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.

As a new transdermal drug delivery system, microneedles can significantly improve skin permeability, enhance drug transdermal delivery, and demonstrate unique advantages in breaking stratum corneum barrier of skin. This feature enables microneedles to demonstrate enormous potential in delivering biotechnology drugs. The traditional delivery method for biotechnology drugs is mainly injection, which brings problems such as pain and skin redness to patients, leading to poor patient compliance. In addition, the production, transportation, and storage of biotechnology drugs require strict low-temperature conditions to maintain their activity and increase cost output. Microneedles, by contrast, have many benefits, providing new avenues and solutions for biomolecular delivery. Accordingly, this review introduced the microneedle drug delivery system for delivery biotechnology drugs, and summarized the research progress of microneedle systems in biotechnology drugs.

Immmunosuppressants are mainly used to reduce rejection after solid organ transplantation,so as to improve the success rate of organ transplantation.However,long-term use of immunosuppressants can also serious-ly impair the immune function of patients,thereby increasing the risk of viral infection and postoperative complica-tions,leading to transplant failure.Therefore,patients need to use both immunosuppressants and antiviral agents.If some immunosuppressants with antiviral effects are found,the patient's burden of taking medicines will be greatly reduced.Currently,the immunosuppressants with antiviral effect have been focused by researchers.The gradual re-vealing of the antiviral mechanism of these immunosuppressants will help to optimize the treatment plan of postope-rative rehabilitation of organ transplant recipients.Based on the mechanism of rejection of transplanted organ,this paper systematically describes the types of viruses which closely related to infection of organ transplant patients and the molecular mechanism of some immunosuppressants in antiviral aspects,which further provides a new idea for clinical prevention and treatment of viral infection due to organ transplantation.

Objective To explore the range of normal female pelvic diameter lines in Tibetan nationality. Methods The subjects were Tibetan nationality female who underwent pelvic CT examination in the Radiology Department from January 2016 to December 2019 at the General Hospital of the Tibet Military Region of PLA. Ninty-six samples between the ages of 22 and 65 years, with an average age (46.06±11.42)years were recruited. Mimics 19.0 software was used to construct the digital three-dimensional model of pelvis, and to measure transverse diameter(TD), obstetric conjugate(OC), interspinous distance(ISD), sagittal midpelvic diameter(SMD), intertuberous distance(ITD), sagittal outlet diameter(SOD),diagonal conjugate diameter(DCD),sacrum length(SL), penal height(PH).Analysis of variance was used to compare different age groups, and Pearson correlation analysis was used to analyze the relationship between age and pelvic diameter. Results The linear measurement of TD was (132.08±6.15) mm, OC was (112.44±9.43) mm, ISD was (107.30±8.70), SMD was (129.06±7.73) mm, ITD was (123.02±12.08) mm, SOD was (118.80±8.87) mm, DCD was (127.49±9.80) mm, SL was (102.56±10.88) mm and PH was (36.57±4.57) mm.Cluster analysis showed that Lhasa Tibetans were closest to Uygurs. Conclusion The close clustering relationship between Tibetans and Uygurs in Lhasa suggests that there is a possibility of gene exchange between Tibetans and Uygurs in Hotan area in ancient times. The pelvic diameter of Tibetan women in Lhasa has changed significantly. Narrower OC, SL and PH make the pelvis flat, which is more and more detrimental to natural childbirth.

H 1-antihistamines are widely used in the treatment of various allergic diseases, but there are still many challenges in the safe and rational use of H 1-antihistamines in pediatrics, and there is a lack of guidance on the prescription review of H 1-antihistamines for children.In this paper, suggestions are put forward from the indications, dosage, route of administration, pathophysiological characteristics of children with individual difference and drug interactions, so as to provide reference for clinicians and pharmacists.

Anti-seizure medications (ASMs) are the main therapy for epilepsy.There are many kinds of ASMs with complex mechanism of action, so it is difficult for pharmacists to examine prescriptions.This paper put forward some suggestions on the indications, dosage forms/routes of administration, appropriateness of usage and dosage, combined medication and drug interaction, long-term prescription review, individual differences in pathophysiology of children, and drug selection when complicated with common epilepsy, for the reference of doctors and pharmacists.

OBJECTIVE: To investigate whether 3D-printed artificial vertebral body can reduce prosthesis subsidence rate for patients with cervical chordomas, through comparing the rates of prosthesis subsidence between 3D printing artificial vertebral body and titanium mesh for anterior spinal reconstruction after total spondylectomy. METHODS: This was a retrospective analysis of patients who underwent surgical treatment for cervical chordoma at our hospital from March 2005 to September 2019. There were nine patients in the group of 3D artificial vertebral body (3D group), and 15 patients in the group of titanium mesh cage (Mesh group). The patients' characteristics and treatment data were extracted from the medical records, including age, gender, CT hounsfield unit of cervical vertebra and surgical information, such as the surgical segments, time and blood loss of surgery, frequency and degree of prosthesis subsidence after surgery. Radiographic observations of prosthesis subsidence during the follow-up, including X-rays, CT, and magnetic resonance imaging were also collected. SPSS 22.0 was used to analysis the data. RESULTS: There was no significant difference between the two groups in gender, age, CT hounsfield unit, surgical segments, time of surgery, blood loss of posterior surgery and total blood loss. Blood loss of anterior surgery was 700 (300, 825) mL in 3D group and 1 500 (750, 2 800) mL in Mesh group (P < 0.05). The prosthesis subsidence during the follow-up, 3 months after surgery, there was significant difference between the two groups in mild prosthesis subsidence (P < 0.05). The vertebral height of the 3D group decreased less than 1 mm in eight cases (no prosthesis subsidence) and more than 1 mm in one case (mild prosthesis subsidence). The vertebral height of the Mesh group decreased less than 1 mm in five cases (no prosthesis subsidence), and more than 1 mm in eight cases (mild prosthesis subsidence). Two patients did not have X-rays in 3 months after surgery. There was a statistically significant difference between the two groups in the prosthesis subsidence rate at the end of 12 months (P < 0.01). The vertebral height of eight cases in the 3D group decreased less than 1 mm (no prosthesis subsidence) and one case more than 3 mm (severe prosthesis subsidence). Four of the 15 cases in the Mesh group decreased less than 1 mm (no prosthesis subsidence), two cases more than 1 mm (mild prosthesis subsidence), and nine cases more than 3 mm (severe prosthesis subsidence). There was a statistically significant difference between the two groups in the prosthesis subsidence rate at the end of 24 months (P < 0.01). The vertebral height of seven cases in the 3D group decreased less than 1 mm (no prosthesis subsidence), one case more than 3 mm (severe prosthesis subsidence), and one case died with tumor. One case in the Mesh group decreased less than 1 mm (no prosthesis subsidence), one case more than 1 mm (mild prosthesis subsidence), 11 case more than 3 mm (severe prosthesis subsidence), one case died with tumor and one lost the follow-up. Moreover, at the end of 12 months and 24 months, there was significant difference between the two groups in severe prosthesis subsidence rate (P < 0.01). CONCLUSION 3D-printed artificial vertebral body for anterior spinal reconstruction after total spondylectomy for patients with cervical chordoma can provide reliable spinal stability, and reduce the incidence of prosthesis subsidence after 2-year follow-up.
Humans ; Chordoma/surgery* ; Retrospective Studies ; Vertebral Body ; Titanium ; Cervical Vertebrae/surgery* ; Printing, Three-Dimensional ; Spinal Fusion/methods* ; Treatment Outcome

OBJECTIVE: To analysis clinical phenotype and potential genetic cause of a family affected with hereditary coagulation factor Ⅻ deficiency. METHODS: The prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), D-Dimer (D-D), coagulation factor Ⅻ activity (FⅫ:C) and coagulation factor Ⅻ antigen (FⅫ:Ag) were determined for phenotype diagnosis of the proband and his family members(3 generations and 5 people). Targeted capture and whole exome sequencing were performed in peripheral blood sample of the proband. Possible disease-causing mutations of F12 gene were obtained and further confirmed by Sanger sequencing. The corresponding mutation sites of the family members were analyzed afterwards. The online bioinformatics software AutoPVS1 and Mutation Taster was used to predict the effects of mutation sites on protein function. RESULTS: The APTT of the proband was significantly prolonged, reaching 180.9s. FⅫ:C and FⅫ:Ag of the proband was significantly reduced to 0.8% and 4.17%, respectively. The results of whole exome sequencing displayed that there were compound heterozygous mutations in F12 gene of the proband, including the c.1261G＞T heterozygous nonsense mutation in exon 11 (causing p.Glu421*) and the c.251dupG heterozygous frameshift mutation in exon 4 (causing p.Trp85Metfs*53). Both mutations are loss of function mutations with very strong pathogenicity, leading to premature termination of the protein. AutoPVS1 and Mutation Taster software predicted both mutations as pathogenic mutations. The results of Sanger sequencing revealed that c.1261G＞T heterozygous mutation of the proband was inherited from his mother, for which his brother and his daughter were c.1261G＞T heterozygous carriers. Genotype-phenotype cosegregation was observed in this family. CONCLUSION The c.1261G＞T heterozygous nonsense mutation in exon 11 and the c.251dupG heterozygous frameshift mutation in exon 4 of the F12 gene probably account for coagulation factor Ⅻ deficiency in this family. This study reports two novel pathogenic F12 mutations for the first time worldwide.
Blood Coagulation Disorders ; Codon, Nonsense ; Factor XII/genetics* ; Female ; Heterozygote ; Humans ; Male ; Mutation ; Pedigree

Brain Neoplasms/surgery* ; Cyclic AMP Response Element-Binding Protein ; Gene Fusion ; Humans ; Oncogene Proteins, Fusion/genetics* ; RNA-Binding Protein EWS/genetics*

Echinococcosis is a zoonotic parasitic disease caused by Echinococcus infections, and this disorder may cause fibrosis of multiple vital organs, which may further progress into cirrhosis. Early-stage hepatic fibrosis is reversible, and unraveling the mechanisms underlying hepatic fibrosis induced by Echinococcus infections is of great significance for the prevention and treatment of early-stage hepatic fibrosis. Recently, the studies pertaining to hepatic fibrosis associated with Echinococcus infections focus on cytokines and immune cells. This review summarizes the advances in the mechanisms underlying host immune cells- and cytokines-mediated hepatic fibrosis in humans or mice following Echinococcus infections.