Effects of radiotherapy on nasopharyngeal carcinoma cell invasiveness.

Radiotherapy is widely used in the treatment of nasopharyngeal carcinoma (NPC), whereas its effects on the NPC growth, survival, and metastases have not been completely evaluated. Here, we compared the detected metastatic NPC tissues after radiotherapy (m-NPC) to the resected primary NPC tissues prior to radiotherapy (p-NPC). We detected higher levels of Snail2 protein, but not mRNA in m-NPC, compared to p-NPC. In vitro, a modest irradiation on NPC cells resulted in significant cell death, but increased Snail2 protein, but mRNA levels in the surviving NPC cells. Bioinformatics analyses showed that miR-613, which was significantly decreased in NPC cells after irradiation, targeted the 3'-UTR of Snail2 mRNA to inhibit its translation. Moreover, miR-613 overexpression inhibited Snail2-mediated cell invasiveness, while miR-613 depletion increased Snail2-mediated cell invasiveness in NPC cells. Finally, we detected significantly lower levels of miR-613 in m-NPC, compared to p-NPC. Together our data suggest that although radiotherapy induced NPC cell death, it may increase Snail2-mediated NPC cell invasiveness through downregulating miR-613.

Comparative efficacy of immune checkpoint inhibitors versus chemotherapy alone in diffuse pleural mesothelioma.

BACKGROUND: This study aimed to investigate the effects of immune checkpoint inhibitors (ICIs) versus chemotherapy on the prognosis of real-world diffuse pleural mesothelioma patients in China. METHODS: Clinical data of 90 patients with diffuse pleural mesothelioma from 2019 to 2022 were collected from Harbin Medical University Cancer Hospital. Patients were divided into two groups: the ICIs-treated group (n = 46) and the chemotherapy-only group (n = 44). The efficacy and safety of immunotherapy relative to chemotherapy at different treatment stages were explored. RESULTS: The median progression-free survival (PFS) was 10.0 and 7.0 months, and the median overall survival (OS) was 24.7 and 15.8 months in the ICIs-treated group and the chemotherapy group, respectively. The ICIs-treated group showed an 11% increase in objective response rate (ORR) (52.2% vs. 41.0%) and an 8.0% increase in disease control rate (DCR) (78.3% vs. 70.0%) compared to the chemotherapy group. The Kaplan-Meier curves demonstrated significant PFS (HR: 0.61; 95% CI: 0.38-0.98; p = 0.038) and OS (HR: 0.47; 95% CI: 0.26-0.86; p = 0.011) benefits of receiving immunotherapy over chemotherapy alone. Subgroup analysis according to treatment timing showed the same trend. CONCLUSION: In patients with nonsurgical diffuse pleural mesothelioma, immunotherapy achieved better survival benefits compared to chemotherapy in both first- and second-/third-line treatments. The early addition of immunotherapy improved survival in patients with nonsurgical diffuse pleural mesothelioma.

Positive response to niraparib in chemo-refractory patients with metastatic appendiceal mucinous adenocarcinoma harboring ATM mutations: A case report.

Background: Appendiceal mucinous adenocarcinoma, one kind of specific colorectal cancer, is lowly prevalent and rarely diagnosed in clinical practice. In addition, there have been limited standard treatment strategies established for patients with appendiceal mucinous adenocarcinoma, especially with metastatic disease. The regimens for colorectal cancer, which were adopted in appendiceal mucinous adenocarcinoma, usually resulted in limited effectiveness. Case presentation: Herein, we presented a case of chemo-refractory patient with metastatic appendiceal mucinous adenocarcinoma harboring ATM pathological mutation of exon 60, c.8734del, p.R2912Efs*26, and who has achieved a persistent response to salvage treatment of niraparib, with disease control time that reached 17 months and still in extension. Conclusions: We supposed that appendiceal mucinous adenocarcinoma patients harboring ATM pathological mutations may respond to the treatment of niraparib, even without a homologous recombination deficiency (HRD) status; however, it needs further confirmation in a larger cohort.

Gap Analysis of Giant Panda Conservation as an Example for Planning China's National Park System.

Protected areas have been the cornerstone for conservation globally [1], but gaps still exist in preserving biodiversity [2]. Meanwhile, areas designated as protected have overlaps between designations and might vary in their management [3, 4]. All three phenomena-coverage gaps, overlapping designations, and disparities in management-are present in China [5, 6]. China plans to establish a national park system for the first time, aiming to reform the existing protected-area system [7-9]. However, there has been no quantitative spatial analysis that can aid the planning of national parks. This study shows how an improved conservation gap analysis can inform the construction of new national parks. Taking the proposed Giant Panda National Park as an example, we analyzed the relationship between panda habitat and the existing protected areas, considering not only de jure designated coverage but also de facto levels of two types of potentially harmful activities (timber extraction and human disturbance). We find that, first, there are coverage gaps in the four mountains comprising the potential national park, and existing protected areas have overlaps between designations. Second, current protected areas have gaps and disparities in terms of restrictions on timber extraction and human disturbance. Third, overlapped designations and less restrictive management appear to have adverse effects on panda protection. On the basis of these results, we propose integrated management under a single national park administration, focusing on the key gaps, which we identify. This study can serve as a reference for the establishment of other national parks in China and the world.

Intracellular levels of hepatitis B virus DNA and mutational patterns of the polymerase gene of hepatitis B virus in peripheral blood mononuclear cells of patients with lamivudine or telbivudine resistance.

Studies are limited regarding the association between the quantity of hepatitis virus B (HBV) DNA loads in serum and peripheral blood mononuclear cells (PBMCs) in patients with drug resistance and few studies focus on the mutational pattern of the polymerase gene of HBV in PBMCs of patients with drug resistance. The aim of the present study was to investigate the association between the quantity of HBV DNA loads in serum and PBMCs in patients with lamivudine (LAM) or telbivudine (LdT) resistance and to explore the mutational pattern of the polymerase gene of HBV in PBMCs of these patients. A total of 51 patients underwent antiviral therapy with LAM or LdT for at least half a year. The present study applied quantitative polymerase chain reaction for the quantification of total HBV DNA, and direct sequencing was used to detect the mutation. In total, 31 patients (60.78%) were detected to have drug resistance. The mean serum HBV DNA levels were significantly higher than the HBV DNA levels of PBMCs, whether in patients with LAM or LdT resistance. The PBMCs HBV DNA loads were correlated with the serum HBV DNA loads in the two groups. Three and two mutational patterns were found in the serum of patients with LAM and LdT resistant, respectively. In total, 85.71% of patients with LAM resistance and 75.00% of patients with LdT resistance presented the same mutational pattern in paired PBMCs and serum. The HBV DNA levels in the PBMCs of patients with LAM or LdT resistance were significantly lower than those in serum and there were positive correlations between them. The majority of the mutational patterns of the polymerase gene of HBV DNA in PBMCs were the same as those in the paired serum. These findings may help to increase knowledge regarding HBV drug resistance.

[Quantitative detection of intrahepatic hepatitis B virus DNA in patients with chronic hepatitis B].

OBJECTIVE: To study the relationships between intrahepatic HBV DNA level and serum HBV DNA level, between intrahepatic HBV DNA level and hepatitis B e antigen (HBeAg) level in patients with chronic hepatitis B (CHB), and assess the valuation of pretreatment liver HBV DNA level in antivirus therapy. METHODS: Liver specimens taken from 41 HBeAg-positive CHB patients before antivirus treatment were divided into two parts, one for histological examination, and the other for intrahepatic HBV DNA quantified detection by PCR-fluorescence. At the same time, serum levels of HBV DNA and HBeAg were detected. The patients were classified into two groups according to the pretreatment intrahepatic HBV DNA level (< or = 10(4)fg/cm(3) in group A, >10(4)fg/cm(3) in group B) and accepted interferon alpha-1b (3MU every day for 26 weeks) in combination with lamivudine (100mg per day for 52 weeks). During the treatment, the serum levels of alanine aminotransferase (ALT), HBV DNA and HBeAg seroconversion rate were monitored. RESULTS: (1) The level of liver HBV DNA was much higher than that of serum HBV DNA (4.081 +/-1.127 vs 3.163 +/-1.010, t = 2.218, P < 0.05). Liver HBV DNA level had positive correlation to serum HBV DNA level (r = 0.840, t = 4.322, P < 0.001) and serum HBeAg level (r = 0.459, t = 3.056, P < 0.005). (2) Intrahepatic HBV DNA level was negative correlation to the severity of liver damage (chi(2) = 3.874, P < 0.05). (3) Serum HBV DNA level in all the patients reduced remarkedly after therapy, especially in group A. At the end of 52 weeks, the rates of HBeAg and anti-HBe seroconversion in group A were higher than those in group B (68.4% vs 36.4%, chi(2) = 4.194, P < 0.05; 73.7% vs 40.9%, chi(2) = 4.447, P<0.05). CONCLUSIONS: Intrahepatic HBV DNA is a more valuable marker than serum HBV DNA or HBeAg to assess HBV replication, and can reflect the status of body immunity indirectly. It may be a useful indicator for the efficacy of antivirus treatment.

Thermal stress associated mortality risk and effect modification by sex and obesity in an elderly cohort of Chinese in Hong Kong.

We assessed the effects of apparent temperature (AT) on mortality and the effect modifications attributable to individual characteristics in Hong Kong with subtropical climate conditions. Two datasets are used for analyses: one from mortality data of the general elderly population in 1998-2009; the other from an elderly cohort with 66,820 subjects recruited in 1998-2001 with mortality outcomes followed up until 2009. We found that AT below 20.8 °C was associated with an increase in mortality risk of 1.99% (95% confidence interval: 0.64%, 2.64%) for all causes, 2.48% (0.57%, 4.36%) for cardiovascular disease, and 3.19% (0.59%, 5.73%) for respiratory disease for every 1 °C decrease in AT over the following 3 days. The associations were modified by sex and body mass index, in particular stronger associations were observed for females and for obese subjects.