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BACKGROUND Compression therapy is a common method for treating breast cancer-related lymphedema. However, no specific evidence exists to guide practitioners on the morbidity of lymphedema, limb volume, and range of motion. OBJECTIVE The aims of this study were to compare the effects of compression therapy and routine nursing during the treatment of breast cancer-related lymphedema and to provide a basis for better clinical decision-making. METHODS The PubMed, Cochrane Library, EMBASE, Web of Science, CBM, CNKI, Wanfang, and VIP databases were searched through January 21, 2021. Meta-analysis and description of the outcomes were performed by using the RevMan 5.3 software. RESULTS A total of 17 studies were included. A meta-analysis of 13 studies was conducted. The experimental group had a lower morbidity of lymphedema, the difference was significant, and there was no heterogeneity (P < .05; odds ratio, 0.35, I2 = 31%). There was no significant difference between the experimental group and control group in limb volume, and there was significant heterogeneity (P = .44, mean difference = 4.51, I2 = 85%). Regarding range of motion, the standardized mean difference of shoulder adduction, shoulder lift, shoulder abduction, and shoulder extension were 1.37, 0.69, 0.56, and 0.87, respectively, and the differences were significant; there was heterogeneity (P < .05, I2 = 92%). CONCLUSIONS Compression therapy can reduce the morbidity of lymphedema and improve limb movement, but the effect on limb volume needs to be further explored. IMPLICATION FOR PRACTICE In terms of therapeutic effectiveness and limb function, the results provide evidence that physicians can reduce the morbidity of lymphedema, reduce the degree of limb, and increase limb mobility by applying compression therapy.

Drug‐mediated or medical condition‐mediated disruption of hERG function accounts for the main cause of acquired long‐QT syndrome (acLQTs), which predisposes affected individuals to ventricular arrhythmias (VA) and sudden death. Many Chinese herbal medicines, especially alkaloids, have risks of arrhythmia in clinical application. The characterized mechanisms behind this adverse effect are frequently associated with inhibition of cardiac hERG channels. The present study aimed to assess the potent effect of Rutaecarpine (Rut) on hERG channels. hERG‐HEK293 cell was applied for evaluating the effect of Rut on hERG channels and the underlying mechanism. hERG current (IhERG) was measured by patch‐clamp technique. Protein levels were analysed by Western blot, and the phosphorylation of Sp1 was determined by immunoprecipitation. Optical mapping and programmed electrical stimulation were used to evaluate cardiac electrophysiological activities, such as APD, QT/QTc, occurrence of arrhythmia, phase singularities (PSs), and dominant frequency (DF). Our results demonstrated that Rut reduced the IhERG by binding to F656 and Y652 amino acid residues of hERG channel instantaneously, subsequently accelerating the channel inactivation, and being trapped in the channel. The level of hERG channels was reduced by incubating with Rut for 24 hours, and Sp1 in nucleus was inhibited simultaneously. Mechanismly, Rut reduced threonine (Thr)/ tyrosine (Tyr) phosphorylation of Sp1 through PI3K/Akt pathway to regulate hERG channels expression. Cell‐based model unables to fully reveal the pathological process of arrhythmia. In vivo study, we found that Rut prolonged QT/QTc intervals and increased induction rate of ventricular fibrillation (VF) in guinea pig heart after being dosed Rut for 2 weeks. The critical reasons led to increased incidence of arrhythmias eventually were prolonged APD90 and APD50 and the increase of DF, numbers of PSs, incidence of early after‐depolarizations (EADs). Collectively, the results of this study suggest that Rut could reduce the IhERG by binding to hERG channels through F656 and Y652 instantaneously. While, the PI3K/Akt/Sp1 axis may play an essential role in the regulation of hERG channels, from the perspective of the long‐term effects of Rut (incubating for 24 hours). Importantly, the changes of electrophysiological properties by Rut were the main cause of VA.

Objective Lower miss rates correlate with lower incidence of post-colonoscopy colorectal cancers and related mortality. This study evaluated the effectiveness of real-time use of a computer-aided detection system on number of polyp per colonoscopy and polyp detection rate ambispectively. Methods Eighty-five videos were retrospectively marked with computer-aided detection. Unmarked videos were reviewed by 2 senior endoscopists. Polyps that were detected in marked and unmarked videos were re-counted in parallel. One endoscopist recruited 128 consecutive patients through prospective evaluation. The endoscopist used standard colonoscopy monitor or computer-aided detection monitor alternately every two weeks. During withdrawal, the endoscopist focused on standard monitor or computer-aided detection monitor for different groups. Numbers of polyp per colonoscopy and polyp detection rate between two groups were prospectively compared. Results Re-counting polyps per colonoscopy in unmarked and marked videos were 73 and 88, mean numbers polyp per colonoscopy were 0.86 and 1.04 (p = 0.001, tested by paired t-test) respectively. The increment proportion of polyp per colonoscopy was 20.5%, where 14.7% marked videos detected more polyps than unmarked videos. Of 128 patients enrolled in prospective study, 186 polyps were detected. The mean number of polyp per colonoscopy were higher in computer-aided detection than in standard colonoscopy (1.66 vs. 1.13, p = 0.039). The polyp detection rate of computer-aided detection colonoscopy was significantly higher than that of standard colonoscopy (78.1% vs. 56.3%, p = 0.008). Conclusion Real-time computer-aided detection system significantly increased polyp detection rate and number of polyp per colonoscopy in a relevant high polyp detection rate situation.

A 33 years’ old male complained of excessive salivation with frequent swallowing and spitting, which resulted in communication disturbance, reduced quality of life, and social embarrassment for 19 years. He had been diagnosed as sialorrhea and submandibular gland hyperfunction by stomatologist, then had unilateral submandibular gland resection 13 years ago, but the symptom relief was not satisfactory. After that, he had been treated with glycopyrrolate for less than a year, which was withdrawn because of the short duration of symptomatic control after each tablet take-in and intolerable side effects. With the wish to receive a new treatment with long term effectiveness, low re-operation risk and normal preserved saliva secretion function, the patient was subject to MWA for the right submandibular gland. After systematic clinical evaluation, US-guided percutaneous MWA was successfully performed with an uneventful post-operative course. The volume of the right submandibular gland and ablated area were measured precisely by an ablation planning software system with automatic volume measurement function based on three-dimensional reconstruction of the pre-operative and post-operative enhanced magnetic resonance imaging (MRI) raw data. Finally, the ablated volume was calculated as 62.2% of the whole right submandibular gland. The patient was discharged 1 day after the operation, with symptoms relieved significantly, the mean value of whole saliva flow rate (SFR) decreased from 11 ml to 7.5 ml per 15 minutes. During the follow up by phone three months after operation, the patient reported that the treatment effect was satisfactory, whereas the SFR value became stable as 7 ml per 15 minutes, drooling frequency and drooling severity (DFDS) score decreased from 6 to 5, drooling impact scale (DIS) score decreased from 43 to 26. US-guided percutaneous MWA of submandibular gland seems to be an alternative, minimal invasive, and effective treatment for refractory sialorrhea. We described a patient with refractory sialorrhea treated successfully with ultrasound (US) guided percutaneous microwave ablation (MWA).

Coronary heart disease (CHD) is a common ischaemic heart disease whose pathological mechanism has not been fully elucidated. Single target drugs, such as antiplatelet aggregation, coronary artery dilation and lipid-lowering medicines, can relieve some symptoms clinically but cannot effectively prevent and treat CHD. Accumulating evidence has revealed that alterations in GM composition, diversity, and richness are associated with the risk of CHD. The metabolites of the gut microbiota (GM), including trimethylamine N-oxide (TMAO), short-chain fatty acids (SCFAs) and bile acids (BAs), affect human physiology by activating numerous signalling pathways. Due to the advantage of multiple components and multiple targets, traditional Chinese medicine (TCM) can intervene in CHD by regulating the composition of the GM, reducing TMAO, increasing SCFAs and other CHD interventions. We have searched PubMed, Web of science, Google Scholar Science Direct, and China National Knowledge Infrastructure (CNKI), with the use of the keywords “gut microbiota, gut flora, traditional Chinese medicine, herbal medicine, coronary heart disease”. This review investigated the relationship between GM and CHD, as well as the intervention of TCM in CHD and GM, and aims to provide valuable insights for the treatments of CHD by TCM.

Lung cancer is the most common type of cancer with the highest mortality rate worldwide. Non-small cell lung cancer (NSCLC) accounts for ~85% of the total number of lung cancer cases. In the past two decades, immunotherapy has become a more promising treatment method than traditional treatments (surgery, radiotherapy and chemotherapy). Immunotherapy has been shown to improve the survival rate of patients and to have a superior effect when controlling lung cancer than traditional therapy. However, only a small number of patients can benefit from immunotherapy, and not all patients who qualify experience long-term benefits. In the clinic, the objective response rate of programmed cell death protein 1 treatment without the prior screening of patients is only 15–20%. Immunotherapy is associated with both opportunities and challenges for patients with NSCLC. The current challenges of immunotherapy include the lack of accurate biomarkers, inevitable resistance and insufficient understanding of immune checkpoints. In previous years, several methods for overcoming the challenges posed by immunotherapy have been proposed, but combination therapy is the most suitable choice. A large number of studies have shown that the combination of drugs can significantly improve their efficacy, compared with monotherapy, and that some therapeutic combinations have been approved by the Food and Drug Administration for the treatment of NSCLC. Traditional Chinese medicine (TCM) is a traditional medical practice in China that can play an important role in immunotherapy. Most agents used in TCM originate from plants, and have the advantages of low toxicity and multiple targets. In addition, TCM includes a unique class of drugs that can improve autoimmunity. Therefore, TCM may be a promising treatment method for all types of cancer.

Patients with liver disease are susceptible to infection with Vibrio vulnificus (V. vulnificus), but the specific reasons remain elusive. Through RNA-seq, we found that when mice with alcoholic liver disease (ALD) were infected with V. vulnificus by gavage, compared with the Pair group, the small intestinal genes affecting intestinal permeability were upregulated; and the number of differentially expressed genes related to immune functions (e.g., such as cell chemotaxis, leukocyte differentiation, and neutrophil degranulation) decreased in the liver, spleen, and blood. Further analysis showed that the number of white blood cells decreased in the Pair group, whereas those in the ALD mice did not change significantly. Interestingly, the blood bacterial load in the ALD mice was about 100 times higher than that of the Pair group. After the ALD mice were infected with V. vulnificus, the concentrations of T cell proliferation-promoting cytokines (IL-2, IL-23) decreased. Therefore, unlike the Pair group, ALD mice had weaker immune responses, lower T cell proliferation-promoting cytokines, and higher bacterial loads post-infection, possibly increasing their susceptibility to V. vulnificus infection. These new findings we presented here may help to advance the current understanding of the reasons why patients with liver disease are susceptible to V. vulnificus infection and provides potential targets for further investigation in the context of treatment options for V. vulnificus sepsis in liver disease patient.

Introduction Staphylococcus aureus is a gram-positive bacterium that causes serious infection. With the increasing resistance of bacteria to current antibiotics, it is necessary to learn more about the molecular mechanism and cellular pathways involved in the Staphylococcus aureus infection. Methods We downloaded the GSE33341 dataset from the GEO database and applied the weighted gene co-expression network analysis (WGCNA), from which we obtained some critical modules. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) were applied to illustrate the biological functions of genes in these modules. We constructed the protein-protein interaction (PPI) network by Cytoscape and selected five candidate hub genes. Five potential hub genes were validated in GSE30119 by GraphPad Prism 8.0. The diagnostic values of these genes were calculated and present in the ROC curve based on the GSE13670 dataset. Their gene functions were analyzed by Gene Set Enrichment Analysis (GSEA). Results A co-expression network was built with 5000 genes divided into 11 modules. The genes in green and turquoise modules demonstrated a high correlation. According to the KEGG and GO analyses, genes in the green module were closely related to ubiquitination and autophagy. Subsequently, we picked out the top five hub genes in the green module. And UBB was determined as the hub gene in the GSE30119 dataset. The expression level of UBB, ASB, and MKRN1 could significantly differentiate between Staphylococcus aureus infection and healthy controls based on the ROC curve. The GSEA analysis indicated that lower expression levels of UBB were associated with the P53 signal pathway. Conclusions We identified some hub genes and significant signal enrichment pathways in Staphylococcus aureus infection via bioinformatics analysis, which may facilitate the development of potential clinical therapeutic strategies.

There is no data regarding prognostic impact of interleukin (IL)-26 on outcomes of patients with hepatocellular carcinoma (HCC). The present study aimed to evaluate the prognostic impact of IL-26 on HCC patients undergoing liver resection.From 2003 to 2008, 122 patients with HCC who received surgical curative resection were enrolled. Patients were stratified into IL-26-upper and -lower groups according to the median expression level from immunohistochemical staining of resected specimens. Prognostic impact of IL-26 was estimated using Kaplan-Meier curves. Univariate and multivariate analyses were performed to evaluate time-dependent prognostic impact and independency of IL-26. Demographic and clinical factors that were associated with IL-26 were comprehensively identified.Prognosis of the patients with high level of IL-26 revealed to be significantly unfavorable in both cumulative recurrence-free survival (P 0.001) and overall survival (P = 0.002). Upper expression of IL-26 (HR: 1.643; 95% CI: 1.021 to 2.644; P = 0.041) and microvascular invasion (HR: 3.303; 95% CI: 1.255 to 8.696; P = 0.016) were identified as significant independent prognostic factors for overall survival in the multivariable analysis.IL-26 is a novel prognostic factor for HCC after resection. Evaluation of IL-26 expression may be potentially valuable in clinical therapy when planning individualized follow-up schedule and evaluating candidates for prophylactic adjuvant treatment to prevent recurrence.

Background & Aims Chemokine-mediated immune cell recruitment plays pivotal roles in liver inflammation. C-C motif chemokine ligand 5 (CCL5) has been shown to be responsible for the recruitment of monocytes/macrophages and has been implicated in various liver diseases, including nonalcoholic fatty liver disease, fibrosis, and hepatocellular carcinoma. Previous studies have also shown that inhibition of CCL5 appears to be a promising therapeutic approach for several chronic liver diseases. However, whether blocking CCL5 could benefit immune cell–mediated hepatitis remains largely elusive. Methods By adopting a specific agonist, alpha-galactosylceramide (α-Galcer), of invariant natural killer T cells (iNKTs), we investigated the function and mechanism of CCL5 in the iNKT induced murine hepatitis model. Results We found significantly increased CCL5 expression in α-Galcer–induced hepatitis murine model. Such an increase in CCL5 is mainly enriched in non-parenchymal cells such as macrophages and iNKTs but not in hepatocytes. Surprisingly, CCL5 blockage by genetic deletion of Ccl5 does not affect the α-Galcer–induced iNKT activation but greatly worsens α-Galcer–induced liver injury accompanied by an increased hepatic neutrophil infiltration. Mechanistically, we demonstrated that greater neutrophil accumulation in the liver is responsible for the enhanced liver injury in Ccl5-/- mice. Such an increased hepatic neutrophil infiltration is mainly caused by an enhanced CXCL1-CXCR2 signal in Ccl5-/- mice. Therapeutically, either antibody-mediated neutrophil depletion or a CXCR2 antagonist, SB225002, mediated CXCR2 signaling blockage significantly ameliorated α-Galcer–induced liver injury in Ccl5-/- mice. Conclusions Our present study demonstrates that (1) α-Galcer–induced murine hepatitis could greatly induce CCL5 production in macrophages and iNKT cells; (2) loss of CCL5 could enhance CXCL1 expression in hepatocytes and activate CXCL1-CXCR2 axis in neutrophils to augment their hepatic infiltration; and (3) neutrophil depletion or blockage of CXCL1-CXCR2 axis greatly improves α-Galcer–induced liver injury in Ccl5-/- mice. This study suggests that clinical utilization of CCL5 blockage may compensatorily induce the activation of other chemokine pathways to enhance neutrophil recruitment and liver injury in hepatitis., Graphical abstract

Objective: To investigate the effects of exogenous α-linolenic acid (ALA) on in vitro maturation (IVM) and developmental competence of human oocytes. Methods: Experiment 1 examined the effects of ALA at different concentrations (0 [control], 10, 50, 100, and 200 μmol/L) in the IVM medium on oocyte maturation. Treatment with 50 μmol/L ALA significantly accelerated oocyte maturation (P < 0.05) and resulted in significantly higher mitochondrial DNA (mtDNA) copy number compared to the control. Hence, 50 μmol/L ALA was selected for combination with follicular fluid (FF) to investigate oocyte developmental potential. mtDNA of the matured oocyte was analyzed by real-time polymerase chain reaction. Experiment 2 investigated the effects of FF with optimal ALA concentration (Group A: ALA + FF + IVM medium) or without ALA (Group B: FF + IVM medium) on oocyte maturation, fertilization, 2 pronuclear cleavage, and embryo and blastocyst development. Malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were measured for maturation medium from Group A, Group B, and Group C (control group, IVM medium only). Results: Treatment with 50 μmol/L ALA obviously accelerated oocyte maturation (P < 0.05) and resulted in significantly higher mtDNA copy number (P < 0.05) in the matured oocytes compared to the control (0 μmol/L ALA). Supplementation of 50 μmol/L ALA and FF (Group A) obviously increased the total maturation rate than FF-treated group (Group B) which has higher (P < 0.05) total maturation rate than that of Group C. However, no significant differences were observed in fertilization, embryo availability, and blastocyst production among Group A, B, and C. Treatment with 50 μmol/L ALA decreased the level of MDA (P < 0.05), but had no effect on the activity of SOD in the IVM medium. Conclusions: Our results suggested that the treatment with 50 μmol/L ALA during IVM improves maturation in human oocytes. It is also likely to improve embryo availability and blastocyst formation. This might be associated with the alteration of mtDNA replication (increased mtDNA copy number) and the reduction of oxidative stress (reduced MDA level).

Liquid chromatography (LC) is a common and straight forward approach used in the evaluation of the quality of Traditional Chinese Medicines (TCMs). Quality control is a critical step when systematically assessing the efficacy of TCMs. In the present study, the spectrum-effect correlation method was used to identify pharmacologically active substances. The aim of the present study was to investigate the underlying correlations between common chemical compounds with antipyretic effects and the anti-endotoxin activity of Lonicera japonica. The common chemical constituents of Lonicera japonica were analyzed using LC, and the antipyretic effects and anti-endotoxin activity were determined using ELISAs. Combining the results of bivariate and principal component analysis methods, eight active constituents were qualitatively and quantitatively analyzed. The results of these analyses indicated that neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid and isochlorogenic acids A, B and C served a synergistic role with respect to antipyretic effects and anti-endotoxin activity. The present study lays a foundation for the future clinical use of Lonicera japonica.

Endometriosis is one of the most common diseases that happen in reproductive women. The main symptoms include ovarian endometrial cyst, pelvic pain, and so on. We report a case of a 23-year-old woman with a refractory long-course ovarian endometrial cyst (OEC). The patient was previously identified to have a hypoechoic mass sized 9.7 cm in diameter on ultrasound (US) in the right ovary and was tentatively diagnosed as OEC in another tertiary hospital, who was then subjected to US-guided cyst sclerotherapy while the procedure was failed since only a very small amount of viscous and sticky fluid can be aspirated. The patient was then referred to our hospital for further treatment. Pretreat contrast-enhanced ultrasound (CEUS) showed non-enhancement of the mass with a thin cyst wall and a cyst-in-cyst pattern was observed. The possibility of ovarian malignancy was ruled out and the initial diagnosis of OEC was confirmed. The patient was then subjected to US-guided cyst sclerotherapy with lauromacrogol. The interventional procedure was eventful that no fluid was aspirated as what happened in the previous hospital. Thus urokinase was used to dissolve the old, viscious and sticky blood and finally, all the fluid was aspirated. The total consumption of urokinase was 60,000 U. Then lauromacrogol as a sclerosant was injected into the cyst cavity and the cyst wall was flushed repeatedly with lauromacrogol until the aspirated fluid became light red. Finally, 20 mL lauromacrogol was reserved in the cyst and the interventional procedure cost 2 hours. The post-procedure course was uneventful without any discomfort, and the volume reduction rate of the cyst was 54%at 3-month follow-up. The visual analogue scale for the pain decreased from 4 before treatment to 1 after treatment, indicating a successful and effective outcome for the refractory long-course OEC.

Background Currently, Chlamydia trachomatis–specific host defense mechanisms in humans remain poorly defined. To study the characteristics of host cells infected early with Chlamydia trachomatis, we used bioinformatics methods to analyze the RNA transcription profiles of the conjunctiva, fallopian tubes, and endometrium in humans infected with Chlamydia trachomatis. Method The gene expression profiles of GSE20430, GSE20436, GSE26692, and GSE41075 were downloaded from the Gene Expression Synthesis (GEO) database. Then, we obtained the differentially expressed genes (DEGs) through the R 4.0.1 software. STRING was used to construct protein–protein interaction (PPI) networks; then, the Cytoscape 3.7.2 software was used to visualize the PPI and screen hub genes. GraphPad Prism 8.0 software was used to verify the expression of the hub gene. In addition, the gene–miRNA interaction was constructed on the NetworkAnalyst 3.0 platform using the miRTarBase v8.0 database. Results A total of 600 and 135 DEGs were screened out in the conjunctival infection group and the reproductive tract infection group, respectively. After constructing a PPI network and verifying the hub genes, CSF2, CD40, and CSF3 in the reproductive tract infection group proved to have considerable statistical significance. Conclusion In our research, the key genes in the biological process of reproductive tract infection with Chlamydia trachomatis were clarified through bioinformatics analysis. These hub genes may be further used in clinical treatment and clinical diagnosis.

Background. Influenza virus mainly causes acute respiratory infections in humans. However, the diagnosis of influenza is not accurate based on clinical evidence, as the symptoms of flu are similar to other respiratory virus. The lateral-flow assay is a rapid method to detect influenza virus. But the effectiveness of the technique in detecting flu viruses is unclear. Hence, a meta-analysis would be performed to evaluate the accuracy of LFA in detecting influenza virus. Methods. Relevant literature was searched out in PubMed, Embase, Web of Science, and Cochrane Library databases with the keywords “lateral flow assay” and “flu virus”. By Meta-DiSc software, pooled sensitivity, pooled specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), summary receiver operating characteristic curve (SROC), and area under the curve (AUC) can be calculated. Results. This meta-analysis contains 13 studies and 24 data. The pooled sensitivity and specificity of the influenza virus detected by LFA were 0.84 (95% CI: 0.82-0.86) and 0.97 (95% CI: 0.97-0.98), respectively. The pooled values of PLR, NLR, DOR, and SROC were 32.68 (17.16-62.24), 0.17 (0.13-0.24), 334.07 (144.27-773.53), and 0.9877. No publication bias was found. Conclusions. LFA exhibited high sensitivity and specificity in diagnosing influenza virus. It is a valuable alternative method which can diagnose influenza virus quickly. However, more evidence is required to confirm whether LFA is comparable to traditional methods for detecting the virus.

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.

Conventional methods in treating non–small cell lung cancer contain surgery, chemotherapy, radiotherapy, and targeted therapy, which have various defects. Recently, with the deeper research on tumor immunity, immunotherapy has made the breakthrough in the treatment of cancers. Especially developments of programmed cell death-1/programmed cell death ligand-1 (PD-1/PD-L1) inhibitors bring the therapy into a new stage. This review mainly focuses on introducing existing monoclonal antibodies containing nivolumab, pembrolizumab, atezolizumab, avelumab, and durvalumab, along with 3 ordinary biomarkers such as PD-L1 expression, tumor mutation burden, and microsatellite instability. By understanding the resistance mechanism of anti-PD-1/L1 blockade, research is further improving the survival benefit and expanding the benefit population. So, PD-1/PD-L1 inhibitors begin to be combined with various therapeutic strategies clinically. Discussion and comparison of their effectiveness and safety are also comprehensively reviewed. Meanwhile, we explore the potential, the impact, and mechanisms of combining traditional Chinese medicine with immunotherapy.

Currently, conventional methods of treating non-small cell lung cancer (NSCLC) have many disadvantages. An alternative effective therapy with minimal adverse reactions is urgently needed. Weijing decoction (WJD), which is a classic ancient Chinese herbal prescription, has been used successfully to treat pulmonary system diseases containing lung cancer in the clinic. However, the key active component and target of Weijing decoction are still unexplored. Therefore, for the first time, our study aims to investigate the pharmacological treatment mechanism of Weijing decoction in treating NSCLC via an integrated model of network pharmacology, metabolomics and biological methods. Network pharmacology results conjectured that Tricin is a main bioactive component in this formula which targets PRKCA to suppress cancer cell growth. Metabolomics analysis demonstrated that sphingosine-1-phosphate, which is regulated by sphingosine kinase 1 and sphingosine kinase 2, is a differential metabolite in plasma between the WJD-treated group and the control group, participating in the sphingolipid signaling. In vitro experiments demonstrated that Tricin had vital effects on the proliferation, pro-apoptosis, migration and colony formation of Lewis lung carcinoma cells. Through a series of validation assays, Tricin inhibited the tumor growth mainly by suppressing PRKCA/SPHK/S1P signaling and antiapoptotic signaling. On the other hand, Weijing formula could inhibit the tumor growth and prolong the survival time. A high dosage of Tricin was much more potent in animal experiments. In conclusion, we confirmed that Weijing formula and its primary active compound Tricin are promising alternative treatments for NSCLC patients.

Nicotinamide (Nam) has recently been characterized as an agent for tissue regeneration due to the observed pro‑proliferation effects. However, the effect of Nam on liver regeneration remains undetermined. In the present study, the potency of Nam as a regimen to promote liver regeneration and restore liver function was evaluated following partial hepatectomy (PH) on C57BL/6 mice. Ki‑67 immunohistochemical and cell cycle analyses demonstrated that exogenous Nam supplementation promoted the proliferation of hepatocytes and accelerated the recovery of liver tissue. The addition of Nam protected liver function following PH, as evidenced by hematoxylin and eosin staining of liver tissue morphology and measurement of serum liver injury markers. Notably, immunoblotting results revealed that the expression and activity of NAD‑dependent protein deacetylase sirtuin‑1 (SIRT1) were significantly upregulated following treatment with Nam, suggesting that Nam may promote liver regeneration through activation of SIRT1. The present study demonstrated that Nam regulated the process of liver regeneration and improved liver function by activating SIRT1, suggesting that Nam has the potency to be used for promoting liver regeneration following surgical resection.

Objective This study aims to study the effect of Rho kinase inhibitor fasudil on the expression endothelin-1 (ET-1) and nitric oxide (NO) in rats with hypoxic pulmonary hypertension (HPH). Methods Twenty-four male SD rats were randomly divided into three groups: control group, model group (HPH group) and HPH+fasudil group. The rat HPH model was established by intermittent hypoxia (IH) at atmospheric pressure. Mean pulmonary artery pressure (mPAP), right ventricular hypertrophy index (RVHI), ET-1 and NO levels, and pulmonary vascular structural changes were observed in all groups. Results MPAP, RVHI and ET-1 levels were significantly higher in HPH group than in control group, while NO was significantly lower than in control group. In addition, mPAP, RVHI and ET-1 were significantly lower in the HPH+fasudil group than in the HPH group. In the HPH group, ET-1 level was significantly and positively correlated with mPAP and RVHI, NO was negatively correlated with mPAP and RVHI levels, and ET-1 level was significantly and negatively correlated with NO level. In the HPH group, pulmonary arteriolar walls were generally thickened, and lumen stenosis was obvious; while after fasudil treatment, pulmonary arteriolar wall thickening and stenosis degree were significantly reduced. Conclusion Fasudil can significantly reduce ET-l level and increase NO level in HPH rats, suppressing the development of pulmonary arterial hypertension.

Hydrogen peroxide (H2O2) causes cell damage via oxidative stress. Heme oxygenase-1 (HO-1) is an antioxidant enzyme that can protect cardiomyocytes against oxidative stress. In this study, we investigated whether the heme precursor 5-aminolevulinic acid (5-ALA) with sodium ferrous citrate (SFC) could protect cardiomyocytes from H2O2-induced hypertrophy via modulation of HO-1 expression. HL-1 cells pretreated with/without 5-ALA and SFC were exposed to H2O2 to induce a cardiomyocyte hypertrophy model. Hypertrophy was evaluated by planar morphometry, 3H-leucine incorporation, and RT-PCR analysis of hypertrophy-related gene expressions. Reactive oxygen species (ROS) production was assessed by 5/6-chloromethyl-2′,7′-ichlorodihydrofluorescein diacetate acetylester. HO-1 and nuclear factor erythroid 2-related factor 2 (Nrf2) protein expressions were analyzed by Western blot. In our experiments, HL-1 cells were transfected with Nrf2 siRNA or treated with a signal pathway inhibitor. We found several results. 1) ROS production, cell surface area, protein synthesis, and expressions of hypertrophic marker genes, including atrial natriuretic peptide, brain natriuretic peptide, atrial natriuretic factor, and β-myosin heavy chain, were decreased in HL-1 cells pretreated with 5-ALA and SFC. 2) 5-ALA and SFC increased HO-1 expression in a dose- and time-dependent manner, associated with upregulation of Nrf2. Notably, Nrf2 siRNA dramatically reduced HO-1 expression in HL-1 cells. 3) ERK1/2, p38, and SAPK/JNK signaling pathways were activated and modulate 5-ALA- and SFC-enhanced HO-1 expression. SB203580 (p38 kinase), PD98059 (ERK), or SP600125 (JNK) inhibitors significantly reduced this effect. In conclusion, our data suggest that 5-ALA and SFC protect HL-1 cells from H2O2-induced cardiac hypertrophy via activation of the MAPK/Nrf2/HO-1 signaling pathway.

// Yan Wang 1, 2 , Jia-Xin Li 1 , Ying-Qing Wang 1 , Ze-Hong Miao 1 1 Division of Antitumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica , Chinese Academy of Sciences, Shanghai 201203, China 2 College of Pharmacy, Nanchang University, Nanchang 330006, China Correspondence to: Ze-Hong Miao, e-mail: zhmiao@simm.ac.cn Ying-Qing Wang, e-mail: yqwang@simm.ac.cn Keywords: tanshinone I, angiogenesis, Stat3, HIF-1α, VEGF Received: February 15, 2015 Accepted: March 23, 2015 Published: April 10, 2015 ABSTRACT Tanshinone I (Tanshinone-1), a major active principle of Salvia miltiorrhiza (Danshen), has been shown to overcome tumor drug resistance and metastasis. Here we report that tanshinone-1 inhibits angiogenesis. Tanshinone-1 inhibited proliferation, migration and tube formation of vascular endothelial cells, rat aortic ring sprouting and the neovascularization of the chick chorioallantoic membrane in a concentration-dependent manner. In endothelial cells, tanshinone-1 almost completely inhibited phosphorylation of Stat3 at Tyr705 regardless of hypoxia or normoxia but only slightly decreased the hypoxia-induced HIF-1α accumulation. In tumor cells, contrastively, tanshinone-1 could not only make phosphorylation of Stat3 at Tyr705 disappear but also reduce the hypoxia-induced accumulation of HIF-1α to its baseline levels at normoxia. Consequently, VEGF secretion from tumor cells was reduced, which could potentiate the direct inhibition of tanshinone-1 on endothelial cells. Together with its overcoming tumor drug resistance and metastasis, our results reveal unique characteristics of tanshinone-1 and its improved derivatives as promising angiogenesis inhibitors.

PML is involved in innate immune mechanisms against both DNA and RNA viruses. Although the mechanism by which PML inhibits highly divergent viruses is unclear, it was recently found that it can increase the transcription of interferon-stimulated genes (ISGs). However, whether human PML inhibits HIV-1 has been debated. Here we provide unambiguous, knockout-based evidence that PML does not restrict the early postentry stages of HIV-1 infection in a variety of human cell types and does not participate in the inhibition of HIV-1 by IFN-I. Although this study does not exclude the possibility of other mechanisms by which PML may interfere with HIV-1, we nonetheless demonstrate that PML does not generally act as an HIV-1 restriction factor in human cells and that its presence is not required for IFN-I to stimulate the expression of anti-HIV-1 genes. These results contribute to uncovering the landscape of HIV-1 inhibition by ISGs in human cells., The PML (promyelocytic leukemia) protein is a member of the TRIM family, a large group of proteins that show high diversity in functions but possess a common tripartite motif giving the family its name. We and others recently reported that both murine PML (mPML) and human PML (hPML) strongly restrict the early stages of infection by HIV-1 and other lentiviruses when expressed in mouse embryonic fibroblasts (MEFs). This restriction activity was found to contribute to the type I interferon (IFN-I)-mediated inhibition of HIV-1 in MEFs. Additionally, PML caused transcriptional repression of the HIV-1 promoter in MEFs. In contrast, the modulation of the early stages of HIV-1 infection of human cells by PML has been investigated by RNA interference, with unclear results. In order to conclusively determine whether PML restricts HIV-1 or not in human cells, we used the clustered regularly interspaced short palindromic repeat with Cas9 (CRISPR-Cas9) system to knock out its gene in epithelial, lymphoid, and monocytic human cell lines. Infection challenges showed that PML knockout had no effect on the permissiveness of these cells to HIV-1 infection. IFN-I treatments inhibited HIV-1 equally whether PML was expressed or not. Overexpression of individual hPML isoforms, or of mPML, in a human T cell line did not restrict HIV-1. The presence of PML was not required for the restriction of nonhuman retroviruses by TRIM5α (another human TRIM protein), and TRIM5α was inhibited by arsenic trioxide through a PML-independent mechanism. We conclude that PML is not a restriction factor for HIV-1 in human cell lines representing diverse lineages. IMPORTANCE PML is involved in innate immune mechanisms against both DNA and RNA viruses. Although the mechanism by which PML inhibits highly divergent viruses is unclear, it was recently found that it can increase the transcription of interferon-stimulated genes (ISGs). However, whether human PML inhibits HIV-1 has been debated. Here we provide unambiguous, knockout-based evidence that PML does not restrict the early postentry stages of HIV-1 infection in a variety of human cell types and does not participate in the inhibition of HIV-1 by IFN-I. Although this study does not exclude the possibility of other mechanisms by which PML may interfere with HIV-1, we nonetheless demonstrate that PML does not generally act as an HIV-1 restriction factor in human cells and that its presence is not required for IFN-I to stimulate the expression of anti-HIV-1 genes. These results contribute to uncovering the landscape of HIV-1 inhibition by ISGs in human cells.

Although many studies have investigated intensity-modulated radiation therapy (IMRT) for nasopharyngeal carcinoma (NPC), sample sizes in the reported studies are usually small and different in outcomes in different T and N subgroups are seldom analyzed. Herein, we evaluated the outcomes of NPC patients treated with IMRT and further explored treatment strategy to improve such outcome. We collected clinical data of 865 NPC patients treated with IMRT alone or in combination with chemotherapy, and classified all cases into the following prognostic categories according to different TNM stages: early stage group (T1-2N0-1M0), advanced local disease group (T3-4N0-1M0), advanced nodal disease group (T1-2N2-3M0), and advanced locoregional disease group (T3-4N2-3M0). The 5-year overall survival (OS), local relapse-free survival (LRFS), and distant metastases-free survival (DMFS) were 83.0%, 90.4%, and 84.0%, respectively. The early disease group had the lowest treatment failure rate, with a 5-year OS of 95.6%. The advanced local disease group and advanced nodal disease group had similar failure pattern and treatment outcomes as well as similar hazard ratios for death (4.230 and 4.625, respectively). The advanced locoregional disease group had the highest incidence of relapse and death, with a 5-year DMFS and OS of 62.3% and 62.2%, respectively, and a hazard ratio for death of 10.402. Comparing with IMRT alone, IMRT in combination with chemotherapy provided no significant benefit to locoregionally advanced NPC. Our results suggest that the decision of treatment strategy for NPC patients should consider combinations of T and N stages, and that IMRT alone for early stage NPC patients can produce satisfactory results. However, for advanced local, nodal, and locoregional disease groups, a combination of chemotherapy and radiotherapy is recommended.

Elite controllers (ECs) are a rare subset of HIV-1 slow progressors characterized by prolonged viremia suppression. HLA alleles B27 and B57 promote the cytotoxic T lymphocyte (CTL)-mediated depletion of infected cells in ECs, leading to the emergence of escape mutations in the viral capsid (CA). Whether those mutations modulate CA detection by innate sensors and effectors is poorly known. Here, we investigated the targeting of CA from B27/B57+ individuals by cytosolic antiviral factors Mx2 and TRIM5α. Toward that aim, we constructed chimeric HIV-1 vectors using CA isolated from B27/B57+ or control subjects. HIV-1 vectors containing B27/B57+-specific CA had increased sensitivity to TRIM5α but not to Mx2. Following exposure to those vectors, cells showed increased resistance against both TRIM5α-sensitive and -insensitive HIV-1 strains. Induction of the antiviral state did not require productive infection by the TRIM5α-sensitive virus, as shown using chemically inactivated virions. Depletion experiments revealed that TAK1 and Ubc13 were essential to the TRIM5α-dependent antiviral state. Accordingly, induction of the antiviral state was accompanied by the activation of NF-κB and AP-1 in THP-1 cells. Secretion of IFN-I was involved in the antiviral state in THP-1 cells, as shown using a receptor blocking antibody. This work identifies innate activation pathways that are likely to play a role in the natural resistance to HIV-1 progression in ECs., Author summary Some HIV-1-infected individuals show a natural capacity to control viral propagation. In individuals that have the HLA B27 or B57 allele, HIV-1 control is associated with mutations in viral proteins that arise as a result of immune pressure from cytotoxic T lymphocytes. HIV-1 capsid protein mutations found in these subjects render HIV-1 more sensitive to detection by TRIM5α, a cytoplasmic innate effector that targets retroviral capsids. We show here that HIV-1 bearing such mutations is restricted by TRIM5α but not by Mx2, another capsid-targeting innate effector. As a result, cells have decreased permissiveness to subsequent HIV-1 infections, a phenomenon that could contribute to the inefficient disease progression observed in these individuals. This knowledge might find applications in the development of immune interventions to increase human cells resistance to HIV-1.

The benefit of CABG over PCI for the patients with ULMCAD is controversial. Although many studies had less favorable short and mid-term outcomes of PCI in patients compare to CABG, there were limited papers on the long term survival outcomes. We sought to compare the long term (10 years) outcomes of

BACKGROUND AND OBJECTIVE At present, although appropriate radiotherapy and combined treatments are widely used for the patients with primary nasopharyngeal carcinoma (NPC), local or regional recurrence rates are still high. According to clinical performance, pathology, and diagnostic imaging of the patients with the first recurrence of NPC, this study analyzed the clinical features of recurrent NPC to provide a reference for tracking the rules of recurrence after the treatment of patients with NPC. METHODS Clinical data of 337 patients diagnosed with recurrent NPC for the first time were collected. The diagnoses were based on pathology and/or imaging and the patients were treated at the Sun Yat-sen University Cancer Center between January 1999 and December 2004. Data used for statistical analysis included clinical performance during the patient visit, the extension of the invasion as shown on imaging, pathologic features, Epstein-Barr virus (EBV) serology, restaging, etc. RESULTS Patients were staged according to the system developed by the International Union Against Cancer (UICC) and the American Joint Committee on Cancer (AJCC) in 2002. Patients with diseases at stages I/II accounted for 25.2%, while those with stage III/IV accounted for 74.8%. The median interval of relapse was 25 months. Patients had local recurrence (69.4%), regional recurrence (4.5%), or both (26.1%). Epistaxis and headache were the most common symptoms. Abduct dysfunction and facial numbness induced by cranial nerve damage were the most common signs. The probability of invasion of structures adjacent to the nasopharynx, such as the oropharynx, the prestyloid space, and the carotid sheath area, was low in patients with recurrent NPC. By contrast, the probability of invasion of structures far from the nasopharynx, such as the base of the skull, the paranasal sinuses, cranial nerves, the cavernous sinus, the brain, the pterygopalatine fossa, the infratemporal fossa, the orbital apex, and the soft palate, was higher in recurrent NPC. CONCLUSIONS The most common interval of relapse is about 2 years. The relapsed disease is usually more widespread and located deeper. Most recurrent NPC is advanced disease.

Differential sensitivity of RIP3-proficient and deficient murine fibroblasts to camptothecin anticancer drugs

Alveolar echinococcosis is a chronically progressive and potentially fatal disease. Patients with multiple giant alveolar echinococcosis have a poor prognosis when radical resection cannot be achieved, but curative resection can be limited by low future remnant liver volumes. In these cases, 2-stage liver resection may be a better choice: after a first-stage hepatectomy with partial resection, liver regeneration is allowed in the residual liver before proceeding to the second-stage hepatectomy. In this study, we therefore retrospectively reviewed and evaluated the safety and feasibility of two-stage hepatectomy in patients with multiple giant alveolar echinococcosis. We reviewed the data for all patients who underwent 2-stage hepatectomy for multiple giant alveolar echinococcosis between August 2013 and December 2015 at either the West China Hospital of Sichuan University or the Hospital of Ganzi Tibetan Autonomous Prefecture. We identified 7 patients in whom 2-stage hepatectomy was completed. During the first-stage hepatectomy, 4 patients underwent right-sided hepatectomy and the other 3 underwent left-sided hepatectomy. The second-stage hepatectomies were successfully performed 3 months after the first-stage procedures. All patients had follow-up durations of >1 year; there were no cases of operation-related mortality, and no patients experienced disease recurrence. Two-stage hepatectomy is safe and feasible for patients with multiple giant alveolar echinococcosis.

Background Serum pepsinogen (PG) levels are valuable in the diagnosis of gastric diseases. However, PG levels are affected by many factors such as the area and race. This study aimed to investigate serum PG levels in patients with different gastric diseases who were Chinese Han people in Hunan Province, midsouth China. Methods A total of 248 gastric disease patients and 34 healthy controls were enrolled. The patients included those with non-atrophic and chronic atrophic gastritis, gastric and duodenal ulcer, early and advanced gastric cancer. Serum PG I and II levels were detected by Biohit ELISA kit (Finland), and PG I/II ratio was calculated. Differences in patients with gastric disease and healthy controls were analyzed using paired t-test. Results Compared with controls, patients with early and advanced gastric cancer had a significantly lower PG I level and PG I/II ratio (p

During aortic surgery, interruption of spinal cord blood flow might cause spinal cord ischemia-reperfusion injury (IRI). The incidence of spinal cord IRI after aortic surgery is up to 28%, and patients with spinal cord IRI might suffer from postoperative paraplegia or paraparesis. Spinal cord IRI includes two phases. The immediate spinal cord injury is related to acute ischemia. And the delayed spinal cord injury involves both ischemic cellular death and reperfusion injury. Inflammation is a subsequent event of spinal cord ischemia and possibly a major contributor to spinal cord IRI. However, the development of inflammatory mediators is incompletely demonstrated. And treatments available for inflammation in spinal cord IRI are insufficient. Improved understanding about spinal cord IRI and the development of inflammatory cells and cytokines in this process will provide novel therapeutic strategies for spinal cord IRI. Inflammatory cytokines (e.g., TNF-αand IL-1) may play an important role in spinal cord IRI. For treatment of several intractable autoimmune diseases (e.g., rheumatoid arthritis), where inflammatory cytokines are involved in disease progression, anti-inflammatory cytokine antagonist is now available. Hence, there is great potential of anti-inflammatory cytokine antagonist for therapeutic use of spinal cord IRI. We here review the mediators and several possibilities of treatment in spinal cord IRI.

Background. To describe the clinical characteristics of the patients who suffered from relapse after conventional irradiation for nasopharyngeal carcinoma (NPC).Methods. Three hundred and fifty-one consecutive patients with first-time recurrent NPC between January 1999 and July 2005 were included. The patients’ clinical data were reviewed, including recurrent interval time, symptoms, signs, imaging characteristics, pathologic features, and restaging.Results. The median interval of relapse was 26.0 months. The most common symptoms in symptomatic patients were nasal bloody discharge (37.9%) and headache (31.1%). Local recurrence alone accounted for 73.5%. Most patients were restaged as stage III (23.1%) and stage IV (51.1%). Subgroup analysis suggested a significantly higher proportion of the long-latent relapses originated from early primary. A series of postreirradiation complications were more frequent in patients with longer latency at reception.Conclusions. Most recurrent nasopharyngeal carcinoma is advanced disease. Patients with different recurrent interval time show different nature behavior.

Purpose Reports of intensity-modulated radiotherapy (IMRT) for early-stage nasopharyngeal carcinoma (NPC) have been limited. The present study evaluated the long-term survival outcomes and toxicity of early-stage NPC patients treated with IMRT alone. Methods and Materials Between February 2001 and January 2008, 198 early-stage (T1-T2bN0-N1M0) NPC patients had undergone IMRT alone. The data from these patients were retrospectively analyzed. The patients were treated to 68 Gy at 2.27 Gy/fraction prescribed to the planning target volume of the primary nasopharygeal gross tumor volume. The Radiation Therapy Oncology Group scoring system was used to assess the toxicity. Results At a median follow-up of 50.9 months (range, 12–104), the 5-year estimated disease-specific survival, local recurrence-free survival, and distant metastasis-free survival rate was 97.3%, 97.7%, and 97.8%, respectively. The 5-year local recurrence-free survival rate was 100% for those with Stage T1 and T2a and 94.2% for those with Stage T2b lesions ( p = 0.252). The 5-year distant metastasis-free survival rate for Stage T1N0, T2N0, T1N1, and T2N1 patients was 100%, 98.8%, 100%, and 93.8%, respectively ( p = .073). All local recurrence occurred in patients with T2b lesions. Five patients developed distant metastasis. Of these 5 patients, 4 had had Stage T2bN1 disease and 1 had had Stage T2bN0 disease with retropharyngeal lymph node involvement. The most common acute toxicities were mainly Grade 1 or 2. At 24 months after IMRT, no Grade 3 or 4 xerostomia had developed, and 62 (96.9%) of 64 evaluated patients were free of trismus; only 2 patients (3.1%) had Grade 1 trismus. Radiation encephalopathy and cranial nerve injury were not observed. Conclusions IMRT alone for Stage T1N0, T2N0, T1N1, and T2N1 yielded satisfactory survival outcomes with acceptable toxicity, and no differences were found in survival outcomes among these four subgroups. Patients with Stage T2b lesions might have relatively greater risk of local recurrence and those with T2bN1 disease mighth have a greater risk of distant metastasis.

Background To investigate the clinical feature and the local failure patterns after intensity-modulated radiotherapy for nasopharyngeal carcinoma. Methods Between March 2007 and July 2009, 710 patients with nasopharyngeal carcinoma were treated with intensity-modulated radiotherapy. The magnetic resonance imagings obtained at recurrence were registered with the original planning computed tomography for dosimetry analysis. Results With a median follow-up of 38 months, 34 patients have developed local recurrence (32 cases valid). The incidence of invasion to nasopharynx, parapharyngeal space and the retropharyngeal space by the primary tumors was 100%, 75.0% and 62.5%, respectively, but 78.1%, 34.4% and 21.9% at recurrence, respectively. The rate of invasion to ethmoid sinus was 3.1% by the primary tumors but 28.1% at recurrence (p = 0.005). The topographic analysis of the local failure patterns showed "central" in 16 patients; "marginal" in 9; and "outside" in 7. The median volumes of primary gross tumor were 45.84 cm3 in the central failure group, 29.44 cm3 in the marginal failure group, and 21.52 cm3 in the outside failure group, respectively (p = 0.012), and the median volumes of primary clinical target1 were 87.28 cm3, 61.90 cm3 and 58.74 cm3 in the three groups, respectively (p = 0.033). Conclusions In patients with nasopharyngeal carcinoma treated with intensity-modulated radiotherapy, the recurrent tumors had their unique characteristic and regularity of invasion to adjacent structures. "Central" failure was the major local failure pattern. The volumes of primary gross tumor and clinical target1 were significantly correlated with recurrent patterns. Employ more aggressive approaches to tumor cells which will be insensitive to radiotherapy may be an effective way to reduce the central failure.