Objective To explore the relationship between angiogenin-1/2 (Ang-1/2) and clinical parameters of idiopathic pulmonary fibrosis (IPF), and to assess the value of Ang-1/2 in predicting the prognosis of patients with IPF.Methods A retrospective analysis was conducted. Ninety-one patients diagnosed as IPF by high resolution CT (HRCT) and lung biopsy admitted to Daqing Oil Field General Hospitalfrom March 2014 to January 2015 were enrolled. The general data, serum parameters and pulmonary function parameters of all patients were collected. After treatment, all of the 91 patients were followed-up to 2 years. The patients were divided into favorable prognosis group and unfavorable prognosis group according to follow-up results. The differences in all parameters between the two groups werecompared. The relationship between Ang-1, Ang-2 and lung function parameters was analyzed by Pearson correlation analysis. Cox proportional hazard regression model was used to evaluate the effect of clinical parameters on the prognosis of patients with IPF. The effect of Ang-2 in predicting prognosis of patients with IPF was analyzed by receiver operating characteristic (ROC) curve.Results During the 2-year follow-up period, 30 of 91 patients showed a favorable prognosis, and 55 showed an unfavorable prognosis with a poor prognosis rate of 64.71%, and 6 patients withdrew from the study due to loss of follow-up and death. Compared with the favorable prognosis group, Ang-2 level in the unfavorable prognosis group was significantly increased (μg/L: 2.88±1.63 vs. 1.89±1.22,t = 2.909,P= 0.005), but Ang-1 only showed a slight increase (μg/L: 28.70±14.26 vs. 25.62±11.95,t = 1.005,P = 0.318). The results of Pearson correlation analysis showed that Ang-2 level was negatively correlated with forced expiratory volume in 1 second (FVC1) and the percentage of carbon monoxide diffusing capacity accounting for the expected value (DLCO%;r value was -0.227 and -0.206, andP value was 0.147 and 0.253, respectively), but no significant correlation between the level of Ang-1 and FVC1 as well as DLCO% was found (r value was -0.153 and -0.121, andP value was 0.147 and 0.253, respectively). Cox proportional hazard regression model analysis showed that the prognosis of patients with IPF was significantly affected by smoking time and Ang-2 (bothP< 0.05), and the influence of Ang-2 was greater [relative risk (RR): 1.236 vs. 1.006, P= 0.037]. Age, gender, smoking and the levels of FVC1, DLCO% and Ang-1 had no significant effect on the prognosis of IPF patients (allP> 0.05). Prognostic analysis showed that the area under ROC curve (AUC) of Ang-2 for predicting prognosis of patients with IPF was 0.692, and the best diagnostic point was 0.35μg/L, the sensitivity was 61.8%, the specificity was 73.3%, the positive predictive value was 69.8%, and the negative predictive value was 65.7% which indicated that Ang-2 could predict the prognosis of patients with IPF.Conclusion Ang-2 could assess the prognosis of patients with IPF, which is expected to be used as an indicator of predicting the prognosis of patients with IPF.

Antibody-drug conjugate (ADC) is a new class of therapeutics composed of a monoclonal antibody and small cytotoxin moieties conjugated through a chemical linker. ADC molecules bind to the target antigens expressed on the tumor cell surfaces guided by the monoclonal antibody component. The binding ADC molecules can be internalized and subsequently the toxin moieties can be released within the tumor cells via chemical and/or enzymatic reactions to kill the target cells. The conjugation combines the merits of both components, i.e., the high target specificity of the monoclonal antibody and the highly potent cell killing activity of the cytotoxin moieties. However, such complexities make the pharmacokinetic and metabolic studies of ADCs highly challenging. The major challenges should include characterization of absorption, distribution, metabolism and excretion, investigation of underlying mechanisms, assessment of pharmacokinetic- pharmacodynamic relationship, and analytical method development of ADC drugs. This review will discuss common pharmacokinetic issues and considerations, as well as tools and strategies that can be utilized to characterize the pharmacokinetic and metabolic properties of ADCs.

Ischemic stroke is a most frequent type of cerebrovascular disease .In recent years ,along with continuous deepening research on cause of cerebrovascular diseases ,autoimmune—mediated cerebrovascular diseases receive a lot of attention .Researches have found that anticardiolipin antibody (ACA) plays an important role in pathogenesis of ischemic stroke .The present article made following review on relationship between ACA and ischemic stroke and its current situation of research .

Objective:To investigate the predictive value of mucosal vascular pattern (MVP) under narrow-band imaging (NBI) enteroscopy in patients with ulcerative colitis (UC) in clinical remission for histological healing and clinical recurrence.Methods:A total of 142 patients with UC in clinical remission who visited the First Affiliated Hospital of Weifang Medical University from January 2018 to January 2021 were included in the study and underwent colonoscopy. The white light and NBI endoscopic images were collected and biopsies were obtained. The Mayo endoscopic score (MES) was calculated based on white light images, and MVP staging was evaluated based on mucosal vascular patterns under NBI. Nancy index (NI) was used to evaluate histological healing and patients were followed up for 1 year. The Spearman correlation coefficients of MES and MVP with histological healing and recurrence were calculated. The receiver operator characteristic (ROC) curve was plotted and the area under curve (AUC) was applied to evaluate the accuracy of white light and NBI endoscopy for predicting histological healing of UC in clinical remission.Results:According to the MVP criteria, 47 were defined as clear, 63 blurred, and 32 invisible. Spearman correlation analysis showed a significant correlation between MVP under NBI and histological healing ( r=0.549, P<0.001) and a moderate correlation between MES under white light and histological healing ( r=0.462, P<0.001). Spearman correlation analysis showed a moderate correlation between MVP under NBI and clinical recurrence ( r=0.451, P<0.001) and a moderate correlation between MES under white light and clinical recurrence ( r=0.352, P<0.001). AUC of NBI for diagnosing histological healing of UC in clinical remission was 0.809 (95% CI: 0.738-0.879), with a sensitivity of 84.6% (77/91) and specificity of 64.7% (33/51), superior to the white light endoscopy, of which AUC, sensitivity and specificity were 0.763 (95% CI: 0.678-0.848), 81.3% (74/91) and 66.7% (34/51). Conclusion:MVP staging under NBI could predict histological healing of UC patients in clinical remission and is superior to white light endoscopy.

Objective: To investigate the usage of medical and health care APP among female college students, and to understand possible influencing factors, so as to provide reference for medical health care behaviors and personal health among college students. Methods: A stratified random sampling method was used to select 891 female college students from 3 colleges in Weifang. A questionnaire survey on their concentration on their own health, the knowledge, cognition and behavior of medical and health care APP, and Logistic regression analysis was used to analyze the influencing factors. Results: There were 55.4% female college students who had used medical and health care APP, and most of them (290) had used fitness and weight loss APP. There was statistical significance of the different usages of students of different degrees, majors and grades(χ2=26.55, 7.72, 13.96, P<0.05). Logistic regression analysis showed that educational background, annual medical costs, awareness of medical and health care APP and attitude towards APP prospect were the factors influencing the utilization of medical and health care APP (OR=0.44，0.69，1.36，1.23，P<0.05). Conclusion The usage rate of medical and health care APP is general, and sustained utilization rate is low, the APP should enrich menstrual period consumption and figure report, add video recommendation, interactive dating, and other functions, improve female students medical and health care APP cognition, female college students to change health care APP attitude.

Objective:To identify gene mutations in a family with incontinentia pigmenti, in order to confirm pathogenic mutations.Methods:Clinical data were collected from all patients in a family with incontinentia pigmenti. DNA was extracted from peripheral blood samples obtained from the patients, healthy members in the family, and 100 unrelated healthy controls, and Sanger sequencing was performed for all exons and their flanking sequences of the NEMO gene.Results:Totally, there were 4 patients in the 4-generation family, who all presented with typical skin lesions and different symptoms. Genetic testing indicated that the proband and the other 3 patients all carried a heterozygous nonsense mutation c.1153C>T (p.Gln385X) at position 1153 in exon 8 of the NEMO gene, which led to the substitution of the glutamine codon (CAG) by the termination codon (TAG) at amino acid position 385. The mutation was not identified in the 14 healthy relatives or 100 unrelated healthy controls. The mutation cosegregated with incontinentia pigmenti in the family. Database searching confirmed the mutation to be a novel nonsense mutation, and it was considered as a very strong pathogenic locus according to the American College of Medical Genetic and Genomics guidelines.Conclusion:The mutation c.1153C>T in the NEMO gene is associated with the occurrence of incontinentia pigmenti in this family.

Objective:To evaluate the effect of neuromuscular electrical stimulation (NMES) on muscle strength and duration of mechanical ventilation through cumulative Meta-analysis and sequential trial analysis (TSA).Methods:Randomized controlled trial (RCT) of NMES intervention in intensive care unit (ICU) patients with mechanical ventilation were searched from PubMed database of US National Library of Medicine, EMbase database of Netherlands Medical Abstract, Web of Science, SinoMed database of China, CNKI, Wanfang data, VIP and other Chinese and English databases from database construction to July 15, 2021. The control group received ICU routine nursing or rehabilitation exercise; the experimental group received NMES (low frequency electric current through electrode stimulation to make muscle groups twitch or contract) based on routine care in ICU. Relevant data were screened, evaluated and extracted by two researchers independently. After extracting data, STATA 15.0 and TSA software were used to analyze the data and evaluate the research results. Results:A total of 9 studies were enrolled, including 619 subjects. Among the 9 articles included, 2 were grade A and 7 were grade B, indicating good overall quality. Cumulative Meta-analysis showed that compared with ICU routine care, NMES improved muscle strength of patients undergoing mechanical ventilation [standardized mean difference ( SMD) = 0.64, 95% confidence interval (95% CI) was 0.07 to 1.21] and shortened the duration of mechanical ventilation ( SMD = -1.84, 95% CI was -2.58 to -1.10). TSA analysis of the two outcomes showed that the sample size of muscle strength outcome index ( n = 518) and mechanical ventilation outcome index ( n = 419) did not meet the expected information (RIS; n values of 618 and 685); the cumulative Z-value line of the muscle strength outcome index crossed the traditional boundary line and TSA boundary line, indicating that more tests were not needed to verify this result. In the outcome index of mechanical ventilation duration, it was found that the cumulative Z-value line only crossed the traditional boundary line, but did not cross the TSA boundary line, indicating that further studies in this area should be carried out in the future to demonstrate this result. Conclusion:NMES can improve ICU patients' muscle strength and reduce the duration of mechanical ventilation.

ObjectiveTo study the effect of apigenin on the proliferation and apoptosis of human colon cancer CL187 cells and the underlying mechanisms. MethodHuman colorectal cancer CL187 cells were treated with different concentrations of apigenin （0， 30， 45， 60 mg·L^-1） according to the results of the preliminary experiment. The proliferation of CL187 cells was detected by methyl thiazolyl tetrazolium （MTT） and colony formation assays， and the apoptosis was observed via Hoechst 33258 staining. Real-time fluorescence quantitative PCR was conducted to determine the mRNA levels of cysteine protease-3 （Caspase-3）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax） in the CL187 cells treated with apigenin. Western blot was employed to measure the protein levels of Caspase-3， Bcl-2， and Bax associated with apoptosis， protein kinase B （Akt） and phosphorylated Akt （p-Akt） in phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） pathway， and extracellular signal-regulated kinases 1/2 （ERK1/2）， p-ERK1/2， c-Jun N-terminal kinase （JNK）， p-JNK， p38 mitogen-activated protein kinase （MAPK）， and p-p38 MAPK protein in MAPK pathway. ResultCompared with the blank group， the apigenin groups had low cell survival rates and high inhibition rates on cell proliferation （P<0.01）. Apigenin decreased the cell clone number and clone formation rate， and increased the inhibition rate on clone formation （P<0.01）. After CL187 cells were treated with different concentrations of apigenin for 48 h， typical apoptosis characteristics such as nuclear pyknosis， chromatin condensation， and enhanced fluorescence reaction were observed. Compared with blank group， 45， 60 mg·L^-1 apigenin treatments down-regulated the mRNA level of anti-apoptotic gene Bcl-2 （P<0.01） and all the apigenin treatments up-regulated those of the pro-apoptotic genes Bax and Caspase-3 （P<0.05， P<0.01）. Similarly， apigenin treatments down-regulated the protein level of Bcl-2 （P<0.05， P<0.01） and up-regulated those of Caspase-3 （P<0.05， P<0.01） and Bax （P<0.01， 45， 60 mg·L^-1）. The blank group had higher protein level of Akt than the 60 mg·L^-1 apigenin group （P<0.01）， higher protein levels of p-Akt， ERK1/2， and p-ERK1/2 than the 45， 60 mg·L^-1 apigenin groups （P<0.01）， and higher protein levels of JNK and p-JNK than the apigenin groups （P<0.05， P<0.01）. Compared with blank group， 60 mg·L^-1 apigenin up-regulated the protein level of p38 MAPK （P<0.05）， and all the apigenin groups up-regulated that of p-p38 MAPK （P<0.01）. Furthermore， apigenin lowered the p-Akt/Akt ratio （P<0.05， P<0.01） and p-ERK1/2/ERK1/2 ratio （P<0.01）， while it increased the p-JNK/JNK ratio （45， 60 mg·L^-1； P<0.05， P<0.01） and p-p38 MAPK/p38 MAPK ratio （P<0.05， P<0.01）. ConclusionApigenin can inhibit the proliferation and promote the apoptosis of CL187 cells by inhibiting the PI3K/Akt signaling pathway and regulating the expression of proteins in the MAPK signaling pathway.

Objective To systematic review the influence of case-based payment on inpatient costs since China′s new medical reform. Methods Studies about inpatient costs before and after the implementation of case-based payment were collected. The literature collected underwent a meta-analysis by RevMan 5. 0. Results A total of 11 articles in compliance were included in the study. The meta-analysis of random effect model showed the overall effect size (SMD) was -1. 54 with 95% CI being -1. 79, -1. 29, showing a significant difference (P<0. 05). The subgroup analysis showed that the overall effect size (MD) in the low-cost disease group was -585. 57 yuan with 95% CI being -750. 34, -420. 80, showing a significant difference (P < 0. 05). The overall effect size (MD) in the high-cost disease group was-4 172.65 yuan with 95% CI being -5 368. 21, -2 977. 10, showing a significant difference ( P <0.05). The funnel plot was approximately symmetrical, suggesting a publication bias as less likely in the study. Conclusions The implementation of case-based payment has reduced the inpatient costs to some extent thanks to China′s new healthcare reform. And the effect in the high-cost disease group was more obvious than that in the low-cost disease group.

Objective To analyze the dilemmas of our hierarchical medical system, in order to seek a viable path for effective implementation.Methods Based on the Meter-horn model, six related factors were used, including policy standards and goals, policy resources, implementation methods, characteristics of the actuator, value orientation of the executive and the system environment, to analyze the dilemmas of the implementation of hierarchical medical system.Results This policy had not achieved the expected effect in the implementation process, which deviated from the original intention of policy designers to some extent. There exist the following setbacks for the roadblocks. For example, policy standard was ambiguous, the policy resources were insufficient, the execution method was not proper, the implementation mechanism was"criticized" , the implementation personnel value orientation was biased and the complex system environment.Conclusions All the factors involved in the implementation of the hierarchical medical policy affect each other.In this consideration, medical institutions at all levels and the relevant departments should coordinate and deal with the relationship between these six related factors, and timely take effective measures to amend and improve the policy, so as to ensure the orderly progress and long-term implementation of the hierarchical medical system.