Eye tracking technique is an examination method to record eye movements and gaze position over time and task,common eye movement parameters include sweep,smooth pursuit,gaze,and visual search.Neurodegenerative diseases such as Alzheimer disease,AD,fronto temporal dementia(FTD),dementia with Lewy bodies(DLB),Parkinson disease,PD,multi-system atrophy(MSA),progressive supranuclear palsy(PSP),motor neuron disease(MND)and corticobasal degeneration(CBD),etc.,have different degrees and manifestations of abnormalities in the above eye movement parameters.For example,there are different degrees of prolonged sweep latency and increased sweep error rate among different diseases.Eye movement tracking technology is of great value in the early identification,diagnosis and auxiliary differential diagnosis of cognitive dysfunction in various neurodegenerative diseases,and is a new method that is non-invasive,convenient,objective and accurate.

AIM:To investigate the activation of Cl-channels by sodium taurocholate(NaTC)in mouse pan-creatic acinar cells.METHODS:The single isolated pancreatic acinar cells from FVB/N mice were prepared using colla-genase digestion method.Whole-cell patch clamp technique was performed to record the currents.Intracellular adenosine triphosphate(ATP)dependence of the channels was examined via eliminating ATP from the pipette solution.Anion per-meability of the channels was investigated with ion-exchange method.The pharmacological characteristics of the channels was confirmed by two Cl-channel blockers.The volume sensitivity of the channels was detected using 47%hypertonic bathing solution.Extracellular Ca2+dependence of activating the channels was examined through eliminating Ca2+from the bathing solution.Intracellular reactive oxygen species(ROS)level was detected by an oxidation-sensitive fluorescent probe,2',7'-dichlorofluorescin diacetate.The experiment was repeated 6 times in each group.RESULTS:Extracellular application of 5 mmol/L sodium taurocholate induced a Cl-current,exhibiting the properties of outward-rectification,a se-lectivity sequence of I->Br-≥Cl->gluconate-and intracellularATP dependence(P<0.01).The currents were inhibited by chloride channel blocker 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid disodium salt hydrate(DIDS)and tamoxifen and by 47%hypertonicity stimulation(P<0.01).When ROS production was scavenged by N-acetyl-L-cysteine,the sodi-um taurocholate-induced Cl-currents were unaffected.The effect of sodium taurocholate on ROS production did not alter with the treatment with DIDS.Sodium taurocholate failed to induce Cl-currents when Ca2+was absent in extracellular bath-ing solution(P>0.05).CONCLUSION:Sodium taurocholate activates Cl-channels in mouse pancreatic acinar cells,which is dependent on extracellular Ca2+but not ROS pathway.

Objective:To analyze the proportion of patients with acute primary angle-closure glaucoma (PACG) after the outbreak of coronavirus disease 2019 (COVID-19) in patients undergoing glaucoma surgery and the factors influencing morbidity.Methods:A cross-sectional study was performed.The cluster sampling method was used to collect 141 glaucoma patients hospitalized for glaucoma surgery after the outbreak of COVID-19 in Xuzhou First People's Hospital from December 16, 2022, to January 16, 2023, and 231 glaucoma patients hospitalized for surgery in the same 1-month period from 2019 to 2020, 2020 to 2021, 2021 to 2022 through the hospital information system.Ninety-two eyes of 92 patients with acute PACG after the outbreak were selected as a study group, and 21 eyes of 21 patients with acute PACG hospitalized during the same 1-month period from 2021 to 2022 were selected as a control group.The proportion of patients with different types of glaucoma during the observation period was analyzed.The proportion of patients with acute PACG and the clinical characteristics of acute PACG were analyzed, including age, sex, visual acuity, intraocular pressure (IOP), and anterior chamber angle status.Epidemiological data such as the use of anti-cold medications, and changes in living habits and moods (including daily water intake and anxiety) of patients after COVID-19 infection were obtained by telephone follow-up.Anxiety levels of patients in the study group were assessed using the Hospital Depression and Anxiety Scale (HADS).The triggering factors of acute PACG attack after the COVID-19 outbreak were analyzed.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Xuzhou First People's Hospital (No.xyyll[2023]114).Written informed consent was obtained from each subject.Results:The proportion of acute PACG patients in Xuzhou First People's Hospital within one month after the outbreak in 2022 to 2023 increased significantly compared with the same period in 2021 to 2022, 2020 to 2021 and 2019 to 2020, and the differences were statistically significant ( χ2=31.066, 33.331, 20.804; all at P<0.001).There was no statistical significance in the distribution of the number of eyes with different grades of visual acuity, IOP, the number of eyes with IOP ≥30 mmHg (1 mmHg=0.133 kPa), and the distribution of the number of eyes with different anterior chamber angles between the two groups (all at P>0.05).Patients in the control group had no history of COVID-19 infection or use of cold medicines at disease onset.During disease onset, all 92 (100%) patients in the study group had positive COVID-19 nucleic acid test results, of which 57 (61.96%) patients had a history of oral anti-cold medication use.During the same period, 49 (100%) hospitalized patients with other types of glaucoma had positive COVID-19 nucleic acid test results, of which 20 (40.82%) patients had a history of oral cold medication.There was a statistically significant difference in the proportion of patients taking oral cold drugs between acute PACG and other types of glaucoma in the study group ( χ2=5.764, P=0.016).During the outbreak of COVID-19, the study group reported that the daily water intake had increased to varying degrees than before.In the study group, 76 patients had anxiety, accounting for 82.6%.Multiple linear regression analysis showed that IOP=19.052+ 0.009×daily water intake+ 0.858×HADS score ( R2=0.780), and the standardized coefficients of daily water intake and HADS score were 0.542 and 0.452, respectively.Daily water intake had a greater effect on IOP than HADS score. Conclusions:The proportion of acute PACG patients among hospitalized surgical glaucoma patients increased significantly after the COVID-19 outbreak, which is related to risk factors such as oral anti-cold medications containing vasoconstrictors or antihistamines, increased daily water intake, anxiety and other lifestyle, and mood changes.

Kirsten rat sarcoma viral oncogene homolog(KRAS)gene is one of the most commonly mutated oncogenes.It has been found that KRAS inhibitors have the potential therapeutic effect on cancer patients with this gene mutation.In this study,machine learning was applied to develop a QSAR(quantitative structure-activity relationship)model for KRAS small molecule inhibitors.A total of 1857data points of IC50 and SMILES(simplified molecular input line entry system)for KRAS inhibitors were collected from three databases:ChEMBL,BindingDB,and PubChem.And nine different classifiers were constructed using three different feature screening methods combined with three machine learning models,namely,random forest,support vector machine,and extreme gradient boosting machine.The results showed that the SVM model combined with mutual information feature selection exhibited the best performance:AUCtest=0.912,ACCtest=0.859,F1test=0.890.Moreover,it also demonstrated good predictive performance on the external validation set(AUCExt=0.944,RecallExt=0.856,FPRExt=0.111).This study provides a new technical route for KRAS inhibitor screening in natural product databases using artificial intelligence methods.

To retrieve, evaluate, and integrate evidence related to the operational procedures of ambulatory blood pressure monitoring (ABPM) in adults, aiming to enhance the accuracy and effectiveness of ambulatory blood pressure monitoring.

[摘 要] 目的：检测食管鳞状细胞癌（ESCC）患者血清中高迁移率族蛋白B1（HMGB1）和吲哚胺-2，3-双加氧酶（IDO）的表达水平并探讨两者与临床病理特征及淋巴细胞亚群的相关性。方法：选取2021年3月至2022年8月在河北医科大学第四医院初次住院治疗的95例ESCC患者作为ESCC组，另选取40例健康体检人群作为对照组。ELISA法检测全部研究对象的血清HMGB1和IDO水平及不同组ESCC细胞培养上清中HMGB1、IDO和p65水平，流式细胞术检测全部研究对象外周血淋巴细胞亚群水平。WB法检测仅敲低HMGB1基因表达或敲低HMGB1后再加入NF-κB信号通路激活剂对ESCC细胞HMGB1、IDO和p65表达的影响。结果：ESCC组患者血清HMGB1和IDO水平明显高于对照组（均P<0.01）；血清HMGB1和IDO表达水平升高是ESCC临床进展的独立危险因素（均P<0.01），二者联合检测对ESCC临床进展预测价值更高（P<0.01）；血清HMGB1和IDO与ESCC患者的T分期、N分期和临床分期有明显关联（均P<0.05）； ESCC组患者血清HMGB1与外周血CD3+ T细胞、CD4+ T细胞、B细胞和NK细胞绝对计数值呈显著负相关，而与Treg细胞百分率呈显著正相关（均P<0.05），血清IDO与外周血CD3+ T细胞百分率和绝对计数值、CD4+ T细胞百分率和绝对计数值、CD8+ T细胞和B细胞绝对计数值呈显著负相关，而与Treg细胞百分率呈显著正相关（均P<0.05）；血清HMGB1和IDO表达水平呈显著正相关（P<0.01）。si-HMGB1组KYSE30和ECA109细胞及其培养上清液中IDO和p65表达水平明显低于si-NC组和si-HMGB1+PMA组（均P<0.05）。结论：血清HMGB1和IDO与ESCC临床进展和机体免疫功能密切相关，具有成为ESCC肿瘤标志物和免疫治疗新靶点的潜力。HMGB1可能通过NF-κB信号通路促进IDO表达，进行双靶点联合治疗可能会取得更好的疗效。

Helicobacter pylori (Hp) is one of most common pathogens causing gastrointestinal disorder including gastric ulcer, duodenal ulcer and gastric cancer, etc. It has been verified as class I carcinogen by WHO. Nowadays, combination antibiotics and proton pump inhibitor are mainly used to erase Hp in clinical application. However, with the increased resistance of Hp, the vaccine against Hp might become the best strategy to eradicate Hp. Elements including urease, virulence factor, outer membrane protein, flagella, play an important role in Hp infection, colonization and reproduction. They have become potential candidate antigens in the development of Hp vaccine, as reported in previous studies. Presently, these antigens-centric vaccines have been tested in animal models. Therefore, this article reviews the studies on Hp vaccine with urease, virulence genes, outer membrane protein and flagella as their candidate antigens, in an attempt to provide insights for research in this regard.
Animals ; Helicobacter pylori ; Urease/genetics* ; Helicobacter Infections/prevention & control* ; Vaccines ; Membrane Proteins

【Objective】 To analyze the causes of a case of hemolytic disease of the fetus and newborn (HDFN),and investigate the genetic background of maternal Rh deletion D--formation. 【Methods】 Blood samples of maternal and fetus were collected, and ABO blood typing, Rh blood typing, antibody screening and identification test were performed to explore the blood group serological characteristics of Rh deletion type D--, and Rh gene sequence was performed on parturient. 【Results】 The maternal blood group was identified to be O type, D--, and the anti-Hr0 antibody against Rh high-frequency antigen was suspected to be caused by multiple pregnancies which passes through the placental barrier and enable fetus to obtain anti Hr0 antibody, leading to HDFN, with genetic testing result as RH RHCE* Ce/RHCE* Ce. 【Conclusion】 In-depth research on the formation mechanism of Rh D-- in parturient should be conducted to provide clinical value for HDFN blood exchange treatment and blood transfusion in special blood group population.

【Objective】 To develop a quick and accurate crossmatching test technology without the power equipment and additional reagents before blood transfusion, so as to improve the timeliness and safety of blood transfusion treatment in sudden situations as war or natural disasters. 【Methods】 The irregular antibodies quickly promote coagulants (QPC) were used as the reaction medium reagent. The 200 μL QPC were wrapped in the bursts bead and preset within different recess of the detection tubes. The bursts beads were squeezed with the reagent left in the well, then the blood samples were dropped in the main(recipient plasma: 200 μL, donor 3%—5% RBC: 100 μL) and secondary(donor plasma: 200 μL, recipient 3%—5% RBC: 100 μL)reaction grooves. The result interpretated by hand wrestling or 1 500 g centrifugation of 15 seconds. Meanwhile, the comparing experiments with the prior methods were implemented to evaluate the method’s reliability. 【Results】 The results of the bursting reagent, being stored at 37℃ for one week, were consistent with those of the freshly prepared cross-matching reagent, indicating that the bursting reagent was practical in the field and had good stability at normal temperature. No statistical difference between the sensitivity and the results of the microcolumn gel method was noticed by paired data t test (P>0.05). The parallel cross matching tests of 50 clinical samples were performed by microcolumn gel method and coagulant-bursting technique; the Kappa value was 0.973 2, and irregular antibodies were detected in 2 cases, with concordance rate at 100%, showing good consistency. 【Conclusion】 The improved method is simple and fast, and also safe and reliable for compatibility testing before blood transfusion, which is especially suitable for the field rescue of the wounded in wartime and sudden natural disasters, and is worthy of popularization.

Objective:To investigate the effect of astragaloside Ⅳ on the apoptosis of thyroid cells in Hashimoto's thyroiditis(HT)rats and Ras homolog gene family member A(RhoA)/Rho-associated coiled-coil containing kinase 2(ROCK2)pathway.Methods:The HT rat model was induced by subcutaneous injection of thyroglobulin combined with high iodine drinking water and randomly divided into model group,astragaloside(80 mg/kg)group,Rhosin(RhoA inhibitor,40 mg/kg)group,astragaloside Ⅳ(80 mg/kg)+ Rhosin(40 mg/kg)group(12 rats in each group),another 12 SD rats were selected and drank water normally and injected the same dose of saline subcutaneously as control group.After the drugs were grouped and processed,the serum anti-thyroglobulin antibody(TGAb),anti-thyroid peroxidase antibody(TPOAb)levels and the inflammatory factors IL-6,IL-17,IL-1β contents were measured by ELISA kits;the pathological changes of thyroid tissue in each group were detected by hematoxylin-eosin(HE)staining;the apopto-sis rate of rat thyroid cells in each group were detected by TUNEL staining;the expressions of RhoA/ROCK2 pathway proteins in thy-roid tissues of rats in each group were detected by Western blot.Results:Compared with the control group,the thyroid follicles in the model group had abnormal structure,some atrophy or disappearance,disordered arrangement,surrounding inflammatory cell infiltra-tion,and obvious pathological damage to the thyroid tissue,the serum TGAb,TPOAb,IL-6,IL-17 and IL-1β levels,thyroid cell apoptosis rate,and thyroid tissue RhoA and ROCK2 protein expression levels were significantly increased(P<0.05);compared with model group,the pathological damage of the thyroid tissue of rats in the drug intervention group were reduced,the serum TGAb,TPOAb,IL-6,IL-17 and IL-1β levels,thyroid cell apoptosis rate,and thyroid tissue RhoA and ROCK2 protein expression levels were decreased(P<0.05);compared with astragaloside Ⅳ group and the Rhosin group respectively,the pathological damage of the thyroid tissue of rats in the astragaloside Ⅳ+Rhosin group were further reduced,the serum TGAb,TPOAb,IL-6,IL-17 and IL-1β levels,thyroid cell apoptosis rate,thyroid tissue RhoA and ROCK2 protein expression levels were decreased(P<0.05).Conclusion:Astragaloside Ⅳ may down-regulate the expression of RhoA/ROCK2 pathway to reduce the inflammatory injury of thyroid tissue,inhib-it thyroid cell apoptosis,and improve the symptoms of HT in rats.