Infectious keratitis(IK)is a major blinding eye disease worldwide. Early diagnosis and treatment are crucial for improving prognosis and reducing the economic burden. This article reviews advances in the diagnosis and treatment of IK, aiming to provide new insights for clinical management. In terms of diagnosis, in addition to conventional methods such as microbial culture and confocal microscopy, molecular diagnostic technologies—including high-throughput sequencing(NGS), CRISPR, and nanotechnology-based systems—have significantly enhanced the sensitivity and specificity of multiplex pathogen detection. These approaches are particularly valuable for identifying mixed infections and rare pathogens. Regarding treatment, in response to the growing challenge of drug resistance, novel drug delivery systems employing nanotechnology and bioactive dressings have markedly improved antibacterial efficacy by enhancing drug penetration and retention. Immunomodulatory therapy and photodynamic therapy effectively control inflammatory responses and improve outcomes. Integrated traditional Chinese and Western medicine, as well as microbiome-based therapies, have demonstrated significant advantages in reducing recurrence rates. Stem cell therapy offers new hope for repairing severe corneal damage, while gene therapy—through gene editing or transduction—strengthens the innate defense mechanisms of the cornea and reduces treatment-related side effects.

Immunotherapy, including immune checkpoint inhibitors, tumor vaccine therapy, oncolytic virotherapy, and adoptive cell therapy, has made remarkably breakthroughs in the field of oncology. Immune checkpoint inhibitors, which block programmed death receptor 1 or programmed death ligand 1, have been included in the first-line clinical treatment for advanced solid tumors, such as non-small cell lung cancer and malignant melanoma. However, primary or secondary drug resistance in tumors severely limits the survival benefits for patients. Immune-related adverse reactions, such as pneumonia, hypothyroidism, hypophysitis, and myocarditis, also greatly affect the quality of life of patients. Fuzheng Jiedu Huayu is an important concept guiding the prevention and treatment of tumors with traditional Chinese medicine (TCM). It is also a curative principle and therapeutic TCM method to reduce the toxicity and enhance the efficacy of immunotherapy. This article summarizes the research progress of immunotherapy and discusses how TCM reduces the toxicity and enhances the efficacy of immunotherapy, hoping to provide a reference for the integrated treatment of tumors with TCM and immunotherapy.

ObjectiveThe theory of homotherapy for heteropathy is one of the classical rules in traditional Chinese medicine. Taking this theory as a breakthrough point， this study employed gas chromatography-mass spectrometry （GC-MS） to elucidate the mechanism underlying the therapeutic effects of Zhuyuwan on both intrahepatic cholestasis （IC） and ulcerative colitis （UC） from the viewpoint of serum metabolic homeostasis. MethodsThe rat models of α-naphthylisothiocyanate （ANIT）-induced cholestasis and 2，4，6-trinitro-benzenesulfonic acid （TNBS）-induced UC were treated with low （0.6 g·kg^-1） and high （1.2 g·kg^-1） doses of Zhuyuwan by gavage. In the experiment regarding IC， 24 Sprague-Dawley （SD） rats were randomly assigned into four groups： normal， ANIT model， low-dose Zhuyuwan， and high-dose Zhuyuwan. In the experiment regarding UC， 24 SD rats were randomly allocated into four groups： normal， TNBS model， low-dose Zhuyuwan， and high-dose Zhuyuwan. Firstly， the two disease models and the intervention effects of Zhuyuwan on the two diseases were evaluated based on serum levels of biochemical indicators ［alanine aminotransferase （ALT）， aspartate transaminase （AST）， γ-glutamyltranspeptidase （γ-GT）， and total bile acid （TBA）］， colon damage score， colon weight index， disease activity index， and histopathological changes in rats. Secondly， the rat serum samples were analyzed by gas chromatography-mass spectrometry （GC-MS） to screen the common core pathways of the two disease models， and the expression of core genes in the pathways was determined by Real-time PCR， on the basis of which the biological mechanism of the treatment of the two disease models by Zhuyuwan was ultimately elucidated. ResultsThe results of the experiment regarding IC showed that the ANIT model group had higher ALT， AST， γ-GT， and TBA levels than the normal group （P<0.01）. Compared with the ANIT model group， the low-dose Zhuyuwan group showed declined ALT and TBA levels （P<0.01） and the high-dose Zhuyuwan group showed lowered ALT， TBA， AST， and γ-GT levels （P<0.01）. The results of the experiment regarding UC showed that compared with the normal group， the TNBS model group presented increases in the colonic damage score， colon weight index， and disease activity index （P<0.01）. Compared with the TNBS model group， the low-dose Zhuyuwan group showcased declines in colon weight index （P<0.01） and disease activity index （P<0.05）， and the high-dose Zhuyuwan group showed reductions in the colon damage score， colon weight index， and disease activity index （P<0.01）. GC-MS metabolomics analysis combined with qRT-PCR demonstrated that Zhuyuwan had a similar inverse regulatory effect on arginine metabolism disruption in the above two disease models. ConclusionZhuyuwan exhibited definite therapeutic effects on both IC and UC， and the regulation of arginine biosynthesis pathway is the core mechanism for the treatment of both diseases by Zhuyuwan.

ObjectiveThe theory of homotherapy for heteropathy is one of the classical rules in traditional Chinese medicine. Taking this theory as a breakthrough point， this study employed gas chromatography-mass spectrometry （GC-MS） to elucidate the mechanism underlying the therapeutic effects of Zhuyuwan on both intrahepatic cholestasis （IC） and ulcerative colitis （UC） from the viewpoint of serum metabolic homeostasis. MethodsThe rat models of α-naphthylisothiocyanate （ANIT）-induced cholestasis and 2，4，6-trinitro-benzenesulfonic acid （TNBS）-induced UC were treated with low （0.6 g·kg^-1） and high （1.2 g·kg^-1） doses of Zhuyuwan by gavage. In the experiment regarding IC， 24 Sprague-Dawley （SD） rats were randomly assigned into four groups： normal， ANIT model， low-dose Zhuyuwan， and high-dose Zhuyuwan. In the experiment regarding UC， 24 SD rats were randomly allocated into four groups： normal， TNBS model， low-dose Zhuyuwan， and high-dose Zhuyuwan. Firstly， the two disease models and the intervention effects of Zhuyuwan on the two diseases were evaluated based on serum levels of biochemical indicators ［alanine aminotransferase （ALT）， aspartate transaminase （AST）， γ-glutamyltranspeptidase （γ-GT）， and total bile acid （TBA）］， colon damage score， colon weight index， disease activity index， and histopathological changes in rats. Secondly， the rat serum samples were analyzed by gas chromatography-mass spectrometry （GC-MS） to screen the common core pathways of the two disease models， and the expression of core genes in the pathways was determined by Real-time PCR， on the basis of which the biological mechanism of the treatment of the two disease models by Zhuyuwan was ultimately elucidated. ResultsThe results of the experiment regarding IC showed that the ANIT model group had higher ALT， AST， γ-GT， and TBA levels than the normal group （P<0.01）. Compared with the ANIT model group， the low-dose Zhuyuwan group showed declined ALT and TBA levels （P<0.01） and the high-dose Zhuyuwan group showed lowered ALT， TBA， AST， and γ-GT levels （P<0.01）. The results of the experiment regarding UC showed that compared with the normal group， the TNBS model group presented increases in the colonic damage score， colon weight index， and disease activity index （P<0.01）. Compared with the TNBS model group， the low-dose Zhuyuwan group showcased declines in colon weight index （P<0.01） and disease activity index （P<0.05）， and the high-dose Zhuyuwan group showed reductions in the colon damage score， colon weight index， and disease activity index （P<0.01）. GC-MS metabolomics analysis combined with qRT-PCR demonstrated that Zhuyuwan had a similar inverse regulatory effect on arginine metabolism disruption in the above two disease models. ConclusionZhuyuwan exhibited definite therapeutic effects on both IC and UC， and the regulation of arginine biosynthesis pathway is the core mechanism for the treatment of both diseases by Zhuyuwan.

Objective To explore the clinical characteristics of immune-related adverse events (irAEs) involving the pituitary gland in malignant tumor patients following the administration of immune checkpoint inhibitors (ICIs), and to compare characteristics of pituitary irAEs with primary hypophysitis. Methods A total of 753 malignant tumor patients who were hospitalized at Sir Run Run Shaw Hospital School of Medicine, Zhejiang University from January 2019 to November 2022 and received ICIs treatment were retrospectively included. The incidence of endocrine irAEs were statistically analyzed. The clinical characteristics of patients with pituitary irAEs were analyzed and compared with those of patients with primary hypophysitis (n＝18). Results Among the 753 patients treated with ICIs, the majority (742, 98.5%) received PD-1/PD-L1 inhibitors. The incidence of endocrine irAEs was 32.0% (241/753), with primary thyroid dysfunction being most common (212, 28.2%), followed by pituitary dysfunction (35, 4.6%). The median time to onset of pituitary irAEs was 5.8 months, with the majority presenting as secondary hypoadrenocorticism (33, 94.3%). Surgery was a protective factor for preventing pituitary irAEs (P＝0.002), whereas higher body mass index (BMI) and dual ICIs combination therapy were recognized as risk factors (P＜0.05). Compared to patients with primary hypophysitis, patients with pituitary irAEs had a higher proportion of males, lower BMI, lower rates of visual field defects and diabetes insipidus, higher rate of secondary hypoadrenocorticism and lower positive rate on MRI (P＜0.05). Conclusions Malignant tumor patients treated with ICIs exhibit a relatively high incidence of endocrine irAEs, with thyroid involvement being most common, followed by the pituitary gland. Pituitary irAEs primarily manifest as secondary hypoadrenocorticism, lacking specific clinical symptoms and exhibiting a low positive rate on MRI. These factors contribute to a high risk of misdiagnosis or missed diagnosis, necessitating heightened clinical vigilance.

Voice biomarkers， as an emerging smart medical technology， are now being used in applications such as assisting in the diagnosis and treatment of diseases， facilitating accurate and personalized medical services for patients. However， it also raises many ethical issues， including informed consent， privacy protection， accuracy and reliability， data security， legal risks， and other issues. This paper systematically sorted out the ethical issues in the applications of voice biomarkers in the medical field， summarized these issues， such as informed consent， privacy protection， accuracy and reliability， data security， and legal risks， as well as explored the corresponding coping strategies. These countermeasures encompassed utilizing new media platforms to raise public awareness of voice biomarkers， strengthening supervision and management to promote the privacy protection of voice biomarkers， reducing algorithm biases to promote the general benefits of voice biomarkers to the public， establishing multidisciplinary teams to protect the data security of voice biomarkers， and encouraging medical professionals and researchers to participate in policy research， with a view to providing references for promoting and regulating the applications of voice biomarkers in the medical field.

Gliomas are the most common primary neuroepithelial tumors of the central nervous system in adults, of which glioblastoma is the deadliest subtype. Apart from the intrinsically indestructible characteristics of glioma (stem) cells, accumulating evidence suggests that the tumor microenvironment also plays a vital role in the refractoriness of glioblastoma. The primary functions of platelets are to stop bleeding and regulate thrombosis under physiological conditions. Furthermore, platelets are also active elements that participate in a variety of processes of tumor development, including tumor growth, invasion, and chemoresistance. Glioma cells recruit and activate resting platelets to become tumor-educated platelets (TEPs), which in turn can promote the proliferation, invasion, stemness, and chemoresistance of glioma cells. TEPs can be used to obtain genetic information about gliomas, which is helpful for early diagnosis and monitoring of therapeutic effects. Platelet membranes are intriguing biomimetic materials for developing efficacious drug carriers to enhance antiglioma activity. Herein, we review the recent research referring to the contribution of platelets to the malignant characteristics of gliomas and focusing on the molecular mechanisms mediating the interaction between TEPs and glioma (stem) cells, as well as present the challenges and opportunities in targeting platelets for glioma therapy.
Humans ; Glioma/metabolism* ; Blood Platelets/physiology* ; Brain Neoplasms/pathology* ; Tumor Microenvironment

Renal autotransplantation (RA) offers significant technical advantages for the management of certain complex renal vascular diseases, such as complex renal aneurysms and renal artery malformations. This report describes a case of a 5-year-old child with a complex left renal artery aneurysm combined with multiple aneurysms. The child was admitted to Peking University People's Hospital in December 2023 due to a one-year history of intermittent abdominal pain, with an abdominal mass detected in the past month. Computed tomography angiography(CTA) revealed multiple vascular anomalies, including: (1) a left renal artery aneurysm, (2) an abdominal aortic aneurysm, and (3) a right iliac artery aneurysm. After a comprehensive evaluation of these findings, the surgical team developed a treatment plan that involved the excision of the left renal artery aneurysm, autotransplantation of the left kidney, and resection of the abdominal aortic aneurysm with an artificial vascular catheterization. During surgery, it was discovered that the left renal artery anatomy was highly complex. The artery had two primary branches, along with an additional polar artery located at the lower pole. The aneurysm was identified at the distal end of the renal artery trunk, with a pronounced bulging at the intersection between the main renal artery trunk and its secondary branches. Due to these structural complexities, the team decided to use an ex vivo surgical approach to repair the aneurysm. Ex vivo repair involves temporarily removing the kidney from the body to repair the renal artery aneurysm with enhanced precision, enabling the surgical team to meticulously reconstruct the complex vascular architecture without the constraints of in vivo manipulation. The ex vivo repair of the renal artery aneurysm was successful, allowing for accurate vascular reconstruction and avoiding potential intraoperative complications. Following the reconstruction, the kidney was autotransplanted back into the child's body, and blood flow was effectively restored to the organ. The therapeutic outcome was excellent, with the child experiencing no postoperative complications. The patient recovered well and was discharged from the hospital in stable condition. This case underscores the value of renal autotransplantation combined with ex vivo repair for pediatric patients with complicated renal artery aneurysms. Through this report, we aim to provide insights and considerations for the surgical treatment of similar cases in children with complex renal vascular anatomy.
Child, Preschool ; Humans ; Aneurysm/surgery* ; Aortic Aneurysm, Abdominal/diagnostic imaging* ; Computed Tomography Angiography ; Iliac Aneurysm/surgery* ; Kidney Transplantation/methods* ; Renal Artery/abnormalities* ; Transplantation, Autologous

The aryl hydrocarbon receptor (AhR) plays a crucial role in regulating many physiological processes. Activating the AhR-CYP1A1 axis has emerged as a novel therapeutic strategy against various inflammatory diseases. Here, a practical in situ cell-based fluorometric assay was constructed to screen AhR-CYP1A1 axis modulators, via functional sensing of CYP1A1 activities in live cells. Firstly, a cell-permeable, isoform-specific enzyme-activable fluorogenic substrate for CYP1A1 was rationally constructed for in-situ visualizing the dynamic changes of CYP1A1 function in living systems, which was subsequently used for discovering the efficacious modulators of the AhR-CYP1A1 axis. Following screening of a compound library, LAC-7 was identified as an efficacious activator of the AhR-CYP1A1 axis, which dose-dependently up-regulated the expression levels of both CYP1A1 and AhR in multiple cell lines. LAC-7 also suppressed macrophage M1 polarization and reduced the levels of inflammatory factors in LPS-induced bone marrow-derived macrophages. Animal tests showed that LAC-7 could significantly mitigate DSS-induced ulcerative colitis and LPS-induced acute lung injury in mice, and markedly reduced the levels of multiple inflammatory factors. Collectively, an optimized fluorometric cell-based assay was devised for in situ functional imaging of CYP1A1 activities in living systems, which strongly facilitated the discovery of efficacious modulators of the AhR-CYP1A1 axis as novel anti-inflammatory agents.

Alzheimer's disease (AD) is a common neurodegenerative disorder among the elderly, and BuChE has emerged as a potential therapeutic target. In this study, we reported the development of compound 8e, a selective reversible BuChE inhibitor (eqBuChE IC₅₀ = 0.049 μmol/L, huBuChE IC₅₀ = 0.066 μmol/L), identified through extensive virtual screening and lead optimization. Compound 8e demonstrated favorable blood-brain barrier permeability, good drug-likeness property and pronounced neuroprotective efficacy. Additionally, 8e exhibited significant therapeutic effects in zebrafish AD models and scopolamine-induced cognitive impairments in mice. Further, 8e significantly improved cognitive function in APP/PS1 transgenic mice. Proteomics analysis demonstrated that 8e markedly elevated the expression levels of very low-density lipoprotein receptor (VLDLR), offering valuable insights into its potential modulation of the Reelin-mediated signaling pathway. Thus, compound 8e emerges as a novel and potent BuChE inhibitor for the treatment of AD, with significant implications for further exploration into its mechanisms of action and therapeutic applications.