Objective: To investigate the molecular mechanisms and pathways of action of total flavonoids of Dracocephalum moldavica L.(TFDM) in treating vascular cognitive impairment(VCI) based on network pharmacology and in vivo animal experiments. Methods : The swiss target prediction database, literature, and PubChem were used to screen the active components and action targets of TFDM. The online mendelian inheritance in man(OMIM) and GeneCards databases were utilized to screen for possible VCI targets. Venny software was used to obtain the intersection target of TFDM and VCI. The search tool for recurring instances of neighbouring genes(String) database and Cytoscape software was used to construct the PPI network. The database for annotation, visualization and integrated discovery(DAVID) database was utilized to screen for the kyoto encyclopedia of genes and genomes(KEGG) pathway and gene ontology(GO) enrichment analyses to explore the molecular mechanism and signaling pathway of TFDM for VCI. 24 rats were divided into Sham, Model, Donepezil, and TFDM groups. Except for the Sham group, the VCI model was created using modified bilateral common carotid artery ligation. After continuous gavage for 21 days, the Morris water maze test was used to evaluate the spatial learning and memory ability of rats. Hematoxy-lineosin(HE) staining was used to observe the pathological changes in the hippocampal CA1 and cortex region of the animals and immunohistochemistry detection of zonula occludens-1(ZO-1) content in the brains of the rats. Western blot was used to detect nuclear factor kappa-B p65(NF-κB p65) and tumor necrosis factor-α(TNF-α) in rat brains. Results : A total of 39 active ingredients of TFDM were screened, 209 corresponding targets, 10 417 gene targets of VCI, and 193 intersecting targets. According to the results of the GO enrichment of function analysis, TFDM could improve the response of reactive oxygen species and metabolic processes of reactive oxygen species, etc. KEGG pathway enrichment analysis suggested that TFDM might regulate TNF, IL-17 signing pathway, etc. The results of animal experiments showed that TFDM improved learning and memory while reduced pathological damage in the brains of VCI rats. In addition, TFDM upregulated the positive expression of ZO-1 and downregulated the protein levels of TNF-α and NF-κB p65(P<0.05). Conclusion TFDM can improve the cognitive function of VCI through multi-components and multi-targets, and its key mechanism may be related to inhibiting TNF-α/NF-κB p65 signaling pathway,reducing neuroinflammation,and improvement of blood-brain barrier permeability.

Lung cancer, a highly prevalent and deadly malignancy globally, poses a significant disease burden in China and is the leading cause of cancer death. Despite rapid advances in medicine, its incidence and mortality rates remain stubbornly high, making it a major challenge in public health. Against the backdrop of rapid progress in precision medicine, the paradigm of lung cancer treatment is shifting from single traditional therapy to multi-dimensional integration. This article comprehensively reviews the innovations and challenges in lung cancer surgery in 2024, aiming to explore the future development of surgical treatment with colleagues and to improve patients' quality of life and achieve the goal of "cure".
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Humans ; Lung Neoplasms/surgery*

Resistance to poly adenosine diphosphate (ADP)-ribose polymerase inhibitor (PARPi) presents a considerable obstacle in the treatment of ovarian cancer. F-box and tryptophan-aspartic (WD) repeat domain containing 11 (FBXW11) modulates the ubiquitination of growth-and invasion-related factors in lung cancer, colorectal cancer, and osteosarcoma. The function of FBXW11 in PARPi therapy is still ambiguous. In this study, RNA sequencing (RNA-seq) showed that FBXW11 expression was raised in ovarian cancer cells that had been treated with PARPi. FBXW11 was abnormally expressed at low levels in high-grade serous ovarian cancer (HGSOC) tissues, and low levels of FBXW11 were associated with shorter overall survival (OS) and progression-free survival (PFS) in HGSOC patients. Overexpressing FBXW11 made ovarian cancer more sensitive to PARPi, while knocking down FBXW11 made it less sensitive. The four-dimensional (4D) label-free quantitative proteomic analysis revealed that FBXW11 targeted S100 calcium binding protein A11 (S100A11) and promoted its degradation through ubiquitination. The increased degradation of S100A11 led to less efficient DNA damage repair, which in turn contributed to increased PARPi-induced DNA damage. The role of FBXW11 in promoting PARPi sensitivity was also confirmed in xenograft mouse models. In summary, our study confirms that FBXW11 promotes the susceptibility of ovarian cancer cells to PARPi via affecting S100A11-mediated DNA damage repair.

Objective:Postoperative neurosurgical bacterial meningitis (PNBM) has been frequently reported, but fewer studies have focused on the contemporaneous comparison of clinical features of PNBM caused by different pathogenic bacteria. This study aimed to simultaneously investigate the clinical characteristics and outcomes of PNBM by Gram-positive bacterial(GPB) or Gram-negative bacterial (GNB) infection.Methods:Inpatients with PNBM at our institution were recruited between February 2013 and October 2023. These PNBM patients were categorized into two groups: GPB infection and GNB infection. Data from electronic medical records were collected and analyzed.Results:A total of 401 patients with PNBM were finally included, with 78 (19.5%) having GPB infections and 323 (80.5%)having GNB infection. The average age of the patients was 56 years, and 55.1% were male. Compared to the GPB group, PNBM patients with GNB infection had significantly higher SOFA and APACHE Ⅱ scores, higher proportions of hyperthermia (body temperature>39°C) and altered consciousness, increased ratios of postoperative cerebral hemorrhage or intracranial aneurysm, as well as greater needs for ICU treatment and mechanical ventilation (all P <0.05). The proportions of inflammatory indicators such as blood CRP and PCT≥2 ng/mL, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL) were significantly higher in the GNB group (all P<0.05). In contrast, The concentrations of hemoglobin and albumin were substantially lower in this group(both P <0.05). Additionally, the cerebrospinal fluid in the GNB group showed significantly higher nucleated cell counts, protein concentration, and adenosine deaminase concentration, and but lower glucose level (all P <0.001). A total of 426 bacterial strains were isolated, with 343 strains (80.5%) being GNB and 83 strains (19.5%) being GPB. Among these, 25 (6.2%) patients had 2 or more gram-positive or gram-negative bacterial infections. The proportions of multidrug-resistant (MDR) bacteria and intrathecal treatment were higher in the GNB group (80.5% vs. 68.7%, 36.5% vs. 2.6%, respectively), while the ratio of correct empirical antibiotic treatment was significantly lower (30.3% vs. 80.0%) (all P <0.05). In terms of outcomes, the length of stay in the ICU was significantly longer in the GNB group [(median (interquartile range, IQR): 11.5 (5.25,22.75) vs. 17.0 (9.0,30.0), P <0.01)], and the rate of septic shock (9.3% vs. 2.6%), poor prognosis (GCS≤8 at discharge) (65.9% vs. 32.1%), and 28-day hospital mortality rate (34.4% vs. 10.3%) were significantly higher compared to the GPB group (all P <0.05). However, there were no differences in 7-day hospital mortality and total hospitalization time. Conclusions:Gram-negative bacterial infections are more prevalent than Gram-positive bacterial infections in PNBM, and they are also associated with more severe symptoms, abnormal cerebrospinal fluid findings, higher severity, and more treatment difficulty. Despite comparable short-term (7-day) mortality rates between Gram-positive and Gram-negative bacterial infections, Gram-negative bacterial infections result in higher medium- to long-term (14-day and 28-day) case-fatality rates among patients with post-neurosurgical bacterial meningitis and are associated with overall poorer prognosis, warranting greater attention from clinicians.

Resistance to poly adenosine diphosphate(ADP)-ribose polymerase inhibitor(PARPi)presents a considerable obstacle in the treatment of ovarian cancer.F-box and tryptophan-aspartic(WD)repeat domain containing 11(FBXW11)modulates the ubiquitination of growth-and invasion-related factors in lung cancer,colorectal cancer,and osteosarcoma.The function of FBXW11 in PARPi therapy is still ambiguous.In this study,RNA sequencing(RNA-seq)showed that FBXW11 expression was raised in ovarian cancer cells that had been treated with PARPi.FBXW11 was abnormally expressed at low levels in high-grade serous ovarian cancer(HGSOC)tissues,and low levels of FBXW11 were associated with shorter overall survival(OS)and progression-free survival(PFS)in HGSOC patients.Overexpressing FBXW11 made ovarian cancer more sensitive to PARPi,while knocking down FBXW11 made it less sensitive.The four-dimensional(4D)label-free quantitative proteomic analysis revealed that FBXW11 targeted S100 calcium binding protein A11(S100A11)and promoted its degradation through ubiquiti-nation.The increased degradation of S100A11 led to less efficient DNA damage repair,which in turn contributed to increased PARPi-induced DNA damage.The role of FBXW11 in promoting PARPi sensitivity was also confirmed in xenograft mouse models.In summary,our study confirms that FBXW11 promotes the susceptibility of ovarian cancer cells to PARPi via affecting S10OA11-mediated DNA damage repair.

Refinement and standardisation of the management of clinical diagnostic and treatment operations is a key aspect of achieving high-quality development in hospitals.By analysing the management status quo of clinical diagnosis and treatment operations in hospitals,it combed the problems existing in this field.Based on the closed-loop management model,it proposed measures and recommendations to promote the continuous optimisation of the management of clinical diagnostic operations in hospitals.Hospitals should establish hospital-level operation catalog and conduct classified management,authorize operators and dynamically adjust them,carry out operation quality management,pay attention to information management of operation management,and combine operation management with physician performance management.

Refinement and standardisation of the management of clinical diagnostic and treatment operations is a key aspect of achieving high-quality development in hospitals.By analysing the management status quo of clinical diagnosis and treatment operations in hospitals,it combed the problems existing in this field.Based on the closed-loop management model,it proposed measures and recommendations to promote the continuous optimisation of the management of clinical diagnostic operations in hospitals.Hospitals should establish hospital-level operation catalog and conduct classified management,authorize operators and dynamically adjust them,carry out operation quality management,pay attention to information management of operation management,and combine operation management with physician performance management.

The comparison between traditional Chinese medicine Jinzhen oral liquid (JZOL) and Western medicine in treating children with acute bronchitis (AB) showed encouraging outcomes. This trial evaluated the efficacy and safety of the JZOL for improving cough and expectoration in children with AB. 480 children were randomly assigned to take JZOL or ambroxol hydrochloride and clenbuterol hydrochloride oral solution for 7 days. The primary outcome was time-to-cough resolution. The median time-to-cough resolution in both groups was 5.0 days and the antitussive onset median time was only 1 day. This randomized controlled trial showed that JZOL was not inferior to cough suppressant and phlegm resolving western medicine in treating cough and sputum and could comprehensively treat respiratory and systemic discomfort symptoms. Combined with clinical trials, the mechanism of JZOL against AB was uncovered by network target analysis, it was found that the pathways in TRP channels like IL-1β/IL1R/TRPV1/TRPA1, NGF/TrkA/TRPV1/TRPA1, and PGE2/EP/PKA/TRPV1/TRPA1 might play important roles. Animal experiments further confirmed that inflammation and the immune regulatory effect of JZOL in the treatment of AB were of vital importance and TRP channels were the key mechanism of action.

Objective: Surgical procedures for patients with posttraumatic syringomyelia (PTS) remain controversial. Until now, there have been no effective quantitative evaluation methods to assist in selecting appropriate surgical plans before surgery. Methods: We consecutively enrolled PTS patients (arachnoid lysis group, n = 42; shunting group, n = 14) from 2003 to 2023. Additionally, 19 intrathecal anesthesia patients were included in the control group. All patients with PTS underwent physical and neurological examinations and spinal magnetic resonance imaging preoperatively, 3–12 months postoperatively and during the last follow-up. Preoperative lumbar puncture was performed and blood-spinal cord barrier disruption was detected by quotient of albumin (Qalb, cerebrospinal fluid/serum). Results: The ages (p = 0.324) and sex (p = 0.065) of the PTS and control groups did not differ significantly. There were also no significant differences in age (p = 0.216), routine blood data and prognosis (p = 0.399) between the arachnoid lysis and shunting groups. But the QAlb level of PTS patients was significantly higher than that of the control group (p < 0.001), and the shunting group had a significantly higher QAlb (p < 0.001) than the arachnoid lysis group. A high preoperative QAlb (odds ratio, 1.091; 95% confidence interval, 1.004–1.187; p = 0.041) was identified as the predictive factor for the shunting procedure, with the receiver operating characteristic curve showing 100% specificity and 80.95% sensitivity for patients with a QAlb > 12.67. Conclusion Preoperative QAlb is a significant predictive factor for the types of surgery. For PTS patients with a QAlb > 12.67, shunting represents the final recourse, necessitating the exploration and development of novel treatments for these patients.

Objective: Surgical procedures for patients with posttraumatic syringomyelia (PTS) remain controversial. Until now, there have been no effective quantitative evaluation methods to assist in selecting appropriate surgical plans before surgery. Methods: We consecutively enrolled PTS patients (arachnoid lysis group, n = 42; shunting group, n = 14) from 2003 to 2023. Additionally, 19 intrathecal anesthesia patients were included in the control group. All patients with PTS underwent physical and neurological examinations and spinal magnetic resonance imaging preoperatively, 3–12 months postoperatively and during the last follow-up. Preoperative lumbar puncture was performed and blood-spinal cord barrier disruption was detected by quotient of albumin (Qalb, cerebrospinal fluid/serum). Results: The ages (p = 0.324) and sex (p = 0.065) of the PTS and control groups did not differ significantly. There were also no significant differences in age (p = 0.216), routine blood data and prognosis (p = 0.399) between the arachnoid lysis and shunting groups. But the QAlb level of PTS patients was significantly higher than that of the control group (p < 0.001), and the shunting group had a significantly higher QAlb (p < 0.001) than the arachnoid lysis group. A high preoperative QAlb (odds ratio, 1.091; 95% confidence interval, 1.004–1.187; p = 0.041) was identified as the predictive factor for the shunting procedure, with the receiver operating characteristic curve showing 100% specificity and 80.95% sensitivity for patients with a QAlb > 12.67. Conclusion Preoperative QAlb is a significant predictive factor for the types of surgery. For PTS patients with a QAlb > 12.67, shunting represents the final recourse, necessitating the exploration and development of novel treatments for these patients.