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Background: There have been previous studies and earlier systematic review on the relationship between inflammatory bowel disease (IBD) and radiation exposure. With the diversification of current test methods, this study intended to conduct a meta-analysis to evaluate the IBD radiation exposure in recent years. Methods: Three databases (PUBMED, EMBASE, and MEDICINE) for relevant literature up to May 1, 2023 were searched. The statistical data meeting requirements were collated and extracted. Results: 20 papers were enrolled. The overall high radiation exposure rate was 15% (95% CI = [12%, 19%]) for CD and 5% (95% CI = [3%, 7%]) for UC. The pooled result found that high radiation exposure rate was 3.44 times higher in CD than in UC (OR = 3.44, 95% CI = [2.35, 5.02]). Moreover, the average radiation exposure level in CD was 12.77 mSv higher than that in UC (WMD = 12.77, 95% CI = [9.93, 15.62] mSv). Furthermore, radiation exposure level of CD after 2012 was higher than those before 2012 (26.42 ± 39.61vs. 23.76 ± 38.46 mSv, P = 0.016), while UC did not show similar result (11.99 ± 27.66 vs. 10.01 ± 30.76 mSv, P = 0.1). Through subgroup analysis, it was found that disease duration (WMD = 2.75, 95% CI = [0.10, 5.40] mSv), complications (OR = 5.09, 95% CI = [1.50, 17.29]), and surgical history (OR = 5.46, 95% CI = [1.51, 19.69]) significantly increased the proportion of high radiation exposure. Conclusion: This study found that radiation exposure level of IBD patients was high, which revealed the radiation risk in the process of diagnosis and treatment of IBD patients. In the future, longer follow-up and prospective studies are needed to reveal the relationship between high radiation exposure and solid tumorigenesis. [ABSTRACT FROM AUTHOR]

Background: KIAA0586, also known as Talpid3, plays critical roles in primary cilia formation and hedgehog signaling in humans. Variants in KIAA0586 could cause some different ciliopathies, including Joubert syndrome (JBTS), which is a clinically and genetically heterogeneous group of autosomal recessive neurological disorders. Methods and Results: A 9-month-old girl was diagnosed as JBTS by the "molar tooth sign" of the mid-brain and global developmental delay. By whole-exome sequencing, we identified a single nucleotide variant c.3303G > A and a 1.38-kb deletion in KIAA0586 in the proband. These two variants of KIAA0586 were consistent with the mode of autosomal recessive inheritance in the family, which was verified using Sanger sequencing. Conclusions: This finding of a compound heterozygote with a 1.38-kb deletion and c.3303G > A gave a precise genetic diagnosis for the patient, and the novel 1.38-kb deletion also expanded the pathogenic variation spectrum of JBTS caused by KIAA0586. [ABSTRACT FROM AUTHOR]

Background: A tourniquet is a device commonly used to control massive hemorrhage during knee replacement surgery. However, the question remains whether the use of tourniquets affects the permeability of the bone cement around the knee prosthesis. Moreover, the long-term effects and stability of the knee prosthesis are still debatable. The aim of this study was to examine whether the use of a tourniquet increases the thickness of the cement mantle and affects the postoperative blood loss and pain during primary total knee arthroplasty (TKA) using meta-analysis. Methods: We searched the Cochrane Central Library, MEDLINE, Embase, PubMed, CNKI, and Wang Fang databases for randomized controlled trials (RCTs) on primary TKA, from inception to November 2019. All RCTs in primary TKA with and without a tourniquet were included. The meta-analysis was conducted using RevMan 5.2 software. Results: A total of eight RCTs (677 knees) were analyzed. We found no significant difference in the age and sex of the patients. The results showed that the application of tourniquet affects the thickness of the bone cement around the tibial prosthesis (WMD = 0.16, 95%CI = 0.11 to 0.21, p < 0.00001). However, in our study, there was no significant difference in postoperative blood loss between the two groups was observed (WMD = 12.07, 95%CI = − 78.63 to 102.77, p = 0.79). The use of an intraoperative tourniquet can increase the intensity of postoperative pain (WMD = 1.34, 95%, CI = 0.32 to 2.36, p = 0.01). Conclusions: Tourniquet application increases the thickness of the bone cement around the prosthesis and may thus increase the stability and durability of the prosthesis after TKA. The application of an intraoperative tourniquet can increase the intensity of postoperative pain. [ABSTRACT FROM AUTHOR]

Objective: By analyzing the perioperative, postoperative complications and long-term overall survival time, we summarized the 8-year experience of minimally invasive McKeown esophagectomy for esophageal cancer in a single medical center.Methods: This retrospective follow-up study included 1023 consecutive patients with esophageal cancer who underwent MIE-McKeown between Mar 2013 and Oct 2020. Relevant variables were collected and evaluated. Overall survival (OS) and disease-free survival (DFS) were analyzed by Kaplan-Meier method.Results: For 1023 esophageal cancer undergoing MIE-McKeown, the main intraoperative complications were bleeding (3.0%, 31/1023) and tracheal injury (1.7%, 17/1023). There was no death occurred during operation. The conversion rate of thoracoscopy to thoracotomy was 2.2% (22/1023), and laparoscopy to laparotomy was 0.3% (3/1023). The postoperative morbidity of complications was 36.2% (370/1023), of which anastomotic leakage 7.7% (79/1023), pulmonary complication 13.4% (137/1023), chylothorax 2.3% (24/1023), and recurrent laryngeal nerve injury 8.8% (90/1023). The radical resection rate (R0) was 96.0% (982/1023), 30-day mortality was 0.3% (3/1023). For 1000 cases with squamous cell carcinoma, the estimated 3-year and 5-year overall survival was 37.2% and 17.8% respectively. In addition, neoadjuvant chemotherapy offered 3-year disease-free survival rate advantage in advanced stage patients (for stage IV: 7.2% vs. 1.8%).Conclusions: This retrospective single center study demonstrates that MIE-McKeown procedure is feasible and safe with low perioperative and postoperative complications' morbidity, and acceptable long-term oncologic results. [ABSTRACT FROM AUTHOR]

Background: Previous studies reported that Epstein–Barr virus (EBV) may play a causal role in the pathogenesis of gastric remnant carcinoma (GRC). However, there was still some controversy. Methods: Articles published until July 15, 2020, in PubMed, MEDLINE, Embase and CNKI databases were selected. According to the inclusion criteria, corresponding data of included articles were abstracted and used for statistical analysis. Results: Thirteen papers were finally enrolled, nine of which showed the result that the risk of EBV infection rate in the GRC was higher than conventional gastric carcinoma (OR = 5.22, 95% CI 3.89–7.00). In addition, we found that EBV associated GRC (EBVaGRC) had higher rate of Billroth-II (OR = 3.80, 95% CI 1.90–7.57), carcinoma in anastomotic site (OR = 2.41, 95% CI 1.27–4.56) and diffuse type (Lauren classification) (OR = 1.97, 95% CI 1.04–3.73),while sex, initial diagnosis and lymphocytic infiltration were calculated no statistical difference. By genetic polymorphism analysis, "V-val" subtype of EBNA1 (OR = 21.84, 95% CI 11.92–31.76) and "C" subtype of BamHI-W1/I1 (OR = 7.07, 95% CI 1.47–34.03) were observed to be highly expressed in EBVaGRC. Conclusion: EBV infection rate in the GRC was higher. Further analysis showed that Billroth-II, carcinoma in anastomotic site and diffuse type (Lauren classification) were associated to EBVaGRC. Through analysis of EBV genome polymorphisms, we thought that "V-val" subtype of EBNA1 and "C" subtype of BamHI-W1/I1 may become predictor of EBVaGRC. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to assess the accuracy and reliability of and time taken by a novel method using the built-in photo-edit function of smartphones compared with PACS in measuring hallux valgus parameters.Methods: Seventy patients (124 ft) admitted to our hospital with a diagnosis of hallux valgus without previous surgical procedures were retrospectively reviewed. The foot radiographs of all the patients were extracted from PACS. The hallux valgus angle (HVA) and the first and second intermetatarsal angles (IMAs) were measured by PACS and by this novel method using the built-in photo-edit function of a smartphone. The results of these two methods were compared, and the accuracy and reliability were assessed between these two methods.Results: The average parameters measured by PACS were as follows: HVA average: 37.43 ± 9.61°; IMA average: 13.37 ± 4.01°. The average parameters measured by smartphones were as follows: HVA average: 37.09 ± 9.52° and IMA average: 13.49 ± 3.91°. When compared by the independent-samples T test, the average parameters between PACS and smartphones were not significantly different (HVA PACS vs HVA smartphones: P = 0.776; IMA PACS vs IMA smartphones: P = 0.816). The variability of the HVA (F = 0.166, P = 0.992) and IMA (F = 0.215, P = 0.982) measurements was similar for the PACS and smartphones. The ICCs of the average parameters of four measurements of HVA and IMA between PACS and smartphones were 0.995 (0.991-0.997) and 0.970 (0.958-0.979), indicating that the two methods were highly correlated. For the smartphone measurement, the interobserver and intraobserver reliability was very good for HVA and IMA. The average measurement time of PACS was 25.41 ± 0.86 s, and the average measurement time of smartphones was 20.29 ± 1.22 s. The smartphone time was significantly faster than that of PACS by approximately 5 s (P<0.001).Conclusion: This novel method using the built-in photo-edit function of smartphones is accurate, reliable, convenient and time-saving in measuring the angles of hallux valgus. [ABSTRACT FROM AUTHOR]

Background: Erectile dysfunction (ED) has often been observed in patients with obstructive sleep apnea (OSA). Research on adipose-derived mesenchymal stem cell (ADSC)-derived exosomes has shown that they have significant therapeutic effects in many diseases including ED. Methods: In this study, ED was induced in Sprague Dawley (SD) rats using chronic intermittent hypoxia (CIH) exposure. CIH-mediated influences were then measured in the corpus cavernous smooth muscle cells (CCSMCs). Results: Our data showed that miR-301a-3p-enriched exosome treatment significantly recovered erectile function in rats and CCSMCs by promoting autophagy and inhibiting apoptosis. The treatment also significantly recovered the level of alpha smooth muscle actin (α-SMA) in rats and CCSMCs. Bioinformatics predicted that phosphatase and tensin homolog (PTEN) and Toll-like receptor 4 (TLR4) might be targets of miR-301a-3p. Conclusions: Our results indicate that PTEN-overexpression vectors or TLR4-overexpression vectors reverse the therapeutic effects achieved by miR-301a-3p in CCSMCs indicating that PTEN/hypoxia-inducible factor-1 alpha (HIF-1α) and TLR4 signaling pathways play key roles in the progression of ED. The findings in this study suggest that miR-301a-3p should be considered a new therapeutic target for treating ED associated with OSA. [ABSTRACT FROM AUTHOR]

Background: Helicobacter pylori (H. pylori) infection is a worldwide threat to human health with high prevalence. In this study, we analyzed the relationship between latitude, average annual temperature, average daily sunshine time and H. pylori infection.Methods: The PubMed, ClinicalTrials.gov , EBSCO and Web of Science databases were searched to identify studies reporting H. pylori infection. Latitude 30° was the cut-off level for low and mid-latitude areas. We obtained information for latitude, average annual temperature, average daily sunshine, and Human Development Index (HDI) from reports of studies of the relationships with H. pylori infection.Results: Of the 51 studies included, there was significant difference in H. pylori infection between the low- and mid-latitude areas (P = 0.05). There was no significant difference in the prevalence of H. pylori infection in each 15°-latitude zone analyzed (P = 0.061). Subgroup analysis revealed the highest and lowest H. pylori infection rates in the developing regions at > 30° latitude subgroup and the developed regions at < 30° latitude subgroup, respectively (P < 0.001). Multivariate analysis showed that average annual temperature, average daily sunshine time and HDI were significantly correlated with H. pylori infection (P = 0.009, P < 0.001, P < 0.001), while there was no correlation between H. pylori infection and latitude.Conclusions: Our analysis showed that higher average annual temperature was associated with lower H. pylori infection rates, while average daily sunshine time correlated positively with H. pylori infection. HDI was also found to be a significant factor, with higher HDI associated with lower infection rates. These findings provide evidence that can be used to devise strategies for the prevention and control of H. pylori. [ABSTRACT FROM AUTHOR]

Objective: This aimed to evaluate the status of return to work (RTW) in patients with osteonecrosis of the femoral head (ONFH) after total hip arthroplasty (THA). Methods: The baseline characteristics of all patients in this retrospective study were obtained from the hospital patient database. The relevant changes in patients' working conditions, as well as the numerical rating scale (NRS), Harris Hip Score (HHS), self-assessment of work ability, and Likert scale satisfaction assessment were obtained through video call follow-ups. Results: 118 patients (response rate: 83%) were ultimately included in this study. The average length of time for the patients to stop working preoperatively was 20.7 weeks. Ninety-four patients (24 women and 70 men) who underwent THA had RTW status, with a mean RTW time of 21.0 weeks. Men had a significantly higher proportion of final RTW and a significantly faster RTW than women. Significant differences in smoking, drinking, cardiovascular diseases, changes in working levels, variations in the types of physical work, changes in working hours, and pain symptoms were observed between the RTW and Non-RTW populations. The patients with a positive RTW status had higher postoperative HHS scores, lower postoperative NRS scores, and higher self-assessment of work ability than patients who had a negative RTW status. Conclusion: Ultimately, 80% of patients achieved RTW status. Drinking, sex, change in working level, variation in the type of physical work, change in working hours, post-surgery HHS score and self-assessment of work ability can serve as predictive factors for RTW. [ABSTRACT FROM AUTHOR]

The study was design to investigate the functional roles of Wilms tumor 1-associated protein (WTAP), an enzyme catalyzes m6A modification, in the pathogenesis of osteoarthritis (OA) and further elucidate its possible regulatory mechanism. Herein, we discovered that WTAP was outstandingly upregulated in chondrocyte stimulated with Lipopolysaccharide (LPS) and cartilage tissue of patients with OA. Functional studies have demonstrated that WTAP knockdown enhances proliferation ability, suppresses apoptosis, and reduces extracellular matrix (ECM) degradation in an LPS—induced OA chondrocyte injury model and ameliorates cartilage damage in a destabilizing the medial meniscus (DMM)—induced OA mice model. Conversely, overexpression of WTAP contributes to the opposite effects. Mechanistically, our data has demonstrated that m6A modification mediated by WTAP promotes the maturation of pri-miR-92b to miR-92b-5p, thereby enhancing the targeted inhibitory function of miR-92b-5p on TIMP4. Furthermore, we have discovered that WTAP can directly facilitate the degradation of TIMP4 mRNAs in a YTHDF2-dependent manner. In a nutshell, our findings suggested that WTAP knockdown alleviated OA progression by modulating the miR-92b-5p/TIMP4 axis in an m6A-dependent manner. Our study disclosed that WTAP-mediated m6A modification displayed a crucial role in OA development and suggested that targeting WTAP could be a promising preventive and therapeutic target for patients with OA. 7QG3J4kX7R4LACdpcrQ_Fq Video Abstract [ABSTRACT FROM AUTHOR]

Background: Recurrence after resection is the main factor for poor survival. The relationship between clinicopathological factors and recurrence after curative distal pancreatectomy for PDAC has rarely been reported separately. Methods: Patients with PDAC after left‑sided pancreatectomy between May 2015 and August 2021 were retrospectively identified. Results: One hundred forty-one patients were included. Recurrence was observed in 97 patients (68.8%), while 44 (31.2%) patients had no recurrence. The median RFS was 8.8 months. The median OS was 24.9 months. Local recurrence was the predominant first detected recurrence site (n = 36, 37.1%), closely followed by liver recurrence (n = 35, 36.1%). Multiple recurrences occurred in 16 (16.5%) patients, peritoneal recurrence in 6 (6.2%) patients, and lung recurrence in 4 (4.1%) patients. High CA19-9 value after surgery, poor differentiation grade, and positive lymph nodes were found to be independently associated with recurrence. The patients receiving adjuvant chemotherapy had a decreased likelihood of recurrence. In the high CA19-9 value cohort, the median PFS and OS of the patients with or without chemotherapy were 8.0 VS. 5.7 months and 15.6 VS. 13.8 months, respectively. In the normal CA19-9 value cohort, there was no significant difference in PFS with or without chemotherapy (11.7 VS. 10.0 months, P = 0.147). However, OS was significantly longer in the patients with chemotherapy (26.4 VS. 13.8 months, P = 0.019). Conclusions: Tumor biologic characteristics, such as T stage, tumor differentiation and positive lymph nodes, affecting CA19-9 value after surgery are associated with patterns and timing of recurrence. Adjuvant chemotherapy significantly reduced recurrence and improved survival. Chemotherapy is strongly recommended in patients with high CA199 after surgery. [ABSTRACT FROM AUTHOR]

Background: The role of serum high-density lipoprotein cholesterol (HDL-c) in tumorigenesis are observed in several endocrine-related cancers. However, its role in pancreatic neuroendocrine neoplasms (PNENs) has not been understood. In the current study, the relationship between HDL-c levels and malignant behavior in PNENs was explored. Methods: One hundred ninety-seven patients with histopathology confirmed PNENs were included. PNENs were divided into three grades (G1, G2 and G3) as 2017 WHO classification based on ki67 index and mitosis count. The demographic data, clinical information, tumor morphological and pathological features (organs invasion, lymph node metastasis, vascular invasion and perineural invasion), and serum tumor biomarkers were collected. The relationships between HDL-c levels and malignant behaviors in PNENs were analyzed using logistic regression analysis. Models were also developed for the identification of high grade PNENs. Results: The levels of serum HDL-c in G2/G3 tumor were significantly lower than that in G1 tumor (P = 0.031). However, no such difference was found between G3 and G1/G2. The proportions of low HDL-c (≤ 0.9 mmol/L) were higher in high-grade PNENs (G2/G3 or G3) than those in low-grade (G1 or G1/G2) (29.0 vs 15.2%, P = 0.032; 37.0 vs 20.5%, P = 0.023). The risk of G2/G3 tumors in patients with high serum HDL-c levels was decreased (odds ratio (OR) = 0.35, 95% confidence interval (CI): 0.12–0.99). Similarly, the risk of G3 PNENs increased in patients with low HDL-c levels (OR = 2.51, 95%CI:1.12–5.60). HDL-c level was also associated with a high ki67 index (> 55%) (OR = 0.10, 95%CI: 0.02–0.51) and neuroendocrine carcinoma G3 (OR = 0.21, 95%CI: 0.06–0.80). The area under the curve (AUC) of HDL-c + tumor size + age was 0.85 (95% CI: 0.79–0.91) in identifying G2/G3 PNENs, and HDL-c (> 0.9 mmol/L) + tumor size + age had an AUC of 0.77 (95% CI: 0.70–0.84) in identifying G3 PNENs. HDL-c level was associated with lymph node metastasis (OR = 0.24, 95%CI:0.08–0.99). Conclusion: Serum HDL-c levels were significantly associated with malignant behaviors in PNENs, in particular to tumor grade and lymph node metastasis. [ABSTRACT FROM AUTHOR]

Background: Noncoding RNAs (ncRNAs), including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), are pivotal regulators involved in the pathogenic mechanism of multiple coronaviruses. Porcine deltacoronavirus (PDCoV) has evolved multiple strategies to escape the innate immune response of host cells, but whether ncRNAs are involved in this process during PDCoV infection is still unknown. Results: In this study, the expression profiles of miRNAs, lncRNAs and mRNAs in IPEC-J2 cells infected with PDCoV at 0, 12 and 24 hours postinfection (hpi) were identified through small RNA and RNA sequencing. The differentially expressed miRNAs (DEmiRNAs), lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) were screened from the comparison group of IPEC-J2 cells at 0 and 12 hpi as well as the comparison group of IPEC-J2 cells at 12 and 24 hpi. The target genes of these DEncRNAs were predicted. The bioinformatics analysis of the target genes revealed multiple significantly enriched functions and pathways. Among them, the genes that were associated with innate immunity were specifically screened. The expression of innate immunity-related ncRNAs and mRNAs was validated by RT–qPCR. Competing endogenous RNA (ceRNA) regulatory networks among innate immunity-related ncRNAs and their target mRNAs were established. Moreover, we found that the replication of PDCoV was significantly inhibited by two innate immunity-related miRNAs, ssc-miR-30c-3p and ssc-miR-374b-3p, in IPEC-J2 cells. Conclusions: This study provides a data platform to conduct studies of the pathogenic mechanism of PDCoV from a new perspective and will be helpful for further elucidation of the functional role of ncRNAs involved in PDCoV escaping the innate immune response. [ABSTRACT FROM AUTHOR]

Background: Patients with salt-sensitive hypertension are often accompanied with severe renal damage and accelerate to end-stage renal disease, which currently lacks effective treatment. Fibroblast growth factor 21 (FGF21) has been shown to suppress nephropathy in both type 1 and type 2 diabetes mice. Here, we aimed to investigate the therapeutic effect of FGF21 in salt-sensitive hypertension-induced nephropathy. Methods: Changes of FGF21 expression in deoxycorticosterone acetate (DOCA)-salt-induced hypertensive mice were detected. The influence of FGF21 knockout in mice on DOCA-salt-induced nephropathy were determined. Recombinant human FGF21 (rhFGF21) was intraperitoneally injected into DOCA-salt-induced nephropathy mice, and then the inflammatory factors, oxidative stress levels and kidney injury-related indicators were observed. In vitro, human renal tubular epithelial cells (HK-2) were challenged by palmitate acid (PA) with or without FGF21, and then changes in inflammation and oxidative stress indicators were tested. Results: We observed significant elevation in circulating levels and renal expression of FGF21 in DOCA-salt-induced hypertensive mice. We found that deletion of FGF21 in mice aggravated DOCA-salt-induced nephropathy. Supplementation with rhFGF21 reversed DOCA-salt-induced kidney injury. Mechanically, rhFGF21 induced AMPK activation in DOCA-salt-treated mice and PA-stimulated HK-2 cells, which inhibited NF-κB-regulated inflammation and Nrf2-mediated oxidative stress and thus, is important for rhFGF21 protection against DOCA-salt-induced nephropathy. Conclusion: These findings indicated that rhFGF21 could be a promising pharmacological strategy for the treatment of salt-sensitive hypertension-induced nephropathy. [ABSTRACT FROM AUTHOR]

Background: Patients with salt-sensitive hypertension are often accompanied with severe renal damage and accelerate to end-stage renal disease, which currently lacks effective treatment. Fibroblast growth factor 21 (FGF21) has been shown to suppress nephropathy in both type 1 and type 2 diabetes mice. Here, we aimed to investigate the therapeutic effect of FGF21 in salt-sensitive hypertension-induced nephropathy. Methods: Changes of FGF21 expression in deoxycorticosterone acetate (DOCA)-salt-induced hypertensive mice were detected. The influence of FGF21 knockout in mice on DOCA-salt-induced nephropathy were determined. Recombinant human FGF21 (rhFGF21) was intraperitoneally injected into DOCA-salt-induced nephropathy mice, and then the inflammatory factors, oxidative stress levels and kidney injury-related indicators were observed. In vitro, human renal tubular epithelial cells (HK-2) were challenged by palmitate acid (PA) with or without FGF21, and then changes in inflammation and oxidative stress indicators were tested. Results: We observed significant elevation in circulating levels and renal expression of FGF21 in DOCA-salt-induced hypertensive mice. We found that deletion of FGF21 in mice aggravated DOCA-salt-induced nephropathy. Supplementation with rhFGF21 reversed DOCA-salt-induced kidney injury. Mechanically, rhFGF21 induced AMPK activation in DOCA-salt-treated mice and PA-stimulated HK-2 cells, which inhibited NF-κB-regulated inflammation and Nrf2-mediated oxidative stress and thus, is important for rhFGF21 protection against DOCA-salt-induced nephropathy. Conclusion: These findings indicated that rhFGF21 could be a promising pharmacological strategy for the treatment of salt-sensitive hypertension-induced nephropathy. [ABSTRACT FROM AUTHOR]

Background: Lactobacilli are often recognized as beneficial partners in human microbial environments. However, lactobacilli also cause diseases in human, e.g. infective endocarditis (IE), septicaemia, rheumatic vascular disease, and dental caries. Therefore, the identification of potential pathogenic traits associated with lactobacilli will facilitate the prevention and treatment of the diseases caused by lactobacilli. Herein, we investigated the genomic traits and pathogenic potential of a novel bacterial strain Lactobacillus paracasei LP10266 which has caused a case of IE. We isolated L. paracasei LP10266 from an IE patient's blood to perform high-throughput sequencing and compared the genome of strain LP10266 with those of closely related lactobacilli to determine genes associated with its infectivity. We performed the antimicrobial susceptibility testing on strain LP10266. We assessed its virulence by mouse lethality and serum bactericidal assays as well as its serum complement- and platelet-activating ability. The biofilm formation and adherence of strain LP10266 were also studied. Results: Phylogenetic analysis revealed that strain LP10266 was allied with L. casei and L. paracasei. Genomic studies revealed two spaCBA pilus clusters and one novel exopolysaccharides (EPS) cluster in strain LP10266, which was sensitive to ampicillin, penicillin, levofloxacin, and imipenem, but resistant to cefuroxime, cefazolin, cefotaxime, meropenem, and vancomycin. Strain LP10266 was nonfatal and sensitive to serum, capable of activating complement 3a and terminal complement complex C5b-9 (TCC). Strain LP10266 could not induce platelet aggregation but displayed a stronger biofilm formation ability and adherence to human vascular endothelial cells (HUVECs) compared to the standard control strain L. paracasei ATCC25302. Conclusion: The genome of a novel bacterial strain L. paracasei LP10266 was sequenced. Our results based on various types of assays consistently revealed that L. paracasei LP10266 was a potential pathogen to patients with a history of cardiac disease and inguinal hernia repair. Strain LP10266 showed strong biofilm formation ability and adherence, enhancing the awareness of L. paracasei infections. [ABSTRACT FROM AUTHOR]

Background: Joubert syndrome (OMIM 213300) is an autosomal recessive disorder with gene heterogeneity. Causal genes and their variants have been identified by sequencing or other technologies for Joubert syndrome subtypes. Case presentation: A two-year-old boy was diagnosed with Joubert syndrome by global development delay and molar tooth sign of mid-brain. Whole exome sequencing was performed to detect the causative gene variants in this individual, and the candidate pathogenic variants were verified by Sanger sequencing. We identified two pathogenic variants (NM_006346.2: c.1147delC and c.1054A > G) of PIBF1 in this Joubert syndrome individual, which is consistent with the mode of autosomal recessive inheritance. Conclusion: In this study, we identified two novel pathogenic variants in PIBF1 in a Joubert syndrome individual using whole exome sequencing, thereby expanding the PIBF1 pathogenic variant spectrum of Joubert syndrome. [ABSTRACT FROM AUTHOR]

Background: There is evidence that circSMYD4 is differentially expressed in hepatocellular carcinoma (HCC), but its mechanism of action remains unclear. Therefore, this study aimed to explore the role of circSMYD4 in the occurrence and development of HCC and its specific molecular mechanism. Methods: The expressions of related genes and proteins in the development of HCC were detected by real-time quantitative-PCR and Western blot. HCC cells treated with RNase R and Actinomycin D were used to examine the stability of circSMYD4. Bioinformatics analysis, RNA pull-down assay, luciferase assay and Spearman correlation analysis were performed to evaluate the interaction between circSMYD4 and miRNA. Cell Counting Kit-8, clone formation assay, wound healing assay, Transwell, flow cytometry, nude tumor formation experiment, and immunohistochemistry were employed to analyze the function of circSMYD4 in HCC. A rescue experiment was conducted to analyze the effect of miR-584-5p on the physiological functions of cells. Results: CircSMYD4 was down-regulated in HCC tissues and cells, and was not easily affected by RNase R and Actinomycin D. The abundances of circSMYD4 and SMYD4 in the cytoplasm were significantly higher than in the nucleus. Up-regulation of circSMYD4 inhibited the proliferation, invasion and migration and promoted the apoptosis of HCC cells in vitro, while it inhibited tumor growth, promoted apoptosis-related proteins, and suppressed alpha-fetoprotein (AFP) levels in vivo. CircSMYD4 could be used as a miRNA sponge to target miR-584-5p. In addition, miR-584-5p overexpression partially reversed the regulatory effect of circSMYD4 on HCC. Conclusion: CircSMYD4 prevents the development of HCC through regulating multiple signaling pathways such as metastasis and apoptosis by sponging miR-584-5p. [ABSTRACT FROM AUTHOR]

Objective: To investigate the lung cancer-promoting mechanism of mesenchymal stem cell-secreted extracellular vesicles (MSC-EV). Methods: EV were isolated from culture media of human bone marrow-derived MSCs that were pre-challenged with or without hypoxia (referred to as H-EV and N-EV, respectively). After treatment with N-EV or H-EV, A549 and H23 cell proliferation, apoptosis, trans-well invasion and epithelial-to-mesenchymal transition (EMT) were examined. Polarization of human primary monocytes-derived macrophages with or without N-EV or H-EV induction were analyzed by flow cytometry and ELISA. PTEN, PDCD4 or RECK gene was overexpressed in A549 cells, while miR-21-5p was knocked down in MSCs, A549 or H23 lung cancer cells or primary monocytes by miR-21-5p inhibitor transfection. Protein level of PTEN, PDCD4, RECK, AKT or STAT3 as well as phosphorylation level of AKT or STAT3 protein were assayed by western blot. Tumorigenicity of A549 and H23 cells with or without MSC-EV co-injection was assayed on immunocompromised mice. The xenograft tumor were examined for cell proliferation, angiogenesis, apoptosis and intra-tumoral M1/M2 macrophage polarization. Results: Comparing to N-EV, H-EV treatment significantly increased A549 and H23 cell proliferation, survival, invasiveness and EMT as well as macrophage M2 polarization. MiR-21-5p knocked down significantly abrogated the cancer-promoting and macrophage M2 polarizing effects of H-EV treatment. H-EV treatment downregulated PTEN, PDCD4 and RECK gene expression largely through miR-21-5p. Overexpressing PTEN, PDCD4 and RECK in A549 cells significantly reduced the miR-21-5p-mediated anti-apoptotic and pro-metastatic effect of H-EV, while overexpressing PTEN in monocytes significantly reduced macrophage M2 polarization after induction with the presence of H-EV. H-EV co-injection significantly increased tumor growth, cancer cell proliferation, intra-tumoral angiogenesis and M2 polarization of macrophages in vivo partially through miR-21-5p. Conclusions: Increased miR-21-5p delivery by MSC-EV after hypoxia pre-challenge can promote lung cancer development by reducing apoptosis and promoting macrophage M2 polarization. [ABSTRACT FROM AUTHOR]

Background: We aimed to evaluate the role of extracorporeal shockwave therapy (ESWT) in improving osteonecrosis of the femoral head (ONFH). Methods: We searched studies focusing on the role of ESWT in ONFH using PubMed, Embase, the Cochrane Library, WanFang, VIP, and CNKI databases updated up to July 28, 2017, without language restriction. Standardized mean difference (SMD) values and 95% confidence intervals (95% CIs) were pooled to compare the pain score and Harris hip score for ESWT treatment and other treatment strategies. Results: Four articles, including 230 ONFH patients, were eligible for the meta-analysis. No significant differences were found in the pain score (SMD = − 1.0104; 95% CI − 2.3279–0.3071) and Harris hip score (SMD = 0.3717; 95% CI − 0.3125–1.0559) between the two groups before treatment. After treatment, significant differences were found between the experimental and control groups in the pain score (SMD = − 2.1148; 95% CI − 3.2332–0.9965) and Harris hip score (SMD = 2.1377; 95% CI 1.2875–2.9880). There were no significant differences in pain score before and after treatment between the two groups (SMD = − 0.7353; 95% CI − 2.1272–0.6566), but significant differences were found in the Harris hip score (SMD = 1.2969; 95% CI 0.7171–1.8767). Conclusion: For patients at an early stage, ESWT may be safe and effective for relief of pain and improvement of motor function. [ABSTRACT FROM AUTHOR]