Ingenious Modulation of Third-Order Nonlinear Optical Response of Zr-MOFs through Defect Engineering Based on a Mixed-Linker Strategy.

Defect engineering plays a pivotal role in regulating electronic structure and facilitating charge transfer, yielding captivating effects on third-order nonlinear optical (NLO) properties. In this work, we utilized a mixed-linker strategy to intentionally disrupt the initial periodic arrangement of UiO-66 and construct defects. Specifically, we incorporated tetrakis(4-carboxyphenyl)porphyrin (TCPP) with an exceptionally electron-rich delocalization system into the framework of UiO-66 using a one-pot solvothermal method, ingeniously occupying the partial distribution sites of the Zr6 clusters. Compared to UiO-66, the NLO absorption and refraction performance of TCPP/UiO-66 were significantly improved. Additionally, due to the presence of nitrogen-rich sites that can accommodate metal ions in the porphyrin ring of TCPP, Co(II), Ni(II), Cu(II), and Zn(II) are introduced into TCPP/UiO-66, extending the d-π conjugation effect to further regulate the defects. The NLO absorption behavior transforms saturation absorption (SA) to reverse saturation absorption (RSA), while the refraction behavior shifts from self-defocusing to self-focusing. This work shows that defects can effectively regulate the electronic structure, while TCPP plays a crucial role in significantly enhancing electron delocalization.

Insight into the Relationship between the Causes of Off-Odour and Microorganism Communities in Xuanwei Ham.

To expound on the correlation between the microorganism communities and the formation of off-odour in Xuanwei ham, the microorganism communities and volatile compounds were investigated in the biceps femoris (BF) and semimembranosus (SM) of Xuanwei ham with different quality grades (normal ham and spoiled ham). The single molecule real-time sequencing showed that differential bacteria and fungi were more varied in normal hams than in spoiled hams. Headspace solid-phase microextraction-gas chromatography (HS-SPME-GC-MS) results indicated that aldehydes and alcohols were significantly higher in spoiled hams than those in normal hams (p < 0.05). The off-odour of spoiled hams was dominated by ichthyic, malodourous, sweaty, putrid, sour, and unpleasant odours produced by compounds such as trimethylamine (SM: 13.05 µg/kg), hexanal (BF: 206.46 µg/kg), octanal (BF: 59.52 µg/kg), methanethiol (SM: 12.85 µg/kg), and valeric acid (BF: 15.08 µg/kg), which are positively correlated with Bacillus cereus, Bacillus subtilis, Bacillus licheniformis, Pseudomonas sp., Aspergillus ruber, and Moraxella osloensis. Furthermore, the physicochemical property and quality characteristics results showed that high moisture (BF: 56.32 g/100 g), pH (BF: 6.63), thiobarbituric acid reactive substances (TBARS) (SM: 1.98 MDA/kg), and low NaCl content (SM: 6.31%) were also responsible for the spoilage of hams with off-odour. This study provided a deep insight into the off-odour of Xuanwei ham from the perspective of microorganism communities and a theoretical basis for improving the flavour and overall quality of Xuanwei hams.

GhCOL2 Positively Regulates Flowering by Activating the Transcription of GhHD3A in Upland Cotton (Gossypium hirsutum L.).

Plants have evolved sophisticated signaling networks to adjust flowering time, ensuring successful reproduction. Two crucial flowering regulators, FLOWERING LOCUS T (FT) and CONSTANS (CO), play pivotal roles in regulating flowering across various species. Previous studies have indicated that suppressing Gossypium hirsutum CONSTANS-LIKE 2 (GhCOL2), a homolog of Arabidopsis CO, leads to delayed flowering in cultivated cotton. However, the underlying regulatory mechanisms remain unknown. In this study, a yeast one-hybrid and dual-LUC expression assays were used to elucidate the molecular mechanism through which GhCOL2 regulates the transcription of GhHD3A. RT-qPCR was used to examine the expression of GhCOL2 and GhHD3A. Our findings reveal that GhCOL2 directly binds to CCACA cis-elements and atypical CORE (TGTGTATG) cis-elements in the promoter regions of HEADING DATE 3 A (HD3A), thereby activating GhHD3A transcription. Notably, GhCOL2 and GhHD3A exhibited high expression levels in the adult stage and low levels in the juvenile stage. Interestingly, the expression of GhCOL2 and GhHD3A varied significant between the two cotton varieties (Tx2094 and Maxxa). In summary, our study enhances the understanding of the molecular mechanism by which cotton GhCOL2-GhHD3A regulates flowering at the molecular level. Furthermore, it contributes to a broader comprehension of the GhCOL2-GhHD3A model in G. hirsutum.

OFDR shape sensor based on a femtosecond-laser-inscribed weak fiber Bragg grating array in a multicore fiber.

An optical frequency domain reflectometry (OFDR) shape sensor was demonstrated based on a femtosecond-laser-inscribed weak fiber Bragg grating (WFBG) array in a multicore fiber (MCF). A WFBG array consisting of 60 identical WFBGs was successfully inscribed in each core along a 60 cm long MCF using the femtosecond-laser point-by-point technology, where the length and space of each WFBG were 2 and 8 mm, respectively. The strain distribution of each core in two-dimensional (2D) and three-dimensional (3D) shape sensing was successfully demodulated using the traditional cross correlation algorithm, attributed to the accurate localization of each WFBG. The minimum reconstruction error per unit length of the 2D and 3D shape sensors has been improved to 1.08% and 1.07%, respectively, using the apparent curvature vector method based on the Bishop frame.

Synergistic Effects of High-Intensity Ultrasound Combined with L-Lysine for the Treatment of Porcine Myofibrillar Protein Regarding Solubility and Flavour Adsorption Capacity.

This study aimed to investigate the synergistic effects of high-intensity ultrasound (0, 5, 10, 15, and 20 min) in combination with L-lysine (15 mM) on improving the solubility and flavour adsorption capacity of myofibrillar proteins (MPs) in low-ion-strength media. The results revealed that the ultrasound treatment for 20 min or the addition of L-lysine (15 mM) significantly improved protein solubility (p < 0.05), with L-lysine (15 mM) showing a more pronounced effect (p < 0.05). The combination of ultrasound treatment and L-lysine further increased solubility, and the MPs treated with ultrasound at 20 min exhibited the best dispersion stability in water, which corresponded to the lowest turbidity, highest absolute zeta potential value, and thermal stability (p < 0.05). Based on the reactive and total sulfhydryl contents, Fourier transform infrared spectroscopy, and fluorescence spectroscopy analysis, the ultrasound treatment combined with L-lysine (15 mM) promoted the unfolding and depolymerization of MPs, resulting in a larger exposure of SH groups on the surface, aromatic amino acids in a polar environment, and a transition of protein conformation from α-helix to ß-turn. Moreover, the combined treatment also increased the hydrophobic bonding sites, hydrogen-bonding sites, and electrostatic effects, thereby enhancing the adsorption capacity of MPs to bind kenone compounds. The findings from this study provide a theoretical basis for the production and flavour improvement of low-salt MP beverages and the utilisation of meat protein.

GOLPH3 promotes tumor malignancy via inhibition of ferroptosis by upregulating SLC7A11 in cholangiocarcinoma.

Golgi phosphoprotein 3 (GOLPH3) has been reported as an oncogene in various tumors; however, the role and function of GOLPH3 and its relevant molecular mechanism in cholangiocarcinoma (CCA) are unclear. Herein, GOLPH3 expression in CCA tissues was observed to be significantly higher than that in paired adjacent noncancerous tissues. Clinicopathological analysis showed that GOLPH3 expression correlated positively with the tumor-node-metastasis stage. In addition, GOLPH3 expression correlated inversely with the overall survival of patients with CCA. Multivariate analysis showed that GOLPH3 was an independent prognostic factor for patients with CCA. Transcriptome analysis (RNA sequencing) of GOLPH3 knockdown cells showed that the expression levels of nine ferroptosis-related genes were significantly changed, indicating the important biological function of GOLPH3 in ferroptosis in CCA cells. Furthermore, GOLPH3 knockdown could significantly promote Erastin-induced ferroptosis in vitro and suppress tumor growth in vivo. Overexpression of GOLPH3 had the opposite effect on this phenotype. Further studies revealed that GOLPH3 knockdown was significantly associated with a decrease in cysteine content, an accumulation of the lipid peroxidation product malondialdehyde, an increase in reactive oxygen species, and sensitized CCA cells to Erastin-induced ferroptosis. Moreover, changes in GOLPH3 expression were found to be consistent with the expression of light chain subunit solute carrier family 7 member 11 (SLC7A11). Thus, our study suggested that GOLPH3 functions as an oncoprotein in CCA and may suppress ferroptosis by facilitating SLC7A11 expression, suggesting that GOLPH3 could serve as a therapeutic target for CCA treatment.

Enhancing bread preservation through non-contact application of starch-based composite film infused with clove essential oil nanoemulsion.

In this study, we have successfully produced a corn starch-based composite film through the casting method, formulated with clove essential oil nanoemulsion (NCEO) and corn starch. The physical and chemical changes of the composite films were investigated at various concentrations (10 %, 20 % and 40 %) of NCEO. Furthermore, the non-contact preservation effects of the composite films on bread during 15-day storage were also examined in this study. As the concentration of NCEO increased, the composite films presented a gradual thinning, roughening, and yellowing in appearance. Following this, the water content, water vapor permeability rate, and elongation at break of the films decreased, while their hydrophobicity, tensile strength, antioxidant and antimicrobial activity increased accordingly. Through FT-IR, X-ray diffraction and thermal gravimetric analysis, it was demonstrated that NCEO has strong compatibility with corn starch. Additionally, the indices' analysis indicated that utilizing the composite film incorporating 40 % NCEO can significantly boost the shelf life and quality of bread. Moreover, it was revealed that application of the non-contact treatment with composite film could potentially contribute certain preservation effects towards bread. In light of these findings, the composite film with non-contact treatment exhibits potential as an effective, safe, and sustainable preservation technique for grain products.

International consensus guidelines on robotic pancreatic surgery in 2023.

Background: With the rapid development of robotic surgery, especially for the abdominal surgery, robotic pancreatic surgery (RPS) has been applied increasingly around the world. However, evidence-based guidelines regarding its application, safety, and efficacy are still lacking. To harvest robust evidence and comprehensive clinical practice, this study aims to develop international guidelines on the use of RPS. Methods: World Health Organization (WHO) Handbook for Guideline Development, GRADE Grid method, Delphi vote, and the AGREE-II instrument were used to establish the Guideline Steering Group, Guideline Development Group, and Guideline Secretary Group, formulate 19 clinical questions, develop the recommendations, and draft the guidelines. Three online meetings were held on 04/12/2020, 30/11/2021, and 25/01/2022 to vote on the recommendations and get advice and suggestions from all involved experts. All the experts focusing on minimally invasive surgery from America, Europe and Oceania made great contributions to this consensus guideline. Results: After a systematic literature review 176 studies were included, 19 questions were addressed and 14 recommendations were developed through the expert assessment and comprehensive judgment of the quality and credibility of the evidence. Conclusions: The international RPS guidelines can guide current practice for surgeons, patients, medical societies, hospital administrators, and related social communities. Further randomized trials are required to determine the added value of RPS as compared to open and laparoscopic surgery.

2-bromoacetamide exposure impairs oocyte maturation in mice and humans primarily via disrupting the cytoskeleton.

2-bromoacetamide (BAcAm) is an emerging class of unregulated disinfection by-products (DBPs), with potent cytogenetic and developmental toxicity in animals. However, whether BAcAm exerts toxic effects on mammalian oocyte quality remains to be elucidate. In this research, we investigated the effect of BAcAm on mouse and human oocyte maturation with an in vitro culture system. Our results revealed that BAcAm exposure hindered the extrusion of the first polar body, disrupted the spindle organization and reduced the competence of embryo development after fertilization in the mouse oocytes. Results of single-cell RNA sequencing (scRNA-seq) showed that 605 differentially expressed genes (DEGs) were identified in the BAcAm exposed mouse oocytes, among which 366 were up-regulated and 239 were down-regulated. Gene Ontology (GO) analysis further revealed that DEGs were mainly enriched in mitochondrial functions, oxidative stress, cytoskeleton, endoplasmic reticulum (ER), Golgi and protein synthesis, DNA damage and apoptosis. We then conducted further tests in these aspects and discovered that BAcAm exposure principally perturbed the function of microtubule and actin cytoskeleton. This finding was confirmed in human oocytes. Overall, our data suggest that BAcAm exposure disturbs the cytoskeleton function, thus impairing oocyte maturation. These data, for the first time, provide a comprehensive view for the toxic effects of BAcAm on oocyte maturation.

CSNK2A1 confers gemcitabine resistance to pancreatic ductal adenocarcinoma via inducing autophagy.

Gemcitabine, a pivotal chemotherapeutic agent for pancreatic ductal adenocarcinoma (PDAC), frequently encounters drug resistance, posing a significant clinical challenge with implications for PDAC patient prognosis. In this study, employing an integrated approach involving bioinformatic analyses from multiple databases, we unveil CSNK2A1 as a key regulatory factor. The patient-derived xenograft (PDX) model further substantiates the critical role of CSNK2A1 in gemcitabine resistance within the context of PDAC. Additionally, targeted silencing of CSNK2A1 expression significantly enhances sensitivity of PDAC cells to gemcitabine treatment. Mechanistically, CSNK2A1's transcriptional regulation is mediated by H3K27 acetylation in PDAC. Moreover, we identify CSNK2A1 as a pivotal activator of autophagy, and enhanced autophagy drives gemcitabine resistance. Silmitasertib, an established CSNK2A1 inhibitor, can effectively inhibit autophagy. Notably, the combinatorial treatment of Silmitasertib with gemcitabine demonstrates remarkable efficacy in treating PDAC. In summary, our study reveals CSNK2A1 as a potent predictive factor for gemcitabine resistance in PDAC. Moreover, targeted CSNK2A1 inhibition by Silmitasertib represents a promising therapeutic strategy to restore gemcitabine sensitivity in PDAC, offering hope for improved clinical outcomes.

Robotic-assisted organ-preserving or parenchymal-sparing pancreatectomy in pancreatic benign or low-grade malignant tumors: a single institute's experience.

AIM: Robotic-assisted pancreatectomy has been widely used. Organ-preserving pancreatectomy (OPP) and parenchymal-sparing pancreatectomy (PSP) has been gradually adopted for pancreatic benign or low-grade malignant tumors. This study aimed to evaluate the safety and efficacy of robotic-assisted OPP/PSP in our institute. METHODS: Patients undergoing robotic-assisted OPS/PSP at First Affiliated Hospital of Sun Yat-sen University between July 2015 and October 2021 were included in this study. The short-term and long-term outcomes of patients were retrospectively analyzed. RESULTS: Seventy-two patients were enrolled, including spleen-preserving distal pancreatectomy, central pancreatectomy, duodenum-preserving pancreatic head resection, and enucleation. Patients included were more likely to be young female (female: 46/72, median age: 47 years old). The median intraoperative blood loss and operation time was 50 ml and 255 min, respectively. Clinically relevant postoperative pancreatic fistula was 20.8% (grade B: 15/72, 20.8%; no grade C). The overall complication rate was 22.2% with the median postoperative length-of-stay of 8 days. At a median follow-up time of 28.5 months, the 5-year overall survival and recurrence-free survival rate were 100.0% and 100.0%, respectively. CONCLUSION: The short-term and long-term outcomes of patients receiving robotic-assisted OPP/PSP were acceptable. Robotic-assisted OPP/PSP was a feasible and safe technique for pancreatic benign or low-grade malignant lesions.

Gene-specific ACMG/AMP classification criteria for germline APC variants: Recommendations from the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel.

PURPOSE: The Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel (VCEP) was established by the International Society for Gastrointestinal Hereditary Tumours and the Clinical Genome Resource, who set out to develop recommendations for the interpretation of germline APC variants underlying Familial Adenomatous Polyposis, the most frequent hereditary polyposis syndrome. METHODS: Through a rigorous process of database analysis, literature review, and expert elicitation, the APC VCEP derived gene-specific modifications to the ACMG/AMP (American College of Medical Genetics and Genomics and Association for Molecular Pathology) variant classification guidelines and validated such criteria through the pilot classification of 58 variants. RESULTS: The APC-specific criteria represented gene- and disease-informed specifications, including a quantitative approach to allele frequency thresholds, a stepwise decision tool for truncating variants, and semiquantitative evaluations of experimental and clinical data. Using the APC-specific criteria, 47% (27/58) of pilot variants were reclassified including 14 previous variants of uncertain significance (VUS). CONCLUSION: The APC-specific ACMG/AMP criteria preserved the classification of well-characterized variants on ClinVar while substantially reducing the number of VUS by 56% (14/25). Moving forward, the APC VCEP will continue to interpret prioritized lists of VUS, the results of which will represent the most authoritative variant classification for widespread clinical use.

Comparison between percutaneous short-segment fixation and percutaneous vertebroplasty in treating Kummell's disease: A minimum 2-year follow-up retrospective study.

BACKGROUND: Percutaneous kyphoplasty (PKP) or percutaneous short-segment fixation (PSSF) is often used to treat Kummell's disease. However, it is not clear which treatment is better for patients. OBJECTIVE: To retrospectively compare the clinical efficacy of PVP and PSSF for the treatment of Kummell's disease. METHOD: 60 patients were involved in this research and the period of follow-up was at least 2 years. 27 of them were treated with PVP (Group I) and the rest who received PSSF (Group II). The visual analog scale (VAS) and radiographic indexes of each participant had been measured preoperatively as well as 1 week, 3 months, and 2 years postoperatively. Additionally, the Oswestry Disability Index (ODI) scores were assessed at the last time point. RESULTS: Comparing the two groups, no statistical significance was found among all parameters preoperatively. The time of operations and blood loss is less in Group I. At each time point after operation, the imaging indices in Group II are lower (P< 0.05). One week after treatments, the VAS scores are lower in Group I, and similarly, 3 months are the same (P< 0.05), while VAS are similar at the last time point. In the aspect of ODI scores, they are lower in Group II during long-term follow-up. CONCLUSION: For the treatment of Kummell's disease, both PVP and PSSF have been found to be effective. PVP can provide rapid pain relief with a shorter operation time. However, in cases with severe kyphosis deformity, PSSF should be given priority.

A radiomics-based interpretable model to predict the pathological grade of pancreatic neuroendocrine tumors.

OBJECTIVES: To develop a computed tomography (CT) radiomics-based interpretable machine learning (ML) model to predict the pathological grade of pancreatic neuroendocrine tumors (pNETs) in a non-invasive manner. METHODS: Patients with pNETs who underwent contrast-enhanced abdominal CT between 2010 and 2022 were included in this retrospective study. Radiomics features were extracted, and five radiomics-based ML models, namely logistic regression (LR), random forest (RF), support vector machine (SVM), XGBoost, and GaussianNB, were developed. The performance of these models was evaluated using a time-independent testing set, and metrics such as sensitivity, specificity, accuracy, and the area under the receiver operating characteristic curve (AUC) were calculated. The accuracy of the radiomics model was compared to that of needle biopsy. The Shapley Additive Explanation (SHAP) tool and the correlation between radiomics and biological features were employed to explore the interpretability of the model. RESULTS: A total of 122 patients (mean age: 50 ± 14 years; 53 male) were included in the training set, whereas 100 patients (mean age: 48 ± 13 years; 50 male) were included in the testing set. The AUCs for LR, SVM, RF, XGBoost, and GaussianNB were 0.758, 0.742, 0.779, 0.744, and 0.745, respectively, with corresponding accuracies of 73.0%, 70.0%, 77.0%, 71.9%, and 72.9%. The SHAP tool identified two features of the venous phase as the most significant, which showed significant differences among the Ki-67 index or mitotic count subgroups (p < 0.001). CONCLUSIONS: An interpretable radiomics-based RF model can effectively differentiate between G1 and G2/3 of pNETs, demonstrating favorable interpretability. CLINICAL RELEVANCE STATEMENT: The radiomics-based interpretable model developed in this study has significant clinical relevance as it offers a non-invasive method for assessing the pathological grade of pancreatic neuroendocrine tumors and holds promise as an important complementary tool to traditional tissue biopsy. KEY POINTS: • A radiomics-based interpretable model was developed to predict the pathological grade of pNETs and compared with preoperative needle biopsy in terms of accuracy. • The model, based on CT radiomics, demonstrated favorable interpretability. • The radiomics model holds potential as a valuable complementary technique to preoperative needle biopsy; however, it should not be considered a replacement for biopsy.

Unmasking Chemokine-Inducing Specificity in Oligosaccharide Biomaterial to Promote Hair Growth.

Hair loss affects over 50 million people worldwide with limited therapeutic options. Despite evidence highlighting the vital role of local immune cells in regulating the life cycle of hair follicles (HFs), accurate regulation of immunocytes to directly promote hair growth remains unachieved. Here, inspired by the physiological feedback in the skin immunity to suppress microbe-triggered inflammation, an oligosaccharide biomaterial with "unmasked" specific activity is developed to recruit regulatory T (Treg ) cells around HFs, leading to accelerated hair growth in mice. By processing the glucomannan polysaccharide via controllable enzymatic cleavage, a series of oligosaccharide fractions with more specific chemokine-inducing functions is obtained. Notably, a hexasaccharide-based fraction (OG6) stimulates macrophages to selectively express Treg -chemoattractant C-C Motif Chemokine Ligand 5 (CCL5) through a mannose receptor-mediated endocytosis and NOD1/2-dependent signaling, as evidenced by molecular docking, inhibition assays, and a Foxp3-reporter mouse model. Intradermal delivery of OG6 to the depilated mouse skin promotes Treg mobilization around HFs and stimulates de novo regeneration of robust hairs. This study demonstrates that unmasking precise immunomodulatory functions in oligosaccharides from their parental polysaccharide can potentially solve the long-lasting dilemma with polysaccharide biomaterials that are widely renowned for versatile activities yet high heterogeneity, opening new avenues to designing glycan-based therapeutic tools with improved specificity and safety.

Learning curve of robotic-assisted splenic vessel-preserving spleen-preserving distal pancreatectomy by one single surgeon: a retrospective cohort study.

AIM: Splenic vessel-preserving spleen-preserving distal pancreatectomy (SVP-SPDP) has a lower risk of splenic infarction than the splenicvessel-sacrificing SPDP, but it is more technically demanding. Learning curve of robotic-assisted SVP-SPDP (RSVP-SPDP) remains unreported. This study sought to analyze the perioperative outcomes and learning curve of RSVP-SPDP by one single surgeon. METHODS: Seventy-four patients who were intended to receive RSVP-SPDP at the First Affiliated Hospital of Sun Yat-sen University between May 2015 and January 2023 were included. The learning curve were retrospectively analyzed by using cumulative sum (CUSUM) analyses. RESULTS: Sixty-two patients underwent RSVP-SPDP (spleen preservation rate: 83.8%). According to CUSUM curve, the operation time (median, 318 vs. 220 min; P < 0.001) and intraoperative blood loss (median, 50 vs. 50 mL; P = 0.012) was improved significantly after 16 cases. Blood transfusion rate (12.5% vs. 3.4%; P = 0.202), postoperative major morbidity rate (6.3% vs. 3.4%; P = 0.524), and postoperative length-of-stay (median, 10 vs. 8 days; P = 0.120) improved after 16 cases but did not reach statistical difference. None of the patients had splenic infarction or abscess postoperatively. CONCLUSION: RSVP-SPDP was a safe and feasible approach for selected patients after learning curve. The improvement of operation time and intraoperative blood loss was achieved after 16 cases.

Wide-range OFDR strain sensor based on the femtosecond-laser-inscribed weak fiber Bragg grating array.

A wide-range OFDR strain sensor was demonstrated based on femtosecond-laser-inscribed weak fiber Bragg grating (WFBG) array in standard SMF. A WFBG array consisting of 110 identical WFBGs was successfully fabricated along a 56 cm-long SMF. Compared with SMF, the cross-correlation coefficient of WFBG array was improved to 0.9 under the strain of 10,000 µÎµ. The position deviation under the strain of 10,000 µÎµ, i.e., 2.5 mm, could be accurately obtained and compensated simply by using peak finding algorithm. The maximum measurable strain of single- and multi-point strain sensing was up to 10,000 µÎµ without using any additional algorithms, where the sensing spatial resolution was 5 mm.

Effects of Genes, Lifestyles, and Noise Kurtosis on Noise-Induced Hearing Loss.

Objective: To explore the association of lifestyles, caspase gene (CASP), and noise kurtosis with noise-induced hearing loss (NIHL). Design: Three hundred seven NIHL individuals and 307 matched controls from factories in Chinese factories participated in this case-control study. Age, sex, noise exposure, exfoliated oral mucosa cells, and lifestyles of participants were gathered by the authors. The single nucleotide polymorphisms (SNPs) were genotyped using the Kompetitive Allele Specific polymerase chain reaction (KASP) method. Results: The risk of NIHL was higher for people who worked in the complex noise environment than for people exposed to steady noise environment (adjusted: OR = 1.806, P = 0.002). Smoking and regular earphone use increased the risk of NIHL (adjusted: OR = 1.486, P = 0.038). The GG genotype of the recessive model and G allele in rs1049216, together with the TT genotype of the recessive model in rs6948 decreased the NIHL risk (adjusted: OR = 0.659, P = 0.017). Oppositely, the AA genotype of additive model in rs12415607 had a higher NIHL risk (adjusted: OR = 1.804, P = 0.024). In the additive models, there was a positive interaction between noise kurtosis and CASP3 polymorphisms (RERI = 1.294, P = 0.013; RERI = 1.198, P = 0.031). Conclusions: Noise kurtosis, three SNPs (rs1049216, rs6948, and rs12415607), smoking and earphone use were found to be related to NIHL, and there was a positive interaction between noise kurtosis and CASP3. Results from this study can be used to prevent and detect NIHL and for genetic testing.

Renin-angiotensin system inhibitors improve the survival of cholangiocarcinoma: a propensity score-matched cohort study.

BACKGROUND: Hypertension is a risk factor for cholangiocarcinoma (CCA). The effect of anti-hypertensive drugs on the prognosis of CCA is not clear. METHODS: This is a retrospective study of 102 patients (56.9% males, median age 66 years) diagnosed with CCA and hypertension concurrently and received radical surgery (R0), with a median follow-up of 36.7 months. Kaplan-Meier analysis, Cox regressions, and propensity score (PS) matching were applied for statistical analysis. RESULTS: Results of multivariable cox analysis showed that renin-angiotensin system inhibitors (RASis) usage was a protective factor for progression-free survival (PFS) (hazard ratio [HR] = 0.55, 95% confidence interval [95% CI]: 0.32-0.96) and overall survival (OS) (HR = 0.40, 95% CI: 0.20-0.79), respectively. Calcium channel blockers, diuretics, and ß-blockers didn't show significant associations. The association of RASis usage and PFS and OS was derived by PS matching, with a cohort of 28 RASis users and 56 RASis non-users. The median PFS and OS of RASis users (PFS, 17.6 months (9.2-34.4); OS, 24.8 months (16.5-42.3)) were longer than RASis non-users (PFS, 10.5 months (4.1-24.1); OS, 14.6 months (10.6-28.4)). The 1 year, 2 years, and 3 years' survival rates of RASis users (89.1%, 77.0%, and 65.5%) were higher than RASis non-users (70.9%, 54.0%, and 40.0%). CONCLUSIONS: RASis usage improves the survival of patients with CCA and hypertension concurrently.