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.

Spontaneous abortion is one of the most common complications of pregnancy， and two or more spontaneous abortions in a row are defined as recurrent spontaneous abortion （RSA）， of which about half of patients have unknown etiology. However， the pathogenesis of unexplained RSA （URSA） has not been elucidated， and the lack of effective treatment has made it one of the key and difficult points in the field of obstetrics and gynecology. This article conducts a literature review of recent research on URSA and finds that the pathogenesis of URSA is related to the imbalance of immune tolerance at the maternal-fetal interface， apoptosis of trophoblast cells， inhibition of angiogenesis， and activation of immune responses. Immunotherapy （including cell therapy， cytokine therapy， and immunosuppressive intervention）， hormone drugs， anticoagulant regimens， and traditional Chinese medicine therapies are commonly used in clinical practice to intervene in URSA， but the safety and effectiveness of some therapies are still controversial.

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.

Type 2 diabetes mellitus(T2DM)can lead to changes in brain structure and function,increasing the risk of cognitive impairment and dementia.The mechanism may be related to insulin resistance(IR),impaired insulin signal transduction,and cerebral vascular disease.Glucagon-like peptide 1 receptor agonists(GLP-1RAs)are a class of new drugs in treating T2DM,which can lower blood glucose,delay gastric emptying,and increase satiety,thereby reduce body weight.In recent years,more and more researchers have conducted animal experiments and clinical trials to explore the effects of GLP-1RAs,especially Liraglutide and Exenatide,on cognitive function in patients with T2DM and related mechanisms.This review summarizes the effects of GLP-1RAs on cognitive function in patients with T2DM and their possible mechanisms.

Objective:To investigate the curative effect of endoscopic cyclophotocoagulation combined with trabeculectomy for primary open angle glaucoma.Methods:From January 2020 to May 2021, 30 eyes of 30 patients with advanced primary open angle glaucoma with cataract who underwent endoscopic cyclophotocoagulation combined with trabeculectomy in the Municipal Hospital Affiliated to Xuzhou Medical University were retrospectively analyzed. The preoperative best corrected visual acuity, preoperative intraocular pressure (IOP) and numbers of anti-glaucoma medication were recorded. IOP, numbers of anti-glaucoma medication at 1 day, 3 months, 6 months and 1 year after operation, postoperative complications, the numbers of absolute success and qualified success were recorded.Results:All cases were followed up for 1 year. The best corrected visual acuity improved by more than one line in 26 eyes at 1 year after operation. Preoperative visual acuity was maintained in 3 eyes visual acuity decreased in 1 eye. The IOP and numbers of anti-glaucoma medication at 1 day, 3 months, 6 months and 1 year after operation were significantly different from those before operation ( P<0.01). At 1 year after operation, 8 patients were qualified successful and 17 patients were absolutely successful. Early hyphema in 30 eyes, transient ocular hypertension in 3 eyes ciliary body detachment in 0 eyes, corneal edema in 9 eyes, and anterior chamber exudation in 8 eyes. Conclusions:In this small sample size of study with follow-up for 12 months, the results showed that endoscopic cyclophotocoagulation combined with trabeculectomy in the treatment of advanced open angle glaucoma has good preliminary efficacy and safety. However, a large sample of cases is still needed to further study its long-term safety and efficacy.

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.

Background Aluminum (Al) can cause irreversible damage to neurons and synapses function, and the mechanism may be connected to mitochondrial damage caused by glycogen synthase kinase-3β (GSK-3β) regulating dynamin-related protein 1 (DRP1), resulting in inhibition of the growth of neuronal protrusions. Objective To investigate the role of GSK-3β regulating DRP1 in the inhibition of primary hippocampal neurite growth induced by Al. Methods Neurons were extracted from the hippocampus of newborn mice (≤24 h old) for primary culture. On day 6, the purity of neurons was detected by immunofluorescence. On day 10, neurons with good growth state were selected for Al exposure and GSK-3β inhibitor SB216763 (SB) intervention. The experiment design included a blank control group, a dimethyl sulfoxide (DMSO) group, an Al (20 μmol·L⁻¹) group, a SB (1 μmol·L⁻¹) group, and a SB (1 μmol·L⁻¹) + Al (20 μmol·L⁻¹) group. After primary hippocampal neurons were treated with Al or SB for 48 h, cell viability was detected by CCK-8 assay, the mitochondrial morphology of primary hippocampal neurons was observed by transmission electron microscopy, the total protrusion length of primary hippocampal neurons was scanned and analyzed by laser confocal imaging, and their complexity was analyzed by Sholl analysis. The expression levels of phospho-GSK-3β, GSK-3β, and DRP1 were detected by Western blotting. Results The immunofluorescent results showed that the purity of primary neurons was higher than 90%. After the Al exposure and the SB intervention for 48 h, compared with the blank control group, there was no obvious difference in cell viability in the DMSO group and the SB group (P>0.05), and the Al group showed reduced cell viability (P=0.006); there was no obvious difference in cell viability between the SB+Al group and the Al group (P>0.05). Compared with the blank control group, there was no obvious difference in the average total length of protrusion in the DMSO group and the SB group (P>0.05), and the Al group showed reduced average total length of neurite (P<0.001); the average total neurite length in the SB+Al group was significantly increased compared with that in the Al group (P=0.001). The results of Sholl analysis revealed that, within 130 μm from the cytosol, the number of intersections of neurons in each group increased with the increase of distance. Above 130 μm from the cytosol, the number of intersections of neurons in each group decreased gradually with increase of distance. At 130 μm and 310 μm from the cytosol, compared with the blank control group, the number of neuronal intersections in the DMSO group and the SB group had no obvious difference (P>0.05), and that in the Al group was significantly reduced (P<0.05); there was no obvious difference in the number of neuronal intersections between the SB+Al group and the Al group (P>0.05). The mitochondrial structure of the blank control group was complete and the crest was clearly visible; there was no apparent variation in the mitochondrial structure in the DMSO group and the SB group; the mitochondria in the Al group were vacuolated and the crista disappeared; the SB+Al group showed clearer crista than the Al group. The difference in GSK-3β phosphorylation level among groups was statistically significant (F=45.841, P<0.001). Compared with the blank control group, the GSK-3β phosphorylation level showed not significantly different in the DMSO group (P>0.05), increased in the SB group (P=0.022), and significantly reduced in the Al group (P<0.001); the GSK-3β phosphorylation level was significantly higher in the SB+Al group than in the Al group (P<0.001). The difference in DRP1 protein level among groups was statistically significant (F=8.389, P=0.003). Compared with the blank control group, the DRP1 protein levels in the DMSO group and the SB group were not significantly different (P>0.05), and significantly increased in the Al group (P=0.001); the DRP1 protein level in the SB+Al group was significantly lower than that in the Al group (P=0.029). Conclusion Al may increase the level of DRP1 protein by activating GSK-3β, causing mitochondrial damage and inhibiting neuronal protrusions growth.

【Objective】 To investigate and summarize the clinical and imaging features of a few patients with coronavirus disease 2019 (COVID-19) in Lanzhou City. 【Methods】 We carried out a retrospective analysis of the epidemiological data, laboratory results and clinical imaging features of eight hospitalized patients with confirmed COVID-19 in The First Hospital of Lanzhou University from January 23 to February 23, 2020. 【Results】 The sex ratio (men to women) of the 8 patients was 5∶3 while their age ranged from 24 to 57 years old. The incubation period was 1-10 days. Of the 8 patients, 7(87.5%) had COVID-19 brought in from other places in China and 1(12.5%) was a secondary infection case. The main clinical manifestations included cough in 6 cases (75%), fever in 4 cases (50%), expectoration in 3 cases (37.5%), and fatigue in 2 cases (25%). All the 8 cases indicated abnormal manifestations in blood routine examinations, 4 cases (50%) decreased in WBC, 7 cases (87.5%) decreased in Lym count, 5 cases (62.5%) increased in LDH, 1 case (12.5%) increased in CK, 1 case(12.5%) increased in CK-MB, 4 cases (50%) increased in CRP, 2 cases (25%) increased in PCT, and 1 case (12.5%) increased in D-dimer. Of the 2 patients examined by chest digital radiography (DR), one DR finding was not typical and the other one suggested increased bilateral lung markings. Six patients were examined by HRCT, of whom four (50%) showed multiple ground glass opacities on both lobes and two (25%) showed multiple ground glass opacities only on the right lobe; none of the 6 imaging findings suggested pleural effusion. Six patients were discharged from hospital after being cured and 1 patient still underwent treatment. 【Conclusion】 Most of these 8 patients had COVID-19 imported from outside the city, and the patients were relatively young with few underlying diseases. Their major symptoms were fever, cough, and expectoration. All of them exhibited abnormal findings in blood routine examinations; half of them suggested increased CRP while a few ones showed abnormal CK and Ddimer values. The imaging manifestations of most patients were multiple ground glass opacities near the peripheral pleura.

OBJECTIVE: To investigate the protective effect of arctiin with anti-inflammatory bioactivity against triptolide-induced nephrotoxicity in rats and explore the underlying mechanism. METHODS: Forty SD rats were divided into 4 groups for gastric lavage of normal saline, arctiin (500 mg/kg), triptolide (500 μg/kg), or both arctiin (500 mg/kg) and triptolide (500 μg/kg). Blood samples were collected for analysis of biochemical renal parameters, and the renal tissues were harvested for determining the kidney index and for pathological evaluation with HE staining. In the RESULTS: In SD rats, arctiin significantly antagonized triptolide-induced elevation of BUN, Scr and kidney index ( CONCLUSIONS Arctiin can protect the kidney from triptolide-induced damages in rats possibly through the anti-inflammatory pathway.
Animals ; Anti-Inflammatory Agents ; Diterpenes/toxicity* ; Epoxy Compounds/toxicity* ; Furans ; Glucosides ; Kidney/drug effects* ; Phenanthrenes/toxicity* ; Rats ; Rats, Sprague-Dawley

Objective: To analyze the association between polycyclic aromatic hydrocarbons(PAHs)exposure and rheumatoid arthritis(RA)based on large sample data. Methods: The RA patients(RA group)and non-RA patients(non-RA group)with complete data were selected from the National Health and Nutrition Survey Database in the United States(NHANES)(2005—2014). The logistic regression model was used to analyze the association between 8 monohydroxylated(OH-)PAH metabolites in the urine and RA. Results: A total of 357 RA patients and 5, 256 non-RA participants were included.After adjusting the confounding factors by logistic analysis, the level of OH-PAHs mixture at the highest quartile(Q4)was associated with increased risk of RA compared with that at the lowest quartile(Q1)(OR=1.60, 95%CI: 1.16-2.23). For a single kind of OH-PAHs, the Q4 levels of 1-hydroxynaphthalene(OR=1.59, 95%CI: 1.14-2.23), 2-hydroxynaphthalene(OR=1.66, 95%CI: 1.19-2.32), 2-hydroxyfluorene(OR=1.61, 95%CI: 1.17-2.22), 3-hydroxyfluorene(OR=1.64, 95%CI: 1.18-2.27)and 1-hydroxyphenanthrene(OR=1.38, 95%CI: 1.00-1.94)were all associated with significantly increased risk of RA compared with the Q1 level(all P<0.05). However, the Q2 level of 1-hydroxypyrene(OR=0.60, 95%CI: 0.43-0.83)was related to a decreased incidence of RA(P<0.01). Conclusions OH-PAHs mixed exposure is a risk factor for RA.The association between the level of individual OH-PAH and the rate of RA is bidirectional and is depended on the type and concentration of OH-PAHs.