OBJECTIVE To observe the clinical effects of the combination of Duhuo Bugu decoction and zoledronic acid in the treatment of malignant bone metastasis.METHODS Fifty patients with bone metastases of malignant tumor were selected from the Department of oncology,Chongqing Hospital of traditional Chinese medicine from September 2014 to February 2016, and were randomly divided into the observation group and the control group.Two groups were both treated by zoledronic acid, and the observation group was also treated by adding Duhuo Bugu Decoction.Changes of the analgesic effects,analgesic dosa-ges and life quality scores(KPS)of two groups were observed before and after treatment.Urinary type I collagen amino termi-nal peptide(uNTX)and bone alkaline phosphatase(BALP)were measured via ELISA method before and after treatment.RE-SULTS Compared with the control group,the analgesic medicinal amount of the observation group reduced significantly(P<0.05),and KPS improved significantly(P<0.05).After the treatment,numerical pain scores(NRS) of two groups had no significant changes(P>0.05).After the treatment,uNTX and sBALP level of the treatment group decreased compared with that before treatment(P<0.01).While compared with the control group,the difference was not significant(P>0.05).CON-CLUSION The combination of Chinese herbs and zoledronic acid is an effective therapy for bone metastasis malignant tumors. Chinese herbs can effectively improve the analgesic effect,reduce the analgesic medicinal amount,improve the patients'life quality,and have a tendency of synergy in improving the bone destruction caused by tumor.

To study the protective effect of Danshen Tongluo capsule on rat hearts in the myocardial infarction (MI) model. After being fed with high fat diets for one month, the SD rats were randomly divided into the sham group and the model group according to the left ventricular ejection fraction (EF). The MI model group was duplicated by ligating coronary artery and then divided into five groups: the model group, the positive control group (model + captopril), the small dose group (model + Danshen Tongluo), the medium dose group (model + Danshen Tongluo) and the high dose group (model + Danshen Tongluo). Four weeks later, changes in myocardium ultra-structure were observed by hemodynamics, cardiac ultrasound and electron microscope. The results showed: (1) All doses of Danshen Tongluo capsule could significantly reduce the left ventricular end diastolic pressure (LVEDP) (P <0.01), increase the maximum internal pressure of the left ventricle (+ dp/dtmax), and lower the drop rate of left ventricular pressure (- dp/dtmax), with statistical significances in medium and high dose groups; (2) The B ultrasound results showed increase in EF and left ventricular shortening fraction (FS) in all dose groups of Danshen Tongluo capsule; (3) The medium dose group showed significant decrease in myocardial infarction index (P <0.01) and injured and fractured myofilament and sarcomere of ischemic myocardium in myocardial ultra-structure; All of Danshen Tongluo capsule-treated groups revealed reduction in myocardial injury and myocardial infraction area. The study preliminarily proves that Danshen Tongluo capsule can improve hemodynamic function, and has a protective effect on myocardial ischemia.
Animals ; Capsules ; Drugs, Chinese Herbal ; therapeutic use ; Hemodynamics ; drug effects ; Male ; Myocardial Infarction ; drug therapy ; pathology ; physiopathology ; Myocytes, Cardiac ; ultrastructure ; Rats ; Rats, Sprague-Dawley ; Ventricular Function, Left ; drug effects

OBJECTIVETo investigate the effects of effective components extracted from medicines compatibility on ischemic myocardial remodeling.

METHODThe animal models of ischemic myocardial remodeling was copied by ligating the left anterior descending branch of coronary artery in rat. And then decoction and effective components extracted from the same medicines were administrated to rats. The heart function was detected by ultrasound diagnostic apparatus and the heart morphology was examined by Hematoxylin and Eosin, picrosirius staining respectively on the 3rd and 56rd day.

RESULTBoth concentrated decoction and effective components compatibility showed good restrained effects on ventricle malignant remodeling, such as improved heart function, reduced the area of myocardial infarction, lowered heart index, mitigated the fibrosis level and decreased apoptosis cell numbers in infarction and non-infarction areas. The difference were statistically significant when compared with the control group (P < 0.01, P < 0.05), and effective components treated group had better effects than concentrated decoction group (P < 0.05). Concentrated decoction group showed little effects on the 3rd day, while effective components group showed significant effect (P < 0.05).

CONCLUSIONEffective components compatibility has better effects on inhibiting the process of ischemic myocardial remodeling than concentrated decoction. Effective components compatibility has better effects on ventricle malignant remodeling by eliminating the interfrence non-pharmacodynamic elements of the medicine.

Animals ; Apoptosis ; drug effects ; Collagen ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Heart ; physiopathology ; Ischemia ; drug therapy ; metabolism ; physiopathology ; Male ; Myocytes, Cardiac ; drug effects ; pathology ; Rats ; Ventricular Remodeling ; drug effects

Adverse drug reactions (ADRs) induced by drug-drug interactions have posed a serious threat to patients′health and caused immense economic losses. With the increase in the number of combined drugs, the occurrence rate of side effects has surged. Since traditional methods for discovering drug interactions are infficient and costly, the biomedical informatics based methods are able to acquire valuable information about ADR by analyzing and mining from biomedical big data at a low cost and with high throughput. Methods of discovering potential drug interactions through literature mining, data mining and physiologically based pharmacokinetic models are systematically reviewed in this paper. Also, the prospect of potential research fields of drug conbination is outlined.

OBJECTIVE: To assess the diagnostic value of copy number variation sequencing (CNV-seq) in the genetic etiology of fetuses with nasal bone dysplasia (NBD). METHODS: A total of 217 fetuses discovered with NBD from December 2017 to December 2020 were divided into the isolated NBD group and NBD combined with other anomalies group, for which copy number variations (CNVs) were analyzed. RESULTS: A total of 40 fetal abnormalities were detected in 217 cases, with an overall abnormal rate of 18.4%. These included 31 cases with aneuploidies (14.3%, 31/217) and 9 cases with genomic CNVs (4.1%, 9/217). Five cases of trisomy 21 (3.5%, 5/144) and two CNVs cases with unknown clinical significance (1.4%, 2/144) were detected in the isolated group. As for the combined NBD group, 26 aneuploidies (35.6%, 26/73), including 19 cases with trisomy 21, 6 cases with trisomy 18, 1 case with trisomy 13, 5 cases with pathogenic CNVs (6.8%, 5/73), and 2 cases with CNVs of unknown clinical significance (2.7%, 2/73) were detected. A significant difference was detected between the two groups (P < 0.01). CONCLUSION The detection rate of CNV-seq is high for chromosomal aneuploidies and pathogenic CNVs in fetuses with NBD, particularly in those combined with other ultrasonic abnormalities.
Aneuploidy ; Bone Diseases, Developmental ; Chromosome Aberrations ; DNA Copy Number Variations ; Down Syndrome/genetics* ; Female ; Fetus/abnormalities* ; Humans ; Pregnancy ; Prenatal Diagnosis ; Trisomy

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*

Background::Hyperthermia in combination with DnaJA4-knockout (KO) obviously affects the anti-viral immunity of HaCaT cells. The mechanisms of this process are not yet fully explored. However, it is known that DnaJA4 interacts with actin cytoskeleton after hyperthermia. Our aim was to investigate the effects of DnaJA4 on F-actin in HaCaT cells following hyperthermia.Methods::Wild-type (WT) and DnaJA4-KO HaCaT cells were isolated at either 37°C (unheated) or 44°C (hyperthermia) for 30 min followed by testing under conditions of 37°C and assessing at 6, 12, and 24 h after hyperthermia. The cytoskeleton was observed with immunofluorescence. Flow cytometry and Western blotting were used to detect the expression of F-actin and relevant pathway protein.Results::DnaJA4-KO and hyperthermia changed the cytoskeleton morphology of HaCaT cells. F-actin expression levels were elevated in DnaJA4-KO cells compared with WT cells (6364.33 ± 989.10 vs. 4272.67 ± 918.50, P < 0.05). In response to hyperthermia, F-actin expression levels of both WT and DnaJA4-KO cells showed a tendency to decrease followed by an obvious recovery after hyperthermia (WT cells: unheated vs. 6 h after hyperthermia or 24 h after hyperthermia: 0.34 ± 0.02 vs. 0.24 ± 0.01, 0.31 ± 0.01, P < 0.001, P < 0.05; DnaJA4-KO cells: unheated vs. 6 h after hyperthermia or 24 h after hyperthermia: 0.44 ± 0.01 vs. 0.30 ± 0.01, 0.51 ± 0.02, P < 0.001, P < 0.01). WT cells restored to baseline levels observed in the unheated condition, while DnaJA4-KO cells exceeded baseline levels in the recovery. As the upstream factors of F-actin, a similar profile in rho-associated serine/threonine kinase 1 (ROCK 1) and RhoA expressions was observed after hyperthermia. While E-cadherin expression was decreased in response to hyperthermia, it was increased in DnaJA4-KO cells compared with WT cells. Conclusions::Hyperthermia affects the expression levels of F-actin in HaCaT cells. DnaJA4 knockout increases the expression of F-actin in HaCaT cells after hyperthermia. DnaJA4 regulates the expressions of F-actin and the related pathway proteins in response to hyperthermia in HaCaT cells.

COVID-19 is caused by coronavirus SARS-CoV-2. Current systemic vaccines generally provide limited protection against viral replication and shedding within the airway. Recombinant VSV (rVSV) is an effective vector which inducing potent and comprehensive immunities. Currently, there are two clinical trials investigating COVID-19 vaccines based on VSV vectors. These vaccines were developed with spike protein of WA1 which administrated intramuscularly. Although intranasal route is ideal for activating mucosal immunity with VSV vector, safety is of concern. Thus, a highly attenuated rVSV with three amino acids mutations in matrix protein (VSV_MT) was developed to construct safe mucosal vaccines against multiple SARS-CoV-2 variants of concern. It demonstrated that spike protein mutant lacking 21 amino acids in its cytoplasmic domain could rescue rVSV efficiently. VSV_MT indicated improved safeness compared with wild-type VSV as the vector encoding SARS-CoV-2 spike protein. With a single-dosed intranasal inoculation of rVSV_ΔGMT-S_Δ21, potent SARS-CoV-2 specific neutralization antibodies could be stimulated in animals, particularly in term of mucosal and cellular immunity. Strikingly, the chimeric VSV encoding S_Δ21 of Delta-variant can induce more potent immune responses compared with those encoding S_Δ21 of Omicron- or WA1-strain. VSV_MT is a promising platform to develop a mucosal vaccine for countering COVID-19.

Breast Neoplasms/surgery* ; China ; Humans ; Mastectomy ; Mastectomy, Modified Radical

Asians ; Biological Assay ; Breast Neoplasms/surgery* ; China ; Female ; Humans ; Mastectomy