Interaction between the albumin-bilirubin score and nutritional risk index in the prediction of post-hepatectomy liver failure.

BACKGROUND: Post-hepatectomy liver failure (PHLF) is the most common postoperative complication and the leading cause of death after hepatectomy. The albumin-bilirubin (ALBI) score and nutritional risk index (NRI) have been shown to assess end-stage liver disease and predict PHLF and patient survival. We hypothesized that the ALBI score and NRI interact in the prediction of PHLF. AIM: To analyze the interaction between the ALBI score and NRI in PHLF in patients with hepatocellular carcinoma. METHODS: This retrospective study included 186 patients who underwent hepatectomy for hepatocellular carcinoma at the Affiliated Hospital of Youjiang Medical University for Nationalities between January 2020 and July 2023. Data on patient characteristics and laboratory indices were collected from their medical records. Univariate and multivariate logistic regression were performed to determine the interaction effect between the ALBI score and NRI in PHLF. RESULTS: Of the 186 patients included in the study, PHLF occurred in 44 (23.66%). After adjusting for confounders, multivariate logistic regression identified ALBI grade 2/3 [odds ratio (OR) = 73.713, 95% confidence interval (CI): 9.175-592.199] and NRI > 97.5 (OR = 58.990, 95%CI: 7.337-474.297) as risk factors for PHLF. No multiplicative interaction was observed between the ALBI score and NRI (OR = 0.357, 95%CI: 0.022-5.889). However, the risk of PHLF in patients with ALBI grade 2/3 and NRI < 97.5 was 101 times greater than that in patients with ALBI grade 1 and NRI ≥ 97.5 (95%CI: 56.445-523.839), indicating a significant additive interaction between the ALBI score and NRI in PHLF. CONCLUSION: Both the ALBI score and NRI were risk factors for PHLF, and there was an additive interaction between the ALBI score and NRI in PHLF.

Glucose attenuates the long-term adverse neurodevelopment effect of neonate pain stimulus via CRF/GR in rats.

BACKGROUND: Neonates undergo numerous painful procedures throughout their hospitalization. Repeated procedural pain may cause adverse long-term effects. Glucose as a non-pharmacological analgesia, is used for neonate pain management. In this study, potential mechanism of attenuate pain induced by glucose in neurodevelopment effect of neonate pain stimulus was investigated. METHODS: Neonatal rats to perform a repetitive injury model and glucose intervention model in the postnatal day 0-7(P0-7). Pain thresholds were measured by von Frey test weekly. The puberty behavioral outcome, tissue loss and protein expression in hippocampus were analyzed. RESULTS: Oral administration of glucose after repeated pain stimulation can maintain the hippocampal structure in, and reduce the expressions of corticotropin releasing factor (CFR) and glucocorticoid receptor (GR), therefore, resulted in long-term threshold of pain and cognitive improvement. CONCLUSION: Exposure to neonatal repeated procedural pain causes persistent mechanical hypersensitivity and the dysfunction of spatial memory retention at puberty. In addition, glucose can relieve these adverse effects, possibly via decreasing CRF/GR levels to change the hypothalamus-pituitary-adrenal (HPA) axis.

Development, validation, and clinical application of a UPLC-MS/MS method for omadacycline determination in human serum.

BACKGROUND: Omadacycline is the first aminomethyl-tetracycline variety to successfully enter clinical applications. To support regular therapeutic drug monitoring (TDM) in clinical practice, an ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) method was developed that would allow omadacycline quantification in human serum. METHODS: Proteins were precipitated from serum samples using methanol. Tigecycline was used as the internal standard. Mobile phase A was formic acid in water (0.1% v/v) and mobile phase B was methanol. UPLC-MS/MS was performed for analyte separation using a gradient elution program at a flow rate of 0.3 mL/min and a total run time of 5 min. The chromatography column was a ZORBAX PRHD SB-Aq (3 × 50 mm, 1.8 µm, Agilent, USA). The multiple reaction monitoring transitions at m/z = 557.4/470.3 and 586.5/513.3 were selected for omadacycline and tigecycline in the positive mode, respectively. RESULTS: The validated curve ranges were 0.5-25.0 µg/mL. This method exhibited acceptable selectivity, matrix effects, and recovery. The inter- and intra-run accuracies ranged from 93.5% to 114.8%, and the inter- and intra-run precisions were between 1.29% and 5.55%. CONCLUSIONS: The LC-MS/MS method provided a simple, specific, and rapid quantification of omadacycline in the serum of patients with pulmonary infection.

Mechanism of R-spondin2 Regulating Wnt/β-catenin Signaling Pathway and Its Influence on Skeletal System / 生物化学与生物物理进展

R-spondin2 (Rspo2) is a member of protein family RSPOs, which can be coupled to receptor 4/5 (leucine-rich repeat-containing g protein-coupled receptor 4/5, LGR4/5), cell surface transmembrane E3 ubiquitin ligase ZNRF3/RNF43 (zinc and ring finger 3/ring finger protein 43), heparan sulfate proteoglycan (heparan sulfate proteoglycans, HSPGs) and the IQ motif (IQ gap 1) containing GTP enzyme activating protein 1, regulating the Wnt/β-catenin signaling pathway, which is the most widely studied signaling pathway and directly related to basic bone biology. Any problem in this pathway may have an impact on bone regulation. In recent years, it has been found that Rspo2 can act on osteoblast, osteoclast and chondrocytes through Wnt/β-catenin, and take part in occureace and development of some bone diseases such as ossification of the posterior longitudinal ligament (OPLL), osteoarthritis (OA) and rheumatoid arthritis (RA), so the study of Rspo2 may become a new therapeutic direction for bone-related diseases. Based on the latest research progress, this paper reviews the structure and main functions of Rspo2, the mechanism of Rspo2 regulating Wnt/β-catenin signaling pathway and its influence on skeletal system, in order to provide new ideas and ways for the prevention and treatment of bone-related diseases.

Screening and mechanism of the best treatment of red light and silver ion dressing for treatment of chronic non-healing wounds / 中国组织工程研究

BACKGROUND:Red light irradiation and silver ion dressing are mostly used to treat chronic difficult healing wounds clinically,but the optimal irradiation time of red light irradiation and silver ion dressing for chronic non-healing wounds,and the combination of different silver ion dressings have not been determined. OBJECTIVE:To investigate the optimal irradiation time and dressing combination of red light and silver ion dressing in the therapy of chronic non-healing wounds. METHODS:The chronic non-healing wound model was made by applying Staphylococcus aureus on the whole skin defect and subcutaneous hydrocortisone injection in SD rats.72 rat models were randomly divided into 4 groups with 18 rats in each group by random number table method.The rats were treated on the basis of standard dressing change and the following therapy:A1B1 group(red irradiation 20 minutes + lipid hydrocolloidal silver sulfate dressing),A1B2 group(red light irradiation 20 minutes + calcium alginate fiber dressing),A2B1 group(red light irradiation 30 minutes + lipid hydrocolloidal silver sulfate dressing),and A2B2 group(red light irradiation 30 minutes + calcium alginate fiber dressing);change dressing,irradiate once,and change dressing every 24 hours.After 14 days of continuous treatment,wound healing rate,bacterial colony number,inflammatory response,histomorphology and angiogenesis were detected in each group. RESULTS AND CONCLUSION:(1)With the extension of treatment time,the wound healing rate of rats in the four groups was increased,and the wound healing rate of rats in the A2B2 group at 3,7,and 14 days after treatment was higher than that in the other three groups(P<0.05).(2)The wound bacterial culture results on day 7 after treatment demonstrated that the number of bacterial colonies in the A2B2 group was lower than that in the other three groups(P<0.05).Western blot assay exhibited that with the extension of treatment time,the protein expressions of tumor necrosis factor α and interleukin-6 in wound tissue of rats in the four groups were decreased,while the protein expressions of interleukin-10 were increased.The protein expressions of tumor necrosis factor α and interleukin-6 in the A2B2 group were lower than those in the other three groups(P<0.05).The protein expression of interleukin-10 in the A2B2 group was higher than that of the other three groups(P<0.05).(3)The wound hematoxylin-eosin staining on day 14 after treatment demonstrated that a large number of collagen fibers in the A2B2 group were parallel distributed and the most closely connected,which was significantly better than the other three groups.(4)The results of immunofluorescence staining indicated that the fluorescence intensity expression of CD31 in the A2B2 group was higher than that in the A1B1,A1B2 and A2B1 groups(P<0.05).q-PCR detection at 3,7,and 14 days after treatment exhibited that the mRNA expressions of vascular endothelial growth factor a and vascular endothelial growth factor receptor 2 in the A2B2 group were higher than those in the other three groups(P<0.05).Western blot assay at 3,7 and 14 days after treatment revealed that the protein expressions of vascular endothelial growth factor a and vascular endothelial growth factor receptor 2 in the A2B2 group were higher than those in the other three groups(P<0.05).(5)These findings confirm that 30 minutes of red light irradiation combined with silver alginate fiber dressing has better results in treatment of chronic non-healing wounds.

Effect on Danggui Shaoyao Powder on mitophagy in rat model of Alzheimer's disease based on PINK1-Parkin pathway / 中国中药杂志

This study investigated the mechanism of Danggui Shaoyao Powder(DSP) against mitophagy in rat model of Alzheimer's disease(AD) induced by streptozotocin(STZ) based on PTEN induced putative kinase 1(PINK1)-Parkin signaling pathway. The AD rat model was established by injecting STZ into the lateral ventricle, and the rats were divided into normal group, model group, DSP low-dose group(12 g·kg~(-1)·d~(-1)), DSP medium-dose group(24 g·kg~(-1)·d~(-1)), and DSP high-dose group(36 g·kg~(-1)·d~(-1)). Morris water maze test was used to detect the learning and memory function of the rats, and transmission electron microscopy and immunofluorescence were employed to detect mitophagy. The protein expression levels of PINK1, Parkin, LC3BⅠ/LC3BⅡ, and p62 were assayed by Western blot. Compared with the normal group, the model group showed a significant decrease in the learning and memory function(P<0.01), reduced protein expression of PINK1 and Parkin(P<0.05), increased protein expression of LC3BⅠ/LC3BⅡ and p62(P<0.05), and decreased occurrence of mitophagy(P<0.01). Compared with the model group, the DSP medium-and high-dose groups notably improved the learning and memory ability of AD rats, which mainly manifested as shortened escape latency, leng-thened time in target quadrants and elevated number of crossing the platform(P<0.05 or P<0.01), remarkably activated mitophagy(P<0.05), up-regulated the protein expression of PINK1 and Parkin, and down-regulated the protein expression of LC3BⅠ/LC3BⅡ and p62(P<0.05 or P<0.01). These results demonstrated that DSP might promote mitophagy mediated by PINK1-Parkin pathway to remove damaged mitochondria and improve mitochondrial function, thereby exerting a neuroprotective effect.

The efficacy of Modified Banxia Xiexin Decoction on patients with functional dyspepsia and its impact on gastric function / 中华消化杂志

Objective:To investigate the efficacy of Modified Banxia Xiexin Decoction on patients with functional dyspepsia (FD) and its impact on gastric function.Methods:From June 2021 to December 2022, at the Department of Gastroenterology, Wenzhou Central Hospital, a total of 56 patients with FD who met the diagnostic criteria of Rome Ⅳ were prospectively enrolled. The patients were treated with Modified Banxia Xiexin Decoction for 4 weeks. The clinical efficacy was evaluated by the upper gastrointestinal symptom severity index score. The gastric function was assessed by standard gastric loading test of liquid nutrient meal and standard gastric emptying test of solid meal. The total scores of dyspeptic symptoms, the maximal satiety threshold of proximal stomach, the initial satiety threshold of proximal stomach and 5-hour solid gastric emptying rate were compared before and after the treatment. During the treatment and in 4-week follow-up after treatment, the adverse events (such as nausea, diarrhea, dizziness and rash) were observed. Wilcoxon rank sum test and paired sample t-test were used for statistical analysis. Results:After the treatment, 14 FD patients were cured, 22 patients showed significant improvement, 12 patients had response, and 8 patients showed no improvement. The total efficacy rate was 85.71%(48/56). The total score of dyspepsia symptoms after the treatment was lower than that before treatment (3.00(1.00, 4.00) vs. 13.00(8.00, 18.00)), and the difference was statistically significant ( Z=-7.96, P<0.001). After the treatment, the maximal satiety threshold of proximal stomach and 5-hour solid gastric emptying rate were both higher than those before treatment ( (897.45±98.82) mL vs. (588.46±60.26) mL, (87.59±12.74)% vs. (36.59±15.95)%), and the differences were statistically significant ( t=19.98 and 18.70, both P<0.001). The initial satiety threshold of proximal stomach before and after treatment was compared((131.84±52.91) mL vs. (130.0±47.61) mL), and the difference was not statistically significant( P>0.05). No adverse events related to this study were observed during treatment period and in the 4-week follow-up. Conclusions:The Modified Banxia Xiexin Decoction can improve proximal gastric compliance and gastric emptying function in patients with FD. Additionally, it can alleviate dyspeptic symptoms and have good clinical efficacy and high safety.

Efficacy and safety of mitoxantrone hydrochloride liposome injection in treatment of peripheral T-cell lymphomas: a multicenter, non-interventional, ambispective cohort, real-world study (MOMENT) / 白血病·淋巴瘤

Objective:To evaluate the efficacy and safety of mitoxantrone hydrochloride liposome injection in the treatment of peripheral T-cell lymphoma (PTCL) in a real-world setting.Methods:This was a real-world ambispective cohort study (MOMENT study) (Chinese clinical trial registry number: ChiCTR2200062067). Clinical data were collected from 198 patients who received mitoxantrone hydrochloride liposome injection as monotherapy or combination therapy at 37 hospitals from January 2022 to January 2023, including 166 patients in the retrospective cohort and 32 patients in the prospective cohort; 10 patients in the treatment-na?ve group and 188 patients in the relapsed/refractory group. Clinical characteristics, efficacy and adverse events were summarized, and the overall survival (OS) and progression-free survival (PFS) were analyzed.Results:All 198 patients were treated with mitoxantrone hydrochloride liposome injection for a median of 3 cycles (range 1-7 cycles); 28 cases were treated with mitoxantrone hydrochloride liposome injection as monotherapy, and 170 cases were treated with the combination regimen. Among 188 relapsed/refractory patients, 45 cases (23.9%) were in complete remission (CR), 82 cases (43.6%) were in partial remission (PR), and 28 cases (14.9%) were in disease stabilization (SD), and 33 cases (17.6%) were in disease progression (PD), with an objective remission rate (ORR) of 67.6% (127/188). Among 10 treatment-na?ve patients, 4 cases (40.0%) were in CR, 5 cases (50.0%) were in PR, and 1 case (10.0%) was in PD, with an ORR of 90.0% (9/10). The median follow-up time was 2.9 months (95% CI 2.4-3.7 months), and the median PFS and OS of patients in relapsed/refractory and treatment-na?ve groups were not reached. In relapsed/refractory patients, the difference in ORR between patients with different number of treatment lines of mitoxantrone hydrochloride liposome injection [ORR of the second-line, the third-line and ≥the forth-line treatment was 74.4% (67/90), 73.9% (34/46) and 50.0% (26/52)] was statistically significant ( P = 0.008). Of the 198 PTCL patients, 182 cases (91.9%) experienced at least 1 time of treatment-related adverse events, and the incidence rate of ≥grade 3 adverse events was 66.7% (132/198), which was mainly characterized by hematologic adverse events. The ≥ grade 3 hematologic adverse events mainly included decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, and anemia; non-hematologic adverse events were mostly grade 1-2, mainly including pigmentation disorders and upper respiratory tract infection. Conclusions:The use of mitoxantrone hydrochloride liposome injection-containing regimen in the treatment of PTCL has definite efficacy and is well tolerated, and it is a new therapeutic option for PTCL patients.

Construction of a "4M" death education intervention program for advanced cancer caregivers based on the theory of knowledge, belief and practice / 中国实用护理杂志

Objective:To construct a death education intervention program for advanced cancer caregivers to improve the reference for death education for advanced cancer caregivers.Methods:Content analysis, semi-structured interview, Delphi expert consultation method were used to develop a preliminary death education program based on the theory of knowledge, belief, and behavior. From April to May 2022, fifteen experts from palliative care, life and death education, oncology nursing, psychological nursing and other related fields were selected for two rounds of expert consultation, and the contents of the program were revised and improved through preliminary experiments.Results:After two rounds of expert consultation, the results showed that the expert opinions tend to be unanimous. The authoritative coefficient of experts was 0.87, and the Kendall coordination coefficients of feasibility, validity and scientificity of the two rounds of consultation were 0.181, 0.303, 0.363 and 0.249, 0.355, 0.366, respectively (both P<0.05). The preliminary experiments revised and improved the intervention frequency and content, and finally formed a death education intervention program for advanced cancer caregivers which included four-stage progressive death themes: made an appointment with death, made a discussion on death, made an embrace with death and made friends with death. Conclusions:The process of constructing a death education program for advanced cancer caregivers is scientific, and the content is feasible, valid, and scientific. In addition, it is of great significance to promote death education in palliative care.

ACSL5, a prognostic factor in acute myeloid leukemia, modulates the activity of Wnt/β-catenin signaling by palmitoylation modification / 医学前沿

Acyl-CoA synthetase long chain family member 5 (ACSL5), is a member of the acyl-CoA synthetases (ACSs) family that activates long chain fatty acids by catalyzing the synthesis of fatty acyl-CoAs. The dysregulation of ACSL5 has been reported in some cancers, such as glioma and colon cancers. However, little is known about the role of ACSL5 in acute myeloid leukemia (AML). We found that the expression of ACSL5 was higher in bone marrow cells from AML patients compared with that from healthy donors. ACSL5 level could serve as an independent prognostic predictor of the overall survival of AML patients. In AML cells, the ACSL5 knockdown inhibited cell growth both in vitro and in vivo. Mechanistically, the knockdown of ACSL5 suppressed the activation of the Wnt/β-catenin pathway by suppressing the palmitoylation modification of Wnt3a. Additionally, triacsin c, a pan-ACS family inhibitor, inhibited cell growth and robustly induced cell apoptosis when combined with ABT-199, the FDA approved BCL-2 inhibitor for AML therapy. Our results indicate that ACSL5 is a potential prognosis marker for AML and a promising pharmacological target for the treatment of molecularly stratified AML.

Baicalin inhibits streptozotocin-induced neuroinflammation in Alzheimer' s disease rat model by TLR4/MyD88/NF-κB pathway / 中国药理学通报

Aim To investigate the effects of baicalin on the inflammatory response and Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD 88)/nuclear factor kappa B (N F-K B) signaling pathway in Alzheimer' s disease (AD) rat model induced by lateral ventricular injection of streptozotocin (STZ). Methods The AD animal model was constructed by lateral ventricular injection of STZ in SD rats, and divided into sham operation group, model group, low-dose (60 mg

Current status of diagnosis and treatment of chronic lymphocytic leukemia in China: A national multicenter survey research / 中华血液学杂志

Objective: To understand the current status of diagnosis and treatment of chronic lymphocytic leukemia (CLL) /small lymphocytic lymphoma (SLL) among hematologists, oncologists, and lymphoma physicians from hospitals of different levels in China. Methods: This multicenter questionnaire survey was conducted from March 2021 to July 2021 and included 1,000 eligible physicians. A combination of face-to-face interviews and online questionnaire surveys was used. A standardized questionnaire regarding the composition of patients treated for CLL/SLL, disease diagnosis and prognosis evaluation, concomitant diseases, organ function evaluation, treatment selection, and Bruton tyrosine kinase (BTK) inhibitor was used. Results: ①The interviewed physicians stated that the proportion of male patients treated for CLL/SLL is higher than that of females, and the age is mainly concentrated in 61-70 years old. ②Most of the interviewed physicians conducted tests, such as bone marrow biopsies and immunohistochemistry, for patient diagnosis, in addition to the blood test. ③Only 13.7% of the interviewed physicians fully grasped the initial treatment indications recommended by the existing guidelines. ④In terms of cognition of high-risk prognostic factors, physicians' knowledge of unmutated immunoglobulin heavy-chain variable and 11q- is far inferior to that of TP53 mutation and complex karyotype, which are two high-risk prognostic factors, and only 17.1% of the interviewed physicians fully mastered CLL International Prognostic Index scoring system. ⑤Among the first-line treatment strategy, BTK inhibitors are used for different types of patients, and physicians have formed a certain understanding that BTK inhibitors should be preferentially used in patients with high-risk factors and elderly patients, but the actual use of BTK inhibitors in different types of patients is not high (31.6%-46.0%). ⑥BTK inhibitors at a reduced dose in actual clinical treatment were used by 69.0% of the physicians, and 66.8% of the physicians had interrupted the BTK inhibitor for >12 days in actual clinical treatment. The use of BTK inhibitors is reduced or interrupted mainly because of adverse reactions, such as atrial fibrillation, severe bone marrow suppression, hemorrhage, and pulmonary infection, as well as patients' payment capacity and effective disease progression control. ⑦Some differences were found in the perceptions and behaviors of hematologists and oncologists regarding the prognostic assessment of CLL/SLL, the choice of treatment options, the clinical use of BTK inhibitors, etc. Conclusion: At present, a gap remains between the diagnosis and treatment of CLL/SLL among Chinese physicians compared with the recommendations in the guidelines regarding the diagnostic criteria, treatment indications, prognosis assessment, accompanying disease assessment, treatment strategy selection, and rational BTK inhibitor use, especially the proportion of dose reduction or BTK inhibitor discontinuation due to high adverse events.

Activities of daily living and its influencing factors for older people with type 2 diabetes mellitus in urban communities of Fuzhou, China.

Background: Type 2 diabetes mellitus (T2DM) is an independent risk factor for functional limitations among the older population. The predicted increase in T2DM cases combined with the ongoing rapidly aging population may further burden the already overloaded healthcare system and aggravate the loss of economic self-sufficiency. This study aimed to investigate the activities of daily living (ADL) and its influencing factors on older people with T2DM, and to provide implications for the development and improvement of community nursing services in the context rapidly aging population in China. Methods: From March 2019 to June 2020, we conducted a cross-sectional questionnaire survey among older T2DM patients in Fuzhou, using a multi-stage cluster sampling approach. Functional status was measured by the Lawton ADL scale. Stata "nptrend" test was used to examine the trend of ordinal variables on ADL. Non-conditional logistic regression was used to identify factors affecting ADL limitations. Results: A total of 2016 questionnaires were received, with a response rate of 96%. 12.4% of participants suffered from varying degrees of functional impairment. ADL limitations increased with age. More comorbidities were associated with a greater risk of developing functional limitations in ADLs. the following sub-groups were more likely to suffer from ADL impairment: those aged 70 and over years (OR = 1.99, 95%CI 1.77-2.56), living in an aged care house or with spouse/children (OR = 2.31, 95%CI 1.25-4.26), low monthly income (OR = 1.49, 95%CI 1.28-1.64), without health insurance (OR = 1.82, 95%CI 1.40-2.40), tight family expenses (OR = 1.95, 95%CI 1.42-2.69), having stroke (OR = 6.70, 95%CI 2.22-20.23) or malignant tumor (OR = 4.45, 95%CI 1.27-15.53), irregular eating habit (OR = 2.55, 95%CI 2.23-2.92), smoking (OR = 1.40, 95%CI 1.22-1.60), sedentary lifestyle (OR = 2.04, 95%CI 1.46-2.85), lack of physical exercise (OR = 1.35, 95%CI 1.19-1.53), sleeping difficulty (OR = 1.25, 95%CI 1.10-1.42), and lack of family support (OR = 1.19, 95%CI 1.10-1.29). Conclusion: Older adults (≥70 years) with T2DM had a high prevalence of functional limitations across a range of daily living tasks, which not only affect individual life of quality but also present a huge burden on the family, health services system, and the whole society. Identified factors associated with ADL limitations may provide useful information for targeted nursing practice and health promotion.

Detecting visually significant cataract using retinal photograph-based deep learning.

Age-related cataracts are the leading cause of visual impairment among older adults. Many significant cases remain undiagnosed or neglected in communities, due to limited availability or accessibility to cataract screening. In the present study, we report the development and validation of a retinal photograph-based, deep-learning algorithm for automated detection of visually significant cataracts, using more than 25,000 images from population-based studies. In the internal test set, the area under the receiver operating characteristic curve (AUROC) was 96.6%. External testing performed across three studies showed AUROCs of 91.6-96.5%. In a separate test set of 186 eyes, we further compared the algorithm's performance with 4 ophthalmologists' evaluations. The algorithm performed comparably, if not being slightly more superior (sensitivity of 93.3% versus 51.7-96.6% by ophthalmologists and specificity of 99.0% versus 90.7-97.9% by ophthalmologists). Our findings show the potential of a retinal photograph-based screening tool for visually significant cataracts among older adults, providing more appropriate referrals to tertiary eye centers.

Gene Set Enrichment Analsyes Identify Pathways Involved in Genetic Risk for Diabetic Retinopathy.

To identify functionally related genes associated with diabetic retinopathy (DR) risk using gene set enrichment analyses applied to genome-wide association study meta-analyses. METHODS: We analyzed DR GWAS meta-analyses performed on 3246 Europeans and 2611 African Americans with type 2 diabetes. Gene sets relevant to 5 key DR pathophysiology processes were investigated: tissue injury, vascular events, metabolic events and glial dysregulation, neuronal dysfunction, and inflammation. Keywords relevant to these processes were queried in 4 pathway and ontology databases. Two GSEA methods, Meta-Analysis Gene set Enrichment of variaNT Associations (MAGENTA) and Multi-marker Analysis of GenoMic Annotation (MAGMA), were used. Gene sets were defined to be enriched for gene associations with DR if the P value corrected for multiple testing (Pcorr) was <.05. RESULTS: Five gene sets were significantly enriched for numerous modest genetic associations with DR in one method (MAGENTA or MAGMA) and also at least nominally significant (uncorrected P < .05) in the other method. These pathways were regulation of the lipid catabolic process (2-fold enrichment, Pcorr = .014); nitric oxide biosynthesis (1.92-fold enrichment, Pcorr = .022); lipid digestion, mobilization, and transport (1.6-fold enrichment, P = .032); apoptosis (1.53-fold enrichment, P = .041); and retinal ganglion cell degeneration (2-fold enrichment, Pcorr = .049). The interferon gamma (IFNG) gene, previously implicated in DR by protein-protein interactions in our GWAS, was among the top ranked genes in the nitric oxide pathway (best variant P = .0001). CONCLUSIONS: These GSEA indicate that variants in genes involved in oxidative stress, lipid transport and catabolism, and cell degeneration are enriched for genes associated with DR risk. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

Bioinformatics screening and analysis of key differentially expressed genes characteristics in nonalcoholic fatty liver disease / 中华肝脏病杂志

Objective: To screen and analyze the key differentially expressed genes characteristics in nonalcoholic fatty liver disease (NAFLD) with bioinformatics method. Methods: NAFLD-related expression matrix GSE89632 was downloaded from the GEO database. Limma package was used to screen differentially expressed genes (DEGs) in healthy, steatosis (SS), and nonalcoholic steatohepatitis (NASH) samples. WGCNA was used to analyze the output gene module. The intersection of module genes and differential genes was used to determine the differential genes characteristic, and then GO function and KEGG signaling pathway enrichment analysis were performed. The protein-protein interaction network (PPI) was constructed using the online website STRING and Cytoscape software, and the key (Hub) genes were screened. Finally, R software was used to analyze the receiver operating characteristic curve (ROC) of the Hub gene. Results: 92 differentially expressed genes characteristic were obtained through screening, which were mainly enriched in inflammatory response-related functions of "lipopolysaccharide response and molecular response of bacterial origin", as well as cancer signaling pathways of "proteoglycan in cancer" and "T-cell leukemia virus infection-related". 10 hub genes (FOS, CXCL8, SERPINE1, CYR61, THBS1, FOSL1, CCL2, MYC, SOCS3 and ATF3) had good diagnostic value. Conclusion: The differentially expressed hub genes among the 10 NAFLD disease-related characteristics obtained with bioinformatics analysis may become a diagnostic and prognostic marker and potential therapeutic target for NAFLD. However, further basic and clinical studies are needed to validate.

Analysis of in vitro activity and compatibility of Dunhuang Yifang Dabupi Decoction on gastric cancer based on computer-aided drug design / 药学学报

Based on the research system of computer-aided drug design combined with complex network analysis, the potential mechanism of Dunhuang Dabupi Decoction in preventing and treating gastric cancer (GC) is analyzed, and the scientific connotation of its prescription rules is explored through the efficacy grouping. To study the effect of Dabupi Decoction freeze-dried powder solution on the proliferation activity of gastric cancer cells through cell experiments; the TCMSP and TCMID databases were used to collect the compound components of Dabupi Decoction. Swiss Target Prediction is used to predict potential targets of compounds. DrugBank, GeneCards, TTD, and DisGeNET were used to collect potential targets for gastric cancer. Analyze protein interactions of potential targets through the STRING database. DAVID database was used for KEGG enrichment analysis; Dabupi Decoction was divided into Wenzhong group (dried ginger), Yiqi group (ginseng, licorice, Atractylodes macrocephala), nourishing Yin group (Ophiopogon japonicus, Schisandra) and Jiangni group according to its efficacy characteristics. The inverse group (inula) has 4 functional compatibility groups. Cytoscape was used to construct a network of "medicinal flavor-potential active ingredient-key target" respectively, and the network was used to analyze the scientific connotation of the compatibility of efficacy groups. The Schrödinger software was used to verify the molecular docking of the core components and the core targets. The material basis of the Dabupi Decoction to prevent and treat gastric cancer was discovered through the combination of pattern analysis and combined free energy calculation. The core drug was analyzed from the perspective of dynamics through molecular dynamics simulation. Potential targets and representative potential compounds interact with each other. Cell experiments confirmed that Dabupitang freeze-dried powder solution can down-regulate the mitochondrial membrane potential of AGS gastric cancer cells, block the cell cycle in the G0/G1 phase (P < 0.05), and inhibit its proliferation (P < 0.05). The pathways enriched by the four functional groups contained in Dabupi Decoction are mainly distributed in the body's energy metabolism, inflammation-immune system regulation, and cycle-apoptotic functions. Each module is connected by a common target gene and has its own focus. The results of molecular docking showed that the compounds liquiritigenin, quercetin, kaempferol, isorhamnetin, methylophiopogonanone A, etc. may be the effective multi-target components of Dabupi Decoction. Estrogen receptor 1, androgen receptor, ATP-binding cassette superfamily G member 2, epidermal growth factor receptor, glycogen synthase kinase-3 beta and other targets have good affinity with each potential active compound, which may be a potential target of Dabupi Decoction for preventing and treating gastric cancer. Among them, kaempferol and the drug target EGFR not only have good binding ability, but also have good binding stability. This study is based on computer-aided drug design combined with complex network analysis strategies to initially reveal the material basis and molecular mechanism of Dabupi Decoction in the prevention and treatment of gastric cancer. It also explores the scientific connotation of Dabupi Decoction in the prevention and treatment of gastric cancer with different efficacy groups, and its clinical application provide chemical bioinformatics basis.

Abivertinib inhibits megakaryocyte differentiation and platelet biogenesis / 医学前沿

Abivertinib, a third-generation tyrosine kinase inhibitor, is originally designed to target epidermal growth factor receptor (EGFR)-activating mutations. Previous studies have shown that abivertinib has promising antitumor activity and a well-tolerated safety profile in patients with non-small-cell lung cancer. However, abivertinib also exhibited high inhibitory activity against Bruton's tyrosine kinase and Janus kinase 3. Given that these kinases play some roles in the progression of megakaryopoiesis, we speculate that abivertinib can affect megakaryocyte (MK) differentiation and platelet biogenesis. We treated cord blood CD34+ hematopoietic stem cells, Meg-01 cells, and C57BL/6 mice with abivertinib and observed megakaryopoiesis to determine the biological effect of abivertinib on MK differentiation and platelet biogenesis. Our in vitro results showed that abivertinib impaired the CFU-MK formation, proliferation of CD34+ HSC-derived MK progenitor cells, and differentiation and functions of MKs and inhibited Meg-01-derived MK differentiation. These results suggested that megakaryopoiesis was inhibited by abivertinib. We also demonstrated in vivo that abivertinib decreased the number of MKs in bone marrow and platelet counts in mice, which suggested that thrombopoiesis was also inhibited. Thus, these preclinical data collectively suggested that abivertinib could inhibit MK differentiation and platelet biogenesis and might be an agent for thrombocythemia.