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*

Collagen, a vital matrix protein for various tissue and functions in animals, is widely applied in biomaterials. In type Ⅰ collagen, missense mutations of glycine (Gly) in the Gly-Xaa-Yaa triplet of the triple helix are a major cause of osteogenesis imperfecta (OI). Clinical manifestations exhibit marked heterogeneity, spanning a broad disease spectrum from mild skeletal fragility (Type Ⅰ) to severe limb deformities (Type Ⅲ) and perinatal lethal forms (Type Ⅱ). This study utilized recombinant collagen as a model to further elucidate whether Gly→Ala/Val mutations at the N-terminus of the integrin-binding sequence GFPGER affect collagen structure and function, and to explore the underlying mechanisms by which missense mutations impact the biological function of collagen. By introducing Ala and Val substitutions at seven Gly positions N-terminal to the GFPGER sequence, we systematically assessed the effects of these amino acid replacements on the triple-helical structure, thermal stability, integrin-binding ability, and cell adhesion of recombinant collagen. All constructs formed a stable triple-helix structure, with slightly compromised thermal stability. Gly→Val substitutions increased the susceptibility of recombinant collagen to trypsin, which suggested local conformational perturbations in the triple helix. In addition, Gly→Val substitutions significantly reduced the integrin-binding affinity and decreased HT1080 cell adhesion, with the effects stronger than Gly→Ala substitutions. Compared with Gly→Ala substitutions, substitution of Gly with the larger residue Val had enhanced negative effects on the structure and function of recombinant collagen. These findings provide new insights into the molecular mechanisms of osteogenesis imperfecta and offer theoretical references and experimental foundations for the design of collagen sequences and the development of collagen-based biomaterials.
Recombinant Proteins/biosynthesis* ; Glycine/genetics* ; Humans ; Osteogenesis Imperfecta/genetics* ; Integrins/metabolism* ; Collagen/metabolism* ; Collagen Type I/metabolism* ; Amino Acid Substitution ; Mutation ; Mutation, Missense

Objective:To analyze the effectiveness and interobserver agreement of the Parer five-tier, the National Institute of Child Health and Human Development (NICHD) three-tier, and the International Federation of Gynecology and Obstetrics (FIGO) three-tier electronic fetal monitoring (EFM) systems in identification of neonatal acidosis during labor.Methods:This retrospective study was conducted on full-term singleton cephalic deliveries with neonatal acidosis (umbilical artery blood gas pH≤7.1) and normal newborns (umbilical artery blood gas pH≥7.2) in the Nanjing Drum Tower Hospital, Nanjing University Medical School from January to December 2020. EFM tracings during the last 30-60 min before delivery were collected. Four obstetricians independently described the features of randomly sorted and coded EFM tracings. Another obstetrician categorized these tracings using the NICHD three-tier, FIGO three-tier, and Parer five-tier evaluation systems based on the features. All researchers were masked to the clinical characteristics and maternal and neonatal outcomes. The sensitivity and specificity for identifying neonatal acidosis, as well as the interobserver agreement, were analyzed for all three systems. Independent sample t-test, Chi-square (or Fisher's exact test) and Mann-Whitney U tests were used for statistical analysis. Inter-group comparisons of sensitivity and specificity between the three evaluation systems were assessed using McNemar's test. The Kappa statistic was used to analyze interobserver agreement. Results:This study included a total of 3 558 cases. After propensity score matching, there were 44 cases of neonatal acidosis and 78 control cases. There were no significant differences in parity, gestational weeks, modes of delivery, placental abruption, or analgesia rates between the two groups. The rates of instrumental vaginal delivery and neonatal intensive care unit (NICU) admission in the acidosis group were significantly higher than those in the control group [15.8% (7/44) vs. 2.6% (2/78), χ2=8.45, P=0.003; 31.8% (14/44) vs. 12.8% (10/78), χ2=8.45, P=0.004], while the umbilical artery blood pH and mean base excess were lower in the acidosis group than in the control group [7.04±0.07 vs. 7.30±0.05, t=4.98; (－12.40±3.32) vs. (－5.64±1.95) mmol/L, t=13.61; both P<0.001]. (2) Using the NICHD three-tier system, 95.5% (42/44) of the acidosis cases and 89.7% (70/78) of the control cases were classified as having category Ⅱ EFM tracings, indicating potential fetal acid-base imbalance; category Ⅲ EFM tracings were only observed in 4.5% (2/44) of the cases in the acidosis group. With the FIGO three-tier system, 81.8% (36/44) of the acidosis cases were categorized as having "pathological" tracings, and with the Parer five-tier system, 86.4% (38/44) of the acidosis cases were correctly classified into the "orange or red" risk zones that indicated acid-base imbalance. Among the control cases, there were 28.2% (22/78) with EFM tracings of "normal patterns" categorized by the FIGO three-tier system, and 41.0% (32/78) classified into the "green or blue" risk zones by the Parer five-tier system, which indicated good fetal conditions. None of the acidosis cases were misdiagnosed as being normal by the Parer five-tier system. (3) Compared with the NICHD three-tier system, both the FIGO three-tier and the Parer five-tier systems showed increased diagnostic sensitivity [4.5% (1.2%- 14.5%) vs. 81.8% (66.8%-89.4%) and 86.4% (71.8%-92.4%)], but decreased specificity [100.0% (95.3%- 100.0%) vs. 87.2% (78.0%-92.9%) and 84.6% (75.0%-91.0%)]. There was no statistically significant difference in the sensitivity or specificity between the FIGO three-tier and Parer five-tier systems for identifying neonatal acidosis ( P=0.727 and 0.791). (4) When reading the tracings of control cases, the total agreement rate for the NICHD three-tier system by different observers was as high as 94.2%, while the total agreement rates for the FIGO three-tier and Parer five-tier systems were 69.7% and 67.7%, respectively. In the interpretation of EFHR tracings for acidosis cases, the interobserver agreement for the Parer five-tier system was excellent [Kappa (95% CI): 0.87 (0.79-0.95)], while both the NICHD three-tier and FIGO three-tier systems showed good agreement [Kappa (95% CI): 0.77 (0.66-0.88) and 0.72 (0.60-0.84)]. Conclusions:The Parer five-tier and the FIGO three-tier systems have higher sensitivity in identifying neonatal acidosis than the NICHD three-tier system, and the Parer five-tier system achieves a higher negative predictive value and a greater agreement in the interpretation of pathological EFM patterns.

Objective: To analyze the current status of work-related musculoskeletal disorders (WMSDs), work fatigue and musculoskeletal pain in Chinese occupational population, and to study the relationship between work fatigue and musculoskeletal pain and WMSDs. Methods: A total of 66 961 employees from 323 enterprises in 15 key industries in China were selected as the study subjects using stratified cluster sampling method. The incidence of WMSDs in the past year was investigated using the Chinese version of the Musculoskeletal Disorders Questionnaire, and the work fatigue and musculoskeletal pain were investigated using Borg 6-20 Rating of Perceived Exertion Scale and visual analogue scale. The data were standardized using the age composition data of 18 to 60 years from the seventh national population census. Results: The standardized annual incidence of WMSDs was higher in the front-line workers than that in the administrative and other supportive staff (38.82% vs 36.30%). The detection rates of work fatigue and musculoskeletal pain in the study subjects were 44.54% and 63.08%, respectively. The result of S-curve fitting showed that the risk of WMSDs increased with the level of work fatigue (P<0.01). Among the front-line workers, the average of monthly fatigue frequency in the neck, shoulder, lower back, upper back, wrist/hand, foot and ankle, knee, leg, and elbow were higher in the group with WMSDs compared to those without WMSDs (all P<0.01). The pain degree of musculoskeletal pain was higher in all nine sites in the fatigued group than in the no-fatigue group (all P<0.01). The standardized detection rate of musculoskeletal pain was higher in the fatigued group than in the non-fatigued group (80.38% vs 25.71%). The work fatigue was moderate and positively correlated with musculoskeletal pain in all seven sites except the lower back and elbow, with Kendall Tau-b correlation coefficients ranging from 0.423 to 0.546 (all P<0.01). Conclusion: There is a good correlation between work fatigue and local musculoskeletal pain, work fatigue and WMSDs in Chinese occupational population. Implementing ergonomic interventions to control the development of work fatigue can be an effective measure for preventing WMSDs.

Background Prolonged awkward postures during occupational activities can lead to excessive musculoskeletal load on the wrist of workers and symptoms such as wrist pain or discomfort. Objective To survey the prevalence of wrist pain among workers in 10 key industries and analyze its correlation with wrist working postures. Methods By using stratified cluster sampling method, workers from 10 key industries, such as footwear manufacturing industry, shipbuilding manufacturing industry, and automobile manufacturing industry, were selected from seven regions in North China, East China, Central China, South China, Southwest China, Northwest China, and Northeast China. The demographic information, wrist working postures, pain in wrist of the workers were collected through a cross-sectional survey. Pearson χ² test was used to compare prevalence by selected factors, trend χ² test for between group comparison, and unconditional logistic regression models for the association of wrist working postures with wrist pain. Results There were 64052 workers enrolled in this survey, and 56286 provided valid questionnaires (the effective rate was 87.8%). According to the survey, the prevalence of wrist pain was 23.3% (13112/56286), and the industries with higher prevalences were footwear manufacturing (27.1%, 1927/7106), automobile manufacturing (24.9%, 5378/21560), and shipbuilding and related equipment manufacturing (24.4%, 850/3488) industries. Finger pinching (OR=2.09, 95%CI: 1.95-2.24), frequent wrist bending (OR=2.03, 95%CI: 1.92-2.15), fixed wrist bending (OR=1.77, 95%CI: 1.69-1.85), wrist on hard edge (OR=1.34, 95%CI: 1.28-1.40), and arms over shoulders (OR=1.11, 95%CI: 1.05-1.17) increased the risk of reporting wrist pain. Conclusion Awkward postures are related to wrist pain among workers in selected 10 key industries. The related factors are wrist on hard edge, frequent wrist bending, finger pinching, fixed wrist bending, and arms over shoulders.

Viruses are powerful tools for the study of modern neurosciences. Most of the research on the connection and function of neurons were done by using recombinant viruses, among which neurotropic herpesvirus is one of the most important tools. With the continuous development of genetic engineering and molecular biology techniques, several recombinant neurophilic herpesviruses have been engineered into different viral tools for neuroscience research. This review describes and discusses several common and widely used neurophilic herpesviruses as nerve conduction tracers, viral vectors for neurological diseases, and lytic viruses for neuro-oncology applications, which provides a reference for further exploring the function of neurophilic herpesviruses.
Herpesviridae/genetics* ; Neurosciences ; Genetic Vectors/genetics* ; Genetic Engineering ; Neurons

Chronic thromboembolic pulmonary hypertension (CTEPH) and chronic thromboembolic pulmonary disease (CTEPD) are diseases that occur after acute pulmonary embolism resulting from residual and organized intra-pulmonary thrombus, with or without pulmonary hypertension(PH). The prognosis of these diseases has been dramatically improved with the continuous progress of treatment and the updated concept of the comprehensive treatment strategy. However, there is a lack of awareness of these diseases among medical practitioners, and a lack of epidemiological data in China, with unknown pathogenesis and non-specific clinical manifestations. Therefore, it is easy to misdiagnosis, underdiagnosis and delay diagnosis in clinical practice. To enhance the understanding of medical personnel, this paper summarizes the definition, epidemiology, pathology, pathogenesis, diagnosis and treatment of CTEPH and CTEPD.

Objective:To summary the mixed infection as well as clinical characteristics and analyze the risk factors for mixed infection of severe adenovirus pneumonia(SAP) in children.Methods:The clinical data of 114 children with SAP were retrospectively analyzed.Multivariate Logistic regression analysis was performed to assess the risk factors for mixed infection.Results:The incidence age was from 6 months to 2 years(62.5%). High fever(94.7%), cough(98.2%), dyspnea(86.8%) and lethargy(95.6%) were the main symptoms.Laboratory examination showed that children with SAP were prone to increased white blood cell count, C-reactive protein, procalcitonin, aspartate aminotransferase, alanine aminotransferase and CK-MB, as well as decreased proportion of CD3 + , CD4 + , CD8 + , CD4 + /CD8 + and NK cells.The main complications intrapulmonary organ were respiratory failure(80.7%). The main complications extrapulmonary organ were circulatory complications (55.3%). SAP was easily combined with other pathogenic infections.Streptococcus pneumoniae(22.9%)was the most common bacterial pathogen.Respiratory syncytial virus(10.0%)were the most common virus, in addition, mycoplasma pneumoniae(17.1%) was also common.Multivariable Logistic regression analysis showed that the decreasing ratio of CD4 + /CD8 + and NK cells, congenital heart disease and congenital airway dysplasia were the independent risk factors for mixed infection of SAP in children( P<0.05). Conclusion:The SAP patients could easily suffer from mixed infection and high fatality rate.Immune dysregulation is the important risk factors for mixed infection of SAP in children.So immunoregulatory treatment is very important.

【Objective】 To explore the clinical efficacy of traditional Chinese medicine(TCM) therapy in patients with transfusion related iron overload diagnosed with chronic aplastic anemia (CAA). 【Methods】 A total of 115 patients with CAA and iron overload who had been admitted to Zhejiang Provincal Hospital of TCM from February 2015 to December 2016 were studied. They were assigned to treatment group(n=69), positive control group(n=16), and negative control group(n=30) according to different treatment plan designed in advance. Patients in the treatment group were treated with TCM of "Bushen Huoxue" recipe once a day, with the formula mixed with astragalus 40 g, rehmannia 12 g, cornus 12 g, deerhorn glue melting by heat 12 g, atractylodes 20 g, radix paeoniae alba 20 g, curculigo orchioides 10 g, herba epimedii 10 g, cistanche 12 g, cassia stem 10 g, dried orange peel 8 g, poria 10, gingembre 6 g, angelica sinensis 20 g, salvia miltiorrhiza 20 g, zedoary 9 g, leonurus 30 g, gromwell 15 g, and prepared liquorice root 6 g. Patients in positive control group were treated with desferrioxamine for more than 8 h per day, 5 to 7 days per week. Patients in negative control group were treated with basic treatment.The serum ferritin (SF) and cytokines of patients of the three groups before and 3 months after therapy were detected according to the blood-stasis of TCM symptom rating scale, and the correlation between the decrease of ferritin after treatment and the improvement of blood stasis syndrome score was analyzed. 【Results】 The level of SF of the treatment group, positive and negative control group before treatment were 1 881.63±1 386.81 vs 6 581.36±5 180.96 vs1 974.25±1 753.06, and were 2 040.14±1 484.27 vs 4 169.18±3 631.64(P<0.05)vs 2 699.80±2 352.34(P<0.05) 3 months after treatment. The treatment was effctive in 16 patients in treatment group, accounted for 23.19%(16/69). The score of blood stasis syndrome of the three groups before and after treatment were 4.26±1.45vs 6.88±1.31 vs 4.17±1.18 and 4.42±1.43 vs 5.00±0.89 vs 4.67±1.51(P<0.01), respectively. The effective rate of improving blood stasis syndrome score in the treatment group was up to 26.09%. The decrease of serum ferritin was positively correlated with the improvement of blood stasis score (P < 0.01). The levels of IL-6 and IL-10 in treatment group were 20.79±14.14 and 56.27±25.54 before treatment, 13.00±6.48 and 41.02±9.93(P<0.05)3 months after treatment, respectively. 【Conclusion】 "Bushen Huoxue" therapy can stabilize the the level of SF and improve the blood stasis syndrome in CAA patients with iron overload.

Objective:To evaluate the effect of Xuebijing injection on the improvement of pneumonia severity index (PSI) and prognosis in patients with severe coronavirus disease 2019 (COVID-19).Methods:A multicenter prospective cohort study was designed. Adult patients with COVID-19 admitted to the intensive care unit (ICU) of 28 designated COVID-19 hospitals in 15 provinces and cities of China from January to March 2020 were enrolled. All patients were treated according to the standard treatment plan of COVID-19 issued by the National Health Commission of the People's Republic of China. They were divided into Xuebijing group and standard treatment group according to whether they received Xuebijing injection or not. In the standard treatment group, routine medical care measures such as antiviral, respiratory support, circulatory support and symptomatic treatment were taken. In the Xuebijing group, on the basis of standard treatment, Xuebijing was used within 12 hours of admission to the ICU, 100 mL each time, twice daily. The minimum duration of Xuebijing administration was 1 day. The improvement rate of PSI risk rating on the 8th day and clinical outcome on the 28th day were recorded.Results:A total of 276 COVID-19 patients were screened continuously, and the data of 144 severe patients who met PSI risk rating Ⅲ-Ⅴ were analyzed. Seventy-two cases were involved each in standard treatment group and Xuebijing group. The average age of the standard treatment group and Xuebijing group were (65.7±7.9) years old and (63.5±10.9) years old, and male accounted for 75.0% (54/72) and 70.8% (51/72), respectively. There were no significant differences in general conditions, comorbidities, PSI risk rating and score, sequential organ failure assessment (SOFA) score, oxygenation index (PaO 2/FiO 2), respiratory support mode and other baseline indicators between the two groups. Compared with the standard treatment group, the improvement rate of PSI risk rating in Xuebijing group on the 8th day after admission was significantly improved [56.9% (41/72) vs. 20.8% (15/72), between-group difference and 95% confidence interval (95% CI) was 36.1% (21.3% to 50.9%), P < 0.01], PSI score, SOFA score and PaO 2/FiO 2 were significantly improved [PSI score: 83.7±34.8 vs. 108.2±25.6, between-group difference (95% CI) was -24.5 (-34.9 to -14.1); SOFA score: 2.0 (1.0, 4.0) vs. 7.0 (4.0, 10.0), between-group difference (95% CI) was -3.5 (-5.0 to -2.0); PaO 2/FiO 2 (mmHg, 1 mmHg = 0.133 kPa): 289.4±111.6 vs. 188.5±98.1, between-group difference (95% CI) was 100.9 (65.3 to 136.5); all P < 0.01]. The 28-day discharge rate of Xuebijing group was 44.5% higher than that of standard treatment group [66.7% (48/72) vs. 22.2% (16/72), P < 0.01], and the 28-day survival rate was 9.8% [91.7% (66/72) vs. 81.9% (59/72), P < 0.01]. There was no significant difference in the combination of antiviral drugs, antibiotics, anticoagulants and vasopressor drugs between the two groups. There was no significant difference in the incidence of adverse events between the Xuebijing group and standard treatment group [41.7% (30/72) vs. 43.1% (31/72), P > 0.05], and no serious adverse events and adverse reactions of Xuebijing were reported. Conclusion:Standard treatment combined with Xuebijing injection can significantly improve the PSI risk score and clinical prognosis of patients with severe COVID-19 without increasing drug safety risk.