ObjectiveTo investigate the expression of serum Aldo-keto reductase family 1 member B10 （AKR1B10） in patients with hepatocellular carcinoma （HCC） in northern China， and to provide a new and valuable biomarker for the clinical diagnosis of HCC. MethodsThis study was conducted among 102 patients with HCC， 119 patients with benign liver disease， and 132 patients with other malignant tumors who attended The Affiliated Hospital of Chengde Medical University and 148 healthy individuals who underwent physical examination from May 2020 to May 2024. ELISA and chemiluminescence were used to measure the serum levels of AKR1B10 and alpha-fetoprotein （AFP）. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups， and the Kruskal-Wallis H test was used for comparison between three groups and further comparison between two groups； the chi-square test was used for comparison of categorical data between groups. The area under the ROC curve （AUC） was used to assess diagnostic efficiency. ResultsThe expression level of AKR1B10 was 3 053.79 （1 475.67‍ ‍—‍ ‍4 605.86） pg/mL in the HCC group， 1 324.42 （659.68‍ ‍—‍ ‍2 023.88） pg/mL in the benign liver disease group， 660.68 （377.56‍ ‍—‍ ‍2 087.77） pg/mL in the other malignant tumor group， and 318.30 （82.73‍ ‍—‍ ‍478.82） pg/mL in the healthy group， with a significant difference between the four groups （H=240.86， P<0.001）， and further comparison between two groups showed that the HCC group had a significantly higher level than the other three groups （all P<0.001）. The ROC curve analysis of the HCC group and the other three groups showed that serum AKR1B10 had an optimal cut-off value of 1 584.97 pg/mL in the diagnosis of HCC， with an AUC of 0.86 （95% confidence interval ［CI］： 0.82‍ ‍—‍ ‍0.90）， a sensitivity of 74.3%， and a specificity of 85.2%. Compared with each indicator alone， a combination of AKR1B10 and AFP could improve the sensitivity （81.8%） and specificity （91.4%） of HCC diagnosis. AKR1B10 had an AUC of 0.84 （95%CI： 0.78‍ ‍—‍ ‍0.90） in the diagnosis of patients with early- or middle-stage HCC， with a sensitivity of 76.2% and a specificity of 81.2%. AKR1B10 had an AUC of 0.85 （95%CI： 0.77‍ ‍—‍ ‍0.92） in the diagnosis of patients with AFP-negative HCC， with a sensitivity of 81.6% and a specificity of 79.9%. ConclusionAKR1B10 is a promising serological marker for the diagnosis of HCC， and a combination of AKR1B10 and AFP can improve the detection rate of HCC patients in northern China， especially those with early- or middle-stage HCC and AFP-negative HCC.

ObjectiveTo explore the correlation between blood stasis constitution （BSC） and diseases based on constitution literature involving “constitution-diseases correlation”. MethodsA comprehensive search was conducted on six Chinese and English electronic databases including CNKI， Wanfang， VIP， SinoMed， PubMed and Embase to find all clinical researches on the correlation between constitution and diseases using the Classification and Identification of Chinese Medicine Constitution standard from April 1st， 2009 to December 31st， 2022， and the participants of the research were BSC related. By analyzing the characteristics of the literature， such as authors， publication institutes， participants， and results， the disease with the highest proportion of BSC distribution or BSC as their risk factors or protective factors were summarized to explore the correlation between BSC and diseases. ResultsTotally 135 clinical studies on diseases highly related to BSC were included， with a total sample size of 71 172 cases.There were 27 keywords in the articles appeared more than 3 times， including the elderly， lumbar disc herniation， coronary heart disease， cardiovascular disease， and endometriosis. In the author's clustering， included studis were mainly from Shenzhen Hospital of Beijing University of Chinese Medicine， Second Affiliated Hospital of Guangzhou University of Chinese Medicine， and Wenzhou Central Hospital. In terms of blood stasis related diseases， 81 studies showed that BSC was the most common type of constitution in the study population， involving 48 disease or morbid states. The diseases and median proportions of BSC with reported literature ≥3 included coronary heart disease （28.8%）， endometriosis （31.3%）， neurocognitive impairment （26.4%）， lumbar disc herniation （26.0%）， ischemic stroke （25.0%）， adenomyosis （34.7%）， and endometrial polyps （25.0%）. Fifty-eight studies found that BSC was a risk factor for disease occurrence，and these diseases reported more than 3 times included hypertension （median OR = 2.956）， type 2 diabetes （median OR = 3.436），osteoporosis （median OR = 5.171）， sudden deafness （median OR = 3.827） and endometriosis （median OR = 5.412）. One study indicated BSC as the protective factor of lateral growth tumor of large intestine （median OR = 0.161）. ConclusionBSC is closely related to circulatory system diseases， urogenital system diseases， and musculoskeletal system diseases.

To construct a recombinant expression system for a single-domain antibody targeting the urease of Helicobacter pylori(Hp),this study employed several strategies.First,using artificial intelligence(AI)auxiliary tools such as Pymol,I-TASSER,and ClussPro2,the molecular interactions between different antibodies and Hp urease subunit B(UreB)were analyzed.The fully humanized single-domain antibody UreBAb was identified as the primary research target.Next,the UreBAb gene sequence was optimized based on Escherichia coli codon preferences,and was inserted into expression vectors such as pET28a and pE-SUMO.The resulting recombinant expression strains were obtained by transforming Escherichia coli Rosetta(DE3).Recombinant antibody proteins were prepared through IPTG induction,and its activity was detected using extracted Hp urease as the antigen.SDS-PAGE analysis confirmed the correct expression of both UreBAb and SUMO-UreBAb,with protein yields of 0.34 mg/mL and 0.41 mg/mL,respectively.Unidirectional immunodiffusion experiments further confirmed that both recombinant antibodies exhibited strong affinity for Hp UreB antigen,with inhibition rates of 51.27%and 74.07%,respectively.Additionally,leveraging artificial intelligence tools such as AlphaFold2,cluspro2,mCSM-AB,OSPREY,and FoldX,the study evaluated and analyzed key binding sites and mutational strategies affecting the stability of the antigen-antibody complex.Subsequently,nine UreBAb evolution mutants were constructed,and their binding activities with the antigen were enhanced.Among these,the I107W mutant showed the most significant improvement,achieving a 24.95%increase compared to the wild-type UreBAb.This research lays a solid foundation for the development of fully humanized single-domain antibodies against Hp.

Objective To analyze the epidemic characteristics of pneumoconiosis in Jingmen City from 2011 to 2022, and to provide theoretical basis for formulating the occupational disease prevention plan of the ^“14th Five-Year Plan^” in Jingmen City. Methods The data of pneumoconiosis cases in Jingmen City from 2011 to 2022 were collected from the Occupational Disease and Health Hazard Factors Monitoring Information System, and the information of disease classification, enterprise economic type, scale distribution, regional distribution, job distribution, dust exposure years and so on was statistically analyzed. Results A total of 260 cases of pneumoconiosis were reported in Jingmen City from 2011 to 2022, with an average of 13.81 years of exposure to dust, including 164 cases of coal workers' pneumoconiosis, 90 cases of silicosis and 6 cases of other pneumoconiosis. The cases were mainly distributed in Dongbao District with 160 cases (61.54%), Zhongxiang City with 72 cases (27.69%), and Duodao District with 18 cases (6.92%). The difference was statistically significant（χ²=217.846，P<0.05）. The cases were mainly distributed in private enterprises (76.54%, 199 cases). The enterprise sizes were mainly medium-sized (28.46%, 74 cases) and small (61.15%, 159 cases) enterprises, and the difference was statistically significant (χ²=46.025，P<0.05). Conclusion Coal workers' pneumoconiosis and silicosis are the main types of occupational pneumoconiosis in Jingmen area, which will become the key prevention and control targets in Jingmen City for a long time and should be paid attention to. The cases are mainly concentrated in joint-stock, private economic type enterprises and small and medium-sized enterprises, which should be monitored intensively.

Objective:To explore the association between polymorphisms of transforming growth factor-β(TGF-β)signaling pathway and non-syndromic cleft lip with or without cleft palate(NSCL/P)among Asian populations,while considering gene-gene interaction and gene-environment interaction.Methods:A total of 1 038 Asian NSCL/P case-parent trios were ascertained from an international consortium,which conducted a genome-wide association study using a case-parent trio design to investigate the genes affec-ting risk to NSCL/P.After stringent quality control measures,343 single nucleotide polymorphism(SNP)spanning across 10 pivotal genes in the TGF-β signaling pathway were selected from the original genome-wide association study(GWAS)dataset for further analysis.The transmission disequilibrium test(TDT)was used to test for SNP effects.The conditional Logistic regression models were used to test for gene-gene interaction and gene-environment interaction.Environmental factors collected for the study in-cluded smoking during pregnancy,passive smoking during pregnancy,alcohol intake during pregnancy,and vitamin use during pregnancy.Due to the low rates of exposure to smoking during pregnancy and al-cohol consumption during pregnancy(＜3％),only the interaction between maternal smoking during pregnancy and multivitamin supplementation during pregnancy was analyzed.The threshold for statistical significance was rigorously set at P=1.46 × 10-4,applying Bonferroni correction to account for multiple testing.Results:A total of 23 SNPs in 4 genes yielded nominal association with NSCL/P(P＜0.05),but none of these associations was statistically significant after Bonferroni's multiple test correction.How-ever,there were 6 pairs of SNPs rs4939874(SMAD2)and rs1864615(TGFBR2),rs2796813(TGFB2)and rs2132298(TGFBR2),rs4147358(SMAD3)and rs1346907(TGFBR2),rs4939874(SMAD2)and rs1019855(TGFBR2),rs4939874(SMAD2)and rs12490466(TGFBR2),rs2009112(TGFB2)and rs4075748(TGFBR2)showed statistically significant SNP-SNP interaction(P＜1.46 × 10-4).In contrast,the analysis of gene-environment interactions did not yield any significant results after being cor-rected by multiple testing.Conclusion:The comprehensive evaluation of SNP associations and interac-tions within the TGF-β signaling pathway did not yield any direct associations with NSCL/P risk in Asian populations.However,the significant gene-gene interactions identified suggest that the genetic architec-ture influencing NSCL/P risk may involve interactions between genes within the TGF-β signaling path-way.These findings underscore the necessity for further investigations to unravel these results and further explore the underlying biological mechanisms.

Senile dementia is a disease that gradually develops with age. At present, the etiology, pathogenesis and treatment of senile dementia cannot be completely determined clinically. Therefore, it is extremely necessary to prevent and treat senile dementia from prevention and disease management. For the non-ill people, this article analyzed the susceptible groups of senile dementia from the perspective of TCM constitution, combined with the current prevention plan of Alzheimer's disease, from the aspects of examination, nutritional supplementation, adjustment of work and rest, exercise, etc., early physical fitness prevention targeting populations at different stages was conducted; the early onset of senile dementia is not obvious, and the early prevention of senile dementia can be carried out from various aspects in combination with constitution identification and inspection of senile dementia; for the exact sick population, disease management guidance can be added on the basis of the above aspects to provide definite and feasible recommendations for disease prevention and management of the elderly.

Objective:To investigate the inhibitory effect of specific inhibitor of necroptosis necrostatin-1 (Nec-1) on necroptosis of retinal ganglion cells (RGCs) in rats with acute ocular hypertension.Methods:Twenty-four adult male Sprague Dawley rats were randomly divided into normal control group, model control group, Nec-1 treatment group and negative control group by random number table method, with 6 rats in each group.High intraocular pressure (IOP)-induced ischemia and reperfusion model was established through anterior chamber irrigation of 0.9% sodium chloride solution in left eyes of the rats, raising the IOP to 110 mmHg (1 mmHg=0.133 kPa) for 60 minutes.Nec-1 (4 mmol/L, 2 μl) or dimethyl sulfoxide (2 μl) was intravitreally injected immediately in Nec-1 treatment group and negative control group following modeling, respectively, according to grouping.No intervention was administered to the normal control group.Paraffin sections of rat retinas of the left eyes in different groups were prepared seven days after modeling.The retinal structure was observed by hematoxylin-eosin staining, and the expression levels of thymocyte antigen-1 (Thy-1) and glial fibrillary acidic protein (GFAP) were detected via immunohistochemical staining.All animal experiments were approved by an Ethics Committee of Tianjin Union Medical Center (No.2017 Quick audit C01).Results:Seven days after modeling, compared with normal control group, the retinal nerve fiber layer was thinner in model control group and negative control group, and the RGCs were arranged loosely, and cells in the inner nuclear layer were reduced and arranged disorderly, and cells in the outer nuclear layer were normal or enlarged.Compared with model control group and negative control group, the nerve fiber layer was thickened and the number of RGCs was significantly increased in Nec-1 treatment group.The number of Thy-1-positive RGCs was decreased in model control group, negative control group and Nec-1 treatment group than normal control group, and there were more Thy-1-positive RGCs in Nec-1 treatment group than model control group and negative control group.The integrated absorbance ( A) value of GFAP protein in normal control group, model control group, negative control group and Nec-1 treatment group was 47.209±15.311, 116.220±18.194, 116.382±19.020, 92.818±10.236, respectively, showing statistically significant differences among them ( F=24.675, P<0.001). The integrated A value of GFAP protein was significantly increased in model control group, negative control group and Nec-1 treatment group than normal control group, and the integrated A value of GFAP protein in Nec-1 treatment group was lower than that in model control group and negative control group, with statistically significant differences (all at P<0.05). Conclusions:Nec-1 can promote RGCs survival by inhibiting the necroptosis of RGCs in rats with acute intraocular hypertension.

Monoclonal antibody is a new treatment for severe asthma in children.It can selectively act on specific cytokines or pathways in the inflammatory cascade of asthma to block the inflammatory reaction, so as to reduce the number of acute attacks of asthma, reduce the dosage of drugs, and improve lung function.The main adverse reactions included injection site reaction and upper respiratory tract infection.At present, monoclonal antibodies for children include Omalizumab, Mepolizumab, Benralizumab, Reslizumab and Dupilumab.Although the efficacy of monoclonal antibody in children with asthma is obvious, its long-term effect and safety still need to be further confirmed by a large number of clinical studies.

Objective:To explore the value of ex- vivo porcine stomach model for endoscopic submucosal dissection (ESD) training for international trainees. Methods:Fifteen international students received ESD training and learning for twenty days. Firstly, students learned basic theory of ESD and completed a questionnaire. Then they were randomized to receive endoscopic training either on the vitro animal (group A) or on training experience (group B) of the clinical observation. At last, one case was assessed by an experienced endoscopist. The total and step-by-step operating time, complete resection, size of specimen and complications were recorded. All students completed the questionnaire once again. SPSS 20.0 was used for t test and chi-square test. Results:There was significant difference in total ESD operation time between group A and group B ( P<0.05). There were significant differences between the two groups on cutting time and dissection time, but there was no difference on marking time, injection time and operating speed. There was only one case of block resection and perforation in each group. For group A, their mastery and clinic confidence of ESD had been obviously increased after the animal training course. Compared with the operation before the training in group A, it was found that the total time and cutting time of the ESD after the training were also significantly improved. Conclusion:Theory combined with endoscopic training on vitro animal model can make the trainees familiar with the basic theory and master the operational skills, which is helpful and valuable for them to perform ESD in further clinic practice.

Purpose: From the perspective of positive psychology, our study aimed to explore depressive symptomsand psychological well-being among Chinese nurses, as well as analyze the impacts of characterstrengths, self-efficacy and social support on the mental health of nurses. Methods: A cross-sectional and descriptive design using five self-reported questionnaires was used toinvestigate a cohort of 4238 nurses during 2018. A structural equation modeling analysis was used toverify a hypothetical model linking character strengths, self-efficacy, social support, depressive symptoms,and psychological well-being. Results: The prevalence of depression among this cohort of Chinese nurses was 58.1%. The mean scoresfor caring, inquisitiveness, and self-control were 19.93 (SD = 2.82), 15.94 (SD = 3.00), and 16.34(SD = 2.95), respectively. The hypothesized model was a good fit of the data (x2/df = 1.77, p = .183, rootmean square error of approximation = 0.04, goodness of fit index = 1.00, comparative fit index = 1.00,TuckereLewis index = 1.00). Except for the path from self-control to depression, the other hypotheticalpaths investigated were statistically significant. Conclusion Character strengths were directly and positively associated with psychological well-being.Inquisitiveness was the strongest direct protective factor for depression. In addition, characterstrengths indirectly alleviated depression and increased psychological well-being through mediatingvariables of social support and self-efficacy. This study should alert nurse managers that more attentionshould be paid to the character strengths and mental health of nurses. This study provides evidence forinterventions based on character strengths as a management strategy to support the mental health ofnurses.