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.

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 compare the analgesic effects and adverse reactions between intercostal nerve block (ICNB) and patient controlled intravenous analgesia (PCIA). Methods From August 2022 to January 2023, 180 patients with lung cancer who underwent thoracoscopic surgery were randomly divided into two groups: ICNB group (n=90) and PCIA group (n=90). The postoperative pain degree (VAS), location, nature; adverse events, such as nausea, vomiting, and dizziness; and other clinical symptoms were analyzed. Results The most common site of postoperative pain in both groups was surgical incision, and the nature of pain was distending pain. At 12 and 24 h after the operation, the pain degree in the ICNB group (1.10±0.91, 3.12±1.29) was markedly lower than that in PCIA group (1.44±0.86, 4.32±1.30, P=0.010, P<0.001). The incidence of nausea, vomiting, and dizziness in the ICNB group (5.56%, 23.33%) was noticeably lower than that in the PCIA group (35.56%, 51.11%, P<0.001, P<0.001). Total hospitalization expense in the ICNB group (41 043.16±10 885.63 yuan) was significantly lower than that in PCIA group (45 283.99±11 036.36 yuan, P=0.010). Conclusion The analgesic effect of intercostal nerve block is better than that of patient-controlled intravenous analgesia pump in patients with lung cancer after minimally invasive surgery, and the incidence of adverse reactions is low.

Objective:To assess the long-term risk of relapse in patients with Crohn's disease (CD) who discontinued infliximab (IFX) monoclonal antibody and to identify risk factors associated with relapse.Methods:A single-center retrospective observational study was conducted from February 2006 to October 2016. The study included CD patients who were treated with scheduled IFX infusions at the First Affiliated Hospital of Sun Yat-sen University and assessed in corticosteroid-free clinical remission at the time of withdrawal were included. The primary outcome was clinical relapse. We evaluated the risk of relapse using Kaplan-Meier method. Factors associated with time to relapse was identified using the multiple Cox proportional hazards regression analysis.Results:We included 97 eligible patients, and 75 (77.3%) experienced a relapse after a median follow-up time of 124 months. Among them, 45 patients (46.4%) relapsed within 3 years after IFX withdrawal. The 1-, 2-, 3-, 5-, and 10-year relapse-free survival were 79.4%, 59.8%, 52.6%, 42.0% and 22.6%, respectively. Risk factors for relapse included age ≤ 16 ( HR = 2.62, 95% CI: 1.30-5.31; P = 0.007) and failure to achieve biological remission (CRP > 3 mg/L, HR = 2.37, 95% CI: 1.29-4.36; P = 0.006) at drug withdrawal. Induction with biologics or systemic steroids were both effective (89%-100% relieved) in relapsers. Conclusions:Nearly half of CD patients relapsed within 3 years after discontinuation of IFX treatment. Early age of discontinuation and failure to achieve serum biological remission at the time of discontinuation are independent predictors of clinical relapse.

Objective:To summarize the clinical and genetic characteristics of late-onset facioscapulohumeral muscular dystrophy type 1 (FSHD1) patients, and to compare the differences between late-onset and classic-onset FSHD1 patients.Methods:A retrospective analysis was conducted on the clinical and genetic data of genetically confirmed late-onset FSHD1 patients (age at onset30 years) between January 2007 and June 2024 from the Department of Neurology of Peking University First Hospital and the First Affiliated Hospital of Fujian Medical University. Classic-onset FSHD1 patients (10 yearsage at onset≤30 years) were matched 1∶1 according to sex and disease duration for comparison. The demographic information, the number of D4Z4 repeat units, the distal D4Z4 methylation levels, FSHD Clinical Score (CS), Clinical Severity Score (CSS), and Age-Corrected Clinical Severity Score (ACSS) of these patients were collected. Survival analysis was performed to compare the outcome of lower extremity involvement between late-onset and classic-onset FSHD1 patients. The correlation of the number of D4Z4 repeat units and D4Z4 methylation level with CS and ACSS was analyzed in late-onset FSHD1 patients.Results:A total of 61 patients with late-onset FSHD1 were enrolled, 33 (54.1%) of whom are female, with an age of 54.0 (46.0, 62.0) years and a disease duration of 14.0 (5.5, 22.5) years. Compared to classic-onset FSHD1 patients, late-onset patients exhibited significantly lower CS [7.0 (5.6, 8.4) vs 6.0 (4.4, 7.7), U=1 416.000, P=0.013], CSS [3.0 (2.8, 3.3) vs 3.0 (2.0, 4.0), U=2 352.000, P=0.010], and ACSS [189.2 (137.1, 241.3) vs 96.8 (61.3, 132.2), U=3 225.500, P0.001], and higher proportion of patients with limb girdle involvement but no facial muscle involvement [18.0% (11/61) vs 6.6% (4/61), χ2=3.725, P=0.054]. Kaplan-Meier survival analysis showed that the onset age of lower extremity involvement in late-onset patients (45 years, 95% CI 42-48 years) was significantly higher than that in classic-onset patients (24 years, 95% CI 21-27 years, χ2=61.012, P0.001). The duration from symptom onset to lower extremity involvement in late-onset patients (15 years, 95% CI 10-20 years) was significantly longer than that in classic-onset patients (8 years, 95% CI 3-13 years, χ2=9.105, P=0.003). Late-onset FSHD1 patients carried higher average distal D4Z4 methylation levels compared to those with classic-onset FSHD1 [46.68% (40.79%,52.57%) vs 41.02% (34.03%,48.00%), U=1 378.500, P=0.014]. Among late-onset FSHD1 patients, cytosine-phosphate-guanine 6 (CpG6) methylation levels were significantly negatively correlated with ACSS ( r=-0.278, P=0.025); the number of D4Z4 repeat units were significantly negatively correlated with ACSS ( r=-0.272, P=0.034);CpG6 methylation levels were significantly negatively correlated with CS ( r=-0.441, P=0.003), while no correlation was found between number of D4Z4 repeat units and CS ( r=-0.161, P=0.310). Conclusions:Compared with classic-onset FSHD1 patients, late-onset FSHD1 patients are associated with a higher degree of distal D4Z4 methylation, along with a milder muscle weakness phenotype, slower disease progression and a higher proportion of cases without facial muscle involvement. The age at onset can be used as a marker of the severity and prognosis in FSHD1.

Aim To investigate the therapeutic effects of a newly developed Tadalafil tablets on pathological myocardial hypertrophy induced by abdominal aortic constriction(AAC)in rats,as well as its influence on the activation of the NF-κB signaling pathway in myo-cardial cells.Methods SD rats were randomly divid-ed into 4 groups:the sham operation group(Sham),the model group(AAC),the tadalafil new tablet treat-ment group(N-Tad,5 mg·kg-1),and the positive control drug treatment group(Cialis,10 mg·kg-1g).The AAC model group and treatment group rats under-went blunt dissection and constrictive ligation of the abdominal aorta at the left renal artery branch point during surgery,while the Sham group rats only had their arteries separated without any constrictive liga-tion.Rats in the treatment groups received either N-Tad or Cialis via gavage three days after modeling,while rats in the sham group and the model group re-ceived physiological saline daily for 8 weeks.Small an-imal ultra-high-resolution echocardiography and hemo-dynamic assessment were applied to evaluate left ven-tricular function in each group of rats,and the calcula-tion of the left ventricular mass index was conducted.By employing Western blot and RT-PCR.we assessed the impact of this treatment on the expression of the hy-pertrophy factor atrial natriuretic peptide(ANP),phosphorylated NF-κB p65 protein(p-NF-κB p65),and phosphorylated IκB-α in the left heart tissue of rats and in H9c2 cardiomyocytes.Results Compared to the Sham group,the AAC rats exhibited a significant decrease in left heart function,an increase in left ven-tricular mass index,and a notable increase in ANP and p-p65 expression in the left heart tissue(P＜0.05).Both N-Tad and Cialis treatments could significantly enhance left ventricular function,decrease left ventric-ular mass index,and inhibit the expression of ANP and phosphorylated NF-κB p65 in rats with myocardial hy-pertrophy(P＜0.05).Notably,the therapeutic effect of low-dose N-Tad was comparable to that of high-dose Cialis.At the cellular level,Tadalafil significantly in-hibited the activation of the NF-κB signaling pathway and reduced the expression of associated proteins in H9c2 cardiomyocytes.Conclusions N-Tad can sig-nificantly inhibit p65 and IκB-α phosphorylation,and the activation of the NF-κB signaling pathway,reduce ANP expression,and improve pathological myocardial hypertrophy,as well as mitigate left heart function damage caused by abdominal aortic constriction.

Severe open tibiofibular fractures account for approximately 28.1% of all open fractures. Among them, Gustilo-Anderson type IIIB/C fractures present significant clinical challenges due to associated bone and soft tissue defects, high infection rates, and risk of amputation. Inadequate preoperative assessment may lead to suboptimal emergency surgical planning or intraoperative complications. Historically, external fixation was often preferred, but this approach has been associated with limitations such as restricted joint mobility, delayed bone union, joint stiffness, and disuse osteoporosis, resulting in poor functional recovery. With advancements of debridement techniques, standardization of antibiotic use, and popularization of early soft tissue coverage, early internal fixation has gained broader acceptance. Nevertheless, controversies persist regarding the choice of fixation method, timing of definitive fixation, use of reamed versus unreamed intramedullary nailing, and necessity of fibular fixation. To standardize the diagnosis and early management of severe open tibiofibular fractures, reduce complication rates, and improve functional recovery, the Society of Microsurgery of the Chinese Medical Association organized a panel of domestic experts to develop the Evidence-based guideline for the diagnosis and early fixation of severe open tibiofibular fractures ( version 2025), using evidence-based methodology. The guidelines provided 12 recommendations covering diagnostic and early fixation strategies of severe open tibiofibular fractures, aiming to provide clinicians with scientifically grounded and standardized guidance.

OBJECTIVE: To investigate the molecular alterations of splenocytes associated with anti-factor Ⅷ (FⅧ) immune response and the underlying mechanisms based on hemophilia A (HA) murine model via RNA sequencing (RNA-seq) technology. METHODS: Severe HA mice were immunized with recombinant human factor Ⅷ (rhF8) weekly for 4 weeks to establish an FⅧ inhibitor model. High quality raw data were obtained by using bulk RNA-seq and CASAVA base identification technology, and the differentially expressed genes (DEGs) were identified. The DEGs were statistically classified by gene ontology (GO) annotation to obtain information on the major signaling pathways and biological processes involved in anti-FⅧ immune response in HA mouse splenocytes. The cell clusters, genes, and signaling pathway datasets were comprehensively analyzed by GO, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and single cell RNA-seq (ScRNA-seq) analysis, respectively. Flow cytometry analysis was used to verify the changes in T follicular helper cells (Tfh) and regulatory T cells (Treg). RESULTS: A total of 3731 DEGs was identified, including 2275 genes with up-regulated expression and 1456 genes with down-regulated expression. The DEGs were enriched in helper T cell differentiation, cytokine receptor, T cell receptor signaling pathway, ferroptosis, etc. Uniform Manifold Approximation and Project (UMAP) downscaling and visualization analysis yielded a total number of 11 T/NK cell subsets, visualizing the overall expression distribution of C-X-C chemokine-specific receptor gene cxcr5 among these T/NK cell subsets. Higher expression of cxcr5 was found in activated Tfh from FⅧ inhibitor mice, in comparison to the control group. The visualization using Upset plot R language showed a close interaction between Tfh and Treg. Moreover, the increased frequencies of Tfh and the decreased frequencies of Treg in inhibitor mouse splenocytes were further verified by flow cytometry analysis. CONCLUSION Multiple immune cell subsets, signaling pathways, and characteristic genes may be involved in the process of anti-FⅧ immune response in HA mouse splenocytes. The molecules involved in the regulation of Tfh/Treg may play key roles, which provide potential biological targets and therapeutic strategies for HA patients with inhibitors in the future.
Animals ; Hemophilia A/genetics* ; Mice ; Sequence Analysis, RNA ; Disease Models, Animal ; Spleen/cytology* ; T-Lymphocytes, Regulatory/immunology* ; Humans ; Signal Transduction ; Factor VIII/immunology* ; T-Lymphocytes, Helper-Inducer/immunology*

Objective To investigate the therapeutic effects and mechanisms of dexmedetomi-dine and remimazolam on neuropathic pain.Methods A total of 60 SD rats were divided into sham operation group(n=12),spinal nerve ligation(SNL)+NC group(n=12),SNL+DEX group(n=12),SNL+REM group(n=12)and DEX+REM group(n=12).Mechanical withdrawal threshold(MWT)was analyzed in each group.The expression level of pain-related protein c-Fos was detected by Western blot.Autophagy was assessed by immunofluorescence analysis.Enzyme-linked immunosorbent assay(ELISA)was used to measure the expression levels of inflammatory factors[tumor necrosis factor-α(TNF-α),interleukin-1 β(IL-1 β),interleukin-6(IL-6)and interleukin-10(IL-10)]of each group.The expression level of oxidative stress factor in each group was ana-lyzed.The expression levels of NFE2L2/NRF2 pathway related proteins were analyzed by Western blot.Results MWT in the SNL+DEX,SNL+REM and DEX+REM groups was significantly high-er than that in the SNL+NC group(P＜0.05).The expression level of c-Fos protein in the SNL+NC group was significantly higher than that in the SNL+DEX,SNL+REM and DEX+REM groups(P＜0.05).The immunofluorescence intensity of LC3 and NeuN in SNL rats was lower than that in sham operation rats,indicating that autophagy of neurons in SNL rats was damaged.The immunofluorescence intensity of LC3 and NeuN in the SNL+DEX group,SNL+REM group and DEX+REM group were significantly higher than those in the SNL+NC group(P＜0.05).The expression levels of TNF-α,IL-1 β and IL-6 in the SNL+DEX group,SNL+REM group and DEX+REM group were signifi-cantly lower than those in the SNL+NC group(P＜0.05).Glutathione(GSH)and catalase(CAT)levels in the SNL+DEX,SNL+REM and DEX+REM groups were significantly higher than those in the SNL+NC group,while malondialdehyde(MDA)levels were significantly lower(P＜0.05).The expression levels of NFE2L2 protein in the SNL+DEX,SNL+REM and DEX+REM groups were significantly lower than that in the SNL+NC group,with the lowest level observed in the DEX+REM group(P＜0.05).Conclusion Dexmedetomidine and remimazolam can re-lieve neuropathic pain in SNL rats by inhibiting the expression of NFE2L2/NRF2 pathway-related proteins and decreasing oxidative stress levels.