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.

ObjectiveTo investigate the mechanism of modified Si Junzitang and Shashen Maidong Tang ［Yiqi Yangyin Jiedu prescription （YQYYJD）］ in enhancing the sensitivity of cisplatin in epidermal growth factor receptor tyrosine kinase inhibitor （EGFR-TKI）-resistant lung adenocarcinoma cells based on aerobic glycolysis. MethodsThe effects of different concentrations of YQYYJD （0， 2， 3， 4， 5， 6， 7， 8 g·L^-1） and cisplatin （0， 3， 6， 9， 12， 15， 18， 21， 24， 27 mg·L^-1） on the proliferation and activity of PC9/GR cells were detected by the cell counting kit-8 （CCK-8） assay after 24 hours of intervention. The half-maximal inhibitory concentration （IC₅₀） for PC9/GR cells was calculated to determine the concentrations used in subsequent experiments. PC9/GR cells were divided into blank group （complete medium）， YQYYJD group （5 g·L^-1）， cisplatin group （12 mg·L^-1）， and combined group （YQYYJD 5 g·L^-1 + cisplatin 12 mg·L^-1）. After 24 hours of intervention， cell viability was measured using CCK-8 assay. Cell proliferation was assessed by colony formation assay， and cell migration was evaluated by scratch and Transwell assays. Glucose consumption， lactate production， and adenosine triphosphate （ATP） levels were measured by colorimetric assays. The expression levels of glycolysis-related proteins， including hexokinase 2 （HK2）， phosphofructokinase P （PFKP）， pyruvate kinase M2 （PKM2）， lactate dehydrogenase A （LDHA）， glucose transporter 1 （GLUT1）， and monocarboxylate transporter 4 （MCT4）， were determined by Western blot. ResultsBoth YQYYJD and cisplatin inhibited the viability of PC9/GR cells in a concentration-dependent manner. The IC₅₀ of PC9/GR cells for YQYYJD and cisplatin were 5.15 g·L^-1 and 12.91 mg·L^-1， respectively. In terms of cell proliferation， compared with the blank group， the cell survival rate and the number of colonies formed in the YQYYJD group， cisplatin group， and combined group were significantly decreased （P<0.01）. Compared with the YQYYJD and cisplatin groups， the combined group showed a further significant reduction in cell survival rate and colony formation （P<0.01）. In terms of cell migration， compared with the blank group， the cell migration rate and the number of cells passing through the Transwell membrane in the YQYYJD group， cisplatin group， and combined group were significantly decreased （P<0.01）. Compared with the YQYYJD and cisplatin groups， the combined group exhibited a further significant reduction in cell migration rate and the number of cells passing through the Transwell membrane （P<0.01）. In terms of glycolysis， compared with the blank group， glucose consumption， lactate production， and ATP levels in the YQYYJD group， cisplatin group， and combined group were significantly decreased （P<0.01）. Compared with the YQYYJD and cisplatin groups， the combined group showed a further significant reduction in glucose consumption， lactate production， and ATP levels （P<0.05）. Compared with the blank group， the protein expression levels of HK2， PFKP， PKM2， and LDHA in the YQYYJD， cisplatin， and combined groups were significantly decreased （P<0.01）. The combined group showed a further significant reduction in the expression levels of these proteins compared with the YQYYJD and cisplatin groups （P<0.01）. No significant differences were observed in the protein expression levels of GLUT1 and MCT4 among the groups. ConclusionYQYYJD can synergistically inhibit the proliferation and migration of PC9/GR cells and enhance their sensitivity to cisplatin. The mechanism may be related to the downregulation of the expression of glycolysis-related rate-limiting enzymes， including HK2， PFKP， PKM2， and LDHA， thereby inhibiting glycolysis.

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 investigate the distribution of traditional Chinese medicine(TCM)syndromes in chronic persistent immunoglobulin A nephropathy(IgAN)and to explore the relationship between TCM syndromes and prognosis based on real-world research.Methods From January 2018 to January 2024,a total of 80 patients with chronic persistent IgAN who were admitted to Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical University were included.The clinical baseline data and prognosis-related information were collected.The main outcome indicators were defined as renal failure events of glomerular filtration rate(eGFR)decreased by＞50%,serum creatinine doubled or end-stage renal disease(ESRD).The distribution of TCM syndromes in chronic persistent IgAN and the relationship between different deficiency syndromes and prognosis were preliminarily discussed.Results(1)Among the 80 patients with chronic persistent IgAN,the syndrome manifestations with an occurrence frequency of more than 30%in descending order were foamy urine(75.00%),fatigue and lassitude(71.25%),waist ache(61.25%),dry mouth(31.25%),lower extremity edema(31.25%),aversion to cold and cold limbs(30.00%),and insomnia(30.00%).(2)The commonly-seen root-deficiency syndrome in patients with chronic persistent IgAN was qi and yin deficiency syndrome,with a total of 28 cases(35.00%).And other root-deficiency syndromes were spleen and kidney yang deficiency syndrome in 22 cases(27.50%),lung and spleen qi deficiency syndrome in 15 cases(18.75%),and liver and kidney yin deficiency syndrome in 15 cases(18.75%).The commonly-seen complicated syndrome was water-damp syndrome,with a total of 17 cases(21.25%).The other complicated syndromes were damp-heat syndrome in 15 cases(18.75%),blood-stasis syndrome in 9 cases(11.25%),phlegm-damp syndrome in 7 cases(8.75%),turbidity-toxin syndrome in 5 cases(6.25%),liver depression syndrome in 3 cases(3.75%),and cold-damp syndrome in 1 case(1.25%).(3)Among the 80 patients with chronic persistent IgAN,21 cases(26.25%)had renal failure events,and their syndrome types were lung and spleen qi deficiency syndrome in 9 cases(60.00%),qi and yin deficiency syndrome in 3 cases(10.71%),liver and kidney yin deficiency syndrome in 3 cases(20.00%),and spleen and kidney yang deficiency syndrome in 6 cases(27.27%).The incidence of renal failure events in patients with lung and spleen qi deficiency syndrome was significantly higher than that in the other three syndrome types,and the chi-square test showed that the difference was statistically significant(P＜0.05).(4)Kaplan-Meier survival analysis showed that the cumulative incidence of 2-year and 5-year endpoint events in patients with lung and spleen qi deficiency syndrome was 23.10%and 46.20%,respectively,and the final incidence was 85.00%.The cumulative incidence of 2-year and 5-year endpoint events in patients with other deficiency syndromes was 4.50%and 19.70%,respectively,and the final incidence was 71.60%.The intergroup comparison(tested by Log-rank)showed that the incidence of renal failure events in patients with lung and spleen qi deficiency syndrome was significantly higher than that in patients with other root-deficiency syndromes,and the difference was statistically significant(P＜0.05).(5)COX proportional hazard regression analysis showed that lung and spleen qi deficiency syndrome(HR=7.755,95%CI 1.631-36.874,P＜0.05)and anemia(HR=8.205,95%CI 1.007-66.857,P＜0.05)were the independent risk factors for renal failure events in patients with chronic persistent IgAN.Conclusion Qi and yin deficiency syndrome is the most common syndrome in the patients with chronic persistent IgAN,and lung and spleen qi deficiency syndrome and anemia are the independent risk factors for renal failure events in IgAN.

Objective To investigate the therapeutic effects and mechanisms of electroacupuncture for stress urinary incontinence(SUI)in rats.Methods A total of 30 rats were randomly divided into three groups:normal group,model group,and electroacupuncture group[electroacupuncture at Shenshu(BL23)and Huiyang(BL35)acupoints],with 10 rats per group.Except for the normal group,a SUI model was established in the other two groups.After grouping interventions,the following assessments including sneeze test,urodynamic parameter measurements(including intravesical pressure),serum levels of lactate dehydrogenase(LDH)and creatine kinase(CK)were conducted,urethral histopathological change was detected by hematoxylin-eosin(HE)staining,and Western Blot was used to detect protein expression of transforming growth factor β1(TGF-β1),Smad2,Smad3,Smad7,typeⅠ collagen(Col Ⅰ),and type Ⅲ collagen(Col Ⅲ)in urethral tissues.Results Compared with the normal group,the model group exhibited significant increases in the number of sneeze test-positive rats,urine volume,residual urine volume,and serum LDH and CK levels,and protein expression of urethral Smad2 and Smad3,moreover,the model group showed significant decreases in urodynamic parameters[maximum bladder capacity(MBC),leak point pressure(LPP),abdominal leak point pressure(ALPP)],voiding efficiency,and protein expression of urethral TGF-β1,Smad7,ColⅠand Col Ⅲ,the differences being statistically significant(P＜0.05).In comparison to the model group,the electroacupuncture group demonstrated significant reductions in sneeze test-positive rats,urine volume,residual urine volume,serum LDH and CK levels,and protein expression of urethral Smad2 and Smad3,additionally,the electroacupuncture group displayed significant improvements in urodynamic parameters(MBC,LPP,ALPP)and voiding efficiency,upregulation of protein expression of urethral TGF-β1,Smad7,Col Ⅰ and Col Ⅲ,the differences being statistically significant(P＜0.05).Conclusion Electroacupuncture may ameliorate SUI by activating the TGF-β1/Smad pathway to promote pelvic collagen synthesis and reduce urethral injury,thus improving urinary function.

Objective To investigate the relationship of mindful attention awareness with sleep quality and occupational stress of soldiers.Methods A questionnaire survey was conducted on 1 100 soldiers by using the mindful attention awareness scale(MAAS),occupational stress scale(OSS),and Pittsburgh sleep quality index(PSQI).Results The PSQI of the soldiers was negatively correlated with mindful attention awareness(r=-0.446,P<0.01),and positively correlated with occupational stress(r=0.569,P<0.01).Mindful attention awareness and occupational stress were effective predictors for sleep quality,accounting for 34.7%of variance.And the mediating effect of occupational stress between mindful attention awareness and sleep quality accounted for 58.86%.Conclusion The mindful attention awareness in soldiers can not only directly affect the sleep quality,but also indirectly affect the sleep quality through their occupational stress.

This study employed 16S r RNA gene high-throughput sequencing and metabolomics to explore the mechanism of Angelicae Dahuricae Radix polysaccharides(RP) in the treatment of ulcerative colitis(UC). A mouse model of UC was induced with 2. 5% dextran sulfate sodium. The therapeutic effects of RP on UC in mice were evaluated based on changes in body weight, disease activity index( DAI), and colon length, as well as pathological changes. RT-qPCR was performed to assess the m RNA levels of interleukin(IL)-6, IL-1β, tumor necrosis factor(TNF)-α, myeloperoxidase(MPO), mucin 2(Muc2), Occludin, Claudin2, and ZO-1 in the mouse colon tissue. ELISA was employed to measure the expression of IL-1β and TNF-α in the colon tissue. The intestinal permeability of mice was evaluated by the fluorescent dye permeability assay. Immunohistochemistry was employed to detect the expression of Muc2 and occludin in the colon tissue. Changes in gut microbiota and metabolites were analyzed by 16S r RNA sequencing and ultra-high-performance liquid chromatography coupled with quadrupole-orbitrap mass spectrometry( UPLC-Q-Exactive Plus Orbitrap MS), respectively. The results indicated that low-dose RP alleviated general symptoms, reduced colonic inflammation and intestinal permeability, and promoted Muc2 secretion and tight junction protein expression in UC mice. In addition, low-dose RP increased gut microbiota diversity in UC mice and decreased the relative abundance of harmful bacteria such as Ochrobactrum and Streptococcus. Twenty-seven differential metabolites were identified in feces, and low-dose RP restored the levels of disturbed metabolites. Notably, arginine and proline metabolism were the most significantly altered amino acid metabolic pathways following lowdose RP intervention. In conclusion, RP can ameliorate general symptoms, inhibit colonic inflammation, and maintain intestinal mucosal barrier integrity in UC mice by modulating gut microbiota composition and arginine and proline metabolism.
Animals ; Gastrointestinal Microbiome/drug effects* ; Colitis, Ulcerative/genetics* ; Mice ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Polysaccharides/administration & dosage* ; Angelica/chemistry* ; Humans ; Colon/metabolism* ; Disease Models, Animal ; Mucin-2/metabolism* ; Tumor Necrosis Factor-alpha/metabolism*