Translation and validation of traditional Chinese version of the pediatric eating assessment Tool-10.

BACKGROUND: /Purpose: The Pediatric Eating Assessment Tool-10 (Pedi-EAT-10) is a caregiver-administrated subjective questionnaire for evaluating swallowing and feeding disorders among children. This study translated the Pedi-EAT-10 into Traditional Chinese and tested the translated version's reliability and validity. METHODS: Pedi-EAT-10 was translated into Traditional Chinese by experts and finalized after discussion and testing. A total of 168 participants, consisting of 32 children with dysphagia from a tertiary medical center and 136 healthy controls from its Children Care Center for Employees, were recruited. All participants were assessed by an otolaryngologist and speech-language pathologist. The reliability, validity, and efficacy of the translated Pedi-EAT-10 were analyzed to ensure it could be used to identify pediatric dysphagia and feeding problems. RESULTS: The Traditional Chinese version of the Pedi-EAT-10 had significant clinical discriminative validity between the dysphagia group and the control group (total score = 9.6 vs. 2.6, P < 0.001), acceptable test-retest reliability (intraclass correlation = 0.63), and excellent internal consistency (Cronbach's α = 0.91 for the entire cohort). The overall performance of the test for distinguishing children with dysphagia from normal controls was acceptable, and the area under the curve was 74.8% (sensitivity = 71.9%; specificity = 69.9%). The optimal cutoff score was ≥3 on the Youdex index. CONCLUSIONS: The Traditional Chinese version of the Pedi-EAT-10 has fair reliability and validity and can be quickly and easily completed by caregivers. The translated Ped-EAT-10 can be used as a first-line tool for assessing the need for further referral and instrumental examination.

Effect of platelet-rich plasma combined with negative pressure wound therapy in treating patients with chronic wounds: A meta-analysis.

A meta-analysis was conducted to comprehensively explore the effects of platelet-rich plasma (PRP) combined with negative pressure wound therapy (NPWT) in treating patients with chronic wounds. Computer searches were conducted, from database infection to November 2023, in EMBASE, Google Scholar, Cochrane Library, PubMed, Wanfang and China National Knowledge Infrastructure databases for randomized controlled trials (RCTs) on the use of PRP combined with NPWT technology for treating chronic wounds. Two researchers independently screened the literature, extracted data and conducted quality assessments according to the inclusion and exclusion criteria. Stata 17.0 software was employed for data analysis. Overall, 18 RCTs involving 1294 patients with chronic wounds were included. The analysis revealed that, compared with NPWT alone, the use of PRP combined with NPWT technology significantly improved the healing rate (odds ratios [OR] = 1.92, 95% confidence intervals [CIs]: 1.43-2.58, p < 0.001) and total effective rate (OR = 1.31, 95% CI: 1.23-1.39, p < 0.001), and also significantly shortened the healing time of the wound (standardized mean difference = -2.01, 95% CI: -2.58 to -1.45, p < 0.001). This study indicates that the treatment of chronic wounds with PRP combined with NPWT technology can significantly enhance clinical repair effectiveness and accelerate wound healing, with a high healing rate, and is worth further promotion and practice.

Isoliquiritigenin inhibits apoptosis and ameliorates oxidative stress in rheumatoid arthritis chondrocytes through the Nrf2/HO-1-mediated pathway.

Rheumatoid arthritis (RA) is a chronic inflammatory condition known for its irreversible destructive impact on the joints. Chondrocytes play a pivotal role in the production and maintenance of the cartilage matrix. However, the presence of inflammatory cytokines can hinder chondrocyte proliferation and promote apoptosis. Isoliquiritigenin (ISL), a flavonoid, potentially exerts protective effects against various inflammatory diseases. However, its specific role in regulating the nuclear factor E2-associated factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway in chondrocytes in RA remains unclear. To investigate this, this study used human chondrocytes and Sprague-Dawley rats to construct in vitro and in vivo RA models, respectively. The study findings reveal that cytokines markedly induced oxidative stress, the activation of matrix metalloproteinases, and apoptosis both in vitro and in vivo. Notably, ISL treatment significantly mitigated these effects. Moreover, Nrf2 or HO-1 inhibitors reversed the protective effects of ISL, attenuated the expression of Nrf2/HO-1 and peroxisome proliferator-activated receptor gamma-coactivator-1α, and promoted chondrocyte apoptosis. This finding indicates that ISL primarily targets the Nrf2/HO-1 pathway in RA chondrocytes. Moreover, ISL treatment led to improved behavior scores, reduced paw thickness, and mitigated joint damage as well as ameliorated oxidative stress in skeletal muscles in an RA rat model. In conclusion, this study highlights the pivotal role of the Nrf2/HO-1 pathway in the protective effects of ISL and demonstrates the potential of ISL as a treatment option for RA.

Leukemic presentation and progressive genomic alterations of MCD/C5 diffuse large B-cell lymphoma (DLBCL).

Diffuse large B-cell lymphoma (DLBCL) is a heterogenous group of lymphoid malignancies. Based on gene expression profiling, it has been subdivided into germinal center (GC)-derived and activated B-cell (ABC) types. Advances in molecular methodologies have further refined the subclassification of DLBCL, based on recurrent genetic abnormalities. Here, we describe a distinct case of DLBCL that presented in leukemic form. DNA sequencing targeting 275 genes revealed pathogenically relevant mutations of CD79B, MyD88, TP53, TBL1XR1, and PIM1 genes, indicating that this lymphoma would be best classified as MCD/C5 DLBCL, an ABC subtype. Despite an initial good clinical response to BTK inhibitor ibrutinib, anti-CD20 antibody rituxan, alkylating agent bendamustine, and hematopoietic stem-cell transplant, the lymphoma relapsed, accompanied by morphologic and molecular evidence of disease progression. Specifically, the recurrent tumor developed loss of TP53 heterozygosity (LOH) and additional chromosomal changes central to ABC DLBCL pathogenesis, such as PRDM1 loss. Acquired resistance to ibrutinib and rituxan was indicated by the emergence of BTK and FOXO1 mutations, respectively, as well as apparent activation of alternative cell-activation pathways, through copy-number alterations (CNAs), detected by high-resolution chromosomal microarrays. In vitro, studies of relapsed lymphoma cells confirmed resistance to standard BTK inhibitors but sensitivity to vecabrutinib, a noncovalent inhibitor active against both wild-type as well as mutated BTK. In summary, we provide in-depth molecular characterization of a de novo leukemic DLBCL and discuss mechanisms that may have contributed to the lymphoma establishment, progression, and development of drug resistance.

SHP1 loss augments DLBCL cellular response to ibrutinib: a candidate predictive biomarker.

SHP1, a tyrosine phosphatase, negatively regulates B-cell receptor (BCR) signaling. Ibrutinib selectively inhibits BTK and has been approved for the treatment of several types of B-cell lymphomas, but not yet in diffuse large B-cell lymphoma (DLBCL). A phase 3 clinical trial of ibrutinib-containing regimen has been completed to evaluate its activity in subtypes or subsets of DLBCL patients. Although the subtype of activated B-cell like (ABC) DLBCL is characterized by chronic active BCR signaling, only a fraction of ABC-DLBCL patients seem to benefit from ibrutinib-containing regimen. New alternative predictive biomarkers are needed to identify patients who better respond. We investigated if SHP1 plays a role in defining the level of the BCR activity and impacts the response to ibrutinib. A meta-analysis revealed that lack of SHP1 protein expression as well as SHP1 promoter hypermethylation is strongly associated with NHL including DLBCL. On a tissue microarray of 95 DLBCL samples, no substantial difference in SHP1 expression was found between the GCB and non-GCB subtypes of DLBCL. However, we identified a strong reverse correlation between SHP1 expression and promoter methylation suggesting that promoter hypermethylation is responsible for SHP1 loss. SHP1 knockout in BCR-dependent GCB and ABC cell lines increased BCR signaling activities and sensitize lymphoma cells to the action of ibrutinib. Rescue of SHP1 in the knockout clones, on the other hand, restored BCR signaling and ibrutinib resistance. Further, pharmacological inhibition of SHP1 in both cell lines and patient-derived primary cells demonstrate that SHP1 inhibition synergized with ibrutinib in suppressing tumor cell growth. Thus, SHP1 loss may serve as an alternative biomarker to cell-of-origin to identify patients who potentially benefit from ibrutinib treatment. Our results further suggest that reducing SHP1 pharmacologically may represent a new strategy to augment tumor response to BCR-directed therapies. Schematic diagram summarizing the major findings. Left panel. When SHP1 is present and functional, it negatively regulates the activity of the BCR pathway. Right pane. When SHP1 is diminished or lost, cells depend more on the increased BCR signaling and making them vulnerable to BTK inhibitor, ibrutinib. Diagram was generated using BioRender.

Light Scattering of Electrospinning Jet with Internal Structures by Flow-Induced Phase Separation.

Herein, the direct morphological evidence of the extension-induced phase-separated structures in the electrospinning jet observed by high-speed video imaging and by light scattering technique is reported. Model solutions of poly(vinyl alcohol) (PVA)/water are electrospun. Two types of internal structures, that is, long strings and short ellipsoids, are found. A light scattering model is derived for the Vv scattering configuration to account for the scattered intensities contributed from the liquid jet itself and those from the internal structures. For the severely stretching jet of PVA/water, the Vv intensity profile is dominant by the internal structures to mask the scattering contribution from the jet itself. Moreover, the Hv intensity profile reflects the anisotropy of the oriented chains parallel to the jet axis. For the 7 wt% solution, the derived extension rate in the vicinity of the Taylor cone apex is about 3420 s-1 , which is higher than the Rouse relaxation rate measured by rheometer. It is concluded that extension-induced phase separation of the single-phase PVA solution is likely to occur in Taylor-cone apex to trigger the self-assembly process for producing strings (and/or bulges) in the flowing jet, which eventually transform to become the nanofibers, after solvent removal, to be collected on the grounded collector.

Two-step artificial intelligence system for endoscopic gastric biopsy improves the diagnostic accuracy of pathologists.

Background: Endoscopic biopsy is the pivotal procedure for the diagnosis of gastric cancer. In this study, we applied whole-slide images (WSIs) of endoscopic gastric biopsy specimens to develop an endoscopic gastric biopsy assistant system (EGBAS). Methods: The EGBAS was trained using 2373 WSIs expertly annotated and internally validated on 245 WSIs. A large-scale, multicenter test dataset of 2003 WSIs was used to externally evaluate EGBAS. Eight pathologists were compared with the EGBAS using a man-machine comparison test dataset. The fully manual performance of the pathologists was also compared with semi-manual performance using EGBAS assistance. Results: The average area under the curve of the EGBAS was 0·979 (0·958-0·990). For the diagnosis of all four categories, the overall accuracy of EGBAS was 86·95%, which was significantly higher than pathologists (P< 0·05). The EGBAS achieved a higher κ score (0·880, very good κ) than junior and senior pathologists (0·641 ± 0·088 and 0·729 ± 0·056). With EGBAS assistance, the overall accuracy (four-tier classification) of the pathologists increased from 66·49 ± 7·73% to 73·83 ± 5·73% (P< 0·05). The length of time for pathologists to manually complete the dataset was 461·44 ± 117·96 minutes; this time was reduced to 305·71 ± 82·43 minutes with EGBAS assistance (P = 0·00). Conclusions: The EGBAS is a promising system for improving the diagnosis ability and reducing the workload of pathologists.

Atomistic simulations of mechanical response of a heterogeneous fcc/bcc nanolayered composite.

Molecular dynamics simulations are performed to study the mechanical properties and deformation mechanisms of a heterogeneous face-centered cubic/ body-centered cubic Cu/Ta nanolayered composite under uniaxial tension and compression. The results show that the stress-strain curves exhibit two main yield points in tension while only one yield point during compression, and the deformation primarily experiences three stages. The first stage is linearly elastic at small strains, followed by the nucleation and propagation of dislocations and stacking faults in the Cu layers, and eventually the Ta layers yield to plastic deformation. The yield of the specimen is mainly determined by the dislocation evolution in the hard phase (i.e. Ta layers), which leads to a sharp drop in the stress-strain curve. We show that the heterogeneous nanolayered composite exhibits a good deformation compatibility during compression but an obvious deformation incompatibility between Cu and Ta layers in tension. The temperature effect is also systematically investigated. It is revealed that the yield of the specimen at higher temperature depends only on the dislocation evolution in the thick Ta layers, and the yield strengths in tension and compression both decrease with the increasing temperature. In particular, our computations show that high temperature can significantly suppress the dislocation activities in the Cu layers during deformation, which results in a lower dislocation density of the Cu layers compared with that of the Ta layers and thus causing an incompatible fashion among the constituent layers.

Natural Compounds Targeting Cancer-Associated Fibroblasts against Digestive System Tumor Progression: Therapeutic Insights.

Cancer-associated fibroblasts (CAFs) are critical for cancer occurrence and progression in the tumor microenvironment (TME), due to their versatile roles in extracellular matrix remodeling, tumor-stroma crosstalk, immunomodulation, and angiogenesis. CAFs are the most abundant stromal component in the TME and undergo epigenetic modification and abnormal signaling cascade activation, such as transforming growth factor-ß (TGF-ß) and Wnt pathways that maintain the distinct phenotype of CAFs, which differs from normal fibroblasts. CAFs have been considered therapeutic targets due to their putative oncogenic functions. Current digestive system cancer treatment strategies often result in lower survival outcomes and fail to prevent cancer progression; therefore, comprehensive characterization of the tumor-promoting and -restraining CAF activities might facilitate the design of new therapeutic approaches. In this review, we summarize the enormous literature on natural compounds that mediate the crosstalk of CAFs with digestive system cancer cells, discuss how the biology and the multifaceted functions of CAFs contribute to cancer progression, and finally, pave the way for CAF-related antitumor therapies.

Distillate Flux Enhancement of Direct Contact Membrane Distillation Modules with Inserting Cross-Diagonal Carbon-Fiber Spacers.

A new design of direct-contact membrane distillation (DCMD) modules with cross-diagonal carbon-fiber spacers of various hydrodynamic angles in flow channels to promote turbulence intensity was proposed to enhance pure water productivity. Attempts to reduce the temperature polarization coefficient were achieved by inserting cross-diagonal carbon-fiber spacers in channels, which create wakes and eddies in both heat and mass transfer behaviors to enhance the permeate flux enhancement. A simplified equation was formulated to obtain the theoretical predictions of heat transfer coefficients in the current DCMD device. The permeate fluxes and temperature distributions of both hot and cold feed streams are represented graphically with the inlet volumetric flow rate and inlet temperature of the hot saline feed stream as parameters. The higher distillate flux of countercurrent-flow operations for saline water desalination was accomplished as compared to the concurrent-flow operations of various hydrodynamic angles. The results show that the agreement between the theoretical predictions and experimental results is reasonably good. The effects of countercurrent-flow operations and inserting carbon fiber spacers have confirmed technical feasibility and device performance enhancement of up to 45%. The influences of operating and design parameters on the pure water productivity with the expense of energy consumption are also discussed.

Influence of Calcium Perchlorate on the Search for Martian Organic Compounds with MTBSTFA/DMF Derivatization.

N-tert-butyldimethylsilyl-N-methyltrifluoroacetamide (MTBSTFA), mixed with the solvent N,N-dimethylformamide (DMF), is used as a derivatizing reagent by the Sample Analysis at Mars (SAM) experiment onboard NASA's Curiosity rover and will soon be utilized by the Mars Organic Molecule Analyzer experiment onboard the ESA/Roscosmos Rosalind Franklin rover. The pyrolysis products of MTBSTFA, DMF, and the MTBSTFA/DMF mixtures, obtained at different temperatures, were analyzed. Two different pyrolysis modes were studied, flash pyrolysis and ramp pyrolysis (35°C/min), to evaluate the potential influence of the sample heating speed on the production of products in space chromatographs. The effect of the presence of calcium perchlorate on the pyrolysis products of MTBSTFA/DMF was also studied to ascertain the potential effect of perchlorate species known to be present at the martian surface. The results show that MTBSTFA/DMF derivatization should be applied below 300°C when using flash pyrolysis, as numerous products of MTBSTFA/DMF were formed at high pyrolysis temperatures. However, when an SAM-like ramp pyrolysis was applied, the final pyrolysis temperature did not appear to influence the degradation products of MTBSTFA/DMF. All products of MTBSTFA/DMF pyrolysis are listed in this article, providing a major database of products for the analysis of martian analog samples, meteorites, and the in situ analysis of martian rocks and soils. In addition, the presence of calcium perchlorate does not show any obvious effects on the pyrolysis of MTBSTFA/DMF: Only chloromethane and TBDMS-Cl (chloro-tertbutyldimethylsilane) were detected, whereas chlorobenzene and other chlorine-bearing compounds were not detected. However, other chlorine-bearing compounds were detected after pyrolysis of the Murchison meteorite in the presence of calcium perchlorate. This result reinforces previous suggestions that chloride-bearing compounds could be reaction products of martian samples and perchlorate.

Association of visual motor processing and social cognition in schizophrenia.

Patients with schizophrenia have difficulties in social cognitive domains including emotion recognition and mentalization, and in sensorimotor processing and learning. The relationship between social cognitive deficits and sensorimotor function in patients with schizophrenia remains largely unexplored. With the hypothesis that impaired visual motor processing may decelerate information processing and subsequently affects various domains of social cognition, we examined the association of nonverbal emotion recognition, mentalization, and visual motor processing in schizophrenia. The study examined mentalization using the verbal subset of the Chinese version of Theory of Mind (CToM) Task, an equivalent task of the Faux Pas Test; emotion recognition using the Diagnostic Analysis of Nonverbal Accuracy 2-Taiwan version (DANVA-2-TW), and visual motor processing using a joystick tracking task controlled for basic motor function in 34 individuals with chronic schizophrenia in the community and 42 healthy controls. Patients with schizophrenia had significantly worse performance than healthy controls in social cognition, including facial, prosodic emotion recognition, and mentalization. Visual motor processing was also significantly worse in patients with schizophrenia. Only in patients with schizophrenia, both emotion recognition (mainly in prosodic modality, happy, and sad emotions) and mentalization were positively associated with their learning capacity of visual motor processing. These findings suggest a prospective role of sensorimotor function in their social cognitive deficits. Despite that the underlying neural mechanism needs further research, our findings may provide a new direction for restoration of social cognitive function in schizophrenia by enhancing visual motor processing ability.

Ibrutinib and venetoclax target distinct subpopulations of CLL cells: implication for residual disease eradication.

Ibrutinib inhibits Bruton tyrosine kinase while venetoclax is a specific inhibitor of the anti-apoptotic protein BCL2. Both drugs are highly effective as monotherapy against chronic lymphocytic leukemia (CLL), and clinical trials using the combination therapy have produced remarkable results in terms of rate of complete remission and frequency of undetectable minimal residual disease. However, the laboratory rationale behind the success of the drug combination is still lacking. A better understanding of how these two drugs synergize would eventually help develop other rational combination strategies. Using an ex vivo model that promotes CLL proliferation, we show that modeled ibrutinib proliferative responses, but not viability responses, correlate well with patients' actual clinical responses. Importantly, we demonstrate for the first time that ibrutinib and venetoclax act on distinct CLL subpopulations that have different proliferative capacities. While the dividing subpopulation of CLL responds to ibrutinib, the resting subpopulation preferentially responds to venetoclax. The combination of these targeted therapies effectively reduced both the resting and dividing subpopulations in most cases. Our laboratory findings help explain several clinical observations and contribute to the understanding of tumor dynamics. Additionally, our proliferation model may be used to identify novel drug combinations with the potential of eradicating residual disease.

Electrochemical metrics for corrosion resistant alloys.

Corrosion is an electrochemical phenomenon. It can occur via different modes of attack, each having its own mechanisms, and therefore there are multiple metrics for evaluating corrosion resistance. In corrosion resistant alloys (CRAs), the rate of localized corrosion can exceed that of uniform corrosion by orders of magnitude. Therefore, instead of uniform corrosion rate, more complex electrochemical parameters are required to capture the salient features of corrosion phenomena. Here, we collect a database with an emphasis on metrics related to localized corrosion. The six sections of the database include data on various metal alloys with measurements of (1) pitting potential, Epit, (2) repassivation potential, Erp, (3) crevice corrosion potential, Ecrev, (4) pitting temperature, Tpit, (5) crevice corrosion temperature, Tcrev, and (6) corrosion potential, Ecorr, corrosion current density, icorr, passivation current density, ipass, and corrosion rate. The experimental data were collected from 85 publications and include Al- and Fe-based alloys, high entropy alloys (HEAs), and a Ni-Cr-Mo ternary system. This dataset could be used in the design of highly corrosion resistant alloys.

Inhibition of B-cell receptor signaling disrupts cell adhesion in mantle cell lymphoma via RAC2.

Inhibition of the B-cell receptor (BCR) signaling pathway is highly effective in B-cell neoplasia through Bruton tyrosine kinase inhibition by ibrutinib. Ibrutinib also disrupts cell adhesion between a tumor and its microenvironment. However, it is largely unknown how BCR signaling is linked to cell adhesion. We observed that intrinsic sensitivities of mantle cell lymphoma (MCL) cell lines to ibrutinib correlated well with their cell adhesion phenotype. RNA-sequencing revealed that BCR and cell adhesion signatures were simultaneously downregulated by ibrutinib in the ibrutinib-sensitive, but not ibrutinib-resistant, cells. Among the differentially expressed genes, RAC2, part of the BCR signature and a known regulator of cell adhesion, was downregulated at both the RNA and protein levels by ibrutinib only in sensitive cells. RAC2 physically associated with B-cell linker protein (BLNK), a BCR adaptor molecule, uniquely in sensitive cells. RAC2 reduction using RNA interference and CRISPR impaired cell adhesion, whereas RAC2 overexpression reversed ibrutinib-induced cell adhesion impairment. In a xenograft mouse model, mice treated with ibrutinib exhibited slower tumor growth, with reduced RAC2 expression in tissue. Finally, RAC2 was expressed in ∼65% of human primary MCL tumors, and RAC2 suppression by ibrutinib resulted in cell adhesion impairment. These findings, made with cell lines, a xenograft model, and human primary lymphoma tumors, uncover a novel link between BCR signaling and cell adhesion. This study highlights the importance of RAC2 and cell adhesion in MCL pathogenesis and drug development.

Comparative study on artificial intelligence systems for detecting early esophageal squamous cell carcinoma between narrow-band and white-light imaging.

BACKGROUND: Non-magnifying endoscopy with narrow-band imaging (NM-NBI) has been frequently used in routine screening of esophagus squamous cell carcinoma (ESCC). The performance of NBI for screening of early ESCC is, however, significantly affected by operator experience. Artificial intelligence may be a unique approach to compensate for the lack of operator experience. AIM: To construct a computer-aided detection (CAD) system for application in NM-NBI to identify early ESCC and to compare it with our previously reported CAD system with endoscopic white-light imaging (WLI). METHODS: A total of 2167 abnormal NM-NBI images of early ESCC and 2568 normal images were collected from three institutions (Zhongshan Hospital of Fudan University, Xuhui Hospital, and Kiang Wu Hospital) as the training dataset, and 316 pairs of images, each pair including images obtained by WLI and NBI (same part), were collected for validation. Twenty endoscopists participated in this study to review the validation images with or without the assistance of the CAD systems. The diagnostic results of the two CAD systems and improvement in diagnostic efficacy of endoscopists were compared in terms of sensitivity, specificity, accuracy, positive predictive value, and negative predictive value. RESULTS: The area under receiver operating characteristic curve for CAD-NBI was 0.9761. For the validation dataset, the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of CAD-NBI were 91.0%, 96.7%, 94.3%, 95.3%, and 93.6%, respectively, while those of CAD-WLI were 98.5%, 83.1%, 89.5%, 80.8%, and 98.7%, respectively. CAD-NBI showed superior accuracy and specificity than CAD-WLI (P = 0.028 and P ≤ 0.001, respectively), while CAD-WLI had higher sensitivity than CAD-NBI (P = 0.006). By using both CAD-WLI and CAD-NBI, the endoscopists could improve their diagnostic efficacy to the highest level, with accuracy, sensitivity, and specificity of 94.9%, 92.4%, and 96.7%, respectively. CONCLUSION: The CAD-NBI system for screening early ESCC has higher accuracy and specificity than CAD-WLI. Endoscopists can achieve the best diagnostic efficacy using both CAD-WLI and CAD-NBI.

Serum eosinophil cationic protein: a prognostic factor for early postoperative recurrence of nasal polyps.

BACKGROUND: The objective of this work was to assess the efficacy of serum eosinophil cationic protein (ECP) concentration in predicting early postoperative recurrence in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). METHODS: We prospectively enrolled CRSwNP patients to receive bilateral functional endoscopic sinus surgery (FESS) and followed them for 1 year. Serum ECP level was measured within 1 week before surgery. Demographics and associated medical factors were analyzed with the surgical outcome, and nasal polyp histology was microscopically examined. RESULTS: Overall, 58 patients met the inclusion criteria and underwent FESS. After at least a 1-year follow-up period, 9 patients had postoperative recurrence, with significantly higher serum ECP levels (p = 0.030). Receiver operating characteristic curve analysis showed the optimal cutoff level of serum ECP concentration for predicting the postoperative recurrence of nasal polyps was 21.8 µg/L (p = 0.030). Regardless of atopy status and histology type, logistic regression analysis showed that a higher ECP level was the sole significant factor related to early postoperative recurrence of nasal polyps (odds ratio, 54.8; p = 0.014). Cox proportional hazard regression analysis revealed that the hazard ratio of CRSwNP patients with an ECP level of >21.8 µg/L resulting in early postoperative recurrence was 7.6 (p = 0.011). CONCLUSION: Serum ECP appears to be a feasible predictor for early postoperative recurrence of nasal polyps. CRSwNP patients with preoperative serum ECP levels of ≥21.8 µg/L had an approximately 55-fold increased risk of early recurrence. CRSwNP patients with higher preoperative serum ECP levels should be closely monitored within the first year after surgery.

Influence of Calcium Perchlorate on the Search for Organics on Mars with Tetramethylammonium Hydroxide Thermochemolysis.

The Mars Organic Molecule Analyzer (MOMA) and Sample Analysis at Mars (SAM) instruments onboard the Exomars 2022 and Mars Science Laboratory rovers, respectively, are capable of organic matter detection and differentiating potentially biogenic from abiotic organics in martian samples. To identify organics, both these instruments utilize pyrolysis-gas chromatography coupled to mass spectrometry, and the thermochemolysis agent tetramethylammonium hydroxide (TMAH) is also used to increase organic volatility. However, the reactivity and efficiency of TMAH thermochemolysis are affected by the presence of calcium perchlorate on the martian surface. In this study, we determined the products of TMAH pyrolysis in the presence and absence of calcium perchlorate at different heating rates (flash pyrolysis and SAM-like ramp pyrolysis with a 35°C·min-1 heating rate). The decomposition mechanism of TMAH pyrolysis in the presence of calcium perchlorate was studied by using stepped pyrolysis. Moreover, the effect of calcium perchlorate (at Mars-relevant concentrations) on the recovery rate of fatty acids with TMAH thermochemolysis was studied. Results demonstrate that flash pyrolysis yields more diversity and greater abundances of TMAH thermochemolysis products than does the SAM-like ramp pyrolysis method. There is no obvious effect of calcium perchlorate on TMAH degradation when the [ClO4-] is lower than 10 weight percent (wt %). Most importantly, the presence of calcium perchlorate does not significantly impact the recovery rate of fatty acids with TMAH thermochemolysis under laboratory conditions, which is promising for the detection of fatty acids via TMAH thermochemolysis with the SAM and MOMA instruments on Mars.

Banxia Xiexin Decoction () Treats Diabetic Gastroparesis through PLC-IP3-Ca2+/NO-cGMP-PKG Signal Pathway.

OBJECTIVE: To test the effect of Banxia Xiexin Decoction (, BXD) on the contraction and relaxation of gastric smooth muscle (SM) in diabetic gastroparesis (DGP) model rats, and to explore the mechanism of BXD in the prevention and treatment of DGP through experiments of signal pathway both in vivo and in vitro. METHODS: Sixty Sprague-Dawley rats were divided into 6 groups according to a random number table: control group, model group, high-, medium- and low-dose BXD groups (9.2, 4.6 and 1.8 g/(kg·d), respectively), and domperidone group (10 mg/(kg·d)), 10 rats per group. DGP model was established initially by a single intraperitoneal injection of streptozotocin (STZ), and was confirmed by recording gastric emptying, intestinal transport velocity and gastric myoelectric activity of rats after 2 months. Each group was treated with a corresponding drug for 4 weeks. The mRNA and protein expressions of phospholipase C (PLC), inositol triphosphate (IP3), neuronal nitric oxide synthase (nNOS), and cyclic guanosine monophosphate (cGMP) dependent protein kinase G (PKG) were detected by reverse transcription-polymerase chain reaction and Western blot, respectively, while nitric oxide (NO) and cGMP expressions were detected by enzyme-linked immunosorbent assay. Gastric tissues were obtained from rats for primary cell culture preparation. Gastric SM cells were treated with 0.8 µmol/L of STZ or STZ plus 1,000, 500 and 200 µg/mL of BXD or STZ plus 2.5 µmol/mL of domperidone for 24, 48, 72 or 96 h, respectively. The length of gastric SM cells and intracellular Ca2+ concentration ([Ca2+]i) before and after BXD treatment was measured. RESULTS: Compared with the model group, high- and medium-dose BXD and domperidone significantly increased the expressions of PLC, IP3, NO, nNOS, cGMP and PKG in rat's gastric tissue (P<0.01). Gastric SM cells treated with BXD showed a time- and dose-dependent increase in cell viability (P<0.01). The treatment with high- and medium-dose BXD and domperidone inhibited the increase in gastric SM cells length and increased [Ca2+]i compared with the model cells (P<0.01). CONCLUSIONS: Treatment with high- and medium-dose BXD significantly attenuated STZ-induced experimental DGP in rats. The therapeutic effect of BXD on DGP rats might be associated with the PLC-IP3-Ca2+/NO-cGMP-PKG signal pathway.

Mitochondrial transport mediates survival of retinal ganglion cells in affected LHON patients.

The mutations in the genes encoding the subunits of complex I of the mitochondrial electron transport chain are the most common cause of Leber's hereditary optic neuropathy (LHON), a maternal hereditary disease characterized by retinal ganglion cell (RGC) degeneration. The characteristics of incomplete penetrance indicate that nuclear genetic and environmental factors also determine phenotypic expression of LHON. Therefore, further understanding of the role of mutant mitochondrial nicotinamide adenine dinucleotide dehydrogenase subunit proteins and nuclear genetic factors/environmental effects in the etiology of LHON is needed. In this study, we generated human-induced pluripotent stem cells (hiPSCs) from healthy control, unaffected LHON mutation carrier, and affected LHON patient. hiPSC-derived RGCs were used to study the differences between affected and unaffected carriers of mitochondrial DNA point mutation m.11778G > A in the MT-ND4 gene. We found that both mutated cell lines were characterized by increase in reactive oxygen species production, however, only affected cell line had increased levels of apoptotic cells. We found a significant increase in retrograde mitochondria and a decrease in stationary mitochondria in the affected RGC axons. In addition, the messenger RNA and protein levels of KIF5A in the LHON-affected RGCs were significantly reduced. Antioxidant N-acetyl-L-cysteine could restore the expression of KIF5A and the normal pattern of mitochondrial movement in the affected RGCs. To conclude, we found essential differences in the mutually dependent processes of oxidative stress, mitochondrial transport and apoptosis between two LHON-specific mutation carrier RGC cell lines, asymptomatic carrier and disease-affected, and identified KIF5A as a central modulator of these differences.