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*

The interaction between m⁶A-methylated RNA and chromatin modification remains largely unknown. We found that targeted inhibition of bromodomain-containing protein 4 (BRD4) by siRNA or its inhibitor (JQ1) significantly decreases mRNA m⁶A levels and suppresses the malignancy of breast cancer (BC) cells via increased expression of demethylase AlkB homolog 5 (ALKBH5). Mechanistically, inhibition of BRD4 increases the mRNA stability of ALKBH5 via enhanced binding between its 3' untranslated regions (3'UTRs) with RNA-binding protein RALY. Further, BRD4 serves as a scaffold for ubiquitin enzymes tripartite motif containing-21 (TRIM21) and ALKBH5, resulting in the ubiquitination and degradation of ALKBH5 protein. JQ1-increased ALKBH5 then demethylates mRNA of extra spindle pole bodies like 1 (ESPL1) and reduces binding between ESPL1 mRNA and m⁶A reader insulin like growth factor 2 mRNA binding protein 3 (IGF2BP3), leading to decay of ESPL1 mRNA. Animal and clinical studies confirm a critical role of BRD4/ALKBH5/ESPL1 pathway in BC progression. Further, our study sheds light on the crosstalks between histone modification and RNA methylation.

Objective:To assess the prognostic value of methylation of interferon regulatory factor 6 ( IRF6) gene promoter in patients diagnosed with Kidney renal clear cell carcinoma (KIRC). Methods:The primary lesions of fifty KIRC patients who were diagnosed at the First Affiliated Hospital of Nanjing Medical University from January 2016 to January 2020 were collected. The expression of IRF6 protein was determined with an immunohistochemical method. The correlation between the level of IRF6 expression and survival and/or metastasis status was analyzed. The mRNA and protein levels of the IRF6 in KIRC and normal renal tissues were compared by using bioinformatic tools. The difference in the methylation rate of the IRF6 gene promoter between tumor and adjacent tissues was analyzed by searching the online databases. Statistical analysis was carried out for the methylation status of the IRF6 gene promoter region to select those negatively correlated with the overall survival (OS) among the patients. In vitro experiments were conducted with cell lines to verify the correlation between the status of promoter methylation and transcription level of the IRF6 gene. Results:The mRNA and protein levels of the IRF6 gene in KIRC tissues were significantly lower than those of the normal controls, and this was more prominent in patients who had died or developed metastasis. The extent of IRF6 gene promoter methylation in the KIRC tissues was much higher compared with that of the adjacent normal renal tissues. There was a significant negative correlation between the methylation of the IRF6 gene promoter and mRNA level of the IRF6 ( R= -0.52). The higher methylation degree in the IRF6 gene promoter regions cg12034118 and cg16030177, the shorter the OS and worse prognosis in the patients. Only twenty CpG sites in cg12034118 were confirmed to be highly methylated in KIRC cell lines. The transcription level of the IRF6 gene was upregulated in a time- and dose-dependent manner after the treatment with demethylation reagent 5-azadeoxycytidine. Conclusion:The methylation of IRF6 gene promoter in the renal tissues of KIRC patients is closely correlated with the OS. Cg12034118 may provide a promising biomarker for laboratory detection, and its high methylation rate has certain reference value for the prognosis.

Objective:To compare the curative effects of butterfly-shaped flap based on the dorsal branch of digital artery (hereinafter referred to as butterfly-shaped flap) and propeller flap based on the dorsal branch of digital artery (hereinafter referred to as propeller flap) in repairing the wound in volar aspect of finger.Methods:A retrospective cohort study was conducted. From August 2018 to April 2022, 16 patients with finger palmar wounds admitted to Ruijin Hospital of Shanghai Jiao Tong University School of Medicine and 7 patients with finger palmar wounds admitted to General Hospital of PLA Central Theater Command met the inclusion criteria, including 14 males and 9 females, aged 25 to 64 years. After debridement or resection of skin benign tumor, the wounds ranged from 0.5 cm×0.5 cm to 1.5 cm×1.5 cm. According to the different rotation axes of flap pedicle during wound repair, the patients were divided into butterfly-shaped flap group (8 cases) and propeller flap group (15 cases), and their wounds were repaired by butterfly-shaped flap (with area of 0.5 cm×0.5 cm-1.5 cm×1.3 cm) or propeller flap (with area of 0.7 cm×0.5 cm-1.5 cm×1.5 cm) , respectively. In propeller flap group, wounds in the donor sites were repaired by full-thickness skin grafts taken from the palms of wrists or the groin. The surgical time, postoperative complications, flap survival, and wound healing time of patients in the two groups were recorded. Data were statistically analyzed with independent sample t test, Mann Whitney U test, or Fisher's exact probability test. Results:The surgical time and postoperative wound healing time of patients in butterfly-shaped flap group ((43±9) min and (13.1±0.8) d, respectively) were both significantly shorter than those in propeller flap group ((87±16) min and (16.7±4.6) d, respectively, with t values of -7.03 and -2.86, respectively, P<0.05). The postoperative flap survival and complications of patients between the two groups were both similar ( P>0.05). Conclusions:For repairing the wound in volar aspect of finger, the butterfly-shaped flap has more advantages in comparison with the traditional propeller flap. The butterfly-shaped flap has a short surgical time and fast postoperative recovery, which is worthy of clinical promotion.

Objective:To investigate the clinical effect of self-designed modified rhomboid flap in repairing rhomboid, round, and teardrop-shaped wounds on the face.Methods:A retrospective observational study was conducted. From August 2018 to April 2020, 30 patients with facial lesions admitted into Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine and the People's Hospital of Jianchuan County in Yunnan province met the inclusion criteria, including 16 males and 14 females, aged 23 to 88 years. The wound area ranged from 1.0 cm×1.0 cm to 7.0 cm×5.0 cm, with 10 cases of rhomboid wounds, 12 cases of round wounds, and 8 cases of teardrop-shaped wounds. The self-designed modified rhomboid flaps were applied to repair the wounds and after that, the patients were followed up for 1 to 18 months to record the survival of flaps, wound tension, scar formation and complications after surgery.Results:No necrosis or blackening was observed at the tip of the flaps after surgery. All the flaps survived and the wounds healed well with little tension, minimal scars, and no complications.Conclusions:The self-designed modified rhomboid flap is especially suitable for facial wounds with multiple important organs, multiple anatomical subunits, and areas with large changes in soft tissue tension, which can reduce not only the rotation of the flap, but also unnecessary excision of normal skin and soft tissue.

Objective: To improve the diagnosis and therapy of childhood pulmonary thromboembolism (PTE) by analyzing the clinical features of this rare condition. Methods: A total of 8 pediatric patients (4 males, 4 females) with PTE diagnosed in the Children′s Hospital of Zhejiang University School of Medicine from March, 2014 to March, 2019 were enrolled. The clinical manifestation, laboratory results, imaging findings, diagnosis and treatment were summarized. Results: Among these 8 cases, aged from 9 hours to 14 years and 10 months. Fever was found in 4 cases, cough aggravation in 4, short of breath in 3, chest pain in 2, abdominal and back pain in one, hemoptysis in 2, cyanosis in 1, and edema of lower extremities in 2. Physical examination found decreased breath sound in 2 cases, phlegm rale in 3, and pleural friction rub in one. Pleural effusion was found in 5 cases by ultrasound. Plasma D-dimer increased in 6 cases (0.66-9.96 mg/L) and hypersensitive C-reactive protein elevated in 5 cases (10.78-78.00 mg/L). Chest enhanced CT showed pulmonary artery or venous filling defects, including pulmonary artery embolism in 7 cases and pulmonary vein embolism in one. The primary disease of these patients included Mycoplasma Pneumoniae pneumonia in 4 cases, nephritis in 2 and postoperative congenital heart disease in 2. Apart from one case who withdrew the treatment and was discharged, the other 7 patients received anticoagulant treatment had good outcome. Conclusions For children with Mycoplasma pneumoniae pneumonia, immune disorders, long-term hormone therapy, cardiovascular invasive operation or other high-risk factors, PTE should be considered when fever, cough aggravation, short of breath, chest and back pain with pleural effusion are present. Chest enhanced CT scan should be performed as soon as possible, and anticoagulation should be started once the diagnosis is confirmed.

Objective To study the effect of multi-disciplinary team (MDT) management on the outcome in neonates with omphalocele.Method A retrospective non-randomized controlled clinical study was conducted.Neonates who were diagnosed as omphalocele and admitted to the surgical neonatal intensive care unit of the Guangzhou Women and Children Medical Center from December 2010 to December 2017 were collected.Because MDT was established in December 2014,infants were assigned into non-MDT group and MDT group according to their dates of admission.The characteristics and outcomes between non-MDT group and MDT group were compared using x2,t-test or rank-sum test.Multivariate analysis was performed by Logistic regression.Result A total of 91 neonates were included in the study,50 were in non-MDT group and 41 were in MDT group.The mortality in MDT group (2.4％,1/41) was lower than that in non-MDT group (18.0％,9/50),the difference was statistically significant (P ＜ 0.05).The median time of mechanical ventilation of giant omphalocele in non-MDT group (18.3 hours) was longer than that in MDT group (41.7 hours),the difference was also statistically significant (P ＜ 0.05).After adjusting for the associated confounding risk factors,the risk of death in non-MDT group was 54 times higher than that in MDTgroup (OR=54.19,95％CI2.64 ～1 113.49,P＜0.05).Conclusion There was significant association between the MDT management and the decreased risk of death of omphalocele.

Objective: To investigate the expression differences of serum tumor markers, such as CEA, CA125 and CA15-3, in different molecular subtypes of breast cancer and their correlations with recurrence and metastasis. Methods: The medical records and follow-up data from 212 patients with breast cancer were retrospectively analyzed. According to the expression of hormone receptor, breast cancer were divided into four molecular subtypes: Luminal A, Luminal B, Her-2 overexpression and Basal-like. The clinical characteristics and levels of CEA, CA125 and CA15-3 in different molecular subtypes of breast cancer patients before operation were compared, and the factors influencing the recurrence and metastasis of breast cancer were analyzed. Results: There were differences in the expression levels of tumor markers for different molecular subtypes of breast cancer. The expression levels of CA15-3 in patients with Her-2 overexpression were significantly higher than that with Luminal A, Luminal B or Basal-like (χ 2 =7.98,P=0. 04). The differentiation degree of tumor cells in different molecular subtypes of breast cancer was different, and the proportion of low differentiation in the patients with Her-2 overexpression was significantly higher than that with Luminal A, Luminal B or Basal-like (χ 2 =12.42,P=0.006). There was also differences in the recurrence and metastasis of tumor for 4 subtypes of breast cancer, and the highest recurrence and metastasis rate existed in the patients with Her-2 overexpression (F=8.69,P=0.034). The multivariate Cox regression analysis showed that tumor diameter, degree of tissue differentiation and presence or absence of vascular tumor thrombus were independent risk factors for the recurrence and metastasis of breast cancer patients (all P＜0.05). Conclusion The breast cancer patients with Her-2 overexpression have high levels of CA15-3 and poor prognosis, which suggests that the individualized treatment of breast cancer should be combined with molecular subtyping, tumor markers and related risk factors.

Objective: To analyze the influencing factors and clinical significance of severe hypocalcemia in patients with extremely severe burns in early stage. Methods: Clinical data of 142 patients with extremely severe burns admitted to our wards from January 2010 to July 2015, conforming to the study criteria, were retrospectively analyzed. (1) The incidence of hypocalcemia and severe hypocalcemia on admission were calculated. (2) Patients were divided into the male group (n=113) and the female group (n=29) according to gender. The levels of serum calcium of patients whose age more than 55 years old and less than or equal to 55 years old in the two groups were compared with t test. (3) Patients were divided into severe hypocalcemia group (n=52) and non-severe hypocalcemia group (n=90) according to the level of serum calcium on admission. The data including gender, age, flame burn, total burn area, inhalation injury, admission time, the pH value, and the albumin level of patients on admission between two groups were compared with chi-square test or t test. Indexes with P<0.1 between two groups were selected, and multivariate logistic regression analysis was conducted to screen the influencing factors of severe hypocalcemia in patients with extremely severe burns in early stage. (4) According to the prognosis, patients were divided into survival group (n=112) and non-survival group (n=30). The data including gender, age, flame burn, total burn area, inhalation injury, admission time, the level of serum calcium, the pH value, and the albumin level of patients on admission between two groups were compared with chi-square test or t test. Indexes with P<0.1 between two groups were selected, and multivariate Cox regression analysis was conducted to screen the influencing factors of prognosis of patients with extremely severe burns. Results: (1) The incidence of hypocalcemia on admission was 97.2% (138/142), and patients diagnosed as severe hypocalcemia accounted for 36.6% (52/142). (2) In the male group, the level of serum calcium of patients with age more than 55 years old was (1.84±0.19) mmol/L, which was close to (1.88±0.21) mmol/L of patients with age less than or equal to 55 years old within the same group and (1.96±0.13) mmol/L of patients with age more than 55 years old in the female group (t=0.833, 1.560, P>0.05). In the female group, the level of serum calcium of patients with age less than or equal to 55 years old was (1.78±0.19) mmol/L, which was significantly lower than that of patients with age less than or equal to 55 years old in the male group and that of patients with age more than 55 years old in the female group (t=-2.197, -2.472, P<0.05). (3) Compared with those of patients in severe hypocalcemia group, the total burn area and the proportion of inhalation injury of patients in non-severe hypocalcemia group were obviously smaller (t=2.379, χ² =13.410, P<0.05 or P<0.01), and the admission time was obviously earlier (t=2.675, P<0.01), while the albumin level was obviously higher (t=-6.163, P<0.01). There were no statistically significant differences between patients of the two groups in gender, flame burn, age, and the pH value on admission (χ²=1.869, 2.850, t=-0.578, 0.645, P>0.05). Multivariate logistic regression analysis showed that only the albumin level on admission was the independent influencing factor of severe hypocalcemia in patients with extremely severe burns (with odds ratio 1.179, 95% confidence interval 1.092-1.273, P<0.01). (4) Compared with those of patients in non-survival group, the total burn area and the proportion of inhalation injury in survival group were smaller (t=-5.515, χ²=27.573, P<0.05 or P<0.01), while the pH value and the albumin level on admission were higher (t=2.208, 3.321, P<0.05 or P<0.01). There were no statistically significant differences between patients of the two groups in gender, flame burn, age, admission time, and the level of serum calcium on admission (χ²=0.198, 2.545, t=-1.316, -1.397, 1.857, P>0.05). Multivariate Cox regression analysis showed that total burn area and inhalation injury were the independent risk factors to predict prognosis of patients with extremely severe burns (with relative risk 1.066 and 4.081, 95% confidence interval 1.023-1.110 and 1.144-14.559, P<0.05 or P<0.01), but the pH value and levels of albumin and serum calcium were not independent risk factors to predict prognosis of patients with extremely severe burns (with relative risk 0.003, 1.025, and 0.634, 95% confidence interval <0.001-1.183, 0.956-1.099, and 0.055-7.321, P>0.05). Conclusions The level of serum calcium of the majority of patients with extremely severe burns on admission is decreasing significantly, especially the female patients less than or equal to 55 years old. Compared with non-severe hypocalcemia patients, patients with severe hypocalcemia are with larger total burn area, higher proportion of inhalation injury, later admission time, and lower albumin level on admission. However, only the albumin level on admission is the independent influencing factor of severe hypocalcemia in patients with extremely severe burns. And the level of serum calcium on admission can not predict the prognosis of patients with extremely severe burns.

Objective: To retrospectively analyze the prognostic value of platelet count recovery in the early stage post burn for patients with extremely severe burn, so as to evaluate their severity. Methods: A study involving 244 adult patients with extremely severe burn admitted to our hospital from January 2006 to December 2015, conforming to the inclusion criteria, was conducted. Data of their demography, injury, transmission, disease change in hospital, and platelet count from post injury day (PID) 1 to 10 were collected. (1) Patients were divided into survival group (n=212) and non-survival group (n=32) according to whether death or not. The dynamic change characteristic of platelet count in patients of two groups from PID 1 to 10 was analyzed and compared. (2) Patients were divided into return to normal group (RN, n=163) and non-return to normal group (NRN, n=81) according to whether platelet count returned to normal within one week post burn. The proportion of patients who received mechanical ventilation and mortality in groups RN and NRN, and length of stay in ICU between patients with platelet count that returned to normal and that did not return to normal in the early stage post burn in survival group were compared. Data were processed with independent samples t test , analysis of variance of repeated measurement, chi-square test, and binomial distribution test. Correlation was analyzed between data of sex, age, weight, total burn area, full-thickness burn area, inhalation injury, length of hospital stay, receiving mechanical ventilation, platelet count recovery condition within one week post burn and death of patients using the univariate and multivariate Cox regression analysis. Receiver operating characteristic (ROC) curve of platelet count on PID 8 was drawn to evaluate predicting value for death of 244 patients. Results: (1) The platelet count kept declining from PID 1 to 4, declined to below the normal low limit on PID 2, and reached its lowest level on PID 4 both in survival group and non-survival group. The platelet count both in survival group and non-survival group rose gradually from PID 4 to 10, and returned to normal on PID 8 and 10, respectively. There was no significant difference in platelet count of patients in two groups on PID 1 (t=1.01, P>0.05), while platelet count of patients in non-survival group was obviously lower than that in survival group from PID 2 to 10 (with t values from 2.64 to 7.17, P values below 0.01). The daily increment of platelet count in survival group from PID 4 to 10 was (26±13)×10⁹/L, obviously higher than that in non-survival group [(19±11)×10⁹/L, t=2.76, P<0.01]. (2) The proportion of patients who received mechanical ventilation was obviously lower than that of patients who did not receive mechanical ventilation in group RN (P<0.01), while the proportion of patients who received mechanical ventilation was obviously higher than that of patients who did not receive mechanical ventilation in group NRN (P<0.05). The proportion of patients who received mechanical ventilation in group NRN was obviously higher than that in group RN (χ²=32.93, P<0.01). The mortality of patients in group NRN was obviously higher than that in group RN (χ²=20.99, P<0.01). The length of stay in ICU of patients whose platelet count did not return to normal in the early stage was significantly longer than that of patients whose platelet count returned to normal in the early stage in survival group (t=4.20, P<0.01). (3) Total burn area, receiving mechanical ventilation, and platelet count did not return to normal within one week post burn were independent risk factors for death of patients with extremely severe burn (with hazard ratio respectively 1.073, 16.552, and 2.249, 95% confidence interval respectively 1.033-1.115, 2.147-127.580, and 0.993-5.096, P<0.05 or P<0.01). (4) The area under the ROC curve of platelet count on PID 8 to predict death of 244 patients with extremely severe burn was 0.745 (with 95% confidence interval 0.645-0.845, P<0.01), and 150×10⁹/L was chosen as the optimal threshold value, with sensitivity of 71.4% and specificity of 71.0%. Conclusions Platelet count recovery in the early stage post burn of patients with extremely severe burn was significantly associated with their prognosis and could be used as an important indicator to evaluate the severity of illness.