Genomic insights into the evolution and mechanisms of carbapenem-resistant hypervirulent Klebsiella pneumoniae co-harboring blaKPC and blaNDM: implications for public health threat mitigation.

BACKGROUND: Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) co-producing blaKPC and blaNDM poses a serious threat to public health. This study aimed to investigate the mechanisms underlying the resistance and virulence of CR-hvKP isolates collected from a Chinese hospital, with a focus on blaKPC and blaNDM dual-positive hvKP strains. METHODS: Five CR-hvKP strains were isolated from a teaching hospital in China. Antimicrobial susceptibility and plasmid stability testing, plasmid conjugation, pulsed-field gel electrophoresis, and whole-genome sequencing (WGS) were performed to examine the mechanisms of resistance and virulence. The virulence of CR-hvKP was evaluated through serum-killing assay and Galleria mellonella lethality experiments. Phylogenetic analysis based on 16 highly homologous carbapenem-resistant K. pneumoniae (CRKP) producing KPC-2 isolates from the same hospital was conducted to elucidate the potential evolutionary pathway of CRKP co-producing NDM and KPC. RESULTS: WGS revealed that five isolates individually carried three unique plasmids: an IncFIB/IncHI1B-type virulence plasmid, IncFII/IncR-type plasmid harboring KPC-2 and IncC-type plasmid harboring NDM-1. The conjugation test results indicated that the transference of KPC-2 harboring IncFII/IncR-type plasmid was unsuccessful on their own, but could be transferred by forming a hybrid plasmid with the IncC plasmid harboring NDM. Further genetic analysis confirmed that the pJNKPN26-KPC plasmid was entirely integrated into the IncC-type plasmid via the copy-in route, which was mediated by TnAs1 and IS26. CONCLUSION: KPC-NDM-CR-hvKP likely evolved from a KPC-2-CRKP ancestor and later acquired a highly transferable blaNDM-1 plasmid. ST11-KL64 CRKP exhibited enhanced plasticity. The identification of KPC-2-NDM-1-CR-hvKP highlights the urgent need for effective preventive strategies against aggravated accumulation of resistance genes.

Co-transfer of IncFII/IncFIB and IncFII plasmids mediated by IS26 facilitates the transmission of mcr-8.1 and tmexCD1-toprJ1.

PURPOSE: This study aimed to characterise the whole-genome structure of two clinical Klebsiella pneumoniae strains co-harbouring mcr-8.1 and tmexCD1-toprJ1, both resistant to colistin and tigecycline. METHODS: K. pneumoniae strains TGC-02 (ST656) and TGC-05 (ST273) were isolated from urine samples of different patients hospitalised at separate times in 2021. Characterisation involved antimicrobial susceptibility testing (AST), conjugation assays, whole-genome sequencing (WGS), and bioinformatics analysis. Comparative genomic analysis was conducted on mcr-8.1-carrying and tmexCD1-toprJ1-carrying plasmids. RESULTS: Both K. pneumoniae isolates displayed a multidrug-resistant phenotype, exhibiting resistance or reduced susceptibility to ampicillin, ampicillin/sulbactam, cefazolin, aztreonam, amikacin, gentamicin, tobramycin, ciprofloxacin, levofloxacin, nitrofurantoin, trimethoprim/sulfamethoxazole, apramycin, tigecycline and colistin. WGS analysis revealed that clinical strain TGC-02 carried the TmexCD1-toprJ1 gene on a 200-Kb IncFII/IncFIB-type plasmid, while mcr-8 was situated on a 146-Kb IncFII-type plasmid. In clinical strain TGC-05, TmexCD1-toprJ1 was found on a 300-Kb IncFIB/IncHI1B/IncR-type plasmid, and mcr-8 was identified on a 137-Kb IncFII/IncFIA-type plasmid. Conjugation experiments assessed the transferability of these plasmids. While transconjugants were not obtained for TGC-05 despite multiple screening with tigecycline or colistin, pTGC-02-tmex and pTGC-02-mcr8 from clinical K. pneumoniae TGC-02 demonstrated self-transferability through conjugation. Notably, the rearrangement of pTGC-02-tmex and pTGC-02-mcr8 via IS26-based homologous recombination was observed. Moreover, the conjugative and fusion plasmids of the transconjugant co-harboured the tmexCD1-toprJ1 gene cluster and mcr-8.1, potentially resulting from IS26-based homologous recombination. CONCLUSION: The emergence of colistin- and tigecycline-resistant K. pneumoniae strains is concerning, and effective surveillance measures should be implemented to prevent further dissemination.

Validation of prognostic signature and exploring the immune-related mechanisms for NR3C2 in clear cell renal cell carcinoma.

Background: Previous studies have verified that NR3C2 inhibits tumor cell proliferation, invasion, and migration. However, there is a lack of independent validation cohorts for verifying the prognostic value of NR3C2 in clear cell renal cell carcinoma (ccRCC), and its underlying antitumor mechanisms remain unclear. Methods: We first obtained dates from the online public databases. Then R language or online public database was used for bioinformatics analyses to evaluate the effect of NR3C2 on the diagnosis, prognosis, and immune microenvironment in ccRCC patients. Finally, the results were verified by our own cohort and immunofluorescence (IF) staining. Results: The present study yielded significant findings regarding the expression of NR3C2 in ccRCC compared to control tissues. Specifically, NR3C2 expression was found to be significantly reduced in ccRCC and was observed to be correlated with tumor stage. Additionally, patients with lower NR3C2 expression exhibited shorter overall survival (OS), disease-specific survival, and progress-free survival. Univariable and multivariate Cox analyses further identified NR3C2 expression as an independent prognostic factor for ccRCC. Receiver operating characteristic (ROC) analysis demonstrated that NR3C2 was a highly accurate marker for distinguishing tumors from normal kidney tissue, with an area under the curve (AUC) of 0.959. Further analyses using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis suggested that NR3C2 may play a role in various biological processes and pathways related to tumor immune microenvironment (TIM). The expression of NR3C2 exhibited significant positive correlations with the levels of infiltration of CD4+ and CD8+ T cells, as well as an association with immune checkpoints. Conclusions: Our exploratory study suggested that NR3C2 could serve as a novel biomarker for predicting survival in patients with ccRCC and the molecular mechanisms owe partly to immune cell infiltration.

Ge2Sb2Te5-based efficient switching between a cross-polarization conversion and a circular-to-linear polarization conversion.

The terahertz (THz) band has a great potential for the development of communication technology, but it has not been fully utilized due to the lack of practical devices, especially actively controllable multifunctional devices. Here, we propose and demonstrate a Ge2Sb2Te5 (GST)-based metamaterial device, where an actively controllable function is experimentally verified by inducing the crystallization process with thermal activation. Cross-polarization conversion in the reflection mode and circular-to-linear polarization conversion in the transmission mode are obtained under crystalline and amorphous GST conditions, respectively. The combination of GST and THz waves has a wide range of applications and will further advance the THz field.

Antimicrobial resistance and molecular epidemiology of carbapenem-resistant Escherichia coli from urinary tract infections in Shandong, China / Resistencia a los antimicrobianos y epidemiología molecular de Escherichia coli resistente a carbapenémicos procedente de infecciones del tracto urinario en Shandong, China

Objectives: Urinary tract infection (UTI) is one of the most common extraintestinal infections, and uropathogenic Escherichia coli (UPEC) is the main cause of UTIs. However, the ability to treat UTI has been compromised by the increase in antimicrobial resistance, especially carbapenem resistance. Here, we aimed to characterize the antimicrobial resistance and molecular epidemiology of carbapenem-resistant UPEC isolated in Shandong, China. Methods: In total, 17 carbapenem-resistant UPEC (CR-UPEC) isolates were collected from July 2017 to May 2020 in the Shandong Provincial Hospital. Whole-genome sequencing and bioinformatics analyses were performed to understand the molecular epidemiology of CR-UPEC. Phylogenetic groups, drug resistance genes, biofilm formation, and virulence-related gene profiles of the isolates were analyzed. Plasmid profiling and conjugation assay were performed to evaluate the ability to transfer carbapenem resistance-related genes to other E. coli isolates. Biofilm formation was also evaluated, as it is important for the persistence of infectious diseases. Results: We observed that 15 out of 17 CR-UPEC strains were blaNDM producers, among which 4 isolates could transfer blaNDM to recipient cells. The predominant sequence type was ST167 (6/17), followed by ST410 (3/17). The most prevalent phylogenetic group was phylogenetic group A (10/17), followed by phylogenetic group C (3/17). One isolate was resistant to polymyxin, which was caused by the carriage of a transferable plasmid harboring mcr-1. Statistical analysis did not reveal any significant difference in the carriage rate of fimbriae-coding genes between strong and weak biofilm producers. Conclusions: Our observations may assist in developing new therapeutic methods for drug-resistant organisms.(AU)

Natural Compounds Derived from Plants on Prevention and Treatment of Renal Cell Carcinoma: A Literature Review.

Renal cell carcinoma (RCC) accounts for roughly 85% of all malignant kidney cancer. Therapeutic options for RCC have expanded rapidly over the past decade. Targeted therapy and immunotherapy have ushered in a new era of the treatment of RCC, which has facilitated the outcomes of RCC. However, the related adverse effects and drug resistance remain an urgent issue. Natural compounds are optional strategies to reduce mobility. Natural compounds are favored by clinicians and researchers due to their good tolerance and low economic burden. Many studies have explored the anti-RCC activity of natural products and revealed relevant mechanisms. In this article, the chemoprevention and therapeutic potential of natural compounds is reviewed and the mechanisms regarding natural compounds are explored.

Screening Serum Biomarkers for Rats Preconditioned with Hyperbaric Oxygen: Potential of Predicting Prognosis for Stroke.

BACKGROUND: Stroke is a major health concern and a leading cause of mortality and morbidity. We and other groups have documented that hyperbaric oxygen preconditioning could significantly alleviate neuronal damage in ischemia‒reperfusion models through various mechanisms. However, we found that some of the subjects did not benefit from preconditioning with hyperbaric oxygen. The preconditioning phenomenon is similar to vaccination, in which the endogenous survival system is activated to fight against further injuries. However, with vaccine inoculations, we could test for specific antibodies against the pathogens to determine if the vaccination was successful. Likewise, this experiment was carried out to explore a biomarker that can reveal the effectiveness of the preconditioning before neuronal injury occurs. METHODS: Middle cerebral artery occlusion (MCAO) was used to induce focal cerebral ischemia-reperfusion injury. 2D-DIGE-MALDI-TOF-MS/MS proteomic technique was employed to screen the differentially expressed proteins in the serum of rats among the control (Con) group (MCAO model without hyperbaric oxygen (HBO) preconditioning), hyperbaric oxygen protective (HBOP) group (in which the infarct volume decreased after HBO preconditioning vs. Con), and hyperbaric oxygen nonprotective (HBOU) group (in which the infarct volume remained the same or even larger after HBO preconditioning vs. Con). Candidate biomarkers were confirmed by western blot and enzyme linked immunosorbent assay (ELISA), and the relationship between the biomarkers and the prognosis of cerebral injury was further validated. RESULTS: Among the 15 differentially expressed protein spots detected in the HBOP group by Two-dimensional fluorescence difference gel electrophoresis (2D-DIGE), 3 spots corresponding to 3 different proteins (haptoglobin, serum albumin, and haemopexin) products were identified by MALDI-TOF-MS/MS. Serum albumin and haemopexin were upregulated, and haptoglobin was downregulated in the HBOP group (p < 0.05 vs. Con and HBOU groups). After the western blot study, only the changes in haemopexin were validated and exhibited similar changes in subjects from the HBOP group in accordance with MALDI-TOF-MS/MS proteomic analysis and enzyme linked immunosorbent assay (ELISA) analysis. The serum level of the hemopexin (HPX) at 2 h after HBO preconditioning was correlated with the infarct volume ratio after MCAO. CONCLUSIONS: Haemopexin may be developed as a predictive biomarker that indicated the effectiveness of a preconditioning strategy against cerebral ischaemic injury.

Stochastic dynamics and first passage analysis of iced transmission lines via path integration method.

The mechanism of stochastic factors in wind load on iced transmission line galloping has attracted widespread attention. In this paper, the random part of wind load is simulated by Gaussian white noise, and a galloping model of the iced transmission line excited by stochastic wind is established. The path integration method based on the Gauss-Legendre formula and short-time approximation is used to solve the steady-state probability density function of the system and the evolution of the transient probability density. The resonance response of the system is considered when the fluctuating wind acts. Meanwhile, through path integration, the stability of galloping motion is evaluated based on the first passage theory. Comparing with the Monte Carlo simulation, the effectiveness of the proposed method is verified. It turns out that the large external excitation intensity and the small natural frequency are not conducive to the stability of iced transmission line galloping.

Hydrogen alleviated cognitive impairment and blood‒brain barrier damage in sepsis-associated encephalopathy by regulating ABC efflux transporters in a PPARα-dependent manner.

Hydrogen (H2) can protect against blood‒brain barrier (BBB) damage in sepsis-associated encephalopathy (SAE), but the mechanism is still unclear. We examined whether it is related to PPARα and its regulatory targets, ABC efflux transporters. After injection with DMSO/GW6471 (a PPARα inhibitor), the mice subjected to sham/caecal ligation and puncture (CLP) surgery were treated with H2 for 60 min postoperation. Additionally, bEnd.3 cells were grown in DMSO/GW6471-containing or saline medium with LPS. In addition to the survival rates, cognitive function was assessed using the Y-maze and fear conditioning tests. Brain tissues were stained with TUNEL and Nissl staining. Additionally, inflammatory mediators (TNF-α, IL-6, HMGB1, and IL-1ß) were evaluated with ELISA, and PPARα, ZO-1, occludin, VE-cadherin, P-gp, BCRP and MRP2 were detected using Western blotting. BBB destruction was assessed by brain water content and Evans blue (EB) extravasation. Finally, we found that H2 improved survival rates and brain dysfunction and decreased inflammatory cytokines. Furthermore, H2 decreased water content in the brain and EB extravasation and increased ZO-1, occludin, VE-cadherin and ABC efflux transporters regulated by PPARα. Thus, we concluded that H2 decreases BBB permeability to protect against brain dysfunction in sepsis; this effect is mediated by PPARα and its regulation of ABC efflux transporters.

Antimicrobial resistance and molecular epidemiology of carbapenem-resistant Escherichia coli from urinary tract infections in Shandong, China.

OBJECTIVES: Urinary tract infection (UTI) is one of the most common extraintestinal infections, and uropathogenic Escherichia coli (UPEC) is the main cause of UTIs. However, the ability to treat UTI has been compromised by the increase in antimicrobial resistance, especially carbapenem resistance. Here, we aimed to characterize the antimicrobial resistance and molecular epidemiology of carbapenem-resistant UPEC isolated in Shandong, China. METHODS: In total, 17 carbapenem-resistant UPEC (CR-UPEC) isolates were collected from July 2017 to May 2020 in the Shandong Provincial Hospital. Whole-genome sequencing and bioinformatics analyses were performed to understand the molecular epidemiology of CR-UPEC. Phylogenetic groups, drug resistance genes, biofilm formation, and virulence-related gene profiles of the isolates were analyzed. Plasmid profiling and conjugation assay were performed to evaluate the ability to transfer carbapenem resistance-related genes to other E. coli isolates. Biofilm formation was also evaluated, as it is important for the persistence of infectious diseases. RESULTS: We observed that 15 out of 17 CR-UPEC strains were blaNDM producers, among which 4 isolates could transfer blaNDM to recipient cells. The predominant sequence type was ST167 (6/17), followed by ST410 (3/17). The most prevalent phylogenetic group was phylogenetic group A (10/17), followed by phylogenetic group C (3/17). One isolate was resistant to polymyxin, which was caused by the carriage of a transferable plasmid harboring mcr-1. Statistical analysis did not reveal any significant difference in the carriage rate of fimbriae-coding genes between strong and weak biofilm producers. CONCLUSIONS: Our observations may assist in developing new therapeutic methods for drug-resistant organisms.

Multifunctional Flexible Sensor Based on PU-TA@MXene Janus Architecture for Selective Direction Recognition.

Multifunctional selectivity and mechanical properties are always a focus of attention in the field of flexible sensors. In particular, the construction of biomimetic architecture for sensing materials can endow the fabricated sensors with intrinsic response features and extra-derived functions. Here, inspired by the asymmetric structural features of human skin, a novel tannic acid (TA)-modified MXene-polyurethane film with a bionic Janus architecture is proposed, which is prepared by gravity-driven self-assembly for the gradient dispersion of 2D TA@MXene nanosheets into a PU network. This obtained film reveals strong mechanical properties of a superior elongation at a break of 2056.67% and an ultimate tensile strength of 50.78 MPa with self-healing performance. Moreover, the Janus architecture can lead to a selective multifunctional response of flexible sensors to directional bending, pressure, and stretching. Combined with a machine learning module, the sensor is endowed with high recognition rates for force detection (96.1%). Meanwhile, direction identification in rescue operations and human movement monitoring can be realized by this sensor. This work offers essential research value and practical significance for the material structures, mechanical properties, and application platforms of flexible sensors.

A 20-Gene Signature Predicting Survival in Patients with Clear Cell Renal Cell Carcinoma Based on Basement Membrane.

Objectives: The most common subtype of renal cell carcinoma, clear cell renal cell carcinoma (ccRCC), has a high heterogeneity and aggressive nature. The basement membrane (BM) is known to play a vital role in tumor metastasis. BM-related genes remain untested in ccRCC, however, in terms of their prognostic significance. Methods: BM-related genes were gleaned from the most recent cutting-edge research. The RNA-seq and clinical data of the ccRCC were obtained from TCGA and GEO databases, respectively. The multigene signature was constructed using the univariate Cox regression and the LASSO regression algorithm. Then, clinical features and prognostic signatures were combined to form a nomogram to predict individual survival probabilities. Using functional enrichment analysis and immune-correlation analysis, we investigated potential enrichment pathways and immunological characteristics associated with BM-related-gene signature. Results: In this study, we built a model of 20 BM-related genes and classified them as high-risk or low-risk, with each having its anticipated risk profile. Patients in the high-risk group showed significantly reduced OS compared with patients in the low-risk group in the TCGA cohort, as was confirmed by the testing dataset. Functional analysis showed that the BM-based model was linked to cell-substrate adhesion and tumor-related signaling pathways. Comparative analysis of immune cell infiltration degrees and immune checkpoints reveals a central role for BM-related genes in controlling the interplay between the immune interaction and the tumor microenvironment of ccRCC. Conclusions: We combined clinical characteristics known to predict the prognosis of ccRCC patients to create a gene signature associated with BM. Our findings may also be useful for forecasting how well immunotherapies would work against ccRCC. Targeting BM may be a therapeutic alternative for ccRCC, but the underlying mechanism still needs further exploration.

Process Engineering and Glycosyltransferase Improvement for Short Route Chemoenzymatic Total Synthesis of GM1 Gangliosides.

Large-scale synthesis of GM1, an important ganglioside in mammalian cells especially those in the nervous system, is needed to explore its therapeutic potential. Biocatalytic production is a promising platform for such a purpose. We report herein the development of process engineering and glycosyltransferase improvement strategies to advance chemoenzymatic total synthesis of GM1. Firstly, a new short route was developed for chemical synthesis of lactosylsphingosine from the commercially available Garner's aldehyde. Secondly, two glycosyltransferases including Campylobacter jejuni ß1-4GalNAcT (CjCgtA) and ß1-3-galactosyltransferase (CjCgtB) were improved on their soluble expression in E. coli and enzyme stability by fusing with an N-terminal maltose binding protein (MBP). Thirdly, the process for enzymatic synthesis of GM1 sphingosines from lactosylsphingosine was engineered by developing a multistep one-pot multienzyme (MSOPME) strategy without isolating intermediate glycosphingosines and by adding a detergent, sodium cholate, to the later enzymatic glycosylation steps. Installation of a desired fatty acyl chain to GM1 glycosphingosines led to the formation of target GM1 gangliosides. The combination of glycosyltransferase improvement with chemical and enzymatic process engineering represents a significant advance in obtaining GM1 gangliosides containing different sialic acid forms by total chemoenzymatic synthesis in a short route and with high efficiency.

Effect of molecular hydrogen treatment on Sepsis-Associated encephalopathy in mice based on gut microbiota.

INTRODUCTION: In our experiments, male wild-type mice were randomly divided into four groups: the sham, SAE, SAE + 2% hydrogen gas inhalation (H2 ), and SAE + hydrogen-rich water (HW) groups. The feces of the mice were collected for 16 S rDNA analysis 24 h after the models were established, and the serum and brain tissue of the mice were collected for nontargeted metabolomics analysis. AIM: Destruction of the intestinal microbiota is a risk factor for sepsis and subsequent organ dysfunction, and up to 70% of severely ill patients with sepsis exhibit varying degrees of sepsis-associated encephalopathy (SAE). The pathogenesis of SAE remains unclear. We aimed to explore the changes in gut microbiota in SAE and the regulatory mechanism of molecular hydrogen. RESULTS: Molecular hydrogen treatment significantly improved the functional outcome of SAE and downregulated inflammatory reactions in both the brain and the gut. In addition, molecular hydrogen treatment improved gut microbiota dysbiosis and partially amended metabolic disorder after SAE. CONCLUSIONS: Molecular hydrogen treatment promotes functional outcomes after SAE in mice, which may be attributable to increasing beneficial bacteria, repressing harmful bacteria, and metabolic disorder, and reducing inflammation.

CDCA3 Predicts Poor Prognosis and Affects CD8+ T Cell Infiltration in Renal Cell Carcinoma.

Background: Cell division cycle associated 3 (CDCA3) mediates the ubiquitination WEE1 kinase at G2/M phase. However, its contribution to cancer immunity remains uncertain. Methods: We first evaluated the effect of CDCA3 on the prognosis of patients with renal cell carcinoma (RCC). The results of bioinformatics analysis were verified by the tissue microarray, immunofluorescence (IF) staining, CCK-8 assay, colony formation, cell cycle, and Western blot. Results: Bioinformatics analysis predicated CDCA3 was an independent predictor of poor prognosis in RCC and was associated with poor TNM stage and grade. CDCA3 was related to the infiltration of CD8+ T cells and Tregs. Tissue microarray demonstrated that CDCA3 was strongly associated with poor prognosis and positively relevant to CD8+ T infiltration. In vitro experiments showed that exgenomic interference of CDCA3 could attenuate cellular proliferation, arrest cell cycle, and blockade accumulation of CDK4, Bub3, and Cdc20 in mitosis process. Conclusion: CDCA3 presents as a good biomarker candidate to predict the prognosis of RCC patients and potentiates the immune tumor microenvironment (TME) of RCC.

Phosphorylation-mediated PI3K-Art signalling pathway as a therapeutic mechanism in the hydrogen-induced alleviation of brain injury in septic mice.

Our previous studies illustrated that 2% H2 inhalation can protect against sepsis-associated encephalopathy (SAE) which is characterized by high mortality and has no effective treatment. To investigate the underlying role of protein phosphorylation in SAE and H2 treatment, a mouse model of sepsis was constructed by caecal ligation and puncture (CLP), then treated with H2 (CLP + H2 ). Brain tissues of the mice were collected to be analysed with tandem mass tag-based quantitative proteomics coupled with IMAC enrichment of phosphopeptides and LC-MS/MS analysis. In proteomics and phosphoproteomics analysis, 268 differentially phosphorylated proteins (DPPs) showed a change in the phosphorylated form in the CLP + H2 group (p < 0.05). Gene ontology analysis revealed that these DPPs were enriched in multiple cellular components, biological processes, and molecular functions. KEGG pathway analysis revealed that they were enriched in glutamatergic synapses, tight junctions, the PI3K-Akt signalling pathway, the HIF-1 signalling pathway, the cGMP-PKG signalling pathway, the Rap1 signalling pathway, and the vascular smooth muscle contraction. The phosphorylated forms of six DPPs, including ribosomal protein S6 (Rps6), tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein gamma (Ywhag/14-3-3), phosphatase and tensin homologue deleted on chromosome ten (Pten), membrane-associated guanylate kinase 1 (Magi1), mTOR, and protein kinase N2 (Pkn2), were upregulated and participated in the PI3K-Akt signalling pathway. The WB results showed that the phosphorylation levels of Rps6, Ywhag, Pten, Magi1, mTOR, and Pkn2 were increased. The DPPs and phosphorylation-mediated molecular network alterations in H2 -treated CLP mice may elucidate the biological roles of protein phosphorylation in the therapeutic mechanism of H2 treatment against SAE.

Clinical treatment of lumbar disc herniation.

OBJECTIVE: To investigate the clinical effect of radiofrequency ozone and injection of anti-inflammatory analgesic solution into the internal orifice of nerve root combined with traditional Chinese medicine hook operation in the treatment of lumbar disc herniation. METHODS: Patients with lumbar disc herniation who were admitted to our hospital on December 20, 2017 and June 19, 2019 were selected as the main research objects, and the included patients were divided into control group, basic group and comprehensive group by random number table method. Control group was treated with radiofrequency ozone therapy, basic group was treated with injection of anti-inflammatory analgesic solution into the internal orifice of nerve root in addition to the control group, comprehensive group was treated with traditional Chinese medicine hook operation in addition to the basic group. The clinical treatment effects were observed. RESULTS: A total of 153 patients were included in this study, including 40 in the control group, 40 in the basic group, and 73 in the comprehensive group. The results showed that the NRS scores of control group were 3±0.98, 2±0.93 and 2±0.85 at 1 month, 3 months and 1 year after treatment, respectively. NRS scores in the basic group were 3±0.18, 2±0.33, and 2±0.15, respectively. NRS scores in the comprehensive group were 2±0.78, 1±0.54, and 1±0.77, respectively. Compared with the control group, there were significant differences in basic group and comprehensive group at each time point (P < 0. 05). At the same time, compared with the basic group, the NRS score of the comprehensive group was statistically different (P < 0.05). CONCLUSION: Radiofrequency ozone and injection of anti-inflammatory analgesic solution into the internal orifice of nerve root combined with hook operation can obtain good short-term and medium-term effects in the treatment of lumbar disc herniation. It is a safe and effective minimally invasive treatment method. KEY WORDS: Internal orifice of nerve root, Lumbar disc herniation, Ozone.

Application of imaging techniques in pancreaticobiliary maljunction.

Imaging techniques are useful tools in the diagnosis and treatment of pancreaticobiliary maljunction (PBM). PBM is a precancerous lesion often relative to the disease of the pancreas and biliary tract, for example, cholecystolithiasis, protein plugs, and pancreatitis. For patients with PBM, early diagnosis and timely treatment are highly important, which is largely dependent on imaging techniques. The continuous development of imaging techniques, including endoscopic retrograde cholangiopancreatography, magnetic resonance cholangiopancreatography, computed tomography, ultrasound, and intraoperative cholangiography, has provided appropriate diagnostic and therapeutic tools for PBM. Imaging techniques, including non-invasive and invasive, have distinct advantages and disadvantages. The purpose of this paper is to review the application of various imaging techniques in the diagnosis and treatment of PBM.

Circulating lnc-LOC as a novel noninvasive biomarker in the treatment surveillance of acute promyelocytic leukaemia.

BACKGROUND: Acute promyelocytic leukaemia (APL) is a unique subtype of acute myeloid leukaemia (AML) characterized by haematopoietic failure caused by the accumulation of abnormal promyelocytic cells in bone marrow (BM). However, indispensable BM biopsy frequently afflicts patients in leukaemia surveillance, which increases the burden on patients and reduces compliance. This study aimed to explore whether the novel circulating long noncoding RNA LOC100506453 (lnc-LOC) could be a target in diagnosis, assess the treatment response and supervise the minimal residual disease (MRD) of APL, thereby blazing a trail in noninvasive lncRNA biomarkers of APL. METHODS: Our study comprised 100 patients (40 with APL and 60 with non-APL AML) and 60 healthy donors. BM and peripheral blood (PB) sample collection was accomplished from APL patients at diagnosis and postinduction. Quantitative real-time PCR (qRT-PCR) was conducted to evaluate lnc-LOC expression. A receiver operating characteristic (ROC) analysis was implemented to analyse the value of lnc-LOC in the diagnosis of APL and treatment monitoring. For statistical analysis, the Mann-Whitney U test, a t test, and Spearman's rank correlation test were utilized. RESULTS: Our results showed that BM lnc-LOC expression was significantly different between APL and healthy donors and non-APL AML. lnc-LOC was drastically downregulated in APL patients' BM after undergoing induction therapy. Lnc-LOC was upregulated in APL cell lines and downregulated after all-trans retinoic acid (ATRA)-induced myeloid differentiation, preliminarily verifying that lnc-LOC has the potential to be considered a treatment monitoring biomarker. PB lnc-LOC was positively correlated with BM lnc-LOC in APL patients, non-APL AML patients and healthy donors and decreased sharply after complete remission (CR). However, upregulated lnc-LOC was manifested in relapsed-refractory patients. A positive correlation was revealed between PB lnc-LOC and PML-RARα transcript levels in BM samples. Furthermore, we observed a positive correlation between PB lnc-LOC and BM lnc-LOC expression in APL patients, suggesting that lnc-LOC can be utilized as a noninvasive biomarker for MRD surveillance. CONCLUSIONS: Our study demonstrated that PB lnc-LOC might serve as a novel noninvasive biomarker in the treatment surveillance of APL, and it innovated the investigation and application of newly found lncRNAs in APL noninvasive biomarkers used in diagnosis and detection.

Tough Engineering Hydrogels Based on Swelling-Freeze-Thaw Method for Artificial Cartilage.

Articular cartilage, which exhibits toughness and ultralow friction even under high squeezing pressures, plays an important role in the daily movement of joints. However, joint soft tissue lesions or injuries caused by diseases, trauma, or human functional decline are inevitable. Poly(vinyl alcohol) (PVA) hydrogels, which have a water content and compressive strength similar to those of many tissues and organs, have the potential to replace tough connective tissues, including cartilage. However, currently, PVA hydrogels are not suitable for complex dynamic environments and lack rebound resilience, especially under long-term or multicycle mechanical loads. Inspired by biological tissues that exhibit increased mechanical strength after swelling, we report a tough engineered hydrogel (TEHy) fabricated by swelling and freeze-thaw methods with a high compressive strength (31 MPa), high toughness (1.17 MJ m-3), a low friction coefficient (0.01), and a low energy loss factor (0.22). Notably, the TEHy remained remarkably resilient after 100 000 cycles of contact extrusion and remains intact after being compressed by an automobile with a weight of approximately 1600 kg. The TEHy also exhibited excellent water swelling resistance (volume and weight changes less than 5%). Moreover, skeletal muscle cells were able to readily attach and proliferate on the surface of TEHy-6, suggesting its outstanding biocompatibility. Overall, this swelling and freeze-thaw strategy solves the antifatigue and stability problems of PVA hydrogels under large static loads (>10 000 N) and provides an avenue to fabricate engineering hydrogels with strong antifatigue and antiswelling properties and ultralow friction for potential use as biomaterials in tissue engineering.