Chronic pancreatitis (CP) is a progressive and irreversible fibroinflammatory disorder, accompanied by pancreatic exocrine insufficiency and dysregulated gut microbiota. Recently, accumulating evidence has supported a correlation between gut dysbiosis and CP development. However, whether gut microbiota dysbiosis contributes to CP pathogenesis remains unclear. Herein, an experimental CP was induced by repeated high-dose caerulein injections. The broad-spectrum antibiotics (ABX) and ABX targeting Gram-positive (G⁺) or Gram-negative bacteria (G^-) were applied to explore the specific roles of these bacteria. Gut dysbiosis was observed in both mice and in CP patients, which was accompanied by a sharply reduced abundance for short-chain fatty acids (SCFAs)-producers, especially G⁺ bacteria. Broad-spectrum ABX exacerbated the severity of CP, as evidenced by aggravated pancreatic fibrosis and gut dysbiosis, especially the depletion of SCFAs-producing G⁺ bacteria. Additionally, depletion of SCFAs-producing G⁺ bacteria rather than G^- bacteria intensified CP progression independent of TLR4, which was attenuated by supplementation with exogenous SCFAs. Finally, SCFAs modulated pancreatic fibrosis through inhibition of macrophage infiltration and M2 phenotype switching. The study supports a critical role for SCFAs-producing G⁺ bacteria in CP. Therefore, modulation of dietary-derived SCFAs or G⁺ SCFAs-producing bacteria may be considered a novel interventive approach for the management of CP.

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.

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*

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

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

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.

Objective To observe the clinical efficacy of balance acupuncture predominantly by puncturing Jiaji points (EX-B2) from C4 to T1and from T12 to L1in treating hemiplegic balance disturbance after cerebral stroke. Method A total of 180 hemiplegia patients were randomized into 3 groups, 60 cases in balance acupuncture group, 60 cases in ordinary acupuncture group, and 60 cases in basic control group. After 1-month treatment and 3 months after the treatment, the motor function (Fugl-Meyer Assessment, FMA), balance function (Berg Balance Scale, BBS; Timed Up and Go Test, TUGT), and activities of daily living (ADL) (Barthel Index, BI) were observed.Result After 1-month treatment and 3 months after the treatment, limb function, balance ability and ADL were significantly different from those before the treatment in balance acupuncture group (P<0.01); after 1-month treatment, limb function in balance acupuncture group was significantly different from that in basic control group (P<0.05), and the differences were more statistically significant in comparing the rest indexes between the two groups (P<0.01); there were significant differences between ordinary acupuncture group and basic control group (P<0.05). Three months after the treatment, there was a significant difference in comparing balance function between balance acupuncture group and basic control group (P<0.05), and the differences were more statistically significant in comparing the rest indexes between the two groups (P<0.01), there was no significant difference in comparing balance function between ordinary acupuncture group and basic control group (P>0.05).Conclusion In combination with basic treatment, balance acupuncture works better than ordinary acupuncture and basic control in improving limb function, ADL and balance function of hemiplegia patients.

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 observe the effects and mechanism of uranium dust on collagen synthesis in fibroblastic cells.METHODS: i) RAW264. 7 macrophages were divided into solvent-control group and dust-affected group,and then treated with 0 and 120 mg / L( final concentration) uranium dust suspension for 0,2,4,8,16,24 and 32 hours. The supernatants of cells from these two groups were collected,and transforming growth factor beta 1( TGF-β1) levels were measured by enzyme-linked immunosorbent assay( ELISA). The best time phase was defined,and the supernatant of RAW264. 7 macrophages culture were separated as the conditioned medium( CM) for subsequent experiments. ii) Normal mouse lung fibroblasts L929 cells were divided into control group and uranium dust group,and treated with the CM of solvent-control group and dust-affected group respectively. After cultivated for 0,6,12,18,24,30 and 36 hours,the expression of α-smooth muscle actin( α-SMA) in L929 cells was detected by immunocytochemistry. The levels of extrac ellular collagen type Ⅰ( Col Ⅰ),collagen type Ⅲ( Col Ⅲ) and hydroxyproline( HYP) were detected by ELISA.RESULTS: i) The level of TGF-β1 in RAW264. 7 macrophages supernatant of the dust-affected group was higher than that of the solvent-control group after treatment with uranium dust for 4 hours,and showed an increasing trend with increasing time during 4-24 hours( P < 0. 05). The peak value was in 24 hours. The best time phase was 24 hours and used for CM of the two groups in subsequent experiments. ii) Compared with the control group at the same time points, the α-SMA expressions of L929 cells in uranium dust group increased after treatment with CM for 18-36 hours( P < 0. 05),the levels of Col Ⅰ,Col Ⅲ and HYP in uranium dust group increased after treatment with CM for 12-36 hours( P < 0. 05); both the expression of α-SMA and levels of Col Ⅲ and HYP increased with increasing time,showing a time-effect relationship( P <0. 05). CONCLUSION: Uranium dust can induce macrophages to secret TGF-β1 and affect fibroblast,increase α-SMAexpression,and increase the Col Ⅰ,Col Ⅲ and HYP synthesis. These might be the important mechanisms of lung fibrosis.

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