Objective:To construct a "local-systemic" dual-track prediction model integrating the resistance index (RI) score of bilateral sacroiliac joints and the systemic immune-inflammation index (SII), and to evaluate its predictive efficacy for the active stage of ankylosing spondylitis (AS).Methods:A total of 205 patients with ankylosing spondylitis (AS) from the Second Hospital of Lanzhou University between April 2022 and April 2025 were retrospectively enrolled and categorized into an active group ( n=113) and a remission group ( n=92). Hematological parameters and ultrasound data were collected. The resistance index (RI) of the synovial area in bilateral sacroiliac joints was measured by Doppler ultrasound and scored as follows: RI < 0.5: 3 points; RI 0.5~0.55: 2 points; RI > 0.55: 1 point; undetectable blood flow: 0 points. A total bilateral RI score (range 0 to 6) was calculated. The systemic immune-inflammation index (SII) was derived as (neutrophils× platelets)/lymphocytes. Normality was tested for all continuous variables; normally distributed data were compared using the t-test, while non-normally distributed data were analyzed with the Mann-Whitney U test. Categorical variables were compared using the χ2 test or analysis of variance.Variable selection was performed using Lasso regression, and a multivariate logistic regression model was developed to assess predictive performance. Results:The proportion of patients with a bilateral RI total score≥5 was significantly higher in the active group compared to the remission group (50 of 113, 44.3% vs 2 of 92, 2.2%, χ2=55.63, P<0.001). Multivariate logistic regression analysis, after adjustment for confounding variables, identified the SII [ OR(95% CI)=1.01(1.00, 1.01), P<0.001], bilateral RI total score [ OR(95% CI)=1.67(1.29, 2.26), P<0.001], erythrocyte sedimentation rate [ OR(95% CI)=1.19(1.11, 1.30), P<0.001], and mean corpuscular hemoglobin concentration [ OR(95% CI)=1.09(1.03, 1.17), P<0.001] as independent risk factors for active AS. Conversely, lymphocyte count [ OR(95% CI)=0.42(0.18, 0.92), P=0.030] and globulin [ OR(95% CI)=0.89(0.80, 0.99), P=0.040] were significantly associated with protective effects. The bilateral RI total score demonstrated the strongest predictive effect, with each 1-point increase associated with a 67% elevation in the risk of active disease. ROC curve analysis indicated that the area under the curve (AUC) for predicting whether AS is in the active disease phase was 0.94 for the combined model (SII+bilateral RI total score), compared with 0.93 for the SII-alone model and 0.92 for the bilateral RI total score-alone model, demonstrating superior predictive performance of the combined model (SII+bilateral RI total score). An online prediction tool has been developed based on the combined model. Conclusion:The dual-track prediction model, which integrates local joint hemodynamic characteristics and systemic immune-inflammatory status, facilitates a multidimensional assessment of the risk of active AS and provides an objective basis for early identification.

ObjectiveTo observe the effect of M1 bone marrow-derived macrophages （M1-BMDM） with Wnt5a knockdown on liver fibrosis and regeneration in a rat model of liver cirrhosis， and to investigate its gain-of-function effect compared with unmodified M1-BMDM. MethodsPrimary bone marrow-derived macrophages were isolated from rats and were polarized to M1 phenotype to construct M1-BMDM^Wnt5a-KD cells. A rat model of liver cirrhosis induced by CCl₄/2-AAF was established， and at the end of week 8， rats were randomly divided into model group， M1-BMDM group， M1-BMDM Wnt5a-knockdown empty vector group （M1-BMDM^KD-EV group）， and M1-BMDM Wnt5a-knockdown group （M1-BMDM^Wnt5a-KD group）， with 6 rats in each group. On the first day of week 9， the rats in each group were given a single injection of the corresponding cells via the caudal vein， along with an intraperitoneal injection of a CCR2 inhibitor. Six rats without any treatment were used as normal control group. Samples were collected at the end of week 12 to assess liver histopathology， serum liver function parameters， hepatic stellate cell activation， and the expression levels of mature hepatocyte markers. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the model group， all cell treatment groups had significant alleviation of liver inflammatory response and significant reductions in the activities of alanine aminotransferase and aspartate aminotransferase （AST） in serum （all P<0.01）， and the M1-BMDM^Wnt5a-KD group had a significantly lower serum level of AST than the M1-BMDM group （P<0.05）. The semi-quantitative analysis based on immunohistochemical staining showed that compared with the model group， all cell treatment groups had a significant reduction in the percentage of CD68-positive area （all P<0.05）， and compared with the M1-BMDM^KD-EV group， the M1-BMDM^Wnt5a-KD group had a significant reduction in the percentage of CD68-positive area and a significant increase in the percentage of CD163-positive area （both P<0.05）. Compared with the model group， all cell treatment groups had significant reductions in the mRNA expression levels of CD68 and tumor necrosis factor-α （all P<0.05） and the protein expression level of CD68 （all P<0.01）； compared with the M1-BMDM^KD-EV group， the M1-BMDM^Wnt5a-KD group had significant increases in the protein and mRNA expression levels of CD163 （both P<0.05）， significant reductions in the protein and mRNA expression levels of CD68 （both P<0.05）， and a significant reduction in the protein expression level of tumor necrosis factor-α （P<0.01）. Sirius Red collagen staining and alpha-smooth muscle actin （α-SMA） immunohistochemical staining showed that compared with the model group， all cell treatment groups had significant alleviation of liver collagen deposition and α-SMA-positive area， with the most significant changes in the M1-BMDM^Wnt5a-KD group， and compared with the M1-BMDM^KD-EV group， the M1-BMDM^Wnt5a-KD group had significantly smaller Sirius Red-positive area and α-SMA-positive area and a significantly lower content of hydroxyproline in liver tissue （all P<0.05）. Compared with the M1-BMDM^KD-EV group， the M1-BMDM^Wnt5a-KD group had significant reductions in the protein and mRNA expression levels of α-SMA and the mRNA expression level of COL-I and TGF-β （all P<0.05）. Compared with the model group， all cell treatment groups had a significant increase in the protein expression level of HNF-4α in liver tissue （all P<0.05）， and the M1-BMDM^Wnt5a-KD group had significantly higher protein and mRNA expression levels of HNF-4α and hepatocyte specific antigen than the M1-BMDM^KD-EV group （both P<0.05）. The M1-BMDM^Wnt5a-KD group had a significantly higher serum level of albumin than the M1-BMDM^KD-EV group （P<0.01）. Immunofluorescence co-staining showed that compared with the model group， all cell treatment groups had a significant increase in the number of cells stained positive for HNF and HNF-4α and Ki67 （all P<0.01）， and the M1-BMDM^Wnt5a-KD group had a significantly higher number of such cells than the M1-BMDM^KD-EV group （P<0.05）. ConclusionInhibition of Wnt5a expression enhances the therapeutic effect of M1-BMDM on rats with liver cirrhosis induced by CCl₄/2-AAF， which provides new ideas for enhancing the anti-cirrhotic effect of M1-BMDM through genetic modification.

Objective:To construct a "local-systemic" dual-track prediction model integrating the resistance index (RI) score of bilateral sacroiliac joints and the systemic immune-inflammation index (SII), and to evaluate its predictive efficacy for the active stage of ankylosing spondylitis (AS).Methods:A total of 205 patients with ankylosing spondylitis (AS) from the Second Hospital of Lanzhou University between April 2022 and April 2025 were retrospectively enrolled and categorized into an active group ( n=113) and a remission group ( n=92). Hematological parameters and ultrasound data were collected. The resistance index (RI) of the synovial area in bilateral sacroiliac joints was measured by Doppler ultrasound and scored as follows: RI < 0.5: 3 points; RI 0.5~0.55: 2 points; RI > 0.55: 1 point; undetectable blood flow: 0 points. A total bilateral RI score (range 0 to 6) was calculated. The systemic immune-inflammation index (SII) was derived as (neutrophils× platelets)/lymphocytes. Normality was tested for all continuous variables; normally distributed data were compared using the t-test, while non-normally distributed data were analyzed with the Mann-Whitney U test. Categorical variables were compared using the χ2 test or analysis of variance.Variable selection was performed using Lasso regression, and a multivariate logistic regression model was developed to assess predictive performance. Results:The proportion of patients with a bilateral RI total score≥5 was significantly higher in the active group compared to the remission group (50 of 113, 44.3% vs 2 of 92, 2.2%, χ2=55.63, P<0.001). Multivariate logistic regression analysis, after adjustment for confounding variables, identified the SII [ OR(95% CI)=1.01(1.00, 1.01), P<0.001], bilateral RI total score [ OR(95% CI)=1.67(1.29, 2.26), P<0.001], erythrocyte sedimentation rate [ OR(95% CI)=1.19(1.11, 1.30), P<0.001], and mean corpuscular hemoglobin concentration [ OR(95% CI)=1.09(1.03, 1.17), P<0.001] as independent risk factors for active AS. Conversely, lymphocyte count [ OR(95% CI)=0.42(0.18, 0.92), P=0.030] and globulin [ OR(95% CI)=0.89(0.80, 0.99), P=0.040] were significantly associated with protective effects. The bilateral RI total score demonstrated the strongest predictive effect, with each 1-point increase associated with a 67% elevation in the risk of active disease. ROC curve analysis indicated that the area under the curve (AUC) for predicting whether AS is in the active disease phase was 0.94 for the combined model (SII+bilateral RI total score), compared with 0.93 for the SII-alone model and 0.92 for the bilateral RI total score-alone model, demonstrating superior predictive performance of the combined model (SII+bilateral RI total score). An online prediction tool has been developed based on the combined model. Conclusion:The dual-track prediction model, which integrates local joint hemodynamic characteristics and systemic immune-inflammatory status, facilitates a multidimensional assessment of the risk of active AS and provides an objective basis for early identification.

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.

Purpose: This study aimed to evaluate the safety and efficacy of gemcitabine and cisplatin (GP) regimen in combination with immune checkpoint inhibitor sintilimab as neoadjuvant therapy for muscle-invasive bladder cancer (MIBC) patients and the feasibility of the following selective bladder sparing surgery. Materials and Methods: Patients with histopathologically confirmed urothelial carcinoma without distant metastases (T2-4a, N ≤ 1, M0, American Joint Committee of Cancer 8th) and with adequate organ function will be enrolled. The therapeutic regimen was sintilimab 200 mg once on day 8, gemcitabine 1,000 mg/m2 and cisplatin 35 mg/m2 once on days 1 and 8, every 21 days for four cycles. The primary endpoint was pathologic complete response (pCR, pT0N0) rate. The secondary end points were ypT < 2 rate, R0 resection rate, event-free survival, and safety. Results: From May 4, 2020, to May 20, 2023, 55 patients were enrolled. Forty-six patients were evaluated for efficacy. Among the 42 patients who underwent surgery, 16 patients (38.0%) achieved pCR. Thirty-three patients (78.6%) achieved pT < 2. With a median follow-up of 15.7 months, the 1-year event-free survival was 91.3%. Notwithstanding the poor pathological baseline characteristic of a high T3-T4a proportion (39.1%), a promising bladder preservation (including 22 patients transurethral resection of bladder tumor, 5 patients partial cystectomy, and 4 surveillances) rate was achieved (67.4%). The most common grade ≥ 3 treatment-related adverse events was neutropenia (n=15, 27.3%), which was related to chemotherapy. There were no grade 3 immune-related adverse events. Conclusion Neoadjuvant GP plus sintilimab is a promising regimen for MIBC patients, with relatively high pT < 2 rate and triggering the emerging roles for the multi-disciplinary team decision-making for bladder sparing surgery.

ObjectiveTo investigate the inhibitory effect of gingerol， an active component of ginger， on Staphylococcus aureus （S. aureus） infection， and to preliminarily explore its mechanism related to extracellular vesicles （EVs）. MethodsS.aureus infection models were established in human umbilical vein endothelial cell （HUVECs）， Vero E6 cells， and C57BL/6 mice. Experimental groups included control， infection， and gingerol-treated groups. Bacterial load and VE-cadherin protein expression were detected using immunofluorescence and Western blot. EVs were isolated by size exclusion chromatography and characterized by transmission electron microscopy and nanoparticle tracking analysis. miRNA sequencing was performed on EVs. ResultsGingerol treatment significantly reduced the bacterial load in both in vitro and in vivo infection models and upregulated VE-cadherin expression. miRNA sequencing of EVs revealed that S. aureus infection upregulated the expression of hsa-miR-320c， while gingerol treatment reversed this abnormal expression. Bioinformatic analysis further predicted that the target genes of hsa-miR-320c were significantly enriched in cell junction-related pathways. ConclusionGingerol exhibits clear antibacterial and host-protective effects， by regulating hsa-miR-320c in EVs to maintain endothelial barrier integrity.

This article describes a new species of Genus Xenodaeria Jordan(1932)(Siphonaptera: Ctenophthalmidae), collected from the southern slope of Cangshan mountain in Dali, Yunnan. The new species is similar to Xenodayia telios, Jordan 1932, and X. laxiproceria Wu, Gu et Liu,1996, but more like X. telios. However, it can be distinguished from X. telios and other known species in the genus based on the following characteristics: The movable process of the male gripper is bent finger shaped, with a blunt end and no angular protrusion extending forward; The posterior St. VII in females has a semi-circular deep depression, with blunt rounded ends of the dorsal and ventral lobes, and the dorsal lobes are wider and longer than the ventral lobes. The type specimen was collected on November 2,1994 from the shrubbery at an altitude of approximately 2 450 m in the southern end of Cangshan Mountain in Dali City, Yunnan Province. The host species were Anourosorex squamipes and Crocidura rapax.

BACKGROUND:Exercise as a form of active rehabilitation can improve the dysfunction caused by peripheral nerve injury,and different exercise modalities target different lesion sites and recovery mechanisms. OBJECTIVE:To comprehensively analyze the application and mechanisms of different exercise modalities in functional recovery from peripheral nerve injury. METHODS:A computerized search was conducted in PubMed and CNKI databases for relevant literature published before January 2024.The search terms used were"peripheral nerve injury,spinal cord,exercise,cerebral cortex,muscle atrophy,mirror therapy,blood flow restriction training"in both English and Chinese.Finally,77 articles were included for review. RESULTS AND CONCLUSION:Peripheral nerve injury can cause systemic pathological changes such as skeletal muscle atrophy,corresponding spinal cord segmental lesions,and sensorimotor cortex remodeling.Aerobic exercise can improve dysfunction by enhancing the immune response,promoting glial cell polarization,and promoting the release of nerve growth factor.Blood flow restriction exercise can regulate the secretion of muscle growth factor,promote muscle growth and enhance muscle strength.Mirror movement has a good effect in activating the cerebral cortex and reducing cortical remodeling.Different exercise modalities have potential benefits in functional recovery after peripheral nerve injury;however,there are still some problems and challenges,such as the choice of exercise modalities,the control of exercise intensity and frequency,and the detailed analysis of mechanisms.

In this experiment, self-assembled nanoparticles(SANs) were prepared by the pH-driven method, and Her-HCP SAN was constructed by using herpetrione(Her) and Herpetospermum caudigerum polysaccharides(HCPs). The average particle size and polydispersity index(PDI) were used as evaluation indexes for process optimization, and the quality of the final formulation was evaluated in terms of particle size, PDI, Zeta potential, and microstructure. The proposed Her-HCP SAN showed a spheroid structure and uniform morphology, with an average particle size of(244.58±16.84) nm, a PDI of 0.147 1±0.014 8, and a Zeta potential of(-38.52±2.11) mV. Her-HCP SAN significantly increased the saturation solubility of Her by 2.69 times, with a cumulative release of 90.18% within eight hours. The results of in vivo unidirectional intestinal perfusion reveal that Her active pharmaceutical ingredient(API) is most effectively absorbed in the jejunum, where both K_a and P_(app) are significantly higher compared to the ileum(P<0.001). However, the addition of HCP leads to a significant reduction in the P_(app) of Her in the jejunum(P<0.05). Furthermore, the formation of the Her-HCP SAN results in a notably lower P_(app) in the jejunum compared to Her API alone(P<0.001), while both K_a and P_(app) in the ileum are significantly increased(P<0.001, P<0.05). The absorption of Her-HCP SAN at different concentrations in the ileum shows no significant differences, and the pH has no significant effect on the absorption of Her-HCP SAN in the ileum. The addition of the transporter protein inhibitors(indomethacin and rifampicin) significantly increases the absorption parameters K_a and P_(app) of Her-HCP SAN in the ileum(P<0.05,P<0.01), whereas the addition of verapamil has no significant effect on the intestinal absorption parameters of Her-HCP SAN, suggesting that Her may be a substrate for multidrug resistance-associated protein 2 and breast cancer resistance proteins but not a substrate of P-glycoprotein.
Nanoparticles/metabolism* ; Polysaccharides/pharmacokinetics* ; Intestinal Absorption/drug effects* ; Animals ; Rats ; Particle Size ; Drugs, Chinese Herbal/pharmacokinetics* ; Male ; Rats, Sprague-Dawley ; Drug Carriers/chemistry* ; Drug Compounding ; Cucurbitaceae/chemistry*

In China, the number of chronic pain patients has exceeded 300 million, making chronic pain the third major health problem after tumors and cardiovascular diseases. Particularly concerning is the gradual emergence of hypertension and chronic low back pain as public health problems that threaten public health and increase the global economic burden. Modern research shows that the incidence of coexisting hypertension is higher among patients with chronic low back pain. Additionally, evidence indicates that the use of NSAIDs for pain relief can have adverse effects on blood pressure, and some antihypertensive medications may trigger symptoms of low back pain. Thus, addressing chronic pain in hypertensive patients while stabilizing blood pressure is one of the important research questions in the modern treatment of hypertension among middle-aged and elderly individuals. From ancient to modern traditional Chinese medicine(TCM) theory, kidney deficiency has been regarded as the core pathogenesis of low back pain. Recent clinical practices and literature indicate that kidney deficiency plays a crucial role in the modern pathogenesis of hypertension. Both hypertension and chronic low back pain are closely associated with kidney deficiency in TCM theory, revealing a potential mechanism linking the two conditions. Combining the theories of " kidney-essence-marrow" and " nourishing water to moisten wood", a therapeutic strategy centered on tobifying kidney was proposed, including selecting single drugs with kidney-tonifying effects as well as compound formulations and elaborating modern research evidence. The aim is to achieve stable blood pressure control in hypertension patients with chronic low back pain while providing a new treatment perspective for chronic low back pain. This article systematically elaborates on the understanding of hypertension combined with chronic low back pain from both TCM and modern medicine, as well as the therapeutic strategy involving kidney-tonifying drugs, to offer useful references for clinical practice.
Humans ; Hypertension/complications* ; Low Back Pain/complications* ; Drugs, Chinese Herbal/therapeutic use* ; Kidney/drug effects* ; Medicine, Chinese Traditional ; Chronic Pain/drug therapy*