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.

Objective: The present study made a retrospective analysis aiming to report chiggers on small mammals (hosts) in Jinping County on the China-Vietnam border, Yunnan of southwest China. Methods: The indexes of chigger infestation and chigger community were routinely calculated. The niche width and overlap were calculated for analyzing chiggers’ host selection. The sample completeness was determined through coverage index (CI). Results: A total of 7,718 chiggers from 274 small mammal hosts were identified as 52 species, 10 genera, three subfamilies and two families, including nine vector species. The CI of chigger species reached 99.84%. The genus Leptotrombidium accounted for 94.86% of 10 chigger genera. The majority of chiggers (constituent ratio [C r ] = 95.35%) came from rodents (Rodentia). The four dominant chigger species (C r = 89.88%, 6,937/7,718) included Leptotrombidium deliense, the most important vector of scrub typhus in China. Conclusions and Relevance: The abundant L. deliense in Jinping, together with other vector chigger species and their low host specificity, increases the potential transmission risk of scrub typhus in China-Vietnam border areas.

Objective To explore the efficacy of the on-demand intermittent total androgen blockade regimen in treating cases with positive surgical margins after radical prostatectomy for pT3 stage prostate cancer. Methods A retrospective analysis was conducted on the clinical data of 21 patients with pT3 stage prostate cancer who underwent radical prostatectomy and had positive surgical margins confirmed by pathology in our hospital during Jan. 2013 and Dec. 2020. Prostate-specific antigen(PSA)was used as the indicator of observation. For those with biochemical recurrence(PSA＞0.2 μg/L), at least 2 months of androgen deprivation therapy(ADT)combined with the maximum androgen receptor antagonist was administered for maximal androgen blockade endocrine therapy. If PSA still exceeded 0.1 μg/L after 2 months of maximal androgen blockade treatment, the maximal androgen blockade was maintained and monthly follow-up was conducted until PSA reached the discontinuation criteria. During the discontinuation period, the serum PSA and testosterone levels were checked every 4 to 6 weeks. The time of application of maximal androgen blockade and the subsequent interval of discontinuation were defined as one treatment cycle. Results Postoperative pathology confirmed that among the 21 patients, 17 were pT3a and 4 were pT3b. The PSA level 1 month after surgery was(0.23±0.45)μg/L. The follow-up lasted for 48 to 126 months, with an average of(68.86 ± 20.43)months. The interval between the first application of maximal androgen blockade and radical prostatectomy was 2 to 35 months, with an average of(12.48±8.83)months. One patient died of post-cerebral infarction complications 74 months after surgery, another progressed to hormone-resistant prostate cancer(CRPC)70 months after surgery and the treatment plan was immediately changed. Up to 90.5%(19/21)of the patients completed 5 to 12 cycles of combined endocrine therapy, with no tumor progression. Conclusion Based on the postoperative PSA level monitored, intermittent administration of the maximum androgen blockade endocrine therapy can effectively control the cancer progression of patients with positive surgical margins after radical prostatectomy, which can also reduce the adverse reactions.

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.

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.

Cardiac fibrosis is characterized by an elevated amount of extracellular matrix (ECM) within the heart. However, the persistence of cardiac fibrosis ultimately diminishes contractility and precipitates cardiac dysfunction. Circular RNAs (circRNAs) are emerging as important regulators of cardiac fibrosis. Here, we elucidate the functional role of a specific circular RNA CELF1 in cardiac fibrosis and delineate a novel feedback loop mechanism. Functionally, circ-CELF1 was involved in enhancing fibrosis-related markers' expression and promoting the proliferation of cardiac fibroblasts (CFs), thereby exacerbating cardiac fibrosis. Mechanistically, circ-CELF1 reduced the ubiquitination-degradation rate of BRPF3, leading to an elevation of BRPF3 protein levels. Additionally, BRPF3 acted as a modular scaffold for the recruitment of histone acetyltransferase KAT7 to facilitate the induction of H3K14 acetylation within the promoters of the Celf1 gene. Thus, the transcription of Celf1 was dramatically activated, thereby inhibiting the subsequent response of their downstream target gene Smad7 expression to promote cardiac fibrosis. Moreover, Celf1 further promoted Celf1 pre-mRNA transcription and back-splicing, thereby establishing a feedback loop for circ-CELF1 production. Consequently, a novel feedback loop involving CELF1/circ-CELF1/BRPF3/KAT7 was established, suggesting that circ-CELF1 may serve as a potential novel therapeutic target for cardiac fibrosis.

Osteosarcoma (OS) is the most prevalent primary malignant bone tumor affecting children and adolescents. Despite ongoing research efforts, the 5-year survival rate has remained stagnant for many years, highlighting the critical need for novel drug development to enhance current treatment protocols. Ziyuglycoside II (ZYG II), a triterpenoid saponin extracted from S. officinalis, has recently demonstrated antitumor properties. This study evaluates the antitumor effect of ZYG II on osteosarcoma and elucidates its mechanism of action through the co-regulation of p53 and estrogen-related receptor gamma (ESRRG), which inhibits disease progression. The research employs in vitro experiments using multiple established osteosarcoma cell lines, as well as in vivo studies utilizing a nude mouse model of orthotopic xenograft osteosarcoma. Additionally, ESRRG shRNA was used to construct stable ESRRG-reducing OS cell lines to investigate the molecular mechanism by which ZYG II exerts its anti-osteosarcoma effects through the co-regulation of ESRRG and p53. Results indicate that ZYG II administration led to decreased OS cell viability and reduced tumor volumes. Furthermore, cell cycles were arrested at the G₀/G₁ phase, while the proportion of apoptotic cells increased. Expression of p53, ESRRG, p21, Bax, Cleaved Caspase-9, and Cleaved Caspase-3 proteins increased, while expression of CDK4, Cyclin D1, and Bcl-2 proteins decreased. Multiple ZYG II and ESRRG docking patterns were simulated through molecular docking. Comparing the pharmacodynamic response of ZYG II to OS cell lines with reduced ESRRG and normal expression demonstrated that ZYG II inhibits osteosarcoma progression, induces cell cycle arrest, and promotes cell apoptosis through the coordination of p53 and ESRRG. In conclusion, ZYG II inhibits osteosarcoma progression, leads to cell cycle arrest, and promotes cell apoptosis through synergistic regulation of p53 and ESRRG.
Osteosarcoma/physiopathology* ; Tumor Suppressor Protein p53/genetics* ; Humans ; Animals ; Saponins/chemistry* ; Bone Neoplasms/physiopathology* ; Signal Transduction/drug effects* ; Cell Line, Tumor ; Mice, Nude ; Mice ; Apoptosis/drug effects* ; Receptors, Estrogen/genetics* ; Mice, Inbred BALB C ; Female ; Male ; Xenograft Model Antitumor Assays