Objective    To investigate the optimal administration combination of β-aminopropionitrile (BAPN) and Angiotensin Ⅱ (Ang-Ⅱ) in the establishment of SD rat aortic dissection (AD) model and the related complications. Methods    Forty-two three-week-old male SD rats were randomly divided into 7 groups: a group A (0.25% BAPN), a group B (0.40% BAPN), a group C (0.80% BAPN), a group D [1 g/(kg·d) BAPN], a group E [1 g/(kg·d) BAPN+ 1 μg/(kg·min) saline], a group F [1 g/(kg·d) BAPN+1 μg/(kg·min) Ang-Ⅱ] and a group G (control group). There were 6 rats in each group. The intervention period was 4 weeks (groups E and F were 4 weeks+5 days). Rats were dissected immediately if they died during the experiment. After the intervention, the surviving rats were sacrificed by pentobarbital sodium, and the whole aorta was separated and retained. Hematoxylin-eosin staining was used to observe the changes of aorta from the pathological morphology. Results    There was no statistical difference in the survival rate among the groups after 4 weeks of BAPN intervention (P>0.05). After 5 days of mini-osmotic pumps implantation, the survival rate of rats was higher in the group E than that in the group F (P=0.008), and the incidence of AD in the group E was lower than that in the group F (P=0.001). BAPN could affect the food and water intake of rats. After BAPN intervention for 4 weeks, the body weight of rats in the group G was higher than those in the intervention groups (P<0.05). BAPN combined with Ang-Ⅱ could make the aortic intima thick, elastic fiber breakage, arrangement disorder, and inflammatory cell infiltration in rats, which conformed to the pathological and morphological changes of AD. BAPN could also affect mental state and gastrointestinal tract. Conclusion    The combination of BAPN [1 g/(kg·d)] and Ang-Ⅱ [1 μg/(kg·min)] can stably establish AD model in rats, which will provide a stable carrier for further study of the pathogenesis and therapeutic targets of AD. However, the complications in this process are an unstable factor. How to balance the influence of BAPN on other tissues and organs in the process of AD model establishment remains to be further studied.

BACKGROUND:Reducing the rate of abnormal fertilization is an effective approach to improving the efficacy of in vitro fertilization and reducing patients'financial strain.However,the current research on abnormal fertilization has focused on exploring the types of prokaryotic nuclei and their generation mechanisms,as well as analyzing embryos formed by abnormal fertilization,chromosomal ploidy and utilization value.There is a lack of clinical prediction models for abnormal fertilization based on retrospective studies. OBJECTIVE:To construct a nomogram model to predict abnormal female factors in in vitro fertilization. METHODS:A total of 5 075 patients undergoing treatment for conventional in vitro fertilization at Nanxishan Hospital of Guangxi Zhuang Autonomous Region from March 2017 to March 2022 were retrospectively analyzed.The male confounders were calibrated on a 1:1 propensity score with a match tolerance of 0.02,and 1 672 cases were successfully matched.According to the Vienna Consensus,patients with≥60%normal fertilization capacity were included in the normal fertilization group(n=836)and those with<60%normal fertilization capacity were included in the abnormal fertilization group(n=836).The model and validation groups were obtained by random sampling at a ratio of 7:3.Factors related to the occurrence of abnormal fertilization following conventional in vitro fertilization in the model group were screened using univariate analysis and the best matching factors were selected using the Least Absolute Shrinkage and Selection Operator(LASSO)and included in a multifactorial forward stepwise Logistic regression to identify their independent influencing factors and plot a nomogram.Finally,the prediction model was validated for discrimination,accuracy and clinical application efficacy using receiver operating characteristic curves,calibration curves,clinical decision curves and clinical impact curves. RESULTS AND CONCLUSION:The univariate analysis indicated the factors influencing the occurrence of abnormal fertilization were age,controlled ovarian hyperstimulation protocol,number of assisted pregnancies,years of infertility,infertility factors,anti-mullerian hormone,sinus follicle count,basal luteinizing hormone,luteinizing hormone concentration on the human chorionic gonadotropin day,and estradiol level on human chorionic gonadotropin injection day(P<0.05).LASSO regression further identified the best matching factors,including age,microstimulation protocol,number of assisted pregnancies,years of infertility,anti-mullerian hormone,luteinizing hormone level on human chorionic gonadotropin injection day,and estradiol level on human chorionic gonadotropin injection day(P<0.05).Multifactorial forward stepwise Logistic regression results showed that age,microstimulation protocol,number of assisted conceptions,years of infertility,anti-mullerian hormone,and estradiol level on human chorionic gonadotropin injection day were independent influencing factors for the occurrence of abnormal fertilization following conventional in vitro fertilization.The receiver operating characteristic curves showed an area under the curve of 0.761(0.746,0.777)for the model group and 0.767(0.733,0.801)for the validation group,indicating that the model has good discrimination.The mean absolute error of the calibration curve was 0.044,and the Hosmer-Lemeshow test indicated that there was no significant difference between the predicted probability of abnormal fertilization and the actual probability of abnormal fertilization(P>0.05),indicating the prediction model has good consistency and accuracy.The clinical decision curves and clinical impact curves showed that the model and validation groups had the maximum net clinical benefit at valve probability values of 0.00-0.52 and 0.00-0.48,respectively,and there was a good clinical application efficacy in this valve probability range.To conclude,the nomogram model has good discrimination and accuracy as well as clinical application efficacy for predicting the occurrence of abnormal fertilization in women undergoing conventional in vitro fertilization based on age,microstimulation protocol,number of assisted conceptions,years of infertility,anti-mullerian hormone,and estradiol level on human chorionic gonadotropin injection day.

Endodontic diseases are a kind of chronic infectious oral disease.Common endodontic treatment concepts are based on the removal of inflamed or necrotic pulp tissue and the replacement by gutta-percha.However,it is very essential for endodontic treatment to debride the root canal system and prevent the root canal system from bacterial reinfection after root canal therapy(RCT).Recent research,encompassing bacterial etiology and advanced imaging techniques,contributes to our understanding of the root canal system's anatomy intricacies and the technique sensitivity of RCT.Success in RCT hinges on factors like patients,infection severity,root canal anatomy,and treatment techniques.Therefore,improving disease management is a key issue to combat endodontic diseases and cure periapical lesions.The clinical difficulty assessment system of RCT is established based on patient conditions,tooth conditions,root canal configuration,and root canal needing retreatment,and emphasizes pre-treatment risk assessment for optimal outcomes.The findings suggest that the presence of risk factors may correlate with the challenge of achieving the high standard required for RCT.These insights contribute not only to improve education but also aid practitioners in treatment planning and referral decision-making within the field of endodontics.

Objective:To explore the association between the frequency of using smoking cessation application (APP) and the effect of smoking cessation in smoking cessation clinic.Methods:A clinical trial with a non-randomized controlled design was conducted in the smoking cessation clinic of China-Japan Friendship Hospital from July 2019 to June 2021. Participants were given a comprehensive smoking cessation intervention of mobile APP combined with bupropion. The primary outcome measures were carbon monoxide validated sustained abstinence at 9-12 weeks.Results:A total of 187 participants were included in the final analysis. After 12-week intervention, the sustained abstinence at 9-12 weeks was 42.2%. For the frequency of APP use, 20.9% (39/187) of the participants used it≥6 days per week, 62.0% (116/187) used it 2-5 days per week, and 17.1% (32/187) used it≤1 day per week. Multivariate analysis showed that smoking cessation rate was associated with smoking duration, cigarettes smoked per day and frequency of APP use. Participants with higher frequency of APP use had a higher likelihood of quitting smoking ( OR=4.95, 95% CI: 1.32-18.63). Conclusion:The increased frequency of mobile smoking cessation APP use is associated with higher probability of quitting smoking in smoking cessation clinic.

Objective:To describe the study methods and baseline characteristics of participants enrolled in mCessation program.Methods:This is a longitudinal, real-world study with non-randomized controlled design. The mCessation program consisted of a WeChat official account, an applet and a website using the same name ‘mCessation Online’. After users followed the WeChat account, filled in baseline information online and set a quit date, they would receive 162 short text messages in the next six and a half months as scheduled. This study collected the information of participants enrolled from May 26, 2021 to September 30, 2022, and analyzed baseline data including demographic characteristics, smoking characteristics, degree of tobacco dependence, reasons for smoking cessation and other related factors.Results:During the study period, a total of 16 746 participants registered, and 13 887 participants (82.9%) were enrolled in final analysis after screening the inclusion and exclusion criteria and completion of main indicators. Each year the number of enrolled participants in May or June was 1 381 to 2 707 per month, higher than the number of enrolled participants in other months (233 to 569 per month). Participants from North China accounted for the largest proportion (29.3%). There were 13 316 men (95.9%) in enrolled participants and the mean age was (36±10) years. Most participants were 25-34 (38.8%) or 35-44 (30.8%) years old. In terms of smoking characteristics, there were 12 564 (90.5%) daily smokers. The starting age of smoking was 18 (15, 20) years old. 11 866 participants (85.4%) were tobacco dependent, mostly with degree of mild (76.4%) or moderate (20.2%). In terms of reasons for quitting, 9 315 participants′ (67.1%) reasons were to prevent disease, 6 742 participants (48.5%) were concerned about impact of smoking on family members, and 6 731 participants (48.5%) were under requested by families.Conclusion:mCessation program can effectively recruit smokers with intention to quit in short time, especially those who were male, young and tobacco dependent.

Objective : To investigate the effect and mechanism of miR⁃145 ⁃3p on mitophagy in 1 ⁃methyl⁃4 ⁃pheny⁃lpyridiniumion ( MPP + ) Ⅳinduced Parkinson ′ s disease ( PD) cell model . Methods : Human neuroblastoma cells SH⁃SY5Y) were divided into control group , model group , mimics group , calmodulin⁃dependent protein kinase kinaseβ (CaMkkβ) inhibitor ( STO⁃609) group , mimics + STO⁃609 group , cyclic adenosine monophosphate response element⁃binding protein (CREB) inhibitor (KG⁃501) group , mimics + KG⁃501 group and STO⁃609 + KG⁃501 group . Cell apoptosis was detected by flow cytometry , autophagosome structure was observed by transmission electron microscopy , and apoptosis , autophagy and CaMkkβ/adenylate activated protein kinase ( AMPK) /CREB pathway related protein expression were detected by Western blot . Results : Compared with control group , the apoptosis rate , Bcl⁃2 ⁃associated X protein (Bax) , cysteine proteinase⁃3 (Caspase⁃3) and microtubule⁃associated protein light chain 3 ⁃I (LC3 ⁃ Ⅰ ) protein expression levels in model group increased (P < 0. 01) , and the autophagosome structure decreased . The protein levels of B cell lymphoma⁃2 (Bcl⁃2) , autophagy gene (Beclin⁃1) , microtubule⁃associated protein light chain 3 ⁃ Ⅱ ( LC3 ⁃ Ⅱ ) , phosphorylated calmodulin⁃dependent protein kinase kinaseβ(p⁃CaMkkβ) , phosphorylated cadenylate activated protein kinase ( p⁃AMPK) , and phosphorylated cyclic adenosine monophosphate response element⁃binding protein ( p⁃CREB) decreased ( P < 0. 01) . Compared with model group , the apoptosis rate , Bax , Caspase⁃3 and LC3 ⁃ Ⅰ protein expression levels in mimics group decreased (P <0. 05 ) , and the autophagosome structure increased . The protein levels of Bcl⁃2 , Beclin⁃1 , LC3 ⁃ Ⅱ , p ⁃CaMkkβ , p ⁃AMPK , p ⁃CREB increased (P < 0. 05) . The trend of STO⁃609 group and KG⁃501 group was the same and opposite to mimics group . Compared with mimics group , the apoptosis rate , Bax , Caspase⁃3 and LC3 ⁃ Ⅰ protein expression levels in the mimics + STO⁃609 group and the mimics + KG⁃501 group increased (P < 0. 01) , and the autophagosome structure decreased . The protein levels of Bcl⁃2 , Beclin⁃1 , LC3 ⁃ Ⅱ , p ⁃CaMkkβ , p ⁃AMPK , p ⁃CREB protein levels decreased (P < 0. 01) . Compared with STO⁃609 group , the apoptosis rate , Bax , Caspase⁃3 and LC3 ⁃ Ⅰ pro⁃tein expression levels of STO⁃609 + KG⁃501 group increased ( P < 0. 01) , and the autophagosome structure decreased . The protein levels of Bcl⁃2 , Beclin⁃1 , LC3 ⁃ Ⅱ , p ⁃CaMkkβ , p ⁃AMPK and p ⁃CREB decreased ( P <0. 05) . Conclusion miR⁃145 ⁃3p can inhibit the apoptosis of MPP + Ⅳinduced PD cell model and promote mitophagy , and its mechanism may be related to the activation of the CaMkkβ/AMPK/CREB pathway .

Microenvironmental biophysical factors play a fundamental role in controlling cell behaviors including cell morphology, proliferation, adhesion and differentiation, and even determining the cell fate. Cells are able to actively sense the surrounding mechanical microenvironment and change their cellular morphology to adapt to it. Although cell morphological changes have been considered to be the first and most important step in the interaction between cells and their mechanical microenvironment, their regulatory network is not completely clear. In the current study, we generated silicon-based elastomer polydimethylsiloxane (PDMS) substrates with stiff (15:1, PDMS elastomer vs. curing agent) and soft (45:1) stiffnesses, which showed the Young's moduli of ~450 kPa and 46 kPa, respectively, and elucidated a new path in cytoskeleton re-organization in chondrocytes in response to changed substrate stiffnesses by characterizing the axis shift from the secreted extracellular protein laminin β1, focal adhesion complex protein FAK to microfilament bundling. We first showed the cellular cytoskeleton changes in chondrocytes by characterizing the cell spreading area and cellular synapses. We then found the changes of secreted extracellular linkage protein, laminin β1, and focal adhesion complex protein, FAK, in chondrocytes in response to different substrate stiffnesses. These two proteins were shown to be directly interacted by Co-IP and colocalization. We next showed that impact of FAK on the cytoskeleton organization by showing the changes of microfilament bundles and found the potential intermediate regulators. Taking together, this modulation axis of laminin β1-FAK-microfilament could enlarge our understanding about the interdependence among mechanosensing, mechanotransduction, and cytoskeleton re-organization.
Cell Adhesion ; Chondrocytes ; Cytoskeleton/metabolism* ; Elastomers/metabolism* ; Laminin/metabolism* ; Mechanotransduction, Cellular

【Objective】 To establish a reasonable and effective blood screening strategy for Hepatitis C virus (HCV), so as to reduce the risk of blood transfusion transmission, ensure blood safety and improve the quality of blood screening. 【Methods】 In order to evaluate HCV screening strategies comprehensively, the unqualified blood donations due to anti-HCV alone positivity in Dalian from 2017 to 2021 was tracked, with combined detection methods of electro-chemiluminescence immunoassay (ECLIA) and HCV-RNA nucleic acid test (NAT). 【Results】 A total of 851 (0.20%) unqualified donations due to anti-HCV alone positivity were screened from 2017 to 2021, with a decreasing trend in both numbers and rate. Among them, the unqualified rate of samples with anti-HCV reactivity in both dural-ELISA-reagent and NAT decreased significantly (P<0.05). A total of 117(0.028%) samples were anti-HCV reactive in dural-ELISA-reagent but nonreactive in NAT; 664 reactive in one-ELISA-reagent, with 70(10.54%) in Reagent Ⅰ and 594(89.46%) in Reagent Ⅱ; 122 (35.88%) out of 340 donations were reactive in ECLIA. Among the 28 participants in the follow-up test, 15 still were reactive in ELISA and 2 reactive in ECLIA. 【Conclusion】 Although the unqualified rate of HCV is decreasing, serological screening of anti-HCV is still an important method for ensuring blood safety, and its complementarity with HCV-RNA NAT should be evaluated. As a new serological assay, ECLIA has high sensitivity and specificity. Miss detection may occur if only one ELISA reagent is adopted for anti-HCV detection. Appropriate ELISA and NAT system for HCV screening should be reasonably chosen, and HCV screening strategy should be developed and adjusted according to the local conditions.

Objective:To establish a disease risk prediction model for the newborn screening system of inherited metabolic diseases by artificial intelligence technology.Methods:This was a retrospectively study. Newborn screening data ( n=5 907 547) from February 2010 to May 2019 from 31 hospitals in China and verified data ( n=3 028) from 34 hospitals of the same period were collected to establish the artificial intelligence model for the prediction of inherited metabolic diseases in neonates. The validity of the artificial intelligence disease risk prediction model was verified by 360 814 newborns ' screening data from January 2018 to September 2018 through a single-blind experiment. The effectiveness of the artificial intelligence disease risk prediction model was verified by comparing the detection rate of clinically confirmed cases, the positive rate of initial screening and the positive predictive value between the clinicians and the artificial intelligence prediction model of inherited metabolic diseases. Results:A total of 3 665 697 newborns ' screening data were collected including 3 019 cases ' positive data to establish the 16 artificial intelligence models for 32 inherited metabolic diseases. The single-blind experiment ( n=360 814) showed that 45 clinically diagnosed infants were detected by both artificial intelligence model and clinicians. A total of 2 684 cases were positive in tandem mass spectrometry screening and 1 694 cases were with high risk in artificial intelligence prediction model of inherited metabolic diseases, with the positive rates of tandem 0.74% (2 684/360 814)and 0.46% (1 694/360 814), respectively. Compared to clinicians, the positive rate of newborns was reduced by 36.89% (990/2 684) after the application of the artificial intelligence model, and the positive predictive values of clinicians and artificial intelligence prediction model of inherited metabolic diseases were 1.68% (45/2 684) and 2.66% (45/1 694) respectively. Conclusion:An accurate, fast, and the lower false positive rate auxiliary diagnosis system for neonatal inherited metabolic diseases by artificial intelligence technology has been established, which may have an important clinical value.

Objective:To further understand the current status of diagnosis and treatment of endometriosis in China, the implementation of guideline in different levels of hospitals, and the need for continuing education in endometriosis among primary doctors.Methods:The survey was conducted in the form of convenience sampling questionnaire among the Wechat public platform. The doctors were free to participate in the investigation without any reward. All questions answered were assessed as valid questionnaire. The datas were collected on the questionnaire network platform and analyzed by SPSS 19.0.Results:Totally 1 494 valid questionnaires were collected in this survey. 60.17% (899/1 494) of them were from tertiary hospital, and 32.60% (487/1 494) were from grade two hospital. Only the hospitals where 9.97% (149/1 494) participants based opened the specialist clinic for endometriosis. 70.35% (1 051/1 494) of participants said they had read the second edition of guideline for the diagnosis and treatment of endometriosis which published in 2015. The American Society for Reproductive Medicine (ASRM) staging system was adopted in the clinical practices of only 25.03% (374/1 494) participants. And 18.74% (280/1 494) participants used the endometriosis fertility index (EFI) scoring during the laparoscopic surgery for endometriosis with infertility. 45.18% (675/1 494) of participants said they had not attended any academic conference on endometriosis in the past six months. 64.46% (963/1 494) of the participants believed their diagnosis and treatment in practice should be improved and standardized. 87.15% (1 302/1 494) of the participants expressed the hope that more conferences or workshops on endometriosis would be held.Conclusions:At presents, the diagnosis and treatment of endometriosis in China has been greatly improved, but the implementation of guidelines and the new concept is still a long-term job. The specialist clinic are held only in a few hospitals. It’s the expectation and voice of primary doctors to the association to organize the more academic congresses on endometriosis.