BACKGROUND:Periprosthetic joint infection is the most common cause of early failure after total knee replacement.The current methods of preventing periprosthetic joint infection by improving the surface of the prosthesis have limitations to varying degrees.OBJECTIVE:To construct a coating material that can stably improve the surface of the implant,prevent the initial floating bacterial infection of periprosthetic infection,and regulate the bone transfer function around the implant.METHODS:(1)Material preparation:YGF polypeptide(which promotes bone formation),LL-37 polypeptide(with antibacterial properties)and YGF+LL-37 composite peptide were prepared by Fmoc solid phase peptide synthesis technology.The titanium-based materials were immersed in the three polypeptide solutions for 2 hours to obtain YGF coating,LL-37 coating and composite peptide coating coated titanium sheets.(2)In vitro experiment:Uncoated titanium sheets and coated titanium sheets were co-cultured with Escherichia coli(or Staphylococcus aureus)and the colonies were counted by plate method.MC3T3 cells were inoculated on the surface of uncoated titanium sheet and coated titanium sheet,respectively.Alizarin red staining was used to observe the calcium salt deposition on the surface of the material.Western blot assay was used to detect the protein expression of RUNX2,osteocalcin,osteopontin,and bone morphogenetic protein 2.(3)Animal experiment:24 SD rats were randomly divided into three groups:the blank group(n=8)was implanted with uncoated titanium nails in the femoral medullary canal;the control group(n=8)was implanted with uncoated titanium nails in the femoral medullary canal+intra-articular injection of Staphylococcus aureus suspension;the experimental group(n=8)was implanted with composite peptide coated titanium nails in the femoral medullary canal+intra-articular injection of Staphylococcus aureus suspension.After 5 weeks of implantation,micro-CT examination,hematoxylin-eosin staining and immunohistochemical staining of femur specimens were performed.RESULTS AND CONCLUSION:(1)In vitro experiment:Compared with uncoated titanium sheet and YGF coated titanium sheet,LL-37 coated and composite peptide coated titanium sheet could significantly inhibit the growth and reproduction of Escherichia coli and Staphylococcus aureus.Compared with uncoated titanium sheets and LL-37-coated titanium sheets,YGF-coated and composite peptide-coated titanium sheets could promote calcium salt deposition in osteoblasts and increase the protein expression of RUNX2,osteocalcin,osteopontin and bone morphogenetic protein 2.(2)Animal experiment:Micro-CT test showed that the control group had less bone mass than the blank group and the experimental group.Hematoxylin-eosin staining showed that there was a large amount of fibrous tissue around the nail channel in the control group,only a small amount of tissue fibrosis around the nail channel in the blank group,and only a small amount of tissue fibrosis around the nail channel in the experimental group.Immunohistochemical staining showed that the protein expression of interleukin 1β and tumor necrosis factor α in the control group was higher than that in the blank group and the experimental group,and the expression of osteocalcin,RUNX2 and osteopontin in the experimental group was higher than that in the blank group and the control group.(3)The results show that the titanium-based material coated with YGF+LL-37 composite peptide coating has good antibacterial ability and can promote bone transfer around the implant.

Neurocritical care involves complex pathophysiological mechanisms, and its incidence is higher, injuries are more severe, and treatment is more challenging in high-altitude environments. This consensus, based on the latest domestic and international evidence-based medical data, establishes a standardized, goal-oriented framework for neurocritical care management applicable in high-altitude regions and nationwide. The consensus was developed following international standards for evidence quality assessment and underwent two rounds of Delphi expert consultation, resulting in 32 recommendation statements covering three parts: management systems, monitoring and assessment, and core strategies. Key updates include: advocating for the establishment of independent neurocritical care units and implementing precise tiered diagnosis and treatment based on the "Five Differences in Critical Care" concept; constructing a "trinity" multimodal brain monitoring system centered on cerebral blood flow, cerebral oxygenation, and brain function, emphasizing routine bedside transcranial Doppler ultrasound, cerebral oximetry, and continuous electroencephalography monitoring; shifting management strategies from mild hypothermia therapy to targeted temperature management, and defining the "446" target management pathway for the supercritical stage; emphasizing the assessment of static and dynamic cerebrovascular autoregulation functions through multimodal methods to achieve individualized optimal mean arterial pressure management; elevating cerebrospinal fluid management goals to the level of "glymphatic system" function maintenance; implementing a multidisciplinary collaborative, whole-process management model focusing on patients' long-term neurological functional outcomes; de-escalation criteria include multidimensional indicators such as recovery of brain structure, restoration of cerebrovascular autoregulation, improvement in cerebrospinal fluid dynamics, and reduction in biomarker levels; and integrating cutting-edge technologies like artificial intelligence into post-critical care management and rehabilitation planning. This consensus systematically integrates the entire process of neurocritical care management, reflecting the modern connotation of goal-oriented, dynamic, and multimodal integration in neurocritical care medicine. It aims to adapt to new trends such as deepening understanding of pathophysiological mechanisms, the integration of medicine and engineering, and the empowerment of artificial intelligence, thereby further advancing the discipline of critical care medicine.

As the core vehicle for preserving and transmitting traditional Chinese medicine（TCM） academic thought and clinical experience， the establishment of a robust quality evaluation system for TCM clinical case reports is a crucial component in the current standardization and modernization of TCM. Based on the practical experience of constructing the China Clinical Cases Library of Traditional Chinese Medicine by the China Association of Chinese Medicine， this study conducted a comprehensive analysis of critical challenges， including insufficient authenticity and unfocused evaluation criteria. It proposed a three-dimensional evaluation framework grounded in the structure-process-outcome logic， encompassing three dimensions of authenticity and standardization， characteristics and advantages， application and translational impact. This framework integrated 12 key evaluation indicators in a systematic manner. The model preserved the academic characteristics of TCM syndrome differentiation and treatment， while aligning with modern scientific research standards， achieving a balance between individualized TCM experience and standardized evaluation. Concurrently， this study provided theoretical foundations and methodological guidance for evaluating the quality of TCM clinical cases， contributing significantly to the inheritance of TCM knowledge， evidence-based practice， and the reform of talent evaluation mechanisms.

Objective To investigate the regulatory mechanism of transforming growth factor-β1 (TGF-β1) in different types of mitral valvular disease (MVD) with atrial fibrillation (AF). Methods From August 2011 to August 2012, patients with moderate to severe MVD accompanied by AF who required mitral valve replacement at the Department of Cardiovascular Surgery, West China Hospital, Sichuan University, were included. Based on echocardiographic results, patients were divided into two groups: a mitral regurgitation (MR) with AF (MR-AF) group and a mitral stenosis (MS) with AF (MS-AF) group. Left atrial tissue samples were collected during surgery. Techniques such as enzyme-linked immunosorbent assay, real-time fluorescence quantitative polymerase chain reaction, immunohistochemistry, and Western blotting were used to detect key molecules in the TGF-β1/JNK pathway. Results Sixteen patients were enrolled. There were 8 patients in the MR-AF group, including 5 males and 3 females, with an average age of (41.38±11.19) years; and 8 patients in the MS-AF group, including 6 males and 2 females, with an average age of (43.12±5.30) years. The left atrial volume load was higher in MR-AF patients, while the left atrial pressure load was higher in MS-AF patients. In MS-AF patients, the relative expression levels of MAPK9, JUN, CASP3, BAX, and BCL2 mRNA in left atrial tissues were significantly upregulated. The serum TGF-β1 protein level and the relative expression levels of p-JNK, p-c-Jun, and Caspase-3 proteins in the left atrial tissues of the MR-AF group were higher. Myocardial cell damage was more severe in the MS-AF group, and the protein expression level of Bcl-2 was higher. Conclusion Different MVD have distinct hemodynamic characteristics. The myocardium of the left atrium in MR-AF patients is more prone to apoptosis, possibly through the activation of the TGF-β1/JNK signaling pathway.

Objective To study the correlation between Periostin, interleukin-33 (IL-33), and chronic cough after thoracoscopic lobectomy in patients with coronary artery bypass grafting (CABG) combined with lung cancer. Methods A total of 102 lung cancer and coronary heart disease patients at Tianjin Chest Hospital from January 2022 to January 2024 were prospectively enrolled, and they were divided into a chronic cough group (n=42) and a non-chronic cough group (n=60) based on whether chronic cough occurred after surgery. Serum levels of Periostin and IL-33 were measured on the 1st, 7th, and 14th days post-lobectomy. The Pearson method was employed to analyze the correlation between Periostin and IL-33 levels and the severity of cough. Univariate and multivariate logistic regression analyses were conducted to identify factors influencing the occurrence of chronic cough. Additionally, receiver operating characteristic (ROC) curve analysis was utilized to assess the potential value of serum Periostin and IL-33 levels in predicting postoperative chronic cough. Results In patients with chronic cough, the peripheral blood Periostin and IL-33 levels measured on days 7 and 14 were significantly higher than those in patients with non-chronic cough, and the interactions between the two groups and at different time points were significant (P<0.001). The degree of cough was positively correlated with the levels of Periostin and IL-33 on days 7 and 14 (P<0.05), but had no significant correlation with the levels on day 1 (P>0.05). In patients with lung cancer, after thoracoscopic lobectomy, Periostin [OR=1.619, 95%CI (1.295, 2.025)] and IL-33 [OR=1.831, 95%CI (1.216, 2.758)] on day 7 and Periostin [OR=1.952, 95%CI (1.306, 2.918)] and IL-33 [OR=1.742, 95%CI (1.166, 2.603)] on day 14 were identified as risk factors for chronic cough. ROC curve analysis showed that the sensitivity of Periostin on day 7 was 69.05%, the specificity was 71.67%, and the area under the curve (AUC) was 0.756 [95%CI (0.616, 0.893)]. The sensitivity of Periostin on day 14 increased to 71.43% and the specificity was 76.67%, AUC was 0.762 [95%CI (0.633, 0.898)]. At the same time, the critical value of IL-33 on day 7 was 45.03 pg/mL, the sensitivity and specificity were both 83.33%, the AUC was 0.884 [95%CI (0.789, 0.980)], and the critical value of IL-33 on day 14 was 56.01 pg/mL, the sensitivity was 85.71%, the specificity was 80.00%, and the AUC was 0.899 [95%CI (0.799, 0.999)]. Joint logistic regression analysis of Periostin and IL-33 levels on days 7 and 14 showed showed that the sensitivity was 95.24%, the specificity was 95.00%, and the AUC reached 0.993 [95%CI (0.979, 1.000)]. Conclusion Periostin and IL-33 levels, measured at various time points, are abnormally elevated following thoracoscopic lobectomy in patients with combined CABG and lung cancer. These levels significantly correlate with cough severity. Given their predictive potential for chronic cough, these markers are deemed valuable biomarkers.

Objective: To investigate the status of antibiotic exposure in third grade primary school students in Shenzhen,so as to provide evidence for the scientific management of antibiotic use and reduction of population health risks. Methods: From 1 September to 30 October 2021, 200 third grade students from 8 primary schools in Luohu District of Shenzhen were selected by cluster random sampling as research subjects. The body composition was measured, urine samples were collected, and the contents of 35 antibiotics in the samples were detected by mass spectrometry. Relevant dietary habit information of the subjects was collected via questionnaires. The Chi square test was used to compare the detection rate of antibiotics among different genders and weight grades. The Logistic regression model was adopted to evaluate the correlation between the target antibiotic detection rate and dietary habits. Results: At least one type of antibiotic was detected in 198 of the subjects with an overall detection rate of 99.0% . Among the 35 target antibiotics, 23 were detected with detection rates ranging from 0.5%-69.5%. Quinolones had the highest detection rate of 86.5% , followed by macrolides and sulfonamides with detection rates of 77.5% and 76.5%, respectively. The detection rate of antibiotics was 98.3% in boys and 100.0% in girls with no statistically significant difference ( χ 2=1.35, P >0.05). The detection rates of quinolones, macrolides, and sulfonamides varied significantly among children with different BMI categories ( χ 2=38.18, 12.45, 9.76 , all P <0.05). The multivariate Logistic regression model analysis showed that the macrolide detection rate was affected by genders( OR =0.42) and the sulfonamide detection rate was significantly correlated with the frequency of dairy product consumption and being overweight( OR =2.01)(both P <0.05). Enrofloxacin was associated with the weekly consumption frequency of livestock meat such as pork, beef and mutton, as well as the weekly consumption frequency of poultry meat such as chicken, duck and goose ( OR = 2.81,2.17,both P <0.05). Trimethoprim was associated with the weekly frequency of drinking pure milk ( OR =5.49, P < 0.05 ). Conclusions Third grade primary school students in Shenzhen are generally exposed to low dose antibiotics. Macrolides, quinolones, and sulfonamides may be associated with the risk of obesity in primary school students.

The Type III Secretion System (T3SS) serves as a pivotal virulence apparatus for numerous Gram-negative bacterial pathogens, enabling them to infect both animal and plant hosts. Functioning as a molecular syringe, the T3SS directly translocates bacterial effector proteins from the bacterial cytoplasm into the interior of eukaryotic host cells. These effectors are central weapons that precisely manipulate a wide spectrum of host cellular physiological processes, ranging from cytoskeletal dynamics to immune signaling, to establish a favorable niche for bacterial survival and proliferation. Among the diverse arsenal of T3SS effectors, the YopJ family constitutes a critical group of virulence factors. Members of this family are characterized by a conserved catalytic triad structure—a hallmark of the CE clan of cysteine proteases that has been evolutionarily repurposed to confer acetyltransferase activity. A defining and intriguing feature of these enzymes is their stringent dependence on a host-derived eukaryotic cofactor, inositol hexakisphosphate (IP₆), for allosteric activation. This requirement acts as a sophisticated molecular safeguard, ensuring enzymatic activity only within the appropriate host environment, thereby preventing detrimental effects on the bacterium itself. While seminal studies on individual members such as Yersinia’s YopJ and Salmonella’s AvrA have provided deep mechanistic insights, a systematic and integrative understanding of the structure-function relationships across the entire family remains fragmented. Key questions persist regarding how a conserved catalytic core has diverged to recognize distinct host substrates in different kingdoms of life. To address this gap, this article provides a systematic review of the YopJ family, focusing on three interconnected aspects: their structural features, their catalytic mechanism, and their divergent immunosuppressive strategies in animal versus plant hosts. By conducting a comparative analysis of the sequences and resolved three-dimensional structures of three representative members (e.g., HopZ1a, PopP2, AvrA), we elucidate regions of significant variation embedded within the conserved core catalytic architecture. These variable regions, often involving surface loops and substrate-binding interfaces, are crucial determinants of target specificity and functional specialization. The functional divergence of this effector family is most apparent when comparing their modes of action in different hosts. In animal hosts, YopJ-family effectors primarily sabotage innate immune signaling pathways. They achieve this by acetylating key serine and threonine residues within the activation loops of critical kinases in the MAPK and NF‑κB pathways. This post-translational modification blocks the phosphorylation and subsequent activation of these kinases, leading to potent suppression of inflammatory cytokine production. Conversely, in plant hosts, the strategy broadens to dismantle the two-tiered plant immune system. YopJ homologs target a more diverse set of substrates, including immune-associated receptor-like cytoplasmic kinases (RLCKs), microtubule networks via tubulin acetylation (which disrupts cellular trafficking and signaling), and transcription factors central to defense gene regulation. This multi-target approach effectively suppresses both Pattern-Triggered Immunity (PTI) and Effector-Triggered Immunity (ETI). In conclusion, this synthesis aims to deepen the mechanistic understanding of YopJ family-mediated pathogenesis by integrating structural biology with cellular function across host kingdoms. Elucidating the precise molecular basis for substrate selection—how conserved platforms achieve target diversity—is a major frontier. Furthermore, this knowledge provides a vital theoretical foundation for developing novel anti-virulence strategies. Targeting the conserved IP₆-binding pocket or the catalytic acetyltransferase activity itself represents a promising avenue for designing broad-spectrum inhibitors that could disarm this critical family of bacterial effectors, potentially offering new therapeutic approaches against a range of pathogenic bacteria.

ObjectiveTo investigate the influencing factors and independent risk factors for lower extremity deep vein thrombosis （DVT） in patients with acute necrotizing pancreatitis （ANP）， to analyze the effectiveness of three commonly used risk assessment models for thrombosis （Caprini score， Padua score， and Wells score）， and to provide a reference for clinical identification of high-risk individuals and optimization of prevention and treatment strategies. MethodsA retrospective analysis was performed for the clinical data of 320 patients with ANP who were admitted to Luzhou People’s Hospital and The Affiliated Hospital of Southwest Medical University from April 2013 to April 2024， and according to the presence or absence of DVT during hospitalization， the patients were divided into thrombosis group with 25 patients and control group with 295 patients. After propensity score matching， the two groups were compared in terms of past history and various examination results during hospitalization. The risk factors for lower extremity DVT in ANP patients during hospitalization were analyzed through univariate and multivariate Logistic regression， and a DVT risk prediction model was established based on independent influencing factors. The receiver operating characteristic （ROC） curve was used to assess the performance of models， and the DeLong test was used for comparison of the area under the ROC curve （AUC）， sensitivity， and specificity. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups； the chi-square test was used for comparison of categorical data between groups. ResultsAfter matching， the patients were divided into thrombosis group with 24 patients and control group with 112 patients. The clinical characteristics analysis showed that compared with the control group， the thrombosis group had significantly higher degree of pancreatic necrosis， D-dimer level， Bedside Index for Severity in Acute Pancreatitis （BISAP） score， and proportion of patients undergoing dialysis （all P<0.05）. The multivariable Logistic regression analysis showed that BISAP score， degree of pancreatic necrosis， and D-dimer level were independent risk factors for lower extremity DVT in ANP patients during hospitalization （all P<0.05）. The BISAP-Caprini score model had an AUC of 0.832 （95% confidence interval： 0.722 — 0.942， P<0.001） in predicting the risk of lower extremity DVT， with a Youden index of 1.661， an optimal cut-off value of 0.26， a sensitivity of 75.0%， and a specificity of 91.1%. ConclusionD-dimer， BISAP score， and the degree of pancreatic necrosis are independent risk factors for lower extremity DVT in patients with ANP during hospitalization， and the BISAP-Caprini score model can effectively predict the risk of DVT in ANP patients.

Metabolic reprogramming， as one of the core hallmarks of malignant tumors， plays a key role in the occurrence， development and treatment of breast cancer （BC）. Abnormal changes in glucose metabolism， amino acid metabolism， lipid metabolism， as well as the tricarboxylic acid （TCA） cycle and oxidative phosphorylation （OXPHOS） pathways significantly influence the pathogenesis and progression of BC. Studies have shown that various active components of traditional Chinese medicine （TCM） （such as berberine， matrine， quercetin， curcumin， etc.） and their compound formulations （e.g. Xihuang pill， Danzhi xiaoyao powder， Yanghe decoction， etc.） can inhibit the proliferation and migration of BC cells and induce apoptosis by regulating key metabolic pathways such as glycolysis， lipid synthesis， and amino acid metabolism. TCM demonstrates multi-target and holistic regulatory advantages in intervening in BC metabolic reprogramming， showing significant potential in modulating key molecules like hypoxia inducible factor-1α， hexokinase-2， pyruvate kinase M2， lactate dehydrogenase A， glucose transporter-1， fatty acid synthase， and signaling pathways such as AKT/mTOR. However， current researches still focus predominantly on glucose metabolism， with insufficient mechanistic studies on lipid metabolism， amino acid metabolism， the TCA cycle， and OXPHOS. The precise targets， molecular mechanisms， and clinical translation value of these interventions require further validation and clarification through more high-quality experimental studies and clinical trials.

BACKGROUND:Periprosthetic joint infection is the most common cause of early failure after total knee replacement.The current methods of preventing periprosthetic joint infection by improving the surface of the prosthesis have limitations to varying degrees.OBJECTIVE:To construct a coating material that can stably improve the surface of the implant,prevent the initial floating bacterial infection of periprosthetic infection,and regulate the bone transfer function around the implant.METHODS:(1)Material preparation:YGF polypeptide(which promotes bone formation),LL-37 polypeptide(with antibacterial properties)and YGF+LL-37 composite peptide were prepared by Fmoc solid phase peptide synthesis technology.The titanium-based materials were immersed in the three polypeptide solutions for 2 hours to obtain YGF coating,LL-37 coating and composite peptide coating coated titanium sheets.(2)In vitro experiment:Uncoated titanium sheets and coated titanium sheets were co-cultured with Escherichia coli(or Staphylococcus aureus)and the colonies were counted by plate method.MC3T3 cells were inoculated on the surface of uncoated titanium sheet and coated titanium sheet,respectively.Alizarin red staining was used to observe the calcium salt deposition on the surface of the material.Western blot assay was used to detect the protein expression of RUNX2,osteocalcin,osteopontin,and bone morphogenetic protein 2.(3)Animal experiment:24 SD rats were randomly divided into three groups:the blank group(n=8)was implanted with uncoated titanium nails in the femoral medullary canal;the control group(n=8)was implanted with uncoated titanium nails in the femoral medullary canal+intra-articular injection of Staphylococcus aureus suspension;the experimental group(n=8)was implanted with composite peptide coated titanium nails in the femoral medullary canal+intra-articular injection of Staphylococcus aureus suspension.After 5 weeks of implantation,micro-CT examination,hematoxylin-eosin staining and immunohistochemical staining of femur specimens were performed.RESULTS AND CONCLUSION:(1)In vitro experiment:Compared with uncoated titanium sheet and YGF coated titanium sheet,LL-37 coated and composite peptide coated titanium sheet could significantly inhibit the growth and reproduction of Escherichia coli and Staphylococcus aureus.Compared with uncoated titanium sheets and LL-37-coated titanium sheets,YGF-coated and composite peptide-coated titanium sheets could promote calcium salt deposition in osteoblasts and increase the protein expression of RUNX2,osteocalcin,osteopontin and bone morphogenetic protein 2.(2)Animal experiment:Micro-CT test showed that the control group had less bone mass than the blank group and the experimental group.Hematoxylin-eosin staining showed that there was a large amount of fibrous tissue around the nail channel in the control group,only a small amount of tissue fibrosis around the nail channel in the blank group,and only a small amount of tissue fibrosis around the nail channel in the experimental group.Immunohistochemical staining showed that the protein expression of interleukin 1β and tumor necrosis factor α in the control group was higher than that in the blank group and the experimental group,and the expression of osteocalcin,RUNX2 and osteopontin in the experimental group was higher than that in the blank group and the control group.(3)The results show that the titanium-based material coated with YGF+LL-37 composite peptide coating has good antibacterial ability and can promote bone transfer around the implant.