%) and pruritus (15%) with monotherapy and pruritus (17%) and rash (14%) with combination therapy. Confirmed ORR was 0% with monotherapy and 7% with combination therapy. In part B, 39 patients had anti-PD-1 (programmed cell death protein 1)/PD-L1 (programmed death-ligand 1)-naive NSCLC (all received combination therapy), and 67 had anti-PD-1/PD-L1-refractory NSCLC (monotherapy, 34; combination therapy, 33). In patients with anti-PD-1/PD-L1-naive NSCLC: 85% had TRAEs-the most common were pruritus (38%) and hypoalbuminemia (31%); confirmed ORR was 26%, with responses occurring in both PD-L1-positive and PD-L1-negative tumors. In patients with anti-PD-1/PD-L1-refractory NSCLC: 56% receiving monotherapy and 70% receiving combination therapy had TRAEs-the most common were rash and fatigue (21% each) with monotherapy and pruritus (36%) and fatigue (24%) with combination therapy; confirmed ORR was 3% with monotherapy and 3% with combination therapy. CONCLUSIONS: Vibostolimab plus pembrolizumab was well tolerated and demonstrated antitumor activity in patients with advanced solid tumors, including patients with advanced NSCLC.

The relationship between hepatitis B virus serum DNA, RNA and quantitative hepatitis B surface antigen, and the predictive value for mother-to-child transmission: an observational cohort study.

OBJECTIVE: To explore the relationships between hepatitis B virus (HBV) DNA, HBV RNA and hepatitis B surface antigen (HBsAg) and to evaluate their predictive value for mother-to-child transmission of HBV. DESIGN: An observational cohort study. SETTING: First Hospital of Jilin University. POPULATION: HBsAg-positive and hepatitis B e antigen (HBeAg) -positive pregnant women were recruited. METHODS: Blood samples were collected from mothers before delivery, and HBV infection of infants was evaluated at 7 months of age. RESULTS: Overall, 268 mothers and 271 infants were enrolled. HBV DNA and HBsAg levels were correlated (rs = 0.699; P < 0.001), and HBV DNA (rs = 0.500; P < 0.001) and HBsAg (rs = 0.372; P < 0.001) were both correlated with HBV RNA. The areas under the curve for HBV DNA, HBsAg and HBV RNA for prediction of infection were 0.69 (95% CI 0.57-0.82), 0.63 (95% CI 0.51-0.76) and 0.65 (95% CI 0.52-0.78), respectively. Higher HBV DNA (odds ratio [OR] 4.77, 95% CI 1.44-15.86), higher HBsAg (OR 4.13, 95% CI 1.12-15.25) and higher HBV RNA (OR 3.19, 95% CI 1.09-9.32) were risk factors for HBV infection. Analysis of the HBV DNA-RNA-HBsAg Score revealed that it was an independent predictive factor for mother-to-child transmission (the OR of Score 3 was 8.81, 95% CI 2.79-27.82). CONCLUSION: HBV DNA, HBV RNA and HBsAg were correlated in HBeAg-positive pregnant women. HBsAg could be considered as a substitute marker of HBV DNA for HBeAg-positive pregnant women in low-income regions. We should pay special attention to pregnant women with high levels of all three markers. TWEETABLE ABSTRACT: HBsAg could be considered as a substitute marker of HBV DNA for HBeAg-positive pregnant women in low-income regions. Special attention should be given to pregnant women with high levels of all three markers (HBV DNA, HBV RNA and HBsAg).

[A randomized double-blinded placebo-controlled clinical trial of minodronate tablet in postmenopausal Chinese women with osteoporosis].

Objective: To verify the efficacy and safety of daily oral minodronate in postmenopausal women with established osteoporosis. Methods: In this randomized, double-blinded, placebo-controlled trial, 262 postmenopausal women were enrolled. Patients were randomized to receive daily oral minodronate 1 mg with supplements of 500 mg calcium and 200 U vitamin D3 (n=130) or placebo (n=132) with daily supplements of 500 mg calcium and 200 U vitamin D3, for 48 weeks. The primary endpoint was the average bone mineral density (BMD) change in the lumbar vertebrae 48 weeks post-treatment. Secondary outcome measures was the incidence of vertebral fractures. Safety assessments included the rate of adverse events. Results: At the end of 48 weeks treatment, the average BMD change rate from baseline were: full analysis set results: (3.52±4.82)% in the minodronate group and (2.00±5.74)% in the placebo group; per-protocol set results: (3.99±5.05)% in the minodronate group and (2.07±6.20)% in the placebo group; the differences were all significant (all P<0.05). Vertebral fracture occured in 3 patients (2.3%, 3/132) in the placebo group, and 1 case (0.8%, 1/130) in the minodronate group (P>0.05). The incidence of adverse events was 71.5% (93/130) in the minodronate group and 78.0% (103/132) in the placebo group (P>0.05). Conclusion: Minodronate is effective and safe in the treatment of postmenopausal osteoporosis without severe side effects.

[Evaluation of safety and immunogenicity of hepatitis E vaccine in maintenance hemodialysis patients].

Objective: To evaluate the safety and immunogenicity of hepatitis E vaccine(HEV)in Maintenance hemodialysis(MHD)patients. Methods: Based on an open-labeled controlled trial, from May 2016 to March 2018, 35 eligible MHD patients were recruited in the Hemodialysis Center of Zhongshan Hospital Affiliated to Xiamen University as the experimental group, and 70 MHD patients with matched age, gender and underlying diseases as the control group. The experimental group received HEV at 0, 1 and 6 months according to the standard vaccination procedures, while the control group received routine diagnosis and treatment without vaccine and placebo injection to observe the safety and immunogenicity of the vaccine. The safety of vaccine in MHD population was evaluated by the incidence of adverse reactions/events in the experimental and control groups. The immunogenicity of HEV in MHD patients was evaluated by comparing the data from the phase Ⅲ clinical trial. Results: The overall incidence of adverse reactions/events was 17.1% (18/105), and there were no grade 3-4 adverse reactions/events related to vaccination. In the experimental group, the incidence of local adverse reactions/events was 20.0% (7/35), and the incidence of systemic adverse reactions/events was 17.1% (6/35).There was no significant difference in the incidence of systemic adverse reactions/events between the experimental group and the control group (P>0.05). There were 23 patients receiving 3 doses with the standard schedule. The positive rate of HEV-IgG antibody was 100% and the GMC was 14.47(95%CI:13.14-15.80) WU/ml, which showed no significant difference compared with the 46 patients in Phase Ⅲ clinical trial (t=-1.04, P>0.05). Conclusion: Recombinant HEV has good safety and immunogenicity in MHD patients.

[Course of disease and related epidemiological parameters of COVID-19: a prospective study based on contact tracing cohort].

Objective: To analyze the course of disease and epidemiological parameters of COVID-19 and provide evidence for making prevention and control strategies. Methods: To display the distribution of course of disease of the infectors who had close contacts with COVID-19 cases from January 1 to March 15, 2020 in Guangdong Provincial, the models of Lognormal, Weibull and gamma distribution were applied. A descriptive analysis was conducted on the basic characteristics and epidemiological parameters of course of disease. Results: In total, 515 of 11 580 close contacts were infected, with an attack rate about 4.4%, including 449 confirmed cases and 66 asymptomatic cases. Lognormal distribution was fitting best for latent period, incubation period, pre-symptomatic infection period of confirmed cases and infection period of asymptomatic cases; Gamma distribution was fitting best for infectious period and clinical symptom period of confirmed cases; Weibull distribution was fitting best for latent period of asymptomatic cases. The latent period, incubation period, pre-symptomatic infection period, infectious period and clinical symptoms period of confirmed cases were 4.50 (95%CI:3.86-5.13) days, 5.12 (95%CI:4.63-5.62) days, 0.87 (95%CI:0.67-1.07) days, 11.89 (95%CI:9.81-13.98) days and 22.00 (95%CI:21.24-22.77) days, respectively. The latent period and infectious period of asymptomatic cases were 8.88 (95%CI:6.89-10.86) days and 6.18 (95%CI:1.89-10.47) days, respectively. Conclusion: The estimated course of COVID-19 and related epidemiological parameters are similar to the existing data.

[Clinicopathological features of verrucous type dysplasia of esophagus].

Objective: To investigate the clinicopathological features of verrucous type (squamous) dysplasia of esophagus. Methods: The clinicopathological data of 18 verrucous type dysplasia of esophagus patients in the 989th Hospital of the Joint Logistics Support Force of the People's Liberation Army (formerly 152 Central Hospital) and Beijing Chaoyang Hospital Affiliated to Capital Medical University from 2009 to 2021 were retrospectively collected. The histomorphologic characteristics and immunophenotype were observed, and human papillomavirus (HPV) genotyping was detected by PCR-fluorescence probe. The relevant literature was reviewed. Results: The median age of the 18 patients was 68 years (range 53-76 years); there were 13 males and 5 females. There were four cases in the upper esophagus, seven in the middle esophagus and seven in the lower esophagus. The median diameter of the lesion was 18 mm (range 6-54 mm). According to the Paris Classification, 11 cases were 0-Ⅱa, one case was 0-Ⅱa+Ⅰ, five cases were 0-Ⅱb, and one case was 0-Ⅱb+Ⅰ. White light endoscopy showed that the surface of the lesion was white plaque, red areas between the plaques, and papillary surface structure could be seen. In narrow-band imaging, some mucosal areas of lesions were opaque or patchy and light brown, and papillary microsurface structures were different in shapes and sizes. Intraepithelial microvessels were elongated, dilated, twisted and varied in diameter. Lugol iodine stain showed nil to faint staining. Histologically, the atypia cells were large with rounded to irregular nuclei, coarse chromatin, mitotic figures, and abundant eosinophilic cytoplasm. The basal cells showed increased atypia, crowding, increased nuclear-cytoplasmic ratio, and active mitosis. The cells were arranged haphazardly. Single cell keratinization, binuclear cells, and hollow-out-like cells, as well as surface epithelial keratinization and parakeratosis were observed in three cases. There were obvious verrucous or papillary structures in the epithelial layer. Five patients had local verrucous carcinoma. Immunohistochemical staining showed that the mutant expression of p53 protein in 6/10 cases; p16 was positive in 5/10 cases; abnormal Ki-67 distribution pattern in 10/10 cases. HPV was negative in all 10 cases tested. The original pathologic diagnosis of preoperative biopsy was high-grade dysplasia in 8 cases, low-grade dysplasia in 6 cases and atypical squamous epithelial cells in 4 cases. Conclusions: Esophageal verrucous dysplasia tumor cells are well differentiated with obvious verrucous or papillary structures. The unique morphological features suggest that it represents a histological subtype of esophageal squamous high-grade dysplasia and it is a precursor of verrucous carcinoma. Its preoperative biopsy diagnosis is challenging.

[Clinical research progress in non-invasive positive pressure ventilation from 2020 to 2021].

Non-invasive positive pressure ventilation (NPPV), an essential respiratory support method, is widely used in acute/chronic respiratory failure and assisting rehabilitation in patients with chronic obstructive pulmonary disease (COPD). We searched the relevant research articles about NPPV published from 1st October 2020 to 30th September 2021 through Medline. Researches focusing on the clinical application and viral transmission protection during high-flow nasal cannula oxygen and NPPV in COVID-19, were mainly retrospective and of small sample size. It demonstrated that high-flow nasal cannula oxygen and NPPV might reduce intubation rates when treating patients with mild-to-moderate respiratory failure, but the risk of delayed intubation should draw particular precaution. When using NPPV in non-COVID-19-related de novo acute respiratory failure, diaphragm thickening fraction and tidal change of esophageal pressure were validated to predict the treatment outcome. In addition, some studies explored the compliance and related influencing factors associated with the treatment effects of early NPPV initiation on amyotrophic lateral sclerosis patients and the effects of NPPV on dynamic hyperinflation during exercise in COPD patients. Furthermore, the effectiveness of neurally adjusted ventilatory assist ventilation and a novel communication device optimizing the use of NPPV were also investigated and outlined.

Safety and efficacy of quavonlimab, a novel anti-CTLA-4 antibody (MK-1308), in combination with pembrolizumab in first-line advanced non-small-cell lung cancer.

BACKGROUND: Quavonlimab (MK-1308), a novel anti-CTLA-4 antibody, in combination with pembrolizumab was investigated in a phase I study. PATIENTS AND METHODS: Dose-escalation (DE) phase: patients with advanced/metastatic solid tumors received an initial flat dose of quavonlimab as monotherapy [25 mg (cohort 1), 75 mg (cohort 2), or 200 mg (cohort 3)] followed by four treatments of the same quavonlimab dose plus pembrolizumab every 3 weeks (Q3W). Dose-confirmation phase (DC): patients with stage IIIB/IV non-small-cell lung cancer (NSCLC) received first-line quavonlimab [25 mg Q3W (arm A), 25 mg Q6W (arm B), 75 mg Q6W (arm C), or 75 mg Q3W (arm E)] plus pembrolizumab. Primary objectives were safety and tolerability and establishment of the recommended phase II dose (RP2D) of quavonlimab when used with pembrolizumab. Objective response rate (ORR) was a secondary endpoint. Efficacy based on PD-L1 expression, tumor mutational burden (TMB), and changes in circulating CD4+/CD8+ cells were exploratory endpoints. RESULTS: Thirty-nine patients were enrolled in DE [n = 14 (cohort 1); n = 17 (cohort 2); n = 8 (cohort 3)] and 134 in DC [n = 40 (arm A); n = 40 (arm B); n = 40 (arm C); n = 14 (arm E)]. Maximum-tolerated dose was not reached. Grade 3-5 treatment-related adverse events (AEs; graded according to NCI CTCAE v4.03) occurred in 0%, 23.5%, and 75.0% of patients in DE cohorts 1, 2, and 3, respectively, and 35.0%, 30.0%, 35.0%, and 57.1% of patients in DC arms A, B, C, and E, respectively. Efficacy was observed at all dose levels/schedules in patients with NSCLC. ORRs were 40.0% [95% confidence interval (CI), 24.9-56.7; arm A], 37.5% (95% CI, 22.7-54.2; arm B), 27.5% (95% CI, 14.6-43.9; arm C), and 35.7% (95% CI, 12.8-64.9; arm E). PD-L1 expression and total number of circulating CD4+ cells correlated with ORR. CONCLUSIONS: Quavonlimab 25 mg Q6W plus pembrolizumab demonstrated similar efficacy and a better safety profile among all quavonlimab doses/schedules evaluated; this regimen was the chosen RP2D.

Synergistic effects ofα-Fe2O3nanoparticles and Fe-doping on gas-sensing performance of NiO nanowires and interface mechanism.

High surface area nickel oxide nanowires (NiO NWs), Fe-doped NiO NWs andα-Fe2O3/Fe-doped NiO NWs were synthesized with nanocasting pathway, and then the morphology, microstructure and components of all samples were characterized with XRD, TEM, EDS, UV-vis spectra and nitrogen adsorption-desorption isotherms. Owing to the uniform mesoporous template, all samples with the same diameter exhibit the similar mesoporous-structures. The loadedα-Fe2O3nanoparticles should exist in mesoporous channels between Fe-doped NiO NWs to form heterogeneous contact at the interface of n-typeα-Fe2O3nanoparticles and p-type NiO NWs. The gas-sensing results indicate that Fe-dopant andα-Fe2O3-loading both improve the gas-sensing performance of NiO NWs sensors.α-Fe2O3/Fe-doped NiO NWs sensors presented the highest response to 100 ppm ethanol gas (55.264) compared with Fe-doped NiO NWs (24.617) and NiO NWs sensors (3.189). The donor Fe-dopant increases the ground state resistance and the absorbed oxygen content in air.α-Fe2O3nanoparticles in electron depletion region result in the increasing resistance in ethanol gas and decreasing resistance in air. In this way,α-Fe2O3/Fe-doped NiO NWs sensor presents the excellent gas-sensing performance due to the formation of heterogeneous contact at the interface.