In addition to providing energy for cells, mitochondria also participate in calcium homeostasis, cell information transfer, cell apoptosis, cell growth and differentiation. Therefore, maintaining mitochondrial homeostasis is very crucial for the body to carry out normal life activities. Ubiquitination, a post-translational modification of proteins, is involved in various physiological and pathological processes of cells by regulating mitochondrial homeostasis. However, the mechanism by which ubiquitination regulates mitochondrial homeostasis has not been summarized, especially the effect of Parkin protein on cardiovascular diseases. In this paper, the specific mechanism of mitochondrial homeostasis regulated by ubiquitination of Parkin protein is discussed, and the influence of mitochondrial homeostasis imbalance on cardiovascular diseases is reviewed, with a view to providing potential therapeutic strategies for the clinical treatment of cardiovascular diseases.

ObjectiveThrough the correlation analysis between intestinal absorption profile and inhibition of macrophage foaming， the pharmacodynamic components of Zhuriheng dripping pills（ZRH） were explored to provide a basis for establishing its quality standard. MethodIntestinal absorption fluids with 0， 5， 10， 15， 20 times clinical equivalent doses were prepared by a rat everted gut sac（EGS）， and the oxidized low density lipoprotein（ox-LDL）-induced RAW264.7 macrophage foaming model was used to investigate the effect of intestinal absorption fluid with different doses on the accumulation of lipids in RAW264.7 cells by oil red O staining and cholesterol content determination， and to screen for the optimal dose. Ultra performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry（UPLC-Q-Exactive Orbitrap MS） was used to analyze and identify intestinal absorption fractions of ZRH intestinal absorption fluids， and partial least squares-discriminant analysis（PLS-DA） and orthogonal partial least squares-discriminant analysis（OPLS-DA） were performed on different doses of ZRH intestinal absorption fluids using SIMCA 13.0 with peak area as the independent variable and the pharmacodynamic indicators as the dependent variables to screen the compounds with variable importance in the projection（VIP） value>1.0 as contributing components， and Pearson correlation analysis was used to determine the spectral effect relationship， determined the compounds and positive correlation with pharmacodynamic were as active ingredients. Molecular docking was used to verify the binding energy of peroxisome proliferator-activated receptor α（PPARα）， PPARγ， PPARβ， human retinoid X receptor α（RXRA） and nuclear transcription factor-κB（NF-κB） with the active ingredients in ZRH intestinal absorption fluids. Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） was performed to detect the mRNA levels of PPARγ， scavenger receptor A1（SRA1） and adenosine triphosphate-binding cassette transporter A1（ABCA1） in RAW264.7 cells， Westen blot was used to detect the expression level of PPARγ protein in RAW264.7 cells， and enzyme-linked immunosorbent assay（ELISA） was used to detect the levels of interleukin（IL）-1β and NF-κB in RAW264.7 cells. ResultAccording to the results of oil red O staining and cholesterol content determination， the ZRH intestinal absorption fluids could significantly reduce macrophage foaming， and intestinal absorption fluids with 15， 20 times clinical equivalent doses had the best effect， the 15-fold ZRH intestinal absorption fluid was finally determined as the study subject. Spectral effect relationship showed that 52 corresponding peaks in the ZRH-containing intestinal fluid were positively correlated with the efficacy， including organic acids， phenylpropanoids， iridoids， flavonoids， bile acids， coumarins and chromones. Target validation results showed that 86.9%-96.2% of the total components processed good binding activities with the key targets of PPARα， PPARγ， PPARβ， RXRA and NF-κB， and the docking energy values were all less than -6.0 kcal·mol^-1（1 cal≈4.19 J）. The results of validation showed that， compared with the normal group， the model group showed a significant increase in the levels of SRA1 and PPARγ mRNA expression， a significant decrease in ABCA1 mRNA expression， a significant increase in the level of PPARγ protein expression， and a significant increase in the levels of IL-1β and NF-κB（P<0.01）， compared with the model group， the 15-fold intestinal absorption fluid group showed a significant decrease in the levels of SRA1 and PPARγ mRNA expression（P<0.05， P<0.01）， ABCA1 mRNA expression level was significantly up-regulated， the levels of IL-1β and NF-κB were significantly reduced（P<0.01）， and PPARγ protein expression level was significantly reduced（P<0.05）. ConclusionThis study identifies 52 components and their metabolites in ZRH intestinal absorption fluid that are positively correlated with the inhibition of macrophage foaming， which may be related to the regulation of the PPARs pathway in cells and the reduction of the levels of inflammatory factors， and can provide a reference for the quality control and clinical application of ZRH.

Objective To compare the positive rate ofthyroid autoantibodies in infertile women with different ovarian reserve function,and investigate the immune factors of diminished ovarian reserve.Methods A cross-sectional study was conducted on infertile women admitted to Department of Reproductive Medicine of Beijing Gynaecology and Obstetrics Hospital from June to December,2020.The levels of anti-Müllerian hormone (AMH ),thyroid stimulating hormone (TSH ),thyroglobulin antibody (TGAb ) and thyroid peroxidase antibody (TPOAb)were detected in the 526 enrolled infertile patients.According to their AMH level,they were divided into normal ovarian reserve group and diminished ovarian reserve group.After they were stratified according to their age,the differences of TSH,TGAb and TPOAb levels were compared in the different age groups to analyze the related factors for diminished ovarian reserve.Results Univariate analysis showed that the diminished ovarian reserve group had significantly higher positive rates of TPOAb (18.8％ vs 11.1％,P=0.024)and TGAb (18.8％ vs 8.0％,P=0.001 )than the normal ovarian reserve group.Multivariate logistic regression analysis indicated that age and TGAb positivity were related to diminished ovarian reserve[OR=1.083(95％ CI:1.021～1.150),P=0.008;OR=1.159(95％ CI:1.034～1.301 ),P=0.011].Subgroup analysis suggested that the positive TGAb and TPOAb were significantly correlated with AMH level in the 36-～40-year-old group (P<0.05).Conclusion The infertile women with diminished ovarian reserve have higher TGAb and TPOAb levels,and the diminishment in those aged 36～40 years might be related to the positive TGAb and TPOAb.

Objective To investigate the application value of combining the Demirjian's method with ma-chine learning algorithms for dental age estimation in northern Chinese Han children and adolescents.Methods Oral panoramic images of 10 256 Han individuals aged 5 to 24 years in northern China were collected.The development of eight permanent teeth in the left mandibular was classified into different stages using the Demirjian's method.Various machine learning algorithms,including support vector re-gression(SVR),gradient boosting regression(GBR),linear regression(LR),random forest regression(RFR),and decision tree regression(DTR)were employed.Age estimation models were constructed based on total,female,and male samples respectively using these algorithms.The fitting performance of different machine learning algorithms in these three groups was evaluated.Results SVR demonstrated superior estimation efficiency among all machine learning models in both total and female samples,while GBR showed the best performance in male samples.The mean absolute error(MAE)of the op-timal age estimation model was 1.246 3,1.281 8 and 1.153 8 years in the total,female and male samples,respectively.The optimal age estimation model exhibited varying levels of accuracy across dif-ferent age ranges,which provided relatively accurate age estimations in individuals under 18 years old.Conclusion The machine learning model developed in this study exhibits good age estimation effi-ciency in northern Chinese Han children and adolescents.However,its performance is not ideal when applied to adult population.To improve the accuracy in age estimation,the other variables can be con-sidered.

Objective:To investigate the immunophenotypic and molecular biological characteristics of patients with elevated serum alpha-fetoprotein (AFP) and enteroblastic differentiated gastric adenocarcinoma (GAED).Methods:The clinicopathological data of 13 patients with elevated serum AFP and GAED admitted to Shanxi Cancer Hospital from 2018 to 2020 were collected. Immunohistochemistry (IHC) and next-generation sequencing (NGS) were used to analyze the immune markers and molecular biological characteristics of the pathological tissues of the patients. Kaplan-Meier method and log rank test were used for survival analysis.Results:Among the 13 patients with GAED, 12 were male and 1 was female, aged 41-70 years, with a median age of 64 years. The lesions were mainly located in the gastric antrum (5 cases) and gastric body (4 cases). IHC results showed that the tumor embryonic protein (AFP, SALL4, GPC3), intestinal epithelial differentiation protein (CDX-2, CD10), and some original intestinal epithelial phenotype markers (OCT3/4, Claudin6) were expressed in the tumor tissues. Combined application of multiple markers can reduce the rate of missed diagnosis. Among the 13 patients, 12 had at least one mutation (1 mutation: 1 case, 2-5 mutations: 3 cases, 6-15 mutations: 8 cases), and 1 case was not detected. The gene with the highest mutation frequency was TP53 (10 cases), and other mutant genes included EPHB1 (3 cases), ATRX (2 cases), EPHA5 (2 cases), GATA3 (2 cases), LRP1B (2 cases) and MAP2K4 (2 cases) were also detected. Three of the 13 patients had structural variations, which were C14orf177- GNAS, AIM1- FGFR3, and EPHA6- ROS1 gene rearrangements. All 13 patients had copy number variation, and 11 patients had copy number variation of more than 2 genes. The common amplification genes were IRS2 (5 cases), PTEN (5 cases), GNAS (4 cases), CCNE1 (3 cases), CEBPA (3 cases), PCK1 (3 cases) and ERBB2 (2 cases). The common deletion genes were SOX2 (5 cases) and MYC (5 cases). Among the 13 patients, 4 died, and 2 of the dead patients had liver metastasis. There were 4 patients with disease-free survival and 5 patients with disease progression, including 3 cases of abdominal metastasis and 2 cases of liver metastasis. The 3-year survival rate of patients was 65.9 %, and the 3-year progression-free survival rate was 30.7 %. Gene LRP1B point mutation was associated with poor prognosis ( P＜0.001). There was no significant improvement in the prognosis of patients treated with immunotherapy compared with those treated with chemotherapy alone ( P=0.595), but the prognosis of patients treated with postoperative chemotherapy or postoperative chemotherapy plus immunotherapy was better than that of patients treated with surgery alone ( P＜0.05). Conclusions:Elevated serum AFP with GAED is a highly invasive tumor with unique molecular characteristics, often accompanied by multiple molecular events. TP53 mutation is the most common type of gene mutation. In addition, some cases are accompanied by HER2 amplification and gene rearrangement.

Objective:To investigate the immunophenotypic and molecular biological characteristics of patients with elevated serum alpha-fetoprotein (AFP) and enteroblastic differentiated gastric adenocarcinoma (GAED).Methods:The clinicopathological data of 13 patients with elevated serum AFP and GAED admitted to Shanxi Cancer Hospital from 2018 to 2020 were collected. Immunohistochemistry (IHC) and next-generation sequencing (NGS) were used to analyze the immune markers and molecular biological characteristics of the pathological tissues of the patients. Kaplan-Meier method and log rank test were used for survival analysis.Results:Among the 13 patients with GAED, 12 were male and 1 was female, aged 41-70 years, with a median age of 64 years. The lesions were mainly located in the gastric antrum (5 cases) and gastric body (4 cases). IHC results showed that the tumor embryonic protein (AFP, SALL4, GPC3), intestinal epithelial differentiation protein (CDX-2, CD10), and some original intestinal epithelial phenotype markers (OCT3/4, Claudin6) were expressed in the tumor tissues. Combined application of multiple markers can reduce the rate of missed diagnosis. Among the 13 patients, 12 had at least one mutation (1 mutation: 1 case, 2-5 mutations: 3 cases, 6-15 mutations: 8 cases), and 1 case was not detected. The gene with the highest mutation frequency was TP53 (10 cases), and other mutant genes included EPHB1 (3 cases), ATRX (2 cases), EPHA5 (2 cases), GATA3 (2 cases), LRP1B (2 cases) and MAP2K4 (2 cases) were also detected. Three of the 13 patients had structural variations, which were C14orf177- GNAS, AIM1- FGFR3, and EPHA6- ROS1 gene rearrangements. All 13 patients had copy number variation, and 11 patients had copy number variation of more than 2 genes. The common amplification genes were IRS2 (5 cases), PTEN (5 cases), GNAS (4 cases), CCNE1 (3 cases), CEBPA (3 cases), PCK1 (3 cases) and ERBB2 (2 cases). The common deletion genes were SOX2 (5 cases) and MYC (5 cases). Among the 13 patients, 4 died, and 2 of the dead patients had liver metastasis. There were 4 patients with disease-free survival and 5 patients with disease progression, including 3 cases of abdominal metastasis and 2 cases of liver metastasis. The 3-year survival rate of patients was 65.9 %, and the 3-year progression-free survival rate was 30.7 %. Gene LRP1B point mutation was associated with poor prognosis ( P＜0.001). There was no significant improvement in the prognosis of patients treated with immunotherapy compared with those treated with chemotherapy alone ( P=0.595), but the prognosis of patients treated with postoperative chemotherapy or postoperative chemotherapy plus immunotherapy was better than that of patients treated with surgery alone ( P＜0.05). Conclusions:Elevated serum AFP with GAED is a highly invasive tumor with unique molecular characteristics, often accompanied by multiple molecular events. TP53 mutation is the most common type of gene mutation. In addition, some cases are accompanied by HER2 amplification and gene rearrangement.

Objective To conduct a scoping review of studies on online health information-seeking behavior interventions for older adults to determine the specific content,outcome indicators and effects of online health information-seeking behavior interventions for older adults,and to provide references for future research and practice.Methods Computer search was conducted to retrieve studies related to health information-seeking behavior intervention for older adults based on digital technology from PubMed,Embase,Web of Science,Cochrane Library,CNKI,Wanfang Database,and China Biomedical Literature Database.The search period was from the construction of the database to 18 January 2024.The included literature was screened and summarized by 2 researchers.Results 19 papers were included.Pre-intervention preparation for an online health information-seeking behavior intervention for older adults included participant recruitment,baseline surveys,and material preparation.Intervention content elements included training in basic computer and Internet knowledge and skills,knowledge and use of online health resources,evaluation of online health information quality,and application of online health information.The intervention sites were mainly places where older people live and work.Intervention time and frequency were 1-3 hours for one-time intervention training,1-2 times/week for 4-6 weeks for short-term intervention in ongoing intervention support,1-3 times/month for 3-4 months for long-term intervention.The outcome indicators are mainly related to computer knowledge and skills indicators,health attitudes indicators,online health information seeking behaviour indicators,and health behaviour indicators.Conclusion Online health information-seeking behaviour interventions for the elderly are feasible and effective,and high-quality empirical studies can be conducted in the future to improve online health information-seeking behaviour of the elderly and promote health management by improving intervention preparation,integrating technological innovations,and promoting the development of personalized intervention programs.

AIM To investigate the clinical effects of Modified Mahuang Lianqiao Chixiaodou Decoction on patients with chronic eczema.METHODS One hundred and ninety-five patients were randomly assigned into Chinese medicine group(65 cases)for 3-week administration of Modified Mahuang Lianqiao Chixiaodou Decoction,western medicine group(65 cases)for 3-week administration of Levocetirizine Hydrochloride,and combined group(65 cases)for 3-week administration of both Modified Mahuang Lianqiao Chixiaodou Decoction and Levocetirizine Hydrochloride.The changes in clinical effects,clinical indices(EASI score,DQOLS score,TCM syndrome score,PINS score),skin physiological function indicesssss(OCTS,TEWL,WCTC),inflammatory factors(EOT,EOS,NK-κB,CCR3),T lymphocyte subsets(Treg,Th1,Th17,Th22),p38MAPK signaling pathway indices(ERK1,ERK2,mMEK 1,MEK2),recurrence rate and incidence of adverse reactions were detected.RESULTS The combined group demonstrated higher total effective rate than the Chinese medicine group and the western medicine group(P＜0.05),along with lower recurrence rate(P＜0.05).After the treatment,the combined group displayed lower EASI score,TCM syndrome score,PINS,TEWL,inflammatory factors,Th1,Th17,Th22 and p38MAPK signaling pathway indices than the control group(P＜0.05),along with higher DQOLS score,OCTS,WCTC,Treg(P＜0.05).The Chinese medicine group exhibited lower incidence of adverse reactions than the other two groups(P＜0.05).CONCLUSION For the patients with chronic eczema,Modified Mahuang Lianqiao Chixiaodou Decoction can safely and effectively alleviate skin lesion degree,enhance skin physiological functions,improve T lymphocyte subset,inflammatory factors levels,and regulate p38MAPK signaling pathway based on"Four-in-One"therapy,which exhibits synergistic effect when combined with Levocetirizine Hydrochloride.

Radiotherapy is widely used in the management of advanced colorectal cancer (CRC). However, the clinical efficacy is limited by the safe irradiated dose. Sensitizing tumor cells to radiotherapy via interrupting DNA repair is a promising approach to conquering the limitation. The BRCA1-BARD1 complex has been demonstrated to play a critical role in homologous recombination (HR) DSB repair, and its functions may be affected by HERC2 or BAP1. Accumulated evidence illustrates that the ubiquitination-deubiquitination balance is involved in these processes; however, the precise mechanism for the cross-talk among these proteins in HR repair following radiation hasn't been defined. Through activity-based profiling, we identified PT33 as an active entity for HR repair suppression. Subsequently, we revealed that BAP1 serves as a novel molecular target of PT33 via a CRISPR-based deubiquitinase screen. Mechanistically, pharmacological covalent inhibition of BAP1 with PT33 recruits HERC2 to compete with BARD1 for BRCA1 interaction, interrupting HR repair. Consequently, PT33 treatment can substantially enhance the sensitivity of CRC cells to radiotherapy in vitro and in vivo. Overall, these findings provide a mechanistic basis for PT33-induced HR suppression and may guide an effective strategy to improve therapeutic gain.

Objective To investigate the nursing clinical practice of ICU ventilator-associated pneumonia(VAP)prevention and control of tertiary hospitals in China,and analyze relevant countermeasures.Methods A self-designed questionnaire consisted of 3 parts and 26 items.A questionnaire survey was conducted among nurses in 380 ICUs in 194 tertiary hospitals in 26 provinces from September 1 to 15,2021,using the convenient sampling method.Results A total of 380 valid questionnaires were collected,with an effective rate of 100%.In the system process,369(97.11%)ICUs had files to prevent VAP;291(76.58%)ICUs had a checklist of measures to prevent VAP clustering;274(72.11%)ICUs had continuous improvement projects about VAP in the last 3 years.In the aspect of body position management,semi-decubitus position was the first choice for the patients with invasive mechanical ventilation of 338(88.95%)ICUs.For nursing operation,224(58.95%)ICUs used Subglottic suction,and 128(33.68%)among them used air shock to remove the retention on the balloon;normal saline is still routinely injected before sputum aspiration in 72(18.95%)ICUs.In terms of balloon pressure monitoring,253(66.58%)ICUs did the oral care 3-4 times a day.In the balloon pressure monitoring,313(82.37%)ICUs use airbag pressure gauges to intermittently monitor airbag pressure;293(77.11%)ICUs replaced the ventilator pipeline once a week.There are significant differences in the current practice status of different types of ICUs in terms of compliance strategies for bed head lifting,subglottic secretion drainage,airbag pressure monitoring,and oral care(P<0.05).Conclusion At present,the relevant systems and procedures to prevent VAP have been improved,but the specific prevention and control measures need to be further unified.Therefore,it is suggested to analyze the weak links of VAP nursing prevention and control practice in various medical structures,carry out relevant training and quality control for the weak links,and further improve the working mechanism of continuous quality improvement,thus effectively reduce the incidence of VAP.