epsis is a systemic inflammatory response syndrome triggered by infection， and its high mortality rate is closely associated with immune imbalance， particularly the imbalance in the differentiation of helper T cell （Th） cell subsets [Th1， Th2， Th17， regulatory T cell （Treg） ] . In recent years， traditional Chinese medicine （TCM）， with its characteristics of multi-component and multi-target actions， has demonstrated unique advantages in regulating Th cell differentiation and function， as well as correcting immune imbalances in sepsis， offering new perspectives for immunotherapy of sepsis. This review summarizes relevant studies on the regulation of Th cell differentiation for sepsis treatment by TCM monomers and active ingredients （such as Astragalus membranaceus ， Scutellaria baicalensis ， Coptis chinensis ， Rheum palmatum ， Ganoderma lucidum ， Ginkgo biloba ， and Cistanche deserticola ）， the alcohol extract of Dai Baijie， and TCM formulas and preparations categorized as blood-activating and stasis-removing， purgative and laxative， warming and tonifying yang， and tonifying qi and nourishing yin. The results indicate that these TCM monomers， active ingredients， extracts， formulas， and preparations can regulate the Th1/Th2 and Th17/Treg balance， target the differentiation balance of Th cell subsets， alleviate inflammatory responses， or improve immune suppression， thereby exerting therapeutic effects on sepsis.

AIM: To compare the clinical outcomes of extended depth-of-focus intraocular lenses(EDOF IOLs)using either micromonovision implantation or mixed implantation of EDOF and diffractive bifocal IOLs.METHODS: This retrospective clinical trial included 130 patients(260 eyes), who were divided into two groups. Group RR comprised 70 patients(140 eyes)bilaterally implanted with ZXR00 IOLs(Tecnis ZXR00, where one target was -0.5 D to -0.75 D and the other was 0 to -0.25 D). Group RM comprised 60 patients(120 eyes)unilaterally implanted with both ZXR00 and ZMB00 IOLs(Tecnis ZMB00, 0 to -0.25 D). Postoperative outcomes were compared after 3 mo, including visual acuity, defocus curves, stereoacuity, modulation transfer functions(MTFs), higher-order aberrations, and Visual Function-14(VF-14)questionnaire responses.RESULTS: Group RR had superior bilateral intermediate vision, while the group RM had superior bilateral near vision(both P<0.05). Group RM also exhibited superior MTFs and reduced higher-order aberrations(both P<0.05). Stereoacuity and VF-14 questionnaire results showed no statistically significant difference between groups(P>0.05).CONCLUSION: The implantation of micromonovision has significantly improved near vision. IOLs and their collocation can be customized according to individual patient needs to achieve precise treatment and provide cataract patients with high-quality vision.

AIM: To compare the clinical outcomes of extended depth-of-focus intraocular lenses(EDOF IOLs)using either micromonovision implantation or mixed implantation of EDOF and diffractive bifocal IOLs.METHODS: This retrospective clinical trial included 130 patients(260 eyes), who were divided into two groups. Group RR comprised 70 patients(140 eyes)bilaterally implanted with ZXR00 IOLs(Tecnis ZXR00, where one target was -0.5 D to -0.75 D and the other was 0 to -0.25 D). Group RM comprised 60 patients(120 eyes)unilaterally implanted with both ZXR00 and ZMB00 IOLs(Tecnis ZMB00, 0 to -0.25 D). Postoperative outcomes were compared after 3 mo, including visual acuity, defocus curves, stereoacuity, modulation transfer functions(MTFs), higher-order aberrations, and Visual Function-14(VF-14)questionnaire responses.RESULTS: Group RR had superior bilateral intermediate vision, while the group RM had superior bilateral near vision(both P<0.05). Group RM also exhibited superior MTFs and reduced higher-order aberrations(both P<0.05). Stereoacuity and VF-14 questionnaire results showed no statistically significant difference between groups(P>0.05).CONCLUSION: The implantation of micromonovision has significantly improved near vision. IOLs and their collocation can be customized according to individual patient needs to achieve precise treatment and provide cataract patients with high-quality vision.

ObjectiveTo investigate the protective effects and mechanisms of Zhenzhu Tiaozhi capsules on the kidneys in the mouse model of diabetic kidney disease. MethodsThirty male C57BL/6J mice were selected as experimental objects. The model of diabetic kidney disease was induced by intraperitoneal injection of streptozotocin （STZ） at 40 mg·kg^-1 for 5 days combined with a high-fat diet （HFD）. Fasting blood glucose （FBG） ≥ 11.1 mmol·L^-1， increased urine volume， and continuous appearance of proteinuria indicated successful modeling. Mice were grouped as follows： Blank， model， low- and high-dose （0.98 and 1.96 g·kg^-1， respectively） Zhenzhu Tiaozhi capsules， and losartan potassium （30 mg·kg^-1）， with six mice in each group. After 12 weeks of continuous gavage， urine and kidney specimens were collected， and the 24-h urinary protein and the urinary albumin-to-creatinine ratio （UACR） in mice were measured. Hematoxylin-eosin （HE） staining， periodic acid-Schiff （PAS） staining， and Masson staining were performed for observation of histopathological changes in kidneys. Immunofluorescence assay was employed to detect the positive expression of the podocyte marker protein nephrin. Oil red O staining was used to detect renal lipid deposition. Enzyme linked immunosorbent assay was employed to measure the levels of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） in the renal tissue. Western blot was employed to determine the expression levels of sterol regulatory element-binding protein cleavage-activating protein （SCAP）， sterol regulatory element-binding protein-1c （SREBP-1c）， and NOD-like receptor protein 3 （NLRP3） in the renal tissue. ResultsCompared with the blank group， the model group showed increases in 24-h urinary protein and UACR （P<0.05）， glomeruli exhibiting capsule adhesion， collagen fiber deposition， mesangial proliferation， and inflammatory cell infiltration， elevated levels of IL-1β， IL-6， and TNF-α （P<0.05）， reduced positive expression of nephrin （P<0.05）， increased lipid deposition （P<0.05）， and up-regulated expression of SCAP， SREBP-1c， and NLRP3 （P<0.05） in the renal tissue. Compared with the model group， the treatment with losartan potassium or high-dose Zhenzhu Tiaozhi capsules for 12 weeks decreased 24-h urinary protein and UACR （P<0.05）， and the treatment with low-dose Zhenzhu Tiaozhi capsules for 12 weeks reduced the 24-h urinary protein （P<0.05）. Pathological staining results revealed that kidney damage in mice from all treatment groups was alleviated， with reduced inflammatory infiltration， collagen fiber deposition， and mesangial proliferation， and increased positive expression of nephrin in the renal tissue （P<0.05）. In addition， all the treatment groups showed reduced lipid droplets （P<0.05）， lowered levels of IL-1β， IL-6， and TNF-α （P<0.05）， and down-regulated expression of SCAP， SREBP-1c， and NLRP3 （P<0.05） in the renal tissue. ConclusionZhenzhu Tiaozhi capsules can ameliorate kidney damage in the mouse model of diabetic kidney disease by inhibiting the activation of the SCAP-SREBP-1c/NLRP3 signaling pathway， which reduces renal lipid deposition and inflammation.

ObjectiveTo investigate the protective effects and mechanisms of Zhenzhu Tiaozhi capsules on the kidneys in the mouse model of diabetic kidney disease. MethodsThirty male C57BL/6J mice were selected as experimental objects. The model of diabetic kidney disease was induced by intraperitoneal injection of streptozotocin （STZ） at 40 mg·kg^-1 for 5 days combined with a high-fat diet （HFD）. Fasting blood glucose （FBG） ≥ 11.1 mmol·L^-1， increased urine volume， and continuous appearance of proteinuria indicated successful modeling. Mice were grouped as follows： Blank， model， low- and high-dose （0.98 and 1.96 g·kg^-1， respectively） Zhenzhu Tiaozhi capsules， and losartan potassium （30 mg·kg^-1）， with six mice in each group. After 12 weeks of continuous gavage， urine and kidney specimens were collected， and the 24-h urinary protein and the urinary albumin-to-creatinine ratio （UACR） in mice were measured. Hematoxylin-eosin （HE） staining， periodic acid-Schiff （PAS） staining， and Masson staining were performed for observation of histopathological changes in kidneys. Immunofluorescence assay was employed to detect the positive expression of the podocyte marker protein nephrin. Oil red O staining was used to detect renal lipid deposition. Enzyme linked immunosorbent assay was employed to measure the levels of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） in the renal tissue. Western blot was employed to determine the expression levels of sterol regulatory element-binding protein cleavage-activating protein （SCAP）， sterol regulatory element-binding protein-1c （SREBP-1c）， and NOD-like receptor protein 3 （NLRP3） in the renal tissue. ResultsCompared with the blank group， the model group showed increases in 24-h urinary protein and UACR （P<0.05）， glomeruli exhibiting capsule adhesion， collagen fiber deposition， mesangial proliferation， and inflammatory cell infiltration， elevated levels of IL-1β， IL-6， and TNF-α （P<0.05）， reduced positive expression of nephrin （P<0.05）， increased lipid deposition （P<0.05）， and up-regulated expression of SCAP， SREBP-1c， and NLRP3 （P<0.05） in the renal tissue. Compared with the model group， the treatment with losartan potassium or high-dose Zhenzhu Tiaozhi capsules for 12 weeks decreased 24-h urinary protein and UACR （P<0.05）， and the treatment with low-dose Zhenzhu Tiaozhi capsules for 12 weeks reduced the 24-h urinary protein （P<0.05）. Pathological staining results revealed that kidney damage in mice from all treatment groups was alleviated， with reduced inflammatory infiltration， collagen fiber deposition， and mesangial proliferation， and increased positive expression of nephrin in the renal tissue （P<0.05）. In addition， all the treatment groups showed reduced lipid droplets （P<0.05）， lowered levels of IL-1β， IL-6， and TNF-α （P<0.05）， and down-regulated expression of SCAP， SREBP-1c， and NLRP3 （P<0.05） in the renal tissue. ConclusionZhenzhu Tiaozhi capsules can ameliorate kidney damage in the mouse model of diabetic kidney disease by inhibiting the activation of the SCAP-SREBP-1c/NLRP3 signaling pathway， which reduces renal lipid deposition and inflammation.

To investigate body composition and associated factors in adolescents undergoing long-term regular sports training.

BACKGROUND: Based on the China-VHD database, this study sought to develop and validate a Valvular Heart Disease- specific Age-adjusted Comorbidity Index (VHD-ACI) for predicting mortality risk in patients with VHD. METHODS & RESULTS: The China-VHD study was a nationwide, multi-centre multi-centre cohort study enrolling 13,917 patients with moderate or severe VHD across 46 medical centres in China between April-June 2018. After excluding cases with missing key variables, 11,459 patients were retained for final analysis. The primary endpoint was 2-year all-cause mortality, with 941 deaths (10.0%) observed during follow-up. The VHD-ACI was derived after identifying 13 independent mortality predictors: cardiomyopathy, myocardial infarction, chronic obstructive pulmonary disease, pulmonary artery hypertension, low body weight, anaemia, hypoalbuminaemia, renal insufficiency, moderate/severe hepatic dysfunction, heart failure, cancer, NYHA functional class and age. The index exhibited good discrimination (AUC, 0.79) and calibration (Brier score, 0.062) in the total cohort, outperforming both EuroSCORE II and ACCI (P < 0.001 for comparison). Internal validation through 100 bootstrap iterations yielded a C statistic of 0.694 (95% CI: 0.665-0.723) for 2-year mortality prediction. VHD-ACI scores, as a continuous variable (VHD-ACI score: adjusted HR (95% CI): 1.263 (1.245-1.282), P < 0.001) or categorized using thresholds determined by the Yoden index (VHD-ACI ≥ 9 vs. < 9, adjusted HR (95% CI): 6.216 (5.378-7.184), P < 0.001), were independently associated with mortality. The prognostic performance remained consistent across all VHD subtypes (aortic stenosis, aortic regurgitation, mitral stenosis, mitral regurgitation, tricuspid valve disease, mixed aortic/mitral valve disease and multiple VHD), and clinical subgroups stratified by therapeutic strategy, LVEF status (preserved vs. reduced), disease severity and etiology. CONCLUSION The VHD-ACI is a simple 13-comorbidity algorithm for the prediction of mortality in VHD patients and providing a simple and rapid tool for risk stratification.

Phantom limb pain (PLP) is a form of neuropathic pain occurring after limb amputation, and its underlying mechanisms remain unclear, posing significant challenges for clinical management. Spinal cord stimulation (SCS), a neuromodulation technique, has shown potential in relieving chronic pain, though its long-term efficacy and safety in treating PLP require further validation. This report presents a case of a 42-year-old male experiencing persistent radiating, lightning-like pain [Visual Analog Scale (VAS) score 8-9], following right upper limb amputation. Preoperative imaging revealed signal loss in the right nerve roots at C₆-T₁. A percutaneous electrode was implanted surgically to achieve full coverage of the painful region. Five days postoperatively, the VAS score dropped to 2-3, and after 1 year of follow-up, the patient continued to experience significant pain relief (VAS 1-2), with complete resolution of depressive symptoms and cessation of analgesic medication. Existing studies suggest that the long-term outcomes of SCS may fluctuate, and attention should be paid to potential complications such as infection and electrode displacement.
Humans ; Phantom Limb/therapy* ; Male ; Adult ; Spinal Cord Stimulation/methods* ; Electrodes, Implanted ; Amputation, Surgical/adverse effects*

Targeting drug delivery systems mediated by nanoparticles has shown great potential in the diagnosis and treatment of cancer. However, influences of different tumor progressions on the accumulation of nanoparticles, especially the ligand-modified active targeting nanoparticles are seldom exploited. In this work, the accumulation and penetration of RGD-modified gold nanoparticles (active AuNPs) with different sizes were investigated in orthotopic breast cancer with different tumor progressions. The results showed that the smallest active AuNPs had better accumulation and permeation effects in early tumor tissues with the relatively looser extracellular matrix, larger gaps, lower interstitial fluid pressure, and less receptor expression, which was due to size effects. However, the larger active AuNPs had better accumulation and penetration effects in late tumor tissues with highly expressed target receptors integrin α _v β ₃ because of the multivalent interactions between larger active nanoparticles and integrin α _v β ₃. In the midterm, tumor accumulation of active AuNPs was equally influenced by size effects and multivalent interactions. Therefore, RGD-modified nanoparticles with sizes of 7 and 90 nm accumulated more in tumors. This study will guide a rational design of active targeting nanoparticles for enhancing the diagnosis and treatment of tumors based on their progressions.

Ovarian tumor (OT) is the most lethal form of gynecologic malignancy, with minimal improvements in patient outcomes over the past several decades. Metastasis is the leading cause of ovarian cancer-related deaths, yet the underlying mechanisms remain poorly understood. Psychological stress is known to activate the glucocorticoid receptor (NR3C1), a factor associated with poor prognosis in OT patients. However, the precise mechanisms linking NR3C1 signaling and metastasis have yet to be fully elucidated. In this study, we demonstrate that chronic restraint stress accelerates epithelial-mesenchymal transition (EMT) and metastasis in OT through an NR3C1-dependent mechanism involving nuclear protein 1 (NUPR1). Mechanistically, NR3C1 directly regulates the transcription of NUPR1, which in turn increases the expression of snail family transcriptional repressor 2 (SNAI2), a key driver of EMT. Clinically, elevated NR3C1 positively correlates with NUPR1 expression in OT patients, and both are positively associated with poorer prognosis. Overall, our study identified the NR3C1/NUPR1 axis as a critical regulatory pathway in psychological stress-induced OT metastasis, suggesting a potential therapeutic target for intervention in OT metastasis.