OBJECTIVE To investigate the effects and mechanism of the Yishen paidu formula on renal fibrosis in rats with chronic renal failure （CRF） through the reactive oxygen species （ROS）/thioredoxin-interacting protein （TXNIP）/NOD-like receptor thermal protein domain associated protein 3 （NLRP3） pathway. METHODS Rats were randomly divided into control group， model group， Yishen paidu formula low-dose （Yishen paidu formula-L） group， Yishen paidu formula high-dose （Yishen paidu formula- H） group， Yishen paidu formula-H+pcDNA-NC group， and Yishen paidu formula-H+ pcDNA-TXNIP group， with 10 rats in each group. Except for control group， all other rats were fed a diet containing 0.5% adenine to establish a CRF model； the rats were then administered corresponding drugs or normal saline intragastrically or via tail vein， once daily， for 8 consecutive weeks. After the last administration， the levels of serum creatinine （Scr）， blood urea nitrogen （BUN）， ROS， superoxide dismutase （SOD）， malondialdehyde （MDA）， tumor necrosis factor-α （TNF-α）， interleukin （IL）-6， and IL-1β were measured in each group. Pathological changes in renal tissue were observed， and the protein expression levels of Collagen Ⅲ， α-smooth muscle actin （α-SMA）， transforming growth factor-β1 （TGF-β1）， TXNIP and NLRP3 in renal tissue were detected. RESULTS Compared with model group， the renal histopathological damage and fibrosis of rats in Yishen paidu formula-L group and Yishen paidu formula-H group were significantly alleviated. The levels of Scr， BUN， ROS， MDA， TNF- α， IL-6 and IL-1β， and the protein expressions of Collagen Ⅲ， α-SMA， TGF-β1， TXNIP and NLRP3 were significantly decreased， while SOD levels were significantly increased （P＜0.05）. Moreover， the changes were more pronounced in the Yishen paidu formula-H group （P＜0.05）. Compared with Yishen paidu formula-H+pcDNA-NC group， above indexes of rats in Yishen paidu formula-H+pcDNA-TXNIP group were reversed significantly （P＜0.05）. CONCLUSIONS Yishen paidu formula can inhibit renal fibrosis in CRF rats by suppressing the ROS/TXNIP/NLRP3 pathway.

BACKGROUND:Several observational studies have found a close relationship between thyroid function levels and sarcopenia,but the causal relationship between thyroid function levels and the onset of sarcopenia is not yet clear. OBJECTIVE:To investigate the causal relationship between thyroid function levels and sarcopenia using a two sample Mendelian randomization method. METHODS:A two sample Mendelian randomization analysis was conducted using genome-wide association study data on thyrotropin,free triiodothyronine,free tetraiodothyronine,subclinical hyperthyroidism,subclinical hypothyroidism,and four related phenotypes of sarcopenia-lefthand grip strength,right hand grip strength,limb lean mass,and gait speed.The inverse-variance weighted method,weighted median method,simple mode method,weighted median estimator method,and MR Egger regression method were used as analysis methods,while heterogeneity test,pleiotropy test,MR-PRESSO,leave-one-out method,funnel plot and other methods were used for sensitivity analysis. RESULTS AND CONCLUSION:Elevated levels of thyroid-stimulating hormone increased left-(β=0.02,SE=0.01,P=0.01)and right-handed grip strength(β=0.02,SE=0.01,P=0.01),an increase in free triiodothyronine decreased left-(β=-0.06,SE=0.02,P=9.5×10-5)and right-handed grip strength(β=-0.07,SE=0.02,P=9.3×10-5),and subclinical hyperthyroidism decreased gait speed(β=-4.4×10-3,SE=1.7×10-3,P=0.01).The sensitivity analysis results were basically consistent with the main analysis results.To conclude,an increase in thyroid-stimulating hormone is a protective factor for sarcopenia,and elevation of free triiodothyronine and subclinical hyperthyroidism may increase the risk of sarcopenia.

Objective To analyze the clinical features of chronic obstructive pulmonary disease (COPD) patients with heart failure (HF) in Nanjing and explore the influencing factors. Methods A total of 773 COPD inpatients were selected from January 2021 to January 2024 in Nanjing Combined Hospital of Traditional Chinese and Western Medicine, Nanjing Qixia District Hospital, Nanjing Lishui District People's Hospital, Nanjing Pukou District Hospital of Traditional Chinese Medicine and Nanjing First Hospital., and were divided into 2 groups according to the presence or absence of combined HF. The general data and medical records of the two groups were compared, the clinical characteristics of COPD patients with HF were summarized, and the influencing factors of COPD patients with HF were analyzed by multivariate logistic regression. Results Among the 242 patients (31.31%) with COPD had HF, chronic paroxysmal dyspnea was the most common first symptom, 169 patients (69.83%) had left heart failure, 63 patients (30.17%) were diagnosed as right heart failure or global heart failure , 17 patients (7.02%) had myocardial infarction. Multivariate logistic regression analysis showed that the risk of HF was 1.678 times and 1.691times higher in COPD groups ≥ 50 years old and male COPD groups than in < 50 years old and female groups, respectively; the risk of HF was 1.491 times higher in COPD groups engaged in physical work than in physical work groups; the risk of HF was 1.447 times and 1.580 times higher in COPD groups with hypertension and coronary heart disease than in COPD groups without hypertension and coronary heart disease, respectively; the risk of HF was 1.859 times higher in COPD groups smoking>400 vial/year than in COPD groups≤400 vial/ year; the risk of HF was 1.757 times higher in COPD groups with acute exacerbation frequency≥2 times/year than in COPD groups<2 times/year; the above differences were statistically significant (P<0.05). Conclusion Attention should be paid to elderly, male and heavy physical work group of COPD patients. Active treatment of hypertension and coronary heart disease, effective tobacco control and reduction of the frequency of acute exacerbation are effective ways to reduce the risk of HF in COPD patients in Nanjing.

OBJECTIVE: To explore the effects of two methods of smear layer removal on the surface properties of dentin. METHODS: Sixty extracted sound third molars were collected in this study, and were prepared as uniform dentin specimens with smear layer. All specimens were randomly divided into three groups: Control group, ultrasonic treatment (UT) group and etched treatment (ET) group. Scanning electron microscope (SEM) were used to observe the surface micromorphology of all three groups. Then, the surface elements, mineral phases and functional groups were analyzed by energy dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD) and flourier transformed infrared spectrometer (FTIR) respectively. The mechanical properties, hydrophilicity and biocompatibility were also further evaluated. RESULTS: It was revealed that dentin tubules of UT and ET groups were exposed, but lots of dentin debris piled up on the surface of the control one which covered up dentin tubules on the surface. The EDX results should that the weaker peak value of calcium and phosphorus in ET group than control and UT groups. Characteristic peaks of hydroxyapatite could be seen by XRD in all of the three groups, but lower distinctive peaks of amide Ⅰ, Ⅱ and Ⅲ bands of collagen of the dentin surface in control group than in ET and UT groups. The microhardness results showed that ET group was lower than control and UT groups, the difference was significant (P < 0.05). Better hydrophilicity of ET group was investigated (P < 0.05) than control group and UT group. Cells could be observed to adhere normally to dentin surface of each group which meant that all of the three groups had good biocompatibility. CONCLUSION Both UT and ET could effectively remove the smear layer on the surface of dentin and had no adverse effect of the dentin micromorphology and biocompatibility. The ultrasonic removal of the smear layer did not influence the mineral structure, hydrophilicity and mechanical properties of dentin surface. Although ET can effectively improve the hydrophilicity of dentin but decreased mechanical properties and the content of calcium and phosphorus.
Dentin/ultrastructure* ; Humans ; Surface Properties ; Smear Layer ; Molar, Third ; Microscopy, Electron, Scanning ; Dental Etching/methods*

Psoriasis is an incurable chronic inflammatory disease that requires new interventions. Here, we found that fibroblasts exacerbate psoriasis progression by promoting macrophage recruitment via CCL2 secretion by single-cell multi-omics analysis. The natural small molecule celastrol was screened to interfere with the secretion of CCL2 by fibroblasts and improve the psoriasis-like symptoms in both murine and cynomolgus monkey models. Mechanistically, celastrol directly bound to the low-density lipoprotein receptor-related protein 1 (LRP1) β-chain and abolished its binding to the transcription factor c-Jun in the nucleus, which in turn inhibited CCL2 production by skin fibroblasts, blocked fibroblast-macrophage crosstalk, and ameliorated psoriasis progression. Notably, fibroblast-specific LRP1 knockout mice exhibited a significant reduction in psoriasis like inflammation. Taken together, from clinical samples and combined with various mouse models, we revealed the pathogenesis of psoriasis from the perspective of fibroblast-macrophage crosstalk, and provided a foundation for LRP1 as a novel potential target for psoriasis treatment.

Dendritic cells (DCs) serve as the primary antigen-presenting cells in autoimmune diseases, like rheumatoid arthritis (RA), and exhibit distinct signaling profiles due to antigenic diversity. Type II collagen (CII) has been recognized as an RA-specific antigen; however, little is known about CII-stimulated DCs, limiting the development of RA-specific therapeutic interventions. In this study, we show that CII-stimulated DCs display a preferential gene expression profile associated with migration, offering a new perspective for targeting DC migration in RA treatment. Then, saikosaponin D (SSD) was identified as a compound capable of blocking CII-induced DC migration and effectively ameliorating arthritis. Optineurin (OPTN) is further revealed as a potential SSD target, with Optn deletion impairing CII-pulsed DC migration without affecting maturation. Function analyses uncover that OPTN prevents the proteasomal transport and ubiquitin-dependent degradation of C-C chemokine receptor 7 (CCR7), a pivotal chemokine receptor in DC migration. Optn-deficient DCs exhibit reduced CCR7 expression, leading to slower migration in CII-surrounded environment, thus alleviating arthritis progression. Our findings underscore the significance of antigen-specific DC activation in RA and suggest OPTN is a crucial regulator of CII-specific DC migration. OPTN emerges as a promising drug target for RA, potentially offering significant value for the therapeutic management of RA.

Sonodynamic therapy (SDT) can potentially induce immunogenic cell death in tumor cells, leading to the release of ATP, and facilitating the initiation of an immune response. Nevertheless, the enzymes CD39 and CD73 can swiftly convert ATP into immunosuppressive adenosine (ADO), resulting in an immunosuppressive tumor microenvironment (TME). This study introduced a nanomedicine (QD/POM1@NP@M) engineered to reprogram TME by modulating the CD39/CD73/ADO pathway. The nanomedicine encapsulated sonosensitizers silver sulfide quantum dots, and the CD39 inhibitor POM1, while also incorporating homologous tumor cell membranes to enhance targeting capabilities. This integrated approach, on the one hand, stimulates the release of ATP via SDT, thereby initiating the immune response. In addition, it reduced the accumulation of ADO by inhibiting CD39 activity, which ameliorated the immunosuppressive TME. Upon administration, the nanomedicine demonstrated substantial anti-tumor efficacy by facilitating the infiltration of anti-tumor immune cells, while reducing the immunosuppressive cells. This modulation effectively transformed the TME from an immunologically "cold" state to a "hot" state. Furthermore, combined with the checkpoint inhibitor α-PDL1, the nanomedicine augmented systemic anti-tumor immunity and promoted the establishment of long-term immune memory. This study provides an innovative strategy for combining non-invasive SDT and ATP-driven immunotherapy, offering new ideas for future cancer treatment.

Objective To scan and accurately reconstruct mandible models printed via fused deposition modeling(FDM)that contain screw path information,using cone-beam CT(CBCT),to achieve the digital transfer of preoperative model screw paths.Methods CBCT scans were conducted on 12 FDM-printed mandibular models(Model1 group)intended for prebending reconstruction plates.Mim-ics software was employed to reconstruct scanned data into mandibular models(Model2 group)and extract digital screw path informa-tion.Model2 was then compared with original models(Model0 group)in three dimensions,evaluating reconstruction accuracy through root mean square(RMS).Reconstruction parameters were optimized to enable automatic matching of Model2 with Model0,facilitating precise digital transfer of screw paths.In clinical application,this method was utilized to produce digital short-segment drilling guides,assisting in the reduction surgery of three mandibular fracture patients.Results Model2 demonstrated automatic matching with Model0,exhibiting detailed surface characteristics and clear screw path position and orientation information.The RMS was measured at(0.32±0.09)mm.Utilization of digital segmented screw path transfer guides assisted in the satisfactory reduction surgery of three pa-tients with comminuted mandibular fractures.Conclusion CBCT scanning of FDM-printed preoperative models accurately captures screw path position and orientation information,enabling digital transfer of screw paths and providing a novel method for precise design of digital surgical guides.

Cancer is a major chronic disease that threatens human health, while traditional Chinese medicine (TCM) is a unique method for cancer prevention and treatment in China. After about 70 years of innovation and development, TCM has made constant progress in areas such as the clinical diagnosis, treatment, evidence-based researches, and mechanism exploration of cancer. It has special advantages in aspects such as reducing toxicity, enhancing treatment efficacy, managing symptoms, accelerating recovery, preventing recurrence and metastasis, and prolonging advanced-stage survival. However, there are still bottlenecks for TCM in cancer care. This paper cuts in the key links between TCM and western medicine in their combined application in cancer prevention and treatment, and take the original TCM theories on cancer as the lead, high-quality evidence-based researches as the drive, and analysis on the dynamic mechanism as the core, to show the advantages and effects of TCM in cancer treatment in an all-round way. It also aims to provide novel strategies for sustainable and innovative development and for formulation of comprehensive schemes that integrate TCM and western medicine for cancer prevention and treatment.

Time rhythm and the immune system play crucial roles in the pathogenesis of allergic rhinitis.Traditional Chinese medicine(TCM)believes that the circulation of qi and blood in lung meridian follows the principle of"yang during the day,yin at night",which has a defensive function to protect the body from external pathogens.Qi stagnation in lung meridian and impaired qi and blood circulation can lead to the invasion of external pathogens,exacerbating allergic reactions,especially during the active period of the lung meridian,when the immune system is most sensitive to allergens.Based on this,this paper proposes the concept of"bidirectional regulation among meridian,time rhythm,and immune system",and in combination with TCM theory of midnight-noon and ebb-flow doctrine,analyzes the fluctuations of allergic rhinitis symptoms and the temporal changes of meridian qi and blood,and reveals the rhythmic relationship between meridian activity and immune response.This paper combines existing clinical and experimental studies to support this hypothesis,integrating the time dimension into traditional TCM syndrome differentiation and treatment,offering a more individualized treatment approach.This concept not only provides novel scientific evidence for TCM treatment of allergic rhinitis,but also offers theoretical support for optimizing treatment timing and intervention strategies.