ObjectiveTo decipher the mechanism by which Zuoguiwan （ZGW） treat hyperthyroidism in rats with kidney-Yin deficiency based on the dopamine receptor D4 （DRD4）/nicotinamide adenine dinucleotide phosphate （NADPH） oxidase 4 （NOX4） signaling pathway. MethodsThe rat model of kidney-Yin deficiency was induced by unilateral intramuscular injection of dexamethasone （0.35 mg·kg^-1）. After successful modeling， the rats were randomized into model， methimazole （positive control， 5 mg·kg^-1）， low-， medium-， and high-dose （1.85， 3.70， 7.40 g·kg^-1， respectively） ZGW， and normal control groups. After 21 days of continuous gavage， the behavioral indexes and body weight changes of rats were evaluated. The pathological changes of the renal tissue were observed by hematoxylin-eosin staining. The serum levels of thyroid hormones ［triiodothyronine （T₃）， thyroxine （T₄）， thyroid-stimulating hormone （TSH）］， renal function indexes ［serum creatine （Scr） and blood urea nitrogen （BUN）］， energy metabolism markers ［cyclic adenosine monophosphate （cAMP） and cyclic guanosine monophosphate （cGMP）］， and oxidative stress-related factors ［superoxide dismutase （SOD）， malondialdehyde （MDA）， and NADPH）］ were measured by enzyme-linked immunosorbent assay （ELISA）. Western blot was employed to analyze the expression of DRD4， NOX4， mitochondrial respiratory chain complex proteins ［NADH：ubiquinone oxidoreductase subunit S4 （NDUFS4） and cytochrome C oxidase subunit 4 （COX4）］， and inflammation-related protein ［tumor necrosis factor-alpha （TNF-α）， interleukin-6 （IL-6）， p38 mitogen-activated protein kinase （MAPK）］ pathway in the renal tissue. ResultsCompared with the normal group， the model group showed mental malaise， body weight decreases （P<0.01）， inflammatory cell infiltration in the renal tissue， a few residual parotid glands in the thyroid， elevations in serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA， and NADPH （P<0.01）， down-regulation in protein levels of TSH， SOD， and DRD4 （P<0.05， P<0.01）， and up-regulation in expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.01）. Compared with the model group， ZGW increased the body weight （P<0.05， P<0.01）， reduced the infiltration of renal interstitial inflammatory cells， restored the thyroid structure and follicle size， lowered the serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA and NADPH （P<0.05， P<0.01）， up-regulated the expression of TSH， SOD and DRD4 （P<0.05， P<0.01）， and down-regulated the expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.05， P<0.01）. Moreover， high-dose ZGW outperformed methimazole （P<0.05）. ConclusionBy activating DRD4， ZGW can inhibit the expression of NOX4 mediated by the p38 MAPK pathway， reduce oxidative stress and inflammatory response， thereby ameliorating the pathological state of hyperthyroidism due to kidney-Yin deficiency. This study provides new molecular mechanism support for the clinical application of ZGW.

Objective To evaluate the safety and efficacy of a self-developed micro-normothermic machine perfusion (NMP) system (micro-perfusion device) for preserving isolated porcine limbs. Methods Five healthy Landrace pigs were selected, and their left and right forelimbs were randomly divided into the NMP group and static cold storage (SCS) group. The NMP group was perfused with the self-developed micro-perfusion device and polymerized hemoglobin perfusate for 32 hours at normothermia, while the SCS group was preserved at 4 ℃. Hemodynamic parameters such as perfusion pressure and flow were monitored. The pH value, partial pressure of oxygen (PO₂), lactic acid (Lac), creatine kinase (CK) and lactate dehydrogenase (LDH) in the perfusate were measured. Hematoxylin-eosin staining was used to assess the muscle tissue structure, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling was employed to evaluate muscle cell apoptosis, and immunohistochemistry staining was applied to detect the expressions of tumor necrosis factor (TNF)-α and interleukin (IL)-6. A mixed-effects model was used to analyze the effects of time and treatment methods on tissue structure, cell apoptosis and inflammatory factors. Results The device could stably maintain a perfusion pressure of (69±15) mmHg and a flow rate of (117±42) mL/min. The pH value and electrolytes of the perfusate were generally stable, with PO₂ maintained at a high level. Lac was maintained at 5.38(3.81, 6.45) mmol/L, while CK and LDH increased over time. After 32 hours of perfusion in the NMP group, both the myocyte spacing and apoptosis rate were better than those in the SCS group. Mixed-effects model analysis showed that there were statistically significant differences in the effects of NMP treatment and SCS treatment on myocyte spacing and apoptosis rate per unit time (both P < 0.05). There were no statistically significant differences in TNF-α and IL-6 between the two groups, and mixed-effects model analysis showed no statistically significant differences in the effects of NMP treatment and SCS treatment on TNF-α and IL-6 per unit time (both P > 0.05). Conclusions The micro-perfusion device used in this study may achieve 32-hour normothermic preservation in a porcine limb amputation model, maintain basic metabolism and ionic homeostasis, reduce muscle structural damage and cell apoptosis without inducing additional inflammatory responses. This technology is expected to significantly extend the time window for replantation of amputated limbs in disaster rescue and long-distance transportation, providing an important technical basis for clinical translation and subsequent replantation research.

This paper summarizes the clinical experience in the syndrome differentiation and treatment of rosacea using the method of venting heat and resolving stagnation. It is considered that the key pathogenesis of rosacea is the accumulation of heat with stagnation. Accordingly， the method of venting heat and resolving stagnation is proposed， which vents and disperses constraint heat by applying approaches such as dredging defensive qi， clearing qi， venting ying （营） level， and cooling blood， while eliminating stagnation and masses through regulating qi， resolving dampness， dispelling phlegm and removing stasis. In clinical practice， a core prescription for venting heat and resolving stagnation is formulated， with flexible modifications made according to the clinical characteristics of different rosacea subtypes， including erythematotelangiectatic， papulopustular， phymatous， and ocular types， thereby providing therapeutic insights for the treatment of rosacea with traditional Chinese medicine.

BACKGROUND:At present,modern medical treatment has certain limitations on the treatment of knee osteoarthritis.Traditional Chinese medicine alkaloids can effectively prevent and treat knee osteoarthritis through various mechanisms. OBJECTIVE:To review the mechanism of alkaloids in traditional Chinese medicine in the prevention and treatment of knee osteoarthritis,providing a scientific basis for the clinical development of drugs for the treatment of knee osteoarthritis. METHODS:CNKI,WanFang,PubMed,Web of Science and Google Scholar were retrieved for relevant literature published from database inception to May 2024.The key words were"knee osteoarthritis""osteoarthritis""osteoclast""chondrocyte""alkaloids"in Chinese and English.Duplicates and obsolete non-referenced literature were excluded,and a total of 68 eligible papers were included for further review. RESULTS AND CONCLUSION:Although traditional Chinese medicine has a long history of treating knee osteoarthritis,only a small number of natural compounds are in the preclinical stage of research against knee osteoarthritis.Alkaloids have a greater potential for the prevention and treatment of knee osteoarthritis,among which,sophocarpidine,oxymatrine,sinomenine,and betaine have been shown to be effective in the prevention and treatment of knee osteoarthritis by modulating multiple signaling pathways.Alkaloids can delay the progression of knee osteoarthritis by inhibiting inflammatory response,exerting antioxidant response,inhibiting chondrocyte apoptosis,promoting chondrocyte proliferation,and inhibiting osteoclast formation and differentiation.

Objective: To evaluate the feasibility of dynamic contrast-enhanced MRI (DCE-MRI) in differentiating tumor deposits (TDs) from metastatic lymph nodes (MLNs) in rectal cancer. Materials and Methods: A retrospective analysis was conducted on 70 patients with rectal cancer, including 168 lesions (70 TDs and 98 MLNs confirmed by histopathology), who underwent pretreatment MRI and subsequent surgery between March 2019 and December 2022. The morphological characteristics of TDs and MLNs, along with quantitative parameters derived from DCE-MRI (K trans , kep, and v e) and DWI (ADCmin, ADCmax, and ADCmean), were analyzed and compared between the two groups.Multivariable binary logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the diagnostic performance of significant individual quantitative parameters and combined parameters in distinguishing TDs from MLNs. Results: All morphological features, including size, shape, border, and signal intensity, as well as all DCE-MRI parameters showed significant differences between TDs and MLNs (all P < 0.05). However, ADC values did not demonstrate significant differences (all P > 0.05). Among the single quantitative parameters, v e had the highest diagnostic accuracy, with an area under the ROC curve (AUC) of 0.772 for distinguishing TDs from MLNs. A multivariable logistic regression model incorporating short axis, border, v e, and ADC mean improved diagnostic performance, achieving an AUC of 0.833 (P = 0.027). Conclusion The combination of morphological features, DCE-MRI parameters, and ADC values can effectively aid in the preoperative differentiation of TDs from MLNs in rectal cancer.

Objective To evaluate the predictive value of a nomogram model developed by integrating clinical and ultrasound multiparameters for HER-2-positive breast cancer.Methods This study retrospectively enrolled 343 patients with pathologically confirmed breast cancer from three medical centers and randomly divided them into training and validation cohorts.Univariate analysis,LASSO regression,and multivariate logistic regres-sion were conducted on the training set to identify independent prognostic factors and construct a nomogram model.Bootstrap resampling with 1000 iterations was performed to evaluate the model's robustness.Model calibration was assessed using calibration curves and the Hosmer-Lemeshow goodness-of-fit test.Receiver operating characteristic(ROC)curves were generated to evaluate model discrimination,and the area under the curve(AUC)along with other performance metrics were calculated.Decision curve analysis was employed to assess the clinical utility of the model,and the validation cohort was used for external validation.Results Univariate,LASSO,and multivariate regression analyses demonstrated that age,TTP(time to peak),and the presence of a filling defect sign were independent predictors of HER-2-positive breast cancer(all P<0.05).Based on these independent predictors,a nomogram model was constructed.Bootstrap validation with 1,000 resamples indicated that the model's predictive performance was stable.The Hosmer-Lemeshow test confirmed satisfactory model calibration,while the calibration curve illustrated accurate prediction probabilities.The area under the curve(AUC)for the training set was 0.863(95%CI:0.806～0.920),and for the validation set,it was 0.846(95%CI:0.764～0.929),indicating strong discriminative and generalization capabilities.Additionally,the clinical decision curve analysis demonstrated favor-able clinical utility.Conclusion A nomogram model integrating clinical and multimodal ultrasound parameters demonstrates potential utility in predicting HER-2-positive breast cancer.

In recent years,the prevalence of overweight/obesity in solid organ transplant recipients has been rising rapidly.Clinical research evidence on obesity in solid organ transplant recipients has been increasing,but there is a lack of standardized diagnostic and treatment guidelines and comprehensive management pathways to guide clinical practice.Based on this,the Expert Consensus on Weight Management in Overweight or Obese Adult Solid Organ Transplant Recipients(2025 Edition)was organized and written by experts from the Diabetes Professional Committee of the Chinese Research Hospital Association.This consensus mainly provides recommendations on the epidemiological data,diagnostic criteria,screening and assessment methods,management pathways,and intervention strategies for overweight/obesity in solid organ transplant recipients.It aims to further improve the management level of medical workers engaged in the whole process of organ transplantation for the population with overweight/obesity combined with solid organ transplantation,standardize clinical diagnosis and treatment,improve patient prognosis,and enhance quality of life.

Objective To explore the protective effects of genetically modified porcine erythrocyte suspension as a subnormothermic normoxic mechanical perfusate on hypoxic-ischemic brain injury in cynomolgus monkeys caused by traumatic hemorrhage.Methods Cynomolgus monkeys were randomly divided into positive and negative control groups(a total of 3 monkeys,with 3 left cerebral hemispheres as the positive control group and 3 right cerebral hemispheres as the negative control group)and the subnormothermic perfusion group(n=3).The positive control group was directly sampled 1 hour after circulatory arrest,while the negative control group was placed at subnormothermic conditions for 6 hours after circulatory arrest.The subnormothermic perfusion group underwent 6 hours of subnormothermic normoxic mechanical perfusion of the bilateral common carotid arteries of the cynomolgus monkey hypoxic-ischemic brain injury model using genetically modified porcine erythrocyte suspension 1 hour after circulatory arrest.Before perfusion,cross-matching experiments were conducted between the six genetically modified pig and the cynomolgus monkeys.After the start of perfusion,the levels of routine blood indicators in the perfusate were detected at 0,1,2,3,4,5 and 6 hours.Blood oxygen saturation was recorded,and the levels of Na+,K+,Ca2+,glucose and blood pH in the perfusate were measured,as well as the levels of IgG and IgM in the perfusate.After 6 hours of perfusion,the water content of the brain tissue was measured.Nissl staining was performed on the frontal cortex and hippocampal regions,and immunofluorescence staining was used to detect the expression of glial fibrillary acidic protein(GFAP),ionized calcium-binding adapter molecule 1(Iba1)and neuronal nuclear antigen(NEUN).Results The cross-matching results between the six genetically modified pig and the cynomolgus monkeys were negative.The number of red blood cells in the perfusate decreased significantly at 3 hours of perfusion,and the hemoglobin level showed a downward trend at 1,3,5 and 6 hours.The number of white blood cells and platelets decreased at all time points.The blood oxygen saturation in the subnormothermic perfusion group remained stable at 95%-98%,and the levels of blood oxygen saturation,Na+,Ca2+,glucose and pH were stable,while the K+level first increased and then decreased.There was no significant difference in the levels of IgG and IgM before and after perfusion.The water content of brain tissue at the end of perfusion in the subnormothermic perfusion group was significantly higher than that in the positive control group(P<0.001).Nissl staining results showed that compared with the positive control group,the pyramidal neurons in the prefrontal cortex of the subnormothermic perfusion group maintained better morphological integrity,with no significant increase in enlarged and deformed cells.In the hippocampal CA1 region,there was a slight increase in enlarged and deformed cells,and a few cells with undamaged structures showed reduced cell size.In the hippocampal dentate gyrus,fewer granule neurons had compromised structural integrity,with increased cell edema.NEUN immunofluorescence staining showed that compared with the positive control group,the pyramidal neurons in the prefrontal cortex and hippocampal CA1 region of the subnormothermic perfusion group had better morphological states,with clear axons.The granule cells in the hippocampal dentate gyrus were well preserved,but the nuclei were less well protected.GFAP immunofluorescence staining showed that compared with the positive control group,the subnormothermic perfusion group had sparser protrusions that were more tightly associated with neurons.Iba1 immunofluorescence staining showed that compared with the positive control group,the subnormothermic perfusion group had thicker and fewer protrusions.Conclusions Compared with the positive control group,subnormothermic normoxic mechanical perfusion with genetically modified porcine erythrocyte perfusate increases brain tissue edema in cynomolgus monkeys,but better preserves the morphological integrity of neurons and glial cells.The protective effects may be related to the continuous oxygen and energy supply,maintenance of ion homeostasis and perfusate pH,reduced rejection,and low metabolic state of the whole brain.

Objective To investigate the characteristics of macrophage depletion by clodronate liposomes(CL)in a carbon tetrachloride(CCl4)-induced liver fibrosis mouse model,and to analyze the transcriptomic features.Methods Thirty-two C57BL/6 mice were divided randomly into plain control liposomes for clophosome(PL)and clodronate liposome(CL)groups(n=16 mice per group),and administered intraperitoneal injections of PL and CL,respectively.On day 5,each group was further divided into normal(N)and model(M)subgroups(n=8 mice per subgroup).Mice in group M received 10％CCl4 intraperitoneally to induce liver fibrosis,while mice in group N received an equal volume of olive oil.After 4 weeks,serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)levels were measured,and hepatic inflammation and collagen deposition were evaluated by hematoxylin/eosin and Sirius red staining,respectively.Total RNA was extracted from liver tissues for transcriptomic sequencing and subsequent differential gene expression analysis.Results Serum ALT and AST levels were significantly elevated in the PL-M group(P＜0.01),with fibrosis staging primarily at S3,compared with S1 in the CL-M group.Totals of 1462 and 2119 differentially expressed genes(|log fold change|＞2 and P＜0.05)were identified in the PL and CL groups,respectively.Gene Ontology analysis revealed enrichment in multiple biological processes,cellular components,and molecular functions in both models,and Kyoto Encyclopedia of Genes and Genomes analysis identified 29 significantly enriched pathways(P＜0.05).The upregulation of genes including Lgals7 and Timp1 and the downregulation of Mup-ps16 and Mup15 were validated by reverse transcription-quantitative polymerase chain reaction,consistent with transcriptomic trends(P＜0.05).Conclusions This study highlights the characteristics and transcriptomic features of macrophage depletion in the CCl4-induced liver fibrosis model,providing a theoretical reference for research on the immune mechanisms of liver fibrosis.

To analyze the standard establishment approach and compilation rationale for metallic pharmaceutical packaging standard development in the 2025 edition of the Pharmacopeia of the People's Republic of China.This article systematically explained the background and process of establishing the guiding principles for metallic materials and containers used in pharmaceutical packaging in the Chinese Pharmacopoeia through basic information,relevant domestic and international standards,the establishment of key quality attributes of metallic pharmaceutical packaging materials,and the construction of metallic pharmaceutical packaging material standards.The newly established guidelines,the Pharmacopeia of the People's Republic of China 9625,prioritized product critical quality attributes(CQAs)and real-world applicability.This dual emphasis on rigidity and adaptability enhances drug safety,meets the regulatory requirements,and promotes the globalization and scientific advancement of China's pharmaceutical packaging industry.