The role of radiotherapy in patients with refractory Hodgkin's lymphoma after treatment with brentuximab vedotin and/or immune checkpoint inhibitors.

Background: Approximately 10%-30% of patients with Hodgkin's lymphoma (HL) experience relapse or refractory (R/R) disease after first-line standard therapy. Brentuximab vedotin (BV) and immune checkpoint inhibitors (ICIs) have important roles in the salvage treatment of R/R HL. However, subsequent treatment for HL refractory to BV and/or ICI treatment is challenging. Methods: We retrospectively analyzed patients in two institutions who had R/R HL, experienced BV or ICI treatment failure, and received radiotherapy (RT) thereafter. The overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS) were analyzed. Results: Overall, 19 patients were enrolled. First-line systemic therapy comprised doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD, 84.2%); AVD plus ICIs (10.5%); and bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP, 5.3%). After first-line therapy, 15 (78.9%) and four patients (21.1%) had refractory disease and relapsed, respectively. After R/R HL diagnosis, six (31.6%), two (10.5%), and 11 (57.9%) patients received BV and ICIs concurrently, BV monotherapy, and ICI monotherapy, respectively. All patients received intensity-modulated RT (n = 12, 63.2%) or volumetric modulated arc therapy (VMAT; n = 7, 36.8%). The ORR as well as the complete response (CR) rate was 100%; the median DOR to RT was 17.2 months (range, 7.9-46.7 months). Two patients showed progression outside the radiation field; one patient had extensive in-field, out-of-field, nodal, and extranodal relapse. With a median follow-up time of 16.2 months (range, 9.2-23.2 months), the 1-year PFS and OS were 84.4% and 100%, respectively. PFS was associated with extranodal involvement (P = 0.019) and gross tumor volume (P = 0.044). All patients tolerated RT well without adverse events of grade ≥ 3. Conclusion: RT is effective and safe for treating HL refractory to BV or ICIs and has the potential to be part of a comprehensive strategy for HL.

Radiomic Prediction of CCND1 Expression Levels and Prognosis in Low-grade Glioma Based on Magnetic Resonance Imaging.

OJECTIVES: Low-grade glioma (LGG) is associated with increased mortality owing to recrudescence and the tendency for malignant transformation. Therefore, it is imperative to discover novel prognostic biomarkers as existing traditional prognostic biomarkers of glioma, including clinicopathological features and imaging examinations, are unable to meet the clinical demand for precision medicine. Accordingly, we aimed to evaluate the prognostic value of cyclin D1 (CCND1) expression levels and construct radiomic models to predict these levels in patients with LGG MATERIALS AND METHODS: A total of 412 LGG cases from The Cancer Genome Atlas (TCGA) were used for gene-based prognostic analysis. Using magnetic resonance imaging (MRI) images stored in The Cancer Imaging Archive with genomic data from TCGA, 149 cases were selected for radiomics feature extraction and model construction. After feature extraction, the radiomic signature was constructed using logistic regression (LR) and support vector machine (SVM) analyses. RESULTS: CCND1 was identified as a prognosis-related gene with differential expression in tumor and normal samples and plays a role in regulating both the cell cycle and immune response. Landmark analysis revealed that high-expression levels of CCND1 were beneficial for survival (P < 0.05) in advanced LGG. Four optimal radiomics features were selected to construct radiomics models. The performance of LR and SVM achieved areas under the curve of 0.703 and 0.705, as well as 0.724 and 0.726 in the training and validation sets, respectively. CONCLUSION: Elevated levels of CCND1 expression could impact the prognosis of patients with LGG. MRI-based radiomics, especially the AUC values, can serve as a novel tool for predicting CCND1 expression and understanding the correlation between elevated CCND1 expression and prognosis. AVAILABILITY OF DATA AND MATERIALS: The datasets analyzed during the current study are available in the TCGA, TCIA, UCSC XENA and GTEx repository, https://portal.gdc.cancer.gov/, https://www.cancerimagingarchive.net/, https://xenabrowser.net/datapages/, https://www.gtexportal.org/home/.

A signal "switch-on" photoelectrochemical sensor based on a 3D-FM/BiOI heterostructure for the sensitive detection of l-ascorbic acid.

A highly efficient 3D flower MoS2 (3D-FM)-based heterostructure photocatalyst (3D-FM/BiOI) was successfully obtained via a simple hydrothermal synthesis strategy. 3D-FM/BiOI showed prominent photoelectrochemical performance, distinguished stability and good selectivity. The introduction of 3D-FM, by promoting the photoelectric property attributed to it, facilitated the separation of photogenerated electron-hole pairs. Since the redox process of l-ascorbic acid (l-AA) resulted in an increasing photocurrent of 3D-FM/BiOI, a signal "switch-on" photoelectrochemical sensor (PECS) was designed to sensitively determine l-AA for the first time. Under optimized conditions, the 3D-FM/BiOI PECS worked over a wide range from 1 µM to 0.8 mM with a low detection limit of 0.05 µM (S/N = 3). The PECS was successfully exploited for l-AA sensing in human urine with excellent accuracy and applicability, demonstrating its practical precision and superb serviceability. Furthermore, the 3D-FM/BiOI PECS exhibited satisfactory selectivity and stability, providing a great potential platform for the construction of an l-AA sensor in various practical samples and complicated environments.

Hypofractionated radiotherapy for refractory or relapsed aggressive B-cell lymphoma in the rituximab era.

BACKGROUND: Radiotherapy (RT) is an effective and available local treatment for patients with refractory or relapsed (R/R) aggressive B-cell lymphomas. However, the value of hypofractionated RT in this setting has not been confirmed. METHODS: We retrospectively analyzed patients with R/R aggressive B-cell lymphoma who received hypofractionated RT between January 2020 and August 2022 at a single institution. The objective response rate (ORR), overall survival (OS), progression-free survival (PFS) and acute side effects were analyzed. RESULTS: A total of 30 patients were included. The median dose for residual disease was 36 Gy, at a dose per fraction of 2.3-5 Gy. After RT, the ORR and complete response (CR) rates were 90% and 80%, respectively. With a median follow-up of 10 months (range, 2-27 months), 10 patients (33.3%) experienced disease progression and three died. The 1-year OS and PFS rates for all patients were 81.8% and 66.3%, respectively. The majority (8/10) of post-RT progressions involved out-of-field relapses. Patients with relapsed diseases, no response to systemic therapy, multiple lesions at the time of RT, and no response to RT were associated with out-of-field relapses. PFS was associated with response to RT (P = 0.001) and numbers of residual sites (P < 0.001). No serious non-hematological adverse effects (≥ grade 3) associated with RT were reported. CONCLUSION: These data suggest that hypofractionated RT was effective and tolerable for patients with R/R aggressive B-cell lymphoma, especially for those that exhibited localized residual disease.

A retrospective study of 134 patients with cervical region Kikuchi-Fujimoto disease.

Background: To explore the clinical and laboratory features, therapy and prognosis of Kikuchi-Fujimoto disease (KFD) in the cervical region. Methods: We retrospectively reviewed the medical records of 134 patients who were diagnosed and treated with KFD from January 2000 to May 2022 in Fujian Medical University Union Hospital (Fujian, China). Their clinical characteristics, affected lymph node size, imaging examinations, and laboratory study results were analyzed. Results: The mean patient age was 24.9 years, and the male-female ratio was 1:1.73. Fever (55.2%, n = 74) was the most common clinical manifestation. Leukopenia (49.3%) was the commonest reported laboratory abnormality. A majority (65.7%) of the 134 patients presented with bilateral nodal involvement. Conclusion: KFD should be considered as a possible diagnosis in a female patient under the age of 30 presenting with cervical lymphadenopathy, fever, leukopenia, and elevated LDH. Level of Evidence: 4.

Dynamic Prediction of Survival for Sinonasal Extranodal Natural Killer/T-cell Lymphoma.

BACKGROUND: Extranodal natural killer/ T-cell lymphoma (ENKTL) is a rare malignant tumor. This study aimed to develop a predictive nomogram and a web-based survival rate calculator for dynamically predicting the survival of patients with sinonasal ENKTL (SN-ENKTL). METHODS: This study investigated patients (n = 134) with SN-ENKTL who had been initially treated in our hospital between Jan 2008 and Dec 2016. The patients were randomly divided into training and validation cohorts, in a 7:3 ratio. Independent prognostic factors were identified and integrated to build a predictive nomogram and a web-based calculator using the Cox-regression model. The nomogram was evaluated by consistency index and calibration curve. RESULTS: Age, lactate dehydrogenase, hemoglobin, Epstein-Barr virus DNA, and Ann Arbor stage were identified as independent risk factors. We constructed a predictive nomogram for survival and a web-based calculator (https://taiqinwang.shinyapps.io/DynNomapp/). CONCLUSION: This study developed a prognostic model and a web-based calculator specifically focused on SN-ENKTL for otolaryngologists to use to facilitate timely treatment decisions for the disease. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:1645-1651, 2023.

Synthetic Antibacterial Quaternary Phosphorus Salts Promote Methicillin-Resistant Staphylococcus aureus-Infected Wound Healing.

Background: Drug-resistant microbes pose a global health concern, requiring the urgent development of effective antibacterial agents and strategies in clinical practice. Therefore, there is an urgent need to explore novel antibacterial materials to effectively eliminate bacteria. The synthesis of quaternary phosphonium salt in haloargentate systems, wherein the phosphorus atom is represented in a cationic form, is a possible strategy for the development of antibacterial materials. Methods: Using (triphenyl)phosphonium-based quaternary phosphorus salts with different spacer lengths (n=2, 4, 6) as a template, we designed three kinds of quaternary phosphorus salts as effective antibacterial agents against drug-resistant bacteria. Results: The synthesized quaternary phosphorus salt of (1,4-DBTPP)Br2 effectively prevented the formation of the bacterial biofilms, and degraded bacterial membranes and cell walls by promoting the production of reactive oxygen species, which exhibited effective therapeutic effects in a rat model of a superficial wound infected with methicillin-resistant Staphylococcus aureus. Conclusion: The quaternary phosphorus salt (1,4-DBTPP)Br2 demonstrated hemocompatibility and low toxicity, revealing its potential in the treatment of clinical infections.

Integrated analysis and identification of hub genes as novel biomarkers for Alzheimer's disease.

Alzheimer's disease (AD) is an intractable and progressive neurodegenerative disorder that can lead to severe cognitive decline, impaired speech, short-term memory loss, and finally an inability to function in daily life. For patients, their families, and even all of society, AD can impart great emotional pressure and economic costs. Therefore, this study aimed to investigate potential diagnostic biomarkers of AD. Using the Gene Expression Omnibus (GEO) database, the expression profiles of genes were extracted from the GSE5281, GSE28146, and GSE48350 microarray datasets. Then, immune-related genes were identified by the intersections of differentially expressed genes (DEGs). Functional enrichment analyses, including Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, Disease Ontology (DO), and Gene Set Enrichment Analysis (GSEA), were performed. Subsequently, random forest models and least absolute shrinkage and selection operator regression were used to further screen hub genes, which were then validated using receiver operating characteristic (ROC) curve analysis. Finally, 153 total immune-related DEGs were identified in relation to AD. DO analysis of these immune-related DEGs showed that they were enriched in "lung disease," "reproductive system disease," and "atherosclerosis." Single GSEA of hub genes showed that they were particularly enriched in "oxidative phosphorylation." ROC analysis of AGAP3 yielded an area under the ROC curve of 0.878 for GSE5281, 0.727 for GSE28146, and 0.635 for GSE48350. Moreover, immune infiltration analysis demonstrated that AGAP3 was related to follicular helper T cells, naïve CD4 T cells, naïve B cells, memory B cells, macrophages M0, macrophages M1, macrophages M2, resting natural killer (NK) cells, activated NK cells, monocytes, neutrophils, eosinophils, and activated mast cells. These results indicate that identifying immune-related DEGs might enhance the current understanding of the development and prognosis of AD. Furthermore, AGAP3 not only plays a vital role in AD progression and diagnosis but could also serve as a valuable target for further research on AD.

Versatile Bilayer Hydrogel for Wound Dressing through PET-RAFT Polymerization.

Multifunctional hydrogel-based wound dressings have been explored for decades due to their huge potential in multifaceted medical intervention to wound healing. However, it is usually not easy to fabricate a single hydrogel with all of the desirable functions at one time. Herein, a bilayer model with an outer layer for hydrogel wound dressing was proposed. The inner layer (Hm-PNn) was a hybrid hydrogel prepared by N-isopropylacrylamide and chitosan-N-2-hydroxypropyl trimethylammonium chloride (HACC), and the outer layer (PVAo-PAmp) was prepared by polyvinyl alcohols and acrylamide. The two hydrogel layers of the bilayer model were covalently connected with excellent interfacial strength by photoinduced electron/energy transfer-reversible addition-fragmentation chain transfer (PET-RAFT) polymerization. The outer layer exposed to the ambient environment exhibited good stretchability and toughness, while the inner-layer hydrogel adhered to the skin exhibited excellent softness, antibacterial activity, thermoresponsivity, and biocompatibility. In particular, the inner layer of a hydrogel demonstrated excellent antibacterial capability toward both Staphylococcus aureus as Gram-positive bacteria and Escherichia coli as Gram-negative bacteria. Cell cytotoxicity showed that the cell viability of all Hm-PNn layer hydrogels exceeds 80%, confirming that the hydrogels bear excellent biocompatibility. In vivo experimental results indicated that the Hm-PNn/PVAo-PAmp bilayer hydrogel has a significant effect on the acceleration of wound healing, which was demonstrated in a full-thickness skin defect model showing improved collagen disposition and granulation tissue thickness. With these results, the established multifunctional bilayer hydrogel exhibits potential as an excellent wound dressing for wound healing applications, especially for open and infected traumas.

Clinical efficacy of the 'sandwich technique' in repairing cholesteatoma with labyrinthine fistula.

BACKGROUND: Labyrinthine fistula is the most common complication of middle ear cholesteatoma. AIMS/OBJECTIVES: To explore the postoperative hearing changes and surgical results of repairing middle ear cholesteatoma with labyrinthine fistula using the 'sandwich technique'. MATERIALS AND METHODS: We retrospectively studied the clinical data of 36 patients (36 ears) who underwent surgical treatment for cholesteatoma with labyrinthine fistula. All patients were treated by completely removing the cholesteatoma matrix and repairing the fistula using the 'sandwich technique'. The hearing, clinical features, radiological data, intraoperative findings, and surgical results were respectively analyzed. RESULTS: Most labyrinthine fistulas were located in the lateral semicircular canal (94%). Fifty percent of fistulas were of medium size. Based on Dornhoffer classification, 17 cases of labyrinthine fistulas were classified as I. In 34 patients, the average bone conduction threshold improved or did not change after surgery. Two patients had preoperative facial paralysis. During follow-up (3-60 months), all patients had no postoperative vertigo symptoms and disease recurrence. CONCLUSIONS: Following the removal of the cholesteatoma matrix, the fistula is repaired using the "sandwich technique", which preserves or increases hearing and achieves an anti-vertiginous effect. SIGNIFICANCE: This finding suggests that, 'sandwich technique' is a feasible procedure to treat cholesteatoma with labyrinthine fistula.

A retrospective study of 44 patients with head and neck Castleman's disease.

PURPOSE: To explore the clinical and pathological features, therapy and prognosis of Castleman's disease (CD) in the head and neck. METHODS: We retrospectively analyzed the clinical and pathological data of 44 patients with head and neck CD who were diagnosed in the Fujian Medical University Union hospital (Fujian, China) between May 2008 and June 2021. According to the clinical classification, they were divided into two groups, the unicentric CD (UCD, n = 20) and the multicentric CD (MCD, n = 24). Their clinical features, imaging findings, laboratory examination, and treatment results were, respectively, analyzed. RESULTS: The age of UCD patients was younger than that of MCD patients. Most of the UCD patients (80%) were female, with asymptomatic single lymphadenectasis, and the prognosis was favorable; while 70.8% of the MCD patients were male, with multiple lymph nodes throughout the body, and more prone to hepatosplenomegaly, pneumonia, serous effusion, anemia, hypoalbuminemia, elevated globulin, coagulation disorders, etc., the prognosis was bleak. Two cases of MCD patients were with systemic lupus erythematosus (SLE). CONCLUSIONS: UCD usually manifests as asymptomatic single lymph node enlargement, complete surgical resection was the mainstay of treatment modality. MCD has relatively complicated clinical symptoms and poor prognosis, and anti-IL-6 therapy may be effective.

Multifunctional Quaternary Phosphorus/Bromoargentate Hybrids: The Achievement of Greenish Blue Luminescence, Repeatable Photocurrent Responses and Durable Antimicrobial Activities with Enhanced Water Stability.

BACKGROUND: The realization of multifunction in one bulk material is fascinating for developing a new generation of devices. Quaternary phosphorus salts were seldom utilized as templates in haloargentate systems, and the hybridization of alkyl(triphenyl)phosphonium with halometallate will be a good strategy for the development of multifunctional material, especially for biological material. METHODS: Under the template of (triphenyl)phosphonium-based quaternary phosphorus salts with different spacer lengths (n=2, 3, 4), three bromoargentate hybrids were constructed via the solution method, ie, (1,2-DBTPP)(Ag2Br4) (1), {(1,3-DBTPP)2(Ag7Br11)]∙CH3CN∙H2O} n (2), and {[(1,4-DBTPP)(Ag5Br7)](CH3CN)2∙H2O} n (3) (1,2-DBTPP2+=ethane-1,2-diylbis (triphenyl)phosphonium, 1,3-DBTPP2+=propane-1,3-diylbis (triphenyl)phosphonium, 1,4-DBTPP2+=butane-1,4-diylbis (triphenyl)phosphonium)). RESULTS: The (Ag7Br11) n 4n- chain in 2 is a new type of 1-D bromoargentate chain constructed from cubane-like Ag4Br4 nodes, AgBr4 tetrahedrons and AgBr3 triangles. Interestingly, by elongating spacer n from 2 to 4, argentophilicity interactions are weakened, and the hydrogen bonds are strengthened. Consequently, their water stabilities and photocurrents are improved, in which the Ag-4d/Br-4p to π* anti-bonding orbital of the quaternary phosphorus transfer is facilitated. Furthermore, the greenish blue emissions can be detected. Finally, high inhabitation rates against Streptococcus mutans and Candida albicans can be observed in 2 and 3. CONCLUSION: In all experiments, by elongating the spacer lengths of quaternary phosphorus salts, multifunctions were integrated in the quaternary phosphorus/bromoargentate hybrids, including greenish blue luminescence, repeatable photocurrent responses and durable antimicrobial activities with enhanced water stability. This work could provide a theoretical guide for the design of new biologically multifunctional materials.

An ELISA based on soluble egg antigens for the serodiagnosis of animal schistosomiasis turkestanica.

BACKGROUND: The existing diagnostic techniques for detecting schistosomiasis turkestanica, such as aetiological assays, identify infection by parasitic worms via the incubation of miracidia from faeces or observing eggs under microscopy. However, they are limited in the diagnosis of low-grade and prepatent infections, which lead to a high misdetection rates. Therefore, a new method for parasite diagnosis with increased sensitivity is urgently needed. METHODS: Goats in Nimu County (Tibet, China) infected with Schistosoma turkestanicum in an epidemic area were selected according positivity for the infection by faecal examination. Adult worms were collected, eggs were extracted by the sodium hydroxide (NaOH) erosion method, and soluble worm antigen preparation (SWAP) and soluble egg antigen (SEA) were isolated. The best coating concentration of the antigens and the best degree of dilution for serum were determined by square array experiments, and the optimal blocking solution and serum diluents were selected. The specificity, sensitivity and crossover of the ELISA method were determined using 48 samples of goat sera positive for S. turkestanicum, 100 samples of goat sera negative for S. turkestanicum, and 54 samples of buffalo sera positive for S. japonicum. Serological assays were established with samples from goats naturally grazed in a rural area of Nimu County, Tibet Province, by using the indirect ELISA method for the diagnosis of schistosomiasis, and faeces were collected for miracidia hatching. The sensitivity of the two detection methods was compared. RESULTS: Eggs of S. turkestanicum were distributed in the host duodenum and small intestine. Eggs in the host intestinal wall were extracted by the NaOH erosion method, which provided intact eggs with reduced impurities. The testing results obtained by isolating SEA were more stable than those obtained by using SWAP and less affected by the coating concentration and serum dilution. Additionally, the value of positive serum/negative (P/N) serum for SEA was much higher than that for SWAP. The optimal coating concentration of SEA was 0.5 µg/ml, and the optimal serum dilution was 1:100. The specificity and sensitivity of the indirect ELISA based on SEA (S. turkestanicum) were both 100%, and no cross-reactivity was found with schistosomiasis japonica. An epidemiological survey of goats in naturally infected areas showed that the prevalence rate of schistosomiasis turkestanica was 93%, and the infection rate increased with the ages of the goats. CONCLUSION: We aimed to develop a sensitive method to utilize in the mass field screening of livestock. As a diagnostic antigen, SEA (S. turkestanicum) was more suitable for serological testing than SWAP (S. turkestanicum). The indirect ELISA using SEA (S. turkestanicum) exhibited good sensitivity, specificity and no cross-reactivity with schistosomiasis japonica. The degree of infectivity and prevalence of S. turkestanicum infection in endemic areas are serious and should be a focus of concern among local departments.

Genetic variation of Echinococcus spp. in yaks and sheep in the Tibet Autonomous Region of China based on mitochondrial DNA.

BACKGROUND: Cystic echinococcosis (CE) in humans and livestock is caused by Echinococcus granulosus (sensu lato). In China where CE is endemic, a number of studies have shown that Echinococcus granulosus (sensu stricto) is majorly responsible for CE. However, E. canadensis (G6) which is the second leading cause of CE is now being detected in most parts of the country. In this study, the species diversity and genetic variation of Echinococcus granulosus (s.l.) in four counties in Tibet Autonomous Region of China were investigated. METHODS: Infection with Echinococcus granulosus (s.s.) in yaks and sheep was identified using NADH dehydrogenase subunit 1 and 5 (nad1 and nad5) mitochondrial genes while the genotype G6 of E. canadensis initially diagnosed with NADH dehydrogenase subunit 1 (nad1) was further confirmed by analysis of the complete mitochondrial genome and a phylogenetic network constructed based on the nad2 and nad5 genes. RESULTS: Out of 85 hydatid cyst samples collected from slaughtered sheep (n = 54) and yaks (n = 31), 83 were identified as E. granulosus (s.s.) G1 (n = 77), G3 (n = 6) and 2 were identified as E. canadensis G6. Analysis of the nad1/nad5 genes revealed 16/17 mutations with 9/14 parsimony informative sites resulting in 15/14 haplotypes, respectively. Haplotype diversity (Hd) and nucleotide diversity (π) of E. granulosus (s.s.) population were 0.650 and 0.00127 for nad1 and 0.782 and 0.00306 for nad5, respectively, with an overall negative Tajima's D and Fu's Fs. A low FST indicated no genetic difference between isolates from sheep and yaks. CONCLUSION: Pockets of infection with E. canadensis (G6, G7, G8 and G10) have been previously reported in sheep, goats, yaks and/or humans in different parts of China. While the G6 genotype has been previously reported in sheep in the Tibet Autonomous Region, the detection in a yak in the present study represents the first to the best of our knowledge. Therefore, we recommend future surveys and control efforts to comprehensively investigate other potential intermediate hosts for the prevalence and genetic diversity of the E. canadensis group (G6, G7, G8 and G10) across the country and their inclusion into the existing CE control programme.

Analysis of genome-wide SNPs based on 2b-RAD sequencing of pooled samples reveals signature of selection in different populations of Haemonchus contortus.

The parasitic nematode Haemonchus contortus is one of the world's most important parasites of small ruminants that causes significant economic losses to the livestock sector. The population structure and selection in its various strains are poorly understood. No study so far compared its different populations using genome-wide data. Here, we focused on different geographic populations of H. contours from China (Tibet, TB; Hubei, HB; Inner Mongolia, IM; Sichuan, SC), UK and Australia (AS), using genome-wide population-genomic approaches, to explore genetic diversity, population structure and selection. We first performed next-generation high-throughput 2b RAD pool sequencing using Illumina technology, and identified single-nucleotide polymorphisms (SNPs) in all the strains. We identified 75,187 SNPs for TB, 82,271 for HB, 82,420 for IM, 79,803 for SC, 83,504 for AS and 78,747 for UK strain. The SNPs revealed low-nucleotide diversity (pi= 0.0092-0.0133) within each strain, and a significant differentiation level (average Fst = 0.34264) among them. Chinese populations TB and SC, along with the UK strain, were more divergent populations. Chinese populations IM and HB showed affinities to the Australian strain. We then analysed signature of selection and detected 44 (UK) and 03 (AS) private selective sweeps containing 49 and 05 genes, respectively. Finally, we performed the functional annotation of selective sweeps and proposed biological significance to signature of selection. Our data suggest that 2b-RAD pool sequencing can be used to assess the signature of selection in H. contortus.

Prevalence and genetic characterization of Enterocytozoon bieneusi and Giardia duodenalis in Tibetan pigs in Tibet, China.

Enterocytozoon bieneusi and Giardia duodenalis are important opportunistic enteric zoonotic pathogens that cause diarrhoea and intestinal diseases in animals and humans. China is the largest producer of pigs, but whether Tibetan pigs, a unique pig breed in Tibet, are infected with E. bieneusi and G. duodenalis is unknown. Therefore, we conducted a molecular epidemiological survey to determine the prevalence of E. bieneusi and G. duodenalis in Tibetan pigs in Tibet, China, and identified the genotypes of these causative agents. A total of 345 faecal specimens were collected from Tibetan pigs from three Tibet counties (Milin, Cuona and Gongbujiangda), examined by nested PCR and sequenced utilizing genetic markers in the ribosomal internal transcribed spacer (ITS) region of the rRNA and glutamate dehydrogenase (gdh) gene for E. bieneusi and G. duodenalis, respectively. Moreover, using multilocus sequence typing, the subtypes of E. bieneusi were identified based on four loci (MS1, MS3, MS4 and MS7). A total of 41 (11.88%) faecal samples from Tibetan pigs were E. bieneusi-positive, and 2 (0.58%) were G. duodenalis-positive. The multivariate logistic regression analysis showed that age was considered a risk factor for Tibetan pig infection of E. bieneusi. Two novel (GB11, GB31) and four known E. bieneusi genotypes (EbpC, EbpD, PigEBITS5 and CHS12) were identified and were all classified as zoonotic group 1 according to the phylogenetic analysis. Two MLGs (MLGI and MLGII) were further identified in the E. bieneusi EbpC genotype by multilocus sequence typing analysis. In addition, two G. duodenalis assemblages (D and E) were found in the present study. To our knowledge, the current study is the first to detect the prevalence and perform genetic characterization of G. duodenalis in Tibetan pigs in Tibet, China. The results could provide essential data for controlling E. bieneusi and G. duodenalis infections in Tibetan pigs that are in contact with other animals and humans, as Tibetan pigs could be a potential source for human infection by these pathogens.

Insights into the binding mechanism of BODIPY-based photosensitizers to human serum albumin: A combined experimental and computational study.

Photodynamic therapy (PDT) is a noninvasive and effective approach in clinical cancer treatments. Boron-dipyrromethene (BODIPY)-based derivatives have emerged as novel and promising photosensitizers (PSs) in PDT, attributed to their strong near-infrared singlet oxygen luminescence emissions and high photostabilities. However, the binding mechanism of BODIPY derivatives to proteins, key for their therapeutic and biomedical applications is still poorly understood. Here, we investigated the molecular interactions of two 2, 6-diiodo-BODIPY derivatives with human serum albumin (HSA) using combined experimental and computational techniques. Our spectroscopic results showed that both BODIPY derivatives formed stable complexes with HSA. Strikingly, the BODIPY/HSA complexes exhibited notably enhanced water solubility and singlet oxygen generation efficiency with respect to the BODIPY alone. Furthermore, molecular docking, molecular dynamics simulations, and binding free energy calculations provided the structural and energetic insights into the binding mechanism of BODIPY-based derivatives to HSA. Our work demonstrated that conjugation of BODIPYs with HSA may be a promising strategy to enhance the performance of BODIPY-based PSs, and the combination of computational and experimental techniques is expected to play key roles in the design and development of novel PSs with improved bioavailability and biocompatibility for cancer therapeutic applications.

DNA in serum extracellular vesicles is stable under different storage conditions.

BACKGROUND: Extracellular vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies, can be secreted by most cell types and released in perhaps all biological fluids. EVs contain multiple proteins, specific lipids and several kinds of nucleic acids such as RNAs and DNAs. Studies have found that EVs contain double-stranded DNA and that genetic information has a certain degree of consistency with tumor DNA. Therefore, if genes that exist in exosomes are stable, we may be able to use EVs genetic testing as a new means to monitor gene mutation. METHODS: In this study, EVs were extracted from serum under various storage conditions (4 °C, room temperature and repeated freeze-thaw). We used western blotting to examine the stability of serum EVs. Then, we extracted DNA from EVs and tested the concentration changing under different conditions. We further assessed the stability of EVs DNA s using polymerase chain reaction (PCR) and Sanger sequencing. RESULTS: EVs is stable under the conditions of 4 °C (for 24 h, 72 h, 168 h), room temperature (for 6 h, 12 h, 24 h, 48 h) and repeated freeze-thaw (after one time, three times, five times). Also, serum DNA is mainly present in EVs, especially in exosomes, and that the content and function of DNA in EVs is stable whether in a changing environment or not. We showed that EVs DNA stayed stable for 1 week at 4 °C, 1 day at room temperature and after repeated freeze-thaw cycles (less than three times). However, DNA from serum EVs after 2 days at room temperature or after five repeated freeze-thaw cycles could be used for PCR and sequencing. CONCLUSIONS: Serum EVs and EVs DNA can remain stable under different environments, which is the premise that EVs could serve as a novel means for genetic tumor detection and potential biomarkers for cancer diagnostics and prognostics.

A phase II study of concurrent chemoradiotherapy and erlotinib for inoperable esophageal squamous cell carcinoma.

Cisplatin-based concurrent chemoradiotherapy for patients with unresectable, locally advanced esophageal squamous cell carcinoma (ESCC) is associated with significant toxicities that are often intolerable. Prognosis for this subgroup of patients remains poor, and new therapeutic approaches are urgently needed. We investigated the efficacy and safety of paclitaxel combined with erlotinib and concurrent radiotherapy in patients with inoperable ESCC. Erlotinib (150 mg) was administered daily for 60 days beginning at the start of radiotherapy, and paclitaxel (45 mg/m²) was administered weekly along with intensity modulated conformal radiotherapy (60 Gy in 30 fractions). The median follow-up time was 21 months. The associations between EGFR and VEGF expression and treatment outcome were evaluated. Among the 21 patients treated, the overall response rate (CR + PR) was 85.6%. The median LPFS, PFS and OS were: 17.5, 14.3, and 22.9 months, respectively. Treatment-related grade 3 toxicities included esophagitis (two patients) and hypoleukemia (one patient). Grade 4 pulmonary toxicity was observed in one patient. Patients expressing EGFR had longer PFS, while those expressing VEGF or with a history of smoking had worse outcomes. Weekly paclitaxel combined with erlotinib and concurrent radiotherapy shows promise as an effective, tolerated regimen for patients with inoperable ESCC.

[Helminth Infections in Goats in Nimu County of Tibet].

Postmortem examinations were made in 99 goats in Nimu County of Tibe, and parasites were collected and identified based on morphology. The collected parasites were categorized, and infection status was analyzed. The helminth infection rate was 100% among the goats, and all showed a pattern of mixed infection. The identified parasites belonged to 21 species, 15 genera, and 9 families. The Trichuris genus（36.4%） was the most prevailing among nematodes in the gastrointestinal tract; Paramphistomum cervi（60.6%） and Paramphistomum gotoi（60.6%） were predominant among trematodes detected; Cysticercus tenuicollis（52.5%） was the predominant cestode detected; and Orientobilharzia turkestanicum was the major parasite detected in the portal vein (69.7%).