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Abstract HER2-positive breast cancer patients carrying the germline TSC2 nonsynonymous variant c.4349 C > G (p.Pro1450Arg) are resistant to anti-HER2 therapy. Multi-predictor in silico analysis reveals that this variant is deleterious. We explore the potential mechanism of this TSC2 variant and investigate methods for overcoming anti-HER2 resistance. TSC2 c.4349 C > G reverses the inhibitory effect on mTOR and downstream signaling by increasing TSC2 phosphorylation at Thr1462 and confers significant lapatinib resistance in vitro and in vivo. The combination of lapatinib and the CDK4/6 inhibitor palbociclib inhibits cyclin D1/CDK4/Rb alternative pathway and TSC2 phosphorylation, thereby partially attenuating mTOR activity and inducing TSC2-mutant cell blockage at G1/G0. In in vitro and xenograft models, palbociclib+lapatinib shows higher anti-tumor activity than monotherapy and overcomes the resistance of the TSC2 c.4349 C > G-related variant to anti-HER2 therapy. We reveal a new mechanism of resistance to anti-HER2 therapy and provide a strategy to increase the efficiency of anti-HER2 therapy in HER2-positive breast cancer.

Abstract In the past period, due to the rapid development of next-generation sequencing technology, accumulating evidence has clarified the complex role of the human microbiota in the development of cancer and the therapeutic response. More importantly, available evidence seems to indicate that modulating the composition of the gut microbiota to improve the efficacy of anti-cancer drugs may be feasible. However, intricate complexities exist, and a deep and comprehensive understanding of how the human microbiota interacts with cancer is critical to realize its full potential in cancer treatment. The purpose of this review is to summarize the initial clues on molecular mechanisms regarding the mutual effects between the gut microbiota and cancer development, and to highlight the relationship between gut microbes and the efficacy of immunotherapy, chemotherapy, radiation therapy and cancer surgery, which may provide insights into the formulation of individualized therapeutic strategies for cancer management. In addition, the current and emerging microbial interventions for cancer therapy as well as their clinical applications are summarized. Although many challenges remain for now, the great importance and full potential of the gut microbiota cannot be overstated for the development of individualized anti-cancer strategies, and it is necessary to explore a holistic approach that incorporates microbial modulation therapy in cancer.

As a type of ultra-high strength steel, AerMet100 steel is used in the aerospace and military industries. Due to the fact that AerMet100 steel is difficult to machine, people have been exploring the process of additive manufacturing to fabricate AerMet100 steel. In this study, AerMet100 steel was produced using an in situ rolling hybrid with wire arc additive manufacturing. Microstructure, tensile properties, and fracture toughness of as-deposited and heat-treated AerMet100 steel were evaluated in different directions. The results reveal that the manufacturing process leads to grain fragmentation and obvious microstructural refinement of the AerMet100 steel, and weakens the anisotropy of the mechanical properties. After heat treatment, the microstructure of the AerMet100 steel is mainly composed of lath martensite and reversed austenite. Alloy carbides are precipitated within the martensitic matrix, and a high density of dislocations is the primary strengthening mechanism. The existence of film-like austenite among the martensite matrix enhances the toughness of AerMet100 steel, which coordinates stress distribution and restrains crack propagation, resulting in an excellent balance between strength and toughness. The AerMet100 steel with in situ rolling is isotropy and achieves the following values: an average ultimate strength of 1747.7 ± 16.3 MPa, yield strength of 1615 ± 40.6 MPa, elongation of 8.3 ± 0.2% in deposition direction, and corresponding values in the building direction are 1821.3 ± 22.1 MPa, 1624 ± 84.5 MPa, and 7.6 ± 1.7%, and the KIC value up to 70.6 MPa/m0.5.

Xylanase is an essential component used to hydrolyze the xylan in wheat flour to enhance the quality of bread. Presently, cold-activated xylanase is popularly utilized to aid in the development of dough. In this study, ancestral sequence reconstruction and molecular docking of xylanase and wheat xylan were used to enhance the activity and stability of a thermophilic xylanase. The results indicated that the ancestral enzyme TmxN3 exhibited significantly improved activity and thermal stability. The Vmax increased by 2.7 times, and the catalytic efficiency (Kcat/Km) increased by 1.7 times in comparison to TmxB. After being incubated at 100 °C for 120 min, it still retained 87.3% of its activity, and the half-life in 100 °C was 330 min, while the wild type xylanase was only 55 min. This resulted in an improved shelf life of bread, while adding TmxN3 considerably enhanced its quality with excellent volume and reduced hardness, chewiness, and gumminess. The results showed that the hardness was reduced by 55.2%, the chewiness was reduced by 40.11%, and the gumminess was reduced by 53.52%. To facilitate its industrial application, we further optimized the production conditions in a 5L bioreactor, and the xylanase activity reached 1.52 × 106 U/mL culture.

BackgroundExposure to high-intensity X-ray irradiation induces numerous defects in the thin films of optical components applied to X-ray free-electron laser (XFEL) facilities. These defects result in structural damage to the material and degradation of macroscopic properties, thereby affecting its service life and significantly compromising the reliability and stability of XFEL facilities.PurposeThis paper aims to design and implement an automated irradiation simulation software based on Python called automatic irradiation simulation based on LAMMPS (AISL) to support the simulation research of XFEL radiation damage to materials using molecular dynamics methods.MethodsAISL was designed to facilitate high-throughput automated studies on XFEL radiation damage by exploring the process of radiation-induced defects and promoting the accumulation of data for radiation-resistant materials. This software package established an automated workflow pipeline for simulation tasks, encompassing aspects such as batch submission management, scheduling of simulation tasks, reliable storage of computational data, and post-processing of thermodynamic information. Additionally, the metadata was automatically recorded in a radiation damage simulation database based on MongoDB, so were the workflow information, and calculation result files of the simulation. Finally, the utilization of AISL in simulating radiation damage in metal thin films of XFEL optical components was demonstrated to verify the validation of AISL.Results & ConclusionsThe demonstration results indicate that AISL is an effective, user-friendly software for conducting high-throughput automated irradiation simulation studies. It significantly enhances the efficiency of material irradiation damage simulation calculations using LAMMPS.

Unmanned aerial vehicle–light detection and ranging (UAV-LiDAR) provides a convenient and economical means of forest data acquisition that can penetrate canopy gaps to obtain abundant ground information, offering huge potential in forest inventory. Individual tree segmentation is a prerequisite to obtain individual tree details but is highly dependent on the accuracy of seed point detection. However, most of the existing methods, such as the local maximum (LM) and CHM-based methods, are strongly dependent on the window size, and, for individual tree segmentation, they can result in over-segmentation and under-segmentation, especially in natural forests. In this paper, we propose an adaptive crown shaped algorithm for individual tree segmentation without consideration of the window size. It was implemented in four plots with different forest types and topographies (i.e., planted coniferous forest with flat terrain, coniferous forest with sloping terrain, mixed forest with flat terrain and broadleaf forest with flat terrain). First, the normalized point clouds were rotated and blocked at multiple angles to extract the surface points of the forest. Then, the crown boundaries were delineated by analyzing the crown profiles to extract the treetops as seed points. Finally, a region growing method based on seed points was applied for individual tree segmentation. Our results showed that the recall, precision and F1-score of seed point detection reached 91.6%, 95.9% and 0.94, respectively, and that the accuracy rates for individual tree segmentation for the four plots were 87.7%, 80.6%, 73.2% and 70.5%, respectively. Our proposed method can effectively detect seed points via the adaptive crown shaped algorithm and reduce the impacts of elongated branches by applying distance thresholds between trees, enhancing the accuracy of seed point detection and subsequently improving the precision of individual tree segmentation. In addition, the proposed algorithm demonstrated superior performance in comparison to LM and CHM-based methods for the calculation of seed points, as well as outperforming PCS in individual tree segmentation. The proposed method demonstrates effectiveness and feasibility in dense forests and natural forests, providing an important reference for future research on seed point detection and individual tree segmentation.

Aniline compounds, as a class of widely used but highly toxic chemical raw materials, are increasingly being released and accumulated in the environment, posing serious threats to environmental safety and human health. Therefore, developing detection methods for aniline compounds is of particular significance. Herein, we synthesized the fluorescent third monomer cyano-stilbene epoxide M and ternary copolymerized it with carbon dioxide (CO2) and propylene oxide (PO) to synthesize carbon dioxide-based polycarbonate (PPCM) with fluorescence recognition functions, as well as excellent performance, for the first time. The results revealed that the PPCM fluorescent probe exhibited typical aggregation-induced luminescence properties and could be quenched by aniline compounds. The probe presented anti-interference-specific selectivity for aniline compounds, and the detection limit was 1.69 × 10−4 M. Moreover, it was found to be a highly sensitive aniline detection probe. At the same time, the aniline biomarker p-aminophenol in urine could also be detected, which could expand the potential applications of polymers in the fluorescence-sensing field.

Investigating the mechanisms by which plants adapt to low phosphorus content in ecosystems is crucial for nutrient dynamics division. Our study investigated the growth adaptation strategies of Pinus massoniana seedlings to low phosphorus conditions, including nutrient and non-structural carbohydrate (NSC) allocation, nutrient stoichiometry, and changes in nutrient resorption efficiency along a fact-based gradient. Our results showed that the total biomass and aboveground biomass proportion increased with substrate phosphorus content, reaching maximum biomass in the one-time phosphorus treatment. The nutrient concentration of components remained relatively stable, with the allocating preference to roots and needles under low phosphorus conditions. NSC was allocated as starch in fine roots and as soluble sugar in needles. Seedlings did not show signs of phosphorus limitation, even in the non-phosphorus group. The nitrogen resorption efficiency to phosphorus resorption efficiency ratio (NRE: PRE) of needles significantly varied between the high and low phosphorus treatments. In response to phosphorus deficiency, seedlings demonstrated homeostatic adjustments to maintain the relative stability of nutrient concentration. Fine roots and needles were prioritized to ensure nutrient uptake and photosynthetic product production. Additionally, it was necessary to differentiate the indicative function of nitrogen/phosphorus for various species and components, and NRE: PRE potentially provides a sensitive indicator of nutrient limitation status.

Objective To observe the effect of brain exercise training on cognitive function and behavioral and psychological symptoms of patients with mild cognitive impairment （MCI）. Methods 80 patients with MCI were randomly divided into the intervention （n = 40） and control groups （n = 40）. In the intervention group， brain exercise training was delivered for 45-60 min twice a week for 12 consecutive weeks. Mini-Mental State Examination Scale （MMSE）， Montreal Cognitive Assessment （MoCA）， Zung’s Self-rating Anxiety Scale （SAS）， Zung’s Self-rating Depression Scale （SDS）， Neuropsychiatric Inventory （NPI） and Pittsburgh Sleep Quality Index （PSQI） between two groups were evaluated at the baseline， 3 months and 6 months， respectively. Results In the control group， the total MMSE scores at 3 and 6 months were significantly declined compared with the baseline value （P < 0.001， P = 0.007）， the scores of attention and calculation domains were significantly decreased （P < 0.001， P = 0.009）， and the score of language domain was also significantly declined at 6-month follow-up （P = 0.012）. No significant differences were observed regarding the total and each domain scores of MMSE at different time points in the intervention group （all P > 0.05）. In the control group， the total MoCA scores at 3- and 6-month follow-up were significantly lower than the baseline value （P = 0.011， P < 0.001）， and the scores of attention and calculation domains were considerably declined （P = 0.002， P = 0.048）. In the intervention group， the total MoCA score at 6 months was significantly higher than the baseline value （P = 0.001）， and the scores of attention and calculation domains at 3- and 6-month follow-up were considerably higher compared with the baseline values （both P < 0.001）， which significantly differed between two groups （both P < 0.001）. In the control group， the SAS scores at 3- and 6-month follow-up were significantly higher than the baseline values （P = 0.001， P = 0.003）， the SDS scores at 3- and 6-month follow-up were also significantly higher compared with the baseline values （P = 0.002， P = 0.007）. In the intervention group， the SDS score at 6 months was significantly lower than the baseline score （P = 0.009）. The SAS and SDS scores at 6-month follow-up significantly differed between two groups （P = 0.002， P = 0.016）. No significant changes were observed in the NPI and PSQI scores between two groups. Conclusion Brain exercise training can improve the cognitive function and stabilize the mood of MCI patients to a certain extent， which might play a positive role in preventing or delaying the progression of MCI into dementia.

Abstract Background Currently, the study outcomes of anthropometric markers to predict the risk of hypertension are still inconsistent due to the effect of racial disparities. This study aims to investigate the most effective predictors for screening and prediction of hypertension (HTN) in the Chinese middle-aged and more elderly adult population and to predict hypertension using obesity and lipid-related markers in Chinese middle-aged and older people. Methods The data for the cohort study came from the China Health and Retirement Longitudinal Study (CHARLS), including 4423 middle-aged and elderly people aged 45 years or above. We examined 13 obesity- and lipid-related indices, including waist circumference (WC), body mass index (BMI), waist-height ratio (WHtR), visceral adiposity index (VAI), a body shape index (ABSI), body roundness index (BRI), lipid accumulation product index (LAP), conicity index (CI), Chinese visceral adiposity index (CVAI), triglyceride-glucose index (TyG-index) and their combined indices (TyG-BMI, TyG-WC, TyG-WHtR). To compare the capacity of each measure to forecast the probability of developing HTN, the receiver operating characteristic curve (ROC) was used to determine the usefulness of anthropometric indices for screening for HTN in the elderly and determining their cut-off value, sensitivity, specificity, and area under the curve (AUC). Association analysis of 13 obesity-related anthropometric indicators with HTN was performed using binary logistic regression analysis. Results During the four years, the incident rates of HTN in middle-aged and elderly men and women in China were 22.08% and 17.82%, respectively. All the above 13 indicators show a modest predictive power (AUC > 0.5), which is significant for predicting HTN in adults (middle-aged and elderly people) in China (P

Abstract Background Familial hypercholesterolemia (FH) is an inherited metabolic disorder with a high level of low-density lipoprotein cholesterol and the worse prognosis. The triglyceride-glucose (TyG) index, an emerging tool to reflect insulin resistance (IR), is positively associated with a higher risk of atherosclerotic cardiovascular disease (ASCVD) in healthy individuals, but the value of TyG index has never been evaluated in FH patients. This study aimed to determine the association between the TyG index and glucose metabolic indicators, insulin resistance (IR) status, the risk of ASCVD and mortality among FH patients. Methods Data from National Health and Nutrition Examination Survey (NHANES) 1999–2018 were utilized. 941 FH individuals with TyG index information were included and categorized into three groups: 9.0. Spearman correlation analysis was used to test the association of TyG index and various established glucose metabolism-related indicators. Logistic and Cox regression analysis were used to assess the association of TyG index with ASCVD and mortality. The possible nonlinear relationships between TyG index and the all-cause or cardiovascular death were further evaluated on a continuous scale with restricted cubic spline (RCS) curves. Results TyG index was positively associated with fasting glucose, HbA1c, fasting insulin and the homeostatic model assessment of insulin resistance (HOMA-IR) index (all p

Highlights Chemical composition of TPRL was identified by UPLC-Q/TOF/MSn in the profile of total ion current. TPRL was initially demostrated the effects of anti-hepatic fibrosis in vitro and in vivo. TPRL ameliorates hepatic fibrosis through apoptosis by TGF-β/Smad signaling pathway.

Germanium-on-silicon (Ge-on-Si) single photon avalanche diodes (SPADs) have received wide attention in recent years due to their potential to be integrated with Si photonics. In this work, we propose and demonstrate a high-performance waveguide coupled Ge-on-Si separate-absorption-charge-multiplication SPAD with three electric terminals. By providing two separate voltage drops on the light absorption and multiplication regions, the drift and multiplication of carriers can be optimized separately. This indeed improves the freedom of voltage regulation for both areas. Moreover, thanks to the separate controlling, doping profile of the charge layer is greatly released compared to that of the conventional device because of the flexible carrier injection. In this scenario, the dark counts of the detector can be largely reduced through decreasing the electric field on the sidewalls of the Ge absorption region without affecting the detection efficiency. The proposed SPAD exhibits a high on-chip single photon detection efficiency of 34.62% and low dark count rates of 279 kHz at 1310 nm with the temperature of 78 K. The noise equivalent power is as low as 3.27 × 10−16 WHz−1/2, which is, to the best of our knowledge, the lowest of that of the reported waveguide coupled Ge-on-Si SPADs. This three-terminal SPAD enables high-yield fabrication and provides robust performance in operation, showing a wide application prospect in applications such as on-chip quantum communication and lidar.

Objective During total knee arthroplasty, femur and tibia parts are regularly replaced, while resurfacing the patellar or not is an ongoing discussion. To compare revision rate, anterior knee pain rate, patient‐reported outcome measures, complication, radiographic, and clinical outcomes after patellar resurfacing versus non‐resurfacing in total knee arthroplasty. Methods PubMed, Medline, EMBASE, CENTRAL, and CINAHL databases were searched on 25 April 2021 to enroll randomized controlled trials that compared patellar resurfacing versus non‐resurfacing. We used the grading of recommendations assessment, development and evaluation (GRADE) framework to assess the certainty of evidence. Our primary outcome was revision rate and secondary outcomes was anterior knee pain rate. Outcomes were pooled using the random‐effect model and presented as risk ratio (RR), or mean difference (MD), with 95% confidence interval (CI). Results Fifty studies (5586 knees) were included. Significant reductions in patellar revision rate (RR 0.41, 95% CI [0.19, 0.88]; P = 0.02; I2 = 24.20%) and non‐patellar revision rate (RR 0.64, 95% CI [0.55, 0.75]; P

The volume and composition of a thin layer of liquid covering the airway surface defend the lung from inhaled pathogens and debris. Airway epithelia secrete Cl– into the airway surface liquid through cystic fibrosis transmembrane conductance regulator (CFTR) channels, thereby increasing the volume of airway surface liquid. The discovery that pulmonary ionocytes contain high levels of CFTR led us to predict that ionocytes drive secretion. However, we found the opposite. Elevating ionocyte abundance increased liquid absorption, whereas reducing ionocyte abundance increased secretion. In contrast to other airway epithelial cells, ionocytes contained barttin/Cl– channels in their basolateral membrane. Disrupting barttin/Cl– channel function impaired liquid absorption, and overexpressing barttin/Cl– channels increased absorption. Together, apical CFTR and basolateral barttin/Cl– channels provide an electrically conductive pathway for Cl– flow through ionocytes, and the transepithelial voltage generated by apical Na+ channels drives absorption. These findings indicate that ionocytes mediate liquid absorption, and secretory cells mediate liquid secretion. Segregating these counteracting activities to distinct cell types enables epithelia to precisely control the airway surface. Moreover, the divergent role of CFTR in ionocytes and secretory cells suggests that cystic fibrosis disrupts both liquid secretion and absorption.

Regulatory T cells (Tregs) are instrumental in maintaining immune tolerance and preventing destructive autoimmunity, but how heterogeneous Treg populations are established remains largely unknown. Here, we show that Zfp335 deletion in Tregs failed to differentiate into effector Tregs (eTregs) and lose Treg-suppressive function and that KO mice exhibited early-onset lethal autoimmune inflammation with unrestricted activation of conventional T cells. Single-cell RNA-Seq analyses revealed that Zfp335-deficient Tregs lacked a eTreg population and showed dramatic accumulation of a dysfunctional Treg subset. Mechanistically, Zfp335-deficient Tregs displayed reduced oxidative phosphorylation and dysfunctional mitochondrial activity. Further studies revealed that Zfp335 controlled eTreg differentiation by regulating fatty acid oxidation (FAO) through direct targeting of the FAO enzyme Hadha. Importantly, we demonstrate a positive correlation between ZNF335 and HADHA expression in human eTregs. Our findings reveal that Zfp335 controls FAO-driven eTreg differentiation to establish immune tolerance.

BackgroundPortal vein thrombosis (PVT) is a serious complication of liver cirrhosis (LC) and is closely related to gut homeostasis. The study aimed to investigate the composition of gut microbiota and its putative role in PVT development in LC.Methods33 patients with LC admitted between January 2022 and December 2022 were enrolled in this study. Based on imaging findings, they were categorized into LC without PVT (n = 21) and LC with PVT (n = 12) groups. Fecal samples were collected from each participant and underwent 16S rDNA sequencing.ResultsD-Dimer and platelet elevations were the main clinical features of LC with PVT. The alpha and beta diversity of the gut microbiota in LC with PVT group was found to be significantly higher compared to the control group. The structure of the gut microbiota was significantly different between the two groups. Based on LEfSe data, the genera Akkermansia, Eubacterium hallii group, Fusicatenibacter, and Anaerostipes were enriched in the LC with PVT, while Enterococcus, Weissella, Bacteroides, and Subdoligranulum were enriched in those of the LC subjects. Changes in microbiota structure result in significant differences in gut microbiota metabolism between the two groups. Altered levels of the microbiota genera were shown to be correlated with coagulation factor parameters. In animal experiments, the addition of Bacteroides reversed the CCl4-induced PVT.ConclusionLiver cirrhosis with PVT led to a disorder in the gut microbiota, which was characterized by an increase in pathogenic bacteria and a decrease in beneficial bacteria. Furthermore, modulating the gut microbiota, especially Bacteroides, may be a promising therapeutic approach to reduce the progression of PVT in LC.

BackgroundAn increasing number of studies have shown the association between traumatic events occurring in childhood and adolescence and post-traumatic stress disorder (PTSD). A gap remains in the literature on the epidemiology and influencing factors of traumatic events and post-traumatic stress disorder in communities in northern China. This study aimed to determine the prevalence of traumatic events and PTSD in communities in northern China, to explore the types of stressful traumatic events and the impact of these traumatic events on children and adolescents, and to investigate the effect of sociodemographic factors on PTSD.MethodsA cross-sectional survey study was conducted among 6,027 students (7–17 years old) from 6 cities in Liaoning Province, China. The sample consisted of 2,853 males (47.34%) and 3,174 females (52.66%). The Essen Trauma-Inventory for Children and Adolescents (ETI-CA) Scale was used. The ETI-CA has 5 sections, which include type of traumatic events, worst traumatic event, post-traumatic symptoms, onset, duration, burden of PTSD, and present difficulties in different areas of life. PTSD symptoms were assessed with 23 items in Part 3 of the ETI-CA.ResultsWe found that 2,068 (34.3%) of 6,027 participants experienced trauma events and 686 (33.2%) of 2,068 reported PTSD. Among trauma-exposed youth (2,068), the sudden death of close relatives (33.9%), serious accidents (20.9%), and parental divorce (15.5%) were reported as the worst traumatic events. Studies have shown that after exposure to stressful life events, more than 30% of people feel nervous or upset (39.8%), scared (33.4%), helpless (32.6%), and about 10% have headaches (15.5%), rapid heartbeat (13.3%), and dizziness (11.8%). Multivariable logistic regression analyses showed that students in middle school [OR = 1.29 (1.016, 1.637)], not a student leader [OR = 0.738 (0.618, 0.881)], and their parents in single marital status significantly predicted higher PTSD prevalence the remarried [OR = 0.474 (0.252, 0.893)], married [OR = 0.42 (0.227, 0.778)].ConclusionThe present study suggests the government to train psychological counselors in schools and communities to provide emotional and psychological support, as well as the school leaders and parents to elevate adolescents' psychological suzhi. Particularly, counseling and professional support should be given to those students whose parents are single.

Abstract Sperm‐induced Ca2+ rise is critical for driving oocyte activation and subsequent embryonic development, but little is known about how lasting Ca2+ oscillations are regulated. Here it is shown that NLRP14, a maternal effect factor, is essential for keeping Ca2+ oscillations and early embryonic development. Few embryos lacking maternal NLRP14 can develop beyond the 2‐cell stage. The impaired developmental potential of Nlrp14‐deficient oocytes is mainly caused by disrupted cytoplasmic function and calcium homeostasis due to altered mitochondrial distribution, morphology, and activity since the calcium oscillations and development of Nlrp14‐deficient oocytes can be rescued by substitution of whole cytoplasm by spindle transfer. Proteomics analysis reveal that cytoplasmic UHRF1 (ubiquitin‐like, containing PHD and RING finger domains 1) is significantly decreased in Nlrp14‐deficient oocytes, and Uhrf1‐deficient oocytes also show disrupted calcium homeostasis and developmental arrest. Strikingly, it is found that the mitochondrial Na+/Ca2+ exchanger (NCLX) encoded by Slc8b1 is significantly decreased in the Nlrp14mNull oocyte. Mechanistically, NLRP14 interacts with the NCLX intrinsically disordered regions (IDRs) domain and maintain its stability by regulating the K27‐linked ubiquitination. Thus, the study reveals NLRP14 as a crucial player in calcium homeostasis that is important for early embryonic development.

PurposeMore effective approaches are needed to improve the prognosis of non-small-cell lung cancer (NSCLC) patients. Thus, we used the E-warm model to assess how early integration of interdisciplinary palliative care was related to the quality of life (QoL), psychological functioning, pain management, and nutrition factors of NSCLC patients.MethodsThis randomized controlled trial enrolled 280 newly diagnosed NSCLC patients, which were randomly divided (1:1) into combined early palliative care (CEPC) and standard oncological care (SC) groups. At baseline and after 24 weeks, the Functional Assessment of Cancer Therapy-Lung (FACT-L) scale, Hospital Anxiety and Depression Scale (HADS), and the Patient Health Questionnaire-9 (PHQ-9) were used to assess QoL and psychological function, respectively. The Numerical Rating Scale (NRS) and Patient-Generated Subjective Global Assessment (PG-SGA) were used to assess cancer patients’ pain and nutrition levels. The primary outcome was overall survival (OS). Secondary outcomes comprised changes in the QoL, psychological functioning, pain, and nutrition state. The intention-to-treat method was applied for analysis. This study was registered at www.chictr.org.cn (ChiCTR2200062617).ResultsOf the 140 patients enrolled in the CEPC and SC groups, 102 and 82 completed the research. The CEPC group presented higher QoL than the SC group (p < 0.05). Additionally, fewer patients presented depressive symptoms in the CEPC group than in the SC group (p < 0.05), as well as better nutritional status (p = 0.007) and pain management (p = 0.003). Compared to the SC group, CEPC patients had significantly longer OS (20.4 vs. 24.6 months, p = 0.042; HR: 0.19; 95% CI: 0.04-0.85, p = 0.029).ConclusionWith combined early palliative care, NSCLC patients lived longer, had better QoL, were psychologically stable, were in less pain, and were more nutritionally satisfied.

Objective: Alterations in behavioral habits of children were analyzed in Shanghai in the winters prior to and following the COVID-19 pandemic, with the aim of assisting in the prevention of children's respiratory diseases in the post-pandemic era. Method: This cross-sectional survey was conducted via an offline questionnaire from January 1 to February 28, 2021. The behavioral habits of Shanghainese children in different age groups during the winter of 2019 and 2020 were statistically analyzed using the SPSS 25.0 software. The parameters surveyed and analyzed included the frequency of outdoor activities, self-protection measures (frequency of wearing masks and washing hands after going out), travel history, time to visit since symptom onset, and influenza vaccination status. Lastly, the number of cases of respiratory diseases in the pediatric outpatient department of our hospital was analyzed during the same period. Result: A total of 1816 questionnaires were investigated and analyzed, and the results revealed that self-protection measures were significantly enhanced in children of all age groups after the COVID-19 pandemic breakout compared with those before the pandemic, whereas the frequency of outdoor activities and traveling were reduced. In the age group over 3 years old, the time to visit since symptom onset was shorter, and the influenza vaccination rate increased following the pandemic. During the same period, the number of cases of children with respiratory diseases in our outpatient department was significantly decreased compared with that prior to the COVID-19 pandemic. Conclusion: The COVID-19 pandemic has had a significant impact on self-protection measures, outdoor activities, and other children's behaviors in all age groups in Shanghai. These changes in habits were correlated with a lower incidence and transmission of respiratory diseases in children. Overall, this study lays a theoretical basis for the prevention of childhood illnesses in the post-pandemic era.