[Effect of glucocorticoids on the efficacy of non-small cell lung cancer patients treated with immune-checkpoint inhibitors].

Lung cancer is a highly lethal malignant tumor worldwide and in China, with non-small cell lung cancer (NSCLC) accounting for approximately 85% of cases globally. In recent years, immune checkpoint inhibitor (ICI) had changed the paradigm of lung cancer treatment, either alone or in combination with chemotherapy and recomended as the first-line treatment for NSCLC. NSCLC patients often required glucocorticoid(GC) due to the cancer itself, tumor complications, or immune-related adverse event (irAE). GC had sparked debates on their impact on the therapeutic effectiveness of ICI in NSCLC patients as a substance with immunomodulatory effects. While some studies suggested that GC use did not influence patients survival, others argued the opposite. Understanding the effects of GC on immunotherapy is crucial for managing complaications in cancer patients and addressing irAE. This review explores the impact of GC on the efficacy of ICI in NSCLC patients, aiming to provide insights for clinical treatment.

[Investigation of the inhibitory potential of caffeic acid phenethyl ester on prion replication, amplification, and fibril formation in vitro].

Objective: To investigate the effects and possible mechanisms of caffeic acid phenethyl ester (CAPE) on the replication, amplification, and fibre formation of prions (PrPSc). Methods: The CCK8 assay was used to detect the cell viability of the prion-infected cell model SMB-S15 after CAPE treatment for 3 days and 7 days and the maximum safe concentration of CAPE for SMB-S15 was obtained. The cells were treated with a concentration within a safe range, and the content of PrPSc in the cells before and after CAPE treatment was analyzed by western blot. Protein misfolding cycle amplification (PMCA) and western blot were used to assess changes in PrPSc level in amplification products following CAPE treatment. Real-time-quaking induced conversion assay (RT-QuIC) technology was employed to explore the changes in fibril formation before and after CAPE treatment. The binding affinity between CAPE and murine recombinant full-length prion protein was determined using a molecular interaction assay. Results: CCK8 cell viability assay results demonstrated that treatment with 1 µmol/L CAPE for 3 and 7 days did not exhibit statistically significant differences in cell viability compared to the control group (all P<0.05). However, when the concentration of CAPE exceeded 1 µmol/L, a significant reduction in cell viability was observed in cells treated with CAPE for 3 and 7 days, compared to the control group (all P<0.05). Thus, 1 µmol/L was determined as the maximum safe concentration of CAPE treatment for SMB-S15 cells. The western blot results revealed that treatment with CAPE for both 3 and 7 days led to a detectable reduction in the levels of PrPSc in SMB-S15 cells (all P<0.05). The products of PMCA experiments were assessed using western blot. The findings revealed a significant decrease in the levels of PrPSc (relative grey value) in the PMCA amplification products of adapted-strains SMB-S15, 139A, and ME7 following treatment with CAPE, as compared to the control group (all P<0.05). The RT-QuIC experimental results demonstrated a reduction in fibril formation (as indicated by ThT peak values) in CAPE-treated mouse-adapted strains 139A, ME7, and SMB-S15, as well as in SMB-S15 cells infected with prions. Furthermore, CAPE exhibited varying degrees of inhibition towards different seed fibrils formation, with statistically significant differences observed (all P<0.05). Notably, CAPE exhibited a more pronounced inhibitory effect on ME7 seed fibrils. Molecular interaction analyses demonstrated significant binding between CAPE and murine recombinant prion protein, and the association constant was (2.92±0.41)×10-6 mol/L. Conclusions: CAPE inhibits PrPSc replication, amplification, and fibril formation in vitro possibly due to specific interactions with the prion protein at the molecular level.

Coherent control of an optical tweezer phonon laser.

The creation and manipulation of coherence continues to capture the attention of scientists and engineers. The optical laser is a canonical example of a system that, in principle, exhibits complete coherence. Recent research has focused on the creation of coherent, laser-like states in other physical systems. The phonon laser is one example where it is possible to amplify self-sustained mechanical oscillations. A single mode phonon laser in a levitated optical tweezer has been demonstrated through appropriate balance of active feedback gain and damping. In this work, coherent control of the dynamics of an optical tweezer phonon laser is used to share coherence between its different modes of oscillation, creating a multimode phonon laser. The coupling of the modes is achieved by periodically rotating the asymmetric optical potential in the transverse focal plane of the trapping beam via trap laser polarization rotation. The presented theory and experiment demonstrate that coherence can be transferred across different modes of an optical tweezer phonon laser, and are a step toward using these systems for precision measurement and quantum information processing.

[Clinical update in critical care of pulmonary medicine 2023].

This article reviewed the clinical progress in the field of pulmonary and critial care medicine, both domestically and internationally during the year 2023 (from October 1, 2022 to September 30, 2023). In 2023, there have been significant modifications to the global definition of Acute Respiratory Distress Syndrome (ARDS). These include the inclusion of SpO2/FiO2 as a diagnostic criterion for ARDS, the addition of parameters for high-flow nasal cannula humidified oxygen therapy as a basis for diagnosing ARDS in non-intubated patients, clarification of the need to diagnose ARDS in non-intubated patients with PEEP≥5 cmH2O under non-invasive positive pressure ventilation, and the increased diagnostic value of ultrasound. Bedside electrical impedance, transpulmonary pressure and severe ultrasound provide effective means for for individualized assessment of critically ill patients. End-tidal alveolar dead space fraction, intestinal microecological imbalance, and ICU-acquired weakness are important warning indicators for the prognosis of critically ill patients. Machine learning models based on big data can effectively predict the prognosis of critically ill patients, and ECMO combined with prone positioning can improve patient outcomes. Cognition and fatigue were the most common persistent symptoms in critically ill patients after discharge. Intervention on specific cellular subtypes of lung injury receptors may be a future target for personalized treatment of lung injury tissue repair.

[Research progress on the prevalence and harm of heated tobacco products].

Heated tobacco products (HTP) are a new type of tobacco product, also known as heat-not-burn (HnB) tobacco products. They are devices that use an electronic heat source to heat tobacco and produce aerosols containing nicotine for smokers to inhale. Currently, traditional combustible cigarettes and electronic nicotine delivery systems (ENDS) are increasingly being regulated under the Framework Convention on Tobacco Control. Tobacco companies have responded by actively promoting heated tobacco products worldwide, which pose new challenges to global tobacco control efforts and may become a challenge for tobacco control work in China. In reviewing the situation and the potential harm of heated tobacco products, it was noted that HTP are rapidly gaining popularity worldwide, and that their harmfulness may be underestimated. Compared to combustible cigarettes (CC) and ENDS, the long-term health effects of HTP are not fully understood, and they may pose new health risks. Potential health risks include an increase in smoking prevalence, the presence of harmful and potentially harmful compounds not found in CC, and the potential gateway effect on non-smokers. Due to differences in laws, regulations, health policies, institutions, and cultural factors related to the tobacco industry in different countries and regions, attitudes, and regulatory measures towards HTP also vary. It is essential for countries and regions around the world to develop appropriate policies to strengthen control of HTP and prevent their widespread use.

[Analysis of the risk factors of persistent inflammation-immunosuppression-catabolism syndrome in patients with extensive burns].

Objective: To investigate the risk factors and treatment outcome of persistent inflammation-immunosuppression-catabolism syndrome (PICS) in patients with extensive burns. Methods: A retrospective case series study was conducted. From January 2017 to December 2021, 220 patients with extensive burns who were admitted to Guangzhou Red Cross Hospital of Jinan University met the inclusion criteria, including 168 males and 52 females, aged 18-84 (43±14) years. According to the occurrence of PICS, the patients were divided into PICS group (84 patients) and non-PICS group (136 patients). The general data such as sex, age, complication of underlying diseases and acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score on admission, sepsis-related organ failure evaluation (SOFA) scores on admission and 14 days post admission, and proportion of patients with mechanical ventilation over 48 h during treatment, special conditions such as total burn area, full-thickness burn area, proportion of patients admitted within 48 h post injury, and exposed deep wound area at the 30th day post injury, outcome indicators such as hospitalization day, total cost of hospital stay, number of surgeries, and death of patients in the 2 groups were collected and analyzed. Data were statistically analyzed with independent sample t test, Mann-Whitney U test, and chi-square test. The multivariate logistic regression analysis was performed on the indicators with statistically significant differences between the two groups except for outcome indicators, and the independent risk factors influencing secondary PICS in patients with extensive burns were screened. Results: The APACHE Ⅱ and SOFA scores on admission, and proportion of patients with mechanical ventilation over 48 h during treatment of patients in PICS group were significantly higher than those in non-PICS group (t=6.78, Z=-4.75, χ2=4.74, respectively, P<0.05). There were no statistically significant differences in the rest of general data of patients between the two groups (P>0.05). The total burn area, full-thickness burn area, and exposed deep wound area at the 30th day post injury in PICS group were significantly greater than those in non-PICS group (t=6.29, Z=-7.25, Z=-8.73, P<0.05), the exposed deep wound areas at the 30th day post injury in PICS group and non-PICS group were respectively 25% (15%, 35%) total body surface area (TBSA) and 8% (0, 13%) TBSA, while the proportion of patients admitted within 48 h post injury was significantly lower than that in non-PICS group (χ2=6.13, P<0.05). The hospitalization day, total cost of hospital stay, and number of surgeries of patients in PICS group were significantly higher than those in non-PICS group (with Z values of -7.12, -8.48, and -6.87, respectively, P<0.05), while the deaths of patients in the 2 groups were similar (P>0.05). The APACHE Ⅱ score on admission and exposed deep wound area at the 30th day post injury both were the independent risk factors for PICS in patients with extensive burns (with odds ratios of 1.15 and 1.07, 95% confidence intervals of 1.06-1.25 and 1.05-1.10, respectively, P<0.05). Conclusions: The APACHE Ⅱ score on admission and exposed deep wound area at the 30th day post injury are the independent risk factors for PICS in patients with extensive burns. The patients with secondary PICS had good prognosis with more surgical intervention and hospitalization day, and higher total cost of hospital stay.

[Biomarkers associated with severity classification of asthma identified by comprehensive bioinformatics analysis].

Using an integrated bioinformatics approach to find novel biomarkers that can predict asthma severity. From June 2022 to December 2022, this clinical medical study was conducted and completed in the Department of Allergy, Zhongnan Hospital of Wuhan University. The gene chip dataset GSE43696 was screened and downloaded from the high-throughput Gene Expression Omnibus (GEO) database, and the gene chip data preprocessing was completed using package "affy" in R and "rma" algorithm in turn. Use the the "edgeR" and "limma" packages to screen out the differentially expressed genes (DEGs) between normal controls, mild to moderate asthma patients and severe asthma patients, and then use the "clusterProfiler" package to perform GO enrichment analysis and KEGG pathway enrichment analysis of DEGs, finally use the STRING website to construct a protein-protein interaction (PPI) network of DEGs to further screen key genes. Using the R language "WGCNA" package, the weighted gene co-expression network analysis (WGCNA) was performed on the dataset GSE43696, and the modules significantly related to the severity of asthma were screened out, then the hub genes were obtained by intersecting the WGCNA analysis results with the DEGs screened by PPI. Datasets GSE43696 and GSE63142 were used to verify the expression of hub genes, and the diagnostic value was evaluated according to the ROC curve, then the potential function of hub genes in dataset GSE43696 was further clarified by gene set enrichment analysis (GSEA). The results showed that a total of 251 DEGs were screened, including 39 in the normal group and mild to moderate asthma group, 178 in the normal group and severe asthma group, and 34 in the mild to moderate asthma group and severe asthma group, mainly involved in biological processes such as response to toxic substance, response to oxidative stress, extracellular structure organization, extracellular matrix organization. Two modules significantly correlated with asthma severity were screened out (red module, P=7e-6, r=0.43; pink module, P=5e-8, r=-0.51), and finally six hub genes were obtained, including B3GNT6, CEACAM5, CCK, ERBB2, CSH1 and DPPA5. The comparison of gene expression levels and ROC curve analysis of datasets GSE43696 and GSE63142 further verified the six hub genes, which may associated with o-glycan biosynthesis, alpha linolenic acid metabolism, linoleic acid metabolism, pentose and glucoronate interconversions. In conclusion, through a variety of bioinformatics analysis methods, this study identified six hub genes significantly related to the severity of asthma, which potentially provided a new direction for the prediction and targeted therapy of asthma.

[Progress in the pharmacological treatment of tobacco dependence in special populations].

Schizophrenic and pregnant smokers with tobacco dependence had always been excluded from most large treatment trials for nicotine dependence. As weight gain was found to be common after smoking cessation, obese people were more likely to have a reduced willingness to quit smoking and an increased risk of relapse. This article reviewed the latest research progress in pharmacological treatment of tobacco dependence in schizophrenia, pregnant women, and obese people.

Genetically elevated bioavailable testosterone level was associated with the occurrence of benign prostatic hyperplasia.

BACKGROUND: Recent studies identified several risk factors of benign prostatic hyperplasia (BPH), including dyslipidemia, type 2 diabetes mellitus, hypertension, and obesity. But they were not so reliable and some studies contradicted with one another. Hence, a reliable method is urgently needed to explore exact factors that facilitated BPH development. METHODS: The study was based on Mendelian randomization (MR) design. All participants were from the most recent genome-wide association studies (GWAS) with large sample size. The causal associations between nine phenotypes (total testosterone level, bioavailable testosterone level, sex hormone-binding globulin, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, type 2 diabetes mellitus, hyper-tension, and body mass index) and BPH outcome were estimated. Two sample MR, bidirectional MR, and multivariate MR (MVMR) were performed. RESULTS: Increase in bioavailable testosterone level was able to induce BPH based on nearly all combination methods [beta (95% confidence interval (CI)): 0.20 (0.06-0.34) for inverse variance weighted (IVW)]. The other traits seemed to interact with testosterone level and did not cause BPH generally. Higher triglycerides level was likely to raise bioavailable testosterone level [beta (95% CI): 0.04 (0.01-0.06) for IVW]. In MVMR model, bioavailable testosterone level was still associated with BPH occurrence [beta (95% CI) 0.27 (0.03-0.50) for IVW]. CONCLUSIONS: We for the first time validated the central role of bioavailable testosterone level in the pathogenesis of BPH. The complex associations between other traits and BPH should be further investigated.

[Extraocular silicone oil migration to orbit: a case report].

Silicone oil insertion is a common modality in vitreoretinal surgeries after ocular perforating injury. It needs surgical removal after several months. Extraocular silicone oil migration to orbit and eyelid is uncommon complication. We reports a case of silicone oil migration to orbit and eyelid. A 41-year-old male presented with left upper eyelid swelling following silicone oil injection 3 years before admission. Orbital computed tomography scan showed multiple high-density well-defined masses in vitreous, left upper eyelid and orbit. We diagnosed the patient with orbital and eyelid mass, meanwhile, speculated mechanical ptosis. Excision of orbital and eyelid masses were performed. Cystic spaces with delicate fibrous wall and small vessels, and clear fluid in cyst were discovered on histologic examination. The patient was followed up after 1 week. The left upper eyelid slightly depressed and the mechanical ptosis was significantly improved.

[m6A methylase WTAP participates in renal ischemia-reperfusion injury by regulating FOXO1 expression].

OBJECTIVE: To investigate the expression of WTAP, a m6A methylase, in a mouse model of renal ischemia-reperfusion (I/R) injury and the effect of WTAP knockdown on biological behavior of renal tubular epithelial cells exposed to I/R injury. METHODS: Sixteen C57BL/6 mice with renal I/R injury or sham operation (n=8) were examined for blood urea nitrogen (BUN) and creatinine (Scr) levels to assess renal function, and renal pathologies were observed with HE staining. The expressions of WTAP and FOXO1 proteins in the kidneys of the mice were detected using immunohistochemistry. Human renal tubular epithelial cells (HK-2) were transfected with si-WTAP or si-NC followed by hypoxia-reoxygenation (H/R) exposure, Protein and mRNA expression were assessed by Western blot and qRT-PCR, and changes and changes in cell viability and apoptosis were assessed using CCK8 assay and TUNEL staining, respectively; LDH release level and caspase-3 activity of the cells were measured using commercial assay kits. FOXO1 m6A modification sites were predicted using SRAMP website (http://www.cuilab.cn/sramp/), and the interaction between WTAP and FOXO1 mRNA was analyzed with RIP experiment; the level of FOXO1 modified by m6A was detected by MeRIP-qPCR. RESULTS: Compared with sham-operated mice, the mice with renal I/R injury showed significantly increased Scr and BUN levels (P < 0.001) and renal expressions of WTAP mRNA and protein (P < 0.001). In cultured HK-2 cells, H/R exposure significantly decreased the cell viability (P < 0.001) and increased cellular LDH release (P < 0.001) and expressions of WTAP mRNA and protein (P < 0.001). WTAP knockdown obviously reduced the cell damage induced by I/R injury and significantly decreased the mRNA and protein levels of FOXO1 in the cells (P < 0.001). RIP experiment confirmed WTAP binding to FOXO1 mRNA, and inhibition of WTAP expression significantly reduced FOXO1 m6A level in HK-2 cells (P < 0.001). CONCLUSION: WTAP expression is up-regulated in the kidneys of mice with renal I/R injury and in HK-2 cells with H/R exposure. Inhibition of WTAP alleviates H/R-induced apoptotic damage in HK-2 cells possibly by inhibiting FOXO1 expression.

Chemical and mechanical activation of resident cardiac macrophages in the living myocardial slice ex vivo model.

Resident cardiac macrophages (rcMACs) are among the most abundant immune cells in the heart. Plasticity and activation are hallmarks of rcMACs in response to changes in the microenvironment, which is essential for in vitro experimentation. The in vivo investigation is confounded by the infiltration of other cells hindering direct studies of rcMACs. As a tool to investigate rcMACs, we applied the ex vivo model of living myocardial slices (LMS). LMS are ultrathin ex vivo multicellular cardiac preparations in which the circulatory network is interrupted. The absence of infiltration in this model enables the investigation of the rcMACs response to immunomodulatory and mechanical stimulations. Such conditions were generated by applying interferon-gamma (IFN-γ) or interleukine-4 (IL-4) and altering the preload of cultured LMS, respectively. The immunomodulatory stimulation of the LMS induced alterations of the gene expression pattern without affecting tissue contractility. Following 24 h culture, low input RNA sequencing of rcMACs isolated from LMS was used for gene ontology analysis. Reducing the tissue stretch (unloading) of LMS altered the gene ontology clusters of isolated rcMACs with intermediate semantic similarity to IFN-γ triggered reaction. Through the overlap of genes affected by IFN-γ and unloading, we identified Allograft inflammatory factor 1 (AIF-1) as a potential marker gene for inflammation of rcMACs as significantly altered in whole immunomodulated LMS. MicroRNAs associated with the transcriptomic changes of rcMACs in unloaded LMS were identified in silico. Here, we demonstrate the approach of LMS to understand load-triggered cardiac inflammation and, thus, identify potential translationally important therapeutic targets.

Synergistic effects of a functional bacterial consortium on enhancing phenanthrene biodegradation and counteracting rare earth biotoxicity in liquid and slurry systems.

The biodegradation of polycyclic aromatic hydrocarbons (PAHs) by micro-organisms in the environment is often inhibited by coexisting metal ions. The aim of this work is to study a bacterial consortium for enhancing phenanthrene biodegradation under the inhibition effect of the rare earth (RE) ions Ce3+ and Y3+ . This bacterial consortium was composed of two bacteria, namely, the RE-adsorbing Bacillus subtilis MSP117 and the phenanthrene-degrading Moraxella osloensis CFP312. Ce3+ and Y3+ at the concentration of 1·15 mmol l-1 inhibited CFP312 from degrading phenanthrene but not glucose. Using glucose as a co-substrate could promote the proliferation of CFP312 but decreased phenanthrene degradation. Adsorption experiments and electron microscopy imaging showed that CFP312 had no RE ions adsorption capacity for RE ions and that RE elements could not be observed on its cell surfaces. MSP117 could adsorb 0·14 and 0·12 mmol g-1 wet cells of Ce3+ and Y3+ in aqueous solution, respectively, thus demonstrating considerable adsorption capacity. The MSP117 cell surface immobilized part of the free RE ions and reduced their bioaccessibility, thereby alleviating their biotoxic effect on phenanthrene degradation by CFP312. In liquid and slurry systems, glucose, which was used as the co-substrate of the bacterial consortium, must be kept at a low level to avoid the catabolism repression of phenanthrene degradation by CFP312.

[Analysis of the clinical characteristics and risk factors of postoperative atrial fibrillation in patients with critical burns].

Objective: To investigate the clinical characteristics and risk factors of postoperative atrial fibrillation (POAF) in patients with critical burns. Methods: A retrospective case series study was conducted. From January 2017 to December 2021, two hundred and twenty-seven critically burned aldult patients who met the inclusion criteria were admitted to Guangzhou Red Cross Hospital of Jinan University, including 173 males and 54 females, aged 19-83 (43±14) years. The admission years of patients were collected, and the percentage of patients complicated with POAF in each year was calculated. According to whether the patients were complicated with POAF or not, they were divided into POAF group (n=17) and non-POAF group (n=210). Following data were collected in patients in POAF group, including operation methods, duration of operation, intraoperative blood loss before occurrence of POAF each time, occurrence time and times of POAF, postoperative body temperature, blood pressure, hemoglobin, blood glucose, blood lactate, sepsis, and electrolyte, and type, duration, and treatment of POAF. General data of patients in the two groups including age, gender, burn reason, total burn area, full-thickness burn area, acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) and sepsis-related organ failure evaluation (SOFA) scores on admission, combined with underlying diseases (hypertension, diabetes, and other types of arrhythmias), and sepsis were collected and analyzed. The mortality and factors influencing the prognosis of patients in the two groups such as mechanical ventilation time, operations times, and burn intensive care unit (BICU) length of stay were also collected and analyzed. Data were statistically analyzed with independent sample t test, Mann-Whitney U test, chi-square test or Kruskal-Wallis H test. The multivariate logistic regression analysis was performed on the general data with statistically significant differences between the two groups, and the independent risk factors influencing the onset of POAF in 227 patients with critical burns were screened. Results: From 2017 to 2021, the percentage of critically burned patients complicated with POAF increased year by year. In POAF group, eschar debridement in limbs was the main surgical procedure prior to POAF complication, with the operation time of (3.5±1.2) h and the intraoperative blood loss volume of (365±148) mL.The POAF occurred 25 times in total in patients of POAF group, mostly within one week after the injury and within 6 hours after the operation with most of these patients having POAF only once. When POAF happened, the patients were often complicated with hypothermia, anemia, hyperglycemia, high blood lactate, sepsis, and electrolyte disturbance, and few patients had complications of hypotension. The POAF lasted (5±3) h, with all being paroxysmal atrial fibrillation, and most of POAF patients were reverted to sinus rhythm after amiodarone intervention. Most patients in the two groups suffered from flame burn, and the gender, age, and SOFA score on admission of patients in the two groups were similar (P>0.05); the APACHEⅡ score on admission, total burn area, full-thickness burn area, incidence proportion of sepsis, combined with diabetes and hypertension and other types of arrhythmias of patients in POAF group were significantly higher or larger than those in non-POAF group (t=3.47, with χ2 values of 7.44, 10.86, 12.63, 14.65, 6.49, and 7.52, respectively, P<0.05 or P<0.01). The full-thickness burn area, combined with other types of arrhythmias, and sepsis were the independent risk factors for POAF in 227 critically burned patients (with odds ratios of 4.45, 0.04, and 3.06, respectively, with 95% confidence intervals of 2.23-8.87, 0.01-0.22, and 1.77-5.30, respectively, P<0.01). Compared with those in non-POAF group, the mechanical ventilation time, BICU length of stay, number of operations, and mortality rate of patients in POAF group were significantly increased (Z=3.89, Z=2.57, t=3.41, χ2=3.72, P<0.05 or P<0.01). Conclusions: POAF is a common postoperative complication in critically burned patients, and the incidence is increasing year by year, which seriously affects the prognosis of patients. The full-thickness burn area together with other types of arrhythmias and sepsis are the high-risk factors for POAF complication in patients with critical burns.

[Prevention and treatment of mucocutaneous adverse reactions associated with epidermal growth factor receptor inhibitors].

The epidermal growth factor receptor (EGFR) signaling is aberrantly overexpressed in many solid malignancies, making it an important target for anti-cancer biologic agents. Among them, epidermal growth factor receptor inhibitors (EGFRIs), which have been widely used in clinical practice, include anti-EGFR monoclonal antibodies and tyrosine kinase inhibitors. A proportion of patients treated with EGFRIs develop specific, dose-dependent skin toxicity such as papulopustular rash, paronychia, xerosis and itch. These side effects can cause physical and psychosocial discomfort that may result in dose reduction, discontinuance, or replacement of the current EGFRIs treatment. Correct diagnosis and treatment of these skin and mucosal adverse effects associated with EGFRIs is of great significance for the tertiary prevention of malignant tumors. A review on EGFRI-related mucocutaneous adverse reactions is presented here, focusing on the pathogenesis, the various clinical manifestations, the strategies for prevention and treatment of these conditions.

Alpha defensin-1 attenuates surgically induced osteoarthritis in association with promoting M1 to M2 macrophage polarization.

OBJECTIVE: Macrophages play an important part in the pathogenesis of osteoarthritis (OA). Our objective was to determine the effects of α-defensin-1 on macrophage polarization and consequently OA. METHODS: OA synovial tissue and synovial fluid were assessed for the presence of M1 (CD68+CD16+CD206-) and M2 (CD68+CD206+CD16-) macrophages by flow cytometry. M0, M1, and M2 macrophages were co-cultured with OA chondrocytes to determine their influence on chondrogenic phenotype. Polarization of THP-1 activated monocytes from M1 to M2 in response to α-defensin-1 was evaluated by flow cytometry, RT-PCR and RNA sequencing. Effects of intra-articular α-defensin-1 in vivo were evaluated in a rat meniscal/ligamentous injury (MLI) model. RESULTS: The quantity of M1 exceeded M2 polarized macrophages in human OA synovial tissue (mean difference 26.1% [13.6-38.6%], P < 0.001) and fluid (mean difference 10.5% [5.0-16.1%], P = 0.003). M1 to M2 polarization in vitro was most effectively promoted with 10 ng/mL α-defensin-1. Compared with untreated macrophages, the α-defensin-1 polarized macrophages modified co-cultured OA chondrocytes from a pro-catabolic state to a pro-anabolic (regenerative-like) state based on expression of COL2A1, ACN, MMP3, MMP13 and ADAMTS5. Intra-articular α-defensin-1 decreased severity of cartilage damage and synovitis in the MLI rat model. RNAseq analyses suggested insulin and Toll-like receptor signaling pathways in the chondroprotective α-defensin-1 mechanism of action. CONCLUSION: α-defensin-1 promotes M1 to M2 macrophage polarization in vitro, has beneficial effects on chondrocytes indirectly via M2 macrophage polarization, and attenuates the severity of OA in vivo, suggesting it might be a candidate treatment for OA.

A machine learning model for predicting the ballistic impact resistance of unidirectional fiber-reinforced composite plate.

It has been a vital issue to ensure both the accuracy and efficiency of computational models for analyzing the ballistic impact response of fiber-reinforced composite plates (FRCP). In this paper, a machine learning (ML) model is established in an effort to bridge the ballistic impact protective performance and the characteristics of microstructure for unidirectional FRCP (UD-FRCP), where the microstructure of the UD-FRCP is characterized by the two-point correlation function. The results showed that the ML model, after trained by 175 cases, could reasonably predict the ballistic impact energy absorption of the UD-FRCP with a maximum error of 13%, indicating that the model can ensure both computational accuracy and efficiency. Besides, the model's critical parameter sensitivities are investigated, and three typical ML algorithms are analyzed, showing that the gradient boosting regression algorithm has the highest accuracy among these algorithms for the ballistic impact problem of UD-FRCP. The study proposes an effective solution for the traditional difficulty of the ballistic impact simulation of composites with both high efficiency and accuracy.

[Efficiency analysis on functional protection of nerve plane-oriented laparoscopic total mesorectal excision].

Objective: Using previous total mesorectal excision with pelvic autonomic nerve preservation (PANP+TME) and simple total mesorectal excision (TME) without emphasis on retained nerves as control, we explore the advantages of nerve plane-oriented laparoscopic total mesorectal excision (NPO+LTME) on urinary and sexual function. Methods: A retrospective cohort study was carried out. Case inclusion criteria: (1) male patients with pathologically confirmed middle and low rectal adenocarcinoma (4 to 11 cm from the anus); (2) stage T1-2tumor; (3) normal sexual life before operation. Exclusion criteria: (1) no pathological diagnosis before surgery; (2) local recurrence or distant metastasis; (3) preoperative neoadjuvant chemoradiotherapy; (4) opensurgery and laparoscopic surgery conversionto open; (5) no follow-up data. According to the above criteria, clinical data of 173 male patients with low and middle rectal adenocarcinoma who underwent radical operation for laparoscopic rectal cancer from July 2003 to July 2018 at the Department of Gastrointestinal Surgery, Wuhan University People's Hospital were collected. According to different surgical methods, patients were divided into TME group (58 cases), PANP+TME group (63 cases) and NPO+LTME group (52 cases). There were no significant differences in the baseline data including age, body mass index and pathological examination between the 3 groups (all P>0.05). The nerve plane referred to the nerve, the adipose tissue, the extremely finecapillaries around the nerve with overlying fine membranous tissue. NPO+LTME referred to the process of laparoscopic TME guided by the nerve plane, performing in the loose connective tissue between the nerve plane and the rectal properfascia, in order to ensure the integrity of the nerve plane, and maximally protect the patient's urinary and reproductive functions. The operation time, intraoperative blood loss, urinary catheter removal time, urinary function grading, postoperative first erection time, and erectile function and ejaculation function were observed and compared among the 3 groups at 3- and 6-month after operation. Results: In the NPO+LTME group, the PANP+TME group and the TME group, the operation time was (181.9±24.5) minutes, (176.7±29.2) minutes and (137.7±16.2) minutes, respectively (F=54.868, P<0.001); the intraoperative blood lost was (6.0±1.4) ml, (6.5±1.8) ml and (12.8±4.6) ml, respectively (F=95.016, P<0.001); the time to postoperative removal of the catheter was (2.4±1.1) days, (3.7 ±1.7) days and (6.5±2.4) days, respectively (F=79.409, P<0.001); the first postoperative erection time was (1.6±0.6) days, (8.9±2.7) days and (15.9±6.8) days (F=177.677, P<0.001), respectively, whose differences were all statistically significant (all P<0.01). In comparison of urinary function grading, the proportion of grade I (normal function, no urinary dysfunction) in the NPO+LTME, the ANP+TME group and the TME group was 84.1% (53/63), 39.7% (23/58) and 19.2% (10/52), respectively, and the difference was statistically significant (H=52.915, P<0.001). At postoperative 3- and 6-month, proportion of patients with grade I erectile function (normal erectile function) was 77.8% (49/63) and 85.7% (54/63), 44.8% (26/58) and 53.4% (31/58), 28.8% (15/52) and 48.1% (25/52) in the NPO+LTME group, the PANP+TME group, and the TME group, respectively. The differences were statistically significant (H=91.709, P<0.001; H=79.692, P<0.001). The proportion of patients with grade I ejaculation function (with ejaculation, no abnormalities in routine semen examination before and after surgery) at 3- and 6-month after surgery in the NPO+LTME group, the PANP+TME group and the TME group was 82.5% (52/63) and 87.3% (55/63), 53.4% (31/58) and 60.3% (35/58), 28.8% (15/52) and 46.1% (24/52), respectively. The differences were statistically significant as well (H=86.543, P<0.001; H=78.667, P<0.001). Patients in the NPO+LTME group had no grade III erections and ejaculation disorders. Conclusion: The surgical procedure of NPO+LTME can promote the recovery of postoperative neurological function and preserve urination and sexual function better.

[Association between polymorphisms of interleukin-17 genes and pneumoconiosis susceptibility].

Objective: To explore the relationship between polymorphisms of interleukin 17(IL-17) gene (rs4711998, rs763780) and the susceptibility of pneumoconiosis, and to provide a basis for prevention of high-risk groups of pneumoconiosis. Methods: A total of 219 pneumoconiosis patients and 242 workers without pneumoconiosis were enrolled in the study. All subjects were photographed with high undulating X-rays anterior chest radiographs, diagnosed according to diagnostic criteria for pneumoconiosis. We collected 3 ml of peripheral venous blood of the study subjects. Polymorphism in IL-17A rs4711998 and IL-17F rs763780 locus were evaluated by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: The IL-17A rs4711998 locus has AA, AG and GG genotypes, there was no the significant difference between case and control groups (P>0.05). IL-17F rs763780 had AA, AG and GG genotypes, there was a significant difference between case and control groups (P<0.05). Allele A and allele G were statistically significant difference between the case group and the control group (P<0.05). Conclusion: No relationship was found between IL-17A gene polymorphisms at rs4711998 and silicosis. IL-17F rs763780 locus gene polymorphism is associated with susceptibility to pneumoconiosis. AG genotype and G allele may have a protective effect.