OBJECTIVE To form an expert consensus on the clinical application of parenteral direct thrombin inhibitors （DTIs） in patients during the perioperative period. METHODS Led by Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital （the Affiliated Hospital of UESTC）， a multidisciplinary working group was established. Through literature review and the Delphi method， clinical questions related to the rational perioperative use of parenteral DTIs were identified. A structured design was adopted using the “Population-Intervention-Comparison-Outcome” framework； systematic searches were conducted in CNKI， Medline， Embase and other databases. Relevant evidence from randomized controlled trials and cohort studies was included and synthesized. Evidence quality was assessed using the Grades of Recommendations Assessment，Development and Evaluation （GRADE） approach， and recommendations were formulated through multiple rounds of Delphi surveys and expert consensus meetings. RESULTS &CONCLUSIONS Seven recommendations （each with an expert consensus rate exceeding 90%） on the use of parenteral DTIs in perioperative patients were developed. These recommendations specify drug selection， dosing ranges， key monitoring points， and safety management strategies for parenteral DTIs in various scenarios， including the perioperative period of ventricular assist device implantation， the perioperative period of cardiac surgery， perioperative patients with lower-extremity atherosclerotic disease， the perioperative period of percutaneous coronary intervention in patients with acute coronary syndrome， the perioperative period of carotid artery stenting in patients with carotid stenosis， the perioperative period of patients with right heart thrombosis， and patients who develop related thrombosis and dysfunction after a central venous catheter insertion. In addition， warning and management pathways for perioperative bleeding and thrombotic events were proposed. This expert consensus， which is formulated based on the best available evidence， provides evidence-based guidance for standardized and individualized use of parenteral DTIs in perioperative period.

OBJECTIVE To investigate the improvement effects and mechanism of astragaloside Ⅳ （AS- Ⅳ ） on lipopolysaccharide （LPS）-induced neuroinflammation. METHODS BV2 cells were divided into control group， LPS group， AS-Ⅳ groups at concentrations of 20 and 40 μmol/L， and dexamethasone group （2 μmol/L）. Except for control group， neuroinflammation model was established with LPS （1 μg/mL） in other groups after medication. The levels of inflammatory factors [interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， and nitric oxide （NO）] in cell supernatant were measured in each group. Mice were randomly divided into normal group， model group， positive control group （Aspirin enteric-coated tablet， 20 mg/kg）， AS-Ⅳ low- and high-dose groups （10， 20 mg/kg）， with 6 mice in each group. Mice in each group were administered the corresponding drug/normal saline via gavage/intraperitoneal injection， once a day， for 14 consecutive days. Except for normal group， other groups were intraperitoneally injected with LPS （250 μg/kg） 1 hour after daily administration of the drug/normal saline to establish neuroinflammation model. Serum levels of IL-6 and TNF-α were measured 2 h after the last medication； histopathological morphology of cerebral tissue in mice were observed； the co-localization of inducible nitric oxide synthase （iNOS）/ionized calcium binding adapter molecule 1 （Iba1） and CD206/Iba1 in the cerebral cortex region of mice was observed； the expressions of proteins related to the nuclear factor-κB （NF-κB）/mitogen-activated protein kinase （MAPK） signaling pathway in brain tissue of mice were also determined， including NF-κB p65， phosphorylated NF-κB p65（p-NF-κB p65）， p38 MAPK， phosphorylated p38 MAPK （p-p38 MAPK）， extracellular signal-regulated kinase （ERK）， and phosphorylated ERK （p-ERK）. RESULTS In the cell experiments， compared with control group， the levels of IL-6， TNF- α and NO in the cell supernatant of the LPS group were increased significantly （P＜0.05）； compared with LPS group， the levels of IL-6， TNF-α and NO were decreased significantly in the administration groups （P＜0.05）. In the animal experiments， compared with the normal group， the serum levels of IL-6 and TNF- α， the number of iNOS/Iba1 co-localization positive cells in the cerebral cortex， and the phosphorylation levels of p38 MAPK， NF- κB p65 and ERK proteins in brain tissue were all significantly increased/elevated in model group （P＜0.05）； the number of CD206/ Iba1 co-localization positive cells in the cerebral cortex region significantly decreased （P＜0.05）. The neurons in the cerebral cortex and the CA3 region of the hippocampus displayed a disordered arrangement. Compared with model group， above quantitative indexes of mice were all reversed significantly in administration groups （P＜0.05）； the neuronal cells in the cerebral cortex and the CA3 region of the hippocampus exhibited a relatively orderly arrangement. CONCLUSIONS AS-Ⅳ may inhibit the activation of the NF-κB/MAPK signaling pathway， promote the M2-type polarization of microglia， and thereby suppress neuroinflammatory responses.

OBJECTIVE To study the ameliorative effect and mechanism of Forsythia suspensa-Lonicera japonica herb pair on acute lung injury （ALI） based on serum exosomal microRNA （miRNA）. METHODS The rats were randomly divided into a blank group （normal saline）， model group （nomal saline）， and F. suspensa-L. japonica herb pair group （2.55 g/kg）， with 10 rats in each group. Except for the blank group， the other groups were used to establish an ALI model by intratracheal dripping of 5 mg/ mL lipopolysaccharides. After modeling， each group was given relevant medicine/normal saline intragastrically， once a day， for 3 consecutive days. After the last medication， the pathological status of lung tissue was observed； lung wet-to-dry weight ratio and leukocyte counts in bronchoalveolar lavage fluid （BALF） were determined. The levels of inflammatory factors [tumor necrosis factor-α（TNF-α）， interleukin-1β （IL-1β）， IL-10] in BALF were determined. Exosomes were isolated from rat serum， and high- throughput sequencing technology was employed to screen differentially expressed miRNA within the exosomes， followed by Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis. Based on the screened differentially expressed miRNA and the enriched KEGG pathways， in vitro cellular experiments were conducted for validation. RESULTS The animal experimental results demonstrated that after intervention with the F. suspensa-L. japonica herb pair， the wet-to-dry weight ratio， the number of leukocytes in BALF， as well as the levels of TNF-α and IL-1β in BALF of ALI rats were all significantly reduced （P＜0.01）， while the level of IL-10 was significantly increased （P＜0.01）. The results of high-throughput sequencing experiments revealed that the F. suspensa-L. japonica herb pair could significantly up-regulate the expressions of miR-345-3p， miR-194-5p， miR-653-5p， and others in exosomes. Among them， the KEGG pathways involved in the target genes of differentially expressed miRNA included the hypoxia-inducible factor-1（HIF-1） signaling pathway， among others. The results of cellular E-mail：huang.haiying@126.com validation experiments showed that overexpressed miR-345-3p could significantly elevate the level of IL-10 in the cell supernatant （P＜0.01）， while significantly reducing the levels of TNF-α and IL-1β in the cell supernatant， as well as the mRNA and protein expression levels of protein kinase B1， phosphatidylinositol 3- kinase， and HIF-1α （P＜0.01）. CONCLUSIONS F. suspensa-L. japonica herb pair can alleviate inflammatory responses and thereby exert a therapeutic effect in improving ALI by up-regulating the expression of miR-345-3p in serum exosomes and inhibiting the activity of the HIF-1 signaling pathway.

Objective To analyze the unexamined items and situations in occupational health examinations of radiation workers, and provide a reference for the revision of occupational health examination standards for radiation workers. Methods A total of 29 630 radiation workers who underwent occupational health examinations at The Third People’s Hospital of Henan Province in 2023 were selected, and the non-examination rates were statistically analyzed according to occupation, gender, and age. Results The overall non-examination rate of non-medical radiation workers was significantly lower than that of the medical radiation workers (P<0.05). The non-examination rate of chest X-rays among medical radiation workers was significantly higher than that of non-medical radiation workers (P<0.05), while no significant differences were found in other items (P>0.05). Gender-stratified analysis showed that the non-examination rate of routine urine tests was higher in females than in males in both medical and non-medical radiation workers (P<0.05). Age-stratified analysis revealed no significant differences in non-examination rates among different age groups in non-medical radiation workers (P>0.05), whereas the chest X-ray non-examination rate was relatively high in medical radiation workers under 30 years old (P<0.05). Conclusion Significant differences were observed in the non-examination rates of occupational health examinations among radiation workers based on occupation, gender, and age. The overall non-examination rate was relatively low in non-medical radiation workers.

OBJECTIVE To investigate the mechanism of Bushen huoxue formula in improving pregnancy outcomes in mice with antiphospholipid antibody-related recurrent spontaneous abortion （aPL-RSA）. METHODS SPF female BALB/c mice were randomly divided into normal control group， adjuvant control group， model group， and Bushen huoxue formula group. The aPL-RSA mouse model was established by immunization with β 2 glycoproteinⅠcombined with Freund’s adjuvant. From gestational day 0， the Bushen huoxue formula group was administered 1.653 6 g/（kg·d） of the prescription by gavage， while the other three groups received an equal volume of normal saline， twice daily for 15 consecutive days. The uterine appearance of pregnant mice was observed； individual embryo weight was recorded， and the embryo resorption rate was calculated. The proportion of activated CD41 + CD62p + platelets in platelet-rich plasma （PRP） was detected. Serum levels of thromboxane B2 （TXB2） and platelet factor 4 （PF4） were measured. Morphological changes of placental tissue were observed. The cell apoptosis rate of placental tissue was detected. The levels of malondialdehyde （MDA） content， tot al superoxide dismutase （T-SOD） activity， the interleukin-1β （IL-1β） and IL-18， the protein expressions of matrix metalloproteinase-3 （MMP-3）， MMP-9， nuclear proliferation antigen-67 （Ki67）， superoxide dismutase 2 （SOD2）， Nod-like receptor protein 3 （NLRP3）， apoptosis-associated speck-like protein containing a CARD （ASC）， and caspase-1， as well as the mRNA expressions of superoxide dismutase 2（SOD2）， NLRP3， ASC and caspase-1 of placental tissue were detected. RESULTS Compared with the normal control group and adjuvant control group， the model group showed significant decreases in individual embryo weight， T-SOD activity of placental tissue， and relative expression levels of SOD2 mRNA and protein （ P ＜0.05）； while significant increases were observed in embryo resorption rate， proportion of activated CD41 + CD62p + platelets in PRP， serum levels of TXB2 and PF4， placental cell apoptosis rate， MDA content in placental tissue， relative protein expressions of MMP-3， MMP-9 and Ki67， relative protein and mRNA expression levels of NLRP3， ASC and caspase-1 as well as IL-1β and IL-18 levels （ P ＜0.05）. The model group also exhibited irregular uterine morphology with localized atrophy in some uterine horns； placental tissue showed fragmentation of decidual cells， extensive vacuolization and necrosis of trophoblast cells in the labyrinthine zone， accompanied by vascular reduction. After intervention with Bushen huoxue formula， the above indicators were significantly reversed （ P ＜0.05）， and uterine morphology and pathological damage were markedly improved. CONCLUSIONS Bushen huoxue formula can effectively improve pregnancy outcomes in aPL-RSA model mice， and its mechanism may be closely related to inhibiting platelet activation， reducing oxidative stress injury， enhancing trophoblast cell function， and suppressing the inflammatory response mediated by the NLRP3 inflammasome pathway.

Triptolide （TP）， the core active component of the traditional Chinese medicine Tripterygium wilfordii ， exhibits remarkable pharmacological activities including anti-inflammatory， immunosuppressive and anti-tumor effects， and holds broad application prospects in the treatment of major diseases such as autoimmune diseases and malignant tumors. However， TP has a narrow therapeutic window and causes multi-organ toxicities including liver， kidney and reproductive toxicities， which severely restrict its safe clinical application and new drug development. Therefore， toxicity reduction and efficacy enhancement has become a core scientific problem urgently to be solved in this field. This paper systematically reviews the four core strategies for TP toxicity reduction and efficacy enhancement， including structural modification， dosage form improvement， herbal compatibility， and external therapies of traditional Chinese medicine. Among them， structural modification optimizes the toxic and efficacy characteristics of TP from the molecular structure level， with typica l derivatives including （5 R ）-5-hydroxy triptolide， ZT01， PG490-88， etc. Dosage form modification achieves toxicity reduction and efficacy enhancement via targeted and sustained-controlled drug release of diverse delivery systems. It includes triptolide preparations such as nanoparticles， liposomes， microemulsion gels and liquid crystals， possessing favorable clinical transformation potential. The herbal compatibility and external therapies of traditional Chinese medicine conform to the holistic view of traditional Chinese medicine and have a profound clinical application foundation， but their mechanisms of action are insufficiently elucidated， and they lack unified standardized specifications and high-quality evidence-based proof. In the future， we should rely on multi-omics technology to elucidate the toxic and efficacy mechanisms， integrate technologies to optimize preparations， improve the evaluation system and promote clinical transformation.

Diabetic kidney disease （DKD）， one of the leading causes of end-stage renal disease， shows increasing prevalence and mortality， seriously affecting the physical and mental health of patients. As a crucial link in the occurrence and development of DKD， pyroptosis can lead to kidney cell injury and inflammation through the abnormal activation of reactive oxygen species （ROS）/thioredoxin-interacting protein （TXNIP）/NOD-like receptor protein 3 （NLRP3）， Toll-like receptor 4 （TLR4）/nuclear factor-κB （NF-κB）/NLRP3， nuclear factor erythroid 2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1）， mitogen-activated protein kinase （MAPK）/NLRP3， and hypoxia-inducible factor-1α （HIF-1α）/NLRP3 signaling pathways， which accelerate the progression of DKD. In recent years， traditional Chinese medicine （TCM） has demonstrated definite efficacy in the treatment of DKD via multiple targets and pathways. Studies have shown that various TCM active components， including glycosides， flavonoids， polyphenols， terpenoids， and alkaloids， as well as TCM compound prescriptions for clearing heat and detoxifying， tonifying deficiency and consolidating root， and eliminating stasis and descending turbidity， can target relevant signaling pathways to inhibit pyroptosis and intervene in the development of DKD， providing new possibilities for precision treatment of DKD. This article systematically reviews the relevant pathways of pyroptosis and summarizes the research achievements and mechanisms of TCM active components and compound prescriptions in the treatment of DKD via pyroptosis in recent years. This review aims to provide new directions and ideas for the treatment and research of DKD with TCM and promote the modernization and development of TCM.

Idiopathic pulmonary fibrosis （IPF） is a chronic interstitial lung disease characterized by dyspnea and progressive deterioration of lung function， which significantly impacts patients' quality of life and imposes a major burden on society. Although modern medicine has increasingly enriched the treatment options for pulmonary fibrosis， unfavorable factors such as high costs and significant side effects contribute to the persistently low survival rate of patients. Studies have shown that the occurrence and development of pulmonary fibrosis are closely related to abnormalities in multiple pathways. Among these， Rho/Rho-associated coiled-coil protein kinase （ROCK） plays a key role in the disease progression of IPF by regulating the cytoskeleton. This pathway not only transmits biochemical molecular signals that promote the progress of fibrosis but also responds to the biomechanical environment， such as the increased lung tissue stiffness caused by the deposition of extracellular matrix （ECM） during the process of pulmonary fibrosis. Therefore， research on this pathway is of great significance for the prevention and treatment of IPF. In recent years， traditional Chinese medicine （TCM） has shown remarkable effects in preventing and treating IPF. Many TCM compounds and active components can reduce the production of α-smooth muscle actin （α-SMA）， CollagenⅠ （ColⅠ）， ColⅢ， and inflammatory factors in lung tissue by regulating the Rho/ROCK signaling pathway. These compounds inhibit the transformation of fibroblasts （FBs） into myofibroblasts （MyoFBs）， intervening in the process of pulmonary fibrosis. Based on this， the article briefly reviews relevant research from recent years， discusses the key role of the Rho/ROCK pathway in pulmonary fibrosis from an interdisciplinary perspective， and summarizes the mechanisms through which TCM regulates Rho/ROCK to prevent and treat IPF， based on resources from PubMed， CNKI， and other databases， in order to provide important references for the broader clinical application of TCM in the prevention and treatment of IPF.

ObjectiveBy exploring the influencing factors of readmission in patients with stable angina of coronary heart disease （CHD） based on real-world clinical data， to establish a risk prediction model of integrated traditional Chinese and western medicine， in order to provide a basis for early identification of high-risk populations and reducing readmission rates. MethodsA prospective clinical study was conducted involving patients with stable angina pectoris of CHD， who were divided into a training set and a validation set at a 7∶3 ratio. General information， traditional Chinese medicine （TCM）-related data， and laboratory test results were uniformly collected. After a one-year follow-up， patients were classified into a readmission group and a non-readmission group based on whether they were readmitted. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors for readmission. A risk prediction model of integrated traditional Chinese and western medicine was constructed and visualized using a nomogram. The model was validated and evaluated in terms of discrimination， calibration， and clinical decision curve analysis. ResultsA total of 682 patients were included， with 477 in the training set and 205 in the validation set， among whom 89 patients were readmitted. Multivariate logistic regression analysis identified heart failure history ［OR = 6.93， 95% CI （1.58， 30.45）］， wiry pulse ［OR = 2.58， 95% CI （1.42， 4.72）］， weak pulse ［OR = 3.97， 95% CI （2.06， 7.67）］， teeth-marked tongue ［OR = 4.38， 95% CI （2.32， 8.27）］， blood stasis constitution ［OR = 2.17， 95% CI （1.06， 4.44）］， phlegm-stasis mutual syndrome ［OR = 3.64， 95% CI （1.87， 7.09）］， and elevated non-high-density lipoprotein cholesterol ［OR = 1.30， 95% CI （1.01， 1.69）］ as influencing factors of readmission. These factors were used as predictors to construct a nomogram-based risk prediction model for readmission in patients with stable angina. The model demonstrated moderate predictive capability， with an area under the receiver operating characteristic curve （AUC） of 0.818 ［95% CI （0.781， 0.852）］ in the training set and 0.816 ［95% CI （0.779， 0.850）］ in the validation set. The Hosmer-Lemeshow test showed good calibration （χ² = 4.55， P = 0.80）， and the model's predictive ability was stable. When the threshold probability exceeded 5%， the clinical net benefit of using the model to predict readmission risk was significantly higher than intervening in all patients. ConclusionHistory of heart failure， teeth-marked tongue， weak pulse， wiry pulse， phlegm-stasis mutual syndrome， blood stasis constitution， and non-high-density lipoprotein cholesterol are influencing factors for readmission in patients with stable angina of CHD. A clinical prediction model was developed based on these factors， which showed good discrimination， calibration， and clinical utility， providing a scientific basis for predicting readmission events in patients with stable angina.

OBJECTIVE: To analyze the clinical characteristics and genotypic changes of six children with RARS2 gene variants. METHODS: The clinical data of 6 children with RARS2 gene variants diagnosed at the Third Affiliated Hospital of Zhengzhou University from January 2017 to August 2024 were collected. Genetic variants were detected using trio-whole exome sequencing. Genomic DNA was extracted from samples and subjected to high-throughput sequencing. Variants were detected and analyzed using relevant databases and software. Pathogenic variants were validated by Sanger sequencing. The protein structure encoded by a previously unreported variant was predicted using a SWISS-MODEL online server. This study was approved by the Medical Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (Ethics No.: 2024-373-01). RESULTS: Among the six children, four were males and two were females, with the most recent follow-up age ranging from 1-year-and-1-month to 7 years old. The age of onset was under 1 year in all cases. All six children exhibited seizures, including infantile spasms in three, spasms and tonic spasms in one, and focal seizures in two. One child became seizure-free for 4 ~ 5 years following Valproic acid combined with topiramate and adrenocorticotropic hormone (ACTH) pulse therapy, but subsequently experienced a relapse. Another child has remained seizure-free for nearly one year with oral sodium valproate, levetiracetam, and a "cocktail" therapy. Seizures were not controlled in the remaining four children. Pontocerebellar hypoplasia was observed on neuroimaging in two children. All six patients exhibited severe psychomotor retardation. A total of 10 RARS2 gene variants were identified, three of which were previously unreported. CONCLUSION The predominant clinical features of Pontocerebellar hypoplasia associated with RARS2 gene variants include infantile onset, severe psychomotor retardation or regression, drug-resistant epilepsy, and feeding difficulties. The characteristic neuroimaging finding is pontocerebellar hypoplasia. However, its appearance may vary widely with time. The majority of affected children have a poor prognosis.
Humans ; Male ; Female ; Child, Preschool ; Infant ; Child ; Olivopontocerebellar Atrophies/genetics* ; Arginine-tRNA Ligase/genetics* ; Mutation ; Cerebellar Diseases