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*

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

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.

Gliomas are commonly central nervous system tumors. The conventional treatment is surgical resection combined with chemoradiotherapy， but glioma patients often have a poor prognosis. Therefore， there is an urgent need to identify new potential targets in gliomas and develop more effective treatments. Valproic acid has the properties of histone deacetylase inhibitor， which has been proven to have inhibitory effects on various tumors. It is confirmed that valproic acid could promote apoptosis and cell arrest of glioma cells， inhibit cell invasion and glioma stem cells， increase the sensitivity of glioma cells to radiotherapy and chemotherapy by regulating ERK/Akt signaling pathway， Akt/mTOR signaling pathway， and regulating expression levels of RECK， MGMT， Nrf2， PON2， Smad4， GSK3β and other proteins. In addition， valproic acid can also enhance the effectiveness of anticancer drugs by inhibiting the growth of glioma stem cells and inducing their differentiation. In conclusion， valproic acid can inhibit glioma through multiple targeted actions， and may become a new targeted drug for the treatment of glioma.

Gallbladder dysplasia is not common but can be associated with chromosome abnormality and/or some severe complications such as biliary atresia and cystic fibrosis. Therefore, prenatal detection of this problem is of great significance for timely management after birth. However, abnormal gallbladder development is often overlooked in routine mid-term fetal ultrasound scanning. Here, we reviewed the research progress on fetal gallbladder dysplasia, including clinical characteristics and perinatal prognosis of gallbladder duplication, echo substances in gallbladder and gallbladder cholelithiasis, ectopic gallbladder, gallbladder enlargement, and cystic fibrosis, and summarized the types, incidence, clinical features, prenatal diagnosis and perinatal prognosis of non-visualized fetal gallbladder, in order to emphasize the prenatal screening of fetal gallbladder dysplasia.

Objective: To establish a triple-color pseudovirion-based neutralization assay (PBNA) and evaluate its capability of detecting immunogenicity of the sera generated by the immunization of HPV 9-valent vaccine. Methods: HPV pseudovirus (PsVs) 6/11/16/18/31/33/45/52/58 with the encapsidated fluorescence expressing red fluorescent plasmid N31-MCHREEY, green fluorescent N31-EGFP or blue fluorescent N31-mTagBFP were generated. The concentration of HPV PsVs and the infection titers of HPV PsVs were detected by double-antibody sandwich ELISA and TCID₅₀, respectively. The single- and triple color HPV 16/33/45 PsVs were used to detect the neutralization titers of mice sera immunized with HPV 9-valent vaccine and confirmed the accuracy and specificity of the triple-color PBNAs. Then, the single- and triple color HPV 6/11/18/31/33/45/52/58 PsVs were employed to detect the neutralization titers of cynomolgus macaques sera immunized with HPV 9-valent vaccine and determined whether the triple-color PBNAs could be applied to evaluate the immunogenicity of the sera generated by the immunization of HPV9-valent vaccine. Results: The concentration of HPV16 PsVs encapsulating green, red or blue fluorescent plasmid was 5.0 to 6.0 μg/ml and HPV6/11/18/31/33/45/52/59 triple-color HPV PsVs was about 1.0 to 3.0 μg/ml. 9 types HPV PsVs containing EGFP, Mcherry or mTagBFP reporter plasmid were obtained and the concentration can meet the need of neutralization detection. 9 types single-color fluorescent HPV PsVs had similar infectivity against 293FT cells with the infection titer values between 1×10⁴ and 1×10⁵. The results of PBNAs showed that there was no significant difference in the anti-HPV neutralization titers of mice sera induced by HPV 9-valent vaccine between single-color and triple-color HPV16/33/45 PsVs (P>0.05). Similarly, there was also no significant difference in the anti-HPV neutralization titers of cynomolgus macaques sera induced by HPV 9-valent vaccine between single-color and triple-color HPV6/11/18/31/33/45/52/58 PsVs (P>0.05). Conclusion We successfully established the triple-color PBNAs and verified the accuracy and specificity of triple-color PBNAs consistent with single-color PBNAs. The triple-color PBNAs can be applied to evaluate the immunogenicity of HPV 9-valent vaccine's immune serum.

Purpose To explore the expression and significance of histone methyltransferase EZH2,clinicopathological features in primary testicular diffuse large B-cell lymphoma (DLBCL).Methods Immunohistochemical of Ventana Ultra View two-step staining was used to detect expression of EZH2 in 17 cases of primary testicular DLBCL.The relationship between EZH2 expression and its clinicopathological features were analyzed.Sanger squencing was used to detect EZH2 Y641 mutation in these cases.Results Morphologically,the tumor cells resembled centroblasts in 11 cases,immunoblasts in 3 cases,and anaplastic variants in 3 cases.Immunophenotypically,14 cases were non-germinal centre B cell like (non-GCB) type and 3 cases were germinal centre B cell like (GCB) subtype.EZH2 overexpressed in all 17 cases.EZH2 overexpressed in nearly tumor celts with uniformly strong intensity in 15 cases,and more than 70％ tumor cells with moderate to strong intensity in 2 cases.The follow-up information was obtained in 9 patients,with a median survival time of 35 months.No association was found between the level of EZH2 expression and outcome of patients.No mutation of EZH2 Y641 was detected.Conclusion Primary testicular DLBCL is a rare aggressive B cell lymphoma with distinctive clinicopathological features.Detection of EZH2 expected to assist in the diagnosis and treatment of tumor.

Objective: To investigate the clinicopathologic features and grading of adenoid cystic carcinoma (ACC) of the breast. Methods: Sixteen cases of ACC of the breast were analyzed and graded according to the previous report. Immunohistochemical (IHC) staining was used to detect the immunophenotype, Ki-67 proliferative index and expression of EZH2, and the association with tumor grade and outcome was analyzed. Results: Of the 16 cases, 11 were grade Ⅰ, with the epithelial and myoepithelial cells being arranged into tubular and cribriform structure with no solid component; three were grade Ⅱ, which were composed of mixed tubular, cribriform and solid component (<30%); and two were grade Ⅲ, which showed mainly solid component (>90%) and the tumor cells showed basaloid features with scanty cytoplasm and hyperchromatic nuclei, and mitotic count was>5/10 HPF. Immunophenotypically, the epithelial cells expressed CK7, CK8/18 and CD117; the myoepithelial cells expressed p63 and CK5/6; while the basaloid cells were positive for CK5/6 and CD117.Tubular and cibriform ACC showed low Ki-67 and EZH2 expression, while the two cases of solid variant with basaloid features showed high level of Ki-67 and EZH2 expression. Follow-up data were available in 13 cases with a median follow-up period of 42 months. Lung metastasis occurred after 12 months in one grade Ⅱ case and the patient died of disease after 34 months. Vertebral metastasis occurred after 12 months in one grade Ⅲ case and axillary lymph node metastasis occurred in another grade Ⅲ case. All other patients were free of disease at the end of the follow-up periods. Conclusions ACC shows morphologic spectrum varying from low to high grade, the latter can may give rise to local and distant metastasis. ACC should not be regarded simply as low malignant potential, and should be graded for optimal treatment.

Objective: To investigate the localization of HBXIP protein over-expression in gastric adenocarcinoma, and its prognostic significance. Methods: HBXIP localization was detected by immunofluorescence in AGS gastric cancer cell line, and by immunohistochemical staining in 97 gastric adenocarcinomas, 41 adjacent non-tumor tissues and 13 gastric adenoma tissues. Correlation between HBXIP expression and clinicopathological features of gastric cancer patients was evaluated by Chi-square and Fisher′s exact tests. Overall survival rates were calculated using Kaplan-Meier method. Results: HBXIP was mainly expressed in the cytoplasm of gastric cancer. The positive and strongly positive expression rates of HBXIP protein in gastric cancers were 68.0% (66/97) and 49.5% (48/97) respectively, and were significantly higher than those in adjacent non-tumor tissues(48.8%, 20/41; 36.6%, 15/41) or gastric adenomas(2/13, 1/13; all P<0.05). HBXIP expression correlated significantly with tumor differentiation and lymph node status (P=0.007; 0.041). Kaplan-Meier survival analysis showed that the overall survival rate was significantly lower in gastric cancer patients with high HBXIP expression (P=0.015). Conclusions HBXIP expression in gastric cancer is mainly expressed in cytoplasmic, and the expression level is closely related to the prognosis. HBXIP expression status may potentially be used as an important prognostic indicator for gastric cancer.

Purpose To investigate the mutations of ID3,TCF3 and MYC genes in Chinese Burkitt lymphoma and discuss their significance.Methods Total DNA was extracted from tumor tissues of 32 patients with Burkitt lymphoma,then the DNA was amplified by polymerase chain reaction (PCR),and the products of PCR were sequenced directly with Sanger sequencing methods.Results The mutation rates of ID3 and TCF3 genes were 35.5％ (11/31) and 18.8％ (6/32) respectively.The mutation rate of MYC was 50％.The mutation rates of MYC exon 1,MYC exon 2 and MYC exon 3 were 3.3％ (1/30),50％ (15/30) and 7.7％ (2/26) respectively.Conclusion Recurrent mutations of the ID3,TCF3 and MYC genes in Chinese Burkitt lymphoma were identified by Sanger sequencing.For TCF3 gene,a novel mutation c.2202G ＞ C p.L569V was found in three cases.In two cases,a novel mutation of c.1070A ＞G p.G182D was found in MYC gene.