Efficacy and safety of dacomitinib as first-line treatment for advanced non-small cell lung cancer patients with epidermal growth factor receptor 21L858R mutation:A multicenter,case-series study in China

Objective:To provide real-world evidence for the application of first-line dacomitinib treatment for epidermal growth factor receptor(EGFR)21L858R mutant non-small cell lung cancer(NSCLC)patients in China and to explore the factors influencing the efficacy and safety.Methods:A longitudinal,consecutive case-series,multicenter study with mixed prospective and retrospective data was conducted.The primary endpoint was progression-free survival(PFS),and the secondary endpoints included duration of treatment(DOT),overall survival(OS),objective response rate(ORR),disease control rate(DCR)and safety.Results:A total of 155 EGFR 21L858R mutant patients treated with first-line dacomitinib were included.The median follow-up time for these patients was 20.4 months.Among 134 patients with evaluable lesions,the ORR was 70.9%and the DCR was 96.3%.The median PFS was 16.3[95%confidence interval(95%CI),13.7−18.9]months.Multivariate Cox regression analysis suggested that the baseline brain metastasis(BM)status[with vs.without BM:hazard ratio(HR),1.331;95%CI,0.720−2.458;P=0.361]and initial doses(45 mg vs.30 mg:HR,0.837;95%CI,0.427−1.641;P=0.604)did not significantly affect the median PFS.The median DOT was 21.0(95%CI,17.5−24.6)months and the median OS was not reached.Genetic tests were performed in 64 patients after progression,among whom 29(45.3%)patients developed the EGFR 20T790M mutation.In addition,among the 46 patients who discontinued dacomitinib treatment after progression,31(67.4%)patients received subsequent third-generation EGFR-tyrosine kinase inhibitors.The most common grade 3−4 adverse events were rash(10.4%),diarrhea(9.1%),stomatitis(7.1%)and paronychia(4.5%).The incidence of grade 3−4 rash was significantly higher in the 45 mg group than that in the 30 mg group(21.9%vs.7.5%,P=0.042).Conclusions:First-line dacomitinib treatment demonstrated promising efficacy and tolerable adverse events among EGFR 21L858R mutant NSCLC patients in China.

Detection of ALK translocation in non-small cell lung carcinoma(NSCLC) and its clinicopathological significance using the Ventana immunohistochemical staining method: a single-center large-scale investigation of 1,504 Chinese Han patients

Objective： The novel fully automated immunohistochemistry （IHC） assay-Ventana anaplastic lymphoma kinase （ALK）-DSF3 for screening ALK rearrangements has been approved by China＇s Food and Drug Administration in 2013, our previous study disclosed a highly specificity and sensitivity nearly 100%, and its efficacy needs to be evaluated in a large cohort of primary lung adenocarcinoma patients, and to compare clinicopathological features with ALK （＋） and ALK （-） lung adenocarcinoma.Methods： A total of 1,504 consecutive surgical lung adenocareinoma eases of Chinese Han population were collected and re-diagnosed according to the 2011 multidisciplinary classification of lung adenocarcinoma. Fully automated Ventana ALK-D5F3 IHC staining with a binary scoring was adopted to evaluate staining and correlated with dinieopathologieal characters, including age, sex, differentiation degree, histological subtype, lymph node metastasis, and clinical staging. ALK （＋） patients were followed-up, and targeted therapy of ALKinhibitors was adopted and observed in patients with stage IV according to the NCCN guideline.Results： ALK positive adenocarcinomas were identified in 6.6% of the surgically resected 1,504 NSCLCs, and significantly younger than the negative group （P〈0.05）.Mucinous adenocarcinoma （28.2%） was determined to be predominant in ALK （＋） cases, followed by the solid type （11.7%）, specific type （6.8%）, papillary type （5.6%）, acinar type （5.5%）, and lepidic type （3.1%）, and the differences were statistically significant （χ2=42.01 1, P〈0.05）. ALK （＋） adenocarcinoma with lymph node metastasis （10.8%） were significantly higher than that without lymph node metastasis （4.5%） （g2=19.809, P〈0.05）; and ALK （＋） in phase Ⅳ （20%） was significantly higher than phaseⅢ （12.9%）, phase Ⅱ （4.2%）, phase Ⅰ （4.5%）, and phase 0 （0） （g2=36.068, P〈0.05）. Multivariate logistic regression disclosed that patient age, AJCC staging, and histological mucinous subtype were correlated with ALK positive staining （OR=0.959, 1.578, 5.036, respectively）. Sixty eight patients had followed-up results, five patients out of which primarily diagnosed or progressed into Stage IV benefited well from targeted therapy with Crizotinib.Conclusions： The ALK fusion protein was seen in 6.6% Chinese NSCLC patients, and mosdy seen in younger, clinically higher staging, mueinous and solid predominant adenoearcinoma. Clinical trials in patients of Stage Ⅳ eonfirmed that ALK-DSF3 Ventana IHC is serviceable in screening ALK-positive candidates for molecular targeted therapy.

Effects of Food Additives on Rehydration Properties of Frozen Dumpling Wrappers

With the vacuum freeze-drying technology, frozen dumpling wrappers were prepared, to investigate the effects of six kinds of food additives, including modified starch, compound phosphate, maltodextrin, guar gum, distilled monoglycerides and transglutaminase （TG enzyme）, on the drying rate, rehydration ratio and sense value of the frozen dumpling wrappers. The results showed that, with respective addition of 6% modified starch, O. 1% compound phosphate, 10% maltodextrin, 0.4% guar gum, 0.4% distilled monoglyceride and 0.3% transglutaminase, the drying rate, rehydration ratio and sense value of the frozen dumpling wrappers were the highest.

Effect of Continuous Nursing on Quality of Life of Patients with Diabetes Mellitus

Objective:To analyze the effect of continuous nursing on the quality of life of patients with diabetes.Methods:From August 2019 to August 2020,76 patients with diabetes were selected and randomly divided into group A and group B.group a received continuous nursing and group B received routine nursing.Results:The compliance of health education in group A was better than that in group B(P<0.05);The score of quality of life in group A was better than that in group B(P<0.05);The scores of anxiety and depression in group A were better than those in group B(P<0.05);The nursing satisfaction of group A was 97.37%,which was better than that of group B 76.32%,P<0.05.Conclusions:Continuous nursing for patients with diabetes can improve the quality of life,relieve anxiety,depression and other negative emotions,and improve nursing satisfaction.

Biological basis of “depression with liver-qi stagnation and spleen deficiency syndrome”: A digital gene expression profiling study

Objective:To investigate the biological basis of“depression with liver-qi stagnation and spleen deficiency syndrome”.Methods:A digital gene expression profiling method was conducted to explore global changes in the mRNA transcriptome in a rat model of depression with liver-qi stagnation and spleen deficiency syndrome.Real-time quantitative polymerase chain reaction(q-PCR)was performed to verify the five genes most interest based on the Kyoto Encyclopedia of Genes and Genome(KEGG)analysis.Sini San,which disperses stagnated liver qi and strengthens the spleen,was administered to the model rats to observe whether it could reverse these genetic changes in the liver.Results:Forty-six differentially expressed genes were identified.Three of the five genes of most interestdHnf4a,Hnf4g and Cyp1a1dbased on KEGG analysis,were confirmed by realtime q-PCR.Sini San reduced the gene expression changes of Hnf4a,Hnf4g and Cyp1a1 in the rat model.Conclusions:Hnf4a,Hnf4g and Cyp1a1 are involved in“depression with liver-qi stagnation and spleen deficiency syndrome”.These findings indicate that depressed rats with liver-qi stagnation and spleen deficiency syndrome are at risk of liver diseases.Furthermore,our results will inform exploration of the etiology of depression and help in the development of effective therapeutic strategies.

Pyrotinib in HER2 heterogeneously mutated or amplified advanced non-small cell lung cancer patients:a retrospective real-world study(PEARL)

Human epidermal growth factor receptor 2(HER2)amplification or activating mutations are found in 1.6%–4%of non-small cell lung cancer(NSCLC).Pyrotinib has been reported to have better potency in NSCLC patients with HER2 exon 20 insertion(ex20ins)mutations;however,more clinical evidence is urgently needed to guide pyrotinib-based therapy in NSCLC with HER2 amplification or heterogeneous mutations.We retrospectively analyzed advanced NSCLC patients with HER2 amplification or mutations who were treated with pyrotinib-based therapy between September 25,2018 and October 30,2020 in our hospital.Molecular dynamics simulation was used to explore the bioactive conformation and binding mechanisms of pan-ErbB tyrosine kinase inhibitors(TKIs)including pyrotinib for different HER2 ex20ins variants.In this study,79 eligible patients were included with 70 ex20ins variants,6 missense mutations and 3 primary HER2 amplifications identified.A775_G776insYVMA insertion was the most common observed subtype.The median progression-free survival(mPFS)was 5.8(95%CI:4.1–7.4)months.Use of pyrotinib-based therapy in first-/second-line settings showed a significantly better prognosis than that observed in third-line settings or above(mPFS:9.1 vs.4.4 months;P=0.0003).Compared with HER2 amplification and exon 20 non-YVMA insertion variants,patients with HER2 missense mutations had a visible mPFS benefit(12.2 vs.6.8 vs.5.2 months).Computational docking simulations revealed that pyrotinib failed to interact with the specific insertion variant P780_Y781insGSP.These results indicated that pyrotinib-based therapy exhibited good anti-tumor activity and acceptable safety profile in HER2-altered advanced NSCLC.

Sequential therapy according to distinct disease progression patterns in advanced ALK-positive non-small-cell lung cancer after crizotinib treatment

Objective: Crizotinib is recommended as the first-line therapy for advanced anaplastic lymphoma kinase(ALK)-positive non-small-cell lung cancer(NSCLC). Despite its initial efficacy, patients ultimately acquire resistance to crizotinib within 1 year. In such patients, the optimal sequential therapy after crizotinib treatment remains unknown. This study explored which sequential therapy option confers the greatest benefit.Methods: A total of 138 patients with advanced ALK-positive NSCLC resistant to crizotinib were studied. Based on patterns of disease progression of metastases, patients were divided into 3 groups: brain progression, non-liver progression, and liver progression. Sequential therapies included crizotinib continuation plus local therapy, nextgeneration ALK inhibitors(ALKi's), and chemotherapy. The primary endpoint was overall survival(OS) from the time of crizotinib resistance to death or last follow-up.Results: The 138 patients included 64 cases with progression in brain, 57 cases in non-liver sites and 17 cases in liver. A significant difference in OS was observed among the distinct progression pattern(median OS, 25.4 months in brain, 15.8 months in non-liver, and 10.8 months in liver, respectively, P=0.020). The difference in OS among sequential therapies was statistically significant in the non-liver progression group(median OS, 27.6 months with next-generation ALKi's, 13.3 months with crizotinib continuation, and 10.8 months with chemotherapy,respectively, P=0.019). However, crizotinib continuation plus local therapy seems to provide non-inferior median OS compared with next-generation ALKi's for patients with brain progression(median OS, 28.9 months vs.32.8 months, P=0.204). And no significant differences in OS were found in patients with progression in liver(P=0.061).Conclusions: Crizotinib continuation together with local therapy might be a feasible strategy for patients with progression in brain beyond crizotinib resistance, as well as next-generation ALKi's. Next-generation ALKi's tended to provide a survival benefit in patients with non-liver progression.

Impact of crizotinib on long-term survival of ALK-positive advanced non-small-cell lung cancer: A Chinese multicenter cohort study

Objective: Crizotinib has demonstrated promising efficacy in patients with anaplastic lymphoma kinase(ALK)-positive non-small-cell lung cancer(NSCLC) in clinical trials. We conducted this retrospective multicenter study to assess the outcomes of crizotinib therapy in, to our knowledge, a large sample cohort of patients with ALKpositive advanced NSCLC.Methods: We reviewed the medical records of 484 unselected ALK-positive NSCLC patients treated with crizotinib at 5 cancer centers in China from January 2013 to November 2017. Clinical data were collected from the initiation of crizotinib therapy to Response Evaluation Criteria in Solid Tumors(RECIST)-defined progressive disease(PD).Results: A total of 428 eligible ALK-positive NSCLC patients were enrolled, 273(63.8%) of whom received crizotinib as first-line treatment. The median progression-free survival(PFS) and overall survival(OS) from the initiation of crizotinib treatment were 14.4 [95% confidence interval(95% CI), 12.4-16.4] months and 53.4(95%CI, 33.7-73.1) months, respectively. In subgroup analyses, patients who received crizotinib as first-line treatment showed a higher disease control rate(DCR) and a longer median OS compared with second-/later-line crizotinib treatment(94.8% and OS not reached vs. 89.0% and 40.5 months, respectively). For 261 patients with RECISTdefined PD, multivariate Cox analysis revealed that in patients who received first-line crizotinib therapy, continued crizotinib beyond progressive disease(CBPD) and next-generation ALK inhibitors after crizotinib failure were associated with improved survival.Conclusions: This study has demonstrated the clinically meaningful benefit of crizotinib treatment in a large cohort of Chinese ALK-positive NSCLC patients. CBPD and next-generation ALK inhibitor treatment may provide improved survival after RECIST-defined progression on crizotinib.

Is there an optimal time to initiate adjuvant chemotherapy to predict benefit of survival in non-small cell lung cancer?

Objective: Adjuvant chemotherapy (AC) after curative resection is known to improve the survival of patients with non-small cell lung cancer (NSCLC); however, few studies have reported the correlation between the time to initiation of AC (TTAC) and survival in NSCLC patients. Methods: The clinical data of 925 NSCLC patients who received curative resection and post-operative AC at the Cancer Hospital of Chinese Academy of Medical Sciences between 2003 and 2013 were retrospectively analyzed. TTAC was measured from the date of surgery to the initiation of AC. Disease-free survival (DFS) was defined as the duration from surgery to the time of tumor recurrence or last follow-up evaluation. The optimal cut-off value of TTAC was determined by maximally selected log-rank statistics. The DFS curve was estimated using the Kaplan-Meier method, and the Cox proportional hazards regression model was used to identify risk factors independently associated with DFS. Propensity score matching (PSM) was performed for survival analysis using the match data. Results: The optimal discriminating cut-off value of TTAC was set at d 35 after curative resection based on which the patients were assigned into two groups: group A (<= 35 d) and group B (> 35 d). There was no significant difference in the DFS between the two groups (P=0.246), indicating that the TTAC is not an independent prognostic factor for DFS. A further comparison continued to show no significant difference in the DFS among 258 PSM pairs (P=0.283). Conclusions: There was no significant correlation between the TTAC and DFS in NSCLC patients. Studies with larger samples are needed to further verify this conclusion.

Analysis of the Effect of Infection Control in Hospital Operation Room

Objective:To explore the implementation effect of nursing management in operating room for hospital infection control.Methods:100 cases of patients who received surgical treatment in our hospital from 2019 to 2020 were selected and divided into observation group and control group according to different nursing management methods in operating room.Patients in the control group received routine nursing management services,while patients in the observation group received systematic and highquality comprehensive management services based on routine nursing management services.Results:The air colony count and hand colony count of the observation group were significantly better than those of the control group.At the same time,the incidence probability of infection in the observation group was also significantly lower than that of the control group,with significant difference between the groups,with statistical value(P<0.05).Conclusions:In view of the occurrence of nosocomial infection,the implementation of high-quality operating room nursing service can effectively control it,reduce the probability of occurrence,and ensure the safety of patient treatment,which is worthy of clinical application.

Clarifying the relationship between PM2.5 and ozone complex pollution and synoptic patterns in a typical petrochemical city in the Bohai Rim region of China:Implications for air pollution forecasting and control

Meteorological conditions are vital to PM_(2.5)and ozone(O_(3))complex pollution.Herein,the T-mode principal com-ponent analysis method was employed to objectively classify the 925-hPa geopotential height field of Dongying from 2017 to 2022.Synoptic patterns associated with four pollution types-namely,PM_(2.5)-only pollution,O_(3)-only pollution,Co-occurring of PM_(2.5)and O_(3)pollution,Non-occurring of PM_(2.5)and O_(3)pollution-were characterized at different time scales.The results indicated that synoptic classes conducive to PM_(2.5)-only pollution were“high-pressure top front”,“offshore high-pressure rear”,and“high-pressure inside”,while those conducive to O_(3)-only pollution were“offshore high-pressure rear”,“subtropical high”,and“high and low systems”.The Co-occurring of PM_(2.5)and O_(3)pollution were influenced by high pressure,and the Non-occurring of PM_(2.5)and O_(3)pollution were linked to precipitation and strong northerly winds.The variation in dominant synoptic patterns is crucial in the frequency changes of the four pollution types,which was further validated through the analysis of typical cases.Under the favorable meteorological conditions of high-pressure control with strong northerly winds or a subtropical high and inverted trough both with strong precipitation,there is potential to achieve coordinated control of PM_(2.5)and O_(3)in Dongying.Additionally,measures like artificially manipulating local humidity could be adopted to alleviate pollution levels.This study reveals the importance of comprehending the meteorological factors contributing to the formation of PM_(2.5)and O_(3)complex pollution for the improvement of urban air quality in the Bohai Rim region of China when emissions are high and the concentration of air pollutants exhibits high meteorological sensitivity.

Development and application of the multi-wavelength cavity ring-down aerosol extinction spectrometer

To better characterize the optical properties of atmospheric aerosols, the multi-wavelength cavity ring-down aerosol extinction spectrometer(MCRD-AES) is developed and applied in this study. By using tunable light source and four parallel cavities, the MCRD-AES covers a wide and atmospherically relevant wavelength range from 360 to 663 nm. Four wavelengths(375 nm, 440 nm, 532 nm, and 620 nm) are particularly tested with ammonium sulfate and nigrosine. The refractive index values obtained from this study agree well with literature data. The stability and accuracy of the MCRD-AES are tested, and the minimum detectable extinction coefficient is 0.5 1/Mm. The high sensitivity, high precision, and wavelength changeable of MCRD-AES indicate its great application prospect in comprehensively quantifying the optical properties of atmospheric aerosols.

Learning-Based Joint Resource Slicing and Scheduling in Space-Terrestrial Integrated Vehicular Networks

In this paper,we investigate the resource slicing and scheduling problem in the space-terrestrial integrated vehicular networks to support both delay-sensitive services(DSSs)and delay-tolerant services(DTSs).Resource slicing and scheduling are to allocate spectrum resources to different slices and determine user association and bandwidth allocation for individual vehicles.To accommodate the dynamic network conditions,we first formulate a joint resource slicing and scheduling(JRSS)problem to minimize the long-term system cost,including the DSS requirement violation cost,DTS delay cost,and slice reconfiguration cost.Since resource slicing and scheduling decisions are interdependent with different timescales,we decompose the JRSS problem into a large-timescale resource slicing subproblem and a small-timescale resource scheduling subproblem.We propose a two-layered reinforcement learning(RL)-based JRSS scheme to find the solutions to the subproblems.In the resource slicing layer,spectrum resources are pre-allocated to different slices via a proximal policy optimization-based RL algorithm.In the resource scheduling layer,spectrum resources in each slice are scheduled to individual vehicles based on dynamic network conditions and service requirements via matching-based algorithms.We conduct extensive trace-driven experiments to demonstrate that the proposed scheme can effectively reduce the system cost while satisfying service quality requirements.

A large-scale outdoor atmospheric simulation smog chamber for studying atmospheric photochemical processes:Characterization and preliminary application

Understanding the formation mechanisms of secondary air pollution is very important for the formulation of air pollution control countermeasures in China.Thus,a large-scale outdoor atmospheric simulation smog chamber was constructed at Chinese Research Academy of Environmental Sciences(the CRAES Chamber),which was designed for simulating the atmospheric photochemical processes under the conditions close to the real atmospheric environment.The chamber consisted of a 56-m^(3) fluorinated ethylene propylene(FEP) Teflon film reactor,an electrically-driven stainless steel alloy shield,an auxiliary system,and multiple detection instrumentations.By performing a series of characterization experiments,we obtained basic parameters of the CRAES chamber,such as the mixing ability,the background reactivity,and the wall loss rates of gaseous compounds(propene,NO,NO_(2),ozone) and aerosols(ammonium sulfate).Oxidation experiments were also performed to study the formation of ozone and secondary organic aerosol(SOA),including α-pinene ozonolysis,propene and 1,3,5-trimethylbenzene photooxidation.Temperature and seed effects on the vapor wall loss and SOA yields were obtained in this work:higher temperature and the presence of seed could reduce the vapor wall loss;SOA yield was found to depend inversely on temperature,and the presence of seed could increase SOA yield.The seed was suggested to be used in the chamber to reduce the interaction between the gas phase and chamber walls.The results above showed that the CRAES chamber was reliable and could meet the demands for investigating tropospheric chemistry.

Kinetic and mechanism of the reaction between Cl and several mono-methyl branched alkanes

Branched alkanes are ubiquitous in the troposphere and play an important role in the chemical processes.In this work,the rate constants and products for the reaction of Cl atoms with 3-methylhexane and 2-methylheptane were measured at room temperature(298±0.2K)and atmospheric pressure using a conventional relative rate method.The rate constants of 3-methylhexane and 2-methylheptane in units of cm~3/(mol·sec)are(3.09±0.31)×10^(-10)and(3.67±0.40)×10^(-10),respectively.Furthermore,the corresponding atmospheric lifetime of the studied branched alkanes with Cl was 6.92-89.90 hours and 5.82-75.69 hours,respectively.The estimated atmospheric lifetimes indicated that the reaction with Cl atoms could be the most important atmospheric degradation pathway for 3-methylhexane and2-methylheptane.Primary gas-phase products of the reactions were identified and quantified,and particle-phase products were also obtained.The atmosphere oxidation mechanism of Cl atoms with 3-methylhexane and 2-methylheptane is proposed.The SOA yields of 3-methylhexane and 2-methylheptane from the reaction of Cl atoms were determined to be7.96%±0.89%and 13.35%±1.50%respectively.Overall,the results reveal that the primary loss process of branched alkanes is the reaction with Cl atoms,which impacts its degradation on a regional scale.

Functional Analysis of Slow Myosin Heavy Chain 1 and Myomesin-3 in Sarcomere Organization in Zebrafish Embryonic Slow Muscles

Myofibrillogenesis, the process of sarcomere formation, requires close interactions of sarcomeric proteins and various components of sarcomere structures. The myosin thick filaments and M-lines are two key components of the sarcomere. It has been suggested that myomesin proteins of M-lines interact with myosin and titin proteins and keep the thick and titin filaments in order. However, the function of myomesin in myofibrillogenesis and sarcomere organization remained largely enigmatic. No knockout or knockdown animal models have been reported to elucidate the role of myomesin in sarcomere organization in vivo. In this study, by using the gene-specific knockdown approach in zebrafish embryos, we carded out a loss-of-function analysis of myomesin-3 and slow myosin heavy chain 1 （smyhcl） expressed specifically in slow muscles. We demonstrated that knockdown of smyhcl abolished the sarcomeric localization of myomesin-3 in slow muscles. In contrast, loss of myomesin-3 had no effect on the sarcomeric organization of thick and thin filaments as well as M- and Z-line structures. Together, these studies indicate that myosin thick filaments are required for M-line organization and M-line localization of myomesin-3. In contrast, myomesin-3 is dispensable for sarcomere organization in slow muscles.

Review of the influencing factors of secondary organic aerosol formation and aging mechanism based on photochemical smog chamber simulation methods

The formation and aging mechanism of secondary organic aerosol(SOA)and its influencing factors have attracted increasing attention in recent years because of their effects on climate change,atmospheric quality and human health.However,there are still large errors between air quality model simulation results and field observations.The currently undetected components during the formation and aging of SOA due to the limitation of current monitoring techniques and the interactions among multiple SOA formation influencing factors might be the main reasons for the differences.In this paper,we present a detailed review of the complex dynamic physical and chemical processes and the corresponding influencing factors involved in SOA formation and aging.And all these results were mainly based the studies of photochemical smog chamber simulation.Although the properties of precursor volatile organic compounds(VOCs),oxidants(such as OH radicals),and atmospheric environmental factors(such as NOx,SO2,NH3,light intensity,temperature,humidity and seed aerosols)jointly influence the products and yield of SOA,the nucleation and vapor pressure of these products were found to be the most fundamental aspects when interpreting the dynamics of the SOA formation and aging process.The development of techniques for measuring intermediate species in SOA generation processes and the study of SOA generation and aging mechanism in complex systems should be important topics of future SOA research.

Evaluation and impact factors of indoor and outdoor gas-phase nitrous acid under different environmental conditions

As an important indoor pollutant,nitrous acid(HONO) can contribute to the concentration of indoor OH radicals by photolysis via sunlight penetrating into indoor environments,thus affecting the indoor oxidizing capability.In order to investigate the concentration of indoor HONO and its impact factors,three different indoor environments and two different locations in urban and suburban areas were selected to monitor indoor and outdoor pollutants simultaneously,including HONO,NO,NO2,nitrogen oxides(NOx),O3,and particle mass concentration.In general,the concentration of indoor HONO was higher than that outdoors.In the urban area,indoor HONO with high average concentration(7.10 ppbV) was well-correlated with the temperature.In the suburban area,the concentration of indoor HONO was only about 1-2 ppbV,and had a good correlation with indoor relative humidity.It was mainly attributed to the heterogeneous reaction of NO2 on indoor surfaces.The sunlight penetrating into indoor environments from outside had a great influence on the concentration of indoor HONO,leading to a concentration of indoor HONO close to that outdoors.

Adjuvant and neo‐adjuvant immunotherapy in resectable non‐small cell lung cancer (NSCLC): Current status and perspectives

Surgery followed by adjuvant chemotherapy is the standard of care for selectedpatients with early‐stage or locally advanced non‐small cell lung cancer(NSCLC). However, many of these patients still experience postoperativerecurrence at 5 years. At present, peri‐operative treatment methods areemerging to prevent early relapse, such as targeted therapy and immunotherapy.Investigation on predictive biomarkers of responses to adjuvant andneoadjuvant therapies is also continuously ongoing. Immunotherapy representedby immune checkpoint inhibitors (ICIs), either by monotherapy or incombination with chemotherapy, has shown benefit in promoting pathologicalresponses and prolonging survival for patients with NSCLC without oncogenicmutations. Exploratory studies have also provided evidence regarding theselection of patients who benefit from ICI‐based perioperative treatment. Thisreview focuses on the existing data of current clinical trials of adjuvant andneoadjuvant strategies with ICIs in resectable NSCLC, the exploration ofpredictive biomarkers, and the perspectives and urgent challenges in thefuture.

Water uptake of multicomponent organic mixtures and their influence on hygroscopicity of inorganic salts

The hygroscopic behaviors of atmospherically relevant multicomponent water soluble organic compounds（WSOCs） and their effects on ammonium sulfate（AS） and sodium chloride were investigated using a hygroscopicity tandem differential mobility analyzer（HTDMA） in the relative humidity（RH） range of 5%–90%. The measured hygroscopic growth was compared with predictions from the Extended-Aerosol Inorganics Model（E-AIM） and Zdanovskii–Stokes–Robinson（ZSR） method. The equal mass multicomponent WSOCs mixture containing levoglucosan, succinic acid, phthalic acid and humic acid showed gradual water uptake without obvious phase change over the whole RH range. It was found that the organic content played an important role in the water uptake of mixed particles.When organic content was dominant in the mixture（75%）, the measured hygroscopic growth was higher than predictions from the E-AIM or ZSR relation, especially under high RH conditions. For mass fractions of organics not larger than 50%, the hygroscopic growth of mixtures was in good agreement with model predictions. The influence of interactions between inorganic and organic components on the hygroscopicity of mixed particles was related to the salt type and organic content. These results could contribute to understanding of the hygroscopic behaviors of multicomponent aerosol particles.