Research progress on novel antibody drug conjugates in cancer therapy. / ç™Œç—‡æ²»ç–—ä¸­æ–°åž‹æŠ—ä½“å¶è”è¯ç‰©çš„ç ”ç©¶è¿›å±•.

Traditional antibody drug conjugates (ADC) combine monoclonal antibodies with cytotoxic drugs to accurately strike cancer cells, but there are still many shortcomings in stability, targeting, efficacy, and safety. Novel ADC, such as bi-specific, site-specific, dual-payload, and pro-drug type ADC, can be optimized by simultaneously binding 2 different antigens or epitopes, selecting more stable linkers, coupling with specific amino acid sites of antibodies, carrying different drug payloads, and adopting prodrug strategies, while retaining the characteristics of traditional ADC. Significantly improving the stability, targeting, efficacy and safety of drugs can better meet the needs of clinical treatment. Novel ADC will play a more important role in cancer treatment in the future. Discussing the progress of novel ADC in cancer treatment and analyzing their advantages and challenges can provide theoretical support for the development of anti-cancer strategies and provide directions for drug research and development.

Synergistic Effects of Redox Couples and Oxygen Vacancies Improve the Tetracycline Degradation Property of La2NiMnO6.

Improving the e- and h+ separation efficiency and promoting the production of more radicals is the key to improving the degradation efficiency of catalytic degradation of antibiotics. On the other hand, intermediate analysis of antibiotics in the dark adsorption and light irradiation process is very important to clarify the entire antibiotic degradation pathway. Here, the La2NiMnO6 (LNMO) catalyst was prepared by the sol-gel method and the calcination method. By changing the calcination temperature (800, 900, and 1000 °C), the LNMO-based catalysts were successfully formed, abbreviated as L-800, L-900, and L-1000. XPS measurements demonstrated the presence of Mn4+, Mn3+, Mn2+, and oxygen vacancies (OVs) in the LNMO-based catalysts. Analysis of PL, PC, EIS, and TR-PL demonstrated that L-900 had the highest separation efficiency and fastest carrier mobility. The LNMO-based catalysts were used to degrade tetracycline (TC). With the optimized catalyst L-900, the decomposition rate of TC reached 99.57% in 120 min. The entire TC degradation pathway was analyzed according to LC-MS measurements. Radical trap experiments and ESR technology revealed that the synergistic effect of Mn4+/Mn3+, Mn4+/Mn2+, and OVs not only effectively separated e- and h+ but also facilitated the formation of superoxide radicals (•O2-) to accelerate TC degradation. Radicals •OH, h+, and •O2- all contributed to TC deterioration in increasing order of importance. In addition, XPS measurements of the L-900 catalyst before and after use indicated that Mn4+/Mn3+, Mn4+/Mn2+, and OVs were not reactants but mediators of e- and h+. Finally, the mechanism of TC degradation with the LNMO-based catalysts was discussed. This work provided new material for TC degradation in the wastewater.

The prevalence of psychological disorders among cancer patients during the COVID-19 pandemic: A meta-analysis.

PURPOSE: We aimed to assess the prevalence rate (PR) of depression, anxiety, posttraumatic stress disorder (PTSD), insomnia, distress, and fear of cancer progression/recurrence among patients with cancer during the COVID-19 pandemic. METHODS: Studies that reported the PR of six psychological disorders among cancer patients during the COVID-19 pandemic were searched in PubMed, Embase, PsycINFO, and Web of Science databases, from January 2020 up to 31 January 2022. Meta-analysis results were merged using PR and 95% confidence intervals, and heterogeneity among studies was evaluated using I2 and Cochran's Q test. Publication bias was examined using funnel plots and Egger's tests. All data analyses were performed using Stata14.0 software. RESULTS: Forty studies with 27,590 participants were included. Pooled results showed that the PR of clinically significant depression, anxiety, PTSD, distress, insomnia, and fear of cancer progression/recurrence among cancer patients were 32.5%, 31.3%, 28.2%, 53.9%, 23.2%, and 67.4%, respectively. Subgroup analysis revealed that patients with head and neck cancer had the highest PR of clinically significant depression (74.6%) and anxiety (92.3%) symptoms. Stratified analysis revealed that patients with higher education levels had higher levels of clinically significant depression (37.2%). A higher level of clinically significant PTSD was observed in employed patients (47.4%) or female with cancer (27.9%). CONCLUSION: This meta-analysis evaluated the psychological disorders of cancer patients during the COVID-19 outbreak. Therefore, it is necessary to develop psychological interventions to improve the mental health of cancer patients during the pandemic.

NETs promote ALI/ARDS inflammation by regulating alveolar macrophage polarization.

Neutrophils activated during acute lung injury (ALI) form neutrophil extracellular traps (NETs) to capture pathogens. However, excessive NETs can cause severe inflammatory reactions. Macrophages are classified as M1 macrophages with proinflammatory effects or M2 macrophages with anti-inflammatory effects. During ALI, alveolar macrophages (AMs) polarize to the M1 phenotype. This study tested the hypothesis that NETs may aggravate ALI or acute respiratory distress syndrome (ARDS) inflammation by promoting alveolar macrophage polarization to the M1 type. Our research was carried out in three aspects: clinical research, animal experiments and in vitro experiments. We determined that NET levels in ARDS patients were positively correlated with M1-like macrophage polarization. NET formation was detected in murine ALI tissue and associated with increased M1 markers and decreased M2 markers in BALF and lung tissue. Treatment with NET inhibitors significantly inhibitor NETs generation, downregulated M1 markers and upregulated M2 markers. Regardless of LPS pre-stimulation, significant secretion of proinflammatory cytokines and upregulated M1 markers were detected from bone marrow-derived macrophages (M0 and M2) cocultured with high concentrations of NETs; conversely, M2 markers were downregulated. In conclusion, NETs promote ARDS inflammation during the acute phase by promoting macrophage polarization to the M1 phenotype. We propose that NETs play an important role in the interaction between neutrophils and macrophages during the early acute phase of ALI.

Research progress in immune checkpoint inhibitors in the treatment of oncogene-driven advanced non-small cell lung cancer. / å ç–«æ£€æŸ¥ç‚¹æŠ‘åˆ¶å‰‚æ²»ç–—é©±åŠ¨åŸºå› é˜³æ€§æ™šæœŸéžå°ç»†èƒžè‚ºç™Œçš„ç ”ç©¶è¿›å±•.

The clinical application of immune checkpoint inhibitors (ICIs) lead to dramatic changes in the treatment strategy for patients with advanced non-small cell lung cancer (NSCLC), but the efficacy of ICIs in oncogene-driven NSCLC is controversial. Existing research shows that the efficacy of ICIs may be related to different types of driver genes, programmed cell death-ligand 1 (PD-L1) level, and tumor mutational burden (TMB). It may involved in other factors, such as clinical characteristics, and immune cell density. ICIs monotherapy or combination therapy may play a role in a subset of oncogene-driven NSCLC patients, but further studies are needed to select these patients, which may be an important direction for the future development of advanced NSCLC.

The antimicrobial cathelicidin peptide hlF(1-11) attenuates alveolar macrophage pyroptosis induced by Acinetobacter baumannii in vivo.

Acinetobacter baumannii is a Gram-negative coccobacillus found primarily in hospital settings that has recently emerged as a source of hospital-acquired infections, including bacterial pneumonia. The hLF(1-11) peptide comprising the first 11 N-terminal residues of human lactoferrin exerts antimicrobial activity in vivo and was highly effective against multidrug-resistant A. baumannii strains in vitro and in vivo. Pyroptosis is a caspase-1-dependent inflammatory cell death process and is induced by various microbial infections. In the present study, we investigated the molecular mechanisms that regulate pyroptosis induced by A. baumannii in macrophages. Our results revealed that A. baumannii induced pyroptosis through caspase-1 activation and IL-1ß production. We also found that caspase-1 activation and IL-1ß maturation in A. baumannii-triggered pyroptotic cell death were reduced by hLF(1-11) treatment. Moreover, hLF(1-11) inhibited the A. baumannii-induced caspase-1 activation and pyroptosis of pulmonary alveolar macrophages in vivo.

Exposure to difenoconazole inhibits reproductive ability in male marine medaka (Oryzias melastigma).

Difenoconazole (DFZ) is a triazole fungicide which has been detected in the aquatic environment, including estuaries and embayments. However, few studies addressing the reproductive toxicity and transgenerational effects of DFZ on marine fishes are available. The present study was conducted to investigate the effects of DFZ on male marine medaka (Oryzias melastigma). After exposure of the embryo to 1, 10, 100 and 1000ng/L DFZ for 180days, the gonadosomatic index was significantly decreased in the 1000ng/L treatment. The number of sperm was reduced while the abundances of spermatocytes and spermatogonia in the testes were increased in all the treatments. The mRNA levels of salmon-type gnrh (sgnrh), the luteinizing hormone (lhß) and the follicle-stimulating hormone (fshß) genes in the brain all exhibited a significant down-regulation, the expression of androgen receptors (arα and arß) was decreased and that of estrogen receptor ß and cytochrome P450 aromatase (cyp19B) was increased in the testes. The expression levels of cyp19A and cyp19B were increased in the liver. The decrease of ars mRNA levels might be one of the reasons causing the reduction of sperm. The down-regulation of sgnrh, lhß and fshß mRNA levels suggested that DFZ might impact the spermatogenesis via the brain-pituitary-gonad pathway. The decrease of the fertilization success, the hatch ability and the swim-up success in the F1 generation indicated that DFZ pollution at environmental levels might cause a decrease of wild fish populations.

Reproductive effects of life-cycle exposure to difenoconazole on female marine medaka (Oryzias melastigma).

Difenoconazole (DFZ) is a widely used triazole fungicide which has been detected in some estuaries and embayments. This study was conducted to investigate the effects of DFZ on ovarian development in female marine medaka (Oryzias melastigma). After 180 days exposure of the embryo to DFZ (0, 1, 10, 100 and 1000 ng/L), the gonadosomatic index and percentage of mature oocytes produced were significantly reduced in the 1, 10 and 100 ng/L treatments but not the 1000 ng/L treatment compared to the control, thus exhibiting a U-shaped dose response curve. The relative mRNA levels of brain follicle-stimulating hormone, ovarian cytochrome P450 aromatase (CYP19s), hepatic estrogen receptors and vitellogenin, and the ratio of 17ß-estradiol to testosterone in the muscle, also showed a U-shaped dose response, which was consistent with the development of oocytes. In addition, glutathione S-transferase activity in the ovary showed a U-shaped dose-response. These results gave an explanation for this U-shaped dose-response. The egg number produced, the hatch ability and the swim-up success in the F1 generation all showed a U-shaped dose response, indicating that exposure to DFZ at low concentrations can cause a decrease of fecundity and viability of the next generation. Thus, a more extensive evaluation of the impact of DFZ on marine fish reproduction at realistic environmental concentrations is needed.

Bioaccumulation and the expression of hepatic cytochrome P450 genes in marine medaka (Oryzias melastigma) exposed to difenoconazole.

This study was conducted to assess the effects of difenoconazole (DFZ), a triazole fungicide, on the hepatic biotransformation system and its bioaccumulation in marine medaka (Oryzias melastigma). Fish were exposed to DFZ (1, 10, 100, 1000ng/L) for 180days. The results showed that: (1) The mRNA levels of hepatic CYP1A1, CYP1B, CYP1C1, CYP27B and CYP3A40 were up-regulated, but those of CYP3A38 and CYP27A1 were down-regulated. (2) The activity of ethoxyresorufin-O-deethylase (EROD) and the content of reduced glutathione (GSH) in the liver were increased in the DFZ-treated groups, and glutathione S-transferase (GST) activity was increased in the 100 and 1000ng/L groups. (3) DFZ was accumulated in the muscle and the biological concentration factors in the 10, 100, and 1000ng/L groups were respectively 149, 81 and 25. These results suggested that long-term exposure to DFZ at low concentrations would result in a bioaccumulation of this compound and disturb the biotransformation system.

Nerve growth factor promotes expression of costimulatory molecules and release of cytokines in dendritic cells involved in Th2 response through LPS-induced p75NTR.

INTRODUCTION: Nerve growth factor (NGF) plays an important role in asthmatic inflammatory responses. However, the effects of NGF on dendritic cells (DCs) in asthmatic inflammation remain unknown. Therefore, we examined the effects of NGF on co-stimulatory molecules and the release of cytokines after ovalbumin (OVA) and a low dose of LPS (low LPS) stimulation of dendritic cells. METHODS: Bone-marrow-derived dendritic cells (BMDCs) were collected from 6- to 8-week-old wide or TLR4(-/-) mice. BMDCs were treated with OVA and/or low LPS for 12h, and then stimulated with NGF for 24h. ELISA and flow cytometry were performed to measure TSLP, IL-6, IL-10, and IL-12 production and MHCII and CD86 expression on BMDCs. BMDCs were exposed to p75 neurotrophin receptor (p75NTR) inhibitor (TAT-Pep5) or NF-kB inhibitor (QNZ) 30 min prior to NGF 1 h after NGF intervention, the levels of RelA and RelB in cytoplasmic and nuclear were detected by west blot. Co-cultured BMDCs with naïve CD4(+) T cells, and ELISA was used to detect IL-4 and INF-γ levels. RESULTS: NGF was found to markedly promote OVA and low LPS-induced expression of MHCII, CD86, secretion of TSLP and IL-6, and Th2-response-stimulating capacity of BMDCs. NGF affected BMDCs through LPS-induced p75NTR expression. TAT-Pep5 or QNZ could attenuate the promotive effect of NGF. CONCLUSIONS: NGF facilitates OVA with lowLPS-induced maturation of mouse BMDCs through LPS-up-regulated p75 NTR via activation of NF-κB pathways, providing another mechanism for the involvement of NGF in the Th2 response.

Influence of difenoconazole on lipid metabolism in marine medaka (Oryzias melastigma).

Difenoconazole (DFZ) is a triazole fungicide that inhibits the biosynthesis of sterols in cell membranes and is widely used in agriculture for effectively treating fungal infections. However, there are few studies available addressing the effects of DFZ on lipid metabolism in marine fishes. The present study was conducted to investigate the effects of DFZ on lipid metabolism in marine medaka (Oryzias melastigma). After exposure to 1, 10, 100 and 1000 ng/L DFZ for 180 days, an increase in condition factor (CF), total lipids and polyunsaturated fatty acids (PUFA) contents accompanied with a decrease in saturated fatty acids was observed in the muscle of DFZ-exposed fish. The expression of peroxisome proliferator-activated receptor γ as well as retinoid X receptors in the muscle was up-regulated, which would be responsible for the lipid accumulation in the muscle. The elevation of Δ6-desaturase (FADS2) and Δ9-desaturase (SCD) mRNA levels in the muscle and liver might result in the increase of PUFA content. The increased CF index and total lipid amounts indicated that DFZ exposure could affect the health of fish. ∑SFA (sum of saturated fatty acids) and DHA (docosahexaenoic acid; 22:6n-3) concentrations decreased, and the levels of ∑PUFA and ∑n-6PUFA increased in the muscle, which suggested that DFZ exposure could change lipid metabolism and profiles in fish.

Intra-Peritoneal Administration of Mitochondrial DNA Provokes Acute Lung Injury and Systemic Inflammation via Toll-Like Receptor 9.

The pathogenesis of sepsis is complex. Mitochondrial dysfunction, which is responsible for energy metabolism, intrinsic apoptotic pathway, oxidative stress, and systemic inflammatory responses, is closely related with severe sepsis induced death. Mitochondria DNA (mtDNA) contain un-methylated cytosine phosphate guanine (CpG) motifs, which exhibit immune stimulatory capacities. The aim of this study was to investigate the role and mechanism of mtDNA release on lipopolysaccharide (LPS) induced acute lung injury (ALI) and systemic inflammation. Following LPS injection, plasma mtDNA copies peak at 8 h. Compared with wild-type (WT) mice, mtDNA in toll like receptor 4 knockout (TLR4 KO) mice were significantly decreased. MtDNA intra-peritoneal administration causes apparent ALI as demonstrated by increased lung injury score, bronchoalveolar lavage fluid (BALF) total protein and wet/dry (W/D) ratio; mtDNA injection also directly provokes systemic inflammation, as demonstrated by increased IL-1ß, IL-6, high-mobility group protein B1 (HMGB1) level; while nuclear DNA (nDNA) could not induce apparent ALI and systemic inflammation. However, compared with WT mice, TLR4 KO could not protect from mtDNA induced ALI and systemic inflammation. Specific TLR9 inhibitor, ODN 2088 pretreatment can significantly attenuate mtDNA induced ALI and systemic inflammation, as demonstrated by improved lung injury score, decreased lung wet/dry ratio, BALF total protein concentration, and decreased systemic level of IL-1ß, IL-6 and HMGB1. MtDNA administration activates the expression of p-P38 mitogen-activated protein kinases (MAPK) in lung tissue and specific TLR9 inhibitor pretreatment can attenuate this activation. Thus, LPS-induced mtDNA release occurs in a TLR4-dependent manner, and mtDNA causes acute lung injury and systemic inflammation in a TLR9-dependent and TLR4-independent manner.

Clinical significance and biological function of interferon regulatory factor 1 in non-small cell lung cancer.

The clinical application and biological function of interferon regulatory factor 1 (IRF1) in non-small cell lung cancer (NSCLC) patients undergoing chemoimmunotherapy remain elusive. The aim of this study was to investigate the predictive and prognostic significance of IRF1 in NSCLC patients. We employed the cBioPortal database to predict frequency changes in IRF1 and explore its target genes. Bioinformatic methods were utilized to analyze the relationship between IRF1 and immune regulatory factors. Retrospective analysis of clinical samples was conducted to assess the predictive and prognostic value of IRF1 in chemoimmunotherapy. Additionally, A549 cells with varying IRF1 expression levels were constructed to investigate its effects on NSCLC cells, while animal experiments were performed to study the role of IRF1 in vivo. Our findings revealed that the primary mutation of IRF1 is deep deletion and it exhibits a close association with immune regulatory factors. KRAS and TP53 are among the target genes of IRF1, with interferon and IL-2 being the predominantly affected pathways. Clinically, IRF1 levels significantly correlate with the efficacy of chemoimmunotherapy. Patients with high IRF1 levels exhibited a median progression-free survival (mPFS) of 9.5 months, whereas those with low IRF1 levels had a shorter mPFS of 5.8 months. IRF1 levels positively correlate with PD-L1 distribution and circulating IL-2 levels. IL-2 enhances the biological function of IRF1 and recapitulates its role in vivo in the knockdown group. Therefore, IRF1 may possess predictive and prognostic value for chemoimmunotherapy in NSCLC patients through the regulation of the IL-2 inflammatory pathway.

miR-375 inhibits autophagy and reduces viability of hepatocellular carcinoma cells under hypoxic conditions.

BACKGROUND & AIMS: Tumor cells survive hypoxic conditions by inducing autophagy. We investigated the roles of microRNAs (miRNAs) in regulating autophagy of hepatocellular carcinoma (HCC) cells under hypoxic conditions. METHODS: We used gain- and loss-of-function methods to evaluate the effect of miRNAs on autophagy in human HCC cell lines (Huh7 and Hep3B) under hypoxic conditions. Autophagy was quantified by immunoblot, immunofluoresence, and transmission electron microscopy analyses, and after incubation of cells with bafilomycin A1. We used a luciferase reporter assay to confirm associations between miRNAs and their targets. We analyzed growth of HCC xenograft tumors in nude mice. RESULTS: miR-375 was down-regulated in HCC cells and tissues; it inhibited autophagy under hypoxic conditions by suppressing the conversion of LC3I to LC3II and thereby autophagic flux. The ability of miR-375 to inhibit autophagy was independent of its ability to regulate 3'-phosphoinositide-dependent protein kinase-1-AKT-mammalian target of rapamycin signaling, but instead involved suppression of ATG7, an autophagy-associated gene. miR-375 bound directly to a predicted site in the 3' untranslated region of ATG7. Up-regulating miR-375 or down-regulating ATG7 inhibited mitochondrial autophagy of HCC cells, reduced the elimination of damaged mitochondria under hypoxia, increased release of mitochondrial apoptotic proteins, and reduced viability of HCC cells. In mice, xenograft tumors that expressed miR-375 had fewer autophagic cells, larger areas of necrosis, and grew more slowly than tumors from HCC cells that expressed lower levels of miR-375. CONCLUSIONS: miR-375 inhibits autophagy by reducing expression of ATG7 and impairs viability of HCC cells under hypoxic conditions in culture and in mice. miRNAs that inhibit autophagy of cancer cells might be developed as therapeutics.

The Evaluation of Prognostic Value and Immune Characteristics of Ferroptosis-Related Genes in Lung Squamous Cell Carcinoma.

Background The purpose of our study was to construct a prognostic model based on ferroptosis-related gene signature to improve the prognosis prediction of lung squamous carcinoma (LUSC). Methods The mRNA expression profiles and clinical data of LUSC patients were downloaded. LUSC-related essential differentially expressed genes were integrated for further analysis. Prognostic gene signatures were identified through random forest regression and univariate Cox regression analyses for constructing a prognostic model. Finally, in a preliminary experiment, we used the reverse transcription-quantitative polymerase chain reaction assay to verify the relationship between the expression of three prognostic gene features and ferroptosis. Results Fifty-six ferroptosis-related essential genes were identified by using integrated analysis. Among these, three prognostic gene signatures (HELLS, POLR2H, and POLE2) were identified, which were positively affected by LUSC prognosis but negatively affected by immune cell infiltration. Significant overexpression of immune checkpoint genes occurred in the high-risk group. In preliminary experiments, we confirmed that the occurrence of ferroptosis can reduce three prognostic gene signature expression. Conclusions The three ferroptosis-related genes could predict the LUSC prognostic risk of antitumor immunity.

Comparison of the baseline characteristics and influencing factors of successful smoking cessation before and during the coronavirus disease pandemic.

INTRODUCTION: Travel and living environment restrictions, which may have positive or negative effects on smoking-related behaviors, were implemented to limit the COVID-19 pandemic. This study aimed to compare the baseline clinical characteristics and smoking cessation (SC) rate at 3 months of patients in an SC clinic in Hunan Province, China before and during the COVID-19 pandemic and identify influencing factors of successful SC. METHODS: Healthy patients at the SC clinic aged ≥18 years before the COVID-19 pandemic and during the COVID-19 pandemic were divided into groups A and B, respectively. The two groups' demographic data and smoking characteristics were compared, and SC interventions were applied by the same medical staff team through telephone follow-up and counselling during the SC procedure. RESULTS: Groups A and B included 306 and 212 patients, respectively, with no significant differences in demographic data. The SC rates of group A (pre COVID-19) and group B (during the COVID-19 pandemic) at 3 months were 23.5% and 30.7%, respectively, after the first SC visit. Those who chose to quit immediately or within 7 days were more successful than those who did not choose a quit date (p=0.002, p=0.000). Patients who learned about the SC clinic via network resources and other methods were more likely to succeed than those who learned about the clinic from their doctor or hospital publications (p=0.064, p=0.050). CONCLUSIONS: Planning to quit smoking immediately or within 7 days of visiting the SC clinic and learning about the SC clinic via the network media or other methods improved the likelihood of successful SC. SC clinics and the harm of tobacco should be promoted via network media. During consultation, the smokers should be encouraged to quit smoking immediately and establish an SC plan, which would help them to quit smoking.

Real-world outcomes of PD-L1 inhibitors combined with thoracic radiotherapy in the first-line treatment of extensive stage small cell lung cancer.

BACKGROUND: The CREST study showed that the addition of thoracic radiotherapy (TRT) could improve the survival rate in patients with extensive stage small cell lung cancer (ES-SCLC), but whether TRT can bring survival benefit in the era of immunotherapy remains controversial. This study aimed to explore the efficacy and safety of adding TRT to the combination of PD-L1 inhibitors and chemotherapy. METHODS: The patients who received durvalumab or atezolizumab combined with chemotherapy as the first-line treatment of ES-SCLC from January 2019 to December 2021 were enrolled. They were divided into two groups, based on whether they received TRT or not. Propensity score matching (PSM) with a 1:1 ratio was performed. The primary endpoints were progression-free survival (PFS), overall survival (OS) and safety. RESULTS: A total of 211 patients with ES-SCLC were enrolled, of whom 70 (33.2%) patients received standard therapy plus TRT as first-line treatment, and 141 (66.8%) patients in the control group received PD-L1 inhibitors plus chemotherapy. After PSM, a total of 57 pairs of patients were enrolled in the analysis. In all patients, the median PFS (mPFS) in the TRT and non-TRT group was 9.5 and 7.2 months, respectively, with HR = 0.59 (95%CI 0.39-0.88, p = 0.009). The median OS (mOS) in the TRT group was also significantly longer than that in the non-TRT group (24.1 months vs. 18.5 months, HR = 0.53, 95%CI 0.31-0.89, p = 0.016). Multivariable analysis showed that baseline liver metastasis and the number of metastases ≥ 3 were independent prognostic factors for OS. Addition of TRT increased the incidence of treatment-related pneumonia (p = 0.018), most of which were grade 1-2. CONCLUSIONS: Addition of TRT to durvalumab or atezolizumab plus chemotherapy significantly improves survival in ES-SCLC. Although it may leads to increased incidence of treatment-related pneumonia, a majority of the cases can be relieved after symptomatic treatment.

Evaluation of the smoking cessation effects of QuitAction, a smartphone WeChat platform.

INTRODUCTION: Many smokers in China desire to quit, though the success rate among adults is low. This study evaluated the effects of QuitAction, a WeChat smoking cessation platform, summarized the intervention experience of the smoking cessation platform, identified aspects of the platform that necessitated improvement, and provided references for further optimization of the smoking cessation platform. METHODS: This single-arm study was conducted in Hunan, China, from September 2020 to October 2021. Regular smokers, who were aged ≥15 years and willing to quit smoking using QuitAction, were recruited. An in-application questionnaire evaluated participants' baseline smoking status and intention to quit smoking. The QuitAction program included questionnaires regarding the participants' ongoing smoking cessation status at 24 hours, one week, one month and three months after quitting. The smoking cessation procedure was discontinued if the participant had no intention of continuing. The smoking cessation rate, influencing success factors, frequency of use satisfaction, and helpfulness of QuitAction were recorded. RESULTS: A total of 303 participants registered and logged into the QuitAction program, including 59 with incomplete information and 64 with no intention of quitting. The study finally included 180 participants. The smoking cessation rate was 33.9% at 24 hours, 27.2% at one week, 26.1% at one month, and 25.0% at three months. QuitAction was reported as helpful by 94.9% of participants and 95.7% were satisfied with the program. Participants with a quitting difficulty score of 80-100 were less likely to quit smoking than participants with a difficulty score of 0-60 (OR=0.28; 95% CI: 0.10-0.78; p=0.015). Participants using the platform ≥5 times were more likely to quit smoking than those who used the platform <5 times (OR=3.59; 95% CI: 1.51-8.52; p=0.004). CONCLUSIONS: The QuitAction platform provides smoking cessation services that can improve smokers' success rate and improve user experience satisfaction.

Baseline characteristics and the factors influencing successful smoking cessation: A comparison between a WeChat smoking cessation mini-program and an offline smoking cessation clinic.

INTRODUCTION: Smoking cessation (SC) clinics are a professional SC services in China. However, studies comparing the characteristics and SC rates of smoking populations in SC clinics with those using mobile SC programs are limited. We compared smokers' characteristics, 3-month SC rates, and the factors influencing 3-month SC success, between a large hospital SC clinic and a WeChat SC mini-program. METHODS: Between January and November 2021, 384 participants voluntarily enrolled in either the hospital SC clinic (Group A: n=243) or the WeChat SC mini-program (Group B: n=141). Both groups underwent a 3-month SC intervention, and their SC status was monitored at 24 hours, 1 week, 1 month, and 3 months after quitting. SC rate was defined as the self-reported rate of continuous SC. RESULTS: The 3-month SC rate was higher in Group A (42.4%) than in Group B (24.8%). Participants with middle school education had a lower likelihood of SC success than those with primary school or lower (p=0.014). Employees in the enterprise/business/services industries were more likely to have SC success than farmers (p=0.013). Participants with SC difficulty scores of 0-60 were more successful than those with scores >60 (p=0.001, p=0.000, respectively). Participants who quit smoking due to their illness, or other reasons, had a higher likelihood of SC success than those who quit due to concerns about their own and their family's health (p=0.006, p=0.098, respectively). While the likelihood of SC success was lower in those who quit because of the influence of their environment than in those who quit due to concerns about their own and their family's health (p=0.057). CONCLUSIONS: Both SC clinics and WeChat SC mini-programs achieved satisfactory SC rates. The high accessibility of mobile SC platforms, which save time spent on transportation and medical visits, renders them worth promoting and publicizing as additional SC options for smokers, particularly young smokers.

GABAergic Neurons in the Nucleus Accumbens are Involved in the General Anesthesia Effect of Propofol.

The mechanism underlying the hypnosis effect of propofol is still not fully understood. In essence, the nucleus accumbens (NAc) is crucial for regulating wakefulness and may be directly engaged in the principle of general anesthesia. However, the role of NAc in the process of propofol-induced anesthesia is still unknown. We used immunofluorescence, western blotting, and patch-clamp to access the activities of NAc GABAergic neurons during propofol anesthesia, and then we utilized chemogenetic and optogenetic methods to explore the role of NAc GABAergic neurons in regulating propofol-induced general anesthesia states. Moreover, we also conducted behavioral tests to analyze anesthetic induction and emergence. We found out that c-Fos expression was considerably dropped in NAc GABAergic neurons after propofol injection. Meanwhile, patch-clamp recording of brain slices showed that firing frequency induced by step currents in NAc GABAergic neurons significantly decreased after propofol perfusion. Notably, chemically selective stimulation of NAc GABAergic neurons during propofol anesthesia lowered propofol sensitivity, prolonged the induction of propofol anesthesia, and facilitated recovery; the inhibition of NAc GABAergic neurons exerted opposite effects. Furthermore, optogenetic activation of NAc GABAergic neurons promoted emergence whereas the result of optogenetic inhibition was the opposite. Our results demonstrate that NAc GABAergic neurons modulate propofol anesthesia induction and emergence.