OBJECTIVE: Based on the PTEN-induced hypothetical kinase 1 (PINK1)/Parkin pathway, the effect of acupuncture pretreatment on the expression of mitochondrial autophagy-related proteins in gastrocnemius muscle tissue of rats with exercise-induced muscle damage (EIMD) was observed, and the underlying mechanism of acupuncture pretreatment for the prevention and treatment of EIMD was explored. METHODS: Of 88 SD male rats, aged 6 weeks, 8 rats were randomly selected as a blank group, and the remaining 80 rats were randomized into a model group and an acupuncture pretreatment group, with 40 rats in each group. Either the model group or the acupuncture pretreatment group was subdivided randomly into 5 subgroups with 8 rats in each one according to the time points of sample collection, 0 h, 12 h, 24 h, 48 h and 72 h after modeling. An intermittent downhill running centrifugal exercise was carried out on an animal experimental treadmill to establish the EIMD model in the model group and the acupuncture pretreatment group. The rats in the acupuncture pretreatment group received acupuncture at "Guanyuan" (CV6) and bilateral "Zusanli" (ST36), once a day for 20 min each time, for 7 consecutive days before EIMD model preparation. Transmission electron microscopy was used to observe the ultrastructure of gastrocnemius muscle tissue in each group. The contents of malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) in serum were detected by ELISA. Western blot was used to detect the protein expression of PINK1, Parkin, sequestosome 1 (p62) and microtubule-associated protein light chain 3B (LC3B) in rat gastrocnemius muscle tissue. Real-time PCR was adopted to detect the mRNA expression of PINK1, Parkin, p62 and LC3B in rat gastrocnemius muscle tissue. RESULTS: Compared with the blank group, the mitochondria of gastrocnemius muscles showed obvious swelling in the 0 h, 12 h, 24 h, and 48 h model subgroups , autophagosomes were formed in the 12 h and 24 h model subgroups, and the mitochondrial morphology returned to normal gradually in the 72 h model subgroup. The serum MDA contents of rats in 5 model subgroups increased (P<0.01, P<0.05). The contents of SOD and CAT in the subgroups of 0 h, 12 h, 24 h and 48 h decreased (P<0.05, P<0.01). The protein and mRNA expression levels of PINK1, Parkin and LC3B in gastrocnemius muscle tissue of rats in 0 h, 12 h and 24 h subgroups were elevated (P<0.01); and the protein and mRNA expression levels of p62 in the 0 h, 12 h, 24 h and 48 h subgroups were reduced (P<0.01, P<0.05). Compared with the model subgroup at the same time point, the myofibril damage and the degree of mitochondrial swelling were mild in each acupuncture pretreatment subgroup, and the numbers of autophagosomes were fewer. The contents of MDA in the acupuncture pretreatment subgroups decreased at 0 h, 12 h, 24 h, and 48 h (P<0.05, P<0.01). The contents of SOD and CAT in the 12 h acupuncture pretreatment subgroup increased (P<0.05, P<0.01). The protein and mRNA expression levels of PINK1 and Parkin in the 0 h, 12 h, and 24 h acupuncture pretreatment subgroups decreased (P<0.01, P<0.05). The protein and mRNA expression levels of LC3B in the 12 h acupuncture pretreatment subgroup decreased (P<0.01), and that of p62 in the 0 h and 24 h acupuncture pretreatment subgroups increased (P<0.01, P<0.05). CONCLUSION The intermittent downhill running centrifugal exercise induces the excessive mitochondrial autophagy. Acupuncture pretreatment may attenuate EIMD, and the underlying mechanism is related to the regulation of PINK1/Parkin signaling pathway expression, reducing oxidative stress damage in skeletal muscle cells, and inhibiting mitochondrial autophagy overactivation.
Animals ; Ubiquitin-Protein Ligases/genetics* ; Male ; Rats ; Acupuncture Therapy ; Protein Kinases/genetics* ; Rats, Sprague-Dawley ; Mitophagy ; Humans ; Muscle, Skeletal/metabolism* ; Physical Conditioning, Animal ; Muscular Diseases/physiopathology* ; Signal Transduction

Postoperative infection of internal fixation of closed fractures the lower limbs in adults represents a devastating complication, characterized by diagnostic challenges, prolonged treatment duration and high disability rates. Current management of these infections faces multiple challenges, such as difficulties in early accurate diagnosis, and various controversies about the treatment plan, leading to poor overall diagnosis and treatment results. To address these issues, based on evidence-based medicine and principles with emphasis on scientific rigor, clinical applicability and innovation, the Trauma Branch of the Chinese Medical Association, Orthopedic Branch of the Chinese Medical Doctor Association, Orthopedics Branch of the Chinese Medical Association, and Trauma Orthopedics and Polytrauma Group of the Resuscitation and Emergency Committee of the Chinese Medical Doctor Association have collaboratively organized a panel of relevant experts to develop the Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults ( version 2025). The guideline proposed 10 recommendations, aiming to provide a foundation for standardized diagnosis and treatment of postoperative infection in adults with closed lower limb fractures.

Objective:To investigate factors influencing frequent episodes (≥ 4 episodes within 1 year) in children with moderate-to-severe atopic dermatitis (AD) in China.Methods:A national multicenter cross-sectional study was conducted. Patients under the age of 18 years diagnosed with moderate-to-severe AD were enrolled at dermatology clinics in 18 medical institutions across 12 provinces and municipalities in China between June 12 and August 8, 2023. At the time of the visit, their guardians completed a structured questionnaire covering demographic characteristics, clinical features of AD, personal and family history, factors associated with frequent episodes of moderate-to-severe AD, compliance with treatment, and disease awareness. Statistical analyses included t tests, one-way analysis of variance, rank-sum tests, and chi-square tests, with multiple-response analysis applied for multiple-choice questions. Results:A total of 965 valid questionnaires were collected, and 965 children with moderate-to-severe AD were included. Among them, there were 531 males and 434 females, 678 (70.3%) were aged 2 - < 12 years, 837 (86.7%) were from urban areas, the age at onset was 2.47 ± 3.03 years, and the median frequency of AD episodes in the past year was 4 times. These children were divided into 2 groups based on the median episode frequency: < 4-episode group (439 cases, 45.5%) and ≥ 4-episode group (526 cases, 54.5%). Compared with the < 4-episode group, children in the ≥ 4-episode group showed younger ages at onset (2.22 ± 2.98 years vs. 2.76 ± 3.06 years, P = 0.006) and higher proportions of patients with comorbid allergic diseases in both the children themselves (82.9% [436/526] vs. 69.7% [306/439], χ2 = 23.42, P < 0.001) and their relatives (66.0% [347/526] vs. 57.4% [252/439], χ2 = 7.46, P = 0.006). Children in the ≥ 4- episode group also had higher monthly usage of moisturizers (150 [30, 300] g vs. 60 [6, 200] g) and daily frequency of moisturizer use, greater disease awareness, but more severe fear of medication use (all P < 0.05). The region and the human development index level were both significantly associated with the episode frequency (both P < 0.001), with the highest proportion of children from South China in the ≥ 4- episode group (36.3%, 191/526). Children in the ≥ 4-episode group also had a longer duration of topical glucocorticoid use than those in the < 4-episode group ( Z = -2.21, P = 0.027). External triggers associated with AD episodes mainly included heat exposure (50.36%, 486/965), hot water bathing (40.73%, 393/965), seafood (23.52%, 227/965), and dust mites (33.37%, 322/965) . Conclusion:In children with moderate-to-severe AD in China, factors influencing frequent episodes may include residence in southern or economically developed regions, earlier age at onset, having a personal or family history of allergic diseases, and fear of medication use.

OBJECTIVE: Gastric cancer (GC) is one of the most common malignancies seen in clinic and requires novel treatment options. Morin is a natural flavonoid extracted from the flower stalk of a highly valuable medicinal plant Prunella vulgaris L., which exhibits an anti-cancer effect in multiple types of tumors. However, the therapeutic effect and underlying mechanism of morin in treating GC remains elusive. The study aims to explore the therapeutic effect and underlying molecular mechanisms of morin in GC. METHODS: For in vitro experiments, the proliferation inhibition of morin was measured by cell counting kit-8 assay and colony formation assay in human GC cell line MKN45, human gastric adenocarcinoma cell line AGS, and human gastric epithelial cell line GES-1; for apoptosis analysis, microscopic photography, Western blotting, ubiquitination analysis, quantitative polymerase chain reaction analysis, flow cytometry, and RNA interference technology were employed. For in vivo studies, immunohistochemistry, biomedical analysis, and Western blotting were used to assess the efficacy and safety of morin in a xenograft mouse model of GC. RESULTS: Morin significantly inhibited the proliferation of GC cells MKN45 and AGS in a dose- and time-dependent manner, but did not inhibit human gastric epithelial cells GES-1. Only the caspase inhibitor Z-VAD-FMK was able to significantly reverse the inhibition of proliferation by morin in both GC cells, suggesting that apoptosis was the main type of cell death during the treatment. Morin induced intrinsic apoptosis in a dose-dependent manner in GC cells, which mainly relied on B cell leukemia/lymphoma 2 (BCL-2) associated agonist of cell death (BAD) but not phorbol-12-myristate-13-acetate-induced protein 1. The upregulation of BAD by morin was due to blocking the ubiquitination degradation of BAD, rather than the transcription regulation and the phosphorylation of BAD. Furthermore, the combination of morin and BCL-2 inhibitor navitoclax (also known as ABT-737) produced a synergistic inhibitory effect in GC cells through amplifying apoptotic signals. In addition, morin treatment significantly suppressed the growth of GC in vivo by upregulating BAD and the subsequent activation of its downstream apoptosis pathway. CONCLUSION Morin suppressed GC by inducing apoptosis, which was mainly due to blocking the ubiquitination-based degradation of the pro-apoptotic protein BAD. The combination of morin and the BCL-2 inhibitor ABT-737 synergistically amplified apoptotic signals in GC cells, which may overcome the drug resistance of the BCL-2 inhibitor. These findings indicated that morin was a potent and promising agent for GC treatment. Please cite this article as: Wang Y, Sun XY, Ma FQ, Ren MM, Zhao RH, Qin MM, Zhu XH, Xu Y, Cao ND, Chen YY, Dong TG, Pan YF, Zhao AG. Morin inhibits ubiquitination degradation of BCL-2 associated agonist of cell death and synergizes with BCL-2 inhibitor in gastric cancer cells. J Integr Med. 2025; 23(3): 320-332.
Humans ; Flavonoids/therapeutic use* ; Stomach Neoplasms/pathology* ; Animals ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Cell Line, Tumor ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Ubiquitination/drug effects* ; Mice ; Drug Synergism ; Mice, Inbred BALB C ; Mice, Nude ; Xenograft Model Antitumor Assays ; Flavones

OBJECTIVE: This study reports the first imported case of Lassa fever (LF) in China. Laboratory detection and molecular epidemiological analysis of the Lassa virus (LASV) from this case offer valuable insights for the prevention and control of LF. METHODS: Samples of cerebrospinal fluid (CSF), blood, urine, saliva, and environmental materials were collected from the patient and their close contacts for LASV nucleotide detection. Whole-genome sequencing was performed on positive samples to analyze the genetic characteristics of the virus. RESULTS: LASV was detected in the patient's CSF, blood, and urine, while all samples from close contacts and the environment tested negative. The virus belongs to the lineage IV strain and shares the highest homology with strains from Sierra Leone. The variability in the glycoprotein complex (GPC) among different strains ranged from 3.9% to 15.1%, higher than previously reported for the seven known lineages. Amino acid mutation analysis revealed multiple mutations within the GPC immunogenic epitopes, increasing strain diversity and potentially impacting immune response. CONCLUSION The case was confirmed through nucleotide detection, with no evidence of secondary transmission or viral spread. The LASV strain identified belongs to lineage IV, with broader GPC variability than previously reported. Mutations in the immune-related sites of GPC may affect immune responses, necessitating heightened vigilance regarding the virus.
Humans ; China/epidemiology* ; Genome, Viral ; Lassa Fever/virology* ; Lassa virus/classification* ; Molecular Epidemiology ; Phylogeny

OBJECTIVE: The study aim was to investigate the effects of exposure to multiple environmental organic pollutants on cardiopulmonary health with a focus on the potential mediating role of oxidative stress. METHODS: A repeated-measures randomized crossover study involving healthy college students in Beijing was conducted. Biological samples, including morning urine and venous blood, were collected to measure concentrations of 29 typical organic pollutants, including hydroxy polycyclic aromatic hydrocarbons (OH-PAHs), bisphenol A and its substitutes, phthalates and their metabolites, parabens, and five biomarkers of oxidative stress. Health assessments included blood pressure measurements and lung function indicators. RESULTS: Urinary concentrations of 2-hydroxyphenanthrene (2-OH-PHE) ( β = 4.35% [95% confidence interval ( CI): 0.85%, 7.97%]), 3-hydroxyphenanthrene ( β = 3.44% [95% CI: 0.19%, 6.79%]), and 4-hydroxyphenanthrene (4-OH-PHE) ( β = 5.78% [95% CI: 1.27%, 10.5%]) were significantly and positively associated with systolic blood pressure. Exposures to 1-hydroxypyrene (1-OH-PYR) ( β = 3.05% [95% CI: -4.66%, -1.41%]), 2-OH-PHE ( β = 2.68% [95% CI: -4%, -1.34%]), and 4-OH-PHE ( β = 3% [95% CI: -4.68%, -1.29%]) were negatively associated with the ratio of forced expiratory volume in the first second to forced vital capacity. These findings highlight the adverse effects of exposure to multiple pollutants on cardiopulmonary health. Biomarkers of oxidative stress, including 8-hydroxy-2'-deoxyguanosine and extracellular superoxide dismutase, mediated the effects of multiple OH-PAHs on blood pressure and lung function. CONCLUSION Exposure to multiple organic pollutants can adversely affect cardiopulmonary health. Oxidative stress is a key mediator of the effects of OH-PAHs on blood pressure and lung function.
Humans ; Oxidative Stress/drug effects* ; Male ; Cross-Over Studies ; Female ; Young Adult ; Environmental Pollutants/toxicity* ; Environmental Exposure/adverse effects* ; Biomarkers/blood* ; Adult ; Blood Pressure/drug effects* ; Polycyclic Aromatic Hydrocarbons/urine* ; Beijing

Based on ultra-performance liquid chromatography-quadrupole-electrostatic field Orbitrap high-resolution mass spectrometry(UPLC-Q-Orbitrap HRMS) technology and molecular docking, the bitter-tasting substances(hereafter referred to as "bitter substances") in Cistanche deserticola extract were investigated, and the bitter taste and efficacy relationship was explored to lay the foundation for future research on de-bittering and taste correction. Firstly, UPLC-Q-Orbitrap HRMS was used for the qualitative analysis of the constituents of C. deserticola, and 69 chemical components were identified. These chemical components were then subjected to molecular docking with the bitter taste receptor, leading to the screening of 20 bitter substances, including 6 phenylethanol glycosides, 5 flavonoids, 3 phenolic acids, 2 cycloalkenyl ether terpenes, 2 alkaloids, and 2 other components. Nine batches of fresh C. deserticola samples were collected from the same origin but harvested at different months. These samples were divided into groups based on harvest month and plant part. The bitterness was quantified using an electronic tongue, and the content of six potential bitter-active compounds(pineconotyloside, trichothecene glycoside, tubulin A, iso-trichothecene glycoside, jinshihuaoside, and jingnipinoside) was determined by high-performance liquid chromatography(HPLC). The total content of phenylethanol glycosides, polysaccharides, alkaloids, flavonoids, and phenolic acids was determined using UV-visible spectrophotometry. Chemometric analyses were then conducted, including Pearson's correlation analysis, gray correlation analysis, and orthogonal partial least squares discriminant analysis(OPLS-DA), to identify the bitter components in C. deserticola. The results were consistent with the molecular docking findings, and the two methods mutually supported each other. Finally, network pharmacological predictions and analyses were performed to explore the relationship between the targets of bitter substances and their efficacy. The results indicated that key targets of the bitter substances included EGFR, PIK3CB, and PTK2. These substances may exert their bitter effects by acting on relevant disease targets, confirming that the bitter substances in C. deserticola are the material basis of its bitter taste efficacy. In conclusion, this study suggests that the phenylethanol glycosides, primarily pineconotyloside, mauritiana glycoside, and gibberellin, are the material basis for the "bitter taste" of C. deserticola. The molecular docking technique plays a guiding role in the screening of bitter substances in traditional Chinese medicine(TCM). The bitter substances in C. deserticola not only contribute to its bitter taste but also support the concept of the "taste-efficacy" relationship in TCM, providing valuable insights and references for future research in this area.
Molecular Docking Simulation ; Taste ; Chromatography, High Pressure Liquid ; Cistanche/chemistry* ; Drugs, Chinese Herbal/chemistry* ; Humans ; Mass Spectrometry

Inflammatory bowel disease is a chronic, idiopathic, and recurrent gastrointestinal disorder with an unclear etiology and uncertain pathogenesis. Traditional treatment strategies rely on frequent administration of high doses of medication to reduce inflammation, whereas these approaches have limitations and may induce potential complications. Therefore, finding more effective and safe therapeutic drugs and methods is particularly important. Plant-derived exosome-like nanovesicles(PDELNs) are nano-sized vesicles with a lipid bilayer structure that are secreted by plant cells. The bioactive molecules contained within, such as lipids, proteins, and nucleic acids, can serve as information carriers, playing a role in the transmission of information and substances between cells and across species. PDELNs can carry and transfer their own bioactive substances or act as carriers for delivering other active components or drugs. Due to the high biocompatibility, low toxicity, and significant bioactivity, PDELNs have garnered widespread attention. Compared with other exosomes, PDELNs are not destroyed in the gastrointestinal tract when taken orally and can reach the intestines. This unique property makes PDELNs a promising oral nanodrug for treating intestinal diseases, showing great potential in this area. This article reviews recent research literature on PDELNs regarding the physicochemical characteristics, extraction and purification methods, functions, application characteristics and mechanisms in the treatment of intestinal diseases, and use as a carrier for treating intestinal diseases, aiming to provide a reference for the use of PDELNs in the treatment of intestinal diseases.
Humans ; Exosomes/metabolism* ; Animals ; Intestinal Diseases/metabolism* ; Plants/metabolism* ; Drug Carriers/chemistry* ; Drugs, Chinese Herbal/chemistry* ; Drug Delivery Systems ; Nanoparticles/chemistry*

OBJECTIVE: A new three-dimensional(3D) classification of posterior cruciate ligament (PCL) tibial avulsion fracture based on computed tomography(CT) features was established and the significance in clinical treatment was explored in this study. METHODS: From May 2013 to November 2023, 43 cases of PCL tibial avulsion fracture in the Second Hospital of Jilin University were analyzed retrospectively, including 29 males and 14 females, aged (34.3±8.5) years. According to traditional Meyers and McKeever classification, 3 cases were typeⅠ;2 cases of typeⅡ;38 cases were type Ⅲ. Based on the characteristics of CT images, 43 patients were given specific treatment strategies and followed up to evaluate the curative effect. According to the degree of fracture displacement, involved range and the integrity of fracture block demonstrated by CT images, the new three-dimensional classification of PCL avulsion fracture was established. Kappa coefficient was used for consistency test. RESULTS: A new 3D classification of PCL tibial avulsion fracture was established. TypeⅠwas the non-displaced fracture (displacement degree ≤3 mm), in which typeⅠa was the avulsion range limited in the posterior intercondylar fossa, and Ib was the avulsion range beyond the posterior intercondylar fossa. TypeⅡrepresented the displaced fracture in the posterior intercondylar fossa (avulsion limited to the posterior intercondylar fossa and fracture displacement>3 mm), in which typeⅡa represented a slight displacement with a intact broken block and the posterior elevation of the avulsion (hinge mechanism), typeⅡb represented the complete separation of fracture ends with a intact fracture block, and typeⅡc was the comminuted fracture. Type Ⅲ was the displaced fracture beyond the posterior intercondylar fossa (avulsion involving the articular surface of the tibial plateau or the intercondylar ridge and the degree of displacement > 3 mm), among which type Ⅲa was the simple fracture with intact broken block, type Ⅲb represented the comminuted fracture, and type Ⅲc was the complex fracture with tibial plateau fracture. According to this new 3D classification, 43 patients were classified as type Ia in 2 cases and typeⅠb in 1 case;typeⅡa in 2 cases, typeⅡb in 15 cases and typeⅡc in 7 cases;type Ⅲa in 2 cases, type Ⅲb in 5 cases and type Ⅲc in 9 cases. All the 43 cases in this study achieved bone union. At the last follow-up, according to the hospital for special surgery knee score(HSS)evaluation system for the knee joint function, 27 cases were excellent, 11 cases were good, 5 cases were fair. The average Kappa value of inter-observer reliability in the first stage was 0.793, and the second stage was 0.855. The average Kappa value of the whole stage was 0.839, indicating high level of consistency. The average Kappa value of intra-observer reliability was 0.893, indicating high level of consistency. CONCLUSION The 3D classification of PCL tibial avulsion fracture is intuitive, demonstrating a high level of reliability. It has a certain guiding significance for the selection of clinical treatment methods, and it is suggested to be promoted and applied as a new classification system in clinical practice.
Humans ; Male ; Female ; Posterior Cruciate Ligament/surgery* ; Adult ; Tibial Fractures/classification* ; Tomography, X-Ray Computed ; Middle Aged ; Retrospective Studies ; Fractures, Avulsion/classification* ; Imaging, Three-Dimensional ; Young Adult