Brimonidine as a possible treatment for myopia.

BACKGROUND: Myopia is becoming a huge burden on the world's public health systems. The purpose of this study was to explore the effect of brimonidine in the treatment of form-deprivation myopia (FDM) and the relationship between intraocular pressure (IOP) and myopia development. METHODS: Monocular form deprivation myopia (FDM) was induced in three-week-old pigmented male guinea pigs. They were treated with 3 different methods of brimonidine administration (eye drops, and subconjunctival or intravitreal injections). Four different concentrations of brimonidine were tested for each method (2µg/µL, 4µg/µL, 20µg/µL, and 40µg/µL). All treatments continued for a period of 21 days. Tonometry, retinoscopy, and A-scan ultrasonography were used to monitor intraocular pressure, refractive error and axial length (AL), respectively. RESULTS: Treatment with subconjunctival brimonidine at 40µg/µL, and intravitreal brimonidine at 2µg/µL and 4µg/µL, inhibited the development of FDM. The myopic refraction, excessive axial length, and elevation of IOP were significantly decreased. Brimonidine in eye drops was ineffective. CONCLUSION: Brimonidine at appropriate doses significantly reduced the development of FD myopia in guinea pigs. The IOP may change with FD myopia.

Comparative visual outcomes of the first versus second eye following small-incision lenticule extraction (SMILE).

BACKGROUND: This study aimed to compare the visual outcomes of the first operated eyes with those of the second operated eyes following small-incision lenticule extraction (SMILE). METHODS: A total of 202 patients (404 eyes) underwent SMILE using the tear film mark centration method for myopia and myopic astigmatism correction. Baseline characteristics, objective optical quality, decentered displacement, induced corneal aberrations, and modulation transfer function (MTF) values were assessed. Linear regression analyzed the relationship between decentration and visual quality parameters, including corneal aberrations and MTF values. RESULTS: No significant difference was observed in objective visual quality, efficacy, and safety indexes between the two groups (all P > 0.05). The average decentered displacement for the first and second surgical eyes was 0.278 ± 0.17 mm and 0.315 ± 0.15 mm, respectively (P = 0.002). The horizontal coma in the first surgical eyes were notably lower than in the second (P = 0.000). MTF values at spatial frequencies of 5, 10, 15, and 20 cycles/degree (c/d) were higher in the first surgical eyes compared to the second (all P < 0.05). Linear regression indicated that high-order aberrations (HOAs), root mean square (RMS) coma, spherical aberration, horizontal coma, vertical coma, and eccentric displacement were all linearly correlated. Furthermore, MTF values exhibited a linear relationship with eccentric displacement across these spatial frequencies. CONCLUSIONS: There was no discernible difference in visual acuity, efficacy, or safety between the two operated eyes. Nonetheless, the first operated eyes exhibited reduced decentered displacement and demonstrated superior outcomes in terms of horizontal coma and MTF values compared to the second operated eyes following SMILE. The variations in visual quality parameters were linearly correlated with decentered displacement.

Aggressive alternative splicing events discovered in cecum ligation and puncture induced lung injury.

AIMS: Acute lung injury (ALI) induced by sepsis and its complications have high morbidity and mortality rates globally. The objective of this study was to enhance our understanding of the underlying mechanism of ALI by identifying potential splicing events that are regulated in this condition. MATERIALS AND METHODS: The CLP mouse model was utilized for mRNA sequencing, and the expression and splicing data were analyzed. Verification of the changes in expression and splicing induced by CLP was conducted using qPCR and RT-PCR. RESULTS: Our results showed that splicing-related genes were regulated, suggesting that splicing regulation may be a key mechanism in ALI. We also found that more than 2900 genes displayed alternative splicing in the lungs of mice with sepsis. Using RT-PCR, we verified that TLR4 and other genes had differential splicing isoforms in the lungs of mice with sepsis. We confirmed the presence of TLR4-s in the lungs of mice with sepsis using RNA-fluorescence in situ hybridization. CONCLUSION: Our results suggest that sepsis-induced ALI can significantly alter splicing in the lungs of mice. The list of DASGs and splicing factors is valuable for further study in the search for new treatment approaches for sepsis-induced ALI.

Barriers and facilitators of implementing the practice programme for upright positions in the second stage of labour: A mixed-method study.

OBJECTIVE: To explore the possible barriers and facilitators to implementing the Upright Positions in the Second Stage of Labour (UPSSL) programme in Chinese healthcare settings. DESIGN: A mixed-method convergent design with the guidance of Consolidated Framework for Implementation Research (CFIR). METHODS: An online survey study and semi-structured interviews were conducted between March and May 2023. Healthcare professionals were recruited from four hospitals in Shijiazhuang, China. One hundred and thirty-one participants completed the survey study, and 23 of them were interviewed individually. Descriptive statistics evaluated the possible barriers and facilitators of implementing the UPSSL programme within the CFIR framework quantitatively. Guided by the CFIR framework, qualitative data were analysed using directed content analysis to summarize healthcare professionals' perspectives on barriers and facilitators of the UPSSL programme. RESULTS: Multiple intersectional barriers and facilitators were identified from the survey and semi-interviews. Healthcare professionals believed that the UPSSL programme has a scientific evidence base, systematic contents, and possible benefits for women. However, various barriers existed at individual, system, and organizational levels. Major barriers included healthcare professionals and women's safety concerns towards the use of upright positions during childbirth, the healthcare professionals' unfamiliarity with assisting an upright position birth, poor adaptability of the programme protocol, inadequate facilities and staffing, and a lack of readiness to change in the clinical setting. CONCLUSIONS: To facilitate the implementation of the UPSSL programme in China, tailored antenatal education on upright positions, especially addressing safety-related issues, should be provided to pregnant women, their families, or peers to enhance their understanding of and familiarity with such positions. Healthcare professionals should also be offered adequate training opportunities and necessary facilities. Furthermore, national-level policy changes might be required to address midwifery workforce shortages. Additionally, further research is warranted to select, adapt, and test effective implementation strategies for programme adoption. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: What problem did the study address? The adoption of upright positions during the second stage of labour could promote better maternal and neonatal outcomes and a positive childbirth experience. However, the adoption of upright positions during the second stage of labour is suboptimal in healthcare settings in China. Barriers and facilitators of implementing upright positions during childbirth are unclear. What were the main findings? A range of barriers and facilitators within the CFIR framework to promote upright positions during childbirth from healthcare professionals' perspectives were identified, and the major barriers included safety concerns towards and unfamiliarity with an upright position birth, inadequate facilities and staffing, and a lack of readiness to change in the clinical setting. Where and on whom will the research have an impact? This study will enable a better understanding of the barriers and facilitators to promoting upright positions in the second stage of labour in China. The smooth and effective implementation of the UPSSL programme could help to promote better maternal and neonatal outcomes and improve women's childbirth experiences. REPORTING METHOD: The reporting of this study followed the Consolidated Criteria for Reporting Qualitative Research (COREQ) and Good Reporting of A Mixed Methods Study (GRAMMS) guidelines. PATIENT OR PUBLIC CONTRIBUTION: In this study, healthcare professionals were involved in refining the topic guides and survey questions. Additionally, findings from the interviews were returned to them for comments and corrections.

Discovery of Novel Pimprinine and Streptochlorin Derivatives as Potential Antifungal Agents.

Pimprinine and streptochlorin are indole alkaloids derived from marine or soil microorganisms. In our previous study, they were promising lead compounds due to their potent bioactivity in preventing many phytopathogens, but further structural modifications are required to improve their antifungal activity. In this study, pimprinine and streptochlorin were used as parent structures with the combination strategy of their structural features. Three series of target compounds were designed and synthesized. Subsequent evaluation for antifungal activity against six common phytopathogenic fungi showed that some of thee compounds possessed excellent effects, and this is highlighted by compounds 4a and 5a, displaying 99.9% growth inhibition against Gibberella zeae and Alternaria Leaf Spot under 50 µg/mL, respectively. EC50 values indicated that compounds 4a, 5a, 8c, and 8d were even more active than Azoxystrobin and Boscalid. SAR analysis revealed the relationship between 5-(3'-indolyl)oxazole scaffold and antifungal activity, which provides useful insight into the development of new target molecules. Molecular docking models indicate that compound 4a binds with leucyl-tRNA synthetase in a similar mode as AN2690, offering a perspective on the mode of action for the study of its antifungal activity. These results suggest that compounds 4a and 5a could be regarded as novel and promising antifungal agents against phytopathogens due to their valuable potency.

Performance assessment of two motion management systems for frameless stereotactic radiosurgery.

BACKGROUND/PURPOSE: Frameless stereotactic radiosurgery (SRS) requires dedicated systems to monitor patient motion in order to avoid inaccurate radiation delivery due to involuntary shifts. The purpose of this study is to assess the accuracy and sensitivity of two distinct motion monitoring systems used for frameless SRS. METHODS: A surface image-guided system known as optical surface monitoring system (OSMS), and a fiducial marker-based system known as high definition motion management (HDMM) as part of the latest Gamma Knife Icon® were compared. A 3D printer-based cranial motion phantom was developed to evaluate the accuracy and sensitivity of these two systems in terms of: (1) the capability to recognize predefined shifts up to 3 cm, and (2) the capability to recognize predefined speeds up to 3 cm/s. The performance of OSMS, in terms of different reference surfaces, was also evaluated. RESULTS: Translational motion could be accurately detected by both systems, with an accuracy of 0.3 mm for displacement up to 1 cm, and 0.5 mm for larger displacements. The reference surface selection had an impact on OSMS performance, with flat surface resulting in less accuracy. HDMM was in general more sensitive when compared with OSMS in capturing the motion, due to its faster frame rate, but a delay in response was observed with faster speeds. Both systems were less sensitive in detection of superior-inferior motion when compared to lateral or vertical displacement directions. CONCLUSION: Translational motion can be accurately and sensitively detected by OSMS and HDMM real-time monitoring systems. However, performance variations were observed along different motion directions, as well as amongst the selection of reference images. Caution is needed when using real-time monitoring systems for frameless SRS treatment.

Molecular subtypes based on DNA methylation predict prognosis in lung squamous cell carcinoma.

BACKGROUND: Due to tumor heterogeneity, the diagnosis, treatment, and prognosis of patients with lung squamous cell carcinoma (LUSC) are difficult. DNA methylation is an important regulator of gene expression, which may help the diagnosis and therapy of patients with LUSC. METHODS: In this study, we collected the clinical information of LUSC patients in the Cancer Genome Atlas (TCGA) database and the relevant methylated sequences of the University of California Santa Cruz (UCSC) database to construct methylated subtypes and performed prognostic analysis. RESULTS: Nine hundred sixty-five potential independent prognosis methylation sites were finally identified and the genes were identified. Based on consensus clustering analysis, seven subtypes were identified by using 965 CpG sites and corresponding survival curves were plotted. The prognostic analysis model was constructed according to the methylation sites' information of the subtype with the best prognosis. Internal and external verifications were used to evaluate the prediction model. CONCLUSIONS: Models based on differences in DNA methylation levels may help to classify the molecular subtypes of LUSC patients, and provide more individualized treatment recommendations and prognostic assessments for different clinical subtypes. GNAS, FZD2, FZD10 are the core three genes that may be related to the prognosis of LUSC patients.

Forsythiae Fructus aqueous extract attenuates cisplatin-induced kaolin consumption (pica) by inhibiting NLRP3 inflammasome activation in rats.

The present study was conducted to evaluate the effect of Forsythiae Fructus aqueous extract (FAE) against cisplatin-induced emesis and to explore the antiemetic mechanism of FAE by focusing on NLRP3 inflammasome activation in a rat pica model. Our results showed that FAE significantly ameliorated cisplatin-induced acute and delayed pica in rats. Moreover, FAE improved the gastrointestinal histopathological injury and reduced the levels of serum ROS, IL-1ß, and IL-18 in cisplatin-treated rats. In addition, the expressions of NLRP3, ASC, caspase-1, and IL-1ß and the colocalization of the NLRP3 with ASC or caspase-1 in rat gastric antrum and ileum were also suppressed by FAE. Taken together, our findings indicate that FAE has a therapeutic effect against CINV, which may be related to its inhibition of the activation of NLRP3 inflammasome.

The combined use of 2D scout and 3D axial CT images to accurately determine the catheter tips for high-dose-rate brachytherapy plans.

PURPOSE: To develop a method combining CT scout images with axial images to improve the localization accuracy of catheter tips in high-dose-rate (HDR) brachytherapy treatments. MATERIALS AND METHODS: CT scout images were utilized along with conventionally reconstructed axial images to aid the localization of catheter tips used during HDR treatment planning. A method was developed to take advantage of the finer image resolution of the scout images to more precisely identify the tip coordinates. The accuracies of this method were compared with the conventional method based on the axial CT images alone, for various slice thicknesses, in a computed tomography dose index (CTDI) head phantom. A clinical case which involved multiple interstitial catheters was also selected for the evaluation of this method. Locations of the catheter tips were reconstructed with the conventional CT-based method and this newly developed method, respectively. Location coordinates obtained via both methods were quantitatively compared. RESULTS: Combination of the scout and axial CT images improved the accuracy of identification and reconstruction of catheter tips along the longitudinal direction (i.e., head-to-foot direction, more or less parallel to the catheter tracks), compared to relying on the axial CT images alone. The degree of improvement was dependent on CT slice thickness. For the clinical patient case, the coordinate differences of the reconstructed catheter tips were 2.6 mm ± 0.9 mm in the head-to-foot direction, 0.4 mm ± 0.2 mm in the left-to-right direction, and 0.6 mm ± 0.2 mm in the anterior-to-posterior direction, respectively. CONCLUSION: Combining CT scout and axial images demonstrates the ability to provide a more accurate identification and reconstruction of the interstitial catheter tips for HDR brachytherapy treatment, especially in the longitudinal direction. The method developed in this work has the potential to be implemented clinically together with automatic segmentation in modern brachytherapy treatment planning systems, in order to improve the reconstruction accuracy of HDR catheters.

Automatic measurement of air gap for proton therapy using orthogonal x-ray imaging with radiopaque wires.

PURPOSE: The main objective of this study was to develop a technique to accurately determine the air gap between the end of the proton beam compensator and the body of the patient in proton radiotherapy. METHODS: Orthogonal x-ray image-based automatic coordinate reconstruction was used to determine the air gap between the patient body surface contour and the end of beam nozzle in proton radiotherapy. To be able to clearly identify the patient body surface contour on the orthogonal images, a radiopaque wire was placed on the skin surface of the patient as a surrogate. In order to validate this method, a Rando® head phantom was scanned and five proton plans were generated on a Mevion S250 Proton machine with various air gaps in Varian Eclipse Treatment Planning Systems (TPS). When setting up the phantom in a treatment room, a solder wire was placed on the surface of the phantom closest to the beam nozzle with the knowledge of the beam geometry in the plan. After the phantom positioning was verified using orthogonal kV imaging, the last pair of setup kV images was used to segment the solder wire and the in-room coordinates of the wire were reconstructed using a back-projection algorithm. Using the wire as a surrogate of the body surface, we calculated the air gaps by finding the minimum distance between the reconstructed wire and the end of the compensator. The methodology was also verified and validated on clinical cases. RESULTS: On the phantom study, the air gap values derived with the automatic reconstruction method were found to be within 1.1 mm difference from the planned values for proton beams with air gaps of 85.0, 100.0, 150.0, 180.0, and 200.0 mm. The reconstruction technique determined air gaps for a patient in two clinical treatment sessions were 38.4 and 41.8 mm, respectively, for a 40 mm planned air gap, and confirmed by manual measurements. There was strong agreement between the calculated values and the automatically measured values, and between the automatically and manually measured values. CONCLUSIONS: An image-based automatic method has been developed to conveniently determine the air gap of a proton beam, directly using the orthogonal images for patient positioning without adding additional imaging dose to the patient. The method provides an objective, accurate, and efficient way to confirm the target depth at treatment to ensure desired target coverage and normal tissue sparing.

Treatment of Skin Reaction Induced by Nivolumab Combined with Radiotherapy in Non-small Cell Lung Cancer: A Case Report.

Skin reaction or dermatological toxicities induced by immunotherapy is common. It usually manifests skin rash or erythema and can be cured by skin lotion or steroid. Nivolumab, a human IgG4 programmed cell death protein 1 (PD-1) inhibitor, blocks T cells activation preventing signal and allows the immune system to clear cancer cells. Nivolumab was approved in the second-line therapy in squamous cell lung cancer by FDA, with less than 10% unusual skin reaction, like sensory neuropathy, peeling skin, erythema multiforme, vitiligo, and psoriasis. Radiotherapy could aggravate this skin reaction through inflammatory response and promotion of immunity. The combined treatment of anti-PD-1 and radiotherapy represented a new promising therapeutic approach in many studies, but the risk of side effects may be high. We reported a patient with advanced squamous cell lung cancer who suffered from serious skin immune-related adverse events when he was treated with nivolumab and radiotherapy. The immune overreaction of the treatment of anti-PD-1 treatment and radiotherapy might cause these serious skin adverse events. Our report warranted careful workup to reduce the risk of side effects by combinative therapy with anti-PD-1 and radiotherapy.

Performance variations among clinically available deformable image registration tools in adaptive radiotherapy - how should we evaluate and interpret the result?

The purpose of this study is to evaluate the performance variations in commercial deformable image registration (DIR) tools for adaptive radiation therapy and further to interpret the differences using clinically available terms. Three clinical examples (prostate, head and neck (HN), and cranial spinal irradiation (CSI) with L-spine boost) were evaluated in this study. Firstly, computerized deformed CT images were generated using simulation QA software with virtual deformations of bladder filling (prostate), neck flexion/bite-block repositioning/tumor shrinkage (HN), and vertebral body rotation (CSI). The corresponding transformation matrices served as a "reference" for the following comparisons. Three commercialized DIR algorithms: the free-form deformation from MIMVista 5.5 and the RegRefine from MIMMaestro 6.0, the multipass B-spline from VelocityAI v3.0.1, and the adap-tive demons from OnQ rts 2.1.15, were applied between the initial images and the deformed CT sets. The generated adaptive contours and dose distributions were compared with the "reference" and among each other. The performance in transfer-ring contours was comparable among all three tools with an average Dice similarity coefficient of 0.81 for all the organs. However, the dose warping accuracy appeared to rely on the evaluation end points and methodologies. Point-dose differences could show a difference of up to 23.3 Gy inside the PTVs and to overestimate up to 13.2 Gy for OARs, which was substantial for a 72 Gy prescription dose. Dose-volume histogram-based evaluation might not be sensitive enough to illustrate all the detailed variations, while isodose assessment on a slice-by-slice basis could be tedious. We further explored the possibility of using 3D gamma index analysis for warping dose variation assessment, and observed differences in dose warping using different DIR tools. Overall, our results demonstrated that evaluation based only on the performance of contour transformation could not guarantee the accuracy in dose warping, while dose-transferring validation strongly relied on the evaluation endpoint. As dose-transferring errors could cause misinterpretations when attempting to accumulate dose for adaptive radiation therapy and more DIR tools are available for clinical use, a standard and clinically meaningful quality assurance criterion should be established for DIR QA in the near future.

Sorafenib in liver function impaired advanced hepatocellular carcinoma.

OBJECTIVE: To explore the efficacy and safty of sorafenib in Child-Pugh class B to class C hepatocellular carcinoma (HCC). METHODS: In this three-center open-label study from November 2011 to May 2013, we randomly assigned 189 patients with advanced Child-Pugh class B or C HCC patients into two groups, one group with 95 patient to receive sorafenib (400 mg a time, twice a day) and the other group with 94 patients to receive best supportive care. The primary end points were progression-free survival and overall survival. RESULTS: The median progression-free survival was 2.2 months and 1.9 months in the sorafenib group and best supportive care group respectively (Hazard ratio in the sorafenib group, 0.55; 95% confidence interval, 0.40-0.75; P=0.002). The median overall survival was 4.0 months and 3.5 months in the sorafenib group and best supportive care group respectively (Hazard ratio in the sorafenib group, 0.48; 95% confidence interval, 0.35-0.68; P<0.001). The main adverse effect of sorafenib was rash and acne of the skin (in 51.7% patients). The incidences of severe rash, diarrhea, and dry skin were 5.6%, 5.6%, and 2.2% in the sorafenib group. One patient reached partial response in the sorafenib group. CONCLUSIONS: Sorafenib is safe in patients with liver function impaired advanced HCC. It is effective in terms of progression-free survival and overall survival compared with best supportive care. Liver functions are the important predictive factors.

An overview of 6-shogaol: new insights into its pharmacological properties and potential therapeutic activities.

Ginger (Zingiber officinale Roscoe) has traditionally been used as a cooking spice and herbal medicine for treating nausea and vomiting. More recently, ginger was found to effectively reduce the risk of diseases such as gastroenteritis, migraine, gonarthritis, etc., due to its various bioactive compounds. 6-Shogaol, the pungent phenolic substance in ginger, is the most pharmacologically active among such compounds. The aim of the present study was to review the pharmacological characteristic of 6-shogaol, including the properties of anti-inflammatory, antioxidant and antitumour, and its corresponding molecular mechanism. With its multiple mechanisms, 6-shogaol is considered a beneficial natural compound, and therefore, this review will shed some light on the therapeutic role of 6-shogaol and provide a theoretical basis for the development and clinical application of 6-shogaol.

The antinociceptive and anti-alpha-glucosidase effects of glucosides from Hemiphragma heterophyllum Wall.

Hemiphragma heterophyllum Wall. is commonly used in traditional Yi herbal medicine for treating bellyache and toothache. In the current study, an unreported monoterpene glucoside, (S)-thymoquinol O-(6-O-oleuropeoyl)-ß-d-glucopyranoside (1), together with 11 known glucosides were obtained from the whole herb of H. heterophyllum. Their structures were determined based on a detailed analysis of spectroscopic data and acid hydrolysis and methanolysis reactions. Bioassay results showed that compounds 1 and 10 at 40 mg/kg exhibited significant antinociceptive activity in the acetic acid-induced writhing model, with inhibitions of 59.80% and 64.07%, respectively. Moreover, five of the isolates showed moderate anti-α-glucosidase activities with IC50 values ranging from 5.67 to 46.16 µM.

Pulmonary MRI with hyperpolarized xenon-129 demonstrates novel alterations in gas transfer across the air-blood barrier in asthma.

BACKGROUND: Individuals with asthma can vary widely in clinical presentation, severity, and pathobiology. Hyperpolarized xenon-129 (Xe129) MRI is a novel imaging method to provide 3-D mapping of both ventilation and gas exchange in the human lung. PURPOSE: To evaluate the functional changes in adults with asthma as compared to healthy controls using Xe129 MRI. METHODS: All subjects (20 controls and 20 asthmatics) underwent lung function measurements and Xe129 MRI on the same day. Outcome measures included the pulmonary ventilation defect and transfer of inspired Xe129 into two soluble compartments: tissue and blood. Ten asthmatics underwent Xe129 MRI before and after bronchodilator to test whether gas transfer measures change with bronchodilator effects. RESULTS: Initial analysis of the results revealed striking differences in gas transfer measures based on age, hence we compared outcomes in younger (n = 24, ≤ 35 years) versus older (n = 16, > 45 years) asthmatics and controls. The younger asthmatics exhibited significantly lower Xe129 gas uptake by lung tissue (Asthmatic: 0.98% ± 0.24%, Control: 1.17% ± 0.12%, P = 0.035), and higher Xe129 gas transfer from tissue to the blood (Asthmatic: 0.40 ± 0.10, Control: 0.31% ± 0.03%, P = 0.035) than the younger controls. No significant difference in Xe129 gas transfer was observed in the older group between asthmatics and controls (P > 0.05). No significant change in Xe129 transfer was observed before and after bronchodilator treatment. CONCLUSIONS: By using Xe129 MRI, we discovered heterogeneous alterations of gas transfer that have associations with age. This finding suggests a heretofore unrecognized physiological derangement in the gas/tissue/blood interface in young adults with asthma that deserves further study.

Chemotherapy-induced gastrointestinal toxicity: Pathogenesis and current management.

Chemotherapy is the most common treatment for malignant tumors. However, chemotherapy-induced gastrointestinal toxicity (CIGT) has been a major concern for cancer patients, which reduces their quality of life and leads to treatment intolerance and even cessation. Nevertheless, prevention and treatment for CIGT are challenging, due to the prevalence and complexity of the condition. Chemotherapeutic drugs directly damage gastrointestinal mucosa to induce CIGT, including nausea, vomiting, anorexia, gastrointestinal mucositis, and diarrhea, etc. The pathogenesis of CIGT involves multiple factors, such as gut microbiota disorders, inflammatory responses and abnormal neurotransmitter levels, that synergistically contribute to its occurrence and development. In particular, the dysbiosis of gut microbiota is usually linked to abnormal immune responses that increases inflammatory cytokines' expression, which is a common characteristic of many types of CIGT. Chemotherapy-induced intestinal neurotoxicity is also a vital concern in CIGT. Currently, modern medicine is the dominant treatment of CIGT, however, traditional Chinese medicine (TCM) has attracted interest as a complementary and alternative therapy that can greatly alleviate CIGT. Accordingly, this review aimed to comprehensively summarize the pathogenesis and current management of CIGT using PubMed and Google Scholar databases, and proposed that future research for CIGT should focus on the gut microbiota, intestinal neurotoxicity, and promising TCM therapies, which may help to develop more effective interventions and optimize managements of CIGT.

The Molecular Mechanism of GhbHLH121 in Response to Iron Deficiency in Cotton Seedlings.

Iron deficiency caused by high pH of saline-alkali soil is a major source of abiotic stress affecting plant growth. However, the molecular mechanism underlying the iron deficiency response in cotton (Gossypium hirsutum) is poorly understood. In this study, we investigated the impacts of iron deficiency at the cotton seedling stage and elucidated the corresponding molecular regulation network, which centered on a hub gene GhbHLH121. Iron deficiency induced the expression of genes with roles in the response to iron deficiency, especially GhbHLH121. The suppression of GhbHLH121 with virus-induced gene silence technology reduced seedlings' tolerance to iron deficiency, with low photosynthetic efficiency and severe damage to the structure of the chloroplast. Contrarily, ectopic expression of GhbHLH121 in Arabidopsis enhanced tolerance to iron deficiency. Further analysis of protein/protein interactions revealed that GhbHLH121 can interact with GhbHLH IVc and GhPYE. In addition, GhbHLH121 can directly activate the expression of GhbHLH38, GhFIT, and GhPYE independent of GhbHLH IVc. All told, GhbHLH121 is a positive regulator of the response to iron deficiency in cotton, directly regulating iron uptake as the upstream gene of GhFIT. Our results provide insight into the complex network of the iron deficiency response in cotton.

Differential diagnosis of prostate cancer and benign prostatic hyperplasia based on DCE-MRI using bi-directional CLSTM deep learning and radiomics.

Dynamic contrast-enhanced MRI (DCE-MRI) is routinely included in the prostate MRI protocol for a long time; its role has been questioned. It provides rich spatial and temporal information. However, the contained information cannot be fully extracted in radiologists' visual evaluation. More sophisticated computer algorithms are needed to extract the higher-order information. The purpose of this study was to apply a new deep learning algorithm, the bi-directional convolutional long short-term memory (CLSTM) network, and the radiomics analysis for differential diagnosis of PCa and benign prostatic hyperplasia (BPH). To systematically investigate the optimal amount of peritumoral tissue for improving diagnosis, a total of 9 ROIs were delineated by using 3 different methods. The results showed that bi-directional CLSTM with ± 20% region growing peritumoral ROI achieved the mean AUC of 0.89, better than the mean AUC of 0.84 by using the tumor alone without any peritumoral tissue (p = 0.25, not significant). For all 9 ROIs, deep learning had higher AUC than radiomics, but only reaching the significant difference for ± 20% region growing peritumoral ROI (0.89 vs. 0.79, p = 0.04). In conclusion, the kinetic information extracted from DCE-MRI using bi-directional CLSTM may provide helpful supplementary information for diagnosis of PCa.

Radiomics for the Prediction of Pathological Complete Response to Neoadjuvant Chemoradiation in Locally Advanced Rectal Cancer: A Prospective Observational Trial.

(1) Background: An increasing amount of research has supported the role of radiomics for predicting pathological complete response (pCR) to neoadjuvant chemoradiation treatment (nCRT) in order to provide better management of locally advanced rectal cancer (LARC) patients. However, the lack of validation from prospective trials has hindered the clinical adoption of such studies. The purpose of this study is to validate a radiomics model for pCR assessment in a prospective trial to provide informative insight into radiomics validation. (2) Methods: This study involved a retrospective cohort of 147 consecutive patients for the development/validation of a radiomics model, and a prospective cohort of 77 patients from two institutions to test its generalization. The model was constructed using T2-weighted, diffusion-weighted, and dynamic contrast-enhanced MRI to understand the associations with pCR. The consistency of physicians' evaluations and agreement on pathological complete response prediction were also evaluated, with and without the aid of the radiomics model. (3) Results: The radiomics model outperformed both physicians' visual assessments in the prospective test cohort, with an area under the curve (AUC) of 0.84 (95% confidence interval of 0.70-0.94). With the aid of the radiomics model, a junior physician could achieve comparable performance as a senior oncologist. (4) Conclusion: We have built and validated a radiomics model with pretreatment MRI for pCR prediction of LARC patients undergoing nCRT.