OBJECTIVE To introduce the development of an intelligent prescription review decision-support system for anti-tumor drugs and assess its clinical application outcomes. METHODS Relevant data sources， including national and local pharmaceutical administration policies， clinical practice guidelines/consensus， hospital information systems data， and genetic testing results， were integrated. Adhering to the principles of structure， standardization and dynamic updating， a knowledge base covering chemotherapeutic， targeted and immunotherapeutic agents was constructed using a dual-dimensional modeling approach that combined “drug attributes” and “clinical contexts”. This knowledge base was then embedded into the hospital’s electronic medical order system to establish the prescription review decision-support system. The application and performance of the system were evaluated at Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. RESULTS A knowledge base containing 18 318 prescription review rules for anti-tumor drugs was constructed， and a closed-loop prescription review system was successfully established， encompassing pre-prescription real-time intervention， in-process interactive review， and post-prescription evaluation and analysis. From 2021 to 2024， the system generated a total of 57 879 alerts for prescriptions of five typical categories of anti-tumor drugs. For platinum-containing prescriptions， 22 577 alerts were generated， with Cisplatin for injection （lyophilized） being the most frequently alerted drug （13 445 alerts）， and “ototoxicity risk due to combined use” alerts remained high （7 682 alerts）. For methotrexate-containing prescriptions， 3 721 alerts were recorded， primarily related to “precaution-related issues” （76.4%， 2 843/3 721）. For doxorubicin-containing prescriptions， 17 301 alerts were triggered， primarily related to “dosage and administration” （14 315 alerts）. For human epidermal growth factor receptor 2-targeted agents-containing prescriptions， 1 007 alerts were issued， mostly related to “reimbursement restrictions” （956 alerts）. For programmed death-1/programmed death-ligand 1 inhibitors-containing prescriptions， the alerts increased year by year， totaling 13 273 alerts， primarily related to “inappropriate indication” （9 118 alerts）. Over the 4 years， the physician response rates to system alerts were 21.4%， 27.1%， 33.5% and 51.6%， respectively. CONCLUSIONS An intelligent decision-support system for anti-tumor drug prescription review， encompassing a closed-loop process of “real-time pre-event intervention， interactive in-event prescription review， post-event evaluation and analysis”， has been successfully constructed and implemented throughout the entire workflow. There is a discernible trend in this hospital， where the focus on monitoring anti-tumor drugs is shifting towards immunotherapy drugs. Additionally， the acceptance rate of physicians regarding prescription review opinions has been steadily increasing year by year.

ObjectiveTo investigate the mechanisms of Tongnao decoction （TND） in mice with acute ischemic stroke （AIS）. MethodsFifty male C57BL/6J mice were randomly divided into a sham operation group， model group， TND low-dose group （1.86 g·kg^-1）， TND high-dose group （3.72 g·kg^-1）， and butylphthalide （NBP） group （10 mg·kg^-1）， with 10 mice in each group. A mouse model of cerebral ischemic injury was established using photochemical thrombosis （PT）. The sham operation group and model group were administered an equal volume of normal saline by gavage. All five groups were treated once daily for 14 consecutive days. Behavioral tests were performed before modeling and at the end of administration. T₂-weighted imaging （T₂WI） was performed 3 days after modeling to evaluate the extent of injury. Hematoxylin-eosin （HE） staining was used to observe histological changes in the cerebral cortex， and Nissl staining was used to observe neuronal morphology. Cerebral blood flow in mice was detected using a laser speckle contrast imaging （LSCI） system. Immunofluorescence staining was used to detect the cell proliferation marker bromodeoxyuridine （BrdU） and the highly glycosylated type I transmembrane glycoprotein CD34. Western blot analysis was used to detect the expression levels of phosphatidylinositol 3-kinase （PI3K）， protein kinase B （Akt）， glycogen synthase kinase-3β （GSK-3β）， and their phosphorylation levels， as well as tight junction-related proteins zonula occludens-1 （ZO-1）， Occludin， and Claudin-5 in the peri-infarct tissue. Thirty-five zebrafish were randomly divided into normal control group， model group， TND low and high dose groups （0.16， 0.32 g·L^-1） and NBP group （10 μmol·L^-1）， with 7 in each group. A stereoscopic fluorescence microscope was used to observe vascular growth in zebrafish. ResultsImaging showed that PT caused ischemia in the right cortical region. Behavioral tests indicated that， compared with the model group， the drug-treated groups reduced the error rate of irregular balance ladder climbing on the affected side and shortened the tape removal time （P<0.05）. HE staining and Nissl staining showed that， compared with the model group， the drug-treated groups exhibited reduced brain tissue damage， fewer scars， and improved neuronal morphology. LSCI results showed that the drug-treated groups partially restored cerebral blood perfusion and promoted the establishment of collateral circulation compared with the model group. Immunofluorescence staining indicated that the drug-treated groups increased the positive rates of BrdU and CD34 compared with the model group （P<0.01）， promoting angiogenesis. Meanwhile， compared with the model group， the drug-treated groups upregulated the expression levels of p-PI3K， p-Akt， p-GSK-3β， and tight junction proteins ZO-1， Occludin， and Claudin-5 （P<0.05，P<0.01）， and increased the number of intersegmental vessels in zebrafish （P<0.05，P<0.01）. ConclusionTND can promote angiogenesis around the infarct in PT model mice by regulating the PI3K/Akt/GSK-3β signaling pathway， thereby improving cerebral ischemic injury.

Objective Isolated bilateral adrenal hematoma(BAH)without other intra-abdominal visceral injuries following trauma is extremely rare. We report a case and review the relevant diagnostic and management experience diagnosis and treatment experience. Case Presentation A 57-year-old male patient presented with systemic pain and discomfort four hours after-traffic collision. Computed tomography(CT)revealed bilateral adrenal contusions with hematoma formation. One week of symptomatic management—including bed rest, oxygen therapy, analgesia, antimicrobial treatment, and nutritional support—was administered. Follow-up abdominal CT demonstrated significant resolution of bilateral adrenal hematomas and surrounding fluid collection. The patient was discharged following rehabilitation therapy. Conclusion For such patients, thorough history-taking regarding past medical history is crucial. When adrenal injury is suspected, contrast-enhanced CT provides definitive diagnosis. Concurrent monitoring of adrenal hormone levels is essential. During bed rest, proactive measures to prevent bed-related complications are required, with long-term follow-up after-discharge.

[This corrects the article DOI: 10.1016/j.apsb.2022.03.002.].

Metformin has been demonstrated to attenuate hyperglycaemia by modulating the gut microbiota. However, the mechanisms through which the microbiome mediates metformin monotherapy failure (MMF) are unclear. Herein, in a prospective clinical cohort study of newly diagnosed type 2 diabetes mellitus (T2DM) patients treated with metformin monotherapy, metagenomic sequencing of faecal samples revealed that Phocaeicola vulgatus abundance was approximately 12 times higher in nonresponders than in responders. P. vulgatus rapidly hydrolysed taurine-conjugated bile acids, leading to ceramide accumulation and reversing the improvements in glucose intolerance conferred by metformin in high-fat diet-fed mice. Interestingly, C22:0 ceramide bound to mitochondrial fission factor to induce mitochondrial fragmentation and impair hepatic oxidative phosphorylation in P. vulgatus-colonized hyperglycaemic mice, which could be exacerbated by metformin. This work suggests that metformin may be unsuitable for P. vulgatus-rich T2DM patients and that clinicians should be aware of metformin toxicity to mitochondria. Suppressing P. vulgatus growth with cefaclor or improving mitochondrial function using adenosylcobalamin may represent simple, safe, effective therapeutic strategies for addressing MMF.

Somatostatin receptor 1 (SSTR1) is a crucial therapeutic target for various neuroendocrine and oncological disorders. Current SSTR1-targeted treatments, including the first-generation somatostatin analog lanreotide (Lan) and the second-generation analog pasireotide (Pas), show promise but encounter challenges related to selectivity and efficacy. This study presents high-resolution cryo-electron microscopy structures of SSTR1 complexed with Lan or Pas, revealing the distinct mechanisms of ligand-binding and activation. These structures illustrate unique conformational changes in the SSTR1 orthosteric pocket induced by each ligand, which are critical for receptor activation and ligand selectivity. Combined with the biochemical assays and molecular dynamics simulations, our results provide a comparative analysis of binding characteristics within the SSTR family, highlighting subtle differences in SSTR1 activation by Lan and Pas. These insights pave the way for designing next-generation therapies with enhanced efficacy and reduced side effects through improved receptor subtype selectivity.

Receptor-interacting protein kinase 1 (RIPK1) plays an essential role in regulating the necroptosis and apoptosis in cerebral ischemia-reperfusion (I/R) injury. However, the regulation of RIPK1 kinase activity after cerebral I/R injury remains largely unknown. In this study, we found the downregulation of protein arginine methyltransferase 1 (PRMT1) was induced by cerebral I/R injury, which negatively correlated with the activation of RIPK1. Mechanistically, we proved that PRMT1 directly interacted with RIPK1 and catalyzed its asymmetric dimethylarginine, which then blocked RIPK1 homodimerization and suppressed its kinase activity. Moreover, pharmacological inhibition or genetic ablation of PRMT1 aggravated I/R injury by promoting RIPK1-mediated necroptosis and apoptosis, while PRMT1 overexpression protected against I/R injury by suppressing RIPK1 activation. Our findings revealed the molecular regulation of RIPK1 activation and demonstrated PRMT1 would be a potential therapeutic target for the treatment of ischemic stroke.

OBJECTIVES: To investigate the therapeutic mechanism of Wendan Decoction for phlegm syndrome in rats with metabolic syndrome (MS). METHODS: Forty Wistar rats were randomly divided into normal control group (n=8) and 3 phlegm syndrome model groups (induced by high-fat, high-sugar, and high-salt feeding and a single-dose intraperitoneal STZ injection; n=24) treated with daily gavage of saline, Wendan Decoction (3.6 g/kg), or metformin (0.1 g/kg) for 4 weeks. General conditions and glucose and lipid metabolism parameters of the rats were monitored, and serum LPS, liver histopathology, hepatic expressions of FXR, CYP7A1 and FGFR4 and ileal expressions of FXR and FGF15 were examined. Gut microbiota structure was analyzed using 16S rDNA sequencing, and serum bile acids were quantified with UHPLC-MS/MS. RESULTS: The rat models of phlegm syndrome exhibited severe hepatic steatosis and necrosis, increased body weight, abdominal circumference, Lee's index, FBG, FINS, HOMA-IR, TG, TC, LDL and LPS, and decreased HDL level. The abundance of Bacteroidetes, Megamonas, and Bacteroides in gut microbiota increased while Firmicutes, Lachnospiraceae_NK4A136_group, isohyodeoxycholic acid, and glycohyodeoxycholic acid decreased significantly; hepatic FXR and FGFR4 expressions and ileal FXR and FGF15 expressions decreased while hepatic CYP7A1 expression increased significantly in the rat models. Treatment with Wendan Decoction effectively alleviated hepatic pathology, reduced body weight and abdominal circumference, improved glucose and lipid metabolic profiles and gut microbiota structure, and reversed the changes in hepatic and ileal protein expressions. Correlation analysis revealed that Firmicutes and Lachnospiraceae_NK4A136_group were positively correlated while Bacteroidetes, Megamonas and Bacteroides were negative correlated with the levels of isohyodeoxycholic acid and hyodeoxycholic acid. CONCLUSIONS Wendan Decoction can significantly improve metabolic profiles in rats with phlegm syndrome of MS possibly by regulating the intestinal flora-bile acid axis to modulate the intestinal flora structure and maintain bile acid homeostasis via the FXR signaling pathway.
Animals ; Gastrointestinal Microbiome/drug effects* ; Metabolic Syndrome/microbiology* ; Bile Acids and Salts/metabolism* ; Rats, Wistar ; Drugs, Chinese Herbal/therapeutic use* ; Rats ; Male ; Fibroblast Growth Factors/metabolism* ; Liver/metabolism* ; Cholesterol 7-alpha-Hydroxylase/metabolism* ; Receptors, Cytoplasmic and Nuclear/metabolism*

Infectious keratitis (IK) is a leading cause of blindness worldwide, primarily resulting from improper contact lens use, trauma, and a compromised immune response. The pathogenic microorganisms responsible for IK include bacteria, fungi, viruses, and Acanthamoeba. This review examines standard therapeutic agents for treating IK, including broad-spectrum empiric antibiotics for bacterial keratitis (BK), antifungals such as voriconazole and natamycin for fungal infections, and antiviral nucleoside analogues for viral keratitis (VK). Additionally, this review discusses therapeutic agents, such as polyhexamethylene biguanide (PHMB), for the treatment of Acanthamoeba keratitis (AK). The review also addresses emerging drugs and the challenges associated with their clinical application, including anti-biofilm agents that combat drug resistance and nuclear factor kappa-B (NF-κB) pathway-targeted therapies to mitigate inflammation. Furthermore, methods of Photodynamic Antimicrobial Therapy (PDAT) are explored. This review underscores the importance of integrating novel and traditional therapies to tackle drug resistance and enhance drug delivery, with the goal of advancing treatment strategies for IK.

The injury of the posterior Angle of the medial meniscus of the knee joint is very common in clinic, and the arthroscopic treatment of the knee joint has been the first choice. However, there are many difficulties in arthroscopic treatment, such as narrow space in the medial posterior corner of the knee joint, insufficient space to deal with the injured meniscus, varion and lateral rotation under 30° flexion, release of the medial collateral ligament of the knee joint, and expansion of the knee joint cavity spinner, all of which could expose and expand the medial space of knee joint. Therefore, it is necessary to master and balance the use to avoid collateral injury. It is also necessary to determine the cause of meniscus injury during arthroscopic treatment, such as degenerative injury, simple meniscus repair and forming can hardly solve the pain of patients. Anterior cross injury is easy to cause instability of the knee joint, which is closely related to the injury of the posterior angle of the medial meniscus of the knee joint. In order to achieve the maximum therapeutic effect, physiological repair should be performed at the same time. There are various types of medial meniscus posterior angle injury, among which the Ramp injury, root fracture and laminae meniscus injury are greatly affected by joint degeneration, narrow knee space or knee stability, and all influencing factors should be fully considered in treatment.
Humans ; Arthroscopy/methods* ; Tibial Meniscus Injuries/surgery* ; Knee Joint/surgery* ; Menisci, Tibial/surgery* ; Knee Injuries/surgery*