Mitochondria are abundant in hepatocytes and play an important role in the normal operation of the liver. Mitochondrial division/fusion is two biological processes that maintain the dynamic balance of mitochondria， and it is closely associated with the change of cell function and the development and progression of diseases. Balance of mitochondrial division/fusion is of key significance in the treatment of many diseases. Recent studies have shown that abnormal mitochondrial division/fusion plays a significant role in fatty liver disease， hepatitis， liver fibrosis， and liver cancer， which are the four stages of the progression of liver diseases， and the therapeutic targets based on the regulation of such abnormalities are constantly being identified. By reviewing the role of mitochondrial division/fusion in different stages of liver disease， this article further demonstrates the role of mitochondrial division/fusion mechanism in chronic liver diseases and also provides a scientific basis for more ideas on the treatment， remission or even reversal of liver disease progression based on mitochondrial division/fusion.

Objective:To evaluate the efficacy and safety of hypomethylating agents (HMA) in patients with myelodysplastic syndromes (MDS) .Methods:A total of 409 MDS patients from 45 hospitals in Zhejiang province who received at least four consecutive cycles of HMA monotherapy as initial therapy were enrolled to evaluate the efficacy and safety of HMA. Mann-Whitney U or Chi-square tests were used to compare the differences in the clinical data. Logistic regression and Cox regression were used to analyze the factors affecting efficacy and survival. Kaplan-Meier was used for survival analysis. Results:Patients received HMA treatment for a median of 6 cycles (range, 4-25 cycles) . The complete remission (CR) rate was 33.98% and the overall response rate (ORR) was 77.02%. Multivariate analysis revealed that complex karyotype ( P=0.02, OR=0.39, 95% CI 0.18-0.84) was an independent favorable factor for CR rate. TP53 mutation ( P=0.02, OR=0.22, 95% CI 0.06-0.77) was a predictive factor for a higher ORR. The median OS for the HMA-treated patients was 25.67 (95% CI 21.14-30.19) months. HMA response ( P=0.036, HR=0.47, 95% CI 0.23-0.95) was an independent favorable prognostic factor, whereas complex karyotype ( P=0.024, HR=2.14, 95% CI 1.10-4.15) , leukemia transformation ( P<0.001, HR=2.839, 95% CI 1.64-4.92) , and TP53 mutation ( P=0.012, HR=2.19, 95% CI 1.19-4.07) were independent adverse prognostic factors. There was no significant difference in efficacy and survival between the reduced and standard doses of HMA. The CR rate and ORR of MDS patients treated with decitabine and azacitidine were not significantly different. The median OS of patients treated with decitabine was longer compared with that of patients treated with azacitidine (29.53 months vs 20.17 months, P=0.007) . The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group. Conclusion:Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.

Objective:To investigate the prevalence and mortality of dementia and assess the impact of geriatric syndromes (GS) on the risk for dementia and death in elderly population in Beijing.Methods:A cross-sectional survey was conducted in the elderly population aged ≥65 years and selected by a multi-stage sampling in Beijing during 2013-2015. Cognitive function was screened using the Chinese Revised Version of the Mini-Mental State Examination (MMSE). Then, neurological examination and psychiatric assessment were performed for those with the MMSE score lower than the cut-off value. The information about GS prevalence was also collected. The study also collected death records for all individuals from baseline until December 31, 2019. Based on the age and gender distribution from Beijing data of the 2010 Six th National Population Census, the dementia prevalence in the study population was directly standardized. Logistic regression analysis was used to evaluate the association of different forms of dementia with GS, and Cox proportional hazards regression model was used to estimate the hazard ratio ( HR) and 95% CI of death. Results:During 2013-2015, a total of 2 935 individuals completed dementia assessments, of which 167 were diagnosed with dementia. The standardized prevalence of dementia was 5.9% (95% CI: 5.0%-17.4%). The individuals with Alzheimer's disease (AD) and vascular dementia (VaD) accounted for 58.7% and 28.1% of total individuals with dementia, respectively. Aging, lower education level, urinary incontinence, and fall were risk factors for AD, while disability of activity of daily life dependence, hypertension, and stroke were found to be risk factors for VaD. After a median follow-up of 5.44 person-years, 399 deaths were recorded. The 5-year mortality risk was 2.87 (95% CI: 1.92-4.17) times and 4.93 (95% CI: 3.23-7.53) times higher for the elderly individuals with AD and VaD, respectively, compared to non-demented individuals. After adjusting for demographic, GS, and cardiovascular risk factors, the mortality risk in the elderly individuals with AD showed no significant difference compared with non-demented individuals ( HR=1.32, 95% CI: 0.89-1.97), while the mortality risk in those with VaD was 2.46 (95% CI: 1.49-4.05) times higher than that in non-demented individuals. Conclusions:The prevalence of dementia in Beijing increased significantly in the context of population aging, especially the prevalence of AD. The presence of GS increased the risks for AD and VaD, as well as the risk for death. Close attention needs to be paid to GS management in dementia prevention in elderly population.

Objective:To explore the talent cultivation model of nursing professional group under the 1+X certificate system, to build a talent cultivation system for nursing professional groups with "three progressions, four integrations, and five cocultivation"Methods:From 1 July 2021 to 31 December 2023, built a professional group course system of "mutual sharing of foundations, mutual generation of majors, mutual selection of positions, and progressive improvement of abilities". Aligned course content with X certificate content. Deepen the reform of the three education systems, create a "dual teacher" teaching team that combines full-time and part-time work, and build teaching resources that connect the cloud and the ground. The application effect of this model was evaluated in 2021 nursing majors in Cangzhou Medical College by cluster sampling.Results:There were 748 students majoring in nursing in class of 2021, 150 boys aged 19-22(20.00 ± 1.23), 598 girls, aged 19-21(19.00 ± 2.57). There were 118 students majoring in midwifery in class of 2021, all of them were girls, aged 18-20(18.00 ± 2.11). There were 128 students majoring in rehabilitation therapy technology in class of 2021, 66 boys aged 19-21(19.00 ± 2.11), 62 girls aged 19-21(19.00 ± 2.54). Nursing professional group completed the "Basic Nursing Technology Training Guidance", "Elderly Care" and other 5 self-compiled textbooks, 730 students had participated in the X certificate assessment, 729 students e passed the assessment, the passing rate was 99.9%.Conclusions:The talent cultivation model of "three progressions, four integrations, and five co cultivation" in the nursing professional group can cultivate students′ professional abilities, and cultivate a composite technical and skilled talent with multiple abilities and interconnections in one job.

BACKGROUND: 3D-printing is widely used in regenerative medicine and is expected to achieve vaginal morphological restoration and true functional reconstruction. Mesenchymal stem cells-derived exosomes (MSCs-Exos) were applyed in the regeneration of various tissues. The current study aimed to explore the effctive of MSCs-Exos in vaginal reconstruction. METHODS: In this work, hydrogel was designed using decellularized extracellular matrix (dECM) and gelatin methacrylate (GelMA) and silk fibroin (SF). The biological scaffolds were constructed using desktop-stereolithography.The physicochemical properties of the hydrogels were evaluated; Some experiments have been conducted to evaluate exosomes’ effect of promotion vaginal reconstruction and to explore the mechanism in this process. RESULTS: It was observed that the sustained release property of exosomes in the hydrogel both in vitro and in vitro.The results revealed that 3D scaffold encapsulating exosomes expressed significant effects on the vascularization and musule regeneration of the regenerative vagina tissue. Also, MSCs-Exos strongly promoted vascularization in the vaginal reconstruction of rats, which may through the PI3K/AKT signaling pathway. CONCLUSION The use of exosome-hydrogel composites improved the epithelial regeneration of vaginal tissue, increased angiogenesis, and promoted smooth muscle tissue regeneration. 3D-printed, lumenal scaffold encapsulating exosomes might be used as a cell-free alternative treatment strategy for vaginal reconstruction.

BACKGROUND: Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a severe congenital disorder characterized by vaginal hypoplasia caused by dysplasia of the Müllerian duct. Patients with MRKH syndrome often require nonsurgical or surgical treatment to achieve satisfactory vaginal length and sexual outcomes. The extracellular matrix has been successfully used for vaginal reconstruction. METHODS: In this study, we developed a new biological material derived from porcine vagina (acellular vaginal matrix, AVM) to reconstruct the vagina in Bama miniature pigs. The histological characteristics and efficacy of acellularization of AVM were evaluated, and AVM was subsequently transplanted into Bama miniature pigs to reconstruct the vaginas. RESULTS: Macroscopic analysis showed that the neovaginas functioned well in all Bama miniature pigs with AVM implants. Histological analysis and electrophysiological evidence indicated that morphological and functional recovery was restored in normal vaginal tissues. Scanning electron microscopy showed that the neovaginas had mucosal folds characteristics of normal vagina. No significant differences were observed in the expression of CK14, HSP47, and a-actin between the neovaginas and normal vaginal tissues. However, the expression of estrogen receptor (ER) was significantly lower in the neovaginas than in normal vaginal tissues. In addition, AVM promoted the expression of b-catenin, c-Myc, and cyclin D1. These results suggest that AVM might promotes vaginal regeneration by activating the b-catenin/cMyc/cyclin D1 pathway. CONCLUSION This study reveals that porcine-derived AVM has potential application for vaginal regeneration.

Objective:To explore the association between α5 subunit of gamma-aminobutyric acid receptor subtype 5(GABRA5) gene polymorphism and executive function in patients with major depressive disorder.Methods:From August 2018 to September 2020, one hundred and eighty depressed patients diagnosed by DSM-Ⅳ-TR criteria were included from Xuzhou Eastern Hospital, meanwhile 120 healthy controls with matching demographic characteristic were recruited.Gene polymorphisms were detected through the elbow vein blood of all subjects. The severity of the patients was assessed by 17 items Hamilton depression scale(HAMD-17). The executive function of subjects was tested by Wisconsin card sorting test (WCST) and event-related potential P300.The t test and χ2 test were used for statistic analysis by SPSS 17.0. Results:The cognitive function of depression patients with GABRA5 receptor gene carrying T allele was significantly lower than that of patients with C allele ( t=2.35-3.45, P<0.05). The cognitive dysfunction was associated with sleep and anxiety/somatization symptoms in depression patients ( r=-0.197-0.409, P<0.05). Anxiety/somatization symptoms in patients with depression partially mediated the association between GABRA5 receptor gene polymorphism and cognitive dysfunction(effect value=-0.611, 95% CI=-1.393--0.057). Conclusion:The GABRA5 receptor gene polymorphism is associated with cognitive dysfunction in patients with depression, and anxiety/somatization symptoms partially mediate the impairment of cognitive function caused by GABRA5 receptor gene polymorphism.

Liver fibrosis is a compensatory response in the process of tissue repair after chronic liver injury, and it is also a necessary pathological process in the progression of a variety of chronic liver diseases. In the pathological state, the imbalance between hepatic oxidative system and antioxidant system can lead to the excessive production or insufficient clearance of reactive oxygen species (ROS)/reactive nitrogen species (RNS), which may induce the injury of hepatocytes, expand inflammatory response, and promote the development and progression of liver fibrosis. As a master regulator of oxidative stress and inflammatory response, NF-κB plays a key role in the process of liver fibrosis. Therefore, the cascade interaction between ROS/RNS and the NF-κB signaling pathway plays a guiding role in further clarifying the pathogenesis of liver fibrosis and exploring effective prevention and treatment strategies. This article reviews and discusses the interaction between ROS/RNS and the NF-κB signaling pathway and its important role in the progression of liver fibrosis, so as to provide strategies and references for targeted therapy for liver fibrosis.

Objective:To investigate the efficacy of Qingruxiao granules combined with tamoxifen in the treatment of breast hyperplasia and its effect on serum hypoxia-inducible factor-alpha (HIF-α), angiopoietin-2 (Ang-2) and prolactin (PRL) levels. Methods:Ninety-eight patients with breast hyperplasia admitted to Xi'an No.3 Hospital from June 2020 to January 2022 were retrospectively included in this study. They were divided into control and observation groups ( n = 49/group) according to different treatments. The control group was treated with tamoxifen alone. The observation group was treated with Qingruxiao granules combined with tamoxifen. Clinical efficacy, symptom score, ultrasound parameters (glandular layer thickness, longest diameter of mass, maximum diameter of hypoechoic area, inner diameter of lactating tube), endocrine hormone levels (estradiol, progesterone, and prolactin), HIF-α, and Ang-2 pre- and post-treatment, as well as the incidence of adverse reactions were compared between the two groups. Results:Total response rate in the observation group was significantly higher than that in the control group [93.88% (4/49) vs. 77.55%, χ2 = 5.33, P < 0.05). After treatment, breast mass score, breast pain, systemic accompanying symptom, and nipple discharge in the observation group were (1.34 ± 0.29) points, (1.02 ± 0.36) points, (0.68 ± 0.17) points, (0.97 ± 0.15) points, respectively, which were significantly lower than (1.57 ± 0.23) points, (1.45 ± 0.41) points, (0.95 ± 0.26) points, and (1.28 ± 0.26) points, respectively, in the control group ( t = 4.35, 5.52, 6.08, 7.23, all P < 0.001). The glandular layer thickness, the longest diameter of mass, the maximum diameter of hypoechoic area, and the inner diameter of lactating duct in the observation group were (9.45 ± 1.67) mm, (11.46 ± 3.68) mm, (14.37 ± 4.22) mm, and (1.23 ± 0.39) mm, respectively, which were significantly lower than (11.26 ± 2.51) mm, (16.33 ± 4.01) mm, (19.87 ± 5.01) mm, (1.54 ± 0.48) mm in the control group ( t = 4.20, 2.26, 5.88, 3.51, all P < 0.001). Serum estradiol and prolactin levels in the observation group were (122.35 ± 29.76) ng/L and (205.64 ± 36.42) IU/L, respectively, which were significantly lower than (139.76 ± 30.48) ng/L and (251.49 ± 41.87) IU/L in the control group ( t = 2.86, 5.78, both P < 0.05). Serum progesterone level in the observation group was (9.22 ± 1.57) μg/L, which was significantly higher than (7.18 ± 1.21) μg/L in the control group ( t = -7.20, P < 0.05). Serum HIF-α and Ang-2 levels in the observation group were (0.15 ± 0.05) ng/L and (0.98 ± 0.11) ng/L, respectively, which were significantly lower than (0.24 ± 0.07) ng/L and (1.49 ± 0.22) ng/L in the control group ( t = 7.32, 14.51, both P < 0.001). There was no significant difference in the incidence of adverse reactions between the two groups ( P > 0.05). Conclusion:Qingruxiao granules combined with tamoxifen can effectively improve clinical symptoms, reduce tumor size, regulate endocrine hormone levels, decrease the expression of angiogenic factors in patients with breast hyperplasia, and is highly safe.

Objective:To investigate serum C-reactive protein (CRP) , procalcitonin (PCT) and neutrophil CD64 in predicting early infection after internal fixation of limb fractures.Methods:A total of 2 572 patients with limb fractures undergoing internal fixation in Taishun County People’s Hospital from January 2016 to December 2022 were enrolled. Postoperative infection occurred in 121 cases (infected group) and did not occur in 2 451 cases (uninfected group). Serum levels of PCT, CRP and CD64 were tested at admission and d1, d3, d5 and d7 after operation. Repeated measurement analysis of variance was used to compare the serum levels of PCT, CRP and CD64 at different time points between two groups, the receiver operating characteristic curve (ROC) was used to evaluate the predictive value of each index or in combination for early infection after internal fixation of limbs fractures.Results:The early infection rate after internal fixation was 4.70% (121/2 572). The levels of PCT, CRP and CD64 in the infection group began to rise after operation and decreased on d7; there were significant differences in PCT, CRP and CD64 levels between the two groups on d3, d5 and d7 after operation (PCT: Ftime=678.607, Fintergroup=2 218.323, Finteraction=653.150; CRP: Ftime=392.724, Fintergroup=1 812.502, FInteraction =379.577; CD64: Ftime=373.686, Fintergroup=4 817.438, Finteraction=528.353, all P< 0.001) . The area under the ROC curve of combined detection of PCT, CPR, and CD64 for predicting early infection was 0.856; the sensitivity and specificity of combined detection were 69.2% and 94.7%, respectively. The combined detection of three indicators showed better prediction values than PCT, CRP and CD64 alone ( Z=6.176, 3.838 and 2.431, P<0.01 or <0.05), and also better than combined detection of PCT and CRP ( Z=2.875, P=0.019). Conclusions:The combined detection of CD64, PCT and CRP is of value in prediction of postoperative infection after internal fixation of limb fractures, which is worthy of clinical application.