Antibiotic resistance is spreading at a faster rate than new antibiotic agents applied for clinical remedies. It is an urgent need to discover potential compounds to combat multidrug-resistant (MDR) bacteria. Marine fungi offer a promising avenue for mining antibiotic-like molecules with chemical diversity. To discover structurally novel and antibiotic metabolites, we screened the in-house marine fungus genome library and found a fungus Stephanonectria keithii LZD-10-1 containing a non-ribosomal peptide synthetase (NRPS) cluster with 18 modules to synthesize a new subfamily of peptaibols with effective eradication against MDR pathogens. Targeting isolation of the cultured fungus afforded six new peptaibols, which exhibit the ability to kill MDR bacteria by targeting bacterial membrane phospholipids, especially phosphatidylglycerol (PG), leading to the dysfunction of bacterial membranes. Furthermore, their efficacies against methicillin-resistant Staphylococcus aureus (MRSA) in both Galleria mellonella and mouse wound infection models were observed. This study underscores the significance of employing genome-guided approaches to identify untapped marine fungi as potential sources for novel antibiotic candidates with unique scaffolds.

Cardiac fibrosis is characterized by an elevated amount of extracellular matrix (ECM) within the heart. However, the persistence of cardiac fibrosis ultimately diminishes contractility and precipitates cardiac dysfunction. Circular RNAs (circRNAs) are emerging as important regulators of cardiac fibrosis. Here, we elucidate the functional role of a specific circular RNA CELF1 in cardiac fibrosis and delineate a novel feedback loop mechanism. Functionally, circ-CELF1 was involved in enhancing fibrosis-related markers' expression and promoting the proliferation of cardiac fibroblasts (CFs), thereby exacerbating cardiac fibrosis. Mechanistically, circ-CELF1 reduced the ubiquitination-degradation rate of BRPF3, leading to an elevation of BRPF3 protein levels. Additionally, BRPF3 acted as a modular scaffold for the recruitment of histone acetyltransferase KAT7 to facilitate the induction of H3K14 acetylation within the promoters of the Celf1 gene. Thus, the transcription of Celf1 was dramatically activated, thereby inhibiting the subsequent response of their downstream target gene Smad7 expression to promote cardiac fibrosis. Moreover, Celf1 further promoted Celf1 pre-mRNA transcription and back-splicing, thereby establishing a feedback loop for circ-CELF1 production. Consequently, a novel feedback loop involving CELF1/circ-CELF1/BRPF3/KAT7 was established, suggesting that circ-CELF1 may serve as a potential novel therapeutic target for cardiac fibrosis.

AIM: To observe and analyze the effectiveness and safety of wearing corneal refractive therapy(CRT)and vision shaping treatment(VST)designed orthokeratology in controlling myopic progression in adolescents with low E-value corneal morphology.METHODS: This prospective study involved 100 cases(100 eyes)of adolescent myopia patients fitted with orthokeratology at our optometry clinic from January 2020 to December 2021. The data of right eye were collected for research, and they were divided into low myopia group(-1.00 to -3.00 D)and moderate myopia group(-3.25 to -5.00 D)according to spherical equivalent, with 50 cases in each group. Each group of patients was further randomly divided into the CRT group and the VST group, with 25 cases in each group. Uncorrected visual acuity, refractive error, axial length(AL), tear film break-up time(BUT), corneal endothelial cell density, corneal staining grading, lens decentration, and refractive power at 15°-30° were measured before and after wearing orthokeratology, with a follow-up duration of 1.5 a.RESULTS: The uncorrected visual acuity of CRT and VST subgroups in the low myopia group showed no statistical significance at any time point after wearing orthokeratology. However, in the moderate myopia group, CRT subgroup showed better uncorrected visual acuity than the VST subgroup, with significant differences at 1 d and 1 wk(t=-9.474, -12.067, both P<0.01); no significant differences were noted at other time points. After wearing lens for 6 mo and 1.5 a, the AL growth for the CRT subgroup in low and moderate myopia was less than the VST subgroup, with no statistically significant differences. There were no statistically significant differences in binocular BUT and corneal endothelial cell density after wearing lens for 6 mo and 1.5 a. Corneal injury was lower in the CRT subgroup than that in the VST subgroup, but the difference was not statistically significant(Z=-1.803, P=0.071). Lens decentration was significantly better in the CRT subgroup than in the VST subgroup(Z=-4.629, P<0.001). In the periphery of the retina at 15°-30°, there were no significant differences in the amount of myopic defocus between the two groups, while it was statistically significant at 1, 3, and 6 mo in the moderate myopia subgroup(t=-3.949, P=0.008; t=-5.833, P<0.001; t=-6.231, P<0.001), indicating that CRT subgroup could produce a greater amount of myopic defocus.CONCLUSION: For patients with low E-value corneal morphology, CRT, using the vector height at 8 mm on the cornea for fitting, is not limited to the corneal E-value. It shapes faster and improves uncorrected visual acuity after shaping, especially for moderate myopia, achieving better daytime vision. In terms of controlling myopia, CRT fitting elevates return zone depth(RZD), creating a small central optical zone to produce more peripheral myopic defocus. However, there was no significant difference between the two groups in controlling AL growth. Both groups showed minimal corneal damage, indicating consistent safety in myopia control.

[Objective] To explore the association between methyltransferase-like 3 (METTL3) and prostate cancer (PCa) prognosis, so as to establish a novel prognostic prediction model for PCa. [Methods] Public datasets and PCa tissue microarray were used to evaluate the gene and protein expressions of METTL3, the association between METTL3 and Gleason score (GS), and the ability of METTL3 to predict poor outcomes of PCa.A nomogram was constructed to quantitatively evaluate the prognosis of PCa. [Results] The gene and protein expressions of METTL3 were significantly upregulated in PCa tissues compared to normal tissues (P<0.05). Moreover, the expressions of METTL3 were significantly higher in high-risk PCa tissues (GS>7) compared to low-moderate risk PCa tissues (GS≤7) (P<0.05). Patients with elevated expressions of METTL3 exhibited poorer short-term and long-term progression-free and overall survival outcomes when compared to those with lower expressions of METTL3 (P<0.05). In addition, a risk model composed of 7 target genes regulated by METTL3 N6-methyladenine (m6A) modification was established.The 7 target genes were closely associated with the cell cycle process.The protein expression of METTL3 exhibited a significant positive correlation with the protein expression of cell cycle protein B1 (CCNB1) (r=0.30, P=0.002 5). [Conclusion] METTL3 exhibits the potential as a prognostic predictor for PCa, which may affect PCa prognosis through the regulation of the expressions of target genes closely associated with the cell cycle process via m6A modification.

Objective:To analyze the detection of colorectal advanced neoplasms in the population who underwent colonoscopy screening in Henan Province as part of the Urban China Cancer Screening Program and its influencing factors.Methods:A cross-sectional study design was employed. Based on the Cancer Screening Program conducted in Henan Province, the study enrolled 7 454 urban residents who manifested no symptoms and were recruited from eight cities in the province, including Zhengzhou, Zhumadian, Anyang, Luoyang, Nanyang, Jiaozuo, Xinxiang, and Puyang from October 2013 to October 2019, and participated in colonoscopy screening. The χ 2 test was used to compare the detection rates of colorectal advanced neoplasms among participants with different characteristics, and a multivariate logistic stepwise regression model was used to analyze the factors affecting the detection rates. Results:A total of 7 454 subjects underwent colonoscopy screening, and 112 cases of colorectal advanced neoplasms were detected. Multivariate logistic regression analysis suggested that older age, smoking, higher meat intake, history of diabetes, and family history of colorectal cancer in a first-degree relative were risk factors for colorectal advanced neoplasms. The detection rate was significantly higher in people aged 60-74 years compared with those aged 40-49 years, with an odds ratio ( OR) of 2.04 (95% CI: 1.23-3.38).The rates were higher in people who smoked than those who did not smoke, with an OR of 2.21 (95% CI: 1.48-3.31), and in people who consumed more meat than those who consumed less, with an OR of 1.53 (95% CI: 1.04-2.26). Those with diabetes had a higher detection rate compared with those without, with an OR of 1.69 (95% CI: 1.07-2.69), and those with a first-degree family history of colorectal cancer had a higher detection rate than those without, with an OR of 1.64 (95% CI: 1.09-2.46). Conclusion:The detection rate of colorectal advanced neoplasms through colonoscopy screening in Henan Province covered by the Urban China Cancer Screening Program is 1.50%. Older age, smoking, higher meat intake, history of diabetes, and family history of colorectal cancer in a first-degree relative are identified as risk factors for colorectal advanced neoplasms.

Objective:To analyze the 5-year relative survival rate of cancer in Henan province based on cancer registration data.Methods:Cancer survival data were extracted from the cancer registration database of Henan province with the diagnosis date between January 1, 2010 and December 31, 2019 were included. The closing date of follow-up was set as December 31, 2019. The 5-year relative survival rate of cancer was calculated using the period survival analysis method and the Ederer II method in the R package "periodR", and the interest period was between 2015 and 2019.Results:During the period of 2015-2019, the overall 5-year relative survival rate of cancer patients in Henan province was 43.6%, and after age-standardization, it was 40.2%. The overall 5-year relative survival rate showed the characteristics of higher survival rate in females than males (45.9% vs 34.7%, Z=39.60, P＜0.001) and higher survival rate in urban areas than rural areas (44.9% vs 39.1%, Z=12.97, P＜0.001). The 5-year relative survival rate for cancer patients among children aged 0-14 was 60.2%, and for adults aged 15 and above, it was 43.5%, which was standardized to 40.2% after age adjustment. There are two types of cancers with a standardized 5-year relative survival rate exceeding 70% (thyroid cancer at 82.2% and breast cancer at 71.6%), and four cancers with a rate below 30% (pancreatic cancer at 18.2%, liver cancer at 19.6%, lung cancer at 24.0%, and gallbladder cancer at 26.6%). Conclusion:The cancer 5-year survival rate in Henan Province is lower than that of the national average, indicating the need for continued enhancement of cancer prevention and control measures.

Objective:To analyze the detection of colorectal advanced neoplasms in the population who underwent colonoscopy screening in Henan Province as part of the Urban China Cancer Screening Program and its influencing factors.Methods:A cross-sectional study design was employed. Based on the Cancer Screening Program conducted in Henan Province, the study enrolled 7 454 urban residents who manifested no symptoms and were recruited from eight cities in the province, including Zhengzhou, Zhumadian, Anyang, Luoyang, Nanyang, Jiaozuo, Xinxiang, and Puyang from October 2013 to October 2019, and participated in colonoscopy screening. The χ 2 test was used to compare the detection rates of colorectal advanced neoplasms among participants with different characteristics, and a multivariate logistic stepwise regression model was used to analyze the factors affecting the detection rates. Results:A total of 7 454 subjects underwent colonoscopy screening, and 112 cases of colorectal advanced neoplasms were detected. Multivariate logistic regression analysis suggested that older age, smoking, higher meat intake, history of diabetes, and family history of colorectal cancer in a first-degree relative were risk factors for colorectal advanced neoplasms. The detection rate was significantly higher in people aged 60-74 years compared with those aged 40-49 years, with an odds ratio ( OR) of 2.04 (95% CI: 1.23-3.38).The rates were higher in people who smoked than those who did not smoke, with an OR of 2.21 (95% CI: 1.48-3.31), and in people who consumed more meat than those who consumed less, with an OR of 1.53 (95% CI: 1.04-2.26). Those with diabetes had a higher detection rate compared with those without, with an OR of 1.69 (95% CI: 1.07-2.69), and those with a first-degree family history of colorectal cancer had a higher detection rate than those without, with an OR of 1.64 (95% CI: 1.09-2.46). Conclusion:The detection rate of colorectal advanced neoplasms through colonoscopy screening in Henan Province covered by the Urban China Cancer Screening Program is 1.50%. Older age, smoking, higher meat intake, history of diabetes, and family history of colorectal cancer in a first-degree relative are identified as risk factors for colorectal advanced neoplasms.

Objective:To analyze the 5-year relative survival rate of cancer in Henan province based on cancer registration data.Methods:Cancer survival data were extracted from the cancer registration database of Henan province with the diagnosis date between January 1, 2010 and December 31, 2019 were included. The closing date of follow-up was set as December 31, 2019. The 5-year relative survival rate of cancer was calculated using the period survival analysis method and the Ederer II method in the R package "periodR", and the interest period was between 2015 and 2019.Results:During the period of 2015-2019, the overall 5-year relative survival rate of cancer patients in Henan province was 43.6%, and after age-standardization, it was 40.2%. The overall 5-year relative survival rate showed the characteristics of higher survival rate in females than males (45.9% vs 34.7%, Z=39.60, P＜0.001) and higher survival rate in urban areas than rural areas (44.9% vs 39.1%, Z=12.97, P＜0.001). The 5-year relative survival rate for cancer patients among children aged 0-14 was 60.2%, and for adults aged 15 and above, it was 43.5%, which was standardized to 40.2% after age adjustment. There are two types of cancers with a standardized 5-year relative survival rate exceeding 70% (thyroid cancer at 82.2% and breast cancer at 71.6%), and four cancers with a rate below 30% (pancreatic cancer at 18.2%, liver cancer at 19.6%, lung cancer at 24.0%, and gallbladder cancer at 26.6%). Conclusion:The cancer 5-year survival rate in Henan Province is lower than that of the national average, indicating the need for continued enhancement of cancer prevention and control measures.

[摘 要] 目的：重新评价卡瑞利珠单抗联合阿帕替尼治疗原发性肝癌（PHC）的有效性和安全性。方法：回顾性收集2019年1月至2021年5月在安徽医科大学附属第一医院确诊的PHC患者的临床资料。所有患者均接受卡瑞利珠单抗200 mg q3w联合阿帕替尼250 mg qd×21 d治疗。应用卡方检验进行基线特征比较，采用Kaplan-Meier法进行生存分析，从中估计中位总生存期（OS），然后采用Log-Rank检验进行比较；采用单因素Cox回归分析预测影响OS的因素。结果：本研究共纳入43例PHC患者，一线治疗患者的客观缓解率（ORR）为23.3%（7/30），二线及以上治疗患者的ORR为15.4%（2/13）。两组患者的疾病控制率（DCR）分别为83.3%（25/30）和61.5%（8/13），中位无进展生存期（PFS）分别为5.0个月（95% CI 3.2，6.8）和4.0个月（95% CI 1.7，6.3）（P=0.514），中位OS分别为13.0个月（95% CI 11.2，14.8）和9.0个月（95% CI 2.8，15.2）（P=0.179）。在43例患者中，33例（76.7%）存在3级或以上的治疗相关不良反应（AE）；最常见的AE为血小板计数下降（14.0%）、高血压（9.3%）和蛋白尿（9.3%）。Cox单因素回归分析显示，Child-Pugh分级是影响PHC患者预后的独立危险因素[HR=0.324，95% CI （0.146，0.716），P<0.05]。结论：卡瑞利珠单抗联合阿帕替尼可显著改善PHC患者的OS、ORR和DCR，AE可控。

Objective:To optimize the extraction process of Shangke Huoxue Granule.Methods:Taking the factors of extraction solvent multiple, extraction time and extraction times as investigation factors, and extraction amount of ferulic acid, paeoniflorin and the ratio of extraction as comprehensive evaluation indices, one-factor experimental design and central composite design-response surface methodology were adopted to optimize the extraction process of Shangke Huoxue Granule.Results:The binomial fitting equation was Y=96.16+2.42 A+0.63 B-3.76 AB-1.57 A2-1.87 B2 ( P<0.01). The optimal extraction process parameters were confirmed to be adding 16 times of water, 64 minutes each time, twice. The deviation rates between the measured values of three verification experiments and the predicted value were 2.00%, 3.23% and 0.66%. Conclusion:The established model of central composite design-response surface methodology has high predictability and the optimized extraction process is stable and feasible.