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Murong Wang,1,* Qunfang Zhou,2,* Hui Li,1 Mingyu Liu,3 Ruixia Li,4 Wei Wang,5 Xiaohui Wang,6 Jinhua Huang,1 Feng Duan2 1Department of Minimally Invasive Interventional Radiology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong province, People’s Republic of China; 2Department of Interventional Radiology, 5th Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China; 3Department of Minimally Invasive Interventional Radiology, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong province, People’s Republic of China; 4Department of Liver Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong province, People’s Republic of China; 5Department of General Surgery, the First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning Province, People’s Republic of China; 6Department of Hepatobiliary Surgery, Hunan Provincial People’s Hospital, Changsha, Hunan Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jinhua Huang, Department of Minimally Invasive Interventional Radiology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong province, People’s Republic of China, Tel/Fax +86-020-87343272, Email huangjh@sysucc.org.cn Feng Duan, Department of Interventional Radiology, 5th Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China, Tel/Fax +8610-66939123, Email duanfeng@vip.sina.comPurpose: The outcome between Lenvatinib plus programmed cell death protein-1 (PD-1) inhibitor and Lenvatinib in HCC beyond oligometastasis was unclear. In this multicenter, we compared the prognosis of Lenvatinib plus PD-1 inhibitor with Lenvatinib in HCC beyond oligometastasis.Patients and Methods: A total of 296 patients from six institutions were included. The patients were divided into two groups: (a) concurrent Lenvatinib plus PD-1 inhibitor treatment (Len+PD-1 group) and (b) Lenvatinib monotherapy (Len group). The primary endpoint was overall survival (OS), the second endpoint was progression-free survival (PFS) and efficacy.Results: The median OS was 20.1 ± 1.2 (17.7– 22.5) months and 15.7 ± 1.5 (12.8– 18.6) months in the Len+PD-1 and Len groups, respectively. The 12-, 24-, and 36-month OS rates were 79.1%, 39.4%, and 10.7% in the Len+PD-1 group, and 76.3%, 29.7%, and 0% in the Len group, respectively. The OS and PFS rates of the Len+PD-1 group were significantly longer compared with the Len group (hazard ratio [HR], 0.88; 95% confidence index [CI], 0.49– 0.94; P = 0.021) and (HR, 0.66; 95% CI, 0.50– 0.87; P = 0.003). A subgroup analysis revealed that OS (HR, 0.57; 95% CI, 0.36– 0.90; P = 0.016) was improved between the Len+PD-1 and Len groups with hepatic artery infusion chemotherapy (HAIC) treatment, whereas OS (HR, 1.11; 95% CI, 0.68– 1.80; P = 0.689) was similar between the Len and Len+PD-1 groups without HAIC.Conclusion: Lenvatinib combined with PD-1 inhibitor significantly improves the survival of HCC beyond oligometastasis. For patients with HAIC, there was obviously significance between Len and Len+PD-1 groups.Plain Language Summary: Lenvatinib as one of system therapy, is recommended treatment for HCC with multimetastases. The LEAP-002 trial, which evaluated Lenvatinib combined with Pembrolizumab exhibited improved progression-free survival (PFS) and overall survival (OS) compared with Lenvatinib alone. However, the combination efficacy on HCC beyond oligometastasis is unknown. In this multicenter study, we found that Lenvatinib combined with PD-1 inhibitor significantly improved both the OS and PFS and this combination could be recommended for HCC beyond oligometastases. OS and PFS were improved in the Len+PD-1 versus the Len group with hepatic artery infusion chemotherapy (HAIC) treatment, whereas the OS and PFS were similar between the Len and Len+PD-1 groups without HAIC. We provided clinical value that HAIC could be recommended as an effective local therapy to improve the prognosis for advanced HCC.Keywords: advanced hepatocellular carcinoma, Lenvatinib, beyond oligometastasis, prognosis, programmed death receptor-1 inhibitor

XiaoYing Yang, Mengda Wei, YanQing Huang, Xi Yang, ZhenMin Yuan, JunJie Huang, JunRen Wei, Lei Tian Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of ChinaCorrespondence: Lei Tian, Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China, Email tianlei@stu.gxmu.edu.cnBackground: Stomach adenocarcinoma (STAD) presents a challenge given its advanced stage at diagnosis and poor prognosis. Integrin subunit alpha 11 (ITGA11) encodes alpha integrin and has been implicated in promoting tumorigenesis and development by participating in cell proliferation and invasion. However, the precise mechanism of ITGA11 in STAD remains unclear.Methods: The differences in ITGA11 expression levels between 375 gastric cancer samples and 32 paracancerous tissue samples from the Cancer Genome Atlas (TCGA) database were examined. The relationship between ITGA11 expression and clinical features and ITGA11 diagnostic and prognostic value were evaluated using the chi-square test and receiver operating characteristic (ROC) assay. Differentially expressed genes were identified based on ITGA11 expression. Subsequently, functional enrichment analyses were conducted using Gene Ontology, the Kyoto Encyclopedia of Genes and Genomes, and Gene Set Enrichment Analysis. Furthermore, immune infiltration and the expression of ITGA11-associated immune checkpoints in patients with tumors were assessed using CIBERSORT, single-sample gene set enrichment analysis, and the TIMER database. Drug sensitivity associated with ITGA11 expression was analyzed using the R oncoPredict package to guide treatment decisions. Finally, the difference in ITGA11 expression between cancer tissue and the adjacent tissues was validated using quantitative PCR (qPCR) and immunohistochemistry.Results: The gastric cancer tissue had significantly upregulated ITGA11 expression compared to paracancerous tissues. ITGA11 demonstrated robust diagnostic and prognostic value in gastric cancer (GC) and was an independent risk factor for adverse outcomes. The patients with STAD with elevated ITGA11 expression levels had heightened immune cell infiltration and increased immune checkpoint marker expression. Notably, patients with increased ITGA11 expression demonstrated reduced responsiveness to oxaliplatin and afatinib.Conclusion: The results indicated the pivotal role of ITGA11 in shaping the tumor immune microenvironment, ultimately establishing ITGA11 as an immune-related prognostic predictor within the intricate landscape of STAD.Keywords: ITGA11, stomach adenocarcinoma, bioinformatics analysis, immune infiltration, prognosis

Jianjun Huang,1 Fangping Shao,2 Bin Chen,1 Guanrong Zheng,1 Jia Shen,1 Shenzhong Qiu1 1Department of Neurosurgery, The First People’s Hospital of Fuyang District of Hangzhou City, Hangzhou, People’s Republic of China; 2Emergency Department, The First People’s Hospital of Fuyang District of Hangzhou City, Hangzhou, People’s Republic of ChinaCorrespondence: Shenzhong Qiu, Department of Neurosurgery, The First People’s Hospital of Fuyang District of Hangzhou City, Hangzhou, People’s Republic of China, Email chengiftboy@163.comBackground: Secreted protein acidic and rich in cysteine-like 1 (SPARCL1) regulates synaptic stability and is up-regulated during axonal regeneration. Here, serum SPARCL1 was determined for estimating severity and prognosticating early neurological deterioration (END) and functional outcomes of acute intracerebral hemorrhage (ICH).Methods: In this prospective observational cohort study of 156 patients with supratentorial ICH, blood samples of 53 were acquired not only at admission but also ad days 1, 3, 5, 7 and 10. Another group of 53 healthy controls were recruited. The modified Rankin Scale (mRS) scores of 3– 6 at poststroke six months were regarded as poor prognosis.Results: As opposed to controls, serum SPARCL1 levels were markedly elevated during the early ten days after ICH, with the highest levels at days 1 and 3. Admission serum SPARCL1 levels were independently correlated with National Institutes of Health Stroke Scale scores and hematoma volume, were significantly increased in the order of six-month mRS scores from 0 to 6 and were independently correlated with six-month mRS scores. Serum SPARCL1 levels were linearly related to risks of poor six-month prognosis and END under restricted cubic spline, had significant efficiency under receiver operating characteristic (ROC) curve and were independently associated with END and poor prognosis. Subgroup analysis confirmed that no interactions existed for associations of serum SPARCL1 levels with other variables, such as age, gender and some specific vascular risk factors. END and poor prognosis prediction models integrating serum SPARCL1 were displayed using the two nomograms. The poor prognosis prediction model, but END prediction model not, performed well under calibration curve, decision curve and ROC curve.Conclusion: A substantial elevation of serum SPARCL1 levels during the early period after ICH is independently related to illness severity and poor neurological outcomes, thus signifying that serum SPARCL1 may appear as a prognostic biomarker of ICH.Keywords: Secreted protein acidic and rich in cysteine-like 1, intracerebral hemorrhage, early neurologic deterioration, prognosis, severity, biomarkers

Huang J, Shao F, Chen B, Zheng G, Shen J, Qiu S. Neuropsychiatr Dis Treat. 2023;19:2709–2728. The authors have advised that the funding statement on page 2727 is incorrect. The text “(No. 202107071918000249496)” should read “(No. 20201203B59)”. The authors apologize for this error.

Peizhuang Zhao,* Jiajia Ning,* Jun Huang,* Binqian Wei, Zhen Wang, Xue Huang Department of Geriatrics and Gastroenterology, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xue Huang, Department of Geriatrics and Gastroenterology, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530000, People’s Republic of China, Email hb960305@163.comPurpose: Microrchidia 2 (MORC2) is a universally expressed molecule that has recently been identified as a chromatin modulator and elevated in many malignancies. However, its prognostic value and immunological role of MORC2 in colon adenocarcinoma (COAD) have never been illustrated.Methods: The clinical parameters and MORC2 expression datasets of COAD patients were obtained from The Cancer Genome Atlas (TCGA). Cancer and adjacent tissue specimens from surgically resected COAD patients were collected, and quantitative real-time PCR was used to detect MORC2 expression. Differentially expressed genes related to MORC2 were discovered and used for functional enrichment analysis. The diagnostic and prognostic values of MORC2 in COAD were conducted using receiver operating characteristics (ROC), Kaplan–Meier survival curve analysis, PrognoScan, Gene Expression Profiling Interactive Analysis (GEPIA) public databases and nomograms. Eventually, the association of MORC2 with tumor microenvironment was analyzed by using TIMER and GSVA package of R (v3.6.3).Results: MORC2 expression was upregulated in COAD tissues, and the RT-qPCR results further verified the reliability of our differential analysis at the transcriptional level. Additionally, higher expression of MORC2 was correlated to a poor prognosis for COAD patients. MORC2 was an independent prognostic factor for COAD and could be a diagnostic factor for early COAD. Furthermore, MORC2 expression was positively correlated with immune cells such as NK cells, TFH cells and so on.Conclusion: The findings demonstrated that overexpression of MORC2 was correlated with worse prognosis and immune infiltrates of COAD. MORC2 can serve as a reliable diagnostic and prognostic biomarker and a target of immunotherapy for COAD patients.Keywords: MORC2, colon adenocarcinoma, diagnosis, prognosis, immune cell infiltration, biomarker

Shirong Li,1,&ast; Wene Wei,1,&ast; Zhaorong Feng,1,&ast; Yingzhen Bian,1 Jinmiao Pan,1 Jinling Mai,1 Shufang Ning,1,2 Jinglei Huang,1 Xiangyang Gao,3,&ast; Litu Zhang1,2,&ast; 1Department of Research, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 2Department of Research, Guangxi Cancer Molecular Medicine Engineering Research Center, Nanning, People’s Republic of China; 3Health Management Institute, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiangyang Gao; Litu Zhang, Email 13811130808@126.com; zhanglitu@gmail.comPurpose: In current studies, the role of serum Cytokeratin-19 fragments (CYFRA 21-1) in colorectal cancer (CRC) remains unclear. This study aimed to clarify the diagnostic and prognostic value of CYFRA 21-1 in CRC.Patients and Methods: Data were collected for 196 stage I–III CRC patients and 50 colorectal liver metastases (CRLM) patients between January 2018 and December 2019. The serum CYFRA 21-1 levels were measured using the chemiluminescent particle immunoassay (CMIA) kit in all objects and common biomarkers such as CA19-9, CEA, HSP90α, and AFP were measured in all colorectal cancer patients. We investigated the association between CYFRA 21-1 level and clinicopathological features. In addition, we evaluated the ability of serum CRFRA21-1 to differentiate CRLM from CRC. To assess the potential prognostic value, we used Cox proportional hazard model for univariate or multivariate analyses.Results: Serum CYFRA 21-1 was significantly elevated in CRLM patients compared to stage I–III CRC patients (5.85 ng/mL vs 2.29 ng/mL, p < 0.001). For all CRC patients cohort, stage I–III CRC patients cohort and CRLM patients cohort, the optimal cutoff levels of CYFRA 21-1 for overall survival (OS) were 3.47 ng/mL, 2.14 ng/mL and 7.63 ng/mL, respectively, and the optimal cutoff levels for progression-free survival (PFS) were 3.47 ng/mL, 2.56 ng/mL and 7.63 ng/mL, respectively. For CRLM patients, Kaplan–Meier analysis showed that patients with high CYFRA 21-1 level had poor OS. Multivariate analysis indicated that the CYFRA 21-1 level was an independent prognostic factor for PFS in stage I–III patients. And CYFRA 21-1 levels and age were independent prognostic factors for OS and PFS in CRLM patients.Conclusion: CYFRA 21-1 can better differentiate CRLM patients from the whole CRC patients and has unique prognostic value for CRLM patients.Keywords: colorectal cancer, colorectal liver metastases, CRLM, prognosis, cytokeratin-19 fragments, CYFRA21-1, overall survival, progression-free survival

Lin Jin,1 Yafen Liang,2 Ying Yu,1 Peng Miao,1 Yihao Huang,1 Liying Xu,1 Huilin Wang,1 Chunsheng Wang,3 Jiapeng Huang,4 Kefang Guo1 1Department of Anesthesia, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Anesthesiology, University of Texas Health Center at Houston, Houston, TX, USA; 3Department of Cardiac Surgery, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 4Department of Anesthesiology & Perioperative Medicine University of Louisville, Louisville, KY, USACorrespondence: Kefang Guo, Department of Anesthesia, Zhongshan Hospital, Fudan University, No. 180, Fenglin Road, Xuhui District, Shanghai, People’s Republic of China, Email dr_guokefang@163.com Jiapeng Huang, Department of Anesthesiology & Perioperative Medicine University of Louisville, Louisville, KY, 40202, USA, Email jiapeng.huang@louisville.eduObjective: To investigate the feasibility of multimodal regimen by paracetamol, gabapentin, ketamine, lidocaine, dexmedetomidine and sufentanil among cardiac surgery patients, and compare the analgesia efficacy with conventional sufentanil-based regimen.Design: A single-center, prospective, randomized, controlled clinical trial.Setting: One participating center, the cardiovascular center of the major integrated teaching hospital.Participants: A total of 115 patients were assessed for eligibility: 108 patients were randomized, 7 cases were excluded.Interventions: The control group (group T) received conventional anesthesia management. Interventions in the multimodal group (group M) were as follows in addition to the standard of care: gabapentin and acetaminophen 1 hour before surgery; ketamine for induction and to maintain anesthesia with lidocaine and dexmedetomide. Ketamine, lidocaine, and dexmedetomidine were added to routine sedatives postoperatively in group M.Measurements and Main Results: The incidence of moderate-to-severe pain on coughing made no significant difference (68.5% vs 64.8%, P=0.683). Group M had significantly less sufentanil use (135.72μg vs 94.85μg, P=0.000) and lower rescue analgesia rate (31.5% vs 57.4%, P=0.007). There was no significant difference in the incidence of chronic pain, PONV, dizziness, inflammation index, mechanical ventilation time, length of stay, and complications between the two groups.Conclusion: Our multimodal regimen in cardiac surgery is feasible, but was not superior to traditional sufentanil-based regimen in the aspects of analgesia effects; however, it did reduce perioperative opioid consumption along with rescue analgesia rate. Moreover, it showed the same length of stay and the incidences of postoperative complications.Keywords: cardiac surgery, multimodal analgesia, prognosis

Jun Huang,&ast; Peizhuang Zhao,&ast; Jialing Shi, Jiajia Ning, Zhen Wang, Yihua Luo, Jingqian Qin, Xue Huang Department of Geriatrics and Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xue Huang, Department of Geriatrics and Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530000, People’s Republic of China, Email hb960305@163.comPurpose: Prolyl 4-hydroxylase subunit alpha 3 (P4HA3) has been proven to participate in the occurrence and development of multiple cancers. However, the functional role of P4HA3 in the tumor immune microenvironment (TIME) of colon adenocarcinoma (COAD) and the prognosis of COAD patients has not been clarified. This study aimed to elucidate the immunological role and prognostic value of P4HA3 in COAD.Methods: P4HA3 expression in COAD tissues was analyzed via experiments and a bioinformatics algorithm. Based on the COAD patients in The Cancer Genome Atlas database, we comprehensively evaluated whether the expression levels of P4HA3 affected clinical prognosis, TIME, and immunotherapy of COAD using the R platforms and several public databases, including GEPIA, TIMER, TISIDB, and TCIA.Results: The results of the pan-cancer analysis indicated that P4HA3 expression was significantly different in most tumor tissues compared with normal tissues. P4HA3 was overexpressed in COAD tissues, and overexpression of P4HA3 was associated with a worse overall survival and a shorted progression-free interval in COAD patients. The expression of P4HA3 was positively correlated with pathological stage, T stage, N stage, perineural infiltration, and lymphatic infiltration. There were significant correlations of P4HA3 expression levels with immune cell infiltration and their makers, as well as immunomodulators, chemokines, and microsatellite status. Moreover, overexpression of P4HA3 was associated with a lower response rate to immunotherapy in the IMvigor210 cohort.Conclusion: Overexpression of P4HA3 is closely related to the poor prognosis of COAD patients, and P4HA3 is a potential target for immunotherapy in COAD patients.Keywords: P4HA3, colon adenocarcinoma, prognosis, immunotherapy, tumor immune microenvironment

Jian Huang,1,&ast; Li Li,2,&ast; Fu-Chen Liu,1 Bi-Bo Tan,3 Yun Yang,1 Bei-Ge Jiang,1 Ze-Ya Pan1 1Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, 201805, People’s Republic of China; 2Department of Nephrology, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, 201805, People’s Republic of China; 3Department of Ultrasonic, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, 201805, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ze-Ya Pan; Bei-Ge Jiang, Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, No. 700, MoYu North Road, Jiading, Shanghai, People’s Republic of China, Tel +86-13391236437 ; +86-13764561303, Email hjluffy@126.com; jiang_beige@aliyun.comObjective: To investigate the survival and independent prognostic factors for single large hepatocellular carcinoma (SLHCC) after surgical resection.Methods: Patients with SLHCC who underwent radical resection from January 2013 to December 2017 were retrospectively analyzed. The Kaplan-Meier method was used to analyze the overall survival (OS) rate and recurrence-free survival (RFS) rates. Cox forward stepwise regression was performed to analyze the independent prognostic factors.Results: A total of 485 cases were included. The average age was 51.2± 11.2 years, 88.9% had a history of hepatitis B virus infection, and most patients had normal liver function. The average tumor diameter was 8.8± 3.0 cm. The 1-, 3-, and 5-year OS and RFS rates were 76.8%, 56.7%, and 45.7%, and 61.0%, 46.2%, and 34.7%, respectively. Multivariate analysis showed that liver cirrhosis (HR=1.456, P=0.004), total bilirubin (TB) ≥ 17.1 μmol/L (HR=1.437, P=0.011), glutamyl transferase (GGT) > 60 U/L (HR=1.438, P=0.020), lactate dehydrogenase (LDH) > 225 U/L (HR=1.442, P=0.007), blood loss ≥ 400 mL (HR=1.339, P=0.027), microvascular invasion (MVI) (HR=1.492, P=0.004), satellite lesions (HR=1.859, P< 0.0001) and Edmondson-Steiner grade III+IV (HR=1.740, P=0.018) were independent risk factors for reduced OS in SLHCC patients. Sex (HR=1.763, P=0.003), liver cirrhosis (HR=1.382, P=0.007), GGT > 60 U/L (HR=1.512, P=0.003), LDH > 225 U/L (HR=1.480, P=0.002), MVI (HR=1.545, P=0.001), and satellite lesions (HR=1.564, P=0.001) were independent risk factors for reduced RFS. OS and RFS nomograms were constructed using risk factors with C-index values of 0.692 (95% CI: 0.659– 0.724) and 0.659 (95% CI: 0.623– 0.693), respectively. The Hosmer-Leme test demonstrated the good fit of both nomograms.Conclusion: Surgical resection is the standard and effective treatment for SLHCC patients. Sex, liver cirrhosis, TB≥ 17.1 μmol/L, GGT> 60 U/L, LDH> 225 U/L, blood loss≥ 400 mL, MVI, Edmondson-Steiner grade III+IV, and satellite lesions were found to be independent prognostic factors in SLHCC patients following radical resection. The OS and RFS nomograms accurately predicted the prognosis of SLHCC patients.Keywords: SLHCC, cancer, hepatectomy, prognosis, risk factor

Rui Song,1,2,&ast; Juntao Huang,1,2,&ast; Chenglei Yang,1,2 Yuankuan Li,1,2 Guohua Zhan,1,2 Bangde Xiang1– 3,&ast; 1Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 2Key Laboratory of Early Prevention and Treatment for Regional High-Frequency Tumors, Ministry of Education, Nanning, People’s Republic of China; 3Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bangde Xiang, Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, 71 Hedi Road, Qingxiu District, Nanning, Guangxi, 530021, People’s Republic of China, Tel +86-7715301253, Email xiangbangde@gxmu.edu.cnPurpose: The extra spindle pole bodies-like 1 (ESPL1) gene is associated with malignant biological behaviors in several tumors. Nevertheless, the correlation between hepatocellular carcinoma (HCC) and ESPL1 has not been determined. The present study analyzed the molecular function and prognostic value of ESPL1 in HCC.Patients and Methods: Samples from 121 HCCs and 119 adjacent normal tissue specimens were subjected to next-generation sequencing. Clinicopathological and genetic data of HCC patients in The Cancer Genome Atlas (TCGA) were also collected. ESPL1 expression was assessed in 20 pairs of HCC and normal liver specimens by qRT-PCR and immunohistochemistry (IHC). The prognostic value of ESPL1 expression was determined by Cox univariate and multivariate regression analyses. ESPL1-related co-expressed genes were evaluated by weighted gene co-expression network analysis (WGCNA). Processes and pathways involving ESPL1 in HCC were determined by Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. The prognostic values of hub genes were determined by joint effect survival analysis.Results: RNA-Seq, RT-qPCR and IHC showed that ESPL1 expression was significantly higher in HCC than in normal liver tissues. Increased ESPL1 expression, greater tumor size and advanced BCLC stage were independently prognostic of poorer overall survival; and increased ESPL1 and advanced BCLC stage were independently prognostic of poorer recurrence-free survival. WGCNA showed that the top 10 co-expressed genes associated with ESPL1 were GTSE1, KIF18B, BUB1B, GINS1, PRC1, KIF23, KIF18A, TOP2A, NEK2 and FANCD2. Enrichment analysis indicated that ESPL1 and its co-expressed genes might be involved in the cell cycle and cell division of HCC. Joint effect survival analysis showed that the mortality rate was approximately 3.37 times higher in HCC patients with high than low expression of ESPL1, GTSE1, BUB1B, PRC1, KIF23, and TOP2A.Conclusion: ESPL1 might be associated with cell cycle and might be an effective prognostic indicator in patients with HCC.Keywords: hepatocellular carcinoma, extra spindle pole bodies-like 1, prognosis

Rui Song,1,2,&ast; Hanghang Ni,1,&ast; Juntao Huang,1,&ast; Chenglei Yang,1 Shangdong Qin,1,3 Huaning Wei,1 Jiefu Luo,1 Yuxiang Huang,1 Bangde Xiang1– 3 1Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 2Key Laboratory of Early Prevention and Treatment for Regional High-Frequency Tumors, Ministry of Education, Nanning, People’s Republic of China; 3Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bangde Xiang, Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, 71 Hedi Road, Qingxiu District, Nanning, Guangxi, 530021, People’s Republic of China, Tel +86-7715301253, Email xiangbangde@gxmu.edu.cnPurpose: The study aimed to investigate the ability of inflammation-immunity-nutrition score (IINS) and inflammatory burden index (IBI), individually or in combination, to predict prognosis of hepatocellular carcinoma (HCC) patients after hepatectomy.Methods: A total of 701 patients who underwent HCC resection at Guangxi Medical University Cancer Hospital were enrolled in the study. An IINS ranging from 0 to 3 was defined based on preoperative C-reactive protein (CRP), lymphocyte count, and serum albumin level, while an IBI was based on CRP and neutrophil-to-lymphocyte ratio. The prognostic value of IINS and IBI was assessed using univariate and multivariate Cox regression and Kaplan–Meier survival curves. The concordance index and calibration curve were used for internal validation of models. Decision curve analysis, net reclassification index and integrated discrimination improvement were used to compare the predictive performance of the models with traditional staging systems.Results: IINS and IBI were able to predict poor prognosis in HCC patients after hepatectomy, and a nomogram based on the IINS predicted survival at 1, 3, and 5 years better than other models or traditional staging systems.Conclusion: IINS may be accurate predictors of survival in HCC patients after hepatectomy, with potentially greater prognostic value than conventional markers.Keywords: hepatocellular carcinoma, inflammation-immunity-nutrition score, inflammatory burden index, prognosis, hepatectomy

Ruoyang Du,1 Qing Xiao,2 Jianfeng Huang,1 Wubing Feng,1 Xiangqi Zheng,1 Tong Yi1 1Department of Urology, Chongqing Emergency Medical Center, Chongqing University Central Hospital, Chongqing, People’s Republic of China; 2Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Tong Yi, Chongqing Emergency Medical Center, Chongqing University Central Hospital, No. 1, Jiankang Road, Yuzhong District, Chongqing, 400014, People’s Republic of China, Email tongy09@sina.comIntroduction: Introduction. Renal cell carcinoma (RCC) is a common malignant tumor worldwide, and to explore, accurate prediction models are essential to the diagnosis and treatment.Methods: In the present study, the profile expression of RCC patients for long non-coding RNAs (lncRNAs) were obtained from the database of The Cancer Genome Atlas (TCGA). The Gene Set Enrichment Analysis (GSEA) showed that the gene sets related to autophagy are significantly differentially expressed among the paired normal tissues and RCC. Multivariate and univariate Cox analyses were used to construct the gene signature related to prognosis. Receiver Operating Characteristic (ROC) dependent on the time factor and the Kaplan-Meier curves are used for evaluating identified signatures. For gene signature combination, a nomogram with associated clinical constraints was designed.Results: Multivariate and Univariate Cox analyses presented seven autophagy-related lncRNAs were significantly correlated with Overall Survival (OS) for people with RCC. Risk scores of lncRNA prognostic signature, related to autophagy helped in distinguishing the patients accurately among the low-risk and high-risk RCC based on age, sex, grade of tumor, T, M, N, and AJCC stages. The RCC condition patients, as per their signature were put into the category of low and high-risk groups, having varying prognostic outcomes. Gene signature is an independent prognosticator for OS, accurately predicting 3– 5 year survival time for RCC patients from either of the two groups. GSEA revealed that high-risk scores of the prognostic seven-long non-coding signature correlate with immune-regulatory and cancer, signaling pathways, whereas a low-risk score correlates with metabolism. The quantitative reverse chain reaction of transcription-polymerase verified differential expression of seven lncRNAs autophagy-related samples.Conclusion: The results depict that seven autophagy-related lncRNA prognostic signature helps in predicting the prognosis accurately among people with RCC.Keywords: autophagy, lncRNA, renal cell carcinoma, prognosis, GSEA

Jinsong He,1,* Jing Huang,2,* Guo Tang,1 Pan Wang,1 Ming He,3 Shoujiang Wei1 1Department of Gastroenterology, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, People’s Republic of China; 2Lung Cancer Institute, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, People’s Republic of China; 3Graduate School of North Sichuan Medical College, Nanchong, 637000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shoujiang Wei, Email nsmcwsj@163.comIntroduction: Zinc finger protein 154 (ZNF154) has been identified as a tumor suppressor gene in multiple carcinomas. Lymph node (LN) metastasis is one of the most intensively negative factor of gastric cancer (GC) prognosis. However, the potential mechanisms of ZNF154-mediated LN metastasis are not elucidated. This study aimed to investigate the role of ZNF154 in LN metastasis of GC and their underlying mechanisms through in vitro and in vivo experiments.Methods: Antitumor effect was measured by growth inhibition by cell counting kit-8 (CCK-8) and colony formation assay. Cell cycle distribution and apoptosis were evaluated by flow cytometry. Cell migration and invasion were measured by wound healing and transwell invasion assays, respectively. The expression levels of proteins were analyzed by Western blot. Xenograft models were used for validation in vivo.Results: Our research showed that ZNF154 was down-regulated in 81.43% (57 of 70) of GC tissues compared with 58.6% of paired non-tumor tissues from patients, ZNF154 was down-regulated in 100% (7 of 7) of GC cell lines, up-regulated expression of ZNF154 in MGC-803 GC cells reduced cell proliferation, viability, migration and invasion, and enhanced cell apoptosis and arrested cell cycle in G2 phase, and suppressed tumorigenicity of MGC-803 cells in mice. Furthermore, up-regulated expression of ZNF154 mRNA reduced the expression of B-cell lymphoma-2 (Bcl-2), matrix metalloproteinase 2 (MMP-1), hepatocyte growth factor (HGF), vascular endothelial growth factor-A/C (VEGF-A/C).Conclusion: ZNF154 inhibited LN metastasis of GC cells by suppressing several biological events of GC cells. ZNF154 was a tumor suppressor gene that is a promising target for blocking nodal involvement in GC.Keywords: ZNF154, gastric cancer, lymph node, metastasis, prognosis

Jinhua Ding,1,2,&ast; Li Jiang,3,&ast; Zheng Xu,4 Yong Chen,4 Weizhu Wu,2 Jian Huang1,5 1Department of Breast Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310009, People’s Republic of China; 2Department of Breast and Thyroid Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang, 315000, People’s Republic of China; 3Department of General Medicine, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang, 315000, People’s Republic of China; 4Ningbo University School of Medicine, Ningbo University, Ningbo, Zhejiang, 315000, People’s Republic of China; 5Key Laboratory of Tumour Microenvironment and Immune Therapy of Zhejiang Province, Second Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, 310009, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian Huang, Department of Breast Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, Zhejiang, 310009, People’s Republic of China, Tel +86-13958123068, Email drhuangjian@zju.edu.cnPurpose: The 8th edition American Joint Committee on Cancer (AJCC) prognostic staging system (PS) has been validated numerous times; however, the prognostic value of PS for breast cancer based on molecular subtype has rarely been explored. This study aimed to investigate the prognostic value of PS in Chinese patients with luminal B-like human epidermal growth factor receptor 2 (HER2)-negative breast cancer.Methods: A total of 407 eligible cases were included in the study. All of the cases were restaged using the 8th edition AJCC Anatomic Staging System (AS) and PS. The Kaplan–Meier method was used to calculate estimated survival and the Log rank test was used to compare the survival differences between groups.Results: The 5-year disease-specific survival (DSS) and overall survival (OS) rates were 90.3% and 93.5%, respectively, and there were statistically significant differences in the 5-year DSS and 5-year OS rates among the different anatomic and prognostic stage groups. The application of the PS resulted in the assignment of 215 (52.8%) patients to a different group. Different prognostic stage groups restaged from anatomic Stage III had significant differences in both DSS (χ2 = 4.366, p = 0.037) and OS (χ2 = 7.549, p = 0.006); additionally, different prognostic stage groups from the anatomic Stage II group had significant differences in DSS (χ2 = 7.724, p = 0.021) but no significant differences in OS (χ2 = 5.182, p = 0.075). However, different prognostic stage groups from anatomic Stage I had no significant differences in either DSS (χ2= 0.159, p = 0.690) or OS (χ2 = 0.099, p = 0.753).Conclusion: The 8th edition AJCC PS refined the anatomic stage grouping in luminal B-like HER2-negative breast cancer and could lead to a more personalized approach to breast cancer treatment.Keywords: breast cancer, staging system, prognosis, survival outcome, human epidermal growth factor receptor 2

Junting Huang,1,* Yating Zhan,1,* Lili Jiang,1,* Yuxiang Gao,1,* Binyu Zhao,1,* Yuxiao Zhang,1 Wenjie Zhang,1 Jianjian Zheng,1 Jinglu Yu2,3 1Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China; 2Department of Laboratory Medicine, Lishui Municipal Central Hospital, Lishui, People’s Republic of China; 3The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang, 323000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jinglu YuDepartment of Laboratory Medicine, Lishui Municipal Central Hospital, The Fifth Affiliated Hospital of Wenzhou Medical University, No. 289 Kuocang Road, Lishui, Zhejiang, 323000, People’s Republic of ChinaEmail yujinglu2482@163.comJianjian ZhengKey Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, No. 2 Fuxue Lane, Wenzhou, Zhejiang, People’s Republic of ChinaEmail 120378196@qq.comAim: This study was done to determine biomarkers for the prognostic prediction of hepatocellular carcinoma (HCC).Materials and Methods: In the Gene Expression Omnibus, the gene expression profiles of HCC were downloaded. Biomarkers were identified by weighted gene co-expression network analysis and protein–protein interaction network analysis.Results: There were 24 modules, which were characterized by the high correlation with HCC. Meanwhile, through enrichment analysis, differentially expressed genes were largely participated in the ubiquitination and autophagy processes. Moreover, PRC1, TOP2A and CKAP2L may be the hub genes involved in HCC tumorigenesis, and their biomarker roles were further demonstrated via Gene Expression Profiling Interactive Analysis (GEPIA) and Oncomine databases. In addition, the levels of PRC1, TOP2A and CKAP2L were obviously up-regulated in the sera of HCC patients.Conclusion: PRC1, TOP2A and CKAP2L may serve as biomarkers for the prognostic prediction of HCC patients.Keywords: hepatocellular carcinoma, biomarker, WGCNA, PPI, prognosis

Tingting Hu,1 Juanjuan Huang,2 Kun Fang3 1Department of Chemoradiation Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People’s Republic of China; 2Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People’s Republic of China; 3Department of Surgery, Yinchuan Women and Children’s Hospital, Yinchuan, Ningxia, 750001, People’s Republic of ChinaCorrespondence: Kun FangDepartment of Surgery, Yinchuan Women and Children’s Hospital, No. 56, Wenhua Street, Yinchuan, Ningxia, 750001, People’s Republic of ChinaEmail k99ftl@163.comPurpose: Mucinous carcinoma of the breast (MCB) is a rare malignant tumour. Therefore, it is urgent to establish a survival prediction model for MCB patients.Methods: Clinicopathological and follow-up data of MCB patients diagnosed between 2010 and 2015 were retrieved from the Surveillance, Epidemiology, and End Result (SEER) database. The significant factors were screened out and generated Kaplan–Meier (K-M) curves for each prognostic factor. Additionally, these factors were then utilized to build a nomogram for predicting 3-, 4-, and 5-year overall survival (OS) of MCB patients. The nomogram was evaluated using calibration curves, receiver operating characteristic (ROC) curves and decision curve analysis (DCA).Results: Moreover, a total of 4326 MCB patients were retrieved. Age, American Joint Committee on Cancer (AJCC) stage, surgery, radiotherapy and bone metastasis were identified as independently prognosis factors for OS. The corresponding areas under the ROC curves (AUCs) of the nomogram at 3, 4 and 5 years in the training and validation set were 0.770, 0.788, 0.805, 0.778, 0.797, and 0.802, respectively. The calibration curves and DCA revealed that the prediction model had an excellent performance. Finally, the risk stratification system confirmed that the powerful role of the nomogram in distinguishing results and risk stratification.Conclusion: Briefly, the nomogram incorporating various clinicopathological indicators was established for MCB patients and may facilitate clinical decision-making.Keywords: mucinous carcinoma of the breast, breast cancer, prognosis, nomogram

Guangxian Zhong,1,&ast; Yunqing Wang,1,&ast; Hongxiang Wei,1 Meifang Chen,2 Huangfeng Lin,1 Zhen Huang,1 Jinlong Huang,3 Shenglin Wang,1 Jianhua Lin1 1Department of Orthopaedics, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350004, People’s Republic of China; 2The Health Management Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350004, People’s Republic of China; 3Department of Hematology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350004, People’s Republic of China&ast;These authors contributed equally to this work.Correspondence: Jianhua Lin; Shenglin Wang Tel/Fax +86 591 87981029Email jianhual@126.com; Shenglinwang0216@163.comPurpose: The aim of this research was to investigate the clinical significance of the expression of flap structure-specific endonuclease 1 (FEN1) in primary osteosarcoma.Methods: The expression of FEN1 was detected by immunohistochemistry analysis. The association of the expression of FEN1 in osteosarcoma with clinicopathological parameters was analyzed by using χ2 test or Fisher’s exact test. Survival analyses were performed by Kaplan–Meier method and Cox proportional hazards regression model.Results: Of the 40 osteosarcoma patients, 19 (47.5%) patients presented with FEN1 high expression, while in the non-neoplastic bone specimens, the FEN1 high expression was observed in 10% (3/30), the positive expression rate in osteosarcoma patients was significantly higher than that of non-neoplastic bone specimens (P< 0.01). Univariate analysis indicated that the progression-free survival (PFS) and overall survival (OS) were correlated with the expression level of FEN1 (PFS, P < 0.001; OS, P = 0.002), Enneking staging (PFS, P = 0.026; OS, P = 0.044) and chemotherapy response (PFS, P = 0.019; OS, P = 0.031). Multivariate analysis demonstrated that FEN1 expression was an independent prognostic factor for the PFS (HR = 4.73, P = 0.002) and OS (HR = 4.01, P = 0.038) of osteosarcoma patients.Conclusion: This study showed that FEN1 was overexpressed in osteosarcoma patients and positively associated with poor prognosis of osteosarcoma patients. Further studies should focus on the relative mechanisms and the targeted FEN1 therapies for osteosarcoma.Keywords: osteosarcoma, flap endonuclease 1, immunohistochemistry, prognosis

Jianhao Huang,1,&ast; Weiwei Li,2,&ast; Suosu Wei,3,&ast; Xing Zhou,1 Yuechou Nong,1 Jingxia Sun,1 Zhenwei Zhai,1 Wensheng Lu1 1Department of Endocrinology and Metabolism, Guangxi Academy of Medical Sciences and the People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, 530021, People’s Republic of China; 2The Office of Guangxi Academy of Medical Sciences and the People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, 530021, People’s Republic of China; 3Editorial Board of Chinese Journal of New Clinical Medicine, Guangxi Academy of Medical Sciences and the People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, 530021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wensheng Lu Email lws2613676@sohu.comAim: The purpose of this study was to explore the association between estimated glomerular filtration rate (eGFR) and clinical outcomes in patients with diabetic foot osteomyelitis (DFO).Methods: This was a retrospective observational study. A total of 199 patients with DFO were recruited and divided into three groups by eGFR: normal kidney function group (eGFR ≥ 90), mildly decreased kidney function group (eGFR 60– 89) and moderately to severely decreased kidney function group (eGFR < 60). The patients were followed-up for a median of 36 months, and the study outcomes were all-cause mortality and major cardiovascular adverse events (MACE). Cox proportional hazard models were used to assess the association between eGFR and the outcomes, and a stratified analysis by sex was conducted.Results: During follow-up, all-cause mortality occurred in 51 (25.63%) patients among 199 participants, 54 (28.72%) had MACE in 188 participants and 26 (48.15%) of them died. After fully adjusting for potential confounders, compared to eGFR < 90 mL/min/1.73 m2, eGFR ≥ 90 mL/min/1.73 m2 had lower incidence of all-cause mortality (HR = 0.43, 95% CI: 0.22– 0.85; P = 0.015) and MACE (HR = 0.51, 95% CI: 0.27– 0.96; P = 0.038). Additionally, compared to eGFR < 90 mL/min/1.73 m2, eGFR ≥ 90 mL/min/1.73 m2 was independently associated with decreased risk of all-cause mortality (HR = 0.33; 95% CI 0.14– 0.76, P = 0.010) and MACE (HR = 0.27; 95% CI 0.11– 0.65, P = 0.004) in male, but not in female.Conclusion: In conclusion, decreased eGFR is a risk factor for all-cause mortality and MACE in individuals with DFO. Additionally, male with decreased eGFR had a higher risk of all-cause mortality and MACE, but female did not.Keywords: diabetic foot osteomyelitis, estimated glomerular filtration rate, prognosis

Qimin Tu,1,2,* Hongjian Gong,3,4,* Chunhui Yuan,3 Gao Liu,5 Jinqi Huang,1 Zhichao Li,4 Jianfei Luo2 1Department of Cardio-Thoracic Surgery, Central Hospital of Enshi Autonomous Prefecture, Enshi Clinical College of Wuhan University, Enshi, Hubei, People’s Republic of China; 2Department of Gastrointestinal Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China; 3Clinical Research Center, Wuhan Medical and Health Center for Women and Children, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 4Department of Rheumatism Immunology, Wuhan Medical and Health Center for Women and Children, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 5Department of Gastrointestinal Surgery, Central Hospital of Enshi Autonomous Prefecture, Enshi Clinical College of Wuhan University, Enshi, Hubei, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhichao LiDepartment of Rheumatism Immunology, Wuhan Medical and Health Center for Women and Children, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of ChinaTel +86-27-82433423Email linyuanmuchun@sina.comJianfei LuoDepartment of Gastrointestinal Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of ChinaTel +86-27-88041911Email afei099@163.comBackground: p53 isoform Δ 133p53 is directly transactivated by p53 and antagonizes p53 activities in cancer progression. However, its correlation with prognosis and cancer recurrence in esophageal squamous cell carcinoma (ESCC) is still unclear.Patients and Methods: Expression of Δ 133p53 and Δ 133p53/full-length p53 (FLp53) in tissues and serums of 180 ESCC patients was evaluated using qRT-PCR. Patients were divided into high- and low-expression groups according to the cutoff value determined by X-tile 3.6.1 software. Survival analysis was performed by the Kaplan–Meier method. Univariate and multivariate Cox survival analyses were applied to assess the hazard ratios (HRs).Results: Tissue Δ 133p53 expression and Δ 133p53/FLp53 ratio were significantly increased in ESCC tissue compared with adjacent normal tissue. Pre-operative Δ 133p53 expression and Δ 133p53/FLp53 ratio in tissue or serum samples were positively associated with TNM stage and post-operative recurrence. Kaplan–Meier curve and multivariate cox regression analyses revealed that the tissue and serum Δ 133p53/FLp53 ratios (cutoff value: 2.9160) were independent prognostic factors for overall survival (OS) and progression-free survival (PFS) in ESCC patients and showed no statistical difference in receiver-operating characteristic curve (ROC) analysis, while serum Δ 133p53 showed no significant prognostic value. More importantly, the serum Δ 133p53/FLp53 ratio in ESCC patients was significantly decreased within 72 h post tumor resection and patients with a consistently high serum Δ 133p53/FLp53 ratio (≥ 2.9160) had higher recurrence rates than those with consistently low ratio values. In addition, dynamic detection in each follow-up timepoint showed that serum Δ 133p53/FLp53 ratios were higher than 2.9160 upon recurrence, and they even increased prior to radiologic progression.Conclusion: The serum Δ 133p53/FLp53 ratio can be a novel predictor for survival outcome and may serve as a real-time parameter for monitoring recurrence in ESCC patients after surgery.Keywords: esophageal squamous cell carcinoma, p53, Δ 133p53, prognosis, recurrence

Jun Wei,1 Ming Jin,2 Yingjie Shao,1 Zhonghua Ning,1 Jin Huang11Department of Radiation Oncology, The Third Affiliated Hospital of Soochow University, Changzhou 213003, People’s Republic of China; 2Department of Clinical Laboratory, The Third Affiliated Hospital of Soochow University, Changzhou 213003, People’s Republic of ChinaCorrespondence: Zhonghua Ning; Jin HuangDepartment of Radiation Oncology, The Third Affiliated Hospital of Soochow University, 185 Juqian Road, Changzhou 213003, People’s Republic of ChinaTel +86 5 196 887 1132Email 13961479694@163.com huangjin1962@163.comPurpose: The current study aimed to explore the prognostic role of preoperative prealbumin in resectedesophageal squamous cell carcinoma (ESCC).Methods: A total of 1374 resected ESCC patients were retrospectively reviewed. Serum for prealbumin analyses was taken within 1–3 days before the operation. Overall survival (OS) was determined using the Kaplan-Meier method; the univariate log-rank test and the multivariate Cox proportional hazard model were used to evaluate the prognostic role of prealbumin. A receiver operating characteristic (ROC) curve was plotted, and the area under the curve (AUC) was calculated to compare the prediction accuracy of prealbumin and albumin for OS.Results: Finally, 532 patients were included in this study. The 5-year OS rate was favourable for the high prealbumin group versus the median and low prealbumin groups (58.1% vs 44.6% and 31.1%, respectively; P

Tian-Yu He, Si-Han Li, Jin Huang, Ming Gong, Guang LiDepartment of Radiation Oncology, The First Hospital of China Medical University, Shenyang, Liaoning, People’s Republic of ChinaPurpose: Numerous studies have reported that the long non-coding RNA colorectal neoplasia differentially expressed (CRNDE) plays important roles in the tumorigenesis, progression, and prognosis of various types of cancer. However, thus far, a systematic analysis of CRNDE in cancers of the digestive system has not been conducted. Thus, the aim of this meta-analysis was to explore the relationship between CRNDE expression and survival or the clinicopathological features of gastrointestinal cancer.Methods: Eligible studies were collected from nine databases (ie, PubMed, Medline, Embase, Cochrane Library, Ovid, Science Citation Index Expanded, China Biology Medicine, Chinese National Knowledge Infrastructure, and Wanfang). The meta-analysis was conducted using the Stata SE.12 Software. The pooled hazard ratio (HR) or odds ratio (OR) with a 95% confidence interval (Cl) was used to assess the clinical value of CRNDE expression in gastrointestinal cancers.Results: A total of 1,053 patients from nine articles were selected. The analysis provided evidence suggesting a significant negative correlation between high CRNDE expression and the rate of overall survival [HR=1.92, 95% CI (1.40–2.64), p5 cm [OR=2.81, 95% CI (1.62–4.88), p

Yu-Jie Zhao,1 Wei-Peng Sun,2 Jian-Hong Peng,1 Yu-Xiang Deng,1 Yu-Jing Fang,1 Jun Huang,2 Hui-Zhong Zhang,3 De-Sen Wan,1 Jun-Zhong Lin,1,* Zhi-Zhong Pan,1,* 1Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 2Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, 3Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China *These authors contributed equally to this work Objective: Increased expression of programmed death-ligand 1 (PD-L1) on tumor cells can be found in various malignancies; however, very limited information is known about its role in anal squamous cell carcinoma (ASCC). This study explored PD-L1 expression in ASCC patients and its association with patients’ clinicopathological features, CD8+ T cell infiltration, and prognosis.Methods: Formalin-fixed paraffin-embedded tumor samples from 26 patients with ASCC were retrieved. The levels of PD-L1 expression on the membrane of both tumor cells and tumor-infiltrating mononuclear cells (TIMCs) were evaluated by immunohistochemistry. CD8+ T cell densities, both within tumors and at the tumor–stromal interface, were also analyzed. Baseline clinicopathological characteristics, human papilloma virus (HPV) status, and outcome data correlated with PD-L1-positive staining.Results: PD-L1 expression on tumor cells and TIMCs was observed in 46% and 50% of patients, respectively. Nineteen patients (73%) were HPV positive, with 7 showing PD-L1-positive staining on tumor cells and 9 showing PD-L1-positive staining on TIMCs. Increasing CD8+ density within tumors, but not immune stroma, was significantly associated with decreased PD-L1 expression by both tumor cells and TIMCs (P=0.0043 and P=0.0007). Patients with negative PD-L1 expression had significantly better progression-free survival (P=0.038 and P=0.0443) and a non-statistically significant trend toward longer overall survival (P=0.0882 and P=0.1222) compared with patients with positive PD-L1 expression.Conclusion: PD-L1 is widely expressed on the membrane of tumor cells and TIMCs in ASCCs. Its negative impact on prognosis may be due to the diminished CD8+ T cell infiltration within tumors. Keywords: CD8, PD-L1, HPV, tumor infiltrating mononuclear cells

OBJECTIVE: Increasing evidence indicated that small nucleolar RNA host gene 16 (SNHG16) acted as a key regulator in the proliferation and metastasis of several cancers, including esophageal squamous cell carcinoma (ESCC). In this research, we aimed to explore biological functions, clinical significance and the underlying molecular mechanisms of SNHG16 in ESCC. PATIENTS AND METHODS: qRT-PCR was performed to examine the expression of SNHG16 in ESCC cell lines and clinical ESCC tissue samples. The association of SNHG16 expression with clinicopathological factors and prognosis was statistically analyzed. Cell Counting Kit-8, flow cytometry, and transwell invasion assays were performed to determine the effect of SNHG16 in the regulation of biological behaviors of ESCC cells. Luciferase assay and Western blot were performed to determine the activation of Wnt/β-catenin signaling pathway. RESULTS: We observed that SNHG16 expression levels were significantly upregulated in ESCC tissues and cell lines compared with the corresponding normal tissues and normal esophageal cell line, respectively. In addition, increased expression of SNHG16 were strongly linked to tumor stage (p = 0.019), lymph nodes metastasis (p = 0.007) and clinical stage (p = 0.026). Kaplan-Meier assay showed that the survival time of patients with high SNHG16 expression was significantly shorter than those with low SNHG16 expression (p = 0.0017). Univariate and multivariate analyses showed that high SNHG16 expression in ESCC was an independent predictor of poor survival. Loss-of-function experiments revealed that knockdown of SNHG16 suppressed proliferation and invasion and induced apoptosis of ESCC cells. Mechanistically, Wnt/β-catenin signaling pathways were actively modulated by SNHG16 in ESCC cells. CONCLUSIONS: Our findings reveal that SNHG16 plays an important role in ESCC proliferation/metastasis via modulating Wnt/β-catenin signaling pathways and could represent a novel biomarker for predicting poor survival as well a promising therapeutic target. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To investigate the effect and clinical significance of long non-coding RNA 00673 (lncRNA00673) in the occurrence and development of colorectal cancer (CRC) through the research on the expression level, biological effect and clinical significance of lncRNA00673 in CRC. PATIENTS AND METHODS: The relative expression of lncRNA00673 in 71 pairs of CRC tissues and cells was detected by quantitative Real- time polymerase chain reaction (qRT-PCR). The correlation of the relative expression of lncRNA00673 with the clinicopathological features of CRC patients was analyzed. The lncRNA00673 interference sequence was designed and synthesized, and its transfection efficiency was detected by qRT-PCR assays. 3-(4,5-Dimethylthiazol- 2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay and clone formation experiments were performed to investigate the effect of lncRNA00673 on the proliferation ability of CRC cells. RESULTS: In CRC tissues of 71 patients, there were 51 patients whose lncRNA00673 level was up-regulated compared with that of cancer-adjacent tissues. The highly expressed lncRNA00673 was positively correlated with tumor, node and metastasis (TNM) staging, regional lymph node metastasis, distant metastasis and tumor size in CRC patients. Cox proportional-hazards regression model showed that the highly expressed lncRNA00673 was an independent risk factor for the overall survival of CRC patients. Kaplan-Meier curve analysis showed that highly expressed lncRNA00673 was significantly associated with the relatively lower overall survival (OS). MTT and clone formation experiments showed that knockdown of lncRNA0673 could inhibit the proliferation of CRC cells. CONCLUSIONS: The expression level of lncRNA00673 is up-regulated in CRC tissues and cells, which is related to the degree of malignancy and poor prognosis. LncRNA00673 can be used as a potential molecular marker for the prognosis of CRC. [ABSTRACT FROM AUTHOR]

Effective intercellular communication is essential for cellular and tissue balance maintenance and response to challenges. Cellular communication methods involve direct cell contact or the release of biological molecules to cover short and long distances. However, a recent discovery in this communication network is the involvement of extracellular vesicles that host biological contents such as proteins, nucleic acids, and lipids, influencing neighboring cells. These extracellular vesicles are found in body fluids; thus, they are considered as potential disease biomarkers. Cardiovascular diseases are significant contributors to global morbidity and mortality, encompassing conditions such as ischemic heart disease, cardiomyopathies, electrical heart diseases, and heart failure. Recent studies reveal the release of extracellular vesicles by cardiovascular cells, influencing normal cardiac function and structure. However, under pathological conditions, extracellular vesicles composition changes, contributing to the development of cardiovascular diseases. Investigating the loading of molecular cargo in these extracellular vesicles is essential for understanding their role in disease development. This review consolidates the latest insights into the role of extracellular vesicles in diagnosis and prognosis of cardiovascular diseases, exploring the potential applications of extracellular vesicles in personalized therapies, shedding light on the evolving landscape of cardiovascular medicine. [ABSTRACT FROM AUTHOR]

Bladder urothelial carcinoma (BUCA) is a common malignant tumor with a high rate of metastasis and recurrence. The lack of specific and sensitive biomarkers for the prognostic assessment makes it important to seek alternatives. Recent studies have demonstrated that long noncoding RNAs (lncRNAs) function as competitive endogenous RNAs (ceRNAs) and play an important role in BUCA prognosis. Therefore, this study aimed to establish a prognosis‐related lncRNAs–microRNAs (miRNAs)–messenger RNA (mRNA) (pceRNA) network and identify novel prognostic biomarkers. Integrated weighted coexpression analysis, functional clustering, and ceRNA network were used for the prognostic assessment of BUCA. The transcriptome sequencing datasets of lncRNA, miRNA, and mRNA from The Cancer Genome Atlas database were used for the identification of key lncRNAs and construction of the lncRNAs expression signature for prognostic prediction of BUCA patients. Then, 14 differentially expressed lncRNAs (DE‐lncRNAs) were identified as candidate prognostic RNAs based on the ceRNAs network and functional clustering. In the Cox regression analysis, two (AC008676.1 and ADAMTS9‐AS1) of all DE‐lncRNAs were significantly associated with overall survival (OS) of BUCA patients. This two DE‐lncRNA signature was significantly correlated with OS and was an independent prognostic factor, which was confirmed in an independent dataset of GSE216037. Moreover, we constructed the pceRNA network that includes 2 DE‐lncRNAs, 9 DE‐miRNAs, and 10 DE‐mRNAs. Pathway enrichment analysis showed that AC008676.1 and ADAMTS9‐AS1 are involved in several cancer‐related pathways such as proteoglycans in cancer and TGF‐beta signaling pathway. The novel‐identified DE‐lncRNA prognostic signature and the pceRNA network in this study will be valuable risk predictors and diagnostic markers for BUCA. [ABSTRACT FROM AUTHOR]

Objective. The purpose was to explore the characteristics and nursing points of surgical and interventional treatment for elderly cerebral aneurysm. Methods. 100 elderly patients with cerebral aneurysm treated in our hospital from January 2017 to December 2019 were selected, and divided into craniotomy group (40 patients with neurosurgical clipping) and interventional surgery group (60 patients with endovascular interventional embolization) according to the treatment method to compare the operation time, hospitalization time, hospitalization expenses, degree of brain injury, complications and prognostic scores of the patients in two groups. Meanwhile, the relationship between the factors (age, aneurysm size, location) and prognosis of patients was analyzed, and the nursing points were summarized. Results. (1) The operation time and hospitalization time of the interventional surgery group were lower than those of the craniotomy group, but the hospitalization expenses were higher than those of the craniotomy group (P = 0.000). (2) The brain injury indexes of the two groups at 6h and 24h after operation were higher than those before operation, and the indexes of the craniotomy group were higher than those of the interventional surgery group (P = 0.00). (3) The overall complication rate was 16.67% in the interventional surgery group, which was lower than 37.50% in the craniotomy group (P = 0.005). (4) The good recovery rate of GCS score in interventional surgery group was 63.33%, which was higher than 42.50% in craniotomy group (P = 0.040). (5) Univariate analysis. The aneurysm location, preoperative Hunt-Hess grade and combined hyperlipidemia were related to the prognosis of patients (P < 0.05). (6) Multivariate analysis. The aneurysm location and preoperative Hunt-Hess grade were independent factors affecting the prognosis of patients (P < 0.05). Conclusion. Interventional surgery for elderly cerebral aneurysm is superior to craniotomy in reducing surgical trauma and accelerating postoperative recovery, but the hospitalization expenses are higher than those of craniotomy. Aneurysm location and preoperative Hunt-Hess grade were independent factors influencing the prognosis of patients. Postoperative nursing for elderly cerebral aneurysm should start from basic nursing, psychological nursing and symptomatic nursing. [ABSTRACT FROM AUTHOR]

BACKGROUND: The new systemic inflammation response index (SIRI) constructed based on neutrophil, monocyte and lymphocyte counts in peripheral blood is considered to be related to the prognosis of a variety of tumours. OBJECTIVE: To evaluate the prognostic value of the SIRI in operable breast cancer patients and establish a nomogram to predict the survival of breast cancer patients. METHODS: A total of 949 patients with operable breast cancer were enrolled in the present study. RESULTS: The overall survival (OS) of breast cancer patients with SIRI ⩽ 0.65 was significantly higher than that of breast cancer patients with SIRI > 0.65 (P < 0.001). A nomogram generated based on SIRI, grade and TNM stage and SIRI predicted the 5- and 10-year survival rates of breast cancer patients more accurately than TNM stage alone. In addition, the change in SIRI relative to baseline at 4 weeks after surgery was closely related to the survival of breast cancer patients. Compared with those with no SIRI changes (absolute value of variation < 25%), breast cancer patients with an increase in SIRI > 75% or 25–75% had worse OS (P < 0.001). CONCLUSIONS: The SIRI before and after surgery is closely related to the prognosis of breast cancer patients. [ABSTRACT FROM AUTHOR]

BACKGROUND: Numerous previous studies explored the influence of matrix metalloproteinase 2 (MMP-2) expressions on renal cell carcinoma (RCC), yet inconsistent results were reported. OBJECTIVE: This study aims to derive a more precise estimation of the associations between MMP-2 and RCC. METHODS: A total of 115 patients with RCC were selected; meanwhile, 45 patients with traumatic rupture of renal cysts or renal calculi were recruited and normal kidney tissues were collected as control group. The expression level of MMP-2 protein was detected by using immunohistochemistry. A meta-analysis was performed by using Comprehensive Meta-analysis 2.0 (CMA 2.0). RESULTS: The positive expression rate of MMP-2 protein in the RCC tissues was evidently higher than that in the normal renal tissues (P <0.001). The positive expression rate of MMP-2 protein in patients with tumor size > 5 cm, with lymph node metastasis (LNM), with well-differentiated RCC, and stage III-IV RCC was significantly higher, compared with the patients with tumor size ≤ 5 cm, without LNM, with moderate/low-differentiated RCC, and with stage I-II RCC, respectively (allP < 0.05). There was statistical significance in the 5-year survival rate between the patients with positive MMP-2 protein expression and those with negative MMP-2 protein expression (P = 0.037). These results were further confirmed by the meta-analysis. CONCLUSION: MMP-2 protein expression is significantly associated with historical grade, TNM stage, tumor size and LNM in RCC, suggesting that MMP-2 may serve as a biological marker for the prognosis in RCC. [ABSTRACT FROM AUTHOR]