Sustainable development policies and spatial planning for maintaining greenery are crucial for all major cities in the world, and the measurement of green space indicators in planning practice needs ...to evolve in response to the demands of the times and technological drivers. This study explores an informal urban green space indicator, the green view index (GVI), which uses the visual perception of an observer to measure the quality of urban space by simulating the pedestrian perspective of the road in street-view image data and then calculating the proportion of vegetation in the road landscape. The GVI is different from macro indicators, such as public recreational green space, forest coverage, and green space rate, which are derived from planning data or remote sensing data in traditional urban planning; it starts from the bottom-up perception of individual residents and is more relevant to their subjective demands. At present, most international cities have made outstanding achievements in controlling public recreational green space, forest coverage, green space rates, and other macrolevel indicators of urban spatial quality; however, with the promotion of the concept of “human-oriented” urban planning, the potential restoration of urban spatial quality at the microlevel is gradually being recognized. To ensure the efficiency and reliability of this study, inspired by computer vision techniques and related GVI studies, a research method based on chromaticity was built to identify the proportions of green vegetation in street view images, and the credibility was improved by eliminating unreliable data. By using this method, we could evaluate a city at an overall scale instead of the previous block scale. The final research result showed that Shenzhen is friendly to human visual senses, and the GVI of the streets in developed areas is generally higher than that in developing areas. The geostatistical analysis of the green viewpoint data provides a more intuitive guide for researchers and planners, and it is believed to inform the planning and design of environmentally friendly, smart, and sustainable future cities.
Abstract
Background:
Immune checkpoint inhibitors (ICIs) are standard treatments for advanced non-small cell lung cancer (NSCLC); however, evidence regarding their relative efficacy and safety is ...lacking. This study compared the efficacy and safety of all currently available ICI treatments in patients with advanced NSCLC to identify optimal treatment regimens.
Methods:
PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase databases were systematically searched for randomized controlled trials (RCTs) published up to August 8, 2022. The primary outcomes were overall survival (OS) and progression-free survival (PFS). Secondary outcomes included objective response rate (ORR) and adverse events (AEs).
Results:
Forty RCTs involving 22,526 patients were selected, and a total of 26 treatment regimens were identified. Treatment with anti-programmed cell death protein-1 (anti-PD-1) provided superior OS compared with anti-programmed death ligand 1 (anti-PD-L1) treatment. ICIs plus platinum-based chemotherapy (PBC) were superior to ICIs treatment alone, although the addition of PBC increased treatment toxicity. Cemiplimab ranked first for OS and lowest for any-grade AEs in advanced NSCLC patients without PD-L1 selection. Regarding grade ≥3 AEs, the toxicity of ICI monotherapy or ICI–ICI combination was consistently lower than that of the other treatments. For patients without PD-L1 selection, cemiplimab showed the best OS, pembrolizumab plus docetaxel (Pem-DXT) showed the best PFS, and atezolizumab plus bevacizumab and PBC (Atezo-Beva-PBC) showed the best ORR. Pembrolizumab plus PBC and Atezo-Beva-PBC were the most likely optimal treatments for OS and PFS in patients with PD-L1 expression <1%, respectively. In patients with PD-L1 expression ≥1%, treatment regimens containing anti-PD-1 provided superior OS benefits compared with those of anti-PD-L1 treatment, and sintilimab plus PBC (Sint-PBC) provided the best OS benefit; as for PFS, ICI plus PBC consistently showed greater PFS benefits than ICI or PBC alone. For patients with anti-PD-L1 expression of 1–49%, camrelizumab plus PBC provided the best benefit for OS and PFS among included treatment. Durvalumab-tremelimumab-PBC and Atezo-Beva-PBC respectively presented the highest OS and PFS for patients with PD-L1 expression ≥50%. Moreover, cemiplimab and Atezo-Beva-PBC yielded the best OS and PFS benefits as first-line treatments for patients with advanced NSCLC, respectively.
Conclusions:
Although ICI plus PBC likely resulted in superior survival outcomes compared to ICI treatment alone, it did increase toxicity. Cemiplimab presented a well-balanced efficacy and safety profile in advanced NSCLC treatment. Our findings with the current ICIs comparisons will aid future trials for cancer immunotherapy.
Registration:
PROSPERO, https://www.crd.york.ac.uk/PROSPERO/, CRD42022323879.
Oxidative stress-induced mitochondrial dysfunction is implicated in the pathogenesis of intervertebral disc degeneration (IVDD). Sirtuin 3 (SIRT3), a sirtuin family protein located in mitochondria, ...is essential for mitochondrial homeostasis; however, the role of SIRT3 in the process of IVDD has remained elusive. Here, we explored the expression of SIRT3 in IVDD in vivo and in vitro; we also explored the role of SIRT3 in senescence, apoptosis, and mitochondrial homeostasis under oxidative stress. We subsequently activated SIRT3 using honokiol to evaluate its therapeutic potential for IVDD. We assessed SIRT3 expression in degenerative nucleus pulposus (NP) tissues and oxidative stress-induced nucleus pulposus cells (NPCs). SIRT3 was knocked down by lentivirus and activated by honokiol to determine its role in oxidative stress-induced NPCs. The mechanism by which honokiol affected SIRT3 regulation was investigated in vitro, and the therapeutic potential of honokiol was assessed in vitro and in vivo. We found that the expression of SIRT3 decreased with IVDD, and SIRT3 knockdown reduced the tolerance of NPCs to oxidative stress. Honokiol (10 μM) improved the viability of NPCs under oxidative stress and promoted their properties of anti-oxidation, mitochondrial dynamics and mitophagy in a SIRT3-dependent manner. Furthermore, honokiol activated SIRT3 through the AMPK-PGC-1α signaling pathway. Moreover, honokiol treatment ameliorated IVDD in rats. Our study indicated that SIRT3 is involved in IVDD and showed the potential of the SIRT3 agonist honokiol for the treatment of IVDD.
To reveal the pharmacokinetic process of narirutin, naringin, and honokiol in normal and different courses of liver-stagnation and spleen-deficiency syndrome depressive rats after intragastric ...administration of Zhi-Zi-Hou-Po decoction (ZZHPD), a rapid ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS) method was proposed in this study. Chronic unpredictable mild stress (CUMS) rat was employed as the depression model. Acetonitrile solution containing 0.1% acetic acid and methyl alcohol-water (50 : 50, v/v) was chosen as the protein precipitant and redissolve solution severally; a Shim-pack GISS C18 column coupled with 0.1% aqueous acetic acid-acetonitrile in gradient elution was employed to separate the mixed constituents in plasma. The WinNonLin software (version 6.1) was chosen as the analytical tool for the pharmacokinetic parameters. The results indicated that compared with rats in the control group, the sucrose preference, scores in the open-field test, and the concentration of 5-HT in plasma of rats in CUMS and CUMS + ZZHPD treatment groups were lower, while the immobility time in the forced swimming test of rats in these two groups was longer, which implied that the depression model was successful. These behavioral and biochemical indexes of rats above in the CUMS + ZZHPD treatment group were improved after oral administration of ZZHPD, which indicated that the antidepressant effect of ZZHPD was definite. The UHPLC-MS/MS method was stabilized, sensitive, and exclusive, and the extraction recovery and matrix effect of three analytes were all above 89%. The Tmax, AUC, and Cmax of three ingredients in CUMS-induced depression rats were significantly larger than control rats, while these pharmacokinetic parameters in CUMS + ZZHPD treatment rats were decreased significantly compared with CUMS-induced depression rats, which may relate with the changes in physiological function of the gastrointestinal tract and liver in CUMS-induced liver-stagnation and spleen-deficiency syndrome depressive rats. This study provided important information for the clinical rational use of ZZHPD in antidepressant treatment.
...MTSS might be used as a referential surface in TKA for its special anatomical position. ...MTSS was just proposed, the objective methodology and matched equipment for its application during TKA ...remain under investigation and preparation. ...subgroup analysis based on the type of disease or preoperative coronal alignment was not performed in this study, which might increase the risk of bias. ...it's important to note that a single referential structure is difficult to precisely determine the rotation due to anatomical variations and poor visibility. ...MTSS was proposed as an auxiliary landmark for the femoral rotational alignment in TKA, but it could not replace the previous reference axes. ...though there are various landmarks and reference axes for the femoral rotational alignment, they are still insufficient due to the anatomical variations and poor vision during TKA. According to this research, MTSS may be an auxiliary landmark to determine the femoral rotational alignment during TKA.
1 Previous research indicated that systemic conditions, particularly cardiovascular and cerebrovascular diseases, are significant risk factors for cognitive impairment, and dysfunction of peripheral ...organs may also contribute to cognitive decline and AD. ...to investigate the association between CK and cerebrospinal fluid (CSF) AD pathology biomarkers, we analyzed data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), a global multi-centered database. After excluding the influence of collinearity on the results, we then used a linear regression model to examine the relationship between CK and Aβ and P-tau, and did not find the significant linear relationship between CK and Aβ (β = 0.044, 95% CI: –0.019 to 0.106; P = 0.173; Supplementary Figure 1H, http://links.lww.com/CM9/B878); however, a decrement of CK associated with increased level of P-tau was found (β = –0.068, 95% CI: –0.132 to –0.003; P = 0.039; Supplementary Figure 1I, http://links.lww.com/CM9/B878). ...future studies should be conducted in participants with comparable age distribution to verify our inference. ...we investigated the relationship between CK levels and AD in this study.
There is still uncertainty regarding whether diabetes mellitus (DM) can adversely affect patients undergoing carotid endarterectomy (CEA) for carotid stenosis. The aim of the study was to assess the ...adverse impact of DM on patients with carotid stenosis treated by CEA.
Eligible studies published between 1 January 2000 and 30 March 2023 were selected from the PubMed, EMBASE, Web of Science, CENTRAL, and ClinicalTrials databases. The short-term and long-term outcomes of major adverse events (MAEs), death, stroke, the composite outcomes of death/stroke, and myocardial infarction (MI) were collected to calculate the pooled effect sizes (ESs), 95% confidence intervals (CIs), and prevalence of adverse outcomes. Subgroup analysis by asymptomatic/symptomatic carotid stenosis and insulin/noninsulin-dependent DM was performed.
A total of 19 studies (n = 122,003) were included. Regarding the short-term outcomes, DM was associated with increased risks of MAEs (ES = 1.52, 95% CI: 1.15-2.01, prevalence = 5.1%), death/stroke (ES = 1.61, 95% CI: 1.13-2.28, prevalence = 2.3%), stroke (ES = 1.55, 95% CI: 1.16-1.55, prevalence = 3.5%), death (ES = 1.70, 95% CI: 1.25-2.31, prevalence =1.2%), and MI (ES = 1.52, 95% CI: 1.15-2.01, prevalence = 1.4%). DM was associated with increased risks of long-term MAEs (ES = 1.24, 95% CI: 1.04-1.49, prevalence = 12.2%). In the subgroup analysis, DM was associated with an increased risk of short-term MAEs, death/stroke, stroke, and MI in asymptomatic patients undergoing CEA and with only short-term MAEs in the symptomatic patients. Both insulin- and noninsulin-dependent DM patients had an increased risk of short-term and long-term MAEs, and insulin-dependent DM was also associated with the short-term risk of death/stroke, death, and MI.
In patients with carotid stenosis treated by CEA, DM is associated with short-term and long-term MAEs. DM may have a greater impact on adverse outcomes in asymptomatic patients after CEA. Insulin-dependent DM may have a more significant impact on post-CEA adverse outcomes than noninsulin-dependent DM. Whether DM management could reduce the risk of adverse outcomes after CEA requires further investigation.
Immune checkpoint inhibitors (ICIs) are increasingly used as first-line therapy for patients with advanced non-small cell lung cancer (NSCLC) harboring no actionable mutations; however, data on their ...efficacy among patients presenting with intracranial lesions are limited. This study aimed to explore the efficacy and safety of ICIs combined with chemotherapy in advanced NSCLC patients with measurable brain metastasis at initial diagnosis.
Our study retrospectively analyzed clinical data of a total of 211 patients diagnosed with driver gene mutation-negative advanced NSCLC with measurable, asymptomatic brain metastasis at baseline from Hunan Cancer Hospital between January 1, 2019 and September 30, 2021. The patients were stratified into two groups according to the first-line treatment regimen received: ICI combined with chemotherapy ( n = 102) or chemotherapy ( n = 109). Systemic and intracranial objective response rates (ORRs) and progression-free survival (PFS) were analyzed. Adverse events were also compared between the groups.
Compared with the chemotherapy-based regimen, the ICI-containing regimen was associated with a significantly higher intracranial (44.1% 45/102 vs . 28.4% 31/109, χ2 = 5.620, P = 0.013) and systemic (49.0% 50/102 vs . 33.9% 37/109, χ2 = 4.942, P = 0.019) ORRs and longer intracranial (11.0 months vs . 7.0 months, P <0.001) and systemic (9.0 months vs . 5.0 months, P <0.001) PFS. Multivariable analysis consistently revealed an independent association between receiving ICI plus platinum-based chemotherapy as a first-line regimen and prolonged intracranial PFS (hazard ratio HR = 0.52, 95% confidence interval CI: 0.37-0.73, P <0.001) and systemic PFS (HR = 0.48, 95% CI: 0.35-0.66, P <0.001). No unexpected serious adverse effects were observed.
Our study provides real-world clinical evidence that ICI combined with chemotherapy is a promising first-line treatment option for driver gene mutation-negative advanced NSCLC patients who present with brain metastasis at initial diagnosis.
https://www.clinicaltrials.gov/ , OMESIA, NCT05129202.
The study was approved by the Medical Research and Ethics Committee of Henan Provincial People's Hospital (No. 2021-21). The level of anti-SARS-CoV-2 IgG in the serum sample was tested with the ...magnetic chemiluminescence enzyme immunoassay (MCLIA) kit provided by the Bioscience company (Bioscience Diagnostic Technology Co.,Ltd., Tianjin, China); and the white blood cell count (WBC), lymphocyte count (LYMPH), neutrophil count (NEUT), and the concentration of hemoglobin (HGB) were tested with Sysmex XN-9100 machine and its supporting reagents (Sysmex Corporation, Kobe, Japan); the concentration of interleukin 2 (IL-2), interferon γ (IFN-γ), tumor necrosis factor α (TNF-α), IL-4, IL-6, and IL-10 was tested by Agilent NovoCyte machine and its supporting reagents (Agilent Technologies, Inc., Beijing, China);finally, BD flow cytometry (Franklin Lake, New Jersey, USA) was used to count the memory B cells and detect the T-lymphocyte subsets stimulated by the SARS-CoV-2 specific ELIspot kit (AmyJet Scientific, Wuhan, China). The evaluation of the characteristics of vaccine-induced cytokines can better characterize the vaccine-induced immune response, and the study of the cytokine response induced after inactivated vaccine inoculation is still rare. 3 However, in our study, the NEUT did not change significantly after vaccination in both groups, and the LYMPH, HGB, and WBC of the positive group at the 24 weeks decreased compared with those at the 2 weeks, but still fluctuated within the normal range, which means that the inactivated vaccine is safe and reliable.
The tumor microenvironment has received great attention in recent years, and growing evidence suggests that inducible nitric oxide synthase (iNOS) is a key mediator of immune activation and ...inflammation. 2 The concentrations of nitric oxide (NO), nitrite, and nitrotyrosine were discovered to be elevated in lung cancer patients. Patients with pulmonary nodules and lung-occupying lesions, who visited the pulmonary function examination unit at Nanfang Hospital of Southern Medical University from May 2021 to June 2022, were included in the study, and eNO testing was performed prior to the pulmonary function tests (PFTs). The fractional exhaled nitric oxide (FeNO) was tested at a flow rate of 50 mL/s (FeNO50), which was eatablished as the standard expiratory flow rate for measuring FeNO by the American Thoracic Society (ATS) and the European Respiratory Society (ERS).
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