Causal linkage between angiotensin-converting enzyme 2 and risk of lung cancer: a bidirectional two-sample Mendelian randomization study.

Background: Observational studies suggest a connection between ACE2 (angiotensin-converting enzyme 2) and lung cancer. However, it's not apparent if confounding variables are interfering with the link. Therefore, we aimed to define the relationships between ACE2 and the risk of lung cancer. Methods: With the aim of developing genetic tools, we selected SNPs substantially associated with ACE2 using a statistically significant criterion. The relevant SNPs were then taken from the lung cancer GWAS dataset for additional research. After that, we used two-sample Mendelian randomization (MR) to ascertain if ACE2 is causally linked to the risk of developing lung cancer. To investigate the causal links' directions, we also performed a reverse MR analysis. Results: According to our findings, there is strong evidence that ACE2 is linked to a decreased chance of developing lung cancer (odds ratio: 0.94; 95% confidence interval: 0.90-0.98; P = 0.0016). The IVW method, the major MR analysis, was not impacted by heterogeneity in any of the analyses, according to Cochrane's Q test ( P Cochran e ' sQ = 0.207). The MR-Egger intercept (P intercept = 0.622) showed no indication of horizontal pleiotropy in any of the investigations. Outlier SNPs were not detected by the MR-PRESSO global test (P globaltest = 0.191). The leave-one-out analysis was performed, and the results showed a steady outcome. Nonsignificant causal estimates between lung cancer and ACE2 were produced by reverse MR analysis. Conclusion: MR investigation revealed a significant causal link between ACE2 and the risk of getting lung cancer. These findings may have implications for public health measures aimed at reducing the incidence of lung cancer.

Prognostic impact of age in advanced non-small cell lung cancer patients undergoing first-line checkpoint inhibitor immunotherapy and chemotherapy treatment.

BACKGROUND: Research on the association between age and clinical outcome in patients with non-small cell lung cancer (NSCLC) treated with immunotherapy combined with chemotherapy as first-line setting is limited. The aim of study is to determine the influence of age on the progress-free survival (PFS) and overall survival (OS) in those patients after adjusting for potential confounders. METHODS: A total of 207 advanced NSCLC patients treated with immunotherapy combined with chemotherapy in the first-line treatment in Guangxi Medical University Cancer Hospital from March 10, 2019, to December 31, 2022, was retrospectively analyzed. χ2 (categorical variables) was used to analyze the differences among the different age groups. Cox regression and Kaplan-Meier analyses were used to assess the association between age and clinical outcomes. P values < 0.05 (two-sided) were considered statistically significant. RESULTS: The mean age of the cohort was 58.8 ± 10.3 years. The percentages of patients < 65, 65-69, 70-74, and ≥ 75 years were 66.7 %, 19.3 %, 9.2 % and 4.8 %, respectively. Compared to the aged < 65 years group, the HR for the risk of disease progression for each group are 0.67 (95 %CI = 0.40-1.12, P = 0.125), 0.66 (95 %CI = 0.31, 1.43, P = 0.298), and 2.27 (95 %CI = 0.80, 6.45, P = 0.124), respectively, with no significant differences in the results. And the HR for risk of death for the 65-69 years and 70-74 years groups was 1.16 (95 %CI = 0.64-2.08, P = 0.628) and 0.93 (95 %CI = 0.39-2.23, P = 0.879), respectively. The difference has no statistical significance. Whereas in patients aged ≥ 75, there is an increased risk of death after adjusted confounders with HR = 4.83 (95 %CI = 2.06-11.35). The difference was statistically significant (P < 0.001). Trend test indicates that with advancing age, the patient's risk of death increases (HR = 1.33, 95 % CI = 1.02-1.75, P = 0.034). CONCLUSION: Age may not be the primary factor influencing the efficacy of immunotherapy combined with chemotherapy, but particular attention should be given to the elderly population.

Er-doped silicate fiber amplifiers in the L-band with flat gain.

We demonstrated an efficient way to enhance and flatten the emission cross sections of Er3+ ions at the L-band in the silicate fiber amplifier by increasing Mg2+ (up to 22.5 mol%) with high field strength. High values of Er3+ concentration, lifetime, and L-band emission cross section were achieved in our silicate fibers. Particularly, the flatness at the L-band was achieved to be 0.8 dB, and a high gain coefficient at 1625 nm (4.7 dB/m) was demonstrated by pumping meter-scale Er-silicate fibers. The as-prepared Er-silicate fibers are attractive for the L-band fiber amplifier.

Single-cell RNA-seq of in vitro expanded cells from cranial neural crest reveals a rare odontogenic sub-population.

Ecto-mesenchymal cells of mammalian tooth germ develops from cranial neural crest cells. These cells are recognised as a promising source for tooth development and regeneration. Despite the high heterogeneity of the neural crest, the cellular landscape of in vitro cultured cranial neural crest cells (CNCCs) for odontogenesis remains unclear. In this study, we used large-scale single-cell RNA sequencing to analyse the cellular landscape of in vitro cultured mouse CNCCs for odontogenesis. We revealed distinct cell trajectories from primary cells to passage 5 and identified a rare Alx3+/Barx1+ sub-population in primary CNCCs that differentiated into two odontogenic clusters characterised by the up-regulation of Pax9/Bmp3 and Lhx6/Dmp1. We successfully induced whole tooth-like structures containing enamel, dentin, and pulp under the mouse renal capsule using in vitro cultured cells from both cranial and trunk neural crests with induction rates of 26.7% and 22.1%, respectively. Importantly, we confirmed only cells sorted from odontogenic path can induce tooth-like structures. Cell cycle and DNA replication genes were concomitantly upregulated in the cultured NCCs of the tooth induction groups. Our data provide valuable insights into the cell heterogeneity of in vitro cultured CNCCs and their potential as a source for tooth regeneration.

GWAS and Meta-QTL Analysis of Yield-Related Ear Traits in Maize.

Maize ear traits are an important component of yield, and the genetic basis of ear traits facilitates further yield improvement. In this study, a panel of 580 maize inbred lines were used as the study material, eight ear-related traits were measured through three years of planting, and whole genome sequencing was performed using the maize 40 K breeding chip based on genotyping by targeted sequencing (GBTS) technology. Five models were used to conduct a genome-wide association study (GWAS) on best linear unbiased estimate (BLUE) of ear traits to find the best model. The FarmCPU (Fixed and random model Circulating Probability Unification) model was the best model for this study; a total of 104 significant single nucleotide polymorphisms (SNPs) were detected, and 10 co-location SNPs were detected simultaneously in more than two environments. Through gene function annotation and prediction, a total of nine genes were identified as potentially associated with ear traits. Moreover, a total of 760 quantitative trait loci (QTL) associated with yield-related traits reported in 37 different articles were collected. Using the collected 760 QTL for meta-QTL analysis, a total of 41 MQTL (meta-QTL) associated with yield-related traits were identified, and 19 MQTL detected yield-related ear trait functional genes and candidate genes that have been reported in maize. Five significant SNPs detected by GWAS were located within these MQTL intervals, and another three significant SNPs were close to MQTL (less than 1 Mb). The results provide a theoretical reference for the analysis of the genetic basis of ear-related traits and the improvement of maize yield.

Insights into accumulation of active ingredients and rhizosphere microorganisms between Salvia miltiorrhiza and S. castanea.

Salvia miltiorrhiza is an important traditional herbal medicine, and its extracts could be used for treating cardiovascular disease. Although these medicinal compounds are functionally similar, their wild relative, S. castanea, produces significantly different concentrations of these compounds. The reason for their differences is still unknown. In a series of soil and plant-based analyses, we explored and compared the rhizosphere microbiome of S. miltiorrhiza and S. castanea. To further investigate the geographical distribution of S. castanea, MaxEnt models were used to predict the future suitable habitat areas of S. castanea in China. Results revealed the distributions and structure of the rhizosphere microbial community of S. miltiorrhiza and S. castanea at different times. In addition, differences in altitude and soil moisture resulting from changes in climate and geographical location are also critical environmental factors in the distribution of S. castanea. The findings of this study increase our understanding of plant adaptation to their geographical environment through secondary metabolites. It also highlights the complex interplay between rhizospheric factors and plant metabolism, which provides the theoretical basis for the cultivation of S. miltiorrhiza and the use of S. castanea resources.

The benefit and risk of PD-1/PD-L1 inhibitors plus anti-angiogenic agents as second or later-line treatment for patients with advanced non-small-cell lung cancer: a systematic review and single-arm meta-analysis of prospective clinical trials.

Background: Previous studies revealed that Programmed cell death protein 1 (PD-1)/Programmed cell death-Ligand protein 1 (PD-L1) inhibitors plus anti-angiogenic agents had extensive anti-tumor activities. However, almost all studies on the efficacy and safety of PD-1/PD-L1 inhibitors plus anti-angiogenic agents as second or later-line treatment for patients with advanced non-small cell lung cancer are non-randomized controlled trials with small sample sizes, which might lead to a lack of effective metrics to assess the effectiveness and safety of the therapeutic regimen. Here, this meta-analysis aimed to evaluate the efficacy and safety of PD-1/PD-L1 inhibitors plus anti-angiogenic agents as second or later-line treatment for patients with advanced non-small cell lung cancer. Methods: A single-arm meta-analysis was performed, and published literature from PubMed, Web of Science and Embase databases as of January 13, 2023, was systematically retrieved. We used the Cochrane risk of bias tool and methodological index for non-randomized studies (MINORS) Methodological items to evaluate the quality of eligible clinical trials. Outcomes including overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were extracted for further analysis. The random effect model is used to calculate the pooled parameters. Results: 19 studies (16 were non-comparative single-arm clinical trials and 3 were randomized controlled trials) were enrolled in this meta-analysis. In terms of tumor response, the pooled ORR and DCR were 22.4% (95% CI, 16.6-28.1%) and 76.8% (95% CI, 72.6-81.1%), respectively. With regard to survival analysis, the pooled PFS and OS were 5.20 (95% CI, 4.46-5.93) months and 14.09 (95% CI, 13.20-14.97) months, respectively. The pooled grade ≥3 adverse effect (AE) rate was 47.6% (95% CI, 33.1-62.0%). Conclusion: PD-1/PD-L1 inhibitors plus anti-angiogenic agents has promising efficacy and safety as second or later-line treatment in patients with advanced non-small cell lung cancer. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023407559.

Rechallenge with EGFR-TKI after failure of immunotherapy is considered an effective treatment for advanced lung adenocarcinoma patients with EGFR exon 19 deletion: a case report.

In advanced lung adenocarcinoma patients with epidermal growth factor receptor (EGFR) mutation, epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have an excellent and long-lasting therapeutic response; however, virtually all patients eventually develop drug resistance and experience disease progression. The use of immunotherapy after EGFR-TKIs may be a successful therapeutic option for individuals who are resistant to them. It is still unclear if EGFR-TKIs can be administered again after immunotherapy has failed. We describe a case of a 37-year-old woman who was found to have T4N3M1a stage IVa lung adenocarcinoma. Amplification refractory mutation system PCR (ARMS-PCR) genetic testing suggested EGFR exon 19 deletion. The patient was initially treated with a regimen of icotinib (125 mg tid) combined with anlotinib (8 mg qd d1-d14) with an optimal efficacy rating of partial response (PR) and was granted a PFS of 7 months. In second-line treatment, the patient received three cycles of a KN046 (KN046 is a bispecific antibody inhibitor of PD-L1 and CTLA-4) 295 mg d1, pemetrexed 800 mg d1, plus carboplatin 750 mg d1 regimen, with an optimal efficacy rating of stable disease (SD) on CT. The third-line therapy was chosen to be afatinib with docetaxel, and the patient was evaluated for PR on CT. Up to 15 August 2022, the patient had a progression free survival (PFS) of 14 months. The successful treatment of this patient is a reminder that EGFR-TKI rechallenge in EGFR exon 19 deletion patients with EGFR-TKI resistance, in which immunotherapy has failed, may be effective.

Ceruminous adenoma of the external auditory canal: 9 cases series with imaging and pathologic findings.

Objectives: Ceruminous adenoma is a rare benign tumor of the external auditory canal. This study aimed to present the clinical characteristics, imaging findings, pathological results and the management outcomes of the ceruminous adenoma. Study design: Retrospective case series review. Setting: Tertiary referral center. Patients and methods: Patients undergoing surgery for ceruminous adenoma of the external auditory canal between the years 2004 to 2018. All patients with ceruminous adenoma were analyzed for demographic, clinical, radiological features and pathologic findings. The outcomes of the management were also evaluated. Results: Nine patients with ceruminous adenoma were included in the study. Hearing loss was the most common complaint (5/9, 56%), followed by otalgia (4/9, 44%), pruritus (4/9, 44%), and otorrhea (2/9, 22%). The tumors originated mostly from the cartilaginous portion of the external auditory canal (8/9, 89%) and merely from the bony portion of the external auditory canal (1/9, 11%). Pathohistological study indicated that the ceruminous adenomas were divided into three types: the ceruminous gland adenoma (6/9, 67%), the ceruminous pleomorphic adenoma (2/9, 22%) and the ceruminous syringocystadenoma papilliferum (1/9, 11%). No recurrence was found during follow-up for two to fifteen years after surgical resection. Conclusion: Ceruminous adenomas are rare entities. They originate mainly from the cartilaginous portion of the EAC, but occasionally from the bony portion of the EAC. The surgical section with enough margin is adequate for management of these tumors.

Extending laser wavelengths to 1630†nm in centimeter-scale Er-phosphate fiber.

The spectral bandwidth of Er-doped fibers limits their lasing wavelength at longer wave band. Here, to the best of our knowledge, we report a broad emission band (1420‒1680 nm) of Er3+ and demonstrate for the first time an Er-phosphate fiber, which supports laser oscillation at the extended wavelengths of 1627 nm and 1630 nm, with the output powers and slope efficiencies of 44 mW/12.5% and 16.5 mW/5.6%, respectively, pumped at 1480 nm. To the best of our knowledge, these are the highest output powers and slope efficiencies at 1627 nm and 1630 nm from an Er3+-doped all-fiber configuration.

Single cell atlas of developing mouse dental germs reveals populations of CD24+ and Plac8+ odontogenic cells.

The spatiotemporal relationships in high-resolution during odontogenesis remain poorly understood. We report a cell lineage and atlas of developing mouse teeth. We performed a large-scale (92,688 cells) single cell RNA sequencing, tracing the cell trajectories during odontogenesis from embryonic days 10.5 to 16.5. Combined with an assay for transposase-accessible chromatin with high-throughput sequencing, our results suggest that mesenchymal cells show the specific transcriptome profiles to distinguish the tooth types. Subsequently, we identified key gene regulatory networks in teeth and bone formation and uncovered spatiotemporal patterns of odontogenic mesenchymal cells. CD24+ and Plac8+ cells from the mesenchyme at the bell stage were distributed in the upper half and preodontoblast layer of the dental papilla, respectively, which could individually induce nonodontogenic epithelia to form tooth-like structures. Specifically, the Plac8+ tissue we discovered is the smallest piece with the most homogenous cells that could induce tooth regeneration to date. Our work reveals previously unknown heterogeneity and spatiotemporal patterns of tooth germs that may lead to tooth regeneration for regenerative dentistry.

PD-1/PD-L1 inhibitors plus anti-angiogenic agents with or without chemotherapy versus PD-1/PD-L1 inhibitors plus chemotherapy as second or later-line treatment for patients with advanced non-small cell lung cancer: A real-world retrospective cohort study.

Background: The aim of this study was to assessment the efficacy and safety of Programmed cell death protein 1 (PD-1)/Programmed cell death-Ligand protein 1 (PD-L1) inhibitors plus anti-angiogenic agents with or without chemotherapy versus PD-1/PD-L1 inhibitors plus chemotherapy as second or later-line treatment for patients with advanced non-small cell lung cancer. Methods: In this study, pre-treatment clinical and laboratory indicators from 73 patients with advanced non-small cell lung cancer were retrieved for retrospective analysis. According to the therapy regimes they received, the patients were separated into groups, PD-1/PD-L1 inhibitors plus chemotherapy group (PC group), PD-1/PD-L1 inhibitors plus anti-angiogenic agents' group (PA group), PD-1/PD-L1 inhibitors plus anti-angiogenic agents plus chemotherapy group (PAC group). Cox's proportional hazards regression model and Kaplan-Meier (KM) curves were used to assess the connection between treatment regimens and progression free survival (PFS) and overall survival (OS). In addition, the association of treatment regimens with the risk of disease progression and death was evaluated by subgroup analysis. Results: The average age of the enrolled patients was 58.2 ± 10.2 years and 75.3% were male. Multivariate analyses showed that patients in PA group (Disease progression: HR 0.4, P=0.005. Death: HR 0.4, P=0.024) and PAC group (Disease progression: HR 0.3, P=0.012. Death: HR 0.3, P=0.045) had a statistically significant lower hazard ratio (HR) for disease progression and death compared to patients in PC group. Kaplan-Meier analysis showed that patients in PA group (mPFS:7.5 vs.3.5, P=0.00052. mOS:33.1 vs.21.8, P=0.093) and PAC group (mPFS:5.1 vs.3.5, P=0.075. mOS:37.3 vs.21.8, P=0.14) had a longer PFS and OS compared to patients in PC group. In all the pre-defined subgroups, patients in PA and PAC groups showed a decreasing trend in the risk of disease progression and death in most subgroups. The patients in PA group (DCR:96.3% vs.58.3%, P=0.001) and PAC group (DCR:100% vs.58.3%, P=0.019) had a better disease control rate (DCR) than patients in PC group. Conclusion: PD-1/PD-L1 inhibitors plus anti-angiogenic agents with or without chemotherapy were superior to PD-1/PD-L1 inhibitors plus chemotherapy as second or later-line treatment in patients with advanced non-small cell lung cancer.

Influence of Mixed Na2O/K2O on Chemical Durability and Spectral Properties of P2O5-Al2O3-BaO-K2O-Na2O-Nd2O3 Phosphate Glasses.

A series of 56P2O5-7.5Al2O3-5.9BaO-(28.56-x)K2O-xNa2O-1.51Nd2O3 phosphate glasses with different Na/(Na+K) ratios, which were specially designed for high-power laser application, were prepared by a high-temperature melting method. Except for the density, refractive index, glass transition temperature, and DC conductivity, the chemical durability and spectral properties, as emphasized by high-power and high-energy laser material, were further measured and analyzed. Regarding the chemical durability, the dissolution rates of these glasses do not show an evident mixed alkali effect with increasing the Na/(Na+K) ratio, although the effect is obvious for the glass transition temperature and DC conductivity. To better understand the nature of the dissolution mechanism, the ionic release concentrations of every element are determined. Both Na and K undergo ion exchange, but the ion exchange rate of K is much larger than that of Na. In terms of the spectral properties, the J-O parameters, emission cross-section, radiation lifetime, fluorescence lifetime, effective bandwidth, fluorescence branching ratio, and quantum efficiency are determined from absorption and emission spectra. The trend of Ω2 deviating from linearity indicates that the coordination environment symmetry of Nd3+ ions and the covalence of Nd-O also present an evident mixed alkali effect. The most important finding is that the emission cross-section and fluorescence lifetime of Nd3+ ions at 1053 nm were not affected by the change in the Na/K ratio. According to the above experimental results, the optimized value of the Na/K ratio was determined, based on which the 56P2O5-7.5Al2O3-5.9BaO-(28.56-x)K2O-xNa2O-1.51Nd2O3 glass maintains a high emission cross-section with good chemical durability.

Nomogram based on circulating lymphocyte subsets for predicting radiation pneumonia in esophageal squamous cell carcinoma.

Purpose: Currently, the relationship between radiation pneumonia (RP) and circulating immune cell in patients with esophageal squamous cell carcinoma (ESCC) remains unclear. This study aimed to explore the relationship between RP and circulating lymphocyte subsets in patients with ESCC receiving chemoradiotherapy (CRT), and develop a nomogram model to predict RP. Since we should implement clinical intervention to ≥ grade 2 RP, a nomogram model for ≥ grade 2 RP was also established to provide an early warning. Patients and methods: This study retrospectively included 121 patients with ESCC receiving CRT from Guangxi Medical University Cancer Hospital from 2013 to 2021. Independent factors associated with occurrence of RP and ≥ grade 2 RP were identified by univariate and multivariate logistic regression analysis in the training cohort, and incorporated into nomograms. The predictive accuracy and discrimination of the model was assessed using Concordance Index (C-index), calibration curve and decision curve analysis (DCA). And each model was internally validated. Additionally, to verify the optimized predictive performance of the nomograms, the area under the ROC curve (AUC) of each nomogram was compared to that of single independent risk factors, lung V10 and lung V20, respectively. Moreover, each model was further evaluated for risk stratification to identify populations at high risk of RP and ≥ grade 2 RP. Results: Multivariate analysis suggested that TNM stage, post-RT percentage of CD8+ T cell, and lung V15 were independent predictive factors of RP. Besides, pre- and post-RT percentage of CD8+ T cell, and V15 were independent factors of ≥ grade 2 RP. The C-indexes of RP and ≥ grade 2 RP nomograms were 0.809 (95% CI: 0.715-0.903) and 0.787 (95% CI: 0.685-0.889) in the training cohort, respectively. And the C-indexes of RP and ≥ grade 2 RP nomograms were 0.718 (95% CI: 0.544-0.892) and 0.621 (95% CI: 0.404-0.837) in the validation cohort, respectively. The calibration curves showed that the predicted values of model agreed well with actual observations. Moreover, DCA results indicated the applicability and accuracy of the models to predict RP and ≥ grade 2 RP. After stratification, the incidence of the high-risk group was significantly higher than that of the low-risk group with respect to either RP or ≥ grade 2 RP. Conclusion: TNM stage, post-RT percentage of CD8+ T cell, and lung V15 were the independent predictors of RP toxicity. Pre- and post-RT percentage of CD8+ T cell, and lung V15 were the independent factors of ≥ grade 2 RP toxicity. The nomograms based on circulating lymphocyte subsets can robustly predict RP and ≥ grade 2 RP, guiding clinicians in risk stratification and early intervention.

Silver-Neodymium Codoped Lithium Aluminum Metaphosphate Glasses for Radio-Photoluminescence Dosimeter.

Commercial radio-photoluminescence (RPL) glass dosimeters generally use Ag single-doped phosphate glass as a single-wavelength sensor. Now, a novel type of Ag-Nd-codoped phosphate glass has been developed, which can be applied to dual-wavelength or multi-wavelength RPL sensors, and can thus improve the accuracy and stability of RPL dosimeters. An anhydrous 99.5 (0.7LiPO3-0.3Al (PO3)3) -0.25Ag2O-0.25Nd2O3 glass was prepared and irradiated at different doses, and then the absorption, fluorescence, infrared transmission spectra, as well as fluorescence lifetimes were tested and analyzed. The results show that there is an energy transfer between the Ag defect center and Nd3+ ions, and the transfer efficiency using 380 nm excitation is greater than that using 310 nm excitation. Aside from the 650 nm fluorescence of the Ag defect center, strong 882 nm and 1054 nm fluorescences of Nd ions are exhibited. It is possible that these fluorescences would allow the developed Ag-Nd-codoped phosphate glass to be applied to new RPL glass sensors and dosimeters.

Plasmatic Levels of HSP90α at Diagnosis: A Novel Prognostic Indicator of Clinical Outcome in Advanced Lung Cancer Patients Treated With PD-1/PD-L1 Inhibitors Plus Chemotherapy.

BACKGROUND: The purpose of this study was set to investigate the prognostic role of plasmatic levels of heat shock protein 90 alpha (HSP90α) at diagnosis in advanced lung cancer patients treated with Programmed cell death protein 1 (PD-1)/Programmed cell death-Ligand protein 1 (PD-L1) inhibitors plus chemotherapy. METHODS: A total of 137 advanced lung cancer patients treated with PD-1/PD-L1 inhibitors plus chemotherapy admitted to the Guangxi Medical University Cancer Hospital were enrolled in this study. Smooth curve fitting was conducted to address the nonlinearity of HSP90α and progression-free survival (PFS) and overall survival (OS). We calculated the inflection point using a recursive algorithm. Kaplan-Meier survival analysis and Cox proportional hazards regression model were used to assess the prognostic value of HSP90α for PFS and OS. Subgroup analysis was performed to evaluate the relationship between high HSP90α and disease progression and death risk. RESULTS: The average age of patients was 58.6 ± 9.8 years, and 73.7% of them were men. We divided patients according to their plasmatic levels of HSP90α into low (HSP90α <52.7 ng/ml) group and high (HSP90α ≥52.7 ng/ml) group. Kaplan-Meier analysis showed a shorter PFS and OS for the high group with log-rank P < 0.05. Univariate and multivariate analyses indicated that high HSP90α was associated with an increased risk of disease progression and death after fully adjusting potential confounders with hazard ratio (HR) 1.8 (95% CI = 1.0-3.2) and HR 2.4 (95% CI = 1.1-5.1), respectively (P < 0.05). After stratification by subgroup analysis, the relationship between high HSP90α and the risk of disease progression and death was consistent across all patient subgroups. CONCLUSION: Plasmatic levels of HSP90α at diagnosis can be considered a potential independent prognostic marker of advanced lung cancer patients treated with PD-1/PD-L1 inhibitors plus chemotherapy. A further large-scale prospective validation study is needed to determine whether these results are widely applicable.

Efficient induction of neural progenitor cells from human ESC/iPSCs on Type I Collagen.

A stable, rapid and effective neural differentiation method is essential for the clinical applications of human embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs) in treating neurological disorders and diseases. Herein, we established a novel and robust monolayer differentiation method to produce functional neural progenitor cells (NPCs) from human ESC/iPSCs on Type I Collagen. The derived cells not only displayed the requisite markers, but also behaved similarly to classic NPCs both in vitro and in vivo. Upon transplantation into traumatic brain injury model, the derived NPCs facilitated recovery from injury. We also found that SMAD signaling stayed down throughout the differentiation process on Type I Collagen, and the pluripotent signals were rapidly downregulated along with raising up of neural early markers on the third day. Meanwhile, ATAC-seq data showed the related mediation of distinct transcriptome and global chromatin dynamics during NPC induction. Totally, our results thus provide a convenient way to generate NPCs from human ESC/iPSCs for neural diseases' treatment.

A case series of dermoids in the middle ear.

OBJECTIVE: Dermoid is a rare disease located in the head and neck and only sporadic cases were previously reported. Surgery with different operational paths is the best solution to the disease. We aimed to analyze the clinical characteristics and outcomes of surgical approach for treating dermoid originated from the middle ear and Eustachian tube. METHODS: In this retrospective case series, four cases of dermoids of the middle ear and Eustachian tube, treated by endoscopic-assisted surgical approach were reviewed and analyzed. RESULTS: Patients' ages ranged from 7 months to 16 years. All cases involved the middle ear, eustachian tube, and the parapharyngeal space. Postoperative follow-up ranged from 6 months to 11 years. No facial nerve paralysis was observed during or after surgeries. Treatment was efficient in the four cases, with no residual symptoms during post-operative follow-up. CONCLUSIONS: Dermoid of the middle ear involving the eustachian tube usually appears in children of early age. Surgical resection with assistance of endoscope has satisfying outcome for these cases.

Complexation-association-extraction spectrophotometric determination of Pt cations based on a multi-reagent analytical system with I- anions and 2-[2-[4-[(2-cyanoethyl)methylamino]phenyl]vinyl]-1,3,3-trimethyl-3H-indolium cations.

A new multi-reagent analytical system with 2-[2-[4-[(2-cyanoethyl)methylamino]phenyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride (CPVTI), which is a styryl hemicyanine cationic dye with good photostability and a high molar absorption coefficient, as its core is first established and utilized successfully to determine the content of Pt ions via a spectrophotometric method. The process involves two treatment steps: adding CPVTI and I solutions to the Pt solution to be detected, and then using butyl acetate for vortex liquid-liquid extraction. A Pt cation can be incorporated into the CPVTI cation with the help of an I- anion, initially converting the Pt cation into a [PtI6]2- complex anion. After forming a [PtI62-·2CPVTI+](aq) ion associate in the aqueous phase, the Pt cation can be extracted selectively by butyl acetate with maximum extraction efficiency, and exists as [PtI62-·2CPVTI+](org) in the extract phase. Via the formation of the iodo-complex of Pt and its ion associate with CPVTI, and the extraction with butyl acetate, Pt is selectively partitioned into the butyl acetate extractant in a step-by-step manner with good interference resistance. In the CPVTI-Pt-I analytical system, the charge state of CPVTI is retained by adjustment with H2SO4; the monovalent CPVTI+ presents a strong spectrophotometric absorbance signal at 530 nm with long-term stability, which allows determination of the Pt content. The system shows a high molar absorption coefficient of 6.52 × 104 L mol-1 cm-1 at 530 nm, a lower limit of detection of 0.07 mg L-1, and a good Sandell's sensitivity of 0.0030 µg cm-2. Mechanistic analysis of the establishment of the system, concentration optimization, standard working curve, system sensitivity and stability, resistance against interference from diverse metal ions, and practical applications are investigated and discussed.

Pretreatment by recyclable Fe3O4@Mg/Al-CO3-LDH magnetic nano-adsorbent to dephosphorize for the determination of trace F- and Cl- in phosphorus-rich solutions.

The magnetic nano-adsorbent Fe3O4@Mg/Al-CO3-LDH (Mg/Al-type layered double hydroxide) with a CO3 2- interlayer anion has been synthesized successfully on Fe3O4 nanoparticles via a urea hydrothermal method. It is confirmed that the nano-adsorbent can adsorb PO4 3- rapidly and efficiently in multi-ion solutions; meanwhile, it did not adsorb any F- and Cl-, even with a high amount of the nano-adsorbent or a longer adsorption time. This behaviour is beneficial for applications to remove PO4 3- in phosphorus-rich solutions, and especially can be utilized to determine trace F- and Cl- anions in phosphorus-rich solutions by physical and chemical analysis methods including ion chromatography without serious interference from PO4 3- for trace determinations. Herein, the hydrothermally synthesized Fe3O4@Mg/Al-CO3-LDH was characterized via SEM, TEM, SAED, XRD, FTIR, magnetic hysteresis loop analysis and adsorption-desorption isotherm analysis. The structure and stability, adsorption mechanism, magnetic saturation value, specific surface area, total pore volume, phosphate adsorption capacity and recyclability are discussed. Using the optimized pretreatment conditions, Fe3O4@Mg/Al-CO3-LDH was utilized successfully to adsorb PO4 3- in real samples and determine trace F- and Cl- accurately by ion chromatography; this would be very beneficial for continuous analysis and on-line tests by physical and chemical analysis methods without interference from PO4 3- in phosphorus-rich samples, leaving F- and Cl- even if in a trace content.