OBJECTIVE To construct a closed-loop management model for externally dispensed intravenous prescriptions， and to provide reference for standardized management of externally dispensed intravenous prescriptions. METHODS Based on the Expert Consensus on Closed-loop Management of Externally Dispensed Intravenous Prescriptions in Guangxi Zhuang Autonomous Region previously formulated by our hospital， risk points during the entire process were systematically identified through multidisciplinary team brainstorming and a fishbone diagram. A series of strategies were subsequently formulated and implemented， including qualifying designated external dispensing pharmacies and the drug catalogs， operating and maintaining the hospital information system and the Pharmacy Intravenous Admixture Service （PIVAS） intelligent management platform， and strengthening differentiated training for staff in the whole workflow. A whole-process closed-loop management system was constructed with PIVAS as the co re hub and the daytime chemotherapy center as the safety terminal. RESULTS A total of 3 cooperating pharmacies and an initial drug list comprising 35 product specifications were selected. A closed‑loop management process encompassing hospital outpatient prescribing， patient drug purchase in designated pharmacies， PIVAS drug dispensing， and medication use in daytime chemotherapy center was successfully established. This system enabled the mandatory grouping and association of externally dispensed intravenous prescriptions with in-hospital diluents， full-process verification based on drug traceability codes， intelligent monitoring of infusion parameters， and whole-process data traceability. CONCLUSIONS The constructed model effectively resolves the coordination and safety oversight during the use of externally dispensed intravenous drugs from out-of-hospital circulation to in-hospital use， and has preliminarily enabled procedural standardization， whole-process information traceability， and proactive control of medication risks.

The study investigated the specific mechanism by which oxocrebanine, the anti-hepatic cancer active ingredient in Stephania hainanensis, inhibits the proliferation of hepatic cancer cells. Firstly, methyl thiazolyl tetrazolium(MTT) assay, 5-bromodeoxyuridine(BrdU) labeling, and colony formation assay were employed to investigate whether oxocrebanine inhibited the proliferation of HepG2 and Hep3B2.1-7 cells. Propidium iodide(PI) staining was used to observe the oxocrebanine-induced apoptosis of HepG2 and Hep3B2.1-7 cells. Western blot was employed to verify whether apoptotic effector proteins, such as cleaved cysteinyl aspartate-specific protease 3(c-caspase-3), poly(ADP-ribose) polymerase 1(PARP1), B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), Bcl-2 homologous killer(Bak), and myeloid cell leukemia-1(Mcl-1) were involved in apoptosis. Secondly, HepG2 cells were simultaneously treated with oxocrebanine and the autophagy inhibitor 3-methyladenine(3-MA), and the changes in the autophagy marker LC3 and autophagy-related proteins [eukaryotic translation initiation factor 4E-binding protein 1(4EBP1), phosphorylated 4EBP1(p-4EBP1), 70-kDa ribosomal protein S6 kinase(P70S6K), and phosphorylated P70S6K(p-P70S6K)] were determined. The results of MTT assay, BrdU labeling, and colony formation assay showed that oxocrebanine inhibited the proliferation of HepG2 and Hep3B2.1-7 cells in a dose-dependent manner. The results of flow cytometry suggested that the apoptosis rate of HepG2 and Hep3B2.1-7 cells increased after treatment with oxocrebanine. Western blot results showed that the protein levels of c-caspase-3, Bax, and Bak were up-regulated and those of PARP1, Bcl-2, and Mcl-1 were down-regulated in the HepG2 cells treated with oxocrebanine. The results indicated that oxocrebanine induced apoptosis, thereby inhibiting the proliferation of hepatic cancer cells. The inhibition of HepG2 cell proliferation by oxocrebanine may be related to the induction of protective autophagy in hepatocellular carcinoma cells. Oxocrebanine still promoted the conversion of LC3-Ⅰ to LC3-Ⅱ, reduced the phosphorylation levels of 4EBP1 and P70S6K, which can be reversed by the autophagy inhibitor 3-MA. It is prompted that oxocrebanine can inhibit the proliferation of hepatic cancer cells by inducing autophagy. In conclusion, oxocrebanine inhibits the proliferation of hepatic cancer cells by inducing apoptosis and autophagy.
Humans ; Apoptosis/drug effects* ; Autophagy/drug effects* ; Cell Proliferation/drug effects* ; Hep G2 Cells ; Liver Neoplasms/genetics* ; Carcinoma, Hepatocellular/genetics* ; Caspase 3/genetics*

Poor water solubility is the primary obstacle preventing the development of many pharmacologically active compounds into oral preparations. Self-nanoemulsifying drug delivery systems(SNEDDS) have become a widely used strategy to enhance the oral bioavailability of poorly soluble drugs by inducing a supersaturated state, thereby improving their apparent solubility and dissolution rate. However, the supersaturated solutions formed in SNEDDS are thermodynamically unstable systems with solubility levels exceeding the crystalline equilibrium solubility, making them prone to drug precipitation in the gastrointestinal tract and ultimately hindering drug absorption. Therefore, maintaining a stable supersaturated state is crucial for the effective delivery of poorly soluble drugs. Incorporating polymers as precipitation inhibitors(PPIs) into the formulation of supersaturated self-nanoemulsifying drug delivery systems(S-SNEDDS) can inhibit drug aggregation and crystallization, thus maintaining a stable supersaturated state. This has emerged as a novel preparation strategy and a key focus in SNEDDS research. This review explores the preparation design of SNEDDS and the technical challenges involved, with a particular focus on polymer-based S-SNEDDS for enhancing the solubility and oral bioavailability of poorly soluble drugs. It further elucidates the mechanisms by which polymers participate in transmembrane transport, summarizes the principles by which polymers sustain a supersaturated state, and discusses strategies for enhancing drug absorption. Altogether, this review provides a structured framework for the development of S-SNEDDS preparations with stable quality and reduced development risk, and offers a theoretical reference for the application of S-SNEDDS technology in improving the oral bioavailability of poorly soluble drugs.
Solubility ; Administration, Oral ; Polymers/chemistry* ; Drug Delivery Systems/methods* ; Humans ; Emulsions/chemistry* ; Biological Availability ; Animals ; Pharmaceutical Preparations/administration & dosage*

OBJECTIVE: To investigate the role and mechanism of the cyclic guanosine monophosphate-adenosine monophosphate synthase/stimulator of interferon gene (cGAS/STING) pathway in oleic acid-induced acute lung injury (ALI) in mice. METHODS: Male wild-type C57BL/6J mice were randomly divided into five groups (each n = 10): normal control group, ALI model group, and 5, 50, 500 μg/kg inhibitor pretreatment groups. The ALI model was established by tail vein injection of oleic acid (7 mL/kg), while the normal control group received no intervention. The inhibitor pretreatment groups were intraperitoneally injected with the corresponding doses of cGAS inhibitor RU.521 respectively 1 hour before modeling. At 24 hours post-modeling, blood was collected, and mice were sacrificed. Lung tissue pathological changes were observed under light microscopy after hematoxylin-eosin (HE) staining, and pathological scores were assessed. Western blotting was used to detect the protein expressions of cGAS, STING, phosphorylated TANK-binding kinase 1 (p-TBK1), phosphorylated interferon regulatory factor 3 (p-IRF3), and phosphorylated nuclear factor-κB p65 (p-NF-κB p65) in lung tissue. Immunohistochemistry was performed to observe STING and p-NF-κB positive expressions in lung tissue. Serum interferon-β (IFN-β) levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Compared with the normal control group, the ALI model group exhibited significant focal alveolar thickening, intra-alveolar hemorrhage, pulmonary capillary congestion, and neutrophil infiltration in the pulmonary interstitium and alveoli, along with markedly increased pathological scores (10.33±0.58 vs. 1.33±0.58, P < 0.05). Protein expressions of cGAS, STING, p-TBK1, p-IRF3, and p-NF-κB p65 in lung tissue significantly increased [cGAS protein (cGAS/β-actin): 1.24±0.02 vs. 0.56±0.02, STING protein (STING/β-actin): 1.27±0.01 vs. 0.55±0.01, p-TBK1 protin (p-TBK1/β-actin): 1.34±0.03 vs. 0.22±0.01, p-IRF3 protein (p-IRF3/β-actin): 1.23±0.02 vs. 0.36±0.01, p-NF-κB p65 protein (p-NF-κB p65/β-actin): 1.30±0.02 vs. 0.53±0.02, all P < 0.05], positive expressions of STING and p-NF-κB in lung tissue were significantly elevated [STING (A value): 0.51±0.03 vs. 0.30±0.07, p-NF-κB (A value): 0.57±0.05 vs. 0.31±0.03, both P < 0.05], and serum IFN-β levels were also significantly higher (ng/L: 256.02±3.84 vs. 64.15±1.17, P < 0.05). The cGAS inhibitor pretreatment groups showed restored alveolar structural integrity, reduced inflammatory cell infiltration, and decreased hemorrhage area, along with dose-dependent lower pathological scores as well as the protein expressions of cGAS, STING, p-TBK1, p-IRF3 and p-NF-κB p65 in lung tissue, with significant differences between the 500 μg/kg inhibitor group and ALI model group [pathological score: 2.67±0.58 vs. 10.33±0.58, cGAS protein (cGAS/β-actin): 0.56±0.03 vs. 1.24±0.02, STING protein (STING/β-actin): 0.67±0.03 vs. 1.27±0.01, p-TBK1 protein (p-TBK1/β-actin): 0.28±0.01 vs. 1.34±0.03, p-IRF3 protein (p-IRF3/β-actin): 0.32±0.01 vs. 1.23±0.02, p-NF-κB p65 protein (p-NF-κB p65/β-actin): 0.63±0.01 vs. 1.30±0.02, all P < 0.05]. Compared with the ALI model group, positive expressions of STING and p-NF-κB in lung tissue were significantly reduced in the 500 μg/kg inhibitor group [STING (A value): 0.40±0.01 vs. 0.51±0.03, p-NF-κB (A value): 0.43±0.02 vs. 0.57±0.05, both P < 0.05], and serum IFN-β levels were also markedly reduced (ng/L: 150.03±6.19 vs. 256.02±3.84, P < 0.05). CONCLUSIONS The cGAS/STING pathway is activated in oleic acid-induced ALI, leading to exacerbated inflammatory responses and increased lung damage. RU.521 can inhibit cGAS, thereby down-regulating the expression of pathway proteins and cytokines, and providing protection to lung tissue.
Animals ; Acute Lung Injury/chemically induced* ; Male ; Nucleotidyltransferases/metabolism* ; Mice ; Signal Transduction ; Mice, Inbred C57BL ; Membrane Proteins/metabolism* ; Oleic Acid/adverse effects* ; Transcription Factor RelA/metabolism* ; Lung/pathology* ; Interferon Regulatory Factor-3/metabolism* ; Disease Models, Animal

Objective To evaluate the application value of four-dimensional CT(4D-CT)in the preoperative localization of primary hyperparathyroidism(PHPT). Methods A retrospective analysis was conducted on the clinical data and parathyroid 4D-CT images of 63 patients who underwent PHPT surgery at Peking Union Medical College Hospital between April 2020 and April 2023.Based on the clinical experience of the hospital's surgeons,parathyroid lesions were categorized into six anatomical regions:around the upper pole of the thyroid,posterior to the mid-thyroid,posterior to the lower pole of the thyroid and the tracheoesophageal groove,below the lower pole of the thyroid and the suprasternal fossa,retrosternal anterior mediastinum,and other rare locations.All images were independently analyzed by two experienced radiologists,with discrepancies resolved through discussion led by a senior radiologist.Using pathological results as the gold standard,the accuracy,sensitivity,specificity,positive predictive value(PPV),negative predictive value(NPV),Youden index,positive likelihood ratio(PLR),and negative likelihood ratio(NLR)of preoperative 4D-CT in diagnosing PHPT were calculated. Results There were no statistically significant differences between preoperative 4D-CT and surgical localization in the following regions:around the upper pole of the thyroid(χ²=0.500,P=0.480),posterior to the mid-thyroid(χ²<0.001,P>0.999),posterior to the lower pole of the thyroid and the tracheoesophageal groove(χ²=0.571,P=0.450),below the lower pole of the thyroid and the suprasternal fossa(χ²<0.001,P>0.999),retrosternal anterior mediastinum(χ²<0.001,P>0.999),and other rare locations(χ²<0.001,P>0.999).The preoperative 4D-CT diagnosis of PHPT lesions demonstrated a sensitivity of 82.09%,specificity of 97.43%,PPV of 87.30%,NPV of 96.19%,accuracy of 94.71%,Youden index of 79.52%,PLR of 31.94,and NLR of 0.18. Conclusion Parathyroid 4D-CT demonstrates good diagnostic efficacy in the preoperative localization of PHPT.
Humans ; Hyperparathyroidism, Primary/surgery* ; Retrospective Studies ; Four-Dimensional Computed Tomography ; Male ; Female ; Middle Aged ; Adult ; Aged ; Parathyroid Glands/diagnostic imaging* ; Preoperative Period

Objective To construct a logistic regression prediction model for stress ulcer(SU)after cerebral hemorrhage.Methods A total of 230 patients with cerebral hemorrhage admitted to our hospital from January 2020 to January 2023 were prospectively selected as the study subjects.They were randomly di-vided into a training group and a validation group using a random number table method,with 115 patients in each group.The incidence of postoperative SU was statistically compared between the two groups.The least absolute shrinkage and selection operator(Lasso)and logistic regression were used to analyze the influencing factors of SU after cerebral hemorrhage,and a logistic regression prediction model was established and valida-ted.Results The incidence of SU was 19.13%in the training group and 20.00%in the validation group.In-crement of age,blood loss≥30 mL,higher levels of neutrophil-to-lymphocyte ratio(NLR),heat shock protein 70(HSP70)and HSP90 were identified as independent risk factors for SU after cerebral hemorrhage(P<0.05),while lower levels of Glasgow Coma Scale(GCS)score and albumin(Alb)were protective factors(P<0.05).The prediction model was logit(P)=0.409×age+1.288×blood loss-1.335×GCS score-1.126×Alb+0.452×NLR+1.483×HSP70+1.593×HSP90-10.325.The areas under the receiver operat-ing characteristic(ROC)curve(AUC)for the training group and the validation group were 0.845(95%CI:0.765-0.906)and 0.855(95%CI:0.777-0.913),respectively.The sensitivities were 81.82%and 90.91%,and the specificities were 76.34%and 70.97%,respectively.Conclusion A logistic regression prediction model was successfully constructed,which has certain predictive value for SU after cerebral hemorrhage.

Glioblastoma (GBM) is a highly aggressive primary brain tumor characterized by poor prognosis. Conventional chemo-radiotherapy demonstrates limited therapeutic efficacy and is often accompanied by significant side effects, largely due to factors such as drug resistance, radiation resistance, the presence of the blood-brain barrier (BBB), and the activation of DNA damage repair mechanisms. There is a pressing need to enhance treatment efficacy, with BRD4 identified as a promising target for increasing GBM sensitivity to therapy. Lacking small molecule inhibitors, BRD4 can be degraded using PROteolysis Targeting Chimera (PROTAC), thereby inhibiting DNA damage repair. To deliver PROTAC, SIAIS171142 (SIS) effectively, we designed a responsive nanocapsule, MPL_(SS)P@SIS, featuring GBM-targeting and GSH-responsive drug release. Modified with 1-methyl-l-tryptophan (MLT), nanocapsules facilitate targeted delivery of SIS, downregulating BRD4 and sensitizing GBM cells to radiotherapy and chemotherapy. After intravenous administration, MPL_(SS)P@SIS selectively accumulates in tumor tissue, enhancing the effects of radiotherapy and temozolomide (TMZ) by increasing DNA damage and oxidative stress. GSH activates the nanocapsules, triggering BRD4 degradation and hindering DNA repair. In mouse models, the nanosensitizer, combined with TMZ and X-ray irradiation, efficiently inhibited the growth of GBM. These findings demonstrate a novel PROTAC-based sensitization strategy targeting BRD4, offering a promising approach for effective GBM therapy.

OBJECTIVES: To explore the efficacy of DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy for management of cancer pain and provide reference for its standardized clinical application. Methods and. RESULTS: Recommendations were formulated based on literature review and expert group discussion, and consensus was reached following expert consultation. The consensus recommendations are comprehensive, covering the entire treatment procedures from preoperative assessment and preparation, surgical operation process, postoperative management and traditional Chinese medicine treatment to individualized treatment planning. The study results showed that the treatment plans combining traditional Chinese with Western medicine effectively alleviated cancer pain, reduced the use of opioid drugs, and significantly improved the quality of life and enhanced immune function of the patients. Postoperative follow-up suggested good treatment tolerance among the patients without serious complications. CONCLUSIONS The formulated consensus is comprehensive and can provide reference for clinicians to use DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy. The combined treatment has a high clinical value with a good safety profile for management of cancer pain.
Humans ; Medicine, Chinese Traditional ; Cancer Pain/therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Drug Delivery Systems ; Pain Management/methods* ; China