[Clinical effect of Saccharomyces boulardii powder combined with azithromycin sequential therapy in treatment of children with diarrhea secondary to Mycoplasma pneumoniae pneumonia].

OBJECTIVE: To investigate the clinical effect of Saccharomyces boulardii powder combined with azithromycin sequential therapy in the treatment of children with diarrhea secondary to Mycoplasma pneumoniae pneumonia. METHODS: A total of 88 children with diarrhea secondary to Mycoplasma pneumoniae pneumonia between June 2015 and March 2017 were divided into control group and study group using a random number table, with 44 children in each group. The children in the control group were given routine treatment combined with azithromycin sequential therapy, and those in the study group were given oral Saccharomyces boulardii powder in addition to the treatment in the control group until the end of azithromycin sequential therapy. After the treatment ended, the two groups were compared in terms of time to improvement of clinical symptoms, length of hospital stay, clinical outcome, defecation frequency before and after treatment, condition of intestinal dysbacteriosis, and incidence of adverse events. RESULTS: Compared with the control group, the study group had significantly shorter time to improvement of clinical symptoms and length of hospital stay (P<0.05). The study group had a significantly higher response rate than the control group (P<0.05). On days 3 and 5 of treatment, the study group had a significant reduction in defecation frequency compared with the control group (P<0.05). The study group had a significantly lower rate of intestinal dysbacteriosis than the control group (P<0.05). There was no significant difference in the incidence of adverse events between the two groups (P>0.05). CONCLUSIONS: In the treatment of children with diarrhea secondary to Mycoplasma pneumoniae pneumonia, Saccharomyces boulardii powder combined with azithromycin sequential therapy can improve clinical symptoms, shorten the length of hospital stay, reduce defecation frequency and the incidence of intestinal dysbacteriosis, and improve clinical outcomes, and does not increase the risk of adverse events.

A smart tailor-made G-clip reporter for sensitive detection of G-triplet-containing sequences.

Taking advantage of the intrinsic characteristics of G-triplet-containing sequences, a pioneering tailor-made clip-like reporter containing three-fourths of a G-quadruplex is established. The reporter can clip the G triplet in the target sequence through a recognition process to form a complete G-quadruplex structure.

Double-layer poly(vinyl alcohol)-coated capillary for highly sensitive and stable capillary electrophoresis and capillary electrophoresis with mass spectrometry glycan analysis.

Glycosylation plays an important role in protein conformations and functions as well as many biological activities. Capillary electrophoresis combined with various detection methods provided remarkable developments for high-sensitivity glycan profiling. The coating of the capillary is needed for highly polar molecules from complex biosamples. A poly(vinyl alcohol)-coated capillary is commonly utilized in the capillary electrophoresis separation of saccharides sample due to the high-hydrophilicity properties. A modified facile coating workflow was carried out to acquire a novel multiple-layer poly(vinyl alcohol)-coated capillary for highly sensitive and stable analysis of glycans. The migration time fluctuation was used as index in the optimization of layers and a double layer was finally chosen, considering both the effects and simplicity in fabrication. With migration time relative standard deviation less than 1% and theoretical plates kept stable during 100 consecutive separations, the method was presented to be suitable for the analysis of glycosylation with wide linear dynamic range and good reproducibility. The glycan profiling of enzymatically released N-glycans from human serum was obtained by the presented capillary electrophoresis method combined with mass spectrometry detection with acceptable results.

Effect of Acute Normovolemic Hemodilution Combined with Controlled Low Central Venous Pressure on Blood Coagulation Function and Blood Loss in Patients Undergoing Resection of Liver Cancer Operation.

BACKGROUND/AIMS: This paper aims to investigate the effect of acute normovolemic hemodilution (ANH) used with controlled low central venous pressure (LCVP) technology on perioperative bleeding and coagulation in hepatocellular carcinoma operation patients. METHODOLOGY: A total of 60 cases undergoing hepatic resection operation were randomly divided into the control group, LCVP group (Group II), and ANH + LCVP group (Group III). The changes of hemodynamic indexes at different time points in each group were observed and recorded, along with the volume of allogenous blood transfusion and the number of patients undergoing allogenous blood transfusion. RESULTS: Compared with Group I (control), there was evident reduction of the bleeding volume, allogenic blood transfusion volume, and number of patients undergoing allogenic blood transfusion in Groups II and III. CONCLUSION: The application of ANH combined with LCVP in hepatic resection can evidently reduce intraoperative hemorrhages and homologous blood transfusions; moreover, it has no significant adverse effect on the coagulation function.

Differential detection of Rhizoma coptidis by capillary electrophoresis electrospray ionization mass spectrometry with a nanospray interface.

A lab prototype CE-nanospray-MS platform with a high sensitivity porous sprayer was successfully applied in differential identification of Rhizoma coptidis in this paper. To obtain a stable and reliable nanospray, detailed optimizations about emitter geometry, buffer composition, emitter position, and spray voltage, as well as emitter cleanliness were discussed. Results showed that the reproducibility and sensitivity for separations of alkaloid standards were satisfactory using CE-nanospray-MS, which were also compared to ultra-HPLC (UHPLC)-MS. Their signal responds were at the same order of magnitude (intensities: 0.8 - 1.5 × 10(8) vs. 3.8 - 6.2 × 10(8) ), even though a 2 nL injection for CE was 2500-fold lower than UHPLC (5 µL injection). The absolute LOD results of CE-MS showed a remarkable superiority (18-24 fg), equal to 1000-fold lower than that of UHPLC-MS. Principal component analysis (PCA) of adulterated R. coptidis showed that this protocol had the ability to profile and qualify complex herb medicines, which also created a great potential for evaluation and qualification of rare and valuable Chinese medicines in future.

Effect of acute normovolemic hemodilution combined with controlled low central venous pressure on cerebral oxygen metabolism of patients with hepalobectomy.

BACKGROUND/AIMS: The effect of acute normovolemic hemodilution (ANH) combined with controlled low central venous pressure (LCVP) on the cerebral oxygen metabolism of patients with hepalobectomy. METHODOLOGY: Undergoing hepatic resection operation in 60 cases, were randomly divided into control group, LCVP group (Group II) and ANH + LCVP group (Group IIl). Before hemodilution (T1), decrease of CVP (T2) and increase of CVP (T3) and at the end of surgery (T4), the blood was sampled via the jugular vein bulb and radial artery for blood gas analysis. RESULTS: Compared with group I, the CaO2 of group II at T3 and T4 was increased; in group III, CaO2 and Da-jvO2 at T2 and T3 were decreased, CjvO2 at T2 decreased, and CaO2 and CjvO2 at T4 increased. Compared with group II, CaO2, CjvO2 and Da-jvO2 of group III at T2 and T3 were decreased. CERO2 of the three groups at T3 and T4 were all decreased (P<0.05 or 0.01). The jugular venous oxygen saturation (SjvO2) and VADL of the three groups at each time point were all within the normal range. CONCLUSION: The moderate ANH combined with LCVP had no adverse effect on the cerebral oxygen metabolism of the patients with the hepalobectomy.

Effect of Chinese quince proanthocyanidins on the inhibition of heterocyclic amines and quality of fried chicken meatballs and tofu.

Heterocyclic amines (HCAs) have potential carcinogenic and mutagenic activity and are generated in cooked protein-rich foods. Adding proanthocyanidins (PAs) to these foods before frying is an effective way to reduce HCAs. In this study, polymeric PAs (PPA) and ultrasound-assisted acid-catalyzed/catechin nucleophilic depolymerized PAs (UAPA, a type of oligomeric PA) were prepared from Chinese quince fruits (CQF). Different levels of PPA and UAPA (0.05%, 0.1%, and 0.15%) were added to chicken meatballs and tofu; then these foods were fried, and the content of HCAs in them after frying was investigated. The results showed that PPA and, particularly, UAPA significantly inhibited the formation of HCAs in fried meatballs and tofu, and this inhibition was dose-dependent. The inhibition of HCAs by both PPA and UAPA was stronger in the chicken meatballs than in fried tofu. The level of total HCAs was significantly reduced by 57.84% (from 11.93 to 5.03 ng/g) after treatment of meatballs with 0.15% UAPA, with inhibition rates of 78.94%, 50.37%, and 17.81% for norharman, harman, and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), respectively. Of note, there was a negative correlation between water, lipid, protein, creatine, and glucose content and HCA content in the crust, interior, and whole (crust-plus-interior) measurements of all fried samples. Interestingly, PPA and UAPA were found more effective in inhibiting HCAs in the exterior crust than in the interior of the fried chicken meatballs. These results provide evidence that further studies on the reduction of the formation of harmful HCAs in fried foods by adding CQF PAs could be valuable to the fried food industry. PRACTICAL APPLICATION: Chinese quince proanthocyanidins treatments significantly inhibited the generation of heterocyclic amines (HCAs) in chicken meatballs and tofu when deep-fried. These results suggest that Chinese quince proanthocyanidins can be used as natural food additive for reducing HCAs in fried foods, laying the foundation for using Chinese quince fruit proanthocyanidins for HCA inhibition in the food industry.

Tripartite motif-containing protein 26 promotes colorectal cancer growth by inactivating p53.

Tripartite motif-containing protein 26 (TRIM26) is an E3 ubiquitin ligase that exhibits divergent roles in various cancer types (oncogenic and anti-oncogenic). This study investigates the interaction of TRIM26 with the tumor suppressor protein p53 in colorectal cancer (CRC) cells by performing a comprehensive set of biochemical, cell-based assays, and xenograft experiments. As a result, we found that overexpression of TRIM26 significantly enhances CRC cell proliferation and colony formation, while knockdown of TRIM26 suppresses these processes. Xenograft experiments further validated the tumor-promoting role of TRIM26 in CRC. Supporting this is that TRIM26 is highly expressed in human CRC tissues as revealed by our analysis of the TCGA database. Biochemically, TRIM26 directly bound to the C-terminus of p53 and facilitated its ubiquitination, resulting in proteolytic degradation and attenuated p53 activity independently of MDM2. Also, TRIM26 increased the MDM2-mediated ubiquitination of p53 by binding to MDM2's C-terminus. This study uncovers the oncogenic potential of TRIM26 in CRC by inhibiting p53 function. Through its ubiquitin ligase activity, TRIM26 destabilizes p53, consequently promoting CRC cell proliferation and tumor growth. These findings shed light on the complex involvement of TRIM26 in cancer and identify this ubiquitin ligase as a potential therapeutic target for future development of CRC treatment.

Utilization of deep neuromuscular blockade combined with reduced abdominal pressure in laparoscopic radical gastrectomy for gastric cancer: An academic perspective.

BACKGROUND: Few studies have examined the specific efficacy of deep neuromuscular blockade (NMB) combined with pneumoperitoneal pressure reduction in laparoscopic radical gastrectomy (LRG) in the elderly. AIM: To investigate the application effect of deep neuromuscular blockade (NMB) combined with reduced pneumoperitoneum pressure in LRG for gastric cancer (GC) in elderly patients and its influence on inflammation. METHODS: Totally 103 elderly patients with GC treated in our hospital between January 2020 and January 2022 were retrospectively analyzed. Among them, 45 patients treated with surgery based on deep NMB and conventional pneumoperitoneum pressure were assigned to the control group, while the rest of the 58 patients who underwent surgery based on deep NMB and reduced pneumoperitoneum pressure were assigned to the observation group. The two groups were compared in the changes of the Leiden-surgical rating scale score, serum tumor necrosis fact-α (TNF-α) and interleukin 6 (IL-6) before and after therapy. The visual analogue scale (VAS) was adopted for evaluating the shoulder pain of patients at 8 h, 24 h and 48 h after the operation. The driving pressure of the two groups at different time points was also compared. Additionally, the operation time, pneumoperitoneum time, infusion volume, blood loss, extubation time after surgery, residence time in the resuscitation room, TOF% = 90% time and post-anesthetic recovery room (PACU) stay time were all recorded, and adverse PACU-associated respiratory events were also recorded. The postoperative hospitalization time and postoperative expenses of the two groups were counted and compared. RESULTS: No significant difference was found between the two groups at the time of skin incision, 60 minutes since the operation and abdominal closure after surgery (P > 0.05). The observation group exhibited significantly lower VAS scores than the control group at 24 and 48h after surgery (P < 0.05). Additionally, the observation group had significantly lower driving pressure than the control group at 5 min and 60 min after the establishment of pneumoperitoneum (P < 0.05). Additionally, the two groups were similar in terms of the operation time, pneumoperitoneum time, infusion volume, blood loss, extubation time after surgery, residence time in the resuscitation room and TOF% = 90% time (P > 0.05), and the observation group showed significantly lower TNF-α and IL-6 Levels than the control group at 24 h after therapy (P < 0.05). Moreover, the incidence of adverse events was not significantly different between the two groups (P > 0.05), and the observation group experienced significantly less hospitalization time and postoperative expenses than the control group (P < 0.05). CONCLUSION: Deep NMB combined with reduced pneumoperitoneum pressure can decrease the VAS score of shoulder pain and inflammatory reaction, without hindering the surgical vision and increasing adverse PACU-associated respiratory events, and can thus shorten the hospitalization time and treatment cost for patient.

CCNB1 is involved in bladder cancer pathogenesis and silencing CCNB1 decelerates tumor growth and improves prognosis of bladder cancer.

In search of an effective therapeutic target for bladder urothelial carcinoma (BLCA), the present study aimed to investigate the expression of cyclin B1 (CCNB1) and its putative mechanism in BLCA. BLCA sequencing data from Gene Expression Omnibus and The Cancer Genome Atlas were used to analyze expression of CCNB1 mRNA and high CCNB1 expression had a poorer prognosis compared with those with low expression. Immunohistochemistry (IHC) samples collected from the Human Protein Atlas database were analyzed for CCNB1 protein expression. Short hairpin (sh) CCNB1-transfected BLCA T24 and 5637 cells were used to investigate the effects of CCNB1 and inhibit the proliferation, migration and invasion of BLCA cells, affect the cell cycle distribution and promote apoptosis of 5637 cells. A sh-CCNB1 BLCA chicken embryo chorioallantoic membrane (CAM) transplantation model was established to observe the impacts of sh-CCNB1 on the tumorigenesis of BLCA in vivo. Analysis of sequencing data showed that CCNB1 mRNA was significantly elevated in tumor and BLCA compared with normal tissues [standardized mean difference (SMD)=1.21; 95% CI: 0.26-2.15; I²=95.9%]. IHC indicated that CCNB1 protein was localized in the nucleus and cytoplasm and was significantly increased in BLCA tumor tissues. The in vitro tests demonstrated that proliferation of T24 and 5637 cells transfected with sh-CCNB1 was significantly inhibited and cell migration and invasion ability were significantly decreased. sh-CCNB1 decreased the percentage of T24 cells in G0/G1, 5637 cells in the G0/G1 phase and S phase and increased percentage of 5637 cells in the G2/M phase and increased early apoptosis of 5637 cells. The in vivo experiments demonstrated that the mass of transplanted tumors was significantly decreased compared with the control group following silencing of CCNB1. The present results suggested that CCNB1 was involve in the development and prognosis of BLCA and silencing of CCNB1 may be a promising targeted therapy for BLCA.

Diffuse large B-cell lymphoma with continuously elevated immunoglobulin M following treatment: a case report with pathologic, immunophenotypic, and molecular analyses.

A rare subtype of diffuse large B-cell lymphoma (DLBCL) has been reported to be accompanied by elevated immunoglobulin M (IgM) paraprotein in the serum at diagnosis, called as IgMs-DLBCL. The monoclonal IgM paraprotein disappears soon after treatment in most of these patients. Here, we described a DLBCL patient with continuously elevated IgM following therapy. A 59-year-old male was diagnosed with DLBCL (GCB subtype per Hans algorithm, stage IA) with involvement of the right cervical lymph node. After six cycles of immuno-chemotherapy with the R-CHOP regimen, complete metabolic remission was achieved, but an elevated level of serum IgM persisted. To investigate the origin of elevated IgM, pathologic, immunophenotypic, and molecular analyses of lymph node and bone marrow (BM) samples were performed pre- and post-treatment. BM infiltration of lymphoplasmacytic cells, and a typical immunophenotypic profile by flow cytometry supported the diagnosis of Waldenström macroglobulinemia (WM). The MCD subtype of DLBCL was identified by next-generation sequencing of the lymph node at initial diagnosis characterized by co-occurring point mutations in MYD88 L265P and CD79B. Additionally, two different dominant clonotypes of the immunoglobulin heavy chain (IGH) were detected in the lymph node and BM by IGH sequencing, which was IGHV 3-11*06/IGHJ 3*02 and IGHV 3-11*06/IGHJ 6*02, respectively, speculating to be two independent clonal origins. This study will provide a panoramic understanding of the origin or biological characteristics of DLBCL co-occurring with WM.

Downregulation of doxorubicin-induced myocardial apoptosis accompanies postnatal heart maturation.

Doxorubicin is a highly effective chemotherapeutic agent used for treating a wide spectrum of tumors, but its usage is limited because of its dose-dependent cardiotoxicity, especially in pediatric patients. Accumulating evidence indicates that caspase-dependent apoptosis contributes to the cardiotoxicity of doxorubicin. However, less attention has been paid to the effects of age on doxorubicin-induced apoptosis signaling in myocardium. This study focused on investigating differential apoptotic sensitivity between neonatal and adult myocardium, in particular, between neonatal and adult cardiomyocytes in vivo. Our results show that caspase-3 activity in normal mouse hearts decreased by ≥ 20-fold within the first 3 wk after birth, associated with a rapid downregulation in the expression of key proapoptotic proteins in intrinsic and extrinsic pathways. This rapid downregulation of caspase-3 activity was confirmed by immunostaining for cleaved caspase-3 and terminal deoxynucleotidyl transferase dUTP-mediated nick-end label staining. Doxorubicin treatment induced a dose-dependent increase in caspase-3 activity and apoptosis in neonatal mouse hearts, and both caspase-8 and caspase-9 activations were involved. Using transgenic mice with a nuclear localized LacZ reporter gene to label cardiomyocytes in vivo, we observed a fourfold higher level of doxorubicin-induced cardiomyocyte apoptosis in 1-wk-old mice compared with that in 3-wk-old mice. This study points to a major difference in apoptotic signaling in doxorubicin cardiotoxicity between neonatal and adult mouse hearts and reveals a critical transition from high to low susceptibility to doxorubicin-induced apoptosis during postnatal heart maturation.

Myotubularin-Related Protein14 Prevents Neointima Formation and Vascular Smooth Muscle Cell Proliferation by Inhibiting Polo-Like Kinase1.

Background Restenosis is one of the main bottlenecks in restricting the further development of cardiovascular interventional therapy. New signaling molecules involved in the progress have continuously been discovered; however, the specific molecular mechanisms remain unclear. MTMR14 (myotubularin-related protein 14) is a novel phosphoinositide phosphatase that has a variety of biological functions and is involved in diverse biological processes. However, the role of MTMR14 in vascular biology remains unclear. Herein, we addressed the role of MTMR14 in neointima formation and vascular smooth muscle cell (VSMC) proliferation after vessel injury. Methods and Results Vessel injury models were established using SMC-specific conditional MTMR14-knockout and -transgenic mice. Neointima formation was assessed by histopathological methods, and VSMC proliferation and migration were assessed using fluorescence ubiquitination-based cell cycle indicator, transwell, and scratch wound assay. Neointima formation and the expression of MTMR14 was increased after injury. MTMR14 deficiency accelerated neointima formation and promoted VSMC proliferation after injury, whereas MTMR14 overexpression remarkably attenuated this process. Mechanistically, we demonstrated that MTMR14 suppressed the activation of PLK1 (polo-like kinase 1) by interacting with it, which further leads to the inhibition of the activation of MEK/ERK/AKT (mitogen-activated protein kinase kinase/extracellular-signal-regulated kinase/protein kinase B), thereby inhibiting the proliferation of VSMC from the medial to the intima and thus preventing neointima formation. Conclusions MTMR14 prevents neointima formation and VSMC proliferation by inhibiting PLK1. Our findings reveal that MTMR14 serves as an inhibitor of VSMC proliferation and establish a link between MTMR14 and PLK1 in regulating VSMC proliferation. MTMR14 may become a novel potential therapeutic target in the treatment of restenosis.

Differential expression of long non-coding RNAs as diagnostic markers for lung cancer and other malignant tumors.

Due to advances in chip and sequencing technology, several types and numbers of long non-coding RNAs (lncRNAs) have been identified. LncRNAs are defined as non-protein-coding RNA molecules longer than 200 nucleotides, and are now thought as a new frontier in the study of human malignant diseases including NSCLC. Diagnosis of numerous malignant tumors has been closely linked to the differential expression of certain lncRNAs. LncRNAs are involved in gene expression regulation at multiple levels of epigenetics, transcriptional regulation, and post-transcriptional regulation. Mutations, deletions, or abnormal expression levels lead to physiological abnormalities, disease occurrence and are closely associated with human tumor diseases. LncRNAs play a crucial role in cancerous processes as either oncogenes or tumor suppressor genes. The expression of lncRNAs can regulate tumor cell in the proliferation, migration, apoptosis, cycle, invasion, and metastasis. As such, lncRNAs are potential diagnostic and treatment targets for cancer. And that, tumor biomarkers need to be detectable in easily accessible body samples, should be characterized by high specificity and sufficient sensitivity. Herein, it is significant clinical importance to screen and supplement new biomarkers for early diagnosis of lung cancer. This study aimed at systematically describing lncRNAs from five aspects based on recent studies: concepts, classification, structure, molecular mechanism, signal pathway, as well as review lncRNA implications in malignant tumor.

Prolactin levels as a criterion to differentiate between psychogenic non-epileptic seizures and epileptic seizures: A systematic review.

OBJECTIVE: Psychogenic non-epileptic seizures (PNES) are conversion disorders with functional neurological symptoms that can resemble epileptic seizures (ES). We conducted a systematic review to obtain an overview of the value of prolactin (PRL) levels in the differential diagnosis between PNES and ES. METHODS: We searched PubMed, EMBASE, and Cochrane Library databases for studies published up to June 4th, 2020. Published studies were included if they fulfilled the following criteria: original research on PRL changes after ES and PNES. By applying Bayes' theorem, we calculated the predicted values of PRL with pretest probabilities of 90 % and 75 % in ES. RESULTS: Sixteen studies were included in this review. All the studies showed that PRL levels increase after ES, especially 10-20 min after ES, when the elevation was most obvious. In studies where capillary PRL level measurements were included, the median sensitivity in the diagnosis of ES (all epileptic seizure types), generalized tonic clonic seizures (GTCS), focal impaired awareness seizures (FIAS), and focal aware seizures (FAS) was 67.3 %, 66.7 %, 33.9 %, and 11.1 %, respectively. The median specificity in the diagnosis of ES was 99.1 %. By using Bayes' theorem, when we used the median specificity and sensitivity for predictive value calculation, assuming a pretest probability of 90 %, a positive PRL measure was highly predictive (99 %) of all types of ES, and negative predictive values were all below 30 %. When we used the lowest specificity and sensitivity for predictive value calculation, assuming a pretest probability of 75 %, ES and GTCS had positive predictive values of 77.2 % and 81.0 %, respectively; the negative predictive values of PRL in ES and GTCS were 26.2 % and 29.6 %, respectively. CONCLUSIONS: The use of PRL could be a useful adjunct to differentiate GTCS from PNES. However, PRL levels are of limited use for differentiating FIAS or FAS from PNES, and a negative PRL measure is not predictive of PNES.

ROCK1 plays an essential role in the transition from cardiac hypertrophy to failure in mice.

Pathological cardiac hypertrophy caused by diverse etiologies eventually leads to cardiac dilation and functional decompensation. We have recently reported that genetic deletion of Rho-associated coiled-coil containing protein kinase 1 (ROCK1) inhibited several pathological events including cardiomyocyte apoptosis in compensated hypertrophic hearts. The present study investigated whether ROCK1 deficiency can prevent the transition from hypertrophy to heart failure. Transgenic mice with cardiac-restricted overexpression of Gαq develop compensated cardiac hypertrophy at young ages, but progress into lethal cardiomyopathy accompanied by increased apoptosis after pregnancy or at old ages. The studies were first carried out using age- and pregnancy-matched wild-type, Gαq, ROCK1(-/-), and Gαq/ROCK1(-/-) mice. The potent beneficial effect of ROCK1 deletion is demonstrated by abolishment of peripartum mortality, and significant attenuation of left ventricular (LV) dilation, wall thinning, and contractile dysfunction in the peripartum Gαq transgenic mice. Increase in cardiomyocyte apoptosis was suppressed by ROCK1 deletion, associated with increased extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) activation and inhibition of mitochondrial translocation of Bax. In addition, ROCK1 deficiency also improved survival, inhibited cardiomyocyte apoptosis, and preserved LV dimension and function in old Gαq mice at 12 months. Furthermore, transgenic overexpression of ROCK1 increased cardiomyocyte apoptosis and accelerated hypertrophic decompensation in Gαq hearts in the absence of pregnancy stress. The present study provides for the first time in vivo evidence for the long-term beneficial effects of ROCK1 deficiency in hypertrophic decompensation and suggests that ROCK1 may be an attractive therapeutic target to limit heart failure progression.

Efficacy of the ketogenic diet in patients with Dravet syndrome: A meta-analysis.

PURPOSE: Dravet syndrome is an infantile epilepsy syndrome with drug resistant seizures and cognitive impairment. The aim of this meta-analysis was to summarize the findings of relevant published studies to identify the efficacy of a ketogenic diet in patients with Dravet syndrome and their compliance thereof, and to provide useful information for clinical practice. METHODS: The PubMed, Embase, Wanfang, and CNKI databases were searched for relevant studies published up to September 25, 2019; the included studies were reviewed. Meta-analyses were performed using R software to determine the combined efficacy rates and retention rate for the ketogenic diet in patients with Dravet syndrome. RESULTS: Seven studies involving 167 patients met the inclusion criteria: four were retrospective studies, and three were prospective studies. The meta-analysis revealed that 63 %, 60 %, and 47 % of responder patients achieved ≥50 % seizure reduction at month 3, 6, and 12, respectively. The pooled retention rate of the ketogenic diet at month 6 and month 12 was 78 % and 49 %, respectively. CONCLUSIONS: Our meta-analysis indicates that the ketogenic diet is a treatment option for patients with Dravet syndrome. The ketogenic diet is safe and its adverse effects are mostly acceptable. However, further investigations, especially high-quality controlled trials with large samples, are required.

Author Correction: Increased circulating ß2-adrenergic receptor autoantibodies are associated with smoking-related emphysema.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

HspX promotes the polar localization of mycobacterial protein aggregates.

Misfolding of translated proteins occurs in all domains of life. In most cells, misfolded proteins coalesce in discrete aggregates at distinct cellular locations. In many bacteria, including mycobacteria, protein aggregates are located at the cellular pole. Yet the mechanism by which aggregates are sorted to the mycobacterial pole is not known. Here, we show that in Mycobacterium smegmatis, the small heat shock protein HspX plays a critical role in the polar localization of aggregates of a model fluorescent misfolded protein, GLR103. HspX itself has a polar localization, which is dependent on its N-terminal domain. In a strain deleted for hspX, GLR103 is less liable to aggregation and no longer localizes to the pole, and redirecting HspX to the septum radically disrupts the normal polar localization of GLR103 aggregates. To further investigate the role of HspX in native protein aggregation, we performed semi-quantitative mass-spectrometry of mycobacterial protein aggregates in wild-type, hspX-deleted and hspX-overexpressing strains. We identified a subset of proteins that appeared to be HspX-dependent for aggregate formation. Furthermore, we demonstrate that for validated native protein aggregates, sorting to the cellular pole following proteotoxic stress required HspX. In summary, we have identified the cellular function of HspX in Mycobacterium smegmatis as both a pro-aggregase and polar sortase.

N-methyl-D-aspartate receptor subunit 1 regulates neurogenesis in the hippocampal dentate gyrus of schizophrenia-like mice.

N-methyl-D-aspartate receptor hypofunction is the basis of pathophysiology in schizophrenia. Blocking the N-methyl-D-aspartate receptor impairs learning and memory abilities and induces pathological changes in the brain. Previous studies have paid little attention to the role of the N-methyl-D-aspartate receptor subunit 1 (NR1) in neurogenesis in the hippocampus of schizophrenia. A mouse model of schizophrenia was established by intraperitoneal injection of 0.6 mg/kg MK-801, once a day, for 14 days. In N-methyl-D-aspartate-treated mice, N-methyl-D-aspartate was administered by intracerebroventricular injection in schizophrenia mice on day 15. The number of NR1-, Ki67- or BrdU-immunoreactive cells in the dentate gyrus was measured by immunofluorescence staining. Our data showed the number of NR1-immunoreactive cells increased along with the decreasing numbers of BrdU- and Ki67-immunoreactive cells in the schizophrenia groups compared with the control group. N-methyl-D-aspartate could reverse the above changes. These results indicated that NR1 can regulate neurogenesis in the hippocampal dentate gyrus of schizophrenia mice, supporting NR1 as a promising therapeutic target in the treatment of schizophrenia. This study was approved by the Experimental Animal Ethics Committee of the Ningxia Medical University, China (approval No. 2014-014) on March 6, 2014.