Expression and bioinformatics analysis of RPL38 protein and mRNA in gastric cancer.

We aimed to clarify the expression of RPL38 in gastric cancer, explore the relationship between the expression level of RPL38 and the clinicopathological parameters and prognosis of gastric cancer patients, and explore whether RPL38 has the potential to be used as a therapeutic target for gastric cancer and a biomarker for assessing prognosis. The mRNA and protein expression of RPL38 in gastric cancer tissues and normal tissues were compared by TIMER, Kaplan-Meier plotter, CCLE and UALCAN databases, respectively. Next, the relationship between the expression level of RPL38 in gastric cancer tissues and clinicopathological features was analysed using the UALCAN database. The Kaplan-Meier plotter database was then used to predict the prognostic value of RPL38 in gastric cancer patients, and overall survival curves were plotted based on the follow-up information of clinical specimens. The relationship between RPL38 expression and the level of immune infiltration in gastric cancer was explored using the TIMER database. Finally, co-expression analysis as well as enrichment analysis of RPL38 was performed using LinkedOmics database and GSEA, respectively. Through comprehensive bioinformatics analysis and immunohistochemistry experiments, we comprehensively concluded that RPL38 was highly expressed in gastric cancer. Univariate analysis showed that TNM stage (P=0.008), radiotherapy (P=0.02), and RPL38 expression level (P=0.0006) were associated with prognosis. Multifactorial analysis showed that RPL38 expression level (P=0.019), TNM stage (P=0.015) and radiotherapy (P=0.039) were independent risk factors affecting the prognosis of gastric cancer. Gastric cancer patients with high expression of RPL38 had poorer OS. In addition, RPL38 was associated with immune infiltration in gastric cancer. RPL38 is highly expressed in gastric cancer tissues, and RPL38 protein plays an important role in the development of gastric cancer, which is one of the important factors in assessing the prognosis of gastric cancer patients.

Exploring the potential mechanism of Rubus corchorifolius L. fruit polyphenol-rich extract in mitigating non-alcoholic fatty liver disease by integration of metabolomics and transcriptomics profiling.

Nonalcoholic fatty liver disease (NAFLD), as the commonest chronic liver disease, is accompanied by liver oxidative stress and inflammatory responses. Herein, the extract obtained from Rubus corchorifolius fruits was purified and characterized for its polyphenol composition. The liver protective effect of the purified R. corchorifolius fruit extract (RCE) on mice with high-fat-diet (HFD)-induced NAFLD were investigated, and the potential mechanisms were explored through the integration of transcriptomics and metabolomics. Results showed that the polyphenolic compounds in RCE mainly included (-)-epigallocatechin, procyanidin B2, keracyanin, vanillin, dihydromyricetin, and ellagic acid. In addition, RCE intervention ameliorated liver and mitochondrial damage, which was evidenced by decreased indices of oxidative stress, liver function markers, and lipid profile levels. The liver metabonomics research revealed that RCE intervention affected the metabolic pathways of metabolites, including linoleic acid metabolism, galactose metabolism, alanine, aspartate and glutamate metabolism, retinol metabolism, glycine, serine and threonine metabolism, tryptophan metabolism, aminoacyl-tRNA biosynthesis, riboflavin metabolism, starch and sucrose metabolism, and arachidonic acid metabolism. Additionally, liver transcriptomics research indicated that pathways like fatty acid degradation, circadian rhythm, valine, leucine and isoleucine degradation, primary bile acid biosynthesis, cytokine-cytokine receptor interaction, adipocytokine signaling pathway, glutathione metabolism, lipid and atherosclerosis were significantly enriched. The transcriptomics and metabolomics analysis demonstrated that RCE intervention had significant modulatory effects on the metabolic pathways associated with glycolipid metabolism. Moreover, RT-PCR results verified that RCE intervention regulated liver mRNA levels associated with the inflammatory response. Therefore, our findings suggest that the intake of RCE might be an effective strategy to alleviate liver damage.

Recurrent pleural effusion as a rare manifestation after prolonged PD1 inhibitor (camrelizumab)-based immunotherapy: A case report.

Immune-related adverse events (irAEs) pose a significant challenge for the widespread adoption of immuno-oncology therapies, but their symptoms can vary widely. In particular, the relationship between irAEs and pleural effusion (PE) in patients with advanced non-small cell lung cancer (NSCLC) remains unclear. In this report, we present the case of an advanced NSCLC patient who developed persistent PE despite receiving camrelizumab (an anti-programmed death receptor 1 [PD-1] antibody) and chemotherapy as first-line treatment. While the patient's tumor biomarkers decreased after multiple cycles of treatment, the PE persisted despite negative findings on cytology and pleural biopsy. Additionally, the use of anti-angiogenic drugs failed to alleviate the PE. Screening for rheumatic connective tissue markers and tuberculosis yielded negative results, but intrathoracic dexamethasone injections in two doses resulted in a significant reduction of the PE. This case suggests that PE may represent a rare type of irAE that should be monitored for during prolonged immuno-oncology therapy.

Corrigendum: Low-frequency repetitive transcranial magnetic stimulation restores dynamic functional connectivity in subcortical stroke.

[This corrects the article DOI: 10.3389/fneur.2021.771034.].

Effects of transcranial combined with peripheral repetitive magnetic stimulation on limb spasticity and resting-state brain activity in stroke patients.

Background and objective: Transcranial magnetic stimulation and peripheral repetitive magnetic stimulation (rPMS), as non-invasive neuromodulation techniques, can promote functional recovery in patients with post-stroke spasticity (PSS), but the effects of transcranial magnetic stimulation combined with peripheral magnetic stimulation on PSS remain largely unknown. Therefore, we examined the effects of low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) combined with rPMS on PSS patients and its potential neural correlates to behavioral improvements. Methods: Forty-nine PSS patients were divided randomly into three groups: a combined group (n = 20), a LF-rTMS group (n = 15), and a control group (n = 14). The combined group received LF-rTMS and rPMS treatment, the rTMS group received LF-rTMS treatment, and the control group received only routine rehabilitation. All patients underwent Ashworth Spasm Scale (MAS), upper extremity Fugl-Meyer (FMA-UE), and modified Barthel Index (MBI) assessments before and after intervention. In addition, resting-state functional magnetic resonance imaging data were collected pre- and post-treatment to observe changes in the amplitude of low-frequency fluctuation (ALFF). Results: The MAS score was decreased, FMA-UE score and MBI scores were increased in the three groups after therapy than before therapy (all P < 0.05). In particular, the combined group showed significant effect on improved motor function and relieved spasticity in PSS (P < 0.01). Moreover, the combined treatment increased ALFF values mainly in the right supplementary motor area, right middle frontal gyrus, and right cerebellum, while reduced ALFF values mainly in the right post-central gyrus compared with pre-treatment. Compared with the LF-rTMS and control groups, the combined treatment increased ALFF values in the right cerebellum and reduced ALFF values mainly in the frontoparietal cortex. Improvements in the MAS score were positively correlated with the change in ALFF values in the right cerebellum (r = 0.698, P = 0.001) and the right supplementary motor area (r = 0.700, P = 0.001) after combined treatment. Conclusion: Transcranial combined with peripheral repetitive magnetic stimulation could improve spastic state and motor function in PSS patients, and this effect may be associated with altered cerebellar and frontoparietal cortical activity. Clinical trial registration: http://www.chictr.org.cn/index.aspx, identifier ChiCTR1800019452.

Neural basis of dysphagia in stroke: A systematic review and meta-analysis.

Objectives: Dysphagia is a major cause of stroke infection and death, and identification of structural and functional brain area changes associated with post-stroke dysphagia (PSD) can help in early screening and clinical intervention. Studies on PSD have reported numerous structural lesions and functional abnormalities in brain regions, and a systematic review is lacking. We aimed to integrate several neuroimaging studies to summarize the empirical evidence of neurological changes leading to PSD. Methods: We conducted a systematic review of studies that used structural neuroimaging and functional neuroimaging approaches to explore structural and functional brain regions associated with swallowing after stroke, with additional evidence using a live activation likelihood estimation (ALE) approach. Results: A total of 35 studies were included, including 20 studies with structural neuroimaging analysis, 14 studies with functional neuroimaging analysis and one study reporting results for both. The overall results suggest that structural lesions and functional abnormalities in the sensorimotor cortex, insula, cerebellum, cingulate gyrus, thalamus, basal ganglia, and associated white matter connections in individuals with stroke may contribute to dysphagia, and the ALE analysis provides additional evidence for structural lesions in the right lentiform nucleus and right thalamus and functional abnormalities in the left thalamus. Conclusion: Our findings suggest that PSD is associated with neurological changes in brain regions such as sensorimotor cortex, insula, cerebellum, cingulate gyrus, thalamus, basal ganglia, and associated white matter connections. Adequate understanding of the mechanisms of neural changes in the post-stroke swallowing network may assist in clinical diagnosis and provide ideas for the development of new interventions in clinical practice.

Aberrant dynamic Functional-Structural connectivity coupling of Large-scale brain networks in poststroke motor dysfunction.

BACKGROUND AND PURPOSE: Stroke may lead to widespread functional and structural reorganization in the brain. Several studies have reported a potential correlation between functional network changes and structural network changes after stroke. However, it is unclear how functional-structural relationships change dynamically over the course of one resting-state fMRI scan in patients following a stroke; furthermore, we know little about their relationships with the severity of motor dysfunction. Therefore, this study aimed to investigate dynamic functional and structural connectivity (FC-SC) coupling and its relationship with motor function in subcortical stroke from the perspective of network dynamics. METHODS: Resting-state functional magnetic resonance imaging and diffusion tensor imaging were obtained from 39 S patients (19 severe and 20 moderate) and 22 healthy controls (HCs). Brain structural networks were constructed by tracking fiber tracts in diffusion tensor imaging, and structural network topology metrics were calculated using a graph-theoretic approach. Independent component analysis, the sliding window method, and k-means clustering were used to calculate dynamic functional connectivity and to estimate different dynamic connectivity states. The temporal patterns and intergroup differences of FC-SC coupling were analyzed within each state. We also calculated dynamic FC-SC coupling and its relationship with functional network efficiency. In addition, the correlation between FC-SC coupling and the Fugl-Meyer assessment scale was analyzed. RESULTS: For SC, stroke patients showed lower global efficiency than HCs (all P < 0.05), and severely affected patients had a higher characteristic path length (P = 0.003). For FC and FC-SC coupling, stroke patients predominantly showed lower local efficiency and reduced FC-SC coupling than HCs in state 2 (all P < 0.05). Furthermore, severely affected patients also showed lower local efficiency (P = 0.031) and reduced FC-SC coupling (P = 0.043) in state 3, which was markedly linked to the severity of motor dysfunction after stroke. In addition, FC-SC coupling was correlated with functional network efficiency in state 2 in moderately affected patients (r = 0.631, P = 0.004) but not significantly in severely affected patients. CONCLUSIONS: Stroke patients show abnormal dynamic FC-SC coupling characteristics, especially in individuals with severe injuries. These findings may contribute to a better understanding of the anatomical functional interactions underlying motor deficits in stroke patients and provide useful information for personalized rehabilitation strategies.

Education level has an effect on the recovery of total knee arthroplasty: a retrospective study.

OBJECTIVE: This study aimed to observe the relationship between education level and outcomes after total knee arthroplasty (TKA). METHODS: One thousand two hundred sixty four patients after TKA in our hospital from April 2016 to April 2020 were reviewed. These patients were divided into 4 groups (A who were illiterate, B who had elementary school degree, C who had junior high school degree, D who had senior high school degree or higher) by the educational level, which was blinded to the observers. The postoperative outcomes of KSS score, pain, joint extension and flexion function were observed 1 year after discharged from hospital. RESULTS: Among 1253 patients met the inclusion criteria, the average age was 68.63 years, the average body mass was 57.73 kg. There are no distinctions among 4 groups one day after the surgery. However, the outcomes of the follow up were that, the KSS score was: 77.84 ± 10.635; 80.70 ± 8.956; 87.92 ± 8.123;91.27 ± 8.262, with significant differences (P < 0.05). The mean VAS scores were: 1.97 ± 1.60; 2.07 ± 1.66; 1.197 ± 1.5265, 1.044 ± 1.4662. Patients in Group C and D had significantly less pain than that in Group A and B (P < 0.05). The knee flexion range of motion (ROM) was: 91.21 ± 11.69°; 91.77 ± 11.95°; 102.12 ± 11.38°; 109.96 ± 10.64°, Group D performed best, with significant differences (P < 0.05). The knee extension ROM were: - 2.41 ± 4.49°; - 0.91 ± 2.82°; - 0.83 ± 2.87°; - 0.35 ± 1.60°, with significant difference between Group D and the others (P < 0.05). CONCLUSION: Education level affects the outcomes such as VAS score, KSS score, the extension and flexion ROM of the knee after TKA. The patients with higher education level have better outcomes.

Lesions causing post-stroke spasticity localize to a common brain network.

Objective: The efficacy of clinical interventions for post-stroke spasticity (PSS) has been consistently unsatisfactory, probably because lesions causing PSS may occur at different locations in the brain, leaving the neuroanatomical substrates of spasticity unclear. Here, we investigated whether heterogeneous lesions causing PSS were localized to a common brain network and then identified the key nodes in this network. Methods: We used 32 cases of PSS and the Human Connectome dataset (n = 1,000), using a lesion network mapping method to identify the brain regions that were associated with each lesion in patients with PSS. Functional connectivity maps of all lesions were overlaid to identify common connectivity. Furthermore, a split-half replication method was used to evaluate reproducibility. Then, the lesion network mapping results were compared with those of patients with post-stroke non-spastic motor dysfunction (n = 29) to assess the specificity. Next, both sensitive and specific regions associated with PSS were identified using conjunction analyses, and the correlation between these regions and PSS was further explored by correlation analysis. Results: The lesions in all patients with PSS were located in different cortical and subcortical locations. However, at least 93% of these lesions (29/32) had functional connectivity with the bilateral putamen and globus pallidus. These connections were highly repeatable and specific, as compared to those in non-spastic patients. In addition, the functional connectivity between lesions and bilateral putamen and globus pallidus in patients with PSS was positively correlated with the degree of spasticity. Conclusion: We identified that lesions causing PSS were localized to a common functional connectivity network defined by connectivity to the bilateral putamen and globus pallidus. This network may best cover the locations of lesions causing PSS. The putamen and globus pallidus may be potential key regions in PSS. Our findings complement previous neuroimaging studies on PSS, contributing to identifying patients with stroke at high risk for spasticity at an early stage, and may point to PSS-specific brain stimulation targets.

Vanadium dioxide-assisted switchable multifunctional metamaterial structure.

A multifunctional design based on vanadium dioxide (VO2) metamaterial structure is proposed. Broadband absorption, linear-to-linear (LTL) polarization conversion, linear-to-circular (LTC) polarization conversion, and total reflection can be achieved based on the insulator-to-metal transition (IMT) of VO2. When the VO2 is in the metallic state, the multifunctional structure can be used as a broadband absorber. The results show that the absorption rate exceeds 90% in the frequency band of 2.17 - 4.94 THz, and the bandwidth ratio is 77.8%. When VO2 is in the insulator state, for the incident terahertz waves with a polarization angle of 45°, the structure works as a polarization converter. In this case, LTC polarization conversion can be obtained in the frequency band of 0.1 - 3.5 THz, and LTL polarization conversion also can be obtained in the frequency band of 3.5 - 6 THz, especially in the 3.755 - 4.856 THz band that the polarization conversion rate is over 90%. For the incident terahertz waves with a polarization angle of 0°, the metamaterial structure can be used as a total reflector. Additionally, impacts of geometrical parameters, incidence angle and polarization angle on the operating characteristics have also been investigated. The designed switchable multifunctional metasurfaces are promising for a wide range of applications in advanced terahertz research and smart applications.

Realization of absorption, filtering, and sensing in a single metamaterial structure combined with functional materials.

In this paper, a hybrid vanadium dioxide (VO2)-graphene-based bifunctional metamaterial is proposed. The realization of the different functions of perfect transmission and high absorption is based on the insulator-metal phase transition of VO2 material. The Fermi energy level of graphene can be treated to dynamically tune the absorption and transmission rates of the metamaterial structure. As a result, when VO2 is in the insulating state, the designed metamaterial can be used as a filter providing three adjustable passbands with center frequencies of 1.892 THz, 1.124 THz, and 0.94 THz, and the corresponding transmittances reach 93.11%, 98.62%, and 90.01%, respectively. The filter also shows good stopband characteristics and exhibits good sensing performance at the resonant frequencies of 1.992 THz and 2.276 THz. When VO2 is in metal state, the metamaterial structure acts as a double-band absorber, with three absorption peaks (>90%) in the range of 0.684 THz to 0.924 THz, 2.86 THz to 3.04 THz, and 3.28 THz to 3.372 THz, respectively. The designed structure is insensitive to the polarization of vertically incident terahertz waves and still maintains good absorption performances over a large range of incidence angles. Finally, the effects of geometric parameters on the absorption and transmission properties of the hybrid bifunctional metamaterials have also been discussed. The switchable metamaterial structures proposed in this paper provide great potential in terahertz application fields, such as filtering, smart sensing, switching, tunable absorbers, and so on.

Effects of whole-body electromyostimulation training on upper limb muscles strength and body composition in moderately trained males: A randomized controlled study.

Resistance training has been known to have a positive effect on muscle performance in exercisers. Whole-body electromyostimulation (WB-EMS) is advertised as a smooth, time-efficient, and highly individualized resistance training technology. The purpose of this study is to evaluate the effects of WB-EMS training on maximum isometric elbow muscle strength and body composition in moderately trained males in comparison to traditional resistance training. The study was a randomized controlled single-blind trial. Twenty, moderately trained, male participants (25.15 ± 3.84, years) were randomly assigned to the following groups: a WB-EMS training group (n = 11) and a traditional resistance training group (the control group [CG]: n = 9). Both training intervention programs consisted of 18 training sessions for six consecutive weeks. All subjects performed dynamic movements with the WB-EMS or external weights (CG). The primary outcome variables included maximum isometric elbow flexor strength (MIEFS), maximum isometric elbow extensor strength (MIEES) and surface electromyography amplitude (sEMGRMS). Secondary outcomes involved lean body mass, body fat content, arm fat mass, and arm lean mass. ANOVAs, Friedman test and post hoc t-tests were used (P = 0.05) to analyze the variables development after the 6-week intervention between the groups. Significant time × group interactions for MIEFS (η2 = 0.296, P Bonferroni = 0.013) were observed, the increase in the WB-EMS group were significantly superior to the CG [23.49 ± 6.48% vs. 17.01 ± 4.36%; MD (95% CI) = 6.48 (1.16, 11.80); d = 1.173, P = 0.020]. There were no significant differences were observed between interventions regarding MIEES, sEMGRMS and body composition. These findings indicate that in moderately trained males the effects of WB-EMS were similar to a traditional resistance training, with the only exception of a significantly greater increase in elbow flexor strength. WB-EMS can be considered as an effective exercise addition for moderately trained males.

RuO2 electronic structure and lattice strain dual engineering for enhanced acidic oxygen evolution reaction performance.

Developing highly active and durable electrocatalysts for acidic oxygen evolution reaction remains a great challenge due to the sluggish kinetics of the four-electron transfer reaction and severe catalyst dissolution. Here we report an electrochemical lithium intercalation method to improve both the activity and stability of RuO2 for acidic oxygen evolution reaction. The lithium intercalates into the lattice interstices of RuO2, donates electrons and distorts the local structure. Therefore, the Ru valence state is lowered with formation of stable Li-O-Ru local structure, and the Ru-O covalency is weakened, which suppresses the dissolution of Ru, resulting in greatly enhanced durability. Meanwhile, the inherent lattice strain results in the surface structural distortion of LixRuO2 and activates the dangling O atom near the Ru active site as a proton acceptor, which stabilizes the OOH* and dramatically enhances the activity. This work provides an effective strategy to develop highly efficient catalyst towards water splitting.

Improved profiling of low molecular weight serum proteome for gastric carcinoma by data-independent acquisition.

Low molecular weight proteins (LMWPs) in the bloodstream participate in various biological processes and are closely associated with disease status, whereas identification of serous LMWPs remains a great technical challenge due to the wide dynamic range of protein components. In this study, we constructed an integrated LMWP library by combining the LMWPs obtained by three enrichment methods (50% ACN, 20% ACN + 20 mM ABC, and 30 kDa) and their fractions identified by the data-dependent acquisition method. With this newly constructed library, we comprehensively profiled LMWPs in serum using data-independent acquisition and reliably achieved quantitative results for 75% serous LMWPs. When applying this strategy to quantify LMWPs in human serum samples, we could identify 405 proteins on average per sample, of which 136 proteins were with a MW less than 30 kDa and 293 proteins were with a MW less than 65 kDa. Of note, pre- and post-operative gastric carcinoma (GC) patients showed differentially expressed serous LWMPs, which was also different from the pattern of LWMP expression in healthy controls. In conclusion, our results showed that LMWPs could efficiently distinguish GC patients from healthy controls as well as between pre- and post-operative statuses, and more importantly, our newly developed LMWP profiling platform could be used to discover candidate LMWP biomarkers for disease diagnosis and status monitoring.

Low-Frequency Repetitive Transcranial Magnetic Stimulation Restores Dynamic Functional Connectivity in Subcortical Stroke.

Background and Purpose: Strokes consistently result in brain network dysfunction. Previous studies have focused on the resting-state characteristics over the study period, while dynamic recombination remains largely unknown. Thus, we explored differences in dynamics between brain networks in patients who experienced subcortical stroke and the effects of low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) on dynamic functional connectivity (dFC). Methods: A total of 41 patients with subcortical stroke were randomly divided into the LF-rTMS (n = 23) and the sham stimulation groups (n = 18). Resting-state functional MRI data were collected before (1 month after stroke) and after (3 months after stroke) treatment; a total of 20 age- and sex-matched healthy controls were also included. An independent component analysis, sliding window approach, and k-means clustering were used to identify different functional networks, estimate dFC matrices, and analyze dFC states before treatment. We further assessed the effect of LF-rTMS on dFCs in patients with subcortical stroke. Results: Compared to healthy controls, patients with stroke spent significantly more time in state I [p = 0.043, effect size (ES) = 0.64] and exhibited shortened stay in state II (p = 0.015, ES = 0.78); the dwell time gradually returned to normal after LF-rTMS treatment (p = 0.015, ES = 0.55). Changes in dwell time before and after LF-rTMS treatment were positively correlated with changes in the Fugl-Meyer Assessment for Upper Extremity (pr = 0.48, p = 0.028). Moreover, patients with stroke had decreased dFCs between the sensorimotor and cognitive control domains, yet connectivity within the cognitive control network increased. These abnormalities were partially improved after LF-rTMS treatment. Conclusion: Abnormal changes were noted in temporal and spatial characteristics of sensorimotor domains and cognitive control domains of patients who experience subcortical stroke; LF-rTMS can promote the partial recovery of dFC. These findings offer new insight into the dynamic neural mechanisms underlying effect of functional recombination and rTMS in subcortical stroke. Registration: http://www.chictr.org.cn/index.aspx, Unique.identifier: ChiCTR1800019452.

High Proton Conduction in Three Highly Water-Stable Hydrogen-Bonded Ferrocene-Based Phenyl Carboxylate Frameworks.

To acquire more new crystalline proton conductive materials, three ferrocene-based phenyl carboxylate frameworks (FCFs), [FcCO(o-C6H4COOH)] (FCF 1) (Fc = (η5-C5H5)Fe(η5-C5H4)), [m-FcC6H4COOH] (FCF 2), and [p-FcC6H4COOH] (FCF 3), supported by hydrogen bonds and π···π interactions were prepared. Their structures and phase purities are clarified by single-crystal X-ray diffraction or powder X-ray diffraction (PXRD). In addition, their high thermal and water stability were confirmed by thermogravimetric analyses, PXRD, and scanning electron microscopy determinations. Proton conductivity (σ) of 1-3 was studied under different relative humidities (RHs) and temperatures, and it was found that their σ boosted with the increase of humidity and temperature. Under 100 °C and 98% RH, their optimal σ values are 0.77 × 10-3, 1.94 × 10-4, and 3.46 × 10-3 S·cm-1, respectively. Consequently, their proton conductive mechanisms were proposed by means of activation energy calculation and structural analysis. Note that they are good proton conductive materials and are expected to be used in proton exchange membrane fuel cells.

Case Report: Nintedanib for Pembrolizumab-Related Pneumonitis in a Patient With Non-Small Cell Lung Cancer.

Pembrolizumab, an immune checkpoint inhibitor (ICI) approved for advanced non-small cell lung cancer (NSCLC) treatment, has shown superior survival benefits. However, pembrolizumab may lead to severe immune-related adverse events (irAEs), such as checkpoint inhibitor-related pneumonitis (CIP). The routine treatment of CIP was based on systemic corticosteroids, but the therapies are limited for patients who are unsuitable for steroid therapy. Here, we present the first successful treatment of nintedanib for pembrolizumab-related pneumonitis in a patient with advanced NSCLC.

[Locking plate external fixation combined with membrane induction technology for the treatment of open and comminuted tibial fractures with bone defects].

OBJECTIVE: To explore clinical effect of locking plate external fixation combined with membrane induction technology in treating open and comminuted tibial fractures with bone defects. METHODS: Totally 92 patients of open and comminuted tibial fractures with bone defects were chosen form January 2018 to July 2019, and randomly divided into external fixation group and internal fixation group, 46 patients in each group. In external fixation group, there were 29 males and 17 females, aged from 25 to 62 years old, with an average of (37.45±10.92) years old;according to AO classification, 15 patients were type A, 22 patients were type B and 9 patients were type C;according to Gustilo classification, 21 patients were typeⅡ, 10 patients were type ⅢA, 10 patients were type ⅢB, 5 patients were type Ⅲ C;treated by fracture reduction with locking plate external fixation. In internal fixation group, there were 31 males and 15 females, aged from 23 to 60 years old, with an average of(36.88±10.64) years old;according to AO classification, 18 patients were type A, 20 patients were type B and 8 patients were type C; according to Gustilo classification, 22 patients were typeⅡ, 11 patients were type ⅢA, 7 patients were type ⅢB, 6 patients were type Ⅲ C;treated by traditional open reduction with plate internal fixation. Operation time, intraoperative blood loss, incision length, hospital stay, fracture healing time and lower limb full weight-bearing time and postoperative complications between two groups were observed and compared, bone mineral density, osteocalcin, blood calcium and phosphorus before operation and 1 month after operation. RESULTS: All patients were followed up from 12 to 18 months with an average of (14.92±2.46) months. Operation time, intraoperative blood loss, incision length, hospital stay, fracture healing time and lower limb full weight-bearing time of external fixation group were significantly better than that of internal fixation group(P<0.05). Postoperative bone mineral density, osteocalcin, blood calcium and phosphorus at 1 month in external group were higher than that of internal fixation group (P<0.05). Four patients in external fixation group occurred complications, 13 patients in internal fixtaion group, and occurrence rate of complications in external fixation group (8.70%) was lower than that of internal fixtaion group (28.26%)(χ2=4.618, P=0.032). CONCLUSION: Locking plate external fixation combined with membrane induction technology in treating open and comminuted tibial fractures with severe post-traumatic bone defects has advantages of less trauma, reliable fixation, shorter fracture healing time, and could improve bone metabolic activity with less postoperative complications.

Case Report: Neoadjuvant and Adjuvant Crizotinib Targeted Therapy in Stage IIIA-N2 ALK-Positive Non-Small-Cell Lung Cancer.

The treatment of anaplastic lymphoma kinase (ALK)-positive locally advanced non-small-cell lung cancer (NSCLC) is challenging because there is no randomized controlled trial has been reported. The value of neoadjuvant and adjuvant targeted therapy remains unclear. Herein, we show that systemic treatment with ALK inhibitor crizotinib before surgery can provide the potential to cure the initially inoperable tumor. A 27-year-old man was diagnosed with a stage IIIAcT3N2M0 (7thUICC/AJCC) upper left lung adenocarcinoma harboring EML4-ALK fusion gene. Clinically, the patient had a large primary lesion adjacent to the pericardium and regional lymph node metastasis at the ipsilateral mediastinum. Poor tumor response was observed after 3 cycles of chemotherapy (gemcitabine plus cisplatin), and upon multidisciplinary discussion, the patient was started with 250 mg crizotinib twice daily. Successive clinical examinations showed a progressive reduction of the lesions. After 2 months of therapy, the patient was downstaged to cT2aN2M0, then video-assisted thoracic surgery was performed and the final histopathological stage was ypT2aN2M0. The treatment with crizotinib (250 mg, qd) was continued more than 30 months post surgery and stopped until intracranial oligometastasis. The patient's overall survival (OS) time is 68 months at last follow-up. This case presented here supports the use of neoadjuvant and adjuvant treatment with ALK inhibitors in ALK positive locally advanced NSCLC.

Imbalance and breakout in the post-epidemic era: Research into the spatial patterns of freight demand network in six provinces of central China.

This study aims to explore the freight demand network spatial patterns in six provinces of central China from the perspective of the spread of the epidemic and the freight imbalance and breakout. To achieve this purpose, the big data of "cart search" demand information provided by small and medium freight enterprises on the freight information platform are analyzed. 343,690 pieces of freight demand big data on the freight information platform and Python, ArcGIS, UCINET, and Gephi software are used. The results show that: (1) The choke-point of unbalanced freight demand network is Wuhan, and the secondary choke-points are Hefei and Zhengzhou. (2) In southern China, a chain reaction circle of freight imbalance is formed with Wuhan, Hefei, and Nanchang as the centers. In northern China, a chain reaction circle of freight imbalance is formed with Zhengzhou and Taiyuan as the centers. (3) The freight demand of the six provinces in central China exhibits typical characteristics of long tail distribution with large span and unbalanced distribution. (4) The import and export of freight in different cities vary greatly, and the distribution is unbalanced. This study indicates the imbalance difference, chain reaction, keys and hidden troubles posed by the freight demand network. From the perspectives of freight transfer breakout, freight balance breakout, freight strength breakout, and breakout of freight periphery cities, we propose solutions to breakouts in the freight market in six provinces of central China in the post-epidemic era.