College of American Pathologists Tumor Regression Grading System for Long-Term Outcome in Patients with Locally Advanced Rectal Cancer.

BACKGROUND: The National Comprehensive Cancer Network's Rectal Cancer Guideline Panel recommends American Joint Committee of Cancer and College of American Pathologists (AJCC/CAP) tumor regression grading (TRG) system to evaluate pathologic response to neoadjuvant chemoradiotherapy for locally advanced rectal cancer (LARC). Yet, the clinical significance of the AJCC/CAP TRG system has not been fully defined. MATERIALS AND METHODS: This was a multicenter, retrospectively recruited, and prospectively maintained cohort study. Patients with LARC from one institution formed the discovery set, and cases from external independent institutions formed a validation set to verify the findings from discovery set. Overall survival (OS), disease-free survival (DFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were assessed by Kaplan-Meier analysis, log-rank test, and Cox regression model. RESULTS: The discovery set (940 cases) found, and the validation set (2,156 cases) further confirmed, that inferior AJCC/CAP TRG categories were closely /ccorrelated with unfavorable survival (OS, DFS, LRFS, and DMFS) and higher risk of disease progression (death, accumulative relapse, local recurrence, and distant metastasis) (all p < .05). Significantly, pairwise comparison revealed that any two of four TRG categories had the distinguished survival and risk of disease progression. After propensity score matching, AJCC/CAP TRG0 category (pathological complete response) patients treated with or without adjuvant chemotherapy displayed similar survival of OS, DFS, LRFS, and DMFS (all p > .05). For AJCC/CAP TRG1-3 cases, adjuvant chemotherapy treatment significantly improved 3-year OS (90.2% vs. 84.6%, p < .001). Multivariate analysis demonstrated the AJCC/CAP TRG system was an independent prognostic surrogate. CONCLUSION: AJCC/CAP TRG system, an accurate prognostic surrogate, appears ideal for further strategizing adjuvant chemotherapy for LARC. IMPLICATIONS FOR PRACTICE: The National Comprehensive Cancer Network recommends the American Joint Committee of Cancer and College of American Pathologists (AJCC/CAP) tumor regression grading (TRG) four-category system to evaluate the pathologic response to neoadjuvant treatment for patients with locally advanced rectal cancer; however, the clinical significance of the AJCC/CAP TRG system has not yet been clearly addressed. This study found, for the first time, that any two of four AJCC/CAP TRG categories had the distinguished long-term survival outcome. Importantly, adjuvant chemotherapy may improve the 3-year overall survival for AJCC/CAP TRG1-3 category patients but not for AJCC/CAP TRG0 category patients. Thus, AJCC/CAP TRG system, an accurate surrogate of long-term survival outcome, is useful in guiding adjuvant chemotherapy management for rectal cancer.

Effects of neoadjuvant chemotherapy with or without intensity-modulated radiotherapy for patients with rectal cancer.

Neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision and adjuvant chemotherapy is the standard regimen for patients with locally advanced rectal cancer (LARC). However, whether and to which extent neoadjuvant radiotherapy could be removed from nCRT for patients with LARC is still unclear. This was a multicenter, retrospectively recruited, prospectively maintained cohort study. A propensity score matching model was employed to minimize potential confounding factors between subgroup patients treated with neoadjuvant chemotherapy (nCT) or nCRT. Overall survival (OS), disease-free survival (DFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were assessed between subgroup patients by Kaplan-Meier analysis, log-rank test, and Cox regression model. In total, 3233 consecutive patients, consist of 571 nCT and 2662 nCRT-treated cases, were included. After propensity score matching (1:4), 565 nCT-treated patients were matched to 1852 nCRT-treated patients. Compared with nCT, nCRT treatment indeed decreased 3-y local recurrence (10.0% vs 6.6%, P = .026), but had no impact on OS, DFS and DMFS (all P > .05) for LARC. Stratified analysis further confirmed that nCRT treatment was associated with higher 3-y LRFS and 3-y DFS than nCT treatment for baseline high-risk subgroup (cT4, cN+, and cIII stage) patients (all P < .05). Conversely, for the baseline low-risk subgroup patients (cT3, cN0, and cII stage), nCRT and nCT treatment had similar 3-y OS, LRFS, DFS, and DMFS (all P > .05). The administration of neoadjuvant radiotherapy for LARC patients might be determined by baseline risk classification, the high-risk individuals could be delivered while low-risk patients might be omitted.

Comparison of the seventh and eighth editions of the UICC/AJCC staging system for nasopharyngeal carcinoma: analysis of 1317 patients treated with intensity-modulated radiotherapy at two centers.

BACKGROUND: In the intensity-modulated radiotherapy (IMRT) era, great improvement has been made in survival of nasopharyngeal carcinoma (NPC). The 7th edition of the International Union against Cancer/American Joint Committee on Cancer (UICC/AJCC) staging system seems "outdated " as it mainly based on the study in 2D/3D era, and thus the 8th edition has made some amendments according to recent studies. We aimed to compare and evaluate these two editions of staging system for NPC in patients treated with intensity-modulated radiotherapy. METHODS: A total of 1317 patients with biopsy-proven, non-metastatic NPC treated with IMRT between 2009 and 2014 at two institutions were retrospectively assessed. All patients were assessed by magnetic resonance imaging and restaged according to the 7th and 8th editions. Prognostic factors for local relapse-free survival (LRFS), distant metastasis-free survival (DMFS), disease-free survival (DFS) and overall survival (OS) were assessed and compared using the Kaplan-Meier method and log-rank test. The Cox proportional hazards model was also used to calculate the hazard ratio (HR). RESULTS: In both 7th and 8th edition, insignificant difference could be observed between T2 and T3 disease, T2 and T4 disease (all P > 0.05) for LRFS, while the difference of LRFS between T3 and T4 disease was significant in the previous edition (P = 0.001) but insignificant (P = 0.279) after revision. For OS, highly similar survival curve could be seen between T2 and T3 disease in both edition (all P > 0.1). DMFS and OS were not significantly different between N3a and N1-3b categories of the 7th edition (all P > 0.05). In contrast, obvious segregation was observed between N3 and the other N categories after the revision and combination in the 8th edition (all P < 0.05). DFS and OS were not significantly different between stage IVA and IVB of the 7th edition (P = 0.057 and P = 0.365, respectively); therefore, combining these stages in the 8th edition was reasonable. CONCLUSION: The overall stages and N categories of the 8th edition of the UICC/AJCC staging system provide better segregation of survival outcomes than the 7th edition. The 8th edition is also more clinically applicable as it has reduced ambiguity and revised out-of-date definitions. However, the T categories need further optimizing as the 8th edition failed to solve the problem of similar survival between adjacent T-classification, which has been exited since 7th edition.

Downregulation of DHRS9 expression in colorectal cancer tissues and its prognostic significance.

Dehydrogenase/reductase (SDR family) member 9 (DHRS9) is aberrantly expressed in colorectal cancer (CRC), but its prognostic value is unknown. The aim of the work was to investigate the prognostic significance of DHRS9 expression in CRC. We found that DHRS9 was frequently downregulated in CRC clinical samples at both the messenger RNA (mRNA) and protein levels. Decreased expression of DHRS9 was significantly correlated with increased lymph node metastasis (p = 0.032), advanced tumor-node-metastasis (TNM) stage (p = 0.021), increased disease recurrence (p = 0.001), and death (p = 0.014). Kaplan-Meier analysis indicated that low DHRS9 expression predicted poor disease-free survival (p = 0.003) and disease-specific survival (p = 0.021). Cox multivariate analysis revealed that reduced expression of DHRS9 was an independent unfavorable prognostic indicator for CRC. Furthermore, combination of DHRS9 with TNM stage was a more powerful predictor of poor prognosis than either of the two parameters alone. Our results suggest that decreased expression of DHRS9 correlates with tumor progression and may serve as a potential prognostic biomarker in CRC.

Is maximum primary tumor diameter still a prognostic factor in patients with nasopharyngeal carcinoma treated using intensity-modulated radiotherapy?

BACKGROUND: Intensity-modulated radiation therapy (IMRT) has represented a technical milestone that has facilitated the clinical implementation. The purpose of this study was to evaluate the prognostic value of maximum primary tumor diameter (MPTD) in patients with nasopharyngeal carcinoma (NPC) treated using IMRT. METHODS: Five-hundred and sixty-six patients with non-metastatic, histologically-confirmed NPC were retrospectively reviewed. MPTD was measured using magnetic resonance imaging (MRI). All patients were treated using IMRT; 87.5% (456/521) of patients with Stage T3-T4/N1-N3 disease also received cisplatin-based chemotherapy. Receiver operating characteristic (ROC) curves were used to identify the optimal MPTD cut-off point and examine the prognostic value of combining MPTD with the current T classification criteria. RESULTS: Median follow-up for all patients was 36 months (range, 1-52 months). The 3-year overall survival (OS), failure-free survival (FFS), distant metastasis-free survival (DMFS), and local relapse-free survival (LRFS) rates for patients with a MPTD ≤41 vs. >41 mm were 96.1% vs. 85.4%, 93.7% vs. 74.7%, 96.1% vs. 79.7%, and 98.1% vs. 92.9%, respectively (all P < 0.05). In multivariate analysis, MPTD was an independent prognostic factor for OS, FFS, DMFS and LRFS in all patients (all P < 0.05). Among stage T3-T4 patients, the 3-year OS, FFS, DMFS, and LRFS rates for patients with a MPTD ≤41 vs. >41 mm were 96.9% vs. 84.5%, 95.4% vs. 73.5%, 96.1% vs. 79.2%, and 99.3% vs. 92.6%, respectively (all P < 0.05). In multivariate analysis, MPTD was also an independent prognostic factor for OS, FFS and DMFS in stage T3-T4 patients (all P < 0.05), and the difference in LRFS was almost statistically significant (P = 0.05). ROC curves verified that inclusion of MPTD improved the predictive value of the current T classification criteria (P < 0.001). CONCLUSIONS: MPTD was an independent prognostic factor in patients with NPC treated using IMRT, and significantly improved the prognostic value of the current T classification criteria for NPC.

Serine threonine tyrosine kinase 1 is a potential prognostic marker in colorectal cancer.

BACKGROUND: Aberrant expression of serine threonine tyrosine kinase 1 (STYK1) has been reported in several human malignancies including colorectal cancer (CRC). However, the prognostic significance of STYK1 expression in CRC remains unknown. METHODS: STYK1 protein expression in paraffin-embedded CRC specimens was determined immunohistochemically. The correlation of STYK1 expression with clinicopathologic features was assessed in a cohort containing 353 patients with primary CRC. Kaplan-Meier and Cox proportional regression analyses were used to evaluate the association between STYK1 expression and patients' survival. RESULTS: STYK1 expression was frequently up-regulated in CRC clinical samples at the protein levels and was significantly associated with tumor differentiation grade (p = 0.030), lymph node metastasis (p = 0.004), TNM stage (p = 0.007) and patient death (p < 0.001). Kaplan-Meier analysis indicated that patients with high intratumoral STYK1 expression had a significantly shorter disease-specific survival (DSS) than those with low expression (p < 0.001). Importantly, high levels of STYK1 protein predicted poor DSS for both stage II (p < 0.001) and stage III (p = 0.004) patients. Furthermore, multivariate analyses revealed that STYK1 protein expression was an independent prognostic indicator for both stage II (hazard ratio [HR], 2.472; p = 0.001) and stage III (HR, 2.001; p = 0.004) patients. CONCLUSIONS: Our results suggest that increased STYK1 protein expression correlates with disease progression and metastasis and may serve as a predictor of poor survival in CRC.

Upregulation of NETO2 expression correlates with tumor progression and poor prognosis in colorectal carcinoma.

BACKGROUND: Neuropilin and tolloid-like 2 (NETO2) has been found to be overexpressed in different human cancers, but its expression pattern and clinical relevance in colorectal carcinoma (CRC) remains unknown. METHODS: Real-time quantitative PCR, western blot and immunohistochemistry analyses were used to analyze the expression of NETO2 in CRC clinical samples. The correlation of NETO2 expression with clinicopathologic features was estimated in a cohort containing 292 patients with primary CRC. Kaplan-Meier and Cox proportional hazards regression analyses were used to assess the prognostic value of NETO2 expression in CRC. RESULTS: The expression of NETO2 was frequently upregulated in CRC clinical samples at both the mRNA and protein levels, and its upregulation was significantly correlated with poor tumor differentiation (p = 0.013), advanced local invasion (p = 0.049), increased lymph node metastasis (p = 0.009), advanced TNM stage (p = 0.041) and increased patient death (p = 0.001). Kaplan-Meier analysis of the complete study cohort revealed that patients with high-NETO2 tumors had a significantly shorter disease-specific survival (DSS) than those with low-NETO2 tumors (p < 0.001). Importantly, high levels of NETO2 protein predicted poor DSS for patients with early stage tumors (p = 0.027) and for those with advanced stage tumors (p = 0.020). Furthermore, multivariate analyses indicated that increased NETO2 expression was an independent unfavorable prognostic factor for patients with early stage tumors (hazard ratio [HR] = 1.937, 95% CI = 1.107-3.390, p = 0.021) as well as patients with advanced stage tumors (HR = 2.241, 95% CI = 1.245-4.035, p = 0.007). CONCLUSIONS: Our findings suggest that NETO2 upregulation could serve as a potential biomarker for the prediction of advanced tumor progression and unfavorable prognosis in patients with CRC.

Prognostic value of carbonic anhydrase VII expression in colorectal carcinoma.

BACKGROUND: Carbonic anhydrases (CAs) have been implicated in the pathogenesis of human cancers. Carbonic anhydrase VII (CA7), a member of the CA gene family, was recently demonstrated to be expressed in several human tissues including colon. Nevertheless, the expression and clinical relevance of CA7 in colorectal carcinoma (CRC) has not been investigated. METHODS: Real-time PCR, western blot, and immunohistochemistry analyses were used to determine CA7 expression in CRC clinical samples. The correlation of CA7 expression with clinicopathologic features was assessed in 228 patients from Luoyang, China (training cohort) and validated in 151 patients from Shanghai, China (validation cohort). Kaplan-Meier and Cox proportional regression analyses were used to estimate the association between CA7 expression and patients' survival. RESULTS: CA7 expression was frequently downregulated in CRC tissues at both the mRNA and protein levels. Reduced expression of CA7 was significantly correlated with poor differentiation, positive lymph node metastasis, advanced TNM stage and unfavorable clinical outcome not only in the training cohort but also in the validation set. Survival analysis indicated that patients with lower CA7 expression had a significantly shorter disease-specific survival (DSS) than those with higher CA7 expression. Importantly, further stage-based analyses revealed that decreased CA7 expression significantly predicted poor DSS and was an independent adverse prognostic indicator for patients with early stage tumors in both cohorts. CONCLUSIONS: Our results indicate that decreased expression of CA7 correlates with disease progression and predicts poor prognosis in CRC, especially for patients with early stage tumors.

MUC15 inhibits dimerization of EGFR and PI3K-AKT signaling and is associated with aggressive hepatocellular carcinomas in patients.

BACKGROUND & AIMS: Aberrant expression of MUC15 correlates with development of colorectal adenocarcinoma, and MUC15 has been reported to prevent trophoblast invasion of human placenta. However, little is known about the role of MUC15 in pathogenesis of hepatocellular carcinoma (HCC). METHODS: We analyzed HCC samples and matched nontumor liver tissues (controls) collected from 313 patients who underwent hepatectomy in Shanghai, China, from January 2006 through September 2009. Levels of messenger RNAs and proteins were determined by immunohistochemical, quantitative reverse transcription polymerase chain reaction, and immunoblot analyses. Statistical analyses were used to associate levels of MUC15 with tumor features and patient outcomes. RESULTS: Levels of MUC15 messenger RNA and protein were reduced in a greater percentage of HCC samples than control tissues. Tumors with reduced levels of MUC15 were more likely to have aggressive characteristics (eg, high levels of α-fetoprotein, vascular invasion, lack of encapsulation, and poor differentiation) than those with low levels. Patients whose tumors had reduced levels of MUC15 had shorter overall survival times (24 months vs 46 months for patients with tumors with high levels of MUC15) and time to disease recurrence. Stable expression of MUC15 in HCC cell lines (SMMC-7721 and HCC-LM3) reduced their proliferation and invasive features in vitro, and ability to form metastatic tumors in mice. MUC15 reduced transcription of the matrix metalloproteinases 2 and 7 increased expression of tissue inhibitor of metalloproteinase-2, which required phosphoinositide 3-kinase-v-akt murine thymoma viral oncogene homolog signaling. Physical interaction between MUC15 and epidermal growth factor receptor led to its relocation and degradation within early endosomes and was required for inactivation of phosphoinositide 3-kinase-v-akt murine thymoma viral oncogene homolog signaling. CONCLUSIONS: Reduced levels of MUC15 in HCCs are associated with shorter survival times of patients and reduced time to disease recurrence. Expression of MUC15 in HCC cells reduces their aggressive behavior in vitro and in mice by inducing dimerization of epidermal growth factor receptor and decreasing phosphoinositide 3-kinase signaling via v-akt murine thymoma viral oncogene homolog.

Primary tumor regression speed after radiotherapy and its prognostic significance in nasopharyngeal carcinoma: a retrospective study.

BACKGROUND: To observe the primary tumor (PT) regression speed after radiotherapy (RT) in nasopharyngeal carcinoma (NPC) and evaluate its prognostic significance. METHODS: One hundred and eighty-eight consecutive newly diagnosed NPC patients were reviewed retrospectively. All patients underwent magnetic resonance imaging and fiberscope examination of the nasopharynx before RT, during RT when the accumulated dose was 46-50 Gy, at the end of RT, and 3-4 months after RT. RESULTS: Of 188 patients, 40.4% had complete response of PT (CRPT), 44.7% had partial response of PT (PRPT), and 14.9% had stable disease of PT (SDPT) at the end of RT. The 5-year overall survival (OS) rates for patients with CRPT, PRPT, and SDPT at the end of RT were 84.0%, 70.7%, and 44.3%, respectively (P < 0.001, hazard ratio [HR] = 2.177, 95% confidence interval [CI] = 1.480-3.202). The 5-year failure-free survival (FFS) and distant metastasis-free survival (DMFS) rates also differed significantly (87.8% vs. 74.3% vs. 52.7%, P = 0.001, HR = 2.148, 95% CI, 1.384-3.333; 91.7% vs. 84.7% vs. 66.1%, P = 0.004, HR = 2.252, 95% CI = 1.296-3.912). The 5-year local relapse-free survival (LRFS) rates were not significantly different (95.8% vs. 86.0% vs. 81.8%, P = 0.137, HR = 1.975, 95% CI, 0.976-3.995). By multivariate analyses, the PT regression speed at the end of RT was the only independent prognostic factor of OS, FFS, and DMFS (P < 0.001, P = 0.001, and P = 0.004, respectively). The 5-year FFS rates for patients with CRPT during RT and CRPT only at the end of RT were 80.2% and 97.1%, respectively (P = 0.033). For patients with persistent PT at the end of RT, the 5-year LRFS rates of patients without and with boost irradiation were 87.1% and 84.6%, respectively (P = 0.812). CONCLUSIONS: PT regression speed at the end of RT was an independent prognostic factor of OS, FFS, and DMFS in NPC patients. Immediate strengthening treatment may be provided to patients with poor tumor regression at the end of RT.

An auxiliary strategy of partial least squares regression in pharmacokinetic/pharmacodynamic studies: A case of application of guhong injection in myocardial ischemia/reperfusion rats.

Guhong injection (GHI) has been applied in the therapy of cardio-cerebrovascular disease in clinic, but there is no report about the pharmacokinetic/pharmacodynamic (PK/PD) research on GHI treating myocardial ischemia/reperfusion (MI/R) injury in rats. In this study, eight compounds of GHI in plasma, including N-acetyl-L-glutamine (NAG), chlorogenic acid (CGA), hydroxysafflor yellow A (HSYA), p-coumaric acid ( pCA), rutin, hyperoside, kaempferol-3-O-rutinoside, and kaempferol-3-O-glucoside, were quantified by LC-MS/MS. We discovered that the values of t1/2ß, k12, V2, and CL2 were larger than those of t1/2α, k21, V1, and CL1 for all compounds. The levels of four biomarkers, creatine kinase-MB (CK-MB), cardiac troponin I (cTn I), ischemia-modified albumin (IMA), and alpha-hydroxybutyrate dehydrogenase (α-HBDH) in plasma were determined by ELISA. The elevated level of these biomarkers induced by MI/R was declined to different degrees via administrating GHI and verapamil hydrochloride (positive control). The weighted regression coefficients of NAG, HSYA, CGA, and pCA in PLSR equations generated from The Unscrambler X software (version 11) were mostly minus, suggesting these four ingredients were positively correlated to the diminution of the level of four biomarkers. Emax and ED50, two parameters in PK/PD equations that were obtained by adopting Drug and Statistics software (version 3.2.6), were almost enlarged with the rise of GHI dosage. Obviously, all analytes were dominantly distributed and eliminated in the peripheral compartment with features of rapid distribution and slow elimination. With the enhancement of GHI dosage, the ingredients only filled in the central compartment if the peripheral compartment was replete. Meanwhile, high-dose of GHI generated the optimum intrinsic activity, but the affinity of compounds with receptors was the worst, which may be caused by the saturation of receptors. Among the eight analytes, NAG, HSYA, CGA, and pCA exhibited superior cardioprotection, which probably served as the pharmacodynamic substance basis of GHI in treating MI/R injury.

Prognostic significance of maximum primary tumor diameter in nasopharyngeal carcinoma.

BACKGROUND: To evaluate the prognostic value of maximum primary tumor diameter (MPTD) in nasopharyngeal carcinoma (NPC). METHODS: Three hundred and thirty-three consecutive, newly-diagnosed NPC patients were retrospectively reviewed. Kaplan-Meier analysis and the log-rank test were used to estimate overall survival (OS), failure-free survival (FFS), distant metastasis-free survival (DMFS) and local relapse-free survival (LRFS). Cox proportional hazards regression analysis was used to assess the prognostic value of MPTD. RESULTS: Median follow-up was 66 months (range, 2-82 months). Median MPTD in stage T1, T2, T3 and T4 was 27.9, 37.5, 45.0 and 61.3 mm, respectively. The proportion of T1 patients with a MPTD ≤ 30 mm was 62.3%; 72% and 62.9% of T2 and T3 patients had a MPTD > 30-50 mm, and 83.5% of T4 patients had a MPTD > 50 mm. For patients with a MPTD ≤ 30 mm, > 30-50 mm and > 50 mm, the 5-year OS, FFS, DMFS and LRFS rates were 85.2%, 74.2% and 56.3% (P < 0.001); 87%, 80.7% and 62.8% (P < 0.001); 88.7%, 86.4% and 72.5% (P = 0.003); and 98.2%, 93.2% and 86.3% (P = 0.012), respectively. In multivariate analysis, MPTD was a prognostic factor for OS, FFS and DMFS, and the only independent prognostic factor for LRFS. For T3-T4 patients with a MPTD ≤ 50 mm and > 50 mm, the 5-year OS, FFS and DMFS rates were 70.4% vs. 58.4% (P = 0.010), 77.5% vs. 65.2% (P = 0.013) and 83.6% vs. 73.6% (P = 0.047), respectively. In patients with a MPTD ≤ 30 mm, 5-year LRFS in T1, T2, T3 and T4 was 100%, 100%, 88.9% and 100% (P = 0.172). CONCLUSIONS: Our data suggest that MPTD is an independent prognostic factor in NPC, and incorporation of MPTD might lead to a further refinement of T staging.

Source apportionment for sediment PAHs from the Daliao River (China) using an extended fit measurement mode of chemical mass balance model.

To minimize the selection uncertainties of source profiles and obtain the higher model performance, an extended fit measurement mode for chemical mass balance model (EFMM-CMB) was proposed and applied to estimate source contributions for sediment PAHs from the Daliao River around which is the important industrial bases with oil, chemical and steel factories in the northeast part of China. Based on least squares fitting method, EFMM-CMB initially calculated the fit measurement index to every one of the possible combinations that can be made from the source profiles. Any successful applications of the fitting method were ranked according to performance measures, and then determined by maximizing an overall fitting index for a unique solution. Apportionment results from two case scenarios showed that the values of performance measures for EFMM-CMB were better to that for CMB8.2 results. With species selection of high molecular weight PAHs, power plant (45.75%), biomass burning (29.34%) and traffic tunnel (10.59%) were identified as the major sources of sediment PAHs from the Daliao River region.

Exosomes may be the carrier of acupuncture treatment for major depressive disorder.

The incidence of major depressive disorder (MDD) is increasing all over the world. There is a great need for complementary or alternative therapies with high safety, few side effects, and precise efficacy to care for MDD. In China, acupuncture has significant laboratory data and clinical trials to demonstrate its antidepressant efficacy. However, there is no clear answer as to how it works. Exosomes are membranous vesicles that rely on cellular multivesicular bodies (MVBs) fused to the cell membrane for release into the extracellular matrix. Almost all cell types are capable of producing and releasing exosomes. As a result, exosomes contain complex RNAs and proteins from their relatives (Cells that secretes exosomes). They can cross biological barriers and participate in biological activities, such as cell migration, angiogenesis, and immune regulation. These properties have made them a popular research topic. Some experts have suggested that exosomes may serve as delivery vehicles for acupuncture to work. This presents both an opportunity and a new challenge for improving the protocols of acupuncture as a treatment for MDD. To better define the relationship between MDD, exosomes, and acupuncture, we reviewed the literature from the last few years. Inclusion criteria included randomized controlled trials and basic trials evaluating acupuncture in the treatment or prevention of MDD, the role of exosomes in the development and progression of MDD, and the role of exosomes in acupuncture. We believe that acupuncture may affect the distribution of exosomes in vivo, and exosomes may be a new carrier for acupuncture treatment of MDD in the future.

Profound impact of gut homeostasis on chemically-induced pro-tumorigenic inflammation and hepatocarcinogenesis in rats.

BACKGROUND & AIMS: Due to its anatomic connection, the liver is constantly exposed to gut-derived bacterial products or metabolites. Disruption of gut homeostasis is associated with many human diseases. The aim of this study was to determine the role of gut homeostasis in initiation and progression of hepatocellular carcinoma (HCC). METHODS: Disruption of intestinal homeostasis by penicillin or dextran sulfate sodium (DSS) and its restoration by probiotics were applied in a diethylnitrosamine (DEN) model of rat hepatocarcinogenesis. RESULTS: Patients with liver cirrhosis and HCC had significantly increased serum endotoxin levels. Chronic DEN treatment of rats was associated with an imbalance of subpopulations of the gut microflora including a significant suppression of Lactobacillus species, Bifidobacterium species and Enterococcus species as well as intestinal inflammation. Induction of enteric dysbacteriosis or intestinal inflammation by penicillin or DSS, respectively, significantly promoted tumor formation. Administration of probiotics dramatically mitigated enteric dysbacteriosis, ameliorated intestinal inflammation, and most importantly, decreased liver tumor growth and multiplicity. Interestingly, probiotics not only inhibited the translocation of endotoxin, which bears pathogen-associated molecular patterns (PAMPs) but also the activation of damage-associated molecular patterns (DAMPs) such as high-mobility group box 1 (HMGB1). As a result, the production of pro- and anti-inflammatory cytokines was skewed in favor of a reduced tumorigenic inflammation in the liver. CONCLUSIONS: The data highlights the importance of gut homeostasis in the pathogenesis of HCC. Modulation of the gut microbiota by probiotics may represent a new avenue for therapeutic intervention to treat or prevent HCC development.

Structure and absolute configuration of liquid molecules based on adamantane derivative cocrystallization.

Liquid molecules are difficult to crystallize, and their structures and absolute configurations cannot be directly determined by X-ray crystallography. We herein report the rapid cocrystallization of tetraaryladamantanes with liquid molecules. The structure of the liquid small molecules can be obtained by determining the crystal structure of the cocrystallized compound. The absolute configuration of chiral molecules can also be assigned, which cannot be accomplished by other methods such as nuclear magnetic resonance. In this paper, liquid compounds such as phenylethanol and phenylpropanol derivatives were selected. 1,3,5,7-Tetrakis(2,4-diethoxyphenyl)adamantane (TEO) powder was heated and dissolved in liquid molecules and allowed to stand overnight to undergo cocrystallization. The results show that the single-crystal structures and the absolute configurations of 16 liquid molecules were determined by cocrystallization, and the homochiral natures of chiral compounds were confirmed by solid circular dichroism spectral measurements.

Green and Rapid Preparation of Fluorosilicone Rubber Foam Materials with Tunable Chemical Resistance for Efficient Oil-Water Separation.

Polydimethylsiloxane (PDMS) foam materials with lightweight, excellent oil resistance and mechanical flexibility are highly needed for various practical applications in aerospace, transportation, and oil/water separation. However, traditional PDMS foam materials usually present poor chemical resistance and easily swell in various solvents, which greatly limits their potential application. Herein, novel fluorosilicone rubber foam (FSiRF) materials with different contents of trifluoropropyl lateral groups were designed and fabricated by a green (no solvents used) and rapid (<10 min foaming process) foaming/crosslinking approach at ambient temperature. Typically, vinyl-terminated poly(dimethyl-co-methyltrifluoropropyl) siloxanes with different fluorine contents of 0−50 mol% were obtained through ring-opening polymerization to effectively adjust the chemical resistance of the FSiRFs. Notably, the optimized FSiRF samples exhibit lightweight (~0.25 g/cm−3), excellent hydrophobicity/oleophilicity (WCA > 120°), reliable mechanical flexibility (complete recovery ability after stretching of 130% strain or compressing of >60%), and improved chemical resistance and structural stability in various solvents, making them promising candidates for efficient and continuous oil−water separation. This work provides an innovative concept to design and prepare advanced fluorosilicone rubber foam materials with excellent chemical resistance for potential oil−water separation application.

Artificial intelligence: Emerging player in the diagnosis and treatment of digestive disease.

Given the breakthroughs in key technologies, such as image recognition, deep learning and neural networks, artificial intelligence (AI) continues to be increasingly developed, leading to closer and deeper integration with an increasingly data-, knowledge- and brain labor-intensive medical industry. As society continues to advance and individuals become more aware of their health needs, the problems associated with the aging of the population are receiving increasing attention, and there is an urgent demand for improving medical technology, prolonging human life and enhancing health. Digestive system diseases are the most common clinical diseases and are characterized by complex clinical manifestations and a general lack of obvious symptoms in the early stage. Such diseases are very difficult to diagnose and treat. In recent years, the incidence of diseases of the digestive system has increased. As AI applications in the field of health care continue to be developed, AI has begun playing an important role in the diagnosis and treatment of diseases of the digestive system. In this paper, the application of AI in assisted diagnosis and the application and prospects of AI in malignant and benign digestive system diseases are reviewed.

Identification of Five Cytotoxicity-Related Genes Involved in the Progression of Triple-Negative Breast Cancer.

Background: Breast cancer is one of the deadly tumors in women, and its incidence continues to increase. This study aimed to identify novel therapeutic molecules using RNA sequencing (RNA-seq) data of breast cancer from our hospital. Methods: 30 pairs of human breast cancer tissue and matched normal tissue were collected and RNA sequenced in our hospital. Differentially expressed genes (DEGs) were calculated with raw data by the R package "edgeR", and functionally annotated using R package "clusterProfiler". Tumor-infiltrating immune cells (TIICs) were estimated using a website tool TIMER 2.0. Effects of key genes on therapeutic efficacy were analyzed using RNA-seq data and drug sensitivity data from two databases: the Cancer Cell Line Encyclopedia (CCLE) and the Cancer Therapeutics Response Portal (CTRP). Results: There were 2,953 DEGs between cancerous and matched normal tissue, as well as 975 DEGs between primary breast cancer and metastatic breast cancer. These genes were primarily enriched in PI3K-Akt signaling pathway, calcium signaling pathway, cAMP signaling pathway, and cell cycle. Notably, CD8+ T cell, M0 macrophage, M1 macrophage, regulatory T cell and follicular helper T cell were significantly elevated in cancerous tissue as compared with matched normal tissue. Eventually, we found five genes (GALNTL5, MLIP, HMCN2, LRRN4CL, and DUOX2) were markedly corelated with CD8+ T cell infiltration and cytotoxicity, and associated with therapeutic response. Conclusion: We found five key genes associated with tumor progression, CD8+ T cell and therapeutic efficacy. The findings would provide potential molecular targets for the treatment of breast cancer.

Prognostic influence of prevertebral space involvement in nasopharyngeal carcinoma: A retrospective study.

PURPOSE: To evaluate how prevertebral space involvement (PSI) and degree of tumor extension within the space affects prognosis in nasopharyngeal carcinoma (NPC). PARTICIPANTS AND METHODS: Data of patients with newly-diagnosed nonmetastatic NPC (n = 757) were retrospectively analyzed. Patients were separated into groups according to presence or absence of PSI and degree of tumor spread. Overall survival (OS), failure-free survival (FFS), local relapse-free survival (LRFS), and distant metastasis-free survival (DMFS) were compared between the groups. RESULTS: Prevalence of PSI, simple prevertebral muscle involvement (PMI), and behind prevertebral muscle involvement (BPMI) were 44.9% (340/757), 22.5% (170/757), and 22.5% (170/757), respectively. OS, FFS, LRFS, and DMFS for patients with and without PSI were 64% vs. 84.8%, 68% vs. 85.6%, 85.8% vs. 94.4%, and 78.5% vs. 92.8%, respectively (all P < 0.001). PSI was an independent predictor of OS, FFS, LRFS, and DMFS. OS, FFS, and DMFS for patients with simple PMI and with BPMI were 72.7% vs. 54.8% (P = 0.002), 75.8% vs. 59.8% (P = 0.003), and 85.5% vs. 71.2% (P = 0.002), respectively. Degree of PSI extension was related to OS, FFS, and DMFS. OS, FFS, LRFS, and DMFS were significantly poorer in patients with PSI in T2-3 stage than in patients without PSI in T3 stage (P < 0.05), but comparable to those in patients with T4 stage (P > 0.05). CONCLUSIONS: PSI predicts poor prognosis in NPC. Survival is poorer in patients with BPMI than in those with simple PMI. NPC with PSI should be classified as T4 stage.