Diabetic retinopathy(DR)is a prevalent microvascular complication of diabetes and a leading cause of vision loss globally.Although anti-vascular endothelial growth factor(anti-VEGF)therapies remain the clinical mainstay, a significant proportion of patients exhibit suboptimal responses, highlighting the urgent need for novel therapeutic targets. Calcitonin gene-related peptide(CGRP), a multifunctional neuropeptide, is gaining attention due to its roles in vascular regulation, neuroprotection, and immunomodulation. This review summarizes the biological characteristics of CGRP and its receptor-mediated signaling, and explores emerging evidence of CGRP's involvement in DR through its vasodilatory effects and regulatory effect on neurodegenerative disorders and release of inflammatory cytokines. Furthermore, the therapeutic potential of targeting the CGRP pathway in DR is evaluated, especially in cases unresponsive to VEGF inhibition. Despite currently the lack of CGRP-targeted drugs applied for DR, the peptide demonstrates efficacy and safety in other diseases, such as migraine, suggests promising translational opportunities. However, CGRP may play a dual role in different pathological stages of DR, thus its treatment strategy needs to be considered precisely. Future research elucidating the precise mechanisms of CGRP in DR may pave the way for innovative intervention strategies.

The armadillo repeat containing 5 (ARMC5) gene is part of a family of protein-coding genes that are rich in armadillo repeat sequences, are ubiquitously present in eukaryotes, and mediate interactions between proteins, playing roles in various cellular processes. Current research has demonstrated that reduced expression or absence of the ARMC5 gene in various tumor tissues can lead to uncontrolled cell proliferation, thereby inducing a range of diseases. The ARMC5 gene was initially extensively studied in the context of bilateral macronodular adrenocortical disease (BMAD), with harmful pathogenic variants in ARMC5 identified in approximately 50% of BMAD patients. With advancing research, scientists have discovered that ARMC5 pathogenic variants may also have potential effects on other diseases and could be associated with increased susceptibility to certain cancers. This review aims to present the latest research progress on how the ARMC5 gene plays its role in tumors. It outlines the basic structure of ARMC5 and the regions where it functions, as well as the diseases currently proven to be associated with ARMC5. Moreover, some evidence suggests its relation to embryonic development and the regulation of immune system activity. In conclusion, the ARMC5 gene is a crucial focal point in genetic and medical research. Understanding its function and regulation is of great importance for the development of new therapeutic strategies related to diseases associated with its pathogenic variants.
Humans ; Neoplasms/genetics* ; Armadillo Domain Proteins/genetics* ; Animals ; Genetic Predisposition to Disease ; Cytoskeletal Proteins/genetics* ; Tumor Suppressor Proteins/genetics*

Objectives:This study aims to explore the clinical significance of lateral pelvic sentinel lymph node biopsy (SLNB) using indocyanine green (ICG) fluorescence navigation in laparoscopic lateral pelvic lymph node dissection (LLND) and evaluate the accuracy and feasibility of this technique to predict the status of lateral pelvic lymph nodes (LPLNs).Methods:The clinical and pathological characteristics, surgical outcomes, lymph node findings and perioperative complications of 16 rectal cancer patients who underwent SLNB using ICG fluorescence navigation in laparoscopic LLND in the Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College during April 2017 and October 2022 were retrospectively collected and analyzed. The patients did not receive preoperative neoadjuvant radiotherapy and presented with LPLNs but without LPLN enlargement (MRI showed the maximum short axes of the LPLNs were ≥5 mm and <10 mm at first visit).Results:All 16 patients were successfully performed SLNB using ICG fluorescence navigation in laparoscopic LLND. Three patients underwent bilateral LLND and 13 patients underwent unilateral LLND. The lateral pelvic sentinel lymph nodes (SLNs) were clearly fluorescent before dissection in 14 patients and the detection rate of SLNs for these patients was 87.5%. Lateral pelvic SLN metastasis was diagnosed in 2 patients and negative results were found in 12 patients by frozen pathological examinations. Among the 14 patients in whom lateral pelvic SLNs were detected, the dissected lateral pelvic non-SLNs were all negative. All dissected LPLNs were negative in two patients without fluorescent lateral pelvic SLNs. The specificity, sensitivity, negative predictive value, and accuracy was 85.7%, 100%, 100%, and 100%, respectively.Conclusions:This study indicates that lateral pelvic SLNB using ICG fluorescence navigation shows promise as a safe and feasible procedure with good accuracy. This technique may replace preventive LLND for locally advanced lower rectal cancer.

Objectives:To assess the prognostic impact of the neoadjuvant rectal (NAR) score following neoadjuvant short-course radiotherapy and consolidation chemotherapy in locally advanced rectal cancer (LARC), as well as its value in guiding decisions for adjuvant chemotherapy.Methods:Between August 2015 and August 2018, patients were eligible from the STELLAR phase III trial (NCT02533271) who received short-course radiotherapy plus consolidation chemotherapy and for whom the NAR score could be calculated. Based on the NAR score, patients were categorized into low (＜8), intermediate (8-16), and high (＞16) groups. The Kaplan-Meier method, log rank tests, and multivariate Cox proportional hazard regression models were used to evaluate the impact of the NAR score on disease-free survival (DFS).Results:Out of the 232 patients, 24.1%, 48.7%, and 27.2% had low (56 cases), intermediate (113 cases), and high NAR scores (63 cases), respectively. The median follow-up period was 37 months, with 3-year DFS rates of 87.3%, 68.3%, and 53.4% ( P＜0.001) for the low, intermediate, and high NAR score groups. Multivariate analysis demonstrated that the NAR score (intermediate NAR score: HR, 3.10, 95% CI, 1.30-7.37, P=0.011; high NAR scores: HR=5.44, 95% CI, 2.26-13.09, P＜0.001), resection status ( HR, 3.00, 95% CI, 1.64-5.52, P＜0.001), and adjuvant chemotherapy ( HR, 3.25, 95% CI, 2.01-5.27, P＜0.001) were independent prognostic factors for DFS. In patients with R0 resection, the 3-year DFS rates were 97.8% and 78.0% for those with low and intermediate NAR scores who received adjuvant chemotherapy, significantly higher than the 43.2% and 50.6% for those who did not ( P＜0.001, P=0.002). There was no significant difference in the 3-year DFS rate (54.2% vs 53.3%, P=0.214) among high NAR score patients, regardless of adjuvant chemotherapy. Conclusions:The NAR score is a robust prognostic indicator in LARC following neoadjuvant short-course radiotherapy and consolidation chemotherapy, with potential implications for subsequent decisions regarding adjuvant chemotherapy. These findings warrant further validation in studies with larger sample sizes.

Objective:To understand the prevalence, blood pressure control, and influencing factors of hypertension in residents aged 35-75 years in Jiangsu Province, and provide data support and basis for hypertension prevention and treatment.Methods:A stratified cluster sampling method was adopted to conduct community population surveys in 22 districts and counties in 12 prefectures in Jiangsu from 2021 to 2022. A total of 123 531 permanent residents aged 35-75 years were included in the study. The questionnaire survey collected the information about the demographic characteristics, disease history, lifestyle, and control of hypertension of study subjects. Statistical software SPSS 23.0 was used for χ2 test and multivariate logistic regression analysis, and Joinpoint 4.9.1.0 software was used to evaluate the trend of age change. Results:The standardized prevalence of hypertension in study subjects was 46.60%, the prevalence was higher in men than in women, and in rural residents than in urban residents, and the standardized blood pressure control rate was 11.24%, and it was lower in men than in women and in rural residents than in urban residents. The hypertension prevalence and control rates showed increasing trends with age (both P<0.001). The multivariate analysis results showed that being man, older age, being rural resident, higher frequency of alcohol consumption, marital status of being separated and widowed, overweight and obese, abdominal obesity and stroke, diabetes mellitus and dyslipidaemic diseases histories, and family history of hypertension were risk factors for hypertension, and being man, being rural resident, living north area, higher frequency of alcohol consumption, and obesity were risk factors for blood pressure control. Conclusions:The prevalence of hypertension in residents aged 35-75 years in Jiangsu was high, and the rate of blood pressure control was low. It is suggested to take integrated intervention measures, especially in in rural residents and people with low levels of education to reduce the disease burden of the patients.

AIM:To explore the effect of the peripheral defocus spectacle lenses and orthokeratology(OK)on the control of myopia progression and the impact on vision related quality of life in children and adolescents.METHODS:Prospective study. A total of 237 children initially diagnosed with myopia in the ophthalmology department of Huzhou Central Hospital from January 2021 to January 2022 were selected and divided into two groups according to different correction methods: peripheral defocus spectacle lenses group(105 cases, 105 eyes)and OK lens group(132 cases, 132 eyes). The Vision Related Quality of Life Questionnaire for Primary and Secondary School Students was used to follow up the both groups of myopic children, and the best corrected visual acuity(BCVA), spherical equivalent(SE), and axial length(AL)were recorded at the first visit and 1 a of follow-up.RESULTS:After wearing lenses for 1 a, both the peripheral defocus spectacle lenses group and OK lens group showed an increase in SE and AL, but there was no statistical difference between two groups(P>0.05). The changes in SE and AL in the peripheral defocus spectacle lenses group were greater than those in the OK lens group(all P=0.001). After 1 a of follow-up, in the emotional dimension scores, the peripheral defocus spectacle lenses group of children's vision-related quality of life scales scored higher than in the OK lens group(P<0.05). Compared with the baseline value, the change in the emotional dimension scores of the OK lens group was greater than that in the peripheral defocus spectacle lens group(P<0.05).CONCLUSION:OK lenses are superior to peripheral defocus spectacle lenses in controlling the progression of myopia in children and adolescents. Both correction methods can significantly improve myopic children's vision-related quality of life, with OK lenses being better at improving the emotional dimension of vision-related quality of life.

Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APC^min/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.

Objective To evaluate the accuracy and clinical application value of the fluorescence quantitative PCR melting curve meth-od for detecting fungal nucleic acid.Methods 460 suspected or confirmed patients with respiratory fungal infections were enrolled in the study.The fluorescence quantitative PCR melting curve method was used as the test method,and the fungal 26S rRNA gene nucleic acid detection kit combined with Sanger sequencing was used as the reference method.Sputum samples from each study subject were collected and detected by the test method and reference method,respectively.The Kappa value of the two methods was calculated to evaluate the consistency of the results.Results Compared with the reference method,the overall conformity rate of the test method was 92.83%(427/460).Compared with the reference method,the positive conformity rates,negative conformity rates,and overall conformity rates of the test method for detecting 8 fungi,including Candida albicans,Candida glabrata,Candida krusei,Candida trop-icalis,Candida parapsilosis,Cryptococcus neoformans,Candida guilliermondii,and Aspergillus,were 97.34%(183/188),97.06%(264/272),and 97.17%(447/460),100.00%(33/33),99.77%(426/427),and 99.78%(459/460),100.00%(16/16),99.55%(442/444),and 99.57%(458/460),98.11%(52/53),99.75%(442/444),and 99.57%(458/460),95.08%(58/61),99.50%(397/399),and 98.91%(455/460),100.00%(9/9),99.56%(449/451),and 99.57%(458/460),85.00%(17/20),99.32%(437/440),and 98.70%(454/460),and 97.59%(81/83),97.88%(369/377),and 97.83%(450/460),respectively.The Kappa values for the consistency evaluation of the two methods'detection results were both greater than 0.8.Upon retesting the inconsistent re-sults of the two methods,it was found that 53.7%(22/41)of the detection results were consistent with the test method,and the others were consistent with the reference method.Conclusion The fluorescence quantitative PCR melting curve method can simultaneously detect 8 kinds of fungi,and the detection results are highly consistent with the reference method.It has unique advantages in fungal de-tection and important clinical application value.

This article systematically elaborates on the origin and development of natural orifice specimen extraction surgery(NOSES)in the treatment of colorectal tumors.By analyzing several retrospective studies,we summarize the scientific basis,feasibility,and clinical advantages of applying NOSES in the treatment of colorectal tumors.Additionally,the article points out certain limitations in terms of operational techniques and the selection of indications for NOSES,which require continuous optimization and improvement.Advancements in technology have enabled NOSES to become increasingly integrated with new technologies.Accordingly,its application prospects in colorectal surgery and across multiple disciplines are broadened.