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In this Letter, a novel, to the best of our knowledge, robust interferometry based on orbital angular momentum (OAM) is proposed for an in-plane displacement measurement. A vortex beam (VB) is incident onto a diffraction grating, and the ±1st order diffraction beams with conjugate OAM interfere with each other. By demodulating the petal-like interferogram, the in-plane displacement of the grating can be determined. Theoretically, a 1° rotation of the interferogram corresponds to a displacement of 2.31 nm. Experimental results revealed that the maximum measurement error was less than 3.35%. The proposed measurement system combines the advantages of both OAM interferometry and grating interferometry. It adopts the grating pitch instead of the wavelength as the measurement reference, providing robust immunity to environmental disturbances while maintaining high resolution simultaneously.

Atractylodis Rhizoma, a traditional Chinese medicine with an extensive history of treating gastrointestinal disorders and other diseases, undergoes various processing methods in China to enhance its therapeutic efficacy for specific conditions. However, a comprehensive report detailing the changes in chemical composition and pharmacological effects due to these processing methods is currently lacking. This article provides a systematic review of the commonly employed processing techniques for Atractylodis Rhizoma, including raw Atractylodis Rhizoma (SCZ), bran-fried Atractylodis Rhizoma (FCZ), deep-fried Atractylodis Rhizoma (JCZ), and rice water-processed Atractylodis Rhizoma (MCZ). It examines the alterations in chemical constituents and pharmacological activities resulting from these processes and elucidates the mechanisms of action of the primary components in the various processed forms of Atractylodis Rhizoma in the treatment of gastrointestinal diseases., (Copyright © 2024 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

Eucommia ulmoides, a plant native to China, is valued for its medicinal properties and has applications in food, health products, and traditional Chinese medicine. Processed Eucommiae Cortex (EC) has historically been a highly valued medicine. Ancient doctors had ample experience processing EC, especially with ginger juice, as documented in traditional Chinese medical texts. The combination of EC and ginger juice helps release and transform the active ingredients, strengthening the medicine's effectiveness and improving its taste and shelf life. However, the lack of quality control standards for Ginger-Eucommiae Cortex (G-EC), processed from EC and ginger, presents challenges for its industrial and clinical use. This study optimized G-EC processing using the CRITIC and Box-Behnken methods. Metabolomics showed 517 chemical changes between raw and processed G-EC, particularly an increase in coniferyl aldehyde (CFA). Explainable artificial intelligence techniques revealed the feasibility of using color to CFA content, providing insights into quality indicators., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: Pressure ulcer refers to ulceration and necrosis caused by local skin and cell tissues being compressed for a long time, continuous ischemia, hypoxia, and malnutrition. However, role of prostaglandin-endoperoxide synthase 2 (PTGS2) in the management of pressure ulcers in with compound Huangbai liquid is still unclear., Methods: Traditional Chinese medicine components and related targets of compound Huangbai liquid were collected through traditional Chinese medicine systems pharmacology (TCMSP) and Batman-traditional Chinese medicine database. Disease-related targets were obtained using the Gene Cards database. The protein-protein interaction (PPI) network was constructed using the Search tool for retrieval of interacting genes (STRING) and analyzed by Cytoscape to obtain the core components. To evaluate the clinical efficacy of the compound Huangbai liquid in the treatment of pressure ulcers, 40 patients with pressure ulcers were selected and divided into an observation group and a control group, with 20 individuals in each group. The observation group received treatment with compound Huangbai liquid., Results: Sixty-five components and 480 targets of compound Huangbai liquid were obtained from TCMSP and Batman - traditional Chinese medicine databases. Two hundred seventy-three pressure ulcer-related targets were obtained. Seventy-two potential targets of compound Huangbai pigment in treatment of pressure ulcer were obtained, and 2 unrelated targets were deleted. There were 70 nodes and 1167 edges in PPI network. Gene ontology (GO) function is involved in biological processes such as reactive oxygen species metabolism and cellular response to chemical stress. Cellular components such as platelet α granules lumen and membrane rafts were involved. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment results showed that compound Huangbai liquid in treatment of pressure ulcer. The clinical results indicate that the compound Huangbai liquid has a good therapeutic effect on pressure ulcers., Conclusion: PTGS2 may be a target for treatment of pressure ulcers with compound Huangbai liquid, providing a new direction for its treatment., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Aim: To obtain an in-depth understanding of women's decision-making experiences related to mastectomy., Design: A descriptive qualitative interview study., Methods: Individual semi-structured interviews were conducted face-to-face with 27 Chinese women with breast cancer who underwent mastectomy at two tertiary hospitals in mainland China between September 2020 and December 2021 after obtaining the appropriate ethical approvals. Interviews were conducted in Mandarin. Data were analysed using inductive content analysis., Results: Mean age of participants was 48 years (range 31-70). Most participants had low education, low monthly family income, had a partner and health insurance, had been diagnosed with early breast cancer, and had not undergone reconstructive surgery. Six categories related to decision-making experiences emerged: (1) Emotions affecting decision-making, (2) Information seeking for decision-making, (3) Beliefs about mastectomy and the breast, (4) Participation in decision-making, (5) People who influence decision-making, and (6) Post-decision reflection. Participants did not mention the role of nurses in their decision-making process for mastectomy., Conclusions: This study adds valuable insights into the limited evidence on women's experience with decision-making about mastectomy from a Chinese perspective, which is important given the continuing high prevalence of mastectomy in many regions. Future studies from other countries and ethnic groups are recommended to gain diverse knowledge., Impact: The findings of this study are useful for nurses and other healthcare professionals in the multidisciplinary team to better support women with breast cancer in their decision-making process regarding mastectomy. The findings could inform future interventions to support treatment decision-making and may be relevant to women living in similar socio-medical contexts to those in mainland China., Reporting Method: The study was reported following the Standards for Reporting Qualitative Research checklist., Patient or Public Contribution: No patient or public contribution., (© 2023 The Authors. Journal of Advanced Nursing published by John Wiley & Sons Ltd.)

Background: Precise staging of hepatic fibrosis with MRI is necessary as it can assist precision medicine. Computer aided diagnosis (CAD) system with distinguishing radiomics features and radiologists domain knowledge is expected to obtain 5-grade meta-analysis of histological data in viral hepatitis (METAVIR) staging., Purpose: This study aims to obtain the precise staging of hepatic fibrosis based on MRI as it predicts the risk of future liver-related morbidity and the need for treatment, monitoring and surveillance. Based on METAVIR score, fibrosis can be divided into five stages. Most previous researches focus on binary classification, such as cirrhosis versus non-cirrhosis, early versus advanced fibrosis, and substantial fibrosis or not. In this paper, a comprehensive CAD system TMM is proposed to precisely class hepatic fibrosis into five stages for precision medicine instead of the common binary classification., Methods: We propose a novel hepatic fibrosis staging CAD system TMM which includes three modules, Two-level Image Statistical Radiomics Feature (TISRF), Monotonic Error Correcting Output Codes (MECOC) and Monotone Multiclassification with Deep Forest (MMDF). TISRF extracts radiomics features for distinguishing different hepatic fibrosis stages. MECOC is proposed to encode monotonic multiclass by making full use of the progressive severity of hepatic fibrosis and increase the fault tolerance and error correction ability. MMDF combines multiple Deep Forest network to ensure the final five-class classification, which can achieve more precise classification than the common binary classification. The performance of the proposed hepatic fibrosis CAD system is tested on the hepatic data collected from our rabbits models of fibrosis., Results: A total of 140 regions of interest (ROI) are selected from MRI T1W of liver fibrosis models in 35 rabbits with F0(n = 16), F1(n = 28), F2(n = 29), F3(n = 44) and F4(n = 23). The performance is evaluated by five-fold cross-validation. TMM can achieve the highest total accuracy of 72.14% for five fibrosis stages compared with other popular classifications. To make a comprehensive comparison, a binary classification experiment have been carried out., Conclusions: T1WI can obtain precise staging of hepatic fibrosis with the help of comprehensive CAD including radiomics features extraction inspired by radiologists, monotonic multiclass according to the severity of hepatic fibrosis, and deep learning classification., (© 2023 American Association of Physicists in Medicine.)

Density imaging is a method that uses the inversion of the gravity and gravity gradient spectra in the wavenumber domain to create accurate 3D reconstructions of subsurface density distributions. This approach offers computational efficiency and rapid calculations. This research used preliminary inversions to examine the spectral characteristics of gravity and gravity gradient anomalies, as well as the resulting models, were scrutinized through preliminary inversions. 3D density imaging of gravity and gravity gradient was performed in the wavenumber domain using depth weighting on both noise-added and theoretical data, producing a density model that was consistent with the theoretical one. The technique was then used in the Decorah region of the United States, where 3D density imaging was performed and an examination of the properties of gravity and gravity gradient anomalies was conducted. The results showed where high-density Decorah complexes, low-density siliceous intrusive rocks, and high-density intrusive rock masses, were the distributed within the surrounding rock. Each of these provided comprehensive insights into the intrusive pathways to the rock mass. Thus, the appropriateness and effectiveness of the density imaging method were confirmed, supporting a deeper understanding of the structural division and geological evolution in the region., (© 2024. The Author(s).)

Pathogenic oomycetes infect a wide variety of organisms, including plants, animals, and humans, and cause massive economic losses in global agriculture, aquaculture, and human health. Salicylic acid (SA), an endogenous phytohormone, is regarded as an inducer of plant immunity. Here, the potato late blight pathogen Phytophthora infestans was used as a model system to uncover the inhibitory mechanisms of SA on pathogenic oomycetes. In this research, SA significantly inhibited the mycelial growth, sporulation, sporangium germination, and virulence of P. infestans . Inhibition was closely related to enhanced autophagy, suppression of translation initiation, and ribosomal biogenesis in P. infestans , as shown by multiomics analysis (transcriptomics, proteomics, and phosphorylated proteomics). Monodansylcadaverine (MDC) staining and Western blotting analysis showed that SA promoted autophagy in P. infestans by probably targeting the TOR signaling pathway. These observations suggest that SA has the potential to control late blight caused by P. infestans .

Through the transfer chain of surroundings from feed to the farmed-animals and ultimately the corresponding livestock and poultry products, people are exposed to large amounts of bisphenol analogues (BPs), such as rational emissions from manufacturing plants, feed packaging bags and food packaging contact. Some BPs have been reported to show certain toxicological effects, especially, estrogen and endocrine disrupting effect. With the increasing application of BPs, the problem is becoming more and more serious. We systematically studied the hormonal effects of 18 BPs and their effects on cell homeostasis and classical signaling pathways by using classical E-SCREEN assay, fluorescent probes and western blotting. The results confirmed the estrogen-like effect of 13 BPs and 6 BPs obtained high docking scores (Scores < -9.0) for the three receptors simultaneously with the main interactions of hydrophobic, hydrogen and π-stacking of T-type bonds. BPAP regulates cells via apoptosis and steroid signaling pathway by intracellular ROS and mitochondrial followed the caspase pathway. BPE and BPS were involved in the classical NF-κB and Hippo signaling pathways. All data provides scientific basis for the safety risk assessment of endocrine disrupting and cellular homeostasis evaluation of BPs as chronic environmental pollution., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Multiple system atrophy (MSA) is a neurodegenerative disorder characterized by autonomic failure and motor dysfunction in parkinsonism and/or cerebellar ataxia. Patients with MSA usually present with depression and anxiety symptoms. This observational study of patients with MSA-cerebellar subtype (MSA-C) with subthreshold depression/anxiety symptoms aimed to compare the efficacy of escitalopram oxalate (an antidepressant drug) and tandospirone citrate (an anxiolytic drug)., Methods: Fifty-six MSA-C patients were included, with 28 patients in each treatment group. One group received escitalopram oxalate 10 mg/day and the other group received tandospirone citrate 30 mg/day. The patients were evaluated at baseline and after 4 weeks. Several psychiatric and neurological tests were performed, including the Hamilton Anxiety Rating Scale (HAMA), Hamilton Depression Rating Scale (HAMD), Scale for the Assessment and Rating of Ataxia (SARA), and the Scale for Outcomes in Parkinson's Disease for Autonomic Symptoms (SCOPA-AUT). Furthermore, post-void residual urine volume (PVR) and blood pressure were measured., Results: There was a more substantial reduction in the HAMA/HAMD, scores of stance, finger tracking, and finger nose test in the SARA, and PVR in the tandospirone group. There was a more substantial reduction in scores of dysuria, light-headed when standing up, syncope and hyperhidrosis in the SCOPA-AUT in the escitalopram group (p's < 0.05)., Conclusions: Tandospirone citrate was more effective in improving depression/anxiety and some cerebellar ataxia symptoms, whereas escitalopram was more effective in improving some autonomic symptoms in MSA-C patients over a short-term period in an open-label observational study without a control group. Further research is needed to evaluate the long-term effects of tandospirone and escitalopram in MSA-C in long-term placebo controlled trials., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Antibodies play an essential role in cancer diagnosis and treatment because of the specificity for target biomolecules and reduction of side effects. However, antibodies separation and purification still face some challenges. Antibody elution from columns using a low-pH aqueous solution leads to aggregation or loss of activity of the antibody drugs. In this paper, a block copolymer-based temperature-responsive affinity chromatography (TRAC) stationary phase, SiO 2 -P[NIPAM- b -4VP]-MEP using the block temperature-responsive copolymer poly( N -isopropylacrylamide- b -4-vinylpyridine) (P[NIPAM- b -4VP]) as the space arms and 4-mercaptoethyl pyridine (MEP) as the ligand was prepared for antibody separation. The TRAC column was tested using bovine serum albumin (BSA) and γ -globulin as model proteins, and the effects of salt concentration in the mobile phase and temperature on their separation were studied in detail. At 40 ℃, the TRAC stationary phase only selectively retained γ -globulin due to the specific affinity interaction between antibodies and the ligand MEP. At 5 ℃, γ -globulin can be eluted from the column with a mass recovery of 92.7% using a Tris-HCl buffer (pH 8.0) solution containing 0.6 mol/L NaCl. The adsorption capacity of γ -globulin on this stationary phase was (71.5 ±2.1) mg/g ( n =3), which was twice that of a traditional temperature-sensitive affinity chromatography stationary phase SiO 2 -PNIPAM-MEP. The stationary phase was also used to separate and purify immunoglobulin (IgG) in human serum in one step by altering the temperature and ion strength of the mobile phase, resulting in a purity of 97.4%±0.7%. Thus, this new technology has specific selectivity for antibodies, as well as mild and green elution conditions, ultimately resolving the problem of traditional affinity chromatography using acid elution, which can lead to the antibodies aggregation/inactivation. This technology has great application potential for the industrial production of antibody drugs.

Background: Some observational studies have shown that immune thrombocytopenia (ITP) is highly associated with the alteration-composition of gut microbiota. However, the causality of gut microbiota on ITP has not yet been determined., Methods: Based on accessible summary statistics of the genome-wide union, the latent connection between ITP and gut microbiota was estimated using bi-directional Mendelian randomization (MR) and multivariable MR (MVMR) analyses. Inverse variance weighted (IVW), weighted median analyses, and MR-Egger regression methods were performed to examine the causal correlation between ITP and the gut microbiota. Several sensitivity analyses verified the MR results. The strength of causal relationships was evaluated using the MR-Steiger test. MVMR analysis was undertaken to test the independent causal effect. MR analyses of reverse direction were made to exclude the potential of reverse correlations. Finally, GO enrichment analyses were carried out to explore the biological functions., Results: After FDR adjustment, two microbial taxa were identified to be causally associated with ITP ( P FDR < 0.10), namely Alcaligenaceae ( P FDR = 7.31 × 10 -2 ) and Methanobacteriaceae ( P FDR = 7.31 × 10 -2 ). In addition, eight microbial taxa were considered as potentially causal features under the nominal significance ( P < 0.05): Actinobacteria , Lachnospiraceae , Methanobacteria , Bacillales , Methanobacteriales , Coprococcus2 , Gordonibacter , and Veillonella . According to the reverse-direction MR study findings, the gut microbiota was not significantly affected by ITP. There was no discernible horizontal pleiotropy or instrument heterogeneity. Finally, GO enrichment analyses showed how the identified microbial taxa participate in ITP through their underlying biological mechanisms., Conclusion: Several microbial taxa were discovered to be causally linked to ITP in this MR investigation. The findings improve our understanding of the gut microbiome in the risk of ITP., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Guo, Chen, Wang, Li and FinnGen consortium.)

Purpose: Cervical cancer (CC) is a highly vascularized tumor with abundant abnormal blood vessel, which could be targeted by therapeutic strategies. Poly(L-glutamic acid)- g -methoxy poly(ethylene glycol)/combretastatin A4 (CA4)/BLZ945 nanoparticles (CB-NPs) have shown great potential as nano vascular disrupting agents (VDAs) in the realm of synergistic cancer therapy., Methods: In this study, we investigated the nanocharacteristics of CB-NPs, focusing on active pharmaceutical ingredients (API), as well as lyophilized samples combining API with protective agents (PAs). The in vivo efficacy of final sample (API + PAs) was evaluated., Results: The assembled sphere of API with complex core and thin-shell structure was confirmed. PAs were found to significantly influence in vivo efficacy. Collaborative efforts between API and PAs, namely mannitol and lactose, resulted in the most promising lyophilized sample, ie, the final sample (FS2) for CC therapy. Impressively, FS2 demonstrated an exceptional 100% cure rate on the CC U14-bearing mice model., Conclusion: FS2 has provided significant insights for cervical cancer therapy. It is also crucial to develop a comprehensive evaluation strategy for the formulation of nanomedicine, which has the potential to serve as a guideline for future clinical trials., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Guo et al.)

To study the anatomical characteristics of the root and root canal system of the mandibular second molars in the population of Gansu province, and to provide theoretical and clinical references for improving the success rate of root canal therapy (RCT) of mandibular second molars. The number of roots and root canals, root canal type and pulp chamber height of mandibular second molars were determined by observing cone-beam computed tomography (CBCT) images of people living in Gansu. The most common type of mandibular second molars in the Gansu province population was a double root with three root canals (47.55%), followed by a C-shaped root (35.56%). There were more females than males with a C-shaped root (p < 0.05). The most common root canal subtype of the C-type root was C3 (13.91%). Most of the population (77.11%) had bilateral mandibular second molars with symmetrical root canal morphology. With an increase in age, the height of the pulp chamber decreased significantly. The incidence of root canal variation of the mandibular second molars is relatively high in the population of Gansu province. Preoperative examination with CBCT is essential for mandibular second molars that need RCT to avoid root canal treatment failure and decrease the occurrence of postoperative pain as much as possible., (© 2022 The Authors. Australian Endodontic Journal published by John Wiley & Sons Australia, Ltd on behalf of Australian Society of Endodontology Inc.)

Background: Most women with breast cancer in China have received a mastectomy despite emerging breast-conserving alternatives. Their decision-making relating to mastectomy is unclear., Objective: To investigate decisional conflict, women's involvement, and psychological factors relating to mastectomy decisions., Methods: Women with breast cancer 18 years and older who had a mastectomy were recruited from 2 hospitals in China. A conceptual framework adapted from the Ottawa Decisional Support Framework was used to guide this study. Data were collected using the 16-item Decisional Conflict Scale, the 9-item Shared Decision-Making Questionnaire, and a 19-item psychological factor list., Results: A total of 304 women participated. Overall, they reported a low-level conflict and high-level involvement. "Cancer not return" was rated as the most important psychological factor influencing mastectomy decisions. Lower decisional conflict was predicted by higher involvement. Higher involvement was predicted by younger age and increased family income., Conclusions: This study is the first to demonstrate decisional conflict, involvement, and the associated factors specifically in Chinese women undergoing mastectomy. Results determined the importance of several psychological factors influencing mastectomy decisions. Future qualitative studies are required to deepen understanding of women's decision-making experiences regarding this surgery., Implications for Practice: Nurses need to provide support to Chinese women in making treatment decisions, especially for older women, and those who are economically disadvantaged. Measures are needed to promote their involvement and improve their understanding of breast cancer and its treatments, which may help reduce decisional conflict, and potentially improve their satisfaction with treatment and quality of life., Competing Interests: J.L. is funded by China Scholarship Council to study at the University of Newcastle, Australia (no. 201808350089). The funder has no role in study design, data collection, and data analysis and manuscript preparation. The other authors have no funding or conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

PM 2.5 seriously endangers human health, and its mutagenicity is considered an important pathogenic mechanism. However, the mutagenicity of PM 2.5 is mainly determined by traditional bioassays, which are limited in the large-scale identification of mutation sites. Single nucleoside polymorphisms (SNPs) can be used for the large-scale analysis of DNA mutation sites but have not yet been used on the mutagenicity of PM 2.5 . The Chengdu-Chongqing Economic Circle is one of China's four major economic circles and five major urban agglomerations, and the relationship between the mutagenicity of PM 2.5 and ethnic susceptibility in this circle remains unclear. In this study, the representative samples are PM 2.5 from Chengdu in summer (CDSUM), Chengdu in winter (CDWIN), Chongqing in summer (CQSUM) and Chongqing in winter (CQWIN) respectively. PM 2.5 from CDWIN, CDSUM and CQSUM induce the highest levels of mutation in the regions of exon/5'Utr, upstream/splice site and downstream/3'Utr respectively. PM 2.5 from CQWIN, CDWIN and CDSUM induce the highest ratio of missense, nonsense and synonymous mutation respectively. PM 2.5 from CQWIN and CDWIN induce the highest transition and transversion mutations respectively. The ability of PM 2.5 from the four groups to induce disruptive mutation effects is similar. For ethnic susceptibility, PM 2.5 in this economic circle is more likely to induce DNA mutation in Chinese Dai from Xishuangbanna among Chinese ethnic groups. PM 2.5 from CDSUM, CDWIN, CQSUM and CQWIN may particularly tend to induce Southern Han Chinese, Dai in Xishuangbanna, Dai in Xishuangbanna and Southern Han Chinese respectively. These findings may assist in the development of a new method for analyzing the mutagenicity of PM 2.5 . Moreover, this study not only promotes attention to ethnic susceptibility to PM 2.5 , but also introduces public protection policies for the susceptible population., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Biomimetic synthesis of guanine crystals has been focused on in the last years. However, multi-functional guanine crystals occluded with fluorescent molecules have not been realized in the laboratory. Here, the controllable synthesis of guanine crystal microplatelets with fluorescence and pearlescence was achieved for the first time by incorporating Nile red (NR) or fluorescein isothiocyanate (FITC) molecules into guanine crystals. The synthesized fluorescent guanine crystals are pure β-phase anhydrous guanine single crystals. Aqueous suspensions with NR- and FITC-doped guanine crystals exhibit distinct pearlescence. The fluorescence intensities of NR and FITC were greatly enhanced after being doped into guanine crystals due to the inhibition of aggregation-caused quenching. Moreover, films composed of fluorescent guanine microplatelets exhibit high diffuse reflection intensity (70 %). This work provides a strategy to synthesize multifunctional materials composed of organic crystals occluded with dyes., (© 2023 Wiley-VCH GmbH.)

Purpose: To explore the effect of role reversal and standardized patient simulation on the training of new nurses., Method: This study was conducted in a territory hospital in China between August 2021 and August 2022. The selected staff were all newly recruited and trained nurses, with a total of 58 cases. This study is a randomised controlled trial. The selected nurses were randomly divided into two groups. One group of 29 nurses (the control group) received routine training and assessment; the other group (the experimental group) was given role reversal combined with a standardized vertebral patient training examination. The implementation effects of different training and assessment methods were compared and analysed., Results: Before the training, the core competence scores of nurses in the two groups were lower, and there was no significant data difference (P > 0.05). After training, the core competence scores of nurses were improved, and the score of nurses in the experimental group was 165.49 ± 22.34. The difference was statistically significant when compared with the score of nurses in the control group (P < 0.05), indicating that nurses in the experimental group had better abilities. At the same time, the satisfaction of the two groups of nurses with the training was 96.55% (experimental group) and 75.86% (control group), and the difference in data was significant (P < 0.05). The satisfaction of the experimental group of nurses was higher, and the training effect was better., Conclusion: In the training of new nurses, the combined application of role interchange and standardized patient training and assessment methods has significant effects, which can improve the core competency of nurses and improve the training satisfaction of nurses, which is significant., (© 2023. The Author(s).)

This study aims to investigate the depth distribution of Mohorovicic discontinuity (Moho) and its relationship with the tectonic pattern of the South China Sea and adjacent areas. To achieve this, the spatial characteristics of the full tensor gravity gradient data are analyzed to identify 17 large and deep faults and to divide the study area into 9 tectonic units with distinct geological structures. Using a three-dimensional (3D) interface inversion method, the Moho depth is determined, constrained by the Moho depth information obtained from sonar-buoy detection and submarine seismograph detection profiles. By analyzing the relationship between the distribution characteristics of Moho and tectonic units, the study summarizes the trend, relief, gradient of Moho, and crustal properties in the study area. Additionally, the seismically constrained Moho undulation combined with the gravity data, gravity gradient anomalies and unconstrained 3D correlation imaging are employed to study the crustal structure of the South China Sea, investigate the vertical and horizontal changes of the crustal structure, and reveal the large-scale crustal and regional structure of the South China Sea. Through the coupling analysis of shallow and deep structures, the study reveals that the gravity gradient anomalies and 3D correlation imaging are consistent with the variations of the Moho depth, indicating the presence of a trench-island arc-back arc basin system and the distribution of continental crust, oceanic crust, and transitional crust in the South China Sea., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (© 2023 The Authors. Published by Elsevier Ltd.)

The chimeric peptide EN-9 was reported as a κ-opioid/neuropeptide FF receptors bifunctional agonist that modulated chronic pain with no tolerance. Many lines of evidence have shown that the effect of the κ-opioid receptor is mediated by not only its specific activation but also downstream events participation, especially interaction with the μ-opioid receptor pathway in antinociception and tolerance on most occasions. The present study investigated the acute and chronic cross-tolerance of EN-9 with μ-opioid receptor agonist EM-2, DAMGO, and morphine after intracerebroventricularly (i.c.v) injection in the mouse tail-flick test. In the acute tolerance test, EN-9 showed symmetrical acute cross-tolerance to DAMGO but no cross-tolerance to EM2. In the chronic tolerance test, EN-9 had no tolerance after eight days of repeated administration. However, EN-9 illustrated complete cross-tolerance to morphine and symmetrical cross-tolerance to EM2. In addition, inhibition of NPFF receptor could induce the tolerance development of EN-9. These findings indicated that supraspinal EN-9-induced antinociception contains additional components, which are mediated by the downstream μ-opioid receptor pathway both in acute and chronic treatment, whereas the subtypes of μ-opioid receptor or NPFF system pathway involved in antinociceptive effects induced by EN-9 are complex. Identifying the receptor mechanism could help design preferable bifunctional opioid compounds., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Multiple myeloma (MM) is still an intractable disease for modern clinical system, and more researches are necessary for development of more effective therapeutic strategies. This study attempted to screen and validates the biomarkers in the progression of MM via excavating Gene Expression Omnibus (GEO) database. Identification of a biomarker may help not only facilitate early diagnosis and management but also identify individuals at risk for poor prognosis and development of MM., Methods: The mRNA expression profile of the GSE87900 dataset was analyzed by GEO2R. Using the SangerBox online program, differentially expressed genes (DEGs) in high-risk MM samples were screened with the filter criteria of P<0.05 and |logFC| >1. The SangerBox online analysis tool was used to analyze the volcano plot. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was performed for DEGs. Twenty patients with high-risk MM and 20 patients with standard-risk MM from Taian City Central Hospital were included. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to verify the selected key genes in MM tissues., Results: A total of 611 DEGs were obtained. GO functional enrichment analysis showed that the DEGs were mainly enriched in the DNA replication process at the biological level, and the top DEGs were CACYBP, PCNA, MCM6, SMC1A, DTL, GINS4, MCM2, CDT1, RRM2, BRCA1, RFC5, MCM4, GINS3, GINS1, MCM10, CDC7, CDAN1, BRIP1, GINS2, CDK1, NFIB, and BARD1. The expression of CDC7 and PCNA was significantly different in high-risk MM and standard-risk MM as determined by RT-qPCR. Receiver operating characteristic (ROC) analysis showed that the areas under the curve predicted by CDC7 and PCNA were 0.900 and 0.8863, respectively, which allowed the identification of CDC7 and PCNA could be a potential biomarker of MM. Kaplan-Meier survival analysis showed that MM patients with high CDC7 and PCNA expression had shorter 2-year overall survival (OS) (P<0.05)., Conclusions: CDC7 and PCNA can be used as biomarkers for the prognosis of high-risk MM and evaluate the prognosis of MM patients, which is helpful for guiding the clinical treatment of MM patients., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-2656/coif). The authors have no conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Context: Scutellaria baicalensis Georgi (SBG) may relieve bone cancer pain (BCP) by regulating cell proliferation, angiogenesis, and apoptosis., Objective: The mechanism of SBG in the treatment of BCP remains to be further explored., Methods: The active compounds and targets of SBG were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and SwissTargetPrediction databases. BCP-related targets were screened from NCBI and GeneCards databases. Additionally, Cytoscape software was applied to construct network diagrams, and OmicShare platform was used to enrich Gene Ontology (GO) and pathways. Finally, the verification of active compounds and core targets was performed based on quantitative real-time PCR (qRT-PCR)., Results: Interestingly, we identified baicalein and wogonin as the main active components of SBG. A total of 41 SBG targets, including VEGFA, IL6, MAPK3, JUN and TNF, were obtained in the treatment of BCP. In addition, pathways in cancer may be an essential way of SBG in the treatment of BCP. Experimental verification had shown that baicalein and wogonin were significantly related to BCP core targets., Conclusions: The active components of SBG have been clarified, and the mechanism of the active components in treating BCP has been predicted and verified, which provides an experimental and theoretical basis for the in-depth elucidation of the pharmacodynamics material basis and mechanism of SBG., Competing Interests: The authors declare that they have no competing interests., (© 2022 Wang et al.)

Aim: If gastric cancer can be detected through early screening, and scientific and reasonable intervention methods can be selected in time, the condition can be effectively controlled. Routine nursing has been unable to obtain satisfactory results, and the effect on improving the compliance of the examiner is not outstanding. The research aims to estimate the outcome of nursing based on health belief combined with knowledge, belief, and practice on gastroscopy in patients with gastric cancer., Methods: 126 patients with clinically diagnosed gastric cancer in the Number Two Hospital of Baoding from May 2020 to May 2022 were randomly divided into belief guidance group and mode group, with 63 instances each. The mode group was intervened via the mode of knowledge, belief, and practice, and the belief guidance group was intervened via the nursing based on health belief on the basis of the mode group. Before and after the nursing, the health belief, examination compliance, inappropriateness, and negative emotion in different time periods were contrasted between the two groups., Results: After the nursing, the scores of health belief scale in the belief guidance group were enhanced than those in the mode group; the compliance rate of the belief guidance group was markedly enhanced than that of the mode group, and the inappropriateness during the insertion and examination was lower than that of the mode group; the scores of self-rating anxiety scale (SAS) and self-rating depression scale (SDS) in the two groups preinsertion and postnursing were markedly lower than those in the mode group., Conclusion: Nursing based on health belief guidance united with knowledge, belief, and practice mode nursing can advance the health belief and compliance of gastroscopy in patients with gastric cancer, reduce discomfort, and effectively advance the negative emotions of patients. It is worthy of clinical application., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Junna Yang et al.)

Type III polyketide synthases (PKSs) are key enzymes involved in the biosynthesis of a variety of plant specialized metabolites, including flavonoids, stilbenes, and sporopollenin, to name a few. These enzymes likely played vital roles in plant adaptation during their transition from aquatic to terrestrial habitats and their colonization of specific ecological environments. Members of this supergene family have diverse functions, but how type III PKSs and their functions have evolved remains poorly understood. Here, we conducted comprehensive phylogenomics analysis of the type III PKS supergene family in 60 species representing the major plant lineages and elucidated the classification, origin, and evolutionary history of each class. Molecular evolutionary analysis of the typical chalcone synthase and stilbene synthase types revealed evidence for strong positive natural selection in both the Pinaceae and Fabaceae lineages. The positively selected sites of these proteins include residues at the catalytic tunnel entrance and homodimer interface, which might have driven the functional divergence between the two types. Our results also suggest that convergent evolution of enzymes involved in plant flavonoid biosynthesis is quite common. The results of this study provide new insights into the origin, evolution, and functional diversity of plant type III PKSs. In addition, they serve as a guide for the enzymatic engineering of plant polyketides., (© 2022 Society for Experimental Biology and John Wiley & Sons Ltd.)

To investigate the value of the radiomic models for differentiating parasellar cavernous hemangiomas from meningiomas and to compare the classification performance with different MR sequences and classifiers. A total of 96 patients with parasellar tumors (40 cavernous hemangiomas and 56 meningiomas) were enrolled in this retrospective multiple-center study. Univariate and multivariate analyses were performed to identify the clinical factors and semantic features of MRI scans. Radiomics features were extracted from five MRI sequences using radiomics software. Three feature selection methods and six classifiers were evaluated in the training cohort to construct favorable radiomic machine-learning classifiers. The performance of different classifiers was evaluated using the AUC and compared to neuroradiologists. The detection rates of T 1 WI, T 2 WI, and CE-T 1 WI for parasellar cavernous hemangiomas and meningiomas were approximately 100%. In contrast, the ADC maps had the detection rate of 18/22 and 19/25, respectively, (AUC, 0.881) with 2.25 cm as the critical value diameter. Radiomics models with the SVM and KNN classifiers based on T 2 WI and ADC maps had favorable predictive performances (AUC > 0.90 and F-score value > 0.80). These models outperformed MRI model (AUC 0.805) and neuroradiologists (AUC, 0.756 and 0.545, respectively). Radiomic models based on T 2 WI and ADC and combined with SVM and KNN classifiers have the potential to be a viable method for differentiating parasellar hemangiomas from meningiomas. T 2 WI is more universally applicable than ADC values due to its higher detection rate for parasellar tumors., (© 2022. The Author(s).)

To analyze the effect of comprehensive nursing intervention based on ERAS's concept in laparoscopic gallbladder polyp (GP) surgery on patients' postoperative quality of life and nursing job satisfaction. Ninety patients with polyps were included in this article until October 2021. In this format, the 45 cases are divided into governing bodies and committees according to their processing time. As recommended by the ERAS committee, the committee provides daily and patient care, as well as training on the WeChat platform. The pain level (visual analogue scale (VAS) score), the quality of life (life quality index (GLQI) score), and the incidence of complications were compared between the two groups before and after the intervention. The VAS score of the control group at 2 h after operation was lower than that of the control group, and the difference was statistically significant ( P < 0.05). After the intervention, the GLQI scores of the two groups were higher than those before the intervention, and the GLQI scores of the control group were higher than those of the control group, with significant differences (all P < 0.05). Studies have shown that comprehensive nursing intervention applied to patients with gallbladder polyps can reduce postoperative pain with less complications and can also improve nursing satisfaction, which is worthy of clinical promotion., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Yan Zhang et al.)

Background: Acute myeloid leukemia (AML) is a molecularly heterogeneous disease that accounts for approximately 25% of childhood leukemia cases. In this study, we aimed to identify survival-associated genes in pediatric AML patients and investigate potential immunotherapy targets., Methods: After retrieving and processing the data from Gene Expression Omnibus (GEO) web resource, we determined hub genes in AML. Bioinformatics technology was applied to identify key genes and perform functional analysis. Finally, we investigated the correlation between the key gene and the infiltration levels of tumor-infiltrating immune cells., Results: High protein tyrosine phosphatase receptor-type C (PTPRC) expression was associated with worse overall survival rate (p < 0.001) in 287 pediatric AML patients. The results of risk subgroup analyses were similar in the high-risk and low-risk groups (p = 0.007; p = 0.013). Meanwhile, high expression of PTPRC was an independent adverse prognostic factor for overall survival (p = 0.04). Moreover, the results of immune infiltration assessment demonstrated that the expression level of PTPRC was significantly correlated with the infiltration level of activated dendritic cells (p < 0.001)., Conclusions: Overexpression of PTPRC indicates poor prognosis, and its expression level is correlated with the infiltration level of activated dendritic cells. PTPRC could be a promising immunotherapy target for pediatric AML.

Chengdu-Chongqing Economic Circle (CD-CQ Economic Circle) is one of China's four major economic circles and five major urban agglomerations located in Southwest China's Sichuan Basin. The CD-CQ Economic Circle, with its strong economic development and dense population, suffers from severe PM 2.5 pollution, which is known to cause chronic and acute respiratory ailments. This study examined the lung disease-related hub genes, functions, and pathways that are affected by PM 2.5 in summer and winter in the two central megacities of Chengdu and Chongqing. PM 2.5 frequently activates lung disease-associated hub genes, most notably the transcription factor TP53. TP53 interacts with the majority of lung disease-related genes and regulates important and commonly occurring biological functions and pathways, including gland development, aging, reactive oxygen species metabolic process, the response to oxygen levels, and fluid shear stress, among others. Thus, PM 2.5 has been shown to target TP53 for regulating lung disease genes/functions/pathways, thereby influencing the occurrence and progression of lung illnesses. Notably, PM 2.5 may be associated with small cell carcinoma of the lung due to the high number of lung disease genes, hub genes, critical functions, and pathways enriched in this kind of cancer. These findings shed fresh light on the molecular pathophysiology of PM 2.5 pollution on the respiratory system in the CD-CQ Economic Circle and aid in the development of novel techniques for mitigating PM 2.5 pollution-associated respiratory illness., (Copyright © 2022. Published by Elsevier Ltd.)

To explore the clinical efficacy of microscope combined with Wechat smart platform in patients with cholecystolithiasis and choledocholithiasis, this paper proposes the effect of microscope combined with Wechat smart platform intervention after laparoscopic lithotomy and choledocholithotomy on the clinical efficacy and gastrointestinal function of patients with cholecystolithiasis combined with choledocholithiasis. From February 2018 to March 2019, 78 patients with gastric cancer were selected by our clinic and included in the research team. Evaluate the efficacy of endoscopic biliary lithotomy (LBL) + bile duct lithotomy (TBL) + T-tube drainage therapy to provide reliable evidence for improved efficacy and efficacy in order to provide a strong reference for improving the effectiveness and safety of surgical treatment of choledocholithiasis. Safety of surgical treatment of diseases. Gallstone disease. The experiments did not show any significant differences between the two groups during surgery. Diabetes was lower in the control group, and hospital incidence was lower in the control group. There were no significant differences between the two groups for preoperative WHOQOL-100 scores. Two weeks and four weeks after surgery, the man-key-100 score was higher than that of the control group. Endoscopic cholecystectomy + choledocholithotomy + choledochoscopic lithotomy + T-tube fluid have been shown to be effective in promoting rapid intestinal function and improving patient quality of life and are appropriate for therapeutic use., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Xu Xu et al.)

Background: Osteoarthritis (OA) is the most common joint disease, and is most frequently seen in the knees. However, there is no effective therapy to relieve the progression of knee OA. Metformin is a safe, well-tolerated oral medication that is extensively used as first-line therapy for type 2 diabetes. Previous observational studies and basic researches suggested that metformin may have protective effects on knee OA, which needs to be verified by clinical trials. This study, therefore, aims to examine the effects of metformin versus placebo on knee cartilage volume loss and knee symptoms in overweight knee OA patients by a randomized controlled trial over 24 months., Methods: This protocol describes a multicenter, randomized, double-blind, and placebo-controlled clinical trial aiming to recruit 262 overweight knee OA patients. Participants will be randomly allocated to the two arms of the study, receiving metformin hydrochloride sustained-release tablets or identical inert placebo for 24 months (start from 0.5 g/day for the first 2 weeks, and increase to 1 g/day for the second 2 weeks, and further increase to 2 g/day for the remaining period if tolerated). Primary outcomes will be changes in tibiofemoral cartilage volume and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score over 24 months. Secondary outcomes will be changes in visual analogue scale (VAS) knee pain, tibiofemoral cartilage defects, effusion-synovitis volume, and tibiofemoral bone marrow lesions maximum size over 24 months. The primary analyses will be intention-to-treat analyses of primary and secondary outcomes. Per-protocol analyses will be performed as the secondary analyses., Discussion: If metformin is proved to slow knee cartilage volume loss and to relieve knee symptoms among overweight knee OA patients, it will have the potential to become a disease modifying drug for knee OA. Metformin is a convenient intervention with low cost, and its potential effects on slowing down the structural progression and relieving the symptoms of knee OA would effectively reduce the disease burden worldwide., Trial Registration: ClinicalTrials. gov NCT05034029 . Registered on 30 Sept 2021., (© 2022. The Author(s).)

CRISPR/Cas system has developed a new technology to modify target genes. In this study, CasΦ2 is a newly Cas protein that we used for genome modification in Arabidopsis and tobacco. PDS and BRI1 of marker genes were chosen for targeting. CasΦ2 has the function to cleave pre-crRNA. In the presence of 10 mM Mg 2+ irons concentration, sgRNA3 type guided CasΦ2 to edit target gene and generate mutation, and a mutant seedling of AtBRI1 gene with an expected male sterile phenotype was obtained. In the process of tobacco transformation, the gene editing activity of CasΦ2 can be activated by 100 nM Mg 2+ irons concentration, and sgRNA1 type guided CasΦ2 to edit target gene. Mutant seedlings of NtPDS gene with an expected albino were obtained. The results indicate that CasΦ2 can effectively edit target genes under the guidance of different sgRNA type in the presence of Mg 2+ ions. Together, our results verify that the CRISPR/CasΦ2 system is an effective and precise tool for genome editing in plants.

Introduction: The prevalence of mastectomy in China is higher than its Western counterparts. Little is known about whether Chinese women with breast cancer have been involved in the decision-making process of mastectomy, the level of decisional conflict, their perceptions of mastectomy and the factors that influence them to undergo a mastectomy. This protocol describes a mixed-methods study that aims to provide an in-depth understanding of decision-making about mastectomy among Chinese women with breast cancer., Methods and Analysis: A three-phase, sequential explanatory mixed-methods design will be adopted. The first phase is a retrospective analysis of medical records to determine the current use of mastectomy. The second phase is a cross-sectional survey to examine women's perceptions of involvement, decisional conflict and the factors influencing them to undergo a mastectomy. The third phase is an individual interview to explore women's decision-making experiences with mastectomy. Quantitative data will be analysed using descriptive statistics, t-test, Fisher's exact test, χ 2 test, analysis of variance, Pearson's correlation and logistic regression. Qualitative data will be analysed by the inductive content analysis., Ethics and Dissemination: Ethical approvals for this study have been obtained from the human research ethics committees of the University of Newcastle, Australia, Zhongshan Hospital Xiamen University, China, and the First Affiliated Hospital of Xiamen University, China. Written informed consent will be obtained from the participants. Findings of this work will be disseminated at international conferences and peer-reviewed publications., Trial Registration Number: Not applicable., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Social cognition impairment has been recognized as an early and characteristic change in behavioral variant frontotemporal dementia (bvFTD). The Mini Social Cognition and Emotional Assessment (mini-SEA) is a clinical tool to rapidly evaluate social cognition. In this study, we explored the diagnostic value of social cognition by assessing the Chinese version of the mini-SEA and other standard neuropsychological tests in 22 patients with mild bvFTD, 26 patients with mild Alzheimer's disease (AD), including mild cognitive impairment (MCI) and mild dementia, and 30 control subjects. The discriminatory powers of these tests were evaluated and compared using the receiver operating characteristic curve (ROC). The mini-SEA scores of the bvFTD patients were significantly lower than those of the controls ( Z = -6.850, adjusted P < 0.001) and AD patients ( Z = -3.737, adjusted P = 0.001). ROC analysis showed that the mini-SEA had a high discriminatory power for differentiating bvFTD from the controls, with an area under the curve (AUC) value of 0.989 (95% CI = 0.905-1.000, P < 0.001). The AUC value of the mini-SEA for differentiating bvFTD from AD was 0.899 (95% CI = 0.777-0.967, P < 0.001), higher than that of the Auditory Verbal Learning Test Delayed Recall (AUC = 0.793), Boston Naming Test (AUC = 0.685) or Frontal Assessment Battery (AUC = 0.691). The Chinese version of mini-SEA is a good clinical tool for the early diagnosis of bvFTD, and has a high sensitivity and specificity to discriminate bvFTD from AD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Zhou, Wei, Zuo, Ma, Zhao, Jin, Li, Guo and Jia.)

Background: Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating lytic brain infection caused by the John Cunningham virus (JCV). JCV manifests primarily in patients with innate immunodeficiency or taking immunomodulatory medications. In this case study, we report a PML patient with comorbid mediastinal teratoma and mild lymphopenia., Case Presentation: A 73-year-old female presented with a 3-month history of progressive hemiplegia, hemianopsia, and cognitive impairment. She was diagnosed as PML by cerebrospinal fluid metagenomics sequencing and brain biopsy. Extensive immunological tests did not reveal an apparent immunodeficiency, but further work-up revealed that the PML was most likely the first presentation of mediastinal teratoma and the mild lymphopenia. Mirtazapine and immunoglobulin were started, the patient's condition was relatively stable and approved to be discharged from hospital. But unfortunately, she died of the lung infection 10 months after first presentation., Conclusions: This case confirms that mediastinal teratoma may induce the lymphopenia and trigger PML, delayed or incorrect diagnosis may worsen the course of the disease and result in poor prognosis., (© 2022. The Author(s).)

Diffuse large B cell lymphoma (DLBCL), the most common type of non-Hodgkin lymphoma worldwide, is aggressive and highly heterogeneous. MiR-665 was found to be lowly expressed in serum exosomes of DLBCL patients and in DLBCL cell lines, but its function in DLBCL progression remains unclear. In this study, miR-665 was overexpressed in SU-DHL-4 cells via miR-665 mimics and knocked down in FARAGE cells via miR-665 inhibitor. Knockdown of miR-665 promoted DLBCL cell proliferation and invasion and decreased cell apoptosis, whereas miR-665 overexpression showed opposite effects on DLBCL cell malignant behaviors. Luciferase reporter assay confirmed LIM and SH3 protein 1 (LASP1) and MYC as target genes of miR-665. Moreover, the expression of LASP1 was negatively correlated with that of miR-665 in LDLBCL cells. LASP1 has tumor-promoting property and its inhibition abolished the effect of miR-665 knockdown on DLBCL cell proliferation, invasion, and apoptosis. SU-DHL-4 cells were inoculated into the flank of nude mice, followed by orthotopic injection with miR-665 agomir. MiR-665 overexpression restricted tumor growth in vivo. Thus, we demonstrates that miR-665 suppresses DLBCL cell malignant behaviors by inhibiting cell proliferation and invasion and inducing apoptosis via targeting LASP1 and MYC, suggesting the importance of miR-665 in DLBCL progression., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Biological guanine crystals in organisms exhibit excellent optical properties and functions, including broad-band and narrow-band reflectors, band-tunable reflectors, mirrors, and stimuli-responsive structural colors, attributed to the high refractive index of guanine (1.85) and the exquisite control of the polymorphs, morphologies, sizes, exposed planes, and the hierarchically ordered assembly of biological guanine crystals in the organisms. Herein, the controlled synthesis of guanine crystals with defined polymorphs and morphologies and their formation processes in organic and aqueous solutions are summarized in detail. In particular, the controlled synthesis of microplatelets or nanoplatelets of the thermodynamically metastable β form of anhydrous guanine (β-AG) exposing the (100) plane in the presence of additives, twinned crystals, and the occlusion of hypoxanthine in β-AG were investigated to mimic biological guanine crystals with superior optical properties. One-dimensional assembly of β-AG microrods was studied as a preliminary work to mimic the highly ordered assembly of guanine crystals with superior optical properties.

Introduction: Bone cancer pain is characterized by persistent pain, usually requiring drugs to relieve pain. Baicalin, a flavonoid compound extracted from Scutellaria baicalensis , which has antioxidant and analgesic effects. But, the effect of baicalin on bone cancer pain is unclear. Thus, this study aimed to explore the mechanism of baicalin on SD rats with bone cancer pain., Materials and Methods: The MADB-106 breast cancer cells-induced bone pain model was constructed and carried out baicalin treatment. The therapeutic effect of baicalin on bone cancer pain model was observed by hematoxylin-eosin staining and immunofluorescence staining. We also performed transcriptome sequencing analysis of baicalin in the treatment of bone metastases. Also, RT-qPCR and ELISA were used to detect the expression levels of inflammation factors., Results: After baicalin treatment, osteoclast activation was inhibited and the number of bone trabeculae was increased. Baicalin inhibited the protein expression level of inflammatory factors (IL-1β, IL-6, TNF-α and PGE2) in the bone metastases group. Based on the transcriptome sequencing of the bone metastases group and the baicalin treatment group, baicalin inhibited the expression of ALPP, DUSP1, CYR61, ALPPL2, SPP1 and TLR4 . RT-qPCR was also used to validate the expression levels of these cytokine genes., Conclusion: Baicalin had a certain inhibitory effect on the SD rat model of bone metastasis cancer. These insights can guide future research on the molecular mechanism of bone cancer pain and provide a theoretical basis for baicalin in the treatment of bone pain caused by breast cancer in the future., Competing Interests: The authors state that they have no conflicts of interest., (© 2021 Wang et al.)

This study analyzed the size-resolved chemical compositions of cigarette-burning particles (CBPs). CBPs in the size range of 0.2-2.0 μm were characterized using a single particle mass spectrometer (SPAMS). CBPs were found to contain polycyclic aromatic hydrocarbons (PAHs), organonitrate, vinylpyridine, indene, guaiacol, methylindane, and metals such as Fe, Cr, Mn, and Cu. Fresh CBPs showed a single modal size distribution which peaked at 0.40 μm. CBPs in the size range of 0.5-0.1 μm contained more biomass burning markers (K + , K 2 Cl + , and levoglucosan), sulfate, naphthalene, and methylindane than CBPs in the size range of 0.2-0.5 μm. Nicotine is favorable to uptake on large particles (>0.5 μm). Among all particles, 57% contained PAHs. Heavy metals Fe, Mn, Cr, and Cu had mixing ratios of 0.06, 0.57, 0.26, and 0.34 respectively; nicotine and guaiacol had mixing ratios of 0.26 and 0.27; and vinylpyridine, indene, and methylindane had mixing ratios of 0.54, 0.55, and 0.65 respectively. Four particle types were resolved: cigarette-burning biomass burning (CB-BB, 50.3%), CB-BB-Metals (49.3%), CB-Nicotine (0.3%), and CB-Aged (0.1%). These results improve the scientific understanding of CBPs and provide useful references for smoking exposure studies that consider the size-resolved chemical compositions and mixing states of particle-phase components. The result can also benefit the study of exposure to secondhand smoking., (Copyright © 2021. Published by Elsevier Inc.)

Background: Myelin oligodendrocyte glycoprotein-antibody (MOG-ab)-associated disease (MOGAD) has highly heterogenous clinical and imaging presentations, in which encephalitis is an important phenotype. In recent years, some atypical presentations in MOG-ab-associated encephalitis (MOG-E) have been increasingly reported but have not yet been described well. The aim of the study was to describe the clinical and imaging features of patients with MOG-E in our center. Atypical phenotypes would be reported, which is expected to expand the spectrum of MOGAD., Methods: We reviewed medical records of 59 patients with MOGAD diagnosed in our center and identified cases who had ever experienced encephalitic symptoms. Three hundred ten patients with autoimmune encephalitis (AE) were also reviewed, and cases with positive MOG-ab were identified. Besides, patients with chronically progressive encephalitis were identified from 13 MOG-E and 310 AE patients. We collected demographic, clinical, laboratory, radiological, and outcome data to explore clinical and imaging characteristics in MOG-E, especially in the atypical phenotype of chronically progressive encephalitis., Results: We identified 13 patients (7 males, 6 females) with MOG-E. The median age at onset was 33 years (range 13~62 years). Most (9/13, 69.2%) of patients showed acute or subacute onset of encephalitic symptoms. Brain MRI abnormalities were observed in all patients. The most common lesion locations on MRI were cortical/subcortical (11/13, 84.6%), deep/periventricular white matter (10/13, 76.9%) and corpus callosum (4/13, 30.8%). Brain MRI patterns were categorized into four phenotypes. The most common pattern was cortical encephalitis with leptomeningeal enhancement/brain atrophy (10/13, 76.9%). Eight (8/13, 61.5%) patients had a good response to immunotherapy. Four (4/13, 30.8%) patients with chronically progressive course were identified from MOG-E cohort. They showed leukodystrophy-like pattern, multifocal hazy lesions, or cortical encephalitis on MRI. With immunotherapy, they only showed mild or no improvement. We also identified four (4/310, 1.3%) patients with chronically progressive course from AE cohort. They had better outcomes than counterparts in MOG-E., Conclusions: This study demonstrates that encephalitic presentations in MOGAD had complex clinical patterns. Chronically progressive encephalitis may be a new phenotype of MOGAD. We recommend to test MOG-ab in subacute and chronic progressive dementia with leukodystrophy-like MRI lesions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wang, Qiu, Li, Yang, Ding, Gao, Liu, Song, Li, Gao, Wang, Wu, Jia, Guo, Zhou, Jia, Huang, Qu, Gao, Dong, Hao and Liu.)

Background: This study aimed to evaluate the diagnostic accuracy of diffusion kurtosis imaging (DKI) in differentiating early hepatic fibrosis (HF) from normal liver and advanced HF in rabbits., Methods: A total of 35 healthy New Zealand white rabbits were included in the study. A model of HF was established in 30 rabbits through subcutaneous injections of 50% carbon tetrachloride (CCl 4 )/olive oil, while 5 rabbits received saline injections. The gradually increased doses of CCl 4 were 0.1, 0.2, and 0.3 mL/kg in weeks 1 to 3, weeks 4 to 6, and weeks 7 to 10, respectively. Two injections were given each week. Two rabbits in the experimental group died. All rabbits underwent DKI with three b values (0, 500, and 1,000 s/mm 2 ) at week 5 (n=8), week 6 (n=9), week 7 (n=8), and week 10 (n=8). Approximately 2 liver lobes per rabbit were selected for histopathology. Mean diffusivity (MD) and mean kurtosis (MK) were calculated. Discrimination capacities of DKI parameters were analyzed and compared by receiver operating characteristic (ROC) analysis., Results: The meta-analysis of histological data in viral hepatitis (METAVIR) scoring system was used to classify liver lobes into the control group (F0, n=0), early HF group (F1-F2, n=28), and advanced HF group (F3-F4, n=28). MD and MK values were significantly different among the three groups (all P<0.05). MD value was negatively correlated with increased fibrosis level, while MK value was positively correlated with increased fibrosis level (ρ=-0.540, 0.614; P<0.05). The area under ROC curves (AUCs) for MD and MK were 0.886 and 0.875, respectively, for characterization of F0 and F1-F2, and 0.975 and 0.957 for F0 and F3-F4. AUC for MK was 0.751 for characterization of F1-F2 and F3-F4. MD performed better than MK for characterization of F0 and F1-F2 as well as F0 and F3-F4. MK showed good differentiation performance between F1-F2 and F3-F4., Conclusions: Our results showed that DKI contributed to discriminating reversible early HF from normal liver and advanced HF and as a result, showed promise for use in HF diagnosis., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/atm-21-4884). All authors reported that this study was supported by the Natural Science Foundation of Liaoning Province, China (No. 201602228). The authors have no other conflicts of interest to declare., (2021 Annals of Translational Medicine. All rights reserved.)

Objective: To evaluate the different pharmacokinetic parameters of the DCE-MRI method on diagnosing and staging of rabbits' liver fibrosis., Methods: We had performed DCE-MRI for rabbits that had been divided into the experiment group and the control group. Then, rabbits' images were transferred to a work station to get three parameters such as K trans , K ep , and V e , which had been measured to calculate. After data were analyzed, ROC analyses were performed to assess the diagnostic performance of K trans , K ep , and V e to judge liver fibrosis., Results: The distribution of the different liver fibrosis group was as follows: F1, n  = 8; F2, n  = 9; F3, n  = 6; F4, n  = 5. No fibrosis was deemed as F0, n  = 6. K ep is statistically significant ( P < 0.05) for F0 and mild liver fibrosis stage, and the K ep shows AUC of 0.814. Three parameters are statistically significant for F0 and advanced liver fibrosis stage ( K trans and K ep , P < 0.01; V e , P < 0.05), and the K trans shows AUC of 0.924; the K ep shows AUC of 0.909; the V e shows AUC of 0.848; K trans and K ep are statistically significant for mild and advanced liver fibrosis stages ( K trans , P < 0.01; K ep , P < 0.05), and the K trans shows AUC of 0.840; the K ep shows AUC of 0.765. Both K trans and K ep are negatively correlated with the liver fibrosis stage. V e is positively correlated with the liver fibrosis stage., Conclusion: K trans is shown to be the best DCE parameter to distinguish the fibrotic liver from the normal liver and mild and advanced fibrosis. On the contrary, K ep is moderate and V e is worst. And K ep is a good DCE parameter to differentiate mild fibrosis from the normal liver., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Qian Cui et al.)

Introduction: Leptomeningeal amyloidosis (LA) represents a rare subtype of familial transthyretin (TTR) amyloidosis, characterized by deposition of amyloid in cranial and spinal leptomeninges. Of >120 TTR mutations identified, few have been associated with LA., Case Report: A 27-year-old male presented with a 2-year history of progressive symptoms including cognitive decline and right-sided weakness and numbness. Cerebrospinal fluid (CSF) analyses demonstrated high protein level. Gadolinium-enhanced magnetic resonance imaging (MRI) revealed extensive leptomeningeal enhancement over the surface of the brain and spinal cord. Pathologic analyses revealed a TTR mutation c.113A>G (p.D38G)., Review Summary: Fifteen mutations and genotype-phenotype correlation of 72 LA patients have been summarized to provide an overview of LA associated with transthyretin mutations. The mean age of clinical onset was 44.9 years and the neurological symptoms primarily included cognitive impairment, headache, ataxia seizures and hearing, visual loss. CSF analysis showed elevated high CSF protein level and MRI revealed extensive leptomeningeal enhancement., Conclusion: Clinicians should be aware of this rare form of familial transthyretin amyloidosis as well as its typical MRI enhancement and high CSF protein. The important role of biopsy, genetic testing and the potential early diagnosis value of contrast MRI were suggested. Early recognition of these characteristics is important to provide misdiagnosis and shorten the time before correct diagnosis. These findings expand the phenotypic spectrum of TTR gene and have implications for the diagnosis, treatment, and systematic study of LA., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Severe neurotoxicity after chimeric antigen receptor T cell (CAR-T) therapy can be a crucial lifethreatening event in diffuse large B-cell lymphoma (DLBCL), and management of those toxicities is still a serious clinical challenge. The underlying mechanisms of CAR-T cell-mediated neurotoxicity remain poorly elucidated because very few studies examine the intact tumor microenvironment before CAR-T cell infusion. Herein, we pur-posed to identify differentially expressed genes (DEGs) related to CAR-T cell-mediated neurotoxicity in the DLBCL microenvironment before CAR-T cell infusion and reveal their potential mechanisms., Methods: The mRNA expression profile data of GSE153438 were obtained from the GEO database. The GSE153438 dataset includes 26 samples with non-severe neurotoxicity (grade 0 - 2) and 10 samples with severe neurotoxicity (grade 3 or higher). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) patway enrichment assessment was carried out. We screened the hub gene by protein-protein interaction (PPI) network analysis and Cytoscape software. Gene set enrichment analysis (GSEA) was also analyzed with the GSEA software. Moreover, the predictive value of the hub gene for severe neurotoxicity was evaluated via receiver operating characteristic (ROC) curve analysis., Results: We identified a total of 25 up-regulated DEGs and 26 downregulated DEGs associated with CAR-T cell-mediated neurotoxicity in the DLBCL microenvironment before CAR-T cell infusion. Results of GO analysis showed that DEGs were mainly enriched in T cell activation, leukocyte cell-cell adhesion, and positive regulation of cell adhesion. The KEGG analysis revealed that DEGs were significantly enriched in T cell receptor signaling pathway, cell adhesion molecules, and Epstein-Barr virus infection. GSEA revealed that the glycolysis pathway was significantly associated with severe neurotoxicity. The top centrality hub gene GZMB was identified from the PPI network. ROC curve analysis showed that GZMB had a potential predictive value for severe neurotoxicity., Conclusions: In DLBCL microenvironment before CAR-T cell infusion, we identified T cell activation and glycolysis pathways significantly associated with CAR-T cell-mediated severe neurotoxicity. GZMB might be used as a predictive and therapeutic molecular marker for neurotoxicity. The study suggested that the tumor microenviron-ment before CAR-T cell infusion plays an essential role in the early prediction of neurotoxicity.

Background: Chemoresistance is emerging as a major barrier to successful treatment in acute myeloid leukemia (AML), and bone marrow stromal cells (BMSCs) protect leukemia cells from chemotherapy eventually leading to recurrence. This study was designed to investigate the role of p21-activated kinase 1 (PAK1) in AML progression and chemosensitivity, highlighting the mechanism of stroma-mediated chemoresistance., Methods: The GEPIA and TCGA datasets were used to analyze the relationship between PAK1 mRNA expression and various clinical parameters of AML patients. Cell proliferation and apoptosis were examined to evaluate the role of PAK1 on chemosensitivity in AML by silencing PAK1 with shRNA or small molecular inhibitor. Human BMSC (HS-5) was utilized to mimic the leukemia bone marrow microenvironment (BMM) in vitro , and co-culture model was established to investigate the role of PAK1 in BMSC-mediated drug resistance., Results: p21-activated kinase 1 high expression was shown to be associated with shorter overall survival in AML patients. The silence of PAK1 could repress cell proliferation, promote apoptosis, and enhance the sensitivity of AML cells to chemotherapeutic agents. More importantly, BMSCs induced PAK1 up-regulation in AML cells, subsequently activating the ERK1/2 signaling pathway. The effect of BMSC-mediated apoptotic-resistance could be partly reversed by knock down of PAK1., Conclusion: p21-activated kinase 1 is a potential prognostic predictor for AML patients. PAK1 may play a pivotal role in mediating BMM-induced drug resistance, representing a novel therapeutic target in AML., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Li, Jia, Li, Zhou, Guo, Teng, Du, Li, Li, Sun, Ma, Ji and Ji.)

Objective: This study aimed to analyze the characteristics of cognitive impairment in adult-onset neuronal intranuclear inclusion disease (NIID)., Methods: Seven patients with adult-onset NIID were collected consecutively from the memory clinic of Xuanwu hospital from February to December 2019. These cases were diagnosed with skin biopsy triggered by DWI high-intensity signals in corticomedullary junction on brain MRI. We used a battery of neuropsychological scales to detect the patient's performance in each cognitive domain, and made a detailed analysis on the characteristics of cognitive impairment., Results: All seven cases had cognitive impairment, and four of them had met the criteria for dementia. The scores of Montreal Cognitive Assessment and Frontal Assessment Battery were abnormal in all patients. The executive dysfunction was confirmed by the abnormal scores of Trail Making Test (5/7, 71%) and Clock Drawing Test (4/7, 57%). Bad performance in Auditory Verbal Learning Test (6/7, 86%) demonstrated that the memory was also a very commonly impaired cognitive domain. The low score on the animal fluency (4/7, 57%), Boston Naming Test (3/7, 43%), and Pentagon and Cube Copying Test (4/7, 57%) indicated that the language and visuospatial skills were also impaired. Fazekas scores were significantly correlated to the global cognition, executive and language functions (r = 0.788-0.906, P < 0.05)., Conclusions: There is obvious impairment in multiple cognitive domains in adult-onset NIID, and both the executive dysfunction and memory deficit are very common. Leukoencephalopathy may be the main course of cognitive impairment in adult-onset NIID.