[This corrects the article DOI: 10.1016/j.apsb.2022.05.019.].

BACKGROUND: Pulmonary arterial hypertension (PAH) presents a significant health burden in Asia and remains a critical challenge. This study aims to delineate the PAH burden in Asia from 1990 to 2021. METHODS: Using the latest data from the Global Burden of Disease 2021, we evaluated and analyzed the distributions and patterns of PAH disease burden among various age groups, sexes, regions, and countries in Asia. Additionally, we examined the associations between PAH disease burden and key health system indicators, including the socio-demographic index (SDI) and the universal health coverage (UHC) index. RESULTS: In 2021, there were 25,989 new PAH cases, 103,382 existing cases, 13,909 PAH-associated deaths, and 385,755 DALYs attributed to PAH in Asia, which accounted for approximately 60% of global PAH cases. The age-standardized rates (ASRs) for prevalence and deaths were 2.05 (95% uncertainty interval [UI]: 1.66-2.52) per 100,000 population and 0.31 (95% UI: 0.23-0.38) per 100,000 population, respectively. From 1990 to 2021, Asia reported the lowest ASRs for PAH prevalence but the highest ASRs for deaths compared to other continents. While the ASRs for prevalence increased slightly, ASRs for mortality and DALYs decreased over time. This increasing burden of PAH was primarily driven by population growth and aging. The burden was especially pronounced among individuals aged ≥60 years and <9 years, who collectively accounted for the majority of deaths and DALYs. Moreover, higher SDI and UHC levels were linked to reduced incidence, but higher prevalence rates. CONCLUSIONS Although progress has been made in reducing PAH-related mortality and DALYs, the disease continues to impose a substantial burden in Asia, particularly among older adults and young children. Region-specific health policies should focus on improving early diagnosis, expanding access to treatment, and effectively addressing the growing PAH burden in the region.
Humans ; Global Burden of Disease ; Male ; Female ; Middle Aged ; Adult ; Asia/epidemiology* ; Prevalence ; Aged ; Pulmonary Arterial Hypertension/mortality* ; Adolescent ; Young Adult ; Child ; Child, Preschool ; Infant ; Hypertension, Pulmonary/epidemiology*

Objective To investigate the inhibitory effect of β-elemonic acid(β-EA)on the proliferation and inva-sion of colon cancer cells and the underlying mechanisms through PI3K/AKT/mTOR signaling pathway.Methods The effects of β-EA on colon cancer cell proliferation were evaluated using the MTT assay and colony formation as-say.Transwell invasion assay were used to assess the impact of β-EA on invasion.Western blot analysis was con-ducted to detect changes in PI3K/AKT/mTOR pathway proteins after treatment.Results MTT assay showed thatβ-EA effectively inhibited the proliferation of colon cancer HCT8 and HCT116 cells in a dose-dependent manner.The colony formation assay confirmed its inhibitory effect on cell proliferation.Transwell invasion assays demonstra-ted that β-elemonic acid reduced the invasion abilities of the cells.Western blot analysis revealed increased expression of apoptosis-related proteins cleaved-caspase 3,cleaved-caspase 9,and Bax,while Bcl-2 expression was decreased.Invasion-related proteins vimentin,snail,MMP2,and MMP9 were downregulated after treatment.Addi-tionally,β-EAA reduced the levels of p-PI3K,p-Akt,and p-mTOR,and these reductions were more pronounced af-ter the addition of the PI3K inhibitor LY294002.Conclusions β-EA may inhibit proliferation and invasion in colon cancer cell lines HCT8 and HCT116 through PI3K/AKT/mTOR signaling pathway,and potentially be transformed as a novel therapeutic agent for colon cancer.

Purpose This study aimed to investigate the expression and clinical significance of TLDC2 in colorec-tal adenocarcinoma.Methods Data from the human protein atlas(HPA)and the cancer genome atlas(TCGA)indi-cated that TLDC2 was highly expressed in colorectal adenocarcinoma.We further analyzed the expression of TLDC2 in 400 colorectal adenocarcinomas and 447 other solid tumors using tissue microarrays and immunohistochemical(IHC)staining.Result The positive expression rate of TLDC2 was significantly higher than that of SATB2 in colorectal ade-nocarcinomas(96.5％vs 87.0％,P＜0.000 1).TLDC2 positivity exceeded that of SATB2 in both low-or high-grade colorectal adenocarcinoma(99.4％vs 88.7％,P＜0.000 1;83.3％vs 79.2％,P=0.669 9).In addition,the expression of TLDC2 and SATB2 was evaluated in 447 cases of other types of solid tumors.TLDC2 was expressed in neuroendocrine tumors as well as in gastric and appendiceal adenocarcinomas,whereas SATB2 was detected in a small number of melanomas,ovarian cancers,breast cancers and gallbladder cancers.The positive and specificity of TLDC2 for colorectal adenocarcinoma were 97％(95％CI=0.94-0.98)and 85％(95％CI=0.81-0.88),respectively.Combined detection of TLDC2 and SATB2 yielded a sensitivity of 96％(95％CI=0.93-0.97)and a specificity of 93％(95％CI=0.90-0.95).Conclusion Analysis of large-scale datasets and IHC staining demonstrated that TLDC2 is a highly sensitive and specific biomarker for colorectal adenocarcinoma.

Objective To compare the clinical efficacy of high-dose tigecycline(TGC)and polymyxin B(PMB)in the treatment of pulmonary infection due to carbapenem-resistant organism(CRO).Methods Clinical data of pa-tients with CRO pulmonary infection and received PMB or high-dose TGC combined with other antimicrobial treat-ment regimens in Department of Critical Care Medicine of Xiangya Hospital,Central South University from January 2019 to March 2022 were analyzed retrospectively,including basic information,pathogen detection results,antimi-crobial use regimen,clinical efficacy,30-day mortality,bacterial clearance rate,etc.Results A total of 173 pa-tients were included in analysis,with 103 in the TGC group and 70 in the PMB group.Compared with TGC group,PMB group had a higher score of acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ)(25.0 vs 20.0,P＜0.001),but clinical efficacy rates were not statistically different(67.1％vs 52.4％,P=0.054).Stratified analysis revealed that when the APACHE Ⅱ score was ≥15 points,compared with TGC group(n=78),PMB group(n=66)had a higher APACHE Ⅱ score(27.0 vs 22.0,P=0.005)and a higher clinical efficacy rate(66.7％vs 47.4％,P=0.020).After adjusting confounding factors through logistic regression analysis,it was found that PMB treatment was a protective factor for clinical efficacy rate compared with TGC treatment.Conclusion For treating pulmonary infection caused by CRO in patients,PMB-based treatment regimen has a significant protec-tive effect on the clinical efficacy rate compared with the high-dose TGC-based treatment regimen.

Purpose This study aimed to investigate the expression and clinical significance of TLDC2 in colorec-tal adenocarcinoma.Methods Data from the human protein atlas(HPA)and the cancer genome atlas(TCGA)indi-cated that TLDC2 was highly expressed in colorectal adenocarcinoma.We further analyzed the expression of TLDC2 in 400 colorectal adenocarcinomas and 447 other solid tumors using tissue microarrays and immunohistochemical(IHC)staining.Result The positive expression rate of TLDC2 was significantly higher than that of SATB2 in colorectal ade-nocarcinomas(96.5％vs 87.0％,P＜0.000 1).TLDC2 positivity exceeded that of SATB2 in both low-or high-grade colorectal adenocarcinoma(99.4％vs 88.7％,P＜0.000 1;83.3％vs 79.2％,P=0.669 9).In addition,the expression of TLDC2 and SATB2 was evaluated in 447 cases of other types of solid tumors.TLDC2 was expressed in neuroendocrine tumors as well as in gastric and appendiceal adenocarcinomas,whereas SATB2 was detected in a small number of melanomas,ovarian cancers,breast cancers and gallbladder cancers.The positive and specificity of TLDC2 for colorectal adenocarcinoma were 97％(95％CI=0.94-0.98)and 85％(95％CI=0.81-0.88),respectively.Combined detection of TLDC2 and SATB2 yielded a sensitivity of 96％(95％CI=0.93-0.97)and a specificity of 93％(95％CI=0.90-0.95).Conclusion Analysis of large-scale datasets and IHC staining demonstrated that TLDC2 is a highly sensitive and specific biomarker for colorectal adenocarcinoma.

Objective To compare the clinical efficacy of high-dose tigecycline(TGC)and polymyxin B(PMB)in the treatment of pulmonary infection due to carbapenem-resistant organism(CRO).Methods Clinical data of pa-tients with CRO pulmonary infection and received PMB or high-dose TGC combined with other antimicrobial treat-ment regimens in Department of Critical Care Medicine of Xiangya Hospital,Central South University from January 2019 to March 2022 were analyzed retrospectively,including basic information,pathogen detection results,antimi-crobial use regimen,clinical efficacy,30-day mortality,bacterial clearance rate,etc.Results A total of 173 pa-tients were included in analysis,with 103 in the TGC group and 70 in the PMB group.Compared with TGC group,PMB group had a higher score of acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ)(25.0 vs 20.0,P＜0.001),but clinical efficacy rates were not statistically different(67.1％vs 52.4％,P=0.054).Stratified analysis revealed that when the APACHE Ⅱ score was ≥15 points,compared with TGC group(n=78),PMB group(n=66)had a higher APACHE Ⅱ score(27.0 vs 22.0,P=0.005)and a higher clinical efficacy rate(66.7％vs 47.4％,P=0.020).After adjusting confounding factors through logistic regression analysis,it was found that PMB treatment was a protective factor for clinical efficacy rate compared with TGC treatment.Conclusion For treating pulmonary infection caused by CRO in patients,PMB-based treatment regimen has a significant protec-tive effect on the clinical efficacy rate compared with the high-dose TGC-based treatment regimen.

Objective:To investigate the clinicopathological characteristics of breast squamous cell carcinoma and to analyze the relationship between its immune microenvironment tumor infiltrating lymphocytes (TILs) and prognosis.Methods:Forty-four cases of primary squamous cell carcinoma of the breast diagnosed and treated in the First Affiliated Hospital of Air Force Medical University, Xi′an, China from January 2006 to July 2022 were selected. Their clinicopathological characteristics were analyzed. The cell composition of TILs was evaluated using immunohistochemistry (Mainly markers of B lymphocytes, T lymphocytes and plasma cells). The relationship between TILs and prognosis was also analyzed.Results:The 44 patients of breast squamous cell carcinoma were all female and all were invasive carcinoma. Eight cases (8/44, 18.2%) were squamous cell carcinoma, while 36 cases (36/44, 81.8%) were mixed squamous cell carcinoma. The mixed components included non-specific carcinoma and spindle cell metaplastic carcinoma (17 cases each). One case contained ductal carcinoma in situ of the breast and 1 case contained tubular carcinoma. The proportion of squamous cell carcinoma was 10% to 90%. The cases with pure squamous cell carcinoma often had a large cystic cavity, which was lined by atypical squamous epithelium, while infiltrating squamous cell carcinoma nests were seen in the breast tissue around the cystic cavity. Immunohistochemical staining showed that p63 and CK5/6 were expressed in the squamous cell carcinoma component, but ER, PR and HER2 were not, except for one case of HER2 1+. The positive rates of TRPS1 and PDL-1 were 76% and less than 1%, respectively. Fifteen cases were in the high TILs group (TILs≥30%) and 29 cases were in the low TILs group (TILs<30%). Twenty-three patients were followed up for 5 to 118 months. Among them, 12 died within 3 years and 9 were alive at the end of the follow up. There was no significant difference in TNM stage, TILs and prognosis between simple squamous cell carcinoma and mixed squamous cell carcinoma.Conclusions:Breast squamous cell carcinoma can be divided into simple squamous cell carcinoma and mixed squamous cell carcinoma. There are differences in gross findings and histology between the simple and mixed squamous cell carcinoma of the breast. Sufficient samples should be taken to avoid missing the diagnosis of a minor squamous component. The prognosis of patients with high TILs is significantly better than that of patients with low TILs. The expression rate of TRPS1 in primary squamous cell carcinoma of breast is high and helpful to the differential diagnosis from metastatic squamous cell carcinoma.

Background Pneumoconiosis is one of the most common and widespread prescribed occupational diseases in China, and there is no cure for it at present. The Healthy China 2030 underlines that the prevention and treatment of pneumoconiosis are the critical element of promoting occupational health. Objective To understand the basic characteristics, social security, and death causes of pneumoconiosis cases in Ninghai County, and to provide a basis for scientific prevention and treatment of pneumoconiosis. Methods Information on pneumoconiosis cases in Ninghai County from 1974 to 2019 was obtained by consulting occupational disease and occupational health information monitoring systems, occupational disease diagnosis institutions, and employers, which may retain original data on occupational pneumoconiosis diagnosis, as well as specialized epidemiological survey projects on pneumoconiosis. Telephone or face-to-face follow-up visits were conducted based on relevant information to complete or verify relevant information such as length of service with dust exposure, type, stage, and diagnosis date of pneumoconiosis. ANOVA, chi-square test, and rank-sum test were used to analyze age of diagnosis and age of death, entitlement to social security and mortality rate of cases/length of service. Results As of the end of 2019, a total of 420 cases of pneumoconiosis were diagnosed among workers exposed to dust in Ninghai County, with 409 cases (97.38%) followed up and 11 cases (2.62%) lost to follow-up. Since the first case of pneumoconiosis was reported in 1974, 39 cases, 278 cases, and 101 cases of pneumoconiosis were reported before 2000, from 2000 to 2009, and from 2010 to 2019, respectively. Two other cases of pneumoconiosis were diagnosed with an unknown year, one as a dead case and one as a lost case. There were 294 surviving pneumoconiosis cases, who mainly lived in Sangzhou Town. The mean age of diagnosis was (58.68±15.37) years old, and the median length of service with exposure to dust was 8.0 (4.0, 15.7) years. The age of diagnosing stage III pneumoconiosis was less than that of stage I and stage II, and the difference between the age of diagnosing stage III and stage II pneumoconiosis was significant (P <0.05). There were 231 cases (78.57%) aged ≥ 60 years, while there were 74 cases aged ≥ 80 years (25.17%). There were 160 cases (54.42%) whose length of service was < 10 years. There were 12.59% and 7.82% of the total cases compensated by work injury insurance and civil compensation by employers, respectively. From the perspective of diagnosis period, the proportion of patients who collected work-related injury insurance and civil compensation from employers in the 2010—2019 year group was higher than that in the <2000 year group or the 2000—2009 year group (P<0.01). There were 115 fatal pneumoconiosis cases, and the fatality rates of stage I, II , and III pneumoconiosis were 23.86%, 18.18%, and 50.75%, respectively. The fatality rate of stage III pneumoconiosis was higher than that of stage I or II (P <0.05). The age of diagnosis and age of death of stage III pneumoconiosis cases were lower than those of stage I and II (P <0.05). The cause of death was definite in 65 patients, including 25 cases (38.46%) of respiratory diseases (except lung cancer) and 28 cases (43.07%) of tumors, and lung cancer accounted for 1/2 of the pneumoconiosis cases that died due to tumors. Conclusion The surviving pneumoconiosis cases in Ninghai are mainly older than 60 years old and largely live in Sangzhou Town. Constructing local rehabilitation stations should be taken as an opportunity to actively prevent and treat pneumoconiosis complications, further improving the quality of life of pneumoconiosis patients.

Metabolic reprogramming is a hallmark of cancer, including lung cancer. However, the exact underlying mechanism and therapeutic potential are largely unknown. Here we report that protein arginine methyltransferase 6 (PRMT6) is highly expressed in lung cancer and is required for cell metabolism, tumorigenicity, and cisplatin response of lung cancer. PRMT6 regulated the oxidative pentose phosphate pathway (PPP) flux and glycolysis pathway in human lung cancer by increasing the activity of 6-phospho-gluconate dehydrogenase (6PGD) and α-enolase (ENO1). Furthermore, PRMT6 methylated R324 of 6PGD to enhancing its activity; while methylation at R9 and R372 of ENO1 promotes formation of active ENO1 dimers and 2-phosphoglycerate (2-PG) binding to ENO1, respectively. Lastly, targeting PRMT6 blocked the oxidative PPP flux, glycolysis pathway, and tumor growth, as well as enhanced the anti-tumor effects of cisplatin in lung cancer. Together, this study demonstrates that PRMT6 acts as a post-translational modification (PTM) regulator of glucose metabolism, which leads to the pathogenesis of lung cancer. It was proven that the PRMT6-6PGD/ENO1 regulatory axis is an important determinant of carcinogenesis and may become a promising cancer therapeutic strategy.