Objective To explore the effects and mechanisms of escitalopram on the expression of glial cell line-derived neurotrophic factor(GDNF) in hippocampus of depression model rats.Methods 40 male SD rats were randomly divided into four groups:control group(group A),control + escitalopram group (group B),depressive group (group C),and depressive + escitalopram group (group D).Chronic mild unpredicted stress (CUMS)with solitary condition was taken to establish rat depression model.And the group B and D were treated with intragastric admistration of escitalopram(10 mg · kg-1 · d-1),the group A and C with sodium chloride.The open-field test and sucrose consumption were used to evaluate the depression behaviors of rats.The apoptotic hippocampal cells were detected by TUNEL.And the expression of GDNF,Bax,Bcl-2 and Caspase3 mRNA were detected by real-time RT-PCR.Results ① Compared with group A(12.0 ± 1.83),the number of apoptotic cells in hippocampus was significantly increased in group C (19.3 ± 1.77) (P ＜ 0.01),while group B (11.9 ± 1.91) was no significant difference (P＞ 0.05).Compared with group C,the group D(12.7 ± 1.77) had a significant reduction in the number of apoptotic cells (P ＜ 0.01).②Compared with group A,GDNF and Bcl-2 mRNA expression was decreased (P ＜ 0.01),but Bax and Caspase3 mRNA expression was both increased significantly in group C(P＜0.01) ;while in group D,GDNF and Bcl-2 mRNA expression was higher (P ＜0.01),but Bax and Caspase3 mRNA expression was lower than that in group C (P ＜0.01).Conclusion Escitalopram can improve depressive behaviors and reduce hippocampal apoptosis,which maybe associate with increasing GDNF protein and mRNA expression,and promoting the regeneration of neurons,up-regulating of mRNA Bcl-2 expression,and down-regulating of mRNA Bax and Caspase3 expression.Finally it may prevent the neuronal apoptosis in hippocampal and play the role of cerebral protection.

Objective To observe the effect of Shenqi Fuzheng injection combined with chemotherapy on reducing the side effects of malignant tumor chemotherapy. Methods Eighty cancer patients in Traditional Chinese Medicine Hospital of PLA General Hospital from January 2015 to March 2017 were randomly divided into treatment group and control group by using random number table method, each group contained 40 cases. The patients in the treatment group were given Shenqi Fuzheng injection combined with chemotherapy, while the control group used chemotherapy only. Results The incidence of WBC and Plt reduction in the treatment group [35.0 % (14/40), 32.5 % (13/40)] was lower than those in the control group [70.0 % (28/40), 57.5 % (23/40)], and the differences were statistically significant (χ 2= 9.825, P = 0.002;χ2=5.051, P=0.025). The incidence rates of digestive tract reaction and oral ulcers[52.5 %(21/40), 32.5 % (13/40)]were lower than those in the control group[75.0 %(30/40), 60.0 %(24/40)], and the differences were statistically significant (χ2= 4.381, P = 0.036; χ2= 6.084, P = 0.014). The quality of life in the treatment group was significantly improved compared with the control group [(51.4 ±5.1) points vs. (48.3±5.5) points], and the difference was statistically significant(t =2.595,P =0.011). Conclusions Shenqi Fuzheng injection combined with chemotherapy can reduce chemotherapy-induced side effects and improve the life quality of the patients.The injection can be used as the adjuvant therapy for chemotherapy in clinic application.

Objective:To study the effects of rolling blood pump parameters and blood concentration on hemolysis during extracorporeal circulation.Methods:According to the extracorporeal hemolysis experiment standard, an extracorporeal circulation experimental device was built to analyze the influences of circulation time (0 ~ 90 min), blood flow rate (1~4 L/min), and blood volume fraction (60%, 70%) on the hemolysis of blood samples in the circulatory system. The results of hemolysis were analyzed using first-order linear regression.Results:The longer the blood pump circulation time, the greater the hemolysis rate; the higher the blood flow rate, the greater the hemolysis rate. When the flow rate is 1 and 2 L/min, the hemolysis rate curve has an inflection point that changes with time, i.e. when the circulation time exceeds 30 min, the slope of the hemolysis rate curve suddenly increases. However, when the flow rate is 3 and 4 L/min, the hemolysis mutation phenomenon is not obvious. Compared to the blood sample with blood volume fraction of 70%, a blood sample with a blood volume fraction of 60% is less prone to hemolysis.Conclusions:The longer the blood pump circulation time and the higher the blood flow rate, the more easily the red blood cells are destroyed, i.e. the hemolysis rate is directly proportional to the circulation time and blood flow rate. When the circulation time increases to a certain degree, an inflection point appears in the hemolysis rate curve, and the hemolysis trend will be significantly enhanced.

Hedgehog （Hh） signaling pathway plays an important regulatory role in the process of cell proliferation， differentiation and tissue formation. Proper intensity and action time of Hh signal are crucial for the normal development of various tissues of the body， and its abnormal activation will lead to the occurrence and development of most malignant tumors， including breast cancer， liver cancer， pancreatic cancer， and lung cancer， which makes Hh signaling pathway an ideal target for anti-tumor drug research and development. At present， the main targets of Hh signaling pathway inhibitors include Hh ligand， receptor Smoothened （Smo） and transcription factor Gli. Among them， the compounds that depend on the Hh ligand pathway still remain at the stage of laboratory research because they cannot act on the non-classical Hh signaling pathway. The special structure of Smo protein enables it to combine with drugs efficiently and selectively， which is a powerful and effective drug target. Therefore， Smo selective inhibitors have been an active field of related research， and many Smo inhibitors have entered the clinical use or trial stage. Gli can regulate multiple carcinogenic genes， promote abnormal cell proliferation and lead to tumor， and can also cause feedback inhibition to Hh signaling pathway. Therefore， the development of drugs that can inhibit the activity of Gli has broad prospects. In the future， a combination of multiple pathway inhibitors can be designed to avoid drug resistance and other side effects.

Autoimmune diseases of the nervous system are a group of diseases caused by the body′s immune system attacking its own nervous system, resulting in structural damage and functional impairment of the corresponding tissues. Interventional clearance of pathogenic auto-antibodies has been shown to be effective in reducing immune damage, inhibiting disease progression and improving prognosis through extensive basic research and long-term clinical practice. The neonatal Fc receptor (FcRn)-mediated circulating protection mechanism of IgG contributes to the long half-life and high plasma levels of IgG. FcRn inhibitors are able to target and block the binding of FcRn to IgG, accelerating IgG clearance and reducing IgG levels. Therefore, the use of FcRn inhibitors in the treatment of autoimmune diseases of the nervous system could theoretically help to accelerate the clearance of pathogenic IgG, achieve good clinical efficacy and have promising applications. Research in this area has made considerable progress in recent years and this article will review this.

Objective:To observe the efficacy and safety of albumin paclitaxel in patients with advanced breast cancer.Methods:A retrospective analysis was performed on 138 patients with advanced breast cancer admitted to Xiangyang Central Hospital from June 2018 to June 2021. The patients were divided into groups according to molecular type, number of treatment lines for albumin paclitaxel, number of metastatic sites, specific metastatic sites, past use of docetaxel and paclitaxel and combination therapy of albumin paclitaxel. Median progression-free survival (mPFS) and treatment-related adverse reactions in different subgroups treated with albumin paclitaxel were investigated. Survival curves were plotted by Kaplan-Meier method and log-rank test was performed, and multivariate analysis was performed by Cox model.Results:The mPFS of the overall population was 8.2 months. The mPFS of triple negative breast cancer, human epidermal growth factor receptor-2 (HER-2) positive breast cancer and Luminal breast cancer were 6.4 months, 11.2 months and 8.1 months respectively, with a statistically significant difference (χ 2=7.42, P=0.025) . The mPFS of patients treated with first- and second-line albumin paclitaxel was 9.5 months, and the mPFS of patients treated with third- to seventh-line was 6.3 months (χ 2=3.86, P=0.049) . The mPFS of patients with ≤3 metastatic sites was 8.1 months, and the mPFS of patients with >3 metastatic sites was 7.0 months (χ 2=0.38, P=0.535) . The mPFS of patients with liver and brain metastases was 6.8 months, and the mPFS of patients with extrahepatic and extracerebral metastases was 9.6 months (χ 2=7.53, P=0.006) . The mPFS of patients who had previously treated with docetaxel and paclitaxel was 8.2 months, and the mPFS of patients who had not previously received docetaxel or paclitaxel was 9.6 months (χ 2=0.03, P=0.862) . The mPFS of patients with albumin paclitaxel combined with targeted therapy, combined with immunotherapy, combined with chemotherapy and monotherapy were 12.1, 7.8, 9.0 and 7.1 months respectively, with a statistically significant difference (χ 2=8.96, P=0.030) . Multivariate analysis showed that molecular type (triple negative breast cancer RR=1.87, 95% CI: 1.24-4.22, P=0.008; HER-2 positive breast cancer RR=0.63, 95% CI: 0.52-0.94, P=0.042) , number of treatment lines ( RR=0.67, 95% CI: 0.32-0.86, P=0.011) , specific metastatic sites ( RR=1.26, 95% CI: 1.12-2.75, P=0.014) and combination therapy (combined with targeted therapy RR=0.74, 95% CI: 0.16-0.86, P=0.021; combined with chemotherapy RR=0.93, 95% CI: 0.48-0.96, P=0.045; combined with immunotherapy RR=0.81, 95% CI: 0.17-0.78, P=0.032) were independent factors for prognosis. The main adverse reactions were alopecia, neutropenia, peripheral neurotoxicity and rash, and there was no death caused by adverse reactions. Conclusion:Albumin paclitaxel is effective in the treatment of advanced breast cancer with controllable adverse reactions.

OBJECTIVE: To explore the genetic basis for a Chinese patient suspected for Canavan disease. METHODS: Whole exome sequencing (WES) was carried out for the proband, and candidate variants were verified by Sanger sequencing of the proband, her parents and brother. Prenatal diagnosis was provided to her mother by chorionic villi sampling (CVS) upon her subsequent pregnancy. RESULTS: The proband, a 4-month-old female infant, had manifested drowsiness, hypotonia and apathy. Urine metabolism screening showed elevated N-acetylaspartic acid. Cranial magnetic resonance imaging revealed abnormal myelination and multiple abnormal signals in large brain areas. WES revealed that the proband has harbored compound heterozygous variants of the ASPA gene, namely c.187A>G (p.Arg63Gly) in exon 1 and c.634+1G>A (P.?) in exon 4. Sanger sequencing confirmed that the c.187A>G (p.Arg63Gly) and c.634+1G>A (p.?) variants were respectively inherited from her mother and father. Her phenotypically normal brother has carried a heterozygous c.634+1G>A (p.?) variant. Prenatal diagnosis by CVS indicated that the fetus was a heterozygous carrier of the c.187A>G variant. CONCLUSION WES can facilitate the diagnosis of Canavan disease, particularly for those lacking specific phenotypes of the disease. The compound heterozygous variants of the ASPA gene probably underlay the Canavan disease in this patient, and the result has enabled prenatal diagnosis for this family.
Canavan Disease/genetics* ; China ; Female ; Humans ; Male ; Mutation ; Pedigree ; Pregnancy ; Prenatal Diagnosis

OBJECTIVE: To explore the clinical and genetic features of a child with autosomal dominant mental retardation type 40 (MRD40) due to variant of the CHAMP1 gene. METHODS: Clinical characteristics of the child were analyzed. Genetic testing was carried out by low-depth high-throughput and whole genome copy number variant sequencing (CNV-seq) and whole exome sequencing (WES). A literature review was also carried out for the clinical phenotype and genetic characteristics of patients with MRD40 due to CHAMP1 gene variants. RESULTS: The child, a 11-month-old girl, has presented with intellectual and motor developmental delay. CNV-seq revealed no definite pathogenic variants. WES has detected the presence of a heterozygous c.1908C>G (p.Y636*) variant in the CHAMP1 gene, which was carried by neither parent and predicted to be pathogenic. Literature review has identified 33 additional children from 12 previous reports. All children had presented with developmental delay and mental retardation, and most had dystonia (94.1%), delayed speech and/or walking (85.2%, 82.4%) and ocular abnormalities (79.4%). In total 26 variants of the CHAMP1 gene were detected, with all nonsense variants being of loss-of-function type, located in exon 3, and de novo in origin. CONCLUSION The heterozygous c.1908C>G (p.Y636*) variant of the CHAMP1 gene probably underlay the WRD40 in this child. Genetic testing should be considered for children featuring global developmental delay, mental retardation, hypertonia and facial dysmorphism.
Humans ; Intellectual Disability/genetics* ; Genetic Testing ; Phenotype ; Exome Sequencing ; Heterozygote ; Mutation ; Chromosomal Proteins, Non-Histone/genetics* ; Phosphoproteins/genetics*

Objective:To detect and analyze the gene variation types of 64 unrelated pedigrees affected with autosomal dominant polycystic kidney disease (ADPKD), and explore the detection efficiency of multiple gene analysis techniques and variation characteristics.Methods:It was a cross-sectional study. The clinical data of 64 pedigrees with ADPKD from Nephrology Department or Genetic and Prenatal Diagnosis Center of the First Affiliated Hospital of Zhengzhou University from December 2017 to August 2020 were retrospectively analyzed. The blood samples of probands and other family members were collected. Genetic analysis was carried out by next generation sequencing, and suspected mutations were verified by multiplex ligation-dependent probe amplification, or long-range PCR combined with Sanger sequencing. Prenatal diagnosis for high-risk fetuses was performed by fetal villi or amniotic fluid cells after genotyping without maternal genomic DNA contamination.Results:Among detected 64 pedigrees, 57 pedigrees (89.06%) had genetic variants in PKD1/PKD2. A total of 49 pathogenic/likely pathogenic variants in PKD1/PKD2 were identified in 51 pedigrees (79.69%), including 14 nonsense variants (28.57%), 14 frameshift variants (28.57%), 11 missense variants (22.45%), 5 splicing variants (10.20%) and 5 deletion variants (10.20%). Of these variants, 87.76% (43/49) were in PKD1 and 12.24% (6/49) were in PKD2. Totally, 14 novel variants in PKD1/ PKD2 were identified, including 7 frameshift variants, 3 splicing variants, 2 nonsense variants, 1 deletion variant and 1 missense variant, of which 11 variants were in PKD1 and 3 variants were in PKD2. Twenty high-risk fetuses from 17 pedigrees received prenatal diagnosis, in whom 6 fetuses had PKD1 variation, and other 14 fetuses had no PKD1/ PKD2-genetic variation. Conclusions:The combination of next-generation sequencing, multiplex ligation-dependent probe amplification, and long-range PCR combined with Sanger sequencing can be helpful for rapid, efficient and accurate genetic diagnosis of ADPKD pedigrees. Point mutations are the most common types in PKD1/PKD2. Fourteen novel variants in PKD1/PKD2 extend its pathogenic variant spectrum and can provide basis for genetic counseling and prenatal diagnosis of ADPKD pedigrees.

The febrile respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become the focus of global attention. Up to now, the infection has been continuing to spread all over the world and it is urgent to develop specific drugs for SARS-CoV-2. Finding effective and safe drugs which are already available in the market for treating coronavirus disease 2019 (COVID-19) is one of the main strategies to solve the problem in time. As quinoline alkaloids against malaria, chloroquine and hydroxychloroquine have been proved to have the anti-SARS-CoV-2 activity. Quinoline alkaloids are expected to be important drugs for the treatment of COVID-19. In this article, the research and application of chloroquine and hydroxychloroquine are reviewed from the aspects of pharmacokinetics, drug interaction, clinical research progress, treatment plan optimization and resolution of optical enantiomers. The possible problems are summarized in order to provide reference for further research and clinical application of quinoline alkaloids in the treatment of COVID-19.