Obiective Alzheimer’s disease (AD) is a degenerative disease of the central nervous system (CNS) caused by a variety of risk factors. There are various pathological changes, but apoptosis of the neurological meridian cells is one of the most important pathological bases. Hyperlipidemia is a high-risk factor for the development of AD, which can lead to increased levels of oxidized low-density lipoprotein (ox-LDL) in brain tissues. PCSK9 is a protease closely related to lipid metabolism, but studies have shown that it may be related to the development of AD. LRP1 is abundantly expressed in neuronal cells, and it is an important transporter for the clearance of Aβ. There is now a large amount of literature confirming that PCSK9 can induce the degradation of LRP1. PI3K/AKT is an important signaling pathway in vivo, which plays an important role in apoptosis, and there is now a large amount of literature confirming that LRP1 activates the PI3K/AKT pathway, which has an anti-apoptotic effect. So can PCSK9 affect the PI3K/AKT pathway through LRP1 and thus regulate neuronal apoptosis? This deserves further investigation.The aim of this study was to explore the role of PCSK9 in mediating ox-LDL pro-apoptotic neuronal cell death and its mechanism, and then further elaborate the mechanism of hyperlipidemia leading to neurodegenerative diseases such as AD. MethodsFirstly, PC12 cells were treated with different concentrations of ox-LDL (0, 25, 50, 75 and 100 mg/L) for 24 h. Oil red O staining was used to detect lipid accumulation in PC12 cells, Hoechst33258 staining and flow cytometry to detect apoptosis in PC12 cells, ELISA to detect the content of Aβ secreted by PC12, Western blot to detect expression of SREBP2, PCSK9 and LRP1. Then PC12 cells were treated with 75 mg/L ox-LDL for different times (0, 6, 12, 24, 48 h), and Western blot were performed to detect the expression of SREBP2, PCSK9 and LRP1. Finally, after transfecting 100 nmol/L PCSK9 siRNA into PC12 cells for 48 h, PC12 cells were treated with 75 mg/L ox-LDL for 24 h, Hoechst33258 staining and flow cytometry to detect apoptosis rate of PC12 cells, and Western blot to detect PCSK9, LRP1, PI3K, AKT, P-PI3K , P-AKT, NF-κB, Bcl-2, Bax, Caspase-9 and Caspase-3 expression, and ELISA detected Aβ content secreted by PC12 cells. Resultsox-LDL increased lipid accumulation and promoted apoptosis and Aβ secretion in PC12 cells, as well as increasing the expression of SREBP2 and PCSK9 and decreasing the expression of LRP1 in PC12 cells. pCsk9 siRNA could be inhibited through the PI3K/AKT pathway and the NF-κB-Bcl-2/Bax-Caspase-9/3 pathway to inhibit ox-LDL-induced apoptosis in PC12 cells while increasing Aβ secretion in PC12 cells. Conclusionox-LDL plays a bidirectional regulatory role in ox-LDL-induced apoptosis of PC12 cells by inducing an increase in PCSK9 expression and a decrease in LRP1 expression in PC12 cells, which in turn affects different signaling pathways downstream.

Di-(2-ethylhexyl) phthalate (DEHP) is currently one of the most widely used plasticizers, widely found in all kinds of items, such as children’s toys and food packaging materials, but also added to wallpaper, cable protective agents and other building decoration materials. DEHP is toxic and absorbed by the human body through respiratory tract, digestive tract and skin contact, which can cause damage to multiple systems, especially the male reproductive system, and testis is an important target organ. Oxidative stress injury is the core mechanism of spermatogenesis disorder caused by DEHP. DEHP exposure can cause oxidative stress or reactive oxygen species (ROS) increase in germ cells, and on this basis, promote cell apoptosis or cause excessive autophagy. The toxicity of DEHP to Leydig cells is mainly to interfere with the synthesis of steroid hormones. For Sertoli cells, ferroptosis and destruction of the blood-testis barrier are common injury mechanisms. In addition, gene methylation caused by DEHP not only affects the spermatogenic process, but also has epigenetic effects on offspring. In this paper, we reviewed the pathological damage, germ cell toxicity and epigenetic effects of DEHP on testis, and focused on the damage and molecular mechanism on testicular spermatogenic cells, Leydig cells and Sertoli cells. Future research is required to elucidate the body’s clearance mechanism and treatment plan after exposure to DEHP and whether DEHP will damage the function of myoid cells. It is hoped that this can provide new ideas for prevention and treatment of male reproductive disorders resulting from long-term exposure to plastic products.

Objective To observe the value of radiomics models based on gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid(Gd-EOB-DTPA)enhanced hepatobiliary phase(HBP)MRI for assessing clinical pathological stage of hepatic fibrosis(HF).Methods Data of 240 patients with pathologically/clinically diagnosed and clinical pathological staged HF who underwent Gd-EOB-DTPA enhanced MR examination were retrospectively analyzed.The liver-to-muscle signal intensity ratio(SIR1)and liver-to-spleen signal intensity ratio(SIR2)were measured based on HBP images.Radiomics features of HBP images were extracted and screened to construct radiomics models.The signal intensity ratio(SIR)-radiomics combined models were constructed based on SIR and radiomics signatures.Receiver operating characteristic(ROC)curves were drawn to evaluate the efficacy of each model for assessing clinical pathological stage of HF.Results The area under the curve(AUC)of SIR1 and SIR2 models for assessing clinical pathological stage of HF were 0.63-0.70 and 0.65-0.71,respectively.The most effective radiomics model for assessing HF,significant HF,advanced HF and early cirrhosis was support vector machine(SVM),SVM,light gradient boosting machine and K-nearest neighbor model,respectively,with the AUC in validation set of 0.87,0.82,0.81 and 0.80,respectively,while the AUC of SIR-radiomics combined models in validation set of 0.88,0.82,0.82 and 0.81,respectively.Conclusion The radiomics models based on Gd-EOB-DTPA enhanced HBP MRI were helpful for assessing clinical pathological stage of HF.Combining with HBP SIR could improve their efficacy.

Morita therapy has been bom for more than 100 years.Inpatient Morita therapy is highly oper-able and easy to master.It can improve many refractory neuroses through four-stage treatment.But more neuroses are treated in outpatient clinics,and Morita therapy cannot be used in hospitalized patients.Therefore,the formula-tion of expert opinions on outpatient operations is particularly important.This paper is based on domestic and for-eign references,and after many discussions by domestic Morita therapy experts,and then drew up the first version of the expert opinions on operation of outpatient Morita therapy.Meanwhile the operation rule of Morita therapy in three stages of outpatient treatment was formulated:in the etiological analysis stage,under the theoretical guidance of Morita therapy,analyze the pathogenic factors,to improve treatment compliance and reduce resistance;during the operating stage,guide patients to engage in constructive and meaningful actions,realizing the achievement of letting nature take its course principle;in the cultivating character and enriching life stage,pay attention to positive infor-mation,expanding the scope and content of actions,improving the ability to adapt to complex life,and preventing recurrence caused by insufficient abilities.It will lay a foundation for the promotion of Morita therapy in domestic outpatient clinics,so that more patients with neurosis and other psychological diseases could receive characteristic Morita therapy treatment in outpatient clinics.

Objective To investigate the status of familial aggregation of Helicobacter pylori (Hp) infection in Jinniu District, Chengdu, and analyze its risk factors so as to provide a basis for developing prevention and control strategies of family aggregation of Hp infection. Methods A total of 172 subjects in the Second Affiliated Hospital of Chengdu Medical College · 416 Hospital of Nuclear Industry from January 2022 to January 2023 were selected as the research subjects. All subjects underwent 13C-urea breath test (13C-UBT) to diagnose whether there was Hp infection. Analyze the current situation of family aggregation of Hp infection in the region, collect general data of survey subjects, analyze the relevant factors affecting Hp family aggregation infection, and develop prevention and control strategies based on this. Results A total of 242 people from 97 households were surveyed, and the Hp family aggregation rate was 29.33%. Univariate analysis showed that there were statistically significant differences in family aggregation of Hp infection in terms of different age groups (χ²=9.719, P=0.008), marital status (χ²=8.496, P=0.014), occupations (χ²=19.462, P<0.001), frequencies of dining out (χ²=5.457, P=0.019), previous Hp test results (χ² =4.131, P=0.042) and test results after treatment (χ²=12.000, P=0.001), with statistical significance (P<0.05). Multivariate logistic regression analysis showed that the frequency of dining out 2 days or more per week and a positive Hp test results in the past were risk factors for family aggregation of Hp infection, while the occupation of teachers/medical staff/management/technology personnel and a negative Hp results after treatment were protective factors (P<0.05). Conclusion Family aggregation of Hp infection is related to family members' occupation, frequency of dining out, previous Hp test results and Hp test results after eradication, which deserves attention in clinical practice.

Objective To explore the correlation between exponential apparent diffusion coefficient(eADC)value before radical hysterectomy and postoperative clinical results in patients with International Federation of Gynecology and Obstetrics(FIGO)stageⅠ/Ⅱ cervical cancer,and to find MR quantitative indicators for predicting the prognosis of patients with early stage cervical cancer.Methods Patients with FIGO stage Ⅰ/Ⅱ cervical cancer who underwent surgical treatment were retrospectively collected.All patients underwent MRI plain scan and diffusion weighted imaging(DWI)scan before surgery.Baseline parameters included age,menopause,stage,tumor size,pathological differentiation and type,lymph node involvement,and postoperative adjuvant therapy.MR parameters included mean apparent diffusion coefficient(ADCmean),normalized apparent diffusion coefficient(nADC),eADC,SIDWI,and SIT2.Baseline and MRI parameters associated with recurrence were determined by Cox regression analysis.Results The progression-free survival(PFS)in the low eADC group was longer than that in the high eADC group(P=0.010).Univariate analysis showed that ADC,nADC and eADC were associated with recurrence(P<0.05).In multivariate analysis,only eADC[hazard ratio(HR)3.610;95%confidence interval(CI)1.467-8.886;P=0.005]was associated with recurrence.Conclusion Preoperative eADC is associated with PFS in patients with surgically treated FIGO stage Ⅰ/Ⅱ cervical cancer and is helpful in evaluating the prognosis of patients with cervical cancer.

Objective: Hypertrophy ligamentum flavum (LFH) is a common cause of lumbar spinal stenosis, resulting in significant disability and morbidity. Although long noncoding RNAs (lncRNAs) have been associated with various biological processes and disorders, their involvement in LFH remains not fully understood. Methods: Human ligamentum flavum samples were analyzed using lncRNA sequencing followed by validation through quantitative real-time polymerase chain reaction. To explore the potential biological functions of differentially expressed lncRNA-associated genes, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed. We also studied the impact of lncRNA PARD3-AS1 on the progression of LFH in vitro. Results: In the LFH tissues when compared to that in the nonhypertrophic ligamentum flavum (LFN) tissues, a total of 1,091 lncRNAs exhibited differential expression, with 645 upregulated and 446 downregulated. Based on GO analysis, the differentially expressed transcripts primarily participated in metabolic processes, organelles, nuclear lumen, cytoplasm, protein binding, nucleic acid binding, and transcription factor activity. Moreover, KEGG pathway analysis indicated that the differentially expressed lncRNAs were associated with the hippo signaling pathway, nucleotide excision repair, and nuclear factor-kappa B signaling pathway. The expression of PARD3-AS1, RP11-430G17.3, RP1-193H18.3, and H19 was confirmed to be consistent with the sequencing analysis. Inhibition of PARD3-AS1 resulted in the suppression of fibrosis in LFH cells, whereas the overexpression of PARD3-AS1 promoted fibrosis in LFH cells in vitro. Conclusion This study identified distinct expression patterns of lncRNAs that are linked to LFH, providing insights into its underlying mechanisms and potential prognostic and therapeutic interventions. Notably, PARD3-AS1 appears to play a significant role in the pathophysiology of LFH.

With the increasing awareness of the adverse effects of long-acting opioids,opioid free anesthesia(OFA)is important in clinical practice.Regional block plays an important role in reducing perioperative opioids demands due to its analgesic effect.In this article,we review the application of regional block in neurosurgery,breast surgery,and thoracic surgery to explore the clinical progress of this kind of anesthetic technique.

To investigate the perinatal features of fetal Kaposiform hemangioendothelioma(KHE)complicated with Kasabach-Merritt syndrome(KMS),we reported an incidental ultrasound finding of a subcutaneous mass on the back of the foetus in a 36-year-old woman at 38 weeks of pregnancy,with no other abnormal prenatal findings.The dorsal mass was hypoechoic,approximately 6-7 cm in diameter,and Doppler showed a striated blood flow signal.Fetal growth measurements were consistent with gestational age,and the amniotic fluid volume was normal.A live-born boy was delivered by caesarean section.The neonate had a large subcutaneous haemangioma on the left dorsum with thrombocytopenia and coagulopathy.He was diagnosed with KMS and was treated with intravenous high dose pulse methylprednisolone,sirolimus,surgical resection and blood transfusion.Histopathological and immunohistochemical findings confirmed tufted hemangioma and KHE.There was no residual recurrence on postoperative follow-up of 6 months.