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*

OBJECTIVE To explore the impact of Shaoyao decoction on the intestinal microecology of rats with damp-heat diarrhea. METHODS Male SD rats were randomly divided into physiological group， model group， and Shaoyao decoction low-， medium- and high-dose groups （single dose of 5.62， 28.10 and 56.20 g/kg， by raw drugs）， with 7 rats in each group. Except for the physiological group， the remaining groups were all fed with high-sugar and high-fat diet， raised in a high-temperature and high- humidity environment， and administered white liquor and Escherichia coli suspension by gavage to establish a rat model of damp- heat diarrhea. On the second day after modeling， rats in each dosage group of Shaoyao decoction were administered the corresponding solution by gavage， once in the morning and once in the evening， for 3 consecutive days. After the last administration， fecal metagenomic sequencing analysis and biological information analysis were performed to detect the activities of intestinal cytochrome P450 （CYP） enzymes and intestinal flora metabolic enzymes. RESULTS There was no significant difference in the α diversity indexes of intestinal flora among the groups （P＞0.05）. The main phyla of rats in each group included Firmicutes， Actinobacteriota and Verrucomicrobiota， and the core dominant genera included Dubosiella， Lactobacillus and Romboutsia； low- ， medium- and high-dose of Shaoyao decoction could reverse the decrease in the relative abundance of Firmicutes， Romboutsia， Bifidobacterium and Monoglobus， as well as the increase in the relative abundance of Proteobacteria， Verrucomicrobiota， Escherichia-Shigella and Corynebacterium （P＜0.05）. Rats in each dosage group of Shaoyao decoction showed higher relative abundance of intestinal flora involved in carbon metabolism and cofactor biosynthesis pathways. Compared with the model group， the elimination rates of aminophenol and midazolam， as well as the concentration （except for the low-dose group） and metabolic rate of p-nitrophenol in rats of each dose group of Shaoyao decoction were significantly increased （P＜0.05）. CONCLUSIONS Shaoyao decoction can correct intestinal flora disorder in rats with damp-heat diarrhea， promote the recovery of intestinal CYP metabolic enzymes and intestinal flora metabolic enzymes， and thereby comprehensively improve intestinal microecology. Δ 基金项目 国家自然科学基金青年科学基金项目 （No. 82104726）；河南省软科学研究项目（No.252400410455）

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.

ObjectiveTo observe the clinical effect of Xiaozhi Hugan capsules in treating patients with non-alcoholic steatohepatitis （NASH） combined with phlegm-dampness and blood stasis syndrome and its effects on serum interleukin-6 （IL-6） and monocyte chemoattractant protein-1 （MCP-1）. MethodsA total of 124 patients with NASH combined with phlegm-dampness and blood stasis syndrome who were admitted to the Department of Spleen， Stomach， and Hepatobiliary Diseases， the First Affiliated Hospital of Henan University of Chinese Medicine from July 2020 to December 2022 were selected. According to the random number table method， patients were randomly divided into an observation group （62 cases） and a control group （62 cases）. The treatment duration was 6 months. The observation group received Xiaozhi Hugan capsules orally， while the control group received polyene phosphatidylcholine capsules. The efficacy indicators included alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， controlled attenuation parameter （CAP）， liver stiffness measurement （LSM）， traditional Chinese medicine （TCM） syndrome scores （discomfort/dull pain/distending pain in liver region， fatigue， etc.）， body mass index （BMI）， waist-to-height ratio （WHtR）， high-density lipoprotein cholesterol （HDL-C）， total cholesterol （TC）， triglycerides （TG）， homeostatic model assessment for insulin resistance （HOMA-IR） ［including fasting blood glucose （FBG） and fasting insulin level （INS）］， free fatty acids （FFA）， IL-6， and MCP-1. Adverse drug reactions were recorded. ResultsAfter treatment， the total effective rate in the observation group was 92.3% （48/52）， while that in the control group was 75.5% （39/49）. The total effective rate in the observation group was higher than that in the control group （χ²=5.339， P<0.05）. After treatment， the TCM syndrome scores in both groups were significantly reduced （P<0.05）， and the post-treatment scores in the observation group were better than those in the control group （P<0.05）. After treatment， the levels of ALT， AST， TC， FFA， fasting insulin （FINS）， HOMA-IR， MCP-1， IL-6， CAP， LSM， BMI， and WHtR were decreased （P<0.05） significantly in both groups， and the observation group showed superior improvement in the above indicators compared to the control group （P<0.05）. The observation group exhibited significant reductions in TG and FBG （P<0.05） and an increase in HDL-C （P<0.05）， while no significant changes were observed in the control group. The observation group was superior to the control group after treatment （P<0.05）. No severe adverse reactions occurred in either group during the treatment. ConclusionXiaozhi Hugan capsules have significant clinical efficacy in treating patients with NASH combined with phlegm-dampness and blood stasis syndrome. It reduces hepatic steatosis， lowers liver stiffness， inhibits the expression of serum inflammatory factors， and alleviates liver inflammation. No obvious adverse reactions occur， suggesting it is suitable for clinical application.

ObjectiveTo observe the clinical effect of Xiaozhi Hugan capsules in treating patients with non-alcoholic steatohepatitis （NASH） combined with phlegm-dampness and blood stasis syndrome and its effects on serum interleukin-6 （IL-6） and monocyte chemoattractant protein-1 （MCP-1）. MethodsA total of 124 patients with NASH combined with phlegm-dampness and blood stasis syndrome who were admitted to the Department of Spleen， Stomach， and Hepatobiliary Diseases， the First Affiliated Hospital of Henan University of Chinese Medicine from July 2020 to December 2022 were selected. According to the random number table method， patients were randomly divided into an observation group （62 cases） and a control group （62 cases）. The treatment duration was 6 months. The observation group received Xiaozhi Hugan capsules orally， while the control group received polyene phosphatidylcholine capsules. The efficacy indicators included alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， controlled attenuation parameter （CAP）， liver stiffness measurement （LSM）， traditional Chinese medicine （TCM） syndrome scores （discomfort/dull pain/distending pain in liver region， fatigue， etc.）， body mass index （BMI）， waist-to-height ratio （WHtR）， high-density lipoprotein cholesterol （HDL-C）， total cholesterol （TC）， triglycerides （TG）， homeostatic model assessment for insulin resistance （HOMA-IR） ［including fasting blood glucose （FBG） and fasting insulin level （INS）］， free fatty acids （FFA）， IL-6， and MCP-1. Adverse drug reactions were recorded. ResultsAfter treatment， the total effective rate in the observation group was 92.3% （48/52）， while that in the control group was 75.5% （39/49）. The total effective rate in the observation group was higher than that in the control group （χ²=5.339， P<0.05）. After treatment， the TCM syndrome scores in both groups were significantly reduced （P<0.05）， and the post-treatment scores in the observation group were better than those in the control group （P<0.05）. After treatment， the levels of ALT， AST， TC， FFA， fasting insulin （FINS）， HOMA-IR， MCP-1， IL-6， CAP， LSM， BMI， and WHtR were decreased （P<0.05） significantly in both groups， and the observation group showed superior improvement in the above indicators compared to the control group （P<0.05）. The observation group exhibited significant reductions in TG and FBG （P<0.05） and an increase in HDL-C （P<0.05）， while no significant changes were observed in the control group. The observation group was superior to the control group after treatment （P<0.05）. No severe adverse reactions occurred in either group during the treatment. ConclusionXiaozhi Hugan capsules have significant clinical efficacy in treating patients with NASH combined with phlegm-dampness and blood stasis syndrome. It reduces hepatic steatosis， lowers liver stiffness， inhibits the expression of serum inflammatory factors， and alleviates liver inflammation. No obvious adverse reactions occur， suggesting it is suitable for clinical application.

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 explore the clinical characteristics and genetic etiology of a patient with Fliedner-Zweier syndrome (FZS). METHODS: A pregnant woman who was diagnosed with FZS at the Affiliated Women and Children's Hospital of Ningbo University in November 2023 for "intellectual disability, epilepsy, delayed language development and facial abnormalities" was selected as the study subject. Peripheral blood samples were collected from the woman and her husband, whilst amniotic fluid sample was obtained from the fetus. Following extraction of genomic DNA, whole-exome sequencing (WES) and chromosomal karyotyping analysis were performed. Candidate variant was validated by Sanger sequencing. Pathogenicity of the variant was classified based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: EC2023-094). RESULTS: The proband, a 23-year-old woman, was at 19⁺² weeks of gestation and had a history of epilepsy, mild intellectual disability, delayed language development, and subtle facial dysmorphism. Chromosomal analysis showed the she has a normal karyotype. WES revealed that the woman and her fetus both harbored a heterozygous c.1489C>T (p.Gln497Ter) nonsense variant of the SCAF4 gene, which was verified by Sanger sequencing as de novo. Based on the ACMG guidelines, the variant was classified as pathogenic (PVS1+PM2_supporting+PS2_supporting). According to pre-set search strategy, five articles were retrieved. Together with the patient in this study, a total of 69 FZS patients were involved (including 7 from China). The main clinical features have included intellectual disability, epilepsy, behavioral abnormalities, and facial dysmorphism. CONCLUSION The heterozygous c.1489C>T (p.Gln497Ter) variant of the SCAF4 gene probably underlyay the FZS in this patient. Above finding has expanded the mutational spectrum of the SCAF4 gene.
Humans ; Female ; Intellectual Disability/genetics* ; Pregnancy ; Young Adult ; Exome Sequencing ; Epilepsy/genetics* ; Abnormalities, Multiple/genetics* ; Mutation ; Karyotyping

Objective To evaluate the diagnostic value of coiled-coil domain containing 83(CCDC83),carcinoembryonic antigen(CEA)and carbohydrate antigen(CA)199 detection in patients with colorectal cancer(CRC).Methods A total of 168 patients with colorectal diseases and 80 healthy physical examination subjects admitted to Hongqi Hospital Affiliated to Mudanjiang Medical University from September 2022 to January 2025 were selected as the study objects.Participants were classified into three groups based on pathological diagnosis and colonoscopy findings:colorectal cancer group(n=80),colorectal benign disease group(n=88),and healthy control group(n=80).Serum samples from all three groups were collected for detection of CCDC83,CEA,and CA199 expression levels.The diagnostic value was analyzed using receiver operating characteristic(ROC)curves.Results Colorectal cancer group exhibited significantly higher expression levels of CCDC83,CEA,and CA199 compared to colorectal benign disease group and healthy control group,with statistically significant differences(P＜0.05).ROC curve analysis demonstrated diagnostic value for CCDC83,CEA,and CA199,with CCDC83 showed superior specificity compared to CEA and CA199.Conclusion CCDC83,CEA and CA199 showed good diagnostic efficacy for colorectal cancer.

Orthokeratology lens is an optical correction method mainly used to control the development of myopia in children and adolescents.In recent years, the material and parameter design of orthokeratology lens has been constantly updated and improved.Despite its customizable, well-permeable, and optically superior properties, the ocular surface microenvironment may be affected by multiple factors after a long-term lens wear, resulting in a homeostatic imbalance of the ocular surface microenvironment due to direct attachment of the lens to the ocular surface.As the incidence of myopia in children and adolescents has increased rapidly in recent years, orthokeratology lens has been widely used as a non-surgical treatment to control the refractive growth of myopia.Understanding the influence of long-term orthokeratology lens wear on the ocular surface microenvironment can help avoid the related risk in myopia prevention and control.Therefore, this paper summarizes the effects of orthokeratology lens wear on ocular surface tissues, cells, tear fluid and microbiota, focuses on the potential risks of long-term orthokeratology lens wear, and leads optometrists to give comprehensive consideration to improving safety and effectiveness during the eyesight testing and follow-up.