ObjectiveTo investigate the heterogeneity of PD-L1 expression profiles between primary tumors and paired metastatic lymph nodes in advanced non-small cell lung cancer （NSCLC）， and to determine the predictive value of key immune marker expression for the efficacy of first-line targeted therapy and chemotherapy. MethodsA retrospective analysis was conducted on 128 patients with histologically confirmed NSCLC and corresponding metastatic lymph nodes， who received first-line tyrosine kinase inhibitors （TKIs） or platinum-based doublet chemotherapy at Guangdong Provincial People's Hospital between April 2017 and February 2020. Immunohistochemistry （IHC） was employed to evaluate PD-L1 expression in primary tumors and metastatic lymph nodes. The Wilcoxon signed-rank test was performed to compare PD-L1 expression characteristics between primary tumors and metastatic lymph nodes. Kaplan-Meier survival curves were constructed， and the Log-rank test was used to compare differences between groups. ResultsAmong 28 paired cases， PD-L1 expression levels were numerically higher in metastatic lymph nodes than in primary NSCLC tumors （median：32.5 vs. 10.0）， although the difference did not reach statistical significance （MD = 5.000， P = 0.083）. Survival analysis revealed that in patients with driver gene-positive NSCLC， high PD-L1 expression （TPS ≥ 50%） in lymph nodes was significantly associated with shorter progression-free survival （PFS） following first-line TKI therapy ［median PFS：4.0（TPS≥50%） vs. 8.9（1%≤TPS＜50%） vs. 18.0 （TPS＜1%） months， χ²=15.284， P＜0.001］. Conversely， in patients with driver gene-negative NSCLC， high PD-L1 expression in lymph nodes was associated with longer PFS ［median PFS：7.9 （TPS≥50%） vs. 3.0 （1%≤TPS＜50%）months， χ²=8.436， P=0.004］ and overall survival （OS） ［median OS：28.8 （TPS≥50%） vs. 14.2 （ 1%≤TPS＜50%） months， χ²=4.010， P=0.045］ after first-line chemotherapy. ConclusionPD-L1 expression in metastatic lymph nodes is largely consistent with that in primary tumors of patients with advanced NSCLC. High PD-L1 expression in lymph nodes is associated with improved survival outcomes in driver gene-negative patients undergoing chemotherapy， whereas it portends a poor prognosis with TKI treatment in driver gene-positive patients. These findings support the application of PD-L1 expression levels in metastatic lymph nodes to guide personalized precision medicine strategies for advanced NSCLC.

This paper explores the therapeutic approach for glaucoma based on the concept of "jueyin （厥阴） as the closing phase" from the perspectives of time and space. In traditional Chinese medicine， jueyin governs inward， converging aspect of qi， representing the crucial turning point between the end of yin and the emergence of yang， as well as the transformation between yin and yang. When the closing and descending function of jueyin operates smoothly， it promotes the inward convergence and smooth descent of qi， enabling the internal retention of blood， spirit， and emotions， which nourishes the internal organs and moistens the meridian-sinews. Conversely， dysfunction of this "closing" mechanism results in a disturbance of yin and yang， a mixture of cold and heat， and disharmony of qi and blood. It is proposed that "failure of jueyin to properly close and descend" is a core pathomechanism of glaucoma. From the perspective of spatiotemporal theory， clinical treatment should focus on "regulating the closing function of jueyin and harmonizing yin and yang". The modified Wumei Pill （乌梅丸） is recommended to adjust the ascending-descending and entering-exiting dynamics of jueyin qi transformation， thereby restoring its free flow， achieving yin and yang balance， and ensuring nourishment to the ocular system.

BACKGROUND: Double-stranded RNA-specific adenosine deaminase 1 (ADAR1) binds to double-stranded RNA and catalyzes the deamination of adenosine (A) to inosine (I). The functional mechanism of ADAR1 in non-small cell lung cancer (NSCLC) remains incompletely understood. This study aimed to investigate the prognostic significance of ADAR1 in NSCLC and to elucidate its potential role in regulating tumor cell proliferation and migration. METHODS: Data from The Cancer Genome Atlas (TCGA) and cBioPortal were analyzed to assess the correlation between high ADAR1 expression and clinicopathological features as well as prognosis in lung cancer. We performed Western blot (WB), cell proliferation assays, Transwell invasion/migration assays, and nude mouse xenograft modeling to examine the phenotypic changes and molecular mechanisms induced by ADAR1 knockdown. Furthermore, the ADAR1 p150 overexpression model was utilized to validate the proposed mechanism. RESULTS: ADAR1 expression was significantly elevated in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) tissues compared with adjacent non-tumor tissues (LUAD: P=3.70×10-15, LUSC: P=0.016). High ADAR1 expression was associated with poor prognosis (LUAD: P=2.03×10-2, LUSC: P=2.81×10-2) and distant metastasis (P=0.003). Gene Set Enrichment Analysis (GSEA) indicated that elevated ADAR1 was associated with mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway activation, matrix metalloproteinase-9 (MMP-9) expression, and cell adhesion. ADAR1 and MMP-9 levels showed a strongly positive correlation (P=6.45×10-34) in 10 lung cancer cell lines, highest in H1581. Knockdown of ADAR1 in H1581 cells induced a rounded cellular morphology with reduced pseudopodia. Concomitantly, it suppressed cell proliferation, invasion, migration, and in vivo tumorigenesis. It also suppressed ERK phosphorylation and downregulated cellular Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog (c-FOS), MMP-9, N-cadherin, and Vimentin. Conversely, ADAR1 p150 overexpression in PC9 cells enhanced ERK phosphorylation and increased c-FOS and MMP-9 expression. CONCLUSIONS High ADAR1 expression is closely associated with poor prognosis and distant metastasis in NSCLC patients. Mechanistically, ADAR1 may promote proliferation, invasion, migration, and tumorigenesis in lung cancer cells via the ERK/c-FOS/MMP-9 axis.
Humans ; Lung Neoplasms/physiopathology* ; Adenosine Deaminase/genetics* ; Matrix Metalloproteinase 9/genetics* ; Cell Proliferation ; Carcinoma, Non-Small-Cell Lung/physiopathology* ; Cell Movement ; Animals ; Mice ; RNA-Binding Proteins/genetics* ; Female ; Male ; Cell Line, Tumor ; Proto-Oncogene Proteins c-fos/genetics* ; Middle Aged ; MAP Kinase Signaling System ; Gene Expression Regulation, Neoplastic ; Mice, Nude ; Extracellular Signal-Regulated MAP Kinases/genetics*

Retinopathy caused by myopia is the first cause of irreversible blinding eye disease in China.The TCM methods to prevent and control myopia mainly include Chinese materia medica and TCM appropriate techniques,which have the advantages of good efficacy,simple operation,and few adverse reactions.This paper believed that internal and external pathogenic factors act on the brain and eyes,breaking their homeostasis,leading to rhythmic disorders,and imbalance of essence,qi and blood is the main pathogenesis of myopia.Based on the idea of"nature and human in the same rhythm"and"the same treatment for common diseases",targeting the above pathogenesis,the method of"brain-eye synchronization"was proposed to restore the homeostasis of the brain and eyes to prevent and control myopia in children and adolescents,and the treatment rules were to regulate the rhythms of the time,harmonize the qi and blood,nourish the blood to soften the tendons,and replenish the essence and blood,so as to achieve the effect of brain-eye synchronization and the treatment of the spirit and the body together.This article summarized the theoretical basis of"brain-eye synchronization"and its clinical application in traditional Chinese and Western medicine,with a view to providing new ideas for the prevention and control of myopia in children and adolescents.

Retinopathy caused by myopia is the first cause of irreversible blinding eye disease in China.The TCM methods to prevent and control myopia mainly include Chinese materia medica and TCM appropriate techniques,which have the advantages of good efficacy,simple operation,and few adverse reactions.This paper believed that internal and external pathogenic factors act on the brain and eyes,breaking their homeostasis,leading to rhythmic disorders,and imbalance of essence,qi and blood is the main pathogenesis of myopia.Based on the idea of"nature and human in the same rhythm"and"the same treatment for common diseases",targeting the above pathogenesis,the method of"brain-eye synchronization"was proposed to restore the homeostasis of the brain and eyes to prevent and control myopia in children and adolescents,and the treatment rules were to regulate the rhythms of the time,harmonize the qi and blood,nourish the blood to soften the tendons,and replenish the essence and blood,so as to achieve the effect of brain-eye synchronization and the treatment of the spirit and the body together.This article summarized the theoretical basis of"brain-eye synchronization"and its clinical application in traditional Chinese and Western medicine,with a view to providing new ideas for the prevention and control of myopia in children and adolescents.

The theory of “rhythmic equilibrium” is developed based on the idea of sharing the same laws between nature and human， and by integrating with the medical concept of homeostasis of calm yin and sound yang. "Rhythmic instability" runs through the entire process of the occurrence and development of myopia， covering four aspects including imbalance of rhythm （high-risk period of myopia）， imbalance of qi and blood （premyopia）， imbalance of sinew-membranes （low myopia）， and imbalance of essence and blood （high myopia）. The treatment should focus on adjusting the rhythm and harmonizing situation， which can help balance yin and yang， and nourish the eye system. For high-risk period of myopia， adjusting sleeping time and increasing outdoor activities are stressed to adjust the rhythm in a timely manner. In the stage of premyopia， appropriate techniques of traditional Chinese medicine （TCM） such as pressing needles can be added to harmonize qi and blood. In the period of low myopia， appropriate TCM techniques such as pressing needles and ear acupuncture are mainly used， supplemented by modified Danggui Buxue Decoction （当归补血汤） to soften tendons and unblock collaterals. During the period of high myopia， it is recommended to control the development of existing disease and put focus on nourishing essence and blood， usually with Zhujing Pill （驻景丸） or modified Siwu Wuzi Decoction （四物五子汤） to restore the stability of the eyes and the whole body.

Objective:To investigate the clinical and pathological features and improve the acknowledgement of intraductal tubulopapillary neoplasm (ITPN) of pancreas.Methods:Six cases with ITPN in the Shandong Provincial Hospital Affiliated to Shandong First Medical University combined with 40 cases from PubMed and CNKI were retrospectively analyzed. There were 25 males and 21 females, aged (58.6±16.0) years. The clinical manifestations, pathological features, treatment and so on were analyzed.Results:All cases were treated with surgery. The main clinical symptoms were upper abdominal pain and discomfort (23 cases, 50.0%), followed by jaundice (9 cases, 19.6%). Seven cases (15.2%) had no clinical symptoms. Three cases (6.5%) had low back discomfort, chills and other rare symptoms, and 4 cases (8.7%) had no clinical symptoms mentioned in the literature. Tumors of 27 cases (58.7%) located in the head of the pancreas, 9 cases (19.6%) in the body and tail, 4 cases (8.7%) in the whole pancreas, 3 cases (6.5%) in the body, 2 cases (4.3%) in ampulla and 1 case (2.2%) in head and body. Most of the tumors located in the main pancreatic duct. Microscopically, back-to-back tubular glands were densely arranged, parts of them with papillary structure, with obvious cell atypia and many mitoses. Twenty-two cases (47.8%) of ITPN were completely confined to the pancreatic duct, and 24 cases (52.2%) were with associated invasive carcinoma. Tumor cells were positive for cytokeratin 7 and mucin 1, but negative for cytokeratin 20, synaptophysin, chromogranin and trypsin. Mucin 2, mucin 5AC and mucin 6 were negative in most cases. Ki-67 ranged from 10% to 70%.Conclusion:Pancreatic ITPNs were mostly located in the pancreatic head, confined to the main pancreatic duct, and were mostly manifested as pain and discomfort in the upper abdomen. Surgery was the main treatment. Tumors cells of ITPN were arranged in tubular and papillary, with severe epithelial atypia and special immunophenotype, parts of cases accompanied with associated invasive carcinoma.

Background Nitrosamines (NAms) are highly carcinogenic and frequently detected in drinking water systems in China, indicating potential human health risk through drinking water. Objective To analyze the distribution of NAms in drinking water in Shanghai and to evaluate relevant human health risk. Methods A total of 94 samples of source water and 120 samples of finished water were collected in February (dry period) and August (wet period) of 2021 from 30 drinking water plants in Shanghai, and eight NAms were quantitatively analyzed by gas chromatography tandem mass spectrometry after solid phase extraction. Cancer risks for different age groups caused by NAms exposure through water were evaluated using Monte Carlo probabilistic method and carcinogens risk assessment model recommended by the United States Environmental Protection Agency. Results The concentrations of total NAms in source and finished water were 12.56-65.86 ng·L⁻¹ and 8.52-57.38 ng·L⁻¹, respectively. The average concentration of total NAms was higher in source water (33.50 ng·L⁻¹) than in finished water (22.07 ng·L⁻¹, P<0.05) during dry season, and lower in source water (16.90 ng·L⁻¹) than in finished water (21.02 ng·L⁻¹, P<0.05) during wet season. The average concentration of total NAms in source water during dry season was twice of that during wet season. The positive rate of N-nitrosodimethylamine (NDMA) was the highest (100%) among the eight NAms. The cancer risk of exposure to NAms in finished water in Shanghai was mainly from the ingestion route, which was mostly caused by NDMA. The cancer risk from exposure to NAms in water for children (median=4.32×10⁻⁵) was slightly higher than that for adults (median=3.34×10⁻⁵) and adolescents (median=2.27×10⁻⁵). The cancer risks of exposure to NAms in water for people of different ages were mainly (80% - 95%) at an acceptable level (1×10⁻⁶ - 1×10⁻⁴). Conclusion NAms contamination is positive in Shanghai’s drinking water and NDMA is the main contaminant. The removal of NAms in water by current water treatment process is season-dependent. The cancer risk of children exposed to NAms in water was slightly higher than that of adults and adolescents, but all at acceptable levels.

Objective:To explore the effect of different diagnostic criteria on occupational noise-induced deafness (Onid) , and to provide theoretical basis for the revision of ONID diagnostic criteria.Methods:From January 2016 to January 2018, the physical examination results of noise-exposed workers during occupational health examination in Qingyuan Occupational Disease Prevention and Treatment Hospital were retrospectively investigated in September 2019, with Gbz 49-2014《diagnosis of occupational noise deafness》as the study object, 471 workers suspected of Onid were weighted with different combinations of high frequency hearing threshold, and the better ear weight was calculated, compared with the diagnostic criteria of 2007 and 2014, the degree of hearing loss was evaluated. SPSS 22.0 was used for statistical analysis, χ 2 test was used for counting data, and non-parametric test was used for measuring bias data. Results:The average age of 471 subjects was (40.32±7.01) years, and the average age of exposure to noise was (7.11±3.44) years. On the basis of the 2007 edition diagnostic standard, the suspected ONID diagnostic rate of different high frequency auditory threshold was increased by 16.35% and 30.15% at 3.0 kHz, 6.0 kHz increased by 20.17%, 3.0 kHz+4.0 kHz increased by 22.29%, 3.0 kHz+6.0 kHz increased by 17.20%, 4.0 kHz+6.0 kHz increased by 25.27%, the differences were statistically significant ( P<0.05) , the frequency of 3.0 kHz+4.0 kHz+6.0 kHz increased by 22.29%. Using the 2014 edition diagnostic standard, the diagnostic rate of Onid was reduced by 30.15% and 13.80%, 6 kHz is 9.98% lower, 3.0 kHz+4.0 kHz is 7.86% lower, 3.0 kHz+6.0 kHz is 12.95% lower, 4.0 kHz+6.0 is 4.88% lower, the high frequency of 3.0 kHz+4.0 kHz+6.0 kHz decreased by 7.86%, the differences were statistically significant ( P<0.05) . Conclusion:The diagnosis rate of suspected Onid is increased by weighting different high frequency hearing threshold, in which the weighted 4kHz high frequency has the greatest influence on the result, and the weighted 3 kHz high frequency has the least.

Objective:To explore the effect of different diagnostic criteria on occupational noise-induced deafness (Onid) , and to provide theoretical basis for the revision of ONID diagnostic criteria.Methods:From January 2016 to January 2018, the physical examination results of noise-exposed workers during occupational health examination in Qingyuan Occupational Disease Prevention and Treatment Hospital were retrospectively investigated in September 2019, with Gbz 49-2014《diagnosis of occupational noise deafness》as the study object, 471 workers suspected of Onid were weighted with different combinations of high frequency hearing threshold, and the better ear weight was calculated, compared with the diagnostic criteria of 2007 and 2014, the degree of hearing loss was evaluated. SPSS 22.0 was used for statistical analysis, χ 2 test was used for counting data, and non-parametric test was used for measuring bias data. Results:The average age of 471 subjects was (40.32±7.01) years, and the average age of exposure to noise was (7.11±3.44) years. On the basis of the 2007 edition diagnostic standard, the suspected ONID diagnostic rate of different high frequency auditory threshold was increased by 16.35% and 30.15% at 3.0 kHz, 6.0 kHz increased by 20.17%, 3.0 kHz+4.0 kHz increased by 22.29%, 3.0 kHz+6.0 kHz increased by 17.20%, 4.0 kHz+6.0 kHz increased by 25.27%, the differences were statistically significant ( P<0.05) , the frequency of 3.0 kHz+4.0 kHz+6.0 kHz increased by 22.29%. Using the 2014 edition diagnostic standard, the diagnostic rate of Onid was reduced by 30.15% and 13.80%, 6 kHz is 9.98% lower, 3.0 kHz+4.0 kHz is 7.86% lower, 3.0 kHz+6.0 kHz is 12.95% lower, 4.0 kHz+6.0 is 4.88% lower, the high frequency of 3.0 kHz+4.0 kHz+6.0 kHz decreased by 7.86%, the differences were statistically significant ( P<0.05) . Conclusion:The diagnosis rate of suspected Onid is increased by weighting different high frequency hearing threshold, in which the weighted 4kHz high frequency has the greatest influence on the result, and the weighted 3 kHz high frequency has the least.