Genetic diversity and prevalence of emerging Rickettsiales in Yunnan Province: a large-scale study.

BACKGROUND: Rickettsia and related diseases have been identified as significant global public health threats. This study involved comprehensive field and systematic investigations of various rickettsial organisms in Yunnan Province. METHODS: Between May 18, 2011 and November 23, 2020, field investigations were conducted across 42 counties in Yunnan Province, China, encompassing small mammals, livestock, and ticks. Preliminary screenings for Rickettsiales involved amplifying the 16S rRNA genes, along with additional genus- or species-specific genes, which were subsequently confirmed through sequencing results. Sequence comparisons were carried out using the Basic Local Alignment Search Tool (BLAST). Phylogenetic relationships were analyzed using the default parameters in the Molecular Evolutionary Genetics Analysis (MEGA) program. The chi-squared test was used to assess the diversities and component ratios of rickettsial agents across various parameters. RESULTS: A total of 7964 samples were collected from small mammals, livestock, and ticks through Yunnan Province and submitted for screening for rickettsial organisms. Sixteen rickettsial species from the genera Rickettsia, Anaplasma, Ehrlichia, Neoehrlichia, and Wolbachia were detected, with an overall prevalence of 14.72%. Among these, 11 species were identified as pathogens or potential pathogens to humans and livestock. Specifically, 10 rickettsial organisms were widely found in 42.11% (24 out of 57) of small mammal species. High prevalence was observed in Dremomys samples at 5.60%, in samples from regions with latitudes above 4000 m or alpine meadows, and in those obtained from Yuanmou County. Anaplasma phagocytophilum and Candidatus Neoehrlichia mikurensis were broadly infecting multiple genera of animal hosts. In contrast, the small mammal genera Neodon, Dremomys, Ochotona, Anourosorex, and Mus were carrying individually specific rickettsial agents, indicating host tropism. There were 13 rickettsial species detected in 57.14% (8 out of 14) of tick species, with the highest prevalence (37.07%) observed in the genus Rhipicephalus. Eight rickettsial species were identified in 2375 livestock samples. Notably, six new Rickettsiales variants/strains were discovered, and Candidatus Rickettsia longicornii was unambiguously identified. CONCLUSIONS: This large-scale survey provided further insight into the high genetic diversity and overall prevalence of emerging Rickettsiales within endemic hotspots in Yunnan Province. The potential threats posed by these emerging tick-borne Rickettsiales to public health warrant attention, underscoring the need for effective strategies to guide the prevention and control of emerging zoonotic diseases in China.

Systematic investigation of the Borrelia miyamotoi spirochetes in ticks, wildlife and domestic animal hosts in Yunnan province, Southwest China.

Background: Borrelia miyamotoi is a spirochete species transmitted via hard ticks. Following its discovery in Japan, this pathogen has been detected around the world, and is increasingly confirmed as a human pathogen causing febrile disease, namely relapsing fever. Its presence has been confirmed in the Northeast China. However, there is little information regarding the presence of B. miyamotoi and other hard-tick-borne relapsing fever spirochetes in southern China including Yunnan province, where tick and animal species are abundant and many people both inhabit and visit for recreation. Methods: For the present study, we collected samples of ticks, wildlife, and domestic animal hosts from different counties in Yunnan province. Nucleic acids from samples were extracted, and the presence of B. miyamotoi and other relapsing fever spirochetes was confirmed using polymerase chain reaction (PCR) for the 16S rRNA specific target gene fragment. The positive samples were then amplified for partial genome of the flaB and glpQ genes. Statistical differences in its distribution were analyzed by SPSS 20 software. Sequence of partial 16S rRNA, flaB and glpQ genome were analyzed and phylogenetic trees were constructed. Results: A total of 8260 samples including 2304 ticks, 4120 small mammals and 1836 blood of domestic animal hosts were collected for screening for infection of B. miyamotoi and other relapsing fever spirochetes. Cattle and sheep act as the main hosts and Rhipicephalus microplus, Haemaphysalis nepalensis, H. kolonini and Ixodes ovatus were identified as the important vector host with high prevalence or wide distribution. Only one Mus caroli (mouse) and one Sorex alpinus (shrew) were confirmed positive for relapsing fever spirochetes. Evidence of vertical transmission in ticks was also confirmed. Two known strains of B. miyamotoi and one novel relapsing fever spirochetes, B. theileri-like agent, were confirmed and described with their host adaptation, mutation, and potential risk of spreading and spillover for human beings. Conclusions: Our results provide new evidence of relapsing fever spirochetes in vector and animal hosts in Yunnan province based on large sample sizes, and offer guidance on further investigation, surveillance and monitoring of this pathogen.

Moschamindole induces glioma cell apoptosis by blocking Mia40-dependent mitochondrial intermembrane space assembly and oxidative respiration.

Glioblastoma multiforme (GBM) is the most frequent, lethal, and aggressive tumor of the central nervous system in adults. In this study, we found for the first time that moschamindole (MCD), a rare phenolic amide with 8/6/6/5/5 rings, is a major bioactive constituent derived from Phragmites communis Trin (Poaceae) that exhibits a potential cytotoxic effect on both TMZ-resistant GBM cell lines and xenograft models. MCD-induced intrinsic apoptosis signals and mitochondrial dysfunction were confirmed by cell cycle arrest, caspase-3/7 activation, and membrane potential depolarization. Furthermore, investigations exploring the mechanism showed that MCD specifically inhibits Mia40-mediated oxidative folding of mitochondrial intermembrane space (IMS) proteins via PCR assay and immunoblot analysis. MCD relies on its positive charge to associate with mitochondrial oxidative respiration, thus blocking energy metabolism and inducing apoptosis. Overexpression and upregulation of Mia40 were proven to reverse MCD-induced apoptosis and were correlated with the chemoresistance of GBM in vitro and in vivo, respectively. Taken together, our study demonstrates that Mia40 is a potential target of the chemoresistance of glioblastoma and suggests that MCD might be a potential agent for the individualized treatment of chemoresistant GBM based on mitochondrial metabolic characteristics and Mia40 expression.

Overexpression of EP300-interacting inhibitor of differentiation 3 predicts poor prognosis in patients with glioblastoma multiforme.

EP300-interacting inhibitor of differentiation 3 (EID3) is a member of the IED family and has been associated with tumorigenesis and tumor development in different cancer types. However, the role of EID3 in glioblastoma multiforme (GBM) prognosis is not clear. Whole transcriptome sequencing data of 249 and 149 GBM patients were collected from the Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) database respectively. The correlation between EID3 expression and overall survival (OS)/clinical pathologic features of GBM patients was investigated. Based on the Wilcoxon rank-sum test, EID3 expression in GBM tissues was significantly lower than in normal brain tissues (P < 0.001), and significantly higher than in LGG (low-grade glioma) (P < 0.001).There was a significant correlation between high EID3 expression with poor OS in CGGA (P = 0.049) and TCGA data (P = 0.024). Gene set enrichment analysis (GSEA) data analysis revealed a significant difference (FDR < 0.25, NOM p-value < 0.05) in the enrichment of MSigDB Collection (h.all.v6.2.symbols.gmt). A total of eight enriched pathways were identified in the high EID3 expression group, including Myc Targets V1, Kras signaling DN, and DNA repair pathways. Multivariate Cox regression analysis indicated that high expression of EID3 correlated with poor OS (P = 0.032, HR = 1.41, CI: 1.03-1.90). We conclude that EID3 could serve as an independent factor for predicting the prognosis of patients with GBM. Moreover, it is associated with GBM development through the regulation of the Myc Targets, Kras signaling DN, and DNA repair pathways.

A rare case of giant cystic adamantinomatous craniopharyngioma in an adult.

Craniopharyngioma is an uncommon intracranial tumor that primarily occurs in the sella turcica. Giant cystic craniopharyngioma is rare in general and extremely rare in adults. We report a rare case of giant cystic craniopharyngioma in the anterior pontine cisterna and suprasellar cisterna. A 27-year-old man presented with double vision, and craniocerebral MRI revealed cystic masses in the anterior pontine cisterna and suprasellar cisterna. The masses were removed surgically and diagnosed as large cystic craniopharyngiomas by pathology and MRI. Giant cystic craniopharyngioma is rare in adults. Through this case report, we hope to increase awareness of this disease among various clinicians, including radiologists.

DSC and DCE Histogram Analyses of Glioma Biomarkers, Including IDH, MGMT, and TERT, on Differentiation and Survival.

RATIONALE AND OBJECTIVES: The World Health Organization 2016 classification of central nervous system tumors added the molecular classification of gliomas and has guiding significance for the operation and prognosis of glioma patients. At present, the perfusion technique plays an important role in judging the malignant degree of glioma. To evaluate the performance of dynamic susceptibility contrast (DSC)- and dynamic contrast-enhanced (DCE)-magnetic resonance imaging (MRI) histogram analyses in discriminating the states of molecular biomarkers and survival in glioma patients. MATERIALS AND METHODS: Forty-three glioma patients who underwent DCE- and DSC-MRI were enrolled. Relevant molecular test results, including those on isocitrate dehydrogenase (IDH), O6-methylguanine-DNA methyltransferase (MGMT) and telomere reverse transcriptase (TERT), were collected. The mean relative cerebral blood volume of DSC-MRI and histogram parameters derived from DCE-MRI (volume transfer coefficient (Ktrans), fractional volume of the extravascular extracellular space (Ve), fractional blood plasma volume (Vp), rate constant between the extravascular extracellular space and blood plasma (Kep) and area under the curve (AUC)) were calculated. Differences in each parameter between gliomas with different expression states (IDH, MGMT, and TERT) were evaluated. The diagnostic efficiency of each parameter was analyzed. The overall survival of all patients was assessed. RESULTS: The 10th percentile AUC (AUC = 0.830, sensitivity = 0.78, specificity = 0.80), the 90th percentile Ve (AUC = 0.816, sensitivity = 0.84, specificity = 0.79), and the mean Kep (AUC = 0.818, sensitivity = 0.76, specificity = 0.78) provided the highest differential efficiency for IDH, MGMT, and TERT, respectively. Kaplan-Meier curves showed a significant difference between subjects with a 10th percentile AUC higher or lower than 0.028 (log-rank = 7.535; p = 0.006) for IDH and between subjects with different 90th percentile Ve values (log-rank = 6.532; p = 0.011) for MGMT. CONCLUSION: Histogram DCE-MRI demonstrates good diagnostic performance in identifying different molecular types and for the prognostic assessment of glioma.

A Stratified Algorithm for Skull Base Reconstruction With Endoscopic Endonasal Approach.

The authors presented our institutional experience with skull base reconstruction techniques and developed a stratified algorithm for different causes of cerebrospinal fluid (CSF) leak. This is a retrospective review of patients who were diagnosed as CSF leak treated with skull base reconstruction or who underwent endoscopic transsphenoidal surgery for sellar and parasellar lesions at our department from August 2012 to April 2017. The authors totally identified 57 (59 operations in total) patients who were divided into 3 groups according to the causes of CSF leak and different reconstruction techniques. All patients underwent skull base reconstruction with specific focus on diagnosis, reconstruction techniques and strategies, and clinical outcome. The reconstruction technique we adopted was the classical multiple-layer technique, as known as "sandwich" technique, with combination of fat tissue, septal bone, autologous fascia lata, artificial dura, and nasoseptal flap (NSF). The NSF was selectively harvested for large defects according to our protocol. The reconstruction failure rate is 4.4% (2 of 45) in patients underwent endoscopic surgery for sellar and parasellar lesions. Reconstruction for postoperative iatrogenic, traumatic, and spontaneous CSF leak achieved 100% success rate; 54.2% (32 of 59) operations were done with "sandwich" plus NSF. The overall failure rate of all reconstructions was 3.4% (2 of 59). A stratified approach with multiple-layer technique and NSF is reliable for skull base reconstruction.