Effectiveness and safety of neoadjuvant apatinib in combination with capecitabine and oxaliplatin for the therapy of locally advanced colorectal cancer: A retrospective study.

The goal of the present study was to appraise the efficacy and safety of neoadjuvant apatinib in combination with capecitabine and oxaliplatin (XELOX) in patients with locally advanced colorectal cancer (CRC), as relevant data on its usage in this setting are lacking. A retrospective analysis was implemented on 100 patients with locally advanced CRC who received either neoadjuvant apatinib in combination with XELOX (N=50) or neoadjuvant XELOX alone (N=50). Radiological response and pathological complete response rates were evaluated. Furthermore, the researchers obtained data pertaining to disease-free survival (DFS), overall survival, as well as adverse events. The consequences of the present study indicated that the neoadjuvant apatinib in combination with XELOX treatment approach yielded higher rates of radiological objective response (86.0 vs. 68.0%, P=0.032) and major pathological response (46.0 vs. 22.0%, P=0.011) compared with XELOX alone. These findings were further confirmed through multivariate logistic regression analyses (P=0.037 and P=0.008, respectively). Interestingly, the neoadjuvant apatinib in combination with XELOX treatment approach significantly prolonged DFS when compared with XELOX alone (P=0.033). In summary, the administration of neoadjuvant apatinib in combination with XELOX demonstrates superiority over the use of XELOX alone in terms of achieving a more favorable pathological response and a longer duration of DFS in patients diagnosed with locally advanced CRC.

Multiple cystic echinococcosis in abdominal and pelvic cavity treated by surgery with a 4-year follow-up: a case report.

We report a case of a male patient who presented with multiple abdominal and pelvic echinococcosis. The patient had been diagnosed with hepatic echinococcosis for 7 years and developed intermittent distension and discomfort in the upper abdomen after an accidental fall. In recent years, the patient's abdominal distention increased gradually. Computed tomography revealed multiple hydatid cysts in the liver, spleen, abdominal cavity, and pelvic cavity. Abdominal organs were severely compressed, such that he could not eat normally except for a liquid diet. The patient underwent radical surgical resection based on the multi-disciplinary treatment (MDT) and the operation lasted 10 h, nearly 100 hydatid cysts were excised, about 18 liters of cyst fluid and cyst contents were removed, and the patient lost 20 kg of weight after surgery. The operation was successful, but there were still some postoperative complications such as hypovolemic shock, postoperative ascites, postoperative bile leakage. Treatment measures for the patient were anti-infection, antishock, clamping the abdominal drainage tube, and negative pressure abdominal puncture drainage. At follow up the patient's quality of life had been significantly improved with 15 kg weight gain compared to before.

Rs11479 in Thymidine Phosphorylase Associated with Prognosis of Patients with Colorectal Cancer Who Received Capecitabine-Based Adjuvant Chemotherapy.

Objective: Thymidine Phosphorylase (TYMP) gene was of potential significance in the process of colorectal cancer (CRC) development and played an important role in capecitabine metabolism. This study was to identify the association between TYMP polymorphism and prognosis of postoperative patients with CRC who received capecitabine-based adjuvant chemotherapy. Methods: A total of 218 patients with CRC who were treated with surgical resection and capecitabine-based adjuvant chemotherapy were included in this study retrospectively. Peripheral blood and peripheral blood mononuclear cell (PBMC) specimen of the patients were collected for the genotyping of TYMP polymorphism and TYMP mRNA expression, respectively. Univariate analysis of genotypes and prognosis was carried out by Kaplan-Meier survival analysis, Cox regression analysis was adopted in multivariate analysis. The mRNA expression of TYMP according to genotype status was analyzed using non-parameter test. Results: Prevalence of rs11479 in TYMP among the 218 patients exhibited that minor allele frequency of rs11479 was 0.20 (GG 141 cases, GA 68 cases and AA 9 cases), which was in accordance with Hardy-Weinberg equilibrium (P=0.825). Association analysis suggested that the median disease-free survival (DFS) of patients with GG genotype and GA/AA genotype was 3.1 and 6.1 years, respectively (P=0.004). Furthermore, the median overall survival of patients with GG genotype and GA/AA genotype was 5.0 and 7.0 years, respectively (P=0.033). Multivariate Cox regression analysis exhibited that rs11479 polymorphism was an independent factor for DFS (HR = 1.64, P=0.009). Additionally, of the 65 PBMC specimens, mRNA expression results indicated that patients with GA/AA genotypes conferred significantly higher mRNA expression of TYMP than that of patients with GG genotype (P<0.001). Conclusion: Polymorphism rs11479 in TYMP gene might predict the prognosis of patients with CRC who received capecitabine-based adjuvant chemotherapy through mediation of the mRNA expression of TYMP. The conclusion of this study should be validated in prospective clinical trials subsequently.

Gallbladder disease is associated with the risk of cardiovascular disease among Uyghurs in Xinjiang: a prospective cohort study.

BACKGROUND: Gallbladder disease (GBD) can increase the risk of cardiovascular disease (CVD). However, GBD has rarely been reported in the less developed, rural areas of Xinjiang. This study aimed to determine the prevalence of GBD and incidence of CVD in a prospective cohort study in rural Xinjiang. Moreover, the study aimed to explore the association between GBD and CVD within this cohort. METHODS: The study cohort included 11,444 Uyghur adults in Xinjiang, 3rd division, from the 51st Mission. Study groups were classified according to whether GBD was present or absent at baseline. The occurrence of CVD was the end event. Demographic, anthropometric, and biochemical data were recorded, and the incidence of CVD in the GBD and non-GBD groups analysed. Cox proportional hazards regression models were used to assess the association between GBD and CVD and factors associated with their incidence. Several subgroup analyses were performed to assess CVD incidence in different subgroups. The interaction between GBD and cardiometabolic risk factors, and subsequent risk of developing CVD, was evaluated. RESULTS: Prevalence of GBD in the study cohort was 10.29%. After a median follow-up of 4.92 years, the cumulative incidence of CVD in the study cohort was 10.49%, 8.43% in males and 12.65% in females. CVD incidence was higher in the GBD group (34.04% vs. 7.78%, HR = 4.96, 95% CI: 4.40-5.59). After multivariate adjustment, the risk of CVD remained higher in the GBD group (HR = 2.89, 95% CI: 2.54-3.29). Subgroup analyses showed male sex, smoking, alcohol consumption, lack of exercise, and abnormal renal function were all associated with increased risk of CVD. Moreover, the risk of CVD was markedly higher in GBD combined with cardiometabolic risk factors (hypertension, T2DM, dyslipidaemia, overweight, and abdominal obesity), than in cardiometabolic risk factors alone and this was higher in the GBD group than in the non-GBD group regardless of whether cardiometabolic risk factors were combined. CONCLUSION: GBD is an important independent risk factor for CVD development. Awareness of these associations will raise concerns among clinicians about the risk of cardiovascular disease in patients with GBD.

Effect of body mass index on surgical site wound infection, mortality, and postoperative hospital stay in subjects undergoing possibly curative surgery for colorectal cancer: A meta-analysis.

We performed a meta-analysis to evaluate the effect of body mass index on surgical site wound infection, mortality, and postoperative hospital stay in subjects undergoing possibly curative surgery for colorectal cancer. A systematic literature search up to March 2022 was performed and 2247 subjects with possibly curative surgery for colorectal cancer at the baseline of the studies; 2889 of them were obese, and 9358 were non-obese. Odds ratio (OR) and mean difference (MD) with 95% confidence intervals (CIs) were calculated to assess the effect of body mass index on surgical site wound infection, mortality, and postoperative hospital stay in subjects undergoing possibly curative surgery for colorectal cancer using the dichotomous or contentious methods with a random or fixed-effect model. The obese subjects had a significantly higher surgical site wound infection after colorectal surgery (OR, 1.87; 95% CI, 1.62-2.15, P < .001), and higher mortality (OR, 1.58; 95% CI, 1.07-2.32, P = .02) in subjects with possibly curative surgery for colorectal cancer compared with non-obese. However, obese did not show any significant difference in postoperative hospital stay (MD, 0.81; 95% CI, -0.030 to 1.92, P = .15) compared with non-obese in subjects with possibly curative surgery for colorectal cancer. The obese subjects had a significantly higher surgical site wound infection after colorectal surgery, higher mortality, and no significant difference in postoperative hospital stay compared with non-obese in subjects with possibly curative surgery for colorectal cancer. The analysis of outcomes should be with caution because of the low number of studies in certain comparisons.

Ubiquitin signaling in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignant tumor of the digestive system, characterized by rapid progression and being prone to metastasis. Few effective treatment options are available for PDAC, and its 5-year survival rate is less than 9%. Many cell biological and signaling events are involved in the development of PDAC, among which protein post-translational modifications (PTMs), such as ubiquitination, play crucial roles. Catalyzed mostly by a three-enzyme cascade, ubiquitination induces changes in protein activity mainly by altering their stability in PDAC. Due to their role in substrate recognition, E3 ubiquitin ligases (E3s) dictate the outcome of the modification. Ubiquitination can be reversed by deubiquitylases (DUBs), which, in return, modified proteins to their native form. Dysregulation of E3s or DUBs that disrupt protein homeostasis is involved in PDAC. Moreover, the ubiquitination system has been exploited to develop therapeutic strategies, such as proteolysis-targeting chimeras (PROTACs). In this review, we summarize recent progress in our understanding of the role of ubiquitination in the development of PDAC and offer perspectives in the design of new therapies against this highly challenging disease.

The value of hsa_circ_0058514 in plasma extracellular vesicles for breast cancer.

The aim of this study was to investigate the diagnostic value of hsa_circ_0058514 in plasma extracellular vesicles (EVs) in BC patients and its predictive value for neoadjuvant chemotherapy. The expression of hsa_circ_0058514 in a large sample of BC plasma and healthy subjects' plasma was detected by qPCR, and the ROC curve was drawn to verify its diagnostic value as a plasma tumor marker. Furthermore, the association between the expression of hsa_circ_0058514 and clinicopathological characteristics before and after treatment was detected in the plasma of 40 pairs of BC patients undergoing neoadjuvant therapy. The expression level of hsa_circ_0058514 in the plasma of BC patients was significantly higher than that of healthy subjects. The ROC curve showed that plasma hsa_circ_0058514 ROC in differentiating non-metastatic BC and healthy people had better diagnostic efficiency than conventional tumor markers CA153, CA125, and CEA. In patients with neoadjuvant therapy, the decrease in plasma hsa_circ_0058514 value before and after treatment correlated with pathological MP grade (r = 0.444, p = 0.004) and imaging tumor regression value (r = 0.43, p = 0.005) positive correlation. The detection of hsa_circ_0058514 in both extracellular vesicles of BC cell culture medium and human plasma was demonstrated. Hsa_circ_0058514 is detected in the plasma from BC cells secreted in the form of vesicles. Hsa_circ_0058514 can be used as an early plasma biological indicator for the diagnosis of BC in clinical applications, with a higher risk of recurrence and metastasis, and as a predictor of the effect of neoadjuvant therapy to guide the clinical use of neoadjuvant therapy.

Impact of a haplotype (composed of the APC, KRAS, and TP53 genes) on colorectal adenocarcinoma differentiation and patient prognosis.

BACKGROUND: Many types of gene mutation are associated with the drug resistance of cancer cells. XELOX is a new and efficient surgical adjuvant chemotherapy for colorectal adenocarcinoma. However, drug-resistant related genetic mutations associated with this treatment remain unknown. METHODS: Next-generation sequencing (NGS) was performed on 36 colorectal cancer patients to identify mutations among patients with residual tumors following preoperative chemotherapy. Enrichment and prognosis of these mutations were evaluated in a TCGA cohort. The pathology of cases with poor prognosis-related mutations was also determined. RESULTS: A sequence of SNPs associated with the APC, KRAS, and TP53 genes in 13 of 19 subjects with residual tumors after preoperative chemotherapy was identified. Using survival analysis data from 317 cases in the TCGA database, a prognosis-related haplotype composed of SNPs from APC, KRAS, and TP53 was assembled. Colorectal cancer patients with these mutations had a lower 5-year tumor-specific survival rate than those without (p < 0.05). Most patients with these mutations were at a higher clinical stage (III-IV) of disease. Enrolled subjects with the identified haplotype tended to have poor cancer cell differentiation. CONCLUSIONS: The prognosis-related haplotype can be used as a marker of drug resistance and prognosis in colorectal cancer patients after preoperative chemotherapy.

Correction: An integrated surgical training program for hepatic cystic echinococcosis in Xinjiang of China.

[This corrects the article DOI: 10.1371/journal.pntd.0008023.].

Automatic Real-Time Space Registration Application for Simulating Dental and Maxillofacial Surgery.

ABSTRACT: Real-time surgical navigation systems are important for preoperative planning and intraoperative navigation. Automatic preoperative multimodal data registration and postoperative spatial registration are extremely crucial in such surgical navigation systems. However, existing automatic multimodal data registration methods have extremely limited application scope due to the lack of accuracy and speed. In addition, the registration results obtained by existing methods are practically lacking and are rarely applied in clinics. To address the above issues, this paper proposes a novel real-time teeth registration algorithm with computed tomography (CT) data and optical tracking scanning data. The proposed method is based on the weighted iterative closest point (ICP) algorithm with 3 improvements: (1) the multilayer spherical point set is generated inside the laser scanning marker sphere, (2) the weight decreases from inside to outside layer by layer, and (3) the weight of the voxel center point set is combined with the CT data of the marker sphere. Specifically, the proposed iCP registration method can overcome the limitation of surface point set registration and tackle the problem of high surface deformity of laser scanning marker spheres. For the registration result of CT and scanning data, the authors employ the real-time spatial registration algorithm based on optical tracking to complete the navigation of the simulated surgical instruments on the multimodal fusion image. The experimental results show that the proposed ICP algorithm reduces the mean square error by 1 order of magnitude and that our method has strong practical value.

Synovial calprotectin for the diagnosis of periprosthetic joint infection: a diagnostic meta-analysis.

BACKGROUND: Periprosthetic joint infections (PJI) are a rare but severe complication of total joint arthroplasty (TJA). However, the diagnosis of PJI remains difficult. It is one of the research that focuses about diagnosis for PJI for majority researchers to discover a novel biomarker. This meta-analysis tried to evaluate diagnostic value of synovial calprotectin for PJI. METHODS: This meta-analysis search of the literature was conducted in PubMed, EMBASE, Web of Science, and the Cochrane Library. Literature quality was appraised using Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) based on RevMan (version 5.3). The diagnostic value of calprotectin for PJI was evaluated by calculating sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), diagnostic score and area under SROC (AUC) based on the Stata version 14.0 software. We conduct subgroup analysis according to the study design, cutoff values, the country of study, and gold standard. RESULTS: Seven studies were included in this meta-analysis. The pooled sensitivity of synovial calprotectin for the diagnosis of PJI was 0.94 (95% CI, 0.87-0.98), and the specificity was 0.93 (95% CI, 0.87-0.96). The pooled AUC, PLR, and NLR for synovial calprotectin were 0.98 (95% CI, 0.96-0.99), 13.65 (95% CI, 6.89-27.07), and 0.06 (95% CI, 0.02-0.15), respectively. The pooled diagnostic score and DOR were 5.4 (95% CI, 3.96-6.85) and 222.32 (95% CI, 52.52-941.12), respectively. CONCLUSION: In summary, this meta-analysis indicates that synovial calprotectin is a promising biomarker of assistant diagnosis for PJI, as well as recommended test for excluding diagnostic tool.

Genomic profiling of a patient with quadruple synchronous colorectal cancer: a case report.

BACKGROUND: Synchronous colorectal cancer (SCRC) is featured by the presence of multiple primary tumor lesions in a single patient at initial diagnosis. It is less common with the prevalence of approximately 3.5% among colorectal cancer (CRC). Some studies of SCRC have been performed in patients with two tumor lesions. However, SCRC cases with three or more tumor lesions were rare and remained to be investigated. CASE PRESENTATION: In this case report, we presented a 56-year-old male SCRC case with quadruple tumor lesions which is rarely seen in clinical practice. After laparoscopic radical resection of sigmoid carcinoma and partial rectum resection, the four tumor samples were subjected to pathological evaluation and next-generation sequencing (NGS) based genetic profiling. The four tumor lesions included two adenocarcinomas with moderate differentiation at sigmoid colon and rectum respectively, a grade 1 neuroendocrine tumor (NET) at rectum and a high-grade intraepithelial neoplasia at ascending colon. Each tumor exhibited distinct histology types and mutation profiles. After surgical resection, the patient remained disease-free after four cycles of chemotherapy with oxaliplatin and capecitabine (XELOX). CONCLUSIONS: The tumor lesions in this case showed different pathological and genetic features which indicats the heterogeneity of SCRC. The genomic profilling might provide novel insights to understand SCRC at molecular level.

Comprehensive Analysis of HDAC Family Identifies HDAC1 as a Prognostic and Immune Infiltration Indicator and HDAC1-Related Signature for Prognosis in Glioma.

Background: The histone deacetylase (HDAC) family limited accessibility to chromatin containing tumor suppressor genes by removing acetyl groups, which was deemed a path for tumorigenesis. Considering glioma remained one of the most common brain cancers with a dichotomy prognosis and limited therapy responses, HDAC inhibitors were an area of intensive research. However, the expression profiles and prognostic value of the HDACs required more elucidation. Methods: Multiple biomedical databases were incorporated, including ONCOMINE, GEPIA, TCGA, CGGA, GEO, TIMER, cBioPortal, and Metascape, to study expression profiles, prognostic value, immune infiltration, mutation status, and enrichment of HDACs in glioma. STRING and GeneMANIA databases were used to identify HDAC1-related molecules. LASSO regression, Cox regression, Kaplan-Meier plot, and receiver operating characteristic (ROC) analyses were performed for HDAC1-related signature construction and validation. Results: HDAC1 was significantly overexpressed in glioma, while HDAC11 was downregulated in glioblastoma. Except for HDAC 6/9/10, the HDAC family expression was significantly associated with glioma grade. Most of the HDAC family also correlated with glioma genetic mutations. Higher HDAC1 expression level predicted more dismal overall survival (OS) (p < 0.0001) and disease-free survival (DFS) (p < 0.0001), but a higher level of HDAC11 held more favorable OS (p = 2.1e-14) and DFS (p = 4.8e-08). HDAC4 displayed the highest mutation ratio, at 2.6% of the family. The prognostic value of HDAC1 was validated with ROC achieving 0.70, 0.77, 0.75, and 0.80 as separability for 1-, 3-, 5-, and 10-years OS predictions in glioma, respectively. Moreover, HDAC1 expression positively correlated with neutrophil (r = 0.60, p = 2.88e-47) and CD4+ T cell infiltration (r = 0.52, p = 3.96e-35) in lower-grade glioma. The final HDAC1-related signature comprised of FKBP3, HDAC1 (Hazard Ratio:1.49, 95%Confidence Interval:1.20-1.86), PHF21A, RUNX1T1, and RBL1, and was verified by survival analysis (p < 0.0001) and ROC with 0.80, 0.84, 0.83, and 0.88 as separability for 1-, 3-, 5-, and 10-years OS predictions, respectively. The signature was enriched in chromatin binding. Conclusion: HDAC family was of clinical significance for glioma. Most of the HDAC family significantly correlated with the glioma grade, IDH1 mutation, and 1p/19q codeletion. HDAC1 was both a prognostic and immune infiltration indicator and a central component of the HDAC1-related signature for precise prognosis prediction in glioma.

The Diagnostic Value of Serum Exosomal Has_circ_0000615 for Breast Cancer Patients.

BACKGROUND: To explore the expression level of has_circ_0000615 in peripheral blood samples and evaluate its diagnostic value for breast cancer patients. METHODS: The peripheral blood samples of 95 breast cancer patients who underwent curative surgical resection and 95 age-matched healthy volunteers in our institutions from September 2019 to November 2020 were systematically collected. The expression level of has_circ_0000615 in the plasma was amplified and detected by qRT-PCR, and its correlation to clinicopathological characteristics of breast cancer patients were analyzed. RESULTS: Breast cancer patients had a significantly higher expression level of has_circ_0000615 in the plasma than healthy controls (P < 0.01), and its high expression was closely associated with advanced tumor stage (P=0.010), lymph node metastasis (P = 0.001) and high grade of recurrence risk (P=0.012). The receiver operator characteristic (ROC) curves showed that the area under curve (AUC) value, sensitivity and specificity of has_circ_0000615 for the diagnosis of non-metastatic breast cancer was 0.904 (95% CI: 0.863-0.944), 76.8% and 88.4%, respectively. Serum has_circ_0000615 expression had a better diagnostic efficiency than routine tumor biomarkers such as CA153, CA125 and CEA for distinguishing breast cancer patients from healthy individuals. TEM revealed that isolated exosomes from the culture medium of breast cancer cells had a disk-like appearance with a diameter of 80-200 nm vesicles, and the expression of exosome markers CD9 and CD81 was markedly increased. More importantly, the expression of has_circ_0000615 was detected in the exosomes and its expression level was markedly upregulated in breast cancer cell lines compared with normal ductal epithelial cells. The stability assay showed that there was no difference between RNA extraction at 0 hour and 24 hours in terms of the expression of has_circ_0000615 (P =0.327). Has_circ_0000615 might as exosomes be secreted into the circulating blood of breast cancer patients, resulting in a high expression level in plasma samples. CONCLUSION: The detection of has_circ_0000615 might be a promising diagnostic method for breast cancer.

Survival benefit of induction chemotherapy for locally advanced nasopharyngeal carcinoma: prognosis based on a new risk estimation model.

BACKGROUND: Although the National Comprehensive Cancer Network (NCCN) Guidelines recommend CCRT+AC and IC + CCRT as level 2A evidence for treatment of the locoregionally advanced NPC (II-IVa), IC + CCRT+AC could also be an alternative but it is seldom used because of the low completion rates. This article aimed to compare the effectiveness of the three radiotherapy regimens using a large-scale retrospective study. METHODS: This retrospective single center analysis enrolled 1812 diagnosed NPC patients at Nanfang Hospital from January 2005 to December 2015 and only 729 patients met the inclusion criteria and were analyzed. Patients without distant metastasis, age of 18-70 years, Karnofsky scores of at least 70,stage III-IVb, and adequate adequate bone marrow, liver and renal function. Were enrolled. Adverse events and other categorical variables were compared by Pearson chi-square test or Fishier exact test. Time-to-event data were described with the Kaplan-Meier curves, time-to-event intervals compared with the log-rank test. We did multivariable analyses with the Cox proportional hazards model to test the independent signifi cance of diff erent factors. Cox proportional hazards model was used to estimate the ß regression coeffi cient, p value, and hazard ratio and its 95% CI for each of the selected risk predictors. RESULTS: The median follow-up time was 47 months. Kaplan-Meier analyses revealed no significant differences among three groups in 3-year failure-free survival (FFS, P = 0.225), 3-year overall survival (OS, P = 0.992), 3-year locoregional failure-free survival (LFFS, P = 0.549), and 3-year distant failure-free survival (DFFS, P = 0.174). Stratified survival analysis based on the risk scoring model revealed no differences in FFS, OS, LFFS, and DFFS between IC + CCRT and CCRT+AC groups for low-risk patients, however, the 3-year OS (88.3% vs. 77.6%, P = 0.049) and 3-year DFFS (84.0% vs.66.8%, P = 0.032) were respectively significantly better in IC + CCRT group compared with CCRT+AC group for high-risk patients. CONCLUSIONS: Compared with CCRT+AC, IC + CCRT lowers distant metastasis rate and improves OS among patients with locally advanced NPC in high risk group.

Long-term monitoring of dynamic changes in plasma EBV DNA for improved prognosis prediction of nasopharyngeal carcinoma.

BACKGROUND: This study was performed to investigate whether long-term monitoring of dynamic changes in plasma Epstein-Barr virus (EBV) DNA could improve prognosis prediction of nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: About 1077 nonmetastatic NPC patients were recruited to retrospectively analyze the prognostic value of plasma EBV DNA load pretreatment and 3, 12, 24, and 36 months posttreatment. We also examined the prognostic value of dynamic changes in plasma EBV DNA at various time points. RESULTS: Patients with plasma EBV DNA load above optimal pre- and posttreatment cut-offs had significantly worse five-year progression-free survival, distant metastasis-free survival, locoregional relapse-free survival, and overall survival (OS) at all-time points, excluding only OS at 36 months posttreatment due to limited mortalities. Patients with persistently undetectable plasma EBV DNA at the first four time points had the best prognosis, followed by those with positive detection pretreatment and consistently negative detection posttreatment, those with negative detection pretreatment and positive detection at one time point posttreatment, and those with positive detection pretreatment and at one time point posttreatment, whereas patients with positive detection at ≥2 time points posttreatment had the worst prognosis. Cox proportional hazard models identified the dynamic change pattern as an independent prognostic factor, and receiver operating characteristic curve analysis demonstrated that the dynamic change at four time point was more valuable than any single time point for predicting disease progression, distant metastasis, locoregional relapse, and mortality. CONCLUSIONS: Dynamic changes in plasma EBV DNA pre- and posttreatment could predict the long-term survival outcome and provide accurate risk stratification in NPC.

Correction: FengLiao affects gut microbiota and the expression levels of Na+/H+ exchangers, aquaporins and acute phase proteins in mice with castor oil-induced diarrhea.

[This corrects the article DOI: 10.1371/journal.pone.0236511.].

Development of Autophagy Signature-Based Prognostic Nomogram for Refined Glioma Survival Prognostication.

The current glioma classification could be optimized to cover such a separate and individualized prognosis ranging from a few months to over ten years. Considering its highly conserved role and potential in therapies, autophagy might be a promising element to be incorporated as a refinement for improved survival prognostication. The expression and RNA-seq data of 881 glioma patients from the Gene Expression Omnibus and The Cancer Genome Atlas were included, mapped with autophagy-related genes. Weighted gene coexpression network analysis and Cox regression analysis were used for the autophagy signature establishment, which composed of MUL1, NPC1, and TRIM13. Validations were represented by Kaplan-Meier plots and receiver operating curves (ROC). Cluster analysis suggested the IDH1 mutant involved in the favorable prognosis of the signature clusters. The signature was also immune-related shown by the Gene Ontology analysis and the Gene Set Enrichment Analysis. The high signature risk group held a higher ESTIMATE score (p = 2.6e - 11) and stromal score (p = 1.8e - 10). CD276 significantly correlated with the signature (r = 0.51, p < 0.05). The final nomogram integrated with the autophagy signature, IDH1 mutation, and pathological grade was built with accuracy and discrimination (1-year survival AUC = 0.812, 5-year survival AUC = 0.822, and 10-year survival AUC = 0.834). Its prognostic value and clinical utility were well-defined by the superiority in the comparisons with the current World Health Organization glioma classification in ROC (p < 0.05) and decision curve analysis. The autophagy signature-based IDH1 mutation and grade nomogram refined glioma classification for a more individualized and clinically applicable survival estimation and inspired potential autophagy-related therapies.

FengLiao affects gut microbiota and the expression levels of Na+/H+ exchangers, aquaporins and acute phase proteins in mice with castor oil-induced diarrhea.

The severe side effects of chemosynthetic anti-diarrhea drugs have created an interest in low-toxic alternative plant-derived compounds. FengLiao consists of Polygonum hydropiper Linn. and Daphniphyllum calycinum Bench., and is widely used in China to treat diarrhea due to low levels of toxicity. In this study, the effects of FengLiao were analyzed in a castor oil-induced diarrhea model, using the anti-diarrhea drug, loperamide, as the positive control. The effects were evaluated using stool characteristics and the expression levels of various diarrhea-related factors in the jejunum and liver, as well as changes in the microbiota of the jejunum. The symptoms of diarrhea and stool consistency were improved through FengLiao and loperamide treatment. Furthermore, FengLiao down-regulated alpha 1-acid glycoprotein (AGP) and C-reactive protein (CRP) levels, and up-regulated transferrin (TRF) mRNA levels in the liver, and down-regulated Aquaporin 3 (AQP3) and Na+/H+ exchanger isoform 8 (NHE8) expression in the epithelial cells of the jejunum. It also increased the relative abundance of Bifidobacterium, Aerococcus, Corynebacterium_1 and Pseudomonas, and lowered the Firmicutes/Bacteroidetes (F/B) ratio, which maintained the balance between immunity and intestinal health. Taken together, FengLiao alleviated castor oil-induced diarrhea by altering gut microbiota, and levels of jejunum epithelial transport proteins and acute phase proteins.

Human serum albumin-based doxorubicin prodrug nanoparticles with tumor pH-responsive aggregation-enhanced retention and reduced cardiotoxicity.

Doxorubicin (DOX) is a widely-used anticancer drug, but its cardiotoxicity severely hampers its potency in chemotherapy. Herein, human serum albumin (HSA) is engaged as a biocompatible nanocarrier to load a pH-sensitive DOX prodrug, DMDOX, generating HSA-DMDOX nanoparticles via self-assembly driven by hydrophobic interactions. HSA-DMDOX disperses well in a physiological environment (∼40 nm) but aggregates in a tumor acidic microenvironment (pH 6.5, ∼140 nm) owing to the hydrophobicity increase of DMDOX by protonation of carboxylic groups. In vitro anticancer study showed that HSA-DMDOX exhibited enhanced cellular uptake by 4T1 cells and superior cytotoxicity in comparison to HSA-DOX nanoparticles. In vivo study suggested that HSA-DMDOX achieved long blood circulation, aggregation enhanced tumor retention, comparable antitumor efficacy and reduced cardiotoxicity relative to free DOX. Our work presents a facile and effective approach to delivering anthracyclines by HSA-based tumor pH-responsive nanoparticles with aggregation-enhanced tumor retention and reduced toxicity.