AIM: To assess the stability of the tear film and the characteristics of corneal nerves in patients with Parkinson's disease(PD).METHODS: This cross-sectional observational study included 72 PD patients and 50 healthy controls. Disease severity was determined using the Hoehn-Yahr(H-Y)scale, dividing patients into mild and moderate PD groups. Dry eye symptoms were evaluated via the ocular surface disease index(OSDI)questionnaire, while tear secretion was quantified using the Schirmer I test. Ocular surface damage was assessed through staining scores, and comprehensive ocular examinations were performed utilizing the LipiView ocular surface interferometer and an ocular surface analyzer. Corneal nerve parameters were examined using corneal confocal microscopy in conjunction with automated analysis software ACCMetrics, with correlations drawn between these parameters, PD course, and severity.RESULTS: PD patients exhibited significantly elevated OSDI scores, indicative of more pronounced dry eye symptoms compared to the control group(F=70.290, P<0.01). Tear film stability was markedly compromised, with significantly shorter tear film breakup time and increased corneal fluorescein staining, both showing statistically significant differences relative to controls(all P<0.01). Tear secretion indices, including Schirmer I test results and tear meniscus height, were significantly reduced in PD patients(all P<0.01), whereas lipid secretion indices, such as lipid layer thickness and meibomian gland dropout score, did not show significant variation. Corneal nerve analysis revealed significant reductions in corneal nerve fiber density, nerve branch density, fiber length, and total branch density in PD patients compared to controls(all P<0.01). Furthermore, blink frequency was markedly prolonged(F=62.353, P<0.01). Correlation analysis demonstrated a significant relationship between alterations in tear film stability and both disease duration and H-Y scores.CONCLUSION: PD patients have obvious dry eye manifestations in the early stage of the disease, including the reduction of tear film stability and corneal nerve fiber density, and gradually aggravate with the progress of the disease. Neurodegenerative disease-related dry eye needs to be diagnosed early and actively treated.

Accurate prediction of drug-induced adverse drug reactions (ADRs) is crucial for drug safety evaluation, as it directly impacts public health and safety. While various models have shown promising results in predicting ADRs, their accuracy still needs improvement. Additionally, many existing models often lack interpretability when linking molecular structures to specific ADRs and frequently rely on manually selected molecular fingerprints, which can introduce bias. To address these challenges, we propose ToxBERT, an efficient transformer encoder model that leverages attention and masking mechanisms for simplified molecular input line entry system (SMILES) representations. Our results demonstrate that ToxBERT achieved area under the receiver operating characteristic curve (AUROC) scores of 0.839, 0.759, and 0.664 for predicting drug-induced QT prolongation (DIQT), rhabdomyolysis, and liver injury, respectively, outperforming previous studies. Furthermore, ToxBERT can identify drug substructures that are closely associated with specific ADRs. These findings indicate that ToxBERT is not only a valuable tool for understanding the mechanisms underlying specific drug-induced ADRs but also for mitigating potential ADRs in the drug discovery pipeline.

Hepatobiliary and pancreatic tumors are common types of digestive system disorders， and their complex pathogeneses have led to difficulties in early diagnosis and a high metastasis rate， with persistently high incidence and mortality rates in China， which greatly affects the quality of life and prognosis of patients. Studies have shown that heparanase （HPSE）， as a key effector molecule in matrix remodeling， plays a crucial regulatory role in tumor invasion and metastasis and microenvironment remodeling， and it is significantly associated with clinical prognosis. This article reviews the molecular mechanism of HPSE in hepatobiliary and pancreatic tumors， in order to provide a strong scientific basis for developing diagnostic markers and targeted interventions for hepatobiliary and pancreatic tumors.

Liver diseases are a group of complex clinical conditions caused by various factors and can lead to hepatocyte damage and liver dysfunction， posing a serious threat to human health. The cyclic GMP-AMP synthase （cGAS）-stimulator of interferon genes （STING） signaling pathway plays a key regulatory role in the course of liver diseases and is involved in the development， progression， and treatment of various diseases such as viral hepatitis， nonalcoholic fatty liver disease， liver fibrosis， and liver cancer. This article reviews the regulatory mechanisms of the cGAS-STING signaling pathway in processes such as inflammation， autophagy， antiviral response， and oxidative stress， analyzes its molecular function in liver diseases， and explores its application prospect as a potential target for the treatment of liver diseases， in order to provide a theoretical basis for developing novel therapeutic strategies for liver diseases.

Objective To investigate the association between microvariants at locus DYS570 and Y-SNPs haplogroup.Methods 89 Y-SNPs and 34 Y-STRs in AIYSNP42,AIYSNP47 and YfilerTM Platinum kits were used to detect the genotype of 116 microvariants at locus DYS570 in Kunming,and the Set-B kit was used to detect the core repeat sequences of the DYS570 locus.The data were statistically analyzed by direct counting method.Then,a network map was drawn by Network 10.2,in order to visualize the genetic information of the sample.Results The results demonstrated that 111 DYS570/18.3-21.3 samples had a core repeat sequence of TTT[TITC]18-21,belonging to subgroup O2a2b1a1a1a4-F14494.A DYS570/20.3 sample had a core repeat sequence of[TTTC]15TTC[TTTC]5,belonging to O2a1b1a1a1a1e-F1365 subgroup.A DYS570/17.1 sample had a core repeat sequence of[TTTC]17 T,belonging to the O2a1b1a1a1a-F11 subgroup.Three DYS570(19.2)samples had[TTTC]3 TT[TTTC]16,belonging to the D1a1a-M15 haplogroup.Conclusion The results indicated that the microvariant with the same core repeat structure at locus DYS570 was associated with haplogroups,and the ancestry origin of samples can be inferenced from microvariant characteristics during the practice of forensic medicine.

An increased level of reactive oxygen species is a key factor in neuronal apoptosis and epileptic seizures. Irisin reportedly attenuates the apoptosis and injury induced by oxidative stress. Therefore, we evaluated the effects of exogenous irisin in a kainic acid (KA)-induced chronic spontaneous epilepsy rat model. The results indicated that exogenous irisin significantly attenuated the KA-induced neuronal injury, learning and memory defects, and seizures. Irisin treatment also increased the levels of brain-derived neurotrophic factor (BDNF) and uncoupling protein 2 (UCP2), which were initially reduced following KA administration. Furthermore, the specific inhibitor of UCP2 (genipin) was administered to evaluate the possible protective mechanism of irisin. The reduced apoptosis, neurodegeneration, and spontaneous seizures in rats treated with irisin were significantly reversed by genipin administration. Our findings indicated that neuronal injury in KA-induced chronic epilepsy might be related to reduced levels of BDNF and UCP2. Moreover, our results confirmed the inhibition of neuronal injury and epileptic seizures by exogenous irisin. The protective effects of irisin may be mediated through the BDNF-mediated UCP2 level. Our results thus highlight irisin as a valuable therapeutic strategy against neuronal injury and epileptic seizures.
Rats ; Animals ; Kainic Acid/toxicity* ; Brain-Derived Neurotrophic Factor/metabolism* ; Fibronectins/metabolism* ; Hippocampus/metabolism* ; Rats, Sprague-Dawley ; Epilepsy/metabolism* ; Seizures/prevention & control*

Objective:By comparing the clinical data and follow-up data of patients with coronary heart disease combined with chronic kidney disease who choose different ways of revascularization for the first time when do PCI revascularization therapy again. To investigate the effect of coronary artery bypass grafting on revascularization for the first time in patients.Methods:A retrospective analysis of clinical data of 358 patients with coronary heart disease combined with chronic kidney disease who received revascularization PCI from January 2008 to December 2017 was made. All the patients were divided into CABG group(75 cases) and PCI group(283 cases) for clinical characteristics and prognosis comparison. According to the occurrence of major adverse cardiovascular events, Cox regression was carried out to establish a risk prediction model. Results:Compared with the patients in the two groups, the ratio of current smoking(17.33% vs. 33.57%, P=0.006) and hospitalized patients with recurrent acute myocardial infarction(28.00% vs. 40.64%, P=0.045) were decreased in CABG group, the ratio of triple-vessel disease(82.67% vs. 55.12%, P<0.001) and road via femoral artery(49.33% vs. 24.03%, P<0.001) were significantly increased in the CABG group, the Gensini score[136.00(100.75, 164.00) vs. 53.00(39.00, 74.00), P<0.001] and contrast agent dosage [300(200, 400)ml vs. 200(200, 300)ml, P<0.001] were significantly higher in CABG group, but the incidence of MACCE was significantly lower in CABG group than in PCI group (40.00% vs. 57.60%, χ2=7.571, P=0.0059). According to the Cox regression of MACCE events, it was found that CABG ( RR=0.586, 95% CI: 0.396-0.867, P=0.007) and higher glomerular filtration rate( RR=0.988, 95% CI: 0.980-0.997, P=0.007) were the protective factors, white blood cell elevation( RR=1.100, 95% CI: 1.020-1.187, P=0.013) and the application of renin-angiotensin-aldosterone system inhibitor( RR=1.380, 95% CI: 1.016-1.875, P=0.039) were independent risk factors. Conclusion:Patients with coronary heart disease combined with chronic kidney disease can benefit from CABG for the first time in revascularization, when they were confronted with PCI revascularization again.

OBJECTIVETo report on a novel HLA-A allele, A*29:49, identified in a Chinese Han population by sequence based typing (SBT).

METHODSA donor from China Marrow Donor Programme (CMDP) was typed with a bi-allelic PCR-SBT kit, and no full matched result was obtained for the HLA-A locus. The novel HLA allele was verified with an allele-specific amplification SBT kit.

RESULTSA novel HLA-A allele was identified, which has differed by one nucleotide from the closest matched allele, HLA-A*29:01:01:01, at position 368(A→T), codon 99 (TAT→TTT), resulting in an amino acid substitution (Y→F). Another allele was verified as A*02:06:01.

CONCLUSIONA novel HLA-A allele was identified and officially named as HLA-A*29:49 by the WHO Nomenclature Committee for Factors of the HLA System.

Alleles ; Amino Acid Substitution ; genetics ; Base Sequence ; China ; HLA-A Antigens ; genetics ; Humans ; Sequence Analysis, DNA ; methods

Objective To explore the expressions and clinical significances of deleted in liver cancer-1 (DLC-1 ) and Rho associated coiledcoil forming protein kinase (ROCK )Ⅰ in non-small lung cancer (NSCLC).Methods The expressions of DLC-1 and ROCKⅠ in NSCLC and adjacent tissue of 48 patients with pathologically confirmed as NSCLC and undergone surgical resection were detected by immunohistochemis-try EnVision method.The correlations among DLC-1 protein,ROCKⅠ protein and the clinical pathological characteristics were analyzed.The prognostic value of DLC-1 in patients with NSCLC was studied.Results The expression of DLC-1 protein in NSCLC tissue was low or missing,and the positive rate was 33.3%(16/48),significantly lower than that in the tissue adjacent to carcinoma 70.8% (34/48),with statistical significance (χ2 =13.523,P<0.01).The positive expression rate of ROCKⅠprotein in NSCLC was 58.3%(28/48),higher than that of tissue adjacent to carcinoma 0(0/48),with statistical significance (χ2 =39.529, P<0.01).The expression of DLC-1 protein was correlated with tumor differentiation,lymph node metastasis and clinical stage,rather than with sex,smoking history and organization type.Through the correlation analy-sis,the expression of ROCKⅠin DLC-1 positive group was 37.5%(6/16),and the expression rate of ROCKⅠ in DLC-1 negative group was 68.8%(22/32).There was negative correlation between DLC-1 and ROCKⅠin NSCLC tissues (r=-2.214,P=0.039).The 3 year survival rate in DLC-1 protein high expression group was obviously higher than that in low expression group,with statistical significance (P=0.043).Conclusion Low or missing expression of DLC-1 and high expression of ROCKⅠ protein may play an important role in the occurrence and development of NSCLC.Detecting the expression of DLC-1 and ROCKⅠprotein may be useful for evaluating the biological behavior and prognosis of NSCLC.

Objective To compare the effect of four-in-one teaching method and traditional teaching method in clinical clerkship teaching in the department of obstetrics and gynecology. Methods Totally 70 clinical probationer were enrolled(35 from 2007 grade were taken as control group and 35 from 2008 grade were taken as experiment group ). Four-in-one teaching method and traditional teaching method were respectively in experiment group and control group. Examination score and clinical skill re-sults were analyzed by t test and satisfaction degree was analyzed byX2 test. P<0.05 signifies statistical sig-nificances . Results Examination score of experiment group and control group were 86 . 9 ± 7 . 7 and 76.5 ±8.7 respectively with statistically significant differences(P=0.000). Clinical skill score of experi-ment group and control group were 87.6±6.9 and 75.9±7.5 respectively with statistically significant dif-ferences(P=0.000). Each questionnaire index was significantly higher in experiment group than in con-trol group with statistically significant differences(P=0.000). Conclusions Four-in-one teaching method can make students understand theoretical knowledge and master obstetrics and gynecology basic clinical skills,enhance interests in learning,build up self-confidence and establish preliminary clinical thinking ability and innovation ability which will lay a solid foundation for future clinical and research practice.