OBJECTIVE To analyze the risk factors for multidrug-resistant organism （MDRO） infection in patients with prolonged invasive mechanical ventilation （IMV） complicated by ventilator-associated pneumonia （VAP） in the intensive care unit （ICU）， thus providing a reference for improving the clinical effect of VAP treatment in this region. METHODS A retrospective analysis was performed on the clinical data of patients who were admitted to the ICU in Shexian Branch of the Second Affiliated Hospital of Zhejiang University School of Medicine （hereinafter referred to as “our hospital”） from October 2022 to February 2025， received prolonged IMV， and developed VAP. The distribution and drug resistance of pathogens were statistically analyzed. Patients were divided into the MDRO group and the non-MDRO group according to whether an MDRO infection occurred. Univariate analysis and multivariate Logistic regression analysis were used to screen independent risk factors for MDRO infection. RESULTS A total of 281 pathogenic strains were cultured from 97 patients， including 262 Gram-negative bacteria （93.24%）， 9 Gram-positive bacteria （3.20%）， and 10 fungi （3.56%）. The main Gram-negative bacteria were Pseudomonas aeruginosa， Klebsiella pneumoniae subspecies pneumoniae， and Acinetobacter baumannii. The former two showed high resistance rates （all≥25%） to common antibiotics such as imipenem， while A. mail：64375689@qq.com baumannii demonstrated high resistance to most antimicrobial agents. The main Gram-positive bacteria were Staphylococcus aureus subspecies aureus and S. haemolyticus， which were resistant to multiple antibiotics such as clindamycin （resistance rates all＞30%）. Among 281 pathogenic strains， 121 were MDRO， 62 were resistant to carbapenems， and 33 produced extended-spectrum β-lactamases. The serum albumin＜28 g/L， ICU stay≥14 days， and use of benzodiazepines were independent risk factors for MDRO infection in patients with prolonged IMV and VAP in our hospital’s ICU （odds ratios were 3.289， 2.991 and 2.680， 95% confidence intervals were 1.183-9.144， 1.021-8.765， and 1.012- 7.094， respectively， P＜0.05）. CONCLUSIONS Pathogens infecting patients with prolonged IMV and VAP in the ICU are mainly Gram-negative bacteria， with P. aeruginosa， K. pneumoniae subspecies pneumoniae and A. baumannii， accounting for a high proportion， and the drug resistance situation is severe. Serum albumin＜28 g/L， ICU stay≥14 days， and use of benzodiazepines are independent risk factors for MDRO infection in such patients.

The activation proteins released by fibroblasts in the tumor microenvironment regulate tumor growth, migration, and treatment response, thereby influencing tumor progression and therapeutic outcomes. Owing to the proliferation and metastasis of tumors, fibroblast activation protein (FAP) is typically highly expressed in the tumor stroma, whereas it is nearly absent in adult normal tissues and benign lesions, making it an attractive target for precision medicine. Radiolabeled agents targeting FAP have the potential for targeted cancer diagnosis and therapy. This comprehensive review aims to describe the evolution of FAPI-based radiopharmaceuticals and their structural optimization. Within its scope, this review summarizes the advances in the use of radiolabeled small molecule inhibitors for tumor imaging and therapy as well as the modification strategies for FAPIs, combined with insights from structure-activity relationships and clinical studies, providing a valuable perspective for radiopharmaceutical clinical development and application.

Objective: To detect the different proteomic characteristics of microvesicles (MVs) and exosomes (EXOs) released from apheresis platelets during storage, and to explore their role in mediating platelet storage damage lesion (PSL). Methods: Apheresis platelets were collected from the retention bag on the third day of storage. MVs and EXOs were isolated using differential centrifugation. Platelet, MVs and EXOs protein samples were extracted respectively, and the differentially expressed proteins were detected by quantitative proteomics technology. Further, the co-incubation model of MVs, EXOs and fresh platelets was adopted to evaluate the effect of extracellular vesicles on PSL. The aggregation response of platelets to collagen agonizers and the changes in ATP release rate were evaluated by optical turbidimetry. Flow cytometry was used to evaluate the changes of platelet early activation indicators (P-selectin and PAC-1) and mitochondrial membrane potentia. Western blot was used to detect the changes in the expression of key proteins for platelet activation and apoptosis (P-selectin, Integrin β3 and Bcl-xl). Results: Proteomic analysis revealed a significantly separation in protein expression profiles of platelet, MVs and EXOs samples within the latent variable space. Energy metabolization-related proteins such as mitochondrial respiratory chain complex and oxidative phosphorylation were enriched specifically, in MVs while EXOs were enriched with inflammation-related proteins. Co-incubation experiments confirmed that extracellular vesicles could significantly induce platelet responses to agonists (the maximum aggregation rate in the MVs group increased by 187.36%, P<0.001; 71.26%, in the EXOs group P=0.002). The maximum ATP release rate of platelets also increased (275.44% in the MVs group, P<0.001; 70.18% in the EXOs group, P=0.015). The expression of P-selectin increased (119.33% in the MVs group, P<0.001; 25.61% in the EXOs group, P=0.013), as detected by flow cytometry. The binding rate of PAC-1 increased (132.18% in MVs group, P<0.001; 21.41% in EXOs group, P=0.043), and the mitochondrial membrane potential decreased (20.49% in MVs group, P<0.001; 9.73% in EXOs group, P=0.044). In the MVs group, platelet P-selectin and Integrin β3 expression were significantly increased (100.83% and 395.64%, P<0.001), while Bcl-xl expression was lower than that in the control group (83.94%, P<0.001). Compared with the control group, P-selectin and Integrin β3 expression were also increased (27.89% and 181.91%, P=0.007和P=0.002), while Bcl-xl was decreased in the EXOs group (36.52%, P<0.001). Conclusion: MVs and EXOs derived from stored platelets show different proteomic characteristics. Compared with EXOs, MVs exhibits a stronger effect in inducing mitochondrial dysfunction. Mvs also promots PSL responses including platelet activation and apoptosis.

Objective:To explore the causal relationship between human immune cells and hypertrophic scar (HS) using two-sample bidirectional Mendelian randomization (MR) method.Methods:This study was based on two-sample MR method, and the datasets of 731 immune cells and HS were obtained from the genome-wide association study (GWAS) catalog database and Finngen database, respectively. A significance threshold was established to discern single nucleotide polymorphism (SNP) significantly correlated with immune cells or HS, thereby eliminating the impact of weak instrumental variable bias. The inverse variance weighted (IVW) method (meanwhile, the Benjamini-Hochberg (BH) procedure of false discovery rate (FDR) to adjust P values) was used for preliminary detection of the causal relationship between immune cells and HS and screen the immune cells that had a significant causal relationship with HS. Further, the causal relationship between the selected immune cells and HS was detected through five two-sample MR methods: IVW method, weighted median method, simple mode method, weighted mode method, and MR-Egger method, and the scatter plot was drawn. SNPs conformed to the hypothesis were subjected to Cochran Q test for heterogeneity assessment, MR-Egger regression coupled with MR-PRESSO to eliminate horizontal pleiotropic effects, and a leave-one-out analysis was also conducted to determine if significant results were driven by individual SNP. Finally, the IVW method contained in the two-sample MR analysis was utilized to inversely examine the causal relationship between HS and immune cells. Results:The number of SNPs in 731 immune cells reaching the significance threshold varied from 7 to 1 786, while in HS, 119 SNPs met the significance threshold, with the F values of all SNPs being greater than 10, suggesting a low likelihood of bias from weak instrumental variables. The IVW method revealed that 60 types of immune cells potentially had a causal relationship with HS (with all P values <0.05), and after adjustment using the BH method, only CD45RA and CD39 positive regulatory T cell (Treg) maintained a potentially strong causal relationship with HS ( PFDR<0.05). The IVW method (with odds ratio of 1.16 and 95% confidence interval of 1.08-1.24, P<0.05, PFDR<0.05), weighted median method (with odds ratio of 1.16 and 95% confidence interval of 1.05-1.28, P<0.05), weighted mode method (with odds ratio of 1.14 and 95% confidence interval of 1.02-1.27, P<0.05), and MR-Egger method (with odds ratio of 1.18 and 95% confidence interval of 1.07-1.30, P<0.05) of scatter plot all suggested a causal relationship between the 14 SNPs of CD45RA and CD39 positive Treg and risk of HS, only simple mode method of scatter plot suggested a not obvious relationship between the 14 SNPs of CD45RA and CD39 positive Treg and risk of HS ( P>0.05). Cochran Q test indicated no heterogeneity in the causal relationship between CD45RA on CD39 positive Treg and HS ( P>0.05). MR-Egger regression and MR-PRESSO analyses showed that there was no horizontal pleiotropy in the significant causal relationship between CD45RA and CD39 positive Treg and HS ( P>0.05). Leave-one-out analysis confirmed that the significant causal relationship between CD45RA and CD39 positive Treg and HS remained stable after sequentially removing individual SNP. Reverse two-sample MR analysis showed that HS had no potential causal relationship with any of the 731 types of immune cells ( P>0.05). Conclusions:From the perspective of genetics, it is revealed that immune cells CD45RA and CD39 positive Treg may increase the risk of HS.

Objective:To construct a targeted and accurate evaluation system for facial and cervical wounds and scars of burn patients.Methods:The method combining literature analysis and survey research was adopted, and the basic principles of item system construction were followed. From June to August 2020, based on the aesthetic standards of facial and cervical plastic surgery, the topographic map assessment system for facial and cervical wounds and scars of burn patients was preliminarily formed, focusing on the assessment of wounds and scars in the necks and faces of patients after burns. In September 2020, 38 experts in the relevant fields were consulted in advance and the questionnaire was revised according to the experts' opinions. From December 2020 to March 2021, the Delphi method was applied to conduct inquiry by correspondence with 35 experts in relevant fields from Guangzhou, Shenzhen, Shanghai, Beijing, and other cities, who met the inclusion criteria, and the items were screened and established. The effective recovery rate of inquiry questionnaire was calculated to determine the level of enthusiasm of experts, the average authority coefficient of all items was calculated to determine the level of expert authority, the average importance expert score, the average coefficient of variation, and the average full score rate of all the third-level items were calculated to determine the concentration of expert opinions, the average coefficients of variation and Kendall's harmony coefficients of the importance, sensitivity, and operability expert scores of all the third-level items were calculated to determine the degree of coordination of expert opinions. The Kendall's harmony coefficients for the importance, sensitivity, and operability expert scores of all the third-level items were statistically analyzed with chi-square test.Results:Among the 35 experts consulted by Delphi method, mainly were male, aged (48±10) years, with 8-38 years of working experience, mainly with associate senior titles and above, all with a bachelor's degree or above education background, and of whom 11 were burn experts, 7 were wound repair experts, 4 were plastic surgery experts, and 13 were rehabilitation medicine experts. Finally, a topographic map assessment system for facial and cervical wounds and scars of burn patients was formed, including 4 first-level items, 21 second-level items, 40 third-level items, and 1 mask. The effective recovery rate of inquiry questionnaire was 100% (35/35). The average authority coefficient of all items was 0.89. The average importance expert score was 4.67, the average coefficient of variation of importance expert score was 0.01, and the average full score rate of all the third-level items was 86.3%. The average coefficients of variation of the importance, sensitivity, and operability expert scores of all the third-level items were 0.01, 0.01, and 0.02, respectively. The Kendall's harmony coefficients for the importance, sensitivity, and operability expert scores of all the third-level items were statistically significant (with χ2 values of 1 201.53, 745.67, and 707.07, respectively , P<0.05). Conclusions:The established topographic map assessment system for facial and cervical wounds and scars of burn patients has high scientificity and reliability, which can be used for the evaluation of facial and neck wounds or scars in burn patients.

Atrial fibrillation (AF), the most common sustained arrhythmia, is associated with a range of symptoms, including palpitations, cognitive impairment, systemic embolism, and increased mortality. It places a significant burden on healthcare systems worldwide. Despite decades of research, the precise mechanisms underlying AF remain elusive. Current understanding suggests that factors like stretch-induced fibrosis, epicardial adipose tissue (EAT), chronic inflammation, autonomic nervous system (ANS) imbalances, and genetic mutations all play significant roles in its development. In recent years, the advent of wearable devices has revolutionized AF diagnosis, enabling timely detection and monitoring. However, balancing early diagnosis with efficient resource utilization presents new challenges for healthcare providers. AF management primarily focuses on stroke prevention and symptom alleviation. Patients at high risk of thromboembolism require anticoagulation therapy, and emerging pipeline drugs, particularly factor XI inhibitors, hold promise for achieving effective anticoagulation with reduced bleeding risks. The scope of indications for catheter ablation in AF has expanded significantly. Pulsed field ablation, as a novel energy source, shows potential for improving success rates while ensuring safety. This review integrates existing knowledge and ongoing research on AF pathophysiology and clinical management, with emphasis on diagnostic devices, next-generation anticoagulants, drugs targeting underlying mechanisms, and interventional therapies. It offers a comprehensive mosaic of AF, providing insights into its complexities.
Humans ; Atrial Fibrillation/drug therapy* ; Stroke ; Risk Factors ; Anticoagulants/therapeutic use* ; Blood Coagulation ; Catheter Ablation ; Treatment Outcome

Objective:To collect and analyze laboratory indicators of patients of different sexes after blood transfusion, evaluate the effectiveness of blood transfusion, and provide a theoretical basis for formulating more scientific blood transfusion plans.Methods:The clinical data of 808 patients who underwent blood transfusion in The First Affiliated Hospital of Anhui University of Science and Technology from January 2020 to December 2021 were retrospectively analyzed. According to the blood transfusion strategy and the department to which the patients were admitted, these patients were divided into four groups: surgical restrictive blood transfusion group (group A: 72 males and 69 females), surgical non-restricted blood transfusion (group B: 77 males and 118 females), medical restrictive blood transfusion (group C: 184 males and 126 females), and medical non-restricted blood transfusion (group D: 110 males and 52 females). Univariate and multivariate Logistic regression analyses were performed.Results:In group A, after blood transfusion, hemoglobin level in female patients was significantly higher than that in male patients [79.0 (71.5, 87.0) g/L vs. 75.5 (69.0, 82.8) g/L, Z = -2.18, P = 0.029], and C-reactive protein in female patients was significantly lower than that in male patients [21.3 (0.0, 56.0) mg/L vs. 37.0 (3.3, 95.5) mg/L, Z = -1.97, P = 0.049]. In groups B, C, and D, there were no significant differences in hemoglobin, C-reactive protein, and hematocrit between male and female patients (all P > 0.05). Multivariate analysis showed that the difference in hemoglobin levels between before and after blood transfusion was statistically significant ( P = 0.009). After a blood transfusion, hemoglobin level in female patients was 1.44 times that in male patients. Conclusion:The tolerance of female patients to blood loss is higher than that of male patients in surgical restrictive blood transfusion, so the threshold value of hemoglobin given to female patients during blood transfusion can be lower than that of male patients. In the case of the same blood loss, priority of blood transfusion can be given to male patients. In the case of scarce blood resources, the total amount of blood transfused for female patients can be approximately reduced.

Objective:To investigate the clinical efficacy of neuroendoscopic hematoma removal versus soft channel drainage in the treatment of chronic subdural hematoma (CSDH) and their effects on neurological function and quality of life. Methods:The clinical data of 97 patients with CSDH who received treatment between February 2018 and December 2019 were retrospectively analyzed. These patients were divided into group A ( n = 48, soft channel drainage) and group B ( n = 49, neuroendoscopic hematoma removal) according to different surgical methods. Clinical indicators, neurological function, quality of life, and incidence of complications were compared between groups A and B. Results:Operative time, length of hospital stay, and latency to hematoma disappearance in group B were (31.3 ± 2.18) minutes, (8.16 ± 1.32) days, (7.45 ± 1.49) days, which were significantly shorter than those in group A [(35.15 ± 4.32) minutes, (13.18 ± 1.56) days, (11.32 ± 1.88) days, t = 5.53, 17.12, 11.25, all P < 0.001]. At 3 months after surgery, the score of each dimension of SF-36 in each group was increased. The scores of physiological functioning, bodily pain, mental health, general health perceptions, social role functioning, vitality, role limitations due to emotional health, role limitations due to physical health in group B were (84.94 ± 7.25) points, (84.02 ± 6.29) points, (82.85 ± 8.16) points, (84.36 ± 9.15) points, (83.51 ± 10.39) points, (82.68 ± 8.36) points, (84.93 ± 10.15) points, (86.12 ± 9.13) points, which were significantly higher than those in group A [(62.68 ± 5.47) points, (71.39 ± 7.42) points, (69.51 ± 6.39) points, (72.68 ± 7.36) points, (72.81 ± 8.15) points, (73.12 ± 10.13) points, (77.91 ± 9.52) points, (75.32 ± 7.51) points, t = 19.82, 18.34, 19.75, 16.71, 17.94, 20.57, 18.22, 16.44, all P < 0.001]. At 7 days after surgery, neurotrophic factor, neuron specific enolase, hydrogen sulfide and S100B protein levels in group B were (42.53 ± 6.09) μg/L, (6.52 ± 2.79) μg/L, (203.17 ± 15.03) μmol/L, (0.25 ± 0.05) μg/L, respectively, which were significantly lower than those in group A [(67.38 ± 7.42) μg/L, (9.18 ± 2.27) μg/L, (242.79 ± 14.08) μmol/L, (0.36 ± 0.07) μg/L, t = 17.94, 5.12, 13.33, 8.86, all P < 0.001]. There was no significant difference in the incidence of complications between group B and group A [8.16% (4/49) vs. 18.75% (9/48), χ2 = 2.22, P = 0.136]. Conclusion:Compared with soft channel drainage, neuroendoscopic hematoma removal can better improve clinical indicators, neurological function, and quality of life in patients with CSDH, and is highly safe Neuroendoscopic hematoma removal is of certain clinical application value and innovation.

Objective:To explore the protective effect of Shen’an decoction on cisplatin induced renal injury in rats by regulating TLR4/NF-κB signaling pathway. Methods:Sixty SD rats were randomly divided into blank group, model group, positive control group, high dose Shen’an Decoction group, medium dose Shen’an Decoction group and low dose Shen’an Decoction group, with 10 rats in each group. Except the blank group, the other groups were intraperitoneally injected with cisplatin 7.5 mg/kg to prepare the acute kidney injured rat model. After the modeling, the high, medium and low dose groups of Shen’an Decoction were gavaged with 0.698, 1.395 and 2.790 g/ml Shen’an Decoction respectively, and the positive control group was gavaged with benazepril hydrochloride suspension of 5 mg/kg, once a day for 14 days. The kidney histopathological changes of rats in each group were observed by HE staining. The content of BUN, creatinine(CR), Cystatin C (Cys-C), TNF-α, and IL-6 in serum were detected by ELISA. The expression of TLR-4, NF-κB p65, myeloid differentiation factor (MyD88), and tumor necrosis factor receptor related factor 6 (TRAF-6) in renal tissue were detected by Western blot. Results:Compared with the model group, the growth condition of rats in each dose group of Shen’an Decoction was significantly improved ( P<0.05), and the kidney coefficient was significantly decreased ( P<0.05). The serum levels of BUN, Cr, Cys-C, TNF-α, IL-6 of rats in each dose group of Shen’an Decoction were significantly decreased ( P<0.05). The expression of TLR-4 (0.54 ± 0.07, 0.52 ± 0.09, 0.41 ± 0.04 vs. 0.86 ± 0.06), NF-κB (0.74 ± 0.02, 0.72 ± 0.06, 0.67 ± 0.05 vs. 0.93 ± 0.03), MyD88 (0.86 ± 0.02, 0.82 ± 0.03, 0.61 ± 0.02 vs. 1.04 ± 0.03), and TRAF-6 (0.65 ± 0.04, 0.58 ± 0.08, 0.54 ± 0.07 vs. 0.90 ± 0.06) in kidney tissue of rats in each dose group of Shen’an Decoction was significantly decreased ( P<0.05). Conclusion:Shen’an Decoction can protect the renal function of rats by inhibiting TLR4/NF-κB signaling pathway and alleviating the pathological changes of renal injury induced by cisplatin.