Proteome-wide association studies have predicted that the protein abundance of LSM6, GMPPB, ICA1L, and CISD2 is associated with attention-deficit/hyperactivity disorder.

Identification of changes in protein abundance for attention-deficit/hyperactivity disorder (ADHD) is important for potential disease mechanisms and therapeutic study for ADHD. In order to identify candidate proteins that confer risk for ADHD, a proteome-wide association study (PWAS) for ADHD was conducted by integrating two human brain proteome datasets and the ADHD genome-wide association study (GWAS) summary statistics released by the Psychiatric Genomics Consortium (PGC). A total of 11 risk proteins were identified as significant candidates that passed the bonferroni corrected proteome-wide significant (PWS) level. The predicted protein abundance level of LSM6, GMPPB, ICA1L and CISD2 are shown significantly associated with ADHD in both proteome datasets, highlighting their potential role in ADHD pathogenesis. A transcriptome-wide association study (TWAS) of ADHD was also conducted, and 13 genes with predicted expression changes related to ADHD were identified. GMPPB, ICA1L and NAT6 were supported by both TWAS and PWASs analysis. This study uncovers the predicted protein abundance changes that confer risk for ADHD and pinpoints a number of high-confidence protein candidates (e.g. LSM6, GMPPB, ICA1L, CISD2) for further functional exploration studies and drug development targeting these proteins.

Joint DNA-RNA-based NGS for diagnosis and treatment of a rare CD47-MET fusion lung adenocarcinoma which was immunoresistant and savoltinib-sensitive: a case report.

Targeted therapy and immunotherapy are both important in the treatment of non-small-cell lung cancer (NSCLC). Accurate diagnose and precise treatment are key in achieving long survival of patients. MET fusion is a rare oncogenic factor, whose optimal detection and treatment are not well established. Here, we report on a 32-year-old female lung adenocarcinoma patient with positive PD-L1 and negative driver gene detected by DNA-based next-generation sequencing (NGS). A radical resection of the primary lesion after chemotherapy combined with PD-1 checkpoint inhibitor administration indicated primary immuno-resistance according to her pathological response and rapid relapse. A rare CD47-MET was detected by RNA-based NGS, which was confirmed by fluorescence in situ hybridization. Multiplex immunofluorescence revealed a PD-L1 related heterogeneous immunosuppressive microenvironment with little distribution of CD4+ T cells and CD8+ T cells. Savolitinib therapy resulted in a progression-free survival (PFS) of >12 months, until a new secondary resistance mutation in MET p.D1228H was detected by re-biopsy and joint DNA-RNA-based NGS after disease progression. In this case, CD47-MET fusion NSCLC was primarily resistant to immunotherapy, sensitive to savolitinib, and developed secondary MET p.D1228H mutation after targeted treatment. DNA-RNA-based NGS is useful in the detection of such molecular events and tracking of secondary mutations in drug resistance. To this end, DNA-RNA-based NGS may be of better value in guiding precise diagnosis and individualized treatment in this patient population.

Accuracy of 12 Intraocular Lens Power Formulas After Corneal Myopic Refractive Surgery.

PURPOSE: To assess the predictive accuracy of new-generation online intraocular lens (IOL) power formulas in eyes with previous myopic laser refractive surgery (LRS) and to evaluate the influence of corneal asphericity on the predictive accuracy. METHODS: The authors retrospectively evaluated 52 patients (78 eyes) with a history of laser in situ keratomileusis (LASIK) or photorefractive keratectomy (PRK) who subsequently underwent cataract surgery. Refractive prediction errors were calculated for 12 no-history new online formulas: 8 formulas with post-LRS versions (Barrett True-K, EVO 2.0, Hoffer QST, and Pearl DGS) using keratometry and posterior/total keratometry measured by IOLMaster 700 and 4 formulas without post-LRS versions (Cooke K6 and Kane) using keratometry and total keratometry. The refractive prediction error, mean absolute error (MAE), and percentages of eyes with prediction errors of ±0.25, ±0.50, ±0.75, ±1.00, and ±1.50 diopters (D) were compared. RESULTS: The MAEs of the 12 formulas were significantly different (F = 83.66, P < .001). The MAEs ranged from 0.62 to 0.94 D and from 1.07 to 1.84 D in the formulas with and without post-LRS versions, respectively. The EVO formula produced the lowest MAE (0.60) and MedAE (0.47), followed by the Barrett True-K (0.69 and 0.50, respectively). Each percentage of eyes with refractive prediction error was also significantly different among the 12 formulas (P < .001). CONCLUSIONS: The EVO and Barrett True-K formulas demonstrate comparable performance to the other existing formulas in eyes with a history of myopic LASIK/PRK. Surgeons should use these formulas with post-LRS versions and input keratometric values whenever possible. [J Refract Surg. 2024;40(6):e354-e361.].

A technique to treat Descemet's membrane detachment following cataract surgery.

We describe a technique to reattach the detached Descemet's membrane, following cataract surgery. From the main clear corneal cataract incision, aqueous humor is ejected completely by apposition of the cornea to the iris for approximately 3 s. This ensures the fluid in the space between the stroma and Descemet's membrane is ejected and the detached Descemet's membrane returns to its original position. Sterile air is injected through a paracentesis 180 degrees away from the Descemet's membrane detachment, to maintain a complete air-filled chamber. Full air tamponade is maintained for 20 min, following which one-third of the air is ejected from the chamber to prevent an increase of postoperative intraocular pressure.

Correlates of sexual and reproductive health service utilization among older adults in China: Findings from the sexual well-being (SWELL) study.

BACKGROUND: Sexual and reproductive health (SRH) is critical to the overall health of older adults. We assessed the utilization of SRH services and its correlates among older adults in China. METHODS: We recruited community-dwelling adults aged 50 and above in five Chinese cities between June 2020 and December 2022. In this study SRH services included reproductive health examination, cervical cancer screening, and sexual life counselling. Logistic regression was used to assess correlates of SRH services utilization. RESULTS: A total of 3001 older adults (1819 men and 1182 women) were enrolled. Among them, 11.4 % (343/3001) of participants received a reproductive health examination, 35.4 % (418/1182) of female participants received cervical cancer screening, and 30.1 % (401/1332) of sexually active participants sought help for their sexual lives. Older men with an annual income of USD 7500 or more (aOR = 3.21, 95%CI: 1.39-7.44), two or more chronic conditions (2.38, 1.39-4.08), and reproductive health problems (2.01, 1.18-3.43) were more likely to receive a urological examination. For older women, individuals who were younger (aged 50-59 years: 5.18, 2.84-9.43; aged 60-69 years: 2.67, 1.49-4.79), lived in an urban area (1.88, 1.31-2.71), were employed (1.73, 1.21-2.47), had two or more chronic conditions (2.04, 1.37-3.05), were sexually active (1.72, 1.15-2.58) and talked about sex (1.69, 1.21-2.36) were more likely to receive a gynecological examination. CONCLUSION: SRH services utilization among older adults was low, with urological examination among older men particularly low. SRH messages and services tailored for older adults are needed to enhance their utilization of SRH services.

The LISA-PPV Formula: An Ensemble Artificial Intelligence-Based Thick Intraocular Lens Calculation Formula for Vitrectomized Eyes.

PURPOSE: To investigate the relationship between effective lens position (ELP) and patient characteristics, and to further develop a new intraocular lens (IOL) calculation formula for cataract patients with previous pars plana vitrectomy (PPV). DESIGN: Cross-sectional study. METHODS: A total of 2793 age-related cataract patients (group 1) and 915 post-PPV cataract patients (group 2) who underwent phacoemulsification with IOL implantation were included. The ELP of 2 groups was compared and the association between ELP and patient characteristics was further evaluated using standardized multivariate regression coefficients. An ensemble artificial intelligence-based ELP prediction model was developed using a training set of 810 vitrectomized eyes, and a thick-lens IOL formula (LISA-PPV) was constructed and compared with 7 existing formulas on an external multi-center testing set of 105 eyes. RESULTS: Compared to eyes with age-related cataract, vitrectomized eyes showed a similar ELP distribution (P = .19), but different standardized coefficients of preoperative biometry for ELP. The standardized coefficients also varied with the type of vitreous tamponade, history of scleral buckling, and ciliary sulcus IOL implantation. The LISA-PPV formula showed the lowest mean and median absolute prediction error (MAE: 0.63 D; MedAE: 0.44 D), and the highest percentages of eyes within ±0.5 D of prediction error (57.14%) in the testing dataset. CONCLUSIONS: The ELP prediction required optimization specifically for vitrectomized eyes based on their biometric and surgical characteristics. The LISA-PPV formula is a useful and accurate tool for determining IOL power in cataract patients with previous PPV (available at http://ppv-iolcalculator.com/).

Metal-Organic Framework Based Sensors for Benzene Vapor.

Sensing of benzene vapor is a hot spot due to the volatile drastic carcinogen even at trace concentration. However, achieving convenient and rapid detection is still a challenge. As a sort of functional porous material, metal-organic frameworks (MOFs) have been developed as detection sensors by adsorbing benzene vapor and converting it into other signals (fluorescence intensity/wavelength, chemiresistive, weight or color, etc.). Supramolecular interaction between benzene molecules and the host framework, aperture size/shape and structural flexibility are influential factors in the performance of MOF-based sensors. Therefore, enhancing the host-guest interactions between the host framework and benzene molecules, or regulating the diffusion rate of benzene molecules by changing the aperture size/shape and flexibility of the host framework to enhance the detection signal are effective strategies for constructing MOF-based sensors. This concept highlights several types of MOF-based sensors for the detection of benzene vapor.

Landscape of adenosine pathway and immune checkpoint dual blockade in NSCLC: progress in basic research and clinical application.

Lung cancer poses a global threat to human health, while common cancer treatments (chemotherapy and targeted therapies) have limited efficacy. Immunotherapy offers hope of sustained remission for many patients with lung cancer, but a significant proportion of patients fail to respond to treatment owing to immune resistance. There is extensive evidence to suggest the immunosuppressive microenvironment as the cause of this treatment failure. Numerous studies have suggested that the adenosine (ADO) pathway plays an important role in the formation of an immunosuppressive microenvironment and may be a key factor in the development of immune resistance in EGFR-mutant cell lung cancer. Inhibition of this pathway may therefore be a potential target to achieve effective reversal of ADO pathway-mediated immune resistance. Recently, an increasing number of clinical trials have begun to address the broad prospects of using the ADO pathway as an immunotherapeutic strategy. However, few researchers have summarized the theoretical basis and clinical rationale of the ADO pathway and immune checkpoint dual blockade in a systematic and detailed manner, particularly in lung cancer. As such, a timely review of the potential value of the ADO pathway in combination with immunotherapy strategies for lung cancer is warranted. This comprehensive review first describes the role of ADO in the formation of a lung tumor-induced immunosuppressive microenvironment, discusses the key mechanisms of ADO inhibitors in reversing lung immunosuppression, and highlights recent evidence from preclinical and clinical studies of ADO inhibitors combined with immune checkpoint blockers to improve the lung cancer immunosuppressive microenvironment.

Effects of selenium-enriched yeast dietary supplementation on egg quality, gut morphology and caecal microflora of laying hens.

Selenium (Se) is an essential micronutrient for humans and animals and is a powerful antioxidant that can promote reproductive and immune functions. The purpose of this study was to evaluate the effects of supplemental dietary selenium-enriched yeast (SeY) on egg quality, gut morphology and microflora in laying hens. In total, 100 HY-Line Brown laying hens (45-week old) were randomly allocated to two groups with 10 replicates and fed either a basal diet (without Se supplementation) or a basal diet containing 0.2 mg/kg Se in the form of SeY for 8 weeks. The Se supplementation did not have a significant effect on egg quality and intestinal morphology of laying hens. Based on the 16S rRNA sequencing, SeY dietary supplementation effectively modulated the cecal microbiota structure. An alpha diversity analysis demonstrated that birds fed 100 mg/kg SeY had a higher cecal bacterial diversity. SeY dietary addition elevated Erysipelotrichia (class), Lachnospiraceae (family), Erysipelotrichaceae (family) and Ruminococcus_torques_group (genus; p < .05). Analysis of microbial community-level phenotypes revealed that SeY supplementation decreased the microorganism abundance of facultatively anaerobic and potentially pathogenic phenotypes. Overall, SeY supplementation cannot significantly improve intestinal morphology; however, it modulated the composition of cecal microbiota toward a healthier gut.

Engineering a Z-Scheme Heterostructure on ZnIn2S4@NH2-MIL-125 Composites for Boosting the Photocatalytic Performance.

Constructing a Z-scheme heterostructure on a metal-organic framework (MOF) composite with an explicit charge transfer mechanism at the interface is considered to be an effective strategy for improving the photocatalytic performance of MOFs. Herein, an internal electric field (IEF)-induced Z-scheme heterostructure on the ZnIn2S4@NH2-MIL-125 composite is designed and fabricated by a facile electrostatic self-assembly process. Systematic investigations reveal that close interfacial contact and difference in work function between NH2-MIL-125 and ZnIn2S4 enable the formation of the IEF, which drives the Z-scheme charge transfer as revealed by the in situ irradiated X-ray photoelectron spectroscopy (ISI-XPS), photoirradiated Kelvin probe force microscope (KPFM) measurement, electron paramagnetic resonance (EPR) radical trapping experiment, as well as density functional theory (DFT) calculation; meanwhile, directions of the interfacial IEFs are determined. Benefiting from the unique merit of IEF-induced Z-scheme charge transfer, the optimized ZnIn2S4@NH2-MIL-125 composite exhibits significantly enhanced photocatalytic activity for the photoreduction of 4-nitroaniline (4-NA) to p-phenylenediamine (PPD) under visible light irradiation. This work not only provides in-depth insights for charge transfer in the IEF-induced Z scheme heterostructure but also affords useful inspirations on designing the Z-scheme MOF composite to boost the photocatalytic performance.

Ferroptosis in cancer immunity and immunotherapy: Multifaceted interplay and clinical implications.

Ferroptosis is a type of cell death characterized by iron-dependent phospholipid peroxidation and reactive oxygen species overproduction. Ferroptosis induces immunogenic cell death and elicits anti-tumor immune responses, playing an important role in cancer immunotherapy. Ferroptosis suppression in cancer cells impairs its immunotherapeutic efficacy. To overcome this issue, ferroptosis inducers (FINs) have been combined with other cancer therapies to create an anti-tumor immune microenvironment. However, the ferroptosis-based crosstalk between immune and tumor cells is complex because oxidative products released by ferroptotic tumor cells impair the functions of anti-tumor immune cells, resulting in immunotherapeutic resistance. In the present article, we have reviewed ferroptosis in tumor and immune cells and summarized the crosstalk between ferroptotic tumor cells and the immune microenvironment. Based on the existing literature, we have further discussed future perspectives on opportunities for combining ferroptosis-targeted therapies with cancer immunotherapies.

Genome-wide meta-analysis, functional genomics and integrative analyses implicate new risk genes and therapeutic targets for anxiety disorders.

Anxiety disorders are the most prevalent mental disorders. However, the genetic etiology of anxiety disorders remains largely unknown. Here we conducted a genome-wide meta-analysis on anxiety disorders by including 74,973 (28,392 proxy) cases and 400,243 (146,771 proxy) controls. We identified 14 risk loci, including 10 new associations near CNTNAP5, MAP2, RAB9BP1, BTN1A1, PRR16, PCLO, PTPRD, FARP1, CDH2 and RAB27B. Functional genomics and fine-mapping pinpointed the potential causal variants, and expression quantitative trait loci analysis revealed the potential target genes regulated by the risk variants. Integrative analyses, including transcriptome-wide association study, proteome-wide association study and colocalization analyses, prioritized potential causal genes (including CTNND1 and RAB27B). Evidence from multiple analyses revealed possibly causal genes, including RAB27B, BTN3A2, PCLO and CTNND1. Finally, we showed that Ctnnd1 knockdown affected dendritic spine density and resulted in anxiety-like behaviours in mice, revealing the potential role of CTNND1 in anxiety disorders. Our study identified new risk loci, potential causal variants and genes for anxiety disorders, providing insights into the genetic architecture of anxiety disorders and potential therapeutic targets.

Effects of dietary supplementation with tea polyphenols and probiotics on laying performance, biochemical parameters intestinal morphology and microflora of laying hens.

This study was conducted to investigate the effects of tea polyphenols (TP) and probiotics (PB) on the production performance, biochemical indices, and gut health of laying hens. A total of 400 Hy-line Brown layers (45 weeks old) were randomly assigned to 8 diet groups for 8-week feeding trial. Compared with the control basal diet (CT), dietary high dosage of TP and PB (HTP-PB) increased egg mass (P < 0.05). Supplementation with HTP-PB improved the levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and decreased the malonic dialdehyde (MDA) content (P < 0.05) without affecting the contents of immunoglobulins in the serum. The combination of HTP and PB supplementation promoted the secretion of estradiol (E2) and progesterone (PROG) compared with treatment with TP or PB alone (P < 0.05). The combined use of HTP and PB induced higher jejunal villus height (VH) than the CT group (P < 0.05). Dietary TP and PB could optimize the functional network of intestinal microflora and the interactions between the intestinal microflora and the host. Therefore, the combined use of the high dosage of TP and PB affected laying performance, improved antioxidant capacity, and promoted intestinal health, which may be associated with regulation of the intestinal microbiota.

Association between dietary flavonoid intake and depressive symptoms: A cross-sectional research.

OBJECTIVE: To investigate the relationship between dietary flavonoid intake and depression symptoms in American adults. METHODS: Data sets were obtained from the National Health and Nutrition Examination Survey (NHANES) 2007-2008, 2009-2010, and 2017-2018 survey cycles. Both males and females aged 18 years and older with complete information about dietary flavonoid intake (isoflavones, anthocyanidins, flavan-3-ols, flavanones, flavones, and flavonols), depression symptoms, and covariates were included. Logistic regression models were conducted to calculate the odds ratio (OR) of single dietary flavonoid subclass intake on depression, and the restricted cubic spline (RCS) models were utilized to explore the corresponding dose-response relationships. Additionally, we implemented the weighted quantile sum (WQS) regression and quantile g-computation (qgcomp) models to estimate the mixed effects of six flavonoid subclasses and identify the predominant types. RESULTS: After multivariable adjustments, people with higher consumption of flavanones (OR: 0.68, 95% CI: 0.52-0.90, p = 0.008), flavones (OR: 0.63, 95% CI: 0.46-0.87, p = 0.007), flavonols (OR: 0.66, 95% CI: 0.49-0.89, p = 0.008), and total flavonoids (OR: 0.69, 95% CI: 0.50-0.95, p = 0.024) had lower odds of depression symptoms. Meanwhile, significant dose-response relationships were supported by the RCS models. However, no obvious associations between isoflavones, anthocyanidins, flavan-3-ols, and the odds of suffering from depression symptoms were found by the logistic regression models and RCS models. As for the mixed effect, the WQS and qgcomp models both demonstrated that the mixture of six flavonoid subclasses was inversely related to the odds ratios of depression symptoms, and flavones, flavanones, and anthocyanidins were the top 3 contributors. CONCLUSION: Our study implied dietary flavonoid intake was associated with the decreased probability of depression symptoms in U.S. adults, among which flavones, flavanones, and anthocyanidins may occupy the predominant roles.

Relationship between dietary carotenoid intake and sleep duration in American adults: a population-based study.

OBJECTIVE: To investigate the relationship between dietary carotenoid intake and sleep duration. METHODS: Adults enrolled in the National Health and Nutrition Examination Survey (NHANES) 2007-2018 without missing information on dietary carotenoid intake (α-carotene, ß-carotene, ß-cryptoxanthin, lycopene, and lutein + zeaxanthin), sleep duration, and covariates were included. Participants' carotenoid consumption was divided into three groups by quartiles and sleep duration was grouped as short (< 7 h/night), optimal (7-8 h/night), and long (> 8 h/night). Multinominal logistic regression was constructed to examine the association between dietary carotenoid intake and sleep duration. Restricted cubic spline (RCS) regression was further utilized to explore their dose-response relationship. The weighted quantile sum (WQS) model was adopted to calculate the mixed and individual effect of 5 carotenoid sub-types on sleep duration. RESULTS: Multinominal logistic regression presented that people with higher intakes of α-carotene, ß-carotene, ß-cryptoxanthin, lycopene, and lutein + zeaxanthin were less likely to sleep too short or too long. Consistent with the findings from multinominal logistic regression, the RCS models suggested a reverse U-shaped relationship between sleep duration and carotenoid intakes. The mixed effects were also significant, where ß-cryptoxanthin and lutein + zeaxanthin were the top 2 contributors associated with the decreased risks of short sleep duration, while ß-carotene, α-carotene, and ß-cryptoxanthin were the main factors related to the lower risk of long sleep duration. CONCLUSION: Our study revealed that the American adults with optimal sleep duration were associated with more dietary carotenoid intake, in comparison to short or long sleepers.

Sexual activity, sexual satisfaction and their correlates among older adults in China: findings from the sexual well-being (SWELL) study.

Background: Sexual activity is important to the holistic health of older adults. However, the sexual lives of older adults are understudied. We aimed to investigate the prevalence and correlates of sexual activity and sexual satisfaction among older adults in China. Methods: In this multi-centre cross-sectional study, individuals aged 50 years and older were recruited from four regions in China between June 2020 and December 2022. An investigator-administered questionnaire was completed to collect information on socio-demographics, health status (general health and specific health), and sexual health characteristics. Sexual activity (including vaginal, oral, or anal sex) in the past year was treated as sexually active. Sexual satisfaction was measured using a validated five-point Likert scale. Logistic regression was used to assess correlates of sexual activity and sexual satisfaction. Findings: 3001 older adults (1182 women and 1819 men, mean age 60.3 ± 7.8 years) were recruited. Most participants were living in urban areas (1688, 56.2%), in a stable relationship (2531, 84.3%), and satisfied with life (2141, 71.3%). 46.8% of men and 40.7% of women were sexually active. Better self-reported general health status (good: aOR 0.53, 95% CI 0.34-0.82; fair: 0.47, 0.29-0.76; bad or very bad: 0.58, 0.35-0.96; versus very good), no difficulty walking upstairs (0.63, 0.41-0.97), diabetes (0.64, 0.42-0.98), and menopause (0.57, 0.36-0.92), were associated with sexual activity among women. Such an association was not found among men. Among sexually active participants, about three-quarters (men: 73.6%, women: 73.4%) were sexually satisfied. Self-reported general health status (men [good: 0.25, 0.12-0.53; fair: 0.17, 0.08-0.37; bad or very bad: 0.15, 0.06-0.34]; women [good: 0.27, 0.10-0.70; fair: 0.11, 0.04-0.30; bad or very bad: 0.11, 0.04-0.32]), life satisfaction (men: 1.73, 1.22-2.46; women: 2.23, 1.34-3.71) and talking about sexual preferences with a partner (men: 1.77, 1.23-2.56; women: 2.93, 1.69-5.09) were associated with sexual satisfaction. Interpretation: Older adults who had better health status and talked easily with their partners about their sex life were more likely to report sexual satisfaction. For women, better self-reported general health status and lack of disability were associated with sexual activity. Further research should address measures that improve sexual satisfaction, especially among sexually active older adults. Funding: This study was supported by the Natural Science Foundation of China International/Regional Research Collaboration Project [72061137001] and the Economic and Social Research Council [ES/T014547/1].

Stable Pyrene-Based Metal-Organic Framework for Cyclization of Propargylic Amines with CO2 and Detection of Antibiotics in Water.

A pyrene-based metal-organic framework, Cd2(PTTB)(H2O)2 (WYU-11), was synthesized from the tetracarboxylic pyrene ligand H4PTTB (H4PTTB = 1,3,6,8-tetrakis(3-carboxyphenyl)pyrene) and Cd(NO3)2·4H2O. Powder X-ray diffraction analysis discloses that the framework is stable in acid, base, and various organic solvent environments. WYU-11 shows excellent catalytic performance on the cyclization reaction of propargylic amines with CO2 into 2-oxazolidinones under mild conditions (60 °C, atmospheric CO2). 1H NMR studies unveiled that WYU-11 and 1,1,3,3-tetramethylguanidine (TMG) can synergistically activate the propargylic amine substrate and promote the reaction. Importantly, WYU-11 represents a rare example of noble metal-free heterogeneous catalyst that can catalyze the cyclization of CO2 with propargylic amines. In addition, by virtue of the excellent water stability and luminescence properties, WYU-11 shows excellent detection performance for sulfathiazole (STZ) and ornidazole (ODZ) in water. Investigation reveals that the coexistence of photoinduced electron transfer and internal filtering effect could reasonably explain the luminescence quenching of WYU-11 by the antibiotics.

Efficacy and safety of reduced-dose chemotherapy plus immunotherapy in patients with lung squamous cell carcinoma: A real-world observational study.

BACKGROUND: Recently, chemotherapy plus immunotherapy has achieved remarkable efficacy in lung squamous cell carcinoma (LUSC). However, some patients, especially frail people, cannot tolerate full-dose chemotherapy in the real world. To reduce toxicity, appropriate dose reduction in chemotherapy is necessary. Therefore, this study aimed to demonstrate the efficacy and safety of reduced-dose chemotherapy plus immunotherapy in LUSC patients in the real world. METHODS: A real-world observational study was conducted concerning patients who received chemotherapy plus immunotherapy in our situation. The primary endpoints were objective response rate (ORR) and disease control rate (DCR), and the secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity. RESULTS: Between December 2018 and January 2022, 110 patients were enrolled, of whom 54 patients were chemotherapy reduced-dose group and 56 patients were chemotherapy standard-dose group. The ORR in the reduced-dose group is similar to standard-dose group (85.19% vs. 71.43%, p = 0.082). Similar DCR were observed (100% vs. 94.64%, p = 0.086). Median PFS was 12 months in the reduced-dose group and standard-dose group, respectively. Median OS was 15 months and 16 months in the reduced-dose group and standard-dose group, respectively. We reported a lower incidence of grade 3-4 toxicity in the reduced-dose group compared with standard-dose group (27.78% vs. 42.86%, p = 0.100). The major toxic reactions were better alleviated in the reduced-dose group than in the standard-dose group, especially in the thrombocytopenia (p = 0.044), peripheral nerve damage (p = 0.001), gastrointestinal reactions (p < 0.0001), and fatigue (p = 0.001). CONCLUSIONS: The modified regimen with attenuated doses of chemotherapy in combination with immunotherapy was effective and well tolerated in patients with LUSC. The efficacy of this modified regimen is similar to that of the full-dose regimen.

Association between frailty and depression: A bidirectional Mendelian randomization study.

Frailty and depression were linked in observational studies, but the causality remains ambiguous. We intended to explore it using Mendelian randomization (MR). We obtained frailty genome-wide association study (GWAS) data from UK Biobank and TwinGen meta-analysis, and depression GWAS data from Psychiatric Genomics Consortium (PGC) and FinnGen (respectively recorded as PD and FD). We performed univariable and multivariable-adjusted MR with adjustments for body mass index (BMI) and physical activity (PA). Frailty was significantly associated with elevated risks of PD (OR, 1.860; 95% CI, 1.439 to 2.405; P < 0.001) and FD (OR, 1.745; 95% CI, 1.193 to 2.552; P = 0.004), and depression was meanwhile a susceptible factor for frailty (PD: ß, 0.146; 95% CI, 0.086 to 0.201; P < 0.001; and FD: ß, 0.112; 95% CI, 0.051 to 0.174; P < 0.001). This association was robust after adjustments for BMI or PA. Our study provides evidence of the bidirectional causal association between frailty and depression from genetic perspectives.