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Tian-Ming Gao,1,&ast; Sheng-Jie Jin,1,&ast; Fang Fang,2,&ast; Jian-Jun Qian,1 Chi Zhang,1 Bao-Huan Zhou,1 Dou-Sheng Bai,1 Guo-Qing Jiang1 1Department of Hepatobiliary Surgery, Clinical Medical College, Yangzhou University, Yangzhou, 225001, People’s Republic of China; 2Department of Gastrointestinal Surgery, Clinical Medical College, Yangzhou University, Yangzhou, 225001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guo-Qing Jiang; Dou-Sheng Bai, Department of Hepatobiliary Surgery, Clinical Medical College, Yangzhou University, 98 West Nantong Road, Yangzhou, 225000, People’s Republic of China, Email jgqing2003@hotmail.com; bdsno1@hotmail.comPurpose: Although laparoscopic splenectomy and azygoportal disconnection (LSD) can significantly decrease portal vein pressure and even the incidence of hepatocellular carcinoma (HCC) in patients with cirrhotic portal hypertension (CPH), postoperative HCC inevitably occurs in certain patients. The purpose of this study was to seek a novel preoperative non-invasive predictive indicator to predict the occurrence of postoperative HCC.Patients and Methods: From April 2012 to April 2022, we collected clinical data of 178 hepatitis B virus (HBV)-related CPH patients. Based on inverse treatment probability weighting, candidate variables for predicting postoperative HCC were determined by means analysis. Then, a novel preoperative non-invasive prediction indicator (ie, type IV collagen-alpha fetoprotein-fibrosis-4 score [IVAF-FIB-4]) was established based on candidate variables, and its predictive ability was explored.Results: Postoperative HCC occurred in 9 (5.1%) patients. Correlation analyses showed that the IVAF-FIB-4 had a significant positive correlation with HCC (r = 0.835, P < 0.001). IVAF-FIB-4 showed a high accuracy (the area under the receiver operating characteristic curve: 0.939, 95% confidence interval [CI]: 0.818– 1.000; sensitivity: 88.9%; specificity: 93.5%). At the end of follow-up, the incidence density of HCC in patients with IVAF-FIB-4 (1) was significant higher than that in patients with IVAF-FIB-4 (0) (138.1/1000 vs 1.1/1000 person-years; rate ratio: 130.475, 95% CI: 16.318– 1043.227). In logistic regression, IVAF-FIB-4 was an independent risk factor for HCC (odds ratio: 668.000, 95% CI: 53.895– 8279.541; P < 0.001).Conclusion: IVAF-FIB-4 is a novel preoperative noninvasive predictive indicator for predicting postoperative HCC in HBV-related CPH patients after LSD, with satisfactory predictive ability.Keywords: liver fibrotic markers, splenectomy, azygoportal disconnection, hepatocellular carcinoma, risk

Jin-Yong Lin,1,2,* Dou-Sheng Bai,1,* Bao-Huan Zhou,1,2,* Ping Chen,1 Jian-Jun Qian,1 Sheng-Jie Jin,1 Guo-Qing Jiang1 1Department of Hepatobiliary Surgery, Clinical Medical College, Yangzhou University, Yangzhou, China; 2Department of Hepatobiliary Surgery, The Second Clinical College, Dalian Medical University, Dalian, China *These authors contributed equally to this work Background: Although the prognostic implications of negative lymph nodes (NLNs) has been reported for a variety of tumors, little information has been published about the NLNs in gallbladder cancer (GBC).Patients and methods: In this study, clinicopathological characteristics and survival times of patients who had undergone surgery for GBC were collected from the Surveillance, Epidemiology, and End Results Program-registered TNM stage database and analyzed. Univariate and multivariate Cox proportional hazards models were used to identify the predictors of survival.Results: It was found that a cutoff of one to two NLNs is optimal when assessing the association with survival, survival rates being consistently better with two or more NLNs than with fewer than two. This optimal cutoff value of 2 was identified as an independent prognostic factor by univariate and multivariate analyses (all P

Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis during chronic stress is essential for depression neurobiology. As the latest member of the RFamide peptide family in mammals, pyroglutamylated RFamide peptide (QRFP) is closely implicated in neuroendocrine maintenance by activating G-protein-coupled receptor 103 (GPR103). We hypothesized that QRFP and GPR103 might contribute to chronic stress-induced depression by promoting corticotropin-releasing hormone (CRH) release from neurons in the paraventricular nucleus (PVN), and various methods were employed in this study, with male C57BL/6J mice adopted as the experimental subjects. Chronic stress induced not only depression-like behaviors but also significant enhancement in QRFP and GPR103 in the PVN. Genetic overexpression of QRFP/GPR103 and stereotactic infusion of QRFP-26/QRFP-43 peptide in the PVN all mimicked chronic stress that induced various depression-like phenotypes in naïve mice, and this was mediated by promoting CRH biosynthesis and HPA activity. In contrast, genetic knockdown of QRFP/GPR103 in the PVN produced notable antidepressant-like effects in mice exposed to chronic stress. Furthermore, genetic knockout of QRFP also protected against chronic stress in mice. In addition, both the C-terminal biological region of QRFP and the downstream PKA/PKC-CREB signaling coupled to GPR103 stimulation underlie the role of QRFP and GPR103 in depression. Collectively, QRFP and GPR103 in PVN neurons could be viable targets for novel antidepressants., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest for this study., (Copyright © 2024. Published by Elsevier Ltd.)

Background: The prevalence of gene fusion is extremely low in unselected patients with colorectal cancer (CRC). Published data on gene fusions are limited by relatively small sample sizes, with a primary focus on Western populations. This study aimed to analyse actionable gene fusions in a large consecutive Chinese CRC population., Methods: This study included 5,534 consecutive CRC patients from the Genecast database. Genomic profiling was performed using a panel of 769 cancer-related genes. Data for 34 CRC patients with actionable gene fusions were also collected from cBioPortal and ChimerSeq., Results: Among 5,534 CRC patients, 54 (0.98%) had actionable gene fusions, with NTRK1/2/3 being the most common fusion (0.38%), accounting for 38.9% (21/54) of those with fusions. Actionable gene fusion enrichment was higher in patients with microsatellite instability-high (MSI-H) (6.7% vs. 0.5%, P  <   0.001), RAS/BRAF wildtype (2.0% vs. 0.2%, P  <   0.001) and RNF43 mutation (7.7% vs. 0.4%, P  <   0.001) than in patients with microsatellite stability/MSI-low, RAS/BRAF mutation and RNF43 wildtype, respectively. When these markers were combined, the fusion detection rate increased. Among patients with RAS/BRAF wildtype and MSI-H, fusions were detected in 20.3% of patients. The fusion detection rate further increased to 37.5% when RNF43 mutation was added. The fusion detection rate was also higher in colon cancer than in rectal cancer. No significant differences in clinical or molecular features were found in patients with actionable gene fusions between the Genecast, cBioPortal, and ChimerSeq databases., Conclusions: Approximately 1% of the unselected Chinese CRC population carries actionable gene fusions, mostly involving NTRK . Actionable gene fusions are more prevalent in MSI-H, RAS/BRAF wildtype, or RNF43 -mutated CRC, as well as in colon cancer. Mapping of these molecular markers can markedly increase the fusion detection rate, which can help clinicians select candidates for fusion testing and targeted therapy., Competing Interests: J.-J.Q., E.-L.Z., and L.-J.Z. are employees of Genecast Biotechnology Co., Ltd. The other authors declare that there are no conflicts of interest in this study., (© The Author(s) 2024. Published by Oxford University Press and Sixth Affiliated Hospital of Sun Yat-sen University.)

Background: Emerging data has demonstrated that in mature neurons, SorCS2 localizes to the postsynaptic density of dendritic spines and facilitates plasma membrane sorting of TrkB by interacting with it, transmitting positive signaling from BDNF on neurons. Thus, it is possible that SorCS2 plays a role in the pathophysiology of depression by regulating the BDNF-TrkB system., Methods: In the present study, SorCS2 expression in different brain regions [hippocampus, medial prefrontal cortex (mPFC), hypothalamus, amygdala, ventral tegmental area (VTA), and nucleus accumbens (NAc)] was thoroughly investigated in the chronic social defeat stress (CSDS) and chronic unpredictable mild stress (CUMS) models of depression. The changes in depressive-like behaviors, the hippocampal BDNF signaling cascade, and amounts of hippocampal immature neurons were further investigated after SorCS2 overexpression by microinjection of the adenovirus associated virus vector containing the coding sequence of mouse SorCS2 (AAV-SorCS2) into the hippocampus of mice exposed to CSDS or CUMS., Results: It was found that both CSDS and CUMS significantly decreased the protein and mRNA expression of SorCS2 in the hippocampus but not in other brain regions. Chronic stress also notably downregulated the level of hippocampal SorCS2-TrkB binding in mice. In contrast, AAV-based genetic overexpression of hippocampal SorCS2 fully reversed the chronic stress-induced not only depressive-like behaviors but also decreased SorCS2-TrkB binding, BDNF signaling pathway, and amounts of immature neurons in the hippocampus of mice., Conclusion: All these results suggest that enhancing the hippocampal SorCS2 expression protects against chronic stress, producing antidepressant-like actions. Hippocampal SorCS2 may participate in depression neurobiology and be a potential antidepressant target., Significance Statement: Targeting of proteins to distinct subcellular compartments is essential for neuronal activity and modulated by VPS10P domain receptors which include SorCS2. In mature neurons, SorCS2 localizes to the postsynaptic density of dendritic spines and facilitates plasma membrane sorting of TrkB by interacting with it, transmitting positive signaling from BDNF on neurons. Our study is the first direct evidence preliminarily showing that SorCS2 plays a role in depression neurobiology. It was found that chronic stress induced not only depressive-like behaviors but also decreased SorCS2 expression in the hippocampus. Chronic stress did not affect SorCS2 expression in the mPFC, hypothalamus, amygdala, VTA, or NAc. In contrast, genetic overexpression of hippocampal SorCS2 prevented against chronic stress, producing antidepressant-like actions in mice. Thus, hippocampal SorCS2 is a potential participant underlying depression neurobiology and may be a novel antidepressant target. Our study may also extend the knowledge of the neurotrophic hypothesis of depression., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest for this study., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: To investigate the clinical and pathological features of osteochondroma in maxillofacial region, and to summarize the clinicopathological features of rare osteochondroma malignant transformation in order to provide clinical guidance., Methods: From January 2018 to September 2023, a total of 171 patients with osteochondroma were retrospectively collected in Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine. Their preoperative CT and clinicopathological features were analyzed., Results: Of the 171 patients with osteochondroma in maxillofacial bone, 66%（113/171） were females and 34% were male. Their age ranged from 11-76 with an average age was 44 years old. Of the 171 cases, 95.3%（163/171）in mandible condyle, 4%(7/171) in mandible processus coronoideus, and 0.5%（1/171） in zygomatic arch. The imaging findings showed that the thickness of cartilaginous cap was less than 1 cm in 98%（159/161） cases with condyle lesions. Only 2 cases(2/171, 1.1%) had malignant transformation. One was diagnosed with secondary chondrosarcoma, another developed low-grade osteosarcoma., Conclusions: Osteochondroma in maxillofacial region mostly occurs in females, and most commonly located in condylar process, with a malignant change rate of 1.1%, which is similar to that of other parts of the body. Imaging findings have important guiding significance for the diagnosis of osteochondroma malignant change.

Osteoporosis has a profound influence on public health. First-line bisphosphonates often cause osteonecrosis of the jaw meanwhile inhibiting osteoclasts. Therefore, it is important to develop effective treatments. The results of this study showed that the increased level of NFATc1 m6A methylation caused by zoledronic acid (ZOL), with 4249A as the functional site, is highly correlated with the decreased bone resorption of osteoclasts. Upstream, METTL14 regulates osteoclast bone absorption through the methylation functional site of NFATc1. Downstream, YTHDF1 and YTHDF2 show antagonistic effects on the post-transcriptional regulation of NFATc1 after the m6A methylation level is elevated by METTL14. In this study, meRIP-Seq, luciferase reporter assays, meRIP and other methods were used to elucidate the NFATc1 regulatory mechanism of osteoclasts from the perspective of RNA methylation. In addition, EphA2 overexpression on exosomes is an effective biological method for targeted delivery of METTL14 into osteoclasts. Importantly, this study shows that METTL14 released by exosomes can increase the m6A methylation level of NFATc1 to inhibit osteoclasts, help postmenopausal osteoporosis patients preserve bone mass, and avoid triggering osteonecrosis of the jaw, thus becoming a new bioactive molecule for the treatment of osteoporosis., (© 2023. The Author(s).)

Background: Posthepatitic cirrhosis is one of the leading risk factors for hepatocellular carcinoma (HCC) worldwide, among which hepatitis B cirrhosis is the dominant one. This study explored whether laparoscopic splenectomy and azygoportal disconnection (LSD) can reduce the risk of HCC among patients with hepatitis B virus (HBV)-related cirrhotic portal hypertension (CPH)., Methods: A total of 383 patients with HBV-related CPH diagnosed as gastroesophageal variceal bleeding and secondary hypersplenism were identified in our hepatobiliary pancreatic center between April 2012 and April 2022, and conducted an 11-year retrospective follow-up. We used inverse probability of treatment weighting (IPTW) to correct for potential confounders, weighted Kaplan-Meier curves, and logistic regression to estimate survival and risk differences., Results: Patients were divided into two groups based on treatment method: LSD (n = 230) and endoscopic therapy (ET; n = 153) groups. Whether it was processed through IPTW or not, LSD group showed a higher survival benefit than ET group according to Kaplan-Meier analysis (P < 0.001). The incidence density of HCC was higher in the ET group compared to LSD group at the end of follow-up [32.1/1000 vs 8.0/1000 person-years; Rate ratio: 3.998, 95% confidence intervals (CI) 1.928-8.293]. Additionally, in logistic regression analyses weighted by IPTW, LSD was an independent protective predictor of HCC incidence compared to ET (odds ratio 0.516, 95% CI 0.343-0.776; P = 0.002)., Conclusion: Considering the ability of LSD to improve postoperative survival and prevent HCC in HBV-related CPH patients with gastroesophageal variceal bleeding and secondary hypersplenism, it is worth promoting in the context of the shortage of liver donors., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Ketamine intravenous therapy (KIT) appears effective for treating depression in controlled trials testing a short series of infusions. A rapidly proliferating number of clinics offer KIT for depression and anxiety, using protocols without a strong evidence basis. Controlled comparison of mood and anxiety from real-world KIT clinics, and the stability of outcomes, is lacking., Methods: We performed a retrospective controlled analysis on patients treated with KIT in ten community clinics across the US, between 08/2017-03/2020. Depression and anxiety symptoms were evaluated using the Quick Inventory of Depressive Symptomatology-Self Report 16-item (QIDS) and the Generalized Anxiety Disorder 7-item (GAD-7) scales, respectively. Comparison data sets from patients who did not undergo KIT were obtained from previously published real-world studies., Results: Of 2758 patients treated, 714 and 836 met criteria for analysis of KIT induction and maintenance outcomes, respectively. Patients exhibited significant and concordant reduction in both anxiety and depression symptoms after induction (Cohen's d = -1.17 and d = -1.56, respectively). Compared to two external datasets of KIT-naive depressed patients or patients starting standard antidepressant therapy, KIT patients experienced a significantly greater reduction in depression symptoms at eight weeks (Cohen's d = -1.03 and d = -0.62 respectively). Furthermore, we identified a subpopulation of late-responders. During maintenance, up to a year post-induction, increases in symptoms were minimal., Limitations: Due to the retrospective nature of the analyses, interpreting this dataset is limited by incomplete patient information and sample attrition., Conclusions: KIT treatment elicited robust symptomatic relief that remained stable up to one year of follow-up., Competing Interests: Declaration of competing interest Drs Hietamies and Klise have no conflicts of interest or disclosures to report. Dr. Worley is an employee of Osmind. Jimmy Qian is an employee of Osmind. Dr. McInnes is an employee of Osmind and a scientific advisor for Clexio Biosciences Ltd. Dr. Williams is a scientific advisor for One Mind Psyberguide and declares US Pants. App. 10/034,645 and 15/820,338: Systems and methods for detecting complex networks in MRI image data. Dr. Heifets is a scientific advisor for Osmind and Journey Clinical and is also a consultant for Clairvoyant Therapeutics and Vine Ventures Dr. Levine was Founder, president, and shareholder of Actify Neurotherapies (ceased operations March 2020). He is currently employed by Compass Pathways LLC., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: To analyze the clinicopathological characteristics of IgG4-related sialadenitis (IgG4-RS). Methods: A total of 40 cases diagnosed with IgG4-RS were collected from the Department of Oral Pathology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine from January 2019 to December 2022. Among them, there were 26 males and 14 females. The age range was 29-77 years old [(59.4±11.8) years old], with 23 patients being older than 60 years. The lesion site, imaging manifestations, histopathological features, serological test and treatment information of patients were collected. The expression of IgG4 and IgG proteins was detected by immunohistochemistry. Results: Submandibular region swelling was the most common initial symptom of IgG4-RS (38/40, 95.0%). All the patients having serum IgG4 levels> 1.35 g/L. Serum IgG4 levels were significantly increased in patients aged>60 years ( Z =-2.45, P =0.014) and those involving multiple glands ( Z =-2.04, P =0.042). Thirty six cases received major salivary gland biopsy, and all the cases showed dense lymphocyte and plasma cell infiltration. Lymphoid follicle, storiform fibrosis and obliterative phlebitis were seen in 88.9% (32/36), 63.9% (23/36), 30.6% (11/36) of the cases, respectively. Twenty one cases received labial salivary gland biopsy, 66.7% (14/21) showed lymphocyte and plasma cell infiltration, 19.0% (4/21) had lymphoid follicle structures, and 33.3% (7/21) showed no obvious histological abnormalities. No signs of fibrosis or obliterative phlebitis were observed in all labial salivary gland biopsies. And 95.0% (38/40) of cases had IgG4 positive plasma cell>10/HPF, 82.5% (33/40) of cases had IgG4/IgG positive plasma cell ratio>40%. All the patients had a decrease in serum IgG4 levels after glucocorticoid treatment, but only 21.4% (6/28) of cases had reduced to normal levels (≤1.35 g/L), and there were still significant fluctuations in serum IgG4 levels thereafter. Conclusions: IgG4-RS has a predilection for middle-aged and elderly male patients, and serum IgG4 levels are significantly related to the patient's age and whether multiple glands are involved. Labial salivary gland biopsy cannot replace submandibular gland for histopathological evaluation. It is a common phenomenon that serum IgG4 levels cannot restored to normal levels after glucocorticoid treatment. This study provides certain assistance for clinical and pathological diagnosis of IgG4-RS. This study is beneficial for further understanding IgG4-RS and improving the clinical and pathological diagnosis of the disease.

Background: Wernicke encephalopathy (WE) is an acute neurological disease resulting from vitamin B1 deficiency, and there are only very few case reports of WE after liver transplantation. The present study aimed to investigate the clinical characteristics, etiology, magnetic resonance imaging (MRI) features, treatment and prognosis of patients with WE after liver transplantation., Methods: Twenty-three patients with WE after liver transplantation from the First Affiliated Hospital, Zhejiang University School of Medicine and Jiangxi Provincial People's Hospital between January 2011 and December 2021 were retrospectively analyzed., Results: Among the 23 patients diagnosed with WE after liver transplantation, 6 (26%) had a classic triad of impaired consciousness, oculomotor palsy and ataxia, and 17 (74%) had two features. The misdiagnosis rate was 65%. After treatment with high-dose vitamin B1, 19 (83%) patients showed improvement, whereas 4 (17%) showed no improvement, including 3 with residual short-term memory impairments and 1 with residual spatial and temporal disorientation and ataxia., Conclusions: The misdiagnosis rate is high in the early stage of WE, and the prognosis is closely associated with whether WE is diagnosed early and treated timely. High-dose glucose or glucocorticoids can trigger WE and cannot be administered before vitamin B1 treatment. Vitamin B1 is suggested to be used as a prophylactic treatment for patients with WE after liver transplantation., Competing Interests: Competing interest No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article., (Copyright © 2022. Published by Elsevier B.V.)

Background: Liver cirrhosis is the highest risk factor for hepatocellular carcinoma (HCC) worldwide. However, etiological therapy is the only option in cirrhosis patients to decrease the HCC risk. The aim of this study was to explore whether laparoscopic splenectomy and azygoportal disconnection (LSD) decreases the risk of HCC for patients with cirrhotic portal hypertension (CPH)., Methods: Between April 2012 and April 2021, we identified 595 CPH patients in our hepatobiliary pancreatic center who were diagnosed with gastroesophageal variceal bleeding and secondary hypersplenism, and performed a 10-year retrospective follow-up. Inverse probability of treatment weighting (IPTW) was used to adjust for potential confounders, weighted Kaplan-Meier curves and logistic regression to estimate survival and risk differences., Results: According to the method of therapy, patients were divided into LSD (n = 345) and endoscopic therapy (ET; n = 250) groups. Kaplan-Meier analysis revealed that patients who underwent LSD had higher survival benefit with those who underwent ET (P < 0.001). At the end of the follow-up, ET group was associated with a higher HCC incidence density compared with LSD group (28.1/1000 vs 9.6/1000 person-years; Rate ratio [RR] 2.922, 95% confidence intervals [CI] 1.599-5.338). In addition, logistic regression analyses weighted by IPTW revealed that, compared with ET, LSD was an independent protective predictor of HCC incidence (odds ratio [OR] 0.440, 95% CI 0.316-0.612; P < 0.001)., Conclusions: Considering the better postoperative survival and the ability to prevent HCC in CPH patients with gastroesophageal variceal bleeding and secondary hypersplenism, LSD is worth popularization in situations where liver donors are scarce., (© 2023. Japanese Society of Gastroenterology.)

Background: How to precisely protect and preserve anterior and posterior vagal trunks and all their branches during the procedure of splenectomy and azygoportal disconnection is studied rarely. We firstly developed a vagus nerve-guided robotic-assisted laparoscopic splenectomy and azygoportal disconnection (VGRSD). The aim of this study was to evaluate whether VGRSD is feasible and safe and to determine whether VGRSD can effectively eliminate postoperative digestive system complications by protecting vagal nerve precisely., Method: In this prospective clinical study, 10 cirrhotic patients with oesophagogastric variceal bleeding and hypersplenism who underwent VGRSD between January 2022 and March 2022 were gathered, and compared with a retrospective cohort who received a part of the vagus nerve-preserving robotic-assisted laparoscopic splenectomy and azygoportal disconnection (VPRSD). They were all followed up for 6 months., Results: In VGRSD group, the operation time was 173.5 ± 16.2 min, blood loss was 68.0 ± 39.1 ml, VAS pain score on the first day was 1.9 ± 0.7, and the postoperative hospital stay was 7.7 ± 0.7 days. There was no incisional complications, pneumonia, gastric fistula, pancreatic fistula, and abdominal infection. No patients suffered from diarrhoea, delayed gastric emptying, and epigastric fullness. Compared with VPRSD, operation time was significantly longer for VGRSD (p < 0.05). However, VGRSD was significantly associated with less diarrhoea and shorter postoperative hospital stay (all p < 0.05)., Conclusion: VGRSD procedure is not only technically feasible and safe, it also effectively eliminate postoperative digestive system complications., Trial Registration: We registered our research at https://www., Clinicaltrials: gov/. The name of research registered is 'Vagus Nerve-guided Robotic-assisted Splenectomy and Azygoportal Disconnection'. The trial registration identifier at clinicaltrials.gov is NCT05300516., (© 2022 John Wiley & Sons Ltd.)

Objective: To explore the diagnostic value of p16/Ki-67 double-stained immunohistochemistry in the diagnosis of human papilloma virus (HPV)-positive oropharyngeal squamous cell carcinoma(opscc) and find out the optimal index to improve the accuracy of HPV detection. Methods: A total of 153 cases, from May 2014 to May 2020, diagnosed OPSCC in Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, were selected. This cohort included 130 males and 23 females, aged (58.6±10.0) years old. HPV RNA in situ hybridization was chosen as the gold standard to detect their HPV status. p16 immunohistochemistry and p16/Ki-67 double-stained immunohistochemistry were performed on all cases, and the p16/Ki-67 double positive index including 20%, 40%, and 60% were used as the thresholds to compare their sensitivity, specificity, and positive prediction value (PPV), negative prediction value (NPV) and prognosis prediction ability. Results: Among the 153 patients with OPSCC, 114 were HPV-negative and 39 were HPV-positive, and the HPV infection rate of OPSCC patients was 25.5% (39/153). Only 58.1% (36/62) of single p16 positive cases were HPV-positive, and the prognosis of patients could not be distinguished using p16 immunohistochemistry only. Using p16/Ki-67 double staining, the accuracy of HPV positive diagnosis has been improved. The HPV diagnostic ability was the highest when the p16/Ki-67 double positive index was 40% (sensitivity=86.8%, specificity=94.8%, PPV=84.6%, NPV=95.6%, area under the curve=0.897), which could distinguish the prognosis of patients ( P= 0.012). Conclusions: The p16/Ki-67 double-stained immunohistochemistry can improve the accuracy of HPV positive diagnosis rate and diagnosis of HPV-positive oropharyngeal cancer is the most accurate when the double-positive index is 40% as the threshold to judge HPV status and could serve as better surrogate marker for HPV detection.

Background: In China, as the population grows older, the number of elderly people who have died from respiratory problems has increased., Aim: To investigate whether enhanced recovery after surgery (ERAS)-based respiratory function training may help older patients who had abdominal surgery suffer fewer pulmonary problems, shorter hospital stays, and improved lung function., Methods: The data of 231 elderly individuals having abdominal surgery was retrospectively analyzed. Based on whether ERAS-based respiratory function training was provided, patients were divided into ERAS group ( n = 112) and control group ( n = 119). Deep vein thrombosis (DVT), pulmonary embolism (PE), and respiratory tract infection (RTI) were the primary outcome variables. Secondary outcome variables included the Borg score Scale, FEV1/FVC and postoperative hospital stay., Results: The percentage of 18.75% of ERAS group participants and 34.45% of control group participants, respectively, had respiratory infections ( P = 0.007). None of the individuals experienced PE or DVT. The ERAS group's median postoperative hospital stay was 9.5 d (3-21 d) whereas the control groups was 11 d (4-18 d) ( P = 0.028). The Borg score decreased on the 4 th d following surgery in the ERAS group compared to the 2 nd d prior ( P = 0.003). The incidence of RTIs was greater in the control group than in the ERAS group among patients who spent more than 2 d in the hospital before surgery ( P = 0.029)., Conclusion: ERAS-based respiratory function training may reduce the risk of pulmonary complications in older individuals undergoing abdominal surgery., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: In Asia, laparoscopic splenectomy and azygoportal disconnection (LSD) has been widely regarded as a preferential treatment modality for cirrhotic portal hypertension (PH). However, LSD involves high surgical risk, technical challenges, and many potential postoperative complications. Technology optimization and innovation in LSD aiming to solve to these difficulties has scarcely been reported. In this retrospective study, we aimed to evaluate the clinical therapeutic effect of our cluster technology optimization and innovation on LSD for PH., Methods: From February 2012 to January 2020, 500 patients with cirrhosis who had esophagogastric variceal bleeding and hypersplenism underwent LSD in our department. According to different operation periods, patients were divided into the early-, intermediate-, and late-period groups. We collected information regarding clinical characteristics of all patients as well as their preoperative and postoperative follow-up data., Results: Compared with the early-period group, operation time and postoperative hospital stay were all significantly different and gradually declined from the intermediate- and late-period groups, respectively (all P &lt; 0.05). Intraoperative blood loss of these three groups was gradually decreased, with significant differences (P &lt; 0.05). The incidences of delayed gastric emptying and diarrhea in the late-period group were all significantly lower than those in the early- and intermediate-period groups, respectively (all P &lt; 0.05). Compared with the early-period group, the incidence of variceal re-bleeding was significantly lower in the intermediate- and late-period groups (all P &lt; 0.05)., Conclusion: Our cluster technology optimization and innovation of LSD not only contributed to faster recovery and fewer complications but also enhanced surgical safety for patients. It is worth promoting this approach among patients with EVB and hypersplenism secondary to cirrhotic PH., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Robotic surgery has been widely accepted in many kinds of surgical procedures. Little is known about clinical effects of robotic-assisted splenectomy and azygoportal disconnection (RSD) for gastroesophageal variceal bleeding and secondary hypersplenism owing to cirrhotic portal hypertension. The aim of this study was to evaluate whether RSD is feasible and safe for patients with cirrhotic portal hypertension and whether RSD is superior to laparoscopic splenectomy and azygoportal disconnection (LSD). We retrospectively investigated the clinical effects of 50 patients with cirrhosis who underwent vagus nerve-preserving RSD (n = 20) and LSD (n = 30) between September 2020 and October 2021. We compared patients' demographic, intraoperative, and perioperative variables. RSD and LSD were successful in all patients. Operative time did not differ significantly between the RSD group and LSD group (151.15 ± 21.78 min vs. 144.50 ± 24.30 min, P > 0.05), but intraoperative blood loss were significantly reduced in the RSD group (61.00 ± 34.93 mL vs. 105.00 ± 68.77 mL, P < 0.05). No statistically significant differences were found regarding intraoperative allogeneic transfusion rate, visual analog scale pain score on the postoperative first day, time to first oral intake, initial passage of flatus, initial off-bed activity, postoperative hospital stay, and overall perioperative complication rate (all P > 0.05). In conclusion, RSD is not only a technically feasible and safe procedure but it was associated with less blood loss than LSD for cirrhotic portal hypertension with gastroesophageal variceal bleeding and secondary hypersplenism. Registered at researchregistery.com: trial registration number is researchregistry7244, date of registration October 10, 2021, registered retrospectively., (© 2022. Italian Society of Surgery (SIC).)

Objective: Previous studies have shown that cMaf-inducing protein (CMIP) promotes tumorigenesis and progression, however, the role of CMIP in lung adenocarcinoma (LUAD) and its molecular mechanism remain unclear., Methods: In this study, the Human Protein Atlas and Kaplan-Meier Plotter database were used to analyze the expression and prognostic value of CMIP in LUAD. Then, the expression levels of CMIP in LUAD tissues and cells were detected by qRT-PCR and western blot. The lentiviral vector was used to establish a stable transfected cell line, and the transfection efficiency was detected by qRT-PCR. MTT assay, colony formation assay, transwell assay, and wound healing assay were used to evaluate the function of CMIP in LUAD. In addition, the effect of CMIP on the MAPK/ERK pathway in LUAD cells was analyzed by western blot., Results: The expression level of CMIP was significantly increased in LUAD cell and tissue samples, and the high expression of CMIP was associated with overall survival (OS) and progression-free survival (PFS) in LUAD patients. In vitro experiments showed that CMIP overexpression significantly promoted the proliferation, migration, and invasion of A549 cells. CMIP knockout significantly inhibited the proliferation, migration, and invasion of H1299 cells. In addition, it was observed that the expression levels of the MAPK/ERK pathway-related proteins were significantly increased in CMIP-overexpressed A549 cells, and promoted cell proliferation, migration, and invasion, while U0126 could significantly reverse the activation of the MAPK/ERK pathway by CMIP overexpression, and inhibit the proliferation, migration, and invasion of A549 cells., Conclusion: Our study shows that CMIP, as an oncogene, is associated with poor patient prognosis, and may promote the proliferation and metastasis of LUAD by activating the MAPK/ERK pathway. Therefore, CMIP may be a new potential therapeutic target for LUAD., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Xiao-Yan Yu et al.)

Emerging evidence suggests that the proper control of mitochondrial dynamics provides a window for therapeutic intervention for Alzheimer's disease (AD) progression. The transcriptional coactivator peroxisome proliferator activated receptor gamma coactivator 1 (PGC-1a) has been shown to regulate mitochondrial biogenesis in neurons. Thus far, the roles of PGC-1a in Alzheimer's disease and its potential value for restoring mitochondrial dysfunction remain largely unknown. In the present study, we explored the impacts of PGC-1a on AD pathology and neurobehavioral dysfunction and its potential mechanisms with a particular focus on mitochondrial dynamics. Paralleling AD-related pathological deposits, neuronal apoptosis, abnormal mitochondrial dynamics and lowered membrane potential, a remarkable reduction in the expression of PGC-1a was shown in the cortex of APP/PS1 mice at 6 months of age. By infusing AAV- Ppargc1α into the lateral parietal association (LPtA) cortex of the APP/PS1 brain, we found that PGC-1a ameliorated AD-like behavioral abnormalities, such as deficits in spatial reference memory, working memory and sensorimotor gating. Notably, overexpressed PGC-1a in LPtA rescued mitochondrial swelling and damage in neurons, likely through correcting the altered balance in mitochondrial fission-fusion and its abnormal distribution. Our findings support the notion that abnormal mitochondrial dynamics is likely an important mechanism that leading to mitochondrial dysfunction and AD-related pathological and cognitive impairments, and they indicate the potential value of PGC-1a for restoring mitochondrial dynamics as an innovative therapeutic target for AD.

Background: Esophagogastric variceal bleeding is the most common lethal factor for patients with cirrhotic portal hypertension. We firstly developed a laparoscopic splenectomy and azygoportal disconnection (LSD) with intraoperative endoscopic variceal ligation (LSDL) technique. In this study, we aimed to evaluate whether LSDL is feasible and safe and whether LSDL can effectively prevent esophagogastric variceal re-bleeding (EVR), as compared with single LSD., Methods: In this randomized controlled single-center study, 88 patients with cirrhosis who had esophagogastric variceal bleeding and hypersplenism were randomly assigned to receive either LSD (n = 44) or LSDL (n = 44) between January 2020 and December 2021. The primary outcome was EVR., Results: No patients withdrew from the study. There were no significant differences in estimated blood loss, incidence of blood transfusion, time to first flatus and off-bed activity, or postoperative hospital stay between the two groups. Compared with that in the LSD group, operation time was significantly longer in the LSDL group (138.5 ± 19.4 min vs. 150.3 ± 19.0 min, P < 0.05); however, LSDL was associated with a significantly decreased EVR rate at 1-year follow-up (8/44 vs. 1/44, P < 0.05). Univariate analysis and multivariate logistic regression revealed that LSDL was a significant independent protective factor against EVR in comparison with LSD (relative risk: 0.105, 95% confidence interval 0.012-0.877; P = 0.037)., Conclusions: Our newly developed LSDL procedure is not only technically feasible and safe; it also contributed to lowering the EVR risk more so than single LSD., Trial Registration: We registered our research at https://www., Clinicaltrials: gov/ . The name of research registered is "Laparoscopic Splenectomy and Azygoportal Disconnection with Intraoperative Endoscopic Variceal Ligation." The trial registration identifier at clinicaltrials.gov is NCT04244487., (© 2022. The Society for Surgery of the Alimentary Tract.)

Purpose: The purpose of this study was to identify the incidence, sites and main pathogens, and risk factors for infectious complications occurring in patients with adult acute myeloid leukemia (AML) during the first course of venetoclax combined with decitabine or azacitidine., Methods: A retrospective cohort analysis was performed of 81 patients with AML older than 14 years who received the first cycle of venetoclax combined with a hypomethylating agent (HMA) between March 2018 and March 2021 at our institution. Infectious complications, if any, were documented., Results: Among a total of 81 cases of AML, 59 (72.8%) patients occurred infections, including fever without an identifiable source (28.8%), clinically documented infections (40.7%), and microbiologically documented infections (30.5%). The most commonly isolated organism in culture was Candida albicans, followed by Klebsiella pneumonia, and Pseudomonas aeruginosa. The 4-week and 8-week mortality rates were 3.7% and 7.4%, respectively. In multivariate analysis, a high proportion of blasts in bone marrow, decreased hemoglobin level, and fever with or without a documented infection at baseline were significant independent risk factors for infectious complications., Conclusion: Compared with conventional chemotherapy, the incidence of infectious complications of venetoclax combined with decitabine or azacitidine significantly decreased. Pretreatment high leukemia burden and fever were independent risk factors for infections., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Outcomes of ketamine intravenous therapy (KIT) for depression in real-world care settings have been minimally evaluated. We set out to quantify treatment response to KIT in a large sample of patients from community-based practices., Methods: We retrospectively analyzed 9016 depression patients who received KIT between 2016 and 2020 at one of 178 community practices across the United States. Depression symptoms were evaluated using the Patient Health Questionnaire-9 (PHQ-9). The induction phase of KIT was defined to be a series of 4-8 infusions administered over 7 to 28 days., Results: Among the 537 patients who underwent induction and had sufficient data, 53.6% of patients showed a response (≥ 50% reduction in PHQ-9 score) at 14-31 days post-induction and 28.9% remitted (PHQ-9 score drop to < 5). The effect size was d = 1.5. Among patients with baseline suicidal ideation (SI), 73.0% exhibited a reduction in SI. A subset (8.4%) of patients experienced an increase in depressive symptoms after induction while 6.0% of patients reported increased SI. The response rate was uniform across 4 levels of baseline depression severity. However, more severe illness was weakly correlated with a greater drop in scores while remission status was weakly inversely correlated with depression severity. Kaplan-Meier analyses showed that a patient who responds to KIT induction has approximately 80% probability of sustaining response at 4 weeks and approximately 60% probability at 8 weeks, even without maintenance infusions., Conclusion: KIT can elicit a robust antidepressant response in community clinics; however, a small percentage of patients worsened., (Copyright © 2021. Published by Elsevier B.V.)

Background: Several recent findings have revealed that targeting of cell cycle reentry and (or) progression may provide an opportunity for the therapeutic intervention of Alzheimer's disease (AD). FOXG1 has been shown to play important roles in pattern formation, cell proliferation, and cell specification. Thus far, the roles of FoxG1 and its involvement in AD are largely unknown., Objective: Our study aimed to explore the intervention effect of FOXG1 on AD pathology and its potential mechanism with a particular focus on cell cycle regulation., Methods: We investigated the association of Foxg1 gene variants with AD-like behavioral deficits, p21 expression, neuronal apoptosis, and amyloid-β (Aβ) aggregate formation; we further determined whether targeting FOXG1-regulated cell cycle has therapeutic potential in AD., Results: Paralleling AD-like behavioral abnormalities, neuronal apoptosis, and Aβ deposits, a significant reduction in the expression of FOXG1 was observed in APP/PS1 mice at 6 months of age. Using the APP/PS1;Foxg1fl/fl-CreAAV mouse line, we found that FOXG1 potentially antagonized cell cycle reentry by negatively regulating the levels of p21-activated kinase (PAK3). By reducing p21cip1-mediated arrest at the G2 stage and regulating cyclin A1- and cyclin B-dependent progression patterns of the cell cycle, FOXG1 blocked neuronal apoptosis and Aβ deposition., Conclusion: These results indicate that FOXG1 contributes to the regulation of the neuronal cell cycle, thereby affecting brain abnormalities in AD. An elevation of the FOXG1 level, either pharmacologically or through other means, could present a therapeutic strategy for AD.

Background: Esophagogastric variceal re-bleeding (EGVR) is a common and potentially lethal complication after open or laparoscopic splenectomy and azygoportal disconnection (LSD) in patients with cirrhosis and portal hypertension. Currently, noninvasive biomarkers for predicting EGVR are lacking. This prospective study focused on developing a noninvasive and convenient clinical model for predicting postoperative EGVR., Methods: Between September 2014 and March 2017, we enrolled 164 patients with cirrhosis who successfully underwent LSD. Based on the absence or presence of EGVR, patients were divided into EGVR and non-EGVR groups. We used correlation analysis to determine significant candidate variables among the liver fibrotic markers procollagen type III (PC-III), hyaluronidase (HA), laminin (LN), and type IV collagen (C-IV)., Results: Postoperative EGVR occurred in 22 (13.41%) patients. Correlation analyses showed that LN (r = 0.375; p < 0.001) and C-IV (r = 0.349; p < 0.001) were significantly positively associated with EGVR. The area under the receiver operating characteristic curve (AUC) of LN was 0.817 (95% confidence interval [CI] 0.722-0.913); that of C-IV was 0.795 (95% CI 0.710-0.881). In logistic multivariate regression, cutoff values LN ≥ 64 µg/L and of C-IV ≥ 65 µg/L were independent risk factors for EGVR. LN ≥ 64 µg/L combined with C-IV ≥ 65 µg/L was the best performing model, with AUC 0.867 (95% CI 0.768-0.967)., Conclusion: LN and C-IV are potential markers to predict EGVR. Combining the two markers showed satisfactory ability to predict EGVR in patients with cirrhosis and portal hypertension after LSD., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

Recent evidence has confirmed the association of glucocorticoid receptor (GR) gene variants with the "stress" endocrine axis in postpartum depression (PPD). Sirtuin 1(SIRT1) is an NAD + -dependent histone deacetylase and transcriptional enhancer of GR. However, to date, the function of the SIRT1 gene in the regulation of GR expression in PPD remains to be fully determined. A hormone-stimulated pregnancy (HSP) and subsequent "postpartum" withdrawal of estrogen was employed to mimic the fluctuations in estradiol associated with pregnancy and postpartum. We confirmed that estradiol benzoate withdrawal (EW)-rats displayed depression- and anxiety-like behaviors. These behavioral dysfunctions are associated with attenuated expression of SIRT1 and GR in the hippocampus. To assess the role of SIRT1, as well as its regulatory target directly, a selective SIRT1 activator (SRT2104) was infused into the hippocampus of EW-rats. We found that pharmacological activation of hippocampal SIRT1 blocks the development of depression-related, but not anxiety-related, phenotypes of PPD. In addition, the activation of SIRT1 leads to an increase in hippocampal GR expression in EW-rats. We further confirmed that SIRT1 physically interacts with GR in a glucocorticoid-dependent manner. Taken together, our results suggest that neuropathology in PPD is caused, at least in part, by the inhibition of the SIRT1-GR signaling pathway. Elevating SIRT1 levels, either pharmacologically or through other means, could represent a therapeutic strategy for PPD., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: The prognosis for patient survival using the tumor-node-metastasis (TNM) staging system may be imperfect, as it based only on biological factors and does not include the socioeconomic factors (SEFs). We integrated the SEFs into the TNM system (TNMSEF), and evaluated whether the novel TNM-SEF staging system showed better prediction capacity and improved clinical guidance in hepatocellular carcinoma (HCC)., Methods: We selected data of 12 514 cases with HCC between 2010 and 2015 from the SEER database. The Kaplan-Meier survival curves and Cox proportional hazards regression were used to analyze cancer-specific survival (CSS) among the TNM-SEF stages., Results: Multivariate Cox analyses showed that insurance status, marital status, year of diagnosis, and income were prominent prognostic SEFs (all P < .05). When compared with the SEF0 stage, the SEF1 stage was significantly associated with a 36.1% increased risk of cancer-specific mortality in HCC overall, a 22.2% increased risk of metastatic HCC, and a 41.8% increased risk of non-metastatic HCC (all P < .001). The concordance index of the TNM-SEF stage (0.768) was better than that of the TNM stage (0.764). Furthermore, patients with SEF0 stage showed higher 5-year CSS than those with SEF1 stage (I: 48.7% vs. 28.1%; II: 41.0% vs. 25.1%; IIIA: 12.8% vs. 5.0%; IIIB: 7.8% vs. 6.0%; IIIC: 6.4% vs. 6.7%; IVA: 8.4% vs. 2.5%; IVB: 2.1% vs. 0.8%; all P < .05)., Conclusion: We have proved that the SEF stage is an independent predictor for HCC. The combined SEF stage with TNM staging warrants more clinical attention, for improved prognostic prediction and clinical guidance.

Background: Hepatocellular carcinoma (HCC) progresses fast and has a poor prognosis, but the growth rate in different TNM stages is not clear. The present study was to estimate the growth rate of HCC with different TNM stages at diagnosis., Methods: Baseline demographics and tumor characteristics were analyzed for 10145 patients in Surveillance, Epidemiology, and End Results (SEER) Program-registered HCC. Multiple linear regression models were used for age adjustment with patient race, sex, marital status, and HCC grade., Results: The age at diagnosis was younger in Caucasians and males. The adjusted average age of patients with stage I HCC was 65.26 years. The adjusted age of patients with stage II, IIIA, IIIB, and IIIC was -0.17, -0.25, -0.29, and -0.55 adjusted-year younger compared with patients with stage I HCC (all P < 0.001). The adjusted average age of patients with T1 was 65.26 years. The age adjustment was -0.17, -0.26, and -0.55 respectively (all P < 0.001) for T2, T3 or T4 tumors without distant metastases., Conclusions: These findings demonstrated that the more advanced the HCC stage at diagnosis, the younger the age at diagnosis and the faster the HCC growth from tumor occurrence., Competing Interests: Competing interest No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article., (Copyright © 2021. Published by Elsevier B.V.)

Background: Anterior cruciate ligament transection surgery (ACLT)-induced OA model was often used to investigate the molecular mechanism of knee osteoarthritis (KOA). Researches have shown that vascular endothelial growth factor (VEGF) played an important role in OA. The present study aimed to investigate the pathological changes after ACLT surgery and reveal the expression characteristics of the VEGF-A/VEGFR2 signaling pathway in this model., Methods: Moderate KOA model was established by ACLT, and 1, 2, 4, 8, and 12 weeks after surgery, hematoxylin-eosin (HE) and Safranin-O(S-O) staining were used to detect the pathological changes in mouse knee cartilage, and the matrix biomarkers A Disintegrin and Metalloproteinase with Thrombospondin Motifs 5(ADAMTS5), Collagen II (COL-II) were detected using immunohistochemistry (IHC), CD31 was detected by immunofluorescence (IF) to show the vascular invasion in cartilage, and proteins expression of VEGF-A pathway were detected by Western blot (WB). Meanwhile, the inflammatory biomarkers cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in cartilage were detected by WB., Results: ACLT surgery can lead to degeneration of cartilage in mice, and the characteristics of the lesion were time-dependent. The ADAMTS5-positive cells increased while COL-II decreased in OA cartilage with time, and new blood vessels labeled by CD31 can be seen from 1 week in OA cartilage, and increased in 8 and 12 weeks. The expression of VEGF-A, VEGFR2, COX-2, and iNOS were higher than control groups, which were basically consistent with the degree of osteoarthritis., Conclusions: The degenerative degree of articular cartilage was time-dependent; angiogenesis and inflammation were important pathological changes of cartilage in KOA. The expression of the VEGF-A/VEGFR2 signaling pathway was basically correlated with the degree of KOA.

Background: The clinical guidance of the American Joint Committee on Cancer (AJCC) tumor, node, metastasis (TNM) staging system is established only in biological factors and does not include nonbiological factors (NBFs). We assessed the clinical value of incorporating NBFs into the TNM staging system in point of the clinical management and prognostic prediction accuracy of rectal cancer., Methods: We used the Surveillance, Epidemiology and End Results (SEER) database and identified 12,515 patients with rectal cancer who were diagnosed between 1 January 2011 and 31 December 2015. Multivariate Cox proportional hazards regression analysis and Kaplan-Meier curves were used to determine the probabilities of cancer-specific survival (CSS) according to different TNM-NBF stages., Results: Multivariate Cox regression analysis showed that county percentage with a bachelor's degree, insurance status, unemployment status, and marital status were all significant prognostic NBFs (p < 0.05). The concordance index of TNM-NBF stages was 0.815 (95% confidence interval (CI) 0.8072-0.8228). Multivariate Cox analyses showed that, compared with NBF0-stage, NBF1-stage was contacted with a 54.5% increased risk of cancer-specific mortality in rectal cancer, which increased to 68.3% in non-metastatic rectal cancer (all p < 0.001). NBF0-stage showed a CSS benefit as compared with NBF1-stage (p < 0.001)., Conclusions: We found that NBF-stage was an independent prognostic factor for survival in rectal cancer. The influence of NBFs on survival in rectal cancer warrants greater clinical attention. Furthermore, the consolidation of NBF-stage into the TNM staging system is crucial to better prognostic prediction accuracy and individualized risk-adaptive therapies., Competing Interests: Declaration of competing interest All authors declare no conflicts of interest., (Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: Digestive system complications are among the most important causes of postoperative poor quality of life after open and conventional laparoscopic splenectomy and azygoportal disconnection (CLSD). We firstly developed a modified vagus nerve-preserving laparoscopic splenectomy and azygoportal disconnection (MVLSD). In this study, we aimed to evaluate whether MVLSD is feasible and safe and to determine whether MVLSD can effectively eliminate postoperative digestive system complications, in comparison with CLSD., Method: In this randomized controlled single-center study, 60 patients with cirrhosis were randomly assigned to undergo either CLSD (n = 30) or MVLSD (n = 30) between April and December 2018. The primary outcome was delayed gastric emptying (DGE). Endoscopic physicians were blinded to group assignments., Results: One patient who received MVLSD withdrew from the study. There were no significant differences in intraoperative blood loss, incidence of blood transfusion, time to off-bed activity, time to first flatus, and postoperative hospital stay between the two groups. Compared with CLSD, operation time and incidences of DGE, diarrhea, epigastric fullness, and overall postoperative complications were all significantly reduced in the MVLSD group (all P < 0.05). Compared with CLSD, MVLSD was associated with significantly increased weight and albumin levels at 1, 6, and 12 months postoperatively versus preoperative values (all P < 0.05). The curative effect of resolving gastroesophageal variceal bleeding was similar between the groups., Conclusion: MVLSD is not only a technically feasible and safe procedure, it is also succinct and convenient. Furthermore, MVLSD effectively reduces postoperative digestive system complications, contributing to improved quality of life.

The identification of genetic risk subgroups of T-cell acute lymphoblastic leukemia (T-ALL) may provide evidence for risk stratification and individualized treatment. We investigated the characteristics and prognostic value of tumor suppressor gene CDKN2A deletions in 101 patients with T-ALL. The CDKN2A deletion was present in 23% (23/101) of T-ALL by fluorescence in situ hybridization (FISH). The most common type of CDKN2A deletion was homozygous deletion (70%, 16/23). A lower frequency of CDKN2A deletion was found in patients with early T-cell precursor (ETP) ALL than in patients with non-ETP-ALL (10.4% vs 34.0%; P = .008). Deletion of CDKN2A was significantly associated with younger age (P = .001), higher white blood cell (WBC) count (P < .001) and higher lactate dehydrogenase (LDH) level (P = .002). Patients with CDKN2A deletion had lower 2-year overall survival (OS) and event-free survival (EFS) rates than patients without CDKN2A deletion (2-year OS: 18.6% ± 8.9% vs 47.4% ± 6.2%, P = .032; EFS: 16.4 ± 8.3 vs 38.6 ± 5.9%, P = .022). In multivariable analysis, CDKN2A deletion was an independent adverse prognostic factor for OS (P = .016). In conclusion, adult T-ALL patients with CDKN2A deletion had a poor prognosis, and these patients might benefit from intensive chemotherapy or allogeneic hematopoietic stem-cell transplantation., (© 2020 Wiley Periodicals LLC.)

Background: Alpha-fetoprotein (AFP) has been widely used as a tumor marker in the treatment of hepatocellular carcinoma (HCC) in patients with cirrhosis. However, a large number of HCC patients are diagnosed without cirrhosis, and the prognostic capability of AFP was unclear in HCC patients without cirrhosis. Our purpose was to investigate the prognostic efficiency of AFP in patients with non-cirrhosis, single, and small HCC who were treated with surgical resection., Methods: Among the 111 374 liver cancer patients included in the Surveillance, Epidemiology, and End Results database, we selected 224 patients without cirrhosis with a single HCC ≤3 cm in diameter who were identified at diagnosis and treated with surgical resection. The AFP test results were recorded as AFP-positive and AFP-negative levels., Results: Kaplan-Meier method showed that there was no significant survival difference between the AFP-positive and AFP-negative groups (P = .566). The same results were found in the subgroups of patients with tumor size ≤2 cm and 2-3 cm (P = .710 and .687, respectively). Receiver operating characteristic (ROC) curve analysis showed that AFP had inadequate accuracy to discriminate survivors and deceased patients in subgroups of patients with tumor size ≤3 cm, 2-3 cm, or ≤2 cm (area under the ROC curve = 0.449, 0.458, 0.443; 95% confidence interval = 0.366-0.533, 0.346-0.571, 0.317-0.569, respectively)., Conclusion: AFP levels have no predictive value in well-compensated non-cirrhosis patients with single, small HCC (≤3 cm) treated with surgical resection for curative intent.

Amyloid-β (Aβ) is the core component of amyloid plaques of Alzheimer's disease (AD). Recent evidence has confirmed that Aβ triggers neurodegeneration by dramatically suppressing vitamin D receptor (VDR) expression. Thus far, the onset mechanisms and means of preventing AD are largely unknown. Perioxisome proliferator-activated receptor-γ coactivator (PGC-1α), as a transcriptional coactivator of VDR could protect cells against oxidative stress. Thus, upregulation of PGC-1α is a candidate therapeutic strategy for AD. To investigate the effect of PGC-1α in AD, and to illuminate the precise involvement of VDR in the neuroprotective strategy, the varies of molecular of PGC-1α and VDR were studied in APP/PS-1 double transgenic (2xTg-AD) mice at 6 months of age, significant reduction in the expression of PGC-1α and VDR was found in their hippocampus and the cortex. Besides, a specific mouse line, Dlx5/6-Cre:PGC-1α fl/fl in which the PGC-1α deficiency was limited to the hippocampus and the cortex, was used to study the target intervention of PGC-1α, decreased expression of VDR and increased oxidative damage were observed in AD-related brain regions by PGC-1α deficiency. To explore the function and therapeutic strategy of PGC-1α in AD, an adeno-associated virus (AAV) was used to induce PGC-1α overexpressed in the hippocampus of 2xTg-AD mice. Overexpressed PGC-1α results in a remarkable increase in the levels of VDR associated with a significant reduction in the expression of Aβ plaques and of 8-oxo-dG in 2xTg-AD mice. These data may have ramifications for neuroprotective strategies targeting overexpression of PGC-1α in Alzheimer's disease., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Our purpose was to establish and validate a nomogram model in early hepatocellular carcinoma (HCC) patients for predicting the cancer-specific survival (CSS)., Methods: We extracted eligible data of relevant patients between 2010 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database. Further, we divided all patients into two groups (training and validation cohorts) at random (7:3). Nomogram was established using effective risk factors based on univariate and multivariate analysis. The effective performance of nomogram was evaluated using concordance index (C-index), calibration plots, decision curve analysis (DCA), and receiver operating characteristic curve (ROC)., Results: We selected 3620 patients with early HCC including the training cohort (70%, 2536) and the validation cohort (30%, 1084). The nomogram-related C-indexes were 0.755 (95% CI: 0.739-0.771) and 0.737 (95% CI: 0.712-0.762), in the training and validation cohorts, respectively. The calibration plots showed good consistency of 3-and 5-year CSS between the actual observation and the nomogram prediction. The 3-, 5-year DCA curves also indicated that the nomogram has excellent clinical utility. The 3-, 5-year area under curve (AUC) of ROC in the training cohort were 0.783, 0.779, respectively, and 0.767, 0.766 in the validation cohort, respectively. With the establishment of nomogram, a risk stratification system was also established that could divide all patients into three risk groups, and the CSS in different groups (i.e., low risk, intermediate risk, and high risk) had a good regional division., Conclusions: We developed a practical nomogram in early HCC patients for predicting the CSS, and a risk stratification system follow arisen, which provided an applicable tool for clinical management., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Laparoscopic splenectomy and azygoportal disconnection (LSD) is widely used for the treatment of esophagogastric variceal haemorrhage and hypersplenism owing to cirrhotic portal hypertension. However, whether LSD improves liver synthesis function and cirrhosis remains unclear. The aim of this study is to investigate the effect of LSD on liver synthesis function and cirrhosis based on a prospective 2-year follow-up study., Methods: A total of 118 patients with cirrhotic portal hypertension who underwent LSD were included in this study. We analysed clinical data including routine blood parameters, liver function, liver-synthesised proteins (antithrombin III, protein S, and protein C), liver fibrotic markers (type IV collagen (IV-C), procollagen type III (PC-III), laminin, and hyaluronidase), portal vein diameter, and portal blood flow velocity., Results: Postoperative portal vein diameter and portal blood flow velocity all showed gradual declines during the 2-year follow-up; compared with preoperative values, these were all significantly decreased from postoperative week (POW) 1 (all P < 0.001). Postoperative Child-Pugh scores and total bilirubin, albumin, international normalised ratio, antithrombin III, protein S, protein C, IV-C, PC-III, laminin, and hyaluronidase levels also all showed gradual improvements during the 2-year follow-up; compared with preoperative levels, these were all significantly improved from postoperative month (POM) 6, POW 1, POM 3, POM 3, POM 3, POM 6, POM 18, POW 1, POM 3, POM 24, and POM 18, respectively (all P < 0.05)., Conclusion: LSD not only decreases portal hypertension and improves liver function, it also enhances liver synthesis function and reduces liver fibrosis.

Background: According to previously published studies, esophagectomy with modified Collard anastomosis has been reported to have low incidences of anastomotic leak and stricture. However, the optional anastomotic method after esophagectomy is still controversial. We conducted this study to compare the incidence of postoperative anastomotic stricture formation and dysphagia over three years after an esophagectomy with modified Collard anastomosis (MC) or end-to-side (ETS) hand-sewn anastomosis. Meanwhile, the early postoperative anastomotic leakage and other complications, hospital stay and 30- and 90-day mortality were also evaluated., Methods: The clinical data of 905 patients undergoing McKeown esophagectomy were retrospectively reviewed. The rate of postoperative stricture formation after three years was demonstrated by stricture-free survival which is the primary end-point of this study. The incidence of dysphagia, first time of onset of stricture and number of dilatations were also recorded during follow-up., Results: The incidence of anastomotic leak tended to be higher in the MC group compared with that in the ETS group (13.0% vs. 8.7%, P = 0.064). The rates of anastomotic stricture in the MC group were significantly less than in the ETS group (P = 0.004). The number of dilatations in the MC group were significantly greater than those in the ETS group (2.34 vs. 2.46, P = 0.011)., Conclusions: A modified Collard cervical esophagogastric anastomosis was associated with lower rates of anastomotic stricture and dysphagia, compared with ETS hand-sewn anastomosis. However, the modified Collard anastomosis is accompanied by an increased anastomotic leakage rate., (© 2020 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: Adult T-cell acute lymphoblastic leukemia (T-ALL) is a rare hematological malignancy and significantly linked to poor outcomes. Early T-cell precursor (ETP) leukemia is a unique subtype of T-ALL. The aim of this study is to compare the differences between ETP and non-ETP ALLs in China. Methods: We retrospectively analyzed the records of 122 adult T-ALL patients diagnosed and treated at our center between January 2014 and June 2019. All the patients enrolled were categorized into ETP and non-ETP ALL by immunophenotype, and further statistical analyses about clinical data and prognostic factors were performed. Results: Among the 122 cases, the male-to-female ratio was 2.8:1, and the median age is 29 (range, 16-82) years. Except for 10 patients with insufficient immunophenotyping results, 47.3% (53/112) are ETP and 52.7% (59/112) are non-ETP. Compared with non-ETP patients, ETP-ALL patients had lower white blood cell counts and lactate dehydrogenase levels, while they were older and had higher platelet counts and fibrinogen levels (all p < 0.05). Complete remission (CR) was achieved in 68.0% (83/122) of patients, 64.2 and 76.3% in ETP and non-ETP, respectively ( p = 0.160). In total, 44.6% (37/83) of patients relapsed. Allogeneic stem cell transplantation (allo-SCT) was successfully performed in 36.1% (44/122) of patients, of which 79.5% (35/44) were in CR1. With a median follow-up of 9.1 (range, 0.5-70.3) months, the estimated 2-year overall survival (OS) and relapse-free survival (RFS) rates for the cohort were 38.0 ± 5.1 and 39.1 ± 6.3%, respectively. In the ETP group, the 2-year OS rate was 40.7 ± 8.2% and the RFS rate was 47.2 ± 10.7%, while in the non-ETP group, the 2-year OS rate was 37.9 ± 7.0% and the RFS rate was 39.2 ± 8.3% (both p > 0.05). In the landmark analysis of CR1 patients who had a survival of more than 6 months, the allo-SCT group had significantly better survival outcomes than the chemotherapy group, and the 2-year OS rates and RFS rates were 80.1 ± 7.3 vs. 28.4 ± 8.4% and 68.9 ± 8.8 vs. 12.8 ± 7.2%, respectively (both p < 0.0001). A multivariate analysis suggests that allo-SCT acts as an independent prognostic factor for both OS and RFS. Conclusions: Our results revealed that ETP accounted for a high proportion of T-ALL in Chinese. There are no CR rates and prognosis differences between ETP and non-ETP. Allo-SCT in CR1 can significantly improve patients' survival., (Copyright © 2020 Zhang, Qian, Zhou, Huang, Li, Li, Li, Wang, Lou, Meng, Yu, Tong, Jin and Zhu.)

Background: Liver cirrhosis is a major risk factor for hepatocellular carcinoma (HCC). However, 10%-20% of patients with HCC do not have cirrhosis. The aim of this study was to explore the potential differences in tumour characteristics of HCC between patients with and without cirrhosis. Methods: In this study, we identified total 10,849 patients with HCC diagnosed between 2010 and 2016, from the SEER database. The degree of fibrosis was categorized as "no cirrhosis" (Ishak score 0-4) or "cirrhosis" (Ishak score 5-6). Among all patients with HCC, patients with no cirrhosis and with cirrhosis accounted for 1800 (16.6%) and 9049 (83.4%), respectively. Results: Significant negative correlations were observed between no cirrhosis/cirrhosis and pathological grade (r =-0.074, P <0.001), tumour size (r =-0.186, P <0.001), N stage (r =-0.024, P =0.025), M stage (r =-0.036, P <0.001), liver metastasis (r =-0.024, P =0.014), and lung metastasis (r =-0.027, P =0.006). Logistic multivariate regression analysis showed that, compared with cirrhosis, no cirrhosis is an independent risk predictor of pathological grade [odds ratio (OR), 0.685; 95% confidence interval (CI), 0.571-0.822; P < 0.001], tumour size (OR, 0.392; 95% CI, 0.351-0.437; P < 0.001), N stage (OR, 0.704; 95% CI, 0.561-0.883; P < 0.001), and M stage (OR, 0.671; 95% CI, 0.561-0.804; P < 0.001). Conclusions: Compared with cirrhosis, no cirrhosis is significantly associated with worse pathological grade, larger tumour size, and more lymph node and distant metastases. Patients without cirrhosis that are otherwise neglected in HCC clinical practice require intensive focus in future studies., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Introduction: A typical feature of hepatocellular carcinoma (HCC) is growth with metastasis to distant organs, which is associated with poor survival. Whether tumor size can predict distant metastases in HCC remains unclear., Methods: We identified 29,170 HCC patients with or without distant metastases between 2010 and 2016 in the Surveillance, Epidemiology and End Results database. According to an optimal cutoff value of tumor size (58 mm) for predicting distant metastases using Youden's index, patients were categorized into groups of tumor size ≤30 cm, 30-58 mm, and ≥58 mm., Results: Tumor size had a significantly positive correlation with distant metastases (r = 0.245, P < 0.001). Among patients with distant metastasis, the most common metastasis site was lung (39.3%), followed by bone (30.0%), and brain (2.0%). Incidence of distant metastases in patients with tumor ≥58 mm was 5.7 times (22.8%/4.0%) that of patients with tumors ≤30 mm and 2.9 times (22.8%/7.9%) that of patients with tumors 30-58 mm. Multivariate analyses showed that compared with ≤30 mm, tumor size ≥58 mm was an independent risk predictor of overall distant metastases (OR, 5.200; 95% CI, 4.635-5.834; P<0.001), lung (OR, 6.036; 95% CI, 5.006-7.278; P<0.001); bone (OR, 3.365; 95% CI, 2.781-4.071; P<0.001); and brain metastasis (OR, 1.905; 95% CI, 1.023-3.547; P<0.05)., Conclusions: Tumor size ≥58 mm is significantly associated with HCC distant metastases. In clinical practice, patients with tumors ≥58 mm may benefit from timely identification of distant metastases., (Copyright © 2020 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.)

Adult patients with relapsed or refractory T-cell acute lymphoblastic leukemia (R/R-T-ALL) have extremely poor prognosis, representing an urgent unmet medical need. Finding an optimal salvage regimen to bridge transplantation is a priority. The CAG (cytarabine, aclarubicin, and G-CSF) regimen was initially used by one group in China, showing unexpectedly promising results in 11 R/R-T-ALL patients. Here, we report the multicenter results of 41 patients who received the CAG regimen as salvage therapy. After one cycle of the CAG regimen, complete remission and partial remission were achieved in 33 (80.5%) and two (4.9%) patients, respectively. Failure to respond was observed in six patients (14.6%). Early T-cell precursor (ETP) (n = 26) and non-ETP (n = 15) patients had a similar CR rate (80.8% vs 80.0%, P = .95). Among 41 patients, allo-HSCT was successfully performed in 27 (66%) patients (22 in CR and 5 in non-CR). With a median follow-up time of 12 months, the estimated 2-year overall survival and event-free survival were 68.8% (95% CI, 47.3%-83.0%) and 56.5% (95% CI, 37.1%-71.9%), respectively. The CAG regimen was well-tolerated, and no early death occurred. Our multicenter results show that the CAG regimen is highly effective and safe, representing a novel choice for adult patients with R/R-T-ALL and providing a better bridge to transplantation., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Cancer-induced bone pain (CIBP) is a highly prevalent symptom, which afflicts vast majority of patients who suffer from cancer. The current treatment options failed to achieve satisfactory effect and the side effects were prominent. Recent randomized controlled trials (RCTs) of animal demonstrate the benefit of acupuncture for CIBP. We sought to determine if the pooled data from available RCTs supports the use of acupuncture for CIBP., Methods: A literature search for randomized controlled trials was conducted in six electronic databases from inception to May 31, 2019. Meta-analysis was performed with Review Manager 5.3 software; the publication bias was assessed by Stata 12.0 software. We used random effects model for pooling data because heterogeneity is absolute among studies to some extent., Results: Twenty-four trials were included in the review, of which 12 trials provided detailed data for meta-analyses. Preliminary evidence indicates that compared to wait list/sham group, acupuncture was effective on increasing paw withdrawal threshold (PWT) and paw withdrawal latency (PWL). Compared to medicine, acupuncture was less effective on PWT, but as effective as medicine on PWL. Acupuncture can reinforce medicine's effect on PWT and PWL. Compared to the control group, acupuncture was superior to increase body weight (BW), decrease spinal cord glial fibrillary acidic protein (GFAP), and interleukin-1 β (IL-1 β ). Furthermore, some studies showed acupuncture delay or partially reverse morphine tolerance. Three studies found acupuncture has no effect on PWT, but 2 of them found acupuncture could enhance small dose of Celebrex's effect on CIBP., Conclusions: Acupuncture was superior to wait list/sham acupuncture on increasing PWT and has no less effect on increasing PWL compared to medicine; acupuncture improved the efficacy of drugs, increased the CIBP animals' body weight, and decreased their spinal cord GFAP and IL-1 β . High-quality studies are necessary to confirm the results., Competing Interests: The authors declare that they have no conflicts of interests., (Copyright © 2020 Mei-ling Yu et al.)

Parkinson's disease (PD) is one of the most common diseases of the nervous system characterized by movement disorders arising from loss of midbrain dopaminergic neurons. The relationship between PD and autophagy has received considerable attention. This study aimed to investigate the involvement of the ATP13A2 gene in damage of dopaminergic neurons induced by abnormal autophagy in a MPTP-induced PD mouse model. MPTP was intraperitoneally injected into C57BL mice at 40 mg/kg for 7 days in experimental group. Saline was injected into mice in the control group. After the injection, the mice were tested at different time points for abnormal limb movement by a swimming test. The brain tissue was collected on day 1, 5, and 7 to measure concentration of intracellular calcium. The expression of ATP13A2 was evaluated by real-time PCR. The expression of α-synclein, LC3, LAMP-2, and CaMKK protein was detected by western blot. We found significant motor dysfunction on day 7 in the experimental group, and the expression of α-synclein in the substantia nigra of the midbrain was significantly increased while the expression of ATP13A2 gene was reduced significantly compared with the control group. The concentration of intracellular calcium in the experimental group was significantly higher than in the control group. Autophagy associated proteins LC3-II and LAMP-2 were downregulated and CaMKK protein was upregulated in midbrain tissues of the experimental group compared to control group. In conclusion, our findings suggest that decreased expression of ATP13A2 may lead to defective autophagy and damage to midbrain dopaminergic neurons., Competing Interests: None., (IJCEP Copyright © 2020.)

The separation of Xe/Kr mixtures in used nuclear fuel (UNF) has attracted lots of attention, but no report on the adsorption and separation of Kr from mixed Kr/Xe at room temperature can be found. From grand canonical Monte Carlo (GCMC) simulation, it is found that by replacing the metal center Ca of SBMOF-1 with Mg, due to the appropriate pore size, the adsorption selectivity ( S Kr/Xe ) was extremely high (250 000) and the adsorption capacity for Kr on Mg-SBMOF-1 modified with -NH 2 was increased by 300% to 1.020 from 0.248 mmol g -1 . Based on the calculations of density functional theory (DFT), we found that the stronger electron-donating ability of a functional group will increase the polarizability of the ligand, and thus increase the adsorption capacity to Kr. In addition, the analysis of electronic structures with independent gradient model (IGM) and energy decomposition analysis (EDA) indicates that van der Waals forces will be responsible for the interaction of Mg-SBMOF-1 and Kr gas. Among them, the interaction of Mg-SBMOF-1 and Kr gas is mainly an induction force, while that of modifications with -CH 3 and -NH 2 is mainly a dispersion force. The present theoretical study represents the first report of the separation of Kr from Xe with MOF adsorption at room temperature. We hope this work may promote the experimental synthesis of Mg-SBMOF-1 for efficient separation of Kr and Xe., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)