Background: To investigate directional deviations between pilot holes and final pedicle screw trajectories in freehand placement and analyze risk factors for misplacement. While pedicle screws are widely used in thoracolumbosacral surgery, directional deviations between pilot holes and final screw trajectories remain understudied as potential risk factors for misplacement. Methods: Thirty-three patients undergoing posterior fixation were prospectively enrolled. Inertial measurement units (IMUs) tracked the spatial positions of pedicle finders and screwdrivers via custom software. Surgeons (n = 6) were stratified into senior, middle, and junior groups. Analyzed variables included the use of tapping, surgeon experience, spinal deformity status, screw tip morphology, and surgical parameters. Results: Among 198 implanted screws (6.00 ± 2.88/patient), all exhibited trajectory deviations (8.12° ± 3.47°). Tapping significantly reduced deviations (7.23° ± 3.23° vs. 8.87° ± 3.31°, p < 0.01). Senior surgeons achieved smaller deviations (7.34° ± 3.33°) than the middle group (8.60° ± 3.51°, p = 0.039) and junior group (8.68° ± 3.49°, p = 0.022). Multivariate analysis confirmed tapping (p = 0.001) and senior experience (p = 0.023) as protective factors. No significant associations emerged for spinal deformity (8.43° ± 3.73° vs. 7.97° ± 3.35°, p = 0.377), screw tip type (cylindrical, 8.43° ± 3.26° vs. tapered, 8.07 ± 3.51°; p = 0.637), obesity, or surgical position parameters. Conclusions Freehand pedicle screw placement consistently produces trajectory deviations from pilot holes, and surgeon experience and tapping are modifiable protective factors. The IMU-based tracking system enables quantitative surgical motion analysis, suggesting its utility for training optimization and technique standardization.

胰腺导管腺癌（pancreatic ductal adenocarcinoma, PDAC）具有高度侵袭性、早期诊断率低且对全身治疗总体反应有限，其致密纤维化基质、异常血管与免疫抑制性肿瘤微环境共同导致药物渗透不足与免疫“冷肿瘤”特征，是疗效受限的重要原因。间充质基质细胞（mesenchymal stromal cell, MSC）具有趋炎性迁移、免疫调控与旁分泌效应，可作为“活体递送载体”将细胞因子、化疗药物、溶瘤病毒及自杀基因等定向输送至肿瘤区域，从而为突破基质屏障与重塑微环境提供策略空间（摘要图）。然而，MSC在肿瘤情境下存在显著可塑性与“双刃剑效应”，可能被肿瘤微环境再教育而表现出免疫抑制、促血管生成、促纤维化、促侵袭及促耐药等不良作用；同时其体内分布与载荷释放缺乏可量化与可控证据链，制备工艺与功能质控标准不统一，构成转化瓶颈。本文重点评述MSC与PDAC微环境相互作用机制及工程化MSC递送治疗性蛋白、药物、溶瘤病毒与自杀基因等研究进展，并探讨安全性、有效性评价与质量控制挑战。发展具有微环境响应释放与安全开关的可编程MSC平台，建立面向肿瘤治疗的功能评价或放行体系，并推进MSC衍生细胞外囊泡等无细胞策略，或将更有利于提升可重复性与降低体内持久性相关风险。

BACKGROUND: Diabetic foot is a complex condition with high incidence, recurrence, mortality, and disability rates. Current treatments for diabetic foot ulcers are often insufficient. This study was conducted to identify potential therapeutic targets for diabetic foot. METHODS: Datasets related to diabetic foot and diabetic skin were retrieved from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified using R software. Enrichment analysis was conducted to screen for critical gene functions and pathways. A protein interaction network was constructed to identify node genes corresponding to key proteins. The DEGs and node genes were overlapped to pinpoint target genes. Plasma and chronic ulcer samples from diabetic and non-diabetic individuals were collected. Western blotting, immunohistochemistry, and enzyme-linked immunosorbent assays were performed to verify the S100 calcium binding protein A9 (S100A9), inflammatory cytokine, and related pathway protein levels. Hematoxylin and eosin staining was used to measure epidermal layer thickness. RESULTS: In total, 283 common DEGs and 42 node genes in diabetic foot ulcers were identified. Forty-three genes were differentially expressed in the skin of diabetic and non-diabetic individuals. The overlapping of the most significant DEGs and node genes led to the identification of S100A9 as a target gene. The S100A9 level was significantly higher in diabetic than in non-diabetic plasma (178.40 ± 44.65 ng/mL vs. 40.84 ± 18.86 ng/mL) and in chronic ulcers, and the wound healing time correlated positively with the plasma S100A9 level. The levels of inflammatory cytokines (tumor necrosis factor-α, interleukin [IL]-1, and IL-6) and related pathway proteins (phospho-extracellular signal regulated kinase [ERK], phospho-p38, phospho-p65, and p-protein kinase B [Akt]) were also elevated. The epidermal layer was notably thinner in chronic diabetic ulcers than in non-diabetic skin (24.17 ± 25.60 μm vs. 412.00 ± 181.60 μm). CONCLUSIONS S100A9 was significantly upregulated in diabetic foot and was associated with prolonged wound healing. S100A9 may impair diabetic wound healing by disrupting local inflammatory responses and skin re-epithelialization.
Calgranulin B/therapeutic use* ; Diabetic Foot/metabolism* ; Humans ; Datasets as Topic ; Computational Biology ; Mice, Inbred C57BL ; Animals ; Mice ; Protein Interaction Maps ; Immunohistochemistry

BACKGROUND: China has made significant progress in medical accessibility and quality over the past decades, and quality improvements in gastroenterology and digestive endoscopy have been consistent. The study aimed to describe the status quo of gastroenterology and digestive endoscopy in the Chinese mainland based on the data from the National Clinical Improvement System (NCIS) and the Hospital Quality Monitoring System (HQMS). METHODS: Data were extracted from the NCIS and the HQMS. Data analysis included general information from the Department of Gastroenterology and Endoscopy centers, management of inpatients and outpatients, and annual volume and quality indicators of digestive endoscopy. Acute pancreatitis, gastrointestinal bleeding, inflammatory bowel disease, and cirrhosis were identified as priority diseases and were subjected to detailed analysis. RESULTS: Data from 4620 and 7074 hospitals were extracted from the NCIS and HQMS, respectively. In 2023, 9.6 gastroenterologists, 6.7 endoscopists, and 37.3 gastroenterology beds per hospital nationwide were observed, achieving 19,252.4 outpatient visits, 1615.2 hospitalizations (97.0 for acute pancreatitis, 146.1 for gastrointestinal bleeding, 40.2 for inflammatory bowel disease, and 111.4 for cirrhosis), and 9432.7 digestive endoscopic procedures per hospital. Overall, the quality of practice improved significantly. The proportion of early cancer among gastrointestinal cancers increased from 11.1% in 2015 to 23.4% in 2023, and the adenoma detection rate during colonoscopy increased from 19.3% in 2019 to 26.9% in 2023. Regarding priority diseases, hospitalizations increased, and 31-day unplanned readmission rates decreased between 2019 and 2023. The median hospitalization costs and median proportion of medication costs decreased for acute pancreatitis, gastrointestinal bleeding, and cirrhosis. However, it increased for inflammatory bowel disease. CONCLUSION This report evaluates the status quo and development of gastroenterology and digestive endoscopy in the Chinese mainland, providing guidance for future quality improvements.
Humans ; China ; Gastroenterology/statistics & numerical data* ; Gastrointestinal Hemorrhage ; Endoscopy, Gastrointestinal/statistics & numerical data* ; Endoscopy, Digestive System/statistics & numerical data*

PURPOSE: Postpancreatectomy hemorrhage (PPH) is a life-threatening complication after pancreatoduodenectomy. Stent-graft implantation is an emerging treatment option for PPH. This study reports the outcome of PPH treated with stent-graft implantation. METHODS: This was a single-center, retrospective study. Between April 2020 and December 2023, 1723 pancreatectomy cases were collected while we screened 12 cases of PPH after pancreatoduodenectomy treated with stent-graft implantation. Patients' medical and radiologic images were retrospectively reviewed. Technical and clinical success, complications, and stent-graft patency were evaluated. Continuous data are reported as means ± standard deviation when normally distributed or as median (Q₁, Q₃) when the data is non-normal distributed. Categorical data are reported as n (%). A p < 0.05 was considered statistically significant. Kaplan-Meier estimates were used for stent patency and patients' survival. RESULTS: Pancreatic fistula was identified in 6 cases (50.0%), and pseudoaneurysm was identified in 3 cases (25.0%), including pancreatic fistula together with pseudoaneurysm in 1 case (8.3%). All pseudoaneurysm or contrast extravasation sites were successfully excluded with patent distal perfusion, thus technical success was achieved in all cases. The overall survival rate at 6 months and 1 year was 91.7% and 78.6%, respectively. One patient had herniation of the small intestine into the thoracic cavity, which caused a broad thoracic and abdominal infection and died during hospitalization. Rebleeding occurred at the gastroduodenal artery stump in 1 case after stent-graft implantation for the splenic artery and was successfully treated with another stent-graft implantation. Two cases of asymptomatic stent-graft occlusion were observed at 24.6 and 26.3 after the operation, respectively. CONCLUSIONS With suitable anatomy, covered stent-graft implantation is an effective and safe treatment option for PPH with various bleeding sites and causes.
Humans ; Pancreaticoduodenectomy/adverse effects* ; Stents ; Male ; Retrospective Studies ; Female ; Middle Aged ; Postoperative Hemorrhage/surgery* ; Aged ; Adult

OBJECTIVE To summarize the implementation experiences of the China Hospital Association’s Clinical Pharmacist Instructor Training Program Reform， and to evaluate the effectiveness of the reform， thus continuously enhancing the quality and standards of clinical pharmacist instructor training. METHODS The study drew on project evaluation methodologies to summarize the main characteristics of the comprehensive system and new model for clinical pharmacist instructor training established through the reform by literature review. The “learning assessment” and “reaction assessment” were conducted by using Kirkpatrick’s four-level model of evaluation in order to evaluate the effectiveness of the clinical pharmacist instructor training reform through statistically processing and analyzing the performance data and teaching evaluation data of the instructor participants. Based on problem and trend analysis， the future development directions were anticipated for the reform of clinical pharmacist instructor training. RESULTS & CONCLUSIONS The latest round of clinical pharmacist instructor training reform initiated by the Chinese Hospital Association had initially established a four-pronged training system encompassing “recruitment， training， assessment， and management”. It had also forged a training 。 model “oriented towards enhancing clinical teaching competency， with practical learning and skill-based assessment conducted on clinical teaching sites as its core”. Following a period of over three years of gradual reform， the new training system and model became increasingly mature. In both 2023 and 2024， the participants achieved relatively high average total scores in their initial completion assessments [with scores of （84.05± 5.83） and （85.82±4.35） points， respectively]. They also reported a strong sense of gain from the training reform [with self- perceived gain scores of （4.80±0.44） and （4.85±0.39） points， respectively]. The operation and implementation effects of the reform were generally satisfactory. In the future， clinical pharmacist instructor training reforms should continue to address the issues remaining from the current phase， while aligning with global trends in pharmacy education and industry development. Additionally， sustained exploration and practice will be carried out around the core objective of “enhancing clinical teaching competence”.

Head and neck squamous cell carcinoma (HNSCC) is a tumor characterized by immunosuppressive tumor microenvironment (TME) and poor prognosis. Its complex immune evasion mechanisms are primarily related to T cell dysfunction and the suppression of anti-tumor immune responses. Immunotherapy aims to modulate the patient’s immune system to recognize and eliminate tumor cells, thereby achieving therapeutic goals. Studies have demonstrated that the TME plays a pivotal role in HNSCC pathogenesis, facilitating tumorigenesis, progression, and therapy resistance, ultimately contributing to adverse clinical outcomes. Advances in technology have deepened understanding of the TME, paving the way for novel therapeutic interventions in HNSCC. This review comprehensively summarizes the efficacy and safety of TME-targeted immunotherapies, integrating evidence from published clinical trials, while proposing insights for future research to develop more effective therapeutic strategies.

Human carboxylesterase 2A (hCES2A) plays pivotal roles in prodrug activation and hydrolytic metabolism of ester-bearing chemicals. Targeted inhibition of intestinal hCES2A represents a feasible strategy to mitigate irinotecan-triggered gut toxicity (ITGT), but the orally active, selective, and efficacious hCES2A inhibitors are rarely reported. Here, a novel drug-like hCES2A inhibitor was developed via three rounds of structure-based drug design (SBDD) and structural optimization. Initially, donepezil was identified as a moderate hCES2A inhibitor from 2000 US Food and Drug Administration (FDA)-approved drugs. Following two rounds of SBDD and structural optimization, a donepezil derivative (B7) was identified as a strong reversible hCES2A inhibitor. Subsequently, nine B7 carbamates were rationally designed, synthesized and biologically assayed. Among all synthesized carbamates, C3 showed the most potent time-dependent inhibition on hCES2A (IC₅₀ = 0.56 nmol/L), excellent specificity and favorable drug-like properties. C3 could covalently modify the catalytic serine of hCES2A with high selectivity, while this agent also showed favorable safety profiles, high intestinal exposure, and impressive effects for ameliorating ITGT in both human intestinal organoids and tumor-bearing mice. Collectively, this study showcases a rational strategy for developing drug-like and serine-targeting covalent inhibitors against target serine hydrolase(s), while C3 emerges as a promising orally active drug candidate for ameliorating ITGT.