Lung transplantation is the ultimate therapeutic option for end-stage pulmonary diseases such as interstitial pneumonia, chronic obstructive pulmonary disease and pneumoconiosis. Currently, the shortage of allogeneic lung donors significantly limits the opportunity for end-stage lung disease patients to receive lung transplantation. In recent years, with the rapid development of biomedical engineering technologies, especially the major breakthroughs in genetic modification and cloning, xenogeneic lung transplantation has shown important potential for clinical translation. Among them, genetically modified pigs have become the most promising xenogeneic lung source due to the close similarity of organ size and physiological characteristics to humans, and the ability to perform targeted gene knockouts (such as α-Gal antigen knockout) to reduce the occurrence of hyperacute rejection. This article focuses on the research progress of porcine xenogeneic lung transplantation, systematically reviews the latest achievements and challenges in animal experiments and human trials, and introduces the technical experience accumulated by Shenzhen Third People's Hospital in the porcine-to-monkey xenogeneic lung transplantation model, in the hope of providing practical references for future research in this field.

Arthritis, encompassing osteoarthritis (OA), rheumatoid arthritis (RA), and gouty arthritis (GA), is a prevalent inflammatory disease that significantly impacts quality of life. Natural products (NPs), derived from animals, plants, marine organisms, and microorganisms, have demonstrated beneficial effects in arthritis treatment both domestically and internationally. These natural compounds offer advantages in drug discovery due to their skeletal diversity, structural complexity, and multi-effect, multi-target, and low-toxicity properties compared to conventional small-molecule medicines. However, unclear mechanisms have hindered the development and clinical application of NPs. This review summarizes recent experimental studies from the past decade on natural medicine for arthritis treatment, emphasizing key NPs with therapeutic effects on OA, RA, and GA. It examines the effects and molecular mechanisms of NPs acting on different cells to treat arthritis. Furthermore, this review provides insights into the future prospects of NP research in this field, which is crucial for advancing NP-based arthritis treatments.
Humans ; Biological Products/therapeutic use* ; Animals ; Arthritis, Rheumatoid/drug therapy* ; Arthritis, Gouty/drug therapy* ; Arthritis/drug therapy* ; Osteoarthritis/drug therapy*

Acute liver failure (ALF) is lack of broadly approved therapeutic strategy except liver transplantation. As a glycogen metabolic intermediate, UDP-glucose (UDP-G) has been considered to accelerate liver repairment. Nevertheless, the role of UDP-G and its receptor P2Y purinoceptor 14 (P2Y₁₄R) in ALF remains unknown. The present study aims to investigate the role and underlying mechanisms of UDP-G/P2Y₁₄R axis in ALF. In this study, hepatic P2Y₁₄R is significantly increased in TAA-induced and partial hepatectomy-induced ALF, while knockout of whole-body P2Y₁₄R aggravates liver failure, manifested by inhibiting β-Catenin-mediated liver regeneration. Consistently, P2Y₁₄R deficiency exhibits impaired liver regeneration in mice suffer partial hepatectomy. Importantly, only hepatocellular specific deletion of P2Y₁₄R (P2Y₁₄R ^flox/flox Alb ^cre/+ ) mice shows a similar phenomenon, rather than stellate cell specific deletion of P2Y₁₄R (P2Y₁₄R ^flox/flox Lrat ^cre/+ ) mice. Mechanistically, P2Y₁₄R induction regulates methylation of Dact-2 through CREB/DNMT3b signals in hepatocytes, subsequently inhibiting the expression of Dact-2 which is a stabilizer of β-Catenin degradation complex, leading to the activation of β-Catenin -mediated liver regeneration. Interestingly, the administration of exogenous UDP-G can accelerate liver regeneration and liver function recovery after partial hepatectomy in hepatocellular carcinoma mice. Together, the findings propose an unrecognized role of P2Y₁₄R in ALF and provide an effective adjuvant strategy for treatment of ALF.

ObjectiveTo investigate how Xiaoyao Shukun decoction （XYSKD） regulates the formation and release of neutrophil extracellular traps （NETs） via the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway， thereby reducing inflammation， inhibiting the excessive proliferation of fibroblasts in pelvic adhesion tissue， decreasing adhesion and fibrosis， and repairing the tissue damage in sequelae of pelvic inflammatory disease （SPID）. MethodsA total of 84 Wistar rats were randomly allocated into seven groups： blank， model， XYSKD （8 mg·kg^-1）， mTOR agonist （10 mg·kg^-1）， mTOR agonist + XYSKD （10 mg·kg^-1+8 mg·kg^-1）， mTOR inhibitor （2 mg·kg^-1）， and mTOR inhibitor + XYSKD （2 mg·kg^-1+8 mg·kg^-1）. The rat model of SPID was constructed by starvation， fatigue， and ascending Escherichia coli infection. After 14 days of drug intervention， the ultrastructure of fibroblasts in the pelvic adhesion tissue was observed by transmission electron microscopy. The general morphology of the uterus， fallopian tube， and ovary was observed by laparotomy. The levels of interleukin-1β （IL-1β）， interleukin-17 （IL-17）， and tumor necrosis factor-α （TNF-α） in the peritoneal flushing fluid were determined by enzyme-linked immunosorbent assay （ELISA）. The expression of myeloperoxidase （MPO） and citrullinated histone 3 （H3） in the fallopian tube was detected by immunofluorescence. Western blot and Real-time quantitative polymerase chain reaction （Real-time PCR） were employed to determine the relative protein and mRNA levels， respectively， of neutrophil elastase （NE）， intercellular adhesion molecule-1 （CD54）， α-smooth muscle actin （α-SMA）， H3， PI3K， and Akt. ResultsCompared with the blank group， the model group presented a large number of collagen fibers in bundles， numerous cytoplasmic folds of fibroblasts， reduced or absent mitochondrial cristae， and disordered and expanded endoplasmic reticulum. By laparotomy， extensive pelvic congestion， connective tissue hyperplasia， thickening and hardening of the tubal end near the uterus， and tubal and ovarian adhesion or cyst were observed in the model group. In addition， the model group showed raised levels of IL-1β， IL-17， and TNF-α in the peritoneal flushing fluid （P<0.01）， increased average fluorescence intensities of MPO and H3 （P<0.01）， and up-regulated protein and mRNA levels of NE， H3， CD54， PI3K， and Akt （P<0.01）. Compared with the model group， the mTOR agonist group showed increased fibroblasts and cytoplasmic folds， absence of mitochondrial cristae， endoplasmic reticulum dilation， and evident collagen fiber hyperplasia. Pelvic adhesions were observed to cause aggravated damage to the uterine， fallopian tube， and ovarian tissues. The levels of IL-1β， IL-17， and TNF-α in the peritoneal lavage fluid elevated （P<0.01） and the average fluorescence intensities of MPO and H3 enhanced （P<0.01） in the mTOR agonist group. In contrast， the XYSKD group and the mTOR inhibitor group showcased decreased fibroblasts and collagen fibers， alleviated mitochondrial crista loss and endoplasmic reticulum dilation， improved morphology and appearance of the uterine， fallopian tube， and ovarian tissues， lowered levels of IL-1β， IL-17， and TNF-α in the peritoneal lavage fluid （P<0.01）， decreased average fluorescence intensities of MPO and H3 （P<0.01）， and down-regulated protein and mRNA levels of NE， H3， CD54， PI3K， and Akt （P<0.05）. Compared with the mTOR agonist group， the mTOR agonist + XYSKD group showed alleviated pathological changes in the pelvic tissue， declined levels of IL-1β， IL-17， and TNF-α （P<0.01）， decreased average fluorescence intensities of MPO and H3 （P<0.01）， and down-regulated protein levels of NE， H3， CD54， α-SMA， p-PI3K/PI3K， and p-Akt/Akt （P<0.01） and mRNA levels of NE， H3， CD54， α-SMA， PI3K， and Akt （P<0.01）. Compared with the mTOR inhibitor group， the mTOR inhibitor + XYSKD group demonstrated reduced pathological severity of the pelvic tissue， reduced levels of IL-1β， IL-17， and TNF-α （P<0.01）， decreased average fluorescence intensities of MPO and H3 （P<0.01）， and down-regulated protein and mRNA levels of NE and CD54 （P<0.05）. ConclusionXYSKD can inhibit the excessive formation and release of NETs via PI3K/Akt/mTOR to ameliorate the inflammatory environment and reduce fibrosis and adhesion of the pelvic tissue， thereby playing a role in the treatment of SPID. It may exert the effects by lowering the levels of IL-1β， IL-17， and TNF-α and down-regulating the expression of NE， H3， CD54， α-SMA， PI3K， and Akt in the pelvic adhesion tissue.

Objective: To analyze the relationship between asthma and nocturia in women based on the National Health and Nutrition Examination Survey (NHANES) database from 2005 to 2018,so as to provide reference for the prevention and treatment of female nocturia. Methods: Female respondents aged ≥20 years with nocturia or asthma were selected from the 2005-2018 NHANES database.Those with both diabetes stroke and obstructive sleep apnea syndrome were excluded.A weighted analysis was conducted using a complex sampling design.The association between asthma and nocturia in women was evaluated with univariate analysis，propensity score matching (PSM)，and multivariate logistic regression models. Results: A total of 14 718 respondents were selected，of whom 1426 (9.7%) were diagnosed with asthma，and 4664 (31.7%) with nocturia.There is a significant correlation between asthma and nocturia (χ =39.846，P<0.01). Age，body mass index (BMI)，smoking and race were also associated with nocturia (P<0.01).Multivariate logistic regression analysis showed that，the age，BMI，smoking，race and asthma were correlated with the risk of nocturia，before PSM matching (P<0.05).To eliminate confounding bias，PSM was applied，and generalized linear mixed model analysis after matching showed that the risk of nocturia remained high in asthma patients (OR=1.540，95% CI：1.320-1.800，P<0.01). Conclusion: Asthma is associated with nocturia in women，indicating that it may be an important risk factor for female nocturia.

Objective To analyze the characteristics of real-world adverse drug events(ADEs)of trabectedin based on the FDA Adverse Event Reporting System(FAERS)database in order to provide references for clinical drug safety management.Methods A total of 1 349 trabectedin-related reports were extracted from the FAERS database from Q1 2007 to Q4 2024.Using the MedDRA coding classification system for system organ class(SOC)and preferred term(PT),signal detection was performed through 4 proportional imbalance methods,including reporting odds ratio(ROR)and proportional reporting ratio(PRR).Subgroup analyses by gender,age,and temporal trends were also conducted.Results Hematological and lymphatic system disorders and hepatobiliary system disorders were the primary SOCs involved.High-frequency PTs included neutropenia(123 cases)and anemia(117 cases).Eight potential ADEs that have not been listed in the drug product instruction were identified.The median onset time of ADEs was 21 d,showing an early failure pattern,with differences observed by gender(females more prone to hematological toxicity)and age(elderly more susceptible to febrile neutropenia).Conclusion Trabectedin requires close attention to hematological toxicity,hepatotoxicity,and newly identified multi-system potential risks.Clinically,monitoring should be strengthened based on time windows and population characteristics to optimize drug regimens.Countermeasure It is recommended to strengthen the full cycle monitoring of anti-tumor drugs,standardize the reporting of adverse reactions,and establish a multi-departmental collaborative research platform.

Objective To quantitatively evaluate the structure and content of the long-term care insurance(LTCI)policy in China's deeply aging areas.Methods Using the Policy Modeling Consistency(PMC)index model indicator design method,a LTCI policy evalua-tion index system was constructed,consisting of nine primary indicators and 34 secondary indicators.A total of 123 provincial-level LTCI policies issued in deeply aging regions of China between June 1,2014,and October 1,2024 were analyzed.High-frequency word extraction was performed using ROSTCM 6.0,and a social network diagram of LTCI policies was created.The policy structure and content were quantitatively evaluated and ana-lyzed based on the established policy evaluation index system.Results The main content of LTCI policies in deeply aging areas of China covered services,institutions and assessment.The highest policy score was 7.28,and the lowest was 2.20,with an average score of 5.00.There were 25 perfect policies,63 excellent policies,28 good policies and seven qualified policies.In the dimension of policy content,the indexes of five primary indicators of policy evaluation,policy target groups,policy nature,policy perspective and policy tools were 0.60 or more;while the indexes of four primary indicators of policy content,incentives and constraints,policy timeliness,and policy level were 0.50 or less.Conclusion LTCI policies issued in China's deeply aging areas provide comprehensive coverage in aspects such as poli-cy evaluation,policy target groups and policy nature,and need to be improved in policy tool selection and the construction of incentive and constraint mechanisms.

This study aims to describe the population and regional distribution characteristics of smoking behavior among adult twins in the China Twin Registry (CNTR), as well as the concordance rates for smoking behavior in monozygotic and dizygotic twins, and estimate the heritability. The study population included adult twins in CNTR who had smoking questionnaire data. A random-effects regression model was used to describe the distribution of smoking behavior among different subgroups based on various characteristics. The concordance of smoking behavior between different zygosity groups was calculated, and heritability was estimated. A total of 28 444 twin pairs were included in this study, with an average age of (36.6±12.0) years. Among male twins, 41.2% were current smokers, while only 1.2% of females smoked. Higher smoking rates were observed among male smokers in the 50-59 age group ( z=23.0, P<0.001), northern regions ( z=2.9, P<0.01), rural areas ( z=-5.2, P<0.001), those who were divorced/widowed ( z=3.8, P<0.001), and first-born twins ( z=-4.3, P<0.001), while lower smoking rates were found in those with higher education ( z=-16.1, P<0.001) and unmarried individuals ( z=-16.0, P<0.001). The smoking concordance rate for male monozygotic twins was 69.6%, significantly higher than the 57.3% concordance rate for dizygotic twins ( χ 2=105.0, P<0.05). The heritability of smoking behavior in male twins was estimated at 28.9% (95% CI: 24.3%-33.4%). Stratified analyses showed differences in heritability across regions and age groups: the heritability in northern regions was 32.6% (95% CI: 27.3%-38.0%), higher than the 21.0% (95% CI: 12.4%-29.5%) observed in southern regions; the highest heritability of 35.1% (95% CI: 26.3%-43.9%) was found in the 18-29 age group, with heritability decreasing with age. In conclusion, the smoking rate and influencing factors in the twin population are similar to those in the general population, with unique characteristics, such as higher smoking rates in first-born twins. Genetic factors have a significant impact on smoking behavior.

Objective To discuss the factors influencing the occurrence of frailty in patients with acute myocardial infarction(AMI)after receiving interventional treatment,and to construct a prediction model,to draw a nomogram,and to make the validation of the model.Methods Using convenient sampling method,a total of 462 patients with AMI,who were admitted to the Department of Cardiovascular Medicine of three Grade Ⅲ-A hospitals in Shandong Province of China from July 2023 to January 2024,were selected as the study subjects.Among them,324 AMI patients encountered from July 2023 to November 2023 were selected as modeling group,and logistic regression was used to construct a risk prediction model and draw a nomogram to visualize the model.The remaining 138 AMI patients encountered from December 2023 to January 2024 were used as the validation group.The receiver operating characteristic(ROC)curve and Hosmer-Lemeshow testing were adopted to verify the predictive effect of the model.Results Of 324 patients in the modeling group,170(52.47％)developed frailty.Univariate analysis showed that significant differences in age,education level,body mass index(BMI),Charlson comorbidity index,grip strength,walking speed,brain natriuretic peptide precursor level,physical exercise,multiple medication,and kinesophobia existed between the two groups(all P＜0.05).Multivariate logistic regression analysis revealed that age,BMI,Charlson comorbidity index,grip strength,walking speed,NT-ProBNP precursor level,physical exercise,multiple medication,and kinesophobia were the influencing factors of frailty in patients with AMI after receiving interventional treatment,with an OR value of 1.061,0.630,1.529,0.931,0.005,0.358,1.783,2.929,and 0.497 respectively.The above nine factors were used as independent variables to draw the nomogram,the area under ROC curve of the model was 0.851(95％CI:0.809-0.892),the optimal critical value was 0.562,the sensitivity was 84.1％,and the specificity was 72.1％.Hosmer-Lemeshow goodness of fit testing showed that the model had anx2=12.957 and P=0.113.Conclusion The frailty condition of AMI patients after receiving interventional treatment is at a low to medium levels.The frailty risk prediction model constructed in this study has good prediction effect,which can provide guidance for clinical nurses to timely identify high-risk patients and to promptly adopt interventional measures.

Objective:To investigate the histopathological subtype and clinical characteristics of vascular malformations in the head and neck.Methods:All patients with head and neck vascular malformations referred to Henan Provincial People′s Hospital between January 2021 and December 2023 were collected, and the clinicopathological features were analyzed by SPSS 26.0 statistical software.Results:A total of 675 patients were included, there were 293 male and 382 female patients with a mean onset age of (26.2±21.8）years and a mean diagnosis age of (31.8±20.6）years. Most vascular malformations were located in oral and maxillofacial region (52.1%, 352/675), with an average diameter of (28.0±19.8）mm. Venous malformations were the most common (71.4%, 482/675). There were 230 patients presented with simultaneous phenomenon, and of them the thrombus was most commonly noted (66.5%, 153/230). Venous malformations more frequently occurred in patients who were older than 20 years, extracranial in site, and mostly involved female patients with complications. Combined vascular malformation more frequently occurred in patients who were under 20 years old, extracranial in site, and mostly involved female patients. Capillary malformations more frequently occurred in patients under 20 years old, extracranial in site, and no complications occurred. Lymphatic vessel malformation more frequently occurred in patients who were under 20 years old, extracranial in site, female and with no complications. Arteriovenous malformations were more common in the intracranial and most of them were without any complications. Two cases (2/21) were associated with PIK3CA gene mutation. There were 109 patients with recurrence after initial treatment.Conclusions:Vascular malformations in the head and neck are more commonly found in the extracranial and maxillofacial regions, and venous malformations are the most common type; while arteriovenous malformations are more common in the intracranial site. Appropriate diagnosis is the premise of appropriate treatment.