Filamentation of a relativistic proton bunch in plasma.

We show in experiments that a long, underdense, relativistic proton bunch propagating in plasma undergoes the oblique instability, which we observe as filamentation. We determine a threshold value for the ratio between the bunch transverse size and plasma skin depth for the instability to occur. At the threshold, the outcome of the experiment alternates between filamentation and self-modulation instability (evidenced by longitudinal modulation into microbunches). Time-resolved images of the bunch density distribution reveal that filamentation grows to an observable level late along the bunch, confirming the spatiotemporal nature of the instability. We provide a rough estimate of the amplitude of the magnetic field generated in the plasma by the instability and show that the associated magnetic energy increases with plasma density.

[Analysis of MTHFR gene variants in fifteen children with hyperhomocysteinemia].

The clinical manifestations, biochemical and metabolic data, genetic variations and treatment data of children with MTHFR gene variant induced hyperhomocysteinemia admitted to Hangzhou Children's Hospital and Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from November 2015 to September 2021 were analysed retrospectively. A total of 15 pediatric patients were included, including 10 males and 5 females, with onset ages ranging from 6 days to 18 years old and confirmed ages ranging from 40 days to 18 years old. One confirmed case was detected through neonatal screening, and the remaining 14 cases were all diagnosed through genetic diagnosis after onset. The main clinical manifestations were feeding difficulties, hypotonia, epilepsy, developmental delay. All patients had elevated levels of blood homocysteine, with blood homocysteine levels before and after treatment being (151.46±57.44) µmol/L and (69.96±32.88) µmol/L, significantly decreased after treatment compared with before treatment, with a statistically significant difference (P<0.001). The blood methionine level before the treatment was 9.40 (6.20, 11.96) µmol/L, normal or slightly decreased compared to the reference range. The methionine level returned to normal after treatment. A total of 19 MTHFR gene variants were detected, with 6 being unreported variants and 13 being known variants. c.1316C>T (p.L439P) was the most common variant(16.6%,5/30). All the patients had varied neurological damages, with 7 patients improved after metabolic therapy by carnitine and folinic acid, 8 patients experiencing developmental delay, and 1 patient experiencing frequent epilepsy. The clinical manifestations of MTHFR gene variation-related hyperhomocysteinemia are complex and variable. Early-onset and homozygous variants often have a poor prognosis. Blood homocysteine, blood amino acid analysis, serum total homocysteine assay and gene testing are helpful for early diagnosis.

[Scientific, transparent and applicable rankings of Chinese pathological guidelines and consensus published in the medical journals in 2022].

The STAR tool was used to evaluate and analyze the science, transparency, and applicability of Chinese pathology guidelines and consensus published in medical journals in 2022. There were a total of 18 pathology guidelines and consensuses published in 2022, including 1 guideline and 17 consensuses. The results showed that the guideline score was 21.83 points, lower than the overall guideline average (43.4 points). Consensus ratings scored an average of 27.87 points, on par with the overall consensus level (28.3 points). Areas that scored above the overall level were "conflict of interest" and "working groups", while areas that scored below the overall level were "proposals", "funding", "evidence", "consensus approaches" and "accessibility". To sum up, the formulation of pathology guidelines and consensuses in 2022 is not standardized, and the evidence retrieval process, evidence evaluation methods and grading criteria for recommendations on clinical issues are not provided in the formulation process; the process and method for reaching consensus are not provided, the plan is lacking, and registration is not carried out. It is therefore suggested that guidelines/consensus makers in the field of pathology should attach importance to evidence-based medical evidence, strictly follow guideline formulation methods and processes, further improve the scientific, applicable and transparent guidelines/consensuses in the field, and better provide support for clinicians and patients.

[Low-dose CT reconstruction based on high-dimensional partial differential equation projection recovery].

OBJECTIVE: We propose a low-dose CT reconstruction method using partial differential equation (PDE) denoising under high-dimensional constraints. METHODS: The projection data were mapped into a high-dimensional space to construct a high-dimensional representation of the data, which were updated by moving the points in the high-dimensional space. The data were denoised using partial differential equations and the CT image was reconstructed using the FBP algorithm. RESULTS: Compared with those by FBP, PWLS-QM and TGV-WLS methods, the relative root mean square error of the Shepp-Logan image reconstructed by the proposed method were reduced by 68.87%, 50.15% and 27.36%, the structural similarity values were increased by 23.50%, 8.83% and 1.62%, and the feature similarity values were increased by 17.30%, 2.71% and 2.82%, respectively. For clinical image reconstruction, the proposed method, as compared with FBP, PWLS-QM and TGV-WLS methods, resulted in reduction of the relative root mean square error by 42.09%, 31.04% and 21.93%, increased the structural similarity values by 18.33%, 13.45% and 4.63%, and increased the feature similarity values by 3.13%, 1.46% and 1.10%, respectively. CONCLUSION: The new method can effectively reduce the streak artifacts and noises while maintaining the spatial resolution in reconstructed low-dose CT images.

The 'D-M-C' strategy for conventional ameloblastoma of the mandible: a retrospective study.

The purpose of this multicentre study was to evaluate the efficacy of the 'dredging-marsupialization-curettage' (D-M-C) strategy in the treatment of conventional intraosseous ameloblastoma of the mandible. A total of 31 patients from three institutions, who had a pathological diagnosis of conventional ameloblastoma of the mandible, were treated with the D-M-C strategy. The surgical protocol comprised a dredging and marsupialization (D-M) step, with additional D-M steps as required. The patients then underwent curettage (C) once an obvious effect of the D-M step had been achieved during follow-up. Eight patients were followed up for ≥36 months but <60 months, while 23 were followed up for ≥60 months. Nineteen of the 23 patients followed up for ≥60 months were disease-free at the last follow-up, with no evidence of recurrence. The D-M step is effective for reducing the tumour size and preserving vital structures. The D-M-C surgical strategy may be a feasible treatment option for conventional ameloblastoma of the mandible.

Mechanisms of Dangua Fang in multi-target and multi-method regulation of glycolipid metabolism based on phosphoproteomics.

OBJECTIVE: To explore the mechanism of Dangua Fang (, DGR) in multi-target and multi-method regulation of glycolipid metabolism based on phosphoproteomics. METHODS: Sprague-Dawley rats with normal glucose levels were randomly divided into three groups, including a conventional diet control group (Group A), high-fat-high-sugar diet model group (Group B), and DGR group (Group C, high-fat-high-sugar diet containing 20.5 g DGR). After 10 weeks of intervention, the fasting blood glucose (FBG), 2 h blood glucose [PBG; using the oral glucose tolerance test (OGTT)], hemoglobin A1c (HbA1c), plasma total cholesterol (TC), and triglycerides (TG) were tested, and the livers of rats were removed to calculate the liver index. Then, hepatic portal TG were tested using the Gross permanent optimization-participatiory action planning enzymatic method and phosphoproteomics was performed using liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis followed by database search and bioinformatics analysis. Finally, cell experiments were used to verify the results of phosphoproteomics. Phosphorylated mitogen-activated protein kinase kinase kinase kinase 4 (MAP4k4) and phosphorylated adducin 1 (ADD1) were detected using western blotting. RESULTS: DGR effectively reduced PBG, TG, and the liver index (P < 0.05), and significantly decreased HbA1c, TC, and hepatic portal TG (P < 0.01), showed significant hematoxylin and eosin (HE) staining, red oil O staining, and Masson staining of liver tissue. The total spectrum was 805 334, matched spectrum was 260 471, accounting for accounting 32.3%, peptides were 19 995, modified peptides were 14 671, identified proteins were 4601, quantifiable proteins were 4417, identified sites were 15 749, and quantified sites were 14659. Based on the threshold of expression fold change ( > 1.2), DGR up-regulated the modification of 228 phosphorylation sites involving 204 corresponding function proteins, and down-regulated the modification of 358 phosphorylation sites involving 358 corresponding function proteins, which included correcting 75 phosphorylation sites involving 64 corresponding function proteins relating to glycolipid metabolism. Therefore, DGR improved biological tissue processes, including information storage and processing, cellular processes and signaling, and metabolism. The metabolic functions regulated by DGR mainly include energy production and conversion, carbohydrate transport and metabolism, lipid transport and metabolism, inorganic ion transport and metabolism, secondary metabolite biosynthesis, transport, and catabolism. In vitro phosphorylation validation based on cell experiments showed that the change trends in the phosphorylation level of MAP4k4 and ADD1 were consistent with that of previous phosphoproteomics studies. CONCLUSION: DGR extensively corrects the modification of phosphorylation sites to improve corresponding glycolipid metabolism-related protein expression in rats with glycolipid metabolism disorders, thereby regulating glycolipid metabolism through a multi-target and multi-method process.

Hosing of a Long Relativistic Particle Bunch in Plasma.

Experimental results show that hosing of a long particle bunch in plasma can be induced by wakefields driven by a short, misaligned preceding bunch. Hosing develops in the plane of misalignment, self-modulation in the perpendicular plane, at frequencies close to the plasma electron frequency, and are reproducible. Development of hosing depends on misalignment direction, its growth on misalignment extent and on proton bunch charge. Results have the main characteristics of a theoretical model, are relevant to other plasma-based accelerators and represent the first characterization of hosing.

[Dislocation into the anterior chamber and spontaneous repositioning of a dexamethasone intravitreal implant: a case report].

A 61-year-old male patient presented with blurred vision in the right eye for 1 day. The patient had previously undergone phacoemulsification with intraocular lens implantation (10 years ago) and intravitreal implantation of dexamethasone (due to uveitis) in the eye. There was edema in the inferior cornea, along with Descemet membrane folds. The rod-shaped dexamethasone implant was visible in the inferior anterior chamber. Without pupil dilation, the patient was asked to keep a supine position and avoid head tilting for 1 day. The implant spontaneously relocated into the vitreous cavity, resulting in a reduction of corneal edema. This suggests that the dislocation of the intravitreal implant into the anterior chamber may be caused by a local zonular abnormality, and the dislocated implant has the potential to reposition itself spontaneously.

The only species of Calvisia (Phasmatodea, Necrosciinae) from China, with a new synonymy and additional descriptions.

Calvisia is a colorful winged stick insect genus consisting of 6 subgenera and 44 species widely distributed in temperate and tropical Asia. C. medogensis syn. nov. was discovered in Mdog, Xizang (Tibet), China and is so far the only species recorded from China. We here propose that C. medogensis syn. nov. is a synonym of C. fuscoalata after checking type specimens of both species. New materials studied are deposited in Yunnan Agricultural University, China (YNAU).

[Effects of immune responses mediated by topological structures of three-dimensional bioprinted scaffolds on hair follicle cycle in mice].

Objective: To explore the effects of the immune responses mediated by topological structures of three-dimensional bioprinted scaffolds on hair follicle cycle in mice. Methods: The study was an experimental research. The alginate-gelatin composite hydrogels were printed into scaffolds using a three-dimensional bioprinter and named T45 scaffolds, T60 scaffolds, and T90 scaffolds according to the 3 topological structures of the scaffolds (the rotation angles of the printhead during printing were 45°, 60°, and 90°, respectively), and the morphology of the three scaffolds was observed after cross-linking by naked eyes. Nine 8-week-old female C57BL/6J mice were divided into T45 group, T60 group, and T90 group, according to the random number table, with three mice in each group, and the T45, T60, and T90 scaffolds were subcutaneously implanted on the back of mice, respectively. On post implantation day (PID) 7, the hair growth in the dorsal depilated area of mice was observed, the thickness of the fiber capsule around the scaffolds was observed by hematoxylin-eosin staining, and the expression levels of CD68, bone morphogenetic protein-2 (BMP-2), and tumor necrosis factor (TNF) protein in the tissue surrounding the scaffolds were observed by immunofluorescence staining. The samples of the above experiments were all 3. Results: The topological structures of the three scaffolds were all clear with high fidelity after cross-linking. On PID 7, the hair growth was obvious in the dorsal depilated area of mice in T45 group and T90 group, while hair growth was slow in the scaffold implantation area of mice in T60 group, which was significantly different from that of the unimplanted area. On PID 7, compared with (18±4) µm in T90 group, the thickness of both the fiber capsule around the scaffolds ((39±4) and (55±8) µm) of mice in T45 group and T60 group was significantly increased (P<0.05); the thickness of the fiber capsule around the scaffolds of mice in T60 group was also significantly increased compared with that in T45 group (P<0.05). On PID 7, the expression level of CD68 protein in the tissue surrounding the scaffolds of mice in T60 group was significantly higher than the levels in T45 group and T90 group (with both P values <0.05). The expression level of BMP-2 protein in the tissue surrounding the scaffolds of mice in T60 group was significantly higher than the levels in T45 group and T90 group (with both P values <0.05), and the expression level of BMP-2 protein in the tissue surrounding the scaffolds of mice in T45 group was significantly higher than that in T90 group (P<0.05). The expression level of TNF protein in the tissue surrounding the scaffolds of mice in T60 group was significantly lower than the levels in T45 group and T90 group (with both P values <0.05). Conclusions: Three-dimensional bioprinted scaffolds with different topological structures mediate different degrees of immune responses after being implanted in mice. A moderate immune response promotes hair growth in depilated area of mice, while an excessive immune response results inhibits the hair follicle entering into the anagen phase.

[Clinicopathological and genetic characteristics of congenital cystic adenomatoid malformation of lung and its associated lung cancer in adults].

Objective: To investigate the clinicopathological features and genetic characteristics of congenital cystic adenomatoid malformation (CCAM) of lung and CCAM associated lung cancer in adults. Methods: A total of 13 cases of CCAM of lung in adults, diagnosed from June 2015 to May 2023, were collected from the Department of Pathology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, China. Their histopathological features were correlated with probable development into lung cancer. Next-generation sequencing was performed on the benign and malignant areas of all cases. Results: The pathological classification of all cases were of CCAM of lung type 1. There were 4 male and 9 female cases, age ranged from 18 to 65 years, with a mean age of 41 years. Six cases were accompanied by lung cancer, all of them were mucinous adenocarcinoma. Next-generation sequencing showed no gene mutation in 2 of the 13 cases; KRAS mutations in exon 2 were detected in 7 cases, in which there were 6 cases complicated with lung mucinous adenocarcinoma and no matter in the malignant or benign regions, the same case exhibited the same mutation sites in KRAS gene. Conclusions: CCAM of the lung is a congenital disease, and in adults, type 1 is most commonly found in the pathological classification, and it is often accompanied by cancer. Gene mutations are frequently detected in CCAM of the lung, KRAS being the most recurrent mutation which may play an important role in the carcinogenesis.

Clinicopathological differences in laterally spreading tumors between rectum and colon / 中南大学学报(医学版)

Objective:To investigate the clinicopathological differences in laterally spreading tumor (LST) from the rectum and colon.Methods:Clinicopathological records of 198 patients with LST (116 cases in rectum,82 cases in colon) from the Second Xiangya Hospital of Central South University between January 2012 and January 2017 were evaluated.Results:A total of 198 colorectal LST were included.According to the endoscopic classification,nodular mixed type (LST-GM),homogeneous type (LST-GH),flat elevated type(LST-FE) and pseudodepressed type (LST-PD) were 127(64.1％),13(6.6％),41(20.7％) and 17(8.6％),respectively.LST-GM was predominant in the rectum (71.7％),while LST-FE was predominant in the colon (78.0％),with significant difference (P＜0.01).The mean size of LST was (52.03±35.62) mm or (25.37±11.56) mm in the rectum or the colon,with significant difference between them (P＜0.01).High grade intraepithelial neoplasia frequency was higher in the rectum than that in the colon (31.0％ vs 18.3％),while the low grade intraepithelial neoplasia frequency was lower in the rectum than that in the colon (61.2％ vs 75.6％) (both P＜0.05).The mean size of LSTGM and LST-GH diameter were larger in the rectum than that in the colon,and the malignant potential of LST-GM was higher in the rectum than that in the colon.The percentage of high grade intraepithelial neoplasia + invasive carcinoma was 41.8％ and 22.2％,respectively (both P＜0.05).LST in colon was mostly treated with endoscopic mucosal resection,while LST in rectum was treated by endoscopic submucosal dissection predominantly.Conclu sion:LSTs from the rectum and colon show different clinicopathological characteristics to some extent.LST-GM is predominant in the rectum,while LST-FE is predominant in the colon.The malignant potential of LST-GM is higher in the rectum than that in the colon.

Can tumor regression grade influence survival outcome in ypT3 rectal cancer?

Purpose: Locally advanced rectal cancer (LARC) patients achieving ypT3 status following neoadjuvant chemoradiation are considered to have poor response with minimal downstaging. However, residual cancer cell amounts vary in the subserosa/perirectal fat. Tumor regression grading (TRG) is an evaluation method based on the proportion of fibrosis and residual cancer cells. The aim of this study is to assess the influence of TRG in ypT3 rectal cancer patients who received neoadjuvant chemoradiation. Methods: We retrospectively reviewed 325 LARC patients who received neoadjuvant chemoradiation and surgery. TRG scores were recorded by two independent pathologists. Among these patients, 143 were staged as ypT3. We analyzed TRG and other clinicopathological factors and their relationship with survival outcome including overall survival (OS) and disease-free survival (DFS). Results: Among 143 ypT3 patients, 44 (30.8 %) were TRG1, 84 (58.7 %) were TRG2 and 15 (10.5 %) were TRG3. Seventy-nine (55.3 %) of these patients had metastatic lymph nodes. In univariate analysis, TRG was not associated with DFS (TRG2 vs TRG1, P = 0.852; TRG3 vs TRG1, P = 0.593) or OS (TRG2 vs TRG1, P = 0.977; TRG3 vs TRG1, P = 0.665). Palliative surgery (HR 3.845; 95 % CI 1.670-8.857; P = 0.002) and metastatic lymph nodes after surgery (HR 5.894; 95 % CI 1.142-3.48; P = 0.015) were significantly associated with decreased DFS, while palliative surgery was the only factor associated with worse OS (HR 6.011; 95 % CI 2.150-16.810; P = 0.001). Palliative surgery (HR 3.923; 95 % CI 1.696-9.073; P = 0.001) and metastatic lymph nodes (HR 2.011; 95 % CI 1.152-3.512; P = 0.014) also showed prognostic significance for DFS in multivariate analysis. Conclusions: Residual cancer cells evaluated by TRG score after neoadjuvant chemoradiation do not influence survival outcome in ypT3 rectal cancer patients. However, lymph node status is a significant prognostic factor in ypT3 patients (AU)

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PKM2 and ACVR 1C are prognostic markers for poor prognosis of gallbladder cancer

PURPOSE: To identify biological markers related to the progression and prognosis of GBC. METHODS: The expressions of pyruvate kinase isoenzyme type M2 (PKM2) and activin A receptor type IC (ACVR 1C) in 46 squamous cell/adenosquamous carcinomas (SC/ASC) and 80 adenocarcinomas (AC) were examined using immunohistochemistry. RESULTS: Positive PKM2 and negative ACVR 1C expressions were significantly associated with lymph node metastasis, invasion and TNM stage of SC/ASCs and ACs. Univariate Kaplan-Meier analysis showed that either elevated PKM2 or loss of ACVR 1C expression significantly correlated with shorter average survival times in both SC/ASC and AC patients. Multivariate Cox regression analysis showed that positive PKM2 expression and loss of ACVR 1C expression were poor prognosis biomarkers in both SC/ASC and AC patients. CONCLUSIONS: Our study suggested that PKM2 overexpression is a marker of metastasis, invasion and poor prognosis of GBC. ACVR 1C is a tumor suppressor, and lowered ACVR 1C expression is an important marker for the metastasis, invasion, and prognosis of GBC (AU)

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Effect of IGF-1 on expressions of VEGF under suppression of HIF-1α by shRNA in cultured human RPE cells / 中华实验眼科杂志

BackgroundProliferative vitreo-retinal disease (PVD)is one group of ocular complications marked by the enhanced proliferation of various cells included retinal pigment epithelial (RPE) cells.Insulin-like growth factor-1 (IGF-1)and vascular endothelial growth factor(VEGF) are implicated in the aberrant cell proliferation and pathological neovascularization that characterizes PVD,but the signaling mechanism is unclear now. Objective This study was to explore the effect of IGF-1 on VEGF in cultured human RPE cells under the small hairpin loop RNA (shRNA) keeping hypoxia-inducible factor-1 α ( HIF-1 α) silencing. Methods Human retinas were isolated from 4 healthy male donors,and the RPE cells were harvested and cultured.The ceils were identified using anti-human keratin antibody.The third to fifth generation of human RPE cells were used in the experiment.One target site of HIF-1α mRNA was chosen by certain design principle,and shRNA was designed and synthesized by the target site and transferred into the cells in vitro,and then the cells were cultivated with 50 μg/L IGF-1 for 24 hours.The mRNA and protein expressions of HIF-1α and VEGF were detected by RT-PCR and Western blot respectively. Results Cultured human RPE cells showed the flat irregularly multangular shape,and 97％cells appeared the positive response for keratin.HIF-1α mRNA expression in human RPE cells was significantly lower in 50 μg/L IGF-1 group than the 0 pg/L IGF-1 group ( 1.49±0.18 vs 1.46±0.17 ) ( t =0.335,P =0.743 ),however,the expressing levels of HIF-1α protein( 1049.86±172.54 vs 0.00±0.00) and VEGF mRNA(0.95±0.15 vs 0.35±0.07) and VEGF protein (391.98±56.77 vs 214.36±37.15)were raised in the 50 μg/L IGF-I group compared with 0 μg/L IGF-1 group (t=16.098,9.935,6.928,P＜0.05).After the HIF-1α-specific shRNA was transferred into cultured RPE cells,the expressions of both HIF-1α mRNA and its protein significantly decreased in RPE cells under 50 μg/L IGF-1 concentration condition( F=68.679,89.904,P=0.000),moreover,the expression of VEGF mRNA and its protein were significantly lowed(F=21.770,6.205,P＜0.05). ConclusionsIGF-1 promotes the accumulation of HIF-1α protein and induce the expression of VEGF in human RPE cells,which probably play a pivotal role in the development of PVD.