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.

Injection lipolysis is emerging as an non-surgical cosmetic procedure in recent years. However related risks should be noted. Non-tuberculous mycobacterium infection caused by Injection lipolysis was rarely reported so far. In October 2020, a patient who developed infection at the injection site after receiving lipolysis injection in a beauty salon was admitted to the Fourth People’s Hospital of Chenzhou. The patient had multiple masses on his right upper arm, abdomen, waist and back, with a size of about 3 cm×4 cm. The local masses was red with high skin temperature, and there was obvious fluctuation and tenderness. Skin abcess was diagnosed. Abscess debridement was performed, the necrotic tissue in the abscess cavity was completely removed and continuous negative pressure drainage was performed. The biopsy showed chronic granulomatous lesions. The secretions were cultured and the results showed rapid growth of non-tuberculous mycobacteria. A microbial genetic test was carried out, and the result was Mycobacterium immunogenun. The medical treatment was amikacin for 1 month and clarithromycin for 6 months. No special discomfort was found during drug administration, and the affected skin was completely healed without recurrence after withdrawal of the drug for half a year.

Injection lipolysis is emerging as an non-surgical cosmetic procedure in recent years. However related risks should be noted. Non-tuberculous mycobacterium infection caused by Injection lipolysis was rarely reported so far. In October 2020, a patient who developed infection at the injection site after receiving lipolysis injection in a beauty salon was admitted to the Fourth People’s Hospital of Chenzhou. The patient had multiple masses on his right upper arm, abdomen, waist and back, with a size of about 3 cm×4 cm. The local masses was red with high skin temperature, and there was obvious fluctuation and tenderness. Skin abcess was diagnosed. Abscess debridement was performed, the necrotic tissue in the abscess cavity was completely removed and continuous negative pressure drainage was performed. The biopsy showed chronic granulomatous lesions. The secretions were cultured and the results showed rapid growth of non-tuberculous mycobacteria. A microbial genetic test was carried out, and the result was Mycobacterium immunogenun. The medical treatment was amikacin for 1 month and clarithromycin for 6 months. No special discomfort was found during drug administration, and the affected skin was completely healed without recurrence after withdrawal of the drug for half a year.

Objective: To explore the efficacy of thoracoscopic bronchial sleeve lobectomy for central non-small cell lung cancer (NSCLC), and to evaluate the safety of this operation. Methods: The clinical data of 29 patients who underwent thoracoscopic bronchial sleeve lobectomy at Shanxi Provincial Cancer Hospital from May 2015 to September 2018 were retrospectively analyzed, and the surgical effect and safety were analyzed. Results: Twenty-nine cases underwent thoracoscopic bronchial sleeve lobectomy. The types of resection included 13 cases of right upper, 10 cases of left upper, and 6 cases of left lower sleeve lobectomy. The operation time was 180-400 min, and the median time was 240 min. The bronchial anastomosis time was 35-60 min, and the median time was 48 min. The intraoperative blood loss was 150-460 ml, and the median blood loss was 220 ml. The number of lymph node dissection was 12-39 lymph nodes per patient, with a median of 19.6 lymph nodes per patient. The thoracic drainage tube was placed for 4-16 days after operation, with a median of 6 days; the postoperative hospital stay was 6-16 days, with a median of 9 days. The postoperative complication rate was 24.1% (7/29), including 1 case with pulmonary air leakage (> 7 days), 2 cases with pulmonary infections, 3 cases with arrhythmia, and 1 patient discharged from the hospital on the 7th day after surgery, but died of anastomotic fistula bleeding on the 40th day. The rest of the patients recovered smoothly after surgery. The median follow-up time was 6 months (3-12 months). No tumor recurrence or anastomotic stenosis was observed. Conclusion Thoracoscopic bronchial sleeve lobectomy is a safe and feasible surgical treatment for central NSCLC.

OBJECTIVE: To observe the expression of interleukin(IL)-23 and IL-17 in the liver of mice sensitized by trichloroethylene(TCE), and to explore the role of IL-23 and IL-17 in polyinosinic: polycytidylic acid(Poly I:C) exacerbated TCE-sensitized mice with immune injury of the liver. METHODS: Female specific pathogens free BALB/c mice were randomly divided into control group(n=5), solvent control group(n=5), TCE group(n=20), and TCE+Poly I:C group(n=20). A TCE-sensitized mouse model was established in TCE group and TCE+Poly I:C group. Three hours before the last challenge, mice in TCE+Poly I:C group was intraperitoneally injected with a mass concentration of 0.5 g/L poly I:C, 100 μL per mouse. The two groups of mice were divided into sensitized and non-sensitized subgroups according to the results of skin sensitization. After 48 hours of the final challenge, serum alanine aminotransferase(ALT) was detected by colorimetric method. The histopathological changes of mouse liver were observed, and the expression of IL-23 and IL-17 in liver tissues was detected by immunohistochemistry and Western blotting method. RESULTS: The sensitization rates of TCE and TCE+Poly I:C groups were 35.0%(7/20) and 40.0%(8/20) respectively, with no significantly statistical difference(P>0.05). Pathological examination showed that there was cell edema in some areas of the liver tissues of mice in the TCE-sensitized subgroup, while the TCE+Poly I:C sensitized subgroup showed cell vacuolar degeneration and loose cytoplasm. Serum ALT activity and the expression of IL-23 and IL-17 in liver tissues in the TCE-sensitized subgroup were higher than that in the blank control group, the solvent control group and the TCE non-sensitized subgroup(P<0.05). Serum ALT activity and IL-23 and IL-17 expression in the TCE+Poly I:C sensitized subgroup were higher than that in the TCE-sensitized subgroup(P<0.05). The relative expression of IL-23 and IL-17 protein in liver tissues in TCE-sensitized subgroup was higher than that of the blank control group and the solvent control group(P<0.05), while that in TCE+Poly I:C sensitized subgroup was higher than that of TCE-sensitized subgroup(P<0.05). CONCLUSION: IL-23/IL-17 axis may play an important role in the development of immune injury of liver in the TCE-sensitized mice and Poly I:C exacerbated TCE-sensitized mice.

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.

Objective To analyze the prognostic factors of patients with adenocarcinoma of gastroesophageal junction (AGEJ) after radical resection. Methods In this retrospective study, 269 patients with AGEJ who underwent curative resection from March 2004 to June 2007 were enrolled.The survival curve was drawn by Kaplan-Meier method and the survival analysis was done by Log-rank test. Univariate and multivariate analyses of the prognostic factors of AGEJ were made by Cox model. Results The overall 5-year survival rate of 269 patients was 25.0 % with the median survival time of 22 months.The Siewert type and the number of positive lymph nodes could influence the survival rate (both P < 0.05). Among the 269 patients, 216 (80.3 %) were Siewert Ⅱ type, their median survival time was 30 and 12 months in the thoracic surgery group and the laparotomy group when the tumor diameter was 3-7 cm, the difference was statistically significant (χ2= 5.036, P= 0.025). Univariate analysis showed that tumor diameter, pT, pN, operation time, age and sex were significantly associated with survival rate (all P < 0.05). Cox multivariate analysis showed that patients with a more advanced tumor size suffered from a poorer prognosis (P< 0.05). The risk of postoperative death in patients with lymph node metastasis was 1.854 times that of patients without lymph node metastasis. Conclusions Patients with AGEJ are predominantly Siewert Ⅱ type, the transthoracic approach or thoracoabdominal approach are reasonable selections for these patients. Tumor diameter and pN are independent prognostic factors of AGEJ patients.

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.