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 clinical characteristics and genetic etiology in a fetus with 12q14 microdeletion syndrome. METHODS: A fetus diagnosed with 12q14 microdeletion syndrome at Wenzhou People's Hospital in July 2019 was selected as the study subject. The fetus was from a twin pregnancy by in vitro fertilization-embryo transfer, with ultrasound findings including growth restriction, cleft lip/palate, ventricular septal defect, tricuspid regurgitation, and pericardial effusion. Clinical data and family history were collected. Amniotic fluid sample was collected from both twins, and peripheral blood samples were obtained from their parents. Amniocytic karyotyping analysis and chromosomal microarray analysis (CMA) were performed, and familial validation was conducted. This study was approved by the Medical Ethics Committee of Wenzhou People's Hospital (Ethics No.: KY-202408-034). RESULTS: Prenatal ultrasound showed no significant abnormality in one of the twins, whilst the other twin exhibited severe growth restriction accompanied by cleft lip/palate, ventricular septal defect, tricuspid regurgitation, and pericardial effusion. Karyotyping and CMA analyses of first twin showed no abnormalities, whilst the second twin had a chromosomal karyotype of 46,XN,t(3;12)(q26.3;q14), and CMA revealed a 4.9 Mb deletion in the 12q14.3-q15 region (arr[hg19]12q14.3q15(65,574,059_70,488,106)x1). Karyotyping and CMA analyses of both parents revealed no abnormalities, confirming that the fetus deletion was de novo in origin. Literature review suggested that prenatal diagnosis of 12q14 microdeletion syndrome has been extremely rare. CONCLUSION The fetus was diagnosed with 12q14 microdeletion syndrome. This de novo deletion may have dervied from chromosomal translocation. As a first-tier prenatal diagnostic technique, CMA can effectively detect microdeletion/microduplications missed by conventional karyotyping analysis.
Humans ; Female ; Pregnancy ; Chromosome Deletion ; Chromosomes, Human, Pair 12/genetics* ; Karyotyping ; Adult ; Prenatal Diagnosis ; Chromosome Disorders/diagnosis* ; Ultrasonography, Prenatal ; Fetus ; Male

With persistent breakthrough and maturity of surgical procedures and postoperative immunosuppressive therapy, the survival rate of liver transplant recipients and grafts has been significantly increased. The shortage of donor liver has become the main obstacle for clinical development of liver transplantation. How to expand the source of donor liver has become an urgent issue. Groundbreaking progresses have been made in the use of common marginal donor livers in clinical liver transplantation, such as elderly donor liver, steatosis donor liver, viral hepatitis donor liver and liver from donation after cardiac death. Nevertheless, multiple restrictions still exist regarding the use of marginal donor liver. Consequently, the definition of marginal donor liver and research progress in the application of common marginal donor livers were reviewed, and the opportunities and challenges of mariginal donoor liver were illustrated, aiming to provide reference for expanding the donor pool for clinical liver transplantation and bringing benefits to more patients with end-stage liver disease.

Objective:To explore the clinical phenotype and gene characteristics of a case of TSC2/PKD1 adjacency gene syndrome, so as to improve the clinical understanding of the disease.Methods:A case of TSC2/PKD1 adjacency gene syndrome diagnosed in the Department of Neurology of the Children′s Hospital Affiliated to Zhengzhou University was analyzed retrospectively. The clinical data, laboratory examination, imaging characteristics and gene variation characteristics of the child were summarized.Results:The patient was a 17 months old girl, with the main complaint of "intermittent convulsion with 17 months of underdevelopment". The clinical manifestations were epileptic seizures, which were in the form of a series of spastic seizures, absence seizures, focal seizures, and depigmentation spots can be seen in the trunk and neck. Cranial magnetic resonance imaging showed multiple patchy signals in the cortex and subcortical areas of the bilateral cerebral hemispheres, multiple small nodular shadows under the ependyma of the bilateral lateral ventricles, the heart color Doppler ultrasound showed patent foramen ovale and pericardial effusion, and the abdomen color Doppler ultrasound showed polycystic kidney. Ophthalmic color Doppler ultrasound showed that there were localized small swelling lesions around the optic disc of the left eye. The whole exon gene sequencing of the pedigree showed the proband had partial deletion of TSC2 gene (NM_000548) at chromosome position chr16: 2125799-2185690. The real-time quantitative detection system verified that exons 23-42 were deleted, and all exons of PKD1 gene were deleted (NM_001009944), and multiple ligation dependent probe amplification verified that exons 1-46 were deleted, and no downstream gene deletion was found. The overall deletion size was about 60 kb. Both of the girl's father and mother had normal phenotypes and were wild-type.Conclusions:TSC2/PKD1 adjacency gene syndrome is relatively rare. It can have clinical manifestations of tuberous sclerosis/autosomal dominant polycystic kidney disease. Most of the nervous system and kidney are seriously affected, and the prognosis is poor. TSC2/PKD1 gene deletion and variation is the genetic cause of the TSC2/PKD1 adjacency gene syndrome.

Objective:To explore the effects of adriamycin（Adc）combined with hyperbaric oxygen（HBO）on the apoptosis of HepG2 cells and immunomodulatory factors in transplanted hepatocellular carcinoma（HCC）tissues in nude mice.Methods:The model of transplanted HCC was established in 20 nude mice，then the mice were divided into four groups：control group，HBO group，Adc group，and HBO + Adc group，with five mice in each group. The control group was reared normally. The HBO group was treated with HBO at 0.20 MPa for 1 h；the Adc group was treated with 10 mg/kg of Adc by gavage；the HBO + Adc group was treated with HBO at 0.20 MPa for 1 h and then given 10 mg/kg of Adc by gavage. All groups were treated once every other day for 21 days. After drug withdrawal，the tumors were dissected from the sacrificed mice，of which the tumor volume and weight were measured. The apoptosis of HepG2 cells was detected by TUNEL. The changes of apoptosis-related proteins in HepG2 cells were detected by western blotting. The changes of the contents of immunomodulatory factors in transplanted tumor tissues of nude mice were detected by ELISA.Results:After 21 days，the tumor volume and weight in the HBO + Adc group were lower than those in the other three groups（ P<0.05）. The proportion of apoptotic cells in the transplanted tumor tissues of nude mice of the HBO + Adc group was the highest. In the HBO + Adc group，the protein expression levels of Bax，caspase-3，and Cytochrome C were significantly increased；the protein expression of Bcl-2 was significantly reduced（ P<0.01）；and the IL-6 was significantly reduced；while the IL-18 and IFN-γ were significantly increased（ P<0.05）. Conclusion:The Adc combined with HBO can promote apoptosis of HepG2 cells in transplanted HCC tissues in nude mice，and effectively regulate the immunomodulatory factors to promote the recovery of the body’s immune function，suggesting obvious sensitizing and detoxifying effects.

Objective:To explore the effects of adriamycin（Adc）combined with hyperbaric oxygen（HBO）on the apoptosis of HepG2 cells and immunomodulatory factors in transplanted hepatocellular carcinoma（HCC）tissues in nude mice.Methods:The model of transplanted HCC was established in 20 nude mice，then the mice were divided into four groups：control group，HBO group，Adc group，and HBO + Adc group，with five mice in each group. The control group was reared normally. The HBO group was treated with HBO at 0.20 MPa for 1 h；the Adc group was treated with 10 mg/kg of Adc by gavage；the HBO + Adc group was treated with HBO at 0.20 MPa for 1 h and then given 10 mg/kg of Adc by gavage. All groups were treated once every other day for 21 days. After drug withdrawal，the tumors were dissected from the sacrificed mice，of which the tumor volume and weight were measured. The apoptosis of HepG2 cells was detected by TUNEL. The changes of apoptosis-related proteins in HepG2 cells were detected by western blotting. The changes of the contents of immunomodulatory factors in transplanted tumor tissues of nude mice were detected by ELISA.Results:After 21 days，the tumor volume and weight in the HBO + Adc group were lower than those in the other three groups（ P<0.05）. The proportion of apoptotic cells in the transplanted tumor tissues of nude mice of the HBO + Adc group was the highest. In the HBO + Adc group，the protein expression levels of Bax，caspase-3，and Cytochrome C were significantly increased；the protein expression of Bcl-2 was significantly reduced（ P<0.01）；and the IL-6 was significantly reduced；while the IL-18 and IFN-γ were significantly increased（ P<0.05）. Conclusion:The Adc combined with HBO can promote apoptosis of HepG2 cells in transplanted HCC tissues in nude mice，and effectively regulate the immunomodulatory factors to promote the recovery of the body’s immune function，suggesting obvious sensitizing and detoxifying effects.

Objective To evaluate the effect of different cold ischemia time (CIT) on early graft function and acute rejection (AR) after liver transplantation. Methods Clinical data of 218 donors and recipients undergoing liver transplantation were collected and analyzed. All patients were divided into three groups according to the CIT of donor liver: group A (CIT≤6 h, n=60), group B (6 h < CIT≤10 h, n=89) and group C (CIT > 10 h, n=69). Blood samples were collected on the 1, 7 and 14 d after liver transplantation. The changes of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and adenosine triphosphate (ATP) in CD4⁺T cells were detected. The incidence of AR and the positive rate of C4d deposition were analyzed. Results The ALT, AST and LDH levels in each group reached the peak on the 1 d after operation, and then gradually decreased. The indexes in each group were almost equivalent on the 14 d. An interaction effect existed between postoperative time and group. After liver transplantation, ATP levels in CD4⁺T cells were gradually increased in each group, peaked at postoperative 7 d, and then decreased gradually. An interaction effect was noted between postoperative time and group. The incidence of AR in groups A, B and C was 10%, 12% and 28%. Compared with group C, the incidence of AR in groups A and B was decreased significantly (both P < 0.05/3). The positive rate of C4d deposition in AR recipients of groups A, B and C was 1/3, 45% and 89% respectively. Compared with group C, the positive rate of C4d deposition in group A was decreased significantly (P=0.015). Conclusions The prolongation of CIT may lead to aggravation of early-stage liver function injury after liver transplantation, which is more easily to induce humoral AR.

Objective: To explore the safety of liver transplantation recipients with Rh blood group mismatchming. Methods: From May 2005 to December 2018, 1 546 cases of liver transplantation in our hospital were retrospectively analyzed. Among these cases, 5 cases of Rh blood group mismatched were Rh(-) recipients receiving Rh(+ ) donor liver. For each Rh blood group mismatched liver transplantation, 5 patients received the same Rh blood group liver allograft were matched according to a certain principle and were defined as Rh-mismatch group and Rh-match group respectively. The serum alanine aminotransferase (ALT), aspartate aminotransferase(AST)and creatinine(SCr)were compared between two groups at Days 7 & 14 post-operation. Serum total bilirubin(TB), gamma-glutamyl transpeptidase(GGT)were compared between two groups at Month 1, 6 & 12 post-operation. Hemoglobin (Hb)were compared between two groups Month 1, 3 & 6 post-operation. The rates of infection, vascular complications and acute rejection was also compared. Indirect antiglobulin test (IAT)was used for detecting the production of anti-RhD antibody in patients in Rh-mismatch group at Month 1, 6 & 12 post-operation. Results: At the mentioned time, no significant inter-group difference existed in serum ALT, AST, SCr, TB, GGT and blood Hb levels(all P>0.05); Also, no significant difference existed in the incidence of infection, vascular complications or acute rejection(all P>0.05). In Rhmismatch group, 4 recipients received Rh(+ )RBC transfusion during perioperative period and no hemolytic anemia occurred after operation. Rh(D) antibody was negative at all timepoints. Conclusions Taking into account the rarity of Rh-negative blood group in Chinese, it is safe and feasible to carry out Rh blood group mismatched liver transplantation when donor or recipient with the same Rh blood group is not available.

Objective To explore the effects of Qa-1 and PD-L1 loaded artificial liposomal treatment in allograft rejection and its outcomes .Methods The extracellular domains of Qa-1 and PD-L1 were loaded on liposome surface by streptavidin-biotin system . Mixed lymphocyte reaction (MLR) was performed for measuring Qa-1/PD-L1 liposome biological function .Then liposome was co-transplanted with allo-islets via portal vein .The levels of blood glucose and C-peptide were detected daily after transplantation .Also hepatic lymphocytes after transplantation were isolated for determining the proportion of activated cells and signaling pathway changes .Results Artificial liposome could be easily loaded with biotinylated peptide and its diameter was between 50 to 500 nm . Qa-1/PD-L1 liposome could significantly suppress lymphocyte proliferation , activation and secretion of IFN-γ in MLR by an activation of SHP1/2 and an inhibition of Syk pathway .Qa-1/ PD-L1 liposomes could suppress the activation of hepatic lymphocytes in vivo by activating SHP1/2 ,protecting islet allografts and maintaining a normal level of blood glucose in recipients .Conclusions Qa-1/PD-L1 loaded liposome can effectively suppress allograft rejection and improve the outcomes of islet transplantation .

Objective To study liver transplantation in the treatment of alcoholic liver disease (ALD).Methods A retrospective study was conducted on 40 patients with ALD who underwent liver transplantation in the Changzheng Hospital of the Second Military Medical University from April 2005 to June 2017.The data were expressed as mean ± standard deviation ((-x) ±s) in populations with a normal distribution,and as median (min～max) in populations with an abnormal distribution.The survival rate was analyzed by life tables,and the Cox regression analysis was used for multivariate analysis.Results All patients were followed up until August 31,2017.The follow-up time was 2 ～ 4518 days,with a median of 997 days.Among the 40 patients,8 had already died (3 died of multiple organ failure,2 of biliary complications,1 of liver failure,1 of sepsis and 1 of recurrence of hepatocellular carcinoma (HCC).The 1-year survival rate was 81.0％,and the 5-year survival rate was 77.0％.Four of 40 patients developed tumor recurrence.The initial recurrence time was 189 ～ 337 days (median 236.5).The recurrence sites included the liver,colon combined with lungs,lungs,and lumbar vertebrae.Six of 40 (15.0％) patients had relapse in alcoholism.Multivariate analysis showed that age was a prognostic factor (RR =1.109,P ＜0.05).Years of drinking,daily amount of alcohol intake,abstinence,a previous history of upper gastrointestinal bleeding,a previous history of splenectomy,co-existing hepatocellular carcinoma,preoperative MELD score,preoperative Child-Pugh score,total operation time,anhepatic period,cold ischemia time,amount of intraoperative bleeding,postoperative alcoholism relapse,tumor recurrence or new onset of tumor were not significantly correlated with the postoperative survival rate (P＞0.05).Conclusions ALD patients were mostly 40 ～ 60 years old.Age was an independent factor affecting survival.The younger the patient,the better the prognosis.Other factors were of no prognostic significance.