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.

ObjectiveTo characterize the features of the gut microbiome and its association with clinical prognosis in patients with intermediate and advanced hepatocellular carcinoma （HCC） treated with transcatheter arterial chemoembolization （TACE） combined with targeted therapy and immunotherapy. MethodsThis retrospective study enrolled patients with intermediate and advanced HCC who received TACE combined with targeted therapy and immunotherapy at the First Affiliated Hospital of Sun Yat-sen University from February 2025 to July 2025. Baseline clinical data and fecal samples were collected from all enrolled patients before the index hospitalization and treatment. Patients were stratified using two independent criteria： ① a good-prognosis group and a poor-prognosis group， based on whether progression-free survival （PFS） reached 6 months； ② a response group and a non-response group， based on tumor response to the first TACE assessed by the modified Response Evaluation Criteria in Solid Tumors （mRECIST）. Metagenomic sequencing was performed on fecal samples. Bioinformatic analysis was conducted to evaluate the diversity and compositional differences of intestinal bacterial and fungal communities between groups in each stratification， and to screen for prognosis-associated characteristic microbial taxa. ResultsA total of 61 patients met the inclusion criteria. Analysis of α-diversity and β-diversity showed no statistically significant differences in bacterial and fungal diversity between groups under either stratification strategy （P＞ 0.05）. At the bacterial level， Lactobacillus johnsonii （prognosis stratification： P=0.048； response stratification： P=0.043）， Bifidobacterium dentium （prognosis stratification： P=0.004； response stratification： P=0.030） and Clostridioides difficile （prognosis stratification： P=0.017； response stratification： P=0.016） were significantly enriched in both the good prognosis group and the response group. At the fungal level， Cryptococcus decaguttatus （P=0.045）， Puccinia striiformis （P=0.002）， and Kwoniella quercicola （P=0.015） were enriched in the good‑prognosis group； Kwoniella bestiolae （P=0.037） was enriched in the response group； and Akanthomyces muscarius （P=0.024） was enriched in the non-response group. Survival analysis based on the common differential bacterial abundance in both groupings showed a significant correlation between the abundance of Bifidobacterium dentium and patient prognosis. ConclusionDifferences in the gut microbiota are associated with the prognosis of patients with intermediate and advanced HCC treated with TACE combined with targeted therapy and immunotherapy. Bifidobacterium dentium may serve as a potential predictive biomarker for the efficacy of this combination regimen， and represents a potential intervention target to modulate treatment response. Differences in gut fungal communities are also potentially associated with the prognosis of intermediate and advanced HCC patients receiving TACE combined with targeted therapy and immunotherapy.

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 observe any influence of combining proprioceptive training with core stability training in rehabilitation motor functioning and balance after extensive burns.Methods:Sixty patients with lower limb motor and balance disorders after extensive burns were randomly divided into a treatment group and a control group, each of 30. Both groups underwent skin grafting on the lower limbs. After the wounds had healed, both groups were given routine rehabilitation treatment, including joint stretching and muscle strength training, but the treatment group was additionally provided with proprioception and core stability training. Before and after 12 weeks of treatment, both groups′ lower limb motor function and walking ability were evaluated using the Fugl-Meyer Assessment (L-FMA), and static and dynamic balance were quantified using Holden Functional Ambulation Classification (FAC). The duration of standing on one leg with the eyes closed was recorded, along with Timed " Up & Go" Test (TUGT) times. After the treatment, each patient′s satisfaction was assessed using a self-designed questionnaire.Results:Significant improvement was observed in the average L- FMA and FAC scores after the treatment, as well as in the ability to stand on one leg with the eyes closed. The average TUGT time in both groups was shorter, but there had been significantly greater improvement of the treatment group than among the controls. Reported satisfaction was significantly higher among the treated group than among the controls.Conclusions:Supplementing basic rehabilitation with proprioception training and core stability training can further improve the motor functioning, balance and walking of persons who have suffered extensive burns.

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.

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.

Objective:To analyze the efficacy of transjugular intrahepatic portosystemic shunt (TIPS) combined with main splenic artery embolization in the treatment of patients with portal hypertension upper gastrointestinal bleeding complicated with extensive portal vein thrombosis (PVT).Methods:This study was a prospective, single-center, open-label, single-arm clinical trial. In the first phase, 81 patients with portal hypertension upper gastrointestinal bleeding who were admitted to Beijing Shijitan Hospital, Capital Medical University from January 2018 to December 2018 were consecutively enrolled, including 57 males and 24 females, with the age of (51.3±10.4) years. During TIPS surgery, the pressure of the portal vein before and after the balloon blocking the splenic artery was measured to clarify the contribution of the splenic artery to portal hypertension. In the second stage, from January 2019 to December 2022, 104 patients with portal hypertension upper gastrointestinal bleeding complicated with extensive PVT were re-enrolled, including 71 males and 33 females, with the age of (50.9±12.5) years. TIPS combined with main splenic artery embolization was performed, and portal vein pressure was measured before and after embolization. Follow up on the postoperative esophageal and gastric varices of the patients in the second stage.Results:The portal vein pressures before and after the first stage of balloon occlusion of the splenic artery were (35.2±8.4) mmHg (1 mmHg=0.133 kPa) and (24.2±6.3) mmHg, respectively. The pressure after occlusion was lower than that before occlusion, and the difference was statistically significant ( t=10.54, P<0.001). The portal vein pressures before and after the second stage embolization were (36.1±9.5) mmHg and (21.1±4.7) mmHg respectively. The pressure after embolization was lower than that before embolization, and the difference was statistically significant ( t=13.47, P<0.001). In the second stage, among the 104 patients, the proportion of those whose varicose veins disappeared or improved 6 months after the operation was 43.3%(45/104) and 51.0%(53/104), respectively. There were no patients with aggravation or rebleeding due to rupture. One year later, 8 patients (7.7%) had aggravated or ruptured esophageal and gastric varices with bleeding. Two years later, 12 patients (11.5%) had aggravated or bleeding. Conclusion:TIPS combined with main splenic artery embolization can effectively reduce the portal vein pressure in patients with portal hypertension upper gastrointestinal bleeding complicated with extensive PVT, improve the degree of esophageal and gastric varices, and reduce the risk of gastrointestinal bleeding.

Objective:To develop a novel ovarian biological age prediction model based on DNA methylation for ovarian aging assessment.Methods:A prospective cohort study method was used. From March 2024 to January 2025, we collected 96 ovarian granulosa cell samples of infertility patients due to fallopian tube factors or male factors from the Reproductive Medicine Center of the Second Affiliated Hospital of Naval Medical University. Then we analyzed DNA methylation patterns across five age-associated gene regions ( ELOVL2, miR29B2C, TRIM59, KLF14 and FHL2) in a discovery cohort comprising 63 human ovarian granulosa cell samples. Targeted bisulfite sequencing was performed through PCR amplification followed by next-generation DNA sequencing. Leveraging elastic net regression analysis, we developed a predictive model incorporating 29 methylation sites that demonstrated strong age correlation. The model was subsequently validated using an independent cohort comprising 33 human ovarian granulosa cell samples. Results:The DNA methylation age prediction model based on ovarian granulosa cells showed the following results in the discovery cohort as follows: median absolute error (MAE) was 2.534 ( R=0.742, P<0.001). In the independent validation cohort, MAE was 3.019 ( R=0.729, P<0.001). Conclusion:In this study, we utilized human ovarian granulosa cells as experimental samples to develop a novel DNA methylation-based model for predicting ovarian biological age. By integrating multiple methylation sites across five age-related gene regions, this model serves as a robust indicator of ovarian aging status.

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.