Search

Yu-Xian Tang,1,&ast; Zhi-Wei Fan,1,&ast; Jing Li,2,&ast; Hao-Dong Pan,3 Wen-Xin Su,1 Yusanjan Matniyaz,2 Hai-Tao Zhang,4 Yuan-Xi Luo,4 Zhi-Kang Lv,2 Wen-Zhe Wang,2 Ya-Xuan Gao,2 Tuo Pan,2,4 Wan-Zi Xu,1,2 Dong-Jin Wang1– 4 1Department of Cardiac Surgery, Nanjing Drum Tower Hospital, Nanjing Drum Tower Hospital Clinical College, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 2Department of Cardiac Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People’s Republic of China; 3Department of Clinical Medicine, Norman Bethune Health Science Center of Jilin University, Changchun, People’s Republic of China; 4Department of Cardiac Surgery, Nanjing Drum Tower Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Graduate School of Peking Union Medical College, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dong-Jin Wang; Wan-Zi Xu, Department of Cardiac surgery, Nanjing Drum Tower Hospital, No. 321 Zhongshan Road, Nanjing, Jiangsu, 210008, People’s Republic of China, Email dongjin_wang@126.com; 582321957@qq.comBackground: Sivelestat, a neutrophil elastase inhibitor, is specifically developed to mitigate the occurrence of acute lung injury (ALI) in individuals who are undergoing cardiovascular surgery. However, its impact on patients who are at a heightened risk of developing ALI after scheduled cardiac surgery has yet to be determined. In order to address this knowledge gap, we undertook a study to assess the efficacy of sivelestat in protecting the lungs of these patients.Methods: We conducted a prospective cohort study involving 718 patients who were at high risk of developing postoperative acute lung injury (ALI) and underwent scheduled cardiac surgery between April 25th, 2022, and September 7th, 2023. Among them, 52 patients received sivelestat (administered at a dosage of 0.2mg/kg/h for 3 days), while 666 patients served as controls, not receiving sivelestat. The control conditions were the same for all patients, including ventilation strategy, extubating time, and fluid management. Subsequently, a propensity-score matched cohort was established, consisting of 40 patients in both the sivelestat and control groups. The primary outcome measure encompassed a composite of adverse outcomes, including 30-day mortality, ALI, acute respiratory distress syndrome (ARDS), and others. Secondary outcomes assessed included pneumonia, ventricular arrhythmias, mechanical ventilation (MV) time, and more.Results: After conducting propensity matching in our study, we observed that there were no significant differences in 30-day mortality between the sivelestat and control groups (0% vs 2.5%, P=0.32). However, the use of sivelestat exhibited a significant reduction in the incidence of acute lung injury/acute respiratory distress syndrome (ALI/ARDS) compared to the control group (0% vs 55%, P< 0.01), pneumonia (0 vs 37.5%, P< 0.01), MV time (median:8 hours, IQR:4– 14.8 hours vs median: 15.2 hours, IQR:14– 16.3 hours, P< 0.01). Compared to the control group, the sivelestat could significantly decrease white cell count (P< 0.01), neutrophile percentage (P< 0.01) and C-reactive protein (P< 0.01) in the period of postoperative 5 days.Conclusion: The prophylactic administration of sivelestat has shown promising results in reducing the occurrence of acute lung injury/acute respiratory distress syndrome (ALI/ARDS) in patients with a heightened risk of developing these conditions after elective cardiac surgery. Our study findings indicate that sivelestat may provide protective effects by suppressing inflammation triggered by neutrophil activation, thereby safeguarding pulmonary function.Registration: ChiCTR2200059102, https://www.chictr.org.cn/showproj.html?proj=166643.Keywords: sivelestat, cardiac surgery, acute lung injury, inflammation

Hai-Tao Zhang,1 Kuo Wang,2 Ze-Shi Li,1 Chuang-Shi Wang,3 Xi-Kun Han,4,5 Wei Chen,6 Fu-Dong Fan,7 Jun Pan,7 Qing Zhou,7 Hai-Long Cao,7 Hao-Dong Pan,8 Xiateke Hafu,9 Chen Li,10 Guo-Liang Fan,10 Tuo Pan,1 Dong-Jin Wang,1,2,6,7 Wei Wang9 1Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Graduate School of Peking Union Medical College, Nanjing, Jiangsu, 210008, People’s Republic of China; 2Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, the Affiliated Clinical College of Xuzhou Medical University, Nanjing, Jiangsu, 210008, People’s Republic of China; 3Medical Research and Biometrics Center, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 102300, People’s Republic of China; 4Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA; 5Program in Genetic Epidemiology and Statistical Genetics, Harvard T. H. Chan School of Public Health, Boston, MA, USA; 6Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, Nanjing Medical University, Nanjing, Jiangsu, 210008, People’s Republic of China; 7Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, 210008, People’s Republic of China; 8Department of Clinical Medicine, Norman Bethune Health Science Center of Jilin university, Changchun, Jilin, 130021, People’s Republic of China; 9The Xinhua Hospital of Ili Kazak Autonomous Prefecture, Ili, Xinjiang, People’s Republic of China; 10Department of Cardiac Surgery, Dong Fang Hospital Affiliated to Tongji University, Shanghai, 200120, People’s Republic of ChinaCorrespondence: Dong-Jin Wang, Chief of department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Number 321 Zhongshan Road, Nanjing, Jiangsu, 210008, People’s Republic of China, Email dongjin_wang@126.com Wei Wang, The Xinhua Hospital of Ili Kazak Autonomous Prefecture, Ili, Xinjiang, People’s Republic of China, Email wangwei3342@163.comBackground: Early postoperative bacterial pneumonia and sepsis (ePOPS), which occurs within the first 48 hours after cardiovascular surgery, is a serious life-threatening complication. Diagnosis of ePOPS is extremely challenging, and the existing diagnostic tools are insufficient. The purpose of this study was to construct a novel diagnostic prediction model for ePOPS.Methods: Least Absolute Shrinkage and Selection Operator (LASSO) with logistic regression was used to construct a model to diagnose ePOPS based on patients’ comorbidities, medical history, and laboratory findings. The area under the receiver operating characteristic curve (AUC) was used to evaluate the model discrimination.Results: A total of 1203 patients were recruited and randomly split into a training and validation set in a 7:3 ratio. By early morning on the 3rd postoperative day (POD3), 103 patients had experienced 133 episodes of bacterial pneumonia or sepsis (15 patients had both). LASSO logistic regression model showed that duration of mechanical ventilation (P=0.015), NYHA class ≥ III (P=0.001), diabetes (P< 0.001), exudation on chest radiograph (P=0.011) and IL-6 on POD3 (P< 0.001) were independent risk factors. Based on these factors, we created a nomogram named DICS-I with an AUC of 0.787 in the training set and 0.739 in the validation set.Conclusion: The DICS-I model may be used to predict the risk of ePOPS after cardiovascular surgery, and is also especially suitable for predicting the risk of IRAO. The DICS-I model could help clinicians to adjust antibiotics on the POD3.Keywords: early postoperative pneumonia and sepsis, IL-6, LASSO, nomogram

Objectives: Colchicine, an anti-inflammatory agent, has been reported to improve myocardial infarction prognosis by inhibiting neutrophil extracellular traps (NETs) release. However, its role in cardiac surgery and the mechanisms behind NETs suppression remain unclear. This study aimed to explore colchicine's cardioprotective effects against perioperative myocardial injury in cardiac surgery, focusing on NETs inhibition as a novel therapeutic strategy., Methods: Male Sprague-Dawley rats were pre-treated with colchicine (0.1 mg/kg/day) or CI-amidine (10 mg/kg/day) for 7 days before undergoing cardiopulmonary bypass and myocardial ischaemia/reperfusion injury. The model was created by subjecting the rats to cardiopulmonary bypass and myocardial ischaemia/reperfusion injury. Under 4.0% sevoflurane anaesthesia, cardiopulmonary bypass was initiated by cannulating the tail artery and right atrium, and perfusion was maintained for 4 h. Immunofluorescence detected NETs, and haematoxylin and eosin staining assessed inflammatory cell., Results: We found colchicine treatment significantly reduced perioperative myocardial injury in rats. Furthermore, we observed a notable elevation of NETs in the myocardial tissue of animal models. Moreover, suppressing peptidylarginine deiminase 4 was found to markedly diminish perioperative myocardial injury in rats. Additionally, colchicine can mitigate the release of NETs by inhibiting peptidylarginine deiminase 4., Conclusions: NETs were significantly elevated during the perioperative period of cardiac surgery. Colchicine significantly mitigated myocardial injury in cardiac surgery by inhibiting NETs formation, with peptidylarginine deiminase 4 inhibition being one of its mechanisms., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Introduction: Taurine is a naturally occurring sulfonic acid involved in various physiological and pathological processes, such as the regulation of calcium signaling, immune function, inflammatory response, and cellular aging. It has the potential to predict tumor malignant transformation and formation. Our previous work discovered the elevated taurine in lung cancer patients. However, the precise impact and mechanism of elevated serum taurine levels on lung cancer progression and the suitability of taurine or taurine-containing drinks for lung cancer patients remain unclear., Objectives: Our study aimed to systematically investigate the role of taurine in lung cancer, with the ultimate goal of contributing novel strategies for lung cancer treatment., Methods: Lung cancer C57 and nude mice models, RNA sequencing, and stable transfection were applied to explored the effects and mechanisms of taurine on lung cancer. Tissues of 129 non-small cell lung cancer (NSCLC) patients derived from 2014 to 2017 for immunohistochemistry were collected in Taihe Hospital., Results: Low doses of taurine, as well as taurine-infused beverages at equivalent doses, significantly enhanced lung tumor growth. Equally intriguing is that the promoting effect of taurine on lung cancer progression wanes as the dosage increases. The Nuclear factor erythroid 2-like 1 (Nfe2l1 or Nrf1)-reactive oxygen species (ROS)-PD-1 axis may be a potential mechanism for dual role of taurine in lung cancer progression. However, taurine's impacts on lung cancer progression and the anti-tumor function of Nfe2l1 were mainly determined by the immune competence. Taurine inhitited lung tumor growth probably by inhibiting NF-κB-mediated inflammatory responses in nude mice rather than by affecting Nfe2l1 function. As patients age increased, Nfe2l1 gene and protein gradually returned to the levels observed in healthy individuals, but lost its anti-lung cancer effects., Conclusions: Taurine emerges as a potential biomarker for lung cancer progression, predicting poor prognosis and unsuitability for specific patients. Lung cancer patients, especially young patients, should be conscious of potential effects of taurine-containing drinks. Conversely, taurine or its drinks may be more suitable for older or immune-deficient patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Production and hosting by Elsevier B.V.)

Ethnopharmacological Relevance: Pulmonary fibrosis (PF) is progressive and terminal lung disease, which is also the most common sequelae of Corona Virus Disease (2019) (COVID-19) survivors. Unfortunately, there is currently no cure for PF. ShaShen-MaiDong decoction (SMT), a traditional Chinese medicine, has been employed in treating various lung diseases, which may offer potential therapeutic benefits for PF., Aim of the Study: To investigate the antifibrotic efficacy of SMT and its major active ingredients as well as the underlying mechanisms for treating PF., Materials and Methods: Fist, we build the UPLC-MS based qualitative and quantitative profiling for the quality control of SMT. Then, the antifibrotic efficacy of SMT was investigated in bleomycin (BLM)-induced PF mice model. Network pharmacology was used to predict the mechanism and active components of SMT for the treatment of PF, which was further verified in vitro and in vivo., Results: SMT improved the weight loss and attenuated hydroxyproline, inflammatory cytokines, and collagen deposition in BLM-induced PF mice model in a dose-dependent manner. Mechanistically, as predicted by network pharmacology analysis, SMT and its active compounds (kaempferol, quercetin, and isorhamnetin) regulated the mitogen-activated protein kinase (MAPK) signaling pathways, TGF-β/Smad signaling pathway, and YAP/TAZ signaling pathway, which was further verified in the PF mice and TGF-β-induced A549 cell model. Moreover, SMT balanced the proportions of increased CD4 + and decreased CD8 + T cells in the peripheral blood of PF mice model., Conclusions: Considering the high mortality and complex pathogenesis of fibrotic diseases, our results provide novel evidence that SMT would be beneficial for pulmonary fibrosis therapy by modulating MAPK, TGF-β/Smad, and YAP/TAZ signaling pathways at same time., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Multiple acyl-CoA dehydrogenase deficiency (MADD) is a disease of rare autosomal recessive disorder. There are three types of MADD. Type I is a neonatal-onset form with congenital anomalies. Type II is a neonatal-onset form without congenital anomalies. Type III is considered to a milder form and usually responds to riboflavin. However, late-onset form could also be fatal and not responsive to treatments., Case Summary: We report a severe case of a young man with onset type III MADD induced by drugs and strenuous exercise characterized by rhabdomyolysis and liver dysfunction. Urine analysis indicated 12 out of 70 kinds of organic acids like glutaric acid-2 were detected. Serum analysis in genetic metabolic diseases revealed 24 out of 43 tested items were abnormal, revealing the elevation of several acylcarnitines and the reduction of carnitine in the patient. By next generation sequencing technology for gene sequencing related to fatty acid oxidation and carnitine cycle defects, a rare ETFDH gene variant was identified: NM&#95;004453:4:C.1448C>T(p.Pro483 Leu). The patient was diagnosed with late-onset GAII. He was not responsive to riboflavin and progressively worsened into multiple organ failure that finally led to death., Conclusion: Type III MADD can also be fatal and not responsive to treatments., Competing Interests: Conflict-of-interest statement: The authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Acute lung injury (ALI) is a continuum of lung changes caused by multiple lung injuries, characterized by a syndrome of uncontrolled systemic inflammation that often leads to significant morbidity and death. Anti-inflammatory is one of its treatment methods, but there is no safe and available drug therapy. Syringic acid (SA) is a natural organic compound commonly found in a variety of plants, especially in certain woody plants and fruits. In modern pharmacological studies, SA has anti-inflammatory effects and therefore may be a potentially safe and available compound for the treatment of acute lung injury., Purpose: This study attempts to reveal the protective mechanism of SA against ALI by affecting the polarization of macrophages and the activation of NF-κB signaling pathway. Trying to find a safer and more effective drug therapy for clinical use., Methods: We constructed the ALI model using C57BL/6 mice by intratracheal instillation of LPS (10 mg/kg). Histological analysis was performed with hematoxylin and eosin (H&E). The wet-dry ratio of the whole lung was measured to evaluate pulmonary edema. The effect of SA on macrophage M1-type was detected by flow cytometry. BCA protein quantification method was used to determine the total protein concentration in bronchoalveolar lavage fluid (BALF). The levels of Interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α in BALF were determined by the ELISA kits, and RT-qPCR was used to detect the expression levels of IL-6, IL-1β and TNF-α mRNA of lung tissue. Western blot was used to detect the expression levels of iNOS and COX-2 and the phosphorylation of p65 and IκBα in the NF-κB pathway in lung tissue. In vitro experiments were conducted with RAW267.4 cell inflammation model induced by 100 ng/ml LPS and A549 cell inflammation model induced by 10 μg/ml LPS. The effects of SA on M1-type and M2-type macrophages of RAW267.4 macrophages induced by LPS were detected by flow cytometry. The toxicity of compound SA to A549 cells was detected by MTT method which to determine the safe dose of SA. The expressions of COX-2 and the phosphorylation of p65 and IκBα protein in NF-κB pathway were detected by Western blot., Results: We found that the pre-treatment of SA significantly reduced the degree of lung injury, and the infiltration of neutrophils in the lung interstitium and alveolar space of the lung. The formation of transparent membrane in lung tissue and thickening of alveolar septum were significantly reduced compared with the model group, and the wet-dry ratio of the lung was also reduced. ELISA and RT-qPCR results showed that SA could significantly inhibit the production of IL-6, IL-1β, TNF-α. At the same time, SA could significantly inhibit the expression of iNOS and COX-2 proteins, and could inhibit the phosphorylation of p65 and IκBα proteins. in a dose-dependent manner. In vitro experiments, we found that flow cytometry showed that SA could significantly inhibit the polarization of macrophages from M0 type macrophages to M1-type macrophages, while SA could promote the polarization of M1-type macrophages to M2-type macrophages. The results of MTT assay showed that SA had no obvious cytotoxicity to A549 cells when the concentration was not higher than 80 μM, while LPS could promote the proliferation of A549 cells. In the study of anti-inflammatory effect, SA can significantly inhibit the expression of COX-2 and the phosphorylation of p65 and IκBα proteins in LPS-induced A549 cells., Conclusion: SA has possessed a crucial anti-ALI role in LPS-induced mice. The mechanism was elucidated, suggesting that the inhibition of macrophage polarization to M1-type and the promotion of macrophage polarization to M2-type, as well as the inhibition of NF-κB pathway by SA may be the reasons for its anti-ALI. This finding provides important molecular evidence for the further application of SA in the clinical treatment of ALI., Competing Interests: Declaration of competing interest Given their role as Editor/Associate Editor/ Editorial board members, «NAME of Editor» had no involvement in the peer-review of this article and has no access to information regarding its peer-review., (Copyright © 2024. Published by Elsevier GmbH.)

Background: Pulmonary cryptococcosis (PC) contributes to the ongoing global disease burden in human immunodeficiency virus (HIV)-negative populations. Since some PC patients are misdiagnosed under existing diagnostic guidelines, new diagnostic markers are needed to improve diagnostic accuracy and therapeutic efficacy and reduce disease risk., Methods: Our previously established sphingolipidomic approach was employed to explore the use of serum sphingolipids (SPLs) in diagnosing HIV-negative patients with PC. A clinical cohort of PC, pulmonary aspergillosis (PA), and tuberculosis (TB) patients and healthy controls was assessed to identify SPL biomarkers., Results: A total of 47 PC, 27 PA, and 18 TB patients and 40 controls were enrolled. PC and TB patients had similar clinical features, laboratory test results and radiological features, excluding plural effusion. The serum ceramide [Cer (d18:1/18:0)] level showed a significant increase in PC patients compared to controls and PA and TB patients (P<0.05). Cer (d18:1/18:0) was identified as a specific diagnostic biomarker for PC. The optimal cut-off value of greater than 18.00 nM showed a diagnostic sensitivity of 76.60% and a specificity of 95.00% and better distinguished PC patients from PA and TB patients. Furthermore, the serum Cer (d18:1/18:0) level gradually decreased after 3 and 6 months of treatment, suggesting the prediction potential for therapeutic efficacy of this biomarker. In addition, Cer (d18:1/18:0) analysis presented a higher sensitivity than the cryptococcal antigen (CrAg) assay., Conclusions: This is the first study to report the use of the SPL Cer (d18:1/18:0) as a serum biomarker for diagnosing Cryptococcus spp. infection in HIV-negative patients., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-125/coif). The authors have no conflicts of interest to declare., (2023 Journal of Thoracic Disease. All rights reserved.)

Response to immunotherapy widely varies among cancer patients and identification of parameters associating with favourable outcome is of great interest. Here we show longitudinal monitoring of peripheral blood samples of non-small cell lung cancer (NSCLC) patients undergoing anti-PD1 therapy by high-dimensional cytometry by time of flight (CyTOF) and Meso Scale Discovery (MSD) multi-cytokines measurements. We find that higher proportions of circulating CD8 + and of CD8 + CD101 hi TIM3 + (CCT T) subsets significantly correlate with poor clinical response to immune therapy. Consistently, CD8 + T cells and CCT T cell frequencies remain low in most responders during the entire multi-cycle treatment regimen; and higher killer cell lectin-like receptor subfamily G, member 1 (KLRG1) expression in CCT T cells at baseline associates with prolonged progression free survival. Upon in vitro stimulation, CCT T cells of responders produce significantly higher levels of cytokines, including IL-1β, IL-2, IL-8, IL-22 and MCP-1, than of non-responders. Overall, our results provide insights into the longitudinal immunological landscape underpinning favourable response to immune checkpoint blockade therapy in lung cancer patients., (© 2023. Springer Nature Limited.)

Non-small cell lung cancer (NSCLC) is one of the main malignant tumors with high mortality and short survival time. Immunotherapy has become the standard treatment for advanced NSCLC, but it has the problems of drug resistance and low response rate. Therefore, obtaining effective biomarkers to predict and enhance immune checkpoint inhibitors (ICIs) efficacy in NSCLC is important. Sphingolipid metabolism is recently found to be closely involved in tumor immunotherapy. CERS4, an important sphingolipid metabolizing enzyme, is positively correlated with the efficacy of anti-PD-1 therapy for NSCLC. Upregulation of CERS4 expression could improve the efficacy of anti-PD-1 therapy for NSCLC. High expression of CERS4 could downregulate the expression of Rhob in tumor. Significantly, the ratio of CD4 + /CD8 + T cell increased and the ratio of Tim-3 + /CD8 + T cell decreased in spleen and peripheral blood cells. When Rhob was knocked out, the efficacy of PD-1 mAb treatment increased, and the frequency of Tim-3 + CD8 + T cell decreased. This finding further confirmed the role of sphingolipid metabolites in regulating the immunotherapeutic function of NSCLC. These metabolites may improve the efficacy of PD-1 mAb in NSCLC by regulating the CERS4/Rhob/Tim-3 axis. Overall, this study provided a potential and effective target for predicting and improving the efficacy of ICIs for NSCLC. It also provided a new perspective for the study on the mechanisms of ICIs resistance for NSCLC., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interests., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Chronic diseases such as tumors and autoimmune disorders are closely linked to metabolism and immunity and require conflicting treatment methods. AMPK can regulate cell growth and inflammation through energy metabolism. Sinomenine is a compound extracted from the traditional Chinese herb sinomenium acutum (Thunb.) Rehd. et Wils. It has been used to treat NSCLC (non-small-cell lung cancer) and RA (rheumatoid arthritis) in some studies, but with limited understanding of its mechanisms., Objective: This study aims to examine the inhibitory effect of sinomenine hydrochloride (SH) on NSCLC and RA and to understand the underlying joint mechanisms., Results: The results indicate that SH has a cytotoxic effect specifically on tumor cells, but not on normal cells. SH was found to induce cell apoptosis by activating the AMPK-mTOR pathway. Additionally, in autoimmune disease cell models, SH was shown to reduce the growth of RA-FLS cells by inhibiting the phosphorylation of AMPK, while having no effect on normal macrophages. Moreover, in vivo studies also showed that SH could reduce the production of pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6 and slow the development of adjuvant arthritis in rats. Furthermore, SH was found to significantly suppress tumor growth in a tumor xenograft experiment in mice., Conclusions: This study provides new insights into the treatment of tumors and autoimmune diseases by demonstrating that SH can selectively inhibit the growth of NSCLC cells and the progression of RA through activation of the AMPK pathway., Competing Interests: Declaration of Competing Interests Run Ze Li, Xiao Xiang Guan, Xuan Run Wang, Wei-Qian Bao, Li-Rong Lian, Seong Wang Choi, Fang Yuan Zhang, Pei-Yu Yan, Elaine Lai Han Leung, Hu-Dan Pan and Liang Liu declare that they have no conflict of interest or financial conflicts to disclose., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Pleural effusion (PE) is a common manifestation of tuberculosis (TB) and malignant tumors but tuberculous PE (TPE) is difficult to distinguish from malignant PE (MPE), especially by noninvasive detection indicators. This study aimed to find effective detection indices in blood and PE for differentiating TB from a malignant tumor. A total of 815 patients who were diagnosed with TB or cancer in Hubei Shiyan Taihe Hospital from 2014 to 2017 were collected. Amongst them, 717 were found to have PE by thoracoscopy. Clinical characteristics, patients' blood parameters and PE indicator information were summarized for analysis. Patients with MPE had higher percentages to be bloody and negative of Rivalta test in PE than those with TPE. For clinical indicators, comparison of the specific parameters in blood showed that 18 indicators were higher in the TPE group than in the MPE group. By contrast, 12 indicators were higher in the MPE group than in the TPE group (P < .01). In addition, in PE tests, 3 parameters were higher in the TPE group, whereas other 4 parameters were higher in the MPE group (P < .01). Then, for clinical diagnosing practice, ROC analysis and principal component analysis were applied. The top 6 relevant indicators with area under curve over 0.70 were screened out as follows: hydrothorax adenosine dehydrogenase (pADA, 0.90), hydrothorax high-sensitivity C reactive protein (0.79), percentage of blood monocyte (sMONp, 0.75), blood high-sensitivity C reactive protein (sHsCRP, 0.73), erythrocyte sedimentation rate (0.71) and blood D-dimer (0.70). Moreover, logistic regression model revealed that a specific combination of 3 biomarkers, namely, pADA, sMONp and sHsCRP, could enhance the distinguishment of TB from malignant tumor with PE (area under curve = 0.944, 95% confidence interval = 0.925-0.964). The diagnostic function of the top single marker pADA in patients from different groups was analyzed and it was found to maintain high specificity and sensitivity. The 6 indicators, namely, pADA, hydrothorax high-sensitivity C reactive protein, sMONp, sHsCRP, sESR and blood D-dimer, showed significant diagnostic value for clinicians. Further, the combination of pADA, sMONp and sHsCRP has high accuracy for differential diagnosis for the first time. Most interestingly, the single marker pADA maintained high specificity and sensitivity in patients with different statuses and thus has great value for rapid and accurate diagnosis of suspected cases., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Biologically active sphingolipids are closely related to the growth, differentiation, aging, and apoptosis of cancer cells. Some sphingolipids, such as ceramides, are favorable metabolites in the sphingolipid metabolic pathway, usually mediating antiproliferative responses, through inhibiting cancer cell growth and migration, as well as inducing autophagy and apoptosis. However, other sphingolipids, such as S1P, play the opposite role, which induces cancer cell transformation, migration and growth and promotes drug resistance. There are also other sphingolipids, as well as enzymes, played potentially critical roles in cancer physiology and therapeutics. This review aimed to explore the important roles of sphingolipid metabolism in cancer. In this article, we summarized the role and value of sphingolipid metabolism in cancer, including the distribution of sphingolipids, the functions, and their relevance to cancer diagnosis and prognosis. We also summarized the known and potential antitumor targets present in sphingolipid metabolism, analyzed the correlation between sphingolipid metabolism and tumor immunity, and summarize the antitumor effects of natural compounds based on sphingolipids. Through the analysis and summary of sphingolipid antitumor therapeutic targets and immune correlation, we aim to provide ideas for the development of new antitumor drugs, exploration of new therapeutic means for tumors, and study of immunotherapy resistance mechanisms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Wang, Wang, Xie, Wang, Pan, Meng, Liang, Li, Yan, Wu, Liu, Yao and Leung.)

A field experiment was conducted to study the effects of different organic material amendments on soil respiration in a flue-cured tobacco field. Five treatments were set up:no fertilizer (NF), chemical fertilizer (NPK), chemical fertilizer+ryegrass (NPKG), chemical fertilizer+wheat straw (NPKS), and chemical fertilizer+tobacco straw biochar (NPKB). The results showed that:① Compared with that under NPK, NPKG and NPKS decreased the temperature sensitivity ( Q 10 ) of total soil respiration and heterotrophic respiration, whereas NPKB increased the Q 10 of heterotrophic respiration. The two-factor fitting model of soil respiration and soil hydrothermal factors accounted for 50%-80% of the variation in soil respiration. ② The addition of organic materials significantly increased the content of soil soluble organic carbon (DOC) and root dry matter. Soil heterotrophic respiration( R h ) was significantly positively correlated with DOC content, and soil autotrophic respiration( R a ) was significantly parabolically correlated with root biomass, with an R 2 of 0.327-0.634. ③ Soil respiration increased first and then decreased during the tobacco growth period. Compared with that under the NF treatment, the NPK treatment significantly promoted soil respiration and its components. Compared with those of the NPK treatment, R s rates were significantly increased by 20.08%, 10.32%, and 9.88% under the NPKG, NPKS, and NPKB treatments, respectively; R h rate increased by 24.21%, 16.51%, and 11.68% respectively, and R a rate was increased by 15.12% in the NPKG treatment. In summary, straw returning and biochar addition significantly increased R h by increasing soil DOC, thereby promoting R s . Incorporation of ryegrass not only increased the R h but also increased R a by promoting the growth and development of roots and therefore the R s .

Background: Currently, the identification of accurate biomarkers for the diagnosis of patients with early-stage lung cancer remains difficult. Fortunately, metabolomics technology can be used to improve the detection of plasma metabolic biomarkers for lung cancer. In a previous study, we successfully utilised machine learning methods to identify significant metabolic markers for early-stage lung cancer diagnosis. However, a related research platform for the investigation of tumour metabolism and drug efficacy is still lacking., Hypothesis/purpose: A novel methodology for the comprehensive evaluation of the internal tumour-metabolic profile and drug evaluation needs to be established., Methods: The optimal location for tumour cell inoculation was identified in mouse chest for the non-traumatic orthotopic lung cancer mouse model. Microcomputed tomography (micro-CT) was applied to monitor lung tumour growth. Proscillaridin A (P.A) and cisplatin (CDDP) were utilised to verify the anti-lung cancer efficacy of the platform. The top five clinically valid biomarkers, including proline, L-kynurenine, spermidine, taurine and palmitoyl-L-carnitine, were selected as the evaluation indices to obtain a suitable lung cancer mouse model for clinical metabolomics research by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS)., Results: The platform was successfully established, achieving 100% tumour development rate and 0% surgery mortality. P.A and CDDP had significant anti-lung cancer efficacy in the platform. Compared with the control group, four biomarkers in the orthotopic model and two biomarkers in the metastatic model had significantly higher abundance. Principal component analysis (PCA) showed a significant separation between the orthotopic/metastatic model and the control/subcutaneous/KRAS transgenic model. The platform was mainly involved in arginine and proline metabolism, tryptophan metabolism, and taurine and hypotaurine metabolism., Conclusion: This study is the first to simulate clinical metabolomics by comparing the metabolic phenotype of plasma in different lung cancer mouse models. We found that the orthotopic model was the most suitable for tumour metabolism. Furthermore, the anti-tumour drug efficacy was verified in the platform. The platform can very well match the clinical reality, providing better lung cancer diagnosis and securing more precise evidence for drug evaluation in the future., (Copyright © 2021. Published by Elsevier GmbH.)

Background: Lung cancer has become the principal cause of cancer-related deaths. Emodin is a Chinese herb-derived compound extracted from the roots of Rheum officinale that exhibits numerous pharmacological characteristics. Secretory phospholipase A2-IIa (sPLA2-IIa) is overexpressed in cancers and plays an important role in cancer development., Purpose: This study aims to investigate the anti-tumor mechanism of emodin in non-small-cell lung cancer (NSCLC)., Methods: MTT assay was applied to detect the sensitivity of emodin to NSCLC cell line. Flow cytometry was used to examine the effect of emodin on cell cycle distribution and evaluate ROS level and apoptosis. Western blot analysis was utilised to examine the expression levels of sPLA2-IIa, PKM2, and AMPK and its downstream pathways induced by emodin. Enzyme inhibition assay was applied to investigate the inhibitory effect of emodin on sPLA2-IIa. The anticancer effect of emodin was also detected using an in vivo model., Results: Emodin significantly inhibited NSCLC proliferation in vivo and in vitro and was relatively less cytotoxic to normal lung cell lines. Most importantly, emodin inhibited the proliferation of KRAS mutant cell lines by decreasing the expression of sPLA2-IIa and NF-κB pathways. Emodin also inhibited mTOR and AKT and activated the AMPK pathway. Furthermore, emodin induced apoptosis, increased the reactive oxygen species (ROS) level, and arrested the cell cycle., Conclusion: Emodin exhibited a novel anti-tumor mechanism of inhibiting the proliferation of KRAS mutant cell lines by decreasing the expression levels of sPLA2-IIa and NF-κB pathways. Hence, emodin can potentially serve as a therapeutic target in NSCLC., (Copyright © 2021. Published by Elsevier GmbH.)

Objectives: Vascularization is an essential step in successful bone tissue engineering. The induction of angiogenesis in bone tissue engineering can be enhanced through the delivery of therapeutic agents that stimulate vessel and bone formation. In this study, we show that cucurbitacin B (CuB), a tetracyclic terpene derived from Cucurbitaceae family plants, facilitates the induction of angiogenesis in vitro., Methods: We incorporated CuB into a biodegradable poly (lactide-co-glycolide) (PLGA) and β-tricalcium phosphate (β-TCP) biomaterial scaffold (PT/CuB) Using 3D low-temperature rapid prototyping (LT-RP) technology. A rat skull defect model was used to verify whether the drug-incorporated scaffold has the effects of angiogenesis and osteogenesis in vivo for the regeneration of bone defect. Cytotoxicity assay was performed to determine the safe dose range of the CuB. Tube formation assay and western blot assay were used to analyze the angiogenesis effect of CuB., Results: PT/CuB scaffold possessed well-designed bio-mimic structure and improved mechanical properties. CuB was linear release from the composite scaffold without affecting pH value. The results demonstrated that the PT/CuB scaffold significantly enhanced neovascularization and bone regeneration in a rat critical size calvarial defect model compared to the scaffold implants without CuB. Furthermore, CuB stimulated angiogenic signaling via up-regulating VEGFR2 and VEGFR-related signaling pathways., Conclusion: CuB can serve as promising candidate compound for promoting neovascularization and osteogenesis, especially in tissue engineering for repair of bone defects., The Translational Potential of This Article: This study highlights the potential use of CuB as a therapeutic agent and strongly support its adoption as a component of composite scaffolds for tissue-engineering of bone repair., Competing Interests: There is no conflict of interest to declare., (© 2021 The Authors.)

Objective: To establish the norm of the Chinese version of Karitane Parenting Confidence Scale (KPCS) in urban areas of China. Methods: From August to December 2017, the parents of 2 216 children (<36 months old) were selected from 15 cities (Beijing, Lianyungang, Hangzhou, Chengdu, Xi'an, Guangzhou, Changsha, Jinan, Guiyang, Ningbo, Dalian, Qinhuangdao, Maanshan, Chongqing and Wuhan) in 14 provinces by stratified random sampling. The general demographic characteristics and parents' parenting confidence were collected by a self-made questionnaire and KPCS Chinese version. The percentile norm was established. P 3 , P 10 and P 25 were used as the criteria to define the degree of lack of parenting confidence. Results: The age of mothers was (30.67±4.29). The age of the father was (32.50±4.99) years old. There were 726 (32.76%), 759 (34.25%) and 731 (32.99%) infants in 6-12, 12-23 and 24-35 months old groups. The total scores of P 50 , P 25 , P 10 and P 3 of KPCS (Chinese version) of infant parents in urban areas in China were 41, 38, 33, and 29 respectively. When the scores of parents were 34-37, 30-33, and ≤ 29, they were judged as mild, moderate, and severe lack of parenting confidence. There was no significant difference in the Chinese version of KPCS between parents of different age groups and parents of different gender (χ²=3.53, P =0.171; χ²=1.41, P =0.236). Each factor score≤ P 3 is defined as the boundary score, and the corresponding boundary scores of "parenting" "support" and "competence" were 13, 9, and 5 respectively. Conclusion: The Chinese version of KPCS can be used to assess the parenting confidence of infants in urban areas of China. It can used as one of the bases for scientific and objective evaluation of the parenting status of families.

Rheumatoid arthritis (RA), the most common inflammatory arthropathy word wild, is a systemic autoimmune disease that mainly affects the synovium of joints with a high disability rate. Metabolic mis-regulation has emerged as a fundamental pathogenesis of RA linked to immune cell dysfunction, while targeting immunometabolism provides a new and effective approach to regulate the immune responses and thus alleviate the symptom of RA. Recently, natural active compounds from traditional Chinese medicines (TCMs) have potential therapeutic effects on RA and regulating immunometabolism. In this review, in addition to updating the connection between cellular metabolism and cell function in immune cells of RA, we summarized that the anti-inflammatory mechanisms of the potential natural compounds from TCM by targeting metabolic reprogramming of immune cells, and discusses them as a rich resource for providing the new potential paradigm for the treatment of RA., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 Tianjin Press of Chinese Herbal Medicines. Published by ELSEVIER B.V.)

Background: Cervical cancer continues to be one of the leading causes of cancer deaths among females in low and middle-income countries. In this study, we aimed to assess the independent prognostic value of clinical and potential prognostic factors in progression-free survival (PFS) in cervical cancer., Methods: We conducted a retrospective study on 92 cervical cancer patients treated from 2017 to 2019 at the Zhuhai Hospital of Traditional Chinese and Western Medicine. Tumor characteristics, treatment options, progression-free survival and follow-up information were collected. Kaplan-Meier method was used to assess the PFS., Results: Results showed that the number of retrieved lymph nodes had a statistically significant effect on PFS of cervical cancer patients (P = 0.002). Kaplan-Meier survival curve analysis showed that cervical cancer patients with initial symptoms age 25-39 had worse survival prognoses (P = 0.020). And the using of uterine manipulator in laparoscopic treatment showed a better prognosis (P < 0.001). A novel discovery of our study was to verify the prognostic values of retrieved lymph nodes count combining with FIGO staging system, which had never been investigated in cervical cancer before. According to the Kaplan-Meier survival curve analysis and receiver operating characteristic (ROC) curve analysis, significant improvements were found after the combination of retrieved lymph nodes count and FIGO stage in predicting PFS for cervical cancer patients (P < 0.001, AUC = 0.826, 95% CI: 0.689-0.962)., Conclusion: Number of retrieved lymph nodes, initial symptoms age, uterine manipulator, and retrieved lymph nodes count combining with FIGO staging system could be potential prognostic factors for cervical cancer patients.

Early diagnosis has been proved to improve survival rate of lung cancer patients. The availability of blood-based screening could increase early lung cancer patient uptake. Our present study attempted to discover Chinese patients' plasma metabolites as diagnostic biomarkers for lung cancer. In this work, we use a pioneering interdisciplinary mechanism, which is firstly applied to lung cancer, to detect early lung cancer diagnostic biomarkers by combining metabolomics and machine learning methods. We collected total 110 lung cancer patients and 43 healthy individuals in our study. Levels of 61 plasma metabolites were from targeted metabolomic study using LC-MS/MS. A specific combination of six metabolic biomarkers note-worthily enabling the discrimination between stage I lung cancer patients and healthy individuals (AUC = 0.989, Sensitivity = 98.1%, Specificity = 100.0%). And the top 5 relative importance metabolic biomarkers developed by FCBF algorithm also could be potential screening biomarkers for early detection of lung cancer. Naïve Bayes is recommended as an exploitable tool for early lung tumor prediction. This research will provide strong support for the feasibility of blood-based screening, and bring a more accurate, quick and integrated application tool for early lung cancer diagnostic. The proposed interdisciplinary method could be adapted to other cancer beyond lung cancer., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

The recent coronavirus disease 2019 (COVID-19) pandemic outbreak has caused a serious global health emergency. Supporting evidence shows that COVID-19 shares a genomic similarity with other coronaviruses, such as severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), and that the pathogenesis and treatment strategies that were applied 17 years ago in combating SARS-CoV and other viral infections could be taken as references in today's antiviral battle. According to the clinical pathological features of COVID-19 patients, patients can suffer from five steps of progression, starting with severe viral infection and suppression of the immune system and eventually progressing to cytokine storm, multi-organ damage, and lung fibrosis, which is the cause of mortality. Therefore, early prevention of disease progression is important. However, no specific effective drugs and vaccination are currently available, and the World Health Organization is urging the development of novel prevention and treatment strategies. Traditional Chinese medicine could be used as an alternative treatment option or in combination with Western medicine to treat COVID-19, due to its basis on historical experience and holistic pharmacological action. Here, we summarize the potential uses and therapeutic mechanisms of Chinese herbal formulas (CHFs) from the reported literature, along with patent drugs that have been recommended by institutions at the national and provincial levels in China, in order to verify their scientific foundations for treating COVID-19. In perspective, more basic and clinical studies with multiple high-tech and translational technologies are suggested to further confirm the therapeutic efficacies of CHFs., (© 2020 THE AUTHORS.)

Purpose: N6-methyladenosine (m6A) is reported to play a critical role in cancer through various mechanisms. We aimed to construct and validate an m6A RNA methylation regulators-based prognostic signature for Esophageal cancer (ESCA)., Materials and Methods: The RNA sequencing transcriptome data of 13 m6A RNA methylation regulators as well as clinical data were obtained from The Cancer Genome Atlas (TCGA) ESCA database. The differential expression of the regulators between ESCA tissues and normal tissues was assessed. Consensus clustering was conducted to explore the different ESCA clusters based on the expression of these regulators. LASSO Cox regression analysis was used to generate a prognostic signature based on m6A RNA methylation regulators expression., Results: Eight regulators (KIAA1429, HNRNPC, RBM15, METTL3, WTAP, YTHDF1, YTHDC1, and YTHDF2) were found to be significantly upregulated in ESCA tissues. Significant differences of survival rate and clinicopathological features were found between the two clusters. A prognostic signature, which consists of HNRNPC and ALKBH5, was constructed based on the TCGA ESCA cohort, which can serve as an independent prognostic predictor. The results of bioinformatics analysis were further successfully validated in the clinical ESCA cohort by qRT-PCR and immunohistochemistry staining., Conclusion: Our study constructed and validated an m6A RNA methylation regulators-based prognostic signature. This might provide important information for developing diagnostic and therapeutic strategies., Competing Interests: The authors report no conflicts of interest in this work., (© 2020 Xu et al.)

Objective: To observe the clinical effectiveness and safety of fire-needle therapy, an external approach of Chinese medicine in treating plaque psoriasis., Methods: This study was a two-parallel-arm randomized controlled trial. A total of 151 participants with plaque psoriasis were randomly assigned to the fire-needle therapy group (treatment group, 76 cases) or the control group (75 cases) at a 1:1 allocation ratio using SAS software. All participants received Oral Huoxue Jiedu Decoction (, HXJDD) and applied externally vaseline cream twice a day. Participants in the treatment group received fire-needle therapy once weekly for 4 weeks plus HXJDD and vaseline cream applied the same as the control group. The primary outcome measure was Psoriasis Area and Severity Index (PASI) score, and the secondary outcomes were Dermatology Life Quality Index (DLQL), and Hamilton Anxiety Rating Scale (HAMA), as well as Chinese medicine (CM) syndrome score and photos of target lesions. The indices were evaluated before and after treatment., Results: Sixty-eight patients in each group completed the study. The treatment group has not yet achieved significant improvement in PASI score (P>0.05) compared to the control group. However, significant differences were found between the two groups in relieving CM syndrome (P<0.05) and improving quality of life (P<0.05)., Conclusion: Fire-needle appears to be safe and may have benefit for psoriasis, the short-term treatment and small sample size limit the conclusions of this study. Further rigorous randomized controlled trials with longer treatment are recommended.

Background: A combination of conventional disease-modifying anti-rheumatic drugs improves the treatment of rheumatoid arthritis but with high side-effects. Methotrexate (MTX) combination therapy that with high therapeutic efficacy and low toxicity is in demand in many countries to replace the use of expensive biological agents., Study Design: This study was an open-label, 24-week, parallel randomized controlled trial conducted between November 2015 and December 2017., Methods: Patients were randomly assigned at a 3:2 ratio to receive MTX combined with sinomenine (SIN) at a dose of 120 mg twice daily, or leflunomide (LEF) at a dose of 20 mg once daily. Efficacy and safety were assessed at weeks 4, 12 and 24. The primary efficacy endpoint was the proportion of patients achieving an American College of Rheumatology (ACR)50 response and a European League Against Rheumatism (EULAR) good response at week 24., Results: A total of 101/120 (84.2%) patients completed 24 weeks of observation. In the intention-to-treat (ITT) analysis, 65.3% of patients treated with MTX + SIN showed improved disease activity as determined by the ACR50 response at week 24 compared to 69.6% of patients treated with MTX + LEF. A similar insignificant pattern was found for the ACR20 and ACR70 responses, as well as the clinical disease activity index, EULAR response, and remission and low disease activity rates between these two treatment groups. The per-protocol analysis showed results consistent with those of the ITT analysis. Notably, significant reductions in gastrointestinal adverse reactions and liver toxicity were found in patients treated with MTX + SIN compared to patients treated with MTX + LEF (p < 0.05)., Conclusion: Considering the balance of efficacy and toxicity, the current study provides evidence that MTX + SIN combination therapy is probably one of the choices for treating patients with active rheumatoid arthritis in addition to MTX + LEF combination therapy., (Copyright © 2019 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Dysregulation of cell metabolism and redox balance is implicated in the pathogenesis and progression of cancer and autoimmune diseases. Because the cell proliferation and apoptotic regulatory pathways are interconnected with metabolic and redox signalling pathways, the current mono-target treatment is ineffective, and multi-drug resistance remains common. Complex diseases are often implicated in a network-based context of pathology; therefore, a new holistic intervention approach is required to block multi-crosstalk in such complicated circumstances. The use of therapeutic agents isolated from herbs to holistically modulate metabolism and redox state has been shown to relieve carcinoma growth and the inflammatory response in autoimmune disorders. Multiple clinically applied or novel herbal chemicals with metabolic and redox modulatory capacity as well as low toxicity have recently been identified. Moreover, new metabolic targets and mechanisms of drug action have been discovered, leading to the exploration of new pathways for drug repositioning, clinical biomarker spectra, clinical treatment strategies and drug development. Taken together with multiple supporting examples, the modulation of cell metabolism and the redox capacity using herbal chemicals is emerging as a new, alternative strategy for the holistic treatment of cancer and autoimmune disorders. In the future, the development of new diagnostic tools based on the detection of metabolic and redox biomarkers, reformulation of optimized herbal compositions using artificial intelligence, and the combination of herbs with mono-targeting drugs will reveal new potential for clinical application., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

Lung cancer is the number one cancer in terms of both mortality and incidence. Cancer cells differ from normal cells in that they can reprogram their metabolism to support a rapid proliferation rate and alter oxidative phosphorylation processes toward lactic acid fermentation, even under aerobic conditions. Therefore, we aimed to identify new compounds that might act as pyruvate kinase M2 isoform (PKM2) activators and to investigate their anti-cancer efficacy in non-small-cell lung cancer (NSCLC) cells. The molecular docking method was applied to screen PKM2 activators from our virtual natural products library. Then, compounds with promising docking scores were examined for cytotoxic effects in a panel of NSCLC cells using the MTT assay. Functional effects and therapeutic mechanisms were investigated by in vitro enzyme assays, western blotting (WB), and flow cytometry. Molecular docking showed that 0089-0022 acts as a potential PKM2 activator by binding to the kinase pocket. An in vitro enzyme activity assay showed that 0089-0022 is a direct PKM2 activator and that it effectively induces apoptosis in A549 and H1975 cells through inhibition of AKT phosphorylation. Our results suggest that 0089-0022 activates PKM2 and thus is a promising anti-cancer therapeutic candidate in NSCLC., (© 2018 John Wiley & Sons A/S.)

Non-small-cell lung cancer (NSCLC) is the predominant histological type of lung cancer and is characterized by the highest mortality and incidence rates among these types of malignancies. Cardiac glycosides, a class of natural products, have been identified as a potential type of chemotherapeutic agent. This study aims to investigate the anti-cancer effects and the mechanisms of action of Proscillaridin A (P.A) in NSCLC cells. In vitro sodium-potassium pump (Na + /K + ATPase) enzyme assays indicated that P.A is a direct Na + /K + ATPase inhibitor. P.A showed potent cytotoxic effects in NSCLC cells at nanomolar levels. Treatment mechanism studies indicated that P.A elevated Ca 2+ levels, activated the AMPK pathway and downregulated phosphorylation of ACC and mTOR. Subsequently, P.A increased death receptor 4 (DR4) expression and downregulated NF-κB. Interestingly, P.A selectively suppressed EGFR activation in EGFR mutant cells but not in EGFR wild-type cells. In vivo, P.A significantly suppressed tumor growth in nude mice compared to vehicle-treated mice. Compared with the Afatinib treatment group, P.A displayed less pharmaceutical toxicity, as the body weight of mice treated with P.A did not decrease as much as those treated with Afatinib. Consistent changes in protein levels were obtained from western blotting analysis of tumors and cell lines. Immunohistochemistry analysis of the tumors from P.A-treated mice showed a significant suppression of EGFR phosphorylation (Tyr 1173) and reduction of the cell proliferation marker Ki-67. Taken together, our results suggest that P.A is a promising anti-cancer therapeutic candidate for NSCLC.

As a surgical procedure which could significantly lower the recurrence rate of cancers, total mesorectal excision (TME) has been the gold standard for middle and lower rectal cancer treatment. However, previous studies have shown that the procedure did not achieve the ideal theoretical local recurrence rates of rectal cancers. Some researchers pointed out it was very likely that not all so-called TME treatments completely removed the mesorectum, implying that some of these TME surgical treatments failed to meet oncological quality standards. Therefore, a suitable assessment tool for the surgical quality of TME is necessary. The notion of "macroscopic assessment of mesorectal excision (MAME)" was put forward by some researchers as a better assessment tool for the surgical quality of TME and has been confirmed by a series of studies. Besides providing rapid and accurate surgical quality feedbacks for surgeons, MAME also effectively assesses the prognosis of patients with rectal cancer. However, as a new assessment tool used for TME surgical quality, MAME has an only limited influence on the current guidelines and is yet to be widely applied in most countries. The aims of this review are to provide a detailed introduction to MAME for clinical practice and to summarize the current prognostic significance of MAME.

Objectives: This study aim to investigate the incidence, timing and risk factors of metachronous pulmonary recurrence after curative resection in patients with rectal cancer., Design: A retrospective cohort study., Setting: This study was conducted at a tertiary referral cancer hospital., Participants: A total of 404 patients with rectal cancer who underwent curative resection from 2007 to 2012 at Beijing Hospital were enrolled in this study., Interventions: The pattern of recurrence was observed and evaluated., Primary and Secondary Outcome Measures: The incidence and timing of recurrences by site were calculated, and the risk factors of pulmonary recurrence were analysed., Results: The 5-year disease-free survival for the entire cohort was 77.0%. The most common site of recurrence was the lungs, with an incidence of 11.4%, followed by liver. Median interval from rectal surgery to diagnosis of pulmonary recurrence was much longer than that of hepatic recurrence (20 months vs 10 months, P=0.022). Tumour location, pathological tumor-node-metastasis (TNM) stage and positive circumferential resection margin were identified as independent risk factors for pulmonary recurrence. A predictive model based on the number of risk factors identified on multivariate analysis was developed, 5-year pulmonary recurrence-free survival for patients with 0, 1, 2 and 3 risk factors was 100%, 90.4%, 77.3% and 70.0%, respectively (P<0.001)., Conclusions: This study emphasised that the lung was the most common site of metachronous metastasis in patients with rectal cancer who underwent curative surgery. For patients with unfavourable risk profiles, a more intensive surveillance programme that could lead to the early detection of recurrence is strongly needed., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Aim: To develop predictive markers in blood for colorectal cancer liver metastasis., Methods: Twenty colorectal cancer patients were selected and divided into two groups. Group A consisted of 10 patients whose pathological TNM stage was IIIC (T3-4N2M0), while another 10 patients with synchronous liver metastasis (TNM stage IV) were recruited for group B. During the surgical procedure, a 10-mL drainage vein (DV) blood sample was obtained from the DV of the tumor-bearing segment prior to the ligation of the DV. At the same time, a 10-mL peripheral vein (PV) blood sample was collected via peripheral venipuncture. The serum levels of 24 molecules that are potentially involved in the mechanism of liver metastasis in both DV blood and PV blood were analyzed by using high-throughput enzyme-linked immunosorbent assay technology., Results: Univariate analysis revealed that platelet-derived growth factor AA (PDGFAA) in DV blood (dPDGFAA) ( P = 0.001), PDGFAA in PV blood (pPDGFAA) ( P = 0.007), and human epidermal growth factor receptor-2 in PV blood (pHER2) ( P = 0.001), pMMP7 ( P = 0.028), pRANTES ( P = 0.013), and pEGF ( P = 0.007) were significantly correlated with synchronous liver metastasis. Multivariate analysis identified dPDGFAA (HR = 1.001, P = 0.033) and pHER2 (HR = 1.003, P = 0.019) as independent predictive factors for synchronous liver metastasis. Besides, high peripheral HER2 level may also be a risk factor for metachronous liver metastasis, although the difference did not reach statistical significance ( P = 0.06). Significant correlations were found between paired DV and PV blood levels for PDGFAA ( r = 0.794, P < 0.001), but not for HER2 ( r = 0.189, P = 0.424)., Conclusion: PDGFAA in tumor drainage and HER2 in PV blood may be useful predictive factors for synchronous liver metastasis of colorectal cancer., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflicts of interest.

Background: Pneumoconiosis is one of the most common occupational diseases, which shows the progressive and irreversible pathological changes. It ultimately can induce pulmonary failure and lead to death. To date, these patients have no curative treatment option under the current standard of care, so it is especially important to delay the onset of the disease and slow down its progression. Therefore, understanding of clinical features of pneumoconiosis is particularly critical for medical intervention., Methods: We collected the clinical data from 118 pneumoconiosis cases of miners admitted in hospital and processed the statistics analysis by using the Chi-square test and the risk assessment., Results: Compared to other types of miners, gold miners are liable to cause Broncho-pulmonary co-infection with Chi-square value 18.748 and the P value <0.001. However, unexpectedly, the smoking miners displayed a better Activities of Daily Living (ADLs) compared to non-smokers, which showed 19.318 of Chi-square score and less than 0.001 of P value. And this connection was associated with the dust exposure time (P<0.05), showing the increasing risk of non-smoking miners occurred as the increasing time exposed to dust. In addition, our analysis indicated that the probability of smoking miners suffered from Broncho-pulmonary co-infection was less than non-smoking miners with Chi-square value 8.044 and P<0.01, which was also associated with the dust exposure time tendentiously, though P>0.05. Moreover, smoking history exhibited a deteriorating effect to the overall survival (OS) with 9.546 of Chi-square value and P<0.05, in accordance with smoking reducing life time. Interestingly, pneumoconiosis drugs could extend the smokers' OS, but not non-smokers'., Conclusions: Our studies suggest that the history of smoking and exposure time of dust play important roles in the development of pneumoconiosis and smoking could be a factor that determines the treatment options depending on patients' smoking history., Competing Interests: The authors have no conflict of interest to declare.

Objective: To investigate the inhibitory effect of high concentration insulin on K562 cell proliferation and its underlying mechanism., Methods: K562 cells were treated by different concentration of insulin and/or anti-IGF-1R antibody (IGF-1R-Ab), MTT assay and flow cytometry were used to detect the K562 cells proliferation and apoptosis, respectivety; Western blot was used to measure the expression and phosphorylation level of IGE-IR, Akt, Erk1/2 in K562 cells under the different concentration of insulin., Results: MTT assay showed that less than 40 mU/ml insulin could promote K562 cell proliferation, while high concentration (> 40 mU/ml) insulin has been shown to inhibit K562 cell proliferation; Flow cytometry showed that 40 mU/ml insulin suppressed K562 cell apoptosis (P < 0.05), while 200 mU/ml insulin could significantly induce K562 cell apoptosis (P < 0.01); 0.01 to 1.0 µg/ml IGF-1R-Ab has significantly enhanced the inhibitory and inducing effects of high concentration (> 40 mU/ml) of insulin on K562 cell proliferation and apoptosis respectively (r = 0.962, P < 0.001); Western blot showed that after K562 cells were treated with different concentrations of insulin ERK, and the p-ERK expression did not change significantly, after K562 cells were treated with 200 mU/ml insulin, the expression of IGF-1R and AKT also not were changed obviously, while the phosphorylation level of IGF-1R and AKT increased., Conclusion: High concentration (>40 mU/ml) of insulin inhibits K562 cell proliferation and induces its apoptosis, and its mechanism may be related with the binding IGF-1R by insulin, competitively inhibiting the binding of IGF-1 and IGF-1R, the blocking the transduction of PI3K/AKT signal pathway.

Background: In patients with colorectal cancer, a defunctioning ileostomy is commonly constructed to reduce anastomotic complications. However, many patients do not undergo a subsequent procedure to have their temporary stoma closed., Objective: This study investigated the incidence of nonclosure of ileostomies and identified factors associated with nonclosure., Design: This study is a retrospective analysis of prospectively collected data., Setting: This study was conducted at a tertiary referral cancer hospital., Patients: A total of 296 patients who received anterior resection with a defunctioning ileostomy with protective intention from 2006 to 2013 were included., Main Outcome Measures: The primary outcomes measured were the incidence of nonclosure of ileostomy and associated risk factors., Results: Patients were followed for a median time of 29 months (range, 21-100 months). At the end of the study, 51 (17.2%) patients were left with a permanent ileostomy. The median time interval from the creation of a defunctioning ileostomy to closure was 192 days (range, 14-865 days). Multivariate analyses using a logistic regression model showed that metastatic diseases (OR, 0.179, p < 0.001), Charlson Comorbidity Index score >1 (OR, 0.268; p < 0.01), and complications from the index surgery (OR, 0.391; p = 0.013) were significant independent risk factors for failing to close a defunctioning ileostomy., Limitations: Although our study has a large patient cohort, it is limited by its retrospective nature. It is difficult to fully evaluate stoma complications after hospital discharge, and the prevalence may be underestimated., Conclusion: One in 6 temporary ileostomies constructed during an elective anterior resection for rectal cancer was not closed. Patients should be told before the index surgery that there is a risk of nonclosure and possible complications associated with permanent ileostomy.

Liquiritigenin (LQG), isoliquiritin (ILQ) and isoliquiritigenin (ILG) are flavonoids derived from liquorice and all possess a similar chemical structural backbone. In the current study, we found that ILQ and ILG had suppressive effects on lipopolysaccharide (LPS)-induced inflammatory responses in murine macrophage by suppressing the iNOS and COX-2 proteins and mRNA expression. A mechanistic study indicated that the effect was associated with an induction of antioxidant and detoxification enzymes, including UGT1A1, NQO1, and heme oxygenase-1 (HO-1) mRNA expression. The regulator of these enzymes, nuclear factor-erythroid 2-related factor 2 (Nrf2), which plays a critical role in LPS-induced inflammatory responses, could be activated by ILQ and ILG. Additionally, ILQ and ILG promoted Nrf2 signaling activation by inhibiting the Kelch-like ECH-associated protein 1 (Keap1) and increasing Nrf2 translocation, inducing the expression of these antioxidant enzymes. We further found that ILQ and ILG induced HO-1 expression independent of Nrf2 expression. With respect to the effect of these compounds on NF-κB signaling, ILG was found to markedly inhibit IκBα degradation and phosphorylation, while LQG and ILQ had no significant effects. These results indicate that there are correlations between the anti-inflammatory responses and the chemical structural properties of these flavonoids., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Purpose: Surgical site infection (SSI) is the most common complication after primary closure of defunctioning ileostomy. We use a subcutaneous vacuum drain (SVD) in our institution to prevent infection. This study aimed to analyze the risk factors of SSI and to assess the utility of an SVD for preventing SSI in patients undergoing primary closure of ileostomy., Methods: Patients undergoing ileostomy closure in the Department of Colorectal Surgery, Peking University Cancer Hospital, from September 2006 to March 2013, were included in this study. The clinical features of these patients with or without a subcutaneous drain were reviewed, and the complication rate of SSI was analyzed. The primary endpoints were the incidence and risk factors of SSI, and the secondary endpoints were the rate of overall complications and their management., Results: A total of 245 consecutive patients were enrolled in the study. The overall incidence of SSI was 8.6%. Eighty-five (34.7%) patients received placement of an SVD. The use of SVDs was associated with a significantly lower incidence of SSI compared with primary closure (PC) without an SVD (1.2 vs. 12.5%, p = 0.001). Multivariate analyses showed that the presence of an SVD (odds ratio (OR) 0.063, p = 0.012), total operation time >90 min (OR 4.862, p = 0.002), and postoperative complications (OR 10.576, p < 0.001) were independent risk factors of SSI., Conclusions: This study shows that an SVD is effective for reducing SSI in patients undergoing PC of ileostomy. Further randomized trials are required to confirm our findings and to compare SVDs with purse-string sutures.

Aim: To analyze tumor regression grade (TRG) for prognosis of locally advanced rectal adenocarcinoma (LARA) treated with preoperative radiotherapy., Methods: One hundred and ninety patients with clinical stage II/III LARA were studied. All patients underwent radical surgery (between 2004 and 2010) after 30-Gy/10-fraction preoperative radiotherapy (pre-RT). All 190 patients received a short course of pre-RT and were reassessed for disease recurrence and survival; the slides of surgical specimens were reviewed and classified according to Mandard TRG. We compared patients with good response (Mandard TRG1 or TRG2) vs patients with bad/poor response (Mandard TRG3-5). Outcomes evaluated were 5-year overall survival (OS), 5-year disease-free survival (DFS), and local, distant and mixed recurrence. Fisher's exact test or χ(2) test, log-rank test and proportional hazards regression analysis were used to calculate the probability that Mandard TRG was associated with patient outcomes., Results: One hundred and sixty-six of 190 patients (87.4%) were identified as Mandard bad responders (TRG3-5). High Mandard grade was correlated with tumor height (41.7% < 6 cm vs 58.3% ≥ 6 cm, P = 0.050), ypT stage (75% ypT0-2 vs 25% ypT3-4, P = 0.000), and ypN stage (75% ypN0 vs 25% ypN1, P = 0.031). In univariate survival analysis, Mandard grade bad responders had significantly worse OS and DFS than good responders (TRG1/2) (OS, 83.1% vs 96.4%, P = 0.000; DFS, 72.3% vs 92.0%, P = 0.002). In multivariate survival analysis, Mandard bad responders had significantly worse DFS than Mandard good responders (DFS 3.8 years (95%CI: 1.2-12.2 years, P = 0.026)., Conclusion: Mandard grade good responders had a favorable prognosis. TRG may be a potential predictor for DFS in LARA after pre-RT.

Aim: To examine the correlation of phosphatidylinositol 3-kinase (PIK3) CB expression with preoperative radiotherapy response in patients with stage II/III rectal adenocarcinoma., Methods: PIK3CB immunoexpression was retrospectively assessed in pretreatment biopsies from 208 patients with clinical stage II/III rectal adenocarcinoma, who underwent radical surgery after 30-Gy/10-fraction preoperative radiotherapy. The relation between PIK3CB expression and tumor regression grade, clinicopathological characteristics, and survival time was statistically analyzed. Western blotting and in vitro clonogenic formation assay were used to detect PIK3CB expression in four colorectal cancer cell lines (HCT116, HT29, LoVo, and LS174T) treated with 6-Gy ionizing radiation. Pharmacological assays were used to evaluate the therapeutic relevance of TGX-221 (a PIK3CB-specific inhibitor) in the four colorectal cancer cell lines., Results: Immunohistochemical staining indicated that PIK3CB was more abundant in rectal adenocarcinoma tissues with poor response to preoperative radiotherapy. High expression of PIK3CB was closely correlated with tumor height (P < 0.05), ypT stage (P < 0.05), and high-degree tumor regression grade (P < 0.001). High expression of PIK3CB was a potential prognostic factor for local recurrence-free survival (P < 0.05) and metastasis-free survival (P < 0.05). High expression of PIK3CB was also associated with poor therapeutic response and adverse outcomes in rectal adenocarcinoma patients treated with 30-Gy/10-fraction preoperative radiotherapy. In vitro, PIK3CB expression was upregulated in all four colorectal cancer cell lines concurrently treated with 6-Gy ionizing radiation, and the PIK3CB-specific inhibitor TGX-221 effectively inhibited the clonogenic formation of these four colorectal cancer cell lines., Conclusion: PIK3CB is critically involved in response to preoperative radiotherapy and may serve as a novel target for therapeutic intervention.

Here in a co-cultivation system of natural killer (NK) cells and K562 cells, monocytes (MO) and/or interleukin (IL)-2/phytohemagglutinin (PHA) were administered. After MO were administered, reactive oxygen metabolites (ROM)/reactive nitrogen metabolites (RNM) productions increased, while tumor necrosis factor (TNF)-β/interferon (IFN)-γ levels and NK cell cytotoxicity (NCC) decreased, the changes of which after administering tiopronin (TIP) or glutamylcysteinylglycine (GSH) were opposite. In conclusions, the activated MO could inhibit the NK cell activity to kill K562 cell by secreting ROM and RNM. And TIP and GSH could scavenge both ROM and RNM to reverse the inhibitory effect of MO.

Objective: To explore the effects of the exogenous and endogenous reactive nitrogen metabolites (RNM) as NK cell inhibitors on NK cell-mediated killing of K562 cells and the influence of Tiopronin (TIP), glutamylcysteinylglycine (GSH) and histamine dihydrochloride (DHT) as RNM scavengers on reversing the suppressing effect of RNM., Methods: The exogenous ONOO(-) was administered in the NK+K562 culture system, then the RNM scavengers were added in the NK+K562+ONOO(-) culture system, respectively. The concentrations of RNM, TNF-beta and IFN-gamma, K562 cell inhibition rate (KIR) and the percentage of living NK cells were examined. IL-2+PHA were used as monocyte (MO) activators in the culture system of MO+NK+K562. Then TIP, GSH and DHT were administered and the parameters of NK cell activity were analyzed., Results: After exogenous ONOO(-) was administered in NK+K562 culture system, the percentage of living NK cells was decreased from (93.17 +/- 2.57)% to (71.87 +/- 1.02)% (P < 0.01) and KIR was decreased from (67.47 +/- 2.64)% to (43.44 +/- 2.87)% (P < 0.01). When TIP, GSH and DHT were administered into the systems, the percentage of living NK cells was increased to (91.13 +/- 3.67)% (P < 0.05), (88.03 +/- 1.46)% (P < 0.05), (73.60 +/- 2.76)% (P > 0.05), respectively; KIR was increased to (61.58 +/- 1.89)% (P < 0.05), (60.68 +/- 2.07)% (P < 0.05) and (45.26 +/- 3.31)% (P > 0.05), respectively. When IL-2/PHA were administered in the NK+K562+MO culture system, RNM products was increased from (82.10 +/- 6.60) micromom/L to (193.65 +/- 5.95) micromom/L(P < 0.01);KIR was decreased from (90.64 +/- 3.06)% to (61.29 +/- 2.22)% (P < 0.01). When the TIP, GSH and DHT were administered in the systems, RNM products were decreased to (91.32 +/- 6.81) micromom/L (P < 0.05), (84.66 +/- 5.99) micromom/L (P < 0.05) and (188.92 +/- 5.00) micromom/L (P > 0.05), respectively; KIR was increased to (84.31 +/- 4.56)%(P < 0.05), (81.65 +/- 3.09)% (P < 0.05) and (72.20 +/- 4.10)% (P < 0.05), respectively., Conclusion: NK Cell-mediated killing of K562 cells can be suppressed by exogenous and endogenous RNM administration. Both of TIP and GSH can protect NK cells by scavenging RNM and enhance the antineoplasmic activity of NK cells.

The purpose of this study was to understand the molecular genetic mechanism of mucopolysaccharidosis type II (MPS II) and to provide a prerequisite for future prenatal gene diagnosis. A preliminary diagnosis was made by qualitative detection of Urinary Glycosaminoglycans of the suspected MPS II proband. Then, mutation detection was performed on the proband and his family members with PCR and direct sequencing of PCR products. After the novel mutation of c.876 del 2 in IDS gene was detected, sequence analysis was performed on exon 6 of IDS gene of the 135 cases, which consisted of 120 randomly selected normal controls, and other 15 patients with MPS I, IV, and VI other than MPS II. Besides, the patho-genicity of the novel mutation was analyzed with the following 2 methods: conservative analysis of the sequence of muta-tion spots of different species and the direct test of the IDS enzyme activity of the patient and his relative family members. The result of uroscopy of the proband was strong positive (GAGs +++). There was a novel deletion mutation of c.876-877 del TC in the coding region of exon 6 of IDS gene, which was a hemizygous mutation. However, the mutation of his mother and sister was a heterozygous mutation. Detection of the exon 6 of IDS gene showed that the mutation was not found among normal controls and other patients with MPS I, IV, and VI other than MPS II. Homology comparison of amino acid sequences from different species showed that the phenylalanine (F) glutamine (Q) of the mutation site of c.876-877 del TC located in p.292-293 was highly conserved. The activity of IDS enzyme of the proband was only 2.3 nmol/4 h/mL, which was much lower than normal; but the activity of IDS enzyme of his father, mother and sister was 641.9 nmol/4 h/mL, 95.8 nmol/4h/mL and 103.2 nmol/4h/mL, respectively. These results illustrated that the deletion and frame-shift mutation of c.876-877 del TC detected was a novel pathologic mutation, which was the underlying cause of MPS II of this patient.

Electrochemical method using a novel Ti/RuO2 anode was employed to inhibit a typical cyanobacteria, Microcystis aeruginosa (M. aeruginosa) under different electrolytic conditions. It is demonstrated that Ti/RuO2 anode was more efficient than traditional graphite anode in M. aeruginosa inhibition. The experimental results showed that the higher current density or longer electrolytic time could effectively improve the inhibition of M. aeruginosa. In addition, sodium chloride was a more effective electrolyte than sodium sulfate to enhance inhibition. The maximum inhibiting rate dose to 100% could be obtained at a current density of 12 mA cm(-2) when sodium chloride was used as a supporting electrolyte. Furthermore, UV-Visible spectra demonstrated that the structures of phycocyanins and chlorophyll a (Chl a) in M. aeruginosa could be changed or destroyed during electrolysis. Moreover, EPR spectra showed the generation of the free radicals through electrolysis, which might be one of the reasons responsible for the inhibition of algal growth.

Objective: To understand the distribution of hepatitis B virus genotype in Guangxi and its clinical significance., Methods: Nested polymerase chain reaction (nPCR) was used for amplification of HBV DNA in sera of asymptomatic carrier (ASC) of hepatitis B virus (HBV) and patients with different liver diseases from southern and northern Guangxi. Specimens from 161 subjects were positive for HBV DNA and HBV genotype was determined by using restriction fragment length polymorphism analysis, direct sequencing or cloning sequencing., Results: The prevalence of genotype A was 3.7% in all samples and that of genotype B, C and D was 21.7%, 72.7% and 1.2%, respectively. No other genotypes (such as genotype E, F, G, H) were found. The prevalence of genotype C showed an increasing trend in ASC, chronic hepatitis, liver cirrhosis and hepatocellular carcinoma (HCC) group; in contrast, the prevalence of genotype B showed an opposite trend, although no statistically significant difference was observed, except between ASC and HCC (P=0.05). The HBeAg positive rate was higher, and the anti-HBe positive rate was lower in patients with chronic genotype C infection than in those with genotype B (P<0.05 for both). Liver function test (ALT) abnormality was more severe in genotype C group than in genotypes A and B groups having acute or chronic infection (P<0.01 for all comparisons). The prevalence of genotype C in southern Guangxi was higher than that in northern Guangxi. In contrast, the prevalence of genotype B in southern Guangxi was lower than that in northern Guangxi., Conclusions: 1. The predominant HBV genotypes in Guangxi were genotypes B and C. The major genotype in southern Guangxi was genotype C; while that in northern Guangxi was genotype B, which implied that the distribution of HBV genotype C was consistent with the incidence of HCC in Guangxi. 2. Genotype C maybe associated with development of severe liver diseases including HCC. 3. Genotype A,D and B+C were mostly found in acute, hepatitis and chronic hepatitis group.