Correlation between Anxiety, Depression, and Intestinal Flora in Breast Cancer Patients: Based on 16S rRNA Sequence Analysis.

Objective: To explore intestinal flora differences in species diversity, community structure, and abundance of breast cancer and non-breast cancer populations with anxiety and depression and the corresponding group without anxiety and depression by 16S rRNA high-throughput sequencing technology. Method: Breast cancer and non-breast cancer participants were recruited based on the inclusion and exclusion criteria as the research subjects. The study employed the anxiety self-assessment scale and the depression self-rating scale in the questionnaire survey to collect data. Results: The scores of anxiety and depression of the four groups are as follows: In the breast cancer with anxiety and/or depression (BCAD) group, the anxiety score is 58.80 ± 5.27 and the depression score is 59.60 ± 4.94. In the breast cancer without anxiety and/or depression (BCWAD) group, the anxiety score is 36.53 ± 4.52 and the depression score is 38.20 ± 3.78. In the non-breast cancer group with anxiety and/or depression (HAD) group, the anxiety score is 57.87 ± 4.53 and the depression score is 59.13 ± 5.24. In the non-breast cancer group without anxiety and depression (HWAD) group, the anxiety score is 35.13 ± 5.28 and the depression score is 32.33 ± 4.37. Conclusion: The intestinal flora of the breast cancer patients is significantly different from those of non-breast cancer patients, suggesting that there is an internal relationship between the changes in the intestinal flora and the occurrence and development of breast cancer. People with anxiety and depression without breast cancer show changes in their intestinal flora, suggesting that the changes of the intestinal flora can indeed trigger anxiety and depression. For the breast cancer patients with anxiety and depression, the intestinal flora shows a decrease in diversity and abundance, suggesting that the intestinal flora of the breast cancer patients with anxiety and depression undergo further changes. Thus the intestinal flora can become a new tool for monitoring, preventing, and treating the breast cancer and negative emotions.

Occurrence and ecological risk of PAHs in urban road runoff in Beijing.

The occurrence and ecological risks of 16 polycyclic aromatic hydrocarbons (PAHs) in different types of urban road runoff in Beijing during two typical rainfall events were studied. The average concentration of PAHs in road runoff particulate was in the order of Guanyuanqiao Road (ring road, 15,175 ng/L) > Huayuanqiao Road (primary road, 4,792 ng/L) > Dongcheng Alley (alley, 4,774 ng/L) > Nansihuan Viaduct (viaduct, 770 ng/L), much higher than dissolved PAHs. The total concentration of ∑16PAHs decreased with runoff scouring. Rainfall conditions and the accumulation of PAHs in the early rainfall period show a significant impact on PAHs pollution. The event mean concentration range of PAHs is 674-21,596 ng/L, following in the order of ring road > primary road > alley > viaduct. The proportion of four-ring PAHs was the highest. The first flush effect of PAHs is found in both rainfall events, and the effect of different ring PAHs is relatively similar. The content of PAHs is positively correlated with the amount of total organic carbon and suspended substance in runoff (r2> 0.72). The ecological risk assessment indicated that PAHs in road runoff except viaduct road corresponded to high risk.

Glioma Single-Cell Biomechanical Analysis by Cyclic Conical Constricted Microfluidics.

Determining the grade of glioma is a critical step in choosing patients' treatment plans in clinical practices. The pathological diagnosis of patient's glioma samples requires extensive staining and imaging procedures, which are expensive and time-consuming. Current advanced uniform-width-constriction-channel-based microfluidics have proven to be effective in distinguishing cancer cells from normal tissues, such as breast cancer, ovarian cancer, prostate cancer, etc. However, the uniform-width-constriction channels can result in low yields on glioma cells with irregular morphologies and high heterogeneity. In this research, we presented an innovative cyclic conical constricted (CCC) microfluidic device to better differentiate glioma cells from normal glial cells. Compared with the widely used uniform-width-constriction microchannels, the new CCC configuration forces single cells to deform gradually and obtains the biophysical attributes from each deformation. The human-derived glioma cell lines U-87 and U-251, as well as the human-derived normal glial astrocyte cell line HA-1800 were selected as the proof of concept. The results showed that CCC channels can effectively obtain the biomechanical characteristics of different 12-25 µm glial cell lines. The patient glioma samples with WHO grades II, III, and IV were tested by CCC channels and compared between Elastic Net (ENet) and Lasso analysis. The results demonstrated that CCC channels and the ENet can successfully select critical biomechanical parameters to differentiate the grades of single-glioma cells. This CCC device can be potentially further applied to the extensive family of brain tumors at the single-cell level.

Construction and validation of a predictive model of pneumonia for ICU patients with traumatic brain injury (TBI).

The incidence of pneumonia in ICU patients with TBI is very high, seriously affecting the prognosis. This study aims to construct a predictive model for pneumonia in ICU patients with TBI and provide help for the prevention of TBI-related pneumonia.Clinical data of ICU patients with TBI were collected from the Medical Information Mart for Intensive Care (MIMIC)-IV database and hospital data. Variables were screened by lasso and multivariate logistic regression to construct a predictive nomogram model, verified in internal validation cohort and external validation cohort by receiver operator characteristic (ROC) curve, calibration curve and decision curve analysis (DCA).A total of 1850 ICU patients with TBI were enrolled in the study from the MIMIC-IV database, including 1298 in the training cohort and 552 in internal validation cohort. The external validation cohort included 240 ICU patients with TBI from hospital data. Nine variables were selected from the training cohort by lasso regression and multivariate logistic regression, and a pneumonia prediction nomogram was constructed. This nomogram has a high discrimination in training, internal validation and external validation cohorts (AUC = 0.857, 0.877, 0.836). The calibration curve and DCA showed that this nomogram had a high calibration and better clinical decision-making efficiency.The nomogram showed excellent discrimination and clinical utility to predict pneumonia, and could identify pneumonia high-risk patients early, thus providing personalised treatment strategies for ICU patients with TBI.

KLF11 promotes the progression of glioma via regulating Holliday junction recognition protein.

Understanding the molecular mechanism of glioma is very important for the diagnosis and treatment of glioma. Recently, a new study illustrated that KLF11 could be a potential prognostic and diagnostic biomarker in glioma, but the critical role is not illustrated. In this study, we found that KLF11 was highly expressed in glioma cancer tissues and cells, and KLF11 high expression of glioblastoma (GBM) and lower-grade glioma (LGG) were correlated with poorer overall survival and disease-free survival percentages. KLF11 knockdown inhibited glioma cell proliferation and migration, while KLF11 overexpression enhanced cell proliferation and migration. In vivo, knockdown of KLF11 reduced the tumor size of glioma. With regard to the molecular regulatory mechanism, we clarified that the Holliday junction recognition protein (HJURP) was positively regulated by KLF11. Meanwhile, we demonstrated that HJURP knockdown also inhibited glioma carcinoma progression. Overexpression of HJURP rescued the suppressed proliferation and migration function of glioma cells with depletion of KLF11. Therefore, our study demonstrated the function of KLF11 in glioma and showed KLF11 and HJURP could be prognostic and diagnostic markers in glioma, which provides a new insight of glioma therapy.

Valproic Acid After Neurosurgery Induces Elevated Risk of Liver Injury: A Prospective Nested Case-Control Study.

BACKGROUND: Valproic acid (VPA) has been widely used to prevent epileptic seizures after neurosurgery in China. We have found that the incidence of liver injury (LI) in patients using VPA after neurosurgery is higher than that in other patients. OBJECTIVE: The objective of this study was to investigate the risk factors of LI in patients using VPA after neurosurgery. METHODS: A nested case-control study was conducted in patients using VPA after neurosurgery between September 2019 and March 2021. Cases of LI were matched to controls by age and body mass index (BMI). Conditional logistic regression was used to estimate matched odds ratios representing the odds of LI. A receiver operating characteristic curve was used to analyze the optimal cutoff condition. RESULTS: A total of 248 people (62 LI and 186 control) were enrolled. Among patients with vs without LI, the matched odds ratio for trough concentration of VPA was significant (matched odds ratio [OR], 1.09; 95% confidence interval [CI]: 1.01-1.19). The course of treatment (OR: 1.17, 95% CI: 1.02-1.33), Glasgow score (OR: 0.26, 95% CI: 0.10-0.67), gene polymorphisms of CYP2C19 (OR: 2.09, 95% CI: 1.03-146.93), and UGT1A6 (OR: 34.61, 95% CI: 1.19-1003.23) were all related to the outcome. The optimal cutoff of the course of treatment was 10 days, while the trough concentration of VPA was determined to be 66.16 mg/L. CONCLUSION: Length of treatment, VPA trough concentration, and Glasgow score were associated with LI in patients after neurosurgery. A gene test may be necessary for people who are prescribed VPA for a long time.

Inhibition of PLK4 might enhance the anti-tumour effect of bortezomib on glioblastoma via PTEN/PI3K/AKT/mTOR signalling pathway.

Glioblastoma (GBM) is one of the most common aggressive cancers of the central nervous system in adults with a high mortality rate. Bortezomib is a boronic acid-based potent proteasome inhibitor that has been actively studied for its anti-tumour effects through inhibition of the proteasome. The proteasome is a key component of the ubiquitin-proteasome pathway that is critical for protein homeostasis, regulation of cellular growth, and apoptosis. Overexpression of polo-like kinase 4 (PLK4) is commonly reported in tumour cells and increases their invasive and metastatic abilities. In this study, we established a cell model of PLK4 knockdown and overexpression in LN-18, A172 and LN-229 cells and found that knockdown of PLK4 expression enhanced the anti-tumour effect of bortezomib. We further found that this effect may be mediated by the PTEN/PI3K/AKT/mTOR signalling pathway and that the apoptotic and oxidative stress processes were activated, while the expression of matrix metalloproteinases (MMPs) was down-regulated. Similar phenomenon was observed using in vitro experiments. Thus, we speculate that PLK4 inhibition may be a new therapeutic strategy for GBM.

Tumor-associated macrophage interleukin-ß promotes glycerol-3-phosphate dehydrogenase activation, glycolysis and tumorigenesis in glioma cells.

Tumor-immune crosstalk within the tumor microenvironment (TME) occurs at all stages of tumorigenesis. Tumor-associated M2 macrophages play a central role in tumor development, but the molecular underpinnings have not been fully elucidated. We demonstrated that M2 macrophages produce interleukin 1ß (IL-1ß), which activates phosphorylation of the glycolytic enzyme glycerol-3-phosphate dehydrogenase (GPD2) at threonine 10 (GPD2 pT10) through phosphatidylinositol-3-kinase-mediated activation of protein kinase-delta (PKCδ) in glioma cells. GPD2 pT10 enhanced its substrate affinity and increased the catalytic rate of glycolysis in glioma cells. Inhibiting PKCδ or GPD2 pT10 in glioma cells or blocking IL-1ß generated by macrophages attenuated the glycolytic rate and proliferation of glioma cells. Furthermore, human glioblastoma tumor GPD2 pT10 levels were positively correlated with tumor p-PKCδ and IL-1ß levels as well as intratumoral macrophage recruitment, tumor grade and human glioblastoma patient survival. These results reveal a novel tumorigenic role for M2 macrophages in the TME. In addition, these findings suggest possible treatment strategies for glioma patients through blockade of cytokine crosstalk between M2 macrophages and glioma cells.

The lncRNA DAPK-IT1 regulates cholesterol metabolism and inflammatory response in macrophages and promotes atherogenesis.

Atherosclerosis is the leading cause of cardiovascular disease (CVD) and the leading reason behind mortality and morbidity in Western countries. The role of long noncoding RNAs (lncRNAs) in CVD is still unexplored with inadequate research on the involvement of lncRNAs in atherogenesis. We found the lncRNA DAPK1-IT1 and lipoprotein lipase (LPL) to be up-regulated in THP-1 macrophage-derived foam cells. We demonstrated that DAPK1-IT1 mediated its promoting effect on LPL expression via regulating an intermediary miRNA hsa-miR-590-3p. This DAPK1-IT1/hsa-miR-590-3p/LPL axis regulates cholesterol metabolism and the inflammatory response in macrophages in vitro. Overexpressing LPL using lentiviral vectors led to decreased circulation of high-density lipoprotein cholesterol (HDL-C), increased circulation of low-density lipoprotein cholesterol (LDL-C) and very-LDL-C (VLDL-C), increased circulating pro-inflammatory cytokine levels (IL-1ß, IL-6, TNF-α), and enhanced atherogenesis in apolipoprotein E-deficient (apoE-/-) mice. In sum, the DAPK1-IT1/hsa-miR-590-3p/LPL axis regulates cholesterol metabolism and the inflammatory response in macrophages and may contribute to atherogenesis in vivo. These findings suggest this axis may be a promising therapeutic target in ameliorating CVD.

Increased versus stable dose of inhaled corticosteroids for asthma exacerbations: A systematic review and meta-analysis.

BACKGROUND: Increasing the dose of inhaled corticosteroids (ICS) is commonly used at early signs of loss of asthma control. However, the potential benefits and harms of this strategy remain unclear. We performed a systematic review and meta-analysis to compare increased dose with stable dose of ICS among adults and children with asthma. METHODS: We searched MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials from inception to August 02, 2018. Randomized clinical trials comparing increased doses vs stable doses of ICS for home management of asthma exacerbations in adults or children were included. RESULTS: The analyses included 8 trials totalling 3866 patients. Four trials were judged as low risk of bias, three were unclear risk, and one was ranked as high risk. Increased dose of ICS was associated with a significantly reduced risk of treatment failure compared with stable dose (OR 0.82, 95% CI 0.70-0.97, I2  = 6%; 314 (281 to 351) vs 358 events per 1000 patients; moderate-quality evidence). There was no significant difference in unscheduled physician visits or hospital admission between increased or stable dose of ICS. However, increased dose of ICS increased the risk of non-serious adverse events (OR 3.50, 95% CI 1.93-6.35, I2  = 0%) but not serious adverse events. CONCLUSIONS: Current evidence of moderate quality supports increasing the dose of ICS as part of a self-initiated action plan to reduce risk of requiring a course of systemic corticosteroids in people with an asthma exacerbation. However, we did not find evidence for an impact on hospital admissions or unscheduled physician visits, and increased ICS dose increased risk of non-serious adverse events.

Efficacy of Minimally Invasive Intervention in Patients With Acute Cerebral Infarction.

Our aim was to explore the efficacy of minimally invasive intervention in patients with acute cerebral infarction (ACI). Seventy patients with ACI were randomized into either an experimental group or a control group. In addition to the regular treatment, patients in the control group also received intravenous thrombolysis with urokinase, while patients in the other group underwent percutaneous transluminal cerebral angioplasty and stenting. Metrics included recanalization rate, serum cytokines, fibrinolytic markers, and 36-Item Short Form Health Survey score and were compared between the 2 groups. After treatment, patients in the experimental group had better recanalization rate, higher SF-36 score and greater levels of vascular endothelial growth factors, neurotrophic factors, and nerve growth factors than those in the control group. Moreover, the values of fibrinolytic markers changed significantly in both groups after treatment. Compared with the control group, the experimental group had lower levels of tissue polypeptide antigen and plasminogen activator inhibitor-1 and a higher level of von Willebrand factor after treatment. In sum, the application of minimally invasive intervention can increase both the recanalization rate and concentrations of serum cytokines, can improve the quality of life in patients with ACI, and has small impacts on the fibrinolytic system in patients.

Protective effect of isoliquiritigenin against cerebral injury in septic mice via attenuation of NF-κB.

BACKGROUND: The study was conducted to scrutinize the outcome of isoliquiritigenin (ISL) against cerebral injury in septic mice. METHODS: The sepsis was introduced using cecal ligation and puncture (CLP) method in experimental mice. The effect of ISL was quantified using the content of brain water and blood brain barrier (BBB) permeability. The effect on the levels of myeloperoxidase (MPO), superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione (GSH) in brain homogenates was also determined. The effect of ISL on the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6 in serum was also estimated. The levels of various inflammatory biomarkers (COX-2 and PGE2) were also studied. The expression of NF-κB signalling cascade and inducible nitric oxide synthase (iNOS) was estimated by Western blot. RESULTS: Compared with CLP group, the brain water content was found to be reduced significantly together with the enhanced BBB integrity in ISL treated group. The level of MDA was reduced together with enhanced level of SOD and GSH in the ISL treated group. The levels of TNF-α, IL-1ß, and IL-6 were also found to be modulated in ISL group. The level of COX-2 and PGE2 was reduced to near normal after ISL administration together with increase in the IκBα expression and reduction of p65 and p-p65 expression in a concentration-dependent manner. The expression of iNOS was also found to be reduced in ISL group. CONCLUSION: These results demonstrate that ISL causes protection of CLP-induced sepsis in experimental mice via multiple pathways.

A Novel Cue-Induced Abdominal Reaction Analysis for Internet Gaming Disorder.

Individuals with Internet gaming disorder (IGD) frequently play online games to achieve satisfaction. Numerous signal processing questions regarding the negative consequences and characteristic respiration in a long-term sitting posture remain unanswered. This study recruited 50 individuals with high-risk and low-risk IGD (HIGD and LIGD); these participants were taught to perform a specific respiration during game-film stimuli. The instantaneous frequencies on abdominal movement (fDF) were calculated with ensemble empirical mode decomposition (EEMD). The difference value (ΔfDF) between rest and stimulus statuses was calculated and found that HIGD showed ΔfDF values of 0.060 during positive stimuli and 0.055 during negative stimuli before the exercise but 0.020 and 0.016, respectively, after the exercise. However, the ΔfDF value for those with LIGD during negative stimuli before the exercise was 0.013, and it increased to 0.025 after the exercise. This is the first approach to IGD discrimination toward abdominal response with EEMD.

microRNA-124a suppresses PHF19 over-expression, EZH2 hyper-activation, and aberrant cell proliferation in human glioma.

Enhancer of Zeste 2 (EZH2) is the key enzymatic factor in Polycomb Repressive Complex 2 (PRC2), a transcriptional repressor which contributes to oncogenesis. Recent research has revealed the key role of aberrant EZH2 hyper-activity in human gliomas. Here, we examined the role of the lesser-known PRC2-associated PHD Finger Protein 19 (PHF19) in human glioma. We found that PHF19 transcript and protein levels were significantly elevated in human glioma tumors, which was negatively associated with expression of the anti-PHF19 microRNA miR-124a. miR-124a over-expression in the A172 and U251MG glioma cell lines and patient glioma cells suppressed PHF19 expression, EZH2 activation, and cell proliferation. However, miR-124a did not suppress cell proliferation with PHF19 silencing or mutation. Knockdown of PHF19 suppressed EZH2 phosphorylation and proliferation of glioma cells. Co-immunoprecipitation confirmed that PHF19 forms the PRC2 with EZH2, EED, and SUZ12. In a nude murine model, subcutaneous and orthotopic xenograft tumor growth was significantly inhibited by miRNA-124a or PHF19 shRNA. In conclusion, miR-124a suppresses PHF19 over-expression, EZH2 hyper-activation, and aberrant glioma cell proliferation. Targeting PHF19 via miR-124a agomir therapy may block aberrant EZH2 hyper-activity in these tumors.

[Neuronavigation-guided pure endoscopic endonasai transsphenoidal approach for pituitary adenomas].

OBJECTIVE: To explore the efficacies of neuronavigation-guided pure endoscopic endonasal transsphenoidal approach for removing pituitary adenomas. METHODS: Retrospective analyses were conducted for the clinical data of 139 patients undergoing pure endoscopic endonasal transsphenoidal surgery for pituitary adenomas between July 2011 and July 2014. There were 55 males and 84 females with a mean age of 48. 9 (21 - 73) years. The classifications of Hardy-Wilson were I (n =16), II (n = 39), III (n = 48) and IV (n = 36). Neuronavigation was used in all patients. And neuro-ophthalmological, neuroimaging and endocrinological follow-ups were conducted postoperatively. RESULTS: Total (n = 95, 68. 3%), subtotal (n = 33, 23. 7%) and partial (n = 11, 7. 9%) removals were achieved. For Hardy-Wilson I, gross total removal was achieved (n = 16, 100%); Hardy-Wilson II (n = 35, 89. 7%), Hardy-Wilson III (n = 34, 70. 8%) and Hardy-Wilson IV (n = 10, 27. 8%). Postoperative visual acuity improved (92. 1%, 70/76) and endocrine remission was observed (59. 6%, 53/89). The postoperative complications included cerebrospinal fluid (CSF) leakage (n = 8, 5. 8%), meningitis (n = 3), sellar hematoma (n = 5) and delayed carotid artery rupture (n = 1). And the patient of hemorrhagic shock underwent emergency interventional procedures and was discharged successfully. CONCLUSION: Pure endoscopic endonasal transsphenoidal approach for removing pituitary adenoma is both safe and effective. And its efficacies may further increased through combined neuronavigation.

[Comparative analysis of neuroendoscope-assisted microsurgery and microscope treatment for small acoustic neuroma].

OBJECTIVE: To explore the outcomes of surgery for the treatment of small acoustic neuroma by the neuroendoscope-assisted microsurgery and microscope. METHODS: From 2008 to 2013, 42 patients with small acoustic neuroma underwent neuroendoscope-assisted microsurgery (n = 20) and microscopic tumoural resection (n = 22). Neurophysiological monitoring, 30-degree rigid neuroendoscope and microscope were employed intra-operatively. For the endoscope group, facial nerve and inner acoustic meatus could be visualized distinctly in each aspect, as for the microscope group, microscopic operation could be accomplished directly. The damage extents of facial nerve and inner acoustic meatus were compared between two groups. RESULTS: Total removal of acoustic neuroma and conservation of facial nerve were achieved in all patients. For the neuroendoscope-assisted group, the postoperative facial functions were Grade I (n = 6), Grade II (n = 10) and Grade III (n = 4). Internal acoustic canal was drilled 2-3 mm in 4 patients and no drilling in others. For the microscope group, Grade I (n = 5), Grade II (n = 6), Grade III (n = 8) and Grade III-IV (n = 3). Internal acoustic canal was drilled at least 3 mm in 12 patients and no drilling in others. No complication such as cerebrospinal fluid leakage occurred during the follow-ups. CONCLUSION: Endosocopic operation of acoustic neuroma surgery is superior to microscopic operation in terms of magnification, illumination, wide-angel and angulation. And the former procedure may yield better outcomes through alleviating the damage of facial nerve and decreasing the drilling degree of inner acoustic meatus.

Enhancing neurosurgical navigation operation flow management through personal digital assistant technology: a prospective cohort study.

Purpose: This prospective cohort study aims to evaluate the impact of digital health technology especially Personal Digital Assistants (PDA) in neurosurgical procedure management, focusing on surgical safety check accuracy, efficiency, and patient satisfaction. Methods: The study included 211 neurosurgical cases from January to December 2022. The control group of 106 patients followed traditional verification methods, while the experimental group of 105 patients used PDA. The PDA system facilitated real-time data collection, verification, and transmission. The study compared both groups in terms of check times, accuracy rates, and patient satisfaction, and used multivariate regression to assess the impact of baseline parameters on these outcomes. Results: The study found that the experimental group using the PDA system reduced the average verification time by approximately 8 min, achieving 100.0% accuracy in preoperative and postoperative checks, significantly better than the control group (91.5% pre- and post-operation). Multivariate regression confirmed a 48.1% reduction in postoperative verification time due to the PDA system (p < 0.001), with the model showing high explanatory power (R2 = 0.911). Other examined factors, including patient age and nurse experience, had no significant effects. Similarly, the PDA's introduction markedly improved verification accuracy, with no significant impact from other variables (p = 0.010). Conclusion: The application of the PDA system in neurosurgical operations significantly enhanced the accuracy and efficiency of surgical safety checks, reduced nursing errors, optimized nursing workflows, and improved patient satisfaction. These results provide valuable insights for the application of PDA technology in high-risk medical fields, demonstrating potential of digital health tools in enhancing surgical safety and efficiency.

Effect of ANKK1 Polymorphisms on Serum Valproic Acid Concentration in Chinese Han Adult Patients in the Early Postoperative Period.

INTRODUCTION: This study aimed to investigate the relationship between gene polymorphisms and clinical factors with the concentrations of valproic acid (VPA) in adult patients who underwent neurosurgery in China. METHODS: A total of 531 serum concentration samples at steady state were collected from 313 patients to develop a population pharmacokinetic (PPK) model. Data analysis was performed using nonlinear mixed effects modeling. Covariates included demographic parameters, biological characteristics, and genetic polymorphism. Bootstrap evaluation showed that the final model was stable. Sensitive analysis was performed to verify the relationship between gene polymorphisms and concentrations of VPA. Linear regression was used to analyze the relationship between VPA concentration, ANKK1, and daily dosage. RESULTS: In the recruited patients, 17 of 25 single-nucleotide polymorphism distributions were consistent with the Hardy-Weinberg equilibrium. A one-compartment model with first-order absorption and elimination was developed for VPA injections. VPA clearance was significantly influenced by three variables: sex (17.41% higher in male than female patients), body weight, and the ANKK1 gene. Typical values for the elimination clearance and the volume of central compartment were 0.614 L/min and 23.5 L, respectively. The model evaluation indicated the stable and precise performance of the final model. After sensitive analysis using Kruskal-Wallis and Mann-Whitney U tests, we found that patients with AA alleles had higher VPA concentrations than those with GG and AG alleles. Linear regression models showed that gene polymorphisms of ANKK1 had little effects on VPA concentration. CONCLUSION: A PPK model of VPA in Chinese Han patients was successfully established; this can be helpful for model-informed precision-dosing approaches in clinical patient care, and for exploring the mechanism of VPA-induced weight gain.

National Brain Tumour Registry of China (NBTRC) statistical report of primary brain tumours diagnosed in China in years 2019-2020.

Background: The lack of a well-designed brain tumour registry with standardized pathological diagnoses in underdeveloped countries hinders the ability to compare epidemiologic data across the globe. The National Brain Tumour Registry of China (NBTRC), created in January 2018, is the first multi-hospital-based brain tumour registry in China. Patient data reported to the NBTRC in years 2019-2020 were assessed. Methods: Tumour pathology was based on the 2016 World Health Organization (WHO) classification of tumours of the central nervous system and ICD-O-3. The anatomical site was coded per the Surveillance, Epidemiology, and End Results (SEER) solid tumour module (version of July 2019). The cases were tabulated by histology and anatomical site. Categorical variables were reported as numbers (percentages). The distribution of tumours by age (0-14, 15-19, 20-39, 40-64, and 65+ years) was analysed. Findings: There were a total of 25,537 brain tumours, foremost among them meningioma (23.63%), followed by tumours of the pituitary (23.42%), and nerve sheath tumours (9.09%). Glioblastoma, the most common and lethal form of primary brain cancer in adults, represented 8.56% of all cases. Of note, 6.48% of the malignant tumours were located in the brain stem. The percentage of malignant brain tumours decreased with increasing age, 24.08% in adults (40+ years), 30.25% in young adults (20-39 years), 35.27% in adolescents (15-19 years), and 49.83% in children (0-14 years). Among the 2107 paediatric patients, the most common sites were ventricle (17.19%), brainstem (14.03%), pituitary and craniopharyngeal duct (13.4%), and cerebellum (12.3%), a distribution that differed from that of the entire cohort. The histology distribution was also unique in children, with glioblastoma much less incident compared to the whole cohort (3% vs. 8.47%, p < 0.01). 58.80% of all patients chose higher-level neurosurgical hospitals outside of their province of residence. The median in-hospital length of stay (LOS) for the various pathologies ranged from 11 to 19 days. Interpretation: The histological and anatomical site distribution of brain tumours in the NBTRC was statistically different in the subgroup of children (0-14 years). Patient choice of pursuing trans-provincial treatment was common and the in-hospital LOS was longer compared to that reported in similar European and American patient populations, which merits further attention. Funding: The National Key Research and Development Program of China (2015BAI12B04, 2013BAI09B03, 2014BAI04B01, and 2021YFF1201104) and Chinese National Natural Science Foundation of China (81971668).