Search

Shu Cui,1,&ast; Zhiwei Liu,1,&ast; Yun Liu,1 Gaofeng Yao,1 Yanhai Wu,1 Juanjuan Li,1 Feng Sun,1,2 Liang Sun,1,2 Longlong Sun1,2 1Department of Psychiatry, Third People’s Hospital of Fuyang, Fuyang, Anhui, 236000, People’s Republic of China; 2School of Mental Health and Psychological Sciences, Anhui Medical University, Hefei, Anhui, 238000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Gaofeng Yao; Yanhai Wu, Department of Psychiatry, Third People’s Hospital of Fuyang, Wenxing Road, Fuyang, Anhui, 236000, People’s Republic of China, Email yao_gaofeng@126.com; wyh0387@163.comObjective: This study aims to investigate the association between the systemic immune-inflammatory index (SII) and suicide attempt (SA) in children and adolescents with first-episode, drug-naïve Major Depressive Disorder (MDD) during the COVID-19 pandemic.Methods: A retrospective study was conducted on 263 MDD patients hospitalized at the Third Hospital of Fuyang City between 2020 and 2022. Patients were categorized into two groups based on the presence of previous SA. The study compared the differences in SII and clinical characteristics between the two groups and used the receiver operating characteristic (ROC) curve to determine the optimal critical value of SII and the area under the curve. Binary logistic regression was used to analyze the independent risk factors for SA.Results: Compared with the patients without SA history, the patients with a personal history of SA had a higher mean HDRS scores (Z=− 2.369, p=0.018), higher mean neutrophil count (Z=− 2.870, p=0.004), higher mean platelet count (Z=− 2.155, p=0.031), and higher mean SII (Z=− 3.170, p=0.002). The optimal critical SII determined by the ROC curve was 548.15 (sensitivity = 63.2%, specificity = 83.1%), and the area under the curve was 0.661. After adjusting for gender, age, BMI, illness duration and HDRS score, the risk of total SA in patients with high SII was 8.296 times higher than in those with low SII (OR = 8.296, 95% CI: 3.803– 18.095, P < 0.001), The risk of recent SA was 13.922 times higher in patients with high SII than in those with low SII (OR = 13.922, 95% CI: 5.587– 34.693, p < 0.001). However, high SII was not a risk factor for past SA (OR = 0.547, 95% CI: 0.062– 4.842, P=0.587).Conclusion: SII may be an inexpensive, easily accessible strategy that can assist in determining suicide risk in adolescents with MDD.Keywords: major depressive disorder, suicide attempt, children and adolescents, systemic immune-inflammation index, first-episode

Zhongyue Huang,1,&ast; Gaoqiong Yao,2,&ast; Chengzhi Zhang,2 Xin Zhou,2 Guanyang Zou,3,&ast; Chao Zhuo4,&ast; 1Institute of Medical Information/Medical Library, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Pharmacy, First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 3School of Public Health and Management, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, People’s Republic of China; 4State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guanyang Zou, No. 232, Waihuan East Road, Panyu District, Guangzhou, Guangdong Province, 510006, People’s Republic of China, Email zgy1021@hotmail.com Chao Zhuo, 195 Dongfeng West Road, Yuexiu District, Guangzhou, Guangdong Province, 510030, People’s Republic of China, Email chaosheep@gzhmu.edu.cnPurpose: With the increasing frequency and intensity of carbapenem consumption, carbapenem-resistant organisms (CRO) have become a focus of anti-infection research. This study aimed to evaluate the rationality of the clinical use of carbapenems among inpatients in the surgical departments of a tertiary hospital in southwest China.Patients and methods: A point-score system was established for evaluation based on the clinical practices in surgical departments and selected carbapenem prescriptions from June 2020 to June 2021 for hepatobiliary surgery, gastrointestinal surgery, and neurosurgery in the study hospital. Prescriptions with a total score ≥ 270 were defined as rational. Descriptive statistics were used to describe the characteristics and rationality of the prescriptions. The chi-square test, Mann–Whitney U-test, and Kruskal–Wallis H-test were used to compare characteristics between rational and irrational prescriptions. Linear regression analysis was used to determine the factors affecting the rationality of carbapenem prescriptions.Results: According to 192 carbapenem prescription records, the median age of patients was 62 years [IQR, 48.0– 73.0], and 20% of patients had abdominal infections, 10% had lung infections, 14% had intracranial infections, and 3% had urinary tract infections. 56% of carbapenem prescriptions were irrational. Compared with rational carbapenem prescriptions, irrational prescriptions had a higher proportion of those with inappropriate indications (49% vs 0%, p < 0.05), incorrect variety selection (15% vs 0%, p< 0.05), and unreasonable assessment of etiology and efficacy (46% vs 8%, p < 0.05). Linear regression analysis suggested that the diagnosis of cholecystitis (standardized regression coefficient=0.183, p< 0.05) and replaced medication (standardized regression coefficient = 0.154, p< 0.05) influenced the rationality of carbapenem prescriptions.Conclusion: Our study shows that the irrational use of carbapenems deserves attention, especially in surgical departments. Interventions for carbapenem use that are based on evaluation criteria should be developed to reduce the emergence and spread of carbapenem-resistant bacteria.Keywords: carbapenem, prescription review, surgery

Yuanliu Nie,1 Guangyue Yao,1 Liang Li,2 Alei Feng,3 Wentao Zhang,4 Xiaoying Xu,5 Qiang Li,1,3 Zhe Yang1,3 1Tumor Research and Therapy Center, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, 250021, People’s Republic of China; 2Department of Thoracic Surgery, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, 250021, People’s Republic of China; 3Tumor Research and Therapy Center, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of China; 4Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of China; 5Shandong First Medical University, College of Basic Medicine, Shandong First Medical University-Shandong Academy of Medical Sciences, Jinan, Shandong, 250000, People’s Republic of ChinaCorrespondence: Qiang Li; Zhe Yang, Tumor Research and Therapy Center, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, 250021, People’s Republic of China, Tel +86 15053162586; +86 13791089059, Email lq1211@126.com; sdslyyyz@sina.comPurpose: The present study assessed the effects of radiotherapy on overall survival (OS) and progression-free survival time (PFS) in patients with stage II or higher esophageal cancer receiving immunotherapy; evaluated factors independently prognostic of OS and PFS in these patients; and utilized these factors to establish a prognostic nomogram.Patients and Methods: This study enrolled 134 patients with stage II or higher esophageal cancer treated with chemotherapy (platinum-based agents plus paclitaxel or fluorouracil) and immunotherapy. These patients were divided into two groups, a radiotherapy (RT) group (n = 55) and a non-radiotherapy (non-RT) group (n = 79). Following 1:1 propensity score matching, OS and PFS were compared by the Kaplan–Meier method, and factors associated with survival were determined by univariate and multifactorial Cox regression analyses. These factors were used to construct a prognostic nomogram.Results: After propensity matching, all covariates were well balanced in the two groups (all P > 0.05). After matching, both median PFS (15.70 months [95% confidence interval (CI) 8.68– 22.72 months] vs 5.70 months [95% CI 3.38– 8.02 months], P = 0.002) and median OS (15.72 months [95% CI 12.94– 18.46 months] vs 12.06 months [95% CI 9.91– 14.20 months], P = 0.036) were significantly longer in the RT than in the non-RT group. Univariate and multifactorial analyses showed that RT, neutrophil-lymphocyte ratios, and tumor differentiation were independently prognostic of OS, with all hazard ratios (HRs) < 1 and all P-values < 0.05. A nomogram based on these factors was constructed, and its accuracy was verified.Conclusion: Immunotherapy plus RT resulted in better survival outcomes than immunotherapy alone. A nomogram based on prognostic factors can guide personalized treatment and monitor prognosis.Keywords: prognosis, combination therapy, survival, neutrophil-lymphocyte ratio, NLR

Hu Ren, Tao Feng, Yaning Hu, Guangqing Yao, Dahai Yu, Jianhui Cao Department of Orthopedic Surgery, Shijiazhuang People’s Hospital, Shijiazhuang, People’s Republic of ChinaCorrespondence: Jianhui Cao, Department of Orthopedic Surgery, Shijiazhuang People’s Hospital, Shijiazhuang, Hebei, 050000, People’s Republic of China, Email cjhspine@163.comPurpose: This retrospective study aimed to verify whether the use of a balloon in balloon kyphoplasty (BKP) could offer a higher degree of vertebral height restoration and deformity correction than percutaneous vertebroplasty (PVP) after adjustment for preoperative dynamic fracture mobility. We expect that this research will help surgeons to determine the optimum operation choice (PVP or BKP) for treating osteoporotic vertebral compression fractures (OVCFs).Patients and Methods: We evaluated retrospectively 262 patients who were treated by PVP or BKP for acute, single-level OVCF at our institution from July 2015 to July 2019. According to the presence or absence of dynamic fracture mobility, the patients were divided into two groups: mobile group and fixed group. We compared the changes in the vertebral height and kyphotic angle for PVP and BKP, respectively, within each group.Results: In the mobile group, the anterior vertebral height restoration (BKP group, 8.73± 5.27%; PVP group, 2.96± 1.59%), middle vertebral height restoration (BKP group, 7.58± 5.18%; PVP group, 2.74± 1.24%) and kyphotic angle correction (BKP group, 4.41± 4.46°; PVP group, 1.38± 1.60°) due to percutaneous vertebral augmentation technique itself were more obvious in BKP group compared with PVP group (P < 0.05). The BKP group has lower incidence of bone cement leakage (BKP group, 10.17%; PVP group, 25.53%, P < 0.05). In the fixed group, differences from comparison of changes were not statistically significant between PVP and BKP (P > 0.05).Conclusion: The use of a balloon in BKP could offer greater kyphosis correction, higher vertebral body height restoration, and lower cement leakage rate than PVP if a fractured vertebral body existed dynamic mobility. However, all these advantages of BKP over PVP are not obvious and could be overrated for a fixed fracture exhibited no mobility. BKP is recommended for a fractured vertebral body with dynamic mobility. PVP is suggested for a fixed fractured vertebral body with no mobility as it produces similar capability of vertebral height restoration, kyphosis correction, and cement leakage as BKP.Keywords: dynamic fracture mobility, optimum operation choice, osteoporotic vertebral compression fracture, balloon kyphoplasty, percutaneous vertebroplasty

Jian Qiu,1 Jiewei Xu,2 Guorong Yao,1 Fengjia Zhu,1 Yanyan Wang,3 Yunfeng Fu4 1Department of Obstetrics and Gynaecology, Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, Huzhou, 313000, People’s Republic of China; 2Department of General Surgery, Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, Huzhou, 313000, People’s Republic of China; 3Department of Pathology, Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, Huzhou, 313000, People’s Republic of China; 4Department of Gynecologic Oncology, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, 310006, People’s Republic of ChinaCorrespondence: Yunfeng Fu, Department of Gynecologic Oncology, Women’s Hospital, School of Medicine, Zhejiang University, Xueshi Road #2, Hangzhou, 310006, People’s Republic of China, Tel +86-571-87061501, Fax +86-571-87061878, Email 5100008@zju.edu.cnAbstract: Large cell neuroendocrine carcinoma (LCNEC) is a rare histological subtype of ovarian cancer. A few cases have been reported in the literature with extreme invasiveness and a poor prognosis. However, there still have not been accepted criteria for diagnosis and treatment of LCNEC. Here we report an unmarried 37 year-old woman who was diagnosed with LCNEC associated with clear cell carcinoma and the tumor index was manifested with a specific increase of AFP. The case received six courses of etoposide and carboplatin chemotherapy as an adjuvant therapy after primary curative surgery. However, she relapsed within 6 months after surgery and metastasized rapidly to distant organs despite combined chemotherapy of paclitaxel, cisplatin, and bevacizumab, and died 18 months after primary surgery. This is the first reported case of LCNEC manifested with a specific increase of AFP and characteristically metastasized to the spine as recurrence. Reviewing our case as well as previously reported cases, LCNEC present with aggressive malignancy and vulnerable to distant metastasis through a hematogenous approach, we conjectured that adding Bevacizumab in primary chemotherapy may be beneficial to extend disease-free survival. But so far there is no recommendation of this regimen for treatment of LCNEC in current guidelines. Further research is needed to confirm this view so as to find the best treatment of LCNEC and improve the prognosis of these patients.Keywords: large cell neuroendocrine carcinoma, ovarian tumors

Xinxin Yang1 ,* Qi You2,3 ,* Guodong Yao,1 Jingshu Geng,1 Rong Ma,4 Hongxue Meng1,2 1Department of Pathology, Harbin Medical University Cancer Hospital, Harbin, People’s Republic of China; 2Department of Pathology, Harbin Medical University, Harbin, People’s Republic of China; 3Department of Gastroenterology, Harbin Medical University Cancer Hospital, Harbin, People’s Republic of China; 4Department of Gynaecology, Harbin Medical University Cancer Hospital, Harbin, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hongxue Meng Department of PathologyHarbin Medical University, 150 Haping Road, Harbin, People’s Republic of ChinaTel +86-451-85718261Email menghongxue15@163.comRong Ma Department of GynaecologyHarbin Medical University Cancer Hospital, 150 Haping Road, Harbin, People’s Republic of ChinaTel +86-451-85718263Email maronghai@163.comBackground: Human papillomavirus (HPV) is a high-risk etiological factor for cervical and ovarian carcinomas. p16 protein can be used as a surrogate biomarker for HPV infection in high-risk tumors. A strong correlation between HPV infection and programmed death ligand 1 (PD-L1) protein expression has consistently been reported.Objective: Given this background, this study investigates the prevalence, prognostic and clinicopathologic features of HPV-related epithelial ovarian cancer (EOC) for the last 10 years in Northeast China to elucidate the involvement of p16 in the PD-L1 protein expression, tumorigenesis, and progression of EOC.Methods: Specimens from 310 patients diagnosed with EOC collected from 2006 to 2016 were analyzed by polymerase chain reaction (PCR) for HPV DNA, and overexpression of p16 by immunohistochemistry was also evaluated. Statistical analysis was performed to estimate the significant difference between HPV positive and negative patients, the correlation among HPV state, p16 and PD-L1 expression, and clinical presentation.Results: Overexpression of p16 protein and HPV DNA were present in 100 (32.3%) of the 310 cases, and correlated with high PD-L1 expression. There was a good concordance between HPV positivity, p16 protein overexpression and PD-L1 expression. The etiological fraction of HPV in EOC is substantially higher in Northeast China than other cohorts previously reported.Conclusion: Our study demonstrates that HPV infection and p16 overexpression is significantly associated with PD-LI expression in EOC, through the cooperative roles of dendritic cells (DCs) and IFN-γ, which may represent a promising strategy for therapeutic intervention in EOC.Keywords: HPV, p16, PD-L1, ovarian cancer, pathogenesis, prognosis

Ning Lin,1,* Wentao Li,2,* Xiefeng Wang,2,* Shiqiang Hou,1 Dong Yu,1 Xingyuan Zhao,1 Chunjing Jin,3 Guoquan Yao,1 Wei Yan,2 Yongping You2 1Department of Neurosurgery, Chuzhou Clinical College of Anhui Medical University, The First People’s Hospital Chuzhou, Chuzhou, People’s Republic of China; 2Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 3Laboratory Medicine Center, Affiliated Hospital of Nantong University, Nantong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ning LinDepartment of Neurosurgery, Chuzhou Clinical College of Anhui Medical University, The First People’s Hospital Chuzhou, Chuzhou, People’s Republic of ChinaEmail lin2007512@vip.163.comYongping YouDepartment of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of ChinaEmail YYPL9@njmu.edu.cnBackground: Epithelial–mesenchymal Transition (EMT) is involved in various cancers including glioblastoma. Our previous study has shown that miR-340 negatively correlated with EMT process in glioblastoma.Purpose: In the present study, we aim to explore the underlying molecular mechanisms of miR-340 in EMT process of glioblastomas.Materials and Methods: Using RT-qPCR assay, we analyzed the expression of miR-340 in glioma cell lines and normal human glia (NHA) cell line. Using CCK8, Colony formation assays, transwell and Western blot assays, we investigated tumor growth and EMT process. Using luciferase reporter assay, we confirmed a target of miR-340.Results: Our results showed that miR-340 was down-regulated in glioma cell lines (U87, U251 and LN229) compared to NHA cells. MiR-340 overexpression remarkably inhibited cell proliferation and invasion as well as up-regulated E-cadherin expression and down-regulated N-cadherin, Vimentin, ZEB1, Slug and Snail expressions in U251 and LN229 cells. Further studies have confirmed c-MET as a target gene of miR-340. The EMT-inhibitory effect of miR-340 was lost after c-MET expression was restored. We also identified the antitumorigenic activity of miR-340 in vivo.Conclusion: These results demonstrated that miR-340 functioned as a tumor suppressor via targeting EMT process and could be a potential therapeutic candidate for treating glioblastomas.Keywords: miR-340, EMT, c-MET, glioblastoma

Guoshu Bi,* Tao Lu,* Guangyu Yao, Yunyi Bian, Mengnan Zhao, Yiwei Huang, Yi Zhang, Liang Xue, Cheng Zhan, Hong Fan Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hong Fan; Cheng ZhanZhongshan Hospital, No. 180 Fenglin Road, Xuhui District, Shanghai 200032, People’s Republic of ChinaTel +86 139 1689 7139Fax +86 21 6404 1990 Ext 2915Email fan.hong@zs-hospital.sh.cn; czhan10@fudan.edu.cnBackground: Lymph node ratio (LNR), defined as the ratio of the number of positive lymph nodes to the total of all resected nodes, has been reported to be a predictor of survival of patients with several types of cancer. However, the prognostic value of LNR and other factors in patients with resected N2 stage lung squamous cell carcinoma has never been considered.Methods: Data from 1778 patients with resected N2 stage lung squamous cell carcinoma were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. The optimal cutoff value of LNR was identified by X-tile. A multivariable Cox model and corresponding nomogram were constructed to predict overall survival (OS) and cancer-specific survival (CSS). Both the cutoff value of LNR and the model were further validated in 146 similar patients treated in Zhongshan Hospital. Heat maps were created to visualize the distribution of LNR and the number of positive lymph nodes with the predicted survival probabilities.Results: The optimal cutoff value for LNR was identified as 0.42. Multivariable analysis showed that age, sex, tumor laterality, type of surgery, T stage, chemotherapy and LNR were independently correlated with OS. Harrell’s C-index of the nomogram (0.64) was significantly higher than the index of the T stage-based model (0.54). Calibration curves showed good agreement between predicted and observed survival probabilities. The robustness of the model was also demonstrated by external validation.Conclusion: LNR less than 0.42 was associated with improved OS and CSS for patients with resected N2 stage lung squamous cell carcinoma.Keywords: lymph node ratio, N2 stage lung squamous cell carcinoma, prognostic model, nomogram, heatmap

Ning Sun,1,2,* Dou Wang,3,* Guoqiang Yao,4 Xiaomei Li,1 Ting Mei,1 Xinke Zhou,1 Kwok-Yin Wong,2 Baishan Jiang,4 Zhiyuan Fang,11The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou 510500, People’s Republic of China; 2State Key Laboratory of Chemical Biology and Drug Discovery, and Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong SAR, People’s Republic of China; 3Department of Hepatobiliary and Pancreatic Surgery, Shenzhen People‘s Hospital, Second Clinical Medical College of Jinan University, Shenzhen 518020, People’s Republic of China; 4Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, People’s Republic of China*These authors contributed equally to this work Background: The intraoperative visualization of tumor cells is a powerful modality for surgical treatment of solid tumors. Since the completeness of tumor excision is closely correlated with the survival of patients, probes that can assist in distinguishing tumor cells are highly demanded.Purpose: In the present study, a fluorescent probe JF1 was synthesized for imaging of tumor cells by conjugating a substrate of cathepsin B (quenching moiety) to Oregon Green derivative JF2 using a self-immolative linker.Methods: JF1 was then loaded into the folate-PEG modified CaCO3 nanoparticles. The folate receptor-targeted, pH-dependent, and cathepsin B activable CaCO3 nanoprobe was test in vitro and in vivo for tumor imaging.Results: CaCO3 nanoprobe demonstrated good stability and fast lighting ability in tumors under low pH conditions. It also showed lower fluorescence background than the single cathepsin B dependent fluorescent probe. The pH-dependent and cathepsin B controlled “turn-on” property enables precise and fast indication of tumor in vitro and in vivo.Conclusion: This strategy of controlled drug delivery enables in vivo imaging of tumor nodules with a high signal-to-noise ratio, which has great potential in surgical tumor treatment.Keywords: cathepsin B, activable probe, fluorescent probe, CaCO3 nanoparticle, tumor imaging

Jian Qiu,1,2 Yunfeng Fu,1 Jiewei Xu,3 Xiaohong Huang,2 Guorong Yao,2 Weiguo Lu1 1Department of Gynecologic Oncology, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, China; 2Department of Obstetrics and Gynaecology, Huzhou Central Hospital, Huzhou, Zhejiang 313000, China; 3Department of General Surgery, Huzhou Central Hospital, Huzhou, Zhejiang 313000, China Purpose: The purpose of this study was to investigate the efficiency, complications, and subsequent fertility outcomes of two methods in treating patients with cesarean scar pregnancy (CSP) after receiving uterine artery embolization (UAE) treatment.Patients and methods: A total of 62 CSP patients who visited our hospital and underwent UAE from January 2013 to January 2018 were retrospectively analyzed. Patients were either treated by dilation and curettage (D&C) guided by ultrasonography or hysteroscopy. The differences of related clinical indicators, clinical efficacy, complications, and subsequent fertility outcomes between the two groups were analyzed.Results: The rates of therapeutic success of the ultrasonography group and hysteroscopy group were 84.6% and 95.7%, respectively, the difference was not statistically significant (P=0.243). However, the intraoperative blood loss, duration of hospitalization, and overall complications were significantly lower in hysteroscopy group compared with D&C guided by ultrasonography group (P

In the present study, we developed Mo- and Zr-added W-Y2O3 composites, and investigated their surface damage, including commercially available W induced by He and D as well as He and D mixture plasmas. Blistering was not observed in the D-plasma-irradiated W and W composites. The thickness of the damaged surface layer due to He plasma exposure of the W-Mo-Y2O3 composite was similar to that of W. However, the thickness of the damaged surface layer of the W-Y2O3 composite was half that of W. In addition, the thickness of the damaged surface layer of the W-Zr-Y2O3 composite was further improved by 5 times. Y2O3 nanoparticles, especially refined Zr-Y-O nanoparticles, act as He trap sites to suppress the formation and growth of He bubbles. Furthermore, the W-O-Y and W-O-Zr-Y nanoparticles increased the solubility of He and delayed He diffusion, hindering the formation of He bubbles. [ABSTRACT FROM AUTHOR]

Botulinum neurotoxins (BoNTs) are among the most deadly toxins known. They act rapidly in a highly specific manner to block neurotransmitter release by cleaving the soluble N-ethylmaleimide sensitive factor attachment protein receptor (SNARE) complex at neuromuscular junctions. The extreme toxicity of BoNTs relies predominantly on their neurotropism that is accomplished by recognition of two host receptors, a polysialo-ganglioside and in the majority of cases a synaptic vesicle protein, through their receptor-binding domains. Two proteins, synaptotagmin and synaptic vesicle glycoprotein 2, have been identified as the receptors for various serotypes of BoNTs. Here, we review recent breakthroughs in the structural studies of BoNT-protein receptor recognitions that highlight a range of diverse mechanisms by which BoNTs manipulate host neuronal proteins for highly specific uptake at neuromuscular junctions.

OBJECTIVE: The aim of this study was to elucidate the relationship between venous lactate levels and the severity of acute pancreatitis (AP). PATIENTS AND METHODS: Retrospective data analysis was conducted on patients diagnosed with acute pancreatitis. The comparative assessment encompassed baseline characteristics, laboratory data, illness severity, local consequences, and organ failure instances. This comparison was performed between patients exhibiting normal serum lactic acid levels (HL) and those displaying elevated HL levels. The association between serum HL levels and other pertinent clinical markers was investigated using linear regression. Logistic regression analysis was employed to evaluate the utility of elevated serum lactate levels in identifying high-risk groups. RESULTS: Significantly elevated serum HL levels were observed in patients with moderately severe acute pancreatitis (MSAP) and severe acute pancreatitis (SAP) in contrast to those with mild acute pancreatitis (MAP) (p<0.01). Multivariate logistic analysis demonstrated that higher lactate levels independently predicted organ failure (95% CI 0.738-0.902, p<0.05). Receiver operating characteristic (ROC) curve analysis indicated that the lactate (LAC) cut-off value of 2.45 mmol/L yielded sensitivity and specificity values of 76.5% and 79.1%, respectively, for predicting AP-associated organ failure. The corresponding area under the curve (AUC) was 0.820. CONCLUSIONS: In AP patients, elevated serum HL levels signify disease severity and hold predictive potential for assessing the risk of organ failure. [ABSTRACT FROM AUTHOR]

To elucidate the genetic factors contributing to melon resistance against Phelipanche aegyptiaca and comprehend the role of differentially resistant materials in responding to changes in P. aegyptiaca parasitisation, we investigated the P. aegyptiaca-resistant line K16 and the susceptible line K27. The parasitism rate of P. aegyptiaca was assessed at 25 days. Results revealed significant differences in parasitisation rates between K16 (15.35%) and K27 (34.2%). We compared inoculated K16 and K27 to their respective controls through transcriptome analysis and contrasted inoculated K16 with inoculated K27. Eight hundred eighteen genes exhibited differential expression across all comparisons. Gene ontology (GO) functional enrichment analysis revealed that differentially expressed genes were significantly enriched in nitrate transport and assimilation, cellular components, extracellular regions, binding and enzyme activities. KEGG pathway enrichment underscored the importance of phytohormone signaling, phenylpropanoid biosynthesis, linolenic acid and linoleic acid metabolism, cyanoamino acid metabolism and nitrogen metabolism in the interaction between melon and P. aegyptiaca. Nine genes potentially associated with P. aegyptiaca resistance were identified, encoding cytochrome protein P450, peroxidases, β-glucosidase, acyltransferase family proteins, histidine phosphotransfer protein, and D-type cyclins. This study aims to provide insights into the mechanism of P. aegyptiaca parasitism on melons and offers implications for breeding resistant varieties

Abstract Background To investigate the prognostic differences following the achievement of a pathological complete response (pCR) through neoadjuvant chemotherapy across different molecular subtypes of breast invasive ductal carcinoma. Methods Data from the Surveillance, Epidemiology, and End Results (SEER) were identified for patients undergoing neoadjuvant chemotherapy who achieved pathological complete response for invasive ductal carcinoma of the breast between 2010 and 2019.Comparing the clinicopathological characteristics of patients across different molecular subtypes. Univariate and Cox multivariate analyses were utilized to identify independent predictors of overall survival (OS) and cancer-specific survival (CSS). The Kaplan–Meier method is used to compare OS and CSS among different molecular subtypes. After propensity score matching, subgroup analysis results were presented through forest plots. Results This study included 9,380 patients diagnosed with invasive ductal carcinoma, who were categorized into four molecular subtypes: 2,721 (29.01%) HR + /HER-2 + , 1,661 (17.71%) HR + /HER2-, 2,082 (22.20%) HR-/HER2 + , and 2,916 (31.08%) HR-/HER-2-. HR + /HER-2- subgroup exhibited a significantly higher proportion of patients under 50 years old than the other subtype groups (54.67% vs 40.2%, 50.35% and 51.82%, p

Abstract Immune-mediated liver injury is a common characteristic of various liver diseases, including autoimmune and viral hepatitis. Here, we investigated the role of DEAD-box helicase 3, X-linked (DDX3X) in immune-mediated liver injury. Liver injury was induced in C57BL/6J mice via concanavalin A (Con A). DDX3X hepatocyte-specific knockout (DDX3XΔHep) mice and control (DDX3Xfl/fl) mice were utilized to investigate the role of DDX3X in liver injury. Primary hepatocytes were treated with tunicamycin (TM) to induce ER stress in vitro. The expression of DDX3X in patients with various liver diseases was evaluated. Hepatic DDX3X expression increased, and DDX3X translocated from the cytoplasm to the nucleus during Con A-induced liver injury. DDX3X deficiency ameliorated mouse liver injury and reduced ER stress in liver tissue. The inhibition of ER stress with 4-PBA significantly attenuated liver injury while decreasing DDX3X levels in liver tissue. However, the upregulation of hepatic DDX3X expression reversed Con A-induced liver injury and negated the protective effect of 4-PBA. Mechanistically, the nuclear translocation of DDX3X promoted ER stress-induced apoptosis through the transcriptional induction of CHOP. Moreover, DDX3X was elevated and translocated into the nucleus in patients with HBV-LF and AIH. Additionally, serum DDX3X levels markedly increased in patients with HBV-LF, and a consistent decrease in DDX3X was associated with a good prognosis. The cytoplasmic-to-nuclear translocation of DDX3X promotes ER stress-induced apoptosis, which is an obligatory step that drives hepatic necrosis and tissue damage. Notably, DDX3X is a potential therapeutic target for immune-mediated liver injury.

Abstract Background A novel positron emission tomography (PET) imaging tracer, [18F] SynVesT-1, targeting synaptic vesicle glycoprotein 2 (SV2A), has been developed to meet clinical demand. Utilizing the Trasis AllinOne-36 (AIO) module, we’ve automated synthesis to Good Manufacturing Practice (GMP) standards, ensuring sterile, pyrogen-free production. The fully GMP-compliant robust synthesis of [18F] SynVesT-1 boosting reliability and introducing a significant degree of simplicity and its comprehensive validation for routine human use. Results [18F] SynVesT-1 was synthesized by small modifications to the original [18F] SynVesT-1 synthesis protocol to better fit AIO module using an in-house designed cassette and sequence. With a relatively small precursor load of 5 mg, [18F] SynVesT-1 was obtained with consistently high radiochemical yields (RCY) of 20.6 ± 1.2% (the decay-corrected RCY, n = 3) at end of synthesis. Each of the final formulated batches demonstrated radiochemical purity (RCP) and enantiomeric purity surpassing 99%. The entire synthesis process was completed within a timeframe of 80 min (75 ± 3.1 min, n = 3), saves 11 min compared to reported GMP automated synthesis procedures. The in-human PET imaging of total body PET/CT and time-of-flight (TOF) PET/MR showed that [18F] SynVesT-1 is an excellent tracer for SV2A. It is advantageous for decentralized promotion and application in multi-center studies. Conclusion The use of AIO synthesizer maintains high production yields and increases reliability, reduces production time and allows rapid training of production staff. Besides, the as-prepared [18F] SynVesT-1 displays excellent in vivo binding properties in humans and holds great potential for the imaging and quantification of synaptic density in vivo.

Abstract Current-driven dynamics of topological spin textures, such as skyrmions and antiskyrmions, have garnered considerable attention in condensed matter physics and spintronics. As compared with skyrmions, the current-driven dynamics of their antiparticles – antiskyrmions − remain less explored due to the increased complexity of antiskyrmions. Here, we design and employ fabricated microdevices of a prototypical antiskyrmion host, (Fe0.63Ni0.3Pd0.07)3P, to allow in situ current application with Lorentz transmission electron microscopy observations. The experimental results and related micromagnetic simulations demonstrate current-driven antiskyrmion dynamics confined within stripe domains. Under nanosecond-long current pulses, antiskyrmions exhibit directional motion along the stripe regardless of the current direction, while the antiskyrmion velocity is linearly proportional to the current density. Significantly, the antiskyrmion mobility could be enhanced when the current flow is perpendicular to the stripe direction. Our findings provide novel and reliable insights on dynamical antiskyrmions and their potential implications on spintronics.

Abstract Score-based diffusion models have shown promising results in unpaired image-to-image translation (I2I). However, the existing methods only perform unpaired I2I in pixel space, which requires high computation costs. To this end, we propose guiding stochastic differential equations in latent space (Latent-SDE) that extracts domain-specific and domain-independent features of the image in the latent space to calculate the loss and guides the inference process of a pretrained SDE in the latent space for unpaired I2I. To refine the image in the latent space, we propose a latent time-travel strategy that increases the sampling timestep. Empirically, we compare Latent-SDE to the baseline of the score-based diffusion model on three widely adopted unpaired I2I tasks under two metrics. Latent-SDE achieves state-of-the-art on Cat $$\rightarrow $$ → Dog and is competitive on the other two tasks. Our code will be freely available for public use upon acceptance at https://github.com/zhangXJ147/Latent-SDE .

Abstract Endometrial cancer (EC) is associated with significant risk factors such as polycystic ovarian syndrome (PCOS) and sedentary behavior. In our study, we aim to employ machine learning algorithms to investigate the potential molecular processes that underlie their interaction and explore their respective roles in the diagnosis and immunotherapy of EC. The GEO database provides access to microarray data, which was utilized in this study to identify gene expression modules associated with PCOS and sedentary behavior, using weighted gene expression network analysis (WGCNA). Cluego software was then employed to investigate the energy enrichment of shared pathways in both PCOS and sedentary individuals, and differential gene analysis was used to confirm another two databases. The miRNAs–mRNAs controlled network was constructed to verify the pathway. The immune-related factors of the shared pathway in EC were then analyzed. Finally, to validate our findings, we conducted cell experiments using EC cell lines (AN3CA, KLE, Ishikawa, RL95-2, and HEC-1A). We found that increased intracellular aromatic compound anabolism is a common feature of both PCOS and sedentary individuals. We then developed a disease pathway model that was based on the common genetic characteristics of PCOS and sedentary behavior. We utilized pathway typing in EC samples and found a significant survival difference between the two subgroups, with the upregulated expression type exhibiting an immune-hot phenotype. Finally, the experimental results confirmed the expression of the hub gene (NAA15) in EC. The findings of our study suggest that genes related to the intracellular aromatic compound metabolic pathway can be used for immunotherapy of EC.