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.

The thymus is a key organ for T-cell development and the establishment of central immune tolerance. Research on immune function changes and long-term health risks following thymectomy is characterized by significant population heterogeneity and controversial conclusions. This article systematically reviews the key immunological alterations after thymectomy - including reduced T-cell receptor (TCR) repertoire diversity, regulatory T cell (Treg) dysfunction, accelerated immune aging, and compensatory immune responses, and clarifies population differences in postoperative risks of infection, autoimmune diseases, and tumors, as well as the impact of surgical approaches. The clinical outcome after thymectomy is not solely determined by thymus loss, but rather depends on a dynamic balance between "immune deficiency risk" and "host compensatory capacity," which is modulated by multiple factors such as age at surgery, extent of resection, and individual immune status. This review proposes a "risk-compensation balance model" framework, providing an integrated theoretical basis for explaining the heterogeneity in outcomes across different populations and surgical methods. It also holds significant implications for future efforts in individualized surgical decision-making, establishment of stratified immune monitoring systems, and exploration of targeted immune intervention strategies.

Organophosphate flame retardants (OPFRs) have been widely used as the main alternatives to bromine-based flame retardants, resulting in their widespread detection in environmental media and even in human blood. The potential health risks arising therefrom, particularly the direct impacts on the blood system, have become a focus in the field of environmental health. This article systematically reviewed the latest research progress on the hematotoxicity of OPFRs, covering three core aspects: the toxic effects aspect, which systematically elaborated on the bidirectional interference of OPFRs with coagulation function, their toxic effects on the hematopoietic system, and their disruptive effects on blood biochemical metabolism; the mechanistic analysis aspect, which dissected the multi-pathway, multi-target toxic mechanism network of OPFRs, including common pathways based on oxidative stress and inflammatory responses, the direct and indirect regulation of coagulation function mediated by nuclear receptors and endocrine disruption, and the disturbance of blood cell production at the source through disruption of the hematopoietic microenvironment; and the risk assessment aspect, which, in response to the limitations of traditional methods, focused on the application prospects and core advantages of novel approaches based on structure-activity relationships in filling data gaps and achieving precise risk prediction. This review aims to systematically summarize the research progress on the mechanisms of OPFR-induced hematotoxicity, providing systematic theoretical support for subsequent in-depth mechanistic studies, targeted epidemiological investigations, and the optimization of risk assessment models.

ObjectiveTo explore the potential mechanism of Xiaoqinglong Decoction （小青龙汤， XD） in the treatment of allergic rhinitis. MethodsForty-five rats were randomly assigned to a control group， a model group， a loratadine group， low-， medium- and high-dose XD groups， and low-， medium- and high-dose Mahuang Decoction and Cang'erzi Powder （麻黄汤合苍耳子散， MDCP） groups. Except for the control group， rats were administered with ovalbumin （OVA） and aluminum hydroxide via intraperitoneal injection for 14 days to establish an allergic rhinitis model. After the 14th-day injection， nasal stimulation was continued with 20 μl of 10% OVA solution to maintain the model. Rats in the control group and the model group received 10 ml/（kg·d） of saline， whereas those in the loratadine group were administered with 0.9 mg/（kg·d） of loratadine. The low-， medium- and high-dose XD groups were administered XD at the dose of 2.7， 5.4， and 10.8 g/（kg·d）， respectively. The low-， medium- and high-dose MDCP groups were administered MDCP at the dose of 2.43， 4.86， and 9.72 g/（kg·d）， respectively. All treatments were administered by gavage once daily for 7 consecutive days. One hour after the final gavage， nasal symptom scores were recorded for all group of rats. The next day， serum levels of immunoglobulin E （IgE）， interleukin-4 （IL-4）， and interleukin-13 （IL-13） were measured. HE staining was used to observe the pathological morphology of the nasal mucosal tissue. Quantitative reverse transcription PCR （RT-qPCR） and Western Blot were performed to assess mRNA and protein expression of thymic stromal lymphopoietin （TSLP） and OX40 ligand （OX40L） in the nasal mucosa. ResultsCompared to the control group， total nasal symptom score in the model group significantly increased （P＜0.01）. HE staining revealed disrupted and adhered cilia， thickened basement membranes， and extensive inflammatory cell infiltration in the nasal mucosa. Serum levels of total IgE， IL-4， and IL-13， as well as TSLP and OX40L mRNA and protein expression in the nasal mucosa， were significantly elevated in the model group （P＜0.05 or P＜0.01）. Compared to the model group， the total nasal symptom scores in all drug intervention groups were significantly reduced； the serum total IgE levels in the loratadine group， the low- and medium-dose XD groups， and the low- and high-dose MDCP groups were significantly reduced； and the serum levels of IL-4 and IL-13 in the high-dose XD group and the high-dose MDCP group decreased （P＜0.05 or P＜0.01）. Nasal mucosal structure was improved. Except for the low-dose MDCP group， all other intervention groups showed a significant reduction in TSLP and OX40L mRNA expression in the nasal mucosa （P＜0.01）. All doses of XD and the medium- and high-dose MDCP groups significantly decreased the protein levels of TSLP and OX40L （P＜0.05）. The medium-dose XD group exhibited more improvement of nasal symptom scores and greater suppression of expression of TSLP and OX40L mRNA， and TSLP protein levels compared to the loratadine group （P＜0.05）. ConclusionXD may protect nasal mucosa of rats and alleviate allergic rhinitis by suppressing the TSLP/OX40L pathway， thereby attenuating Th2-mediated immune responses.

ObjectiveTo explore the potential mechanism of Xiaoqinglong Decoction （小青龙汤， XD） in the treatment of allergic rhinitis. MethodsForty-five rats were randomly assigned to a control group， a model group， a loratadine group， low-， medium- and high-dose XD groups， and low-， medium- and high-dose Mahuang Decoction and Cang'erzi Powder （麻黄汤合苍耳子散， MDCP） groups. Except for the control group， rats were administered with ovalbumin （OVA） and aluminum hydroxide via intraperitoneal injection for 14 days to establish an allergic rhinitis model. After the 14th-day injection， nasal stimulation was continued with 20 μl of 10% OVA solution to maintain the model. Rats in the control group and the model group received 10 ml/（kg·d） of saline， whereas those in the loratadine group were administered with 0.9 mg/（kg·d） of loratadine. The low-， medium- and high-dose XD groups were administered XD at the dose of 2.7， 5.4， and 10.8 g/（kg·d）， respectively. The low-， medium- and high-dose MDCP groups were administered MDCP at the dose of 2.43， 4.86， and 9.72 g/（kg·d）， respectively. All treatments were administered by gavage once daily for 7 consecutive days. One hour after the final gavage， nasal symptom scores were recorded for all group of rats. The next day， serum levels of immunoglobulin E （IgE）， interleukin-4 （IL-4）， and interleukin-13 （IL-13） were measured. HE staining was used to observe the pathological morphology of the nasal mucosal tissue. Quantitative reverse transcription PCR （RT-qPCR） and Western Blot were performed to assess mRNA and protein expression of thymic stromal lymphopoietin （TSLP） and OX40 ligand （OX40L） in the nasal mucosa. ResultsCompared to the control group， total nasal symptom score in the model group significantly increased （P＜0.01）. HE staining revealed disrupted and adhered cilia， thickened basement membranes， and extensive inflammatory cell infiltration in the nasal mucosa. Serum levels of total IgE， IL-4， and IL-13， as well as TSLP and OX40L mRNA and protein expression in the nasal mucosa， were significantly elevated in the model group （P＜0.05 or P＜0.01）. Compared to the model group， the total nasal symptom scores in all drug intervention groups were significantly reduced； the serum total IgE levels in the loratadine group， the low- and medium-dose XD groups， and the low- and high-dose MDCP groups were significantly reduced； and the serum levels of IL-4 and IL-13 in the high-dose XD group and the high-dose MDCP group decreased （P＜0.05 or P＜0.01）. Nasal mucosal structure was improved. Except for the low-dose MDCP group， all other intervention groups showed a significant reduction in TSLP and OX40L mRNA expression in the nasal mucosa （P＜0.01）. All doses of XD and the medium- and high-dose MDCP groups significantly decreased the protein levels of TSLP and OX40L （P＜0.05）. The medium-dose XD group exhibited more improvement of nasal symptom scores and greater suppression of expression of TSLP and OX40L mRNA， and TSLP protein levels compared to the loratadine group （P＜0.05）. ConclusionXD may protect nasal mucosa of rats and alleviate allergic rhinitis by suppressing the TSLP/OX40L pathway， thereby attenuating Th2-mediated immune responses.

Objective To investigate the anti-intrahepatic cholangiocarcinoma （ICC） activity and mechanism of 2-heptyl-3-hydroxy-4（1H）-quinolone （PQS）, a secondary metabolite of polar marine microorganisms. Methods Patient-derived organoid （PDO） models were established using intrahepatic cholangiocarcinoma （ICC） tumor tissues obtained from Renji Hospital, Shanghai Jiao Tong University School of Medicine. Hematoxylin and eosin （HE） staining was performed to assess the histomorphological characteristics of both patient ICC tissues and corresponding PDOs. Immunohistochemistry （IHC） was employed to evaluate CYP3a expression in patient ICC tissues and PDOs. The antiproliferative activity of PQS against stably passaged PDOs was determined using an adenosine triphosphate （ATP）-based bioluminescence assay, and dose-response curves were fitted to calculate the half-maximal inhibitory concentration （IC₅₀） for assessing the anti-ICC efficacy of PQS. In the human intrahepatic cholangiocarcinoma RBE cell model, the effects of PQS on RBE cell proliferation were evaluated by the cell counting kit-8 （CCK-8） assay; colony formation capacity was assessed by the plate colony formation assay; cell cycle distribution and apoptosis were analyzed by flow cytometry; and the protein expression levels of cyclin-dependent kinase 2（CDK2）, CDK4, RelA（p65）, and nuclear factor-κB1（p50） were detected by Western blotting. Results Two ICC PDO models were successfully established. Histomorphological observation revealed that the PDO tissues after serial passaging exhibited morphological features essentially consistent with the corresponding patient ICC tissues, both presenting as cystic vesicle-like structures. Immunohistochemical analysis demonstrated that CYP3a was expressed in both PDO tissues and patient ICC tissues. ATP-based bioluminescence assay results indicated that PQS effectively suppressed ATP content in PDO tissues, with a fitted dose-response curve yielding an IC₅₀ value of 2.49 µmol/L. In the RBE cell model, PQS inhibited RBE cell viability in a concentration-dependent manner, and the fitted dose-response curve yielded an IC₅₀ value of 1.05 µmol/L. Furthermore, PQS at concentrations of 1, 2, and 4 µmol/L significantly suppressed colony formation of RBE cells, arrested the cell cycle at the S phase, induced apoptosis, and downregulated the expression of proteins associated with the NF-κB signaling pathway. Conclusion ICC PDO models were successfully established, confirming the anti-ICC activity of PQS. PQS inhibited RBE cell proliferation, potentially via the NF-κB signaling pathway, by arresting the cell cycle at the S phase and inducing apoptosis of RBE cells

Objective To investigate the anti-intrahepatic cholangiocarcinoma （ICC） activity and mechanism of 2-heptyl-3-hydroxy-4（1H）-quinolone （PQS）, a secondary metabolite of polar marine microorganisms. Methods Patient-derived organoid （PDO） models were established using intrahepatic cholangiocarcinoma （ICC） tumor tissues obtained from Renji Hospital, Shanghai Jiao Tong University School of Medicine. Hematoxylin and eosin （HE） staining was performed to assess the histomorphological characteristics of both patient ICC tissues and corresponding PDOs. Immunohistochemistry （IHC） was employed to evaluate CYP3a expression in patient ICC tissues and PDOs. The antiproliferative activity of PQS against stably passaged PDOs was determined using an adenosine triphosphate （ATP）-based bioluminescence assay, and dose-response curves were fitted to calculate the half-maximal inhibitory concentration （IC₅₀） for assessing the anti-ICC efficacy of PQS. In the human intrahepatic cholangiocarcinoma RBE cell model, the effects of PQS on RBE cell proliferation were evaluated by the cell counting kit-8 （CCK-8） assay; colony formation capacity was assessed by the plate colony formation assay; cell cycle distribution and apoptosis were analyzed by flow cytometry; and the protein expression levels of cyclin-dependent kinase 2（CDK2）, CDK4, RelA（p65）, and nuclear factor-κB1（p50） were detected by Western blotting. Results Two ICC PDO models were successfully established. Histomorphological observation revealed that the PDO tissues after serial passaging exhibited morphological features essentially consistent with the corresponding patient ICC tissues, both presenting as cystic vesicle-like structures. Immunohistochemical analysis demonstrated that CYP3a was expressed in both PDO tissues and patient ICC tissues. ATP-based bioluminescence assay results indicated that PQS effectively suppressed ATP content in PDO tissues, with a fitted dose-response curve yielding an IC₅₀ value of 2.49 µmol/L. In the RBE cell model, PQS inhibited RBE cell viability in a concentration-dependent manner, and the fitted dose-response curve yielded an IC₅₀ value of 1.05 µmol/L. Furthermore, PQS at concentrations of 1, 2, and 4 µmol/L significantly suppressed colony formation of RBE cells, arrested the cell cycle at the S phase, induced apoptosis, and downregulated the expression of proteins associated with the NF-κB signaling pathway. Conclusion ICC PDO models were successfully established, confirming the anti-ICC activity of PQS. PQS inhibited RBE cell proliferation, potentially via the NF-κB signaling pathway, by arresting the cell cycle at the S phase and inducing apoptosis of RBE cells

OBJECTIVE: To observe the effects of point-moxibustion with Zhuang medicinal thread on differentially expressed genes (DEGs) in the dorsal root ganglion (DRG), tissue morphology, and the expression of Fc epsilon RI (FcεRI) pathway proteins spleen tyrosine kinase (Syk) and membrane spanning 4-domain A2 (MS4A2) in rat model of postherpetic neuralgia (PHN), and to explore the potential mechanism by which this therapy alleviates pain sensitization. METHODS: Thirty-nine male Sprague-Dawley (SD) rats were randomly divided into a control group, a model group, and a moxibustion group, with 13 rats in each group. The PHN model was established in the model and moxibustion groups by intraperitoneal injection of resiniferatoxin. In the moxibustion group, bilateral L₄-L₆ "Jiaji" (EX-B2) points were treated with point-moxibustion with Zhuang medicinal thread from day 7 post-modeling, with two cones per acupoint per session, every other day for a total of 10 sessions. Mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were measured at 1 day before modeling and on days 1, 4, 7, 13, 19, and 25 after modeling. After intervention, HE staining was used to observe DRG morphology. RNA sequencing was performed to analyze DEGs in DRG and conduct bioinformatics analysis. The expression of Syk and MS4A2 mRNA and proteins in the FcεRI pathway in DRG was detected by quantitative PCR and Western blot. RESULTS: Compared with the control group, the model group exhibited decreased MWT (P<0.05) and increased TWL (P<0.05); histopathological analysis revealed neuronal atrophy, nuclear displacement, and intracellular vacuoles, with a slightly loose arrangement; the RNA-Seq identified 3,207 DEGs (1,997 upregulated and 1,210 downregulated); the mRNA and protein expression levels of Syk and MS4A2 were significantly increased (P<0.01). Compared with the model group, the moxibustion group showed increased MWT (P<0.05) and decreased TWL (P<0.05), with relatively normal neuronal morphology; the RNA-Seq identified 426 DEGs (250 upregulated and 176 downregulated); the mRNA and protein expression levels of Syk and MS4A2 were significantly decreased (P<0.05). Venn diagram analysis identified 156 DEGs that showed a reversal in expression trends after treatment, including Syk and MS4A2, which are associated with pain sensitization. KEGG pathway analysis indicated that these DEGs were primarily enriched in the FcεRI pathway. CONCLUSION Point-moxibustion with Zhuang medicinal thread could alleviate pain sensitization in PHN rats, possibly by inhibiting the FcεRI signaling pathway and downregulating the expression of Syk and MS4A2.
Animals ; Rats, Sprague-Dawley ; Male ; Rats ; Moxibustion ; Neuralgia, Postherpetic/physiopathology* ; Syk Kinase/metabolism* ; Acupuncture Points ; Humans ; Ganglia, Spinal/metabolism* ; Signal Transduction

Objective:To compare the efficacy of 18F-AlF-1, 4, 7-triazacyclononane-1, 4, 7-triacetic acid (NOTA)-octreotide (OC) PET/CT and MRI in detecting liver metastases (LM) of neuroendocrine neoplasm (NENLM). Methods:18F-AlF-NOTA-OC PET/CT and MRI findings (dynamic contrast enhanced MRI and diffusion weighted imaging) of 44 patients (26 males, 18 females, age (53.8±13.4) years) with neuroendocrine neoplasm (NEN) confirmed by pathological or clinical follow-up in the First Affiliated Hospital of Zhengzhou University from July 2021 to December 2023 were retrospectively analyzed. According to the size of LM, patients were divided into 3 groups with long diameter ≤1 cm, 1 cm< long diameter ≤2 cm and long diameter >2 cm. According to the 2019 WHO pathological grade, patients were divided into G1, G2, G3 and neuroendocrine carcinoma groups. McNemar χ2 test was used to compare the difference in detecting LM and lesions between the two methods. Results:The detection rate of 18F-AlF-NOTA-OC PET/CT and MRI in patients with NENLM was 95.45%(42/44). Among 44 patients, 227 lesions were detected by PET/CT and 303 were detected by MRI. Based on lesion analysis ( n=307), the detection rate of 18F-AlF-NOTA-OC PET/CT for NENLM was lower than that of MRI (73.94%(227/307) vs 98.70%(303/307); χ2=66.96, P<0.001). For NENLM with long diameter ≤1 cm, 1 cm < long diameter ≤2 cm, long diameter >2 cm, the detection rates of MRI were higher than those of 18F-AlF-NOTA-OC PET/CT (98.72%(77/78), 93.55%(116/124), 97.35%(110/113) vs 47.44%(37/78), 73.39%(91/124), 87.61%(99/113); χ2 values: 5.88-36.21, all P<0.05). Conclusions:Compared with 18F-AlF-NOTA-OC PET/CT, MRI has a higher detection rate for NENLM with different long diameters of NEN, especially for lesions with long diameter≤1 cm.

Marine work environment is associated with unique risk factors,such as high salinity,high humidity,noise and vibration,and chemical pollution.Males make up the majority of marine workers.Prolonged exposure to these environmental factors may have adverse effects on male fertility,resulting in sperm quality reduction,endocrine disorder,and reproductive organ damage.Therefore,the potential harm of marine work environment to male reproductive health deserves attention.This review focused on the key exposure factors in marine work environment,and systematically explored the factors affecting male fertility,mechanisms,and physiological pathways.The aim is to provide scientific evidences to improve marine work environment,develop protective measures,and safeguard the reproductive health of workers,while also offering guidance for future research in this field.