AIM:To investigate the effects of high-altitude hypoxic exposure on retinal injury and the associated changes in oxidative stress-related indicators in rats. METHODS: Twenty-four healthy male Sprague-Dawley(SD)rats were randomly divided into a plain group and a high-altitude group, with 12 rats(24 eyes)in each group. Rats in the plain group were housed under normoxic conditions in an SPF-grade animal facility, whereas rats in the high-altitude group were placed in a special environmental chamber simulating an altitude of 6 000 m for 7 d. Optical coherence tomography(OCT)was used to assess retinal layer architecture and quantify retinal thickness. Hematoxylin-eosin(HE)staining was performed to observe retinal histopathological changes. Immunofluorescence(IF)was used to detect the expression of hypoxia-inducible factor-1α(HIF-1α)in retinal tissue. Transmission electron microscopy(TEM)was applied to examine the ultrastructure of retinal ganglion cells(RGCs). Enzyme-linked immunosorbent assay(ELISA)was used to measure the levels of malondialdehyde(MDA), total superoxide dismutase(T-SOD), and reduced glutathione(GSH)in retinal tissue. In addition, intracellular reactive oxygen species(ROS)levels in retinal tissue were assessed using the 2',7'-dichlorodihydrofluorescein diacetate(DCFH-DA)fluorescent probe. RESULTS: OCT examination revealed disorganized retinal architecture in the high-altitude group, with increased inner and middle ring thickness and decreased outer ring thickness compared with the plain group(all P<0.05). HE staining showed varying degrees of retinal layer damage, blurred layer boundaries, loosely arranged RGCs, and partial cellular necrosis in the high-altitude group. IF analysis demonstrated significantly increased HIF-1α expression in the inner nuclear layer of the high-altitude group(P<0.01). TEM revealed mitochondrial swelling, disrupted cristae, and reduced matrix electron density in RGCs of the high-altitude group. ELISA and fluorescence probe assays showed significantly elevated MDA levels and ROS fluorescence intensity, accompanied by decreased T-SOD and GSH levels in the retinal tissue of the high-altitude group(all P<0.05). CONCLUSION: Exposure to a high-altitude hypoxic environment induces marked morphological and ultrastructural damage in the rat retina and significantly enhances oxidative stress, suggesting that oxidative stress may play a critical role in retinal injury induced by high-altitude hypoxia.

Objective To explore the feasibility and safety of using indocyanine green combined with autologous blood and methylene blue for localization of small lung nodules during thoracoscopic wedge resection. Methods Patients who underwent CT-guided percutaneous lung puncture injection of localization agents to locate lung nodules at the First Affiliated Hospital of Fujian Medical University from November 2023 to January 2024 were selected. Under thoracoscopy, lung nodules were located by white light mode, fluorescence mode, or near-infrared mode and wedge resection was performed. The feasibility of using indocyanine green combined with autologous blood and methylene blue for localization of small lung nodules was preliminarily verified by evaluating whether the localization agent concentrated around the nodules, and the safety of this method was verified by analyzing the incidence of adverse reactions during patient puncture and surgery. Results A total of 30 patients with lung nodules were included, including 10 males and 20 females, with an average age of (55.5±11.2) years. In 26 patients, the amount of localization agent used was moderate, the localization agent concentrated around the nodules, and successful precise localization of small lung nodules was achieved. In 4 patients, due to excessive use of localization agent, the marker was diffuse with pleural staining. The overall localization success rate was 86.7%, and when the injection volume of localization agent was 0.2-0.5 mL, the localization success rate was 100.0%. All patients successfully completed thoracoscopic wedge resection and found nodule lesions, with negative margins and a distance from the margin to the lesion that met the requirements. There were no complications. Conclusion Thoracoscopic surgery using indocyanine green combined with autologous blood and methylene blue for localization of small lung nodules is safe and feasible.

Objective To investigate the prognosis and satisfaction of the R2 intervention procedure and develop related predictive models. Methods The clinical data of 64 patients with primary craniofacial hyperhidrosis who underwent R2 intervention surgery at the First Affiliated Hospital of Fujian Medical University from November 2018 to October 2022 were retrospectively analyzed. By statistically analyzing the risk factors for compensatory hyperhidrosis (CH) and satisfaction, and conducting feature screening, a relevant prediction model was established. Results Finally, 51 patients were collected, including 43 (84.3%) males and 8 (15.7%) females, with an average age of (30.27±7.22) years. Overall postoperative satisfaction was high, with only 5.9% of patients expressing regret about the surgery. However, 92.2% of patients experienced CH. The onset of postoperative CH was most prominent within the first 3 months postoperatively, with the incidence rate stabilizing thereafter. Preoperative heart rate and R2 sympathetic nerve clipping were identified as independent risk factors for severe CH. The preoperative body mass index, the degree of sweating in the chest and abdomen, are significantly correlated with postoperative satisfaction. Conclusion The R2 intervention surgery effectively alleviates the symptoms of primary craniofacial hyperhidrosis, and patient satisfaction is high.

Breast milk is the optimal natural food for newborns. However， some newborns cannot receive maternal breast milk due to reasons such as mother-infant separation or insufficient lactation. The establishment of human milk banks （HMB） can effectively address these issues， thereby increasing the breastfeeding rate among hospitalized newborns and improving their quality of survival. However， HMB in China is still in the development and improvement stage. Its implementation involves a series of ethical issues， such as informed consent， privacy protection， economic incentives， quality and safety， and fair resource distribution， which hinder HMB’s widespread promotion. Therefore， discussing the ethical dilemmas faced by the widespread establishment of HMB in China’s hospitals and analyzing coping strategies are crucial for improving the breastfeeding rate of newborns. This paper deeply analyzed and sorted out the ethical issues and challenges currently faced by HMB in China， and proposed corresponding strategies， including “ensuring informed consent and voluntary participation of both donors and recipients，” “protecting the privacy of donors and recipients，” “establishing an ethics-based moral incentive and social support system，” “strictly controlling quality and safety issues”， and “developing fair and rational policies，” aiming to provide a reference solution for addressing ethical concerns in the establishment and operation of HMB.

BACKGROUND: Disease-modifying therapies have been approved for the treatment of relapsing multiple sclerosis (RMS). The present study aims to examine the safety of teriflunomide in Chinese patients with RMS. METHODS: This non-randomized, multi-center, 24-week, prospective study enrolled RMS patients with variant (c.421C>A) or wild type ABCG2 who received once-daily oral teriflunomide 14 mg. The primary endpoint was the relationship between ABCG2 polymorphisms and teriflunomide exposure over 24 weeks. Safety was assessed over the 24-week treatment with teriflunomide. RESULTS: Eighty-two patients were assigned to variant ( n  = 42) and wild type groups ( n  = 40), respectively. Geometric mean and geometric standard deviation (SD) of pre-dose concentration (variant, 54.9 [38.0] μg/mL; wild type, 49.1 [32.0] μg/mL) and area under plasma concentration-time curve over a dosing interval (AUC tau ) (variant, 1731.3 [769.0] μg∙h/mL; wild type, 1564.5 [1053.0] μg∙h/mL) values at steady state were approximately similar between the two groups. Safety profile was similar and well tolerated across variant and wild type groups in terms of rates of treatment emergent adverse events (TEAE), treatment-related TEAE, grade ≥3 TEAE, and serious adverse events (AEs). No new specific safety concerns or deaths were reported in the study. CONCLUSION: ABCG2 polymorphisms did not affect the steady-state exposure of teriflunomide, suggesting a similar efficacy and safety profile between variant and wild type RMS patients. REGISTRATION NCT04410965, https://clinicaltrials.gov .
Humans ; Crotonates/adverse effects* ; Toluidines/adverse effects* ; Nitriles ; Hydroxybutyrates ; Female ; Male ; Adult ; ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics* ; Middle Aged ; Multiple Sclerosis, Relapsing-Remitting/genetics* ; Prospective Studies ; Young Adult ; Neoplasm Proteins/genetics* ; East Asian People

Prostate cancer (PCa) ranks as the second most prevalent malignancy among men worldwide. Early diagnosis, personalized treatment, and prognosis prediction of PCa play a crucial role in improving patients' survival rates. The advancement of artificial intelligence (AI), particularly the utilization of deep learning (DL) algorithms, has brought about substantial progress in assisting the diagnosis, treatment, and prognosis prediction of PCa. The introduction of the foundation model has revolutionized the application of AI in medical treatment and facilitated its integration into clinical practice. This review emphasizes the clinical application of AI in PCa by discussing recent advancements from both pathological and imaging perspectives. Furthermore, it explores the current challenges faced by AI in clinical applications while also considering future developments, aiming to provide a valuable point of reference for the integration of AI and clinical applications.
Humans ; Prostatic Neoplasms/diagnosis* ; Male ; Artificial Intelligence ; Deep Learning ; Prognosis

Objective: To evaluate the feasibility of dynamic contrast-enhanced MRI (DCE-MRI) in differentiating tumor deposits (TDs) from metastatic lymph nodes (MLNs) in rectal cancer. Materials and Methods: A retrospective analysis was conducted on 70 patients with rectal cancer, including 168 lesions (70 TDs and 98 MLNs confirmed by histopathology), who underwent pretreatment MRI and subsequent surgery between March 2019 and December 2022. The morphological characteristics of TDs and MLNs, along with quantitative parameters derived from DCE-MRI (K trans , kep, and v e) and DWI (ADCmin, ADCmax, and ADCmean), were analyzed and compared between the two groups.Multivariable binary logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the diagnostic performance of significant individual quantitative parameters and combined parameters in distinguishing TDs from MLNs. Results: All morphological features, including size, shape, border, and signal intensity, as well as all DCE-MRI parameters showed significant differences between TDs and MLNs (all P < 0.05). However, ADC values did not demonstrate significant differences (all P > 0.05). Among the single quantitative parameters, v e had the highest diagnostic accuracy, with an area under the ROC curve (AUC) of 0.772 for distinguishing TDs from MLNs. A multivariable logistic regression model incorporating short axis, border, v e, and ADC mean improved diagnostic performance, achieving an AUC of 0.833 (P = 0.027). Conclusion The combination of morphological features, DCE-MRI parameters, and ADC values can effectively aid in the preoperative differentiation of TDs from MLNs in rectal cancer.

ObjectiveTo investigate the effects of three traditional Chinese medicine formulas for nourishing kidney Yin on the occurrence of breast cancer， including Zuoguiwan（ZGW）， Liuwei Dihuangwan（LWDHW） and Erzhiwan（EZW）， and to explore their preventive mechanisms from the phagocytic function of macrophages. MethodsTen-month-old post-breeding female mice were randomly divided into the blank group， soy isoflavone group（0.13 g·kg^-1·d^-1， mixed with feed）， ZGW group（2.34 g·kg^-1·d^-1）， LWDHW group（0.56 g·kg^-1·d^-1）， and EZW group（4.68 g·kg^-1·d^-1）. The mice were palpated every 3 d until the age of 18 months， and those with detected lumps were confirmed for tumor development through hematoxylin-eosin（HE） staining， and the incidence of breast cancer in mice was calculated. A total of 40 SPF-grade female SD rats were randomly divided into the blank serum group（physiological saline）， ZGW drug-containing serum group（16.20 g·kg^-1·d^-1of ZGW）， LWDHW drug-containing serum group（3.89 g·kg^-1·d^-1 of LWDHW） and EZW drug-containing serum group（32.40 g·kg^-1·d^-1 of EZW）， each group was orally administered 3 times a day for 5 consecutive days. On the 5^th day， blood was collected from the abdominal aorta 1 h after the last gavage to prepare drug-containing serum. The effect of drug-containing serum with different concentrations on the viability of RAW264.7 cells was assessed by cell counting kit-8（CCK-8）. Taking 20% of drug-containing serum concentration as the research object， its effect on the expression levels of major histocompatibility complex-Ⅱ（MHC-Ⅱ）， CD80 and CD86 on the surface of RAW264.7 cells was detected by immunofluorescence（IF）， the phagocytic function of RAW264.7 cells was examined by flow cytometry， and the levels of interleukin-6（IL-6） and nitric oxide（NO） in RAW264.7 cells in the conditioned medium（CM） co culture system of 4T1 cells were detected by enzyme-linked immunosorbent assay（ELISA） and Griess assay. ResultsAfter prophylactic administration， the tumor incidence rates in the soy isoflavone group（4%）， ZGW group（4%）， LWDHW group（4%）， and EZW group（6%） were lower than that in the blank group（8%）. Compared with the blank serum group， the drug-containing serum of the three nourishing kidney Yin formulas could enhance the expression levels of MHC-Ⅱ， CD80 and CD86 on the surface of RAW264.7 cells， enhance phagocytic ability towards tumor cells， and reduce the content of IL-6 and increase the level of NO（P<0.05， P<0.01）. ConclusionThe three nourishing kidney Yin formulas can reduce the incidence of tumor in mice， the mechanism may be related to activating RAW264.7 cells， increasing their phagocytosis to breast cancer cells， and regulating the secretion of IL-6 and NO.

ObjectiveTo investigate the influence of histone deacetylase 3 (HDAC3) on the occurrence, development of psoriasis-like inflammation in mice, and the relative immune mechanisms. MethodsHealthy C57BL/6 mice aged 6-8 weeks were selected and randomly divided into 3 groups: control group (Control), psoriasis model group (IMQ), and HDAC3 inhibitor RGFP966-treated psoriasis model group (IMQ+RGFP966). One day prior to the experiment, the back hair of the mice was shaved. After a one-day stabilization period, the mice in Control group was treated with an equal amount of vaseline, while the mice in IMQ group was treated with imiquimod (62.5 mg/d) applied topically on the back to establish a psoriasis-like inflammation model. The mice in IMQ+RGFP966 group received intervention with a high dose of the HDAC3-selective inhibitor RGFP966 (30 mg/kg) based on the psoriasis-like model. All groups were treated continuously for 5 d, during which psoriasis-like inflammation symptoms (scaling, erythema, skin thickness), body weight, and mental status were observed and recorded, with photographs taken for documentation. After euthanasia, hematoxylin-eosin (HE) staining was used to assess the effect of RGFP966 on the skin tissue structure of the mice, and skin thickness was measured. The mRNA and protein expression levels of HDAC3 in skin tissues were detected using reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB), respectively. Flow cytometry was employed to analyze neutrophils in peripheral blood and lymph nodes, CD4⁺ T lymphocytes, CD8⁺ T lymphocytes in peripheral blood, and IL-17A secretion by peripheral blood CD4⁺ T lymphocytes. Additionally, spleen CD4⁺ T lymphocyte expression of HDAC3, CCR6, CCR8, and IL-17A secretion levels were analyzed. Immunohistochemistry was used to detect the localization and expression levels of HDAC3, IL-17A, and IL-10 in skin tissues. ResultsCompared with the Control group, the IMQ group exhibited significant psoriasis-like inflammation, characterized by erythema, scaling, and skin wrinkling. Compared with the IMQ group, RGFP966 exacerbated psoriasis-like inflammatory symptoms, leading to increased hyperkeratosis. The psoriasis area and severity index (PASI) skin symptom scores were higher in the IMQ group than those in the Control group, and the scores were further elevated in the IMQ+RGFP966 group compared to the IMQ group. Skin thickness measurements showed a trend of IMQ+RGFP966>IMQ>Control. The numbers of neutrophils in the blood and lymph nodes increased sequentially in the Control, IMQ, and IMQ+RGFP966 groups, with a similar trend observed for CD4⁺ and CD8⁺ T lymphocytes in the blood. In skin tissues, compared with the Control group, the mRNA and protein levels of HDAC3 decreased in the IMQ group, but RGFP966 did not further reduce these expressions. HDAC3 was primarily located in the nucleus. Compared with the Control group, the nuclear HDAC3 content decreased in the skin tissues of the IMQ group, and RGFP966 further reduced nuclear HDAC3. Compared with the Control and IMQ groups, RGFP966 treatment decreased HDAC3 expression in splenic CD4⁺ and CD8⁺ T cells. RGFP966 treatment increased the expression of CCR6 and CCR8 in splenic CD4⁺ T cells and enhanced IL-17A secretion by peripheral blood and splenic CD4⁺ T lymphocytes. Additionally, compared with the IMQ group, RGFP966 reduced IL-10 protein levels and upregulated IL-17A expression in skin tissues. ConclusionRGFP966 exacerbates psoriatic-like inflammatory responses by inhibiting HDAC3, increasing the secretion of the cytokine IL-17A, and upregulating the expression of chemokines CCR8 and CCR6.

In January 2025， the European Society for Medical Oncology （ESMO） released the ESMO clinical practice guideline interim update on the management of biliary tract cancer as a supplementary update to Biliary tract cancer： ESMO clinical practice guideline for diagnosis， treatment and follow-up published in November 2022. This interim update mainly revises the latest evidence-based medical recommendations in the key fields of molecular diagnostics and clinical management since the release of the original guidelines， and it is not a comprehensive update of the entire document. This article summarizes and makes an excerpt of the new recommendations from this interim update.