Biology-guided radiotherapy (BgRT) is a novel technique of external beam radiotherapy, combining positron emission tomography-computed tomography (PET-CT) with a linear accelerator (LINAC). The key innovation is to utilize PET signals from tracers in tumor tissues for real-time tracking and guiding beamlets. Compared with a traditional LINAC system, a BgRT system is more complex in hardware design, software algorithm, system integration and clinical workflow. RefleXion Medical has developed the world's first BgRT system. Nevertheless, its actively advertised function, PET-guided radiotherapy, is still in the research and development phase. In this review study, we presented a number of issues related to BgRT, including its technical advantages and potential challenges.
Positron Emission Tomography Computed Tomography ; Radiotherapy Planning, Computer-Assisted/methods* ; Algorithms ; Particle Accelerators ; Biology ; Radiotherapy, Image-Guided/methods* ; Radiotherapy Dosage

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

The nucleocapsid (N) protein of SARS-CoV-2 has been reported to have a high ability of liquid-liquid phase separation, which enables its incorporation into stress granules (SGs) of host cells. However, whether SG invasion by N protein occurs in the scenario of SARS-CoV-2 infection is unknow, neither do we know its consequence. Here, we used SARS-CoV-2 to infect mammalian cells and observed the incorporation of N protein into SGs, which resulted in markedly impaired self-disassembly but stimulated cell cellular clearance of SGs. NMR experiments further showed that N protein binds to the SG-related amyloid proteins via non-specific transient interactions, which not only expedites the phase transition of these proteins to aberrant amyloid aggregation in vitro, but also promotes the aggregation of FUS with ALS-associated P525L mutation in cells. In addition, we found that ACE2 is not necessary for the infection of SARS-CoV-2 to mammalian cells. Our work indicates that SARS-CoV-2 infection can impair the disassembly of host SGs and promote the aggregation of SG-related amyloid proteins, which may lead to an increased risk of neurodegeneration.
Amyloidogenic Proteins/metabolism* ; Amyotrophic Lateral Sclerosis/genetics* ; Animals ; COVID-19 ; Cytoplasmic Granules/metabolism* ; Mammals ; SARS-CoV-2 ; Stress Granules

The aim of this paper was to investigate the mechanism of the active peptide DP17 of Eupolyphaga steleophaga in the treatment of hyperlipidemia rats. HPLC and MADIL-TOF/TOF-MS were used for the amino acid sequence analysis and solid-phase synthesis on the active peptide of E. steleophaga which were obtained by biomimetic enzymatic hydrolysis, separation and purification. The hyperlipidemia model was established by feeding with high-fat diet.Twenty days later, the rats in the blank group and the model group were given the saline and the rats in remaining groups were given the corresponding drugs by oral administration. After administration for 4 weeks, the levels of triglyceride(TG), total cholesterol(TC) and low density lipoprotein(LDL) in serum, the levels of TG, TC, adenosine monophosphate(AMP), adenosine triphosphate(ATP) in liver tissues and TG in feces were detected, respectively. Hematoxylin-eosin(HE) staining was used to observe the pathological changes of liver tissues. The Real-time fluorescence quantitative PCR method was used to detect the expression of acetyl coa carboxylase(ACC) and hydroxymethylglutaryl-coa reductase(HMGCR) mRNA in liver tissues. The expression of mammalian target of rapamycin(mTORC1) protein and adenosine 5'-monophosphate-activated protein kinase(AMPK) in liver tissues were detected by Western blot. The analysis showed that the amino acid sequence of active peptide from E. steleophaga was DAVPGAGPAGCHPGAGP(DP17). The results of pharmacological experiments showed that after oral administration of DP17 in rats, the levels of TG, TC and LDL in serum as well as TG and TC levels in liver tissues were significantly decreased(P<0.05), while the levels of AMP, ATP in liver tissues and TG content in feces were significantly increased(P<0.05); the liver steatosis of rats was significantly relieved; the expression of ACC, HMGCR mRNA and mTORC1 protein in liver tissues were significantly reduced, while the expression of AMPK phosphorylated protein was significantly increased(P<0.05). DP17, the active peptide of E. steleophag can significantly reduce lipid accumulation in liver tissues, and it may play a role in reducing blood lipids by regulating the energy metabolism balance in the body and activating AMPK/mTOR signaling pathway.
Animals ; Diet, High-Fat/adverse effects* ; Hyperlipidemias/genetics* ; Lipids ; Liver ; Peptides ; Rats ; Triglycerides

BRAF is a serine/threonine kinase that harbors activating mutations in ∼7% of human malignancies and ∼60% of melanomas. Despite initial clinical responses to BRAF inhibitors, patients frequently develop drug resistance. To identify candidate therapeutic targets for BRAF inhibitor resistant melanoma, we conduct CRISPR screens in melanoma cells harboring an activating BRAF mutation that had also acquired resistance to BRAF inhibitors. To investigate the mechanisms and pathways enabling resistance to BRAF inhibitors in melanomas, we integrate expression, ATAC-seq, and CRISPR screen data. We identify the JUN family transcription factors and the ETS family transcription factor ETV5 as key regulators of CDK6, which together enable resistance to BRAF inhibitors in melanoma cells. Our findings reveal genes contributing to resistance to a selective BRAF inhibitor PLX4720, providing new insights into gene regulation in BRAF inhibitor resistant melanoma cells.

Our study aimed to amplify and explain the items of statistical reporting requirements proposed by medical journals, and to improve the statistical reporting quality of medical articles. Statistical reporting requirements were obtained from the reporting standards published by the International Committee of Medical Journal Editors (ICMJE), the Enhancing the QUAlity and Transparency of Health Research (EQUATOR) network, and the editorial board of Chinese Medical Journal, etc. The items involved in statistical reporting requirements were summarized as issues of study design, statistical analysis, and interpretation of results. Each item was amplified based on cases of original articles. It is noticeable that the statistical reporting requirements of English medical journals generally referring to guidance documents, including "Recommendations for the conduct, reporting, editing, and publication of scholarly work in medical journals" proposed by the ICMJE, or the statements for different study types published by the EQUATOR network, where the statistical reporting of medical articles had been detailed specified. The statistical reporting requirements of Chinese medical journals, however, were usually stated by the editorial boards. Although the formats and contents of statistical analysis had been regulated, the requirements of Chinese medical journals were to some extent insufficient and should be enhanced in accordance with the international standards. In conclusion, the amplification and explanation of statistical reporting requirements were expected to help investigators understand the requirements for statistical reporting in medical researches, so as to effectively improve the quality of medical articles.
Biomedical Research ; Editorial Policies ; Humans ; Periodicals as Topic/standards* ; Publishing/standards* ; Reference Standards ; Research Design

Objective: To analyze the pathogenic surveillance programs and related factors on bacillary dysentery in Beijing, 2008-2017, to provide evidence for the practices of diagnosis, treatment and prevention of the disease. Methods: Analysis was conducted on surveillance data of bacillary dysentery, collected from the surveillance areas of national bacillary dysentery in Beijing. Shigella positive rate of stool samples were used as the gold standard while detection rate of Shigella, diagnostic accordance rate and resistance were computed on data from the surveillance programs. Chi-square test was used to compare the rates and unconditional logistic regression was used to analyze the related factors of Shigella infection. Results: Both the reported incidence rate on bacillary dysentery and detection rate of Shigella in diarrhea patients showed significantly decreasing trend, from 2008 to 2017. The accordance rate of bacillary dysentery was only 7.80% (111/1 423). Shigella sonnei was the most frequently isolated strain (73.95%, 159/215) followed by Shigella flexnery. Results from the multivariate logistic regression of Shigella positive rate revealed that among those patients who were routine test of stool positive vs. routine test of stool positive (OR=1.863, 95%CI: 1.402-2.475), onset from July to October vs. other months'time (OR=7.271, 95%CI: 4.514-11.709) temperature ≥38 ℃vs. temperature <38 ℃(OR=4.516, 95%CI: 3.369-6.053) and age from 6 to 59 years old vs. other ages (OR=1.617, 95%CI: 1.085-2.410), presenting higher positive detection rates of Shigella from the stool tests. The resistant rates on ampicillin and nalidixic acid were 97.57% (201/206) and 94.90% (186/196), both higher than on other antibiotics. The resistant rates on ciprofloxacin (16.33%, 32/196), ofloxacin (9.57%, 11/115) and on amoxilin (15.05%, 31/206) were relatively low. The resistant rate appeared higher on Shigella flexnery than on Shigella sonnei. The proportion of strains with resistance on 3 more drugs, was 30.00%(21/70). Conclusions: The diagnostic accordance rate of bacillary dysentery in Beijing was low, with severe resistance of Shigella. Our findings suggested that clinicians should take multiple factors into account in their practices about epidemiological history, clinical symptom and testing results for diarrhea patients.
Adolescent ; Adult ; Anti-Bacterial Agents/therapeutic use* ; Beijing/epidemiology* ; Child ; China/epidemiology* ; Dysentery, Bacillary/prevention & control* ; Feces/microbiology* ; Humans ; Middle Aged ; Population Surveillance/methods* ; Sentinel Surveillance ; Shigella/isolation & purification* ; Shigella flexneri/isolation & purification* ; Shigella sonnei/isolation & purification* ; Young Adult

There is no national referral criteria for burns in China till now, which brings inconvenience and confusion. Based on the oversea experiences and the actual situation in China, many famous experts on burns discussed and developed this Chinese burn referral criteria (2018 version). We hope these referral criteria will be helpful in clinical practice in burn field and can be improved continuously during application.
Burn Units ; standards ; Burns ; therapy ; China ; Humans ; Practice Guidelines as Topic ; standards ; Referral and Consultation ; standards

Objective: To investigate the prevalence of physical activity and its influencing factors in rural residents in Shanxi and Chongqing. Methods: In four counties (districts) of Shanxi and Chongqing, local residents aged ≥18 who lived there for more than one year and had no plan to migrate to other areas in 2 years were surveyed through face to face questionnaire interviews to collect the information about their daily physical activity time, sedentary time, related knowledge and attitude, and others. Results: The physical inactivity rate of the residents was 14.9%, and 88.7% of residents never took daily physical activity. The average sedentary time was (3.91±2.06) hours. The results of multivariate analysis showed that education level, per capita monthly income and activity degree were the factors influencing physical inactivity. Conclusion: The proportion of people who never took daily physical activity in the survey area was higher than the average level in rural areas in China, so measures should be taken to improve the overall rate of physical activity. For people who have exercise willingness, but have no practice, and those who have already increased their physical activities, targeted guidance is needed on the basis of strengthened health education.
China ; Educational Status ; Exercise ; Health Education ; Humans ; Income ; Motivation ; Motor Activity ; Physicians ; Prevalence ; Rural Population ; Surveys and Questionnaires