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Owing to the complex anatomical structure and biomechanics, the current standard palliative treatments for cervical spinal metastases are associated with a high risk of recurrence and complications. Stereotactic body radiotherapy (SBRT) can provide radical dose to tumors while protecting normal organs to the maximum extent. However, the efficacy and safety of SBRT for cervical spinal metastases is not well characterized. Data from 71 patients with cervical spine metastases who were treated with SBRT using CyberKnife between 2006 and 2021 were obtained from our prospectively maintained database. Primary endpoint was pain response at 12 weeks following SBRT completion; secondary endpoints included local control (LC), overall survival (OS), and adverse events. Standard-risk patients were planned to receive 30 Gy (range 21-36) with median fractions of 3 (range 1-3) and high-risk patients 35 Gy (range 24-50) with median fractions of 5 (range 4-5) according to the spinal cord and esophagus dose constraints. The median follow-up time was 17.07 months (range 3.1-118.9). After 12 weeks of SBRT completion, 54 (98.2%) of 55 patients with baseline pain achieved pain response and 46 (83.6%) achieved complete pain response. LC rates were 93.1% and 90% at 1 year and 2 year, respectively. The 1-year and 2-year OS rates were 66.2% and 37.4%, respectively. Eight patients experienced grades 1-4 adverse events (six vertebral compression fracture [VCF], five of them had VCF before SBRT; and two hemiparesis). No grade 5 adverse events were observed. Therefore, risk-adapted SBRT for cervical spine metastases achieved high pain control and LC rates with acceptable adverse events.

Thailand is a global biodiversity hotspot, harboring a striking diversity of species and endemism. However, the amphibian diversity in the region is poorly understood. In this study, the frogs Kurixalus odontotarsus and Raorchestes longchuanensis were collected and recorded for the first time in northern Thailand. This determination was based on specimens previously collected from this region. Morphologically, these specimens displayed good agreement with the original descriptions provided for K. odontotarsus and R. longchuanensis. Phylogenetically, the specimens clustered according to the sequences of type locality of K. odontotarsus and R. longchuanensis with only a small degree of genetic distance. Based on our work, we have extended the latitudinal distribution of K. odontotarsus and R. longchuanensis southward into northern Thailand. Notably, our discovery increases the number of amphibian species recorded in Thailand to 195, and the number of rhacophorid species known to occur in Thailand to 40.

Amolops splendissimus Orlov and Ho, 2007 and A. caelumnoctis Rao and Wilkinson, 2007 were described almost simultaneously from either side of the China-Vietnam border. The two species share a strong morphological resemblance, and their taxonomic distinctiveness has been questioned, yet no one has confirmed the taxonomic relationship and status between the two taxa. To resolve this taxonomic issue, we collected additional topotypic and near-topotypic specimens of A. splendissimus and A. caelumnoctis from both China (A. caelumnoctis: Wenshan County, Yunnan Province; type locality Luchun County, Yunnan Province), and Vietnam (A. splendissimus: Tam Duong District, Lai Chau Province; type locality Mount Ky Quan San, Bat Xat, Lao Cai Province). Molecular analysis based on a 16S rRNA fragment revealed minimal genetic divergences between the two taxa (0.0%–0.4% uncorrected p-distance), and both species are closely related to A. viridimaculatus (2.1%–2.3%) and A. medogensis (3.5%–3.7%). Morphological comparisons between the newly collected specimens and the original descriptions of both species further support the lack of distinctiveness of the two species, hence, we conclude that A. caelumnoctis is a junior synonym of A. splendissimus.

Evolutionary biologists are always interested in deciphering the geographic context of diversification, therefore they introduced the concept of comparative phylogeography, which helps to identify common mechanisms that contribute to shared genetic structures among organisms from the same region. Here, we used multi-locus genetic data along with environmental data to investigate shared phylogeographic patterns among three Asian-endemic newt genera,复杂地理环境对物种多样性地理格局的影响是进化生物学家研究的热点问题之一，基于多类群的比较系统地理学研究有助于理解来自同一地区的不同生物类群间遗传结构形成的驱动机制。亚洲蝾螈类的三个属（

Yan, Fang, Liu, Xiaolong, Zhang, Yinpeng, Yuan, Zhiyong (2021): Direct development of the bush frog Raorchestes longchuanensis (Yang and Li 1978) under laborary conditions in Southern China. Journal of Natural History 55 (1-2): 125-132, DOI: 10.1080/00222933.2021.1895349, URL: http://dx.doi.org/10.1080/00222933.2021.1895349

We describe a new species of the genus Hebius and provide evidence for the validity of H. septemlineatus comb. nov. . Morphological and molecular analyses of Hebius specimens collected in Yunnan Province, China, revealed three distinct lineages, namely the newly described Hebius weixiensis sp. nov. , as well as H. octolineatus (Boulenger, 1904), and H. septemlineatus comb. nov. (Schmidt 1925), which is removed from synonymy with H. octolineatus. Based on mitochondrial genealogy, Hebius weixiensis sp. nov. is sister to H. septemlineatus comb. nov. , while H. octolineatus is sister to H. bitaeniatus. The new species and H. septemlineatus comb. nov. showed considerable genetic divergence from their recognized congeners (uncorrected P-distance ≥3.9%). Furthermore, the new species and H. septemlineatus comb. nov. can be diagnosed from closely related congeners by a combination of pholidosis characters.

A new poroid wood-inhabiting fungal species, Cinereomyces fimbriatus sp. nov., is proposed based on morphological and molecular characteristics. The species is characterized by resupinate, brittle basidiomata with cream pore surface, a dimitic hyphal system with clamped generative hyphae, broad allantoid, hyaline, thin-walled, smooth basidiospores (3.6–4.6 × 0.8–1.1 µm). The internal transcribed spacer (ITS) region of nuclear ribosomal RNA gene sequences of the studied samples were generated, and phylogenetic analyses were performed with maximum likelihood, maximum parsimony and bayesian inference methods. The phylogenetic analysis based on ITS sequences showed that C. fimbriatus formed a monophyletic lineage with strong supports (100% BS, 100% BT, 1.00 BPP) sister to C. lindbladii.

Asian leaf-litter toads of the genus Leptobrachella represent a great anuran diversification in Asia. Previous studies have suggested that the diversity of this genus is still underestimated. During herpetological surveys from 2013 to 2018, a series of Leptobrachella specimens were collected from the international border areas in the southern and western parts of Yunnan Province, China. Subsequent analyses based on morphological and molecular data revealed three distinct and previously unknown lineages, which we formally describe as three new species herein. Among them, we describe a new species that occurs at the highest known elevation for Leptobrachella in China. Four species of Leptobrachella, including two new species, are found in the same reserve. Furthermore, our results suggest that the population from Longchuan County, Yunnan, may represent an additional new species of Leptobrachella, although we tentatively assigned it to Leptobrachella cf. yingjiangensis due to the small sample size examined. Lastly, we provide the first description of females of L. yingjiangensis. Our results further highlight that both micro-endemism and sympatric distributions of species are common patterns in Leptobrachella, that contribute to taxonomic and conservation challenges in these frogs. We provide an identification key for Leptobrachella known to occur in Yunnan. Given the lack of knowledge on species diversity of Leptobrachella along international border areas, we recommend that future studies include trans-boundary collaborative surveys.

Derived from our original nomogram study by using the risk variables from multivariable analyses in the derivation cohort of 1383 patients with extranodal NK/T-cell lymphoma, nasal-type (ENKTCL) who were mostly treated with anthracycline-based chemotherapy, we propose an easily used nomogram-revised risk index (NRI), validated it and compared with Ann Arbor staging, the International Prognostic Index (IPI), Korean Prognostic Index (KPI), and prognostic index of natural killer lymphoma (PINK) for overall survival (OS) prediction by examining calibration, discrimination, and decision curve analysis in a validation cohort of 1582 patients primarily treated with non-anthracycline-based chemotherapy. The calibration of the NRI showed satisfactory for predicting 3- and 5-year OS in the validation cohort. The Harrell’s C-index and integrated Brier score (IBS) of the NRI for OS prediction demonstrated a better performance than that of the Ann Arbor staging system, IPI, KPI, and PINK. Decision curve analysis of the NRI also showed a superior outcome. The NRI is a promising tool for stratifying patients with ENKTCL into risk groups for designing clinical trials and for selecting appropriate individualized treatment.

To determine the therapeutic efficacy and safety of risk‐adapted stereotactic body radiation therapy (SBRT) schedules for patients with early‐stage central and ultra‐central inoperable non‐small cell lung cancer. From 2006 to 2015, 80 inoperable T1‐2N0M0 NSCLC patients were treated with two median dose levels: 60 Gy in six fractions (range, 48‐60 Gy in 4‐8 fractions) prescribed to the 74% isodose line (range, 58%‐79%) for central lesions (ie within 2 cm of, but not abutting, the proximal bronchial tree; n = 43), and 56 Gy in seven fractions (range, 48‐60 Gy in 5‐10 fractions) prescribed to the 74% isodose line (range, 60%‐80%) for ultra‐central lesions (ie abutting the proximal bronchial tree; n = 37) on consecutive days. Primary endpoint was overall survival (OS); secondary endpoints included progression‐free survival (PFS), tumor local control rate (LC), and toxicity. Median OS and PFS were 64.47 and 32.10 months (respectively) for ultra‐central patients, and not reached for central patients. Median time to local failure, regional failure, and any distant failures for central versus ultra‐central lesions were: 27.37 versus 26.07 months, 20.90 versus 12.53 months, and 20.85 versus 15.53 months, respectively, all P

Significance Batrachochytrium dendrobatidis [Bd] is one of the most devastating wildlife pathogens ever documented. Most surveys for Bd report only the presence/absence of the pathogen. However, Bd has distinct genetic lineages that vary in geographic extent and virulence, thus reporting Bd presence alone is not particularly informative. Our study uses a custom method for genotyping degraded Bd DNA samples, such as those nondestructively collected from live animal or museum specimen skin swabs, and presents the discovery of a divergent lineage of Bd—BdASIA3. This study advances our understanding of the evolutionary origins of Bd, highlights areas of the world where Bd lineages are coming into contact, and opens the door to affordable, rapid genetic monitoring of this pathogen., Biodiversity loss is one major outcome of human-mediated ecosystem disturbance. One way that humans have triggered wildlife declines is by transporting disease-causing agents to remote areas of the world. Amphibians have been hit particularly hard by disease due in part to a globally distributed pathogenic chytrid fungus (Batrachochytrium dendrobatidis [Bd]). Prior research has revealed important insights into the biology and distribution of Bd; however, there are still many outstanding questions in this system. Although we know that there are multiple divergent lineages of Bd that differ in pathogenicity, we know little about how these lineages are distributed around the world and where lineages may be coming into contact. Here, we implement a custom genotyping method for a global set of Bd samples. This method is optimized to amplify and sequence degraded DNA from noninvasive skin swab samples. We describe a divergent lineage of Bd, which we call BdASIA3, that appears to be widespread in Southeast Asia. This lineage co-occurs with the global panzootic lineage (BdGPL) in multiple localities. Additionally, we shed light on the global distribution of BdGPL and highlight the expanded range of another lineage, BdCAPE. Finally, we argue that more monitoring needs to take place where Bd lineages are coming into contact and where we know little about Bd lineage diversity. Monitoring need not use expensive or difficult field techniques but can use archived swab samples to further explore the history—and predict the future impacts—of this devastating pathogen.

Keloid resection followed by adjuvant radiotherapy is the most efficacious treatment for keloids. However, for earlobe keloids, an optimal protocol for the total dose and fractions of adjuvant radiation has not yet been established. We retrospectively analyzed the efficacy and safety of immediate three-fraction electron radiotherapy after operation for resistant earlobe keloids. From 2011 to 2017, three-fraction electron radiotherapy with single dose of 5 Gy was given postoperatively to 23 patients with 30 keloids in our hospital. The first fraction of adjuvant radiotherapy was administered within 2 h of surgery, and the other two sessions were completed within the next day or two. Five (16.7%) primary keloids and 25 (83.3%) recurrent keloids were examined in this study. The primary endpoint was the local control rate, which was 86.7% after a median follow-up of 26 months (14–93 months). Secondary endpoints were acute and late procedure-related complications, and no severe complications were observed after combination therapy. Our results suggest that three-fraction electron radiotherapy after excision within 2 days of surgery is a safe and effective protocol for the prevention of earlobe keloid recurrence that can also improve patient compliance and comfort.

Combining the results from morphological and molecular analyses, we explore the taxonomy of the genus Achalinus from Southwest China. As a result, we describe two new species, A. panzhihuaensis sp. nov. and A. yangdatongi sp. nov. from southern Sichuan and southern Yunnan provinces, respectively, and we record a new country record, A. emilyae, from Guangxi Zhuang A. R.. The mitochondrial genealogy suggests that A. panzhihuaensis sp. nov. is sister to A. meiguensis, while A. yangdatongi sp. nov. clusters with the sister species A. juliani and A. ater. Both new species show considerable genetic divergence from their recognized congeners (uncorrected p-distance > 6.2 % in COI gene). Furthermore, both new species can be diagnosed from closely related congeners by a combination of pholidosis characters. With our discovery, we provide a revised key to the 13 species from China and discuss some of the remaining issues regarding the taxonomy of the genus in China.

Approximately half of the species in speciose genus Raorchestes were described during the past 10 years, yet only 11 species are known from Southeast Asia and southern China (SEA-SC), adjacent Himalayas, and northeastern India. Field work in northwestern Yunnan province, China resulted in the discovery of one new species in the genus based on morphological and molecular analyses. The new species is diagnosed by small size with 15.0–19.0 mm SVL in adult males (n=3); tongue pyriform, notched posteriorly; rudimentary webbing between toes; fingers and toes with narrow lateral dermal fringes; tibiotarsal articulation reaching anterior of the eye when hindlimb is stretched along the side of the body; relative finger lengths: I < II < IV < III, relative toe lengths: I < II < V < III < IV; inner metatarsal tubercle oval, outer metatarsal tubercle absent; finger discs and toe discs greyish or orange; flank near the crotch with a distinct black region between two creamy white patches, and the thigh having a similar black patch near the groin, proximal to another creamy white patch; a distinct “) (”-shaped dark marking on the back; male with external single subgular vocal sac; nuptial pad absent. A phylogenetic tree was reconstructed based on the mitochondrial genes for 16S rRNA and ND1. The results indicated that these individuals form a monophyletic group, and show high genetic divergence to their closest relatives within the genus (uncorrected p-distances > 3.2%) by distance of 16S comparable to the divergence between recognized Raorchestes species. This study further enriches the diversity of rhacophorids, especially in northwestern Yunnan.

The Chinese-Myanmar border area forms part of a long-acknowledged biodiversity hotspot. This region is characterised by dramatic topography and diverse landscapes, which support a high degree of biodiversity and endemism that remains largely understudied. Based on recent survey efforts we here describe a new frog species of the genus Odorrana from this area. Found in Dulongjiang village, Yunnan, China, the new species differs from a morphological perspective from its congeners through the combination of a grass-green dorsum with black posterior spots, absence of dorsolateral folds, a distinct pineal body, presence of supratympanic folds, absence of outer metacarpal, metatarsal and supernumerary tubercles, and a pair of external subgular vocal sacs. From a molecular perspective, pairwise genetic distances of 4.8% to 11.6% for DNA sequences of the mitochondrial gene for 16S ribosomal RNA differentiate the new species from other Odorrana. Our mitochondrial phylogeny suggests that the new species is a deeply divergent genetic lineage clustering with the clade including Odorrana wuchuanensis, and the Odorrana andersonii and Odorrana margaretae groups. The discovery of this new species emphasizes the need for further herpetological studies in the China-Myanmar border region.

Aiming at the problem that the fault location accuracy of multi-terminal transmission line is not high, a fault location method based on multi-terminal traveling wave time difference is proposed. By analyzing the difference among multi-terminal traveling wave time difference in different fault locations, the multi-terminal traveling wave time difference matrix is established, which shows that the multi-terminal traveling wave time difference reflects the characteristics of different fault locations. F norm is used to analyze quantitatively the difference among the different fault location. By comparing the matrix F norm of each simulated fault point with the actual fault, the fault location is determined. Thus, the accurate fault location is calculated by the double-ended fault location PSCAD simulation result show that the proposed method is simple to implement and determine accurately the fault location. It has some certain practical vaule.

Purpose To evaluate the safety and efficacy of Cyberknife® (CK) for the treatment of primary or recurring thymic tumours. Materials and methods We retrospectively reviewed 12 patients (16 tumour lesions) with primary or recurring thymic tumours who were treated with CK between March 2008 and October 2017. Their data was stored in prospectively collected database. Kaplan–Meier method was used to calculate survival curves. Results Five patients (41.7%), who had inoperable disease or refused surgery, were treated with CK initially, and 7 patients (58.3%) were treated with CK when they had recurrence diseases. The disease sites treated with CK were primary tumour site (5), regional lymph nodes (4), tumour bed (3), chest wall (2), pleura (1), and bone (1). The median target volume was 43.8 cm3 (range, 13.1–302.5 cm3) for the 16 tumour lesions. The median follow-up time was 69.3 months (range, 9.7–124.8 months). The median survival time was 48.2 months, and the 5-year and 10-year OS rates were 68.2% and 45.5%, respectively. A high response rate for the tumour lesions irradiated with CK was obtained. Only one patient (8%) experienced in-field recurrence, and the 5-year local recurrence free survival was 90.9%. A case indicated that CK may induce the abscopal effect, which provides the potential to combine CK and immunotherapy. No severe radiation related toxicities were observed, and no treatment related death occurred. Conclusion CK treatment resulted in good outcomes, particularly local control, with minimal side effects, in highly selected patients with primary and recurring thymic tumours. More studies with larger sample are needed.

We aimed to determine the survival benefits of chemotherapy (CT) added to radiotherapy (RT) in different risk groups of patients with early-stage extranodal nasal-type NK/T-cell lymphoma (ENKTCL), and to investigate the risk of postponing RT based on induction CT responses. A total of 1360 patients who received RT with or without new-regimen CT from 20 institutions were retrospectively reviewed. The patients had received RT alone, RT followed by CT (RT + CT), or CT followed by RT (CT + RT). The patients were stratified into different risk groups using the nomogram-revised risk index (NRI). A comparative study was performed using propensity score-matched (PSM) analysis. Adding new-regimen CT to RT (vs RT alone) significantly improved overall survival (OS, 73.2% vs 60.9%, P < .001) and progression-free survival (PFS, 63.5% vs 54.2%, P < .001) for intermediate-risk/high-risk patients, but not for low-risk patients. For intermediate-risk/high-risk patients, RT + CT and CT + RT resulted in non-significantly different OS (77.7% vs 72.4%; P = .290) and PFS (67.1% vs 63.1%; P = .592). For patients with complete response (CR) after induction CT, initiation of RT within or beyond three cycles of CT resulted in similar OS (78.2% vs 81.7%, P = .915) and PFS (68.2% vs 69.9%, P = .519). For patients without CR, early RT resulted in better PFS (63.4% vs 47.6%, P = .019) than late RT. Risk-based, response-adapted therapy involving early RT combined with CT is a viable, effective strategy for intermediate-risk/high-risk early-stage patients with ENKTCL in the modern treatment era.

The present study investigated the survival benefit of non–anthracycline (ANT)-based vs ANT-based regimens in a large-scale, real-world cohort of patients with extranodal natural killer (NK)/T-cell lymphoma, nasal type (ENKTCL). Within the China Lymphoma Collaborative Group (CLCG) database (2000-2015), we identified 2560 newly diagnosed patients who received chemotherapy with or without radiotherapy. Propensity score matching (PSM) and multivariable analyses were used to compare overall survival (OS) and progression-free survival (PFS) between the 2 chemotherapy regimens. We explored the survival benefit of non–ANT-based regimens in patients with different treatments in early-stage disease and in risk-stratified subgroups. Non–ANT-based regimens significantly improved survivals compared with ANT-based regimens. The 5-year OS and PFS were 68.9% and 59.5% for non–ANT-based regimens compared with 57.5% and 44.5% for ANT-based regimens in the entire cohort. The clinical advantage of non–ANT-based regimens was substantial across the subgroups examined, regardless of stage and risk-stratified subgroup, and remained significant in early-stage patients who received radiotherapy. The survival benefits of non–ANT-based regimens were consistent after adjustment using multivariable and PSM analyses. These findings provide additional evidence supporting non–ANT-based regimens as a first-line treatment of patients with ENKTCL.

This study evaluated the survival benefit of intensity-modulated radiation therapy (IMRT) compared with 3-dimension conformal radiation therapy (3D-CRT) in a large national cohort of patients with early-stage extranodal nasal-type natural killer/T-cell lymphoma (NKTCL). This retrospective study reviewed patients with early-stage NKTCL treated with high-dose radiation therapy (RT; ≥45 Gy) at 16 Chinese institutions. Patients were stratified into 1 of 4 risk groups based on the number of risk factors: low risk (no factors), intermediate-low risk (1 factor), intermediate-high risk (2 factors), and high-risk (3-5 factors). Of the 1691 patients, 981 (58%) received IMRT, and 710 (42%) received 3D-CRT. Unadjusted 5-year overall survival (OS) and progression-free survival (PFS) were 75.9% and 67.6%, respectively, for IMRT compared with 68.9% (P = .004) and 58.2% (P < .001), respectively, for 3D-CRT. After propensity score match and multivariable analyses to account for confounding factors, IMRT remained significantly associated with improved OS and PFS. The OS and PFS benefits of IMRT persisted in patients treated with modern chemotherapy regimens. Compared with 3D-CRT, IMRT significantly improved OS and PFS for high-risk and intermediate-high–risk patients but provided limited benefits for low-risk or intermediate-low–risk patients. A risk-adapted survival benefit profile of IMRT can be used to select patients and make treatment decisions.

Aim: Identifying hosts and regions susceptible to invasion by an emerged pathogen is vital to inform early risk assessments. We here show how differences between a pathogen's native and invasive observed niche and their underlying environments affect this process, using the recent emergence of Batrachochytrium salamandrivorans (Bsal) as a critical, empirical example. Location: Palaearctic. Methods: To quantify observed niches, we first gathered occurrences from the native Asian and invasive European distribution of Bsal. Through ordination in PCA-bound environmental space, we then applied overlap tests to compare native and invasive Bsal niches with those of 56 putative Western Palaearctic host species. At last, we ensembled bivariate niche models (ESMs) for each Bsal niche to assess how differences in observed niches influenced suitability predictions. Results: The observed invasive Bsal niche is a conservative, partially filled subset of its wider native niche. Pathogen-host overlap measured using the narrow invasive niche was nevertheless found to be significantly higher than that of the native niche, which is partly situated in subtropical conditions absent from the Western Palaearctic. ESMs created using the native niche predict high suitability for Bsal throughout Europe. Conversely, a more restricted range was predicted using the invasive niche, which coincides with the presence of oceanic climates in north-western Europe and several Mediterranean mountain ranges. Main conclusions: Unequal relative availability of environments in native and invasive ranges may lead to underestimation of observed niche overlap between native pathogen populations and putative hosts in the invasive range. The existence of partially filled niches may add uncertainty to overlap measurements, and predictions of potential further spread. Results based on the invasive niche therefore provide a conservative estimate; yet demonstrate, in our case, that Bsal is already present in conditions shared by numerous host species. Further niche filling may accordingly increase risk of salamander diversity across the Western Palaearctic.

Purpose To investigate how necroptosis (ie, programmed necrosis) is involved in killing of non-small cell lung cancer (NSCLC) after ablative hypofractionated radiation therapy (HFRT). Methods and Materials Deoxyribonucleic acid damage, DNA repair, and the death form of NSCLC cells were assessed after radiation therapy. The overexpression and silencing of receptor-interacting protein kinases 3 (RIP3, a key protein involved activation of necroptosis)-stable NSCLC cell lines were successfully constructed. The form of cell death, the number and area of colonies, and the regulatory proteins of necroptosis were characterized after radiation therapy in vitro. Finally, NSCLC xenografts and patient specimens were used to examine involvement of necroptosis after ablative HFRT in vivo. Results Radiation therapy induced expected DNA damage and repair of NSCLC cell lines, but ablative HFRT at ≥10 Gy per fraction preferentially stimulated necroptosis in NSCLC cells and xenografts with high RIP3 expression, as characterized by induction and activation of RIP3 and mixed-lineage kinase domain-like protein and release of immune-activating chemokine high-mobility group box 1. In contrast, RNA interference of RIP3 attenuated ablative HFRT-induced necroptosis and activation of its regulatory proteins. Among central early-stage NSCLC patients receiving stereotactic body radiation therapy, high expression of RIP3 was associated with improved local control and progression-free survival (all P Conclusions Ablative HFRT at ≥10 Gy per fraction enhances killing of NSCLC with high RIP3 expression via preferential stimulation of necroptosis. RIP3 may serve as a useful biomarker to predict favorable response to stereotactic body radiation therapy.

Montane frogs of the genus Quasipaa Dubois, 1992 occur from southern China to Southeast Asia (Frost 2021). Analyses of mtDNA (Cytb) and nuDNA data (Rag1, Rag2, Rhod, Tyr) for samples from 93 localities throughout its distribution yield a phylogeny. Clades A and B occur in Southeast Asia, clade C in northern Yangtze River, China, clade D in southwestern China, and clades E and F in southeastern China. Results place Q. yei within monophyletic Quasipaa and identify two new species. Based on nuDNA data, the basal split of clade A and B indicates an Indochinese origin of Quasipaa. The west–east diversification of five species across South China (Q. spinosa, Q. exilispinosa, Q. jiulongensis, Q. shini, Q. boulengeri) corresponds to topographic terrains II and III of China. Divergence of species from southeastern China (Q. shini, Q. jiulongensis, Q. spinosa, Q. exilispinosa) and southwestern China (Q. boulengeri) dates to 15.30–16.56 Ma (million years ago). A principal component analysis (PCA) and t-test involving 19 bioclimatic variables identifies significantly different environmental conditions between the two regions. Species’ distribution models (SDM) for Q. spinosa and Q. boulengeri identify the best areas to be eastern and western South China, respectively. Thus, environmental variation appears to have influenced the genetic divergence and distributions of Quasipaa in South China. Mito-nuclear discordance indicates that some individuals of Q. exilispinosa and Q. spinosa hybridized historically.

We describe a new species, Fejervarya muangkanensis sp. nov., based on a series of specimens collected from Ban Tha Khanun, Thong Pha Phum District, Kanchanaburi Province, Thailand. The new species is easily distinguished from its congeners by morphological and molecular data, and can be diagnosed by the following characters: (1) small size (adult male snout-vent length (SVL) 33.5 mm; female SVL 40.0-40.9 mm); (2) tympanum small, discernible but unclear; (3) poorly developed toe webbing; (4) no lateral line system in adults; (5) characteristic "Fejervaryan" lines present in females; and (6) femoral glands absent. Molecular phylogenetic analysis of mitochondrial 16S rRNA further supports it as a distinct lineage and distinguishes it from its congeners for which sequences are available.

A new species of brown frog Rana luanchuanensis Zhao & Yuan, sp. n. is described from Luanchuan County, western Henan, central China. The mitochondrial genealogy suggests that the new species is the sister taxon to the clade including R. amurensis and R. coreana, and is separated by uncorrected pairwise distances more than 12.5%. Morphologically, this new species differs from its congeners by a suite of characters. Analyses of partial sequences of cytochrome oxidase subunit I (COI) resolve the new species as a single matriline.

// Huan-Huan Wang 1, * , Lei Deng 2, * , Qing-Lian Wen 3, * , Chun-Ze Zhang 4, * , Nicholas G. Zaorsky 5 , Bai-Lin Zhang 1 , Jie Chen 1 , Xian-Liang Zeng 1 , Yao-Li Cui 6 , Yang-Yang Shi 7 , Hai-Ling Hou 1 , Wei Wang 1 , Bo Jiang 1 , Jun Wang 1 , Qing-Song Pang 1 , Lu-Jun Zhao 1 , Zhi-Yong Yuan 1 , Ping Wang 1 and Mao-Bin Meng 1 1 Department of Radiation Oncology and CyberKnife Center, Tianjin’s Clinical Research Center for Cancer and Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin 300060, China 2 Department of Thoracic Cancer, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, West China School of Medicine, Sichuan University, Chengdu 610041, China 3 Department of Oncology, Affiliated Hospital of Southwest Medical University, Luzhou 646000, China 4 Department of Surgery, Nankai University Tianjin People’s Hospital, Tianjin People’s Hospital, Tianjin 300121, China 5 Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA 19111, USA 6 Department of Lymphoma, Tianjin’s Clinical Research Center for Cancer and Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin 300060, China 7 Stanford University School of Medicine, Stanford, CA 94305, USA * These authors have contributed equally to this work Correspondence to: Mao-Bin Meng, email: doctormm991@hotmail.com Keywords: non-small cell lung cancer, postoperative radiotherapy, postoperative chemotherapy, multimodality therapy, overall survival Received: December 10, 2016 Accepted: April 24, 2017 Published: May 23, 2017 ABSTRACT Aims: The aim of this study was to evaluate the ideal timing of PORT in the management of completely resected (R0) Stage IIIA-N2 NSCLC. Patients and Methods: Between January 2008 and December 2015, patients with known histologies of pathologic Stage IIIA-N2 NSCLC who underwent R0 resection and received PORT concurrent with or prior to two sequential cycles of chemotherapy (“early PORT”) or with PORT administered after two cycles of chemotherapy (“late PORT”) at multiple hospitals. The primary endpoint was OS; secondary end points included pattern of the first failure, LRRFS, and DMFS. Kaplan–Meier OS, LRRFS, and DMFS curves were compared with the log-rank test. Cox regression analysis was used to determine prognosticators for OS, LRRFS, and DMFS. Results: Of 112 included patients, 41 (36.6%) and 71 (63.4%) patients received early PORT and late PORT, respectively. The median OS, LRRFS, and DMFS were longer for those who received early PORT than for those who received late PORT at the median follow-up of 29.6 months (all p < 0.05). Uni- and multi-variate analyses showed that number of POCT cycles and the combination schedule of PORT and POCT were independent prognostic factors for OS, LRRFS, and DMFS. Conclusions: Early PORT is associated with improved outcomes in pathologic Stage IIIA-N2 R0 NSCLC patients.

BACKGROUND Radiosensitivity by blocking the epidermal growth factor receptor and cyclooxygenase-2 pathways with erlotinib and celecoxib in A549 human lung cancer cell was investigated. METHODS MTT assays were used to detect the antitumor effects of erlotinib and celecoxib in A549 cells. Colony formation assays were used to evaluate the antitumor effects. Flow cytometry analysis was used to assess the cell cycle and cell apoptosis, and western blotting analysis was performed to evaluate the expression of AKT and phosphorylated AKT. RESULTS Either erlotinib or celecoxib inhibited the A549 cell proliferation in a dose-dependent manner. Combining Erlotinib or celecoxib with radiation can suppress the cell colony formation and the Dq, D0, SF2 of the combining erlotinib or celecoxib with radiation was lower than in the combinations either erlotinib or celecoxib with radiation (t= 6.62, P< 0.05). The SER of radiation with celecoxib or erlotinib and celecoxib and erlotinib were 1.299, 1.503 and 2.217, respectively. The Flow cytometry analysis results showed that either celecoxib or erlotinib could induce G0/G1 arrest, and reduction of S phase cell proportion, especially when combinations erlotinib-celecoxib with radiation. Either celecoxib or erlotinib could enhance radiation-induced apoptosis, especially significant when combinations erlotinib-celecoxib with radiation. Moreover, radiation can promote the expression of pAKT, and the pAKT was remarkably lowest in the combinations erlotinib-celecoxib with radiation group (t= 4.89, P< 0.05). CONCLUSIONS Blocking both EGFR- and COX-2-related pathways could enhance the antitumor effect of radiation. The underlying mechanisms including the enhancement of apoptosis and radiation-induced G0/G1 arrest, possibly via inhibiting the PI3K/AKT signaling pathway.

Purpose: The aim of this study was to determine the impact of analyzing age as a continuous variable on survival outcomes and treatment selection for extranodal nasal-type NK/T-cell lymphoma. Results: The risk of mortality increased with increasing age, without an apparent cutoff point. Patients’ age, as a continuous variable, was independently associated with overall survival after adjustment for covariates. Older early-stage patients were more likely to receive radiotherapy only whereas young-adult advanced-stage patients tended to receive non-anthracycline-based chemotherapy. A decreased risk of mortality with radiotherapy versus chemotherapy only in early-stage patients (HR, 0.347, P < 0.001) or non-anthracycline-based versus anthracycline-based chemotherapy in early-stage (HR, 0.690, P = 0.001) and advanced-stage patients (HR, 0.678, P = 0.045) was maintained in patients of all ages. Conclusions: These findings support making treatment decisions based on disease-related risk factors rather than dichotomized chronological age. Patients and Methods: Data on 2640 patients with extranodal nasal-type NK/T-cell lymphoma from the China Lymphoma Collaborative Group database were analyzed retrospectively. Age as a continuous variable was entered into the Cox regression model using penalized spline analysis to determine the association of age with overall survival (OS) and treatment benefits.

The China-Vietnam border region is a well-known biodiversity hotspot, harboring a striking diversity of species and endemism. However, the largest part of this region is so far understudied due to restrictions by political boundaries and difficulties in accessibility. Consequently, many species have only been reported from one side of the political boundary, despite the presence of continuous habitat on both sides. In this study, we present our discovery of the frog Nidirana chapaensis in southern Yunnan Province, China. This species was previously known only from Vietnam. All major morphometric characters of these Chinese specimens were found to match with the Vietnamese specimens. In addition, our mitochondrial phylogeny suggests that the Chinese population is monophyletic with respect to topotypic Nidirana chapaensis, with uncorrected pairwise distances of 0.2% at the COI gene fragment analyzed. Therefore, we report Nidirana chapaensis as a new member of amphibian fauna of China, describe the morphological variation of the Chinese population, and provide additional natural history data of this species based on our observation from China.

This cohort study assesses changes in survival probabilities and failure hazard after radiotherapy in adult patients with early-stage extranodal natural killer/T-cell lymphoma based on risk categories, previous survival, and treatment., Key Points Question How do survival probabilities change over time for patients with early-stage extranodal natural killer/T-cell lymphoma after radiotherapy? Findings In this cohort study of 2015 patients in China with early-stage natural killer/T-cell lymphoma, survival probabilities increased and failure hazard decreased over time in a risk-dependent manner after radiotherapy. Patients with an initially higher risk and constantly lower risk were identified. Meaning The posttreatment information on disease processes may permit risk-adapted therapy, follow-up, and counseling., Importance Prognosis of early-stage extranodal natural killer/T-cell lymphoma (NKTCL) is usually estimated and stratified at diagnosis, but how the prognosis actually evolves over time for patients who survived after curative treatment is unknown. Objective To assess conditional survival and failure hazard over time based on risk categories, previous survival, and treatment. Design, Setting, and Participants This retrospective cohort study reviewed the clinical data of 2015 patients with early-stage NKTCL treated with radiotherapy identified from the China Lymphoma Collaborative Group multicenter database between January 1, 2000, and December 31, 2015. Patients were stratified into low-, intermediate- and high-risk groups according to a previously established prognostic model. Median follow-up was 61 months for surviving patients. Data analysis was performed from December 1, 2017, to January 30, 2018. Exposures All patients received radiotherapy with or without chemotherapy. Main Outcomes and Measures Conditional survival defined as the survival probability, given patients have survived for a defined time, and annual hazard rates defined as yearly event rate. Results A total of 2015 patients were included in the study (mean [SD] age, 43.3 [14.6] years; 1414 [70.2%] male); 1628 patients (80.8%) received radiotherapy with chemotherapy, and 387 (19.2%) received radiotherapy without chemotherapy. The 5-year survival rates increased from 69.1% (95% CI, 66.6%-71.4%) at treatment to 85.3% (95% CI, 81.7%-88.2%) at year 3 for conditional overall survival and from 60.9% (95% CI, 58.3%-63.3%) at treatment to 84.4% (95% CI, 80.6%-87.6%) at year 3 for conditional failure-free survival. The annual hazards decreased from 13.7% (95% CI, 13.0%-14.3%) for death and 22.1% (95% CI, 21.0%-23.1%) for failure at treatment to less than 5% after 3 years (death: range, 0%-3.9% [95% CI, 3.7%-4.2%]; failure: 1.2% [95% CI, 1.0%-1.4%] to 4.2% [95% CI 3.9%-4.6%]). Intermediate-risk (11.4% [95% CI, 10.5%-12.3%]) and high-risk (21.6% [95% CI, 20.0%-23.2%]) patients had initially higher but significantly decreased death hazards after 3 years (

We describe a new species, Fejervarya muangkanensis sp. nov ., based on a series of specimens collected from Ban Tha Khanun, Thong Pha Phum District, Kanchanaburi Province, Thailand. The new species is easily distinguished from its congeners by morphological and molecular data, and can be diagnosed by the following characters: (1) small size (adult male snout-vent length (SVL) 33.5 mm; female SVL 40.0-40.9 mm); (2) tympanum small, discernible but unclear; (3) poorly developed toe webbing; (4) no lateral line system in adults; (5) characteristic "Fejervaryan" lines present in females; and (6) femoral glands absent. Molecular phylogenetic analysis of mitochondrial 16S rRNA further supports it as a distinct lineage and distinguishes it from its congeners for which sequences are available.

The interleukin (IL)-17/IL-17 receptor (IL-17R) complex has been shown to be important for the regulation of inflammation; however, its role in the regulation of tumor processes has recently emerged as a research focus. The present study demonstrated that oxaliplatin was able to increase the levels of IL-17/IL-17R in hepatocellular carcinoma (HCC) patients and cells lines, and that it had important roles in reducing the susceptibility of the cells to oxaliplatin-induced apoptosis. Furthermore, the expression of autophagy-related proteins was induced by IL-17/IL-17R and autophagy was shown to induce resistance to oxaliplatin in HCC. In addition, the janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway was shown to be an important pathway in the induction of autophagy in response to oxaliplatin. Autopjhagy was inhibited by 3-methyladenine and JAK2/STAT3 signaling was blocked by AG490, which induced apoptosis in SMMC7721 cells treated with oxaliplatin. The results of the present study may help to elucidate the mechanism underlying the role of IL-17/IL-17R-induced autophagy in the chemoresistance of HCC, as well as help to establish and develop measures to overcome chemoresistance in HCC.

Xian-Liang Zeng,* Huan-Huan Wang,* Mao-Bin Meng, Zhi-Qiang Wu, Yong-Chun Song, Hong-Qing Zhuang, Dong Qian, Feng-Tong Li, Lu-Jun Zhao, Zhi-Yong Yuan, Ping Wang Department of Radiation Oncology, Tianjin’s Clinical Research Center for Cancer and Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, People’s Republic of China *These authors contributed equally to this work Background and aim: The aim of this study is to evaluate the efficacy and safety of stereotactic body radiation therapy (SBRT) using CyberKnife in the treatment of patients with recurrent pancreatic adenocarcinoma at the abdominal lymph node or stump after surgery. Patients and methods: Between October 1, 2006 and May 1, 2015, patients with recurrent pancreatic adenocarcinoma at the abdominal lymph node or stump after surgery were enrolled and treated with SBRT at our hospital. The primary end point was local control rate after SBRT. Secondary end points were overall survival, time to symptom alleviation, and toxicity, assessed using the Common Terminology Criteria for Adverse Events version 4.0. Results: Twenty-four patients with 24 lesions (17 abdominal lymph nodes and seven stumps) were treated with SBRT, of which five patients presented with abdominal lymph nodes and synchronous metastases in the liver and lung. The 6-, 12-, and 24-month actuarial local control rates were 95.2%, 83.8%, and 62.1%, respectively. For the entire cohort, the median overall survival from diagnosis and SBRT was 28.9 and 12.2months, respectively. Symptom alleviation was observed in eleven of 14 patients (78.6%) within a median of 8days (range, 1–14days) after SBRT. Nine patients (37.5%) experienced Common Terminology Criteria for Adverse Events version 4.0 grade 1–2 acute toxicities; one patient experienced grade 3 acute toxicity due to thrombocytopenia. Conclusion: SBRT is a safe and effective treatment for patients with recurrent pancreatic adenocarcinoma at the abdominal lymph node or stump after surgery. Further studies are needed before SBRT can be recommended routinely. Keywords: stereotactic body radiation therapy, pancreatic adenocarcinoma, recurrent disease, overall survival

South China and Indochina host striking species diversity and endemism. Complex tectonic and climatic evolutions appear to be the main drivers of the biogeographic patterns. In this study, based on the geologic history of this region, we test 2 hypotheses using the evolutionary history of Microhyla fissipes species complex. Using DNA sequence data from both mitochondrial and nuclear genes, we first test the hypothesis that the Red River is a barrier to gene flow and dispersal. Second, we test the hypothesis that Pleistocene climatic cycling affected the genetic structure and population history of these frogs. We detect 2 major genetic splits that associate with the Red River. Time estimation suggests that late Miocene tectonic movement associated with the Red River drove their diversification. Species distribution modeling (SDM) resolves significant ecological differences between sides of the Red River. Thus, ecological divergence also probably promoted and maintained the diversification. Genogeography, historical demography, and SDM associate patterns in southern China with climate changes of the last glacial maximum (LGM), but not Indochina. Differences in geography and climate between the 2 areas best explain the discovery. Responses to the Pleistocene glacial-interglacial cycling vary among species and regions.

Segmenting the lesion regions from the ultrasound (US) images is an important step in the intra-operative planning of some computer-aided therapies. High-Intensity Focused Ultrasound (HIFU), as a popular computer-aided therapy, has been widely used in the treatment of uterine fibroids. However, such segmentation in HIFU remains challenge for two reasons: (1) the blurry or missing boundaries of lesion regions in the HIFU images and (2) the deformation of uterine fibroids caused by the patient’s breathing or an external force during the US imaging process, which can lead to complex shapes of lesion regions. These factors have prevented classical active contour-based segmentation methods from yielding desired results for uterine fibroids in US images. In this paper, a novel active contour-based segmentation method is proposed, which utilizes the correlation information of target shapes among a sequence of images as prior knowledge to aid the existing active contour method. This prior knowledge can be interpreted as a unsupervised clustering of shapes prior modeling. Meanwhile, it is also proved that the shapes correlation has the low-rank property in a linear space, and the theory of matrix recovery is used as an effective tool to impose the proposed prior on an existing active contour model. Finally, an accurate method is developed to solve the proposed model by using the Augmented Lagrange Multiplier (ALM). Experimental results from both synthetic and clinical uterine fibroids US image sequences demonstrate that the proposed method can consistently improve the performance of active contour models and increase the robustness against missing or misleading boundaries, and can greatly improve the efficiency of HIFU therapy.

Rhacophoridae are one of the most speciose and ecologically diverse families of amphibians. Resolution of their evolutionary relationships is key to understanding the accumulation of biodiversity, yet previous hypotheses based on Sanger sequencing exhibit much discordance amongst generic relationships. This conflict precludes the making of sound macroevolutionary conclusions. Herein, we conduct the first phylogenomic study using broad-scale sampling and sequences of 352 nuclear DNA loci obtained using anchored hybrid enrichment targeted sequencing. The robust time-calibrated phylogenetic hypothesis clarifies several long-disputed relationships and facilitates the testing of evolutionary hypotheses on spatiotemporal diversification and reproductive modes. The major extant lineages of Rhacophoridae appear to have radiated in mainland Asia, and the spatiotemporal process corresponds with several common accumulations of biodiversity in Asia. Analyses do not detect any case of “Out of Himalaya” in Rhacophoridae. All transitions of reproductive modes appear to have evolved in an ordered, gradual sequence associated with gaining independence of standing water for larval development. The different reproductive modes are phylogenetically conserved and the completion of their transitions appear to have occurred over a period of ~30 Ma, which does not fit a pattern of a rapid burst of diversification. Innovations in reproductive modes associate statistically with the uneven distribution of species-richness between clades, where higher diversification is linked to increased terrestrial modes of reproduction. These results strengthen the hypothesis that breeding innovations drive diversification by providing new opportunities for ecological release and dispersion.

Summary Overexploitation, habitat destruction, human-driven climate change and disease spread are resulting in the extinction of innumerable species, with amphibians being hit harder than most other groups [1]. Few species of amphibians are widespread, and those that are often represent complexes of multiple cryptic species. This is especially true for range-restricted salamanders [2]. Here, we used the widespread and critically endangered Chinese giant salamander ( Andrias davidianus ) to show how genetically uninformed management efforts can negatively affect species conservation. We find that this salamander consists of at least five species-level lineages. However, the extensive recent translocation of individuals between farms, where the vast majority of extant salamanders now live, has resulted in genetic homogenization. Mitochondrial DNA (mtDNA) haplotypes from northern China now predominate in farms. Unfortunately, hybrid offspring are being released back into the wild under well-intentioned, but misguided, conservation management. Our findings emphasize the necessity of genetic assessments for seemingly well-known, widespread species in conservation initiatives. Species serve as the primary unit for protection and management in conservation actions [3], so determining the taxonomic status of threatened species is a major concern, especially for amphibians. The level of threat to amphibians may be underestimated, and existing conservation strategies may be inadvertently harmful if conducted without genetic assessment.