Glutamate-ammonia ligase (GLUL, also known as glutamine synthetase) is a crucial enzyme that catalyzes ammonium and glutamate into glutamine in the ATP-dependent condensation. Although GLUL plays a critical role in multiple cancers, the expression and function of GLUL in gastric cancer remain unclear. In the present study, we have found that the expression level of GLUL was significantly lower in gastric cancer tissues compared with adjacent normal tissues, and correlated with N stage and TNM stage, and low GLUL expression predicted poor survival for gastric cancer patients. Knockdown of GLUL promoted the growth, migration, invasion and metastasis of gastric cancer cells in vitro and in vivo, and vice versa, which was independent of its enzyme activity. Mechanistically, GLUL competed with β-Catenin to bind to N-Cadherin, increased the stability of N-Cadherin and decreased the stability of β-Catenin by alerting their ubiquitination. Furthermore, there were lower N-Cadherin and higher β-Catenin expression levels in gastric cancer tissues compared with adjacent normal tissues. GLUL protein expression was correlated with that of N-Cadherin, and could be the independent prognostic factor in gastric cancer. Our findings reveal that GLUL stabilizes N-Cadherin by antagonizing β-Catenin to inhibit the progress of gastric cancer.

Objective To establish the UPLC fingerprint chromatogram combined with chemometric analysis for the quality evaluation of classical formula Linggui Zhugan Decoction.Methods SHIMADZU Shim-Pack GIST C18 column(100 mm×2.1 mm,2.0 μm)was used with acetonitrile-0.1%phosphoric acid aqueous solution as mobile phase,gradient elution;flow rate was 0.2 mL/min;the detection wavelength was 266 nm for the first 30 minutes and 235 nm for the last 36 minutes;the column temperature was 30℃.The UPLC fingerprint of Linggui Zhugan Decoction was established by Similarity Evaluation System for Chromatographic Fingerprint of TCM(2012.130723 version),and the common peak was determined and the similarity evaluation was carried out.Based on the peak area determination results of the common peak of the fingerprint,the quality of different batches of Linggui Zhugan Decoction was evaluated by chemometrics such as clustering analysis and principal component analysis.Results A total of 24 common peaks were confirmed and 14 components were identified by using reference substances.The similarity of 10 batches of Linggui Zhugan Decoction samples was greater than 0.950,which could be divided into two categories by chemometrics,and the principal component 1-4 were the main factors affecting its quality evaluation.OPLS-DA identified 6 differential markers.Conclusion The fingerprint research method established in the study is simple,reliable and reproducible.Through the method of fingerprint combined with chemometrics analysis,the differences between Linggui Zhugan Decoction from different origins of medicinal materials are identified,which provides a reference for the internal quality evaluation of Linggui Zhugan Decoction.

Objective:To explore the potential of integrating virtual surgery with three-dimensional (3D) printed guides in the surgical management of mandibular benign tumors and subsequent reconstruction of bone defects.Methods:A retrospective analysis was conducted on the clinical data of patients who underwent computer-assisted resection and vascularized fibular flap reconstruction for benign mandibular tumors at the Department of Oral and Maxillofacial Surgery, First Affiliated Hospital of Zhengzhou University, from June 2013 to December 2020. According to the utilization of guide plates for mandibular and fibular osteotomy during surgical procedures or not, the patients were categorized into two cohorts: a guide plate cohort and a non-guide plate cohort. In the guide plate group, custom-designed gudie plates based on virtual surgical plans were fabricated using 3D printing technology and employed intraoperatively; In the non-guide plate group, surgery was exclusively performed based on virtual surgical plan and prebent titanium plate without any supplementary plating. The measured outcomes included fibular flap osteotomy, operation duration, and clinical flap survival. Computed tomography images obtained one week post-surgery were utilized to assess the intersegmental commissure degree between fibular segments as well as between fibular segments and mandible, commissure degree between fibular segments and prebent titanium plate, and condyle position. The satisfaction of patients with their facial appearance was evaluated 6 months after the surgery using a visual analogue scale. Statistical analysis was conducted using SPSS 21.0 software. Independent sample t-tests was utilized to compare the duration of operation and and postoperative evaluation of facial appearance, the Chi-square tests was utilized for condyle position, commissure degrees among interactions involving fibular segments, prebent titanium plates, bone segments( P<0.05 denoted statistical significance). Results:A total of 30 patients were enrolled, comprising 17 males and 13 females, with a median age of 24 years (16-64 years). The preparation process of fibular flaps proceeded smoothly. The required length of fibula was measured as (14.1 ± 1.9) cm (5.7-18.1 cm), while the number of fibular segments ranged from 2 to 4, averaging at approximately 2.9 ± 0.6. The mandibular defects were repaired using a single-layer fibula in 12 cases, a vascularized folded fibula in 7 cases and a combination of vascularized and non-vascularized fibula in 11 cases. The operation time for the guide plate group was recorded as ( 335.9 ± 64.0) min (240-433 min), while it was observed to be (470.7 ± 140.5 ) min (280-680 min) for the non-guide plate group.The postoperative follow-up duration ranged from 9 to 23 months, with an average period of 11 months. All fibular flaps demonstrated clinical survival. The number of patients with good commissure degree between fibular and mandibular segments, between prebent titanium plate and fibular and mandibular segments and the position of condyle were 15, 15 and 13 cases in guide plate group, 10, 13 and 11 cases in non-guide plate group respectively. The statistical analysis revealed a significant difference ( P<0.05) in the degree of commissure between the fibular and the mandibular segments (15/15 vs. 10/15) in the two groups. Both groups exhibited high levels of satisfaction regarding their postoperative facial appearance at the 6 months follow-up, observed to be 9.6±0.5 and 9.3±0.5 respectively, and the statisticla analysis revealed non-significant difference ( P>0.05). Conclusion:The integration of virtual surgery with 3D printed guide plates can effectively reduce operative time and improve precision in the repair and reconstruction of free-fibular flaps following resection of benign tumors of the mandible.

Objective:To explore the potential of integrating virtual surgery with three-dimensional (3D) printed guides in the surgical management of mandibular benign tumors and subsequent reconstruction of bone defects.Methods:A retrospective analysis was conducted on the clinical data of patients who underwent computer-assisted resection and vascularized fibular flap reconstruction for benign mandibular tumors at the Department of Oral and Maxillofacial Surgery, First Affiliated Hospital of Zhengzhou University, from June 2013 to December 2020. According to the utilization of guide plates for mandibular and fibular osteotomy during surgical procedures or not, the patients were categorized into two cohorts: a guide plate cohort and a non-guide plate cohort. In the guide plate group, custom-designed gudie plates based on virtual surgical plans were fabricated using 3D printing technology and employed intraoperatively; In the non-guide plate group, surgery was exclusively performed based on virtual surgical plan and prebent titanium plate without any supplementary plating. The measured outcomes included fibular flap osteotomy, operation duration, and clinical flap survival. Computed tomography images obtained one week post-surgery were utilized to assess the intersegmental commissure degree between fibular segments as well as between fibular segments and mandible, commissure degree between fibular segments and prebent titanium plate, and condyle position. The satisfaction of patients with their facial appearance was evaluated 6 months after the surgery using a visual analogue scale. Statistical analysis was conducted using SPSS 21.0 software. Independent sample t-tests was utilized to compare the duration of operation and and postoperative evaluation of facial appearance, the Chi-square tests was utilized for condyle position, commissure degrees among interactions involving fibular segments, prebent titanium plates, bone segments( P<0.05 denoted statistical significance). Results:A total of 30 patients were enrolled, comprising 17 males and 13 females, with a median age of 24 years (16-64 years). The preparation process of fibular flaps proceeded smoothly. The required length of fibula was measured as (14.1 ± 1.9) cm (5.7-18.1 cm), while the number of fibular segments ranged from 2 to 4, averaging at approximately 2.9 ± 0.6. The mandibular defects were repaired using a single-layer fibula in 12 cases, a vascularized folded fibula in 7 cases and a combination of vascularized and non-vascularized fibula in 11 cases. The operation time for the guide plate group was recorded as ( 335.9 ± 64.0) min (240-433 min), while it was observed to be (470.7 ± 140.5 ) min (280-680 min) for the non-guide plate group.The postoperative follow-up duration ranged from 9 to 23 months, with an average period of 11 months. All fibular flaps demonstrated clinical survival. The number of patients with good commissure degree between fibular and mandibular segments, between prebent titanium plate and fibular and mandibular segments and the position of condyle were 15, 15 and 13 cases in guide plate group, 10, 13 and 11 cases in non-guide plate group respectively. The statistical analysis revealed a significant difference ( P<0.05) in the degree of commissure between the fibular and the mandibular segments (15/15 vs. 10/15) in the two groups. Both groups exhibited high levels of satisfaction regarding their postoperative facial appearance at the 6 months follow-up, observed to be 9.6±0.5 and 9.3±0.5 respectively, and the statisticla analysis revealed non-significant difference ( P>0.05). Conclusion:The integration of virtual surgery with 3D printed guide plates can effectively reduce operative time and improve precision in the repair and reconstruction of free-fibular flaps following resection of benign tumors of the mandible.

According to the International League Against Epilepsy (ILAE) standards, the Newborn Working Group of the ILAE put forward 6 necessary questions about the management of neonatal anti-seizure medication and gave evidence-based recommendations in 2023. The basic framework is systematic review+expert consensus. The clinical recommendations of ILAE guidelines 2023 and the similarities and differences between ILAE guidelines 2023 and ILAE guidelines 2011 were analyzed and interpreted in this paper, in order to provide reference for colleagues involved in neonatal convulsion management in China.

Objective:To evaluate the predictive value of anthropometric indicators in predicting cardiovascular risk in the population with metabolic syndrome(MS).Methods:A cross-sectional study was used to analyze the correlation between anthropometric measures and cardiovascular risk in subjects with MS. Cardiometabolic risk was assessed with cardiometabolic risk index(CMRI). Receiver operating characteristic(ROC) curve analysis was used to assess the predictive power of anthropometric measures for cardiometabolic risk.Results:(1) The anthropometric measures [body mass index(BMI), waist-hip ratio(WHR), waist-to-height ratio(WtHR), body fat percentage(BFP), visceral fat index(VFI), conicity index(CI), a body shape index(ABSI), body roundness index(BRI), abdominal volume index(AVI)] in the MS group were significantly higher than those in the non-MS group( P<0.05). Moreover, there were significant differences in CMRI score and vascular risk between the two groups( P<0.05). (2) Logistic regression analysis showed that the cardiovascular risk was increased with the increases of BMI, VFI, WHR, WtHR, CI, BRI, and AVI after adjusting for confounding factors in the overall population, the non-MS population, and the MS population( P<0.05). (3) In the ROC analysis, the AUC values of BMI, VFI, and AVI were 0.767, 0.734, and 0.770 in the overall population; 0.844, 0.816, and 0.795 in the non-MS population; 0.701, 0.666, and 0.702 in the MS population, respectively. For the overall population and non-MS population, the optimal cut points of BMI to diagnose high cardiovascular risk were 26.04 kg/m 2 and 24.36 kg/m 2; the optimal cut points of VFI were 10.25 and 9.75; the optimal cut points of AVI were 17.3 cm 2 and 15.53 cm 2, respectively. In the MS population, the optimal cut point as a predictor of high cardiovascular risk in young and middle-aged men with MS was 27.63 kg/m 2, and the optimal cut point of AVI in women was 18.08 cm 2. Conclusion:BMI, VFI, and AVI can be used as predictors of cardiovascular risk in the general population. BMI can be used as a predicator of high cardiovascular risk in young and middle-age men with MS. AVI can be used as a predicator of high cardiovascular risk in women with MS.

Nonpharmaceutical interventions (NPIs) have been commonly deployed to prevent and control the spread of the coronavirus disease 2019 (COVID-19), resulting in a worldwide decline in influenza prevalence. However, the influenza risk in China warrants cautious assessment. We conducted a cross-sectional, seroepidemiological study in Shandong Province, Northern China in mid-2021. Hemagglutination inhibition was performed to test antibodies against four influenza vaccine strains. A combination of descriptive and meta-analyses was adopted to compare the seroprevalence of influenza antibodies before and during the COVID-19 pandemic. The overall seroprevalence values against A/H1N1pdm09, A/H3N2, B/Victoria, and B/Yamagata were 17.8% (95% CI 16.2%-19.5%), 23.5% (95% CI 21.7%-25.4%), 7.6% (95% CI 6.6%-8.7%), and 15.0 (95% CI 13.5%-16.5%), respectively, in the study period. The overall vaccination rate was extremely low (2.6%). Our results revealed that antibody titers in vaccinated participants were significantly higher than those in unvaccinated individuals (P < 0.001). Notably, the meta-analysis showed that antibodies against A/H1N1pdm09 and A/H3N2 were significantly low in adults after the COVID-19 pandemic (P < 0.01). Increasing vaccination rates and maintaining NPIs are recommended to prevent an elevated influenza risk in China.

Objective:To investigate the relationship between serum uric acid (SUA) and 3-month outcomes in patients with acute ischemic stroke undergoing intravenous thrombolysis.Methods:A total of 386 patients with acute ischemic stroke received intravenous thrombolysis therapy from 1 January 2017 to 31 December 2019 in the Affiliated Hospital of Lianyungang, Xuzhou Medical University were enrolled prospectively. The National Institute of Health Stroke Scale (NIHSS) was used to evaluate the severity of stroke. The functional outcome was evaluated by the modified Rankin Scale at discharge or 3 months after onset. Pearson′s correlation was used to assess the relationship between SUA and NIHSS scores at baseline and discharge. Propensity score matching was used to balance confounding factors. Multivariate logistic regression model was used to identify the correlation between SUA and prognostic outcome after thrombolysis.Results:A total of 386 eligible patients were included. Two hundred and thirty patients (59.6%) had good outcomes in the follow-up after 3 months. The levels of SUA are negatively associated with the NIHSS score at discharge ( r=-0.171, P=0.003). A positive correlation was observed between the levels of SUA and the difference of NIHSS at baseline and discharge ( r=0.118, P=0.032). Patients were divided into three groups according to the quartile of SUA. Multivariate logistic regression analysis showed that high SUA levels were independently associated with good outcome three months after stroke ( OR=0.421, 95% CI 0.327-0.541, P<0.001). Conclusion:In patients with acute ischemic stroke, elevated SUA levels can predict better recovery and short-term outcomes in patients undergoing intravenous thrombolysis.

Liposomes have made remarkable achievements as drug delivery vehicles in the clinic. Liposomal products mostly benefited from remote drug loading techniques that succeeded in amphipathic and/or ionizable drugs, but seemed impracticable for nonionizable and poorly water-soluble therapeutic agents, thereby impeding extensive promising drugs to hitchhike liposomal vehicles for disease therapy. In this study, a series of weak acid drug derivatives were designed by a simplistic one step synthesis, which could be remotely loaded into liposomes by pH gradient method. Cabazitaxel (CTX) weak acid derivatives were selected to evaluate regarding its safety profiles, pharmacodynamics, and pharmacokinetics. CTX weak acid derivative liposomes were superior to Jevtana® in terms of safety profiles, including systemic toxicity, hematological toxicity, and potential central nerve toxicity. Specifically, it was demonstrated that liposomes had capacity to weaken potential toxicity of CTX on cortex and hippocampus neurons. Significant advantages of CTX weak acid derivative-loaded liposomes were achieved in prostate cancer and metastatic cancer therapy resulting from higher safety and elevated tolerated doses.

Objective: To assess the relationship between hemoglobin A₁c (HbA₁c) and hemorrhagic cerebral infarction (HI) in patients with acute cerebral infarction. Methods: From January 2014 to June 2016, in the Lianyungang Hospital Affiliated to Xuzhou Medical University, 426 patients with acute anterior circulation infarction were included. The blood sugar status before stroke was expressed by HbA₁c. HbA₁c and fasting blood glucose (FBG) were measured on the second day after admission. The National Institutes of Health Stroke Scale (NIHSS) was used to assess the severity of neurological function at admission. The modified Rankin scale (mRS) was used to evaluate the prognosis at discharge. CT or MRI/SWI examination was performed to determine whether there was HT. Logistic regression was used to evaluate the risk factors for HT and short-term prognosis after cerebral infarction. Results: Of the 426 patients enrolled, 93 (21.8%) appeared HT, 60 (14.1%) had hemorrhagic cerebral infarction (HI) and 33 (7.7%) had parenchymal hemorrhage (PH). Multivariate analysis showed that HbA₁c and infarct volume were independent predictor of HT. When patients were grouped according to fasting blood glucose (FBG<7.8 mmol/L or ≥ 7.8 mmol/L), the predictive effect of HbA₁c on HT was found in both groups. In multiple Logistic regression analysis, HbA₁c was also a predictor of poor prognosis after stroke (OR=1.482, 95% CI 1.228 -1.788). Conclusions In patients with ischemic stroke, elevated HbA₁c is independently associated with post-infarction HT, and this result doesn′t change even in patients with well-controlled blood glucose. HbA₁c is also a predictor of poor prognosis after stroke. These findings are important for blood glucose management in patients with diabetes and acute anterior circulation infarction.