Molecular phylogeny of the family Rhabdiasidae (Nematoda: Rhabditida), with morphology, genetic characterization and mitochondrial genomes of Rhabdias kafunata and R. bufonis.

BACKGROUND: The family Rhabdiasidae (Nematoda: Rhabditida) is a globally distributed group of nematode parasites, with over 110 species parasitic mainly in amphibians and reptiles. However, the systematic position of the family Rhabdiasidae in the order Rhabditida remains unsolved, and the evolutionary relationships among its genera are still unclear. Moreover, the present knowledge of the mitochondrial genomes of rhabdiasids remains limited. METHODS: Two rhabdiasid species: Rhabdias kafunata Sata, Takeuchi & Nakano, 2020 and R. bufonis (Schrank, 1788) collected from the Asiatic toad Bufo gargarizans Cantor (Amphibia: Anura) in China, were identified based on morphology (light and scanning electron microscopy) and molecular characterization (sequencing of the nuclear 28S and ITS regions and mitochondrial cox1 and 12S genes). The complete mitochondrial genomes of R. kafunata and R. bufonis were also sequenced and annotated for the first time. Moreover, phylogenetic analyses based on the amino acid sequences of 12 protein-coding genes (PCGs) of the mitochondrial genomes were performed to clarify the systematic position of the family Rhabdiasidae in the order Rhabditida using maximum likelihood (ML) and Bayesian inference (BI). The phylogenetic analyses based on the 28S + ITS sequences, were also inferred to assess the evolutionary relationships among the genera within Rhabdiasidae. RESULTS: The detailed morphology of the cephalic structures, vulva and eggs in R. kafunata and R. bufonis was revealed using scanning electron microscopy (SEM) for the first time. The characterization of 28S and ITS regions of R. kafunata was reported for the first time. The mitogenomes of R. kafunata and R. bufonis are 15,437 bp and 15,128 bp long, respectively, and both contain 36 genes, including 12 PCGs (missing atp8). Comparative mitogenomics revealed that the gene arrangement of R. kafunata and R. bufonis is different from all of the currently available mitogenomes of nematodes. Phylogenetic analyses based on the ITS + 28S data showed Neoentomelas and Kurilonema as sister lineages, and supported the monophyly of Entomelas, Pneumonema, Serpentirhabdias and Rhabdias. Mitochondrial phylogenomic results supported Rhabdiasidae as a member of the superfamily Rhabditoidea in the suborder Rhabditina, and its occurrance as sister to the family Rhabditidae. CONCLUSIONS: The complete mitochondrial genome of R. kafunata and R. bufonis were reported for the first time, and two new gene arrangements of mitogenomes in Nematoda were revealed. Mitogenomic phylogenetic results indicated that the family Rhabdiasidae is a member of Rhabditoidea in Rhabditina, and is closely related to Rhabditidae. Molecular phylogenies based on the ITS + 28S sequence data supported the validity of Kurilonema, and showed that Kurilonema is sister to Neoentomelas. The present phylogenetic results also indicated that the ancestors of rhabdiasids seem to have initially infected reptiles, then spreading to amphibians.

Smoking contribution to the global burden of metabolic disorder: A cluster analysis.

INTRODUCTION AND OBJECTIVES: Smoking is associated with various health risks, including cancer, cardiovascular disease, and chronic obstructive pulmonary disease. In this retrospective cohort study, we aimed to determine whether smoking is harmful to the whole metabolic system. METHODS: We collected data from 340 randomly selected participants who were divided into three groups: smokers (n=137), non-smokers (n=134), and ex-smokers (n=69). We obtained information on participants' body mass index, waist circumference, indicators of glucose metabolism, lipid metabolism, bone metabolism, and uric acid from health screen data during the past three years. A cluster analysis was used to synthesize each participant's overall metabolic characteristics. RESULTS: According to the cluster analysis, the 340 participants were divided into three groups: excellent metabolizers (137, 40.3%), adverse metabolizers (32, 9.4%), and intermediate metabolizers (171, 50.3%). The Chi-squared test analysis shows that people with different smoking statuses have different metabolic patterns. Non-smokers had the highest proportion of excellent metabolizers (56%), and current smokers had the highest proportion of adverse metabolizers (15.3%). The proportion of adverse metabolizers (5.8%) in the ex-smoker group was clinically relevantly lower than that of current smokers. CONCLUSION: The statistically significant differences in the distribution of smokers into different metabolic clusters indicate that smoking has adverse effects on the whole metabolic system of the human body, which further increases the existing global burden of metabolic disorders.

Similar incidence of graft glomerulonephritis in recipients with definitively diagnosed glomerulonephritis and those with unknown etiology: a retrospective observational study.

OBJECTIVE: In China, most of the patients who underwent kidney transplants have unknown causes of end-stage renal disease (uESRD). However, little is known regarding the incidence of graft glomerulonephritis (GN) and graft survival in kidney transplant recipients (KTRs) with uESRD. METHODS: In this retrospective cohort study, 473 of the 565 KTRs who underwent kidney transplantation (KTx) from 2015 to 2020 were included. We mainly observed the occurrence of graft GN between uESRD group and definitively diagnosed GN group, and repeatedly compared after propensity score matching (PSM). RESULTS: The median follow-up was 50 months in 473 KTRs, and about 75% of KTRs of native kidney disease of unknown etiology. The total cumulative incidence of graft GN was 17%, and no difference was observed between the definitively diagnosed GN group and the uESRD group (p = 0.76). Further, PSM analysis also showed no difference in the incidence of graft GN between the 2 groups. Multivariable analysis disclosed males (p = 0.001), younger age (p = 0.03), and anti-endothelial cell anti-body (AECA) positive pre-KTx (p = 0.001) were independent risk factors for graft GN. CONCLUSIONS: The incidence of graft GN was similar between uESRD and definitively diagnosed GN group. The allograft survival was also similar between two groups.

Austraplectana extranes sp. n. (Nematoda: Cosmocercoidea) from Australian amphibians Mixophyes carbinensis Mahony, Donnellan, Richards & McDonald (Anura: Myobatrachidae) and Rhinella marina (Linnaeus) (Anura: Bufonidae).

The genus Austraplectana Baker, 1981 is a poorly known group of cosmocercoid nematodes. In the present study, a new species of Austraplectana, A. extranes sp. n., was described using both light and scanning electron microscopy, based on specimens collected from the carbine barred frog Mixophyes carbinensis Mahony, Donnellan, Richards & McDonald (Anura: Myobatrachidae) and the cane toad Rhinella marina (Linnaeus) (Anura: Bufonidae) in Australia. Austraplectana extranes sp. n. can be easily distinguished from its congener by the much longer and different morphology of tails in both sexes, the different number and arrangement of caudal papillae, the presence of single precloacal median heart-shaped papilla and large posterior protuberance with cuticular comb-like fringe in male.

Poor outcomes of proliferative glomerulonephritis with monoclonal IgG deposits in renal allografts: a retrospective multicenter study.

BACKGROUND: Proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) in renal allografts is a rare, renal-limited disease. No study has reported the long-term outcomes and prognostic features of PGNMID in renal allografts in the Chinese population. METHODS: We retrospectively included transplant patients diagnosed with PGNMID who underwent renal allograft biopsy at three transplant centers from April 2012 to July 2020. We observed the clinicopathologic features, explored the long-term graft survival, and investigated the characteristics associated with the prognosis. RESULTS: A total of 13 transplant patients with PGNMID were included, out of 3821 biopsies. The mean follow-up time was 55 months since kidney transplantation (KTx). At diagnosis, all patients presented with proteinuria (100%) and most of them with hematuria (92%). IgG3κ (69%) was the main immunofluorescence (IF) subtype. The median graft survival of the total cohort was 17 months from diagnosis and 49 months from kidney transplantation. During follow-up, 9 patients needed dialysis and 2 out of 9 patients who progressed to dialysis died of infection. Primary membranoproliferative glomerulonephritis (MPGN) (P = 0.014) and MPGN pattern at diagnostic biopsy (P < 0.001) were associated with a higher risk of graft loss. CONCLUSIONS: The long-term outcome of allograft PGNMID was relatively poor in the Chinese population. Primary MPGN and MPGN pattern in renal allograft were associated with  poor outcomes.

Native species Maxvachonia chabaudi Mawson, 1972 (Nematoda: Cosmocercoidea) found in the invasive marine toad Rhinella marina (Linnaeus) (Anura: Bufonidae) in Australia.

The genus Maxvachonia Chabaud et Brygoo, 1960 (Ascaridomorpha: Cosmocercidae) is a poorly known group of parasitic nematodes. Species of Maxvachonia are native to Madagascar-Australo-Papuan Region, where they are known to parasitise frogs, snakes and skinks. Unfortunately, most of Maxvachonia species have been inadequately described. In the present study, we report the native species Maxvachonia chabaudi Mawson, 1972 from the intestine of the invasive marine toad Rhinella marina (Linnaeus) in Australia for the first time. We speculate that the marine toads infected with M. chabaudi are likely related to their eating skinks or the similarity in diet/habitat/ecology between the toad and the skinks. The detailed morphology of M. chabaudi was studied using light microscopy and, for the first time, scanning electron microscopy, based on the newly collected specimens. Some characters important for the specific diagnosis of M. chabaudi are reported for the first time, including each lip with distinct inner flanges, the location of vulva varying from anterior to posterior of the oesophageal bulb and the presence of single medio-ventral precloacal papilla. An identification key to the species of Maxvachonia is provided.

Case report: Complete response to pembrolizumab in a liver metastatic colon adenocarcinoma patient with a novel likely pathogenic germline MSH2 mutation.

Lynch syndrome (LS) is a genetic disorder mainly caused by germline mutations in mismatched repair (MMR) genes (MSH2, MLH1, MSH6, and PMS2) or deletions of the epithelial cell adhesion molecule gene (EPCAM). A 43-year-old Chinese male patient underwent radical surgery and was pathologically confirmed to have stage IIIB colon adenocarcinoma. After four cycles of standard adjuvant chemotherapy, the tumor reoccurred in situ with intestinal obstruction. The patient received secondary colectomy. Immunohistochemistry analysis revealed a loss of MSH2 protein expression in the surgical specimen. Noticing that the patient's mother and grandfather all were diagnosed with LS-related cancers, we collected the patient's and his mother's peripheral blood for genetic testing, and the result showed a six-base deletion of MSH2. Thus, we concluded that our patient had LS. Subsequently, the patient accepted pembrolizumab as the first-line systemic therapy after liver metastases. He achieved clinical complete response (cCR) within 2 months and remained progression-free for more than 2 years. The case report showed that MSH2 mutation (c.489_494deTGGGTA) is a likely pathogenic mutation, and immunotherapy (pembrolizumab) is effective for this patient.

LncRNA HCG18 promotes M2 macrophage polarization to accelerate cetuximab resistance in colorectal cancer through regulating miR-365a-3p/FOXO1/CSF-1 axis.

BACKGROUND: Cetuximab (CET) resistance in colorectal cancer (CRC) is responsible to poor prognosis to some extent. M2 macrophage polarization is closely correlated with drug resistance to cancers. Therefore, this study aims to investigate whether the mechanism of HCG18 on CET resistance to CRC involving in M2 macrophage polarization. METHODS: Clinic samples and SW620 cells with/without M0 macrophage co-culture served as experimental subjects. CET treatment was performed to induce SW620 cell resistant to CET. qRT-PCR and western blot were employed to evaluate the mRNA and protein expression of genes. The capabilities of cell viability, proliferation, migration and invasion were examined using CCK-8, clone formation assay and transwell. ELISA was employed to examine the protein concentrations of IL-10 and TGF-ß1. StarBase and luciferase activity assay were conducted to consolidate the interactions among HCG18, miR-365a-3p and FOXO1. RESULTS: In clinical samples and CRC cells, the abundance of HCG18 was enhanced whereas miR-365a-3p was reduced. Besides, HCG18 expression in CET-resistant tumor tissues was higher than that in CET-sensitive tumor tissues and the trend of miR-365a-3p was opposite to that of HCG18. HCG18 knockdown attenuated macrophage-induced CET resistance in SW620 cells and suppressed M2 polarization of THP-1 cells. Mechanistically, HCG18 interacted with miR-365a-3p and miR-365a-3p targeted FOXO1. MiR-365a-3p inhibitor abolished HCG18 knockdown-mediated inhibition of CET resistance, while FOXO1 knockdown compromised the influences of miR-365a-3p inhibitor. FOXO1 could positively regulate CSF-1 expression to promote M2 macrophage polarization and macrophage-induced CET resistance. CONCLUSION: Our results revealed that HCG18 promoted M2 macrophage polarization to facilitate CET resistance to CRC cells through modulating miR-365a-3p/FOXO1/CSF-1 axis.

Perfusion and oxygenation in allografts with transplant renal artery stenosis: Evaluation with functional magnetic resonance imaging.

BACKGROUND: Transplant renal artery stenosis (TRAS) has been shown to reduce kidney perfusion leading to post-operative hypertension. We aimed to measure the perfusion and oxygenation changes in TRAS with arterial spin labeling (ASL) and blood oxygen level-dependent (BOLD) imaging, respectively. METHODS: In this single-center prospective study, a total of seven patients with TRAS and seven age- and sex-matched normal kidney transplant recipients underwent both ASL and BOLD imaging. Moreover, measurements of ASL and BOLD were also performed in five patients after successful angioplasty for TRAS. RESULTS: Allograft cortical perfusion as measured by ASL in the TRAS group was significantly decreased as compared with normal control group (129.9 ± 46.6 ml/100 g vs. 202.4 ± 47.7 ml/100 g, P = .01). Interestingly, allograft oxygenation as indicated by R2* derived from BOLD in both the cortex (16.42 ± 1.90 Hz vs. 18.25 ± 4.34 Hz, P = .33) and the medulla (30.34 ± 2.35 Hz vs. 30.43 ± 6.85 Hz, P = .97) showed no statistical difference between the TRAS and normal control group. In addition, both cortical and medullary oxygenation remained unchanged despite significantly improved cortical perfusion in those undergone successful angioplasty. CONCLUSION: Cortical and medullary oxygenation were preserved in the presence of reduced allograft perfusion in clinically significant TRAS. Prospective larger studies are needed to conclusively establish perfusion and oxygenation changes in TRAS.

Case Report: An Adolescent Soft Tissue Sarcoma With YWHAE-NUTM2B Fusion Is Effectively Treated With Combined Therapy of Epirubicin and Anlotinib.

Soft tissue sarcoma is a relatively rare entity that comprises heterogeneous types of tumors. Here we report the case of a 14-year-old girl with pelvic sarcoma with a YWHAE-NUTM2B fusion gene. This fusion transcript has been reported in endometrial stromal sarcomas and clear cell renal sarcomas, but its description in pelvic sarcomas is recent. To our knowledge, this is the first case report describing this translocation in an adolescent patient with soft tissue sarcoma. The patient underwent cytoreductive surgery, followed by systemic chemotherapy and targeted drug treatment. Surprisingly, the treatment was effective, and the young patient is being followed up in our department.

Morphology, genetic characterization and molecular phylogeny of the poorly known nematode parasite Cissophyllus leytensis Tubangui & Villaamil, 1933 (Nematoda: Ascaridida) from the Philippine sailfin lizard Hydrosaurus pustulatus (Eschscholtz, 1829) (Reptilia: Squamata).

BACKGROUND: The genus Cissophyllus (Cosmocercoidea: Kathlaniidae) is a rare group of nematodes parasitic in turtles and lizards. To date, only four species have been reported in Asia and North America. However, most of them are inadequately described. The species Cissophyllus leytensis has never been reported since it was originally described by Tubangui and Villaamil in 1933 from the Philippine sailfin lizard Hydrosaurus pustulatus (Eschscholtz, 1829) (Reptilia: Squamata). Furthermore, the systematic status of Cissophyllus/Cissophyllinae in the family Kathlaniidae of the superfamily Cosmocercoidea remains under debate. METHODS: The detailed morphology of C. leytensis was studied using light microscopy (LM) and, for the first time, scanning electron microscopy (SEM), based on newly collected specimens from the type host H. pustulatus. Six different genetic markers, including nuclear sequences [small ribosomal subunit (18S), internal transcribed spacer (ITS) and large ribosomal subunit (28S)], plus mitochondrial genes [cytochrome c oxidase subunit 1 (cox1), cytochrome c oxidase subunit 2 (cox2) and 12S small subunit ribosomal RNA gene] of C. leytensis were sequenced. Additionally, in order to test the validity of the subfamily Cissophyllinae and clarify the phylogenetic relationships of Cissophyllus and the other genera in the family Kathlaniidae, phylogenetic analyses based on 18S + 28S and ITS sequence data were performed using maximum likelihood (ML) and Bayesian inference (BI) analyses, respectively. RESULTS: Our observations using LM and SEM revealed some previously unreported morphological features, necessitating the redescription of this poorly known species. The presence of remarkable morphological variation in the isthmus and the position of excretory pore among different individuals was found. Molecular analysis showed no intraspecific nucleotide divergence detected in the 18S, ITS, 28S, cox2 and 12S regions among different individuals of C. leytensis, but a low level of intraspecific genetic variation was found in the cox1 (0.52%). Our phylogenetic results showed the representatives of the Cosmocercoidea divided into four large clades (Cosmocerca + Aplectana + Cosmocercoides representing the family Cosmocercidae, Cruzia representing the subfamily Cruzinae of Kathlaniidae, Falcaustra + Cissophyllus + Megalobatrachonema representing the subfamily Kathlaniinae of Kathlaniidae, and Orientatractis + Rondonia representing the family Atractidae). The genus Cissophyllus clustered together with the genus Megalobatrachonema in both the ML and BI trees using ITS sequence data, but displayed a sister relationship to the genus Falcaustra in the ML tree and to the genera Falcaustra + Megalobatrachonema in the BI tree using 18S + 28S sequence data. CONCLUSIONS: Molecular phylogenetic results further confirmed that the family Kathlaniidae is not a monophyletic group. The subfamily Cruziinae should be moved from the hitherto-defined family Kathlaniidae and elevated as a separate family Cruziidae. The present phylogenetic results also negated the validity of the subfamily Cissophyllinae and supported the genus Cissophyllus assigned in the subfamily Kathlaniinae. Molecular analysis indicated that the morphological variation in the isthmus and position of excretory pore among different individuals should be considered as intraspecific variation. Moreover, some characters important for the specific diagnosis of C. leytensis are reported for the first time: the number of acuminate denticles (lamellae) on each lip, the chitinized pharynx with three flabellate pharyngeal plates, the presence of single medioventral precloacal papilla and the detailed morphology of caudal papillae. The present study is only the second record of C. leytensis.

Time-dependent cardiac structural and functional changes after kidney transplantation: a multi-parametric cardiac magnetic resonance study.

OBJECTIVES: To map time-dependent cardiac structural and functional change patterns after renal transplantation (KT) using cardiac magnetic resonance (CMR). METHODS: Fifty-three patients with pre-KT and post-KT CMR exams were retrospectively analyzed. Patients were divided into three groups according to the time of post-KT CMR: group 1 (3 months post-KT, n = 16), group 2 (6 months post-KT, n = 21), and group 3 (over 9 months post-KT, n = 16). Twenty-one age- and sex-matched healthy controls (HC) were recruited for the study. CMR-derived left ventricular (LV) volumes, LV mass index (LVMi), LV ejection fraction (LVEF), global radial strain (GRS), global circumferential strain (GCS), global longitudinal strain (GLS), and native T1 value were compared. The association between the changes of CMR parameters was assessed. RESULTS: LVMi post-KT decreased in groups 2 (p < 0.001) and 3 (p = 0.004) but both groups had higher LVMi values compared to HC (both p < 0.001). GLS post-KT was decreased in group 1 (p = 0.021), but slightly increased in group 2 (p = 0.728) and group 3 (p = 0.100) without significant difference. GLS post-KT in group 3 was not different from HC (p = 0.104). LVEF, GRS, and GCS post-KT in groups 2 and 3 significantly increased and showed no significant difference from HC. The post-KT native T1 value in all three groups significantly decreased; however, no group showed any significant difference from HC. The change of LVEF was associated with the change of GCS, GRS, and GLS. CONCLUSIONS: Although GRS, GCS, GLS, and native T1 values reversed to normal level, LVMi remained impaired in median 14 months after KT. KEY POINTS: • Kidney transplantation has favorable effects on cardiac structure and function. • In a median 14 months of follow-up after KT, left ventricle strain and native T1 value reversed to normal level while LV mass index (LVMi) did not. Left ventricular hypertrophy may help to explain why KT recipients are still at increased cardiovascular risk. • The reason for the decrease of native T1 value after KT may be more than myocardial fibrosis and needs to be further studied.

Morphological and molecular characterization of Paraleptus chiloscyllii Yin & Zhang, 1983 (Nematoda: Physalopteridae) from the brownbanded bambooshark Chiloscyllium punctatum Müller & Henle (Elasmobranchii: Orectolobiformes).

Paraleptus (Spirurida: Physalopteridae) is a small genus of nematodes, parasitic in fishes, most species of which are inadequately described. Genetic data for these congeners have not been reported. The detailed morphology of P. chiloscyllii was studied using light and scanning electron microscopy, based on newly collected specimens from the brownbanded bambooshark C. punctatum Müller & Henle (Elasmobranchii: Orectolobiformes) in the Taiwan Strait. Some previously unreported morphological features of taxonomic significance were observed, i.e., pseudolabium with two sublateral rows of 6-7 small spines, 7-8 small spines on each lower rim between pseudolabia, deirids not distally bifurcated, vulva with remarkable protruding lip, presence of 1 pair medio-ventral precloacal papillae and 1 pair of discoid protrusions of postcloacal lip in male. The specimens described by González-Solís & Ali's (2015) as P. chiloscyllii from the Arabian carpetshark C. arabicum off Iraq are considered a new species, for which the name P. moraveci n. sp. is proposed. The genetic characterization of the partial small (18S) and large (28S) ribosomal DNA, and the partial mitochondrial cytochrome c oxidase subunit 1 (cox1) of P. chiloscyllii are provided for the first time. There was no intraspecific nucleotide divergence detected in the 18S and 28S regions among different individuals of P. chiloscyllii, but a low level of intraspecific genetic variation was found in the cox1 (0.62-0.92%). The present genetic data is very important for molecular identification, and will be valuable for further invertigantions on the population genetics and phylogeny of this group.

Conversion from mycophenolate mofetil to mizoribine in the early stages of BK polyomavirus infection could improve kidney allograft prognosis: a single-center study from China.

BACKGROUND: Some studies have suggested mizoribine (MZR) could inhibit the replication of BK polyomavirus (BKPyV). The purpose of this study was to explore whether conversion from mycophenolate mofetil (MMF) to MZR in the early stages of BKPyV infection can improve kidney allograft prognosis. METHODS: Twenty-one kidney transplant recipients with BKPyV viruria/viremia and ten with BK polyomavirus-associated allograft nephropathy (BKPyVAN) received MZR conversion therapy were retrospectively identified. The clearance rate of urine and blood BKPyV DNA, change of serum creatinine (SCr), uric acid (UA), hemoglobin (HB), white blood cell (WBC), lymphocyte ratio, platelet (PLT), routine urinalysis, panel reactive antibody (PRA), and gastrointestinal disorders during follow-up of the 2 groups were evaluated and compared. RESULTS: After MZR conversion therapy, the clearance rate of urine and blood viral load in BKPyV viruria/viremia group were 85.7 and 100 %, while that in BKPyVAN were 40 and 87.5 %, respectively. Stable SCr were observed in all cases of BKPyV viruria/viremia group, while that of BKPyVAN was only 40 % (P < 0.001) and one even progressed to end-stage renal disease. The results of routine urinalysis in the two groups showed no significant changes before and after MZR conversion therapy. However, in BKPyV viruria/viremia group, four cases developed acute rejection and one had positive PRA-II but no donor specific antibody, requiring conversion back to MMF. Hyperuricemia was the common adverse effect of MZR. CONCLUSIONS: Conversion from MMF to MZR could help clear BKPyV infection. As compared to BKPyVAN, patients who underwent initiation of MZR conversion therapy in the early stages of BKPyV infection maintained stable allograft function. Prospective studies with larger sample size are needed to ascertain this preliminary finding.

Morphology, genetic characterization and phylogeny of Aplectana dayaoshanensis n. sp. (Nematoda: Ascaridida) from frogs.

Cosmocercoid nematodes are common parasites in the digestive tract of amphibians. However, our knowledge of the species diversity, genetic data and molecular phylogeny of the superfamily Cosmocercoidea are far from being well understood. In the present study, large numbers of cosmocercoid nematodes were collected from the fine-spined frog Sylvirana spinulosa (Smith) (Anura: Ranidae) and the white-spotted thigh tree-frog Polypedates megacephalus (Hallowell) (Anura: Rhacophoridae) in Guangxi Province, China. Integrated morphological and genetic evidence reveals these nematode specimens to be a new species of the genus Aplectana, A. dayaoshanensis n. sp. (Cosmocercoidea: Cosmocercidae). The molecular characterization of small ribosomal DNA (18S), internal transcribed spacer (ITS) and large ribosomal DNA (28S) of A. dayaoshanensis n. sp., together with the 28S of A. chamaeleonis (Baylis, 1929) (collected from Hyperolius kivuensis Ahl in Rwanda), were reported for the first time. Moreover, phylogenetic analyses using maximum likelihood (ML) inference based on 18S + 28S and ITS sequence data, respectively, both supported the family Cosmocercidae to be a monophyletic group and the family Kathlaniidae to be a paraphyletic group. Our phylogenetic results rejected the monophyly of the genus Aplectana. The present results contribute to the knowledge of the species diversity and genetic data of cosmocercoid nematodes, and preliminarily revealed the phylogenetic relationships of the major families and some genera in the Cosmocercoidea.

LncRNA HCG18 suppresses CD8+ T cells to confer resistance to cetuximab in colorectal cancer via miR-20b-5p/PD-L1 axis.

Aim: We aimed to explore the effect of long noncoding RNA HCG18 in colorectal cancer (CRC). Materials & methods: Relative gene and protein expression were screened. Colony formation and flow cytometry assays were performed to determine proliferation and apoptosis. Dual luciferase and RNA immunoprecipitation assays were conducted to validate the interaction between indicated molecules. Xenograft in nude mice was applied to verify the conclusion in vivo. Results:HCG18 and PD-L1 were upregulated while miR-20b-5p was downregulated in CRC tissue. Functional analysis revealed that lncRNA HCG18 promoted proliferation, migration and resistance to cetuximab of CRC cells via the miR-20b-5p/PD-L1 axis. Conclusion:HCG18 facilitated progress of the tumor, conferred to cetuximab resistance and suppressed CD8+ T cells via the miR-20b-5p/PD-L1 axis.

Lay abstract In the present study, we found a long noncoding RNA (lncRNA), HCG18 (a recently discovered lncRNA that facilitates tumor progression via multiple mechanisms), was upregulated in colorectal cancer (CRC). Further studies revealed that HCG18 suppressed CD8⁺ T-cell (cytotoxic T lymphocyte which kills cancer cell) activation to induce cetuximab (a first-line drug in CRC) resistance. Mechanically, HCG18 elevated expression of PD-L1 (a receptor in T-cell membranes, thus suppressing the proliferation of CD8⁺ cytotoxic T lymphocytes) via sponging (lncRNA binds with miRNA) miR-20b-5p. This study might provide a deeper insight into understanding cetuximab resistance in CRC.

Relationship Between Non-Alcoholic Fatty Liver Disease and Abdominal and Pericardial Adipose Tissue in Middle-Aged and Elderly Subjects.

OBJECTIVE: The present study aimed to explore the relationship between non-alcoholic fatty liver disease (NAFLD) and abdominal and pericardial adipose tissue in middle-aged and elderly subjects. METHODS: Between July 2019 and July 2020, 471 subjects attending the Health Care Medical Department of Peking Union Medical College Hospital for a medical examination were enrolled in the study. The volume and distribution of abdominal adipose tissue together with the volume of pericardial adipose tissue were calculated according to the results of the abdominal computed tomography. The differences between subjects with NAFLD and the normal population were analyzed. RESULTS: The volume of pericardial adipose tissue, abdominal visceral and subcutaneous adipose tissue, the total volume of abdominal adipose tissue, and volume of pelvic visceral adipose tissue were all significantly increased in subjects with NAFLD. For every 100 cm3 increase in the volume of abdominal visceral adipose tissue, the incidence of developing NAFLD increased by 9.4%. According to the results of the receiver operating curve, the cut-off point of abdominal visceral adipose tissue for the diagnosis of NAFLD was 2691.1 cm3. CONCLUSION: Overall, the risk of NAFLD increases significantly with the increase in the volume of adipose tissue.

Hsa_circ_0136666 activates Treg-mediated immune escape of colorectal cancer via miR-497/PD-L1 pathway.

PURPOSE: In the rankings of cancer mortality and incidence worldwide, colorectal cancer ranks fourth and the third, respectively. Circular RNA hsa_circ_0136666 (hsa_circ_0136666) is reported to participate in the growth of colorectal cancer. However, the mechanism by which hsa_circ_0136666 regulates the tumorigenesis of colorectal cancer needs to be further explored. In this study, we report here the role of hsa_circ_0136666 in the aberrant activation of Treg cells and immune evasion of tumor cells, providing a new strategy for the treatment of colorectal cancer. METHODS: Western blotting assay and qRT-PCR assay were used to determine protein and mRNA expression levels. Dual-luciferase reporter assay was used to evaluate the targeted regulatory relationship. RNA immunoprecipitation was used to detect RNA binding. Colony formation assay was utilized to measure the cell proliferation. Flow cytometry was used to assess cell apoptosis. Xenograft model was setup to evaluate tumor growth. RESULTS: The results showed that hsa_circ_0136666 and PD-L1 was increased in colorectal cancer cells while miR-497 was decreased in colorectal cancer cells when compared with normal colon epithelial cell line. Hsa_circ_0136666 was demonstrated to directly target miR-497, which also regulated PD-L1 by binding to its 3'UTR. Further mechanistic studies identified that hsa_circ_0136666 controlled cell proliferation and apoptosis via targeting miR-497 and regulating PD-L1 expression. Of note, hsa_circ_0136666 stimulated Treg cells mediated by miR-497/PD-L1 axis and its downstream signal pathway in Treg cells. Finally, hsa_circ_0136666 was found to accelerate the tumor growth in vivo. CONCLUSIONS: Our findings demonstrated that hsa_circ_0136666 promoted the expression of PD-L1 by inhibiting miR-497 level in colorectal cancer, thus inducing the activation of Treg cells and leading to the immune escape of tumor, providing a novel mechanistic insight into the pathogenesis of colorectal cancer.

Correlation Between the Distribution of Abdominal, Pericardial and Subcutaneous Fat and Muscle and Age and Gender in a Middle-Aged and Elderly Population.

OBJECTIVE: The present study aimed to explore the relationships between the distribution of abdominal fat and muscle and age and gender in a middle-aged and elderly population. METHODS: The levels of abdominal (visceral and subcutaneous) fat, pericardial fat, and psoas major muscle were measured in subjects who had physical examinations at the Health and Medical Department of Peking Union Medical College Hospital from July 2019 to June 2020. The relationship between fat in different areas (ie, different types of fat) and the relationship between different types of fat and the psoas major muscle were investigated in the context of different genders and ages. RESULTS: The distribution of fat and muscle differed between males and females of the middle-aged and elderly study sample. Volumes of pericardial fat, total abdominal fat, and visceral fat were significantly lower in females than in males, and the area of the psoas major muscle was also significantly lower in females than in males. Levels of subcutaneous fat and total abdominal fat showed no significant correlation with age. The level of muscle showed a significant negative correlation with age. CONCLUSION: 1) Within the middle-aged and elderly sample, male subjects had higher levels than females of all types of fat except for abdominal subcutaneous fat, and had higher levels of psoas muscle than females. 2) Pericardial fat increased with age, whereas levels of abdominal fat did not change significantly with age. 3) The area of psoas major muscle appears to be positively correlated with volumes of all types of fat: subjects with more fat tended to have higher levels of psoas major muscle.