PRSS50-mediated inhibition of MKP3/ERK signaling is crucial for meiotic progression and sperm quality.

Serine protease 50 (PRSS50/TSP50) is highly expressed in spermatocytes. Our study investigated its role in testicular development and spermatogenesis. Initially, PRSS50 knockdown was observed to impair DNA synthesis in spermatocytes. To further explore this, we generated PRSS50 knockout ( Prss50 -/- ) mice ( Mus musculus), which exhibited abnormal spermatid nuclear compression and reduced male fertility. Furthermore, dysplastic seminiferous tubules and decreased sex hormones were observed in 4-week-old Prss50 -/- mice, accompanied by meiotic progression defects and increased apoptosis of spermatogenic cells. Mechanistic analysis indicated that PRSS50 deletion resulted in increased phosphorylation of extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) and elevated levels of MAP kinase phosphatase 3 (MKP3), a specific ERK antagonist, potentially accounting for testicular dysplasia in adolescent Prss50 -/- mice. Taken together, these findings suggest that PRSS50 plays an important role in testicular development and spermatogenesis, with the MKP3/ERK signaling pathway playing a significant role in this process.

A pan-KRAS degrader for the treatment of KRAS-mutant cancers.

KRAS mutations are highly prevalent in a wide range of lethal cancers, and these mutant forms of KRAS play a crucial role in driving cancer progression and conferring resistance to treatment. While there have been advancements in the development of small molecules to target specific KRAS mutants, the presence of undruggable mutants and the emergence of secondary mutations continue to pose challenges in the clinical treatment of KRAS-mutant cancers. In this study, we developed a novel molecular tool called tumor-targeting KRAS degrader (TKD) that effectively targets a wide range of KRAS mutants. TKD is composed of a KRAS-binding nanobody, a cell-penetrating peptide selectively targeting cancer cells, and a lysosome-binding motif. Our data revealed that TKD selectively binds to KRAS in cancer cells and effectively induces KRAS degradation via a lysosome-dependent process. Functionally, TKD suppresses tumor growth with no obvious side effects and enhances the antitumor effects of PD-1 antibody and cetuximab. This study not only provides a strategy for developing drugs targeting "undruggable" proteins but also reveals that TKD is a promising therapeutic for treating KRAS-mutant cancers.

Pediatric primary renal lymphoma presenting with multiple masses: A challenging case report and narrative review.

RATIONALE: Only 20 cases of pediatric primary renal non-Hodgkin's lymphoma have been reported since 1995, rare cases and a variety of imaging manifestations have led to difficulties in its diagnosis and treatment. PATIENT CONCERNS: Herein, we share in detail a case of primary renal lymphoma (PRL) in a child and summarize the common clinical manifestations, imaging features, and prognostic factors of pediatric PRL by retrospectively analyzing cases reported in the literature. A 2-year-old boy presented to the clinic with a large mass on the right side of his abdomen along with loss of appetite. DIAGNOSES: Imaging revealed a large right renal mass, nearly replacing the entire renal tissue, along with numerous small nodules in the left kidney. Given no local adenopathy and metastases, the diagnosis was unclear. A percutaneous renal puncture was performed, which proved the diagnosis of Burkitt's lymphoma. Since no bone marrow involvement, this child was diagnosed with pediatric PRL. INTERVENTIONS: This PRL boy was treated with the NHL-BFM95 protocol and supportive care. OUTCOMES: Unfortunately, this boy died of multiple organ failure in the fifth month of treatment. LESSONS: As per literature review, the presentation of pediatric PRL is fatigue, loss of appetite, weight loss, abdominal swelling, or other nonspecific symptoms. Although in 81% of cases it often infiltrates the bilateral kidneys, urine abnormalities caused by pediatric PRL are uncommon. 76.2% of pediatric PRL were boys and 2/3 of all cases presented as diffuse renal enlargement. Those PRL presented as masses could easily be misdiagnosed as WT or other malignancies. Absent of local enlarged lymph node, no necrosis or calcification suggest atypical presentation of renal masses and a percutaneous biopsy is needed in timely establishing the accurate diagnosis for appropriate treatment. Based on our experience, percutaneous renal puncture core biopsy is a safe procedure.

Structural characterization and immunoregulatory activity of a neutral polysaccharide from the roots of Apocynum venetum L.

The structural characteristics and immunoregulatory activities of neutral heteropolysaccharide (AVRP-N) separated from the roots of Apocynum venetum L. were extensively investigated. The results showed that the weight average molecular mass (Mw) of AVRP-N was 6.430 × 103 Da. Moreover, the backbone is composed of natural acetylated (1 â†’ 4)-ß-D-Man and (1 â†’ 5)-α-L-Ara domains. The mannan is composed of →4)-ß-D-Manp-(1→, →4)-ß-D-Glcp-(1→, and the terminal group α-D-Galp-(1→ attached to →4,6)-ß-D-Manp-(1→ at O-6. Araban is composed of →5)-α-L-Araf-(1→; the terminal group α-L-Araf-(1→attached to→2,3,5)-α-L-Araf-(1→ at O-2, O-3 and →3,5)-α-L-Araf-(1→ at O-3. In addition, the senior structure shows that AVRP-N has a triple-helix conformation. Furthermore, AVRP-N exhibited immunomodulatory effects, which could significantly regulate the proliferation of mouse splenic lymphocytes by enhancing the secretion of the cytokines (IFN-γ, IL-2, IL-4, and IL-10). Our results provide new structural and immunoregulatory information for natural polysaccharides derived from Apocynum venetum L.

A Nomogram to Predict Survival in Patients With Locoregional Recurrent Nasopharyngeal Carcinoma Receiving Comprehensive Treatment.

Objective: This study aimed to establish a prognostic stratified model of chemotherapy-based comprehensive treatment for patients with locoregional recurrent nasopharyngeal carcinoma (lrNPC), to help individualized treatment decision-making. Materials and Methods: This study retrospectively reviewed patients with lrNPC who received chemotherapy-based comprehensive treatment from January 1, 2010, to December 31, 2018. A total of 422 eligible patients were divided into test (n = 338) and validation (n = 84) cohorts. A LASSO cox regression model was used to identify significant prognostic factors for overall survival (OS) in the test cohort. A nomogram was then developed based on a combined consideration of clinically meaningful prognostic factors and statistically significant prognostic factors. The performance of the nomogram was assessed with Harrell's concordance index (C-index) and calibration plots. Results: Five significant factors were identified: age, albumin (ALB), T stage after recurrent (rT), neutrophil to lymphocyte ratio (NLR), and systematic immune-inflammation index (SII). The nomogram was established with these five factors. C-index was 0.636 in the test cohort and 0.610 in the validation cohort. The calibration curves for the OS rate at 3, and 5 years showed an excellent agreement in both cohorts. In addition, the corresponding risk classification system successfully classified patients into low- and high-risk groups and performed well in stratification (P < 0.001). Conclusions: The nomogram shows well prognostic performance for lrNPC patients receiving chemotherapy-based comprehensive treatment.

A retrospective study on the clinicopathological and molecular features of 22 cases of natural killer/T-cell lymphoma in children and adolescents.

Natural killer/T-cell lymphoma (NKTCL) in children and adolescents is a rare type of T/NK cell neoplasms. The aim of the present study was to analyze the clinicopathological and genetic features of this rare entity of lymphoma. We evaluated the clinical, histopathological and molecular features of 22 young people with NKTCL, including 15 males and 7 females, with a median age of 15 years. The results revealed that the nasal site was the most involved region while non-nasal sites were observed in 27.3% out of all cases. The tumor cells were composed of small­sized to large cells and 19 (86.4%) cases exhibited coagulative necrosis. The neoplastic cells in all patients were positive for CD3 and the cytotoxic markers. Nineteen (86.4%) cases were positive for CD56. Reduced expression of CD5 was observed in all available cases. CD30 was heterogeneously expressed in 15 (75.0%) cases. All 22 patients were EBV positive. Seven (36.8%) out of all the 19 patients during the follow-up died of the disease, and the median follow­up period was 44 months. Moreover, patients treated with radiotherapy/chemotherapy showed significantly inferior OS compared with the untreated patients. High mutation frequencies were detected including KMT2C (5/5), MST1 (5/5), HLA-A (3/5) and BCL11A (3/5), which involved in modifications, tumor suppression and immune surveillance. These results suggest that NKTCL in children and adolescents exhibits histopathological and immunohistochemical features similar to the cases in adults. Active treatment is necessary after the diagnosis of NKTCL is confirmed. Furthermore, genetic analyse may provide a deep understanding of this rare disease.

Interpretation of ischiofemoral impingement via a clinical test using hip triaxial dynamic magnetic resonance imaging.

BACKGROUND: The present study aimed to use magnetic resonance (MR) to explore the dynamic changes of the ischiofemoral space (IFS) under the triaxial motion of the hip joint and verify the clinical test mechanism for ischiofemoral impingement (IFI). METHODS: A prospective design was used to screen 37 patients with clinically confirmed IFI, which included a total of 67 lateral hips, and 39 healthy controls with a total of 69 lateral hips. A dynamic MR examination was performed in positions designed by a simulated IFI test (adduction, adduction with 30° external rotation, 30° internal rotation, supine with 30° flexion, and prone with 30° backward extension). The IFS (mm) and quadratus femoris space (QFS, mm) were measured in different positions. All the data were evaluated independently by three musculoskeletal radiologists. The differences between the two groups were compared using the two-tailed t-test. RESULTS: The IFS and QFS in the case group were smaller than those in the control group. The IFS and QFS were significantly reduced in the prone with backward extension and adduction with external rotation positions of the hip. The correlation coefficients of the IFI test and long-stride walking (LSW) test were -0.621 and -0.715 for IFS and -0.653 and -0.696 for QFS, respectively. CONCLUSIONS: In this study, the mechanism of the IFI-specific clinical examination (IFI and LSW tests) was verified by triaxial dynamic MR imaging of the hip joint, which provided a dynamic imaging basis for the clinical application of the IFI-specific impingement test. The IFI impingement test can be used as a specific clinical test for IFI screening.

Addition of chemoradiotherapy to palliative chemotherapy in de novo metastatic nasopharyngeal carcinoma: a real-world study.

BACKGROUND: To determine whether concurrent chemotherapy is necessary during locoregional radiotherapy (RT) after palliative chemotherapy (PCT) in patients with de novo metastatic nasopharyngeal carcinoma (mNPC). METHODS: A total of 746 patients with mNPC from 2000 to 2017 at our hospital were retrospectively reviewed. Among them, 355 patients received PCT followed by RT. Overall survival (OS) and progression-free survival (PFS), including locoregional progression-free survival (LRPFS) and distant progression-free survival (DPFS) were estimated with the Kaplan-Meier method and log-rank test. Cox proportional-hazards models, landmark analyses, propensity score matching, and subgroup analyses were used to address confounding. RESULTS: Of the patients included in our study, 192 received radiotherapy alone after PCT (PCT + RT), and 163 received concurrent chemoradiotherapy after PCT (PCT + CCRT). The prognosis of PCT + CCRT was significantly better than that of PCT + RT (5 year OS, 53.0 vs 36.2%; P = 0.004). After matching, the 5 year OS rates of the two groups were 55.7 and 39.0%, respectively (P = 0.034) and the median DPFS were 29.4 and 18.7 months, respectively (P = 0.052). Multivariate Cox regression analysis indicated that PCT + CCRT was an independent favorable prognostic factor (P = 0.009). In addition, conducting concurrent chemoradiotherapy after 4-6 cycles of PCT or conducting concurrent chemotherapy with single-agent platinum was associated with significant survival benefit in the matched cohort (5 year OS rate, 60.4 or 57.4%, respectively). The survival difference between groups remained significant when evaluating patients who survived for ≥ 1 year (P = 0.028). CONCLUSIONS: The optimal treatment strategy of mNPC is the combination of PCT followed by concurrent chemoradiotherapy. More specifically, concurrent chemoradiotherapy with single-agent platinum after 4-6 cycles of PCT is suggested.

Treatment and Survival Outcomes Associated With Platinum Plus Low-Dose, Long-term Fluorouracil for Metastatic Nasopharyngeal Carcinoma.

Importance: The treatment of metastatic nasopharyngeal carcinoma (mNPC) is a major challenge because of drug resistance and the toxic effects of chemotherapy. Objective: To evaluate the survival and toxicity outcomes and safety associated with the use of a modified low-dose fluorouracil protocol compared with standard regimens recommended in current guidelines for treatment of mNPC. Design, Setting, and Participants: This retrospective cohort study was based on data retrieved from electronic medical records from Sun Yat-sen University Cancer Center in China for 1397 patients with mNPC diagnosed from January 1, 2006, to December 31, 2017. Data analyses were conducted from October 1, 2020, to May 1, 2021. Exposures: Patients received chemotherapy, including platinum plus low-dose, long-term fluorouracil (PFLL); cisplatin plus standard dose, short-term fluorouracil (PFSS); cisplatin plus gemcitabine (GP); cisplatin plus taxane (TP); and cisplatin plus taxane plus fluorouracil (TPF). Main Outcomes and Measures: The main outcomes included overall survival (OS); subsequent-line, treatment-free survival (sTFS), defined as the period from metastasis to the date requiring subsequent-line treatment or death; and the survival to toxicity ratio (STR), defined as person-year rate of OS divided by person-year rate of severe hematologic toxic effects. Cox regression models were used to compare the outcomes of patients receiving PFLL vs other regimens, adjusting for baseline characteristics. Results: Of 1397 patients with mNPC included in this study (1152 men; median age, 46 years [range, 18-70 years]) 134 received PFLL, 203 received GP, 330 received PFSS, 366 received TP, and 364 received TPF. A total of 764 patients died (75 in treatment group PFLL; 107 in group GP; 204 in group PFSS; 207 in group TP; and 171 in group TPF), and 979 patients had subsequent-line treatment or died, whichever occurred first (PFLL, 77; GP, 144; PFSS, 262; TP, 269; and TPF, 227). The median follow-up was 46.9 months (IQR, 25.4-82.4 months), and the 5-year OS rate among patients who received PFLL was 25.4% (95% CI, 16.7%-38.8%), which was not significantly different from that among patients who did not receive PFLL (30.2%; 95% CI, 27.1%-33.5%; P = .13) or who received GP (25.1%; 95% CI, 18.1%-35.0%; P = .81), PFSS (23.6%; 95% CI, 18.5%-30.0%; P = .80), or TP (28.1%; 95% CI, 22.8%-34.7%; P = .99) but was lower than that for patients who received TPF (40.4%; 95% CI, 34.7%-47.1%; P = .001). The 5-year sTFS among patients who received PFLL (24.1%; 95% CI, 15.4%-37.6%) was significantly higher than that among patients who did not receive PFLL (18.5%; 95% CI, 16.1%-21.3%; P = .005) or who received GP (14.3%; 95% CI, 9.1%-22.5%; P = .001) but similar to that for patients who received TPF (28.0%; 95% CI, 23.0%-34.0%; P = .74). The STR of PFLL was 0.81, substantially better than that of GP (0.41) and TPF (0.65). Conclusions and Relevance: The results of this cohort study suggest that, compared with the use of standard treatment regimens, administration of PFLL was associated with similar OS but prolonged sTFS. PFLL also had better STR than other regimens, which could indicate less severe toxic effects. Thus, PFLL may be an option for first-line treatment of mNPC.

Prognostic value of hepatitis B viral infection in patients with nasopharyngeal carcinoma in the intensity-modulated radiotherapy era.

BACKGROUND: Whether hepatitis B virus (HBV) infection poses risk to patients with nasopharyngeal carcinoma (NPC) in the intensity-modulated radiotherapy (IMRT) era remains unclear. METHODS: 953 patients with non-metastatic, newly diagnosed NPC who received detection of serologic hepatitis B surface antigen (HBsAg) and treated with IMRT were retrospectively reviewed. 171 patients had HBV infection (HBsAg seropositive). Propensity score matching method (PSM) and stabilized inverse probability of treatment weighting (IPTW) were used to address confounding. The survival rates were evaluated by Kaplan-Meier analysis and the survival curves were compared by Log-rank test. Prognostic factors were explored by multivariate analysis. RESULTS: No significant survival differences were observed between HBsAg-negative group and HBsAg-positive group [5-year overall survival (OS), 87.7% vs. 83.9%, P=0.181; locoregional recurrence-free survival (LRFS), 83.5% vs. 78.3%, P=0.109; distant metastasis-free survival (DMFS), 80.2% vs. 77.9%, P=0.446; progression-free survival (PFS), 77.4% vs. 71.4%, P=0.153], consistent with the results of PSM and IPTW analysis. Further analyses revealed that HBV infection was an independent prognostic factor for poor OS [multivariate analysis; hazard ratio (HR), 3.74; 95% confidence interval (CI), 1.45-9.68; P=0.006], LRFS (HR, 2.86; 95% CI, 1.37-5.95); P=0.005] in patients with stage N1, DMFS (HR, 2.65; 95% CI, 1.15-6.09; P=0.022) and PFS (HR, 2.63; 95% CI, 1.34-5.14; P=0.005). Among HBsAg-positive patients, liver protection improved OS (90.3% vs. 77.2%; P=0.022). CONCLUSIONS: HBV infection is an independent risk factor for patients with stage N1 NPC in the IMRT era. Hepatic protection may benefit the survival of HBsAg-positive patients.

Single-cell transcriptomic analysis defines the interplay between tumor cells, viral infection, and the microenvironment in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated malignancy with a complex tumor ecosystem. How the interplay between tumor cells, EBV, and the microenvironment contributes to NPC progression and immune evasion remains unclear. Here we performed single-cell RNA sequencing on ~104,000 cells from 19 EBV+ NPCs and 7 nonmalignant nasopharyngeal biopsies, simultaneously profiling the transcriptomes of malignant cells, EBV, stromal and immune cells. Overall, we identified global upregulation of interferon responses in the multicellular ecosystem of NPC. Notably, an epithelial-immune dual feature of malignant cells was discovered and associated with poor prognosis. Functional experiments revealed that tumor cells with this dual feature exhibited a higher capacity for tumorigenesis. Further characterization of the cellular components of the tumor microenvironment (TME) and their interactions with tumor cells revealed that the dual feature of tumor cells was positively correlated with the expression of co-inhibitory receptors on CD8+ tumor-infiltrating T cells. In addition, tumor cells with the dual feature were found to repress IFN-γ production by T cells, demonstrating their capacity for immune suppression. Our results provide new insights into the multicellular ecosystem of NPC and offer important clinical implications.

Clinical and radiologic features of the first cured Coronavirus disease 2019 (COVID-19) patient in Guangzhou City, China.

To determine changes in clinical and radiologic findings associated with Coronavirus disease 2019 (COVID-19) from diagnosis to recovery, we retrospectively reviewed the diagnosis and treatment records of the first patient cured of COVID-19 in Guangzhou. A 55-year-old woman from Wuhan was admitted to the hospital isolation ward with the chief complaint of "cough for 11 days and once fever 8 days ago" on January 22, 2020. COVID-19 was laboratory confirmed by reverse transcription polymerase chain reaction (RT-PCR) assay, and she received conventional antiviral therapy, such as moxifloxacin, traditional Chinese medicine, and arbidol. Repeat chest-computed tomography (CT) scans were performed on days 13 and 19 of her illness. The former showed radiologic findings, including ground-glass opacities (GGOs), which revealed viral pneumonia; the latter revealed that the previous lesions had been significantly absorbed. The lesions on CT scans were consistent with the changes in the course of disease. Some drugs, such as traditional Chinese medicine and arbidol, might play an important role in the recovery of COVID-19 patients. This study provides some new insights into the formulation of a timely and effective diagnostic and therapeutic strategy to cure patients with COVID-19.

The prognostic significance of PD-L1 and PD-1 expression in patients with nasopharyngeal carcinoma: a systematic review and meta-analysis.

BACKGROUND: Whether PD-L1/PD-1 expression plays a significant role in the prognosis of NPC is still controversial. The present study mainly aimed to investigate the prognostic significance of PD-L1/PD-1 expression in patients with NPC. METHODS: A systematical research was performed in the PubMed, Web of Science, EMBASE, and the Cochrane Library databases up to January 06, 2019. Eighteen studies met eligible criteria were included in the meta-analysis. Quality assessment of included articles was evaluated by Newcastle-Ottawa quality assessment scale (NOS). Pooled hazard ratios (HRs) and their corresponding 95% confidence intervals (95% CIs) were used to elucidated the primary endpoint, overall survival (OS), and the secondary endpoints. Furthermore, the relationship between clinicopathological features of NPC and PD-L1/PD-1 expression was estimated by relative ratios (RRs) and 95% CIs. RESULTS: A total of 1836 patients from 15 included studies concerning PD-L1 and 678 patients from six studies regarding PD-1 were included in the meta-analysis. Pooled results revealed that PD-L1 expression in NPC did not correlate with OS (HR 1.34 95% CI 0.93-1.93, p = 0.11), DFS (HR 1.82, 95% CI 0.86-3.85, p = 0.12), PFS (HR 1.19, 95% CI 0.46-3.08, p = 0.72), and DMFS (HR 2.26, 95% CI 0.60-8.56, p = 0.23). Meanwhile, no statistically significant differences existed between the expression level of PD-1 in tumor infiltrating lymphocytes (TILs) and the OS in NPC, with the pooled HR 1.29 (95% CI 0.68-2.42, p = 0.44). In subgroup analysis, higher expression of PD-L1 in immune cells correlated with better OS in patients with NPC, with a pooled HR 0.68 (95% CI 0.47-0.99, p = 0.04). Among the clinicopathological features included in our study, we found that the positive expression of PD-L1 in NPC associated with the higher expression of PD-1 (RR 1.25, 95% CI 1.02-1.52, p = 0.03). CONCLUSIONS: Our meta-analysis indicated that higher/positive expression of PD-L1/PD-1 may not serve as suitable biomarkers for the prognosis of NPC, which was not in consistent with some previous studies about the prognostic value of PD-L1/PD-1 in other types of tumors. Despite the positive results in subgroup analysis and study about clinicopathological features, it may still need corroboration of prospective and large-scale studies.

The expression of long noncoding RNA CRCAL-3 in colorectal cancer and its impacts on cell proliferation and migration.

Long noncoding RNAs (lncRNAs) have been implicated in colorectal cancer (CRC). And lncRNA RP11-138J23.1 (CRCAL-3) was previously reported as a candidate regulator of CRC development. But its regulating functions have not been fully elucidated. Here, we analyzed RNA sequencing data from the Cancer Genome Atlas (TCGA) and 253 CRC patients treated in our hospital to assess expression dysregulation of CRCAL-3, and the correlation between CRCAL-3 expression and disease progression. Further, polymerase chain reaction (PCR) assay on different cell lines and knockdown experiments by small interfering RNA were performed to assess functions of CRCAL-3 in proliferation and migration of CRC cells. As a result, analyses on TCGA datasets showed an upregulated CRCAL-3 expression in 14 solid tumors, including CRC. PCR assay on 253 cases of CRC tissue and 114 cases of normal adjacent tissue confirmed this expression upregulation. Also, CRCAL-3 expression was exhibited by survival analyses on the 253 CRC patients, to have a negative correlation with patients' overall and progression-free survivals. PCR assay on different cell lines showed that CRC cells expressed a higher level of CRCAL-3, compared with normal colonic epithelial cells. In vitro knockdown of CRCAL-3 resulted in an obvious retardation of proliferation and migration in two CRC cell lines (HCT116 and DLD-1). Moreover, CRCAL-3 knockdown was observed in xenograft models to repress cell proliferation and enhance cisplatin sensitivity. Taking these results together, CRCAL-3 emerged as a biomarker for early diagnosis, prognosis prediction, and individualized treatment of CRC.

O Blood Type Is Associated with Unfavorable Distant-metastasis-free Survival in Female Patients with Nasopharyngeal Carcinoma: A Retrospective Study of 2439 Patients from Epidemic Area.

Purpose: To identify the association between ABO blood type and the survivals in nasopharyngeal carcinoma patients. Patients and methods: We retrospectively analyzed 2439 consecutive non-metastasis nasopharyngeal carcinoma patients between January 2001 and December 2004 at the Sun Yat-sen University Cancer Center. Survival outcomes were compared using Kaplan-Meier method. Univariate and multivariate analysis was performed by Cox regression model. Chi-square test was performed to compare categorical variables. Results: In the whole patients, compared with non-O blood type (A, B, and AB) patients, O blood type patients had significantly lower 5-year distant metastasis-free survival (DMFS) (adjusted hazard ratio (aHR)= 1.268, 95% CI 1.010-1.592, P=0.041). Moreover, we observed in female patients, O blood type patients had significantly lower 5-year overall survival (OS), disease-specific survival (DSS) and DMFS than those with non-O blood type (aHR=1.495, 95% CI 1.032-2.165, P=0.034 for OS; aHR=1.566, 95% CI 1.054-2.328, P=0.026 for DSS; aHR=1.779, 95% CI 1.056-2.998, P=0.030 for DMFS). In male patients, there was no significant difference observed between O blood type patients and non-O blood type patients in any survival endpoints. Conclusion: O blood type was associated with an unfavorable DMFS in female patients with nasopharyngeal carcinoma in epidemic area, which might contribute to unfavorable OS and DSS in female patients, even contribute to a lower DMFS in the whole patients. It might be beneficial to predict metastasis so as to guide the treatment in female patients with nasopharyngeal carcinoma in epidemic area.

Blocking OLFM4/HIF-1α axis alleviates hypoxia-induced invasion, epithelial-mesenchymal transition, and chemotherapy resistance in non-small-cell lung cancer.

Hypoxia is a common biological hallmark of solid cancers, which has been proposed to be associated with oncogenesis and chemotherapy resistance. The purpose of the present study was to investigate the role and underlying mechanisms of olfactomedin 4 (OLFM4) in the hypoxia-induced invasion, epithelial-mesenchymal transition (EMT), and chemotherapy resistance of non-small-cell lung cancer (NSCLC). We observed dramatically upregulated expression of OLFM4 in several NSCLC cell lines, and this effect was more pronounced in A549 and H1299 cells. In addition, our data revealed that OLFM4 expression was remarkably increased in both A549 and H1299 cells under hypoxic microenvironment, accompanied by enhanced levels of hypoxia-inducible factor (HIF)-1α protein. The HIF-1α level was elevated in response to hypoxia, resulting in the regulation of OLFM4. Interestingly, OLFM4 was a positive regulator of hypoxia-driven HIF-1α production. Moreover, depletion of OLFM4 modulated multiple EMT-associated proteins, as evidenced by the enhanced E-cadherin levels along with the diminished expression of N-cadherin and vimentin in response to hypoxia, and thus blocked invasion ability of A549 and H1299 cells following exposure to hypoxia. Furthermore, ablation of OLFM4 accelerated the sensitivity of A549 cells to cisplatin under hypoxic conditions, implying that OLFM4 serves as a key regulator in chemotherapeutic resistance under hypoxia. In conclusion, OLFM4/HIF-1α axis might be a potential therapeutic strategy for NSCLC.

Clinicopathological analysis of the hydroa vacciniforme-like lymphoproliferative disorder with natural killer cell phenotype compared with cutaneous natural killer T-cell lymphoma.

Hydroa vacciniforme-like lymphoproliferative disorder (HVLPD) is defined as a distinctive clinicopathological type of cutaneous lymphoma and a subset of patients with this disease exhibit the natural killer (NK)-cell phenotype. The HVLPD-NK cell phenotype may be difficult to distinguish from cutaneous natural killer T-cell lymphoma (CNKTL), as these two diseases share similar immunophenotypic markers. Therefore, the aim of the present study was to analyze the clinicopathological features of this rare disease and compare these features with those of CNKTL. The clinical, histopathological and molecular features of 5 patients with the HVLPD-NK cell phenotype and 11 patients with CNKTL were evaluated. As well as certain subtle histopathological differences, there marked differences the age, distribution of lesions and clinical course differed between patients with these two diseases. These results suggest that the HVLPD-NK cell phenotype should be classified as a separate disorder and treated accordingly.

Surrogate endpoints shortening the therapeutic evaluation duration for different subgroups of patients with nasopharyngeal carcinoma receiving intensity-modulated radiotherapy: A retrospective analysis of 830 patients stratified by the 8th edition of the UICC/AJCC staging system and plasma Epstein-Barr viral.

Purpose: Investigating surrogate endpoints shortening the time of therapeutic evaluation in nasopharyngeal carcinoma (NPC) after radical treatment. Patients and Methods: We retrospectively analyzed 830 patients receiving intensity-modulated radiotherapy (IMRT) from 2008 to 2010 and being stratified by the 8th edition of UICC/AJCC staging system and the plasma Epstein-Barr virus DNA (EBV DNA). The annual rates of overall survival (OS), progression-free survival (PFS), loco-regional recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were sequentially calculated using the life table and compared by the McNemar method. Results: The time of shortening therapeutic evaluation by surrogate endpoints: OS, PFS, LRFS and DMFS could be shortened to 1-year (100% vs 100%, P=1) in patients with stage I; OS, PFS, LRFS and DMFS could be shortened to 3-year (96.9% vs 96.1%, P = 1; 94.6% vs 92.2%, P = 0.125; 96.9% vs 95.3%, P = 0.5) and 4-year (92.2% vs 91.2%, P = 0.125) in stage II; In the high EBV DNA group , OS and DMFS could be shortened to 1-year (100% vs 100%, P = 1;100% vs 100%, P = 0.25) in stage II; OS and PFS could be shortened to 3-year (94.3% vs 91.4%, P = 1;82.9% vs 74.3%, P = 0.25) in stage III; OS could be shortened to 4-year (75% vs 72.7%, P = 1) in stage IVA. Conclusions: The time of therapeutic evaluation could be shortened to <5-year in stages I-II patients. The year of surrogate endpoints could be ahead in stages II-IVA with high EBV DNA.

Expression of WNT1 in ameloblastoma and its significance.

The present study aimed to measure the expression of WNT1 in ameloblastoma (AB). Immunohistochemistry was used to observe changes in WNT1 expression in 80 AB samples, 10 keratocystic odontogenic tumor (KCOT) samples and 10 normal oral mucosa (NOM) samples. Western blotting and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were used to measure WNT1 protein and mRNA expression, respectively, in 30 AB samples, 5 KCOT samples, 5 NOM samples and 3 tooth germ samples. Ectopic cytoplasmic expression of WNT1 was detected in AB; 88.8% (71/80) of the samples were WNT1-positive. The western blotting results demonstrated that compared with NOM (0.57±0.05), WNT1 expression was significantly higher in AB tissue (1.74±0.36, P<0.05), whereas it was not significantly different between AB and KCOT samples (0.80±0.06, P>0.05). RT-qPCR revealed that the level of WNT1 gene expression in AB was increased 2.43-fold compared with normal mucosa, and 1.77-fold compared with tooth germ tissue. In conclusion, WNT1 protein and mRNA expression were increased in AB, and there was ectopic cytoplasmic expression. This indicates that WNT1 may serve an important role in AB occurrence and development.

The relationship between growth performance and metabolic rate flexibility varies with food availability in juvenile qingbo (Spinibarbus sinensis).

Phenotypic flexibility in traits can allow organisms to cope with environmental challenges. However, the ecological consequences (e.g., growth) of SMR flexibility in fish are poorly understood. Juvenile qingbo (Spinibarbus sinensis) were reared individually with two levels of food resources (satiation or limited) with either continuous feeding (CF) or starvation-refeeding (SR). In the CF experiment, SMR increased when individuals were fed either the satiation or limited diets, but no difference was found in average specific growth rate somatic growth (SGR) between the two food availabilities. The relationship between flexibility in SMR and SGR, feeding efficiency (FE) and food intake (FI) was positive in the satiation group but not in the limited food group. In the SR experiment, the initial SMR of individuals was negatively correlated with the SGR during starvation. During refeeding, the starved individuals increased both body mass and SMR under both food availabilities. Individuals with a greater increase in SMR were fed more and also had greater SGR and FE under the satiation diet, but these results were not observed under the limited diet. The average FE under the limited diet was greater than that under the satiation diet, causing there to be no significant difference in final body mass between the diet treatments at the end of refeeding. Our study suggested that SMR flexibility can allow individuals to maximize their potential growth performance in an environment with changing food availability, and the benefits from greater flexibility in SMR could be offset by their maintenance metabolism under environmental stress.