ROR2 Downregulation Activates the MSX2/NSUN2/p21 Regulatory Axis and Promotes Dental Pulp Stem Cell Senescence.

Cellular senescence severely limits the research and the application of dental pulp stem cells (DPSCs). A previous study conducted by our research group revealed a close implication of ROR2 in DPSC senescence, although the mechanism underlying the regulation of ROR2 in DPSCs remains poorly understood so far. In the present study, it was revealed that the expression of the ROR2-interacting transcription factor MSX2 was increased in aging DPSCs. It was demonstrated that the depletion of MSX2 inhibits the senescence of DPSCs and restores their self-renewal capacity, and the simultaneous overexpression of ROR2 enhanced this effect. Moreover, MSX2 knockdown suppressed the transcription of NOP2/Sun domain family member 2 (NSUN2), which regulates the expression of p21 by binding to and causing the 5-methylcytidine methylation of the 3'- untranslated region of p21 mRNA. Interestingly, ROR2 downregulation elevated the levels of MSX2 protein, and not the MSX2 mRNA expression, by reducing the phosphorylation level of MSX2 and inhibiting the RNF34-mediated MSX2 ubiquitination degradation. The results of the present study demonstrated the vital role of the ROR2/MSX2/NSUN2 axis in the regulation of DPSC senescence, thereby revealing a potential target for antagonizing DPSC aging.

Evaluation of the safety and effectiveness of tubal inflammatory drugs in patients with incomplete tubal obstruction after four-dimensional hysterosalpingo-contrast-sonography examination.

BACKGROUND: To investigate the safety and effectiveness of tubal inflammatory drugs in patients with incomplete tubal obstruction of at least one side after four-dimensional hysterosalpingo-contrast-sonography (4D-HyCoSy) examination. METHODS: Two hundred fifteen cases of tubal incomplete obstruction were diagnosed by ultrasonography from February 2019 to November 2020.According to retrospective analysis,the patients in this study were divided into experimental and control groups; the experimental group combined with salpingitis drugs, and the control group received blank control. Basic information, degree of pain, postoperative complications, and pregnancy rate were then compared between the two groups. RESULTS: Compared with the control group, there was no significant difference in the basic information; in preoperative, intraoperative, or postoperative pain; or in postoperative complications (P > 0.05). The cumulative pregnancy rate of the experimental group (26.8%) was statistically different from that of the control group (14.4%) (P < 0.05). CONCLUSIONS: We observed that for infertile patients with incomplete obstruction of at least one fallopian tube as diagnosed by contrast-enhanced ultrasonography, salpingitis-treatment drugs effectively improved the pregnancy rate postoperatively, with high effectiveness and safety. This regimen is thus worthy of further investigation and promotion in the future.

[Effect of low-dose methylprednisolone on serum TNF-α level in children with Mycoplasma pneumoniae pneumonia].

OBJECTIVE: To investigate the effect of low-dose methylprednisolone on serum tumor necrosis factor alpha (TNF-α) level in children with Mycoplasma pneumoniae pneumonia (MPP). METHODS: A case-control study was conducted among 38 children with MPP who received treatment in the Affiliated Hospital of Yan'an University between January and December 2012, and who had not received glucocorticoids before hospitalization. They were randomly divided into methylprednisolone treatment (n=20) and conventional treatment groups (n=18). The methylprednisolone treatment group was administered with methylprednisolone (1 mg/kg·d) by intravenous drip for three days in addition to conventional treatment. Serum samples were collected from both groups before treatment and on days 4 and 7 of treatment. Twenty-five children who underwent physical examination in the healthcare clinic during the same period were randomly selected as a normal control group, and serum samples were collected on the same day that the physical examination was performed. Serum TNF-α levels in the three groups were measured using enzyme-linked immunosorbent assay. RESULTS: On admission, the methylprednisolone treatment and conventional treatment groups had significantly higher serum TNF-α levels than the normal control group (P<0.01), but there was no significant difference between the methylprednisolone treatment and conventional treatment groups. On days 4 and 7 of treatment, the methylprednisolone treatment group had significantly lower serum TNF-α levels than the conventional treatment group (P<0.05; P<0.01). On day 7 of treatment, there was no significant difference in serum TNF-α level between the methylprednisolone treatment and normal control groups, but the conventional treatment group still had a significantly higher serum TNF-α level than the normal control group (P<0.01). CONCLUSIONS: Low-dose methylprednisolone can significantly decrease serum TNF-α level and inhibit inflammatory response in children with MPP, and may reduce damage caused by inflammatory response.

[Effect of arsenic trioxide and daunorubicin on procoagulant activity of acute promyelocytic leukemia cells].

OBJECTIVE: To explore the effect of arsenic trioxide (ATO) and daunorubicin (DNR) on phosphatidylserine (PS) exposure and related procoagulant activity of acute promyelocytic leukemia (APL) cells. METHODS: Mononuclear cell and neutrophil isolated from whole blood of 12 healthy volunteers were used as control group while APL cells obtained from 12 newly diagnosed APL patients at First Affiliated Hospital, Harbin Medical University from March 2007 to February 2009 were used as experimental group. APL cells were treated with 1 µmol/L ATO and 1 µmol/L DNR for 24 h. PS exposure of APL cells were measured by flow cytometry and confocal microscopy. And the related procoagulant activity was detected by the assays of coagulation time and coagulation factor formation. Lactadherin was used as a probe for PS exposure and anticoagulant on the cells of 12 APL patients. RESULTS: ATO induced a decrease of PS exposure on APL cells by flow cytometry and no staining with lactadherin was observed under confocal microscopy. However, DNR induced the significantly elevated PS exposure and staining green with a rim pattern on membrane of APL cells was obtained. Coagulation time was (180 ± 25) s and (220 ± 41) s before and after treatment with ATO, respectively (P < 0.05). The formation of coagulation factors decreased after treatment with ATO (P < 0.05). While coagulation time was (180 ± 25) s and (80 ± 20) s before and after treatment with DNR, respectively (P < 0.05). The formation of coagulation factors increased after treatment with DNR (all P < 0.05). Lactadherin inhibited the procoagulant activities of DNR-treated APL cells (all P < 0.05). CONCLUSIONS: Procoagulant activity is positively correlated with the exposed PS of APL cells. ATO and DNR inhibited and enhanced procoagulant activity with decreased and increased PS exposure, respectively.

VEGF-Loaded Heparinised Gelatine-Hydroxyapatite-Tricalcium Phosphate Scaffold Accelerates Bone Regeneration via Enhancing Osteogenesis-Angiogenesis Coupling.

Background: Bone tissue defect, one of the common orthopaedicdiseases, is traumatizing and affects patient's lifestyle. Although autologous and xenograft bone transplantations are performed in bone tissue engineering, clinical development of bone transplantation is limited because ofvarious factors, such as varying degrees of immune rejection, lack of bone sources, and secondary damage to bone harvesting. Methods: We synthesised a heparinised gelatine-hydroxyapatite-tricalcium phosphate (HG-HA-TCP) scaffold loaded with sustained-release vascular endothelial growth factor (VEGF) analysed their structure, mechanical properties, and biocompatibility. Additionally, the effects of HG-HA-TCP (VEGF) scaffolds on osteogenic differentiation and vascularisation of stem cells from human exfoliated deciduous teeth (SHED) in vitro and bone regeneration in vivo were investigated. Results: HG-HA-TCP scaffold possessed good pore structure, mechanical properties, and biocompatibility. HG-HA-TCP scaffold loaded with VEGF could effectively promote SHED proliferation, migration, and adhesion. Moreover, HG-HA-TCP (VEGF) scaffold increased the expression of osteogenesis- and angiogenesis-related genes and promoted osteogenic differentiation and vascularisation in cells. In vivo results demonstrated that VEGF-loaded HG-HA-TCP scaffold improved new bone regeneration and enhanced bone mineral density, revealed byhistological, micro-CT and histochemical straining analyses. Osteogenic and angiogenic abilities of the three biological scaffolds wereranked as follows: HG-HA-TCP (VEGF) > G-HA-TCP (VEGF) > G-HA-TCP. Conclusion: HG-HA-TCP (VEGF) scaffold with good biocompatibility could create an encouraging osteogenic microenvironment that could accelerate vessel formation and osteogenesis, providing an effective scaffold for bone tissue engineering and developing new clinical treatment strategies for bone tissue defects.

TAT&RGD Peptide-Modified Naringin-Loaded Lipid Nanoparticles Promote the Osteogenic Differentiation of Human Dental Pulp Stem Cells.

Background: Naringin is a naturally occurring flavanone that promotes osteogenesis. Owing to the high lipophilicity, poor in vivo bioavailability, and extensive metabolic alteration upon administration, the clinical efficacy of naringin is understudied. Additionally, information on the molecular mechanism by which it promotes osteogenesis is limited. Methods: In this study, we prepared TAT & RGD peptide-modified naringin-loaded nanoparticles (TAT-RGD-NAR-NPs), evaluated their potency on the osteogenic differentiation of human dental pulp stem cells (hDPSCs), and studied its mechanism of action through metabolomic analysis. Results: The particle size and zeta potential of TAT-RGD-NAR-NPs were 160.70±2.05 mm and -20.77±0.47mV, respectively. The result of cell uptake assay showed that TAT-RGD-NAR-NPs could effectively enter hDPSCs. TAT-RGD-NAR-NPs had a more significant effect on cell proliferation and osteogenic differentiation promotion. Furthermore, in metabolomic analysis, naringin particles showed a strong influence on the glycerophospholipid metabolism pathway of hDPSCs. Specifically, it upregulated the expression of PLA2G3 and PLA2G1B (two isozymes of phospholipase A2, PLA2), increased the biosynthesis of lysophosphatidic acid (LPA). Conclusion: These results suggested that TAT-RGD-NPs might be used for transporting naringin to hDPSCs for modulating stem cell osteogenic differentiation. The metabolomic analysis was used for the first time to elucidate the mechanism by which naringin promotes hDPSCs osteogenesis by upregulating PLA2G3 and PLA2G1B.

Rosmarinic acid exerts anti-inflammatory effect and relieves oxidative stress via Nrf2 activation in carbon tetrachloride-induced liver damage.

Background: Rosmarinic acid (RA) has biological and pharmaceutical properties and shows hepatoprotective potential. However, the hepatoprotective mechanism of RA needs to be further elucidated in vivo and in vitro. Objective: This study was aimed to evaluate the protective effect of RA on carbon tetrachloride (CCl4)-induced liver injury and elucidate the hepatoprotective mechanism of RA in vivo and in vitro. Design: In vivo, the mice were orally administrated with RA (10, 20, and 40 mg/kg bw) daily for 28 consecutive days, and 1% CCl4 (5 mL/kg bw, dissolved in peanut oil) was used to induce liver injury. In vitro, the big rat liver (BRL) hepatocytes were pretreated with RA (0.2, 0.4, and 0.8 mg/mL) for 3 h, and then the hepatocytes were treated with CC14 (final concentration, 14 mM) for 3 h to induce cell injury. The related indexes, including hepatic function, oxidative stress, protein expression of nuclear-factor erythroid 2-related factor 2 (Nrf2) pathway, inflammation, histopathological change, hepatocyte apoptosis, and mitochondrial membrane potential, were evaluated. Results: Oral administration of RA to mice considerably decreased the CCl4-induced elevation of serum alanine aminotransferase (ALT), alkaline phosphatase (ALP), triacylglycerols (TG), total cholesterol (TC), total bilirubin (TBIL), hepatic reactive oxygen species (ROS), malondialdehyde (MDA), nitric oxide (NO), 8-hydroxydeoxyguanosine (8-OHdG), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-8 (IL-8). RA also increased the levels of hepatic glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) and the protein expressions of Nrf2, quinine oxidoreductase (NQO1), and heme oxygenease-1 (HO-1). Histopathological examinations indicated that RA (20 and 40 mg/kg bw) alleviated the liver tissue injury induced by CCl4. Moreover, RA inhibited the hepatocyte apoptosis caused by CCl4 based on TUNEL assay. In vitro, RA pretreatment remarkably recovered the cell viability and reduced the CCl4-induced elevation of AST, ALT, lactate dehydrogenase (LDH), ROS, and 8-OHdG. Immunohistochemistry staining demonstrated that pretreatment with RA markedly inhibited the expression of IL-6, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and Caspase-3 in CCl4-treated hepatocytes. Additionally, RA pretreatment significantly decreased the elevation of mitochondrial membrane potential in CCl4-treated hepatocytes. Conclusions: RA exerted a protective effect against CCl4-induced liver injury in mice through activating Nrf2 signaling pathway, reducing antioxidant damage, suppressing inflammatory response, and inhibiting hepatocyte apoptosis. RA could attenuate BRL hepatocyte ROS production, DNA oxidative damage, inflammatory response, and apoptosis induced by CCl4 exposure.

Anti-adenovirus activities of shikonin, a component of Chinese herbal medicine in vitro.

Radix Lithosperm eyrthrorhizon is a common prescription compound in traditional Chinese medicine. Shikonin is a major component of Radix Lithospermi and has various biological activities. We have investigated the inhibitory effect of shikonin on the growth of adenovirus type 3 (AdV3) in vitro. The antiviral function of shikonin against AdV3 and its virus inhibition ratio were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method (MTT). The expression of hexon protein in AdV3 was determined by immunofluorescence assay using laser scanning confocal microscopy (LSCM) and Western blot analysis. In addition, the rate of apoptosis in cells infected by AdV3 was determined by flow cytometry. Shikonin (0.0156-1 µM) inhibited growth of AdV3 in a concentration-dependent manner with a virus inhibition rate of 23.8-69.1%. Expression of hexon protein in AdV3 was higher in the virus control group than in the shikonin-treated groups as determined by immunofluorescence assay and Western blotting (p<0.05). The rate of shikonin-treated HeLa cell apoptosis had a statistically significant decrease with increasing concentration of drug (p<0.05). Our data demonstrate that shikonin possesses anti-AdV3 capabilities and that the potential antiviral mechanism might involve inhibiting the degree of apoptosis and hexon protein expression of AdV.

Downregulation of ROR2 promotes dental pulp stem cell senescence by inhibiting STK4-FOXO1/SMS1 axis in sphingomyelin biosynthesis.

Dental pulp stem cells (DPSCs) play a vital role in tooth restoration, regeneration, and homeostasis. The link between DPSC senescence and tooth aging has been well-recognized. ROR2 plays an important role in aging-related gene expression. However, the expression and function of ROR2 in DPSC aging remain largely unknown. In this study, we found that ROR2 expression was significantly decreased in aged pulp tissues and DPSCs. The depletion of ROR2 in young DPSCs inhibits their self-renewal capacity, while its overexpression in aged DPSCs restores their self-renewal capacity. Interestingly, we found that sphingomyelin (SM) is involved in the senescence of DPSCs regulated by ROR2. Mechanistically, we confirmed that ROR2 inhibited the phosphorylation of STK4, which promoted the translocation of Forkhead Box O1 (FOXO1) to the nucleus. STK4 inhibition or knockdown of FOXO1 markedly increased the proliferation of DPSCs and upregulated the expression of SMS1, which catalyzed SM biogenesis. Moreover, FOXO1 directly bound to the SMS1 promoter, repressing its transcription. Our findings demonstrated the critical role of the ROR2/STK4-FOXO1/SMS1 axis in the regulation of SM biogenesis and DPSC senescence, providing a novel target for antagonizing tooth aging.

Investigation of a Novel LRP6 Variant Causing Autosomal-Dominant Tooth Agenesis.

BACKGROUND: The low-density lipoprotein receptor-related protein 6 (LRP6) gene is a recently defined gene that is associated with the autosomal-dominant inherited tooth agenesis (TA). In the present study, a family of four generations having TA was recruited and subjected to a series of clinical, genetic, in silico, and in vitro investigations. METHODS: After routine clinical evaluation, the proband was subjected to whole-exome sequencing (WES) to detect the diagnostic variant. Next, in silico structural and molecular dynamics (MD) analysis was conducted on the identified novel missense variant for predicting its intramolecular impact. Subsequently, an in vitro study was performed to further explore the effect of this variant on protein maturation and phosphorylation. RESULTS: WES identified a novel variant, designated as LRP6: c.2570G > A (p.R857H), harbored by six members of the concerned family, four of whom exhibited varied TA symptoms. The in silico analysis suggested that this novel variant could probably damage the Wnt bonding function of the LRP6 protein. The experimental study demonstrated that although this novel variant did not affect the LRP6 gene transcription, it caused a impairment in the maturation and phosphorylation of LRP6 protein, suggesting the possibility of the disruption of the Wnt signaling. CONCLUSION: The present study expanded the mutation spectrum of human TA in the LRP6 gene. The findings of the present study are insightful and conducive to understanding the functional significance of specific LRP6 variants.

Synthesis and Electrorheological Response of Graphene Oxide/Polydiphenylamine Microsheet Composite Particles.

Conducting graphene oxide/polydiphenylamine (GO/PDPA) microsheet nanocomposite particles were fabricated via in-situ oxidative polymerization using diphenylamine in the presence of GO. The morphological structures and dimensions of the fabricated GO/PDPA composites were evaluated using transmission electron microscopy and scanning electron microscopy. Electrorheological (ER) responses and creep behaviors of an ER fluid consisting of the GO/PDPA composites when suspended in silicone oil were evaluated using a rotational rheometer under input electric field. Three different types of yield stresses were examined along with dielectric analysis, demonstrating their actively tunable ER behaviors.

Distribution of Carbapenemases and Efflux Pump in Carbapenem-resistance Acinetobacter baumannii.

Acinetobacter baumannii has emerged as an important pathogen related to serious infections and nosocomial outbreaks around the world. In this study, 100 isolates of carbapenem-resistance in Acinetobacter baumannii (CRAB) were collected from clinical specimens. Agar dilution was conducted to determine the minimum inhibitory concentrations (MICs) for 15 kinds of antibiotics. Genes of carbapenemases and efflux pumps were amplified by PCR. The expression difference of pump genes was analyzed by real-time PCR between CRAB and carbapenems-sensitive Acinetobacter baumannii (CSAB). We found that most antibiotics, including aminoglycosides, fluoroquinolones, and cephalosporins showed high MIC values in CRAB. All isolates were sensitive to polymyxin B. Among the CRAB specimens, 54, 32 and 16 isolates were positive for SHV-12, PER-1 and TEM-1, respectively. 86 isolates were positive for OXA-23. 55 and 33 isolates carried adeB and adeJ genes, respectively. The expression level of adeB in CRAB was ten times higher than that in CSAB. We speculate that SHV-12, PER-1, TEM-1, OXA-23 and the AdeABC efflux pump may participate in high-level carbapenems resistance in Acinetobacter baumannii Moreover, adeE may be related to low-level resistance of carbapenems and quinolones in Acinetobacter baumannii.

Contrast-Enhanced Ultrasound Evaluation of Mifepristone for Treatment of Low-Risk Cesarean Scar Pregnancy.

Purpose: The effect of mifepristone for treatment of low-risk cesarean scar pregnancy (CSP) was monitored by contrast-enhanced ultrasound (CEUS). Methods: Data were collected from 23 CSP patients with a 10-point risk score <5 (low-risk CSP) and from 23 intrauterine pregnancy (IUP) patients with a scar from a previous cesarean delivery. All patients were prescribed 75 mg mifepristone daily for 2 days and underwent transvaginal CEUS before and after administration of mifepristone. On the third day, uterine curettage was performed after transvaginal CEUS. Arrival time (AT), peak intensity (PI), and area under the curve (AUC) around the gestational sac were monitored by CEUS before and after application of mifepristone, and the rate of effective treatment was compared between the two patient groups. Results: No patients experienced side effects from either the CEUS procedure or the mifepristone treatment. Changes in AT, PI, and AUC index from before vs. after mifepristone treatment did not differ significantly between the two groups (all p values >0.05). There was also no significant difference in the rate of effective treatment between the two groups (95.65% in the CSP group vs. 100% in the IUP group; p > 0.05). Conclusions: Based on monitoring by CEUS, the effect of mifepristone in low-risk CSP was comparable to that in IUP.

Homology analysis of 51 penicillin-intermediate Streptococcus pneumoniae isolates from Wenzhou City, China.

OBJECTIVE: To investigate drug resistance features and homology among penicillin-intermediate Streptococcus pneumoniae isolates from Wenzhou City, China. METHODS: Fifty-one penicillin-intermediate S. pneumoniae isolates were obtained from respiratory samples of infants and children hospitalized with lung infections. An antimicrobial susceptibility test was used to assess drug resistance. Polymerase chain reaction and agarose gel electrophoresis were used to identify S. pneumoniae isolates and pulsed-field gel electrophoresis (PFGE) was used to analyze molecular subtypes. Hierarchical cluster analysis of PFGE fingerprints was used to compare genetic diversity and relatedness of S. pneumoniae isolates. The Quellung test was used for serotyping. RESULTS: Fifty-one penicillin-intermediate S. pneumoniae isolates showed evidence of multi-drug resistance and polyclonal origins. The isolates were classified into 25 subtypes through hierarchical cluster analysis of PFGE fingerprints. Three of these subtypes formed a supertype (15/51, 16/51 and 8/51 isolates), while the remaining subtypes occurred sporadically (12/51 isolates). CONCLUSIONS: Transmission of penicillin-intermediate S. pneumoniae is mostly vertical and to a lesser extent horizontal. Effective prevention strategies, including respiratory tract management and contact isolation, are essential to control nosocomial S. pneumoniae infection. Once susceptibility is confirmed, vancomycin, high-dose penicillin or third-generation cephalosporins (cefotaxime and ceftriaxone) may be used to treat penicillin-intermediate S. pneumoniae.

Validation of a 10-Point Scoring System for Treatment of Cesarean Scar Pregnancy.

PURPOSE: To validate a 10-point scoring system for the prediction of successful treatment modality in patients with cesarean scar pregnancy (CSP). PATIENTS AND METHODS: Data were collected from women seen between April 1, 2018, and June 30, 2019, at the Second Affiliated Hospital of Army Medical University of China who were diagnosed with CSP and underwent evacuation, followed by uterine artery embolization (UAE) and successive laparoscopic local resection as salvage treatment if necessary. A score was computed based on clinical and ultrasonographic parameters included in a previously developed scoring system. Treatment indicated by the scoring system was compared with actual treatment received. Receiver operating characteristic (ROC) curves were used to identify cut-off scores for salvage treatment. RESULTS: Of 183 women, 108 were successfully treated by evacuation, 57 required UAE, and 18 eventually underwent laparoscopic surgery. Among 97 women scoring 0-4, 89 (91.8%) were treated by evacuation only. Of 69 women scoring between 5 and 7, 44 (63.8%) needed UAE following evacuation. Of 17 women scoring 8-10, 10 women (58.8%) underwent laparoscopic surgery. A cut-off of 4.145 was obtained by ROC curve for prediction of any salvage treatment; this was comparable to the scale's conventional cut-off of 4. The cut-off score for women requiring laparoscopic surgery was 6.580, which was lower than 8 obtained in the scale's initial validation. CONCLUSION: The overall performance of the 10-point scoring system was moderate for predicting successful treatment modalities of women with CSP, but the scale showed good predictive ability in recognizing women needing only evacuation before recovery.

Association between inflammation factors and Mycoplasma pneumoniae in children: Protocol for a systematic review.

BACKGROUND: Several clinical studies have reported that inflammation factors (IF) are associated with Mycoplasma pneumoniae in children. However, no study systematically investigated the association between IF and M pneumoniae in pediatric population. Thus, this study will explore the association between IF and pediatric M pneumoniae systematically. METHODS: This study will search following databases of PUBMED, PsycINFO, Scopus, Cochrane Library, EMBASE, Web of Science, and Chinese Biomedical Literature Database from inception to the February 28, 2019 without any language limitations. We will cover clinical studies of M pneumoniae that report associations between IF and M pneumoniae. In addition, reference lists of relevant studies will also be identified to avoid missing any eligible studies. Two investigators will independently screen and select studies, and will assess the methodological quality for each study, which is evaluated by using Newcastle Ottawa Scale. Any disagreements will be settled down through discussion with a third investigator until consensus is reached. RESULTS: This study will explore the associations between IF and M pneumoniae by assessing the changes of IF, such as interleukin (IL)-4, IL-5, IL-6, IL-10, IL-13, and IL-17 at different stages of M pneumoniae. CONCLUSION: The findings of this study may provide most recent evidence for the associations between IF and M pneumoniae in pediatric populations. ETHICS AND DISSEMINATION: Ethical approval is not needed in this study, because no individual patient data will be utilized in this study. The findings of this study are expected to be published at peer-reviewed journal or will be presented at professional conference. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42019125359.

c.753_754delAG, a novel CFTR mutation found in a Chinese patient with cystic fibrosis: A case report and review of the literature.

BACKGROUND: Cystic fibrosis (CF) is rare in Asian populations relative to the Caucasian population. In this paper, we report the cystic fibrosis transmembrane conductance regulator (CFTR) variation in a family of Chinese CF patients, and systematically review the previous literature. CASE SUMMARY: Here we report a 30-month-old Chinese girl who was diagnosed with CF based on her history and symptoms such as recurrent productive cough, wheezing with repeated infection of Pseudomonas aeruginosa, and parasinusitis. Chest computed tomography (CT) scanning revealed obvious exudative lesions and bilateral bronchiectasis. Liver CT scanning revealed a low-density lesion in the left lobe of the liver. A diagnosis of CF was made based upon CFTR gene tests. The CFTR gene was sequenced using the blood samples of her and her parents and showed a heterozygous novel missense mutation of c.753_754delAG in exon 7. In addition, a heterozygous c.1240 C>T mutation was found in exon 10 of the CFTR. The mutation c.753_754delAG was verified to have been inherited from her mother, and the c.1240 C>T mutation was from her father who was diagnosed with congenital absence of vas deferens. CONCLUSION: A novel mutation of CFTR, c.753_754delAG, was found in a Chinese CF child. c.2909G>A is the most common mutation among Chinese CF patients.

Multisystem smooth muscle dysfunction syndrome in a Chinese girl: A case report and review of the literature.

BACKGROUND: Multisystemic smooth muscle dysfunction syndrome (MSMDS) is a rare genetic disease worldwide. The main mutation is the actin alpha 2 (ACTA2) gene p.R179H. In this paper, we report a Chinese MSMDS patient and systematically review the previous literature. CASE SUMMARY: Here, we report a 9.6-month-old Chinese girl who was diagnosed with MSMDS based on her history and symptoms, such as recurrent cough, wheezing, and complications with congenital fixed dilated pupils. Chest high-resolution computed tomography revealed inhomogeneous lung transparency, obvious exudative lesions, and some lung fissures that were markedly thickened. Cranial magnetic resonance imaging excluded bleeding and infarction but showed abnormal signals in the centrum ovale majus and bilateral periventricular regions. Echocardiography only showed patent foramen ovale, and no patent ductus arteriosus, pulmonary artery dilatation, or pulmonary hypertension was found. Bronchoscopy indicated moderate bronchial malacia. These examinations in conjunction with the typical eye abnormality suggested a diagnosis of MSMDS, and sequencing of exon 6 of the ACTA2 gene demonstrated the heterozygous mutation c.536G>A, p.R179H. However, her parents' gene analyses were normal. CONCLUSION: MSMDS is a rare genetic disease mainly caused by the mutation of the ACTA2 gene p.R179H. Early genetic diagnosis should be performed for children presenting with congenital fixed dilated pupils and patent ductus arteriosus. During the process of diagnosis and treatment, clinicians should be on high alert for cerebrovascular, cardiovascular, and pulmonary complications.

Scoring system for the prediction of the successful treatment modality in women with cesarean scar pregnancy.

OBJECTIVE: To establish a risk scoring system to predict the successful treatment of cesarean scar pregnancy. METHODS: A prospective observational study was conducted between June 2016 and March 2018 in a tertiary care center. Patients received evacuation followed by uterine artery embolization and laparoscopic local resection/hysterectomy successively as salvage measures if necessary. Optimal scaling regression determined the extent of each potential prognostic factor predicted. RESULTS: Out of 228 women, 144 cases required evacuation before recovery, 73 women required uterine artery embolization, and 11 women eventually required laparoscopic surgery. Six variables were included in the predictive model: number of cesarean deliveries; maximal diameter of gestational sac; remnant myometrial thickness; grading of Doppler signals; presence of fetal heartbeat; and location of gestational sac. A 10-point scoring system was established by weighting their prediction of the method of successful treatment. In the risk score rank of 1-4, only 4 (2.8%) out of 142 women needed uterine artery embolization as a salvage treatment, while in the risk score rank of 8-10, 41 (80.4%) cases needed uterine artery embolization; laparoscopic operations were performed by physicians for the other 10 (19.6%) cases. CONCLUSION: The successful treatment of cesarean scar pregnancy was accurately predicted by a 10-point scoring system. CHINESE CLINICAL TRIALS REGISTRY: ChiCTR-OOC-16008467.

Protective effect of free phenolics from Lycopus lucidus Turcz. root on carbon tetrachloride-induced liver injury in vivo and in vitro.

Protective effect of free phenolics from Lycopus lucidus Turcz. root (FPLR) on CCl4-induced hepatotoxicity in vivo and in vitro was first evaluated. Oral administration of FPLR (100 mg/kg bw) to mice significantly reduced the CCl4-induced elevation of serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, triacylglycerols, total cholesterol, and total bilirubin. FPLR also increased the hepatic GSH contents and antioxidant enzyme activities of SOD and CAT and decreased the hepatic MDA level. Histopathological examinations further confirmed that the FPLR could protect the liver from CCl4-induced damage. Further research indicated that FPLR prevented the DNA fragmentation caused by CCl4 based on TUNEL assay. Moreover, immunohistochemistry staining demonstrated that pretreatment with FPLR significantly inhibited the elevation of hepatic TNF-α, IL-6, IL-8, iNOS, COX-2, and Caspase-3 in CCl4-treated mice. In vitro experiments showed that FPLR remarkably reduced BRL hepatocyte apoptosis and damage caused by CCl4 treatment. These findings indicate that FPLR could be developed as a functional food or medication for therapeutic purpose and prevention of hepatic injury.