Objective:To investigate the pathological characteristics of post-cholecystectomy specimens from patients with benign gallbladder diseases.Methods:This retrospective case series study analyzed clinical and pathological data from 1 712 patients who underwent cholecystectomy for benign gallbladder diseases at the Sixth People′s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine between September 2022 and August 2024. The cohort included 757 males and 955 females, with an age ( M(IQR)) of 57(23) years (range: 14 to 91 years). Clinical and pathological features were analyzed. The χ2 test was used to compare clinical characteristics between patients with neoplastic and non-neoplastic polyps. Factors statistically significant in the χ2 test were subsequently included in a binary logistic regression analysis. Results:Postoperative pathological examination revealed gallbladder cancer in 7 patients (0.41%). These 7 cases, including 2 with pT3 stage cancer, were not detected preoperatively by various imaging examinations (ultrasound+magnetic resonance cholangiopancreatography/MRI plain scan in 3 cases, ultrasound+enhanced MRI in 1 case, ultrasound+enhanced CT in 2 cases, enhanced CT+enhanced MRI in 1 case). Gallbladder adenoma was found in 23 cases (1.34%), neoplastic polyps (including cholesterol polyps with dysplasia) in 29 cases (1.69%), and non-neoplastic polyps in 154 cases (9.00%). Statistically significant differences were observed in age and polyp number between patients with neoplastic and non-neoplastic polyps ( χ2=10.436 and 8.030; both P<0.05). Binary logistic regression analysis identified age ≥60 years ( P=0.003) and solitary polyps ( P=0.009) as risk factors for neoplastic polyps. Mucosal dysplasia was present in 164 cases (9.58%), including 9 cases of severe dysplasia, 4 of which exhibited focal carcinomatous transformation. Gallbladder polyps combined with stones were found in 90 cases (5.26%), among which 10 were associated with adenoma and mucosal dysplasia, and 2 showed focal carcinomatous transformation. Conclusions:The incidence of incidental gallbladder carcinoma was 0.41%. Intraoperative bile spillage can severely compromise prognosis. Preoperative imaging demonstrates a low detection rate for neoplastic polyps. Particular vigilance for neoplastic polyps is warranted in patients aged ≥60 years or with solitary polyps. Cholecystectomy should be performed promptly for benign gallbladder diseases meeting surgical indications.

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.

ObjectiveTo explore the potential mechanism of Xiaoqinglongtang（XQL） in the prevention and treatment of high altitude pulmonary edema（HAPE） by network pharmacology， molecular docking， and molecular dynamics simulation， and to verify it by in vivo animal model. MethodsIn this study， the active ingredients， drug targets， and HAPE-related targets of XQL were collected from BATMAN-TCM， GeneCards， and Online Mendelian Inheritance in Man（OMIM） databases. The protein-protein interaction（PPI） network was constructed by using intersection targets， and the core targets were screened and visualized by Cytoscape software. Functional annotation and pathway analysis of the intersection targets were performed by gene ontology （GO） and Kyoto encyclopedia of genes and genomes （KEGG） functional enrichment. AutoDock and GROMACS were used to evaluate the binding ability of active ingredients to key targets. In the experimental verification part， a mouse model of HAPE induced by hypobaric hypoxia（simulated 6 000 m altitude for 48 h） was established. The control effect was evaluated by hematoxylin-eosin（HE） staining， lung tissue water content， lung tissue wet/dry weight ratio， real-time quantitative polymerase chain reaction（Real-time PCR） detection of gene expression levels， and immunohistochemistry and Western blot detection of key protein expression. ResultsA total of 355 active ingredients of XQL， 2 142 targets， 716 HAPE-related targets， and 236 intersection targets were obtained by network pharmacology analysis. Key core targets such as interleukin （IL）-6， tumor necrosis factor （TNF）， protein kinase B1 （Akt1）， and hypoxia-inducible factor-1α （HIF-1α） were screened. The results of GO analysis of common targets involved 738 biological processes（BP）， 72 cellular components（CC）， and 135 molecular functions（MF）. KEGG analysis effectively enriched two important signaling pathways： Phosphoinositol 3-kinase （PI3K）/Akt and HIF-1α. The results of molecular docking and molecular dynamics simulation showed that the screened active ingredients had good binding ability with key targets. In the HAPE model induced by hypobaric hypoxia（6 000 m， 48 h）， the lung tissue water content， lung tissue wet/dry weight ratio， and pathological injury score of the model group were significantly increased（P<0.01）， accompanied by exudation of a large number of red blood cells in the alveoli and alveolar interstitium， a significant increase in inflammatory cells， a significant widening of the alveolar septum， and mutual fusion between the alveoli. The XQL administration group significantly improved the above pathological changes（P<0.01）. The results of inflammatory factor expression showed that compared with the control group， the model group showed significantly up-regulated expression of TNF-α， IL-6， and IL-1β in the lung tissue（P<0.01）. Compared with the model group， the XQL administration group had significantly decreased expression of inflammatory factors（P<0.05， P<0.01）. The mRNA expression of key pathway related genes PI3K， Akt1， mammalian target of rapamycin（mTOR）， and HIF-1α was significantly increased in the model group（P<0.01）， and decreased in a concentration-dependent manner after XQL administration（P<0.05， P<0.01）. The expression levels of key proteins PI3K， phosphorylation（p）-PI3K， Akt1， p-Akt1， mTOR， p-mTOR， and HIF-1α in lung tissue were analyzed by immunohistochemistry and Western blot. Compared with the blank group， the model group showed increased expression of key proteins（P<0.05， P<0.01）. Compared with the model group， the XQL administration group exhibited decreased expression of key proteins（P<0.05， P<0.01）. ConclusionXQL can reduce lung inflammation and improve HAPE. The mechanism may be related to the regulation of PI3K/Akt/mTOR and HIF-1α pathways. This study provides a new idea and a theoretical basis for the treatment of HAPE with XQL.

ObjectiveTo explore the potential mechanism of Xiaoqinglongtang（XQL） in the prevention and treatment of high altitude pulmonary edema（HAPE） by network pharmacology， molecular docking， and molecular dynamics simulation， and to verify it by in vivo animal model. MethodsIn this study， the active ingredients， drug targets， and HAPE-related targets of XQL were collected from BATMAN-TCM， GeneCards， and Online Mendelian Inheritance in Man（OMIM） databases. The protein-protein interaction（PPI） network was constructed by using intersection targets， and the core targets were screened and visualized by Cytoscape software. Functional annotation and pathway analysis of the intersection targets were performed by gene ontology （GO） and Kyoto encyclopedia of genes and genomes （KEGG） functional enrichment. AutoDock and GROMACS were used to evaluate the binding ability of active ingredients to key targets. In the experimental verification part， a mouse model of HAPE induced by hypobaric hypoxia（simulated 6 000 m altitude for 48 h） was established. The control effect was evaluated by hematoxylin-eosin（HE） staining， lung tissue water content， lung tissue wet/dry weight ratio， real-time quantitative polymerase chain reaction（Real-time PCR） detection of gene expression levels， and immunohistochemistry and Western blot detection of key protein expression. ResultsA total of 355 active ingredients of XQL， 2 142 targets， 716 HAPE-related targets， and 236 intersection targets were obtained by network pharmacology analysis. Key core targets such as interleukin （IL）-6， tumor necrosis factor （TNF）， protein kinase B1 （Akt1）， and hypoxia-inducible factor-1α （HIF-1α） were screened. The results of GO analysis of common targets involved 738 biological processes（BP）， 72 cellular components（CC）， and 135 molecular functions（MF）. KEGG analysis effectively enriched two important signaling pathways： Phosphoinositol 3-kinase （PI3K）/Akt and HIF-1α. The results of molecular docking and molecular dynamics simulation showed that the screened active ingredients had good binding ability with key targets. In the HAPE model induced by hypobaric hypoxia（6 000 m， 48 h）， the lung tissue water content， lung tissue wet/dry weight ratio， and pathological injury score of the model group were significantly increased（P<0.01）， accompanied by exudation of a large number of red blood cells in the alveoli and alveolar interstitium， a significant increase in inflammatory cells， a significant widening of the alveolar septum， and mutual fusion between the alveoli. The XQL administration group significantly improved the above pathological changes（P<0.01）. The results of inflammatory factor expression showed that compared with the control group， the model group showed significantly up-regulated expression of TNF-α， IL-6， and IL-1β in the lung tissue（P<0.01）. Compared with the model group， the XQL administration group had significantly decreased expression of inflammatory factors（P<0.05， P<0.01）. The mRNA expression of key pathway related genes PI3K， Akt1， mammalian target of rapamycin（mTOR）， and HIF-1α was significantly increased in the model group（P<0.01）， and decreased in a concentration-dependent manner after XQL administration（P<0.05， P<0.01）. The expression levels of key proteins PI3K， phosphorylation（p）-PI3K， Akt1， p-Akt1， mTOR， p-mTOR， and HIF-1α in lung tissue were analyzed by immunohistochemistry and Western blot. Compared with the blank group， the model group showed increased expression of key proteins（P<0.05， P<0.01）. Compared with the model group， the XQL administration group exhibited decreased expression of key proteins（P<0.05， P<0.01）. ConclusionXQL can reduce lung inflammation and improve HAPE. The mechanism may be related to the regulation of PI3K/Akt/mTOR and HIF-1α pathways. This study provides a new idea and a theoretical basis for the treatment of HAPE with XQL.

Infective endocarditis (IE) is a life-threatening infectious disease. Although histopathological examination remains the gold standard for definitive diagnosis, it is performed in only a minority of patients; thus, the diagnosis of IE continues to rely predominantly on clinical manifestations. However, IE presents with highly variable systemic symptoms that often lack cardiac-specific features, posing significant diagnostic challenges. To address this complexity, multiple diagnostic criteria have been developed, integrating clinical presentation, imaging findings, and microbiological evidence. Over the past three decades, substantial shifts in the microbiological and epidemiological profiles of IE, coupled with advances in imaging modalities and laboratory diagnostics, have profoundly influenced diagnostic approaches, driving continuous refinement of diagnostic criteria. This review provides a comprehensive overview of the major diagnostic criteria for IE, traces their historical evolution, evaluates recent updates and diagnostic performance, and offers theoretical insights and practical implications to guide future research.

Objective To investigate the expression profile, prognostic value, gene co-expression network, and immunomodulatory role of BRF1 in a pan-cancer context, and to explore its biological functions and molecular regulatory mechanisms in esophageal squamous cell carcinoma (ESCC). Methods The pan-cancer dataset from The Cancer Genome Atlas (TCGA) was utilized to analyze the differential expression of BRF1 in tumor versus normal tissues, its association with patient survival, pathway enrichment for co-expressed genes, and immune features (including immune checkpoints, cytokines, and immune cell infiltration). The expression profile of BRF1 in ESCC was validated using the Gene Expression Omnibus (GEO) database. In vitro, BRF1 was knocked down in ESCC cells using siRNA. Cell proliferation and migration were assessed by MTT and Transwell assays, respectively. The expression levels of proliferation- and migration-related proteins were detected by Western blotting. The correlation between BRF1 and ferroptosis was analyzed using TCGA data. Results BRF1 was significantly upregulated in over 20 types of cancer, and its high expression was associated with poor prognosis in patients with adrenocortical carcinoma and prostate adenocarcinoma. BRF1 was found to positively regulate the T-cell-mediated cell death pathway in esophageal adenocarcinoma and was associated with the circadian rhythm regulation pathway in pancreatic adenocarcinoma. The correlation of BRF1 with immune checkpoints, cytokine networks, and immune cell infiltration was found to be cancer type-specific. In vitro experiments demonstrated that knocking down BRF1 significantly inhibited the proliferation of ESCC cells, accompanied by the downregulation of the proliferation marker PCNA. Cell migration was also significantly impaired, with decreased expression of Vimentin and MMPs and increased expression of E-cadherin. Furthermore, the expression of BRF1 was positively correlated with that of ferroptosis-antagonizing genes, such as GPX4, HSPA5, and SLC7A11. Conclusion BRF1 plays complex roles in pan-cancer, participating in the regulation of tumorigenesis, progression, and immune infiltration. BRF1 promotes the proliferation and migration of ESCC cells, a mechanism potentially associated with the regulation of ferroptosis resistance. These findings suggest that BRF1 could be a potential therapeutic target for ESCC.

Patients with Takayasu arteritis combined with aortic valve disease often have a poor prognosis following surgical valve replacement, frequently encountering complications such as perivalvular leakage, valve detachment, and anastomotic aneurysm. This article presents a high-risk case wherein severe aortic valve insufficiency associated with Takayasu arteritis was successfully managed through transcatheter aortic valve implantation via the transapical approach. The patient had satisfactory valve function with no complications observed during the six-month postoperative follow-up. This case provides a minimally invasive and feasible alternative for the clinical management of such high-risk patients.

ObjectiveTo explore the complex network relationships among pain, kinesiophobia, social participation and knee function in patients after total knee arthroplasty (TKA), and to analyze the moderating effects of different socio-structural factors on the rehabilitation network from an ethical equity perspective. MethodsA convenience sampling method was used to select 291 patients who underwent TKA in Qilu Hospital of Shandong University from May to July, 2023. Pain was assessed using Numerical Rating Scale, kinesiophobia with Chinese short version of the Tampa Scale for Kinesiophobia, social participation with Impact on Participation and Autonomy Questionnaire, and knee function with Hospital for Special Surgery Knee Score. A partial correlation network among pain, kinesiophobia, social participation and knee function was constructed using Graphical Least Absolute Shrinkage and Selection Operator. Key variables were identified through node centrality and bridge centrality analysis. Network Comparison Tests (NCT) were used to analyze network differences among subgroups based on different socio-structural characteristics. ResultsIn the network model, the nodes with the highest strength centrality were indoor participation, activity behavior and activity pain. Bridge centrality analysis indicated that activity pain, knee function, indoor participation and activity cognition were key bridge nodes. NCT revealed no significant differences in overall network structure or global strength among subgroups based on residence, education level or payment method (P > 0.05). However, significant differences in edge weights were found for specific edges such as activity cognition-activity behavior and knee function-indoor participation (P < 0.05). ConclusionThere is a network of interactions among pain, kinesiophobia, social participation and knee function in patients after TKA, with nodes such as indoor participation and activity pain playing key roles in the rehabilitation process. Although the overall rehabilitation network is similar across different socio-structural groups, variations exist in specific relational pathways among patients from rural areas, those with lower education levels, and those with out-of-pocket payment. This suggests that clinical rehabilitation interventions should focus on these core nodes and implement targeted support strategies for socio-structurally disadvantaged groups to promote rehabilitation equity.

ObjectiveTo explore the complex network relationships among pain, kinesiophobia, social participation and knee function in patients after total knee arthroplasty (TKA), and to analyze the moderating effects of different socio-structural factors on the rehabilitation network from an ethical equity perspective. MethodsA convenience sampling method was used to select 291 patients who underwent TKA in Qilu Hospital of Shandong University from May to July, 2023. Pain was assessed using Numerical Rating Scale, kinesiophobia with Chinese short version of the Tampa Scale for Kinesiophobia, social participation with Impact on Participation and Autonomy Questionnaire, and knee function with Hospital for Special Surgery Knee Score. A partial correlation network among pain, kinesiophobia, social participation and knee function was constructed using Graphical Least Absolute Shrinkage and Selection Operator. Key variables were identified through node centrality and bridge centrality analysis. Network Comparison Tests (NCT) were used to analyze network differences among subgroups based on different socio-structural characteristics. ResultsIn the network model, the nodes with the highest strength centrality were indoor participation, activity behavior and activity pain. Bridge centrality analysis indicated that activity pain, knee function, indoor participation and activity cognition were key bridge nodes. NCT revealed no significant differences in overall network structure or global strength among subgroups based on residence, education level or payment method (P > 0.05). However, significant differences in edge weights were found for specific edges such as activity cognition-activity behavior and knee function-indoor participation (P < 0.05). ConclusionThere is a network of interactions among pain, kinesiophobia, social participation and knee function in patients after TKA, with nodes such as indoor participation and activity pain playing key roles in the rehabilitation process. Although the overall rehabilitation network is similar across different socio-structural groups, variations exist in specific relational pathways among patients from rural areas, those with lower education levels, and those with out-of-pocket payment. This suggests that clinical rehabilitation interventions should focus on these core nodes and implement targeted support strategies for socio-structurally disadvantaged groups to promote rehabilitation equity.

ObjectiveTo analyze the infection characteristics of human respiratory syncytial virus (HRSV) among children hospitalized with acute lower respiratory tract infection (ALRTI) in a specialized pediatric hospital in Shanghai, so as to provide evidence-based support for optimizing the prevention and control strategies and clinical diagnosis and treatment of respiratory tract infections in children in this region. MethodsA retrospective analysis was performed to the clinical and etiological data of 29 260 children hospitalized for ALRTI in Shanghai Children’s Hospital from January 2021 to December 2024. HRSV and 12 other common respiratory pathogens were detected with multiplex polymerase chain reaction (PCR) and capillary electrophoresis. Demographic and clinical data were collected for statistical analyses. A total of2 412 cases with positive HRSV were divided into the severe group and the non-severe group. Clinical characteristics between the two groups were compared using the Mann-Whitney U test and the chi- square (χ²) test. Additionally, the related influencing factors of severe HRSV infection were explored. ResultsThe overall positivity rate of HRSV from 2021 to 2024 was 8.24% (2 412/29 260), with statistically significant differences observed across the four years (χ²=389.42, P<0.001). The highest positivity rate was in 2021 (14.76%), with a high prevalence throughout the year. In 2022, when non-pharmaceutical interventions (NPIs) were implemented, the HRSV positivity rate was the lowest (4.93%), with a winter-dominant epidemic pattern. In 2023, after the NPIs were lifted, the HRSV positivity rate showed a slight rebound (8.14%), presenting a double-peak pattern. In 2024, the HRSV positivity rate slightly decreased compared to that in 2023 (6.29%), exhibiting a winter and spring-dominant epidemic pattern. Among the hospitalized children with ALRTI, the HRSV positivity rate in males (8.85%) was higher than that in females (7.51%), and the difference was statistically significant (χ²=17.33, P<0.001). Age distribution showed that 82.26% (1 984/2 412) of HRSV infections occurred in children aged 3 years old and below. Besides, as age increased, the infection rate of HRSV showed a gradually decreasing trend (P<0.001). Among the 2 412 children with HRSV infection, the proportion of severe cases was 22.31% (538/2 412), while the non-severe cases accounted for 77.69% (1 874/2 412). Compared with non-severe cases, severe cases were more frequently presented with high fever, longer duration of wheezing, as well as higher rates of underlying diseases or co-infection with Mycoplasma pneumoniae (P<0.001). ConclusionThe prevalence intensity of HRSV varied yearly from 2021 to 2024. After the removal of NPIs in 2023, a slight rebound with a double-peak epidemic pattern was observed. HRSV remained a common pathogen in children hospitalized for ARLTI, and children aged 3 years old and below constituted the highest proportion for infection. Compared with non-severe cases, those with severe HRSV infections were more prone to presenting with high fever and a longer duration of wheezing. Children with positive HRSV who had underlying diseases or co-infection with Mycoplasma pneumonia were more likely to develop severe conditions.