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Background: Medical history contributes approximately 80% to a diagnosis, although physical examinations and laboratory investigations increase a physician's confidence in the medical diagnosis. The concept of artificial intelligence (AI) was first proposed more than 70 years ago. Recently, its role in various fields of medicine has grown remarkably. However, no studies have evaluated the importance of patient history in AI-assisted medical diagnosis., Objective: This study explored the contribution of patient history to AI-assisted medical diagnoses and assessed the accuracy of ChatGPT in reaching a clinical diagnosis based on the medical history provided., Methods: Using clinical vignettes of 30 cases identified in The BMJ, we evaluated the accuracy of diagnoses generated by ChatGPT. We compared the diagnoses made by ChatGPT based solely on medical history with the correct diagnoses. We also compared the diagnoses made by ChatGPT after incorporating additional physical examination findings and laboratory data alongside history with the correct diagnoses., Results: ChatGPT accurately diagnosed 76.6% (23/30) of the cases with only the medical history, consistent with previous research targeting physicians. We also found that this rate was 93.3% (28/30) when additional information was included., Conclusions: Although adding additional information improves diagnostic accuracy, patient history remains a significant factor in AI-assisted medical diagnosis. Thus, when using AI in medical diagnosis, it is crucial to include pertinent and correct patient histories for an accurate diagnosis. Our findings emphasize the continued significance of patient history in clinical diagnoses in this age and highlight the need for its integration into AI-assisted medical diagnosis systems., (© Fumitoshi Fukuzawa, Yasutaka Yanagita, Daiki Yokokawa, Shun Uchida, Shiho Yamashita, Yu Li, Kiyoshi Shikino, Tomoko Tsukamoto, Kazutaka Noda, Takanori Uehara, Masatomi Ikusaka. Originally published in JMIR Medical Education (https://mededu.jmir.org).)

FOXM1 (forkhead box M1) is an important member of the FOX transcription factor family and plays a critical role in driving the progression of multiple malignancies through its transcriptional regulatory functions. Moreover, the overexpression of FOXM1 is associated with poor prognosis in many types of cancer, as it regulates a variety of biological processes such as gene expression, cell proliferation, invasion, metastasis, and apoptosis. Presently, aberrant metabolic reprogramming has been considered as the major characteristic of cancer development, determining the survival, growth, and proliferation of tumor cells. Accumulating evidence suggests that FOXM1 serves as a "bridge" between metabolism and tumorigenesis. This review aims to provide a comprehensive summary of the research progress in the relationship between FOXM1 and tumor cell metabolism, offering theoretical insights for the development of novel anti-cancer drugs targeting FOXM1.

Abstract An increasing number of studies indicate that long noncoding RNAs (lncRNAs) play important roles in tumour proliferation, migration and other vital processes and are expected to become novel biomarkers for early cancer screening. The expression of the lncRNA NBR2 (adjacent breast cancer suppressor BRCA1) has been found to decrease in several cancer types. However, it is still unknown whether the lncRNA NBR2 is involved in breast cancer and autophagy. According to the Kaplan–Meier plotter survival curve analysis, the survival rate of the group with high lncRNA-NBR2 expression was higher than that of the group with low lncRNA-NBR2 expression. The suppression of cancer cell proliferation, invasion and migration by the lncRNA NBR2 has been demonstrated, suggesting that this lncRNA is involved in the development and progression of cancer. Our subsequent study revealed that the lncRNA NBR2 inhibited autophagy in breast cancer cells, and that starvation conditions enhanced this inhibitory effect. Moreover, this lncRNA changed the proliferation ability of breast cancer cells by affecting protective autophagy. The aim of this study was to investigate the link between starvation and lncRNAs by evaluating changes in autophagy-related proteins, cell proliferation and other biological processes. Together, these studies provide strategies for the early screening of breast cancer and suggest that starvation therapy can be used as a new approach for the treatment of cancer.

Abstract Temozolomide (TMZ) resistance is a major challenge in the treatment of glioblastoma (GBM). Tumour reproductive cells (TRCs) have been implicated in the development of chemotherapy resistance. By culturing DBTRG cells in three-dimensional soft fibrin gels to enrich GBM TRCs and performing RNA-seq analysis, the expression of stanniocalcin-1 (STC), a gene encoding a secreted glycoprotein, was found to be upregulated in TRCs. Meanwhile, the viability of TMZ-treated TRC cells was significantly higher than that of TMZ-treated 2D cells. Analysis of clinical data from CGGA (Chinese Glioma Genome Atlas) database showed that high expression of STC1 was closely associated with poor prognosis, glioma grade and resistance to TMZ treatment, suggesting that STC1 may be involved in TMZ drug resistance. The expression of STC1 in tissues and cells was examined, as well as the effect of STC1 on GBM cell proliferation and TMZ-induced DNA damage. The results showed that overexpression of STC1 promoted and knockdown of STC1 inhibited TMZ-induced DNA damage. These results were validated in an intracranial tumour model. These data revealed that STC1 exerts regulatory functions on MGMT expression in GBM, and provides a rationale for targeting STC1 to overcome TMZ resistance.

Objective·To find out the risk factors leading to adverse pregnancy outcome by analyzing the correlation of clinical data and adverse pregnancy outcomes in patients with pregnancy complicated with chronic kidney disease.Methods·The clinical data before 20 weeks of gestation of single pregnant patients discharged with a diagnosis of chronic kidney disease who conducted standardized prenatal examination and delivered in Renji Hospital, Shanghai Jiao Tong University School of Medicine from January 1, 2017 to December 31, 2021 were collected retrospectively. According to the pregnancy outcomes, patients were divided into adverse pregnancy outcome group (study group) and good pregnancy outcome group (control group). The clinical data, laboratory test results and pregnancy outcomes of the two groups of pregnant women were compared, and the risk factors leading to adverse pregnancy outcomes were analyzed.Results·Maternal clinical data of 359 pregnant patients were collected, 6 cases of twin pregnancy were excluded, and the remaining 353 cases of pregnancy with chronic kidney disease were included in this study. Among them, 230 cases of pregnancy without related maternal and fetal complications were included in the good pregnancy outcome group (control group), and 123 cases of pregnancy with adverse maternal and fetal outcomes were included in the adverse pregnancy outcome group (study group). The adverse pregnancy outcome group (one pregnancy can have multiple adverse pregnancy outcomes) includes 69 cases of preeclampsia (including 43 cases of severe preeclampsia), 29 cases of acute kidney injury, 69 cases of premature delivery, 34 cases of infants smaller than gestational age, 46 cases of low birth weight infants, 41 cases of neonatal admission to NICU, and 7 cases of miscarriage after 20 weeks of gestation or neonatal death. There were no differences in age, body mass index, pregnancy times and birth times between the study group and control group. In patients with chronic kidney disease, those who had chronic hypertension (OR=3.385, 95% CI 1.115—10.726, P=0.031), serum creatinine over 60 μmol/L (OR=2.828, 95% CI 1.439—5.557, P=0.003), 24-hour urine protein≥0.3 g (OR=2.234, 95% CI 1.122—4.448, P=0.022), and lupus nephritis before 20 weeks of gestation (OR=4.917, 95% CI=1.967—12.290, P=0.001) were at significantly higher risk of adverse pregnancy outcomes. The area under the ROC curve was 0.759, the sensitivity was 52.8%, and the specificity was 84.2% for predicting adverse pregnancy outcomes in pregnant women with chronic kidney disease.Conclusion·Chronic hypertension, 24-hour urine protein≥0.3 g, nephritis type of lupus nephritis and serum creatinine≥ 60 μmol/L before 20 weeks of gestation are independent risk factors for adverse pregnancy outcome in CKD patients. The combination of the above four indicators have a good predictive value for adverse pregnancy outcomes.

Abstract Hemodynamic parameters have been correlated with stroke, hypertension, and arterial stenosis. While only a few small studies have examined the link between hemodynamics and diabetes mellitus (DM). This case-control study enrolled 417 DM patients and 3475 non-DM controls from a community-based cohort. Peak systolic velocity (PSV), end-diastolic velocity (EDV), blood flow velocity (MFV), pulsatility index (PI), and the resistance index (RI) of the common carotid arteries were measured by color Doppler ultrasonography. Generalized linear regression analyses showed that as compared to the non-DM controls, the age-sex-adjusted means of PSV, EDV, and MFV were − 3.28 cm/sec, − 1.94 cm/sec, and − 2.38 cm/sec, respectively, lower and the age-sex-adjusted means of RI and PI were 0.013 and 0.0061, respectively, higher for the DM cases (all p-values

Abstract Chemotherapeutic agents can inhibit the proliferation of malignant cells due to their cytotoxicity, which is limited by collateral damage. Dihydroartemisinin (DHA), has a selective anti-cancer effect, whose target and mechanism remain uncovered. The present work aims to examine the selective inhibitory effect of DHA as well as the mechanisms involved. The findings revealed that the Lewis cell line (LLC) and A549 cell line (A549) had an extremely rapid proliferation rate compared with the 16HBE cell line (16HBE). LLC and A549 showed an increased expression of NRAS compared with 16HBE. Interestingly, DHA was found to inhibit the proliferation and facilitate the apoptosis of LLC and A549 with significant anti-cancer efficacy and down-regulation of NRAS. Results from molecular docking and cellular thermal shift assay revealed that DHA could bind to epidermal growth factor receptor (EGFR) molecules, attenuating the EGF binding and thus driving the suppressive effect. LLC and A549 also exhibited obvious DNA damage in response to DHA. Further results demonstrated that over-expression of NRAS abated DHA-induced blockage of NRAS. Moreover, not only the DNA damage was impaired, but the proliferation of lung cancer cells was also revitalized while NRAS was over-expression. Taken together, DHA could induce selective anti-lung cancer efficacy through binding to EGFR and thereby abolishing the NRAS signaling pathway, thus leading to DNA damage, which provides a novel theoretical basis for phytomedicine molecular therapy of malignant tumors.

In the study of age estimation in living individuals, a lot of data needs to be analyzed by mathematical statistics, and reasonable medical statistical methods play an important role in data design and analysis. The selection of accurate and appropriate statistical methods is one of the key factors affecting the quality of research results. This paper reviews the principles and applicable principles of the commonly used medical statistical methods such as descriptive statistics, difference analysis, consistency test and multivariate statistical analysis, as well as machine learning methods such as shallow learning and deep learning in the age estimation research of living individuals, and summarizes the relevance and application prospects between medical statistical methods and machine learning methods. This paper aims to provide technical guidance for the age estimation research of living individuals to obtain more scientific and accurate results.

Objective To investigate the protective effect of sevoflurane postconditioning against cerebral ischemia/reperfusion (I/R) injury in rats and its mechanism of action. Methods A total of 80 specific pathogen-free healthy adult male Sprague-Dawley rats were selected and randomly divided into sham-operation group (S group), cerebral I/R group (I/R group), cerebral I/R+sevoflurane postconditioning group (ISP group), and cerebral I/R+sevoflurane postconditioning+nuclear factor ery-throid 2-related factor 2 (Nrf2) inhibitor group (ISPB group), with 20 rats in each group. All rats except those in the S group were used to establish a rat model of cerebral I/R injury using the suture method for occlusion of the middle cerebral artery for 2 h, followed by reperfusion for 24 h, and for the rats in the S group, threading was performed below the middle cerebral artery without ligation. The rats in the ISP group were given inhalation of 3% sevoflurane immediately after reperfusion for 30 min, and those in the ISPB group were given intraperitoneal injection of the Nrf2 inhibitor brusatol (2 mg/kg) at 30 min before ischemia in addition to the treatment in the ISP group. After successful modeling, neurological deficit score was used to eval-uate the degree of neurological impairment. Left ventricular blood samples and pathological sections of brain tissue were obtained, and 2,3,5-triphenyltetrazolium chloride staining was used to determine the percentage of cerebral infarct volume; enzyme-linked immunosorbent assay was used to measure the serum levels of inflammatory factors (interleukin-1β [IL-1β] and tumor necrosis factor-α [TNF-α]) and oxidative stress-related factors (malondialdehyde [MDA] and superoxide dismutase [SOD]); Western blotting was used to mea-sure the expression of apoptosis-related proteins (B-cell lymphoma-2 [Bcl-2], Bcl-2 related x [Bax], and Caspase-3) and Nrf2 signaling pathway-related proteins (Nrf2 and heme oxygenase-1 [HO-1]) in brain tissue; immunofluorescence assay was used to measure the expression of Nrf2 inside and outside the nucleus of brain tissue cells. Results Compared with the I/R group, the ISP group had significant reductions in neurological deficit score, the percentage of cerebral infarct volume, the serum levels of IL-1β, TNF-α, and MDA, and the levels of Bax and Caspase-3 in brain tissue (t=5.76-18.39,P

Background Systemic lupus erythematosus (SLE) is distinguished by an extensive range of clinical heterogeneity with unpredictable disease flares and organ damage. This research investigates the potential of aberrant signatures on T cell genes, soluble Co-IRs/ligands, and Co-IRs expression on T cells as biomarkers for lupus disease parameters. Methods Comparative transcriptome profiling analysis of non-renal and end-stage renal disease (ESRD) phenotypes of SLE was performed using CD4 + and CD8 + cDNA microarrays of sorted T cells. Comparing the expression of Co-IRs on T cells and serum soluble mediators among healthy and SLE phenotypes. Results SLE patients with ESRD were downregulated CD38, PLEK, interferon-γ, CX3CR1, FGFBP2, and SLCO4C1 transcripts on CD4 + and CD8 + T cells simultaneously and NKG7, FCRL6, GZMB/H, FcγRIII, ITGAM, Fas ligand, TBX21, LYN, granulysin, CCL4L1, CMKLR1, HLA-DRβ, KIR2DL3, and KLRD1 in CD8 T cells. Pathway enrichment and PPI network analyses revealed that the overwhelming majority of Differentially Expressed Genes (DEGs) have been affiliated with novel cytotoxic, antigen presentation, and chemokine-cell migration signature pathways. CD8 + GZMK + T cells that are varied in nature, including CD161 + Mucosal-associated invariant T (MAIT) cells and CD161- aged-associated T (Taa) cells and CD161-GZMK + GZMB + T cells might account for a higher level of GZMK in CD8 + T cells associated with ESRD. SLE patients have higher TIGIT + , PD1 + , and lower CD127 + cell percentages on CD4 + T cells, higher TIM3 + , TIGIT + , HLA-DR + cell frequency, and lower MFI expression of CD127, CD160 in CD8 T cells. Co-IRs expression in T cells was correlated with soluble PD-1, PDL-2, and TIM3 levels, as well as SLE disease activity, clinical phenotypes, and immune-therapy responses. Conclusion The signature of dysfunctional pathways defines a distinct immunity pattern in LN ESRD patients. Expression levels of Co-IRs in peripheral blood T cells and serum levels of soluble PD1/PDL-2/TIM3 can serve as biomarkers for evaluating clinical parameters and therapeutic responses.

Abstract Accurately identification of the seizure onset zone (SOZ) is pivotal for successful surgery in patients with medically refractory epilepsy. The purpose of this study is to improve the performance of model predicting the epilepsy surgery outcomes using genetic neural network (GNN) model based on a hybrid intracranial electroencephalography (iEEG) marker. We extracted 21 SOZ related markers based on iEEG data from 79 epilepsy patients. The least absolute shrinkage and selection operator (LASSO) regression was employed to integrated seven markers, selected after testing in pairs with all 21 biomarkers and 7 machine learning models, into a hybrid marker. Based on the hybrid marker, we devised a GNN model and compared its predictive performance for surgical outcomes with six other mainstream machine-learning models. Compared to the mainstream models, underpinning the GNN with the hybrid iEEG marker resulted in a better prediction of surgical outcomes, showing a significant increase of the prediction accuracy from approximately 87% to 94.3% (P = 0.0412). This study suggests that the hybrid iEEG marker can improve the performance of model predicting the epilepsy surgical outcomes, and validates the effectiveness of the GNN in characterizing and analyzing complex relationships between clinical data variables.

Pancreatic adenocarcinoma (PAAD) is a prevalent and aggressive malignancy in the digestive tract, requiring accurate prediction and effective treatment strategies. Recently, the discovery of disulfidptosis, a novel form of programmed cell death characterized by abnormal disulfide accumulation, has sparked interest in its role in PAAD. In this study, we aimed to investigate the involvement of disulfidptosis-related genes (DRGs) in PAAD. Using publicly available databases, we conducted a comprehensive analysis exploring the complex relationships between DRGs and important aspects of PAAD, including gene expression, immune response, mutation, drug sensitivity, and functional enrichment. Notably, we observed significant heterogeneity among different disulfidptosis subclusters and identified specific differentially expressed genes in PAAD. Through machine learning techniques, we identified SLC7A11, S100A4, DIAPH3, PRDX1, and SLC7A7 as the most relevant hub genes. We further validated their significance in PAAD by considering their expression patterns, prognostic value, diagnostic potential, diagnostic model, and immune infiltration. This study presents exciting opportunities and challenges in unraveling the underlying mechanisms of PAAD prognosis. It also establishes a foundation for personalized cancer care and the development of innovative immunotherapeutic strategies. By shedding light on the role of DRGs, particularly hub genes, we enhance our understanding and management of PAAD.

Background Finding a simple, effective and rapid diagnostic method to improve the diagnosis of gastroesophageal reflux-induced chronic cough (GERC) is indicated. Our objective was to determine the diagnostic value of the pepsin concentration in saliva and induced sputum for GERC. Methods 171 patients with chronic cough were enrolled. The diagnosis and treatment followed the chronic cough diagnosis and treatment protocol. Saliva and induced sputum were collected, and the pepsin concentration was determined using Peptest. A Gastroesophageal Reflux Diagnostic Questionnaire (GerdQ) was completed. The diagnostic value of the pepsin concentration in saliva and induced sputum for GERC was analysed and compared. Results The salivary pepsin concentration predicted GERC with an area under the receiver operating characteristic curve (AUC) of 0.845. The optimal cut-off value was 76.10 ng·mL−1, the sensitivity was 83.58% and the specificity was 82.69%. The pepsin concentration in the induced sputum supernatant for GERC had an AUC of 0.523. When GerdQ was used for GERC diagnosis, the AUC was 0.670 and the diagnostic value of salivary pepsin was better compared to GerdQ (DeLong test, p=0.0008). Salivary pepsin had a comparable diagnostic value to GerdQ (AUC 0.779 versus 0.826; p=0.4199) in acidic GERC. Salivary pepsin had superior diagnostic value compared to GerdQ (AUC 0.830 versus 0.533; p76.10 ng·mL−1 is of good diagnostic value for GERC, especially in non-acidic GERC. The pepsin concentration in induced sputum has a low diagnostic value.

Abstract Glioblastoma multiforme (GBM) is a complex disease to treat owing to its profound chemoresistance. Therefore, we evaluated the combined effect and therapeutic efficacy of temozolomide (TMZ), a potent alkylating agent and the current gold standard therapy for GBM, and cryptotanshinone (CTS), which inhibits glioma cell proliferation in GBM cells. Using LN229 and U87-MG human GBM cells in a short-term stimulation in vitro model, the cytotoxic and anti-proliferative effects of single and combined treatment with 4 μM CTS and 200 μM TMZ were investigated. Furthermore, cell viability, DNA damage, apoptosis rate, and signal transducer and activator of transcription 3 (STAT3) protein were measured using cytotoxic assay, comet assay, flow cytometry, and western blotting analysis, respectively. The two drugs’ synergistic interaction was validated using the synergy score. We found that the anti-proliferative effects of combination therapy using the two drugs were greater than that of each agent used alone (CTS or TMZ). Western blot analysis indicated that treatment of GBM cells with CTS combined with TMZ more significantly decreased the expression of MGMT and STAT3, than that with TMZ alone. Combined treatment with CTS and TMZ might be an effective option to overcome the chemoresistance of GBM cells in a long-term treatment strategy.

Abstract Heart rhythm complexity (HRC), a subtype of heart rate variability (HRV), is an important tool to investigate cardiovascular disease. In this study, we aimed to analyze serial changes in HRV and HRC metrics in patients with inferior ST-elevation myocardial infarction (STEMI) within 1 year postinfarct and explore the association between HRC and postinfarct left ventricular (LV) systolic impairment. We prospectively enrolled 33 inferior STEMI patients and 74 control subjects and analyzed traditional linear HRV and HRC metrics in both groups, including detrended fluctuation analysis (DFA) and multiscale entropy (MSE). We also analyzed follow-up postinfarct echocardiography for 1 year. The STEMI group had significantly lower standard deviation of RR interval (SDNN), and DFAα2 within 7 days postinfarct (acute stage) comparing to control subjects. LF power was consistently higher in STEMI group during follow up. The MSE scale 5 was higher at acute stage comparing to control subjects and had a trend of decrease during 1-year postinfarct. The MSE area under scale 1–5 showed persistently lower than control subjects and progressively decreased during 1-year postinfarct. To predict long-term postinfarct LV systolic impairment, the slope between MSE scale 1 to 5 (slope 1–5) had the best predictive value. MSE slope 1–5 also increased the predictive ability of the linear HRV metrics in both the net reclassification index and integrated discrimination index models. In conclusion, HRC and LV contractility decreased 1 year postinfarct in inferior STEMI patients, and MSE slope 1–5 was a good predictor of postinfarct LV systolic impairment.

Background Acute hypoxic injury caused by acute altitude exposure is manifested by different degrees of clinical symptoms, some of which may develop into acute mountain sickness (AMS). However, the current prevention and treatment methods are limited and there is a lack of safe and effective methods to prevent and reduce the severity. Objective To investigate the efficacy and safety of intermittent hypoxic (IH) training in preventing acute hypoxic injury by simulating hypoxic environment at an altitude of 4 400 meters. Methods A total of 40 subjects were recruited by public recruitment in Beijing Xiaotangshan Hospital from 2022-08-01 to 10-31 and randomly divided into the IH group (experimental group, n=20) and sham training group (control group, n=20). The experimental group received the IH exposure intervention with the total duration of 55 min twice a day for 5 d, including 10 min of low oxygen (oxygen concentration of 13%, simulated altitude of 3 800 m), 5 min of normoxia (oxygen concentration of 21%). The control group received the simultaneous long normoxia intervention. On the first day after the IH intervention training, the subjects entered into the simulated high-altitude hypoxia environment for 6 h, and the oxygen concentration was set at 12% (equivalent to the altitude of 4 400 m). The Lake Louise Scale (LLS) was used to assess the severity of AMS. Peripheral oxygen saturation (SpO2), cerebral oxygen saturation (ScO2) and intracranial pressure (ICP) were collected at baseline, before and 6 h after the simulated high-altitude hypoxia environment. Results After 6 h of acute high-altitude hypoxia environment simulation, the incidence of AMS and LLS in the experimental group were significantly lower than those in the control group (P

Background Obstructive sleep apnea (OSA) has a high prevalence, and it has been shown to be an independent risk factor for various diseases. Therefore, it is important to strengthen screening for population at highrisk of OSA. OSA patients are prone to combine with lipid metabolism disorders, but it remains unclear whether the atherogenic index of plasma (AIP), visceral adiposity index (VAI), lipid accumulation product (LAP), cardiometabolic index (CMI), and Chinese visceral adiposity index (CVAI), which are used asmetabolic indexes, can be used to predict OSA. Objective To analyze the correlation between metabolic indexes and OSA, and evaluate the predictive efficacy of each metabolic index through a case-control study. Methods A total of 2 968 inpatients with suspected OSA and aged ≥18 years who completed polysomnography (PSG) in the First Affiliated Hospital of Xinjiang Medical University from March 2017 to June 2022 were selected, with 2 850 patients finally included based on the inclusion and exclusion criteria and divided into the OSA group 〔apnea-hypopnea index (AHI) ≥5 times/h, n=2 193〕 and non-OSA group (AHI0.05), but AIP and CVAI were associated with OSA (P

Objective To investigate the characteristics and objective assessment method of visual field defects caused by optic chiasm and its posterior visual pathway injury. Methods Typical cases of visual field defects caused by injuries to the optic chiasm, optic tracts, optic radiations, and visual cortex were selected. Visual field examinations, visual evoked potential （VEP） and multifocal visual evolved potential （mfVEP） measurements, craniocerebral CT/MRI, and retinal optical coherence tomography （OCT） were performed, respectively, and the aforementioned visual electrophysiological and neuroimaging indicators were analyzed comprehensively. Results The electrophysiological manifestations of visual field defects caused by optic chiasm injuries were bitemporal hemianopsia mfVEP abnormalities. The visual field defects caused by optic tract, optic radiation, and visual cortex injuries were all manifested homonymous hemianopsia mfVEP abnormalities contralateral to the lesion. Mild relative afferent pupil disorder （RAPD） and characteristic optic nerve atrophy were observed in hemianopsia patients with optic tract injuries, but not in patients with optic radiation or visual cortex injuries. Neuroimaging could provide morphological evidence of damages to the optic chiasm and its posterior visual pathway. Conclusion Visual field defects caused by optic chiasm, optic tract, optic radiation, and visual cortex injuries have their respective characteristics. The combined application of mfVEP and static visual field measurements, in combination with neuroimaging, can maximize the assessment of the location and degree of visual pathway damage, providing an effective scheme for the identification of such injuries.

Objective To study the detection efficiency of trio full sibling with another known full sibling reference added under different number of autosomal STR typing systems. Methods Based on 43 detection systems consisting of 13 to 55 representative autosomal STR loci，10 000 true families （full sibling group） and 10 000 false families （unrelated individual group） were randomly simulated. The full sibling index （FSI） was calculated based on the method of family reconstruction. The cumulative sibling relationship index （CFSI） of 0.000 1 and 10 000 were used as the evaluation thresholds, and the detection efficiency parameters were calculated and compared with the identification of the duo full sibling testing. Results With the increasing number of STR loci， the error rate and inability of judgement rate gradually decreased; the sensitivity， specificity, correct rate of judgment and other parameters gradually increased, and the system efficiency gradually improved. Under the same detection system， trio full sibling testing showed higher sensitivity， specificity， system efficiency and lower inability of judgement rate compared with duo full sibling testing. When the system efficiency was higher than 0.85 and inability of judgement rate was less than 0.01%， at least 20 STRs should be detected for trio full sibling testing， which was less than 29 STRs required by duo full sibling testing. Conclusion The detection efficiency of trio full sibling testing is superior to that of duo full sibling testing with the same detection system， which is an effective identification scheme for laboratories with inadequate detection systems or for materials with limited conditions.

Objective To establish an analytical method for half sibling testing involving common three relatives’ participation. Methods Based on the half sibling testing scenarios with the known biological mother, grandfather or uncle, and two unidentified controversial half siblings participating， two opposing hypotheses were set. Lineage reconstruction according to Mendel’s law of heredity was carried out, and the calculation formula of the half sibling kinship index was derived. Verification of actual cases was carried out and the results were compared with duo half sibling testing. Results In the scenarios of the known biological mother， grandfather and uncle participating in half sibling testing, the kinship calculation formulae of 54， 91 and 99 genotype combinations for kinship index calculation were deduced respectively. The actual cases showed higher kinship indexes in trio half sibling testing compared with duo half sibling testing. Conclusion It is beneficial to obtain more genetic information for family reconstruction and improvement of the strength of genetic evidence for half sibling testing by adding known relatives.

Most elderly persons suffer from chronic diseases. To treat chronic diseases, good medication adherence and refilling medication as physicians’ advice are key points of pharmaceutical therapy. However, the literature revealed that only limited studies have focused on the medication adherence of the elderly in rural communities. This study evaluated the adherence to medication and the degree of refilling prescriptions as physician’s advice by the Adherence to Refills and Medications Scale (ARMS) and evaluated the factors associated with poor adherence to medication. This cross-sectional study focused on the medication use of the elderly population in rural areas in western Taiwan and analyzed related personal and social factors which influence the behaviors of pharmaceutical therapy. In conclusion, most of the elderly who lived in rural areas in western Taiwan have poor adherence (ARMS score over 12) to medication and a poor degree of refilling prescriptions as per physicians’ advice. Moreover, age ≥75 years and low urbanization were significantly associated with poor adherence. Future research is warranted to assess the effect of the interventions to improve medication adherence on chronic disease control, disability, and mortality.

BackgroundA retrospective study was conducted to explore the urinary expression of α 1-microglobulin (α1MG) and β2-microglobulin (β2MG) in patients with human immunodeficiency virus (HIV) infection, aiming to evaluate their predictive capability for renal injury.MethodOne hundred and five male HIV-infected patients treated with Tenofovir (TDF) regimen (TDF+3TC or the third drug TDF/FTC+) were selected between March 1, 2021, and March 1, 2022, in Wuhan Jinyintan Hospital. Three months after TDF treatment, the renal function injury was evaluated with the standard creatinine clearance rate. The urinary levels of α1MG and β2MG were compared between the initiation of TDF treatment and three months thereafter. Spearman correlation was utilized to analyze the correlation between the urinary expression of α1MG and β2MG and renal injury in HIV patients. The logistic regression was used to analyze the predictive value of urinary α1MG and β 2-microglobulin expression in renal injury.ResultsUp to the first follow-up, 29 (27.6%) cases of the 105 male HIV patients had varying degrees of renal function injury, including 14 (13.3%) mild injury, 9 (8.6%) moderate injury, and 6 (5.7%) severe injury cases. Patients with severe renal injury had the highest levels of urinary α1MG and β2MG expression while those with mild injury demonstrated higher levels compared to the non-injury group (P < 0.05). Spearman correlation analysis indicated that urinary α1MG and β2MG were positively correlated with renal impairment in HIV patients (Rho = -0.568, and -0.732; P < 0.001). The ROC curve analysis demonstrated that the area under the curve (AUC) for urine α1MG and β2MG in predicting kidney damage among HIV patients were 0.928, 0.916, and 0.889, respectively. The sensitivity values were 96.55%, 82.76%, and 89.66% while the specificity values were 84.07%, 94.51%, and 89.29% for urine α1MG and β2MG, respectively.ConclusionThe expression level of urinary α1MG and β2MG in HIV patients was significantly higher compared to normal people. Detection of these two indexes can enable early determination of renal injury and its severity in HIV patients.

ObjectiveTo explore the cytotoxicity of four wild mushrooms involved in a case of Yunnan sudden unexplained death （YNSUD）, to provide the experimental basis for prevention and treatment of YNSUD.MethodsFour kinds of wild mushrooms that were eaten by family members in this YNSUD incident were collected and identified by expert identification and gene sequencing. Raw extracts from four wild mushrooms were extracted by ultrasonic extraction to intervene HEK293 cells, and the mushrooms with obvious cytotoxicity were screened by Cell Counting Kit-8 （CCK-8）. The selected wild mushrooms were prepared into three kinds of extracts, which were raw, boiled, and boiled followed by enzymolysis. HEK293 cells were intervened with these three extracts at different concentrations. The cytotoxicity was detected by CCK-8 combined with lactate dehydrogenase （LDH） Assay Kit, and the morphological changes of HEK293 cells were observed under an inverted phase contrast microscope.ResultsSpecies identification indicated that the four wild mushrooms were Butyriboletus roseoflavus, Boletus edulis, Russula virescens and Amanita manginiana. Cytotoxicity was found only in Amanita manginiana. The raw extracts showed cytotoxicity at the mass concentration of 0.1 mg/mL, while the boiled extracts and the boiled followed by enzymolysis extracts showed obvious cytotoxicity at the mass concentration of 0.4 mg/mL and 0.7 mg/mL, respectively. In addition to the obvious decrease in the number of HEK293 cells, the number of synapses increased and the refraction of HEK293 cells was poor after the intervention of Amanita manginiana extracts.ConclusionThe extracts of Amanita manginiana involved in this YNSUD case has obvious cytotoxicity, and some of its toxicity can be reduced by boiled and enzymolysis, but cannot be completely detoxicated. Therefore, the consumption of Amanita manginiana is potentially dangerous, and it may be one of the causes of the YNSUD.

The circulating severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variant presents an ongoing challenge for surveillance and detection. It is important to establish an assay for SARS-CoV-2 antibodies in vaccinated individuals. Numerous studies have demonstrated that binding antibodies (such as S-IgG and N-IgG) and neutralizing antibodies (Nabs) can be detected in vaccinated individuals. However, it is still unclear how to evaluate the consistency and correlation between binding antibodies and Nabs induced by inactivated SARS-CoV-2 vaccines. In this study, serum samples from humans, rhesus macaques, and hamsters immunized with inactivated SARS-CoV-2 vaccines were analyzed for S-IgG, N-IgG, and Nabs. The results showed that the titer and seroconversion rate of S-IgG were significantly higher than those of N-IgG. The correlation between S-IgG and Nabs was higher compared to that of N-IgG. Based on this analysis, we further investigated the titer thresholds of S-IgG and N-IgG in predicting the seroconversion of Nabs. According to the threshold, we can quickly determine the positive and negative effects of the SARS-CoV-2 variant neutralizing antibody in individuals. These findings suggest that the S-IgG antibody is a better supplement to and confirmation of SARS-CoV-2 vaccine immunization.

Background Diabetes mellitus is an important risk factor for the onset, recurrence, disability and lethality of ischemic stroke. Assessing the prevalence of diabetes in patients with ischemic stroke, and carrying out targeted comprehensive prevention and control can effectively improve the prognosis of patients. Objective To understand the current situation of ischemic stroke patients complicated with diabetes in Liaoning Province, and to provide a theoretical basis for targeted intervention. Methods From 2017 to 2018, a cross-sectional survey of ischemic stroke patients (≥40 years old) in 28 villages/communities in 6 counties and districts in Liaoning Province was conducted by a combination of stratified sampling, cluster sampling, and random sampling. Multivariate logistic regression was used to analyze the influencing factors of diabetes prevalence, awareness, treatment and control of ischemic stroke patients. Results The prevalence, awareness, treatment, and control rates of diabetes among ischemic stroke patients in Liaoning Province were 29.5% (289/980) , 63.3% (183/289) , 56.4% (163/289) , and 47.2% (77/163) , respectively. Multivariate logistic regression suggested that urban residence〔OR=1.818, 95%CI (1.317, 2.508) , P

Objective To explore a newly discovered T cell antigen [the group-specific antigen(Gag)of endogenous retrovirus (ERV)] associated with type 1 diabetes (T1D) and the pathogenesis of T1D. Methods First, to analyze the amino acid sequence of an islet-expressing Gag antigen, Gag 194 and identified one peptide[P193-P210(VSRLRGRRDPPAVDSTTS)], for production of Gag-specific monoclonal antibodies (mAbs). Second, ELISA and Western blot methods were performed to evaluate antigen specificity of the mAbs. Third, the expression of Gag antigen in pancreatic islets of T1D-susceptible non-obese diabetic (NOD) mice and T1D-resistant C57BL/6 mice was examined by immunohistochemical experiments. Results Five mAbs, namely 1F4C8,2D4C6,3C3B9,4D6B3 and 5F9E4 were obtained, and all of them were IgG2b subtype. Their antigen specificity and titer varied slightly. Three mAbs (1F4C8, 2D4C6 and 5F9E4) specifically recognize the ERV Gag antigen expressed in the pancreatic islets of NOD mice and at the age of 3 weeks, the antigen was detectable. Within the islets, the Gag antigen located near β-cells rather than the area infiltrated by lympho- cytes.In contrast, the T1D-resistant C57BL/6 mice do not express the Gag antigen as detected using the same mAb. Conclusions The expression of ERV Gag antigen in pancreatic islets of NOD mice occurs at very young age, suggesting that genetic factors of this diabetes-prone mouse strain may contribute to the expression.

Objective To explore epidemiological and clinical characteristics of corona virus disease 2019(COVID-19) in southern Liaoning Province aiming for its pathogenesis and providing evidence to support and optimize the diagnosis, treatment and prevention. Methods A retrospective analysis was performed by collecting the case information, case history and clinical indicators in 24 hours of admission including asymptomatic and mild/moderate type confirmed cases from February 2020 to January 2021 in southern Liaoning Province. The epidemiological characteristics were studied by descriptive analysis.The clinical characteristics of asymptomatic infection group and mild/moderate infection group were compared by t test, Mann-Whitney U test or pearson χ2 test. The differential indexes were included in the binary Logistic regression model for further analysis. Results In 218 cases of COVID-19, 59 were asymptomatic(27.06%) and 159 were mild/moderate(72.94%). The ratio of males to females was 0.79∶1.00. Among all the patients,155 cases(71.10%) aged 31-60 years old, 78 cases(35.78%) were workers and 212 cases(97.25%) were located in Dalian. There were significant differences in age, length of hospital stay, platelet(PLT), lactic dehydrogenase(LDH), total protein(TP), albumin (ALB), blood uric acid (BUA) and c-reactive protein (CRP) between the two groups. The logistic regression model showed that age, LDH and CRP were the risk factors of clinical symptoms after virus infection (P＜0.05). Conclusions In southern Liaoning Province most of COVID-19 cases are mild/moderate. The majority of patients come from Dalian and the main age distribution is 31-60 years old. In terms of clinical diagnosis and treatment, it is suggested that LDH and CRP should be examined as soon as possible for older risk population, that may support early prediction of the disease progress and take more effective prevention and control measures.

Abstract There is a gap in knowledge how maternal exposure to environmental tobacco smoke (ETS) is associated with offspring congenital heart defects (CHDs). In this case–control study, we collected data on 749 fetuses with CHDs and 880 fetuses without any congenital anomalies to examine the association of maternal ETS with fetal CHDs and the potentially moderating effect by maternal hazardous and noxious substances (HNS), periconceptional folate intake and paternal smoking. Maternal exposure to ETS in first trimester was associated with increased risk of CHDs in a dose–response gradient, with the AORs (95% CI) were1.38 (1.00–1.92), 1.60 (1.07–2.41), and 4.94 (2.43–10.05) for ETS

This study aimed to explore the mechanisms through which salvianolic acid B (Sal-B) exerts its effects during myocardial ischemia-reperfusion injury (MI/RI), aiming to demonstrate the potential pharmacological characteristics of Sal-B in the management of coronary heart disease. First, Sal-B-related targets and MI/RI-related genes were compiled from public databases. Subsequent functional enrichment analyses using the protein–protein interaction (PPI) network, gene ontology (GO), and the Kyoto Encyclopedia of Genes and Genomes (KEGG) predicted the core targets and approaches by which Sal-B counters MI/RI. Second, a Sal-B-treated MI/RI mouse model and oxygen–glucose deprivation/reoxygenation (OGD/R) H9C2 cell model were selected to verify the main targets of the network pharmacological prediction. An intersectional analysis between Sal-B and MI/RI targets identified 69 common targets, with a PPI network analysis highlighting caspase-3, c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (p38) as central targets. GO and KEGG enrichment analyses indicated remarkable enrichment of the apoptosis pathway among these targets, suggesting their utility in experimental studies in vivo. Experimental results demonstrated that Sal-B treatment not only mitigated myocardial infarction size following MI/RI injury in mice but also modulated the expression of key apoptotic regulators, including Bcl-2-Associated X (Bax), caspase-3, JNK, and p38, alongside enhancing the B-cell lymphoma-2 (Bcl-2) expression, thereby inhibiting myocardial tissue apoptosis. This study leveraged an integrative network pharmacology approach to predict Sal-B’s potential targets in MI/RI treatment and verified the involvement of key target proteins within the predicted signaling pathways through both in vivo and in vitro experiments, offering a comprehensive insight into Sal-B’s pharmacological mechanism in MI/RI management.

Recent studies have indicated that sequentially administering SARS-CoV-2 vaccines can result in increased antibody and cellular immune responses. In this study, we compared homologous and heterologous immunization strategies following two doses of inactivated vaccines in a mouse model. Our research demonstrates that heterologous sequential immunization resulted in more immune responses displayed in the lymph node germinal center, which induced a greater number of antibody-secreting cells (ASCs), resulting in enhanced humoral and cellular immune responses and increased cross-protection against five variant strains. In further single B-cell analysis, the above findings were supported by the presence of unique B-cell receptor (BCR) repertoires and diversity in CDR3 sequence profiles elicited by a heterologous booster immunization strategy.

Objective To investigate the expression of immune-related molecules and the infiltration of immune cells from mouse breast cancer stem cells (BCSCs). Methods Mouse BCSCs of 4T1 and 4T07 were enriched by spheroid culturing; the expression of immune checkpoint-and antigen presentation-associated genes in BCSCs was detected by RT-qPCR; the proportion of various types of immune cells in spleen or tumor tissue of orthotopic tumor model mouse was detected by flow cytometry. Results The mouse BCSCs 4T1 and 4T07 were successfully enriched by spheroid culturing; the expression of immune checkpoints-and antigen presentation-associated genes were significantly different as compared with the adherent cancer cells; the proportion of both CD4+ and CD8+ T cell increased. However, the proportion of macrophage (CD11b+/F480+) was decreased in tumors formed by spheroid cells as compared with that in the tumors formed by adherent cells. Conclusions The expression of immune checkpoint-and antigen presentation-associated genes in BCSCs were significantly different and the infiltration of T cells increased in tumors formed by BCSCs.

Objective To investigate the expression and clinical significance of chomobox homolog 7 (CBX7) in cervical cancer(CC)tissues. Methods Tissue samples of 71 patients with CC who were first diagnosed with CC and underwent cervical resection in the First Affiliated Hospital of Xinjiang Medical University from 2013 to 2020 were retrospectively collected. The expression of CBX7 was detected by immunohistochemistry(IHC). At the same time, data of clinical pathology from the patients were collected and survival analysis was conducted after following-up. Results CBX7 was highly expressed in 10 CC tissues, moderately low in 19 CC tissues, and negative in 42 CC tissues(P＜0.05). The expression of CBX7 was different and rlated to clinical stages, lymphatic metastasis and vascular invasion(P＜0.05). Compared with the negative and low CBX7 expression groups, the survival rate of CC patients with high CBX7 expression was significantly enhanced (P＜0.05)and the survival rate of patients with different CBX7 expression levels were significantly different (P＜0.05). Conclusions The negative expression of CBX7 protein in CC tissues may be associated with poor prognosis of CC patients.CBX7 expression in CC tissues is a potential prognostic fact of CC patients.

Abstract Microbial enhanced oil recovery (MEOR) technology is an environmental-friendly EOR method that utilizes the microorganisms and their metabolites to recover the crude oil from reservoirs. This study aims to research the potential application of strain SL in low permeability reservoirs. Strain SL is identified as Bacillus subtilis by molecular methods. Based on the mass spectrometry, the biosurfactant produced by strain SL is characterized as lipopeptide, and the molecular weight of surfactin is 1044, 1058, 1072, 1084 Da. Strain SL produces 1320 mg/L of biosurfactant with sucrose as the sole carbon source after 72 h. With the production of biosurfactant, the surface tension of cell-free broth considerably decreases to 25.65 ± 0.64 mN/m and the interfacial tension against crude oil reaches 0.95 ± 0.22 mN/m. The biosurfactant exhibits excellent emulsification with crude oil, kerosene, octane and hexadecane. In addition, the biosurfactant possesses splendid surface activity at pH 5.0–12.0 and NaCl concentration of 10.0% (w/v), even at high temperature of 120 °C. The fermentation solution of strain SL is applied in core flooding experiments under reservoir conditions and obtains additional 5.66% of crude oil. Hence, the presented strain has tremendous potential for enhancing the oil recovery from low-permeability reservoirs.

Abstract Ginkgo biloba L. is an ancient relict plant with rich pharmacological activity and nutritional value, and its main physiologically active components are flavonoids and terpene lactones. The bZIP gene family is one of the largest gene families in plants and regulates many processes including pathogen defense, secondary metabolism, stress response, seed maturation, and flower development. In this study, genome-wide distribution of the bZIP transcription factors was screened from G. biloba database in silico analysis. A total of 40 bZIP genes were identified in G. biloba and were divided into 10 subclasses. GbbZIP members in the same group share a similar gene structure, number of introns and exons, and motif distribution. Analysis of tissue expression pattern based on transcriptome indicated that GbbZIP08 and GbbZIP15 were most highly expressed in mature leaf. And the expression level of GbbZIP13 was high in all eight tissues. Correlation analysis and phylogenetic tree analysis suggested that GbbZIP08 and GbbZIP15 might be involved in the flavonoid biosynthesis. The transcriptional levels of 20 GbbZIP genes after SA, MeJA, and low temperature treatment were analyzed by qRT-PCR. The expression level of GbbZIP08 was significantly upregulated under 4°C. Protein–protein interaction network analysis indicated that GbbZIP09 might participate in seed germination by interacting with GbbZIP32. Based on transcriptome and degradome data, we found that 32 out of 117 miRNAs were annotated to 17 miRNA families. The results of this study may provide a theoretical foundation for the functional validation of GbbZIP genes in the future.

Objective To investigate the effects of sepsis and HIF-1α agonist or inhibitor on intestinal mucosal barrier(IBM) function. Methods SD rats were randomly divided into four groups with 6 in each as follows:sham operation group (sham), sepsis group treated with cecal ligation and perforation (CLP), (sepsis+HIF-1α agonist)/(sepsis+DMOG) group receiving intra-peritoneal injection of HIF-1α agonist DMOG (40 mg/kg) for 7 consecutive days before CLP, (sepsis+HIF-1α inhibitor)/(sepsis+BAY87-2243) group orally administered with HIF-1α inhibitor BAY87-2243(9 mg/kg) for 3 consecutive days before CLP. Plasma intestinal permeability markers of diamine oxidase (DAO), intestinal type fatty acid binding protein 2 (FABP2), D-lactic acid and fluorescein isothiocyanate-dextran (FD4) were detected by ELISA. Morphological changes of intestinal mucosa were detected by HE staining. HIF-1α and TJs protein expression were detected by Western blot. Results Sepsis caused pathological damage, increased permeability (P＜0.05), up-regulation of HIF-1α and down-regulation of tight junctions (TJs) expression in intestinal mucosa of rats with sepsis(P＜0.05); Addition of DMOG alleviated intestinal mucosal pathological damage and decreased intestinal mucosal per- meability (P＜0.05); While rats treated with BAY87-2243 showed the opposite result. Conclusions HIF-1α agonist can significantly reduce intestinal mucosal permeability in sepsis, and this effect is significantly counteracted by its inhibitor. It is suggested that HIF-1α upregulation may protect intestinal mucosa aganist sepsis.

Objective To investigate the effect of Bletila striata polysaccharide(BSP) on ulcerative colitis (UC) mice induced by dextran sodium sulfate (DSS) and its effect on tight junction occludin protein in intestinal mucosa. Methods Mice were randomly divided into control group, DSS model group (freely drinking 2.5% DSS solution for 7 days), salazosulfopyridine(300 mg/kg) positive control group, BSP low-dose (125 mg/kg) and high-dose groups (250 mg/kg). From the beginning of modeling, mice were given intragastric administration once a day for consecutive 7 days. The change of body weight, disease activity index (DAI) score, histopathology score and colon length were recorded to evaluate the inflammatory reaction. Expression of occludin protein in mice colon tissue was detected by Western blot. Results Compared with control group, the body weight of the model group mice was significantly reduced, the colon was shortened, the DAI and histopathology scores were significantly increased(P＜0.01), and the expression of occludin protein in colon tissue was significantly reduced (P＜0.01). Compared with DSS model group, BSP significantly alleviated body weight loss and colon shortening, and decrease DAI and histological scores, and up-regulated the expression of occludin protein in colon tissue of UC mice. Conclusions BSP alleviates inflammatory reactions of colonic mucosa in UC mice. The mechanism may be the improvement of intestinal epithelial barrier function mediated by increased expression of colonic mucosa occludin protein.

Objective To evaluate the necessity and effect of knowledge needed for research in the education of research-oriented medical graduates. Methods In March 2021, medical experts introduced the knowledge needed for the first-year medical graduates in Qinghai University Affiliated Hospital. Questionnaire survey was conducted to understand the current situation of graduates' understanding of the aim of training for the physician-scientists before the training and evaluate its necessity. The learning outcomes were evaluated by the comparison before and after the training. Results Only 55.16% of graduates understood the difference between traditional clinicians and physician-scientists before training, and 54.37% knew the difference between traditional clinical reasoning and clinical research logics, which indicated that it was very necessary to carry out teaching of knowledge as physician-scientists to medical graduates. After training, 95.78% of graduate students knew the difference between traditional clinicians and physician-scientists, and 86.75% of them knew the difference between traditional clinical reasoning and physician-scientists logics, which was significantly higher than that before training (P＜0.01). Conclusions Medical graduates have insufficient knowledge needed by physician-scientists. Training can significantly improve their understanding of physician-scientists.

Objective To investigate the effect of interleukin-22(IL-22) on intestinal epithelial barrier tight junction and its mechanism. Methods Human colon cancer HT29 cells were divided into control group, IL-22 group(100 ng/mL), FLLL32 group(pretreatment with FLLL32 before IL-22 intervention) and colivelin group(pretreatment with colivelin before IL-22 intervention). The transfection treatment groups included: shNC group, shNC+ IL-22 group(infection with negative control virus before IL-22 intervention), shSTAT3 group(infection with LV-STAT3-RNAi virus), and shSTAT3+ IL-22 group(LV-STAT3-RNAi virus infection before IL-22 intervention). Western blot and real-time PCR were used to detect the protein and mRNA expression of STAT3, p-STAT3 tight junction protein ZO-1, occludin, claudin-1 and claudin-2 in HT29 cells. Transmission electron microscopy(TEM) was used to observe the changes in the structure of tight junctions of HT29 cells. Results The protein and mRNA expression level of STAT3, p-STAT3, ZO-1, occludin, claudin-1 and claudin-2 in IL-22 group were significantly higher than those in the control group(P＜0.05) with more compact, tight junction. Compared with IL-22 group, protein and mRNA expression level of the above indexes in FLLL32 group were significantly decreased(P＜0.05), the tight junction was poor, the expression of colivelin group was up-regulated(P＜0.05), the tight junction was intact. The shNC+ IL-22 group significantly increased the expression of all tightly bound proteins and mRNA compared with the shNC group(P＜0.05), the tight junction structure was more dense, while the shSTAT3+ IL-22 group showed no significant difference in protein and mRNA expression level when compared with theose of shSTAT3 group. Conclusions STAT3 signaling pathway is involved in IL-22 to promote the expression of tight junction proteins ZO-1, occludin, claudin-1 and claudin-2 in HT29 cells.

Abstract The indica ecotypes, IR64, an elite drought-susceptible variety adapted to irrigated ecosystem, and Apo (IR55423-01 or NSIC RC9), a moderate drought-tolerant upland genotype together with their hybrid (IR64 × Apo) were exposed to non- and water-stress conditions. By sequencing (RNA-seq) these genotypes, we were able to map genes diverging in cis and/or trans factors. Under non-stress condition, cis dominantly explains (11.2%) regulatory differences, followed by trans (8.9%). Further analysis showed that water-limiting condition largely affects trans and cis + trans factors. On the molecular level, cis and/or trans regulatory divergence explains their genotypic differences and differential drought response. Between the two parental genotypes, Apo appears to exhibit more photosynthetic efficiency even under water-limiting condition and is ascribed to trans. Statistical analyses showed that regulatory divergence is significantly influenced by environmental conditions. Likewise, the mode of parental expression inheritance which drives heterosis (HET) is significantly affected by environmental conditions indicating the malleability of heterosis to external factors. Further analysis revealed that the HET class, dominance, was significantly enriched under water-stress condition. We also identified allelic imbalance switching in which several genes prefer IR64- (or Apo-) specific allele under non-stress condition but switched to Apo- (or IR64-) specific allele when exposed to water-stress condition.

Objective To study whether salvianolic acid B(SAB) can reduce lipopolysaccharide(LPS)-induced acute lung injury. Methods Fourty-eight mice were randomly divided into control group, model group (intratracheal instillation of LPS), SAB low/medium/high dose intervention group, and sulforaphane positive control group. The lung wet / dry weight ratio (W/D) was recorded; The protein concentration of alveolar lavage fluid (BALF) was detected; Lung tissue pathological damage was evaluated by HE staining and microoscopy; TNF-α,IL-1β and IL-6 in BALF were detected by ELISA.Western blot was used to detect the protein expression of Nrf2, NQO1, HO1, Keap1,NF-κB and p-NF-κB in lung tissue. Results Compared with the control group, pathological changes were observed in the lung tissue of the model group, W/D, protein concentration in BALF and inflammatory cytokine content were significantly increased (P＜0.05). Compared with the model group, SAB intervention group had significant changes (P＜0.05) that alleviated the oxidative stress induced by LPS, increased the expression of Keap1(P＜0.01), increased the expression of Nrf2, NQO1 and HO1 (P＜0.01), and inhibited the activation of NF-κB and p-NF-κB induced by LPS. Conclusions SAB can alleviate LPS-induced acute lung injury of mice.

Abstract Strong electromagnetic coupling among plasmonic nanostructures paves a new route toward efficient manipulation of photons. Particularly, plasmon-waveguide systems exhibit remarkable optical properties by simply tailoring the interaction among elementary elements. In this paper, we propose and demonstrate a freestanding bilayer plasmonic-waveguide structure exhibiting an extremely narrow transmission peak with efficiency up to 92%, the linewidth of only 0.14 nm and an excellent out of band rejection. The unexpected optical behavior considering metal loss is consistent with that of electromagnetic induced transparency, arising from the destructive interference of super-radiative nanowire dipolar mode and transversal magnetic waveguide mode. Furthermore, for slow light application, the designed plasmonic-waveguide structure has a high group index of approximately 1.2 × 105 at the maximum of the transmission band. In sensing application, its lowest sensing figure of merit is achieved up to 8500 due to the ultra-narrow linewidth of the transmission band. This work provides a valuable photonics design for developing high performance nano-photonic devices.

AbstractObjective To illustrate the effect of corticosteroids and heparin, respectively, on coronavirus disease 2019 (COVID-19) patients’ CD8+ T cells and D-dimer.Methods In this retrospective cohort study involving 866 participants diagnosed with COVID-19, patients were grouped by severity. Generalized additive models were established to explore the time-course association of representative parameters of coagulation, inflammation and immunity. Segmented regression was performed to examine the influence of corticosteroids and heparin upon CD8+ T cell and D-dimer, respectively.Results There were 541 moderate, 169 severe and 156 critically ill patients involved in the study. Synchronous changes of levels of NLR, D-dimer and CD8+ T cell in critically ill patients were observed. Administration of methylprednisolone before 14 DFS compared with those after 14 DFS (β = 0.154%, 95% CI=(0, 0.302), p=.048) or a dose lower than 40 mg per day compared with those equals to 40 mg per day (β = 0.163%, 95% CI=(0.027, 0.295), p=.020) significantly increased the rising rate of CD8+ T cell in 14–56 DFS.Conclusions The parameters of coagulation, inflammation and immunity were longitudinally correlated, and an early low-dose corticosteroid treatment accelerated the regaining of CD8+ T cell to help battle against SARS-Cov-2 in critical cases of COVID-19.

Objective To explore clinical and genetic manifestation of pheochromocytoma patients with RET gene mutation. Methods Clinical data, laboratory examination results and RET gene mutations of 23 pheochromocytoma patients with RET mutation treated in Peking Union Medical College Hospital from 2013 to 2019 were retrospectively analyzed. Results The diagnosis age of pheochromocytoma in 23 patients was 32±10 years. In 22 patients with multiple endocrine neoplasia (MEN) 2A, mutations were clustered in exon 16 (18 cases), especially in codon 634 (16 cases), followed by exon 10 and 14, and one patient with MEN2B had M918T in exon 16. Among the 23 patients, 9 had paroxysmal hypertension, 5 had sustained hypertension, 3 were normotensive, and 6 had episodic palpitations but their blood pressures were not measured during the attacks. 24 h urinary catecholamine excretion was as following: norepinephrine (NE): 65.8 (36.9,235.9) μg/24 h, Epinephrine (E): 5.4 (2.8, 37.2) μg/24 h and Dopamine (DA): 277 (198, 297) μg/24 h. 15 patients had abnormally increased NE, E or DA, while 8 patients had normal catecholamine excretion. The median diameter of the tumors was 4 (3, 6) cm. Fifteen patients had bilateral pheochromocytoma and 17 had medullary thyroid carcinoma. Conclusions Pheochromocytoma patients with RET mutation are consistent with those reported in western countries in terms of age at diagnosis, tumor size and mutation profile. Most patients have paroxysmal hypertension or normal pressure, and some of them have normal urinary catecholamine excretion, which are potential risk factors of missed diagnosis.

Pregnancy-induced hypertension, especially preeclampsia (PE), is one of the leading causes of increased maternal and perinatal morbidity and mortality worldwide. And the circulating cell free fetal nucleic acid (cff-DNA) analysis of pregnant women can be used as an early prediction of the occurrence and development of PE. By summarizing and analyzing the correlation between cff-DNA and PE and its possible mechanism, this paper further explained that the occurrence of PE may be related to DNA methylation, and discussed its limitations as a biomarker, so as to provide reference for the effective prediction of preeclampsia.

Objective To compare the clinical outcomes of high tibial closed osteotomy and open osteotomy, as well as the changes in posterior tibia slope and patellar height. Methods A total of 120 patients (155 knees) with high tibial osteotomy performed from January 2017 to June 2018 were collected. Twenty cases (25 knees) used lateral tibial closed wedge osteotomy (LCWHTO), and 100 cases (130 knees) used medial tibial open wedge osteotomy (MOWHTO). The follow-up time was 20.7 months and 18.9 months respectively. Lysholm score and joint mobility (ROM) were evaluated at the last follow-up. The changes of mechanical axis deviation (MAD), proximal medial tibial angle (MPTA), posterior tibia slope(PTS) and M-K index were compared between the two groups of patients. Results In the LCWHTO group, the M-K index was 0.79±0.07 after operation and 0.78±0.08 after operation. There was no change before and after operation 0.78±0.05 before MOWHTO operation was significantly higher than 0.75±0.05 after operation (P＜0.05). The postoperative PTS in the LCWHTO group was 8.1°±3.4°, which was significantly lower than the preoperative 10.8°±3.0° (P＜0.05); the postoperative PTS in the MOWHTO group was 10.9°±4.0°, and 10.2°±3.1° before operation. No change before and after operation. Conclusions Both LCWHTO and MOWHTO can obtain satisfactory clinical outcomes. LCWHTO reduces PTS and has no effect on the patellar height. MOWHTO has no effect on PTS, but it reduces the patellar height. The choice of osteotomy should be individualized according to the characteristics of the patients.

Objective To observe the preventive effect of metoclopramide tablets on opioid-induced nausea and vomiting(OINV)caused by oxycodone sustained-release tablets during the treatment of cancer pain. Methods The method of prospective observation was used by collecting 120 patients with malignant tumors who were treated with oxycodone sustained-release tablets for the first time. According to the NRS scores, the patients were divided into two groups: moderate pain (4-6 points) and severe pain (7-10 points). The patients were treated with oxycodone sustained-release tablets with an initial dose of 10 mg and 20 mg q12 h respectively, and then titrated according to the pain control. The patients were divided into observation group (n=60) and control group (n=60) by using the method of random number table. The observation group received oral oxycodone sustained release tablets and metoclopramide tablets of 10 mg tid for preventive treatment, and ondansetron tablets of 8 mg antiemetics when OINV reaching degree Ⅱ. The control group did not receive preventive antiemetic treatment until OINV reached grade Ⅱ when metoclopramide tablet of 10 mg tid for antiemetic treatment was added. If the symptoms did not relieve, ondansetron tablets of 8 mg for intensive treatment would be added. The differences between the incidence of adverse reactions such as OINV, constipation, urinary retention, drowsiness, respiratory depression, QOL score, and NRS score were compared between the two groups after the observation period of 14 days. Results The incidence of OINV of the observation group was significantly lower than that of the control group (P＜0.05) on days 1, 2, 3, and 7. There was no significant difference in the prescription frequence of ondansetron between the two groups (10.0% vs 15.0%).The incidence of constipation in the observation group was significantly lower than in the control group (45.0% vs 65.0%)(P＜0.05). There was no significant difference in NRS scores on day 14 between the observation group and the control group. The QOL scores of the observation group were significantly higher than those of the control group (P＜0.05) on days 1, 2, 3, and 14. There was no significant difference in the incidence of other adverse events between the two groups. Conclusions The preventive application of metoclopramide tablets in the treatment of cancer pain can effectively reduce the early incidence of OINV and the constipation without affecting the analgesic effect of oxycodone sustained-release tablets or producing other adverse events which can effectively improve the life quality of the patients.

Objective To explore the protective effect of oral glycerol on sepsis induced intestinal mucosal barrier function. Methods Mice were randomly divided to four groups: sham operation (n=6); sham operation with oral glycerol (n=6); Mouse sepsis model (n=30)was established using cecal ligation and puncture (CLP), of which 24 mice were executed at 0, 6, 12 and 24 h after CLP respectively (6 mice at each time point) as a time-dependent group,and sepsis with oral glycerol group (n=6). Besides the time-dependent group, four groups of mice were executed at 24 h after modeling. Blood and intestinal mucosal tissue samples were collected. HE staining was used to detect pathological damage of intestinal mucosa. The plasma diamine oxidase (DAO) concentration and intestinal- type fatty acid-binding protein 2(FABP2) concentration were measured by ELISA to assess intestinal mucosal permeability. Immunohistochemistry, real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and Western blot were used to detect the expression of AQP3 in intestinal mucosa. Results Sepsis induced morphological damage of intestinal mucosa, and the ChiÚs score increased in a time-dependent manner (P＜0.05). The concentrations of DAO and FABP2 in plasma were significantly increased (P＜0.05), and the expression of AQP3 significantly down-regulated with the aggravation of injury (P＜0.05). The administration of oral glycerol partially improved the sepsis-induced injury of the intestinal mucosa, as shown by partial recovery of the morphological structure, with decreased ChiÚs score, decreased plasma concentrations of DAO and FABP2 (sepsis vs sepsis+glycerol, P＜0.05). Conclusions Oral treatment with glycerol may alleviate intestinal mucosal barrier damage in sepsis mice through aquaporin-3. The specific mechanism needs to be further studied.

Calcium sensing receptor (CaSR) is a member of the G protein-coupled receptor C family.It is widely expressed in different tissue cells in the body and functions in various pathophysiological processes of the body. CaSR can participate in the development of atherosclerosis by regulating vascular endothelial cell injury,inflammatory response,proliferation and migration of vascular smooth muscle cells and vascular calcification.

BackgroundThe incineration and burying of the soiled bedding of laboratory animals, as well as using detergents to treat their feces, is hazardous to the environment. This highlights the need for an alternative, environmentally friendly solution for the treatment of the waste of laboratory animal facilities. This study aims to evaluate the efficacy of ozone disinfection of the soiled bedding and feces of laboratory animals.MethodsTwo grams of soiled beddings were randomly sampled from the cages of mice and rats. These samples were mixed in a beaker with 40ml saline. Ozone was piped into the beaker at a concentration of 500mg/h. Samples were taken from the beaker at time 0min, 30min, 45min and 60min after ozone treatment for microbiological culturing in an incubator for 48h. Colony form unit of each plate (CFU/plate) at each time point were counted, the mean CFU/plate at each time point after ozone treatment were compared with that present at time zero. Feces of rabbits and dogs were treated and pathogens were counted the similar way as that of bedding of the mice and rats; samples being taken at 0min, 15min, 30min, 45min and 60min.ResultsPathogens were observed in beddings of both mice and rats as well as in feces of rabbits and dogs. Ozone treatment for 30min killed more than 93% of pathogens in the bedding of the two rodent species and 60min of treatment killed over 99% of pathogens. Treatment of rabbit and dog feces for 30min killed over 96% pathogens present, and 60min's treatment killed nearly all the pathogens. Both Gram positive and Gram negative pathogens were sensitive to ozone treatment.ConclusionOzone treatment of bedding and feces is an effective and environment friendly way to deal with the waste of animal facilities, saving energy and potentially enabling their reuse as fertilizer.