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Osteonecrosis of the femoral head (ONFH) is a condition caused by a disruption or damage to the femoral head's blood supply, which causes the death of bone cells and bone marrow components and prevents future regeneration. Ferroptosis, a type of controlled cell death, is caused by iron‐dependent lipid peroxidation. Here, we identified ferroptosis‐related genes and infiltrating immune cells involved in ONFH and predicted the underlying molecular mechanisms. The GSE123568 dataset was subjected to differential expression analysis to identify genes related to ferroptosis. Subsequently, GO and KEGG pathway enrichment analyses, as well as protein–protein interaction (PPI) network analysis, were conducted. Hub genes involved in ferroptosis were identified using machine learning and other techniques. Additionally, immune infiltration analysis and lncRNA–miRNA‐mRNA network prediction analysis were performed. Finally, we determined whether ferroptosis occurred by measuring iron content. The hub genes were validated by ROC curve analysis and qRT–PCR. Four ferroptosis‐related hub genes (MAPK3, PTGS2, STK11, and SLC2A1) were identified. Additionally, immune infiltration analysis revealed a strong correlation among ONFH, hub genes, and various immune cells. Finally, we predicted the network relationship between differentially expressed lncRNAs and hub genes in the lncRNA–miRNA–mRNA network. MAPK3, PTGS2, STK11, and SLC2A1 have been identified as potential ferroptosis‐related biomarkers and drug targets for the diagnosis and prognosis of ONFH, while some immune cells, as well as the interaction between lncRNA, miRNA, and mRNA, have also been identified as potential pathogenesis markers and therapeutic targets.

Abstract Radiation proctopathy (RP) is a common complication of radiotherapy for pelvic malignancies with high incidence. RP accompanies by microbial dysbiosis. However, how the gut microbiota affects the disease remains unclear. Here, metabolomics reveals that the fecal and serous concentrations of microbiota‐derived 3‐hydroxybutyrate (3HB) are significantly reduced in RP mice and radiotherapeutic patients. Moreover, the concentration of 3HB is negatively associated with the expression of proinflammatory IL6 that is increased along with the severity of radiation damage. 3HB treatment significantly downregulates IL6 expression and alleviates IL6‐mediated radiation damage. Irradiated cell‐fecal microbiota co‐culture experiments and in vivo assays show that such a radioprotection of 3HB is mediated by GPR43. Microbiome analysis reveals that radiation leads to a distinct bacterial community compared to untreated controls, in which Akkermansia muciniphila is significantly reduced in RP mice and radiotherapeutic patients and is associated with lower 3HB concentration. Gavage of A. muciniphila significantly increases 3HB concentration, downregulates GPR43 and IL6 expression, and ameliorates radiation damage. Collectively, these results demonstrate that the gut microbiota, including A. muciniphila, induce higher concentrations of 3HB to block GPR43‐mediated IL6 signaling, thereby conferring radioprotection. The findings reveal a novel implication of the gut‐immune axis in radiation pathophysiology, with potential therapeutic applications.

Abstract The development of highly active, reusable catalysts for aqueous‐phase reactions is challenging. Herein, metallic nickel is encapsulated in a nitrogen‐doped carbon–silica composite (SiO2@Ni@NC) as a catalyst for the selective hydrogenation of vanillin in aqueous media. The constructed catalyst achieved 99.8% vanillin conversion and 100% 4‐hydroxymethyl‐2‐methoxyphenol selectivity at room temperature. Based on combined scanning transmission electron microscopy, X‐ray photoelectron spectroscopy, and Raman analyses, the satisfactory catalytic performance is attributed to the composite structure consisting of an active metal, carbon, and silica. The hydrophilic silica core promoted dispersion of the catalyst in aqueous media. Moreover, the external hydrophobic NC layer has multiple functions, including preventing oxidation or leaching of the internal metal, acting as a reducing agent to reduce the internal metal, regulating the active‐site microenvironment by enriching the concentrations of H2 and organic reactants, and modifying the electronic structure of the active metal via metal–support interactions. Density functional theory calculations indicated that NC facilitates vanillin adsorption and hydrogen dissociation to promote aqueous‐phase hydrogenation. This study provides an efficient strategy for constructing encapsulated Ni‐based amphiphilic catalysts to upgrade biomass‐derived compounds.

Abstract Background Esophageal cancer (ESCA) is one of the most aggressive and lethal human malignant cancers. MicroRNA‐1301‐3p (miR‐1301‐3p) plays vital roles in a majority of malignancies. The aim of this study was to investigate the role of miR‐1301‐3p/NBL1 axis on ESCA cell invasion, migration, epithelial‐mesenchymal transition (EMT) process, as well as its association with prognosis of ESCA patients. Methods The expression levels of miR‐1301‐3p and NBL1 were predicted by bioinformatics and further verified by RT‐qPCR assays. Kaplan–Meier (K–M) plotter analysis and univariate and multivariate Cox analyses were used to evaluate the relationship between miR‐1301‐3p and clinicopathological variables and prognosis. The role of miR‐1301‐3p on cell invasion, migration was detected by transwell invasion, and wound healing assays, respectively. The EMT‐related proteins were detected by western blot. The target genes and the target binding sites were predicted by bioinformatics and further determined by RT‐qPCR assay. Results MiR‐1301‐3p was remarkably upregulated in ESCA tissues and cells, and its high expression was associated with poor prognosis of ESCA. Overexpression of miR‐1301‐3p promoted ESCA cell invasion, migration and mediated EMT process in vitro, whereas knockdown of miR‐1301‐3p showed the opposite effects. Moreover, NBL1 was predicted as a target gene of miR‐1301‐3p. NBL1 was lowly expressed in ESCA cells and significantly decreased after upregulation of miR‐1301‐3p. Meanwhile, we found that low expression of NBL1 was significantly associated with poor prognosis of ESCA patients. Conclusion MiR‐1301‐3p is a potential biomarker for predicting the prognosis of ESCA patients. It may promote ESCA invasion, migration and EMT progression by regulating NBL1 expression.

Abstract Thoracoscopic segmentectomy might be an alternative to lobectomy for small size lung cancer. Precise identification of the pulmonary intersegmental plane was needed for an optimal segmentectomy. Recently, (1) the ultra‐high‐definition 4K systems had claimed to overcome the lack of depth perception by secondary visual cues; (2) the no‐waiting procedure was induced as an alternative and optimized method for identifying the plane. It was unclear whether combined ultra‐high‐definition 4K endovision systems with “no‐waiting” technique in thoracoscopic segmentectomy could achieve an excellent result. A 68‐year‐old female patient was admitted into our hospital for occasional pulmonary nodule during her routine physical examination. The nodule is located between S8 and S9 segment, and was suspected to be an early‐stage lung cancer. She underwent a thoracoscopic S89 complex segmentectomy using ultra‐high‐definition 4K endovision systems and “no‐waiting” surgical technique. The intersegmental plane was clearly detected and easily treated by the endoscopic linear cutting staplers. The patient recovered well and was discharged without complications. Combining ultra‐high‐definition 4K endovision systems with “no‐waiting” technique seems to be an optimal thoracoscopic segmentectomy approach for the management of lung cancers.

Abstract Stage III non‐small cell lung cancer (NSCLC) encompasses a group of diseases with high heterogeneity. Such patients should actively receive comprehensive treatments. It is imperative for all stage III NSCLC patients to receive consultation with a multiple disciplinary team, which allows the development of a proposal for clinical diagnosis and treatment. In this consensus, stage III NSCLC is divided into two types (operable and inoperable) according to different clinical conditions. Resectable NSCLC is further subdivided into two conditions (with or without driver genes). For each clinical scenario, this consensus emphasizes that the foundation of any medical decisions regarding the optimal diagnostic or therapy procedure is scientific evidence from clinical research. Finally, based on the level of evidence and strength of recommendations, this consensus provides recommendations for the management of stage III NSCLC from six perspectives. The objective of this consensus is to help clinicians choose the best treatment and promote the standardization of stage III NSCLC diagnosis and treatment in China.

Abstract Introduction The heterocyclic compound 4‐hydroxy‐(2,2,6,6‐Tetramethylpiperidin‐1‐yl)oxyl (TEMPOL) has a protective effect on neurological function in brain tissues damaged by ischemia and hypoxia. This study explored the effects of TEMPOL pretreatment on postoperative cognitive function in aged rats under sevoflurane anesthesia, focusing on inflammatory response and oxidative stress. Methods Sixty male rats were divided into normal control (C), sevoflurane anesthesia (S), TEMPOL pretreatment (T), and sevoflurane anesthesia + TEMPOL pretreatment (ST) groups (15 per group). Groups T and ST rats received continuous intraperitoneal TEMPOL (100 mg/kg) for 3 days, while groups C and S rats were injected with 0.9% saline. After pretreatment, groups S and ST received 3% sevoflurane anesthesia. Results Rats in group S exhibited a longer swimming distance, longer escape latency, lower frequency of platform crossing, and shorter dwell time in the targeted quadrant than those in groups C and T. Rats in group ST exhibited a shorter swimming distance, shorter escape latency, higher frequency of platform crossing, and longer dwell time in the targeted quadrant than those in group S. The expressions of interleukin‐6, tumor necrosis factor‐α, inducible nitric oxide synthase, and Ym1/2 messenger ribonucleic acid were higher in groups S and ST rats than in groups C and T rats and lower in group ST rats than in group S rat (p

Abstract Background In clinical practice, combined segmental resection (CSS) can avoid resection of multiple segments to preserve lung function. When two or more distant lung segments or subsegments of the same lobe present with a ground glass opacity (GGO) that meets the indications for sublobar resection, conventional CSS or wedge resection could not remove all the nodules, and lobectomy is performed in most of these patients. For these particular types of nodules, we perform a single lobe noncombined subsegmental resection, or “separated” precise subsegmentectomy, to preserve more lung tissue. This study was designed to initially assess the feasibility and safety of “separated” precise subsegmentectomy. Methods Selected cases of specific GGO were subjected to “separated” precise subsegmentectomy and the results of general clinical data, perioperative operative time, bleeding, length of stay, computed tomography (CT) review, lung function and its dynamic changes were collected and analyzed in these patients. Results “Separated” precise subsegmentectomy was performed in 12 patients and successfully completed. The median operation time, bleeding amount, and length of hospital stay were 96 min, 50 ml and 4 days, respectively. There was one case of pulmonary infection and one case of persistent air leakage, no death or pulmonary torsion, bronchopleural fistula and other pulmonary complications occurred. After 3 months, the median percentage of lung function retention was 91.7%, and the CT scan showed that the reserved lung tissue of 12 patients was well inflated and there was no obvious imaging manifestation of atelectasis. Conclusion “Separated” precise subsegmentectomy is a novel and safe surgical method that provides a more optimized way for patients with specific multiple nodules to preserve lung function. Further prospective large studies are needed to verify this finding.

Abstract Background To compare the diagnostic positive rate and complication rate between the electromagnetic navigation bronchoscopy (ENB) technique and computed tomography (CT)‐guided lung puncture for the biopsy of lung nodules located in the middle of an anatomic lung segment. Methods Electronic medical records of 114 patients who underwent lung nodule biopsy between June 2021 and June 2022 were retrospectively evaluated. In all patients, the nodules were located in the middle third lung segment. To compare the diagnostic positive and complication rates between the two biopsy modalities performed in this lung region, clinical data, complication rates, nodule pathology, and imaging results were reviewed based on nodule characteristics retrieved from the electronic medical records. Results Ninety‐three patients underwent CT‐guided lung puncture, while the remaining 21 patients underwent the ENB technique. No significant difference was observed in the diagnostic positive rate between the two groups (73.6 and 76.1%, respectively). In the CT‐guided lung puncture group, pneumothorax incidence, tube placement, postoperative hemorrhage, and symptomatic hemorrhage rates were 16.1, 6.5, 6.5, and 1.1%, respectively. In contrast, no complications occurred in the ENB group. Conclusions The ENB technique is a safe and effective method for performing biopsies of pulmonary nodules with a diagnostic positive rate comparable to that of CT‐guided lung puncture and with a lower postoperative complication rate.

Abstract Purpose We aim to assess whether osimertinib postoperative adjuvant therapy, compared with placebo, is cost‐effective in China. Methods We set up the Markov model that contains three health states over a 20‐year period. Data were collected from the ADAURA trial that included transition probabilities and safety data. Through the analysis of literature and local charges, we explore both the cost and utility values. Sensitivity analyses were employed using TreeAge Pro software to access model stability. Findings Patients in the osimertinib group had 1.46 more Quality‐adjusted Life Years (8.45 QALYs vs 6.99 QALYs) than the placebo group at an incremental cost of $14098.51($39962.99 vs $25864.48). Compared with the placebo group, the treatment strategy with osimertinib postoperative adjuvant therapy had an incremental cost‐effectiveness ratio of $9661.97/QALY. The probability of the osimertinib‐assisted therapy strategy being cost‐effective will reach 100% if the threshold of willingness to pay is above $15,000/QALY. Implications From the perspective of the Chinese Healthcare System, the treatment strategy with osimertinib postoperative adjuvant therapy is more cost‐effective than the placebo strategy.

Abstract Patient enrollment, data sharing, and data privacy are enormous medical challenges for clinical trial studies. In recent years, blockchain technology has drawn the attention of various researchers and institutes. As a new and innovative distributed ledger technology, blockchain can be critical to addressing these challenges, thus making clinical research transparent and building public trust fairly and openly. However, the existing literature lacks a comprehensive survey on the adoption of blockchain in clinical trials. To fill the research void, this paper presents a punctilious taxonomy of blockchain technology in clinical trials according to the literature. This taxonomy comprises decentralized scenarios, decentralized practices, blockchain types, deployment methods, and consensus algorithms. The results show that blockchain technology can cover all aspects of the clinical trial study in a decentralized, secure, transparent manner. Besides, some open research challenges of blockchain are categorized into three groups: technical challenges, security challenges, and organizational challenges. Moreover, some recent blockchain projects, micro applications in clinical trials, and several research areas or technologies for future research and development are discussed.

Abstract The increasingly accurate sublobar anatomical resection is constantly being explored and practiced. Surgeons try to preserve as much viable lung tissue as possible. Sublobar resection of the target tissue is similar with a cone‐shaped structure which penetrates deeply into the pulmonary parenchyma and runs through the lobe at both ends. This has not previously been described. The remaining lung tissue resembles the Triumphal Arch in Paris, France. Here, we describe triumphal arch‐like sublobectomy in detail, aiming to provide clinicians with an idea to explore this novel sublobectomy under similar conditions.

Abstract Purpose In this article, we aimed to reconstruct the cervical–thoracic junction plane (CTJP) using a three‐dimensional (3D) reconstruction system. Thus, the CTJP can be judged during surgery to better distinguish cervical–thoracic lymph nodes. Methods We included patients in Fujian Medical University Union Hospital from December 2019 to March 2020. All patients underwent a thin‐slice and enhanced computed tomography scan of the chest with 3D reconstruction using the IQQA system (EDDA technology) to reconstruct the CTJP, brachiocephalic trunk, right common carotid artery, and right subclavian artery. The distance from the intersection of the right subclavian artery and the CTJP to the origin of the right subclavian artery (ORSA) was measured, and the relationship between this distance and the patient's sex, BMI and height was analyzed. Results Seventy‐three patients were enrolled, of whom 12 had ORSA above the CTJP, while 61 had ORSA below the plane. There was a significant difference in age between the two groups (p = 0.04), compared with height, weight and BMI (p > 0.05). In 61 patients with the ORSA below the CTJP, the average distance was 24.7 ± 7.6 mm. The difference between the distance and BMI (p = 0.02) was statistically significant, and it was increased with increasing BMI. Conclusions The relationship between the ORSA and CTJP can be clarified through 3D reconstruction. The cervical‐thoracic recurrent laryngeal nerve lymph nodes can be distinguished clearly in minimally invasive esophagectomy, contributing to the accurate N staging of middle‐thoracic esophageal cancer.

Abstract Introduction The incidence and mortality rates of esophageal carcinoma are higher than those of most malignancies in humans. Radical esophagectomy is the preferred treatment for early‐stage esophageal cancer. However, the extent of lymphadenectomy during radical esophagectomy remains controversial. Indocyanine green (ICG) is the most commonly used imaging agent for the diagnosis of tumors and metastatic lymph nodes in clinical settings. Thus, the main aim of this study was to evaluate pericancerous lymph nodes imaging in video‐assisted thoracoscopic surgery radical esophagectomy using a near‐infrared (NIR) ICG imaging system and to improve the detection rate of sentinel lymph nodes (SLNs) and overall survival of patients with esophageal cancer. Methods This was a single‐center, prospective, randomized controlled clinical trial (allocation rate = 1:1). Forty treatment‐naive esophageal cancer patients were recruited and divided into two groups: the ICG and control groups. The inclusion criteria were age, absence of preoperative neoadjuvant therapy, elective surgery, and signed informed consent. Data of participants at four different time points (preoperation, intraoperation, postoperative 1 week and 3 months) were collected and recorded. The main endpoint of this study was to explore the accuracy and false‐negative rate of lymphadenectomy using NIR‐ICG fluorescence imaging and to identify the location of esophageal cancer SLN combined with postoperative pathological reports. Discussion This trial will provide more evidence on the extent of lymph node dissection for esophageal cancer and contribute to the development of treatment guidelines for esophageal cancer. Trial registration number NCT04615806.

Abstract Background As an endocytic nanosicle involved in intercellular communication, an exosome can efficiently deliver drugs from one cell to another and deliver therapeutic short interfering RNA (siRNA) to target cells. This is conducive to gene therapy for cancers. In this study, an exosome was used as the siRNA‐loaded substrate to prepare a targeted siRNA‐loaded PD‐L1 exosome and evaluate its function against lung cancer. Methods The optimal preparation process and binding ratio of the targeted nanovesicle/siRNA complex was determined by detecting the particle size, potential, and other physical parameters in combination with cell binding and uptake capacity of exosome complexes. The biological cell behavior of targeted exosome nanosicles was evaluated through cytotoxicity, apoptosis, and the cell uptake capacity. Results A targeted exosome nanovesicle capable of loading siRNA and characterized with low toxicity, high loading rate, and the ability to be used for targeted tumor cell gene therapy was constructed. Conclusion The PD‐L1 targeting exosome can be used as an efficient siRNA delivery carrier, which is an efficient and safe nanocarrier for tumor targeted gene therapy.

Abstract Purpose This study aimed to compare the value of a modified chest tube drainage strategy to a traditional drainage strategy in single‐port thoracoscopic pulmonary wedge resection. Methods From January 2019 to July 2021, we collected clinical data on 405 patients who underwent single‐port thoracoscopic pulmonary wedge resection in the No.1 Department of Thoracic Surgery at Fujian Medical University Union Hospital, with 121 (29.9%) cases in the modified drainage strategy group and 284 (70.1%) cases in the traditional drainage strategy group. The propensity score matching method (Match Ratio = 1:1) was used to reduce differences in clinical characteristics between the two groups. Results Following 1:1 propensity score matching, 120 matched pairs (240 patients) were included in the study. There was no significant difference in general clinical characteristics between the two groups. There was no statistical difference in intraoperative factors except for operative times (71.42 ± 22.98 min vs. 86.80 ± 36.75 min, p

Abstract Background Clinically, some specific pulmonary nodules have safe resection margins that are located in multiple subsegments in the center of lung lobe. It is therefore difficult to ensure the resection margins through conventional combined subsegmentectomy or wedge resection, and thus lobectomy is required. For these types of pulmonary nodules, “split” operation was performed to fully inflate the reserved lung tissues on both sides. This study aimed to preliminarily assess the feasibility and safety of “split” operation. Methods Cases with these types of pulmonary nodules were selected. Some of the cases were subjected to “split” operation and the operation conditions, including operation time, bleeding amount, length of hospital stay, computed tomography (CT) reexaminations, and pulmonary function, were analyzed. Results The “split” operation was performed and successfully completed for seven patients. There was no case of conversion to thoracotomy and the median operation time, bleeding amount, and length of hospital stay were 219 min, 30.0 ml, and 4 days, respectively. No death or pulmonary complications such as pulmonary infection, lung torsion, and bronchopleural fistula occurred, and only one patient had incision fat liquefaction. After 3 months, the median percentage of preserved pulmonary function was 85.8% and a CT scan showed that the reserved lung tissues of the seven patients were well inflated and without obvious imaging findings of atelectasis. Conclusion “Split” combined subsegmentectomy can be used as a new and safe operative method for deep pulmonary nodules with safe resection margins involving multiple subsegments in the center of the lung lobe.

Abstract Direct electrocatalytic oxidation of benzene has been regarded as a promising approach for achieving high‐value phenol product, but remaining a huge challenge. Here an oxygen‐coordinated nickel single‐atom catalyst (Ni–O–C) is reported with bifunctional electrocatalytic activities toward the two‐electron oxygen reduction reaction (2e− ORR) to H2O2 and H2O2‐assisted benzene oxidation to phenol. The Ni–(O–C2)4 sites in Ni–O–C ar proven to be the catalytic active centers for bifunctional 2e− ORR and H2O2‐assisted benzene oxidation processes. As a result, Ni–O–C can afford a benzene conversion as high as 96.4 ± 3.6% with a phenol selectivity of 100% and a Faradaic efficiency (FE) of 80.2 ± 3.2% with the help of H2O2 in 0.1 m KOH electrolyte at 1.5 V (vs RHE). A proof of concept experiment with Ni–O–C concurrently as cathode and anode in a single electrochemical cell demonstrates a benzene conversion of 33.4 ± 2.2% with a phenol selectivity of 100% and a FE of 44.8 ± 3.0% at 10 mA cm−2.

Abstract Background Transketolase (TKT), a key rate‐limiting enzyme in the non‐oxidative branch of the pentose phosphate pathway (PPP), provides more than 85% of the ribose required for de novo nucleotide biosynthesis and promotes the development of hepatocellular carcinoma (HCC). Pharmacologic inhibition of TKT could impede HCC development and enhance treatment efficacy. However, no safe and effective TKT inhibitor has been approved. Methods An online two‐dimensional TKT protein immobilised biochromatographic system was established for high‐throughput screening of TKT ligands. Oroxylin A was found to specifically bind TKT. Drug affinity responsive target stability, cellular thermal shift assay, surface plasmon resonance, molecular docking, competitive displacement assay, and site mutation were performed to identify the binding of oroxylin A with TKT. Antitumour effects of oroxylin A were evaluated in vitro, in human xenograft mice, diethylnitrosamine (DEN)‐induced HCC mice, and patient‐derived organoids (PDOs). Metabolomic analysis was applied to detect the enzyme activity. Transcriptome profiling was conducted to illustrate the anti‐HCC mechanism of oroxylin A. TKT knocking‐down HCC cell lines and PDOs were established to evaluate the role of TKT in oroxylin A‐induced HCC suppression. Results By targeting TKT, oroxylin A stabilised the protein to proteases and temperature extremes, decreased its activity and expression, resulted in accumulation of non‐oxidative PPP substrates, and activated p53 signalling. In addition, oroxylin A suppressed cell proliferation, induced apoptosis and cell‐cycle arrest, and inhibited the growth of human xenograft tumours and DEN‐induced HCC in mice. Crucially, TKT depletion exerted identical effects to oroxylin A, and the promising inhibitor also exhibited excellent therapeutic efficacy against clinically relevant HCC PDOs. Conclusions These results uncover a unique role for oroxylin A in TKT inhibition, which directly targets TKT and suppresses the non‐oxidative PPP. Our findings will facilitate the development of small‐molecule inhibitors of TKT and novel therapeutics for HCC.

Abstract In fragmented forests, edge effects can drive intraspecific variation in seedling performance that influences forest regeneration and plant composition. However, few studies have attempted to disentangle the relative biotic and abiotic drivers of intraspecific variation in seedling performance. In this study, we carried out a seedling transplant experiment with a factorial experimental design on three land‐bridge islands in the Thousand Island Lake, China, using four common native woody plant species. At different distances from the forest edge (2, 8, 32, 128 m), we transplanted four seedlings of each species into each of three cages: full‐cage, for herbivore exclusion; half‐cage, that allowed herbivore access but controlled for caging artifacts; and no‐cage control. In the 576 cages, we recorded branch architecture, leaf traits, and seedling survival for each seedling before and after the experimental treatment. Overall, after one full growing season, edge‐induced abiotic drivers and varied herbivory pressure led to intraspecific variation in seedling performance, including trade‐offs in seedling architecture and resource‐use strategies. However, responses varied across species with different life‐history strategies and depended on the driver in question, such that the abiotic and biotic effects were additive across species, rather than interactive. Edge‐induced abiotic variation modified seedling architecture of a shade‐tolerant species, leading to more vertical rather than lateral growth at edges. Meanwhile, increased herbivory pressure resulted in a shift toward lower dry matter investment in leaves of a light‐demanding species. Our results suggest that edge effects can drive rapid directional shifts in the performance and intraspecific traits of some woody plants from early ontogenetic stages, but most species in this study showed negligible phenotypic responses to edge effects. Moreover, species‐specific responses suggest the importance of interspecific differences modulating the degree of trait plasticity, implying the need to incorporate individual‐level responses when understanding the impact of forest fragmentation on plant communities.

Abstract Perioperative adjuvant treatment has become an increasingly important aspect of the management of patients with non‐small cell lung cancer (NSCLC). In particular, the success of immune checkpoint inhibitors, such as antibodies against PD‐1 and PD‐L1, in patients with lung cancer has increased our expectations for the success of these therapeutics as neoadjuvant immunotherapy. Neoadjuvant therapy is widely used in patients with resectable stage IIIA NSCLC and can reduce primary tumor and lymph node stage, improve the complete resection rate, and eliminate microsatellite foci; however, complete pathological response is rare. Moreover, because the clinical benefit of neoadjuvant therapy is not obvious and may complicate surgery, it has not yet entered the mainstream of clinical treatment. Small‐scale clinical studies performed in recent years have shown improvements in the major pathological remission rate after neoadjuvant therapy, suggesting that it will soon become an important part of NSCLC treatment. Nevertheless, neoadjuvant immunotherapy may be accompanied by serious adverse reactions that lead to delay or cancellation of surgery, additional illness, and even death, and have therefore attracted much attention. In this article, we draw on several sources of information, including (i) guidelines on adverse reactions related to immune checkpoint inhibitors, (ii) published data from large‐scale clinical studies in thoracic surgery, and (iii) practical experience and published cases, to provide clinical recommendations on adverse events in NSCLC patients induced by perioperative immunotherapy.

Abstract The unbound concentrations of 14 commercial drugs, including five non‐efflux/uptake transporter substrates—Class I, five efflux transporter substrates—class II and four influx transporter substrates—Class III, were simultaneously measured in rat liver, muscle, and blood via microanalysis. Kpuu,liver and Kpuu,muscle were calculated to evaluate the membrane transport activity and cell metabolism on the unbound drug concentrations in the skeletal muscle and liver. For Class I compounds, represented by antipyrine, unbound concentrations among liver, muscle and blood are symmetrically distributed when compound hepatic clearance is low. And when compound hepatic clearance is high, unbound concentrations among liver, muscle and blood are asymmetrically distributed, such as Propranolol. For Class II and III compounds, overall, the unbound concentrations among liver, muscle, and blood are asymmetrically distributed due to a combination of hepatic metabolism and efflux and/or influx transporter activity.

Abstract In clinical pharmacology, the free drug hypothesis has been widely applied in the interpretation of the relationship between pharmacokinetics and pharmacodynamics (PK/PD). The free drug hypothesis assumes that the unbound drug concentration in blood is the same as that in the site of action at steady state. The objective of this study is to demonstrate whether the free drug hypothesis is universally applicable for all drugs. The unbound concentrations of the 18 compounds in blood and in brain interstitial fluids (ISF) at steady state following constant intravenous infusion were simultaneously monitored up to 6 hours via in vivo microdialysis technique. Based on the permeability and efflux ratio (ER), the test compounds can be divided into two classes. Class I includes the compounds with good membrane permeability that are not substrates of efflux transporters (eg, P‐gp, BCRP, and MRPs), whereas Class II includes the compounds that are substrates of efflux transporters. The steady‐state unbound drug concentrations in blood, brain, and CSF are quantitatively very similar for Class I compounds, whereas the steady‐state unbound concentrations in the brain and CSF are significantly lower than those in blood for Class II compounds. These results strongly suggest that the free drug hypothesis is not universal for all drugs but is only applicable for drugs with good permeability that are not substrates of efflux transporters.