BACKGROUND:Some studies have found that local application of alendronate can promote osteogenesis,but less is reported on the process of distraction osteogenesis. OBJECTIVE:To observe the promoting effect of alendronate on rapid mandibular distraction in a rabbit model and explore its possible mechanism. METHODS:Thirty-six male New Zealand white rabbits were randomly divided into groups A,B and C(n=12 per group)after operation and rapid distraction(3-day delay period followed by 3-day distraction at 1.5 mm/12 hours).At the 1st,3rd and 7th days of the consolidation period,animal were injected with 200 μg/kg alendronate in group A and 100 μg/kg alendronate in group B,while those in group C were treated as controls.CT scanning and dual energy X-ray bone mineral density measurement were performed at 4 and 8 weeks of the consolidation period.After the radionuclide scanning was completed at the 4th week,several animals were sacrificed and the samples were collected for western blot assay and tartrate resistant acid phosphatase staining.A three-point bending test was performed after the animals were sacrificed at the 8th week. RESULTS AND CONCLUSION:CT results showed that bone formation in the distraction space of group B was significantly better than that in groups A and C.At the 4th week,the bone mineral density in group B was(0.092±0.010)g/cm2,which was 1.26 times higher than that in group A(P＜0.001)and 1.28 times higher than that in group C(P＜0.001).At the 8th week,the bone mineral density in group B was(0.175±0.029)g/cm2,which was 1.38 times higher than that in group A(P＜0.001)and 1.45 times higher than that in group C(P＜0.001).Tartrate resistant acid phosphatase staining showed that the number of osteoclast-like cells in group C were 2.83 times more than that in group A(P＜0.001)and 2.21 times more than that in group B(P＜0.001).The radionuclide intensity was higher in group C than in groups A and B.Western blot assay results showed that the expression of Runx2 was significantly stronger in group B than in groups A and C.The maximum biomechanical load in group B was(158.48±23.21)N,which was 1.26 times higher than that in group A(P=0.007)and 1.31 times higher than that in group C(P=0.003).To conclude,the low concentration of alendronate may promote rapid distraction osteogenesis of the rabbit mandible by inhibiting osteoclast signals.

Background The current increasing trend of new cases of occupational noise-induced deafness indicates that the hearing loss of occupational population has not been effectively controlled in China. It is of great significance to study the characteristics of hearing loss among noise-exposed workers and its related factors. Objective To investigate characteristics and influencing factors of hearing loss among occupational noise-exposed workers in a large machinery maintenance enterprise, and to provide a scientific basis to prevent and control noise-induced hearing loss. Methods A cross-sectional survey was conducted to investigate male Han occupational noise-exposed workers in a large mechanical maintenance enterprise. We acquired demographic characteristics, occupational exposure history, and individual life behavior characteristics of the workers through questionnaires, collected occupational exposure level data from annual occupational disease hazard factor surveillance reports, obtained pure tone hearing threshold test data through occupational health examinations, and estimated individual noise exposure levels using cumulative noise exposure (CNE). According to the results of pure tone air conduction hearing threshold test, the workers were divided into a hearing loss group and a normal hearing group. The chi-square test was employed to compare the occupational exposure characteristics and individual life behavior characteristics between the two groups. Additionally, the trend chi-square test was utilized to analyze the changing trends of age, length of service, CNE, and hearing loss rate within the two groups. The relationship between high-frequency hearing loss in both ears and its related influencing factors was assessed by a multiple logistic regression model. Results The M (P₂₅, P₇₅) of CNE for the 2531 occupational noise-exposed workers was 97.51 (95.39, 99.96) dB(A)·year. The incidence of hearing anomaly, binaural high-frequency hearing anomaly, random ear high-frequency hearing anomaly, binaural low-frequency hearing anomaly, and random ear low-frequency hearing anomaly were 22.48%, 16.59%, 22.13%, 2.77%, and 3.52%, respectively. High-frequency hearing threshold increase was the main reason for hearing anomaly (98.42%). In comparison to the CNE ≤ 97 dB(A)·year group, the 97 dB(A)·year100 dB(A)·year group experienced a 36.4% and 52.3% increase in the risk of bilateral high-frequency hearing loss, respectively. The smoking group exhibited a 43.5% elevated risk of bilateral high-frequency hearing loss when compared to the non-smoking group. Conversely, the group frequently wearing hearing protection equipment demonstrated a 23.6% lower risk of bilateral high-frequency hearing loss in comparison to the group occasionally wearing protective equipment. The data suggested that CNE＞97 dB(A)·year and smoking might be independent risk factors for bilateral high-frequency hearing loss, and frequently wearing hearing protection equipment might be an important protective factor. Conclusion Increased CNE and smoking can elevate the risk of high-frequency hearing loss, while personal hearing protection can effectively reduce the risk of hearing loss.

Objective To investigate the value of unenhanced CT combined with clinical features in predicting adnexal torsion in women with abdominal pain and an adnexal mass. Methods A retrospective selection of patients with abdominal pain and an adnexal mass underwent operation in 2 tertiary hospitals from January 2018 to September 2023. The torsion group (n＝53) and non-torsion group (n＝53) were matched in a 1∶1 ratio. 15 CT signs of adnexal masses were reviewed independently by two radiologists using a double-blind method. The high-risk factors were screened using multivariate logistic regression analysis. The diagnostic values of high-risk factors for adnexal torsion were assessed using receiver operating characteristic (ROC) curves. Results According to the surgical and pathological results, the most common adnexal mass in torsion group was mature cystic teratoma (32.1%), and the most common mass in the non-torsion group was adnexal abscess (20.8%). The age, fever rate, white blood cell count, location of mass, thickened fallopian tube rate, and pelvic effusion rate were not statistically different between the two groups, the nausea and vomiting and remaining CT signs were significant different between the two groups (P＜0.05). Multivariate logistic analysis showed that nausea and vomiting (OR＝4.886), navel sign (OR＝22.733), and whirl sign (OR＝43.462) were independently associated with adnexal torsion (P＜0.05). The area under the curve (AUC) of nausea and vomiting, navel sign, and whirl sign were 0.717, 0.802, and 0.840, respectively; AUC of the combination of all three was 0.877 with 92.45% of sensitivity, 84.91% of specificity, 85.96% of positive predictive value, 91.84% of negative predictive value, and 88.68% of accuracy. Conclusions For women with abdominal pain and an adnexal mass, nausea and vomiting, navel sign, and whirl sign are help of predicting adnexal torsion, and combination value of all three is best.

Objective To investigate the correlations of the expression levels of plasma long non-coding RNA plasmacytoma variant translocation 1 (LncRNA PVT1) and microRNA-143-3p (miR-143-3p) with disease activity and prognosis in patients with rheumatoid arthritis (RA). Methods A total of 129 RA patients admitted to our hospital from April 2021 to April 2023 were selected as disease group. According to the 28-joint disease activity scores (DAS28), the patients were divided into stable disease group (n=28), mildly active group (n=42), moderately active group (n=35), and severely active group (n=24). According to the prognosis of the patients after 6 months of treatment, they were divided into good prognosis group (n=88) and poor prognosis group (n=41), and 110 healthy people who underwent physical examinations in our hospital during the same period were included as control group. The expression levels of plasma LncRNA PVT1 and miR-143-3p were detected using quantitative real-time fluorescent polymerase chain reaction (qRT-PCR). The targeting relationship between LncRNA PVT1 and miR-143-3p was predicted using the Target Scan Human website. Multivariate Logistic regression analysis was conducted to explore the factors influencing the prognosis of RA patients. Receiver operating characteristic (ROC) curve was performed to assess the predictive value of plasma LncRNA PVT1 and miR-143-3p for the prognosis of RA patients. Results The plasma LncRNA PVT1 level in the disease group was higher than that in the control group, while the plasma miR-143-3p level was lower (P < 0.05). The plasma LncRNA PVT1 levels decreased sequentially in the severe activity, moderate activity, mild activity, and disease stable groups, while the plasma miR-143-3p levels increased sequentially (P < 0.05).The proportion of patients positive for human leukocyte antigen-DR4 (HLA-DR4), DAS28, and plasma LncRNA PVT1 expression level were higher in the poor prognosis group than in the good prognosis group, while the plasma miR-143-3p level was lower (P < 0.05). Plasma LncRNA PVT1, miR-143-3p expression, HLA-DR4 positivity, and DAS28 were factors influencing the prognosis of RA patients (P < 0.05). LncRNA PVT1 and miR-143-3p had targeted binding sites, and there was a negative correlation between them (P < 0.05). The area under the curve (AUC) for the combined prediction of plasma LncRNA PVT1 and miR-143-3p for prognosis of RA patients was 0.914, which was superior to the individual diagnosis of LncRNA PVT1 or miR-143-3p (Z=2.159, P=0.031; Z=2.108, P=0.035). The sensitivity and specificity of the combined diagnosis were 95.12% and 78.41%, respectively. Conclusion The plasma LncRNA PVT1 level gradually increases, while the plasma miR-143-3p level gradually decreases with increasing RA disease activity. The combined detection of the two biomarkers has high predictive value for the prognosis of RA patients.

Background::Hepatic ischemia-reperfusion injury (HIRI) remains a common complication during liver transplantation (LT) in patients. As a key downstream effector of the Hippo pathway, Yes-associated protein (YAP) has been reported to be involved in various physiological and pathological processes. However, it remains elusive whether and how YAP may control autophagy activation during ischemia-reperfusion.Methods::Human liver tissues from patients who had undergone LT were obtained to evaluate the correlation between YAP and autophagy activation. Both an in vitro hepatocyte cell line and in vivo liver-specific YAP knockdown mice were used to establish the hepatic ischemia-reperfusion models to determine the role of YAP in the activation of autophagy and the mechanism of regulation. Results::Autophagy was activated in the post-perfusion liver grafts during LT in patients, and the expression of YAP positively correlated with the autophagic level of hepatocytes. Liver-specific knockdown of YAP inhibited hepatocytes autophagy upon hypoxia-reoxygenation and HIRI ( P <0.05). YAP deficiency aggravated HIRI by promoting the apoptosis of hepatocytes both in the in vitro and in vivo models ( P <0.05). Attenuated HIRI by overexpression of YAP was diminished after the inhibition of autophagy with 3-methyladenine. In addition, inhibiting autophagy activation by YAP knockdown exacerbated mitochondrial damage through increasing reactive oxygen species ( P <0.05). Moreover, the regulation of autophagy by YAP during HIRI was mediated by AP1 (c-Jun) N-terminal kinase (JNK) signaling through binding to the transcriptional enhanced associate domain (TEAD). Conclusions::YAP protects against HIRI by inducing autophagy via JNK signaling that suppresses the apoptosis of hepatocytes. Targeting Hippo (YAP)-JNK-autophagy axis may provide a novel strategy for the prevention and treatment of HIRI.

Objective:To evaluate the efficacy and safety of chimeric antigen receptor T-cell (CAR-T) therapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with Ph-like acute lymphoblastic leukemia (Ph-ALL) .Methods:Patients with Ph-ALL who underwent CAR-T therapy followed by allo-HSCT from March 2018 to August 2023 at the First Affiliated Hospital of Soochow University were included, and their clinical data were retrospectively analyzed.Results:Of the 21 patients, 14 were male and 7 were female. The median age at the time of CAR-T therapy was 22 (6-50) years. Seven patients had ABL1-like rearrangements, and 14 had JAK-STAT rearrangements. Prior to CAR-T therapy, 12 patients experienced hematologic relapse; 7 were multiparameter flow cytometry minimal residual disease (MFC-MRD) -positive and 2 were MFC-MRD-negative. CAR-T cells were derived from patients’ autologous lymphocytes. Nine patients were treated with CD19 CAR-T cells, and 12 were treated with CD19/CD22 CAR-T cells. After assessment on day 28 after CAR-T therapy, 95.2% of the patients achieved complete remission, with an MRD-negative remission rate of 75%. Nineteen patients developed grade 0–2 cytokine release syndrome (CRS) and 2 patients suffered grade 3 CRS, all cases of which resolved after treatment. All patients underwent allo-HSCT after CAR-T therapy. The median time from CAR-T therapy to allo-HSCT was 63 (38-114) days. Five patients experienced relapse after CAR-T therapy, including four with hematologic relapse and one with molecular relapse. The 3-year overall survival (OS) rates in the ABL1 and JAK-STAT groups were (83.3±15.2) % and (66.6±17.2) %, respectively ( P=0.68) . The 3-year relapse-free survival (RFS) rates were (50.0±20.4) % and (55.6±15.4) % in the ABL1 and JAK-STAT groups, respectively. There was no significant difference in 3-year OS or RFS between the two groups. Conclusions:CAR-T therapy followed by allo-HSCT leads to rapid remission in most patients with Ph-ALL and prolongs leukemia-free survival.

Objective:To explore the relationship between atherosclerotic index of plasma(AIP)and vulnerable plaque of coronary under computed tomography(CT)based on coronary CT angiography(CCTA).Methods:Data were retrospectively collected on 213 patients with coronary heart disease(CHD)who underwent CCTA examination from January 2021 to February 2024 at the Second Affiliated Hospital of Shenyang Medical College,and they were divided into a vulnerable plaque group(123 cases)and a non-vulnerable plaque group(90 cases)according to whether existed vulnerable plaque of coronary artery.General clinical data such as age,gender,history of smoking,history of alcohol consumption,history of diabetes,and serum indicators such as AIP were collected.The differences in AIP and other factors between the two groups were compared.The independent influencing factors of vulnerable plaque of coronary artery were determined by multifactorial logistic regression analysis,and the predictive value of AIP for vulnerable plaque was assessed by drawing a receiver operating characteristic(ROC)curve.Results:AIP of vulnerable plaque group was 0.22±0.31,which was higher than that 0.05±0.27 of the vulnerable plaque group,and the difference of AIP between two groups was significant(t=4.223,P<0.001).Multifactorial logistic analysis showed there was independent correlation between AIP and vulnerable plaque under CT(OR=7.556,95%CI:2.442～23.385,P=0.002).The ROC curve showed that the best cut-off value of AIP was 0.20 in predicting vulnerable plaque under CT,and the value of area under curve(AUC)was 0.665,and the sensitivity was 55.56%and the specificity was 73.98%.Conclusion:AIP is an independent influencing factor for CHD patients who complicate vulnerable plaques,and it has a certain of predictive value for vulnerable plaques.

Objective:To explore the relationship between challenge-hindrance stressors and thriving at work in clinical nurses, and to analyze the mediating role of intrinsic motivation.Methods:This was a cross-sectional survey. A total of 319 nurses from the Provincial Hospital Affiliated to Shandong First Medical University, Qilu Hospital of Shandong University, Shandong Provincial Qianfoshan Hospital from May to June 2022 were investigated by general data questionnaire, Challenge-Hindrance Stressors Scale, Intrinsic Motivation Scale and Thriving At Work Scale. Pearson was used to analyze the correlation between various variables, and Amos 23.0 was used to construct a structural equation model to analyze the mediating role of intrinsic motivation between challenging stressors, hindrance stressors, and thriving at work.Results:The score for challenging stressors was (21.22 ± 4.42) points, the score for hindrance stressors was (13.51 ± 3.59) points, the score for intrinsic motivation was (78.96 ± 11.52) points, and the score for thriving at work was (51.27 ± 8.03) points. Challenging stressors was positively associated with intrinsic motivation and thriving at work ( r=0.222, 0.221, both P<0.01), hindrance stressors was negatively associated with intrinsic motivation and thriving at work ( r=-0.152, -0.337, both P<0.01), intrinsic motivation was positively correlated with thriving at work ( r=0.564, P<0.01). Intrinsic motivation was partially mediated between challenging stressors, hindrance stressors and thriving at work, respectively accounting for 16.02% and 13.79%. Conclusions:Challenging stressors and hindrance stressors can indirectly influence their thriving at work through intrinsic motivation. Nursing managers should help nurses treat different stressors correctly to enhance their intrinsic motivation and promote their thriving at work.

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 explore the effect of different HER2 expression levels and gene amplification on the efficacy of immunotherapy in metastatic urothelial carcinoma (UC).Methods:The clinical data of 77 patients with metastatic UC who received immunotherapy from June 2017 to April 2021 after failure to the previous chemotherapy were analyzed retrospectively, including 49 males and 28 females with the median age of 62 years. The primary tumors located in bladder in 28 cases (36.4%), renal pelvis in 25 cases (32.5%) and ureter in 24 cases (31.2%). The common metastatic sites included: lymph nodes (n = 45, 58.4%), lung (n = 40, 51.9%), bone (n = 20, 26.0%) and liver (n = 16, 20.8%). 27 patients with bladder UC received surgery on the primary tumors including radical cystectomy (n = 18), partial cystectomy (n = 4) and transurethral resection (n = 5). 43 patients with renal pelvis or ureteral UC received surgery on the primary tumors including radical nephroureterectomy (n = 38), local resection (n = 3) and palliative resection (n = 2). Postoperative intravesical chemotherapy was performed in 15 cases, adjuvant radiotherapy was performed in 6 cases. 3 patients who emerged postoperative bladder recurrence received local radiotherapy. 7 patients received radiotherapy and 1 case received microwave ablation to their metastatic sites. All patients had received first-line chemotherapy and 30 patients (40.0%) had received at least second-line treatment including 70 cases (90.9%) with platinum containing chemotherapy. All 77 patients received anti-PD-1 treatment. 38 patients received sequential regimen after failed to the anti-PD-1 therapy, including antibody-drug conjugate (n = 17), chemotherapy (n = 18) and chemotherapy combined with anti-angiogenesis drugs (n = 12). Immunohistochemical (IHC) staining was used to detect the expression level of HER2 protein in the tumor tissues (74 cases from primary tumors and 3 cases from metastatic tumors) obtained from the initial diagnosis. For patients with HER2 IHC (+ + ), the copy number (CN) of HER2 gene was detected by next-generation sequencing (NGS). HER2 copy number amplification [CN (+ )] was defined as CN ≥ 4, and HER2 copy number non-amplification [CN(-)] was defined as CN < 4. HER2 IHC (0) was defined as HER2 negative, IHC (+ ) or IHC (+ + ) / CN (-)was defined as HER2 low expression, while IHC (+ + ) / CN(+ ) and IHC (+ + + ) were defined as HER2 high expression. Chi-square test or Fisher exact test were used to evaluate the correlation between HER2 expression and objective response rate (ORR) after anti-PD-1 treatment. Kaplan-Meier method and log-rank test were used to compare the differences of median progression free survival (PFS) and overall survival (OS) under different HER2 expression status.Results:All the 77 patients received a median of 11 (range: 2 - 45) doses of anti-PD-1 treatment with a median duration of treatment of 6.4 (range: 1.5 - 47.8) months and the ORR was 33.8% (26/77). The median follow-up time was 30.9 months. The overall median PFS time was 5.8 (95% CI: 3.0 - 8.6) months and the median OS time was 23.6 (95% CI: 8.5 - 38.7) months. HER2 IHC tests were performed in 77 patients. HER2 IHC levels of (0), (+ ), (+ + ) and (+ + + ) were found in 33 (42.9%), 19 (24.7%), 20 (26.0%) and 5 (6.5%) patients, respectively. HER2 copy number was detected in 20 patients with IHC (+ + ), while 1 CN(+ ) and 19 CN(-) were found. The ORR of HER2 negative, low expression and high expression patients were 42.4% (14/33) vs. 31.6% (12/38) vs. 0 (0/6) ( P = 0.08), respectively. The median PFS of the three groups were 11.0 months, 3.7 months and 1.8 months, respectively, with significant differences in overall and pairwise comparison( P=0.001). The median OS of patients with HER2 negative and low expression after anti-PD-1 treatment were 23.6 months and 22.7 months, respectively, while the median OS of patients with HER2 high expression had not been reached, with no significant difference in the overall comparison ( P=0.623). Conclusions:For patients with metastatic UC received anti-PD-1 treatment, the PFS of patients with high HER2 expression was significantly worse than that of patients with low or negative HER2 expression. HER2 expression may have potential value in predicting the efficacy of immunotherapy for metastatic UC who failed the previous chemotherapy, which needs further research.