OBJECTIVES: To explore the potential of pyrroline-5-carboxylate reductase 1 (PYCR1) as a pan-cancer biomarker and investigate its expression, function, and clinical significance in bladder cancer (BLCA). METHODS: Bioinformatics analysis was conducted to evaluate the associations of PYCR1 with prognosis, immune microenvironment remodeling, tumor mutation burden (TMB), and microsatellite instability (MSI) in cancer patients. Using the TCGA-BLCA dataset, univariate and multivariate regression analyses were performed to assess the potential of PYCR1 as an independent prognostic risk factor for BLCA, and a clinical decision model was constructed. The IMvigor210 cohort was utilized to evaluate the potential of PYCR1 for independently predicting the efficacy of immunotherapy. The pRRophetic was employed to screen candidate chemotherapeutic agents for treating BLCA with high PYCR1 expression. The CMap-XSum algorithm and molecular docking techniques were used to explore and validate small molecule inhibitors of PYCR1. RESULTS: A high expression of PYCR1 was significantly associated with poor prognosis, immune cell infiltration, TMB and MSI in various tumors (r>0.3). PYCR1 was overexpressed in BLCA, and high PYCR1 expression was closely related to poor prognosis in BLCA patients (HR: 1.14, 95% CI: 1.02-1.68, P=0.006). The IC₅₀ of the anti-cancer drugs cetuximab, 5-fluorouracil, and doxorubicin increased significantly in BLCA cell lines with high PYCR1 expressions (P<0.0001). CONCLUSIONS High PYCR1 expression is an independent risk factor for poor prognosis in BLCA patients and can serve as a significant indicator for clinical decision-making as well as a marker for predicting sensitivity to chemotherapeutic agents and the efficacy of immunotherapy.
Humans ; Urinary Bladder Neoplasms/genetics* ; Immunotherapy ; Prognosis ; Pyrroline Carboxylate Reductases/metabolism* ; Biomarkers, Tumor/genetics* ; delta-1-Pyrroline-5-Carboxylate Reductase ; Microsatellite Instability ; Tumor Microenvironment ; Mutation ; Computational Biology ; Molecular Docking Simulation

Bacillus is a class of spore-producing Gram-positive bacteria that produce a variety of antimicrobial substances with different structures and functions. The application of the antimicrobial substances produced by Bacillus can effectively inhibit the activity of harmful bacteria and fungi and promote the sustainable development of green agriculture. The antimicrobial substances produced by Bacillus mainly include proteins, lipopeptides, polyketones, and polypeptides. This paper reviews the synthesis gene clusters, synthesis pathways, structures, and mechanisms of various antimicrobial substances produced by Bacillus and discusses the challenges in the industrial application of these antimicrobial substances. Furthermore, this paper clarifies the future research and development focuses and prospects the application prospects, and provides comprehensive theoretical support for the in-depth research and wide application of the antimicrobial substances produced by Bacillus.
Bacillus/genetics* ; Anti-Infective Agents/metabolism* ; Bacterial Proteins/genetics* ; Antimicrobial Peptides/biosynthesis* ; Lipopeptides/biosynthesis*

Objective:To explore the advantages of internet-based smart healthcare for full-cycle transcatheter edge-to-edge repair (TEER) management in reducing postoperative adverse events rate, improving cardiac function, and enhancing quality of life.Methods:This retrospective study enrolled patients with mitral regurgitation who underwent transcatheter TEER at Beijing Anzhen Hospital Valve Intervention Center between June 2021 and September 2023. Patients were classified into degeneration mitral regurgitation (DMR) and functional mitral regurgitation (FMR) according to etiology, with further stratification by enrollment period into usual care group (June 2021 to October 2022) and full-cycle management group (November 2022 to September 2023). The 1-year postoperative follow-up data were collected and compared between subgroups with the same etiology. Kaplan-Meier survival curves were plotted, and log-rank tests were used to compare the differences in major endpoint event-free survival rates between the two groups. Univariate and multivariate Cox regression and logistic regression analyses were performed to evaluate the impact of the full-cycle management system on patients′ outcomes.Results:A total of 130 patients were included, aged (72.0±8.6) years, including 82 (63%) males. DMR was identified in 84 cases (40 in the usual care group and 44 in the full-cycle management group), while FMR was observed in 46 cases (27 in the usual care group and 19 in the full-cycle management group). Kaplan-Meier analysis demonstrated higher 1-year major endpoint event-free survival rates in the full-cycle management group compared to the usual care group, though the difference was not statistically significant (log-rank P>0.05). Compared to the usual care group, the full-cycle management group showed significantly higher proportions of New York Heart Association classification Ⅰ-Ⅱ patients (DMR: 67% vs. 52%, P=0.031; FMR: 68% vs. 52%, P=0.021), greater 6-minute walking distances (DMR: (346.39±70.41) m vs. (294.11±60.47) m, P=0.012; FMR: (356.60±54.68) m vs. (318.55±39.02) m, P=0.004), and superior Kansas City Cardiomyopathy Questionnaire scores (DMR: 81.50 (74.50, 85.00) points vs. 71.00 (66.00, 82.25) points, P=0.014; FMR: 83.00 (76.00, 85.00) points vs. 74.00 (70.75, 80.00) points, P=0.030). Multivariate logistic regression confirmed the full-cycle management system as an independent predictor for the above improved outcomes (all P<0.05). Conclusion:Smart healthcare-based full-cycle management improves cardiac function and quality of life in mitral regurgitation patients after TEER, demonstrating lower rates of major endpoint events compared to usual care.

Objective:To evaluate the effects of wearing defocus incorporated multiple segments (DIMS) spectacle lenses on binocular visual function and visual quality in myopic children.Methods:A randomized double-blind controlled study was conducted.A total of 176 children (352 eyes) with myopia aged 6 to 15 years were enrolled in the West China Hospital of Sichuan University from January 2021 to March 2022.They were randomly divided into DIMS group of 85 cases (170 eyes) and single-vision group of 91 cases (182 eyes) wearing DIMS and single-vision lenses, respectively, using the random number table method.A total of 151 cases (302 eyes) who completed follow-up visits were included in the analysis, including 72 cases (144 eyes) in the DIMS group and 79 cases (158 eyes) in the single-vision group.Before and after 6 and 12 months of lens wear, accommodation amplitude, binocular accommodative sensitivity, distance/near horizontal eye position, and accommodative convergence/accommodation (AC/A) of subjects were measured.Changes in visual function over the year were compared between the two groups.In addition, subjective contrast sensitivity (CS) was assessed at each follow-up visit to evaluate the effect of the lenses on visual quality.The study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of West China Hospital of Sichuan University (No.2020-06).Parents or legal guardians signed written informed consent before the child's participation.Results:There were significant differences in monocular accommodation amplitude and binocular accommodation sensitivity at different time points between before and after lens wear in both groups (Wald χ2time=84.435, 48.201; both P<0.001).In both groups, monocular accommodation amplitude was decreased and the biocular accommodation sensitivity was increased at 6 and 12 months after wearing glasses compared with baseline (all P<0.001).After 12 months of lens wear, the monocular accommodation amplitude decreased by 2.68 D (95% CI: 1.60-3.75 D) in DIMS group and 2.82 D (95% CI: 1.81-3.84 D) in single-vision group.There were statistically significant differences in distance and near horizontal eye position between the two groups at different time points before and after wearing glasses (Wald χtime2=10.398, 23.947; both P<0.01).In the DIMS group, after 12 months of wearing lenses, the distance horizontal eye position drifted outward by 0.68 △(95% CI: 0.06-1.25 △) compared to baseline, with a significant difference ( P<0.05).There was 1.67 △ (95% CI: 0.15-3.20 △) outward drift at near horizontal eye position in the DIMS group and 1.73 △ (95% CI: 0.49-2.96 △) outward drift in the single-vision group compared with baseline, with significant differences (both P<0.05).There were statistically significant differences in gradient AC/A values and calculated AC/A values between the two groups at different time points before and after wearing glasses (Wald χtime2=22.001, 13.411; both P<0.01).After 12 months of wearing glasses, the gradient AC/A values significantly decreased in both groups compared to respective baseline, and the calculated AC/A values in the single-vision group showed a significant decrease compared to baseline (all P<0.05).There were no significant difference in the monocular accommodation amplitude, binocular accommodation sensitivity, distance and near horizontal eye position, gradient AC/A values and calculated AC/A values between the two groups (Wald χgroup2=2.385, 2.266, 2.070, 0.571, 0.578, 0.053; all P>0.05).There was no significant difference in the CS at 3, 6, 12, and 18 cpd spatial frequencies between the two groups at different time points before and after wearing lenses (Wald χ2group=1.104, 2.263, 1.861, 3.671; all P>0.05.Wald χ2time=2.260, 5.382, 2.573, 1.637; all P>0.05). Conclusions:Visual function performance after wearing DIMS lenses is consistent with that after wearing single-vision lenses.Wearing DIMS lenses has no obvious negative effect on the long-term visual quality in children.

Objective:To explore the characteristics of peripheral retinal defocus distribution in adult myopia and its relationship with refractive error.Methods:A cross-sectional study was conducted.A total of 270 myopic patients aged 18 to 46 years were enrolled at Tianjin Eye Hospital from January to March 2024.Data from the right eye were included in the analysis.Spherical power and cylindrical power were obtained using an autorefractor and the spherical equivalent (SE) was calculated.Corneal curvature parameters including flap keratometry (K1), steep keratometry (K2), and average keratometry (Km) were measured using the Pentacam anterior segment imaging analyzer.Central corneal thickness (CCT) and axial length (AL) were measured using the IOLMaster optical biometer.Peripheral defocus within a 53° area centered on the fovea was assessed using multispectral refractive topography.Based on the peripheral defocus data, the distribution patterns were classified into four types: hemilateral upturn type, saddle type, crater type, and relatively flat type.Characteristics of different tpes and their correlation with diopter were analyzed.This study followed the Declaration of Helsinki.The study protocol was reviewed and approved by the Medical Ethics Committee of Tianjin Eye Hospital (No.KY-2024020).All participants voluntarily participated and signed the informed consent form.Results:Of the different types of peripheral retinal defocus, 186 eyes (68.63%) were hemilateral upturn type, 45 eyes (16.61%) were crater type, 36 eyes (13.28%) were relatively flat type, and 3 eyes (1.11%) were saddle type.The crater type exhibited the lowest mean SE of (-6.18±1.50)D, while the relatively flat type showed the highest mean SE of (-3.88±0.87)D.There were significant differences in SE and AL among different peripheral defocus types ( F=15.469, 17.928, 3.431; all P<0.05).The hemilateral upturn type had significantly lower SE and spherical diopter than the relatively flat type, and crater type had significantly lower SE and spherical diopter compared to the hemilateral upturn type and relatively flat type significantly, and the hemilateral upturn type had longer AL than the relatively flat type (all P<0.05).There was no statistically significant difference in CCT, K1, K2, or Km among different peripheral defocus types ( F=0.861, 1.761, 2.603, 2.248; all P>0.05).Spherical power was weakly negatively correlated with superior, inferior, and temporal peripheral defocus ( r=-0.269, P<0.001; r=-0.176, P<0.01; r=-0.292, P<0.001).Age was positively correlated with superior and temporal peripheral defocus ( rs=0.213, P<0.001; rs=0.181, P=0.003), and negatively correlated with nasal peripheral defocus ( rs=-0.138, P=0.023). Conclusions:Among adult peripheral defocus patterns, the hemilateral upturn type is predominant.The crater type has the lowest mean spherical equivalent, while the relatively flat type has the highest.There are negative correlations between spherical power and the superior, inferior, and temporal peripheral defocus.

Objective:To explore the advantages of internet-based smart healthcare for full-cycle transcatheter edge-to-edge repair (TEER) management in reducing postoperative adverse events rate, improving cardiac function, and enhancing quality of life.Methods:This retrospective study enrolled patients with mitral regurgitation who underwent transcatheter TEER at Beijing Anzhen Hospital Valve Intervention Center between June 2021 and September 2023. Patients were classified into degeneration mitral regurgitation (DMR) and functional mitral regurgitation (FMR) according to etiology, with further stratification by enrollment period into usual care group (June 2021 to October 2022) and full-cycle management group (November 2022 to September 2023). The 1-year postoperative follow-up data were collected and compared between subgroups with the same etiology. Kaplan-Meier survival curves were plotted, and log-rank tests were used to compare the differences in major endpoint event-free survival rates between the two groups. Univariate and multivariate Cox regression and logistic regression analyses were performed to evaluate the impact of the full-cycle management system on patients′ outcomes.Results:A total of 130 patients were included, aged (72.0±8.6) years, including 82 (63%) males. DMR was identified in 84 cases (40 in the usual care group and 44 in the full-cycle management group), while FMR was observed in 46 cases (27 in the usual care group and 19 in the full-cycle management group). Kaplan-Meier analysis demonstrated higher 1-year major endpoint event-free survival rates in the full-cycle management group compared to the usual care group, though the difference was not statistically significant (log-rank P>0.05). Compared to the usual care group, the full-cycle management group showed significantly higher proportions of New York Heart Association classification Ⅰ-Ⅱ patients (DMR: 67% vs. 52%, P=0.031; FMR: 68% vs. 52%, P=0.021), greater 6-minute walking distances (DMR: (346.39±70.41) m vs. (294.11±60.47) m, P=0.012; FMR: (356.60±54.68) m vs. (318.55±39.02) m, P=0.004), and superior Kansas City Cardiomyopathy Questionnaire scores (DMR: 81.50 (74.50, 85.00) points vs. 71.00 (66.00, 82.25) points, P=0.014; FMR: 83.00 (76.00, 85.00) points vs. 74.00 (70.75, 80.00) points, P=0.030). Multivariate logistic regression confirmed the full-cycle management system as an independent predictor for the above improved outcomes (all P<0.05). Conclusion:Smart healthcare-based full-cycle management improves cardiac function and quality of life in mitral regurgitation patients after TEER, demonstrating lower rates of major endpoint events compared to usual care.

Objective:To evaluate the effects of wearing defocus incorporated multiple segments (DIMS) spectacle lenses on binocular visual function and visual quality in myopic children.Methods:A randomized double-blind controlled study was conducted.A total of 176 children (352 eyes) with myopia aged 6 to 15 years were enrolled in the West China Hospital of Sichuan University from January 2021 to March 2022.They were randomly divided into DIMS group of 85 cases (170 eyes) and single-vision group of 91 cases (182 eyes) wearing DIMS and single-vision lenses, respectively, using the random number table method.A total of 151 cases (302 eyes) who completed follow-up visits were included in the analysis, including 72 cases (144 eyes) in the DIMS group and 79 cases (158 eyes) in the single-vision group.Before and after 6 and 12 months of lens wear, accommodation amplitude, binocular accommodative sensitivity, distance/near horizontal eye position, and accommodative convergence/accommodation (AC/A) of subjects were measured.Changes in visual function over the year were compared between the two groups.In addition, subjective contrast sensitivity (CS) was assessed at each follow-up visit to evaluate the effect of the lenses on visual quality.The study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of West China Hospital of Sichuan University (No.2020-06).Parents or legal guardians signed written informed consent before the child's participation.Results:There were significant differences in monocular accommodation amplitude and binocular accommodation sensitivity at different time points between before and after lens wear in both groups (Wald χ2time=84.435, 48.201; both P<0.001).In both groups, monocular accommodation amplitude was decreased and the biocular accommodation sensitivity was increased at 6 and 12 months after wearing glasses compared with baseline (all P<0.001).After 12 months of lens wear, the monocular accommodation amplitude decreased by 2.68 D (95% CI: 1.60-3.75 D) in DIMS group and 2.82 D (95% CI: 1.81-3.84 D) in single-vision group.There were statistically significant differences in distance and near horizontal eye position between the two groups at different time points before and after wearing glasses (Wald χtime2=10.398, 23.947; both P<0.01).In the DIMS group, after 12 months of wearing lenses, the distance horizontal eye position drifted outward by 0.68 △(95% CI: 0.06-1.25 △) compared to baseline, with a significant difference ( P<0.05).There was 1.67 △ (95% CI: 0.15-3.20 △) outward drift at near horizontal eye position in the DIMS group and 1.73 △ (95% CI: 0.49-2.96 △) outward drift in the single-vision group compared with baseline, with significant differences (both P<0.05).There were statistically significant differences in gradient AC/A values and calculated AC/A values between the two groups at different time points before and after wearing glasses (Wald χtime2=22.001, 13.411; both P<0.01).After 12 months of wearing glasses, the gradient AC/A values significantly decreased in both groups compared to respective baseline, and the calculated AC/A values in the single-vision group showed a significant decrease compared to baseline (all P<0.05).There were no significant difference in the monocular accommodation amplitude, binocular accommodation sensitivity, distance and near horizontal eye position, gradient AC/A values and calculated AC/A values between the two groups (Wald χgroup2=2.385, 2.266, 2.070, 0.571, 0.578, 0.053; all P>0.05).There was no significant difference in the CS at 3, 6, 12, and 18 cpd spatial frequencies between the two groups at different time points before and after wearing lenses (Wald χ2group=1.104, 2.263, 1.861, 3.671; all P>0.05.Wald χ2time=2.260, 5.382, 2.573, 1.637; all P>0.05). Conclusions:Visual function performance after wearing DIMS lenses is consistent with that after wearing single-vision lenses.Wearing DIMS lenses has no obvious negative effect on the long-term visual quality in children.

Objective:To explore the characteristics of peripheral retinal defocus distribution in adult myopia and its relationship with refractive error.Methods:A cross-sectional study was conducted.A total of 270 myopic patients aged 18 to 46 years were enrolled at Tianjin Eye Hospital from January to March 2024.Data from the right eye were included in the analysis.Spherical power and cylindrical power were obtained using an autorefractor and the spherical equivalent (SE) was calculated.Corneal curvature parameters including flap keratometry (K1), steep keratometry (K2), and average keratometry (Km) were measured using the Pentacam anterior segment imaging analyzer.Central corneal thickness (CCT) and axial length (AL) were measured using the IOLMaster optical biometer.Peripheral defocus within a 53° area centered on the fovea was assessed using multispectral refractive topography.Based on the peripheral defocus data, the distribution patterns were classified into four types: hemilateral upturn type, saddle type, crater type, and relatively flat type.Characteristics of different tpes and their correlation with diopter were analyzed.This study followed the Declaration of Helsinki.The study protocol was reviewed and approved by the Medical Ethics Committee of Tianjin Eye Hospital (No.KY-2024020).All participants voluntarily participated and signed the informed consent form.Results:Of the different types of peripheral retinal defocus, 186 eyes (68.63%) were hemilateral upturn type, 45 eyes (16.61%) were crater type, 36 eyes (13.28%) were relatively flat type, and 3 eyes (1.11%) were saddle type.The crater type exhibited the lowest mean SE of (-6.18±1.50)D, while the relatively flat type showed the highest mean SE of (-3.88±0.87)D.There were significant differences in SE and AL among different peripheral defocus types ( F=15.469, 17.928, 3.431; all P<0.05).The hemilateral upturn type had significantly lower SE and spherical diopter than the relatively flat type, and crater type had significantly lower SE and spherical diopter compared to the hemilateral upturn type and relatively flat type significantly, and the hemilateral upturn type had longer AL than the relatively flat type (all P<0.05).There was no statistically significant difference in CCT, K1, K2, or Km among different peripheral defocus types ( F=0.861, 1.761, 2.603, 2.248; all P>0.05).Spherical power was weakly negatively correlated with superior, inferior, and temporal peripheral defocus ( r=-0.269, P<0.001; r=-0.176, P<0.01; r=-0.292, P<0.001).Age was positively correlated with superior and temporal peripheral defocus ( rs=0.213, P<0.001; rs=0.181, P=0.003), and negatively correlated with nasal peripheral defocus ( rs=-0.138, P=0.023). Conclusions:Among adult peripheral defocus patterns, the hemilateral upturn type is predominant.The crater type has the lowest mean spherical equivalent, while the relatively flat type has the highest.There are negative correlations between spherical power and the superior, inferior, and temporal peripheral defocus.

A young female patient with acne and elevated testosterone level underwent plasma steroid hormones testing and found a significant increase in aldosterone. We excluded testing interference and verified the absence of hypertension, hypokalemia, and adrenal occupancy, as well as primary and secondary hyperaldosteronism. During follow-up, a temporal correlation was found between aldosterone levels and the use of drospirenone and ethinylestradiol tablets. It was observed that the combination of drospirenone and ethinylestradiol could lead to the increase of aldosterone level and the concentration ratio of aldosterone to direct renin through different mechanisms. Drospirenone exerts an antagonistic effect on mineralocorticoid receptor to prevent the development of hypertension or hypokalemia. In clinical practice, it is necessary to pay attention to the effect of this drug on screening markers for primary aldosteronism. In the laboratory examination, when female patients with no symptoms of hypertension and hypokalemia but with elevated aldosterone levels are encountered, it can be verified whether they have a history of use of compound estrogen-progestin such as drospirenone and ethinylestradiol tablets, and appropriate tips are provided in the report.