Biliary fibrosis (BF) is the result of pathological repair of bile tract injury, characterized by thickening and sclerosis of the bile duct wall and progressive stricture of the lumen, which may ultimately lead to serious adverse outcomes such as biliary obstruction, biliary cirrhosis, liver failure, and hepatobiliary malignancies. Current research describes BF as a pathological feature of certain bile tract diseases, lacking a systematic summary of its etiology, pathophysiology, molecular mechanisms, and treatment. BF is a common but easily neglected disease state in biliary system, which may promote the development and progression of hepatobiliary diseases through abnormal repair mechanism after pathological biliary tract injury. Based on the latest research progress from both domestic and international perspectives, the authors review the concept, clinical manifestation, etiology, pathogenesis, and therapeutic strategies of BF to provide a reference for clinical physicians.

Humans ; Immunoglobulin G ; Lymphadenopathy ; Diagnosis, Differential

Objective: To investigate the clinicopathological, immunophenotypic, and genetic features of malignant peripheral nerve sheath tumor (MPNST). Methods: Twenty-three cases of MPNST were diagnosed at the Jiangsu Province Hospital (the First Affiliated Hospital of Nanjing Medical University), China, between January 2012 and December 2022 and thus included in the study. EnVision immunostaining and next-generation sequencing (NGS) were used to examine their immunophenotypical characteristics and genomic aberrations, respectively. Results: There were 10 males and 13 females, with an age range of 11 to 79 years (median 36 years), including 14 cases of neurofibromatosis type I-associated MPNST and 9 cases of sporadic MPNST. The tumors were located in extremities (7 cases), trunk (4 cases), neck and shoulder (3 cases), chest cavity (3 cases), paraspinal area (2 cases), abdominal cavity (2 cases), retroperitoneum (1 case), and pelvic cavity (1 case). Morphologically, the tumors were composed of dense spindle cells arranged in fascicles. Periphery neurofibroma-like pattern was found in 73.9% (17/23) of the cases. Under low magnification, alternating hypercellular and hypocellular areas resembled marbled appearance. Under high power, the tumor cell nuclei were irregular, presenting with oval, conical, comma-like, bullet-like or wavy contour. In 7 cases, the tumor cells demonstrated marked cytological pleomorphism and rare giant tumor cells. The mitotic figures were commonly not less than 3/10 HPF, and geographic necrosis was often noted. Immunohistochemically, tumor cells were positive for S-100 (14/23, 60.9%) and SOX10 (11/23, 47.8%). The loss of the CD34-positive fibroblastic network encountered in neurofibromas was observed in 14/17 of the MPNST cases. The loss of H3K27me3 expression was observed in 82.6% (19/23) of the cases. Moreover, SDHA and SDHB losses were presented in one case. NGS revealed that NF1 gene loss of function (germline or somatic) were found in all 5 cases tested. Furthermore, four cases accompanied with somatic mutations of SUZ12 gene and half of them had somatic mutations of TP53 gene, while one case with germline mutation in SDHA gene and somatic mutations in FAT1, BRAF, and KRAS genes. Available clinical follow-up was obtained in 19 cases and ranged from 1 to 67 months. Four patients died of the disease, all of whom had the clinical history of neurofibromatosis type Ⅰ. Conclusions: MPNST is difficult to be differentiated from a variety of spindle cell tumors due to its wide spectrum of histological morphology and complex genetic changes. H3K27me3 is a useful diagnostic marker, while the loss of CD34 positive fibroblastic network can also be a diagnostic feature of MPNST. NF1 gene inactivation mutations and complete loss of PRC2 activity are the common molecular diagnostic features, but other less commonly recurred genomic aberrations might also contribute to the MPNST pathogenesis.
Female ; Male ; Humans ; Child ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; Neurofibrosarcoma ; Neurofibromatosis 1 ; Histones ; Genes, p53 ; Nerve Sheath Neoplasms

Background: and Purpose Randomized trials proved the benefits of mechanical thrombectomy (MT) for select patients with large vessel occlusion (LVO) within 24 hours of last-known-well (LKW). Recent data suggest that LVO patients may benefit from MT beyond 24 hours. This study reports the safety and outcomes of MT beyond 24 hours of LKW compared to standard medical therapy (SMT). Methods: This is a retrospective analysis of LVO patients presented to 11 comprehensive stroke centers in the United States beyond 24 hours from LKW between January 2015 and December 2021. We assessed 90-day outcomes using the modified Rankin Scale (mRS). Results: Of 334 patients presented with LVO beyond 24 hours, 64% received MT and 36% received SMT only. Patients who received MT were older (67±15 vs. 64±15 years, P=0.047) and had a higher baseline National Institutes of Health Stroke Scale (NIHSS; 16±7 vs.10±9, P<0.001). Successful recanalization (modified thrombolysis in cerebral infarction score 2b-3) was achieved in 83%, and 5.6% had symptomatic intracranial hemorrhage compared to 2.5% in the SMT group (P=0.19). MT was associated with mRS 0–2 at 90 days (adjusted odds ratio [aOR] 5.73, P=0.026), less mortality (34% vs. 63%, P<0.001), and better discharge NIHSS (P<0.001) compared to SMT in patients with baseline NIHSS ≥6. This treatment benefit remained after matching both groups. Age (aOR 0.94, P<0.001), baseline NIHSS (aOR 0.91, P=0.017), Alberta Stroke Program Early Computed Tomography (ASPECTS) score ≥8 (aOR 3.06, P=0.041), and collaterals scores (aOR 1.41, P=0.027) were associated with 90-day functional independence. Conclusion In patients with salvageable brain tissue, MT for LVO beyond 24 hours appears to improve outcomes compared to SMT, especially in patients with severe strokes. Patients’ age, ASPECTS, collaterals, and baseline NIHSS score should be considered before discounting MT merely based on LKW.

Humans ; COVID-19/epidemiology* ; Operating Rooms ; SARS-CoV-2 ; Learning ; Delivery of Health Care

Rhipicephalus sanguineus, commonly known as brown dog tick is a widespread species with considerable public health and economic importance. Tremendous efforts were performed to control the tick populations with the concern of resistance build-up and environmental issues. Alternative towards microbial control thus emerged as one option to reduce tick populations. In this study, the ovicidal efficacy of a native isolate entomopathogenic hyphomycetes fungi, Metarhizium anisopliae strain HSAH5 was evaluated against eggs of R. sanguineus. Spray applications with three different conidial concentrations of 105, 106 and 107 conidia mL-1; 40 ppm of Flumethrin and a negative control. The M. anisopliae strain was found highly virulent to R. sanguineus eggs by reducing the hatching percentages to ≈30% compared with 8.9% in Flumethrin eggs. The result showed a significantly higher mortality in M. anisopliae group than those of the control groups (F = 42.08, df = 32, P < 0.001) at 30 days post-infection. However, there are no significant differences within the M. anisopliae group, in which the mortality between different conidial concentrations is almost the same. The estimated LC50 of M. anisopliae against eggs of R. sanguineus is 1.36 × 103 conidia ml-1. Thus, these results suggest M. anisopliae strain HSAH5 could be a potential biocontrol agent of R. sanguineus in the integrated approach to managing ticks in the residential landscape by targeting on the eggs.

Chigger mites is a group of arthropods and some of them are vectors of scrub typhus. As a common synanthropic rodent species, the Brown rat (Rattus norvegicus) often harbors lots of ectoparasites including chigger mites. According to some “data mining” strategies, the present study took the advantage of the abundant original data from a long-term field ecological investigation between 2001 and 2015 to make a detailed analysis of chigger mites on R. norvegicus in Yunnan Province, Southwest of China. From 18 of 33 investigated counties, only 1414 chigger mites were collected from 1113 Brown rats with relatively low infestations. The 1414 individual chigger mites were identified as comprising 61 species, 11 genera and 2 subfamilies of the family Trombiculidae with a high species diversity (S=61, H’=3.13). Of 61 mite species, there were four main species, Walchia ewingi, Ascoschoengastia indica, W. koi and A. rattinorvegici, which accounted for 44.41% of the total mites. All the chigger mites were of aggregated distribution among different individuals of R. norvegicus. The Brown rats in the outdoor habitats harbored much more individuals and species of chigger mites with a higher mean abundance (MA=1.46) and mean intensity (MI=12.53) than in the indoor habitats (P<0.05). The overall infestation of the rats was significantly higher in the mountainous landscapes than in the flatland landscapes (P<0.001). The species similarity (Css) of the mites on the male and female rats reached 64.44% with sex biased infestations. The male rats harbored more species and individuals of the mites than the female rats. The adult rats harbored more species and individuals of the mites than the juvenile rats. The species abundance distribution of the mites was successfully fitted by Preston’s lognormal model with S ^ (R)=15e–[0.31(R–1)]2 (α=0.31, R2=0.95). On the basis of fitting the theoretical curve by Preston’s model, the total mite species on R. norvegicus was estimated to be 86 species, and 25 rare mite species were missed in the sampling field investigation. The curve tendency of the species-plot relationship indicates that R. norvegicus have a great potential to harbor many species of chigger mites, and more species of the mites would be collected if more rats are sampled.

OBJECTIVE：To prelimi narily investigate the possible mechanism of orazamide to prevent anti-tuberculosis drug-induced liver injury （ATB-DILI）. METHODS ：A total of 60 Kunming mice were randomly divided into blank group ，model group，positive control group [diammonium glycyrrhizinate 60 mg/（kg·d）]，orazamide low-dose ，medium-dose and high-dose groups [ 80，160，320 mg/（kg·d）]，with 10 mice in each group. Except for blank group ，other groups were given isoniazid [ 75 mg/（kg·d）]+rifampicin [ 75 mg/（kg·d）] for 14 days intragastrically to induce ATB-DILI model. At the same time ，administration groups were given relevant medicine intragastrically ，blank group and model group were given normal saline intragastrically. The administration volume was 20 mL/（kg·d），once a day ，for consecutive 14 days. The general conditions of the mice were observed and recorded every day ，such as growth and development ，mental and diet state. After last medication ，liver index was calculated ， and HE staining was adopted to observe pathological changes of liver tissue of mice. The positive expression of high mobility group protein B 1 （HMGB1） and NF-κ B in liver tissue were detected by streptavidin biotin-peroxidase complex （SABC） immuno- histochemistry. The serum levels of liver function indexes in serum ，the protein expression of advanced glycation end product receptor（RAGE）and TNF-α in liver tissue were detected by ELISA. RESULTS：Compared with blank group ，the growth and development of mice in the model group were slow ，and their appetite and spirit were poor. The liver index ，serum levels of TBIL ， DBIL，ALT，AST，ALP，TBA and γ-GT were increased significantly （P＜0.05）. Structural disorder of liver lobules ，degeneration and necrosis of liver cells and inflammatory cell infiltration were observed. The expression of HMGB 1，NF-κB，RAGE and TNF-α in liver tissue were elevated significantly （P＜0.05）. Compared with model group ，the general condition of mice were all improved to different extents in orazamide low-dose ，medium-dose and high-dose groups ，positive control group ，while liver index and above serum indexes were all decreased significantly （P＜0.05）. The pathological changes of liver tissue were all improved to different extents ，while the protein expression of HMGB 1，NF-κB，RAGE and TNF-α were all decreased significantly（P＜0.05）. The improvement of above indexes in orazamide high-dose group were all significantly better than orazamide low-dose and medium-dose groups （P＜0.05）；the levels of ALP and TBA in orazamide high-dose group were significantly lower than positive control group （P＜0.05）. CONCLUSIONS ：Orazamide can prevent ATB-DILI induced by isoniazid combined with rifampicin in mice，the mechanism of which may be associated with down-regulating the protein expression of HMGB 1 and RAGE in liver tissue and inhibiting the secretion of inflammatory factors.

Objective: A high rate of cerebral aneurysm recurrence following endovascular coiling has prompted the use of digital subtraction angiography (DSA) for interval follow-up. However, the utility of skull x-rays as an alternative screening method for aneurysm recurrence is unproperly characterized. Methods: Retrospective review of a prospective registry of ruptured and unruptured cerebral aneurysms. Anteroposterior and lateral skull x-rays were obtained immediately at the end of the procedure and at 6-month follow-up. Aneurysm recurrence was defined by comparing post-procedure and 6-month DSA imaging. A true positive was defined as a change in coil mass morphology on at least one projection with aneurysm recurrence on DSA, and a true negative defined as a stable coil mass on both projections and no recurrence on DSA. Receiver operating characteristic area under the curve (AUC) statistics was used to assess the performance of skull x-rays in identifying aneurysm recurrence. Results: A total of 118 cerebral aneurysms were evaluated with DSA imaging and skull x-rays. A change in coil mass morphology on one projection of skull x-rays correctly detected all true recurrences with a sensitivity of 100% (95% confidence interval [CI], 91-100%). Skull x-rays failed to identify a stable aneurysm coil mass in 15 cases, with a specificity of 79% (68-88%). Skull x-rays performed with AUC 0.8958 (95% CI, 0.8490-0.9431) in identifying aneurysm recurrence. Conclusions The findings of our study suggest that skull x-rays may represent a lowcost, non-invasive screening tool to rule out aneurysm recurrence, which can potentially aid in decreasing the utilization of DSA in the follow-up of patients with coiled cerebral aneurysms.