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*

OBJECTIVE To investigate the types of neurons that influence the head twitch response(HTR)induced by 5-hydroxytryptaminergic(5-HTergic)psychedelic mescaline in mice.METHODS①Adult male C57BL/6J mice were randomly divided into the normal control group and mescaline(1.56,3.125,6.25,12.5,25 and 50 mg·kg-1)groups,with 15 mice in each group.The drugs of the corresponding groups were ip given,and the HTR frequency of mice was recorded for 30 min.② 5-HT 2A receptor(5-HT2AR)gene bilateral LoxP homozygous mice(5-HT2A flox/flox)were hybridized with calmodulin depen-dent protein kinaseⅡα cyclization recombination enzyme positive(CaMKⅡαcre/+),parvalbumin(PV)cre/+,somatostatin(SOM)cre/+or vasoactive intestinal peptide(VIP)cre/+mice to obtain 5-HT2A R conditional knockout(cKO)mice(5-HT2AΔCaMKⅡα,5-HT2AΔPV,5-HT2AΔSOM and 5-HT2AΔVIP).Each type of cKO mice was randomly divided into the normal control group and mescaline 12.5 mg·kg-1 group,with 15 mice in each group.The drugs of the corresponding groups were ip given before the HTR frequency of mice within 30 min was recorded.③ Each type of cKO mice was randomly divided into the normal control group and mescaline 12.5 mg·kg-1 group,with 12 mice in each group.After receiving the corresponding drug via ip,they were placed in a spontaneous activity test box for 30 minutes and their activity levels were recorded.RESULTS ① Compared with the normal control group,mescaline 3.125,6.25,12.5 and 25 mg·kg-1 significantly increased the HTRs of mice(P<0.05,P<0.01).② Among the different neuronal types of 5-HT2AR cKO mice,only 5-HT2A ΔCaMKⅡα mice had no difference in HTR frequency between the normal control group and the mescaline 12.5 mg·kg-1 group.In 5-HT2AΔPV,5-HT2AΔSOM and 5-HT2AΔVIP mice,the HTRs of mice in the mescaline 12.5 mg·kg-1 group were significantly increased(P<0.01)compared with the normal control group.③ There was no difference in spontaneous activity between the normal control group and the mescaline 12.5 mg·kg-1 group of all cKO mice.CONCLU-SION Pyramidal neurons are involved in mediating the induction of mescaline on HTRs in mice.

Objective:To evaluate the detection rate and distribution characteristics of lesions in patients with biochemical recurrence (BCR) after radical prostatectomy for prostate cancer by 68Ga-prostate specific membrane antigen (PSMA)-11 PET/CT. Methods:From January 2020 to March 2024, 68Ga-PSMA-11 PET/CT examination results of 172 patients (age (69.4±6.5) years) with BCR after radical prostatectomy in Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine were retrospectively analyzed. The relationship between prostate specific antigen (PSA) levels and 68Ga-PSMA-11 PET/CT detection rate was explored. The location and quantity of lesions detected by 68Ga-PSMA-11 PET/CT were analyzed in BCR patients with clear location after local treatment, and data were analyzed by Fisher exact test. Results:The detection rate of 68Ga-PSMA-11 PET/CT in patients with BCR was 70.35%(121/172). The positive detection rate increased with the increase of PSA level, with detection rates of 0.2 μg/L≤PSA<0.5 μg/L, 0.5 μg/L≤PSA<1.0 μg/L, 1.0 μg/L≤PSA<1.5 μg/L and PSA≥1.5 μg/L groups of 49.12%(28/57), 67.24%(39/58), 15/16 and 95.12%(39/41), respectively. After local treatment, 64 cases were diagnosed with 95 recurrent and metastatic lesions. Among them, 22(34.38%) had simple prostate bed recurrence, 23(35.94%) had simple lymph node metastasis, 7(10.94%) had simple bone metastasis, and 12(18.75%) had multi regional metastasis. The proportion of bone metastasis (18.75%, 12/64) was significantly lower than that of prostate bed recurrence and lymph node metastasis (both 50.00%(32/64); both P=0.002). Conclusions:68Ga-PSMA-11 PET/CT has a high detection rate in patients with BCR after radical prostatectomy, especially in patients with high PSA levels. The lesions are mainly distributed in the prostate bed and lymph nodes, while bone metastases are relatively rare, which provide a theoretical basis for the selection of more accurate treatment plans for BCR patients in the future.

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 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.

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.