Comparing Balloon Dilation to Non-Balloon Dilation for Access in Ultrasound-Guided Percutaneous Nephrolithotomy: A Systematic Review and Meta-Analysis.

PURPOSE: This study aims to evaluate the safety and efficacy of ultrasound-guided balloon dilation compared to non-balloon dilation for percutaneous nephrolithotomy (PCNL). MATERIALS AND METHODS: A systematic review and meta-analysis were conducted by searching PubMed, EMBASE, and the Cochrane Library. Results were filtered using predefined inclusion and exclusion criteria as described and meta-analysis was performed using Review Manager 5.4 software. RESULTS: A total of six studies involving 1189 patients who underwent PCNL were included. The meta-analysis results demonstrated that compared to non-balloon dilation, balloon dilation was associated with reduced haemoglobin drop [mean difference (MD) = -0.26, 95% CI = -0.40 ~ -0.12, P = 0.0002], decreased transfusion rate [odds ratio (OR) = 0.47, 95% CI = 0.24 ~ 0.92, P = 0.03], shorter tract establishment time (MD = -1.30, 95% CI = -1.87 ~ -0.72, P < 0.0001) and shorter operation time (MD = -5.23, 95% CI = -10.19 ~ -0.27, P = 0.04). CONCLUSIONS: Overall, ultrasound-guided balloon dilatation offered several advantages in PCNL procedures. It facilitated faster access establishment, as evidenced by shorter access creation time. Additionally, it reduced the risk of kidney injury by minimizing postoperative haemoglobin drop and decreasing the need for transfusions. Moreover, it enhanced the efficiency of surgery by reducing the operation time. However, it is important to note that the quality of some included studies was subpar, as they did not adequately control for confounding factors that may affect the outcomes. Therefore, further research is necessary to validate and strengthen these findings.

Tribbles pseudokinase 3 promotes enterovirus A71 infection via dual mechanisms.

Enterovirus A71 (EV-A71) is the main pathogen causing hand, foot and mouth disease (HFMD) in children and occasionally associated with neurological diseases such as aseptic meningitis, brainstem encephalitis (BE) and acute flaccid paralysis. We report here that cellular pseudokinase tribbles 3 (TRIB3) facilitates the infection of EV-A71 via dual mechanisms. In one hand, TRIB3 maintains the metabolic stability of scavenger receptor class B member 2 (SCARB2), the bona fide receptor of EV-A71, to enhance the infectious entry and spreading of the virus. On the other hand, TRIB3 facilitates the replication of EV-A71 RNA in a SCARB2-independent manner. The critical role of TRIB3 in EV-A71 infection and pathogenesis was further demonstrated in vivo in mice. In comparison to wild-type C57BL/6 mice, EV-A71 infection in TRIB3 knockdown mice (Trib3+/-) resulted in significantly lower viral loads in muscular tissues and reduced lethality and severity of clinical scores and tissue pathology. In addition, TRIB3 also promoted the replication of coxsackievirus B3 (CVB3) and coxsackievirus A16 (CVA16) in vitro. In conclusion, our results suggest that TRIB3 is one of key host cellular proteins required for the infection and pathogenesis of EV-A71 and some other human enteroviruses and may thus be a potential therapeutic target for combating the infection of those viruses.

Evaluation and mechanism study of Pien Tze Huang against EV-A71 infection.

Hand, foot, and mouth disease (HFMD) caused by enterovirus A71 (EV-A71) infection, currently lacks specific preventive and therapeutic interventions. Here, we demonstrated that Pien Tze Huang (PZH) could dose-dependently inhibit EV-A71 replication at the cellular level, resulting in significant reductions in EV-A71 virus protein 1 (VP1) expression and viral yields in Vero and human rhabdomyosarcoma cells. More importantly, we confirmed that PZH could protect mice from EV-A71 infection for the first time, with Ribavirin serving as a positive control. PZH treatment reduced EV-A71 VP1 protein expression, viral yields in infected muscles, and improved muscle pathology. Additionally, we conducted a preliminary mechanism study using quantitative proteomics. The results suggested that the suppression of the PI3K/AKT/mTOR and NF-κB signaling pathways may contribute to the anti-EV-A71 activity of PZH. These findings provide strong evidence supporting the potential therapeutic application of PZH for EV-A71 infection management.

Declaration: Novel SLC3A1 mutation in a cystinuria patient with xanthine stones: a case report.

BACKGROUND: Cystinuria and xanthinuria are both rare genetic diseases involving urinary calculi. However, cases combining these two disorders have not yet been reported. CASE PRESENTATION: In this study, we report a case of cystinuria with xanthine stones and hyperuricemia. The 23-year-old male patient was diagnosed with kidney and ureteral stones, solitary functioning kidney and hyperuricemia after admission to the hospital. The stones were removed by surgery and found to be composed of xanthine. CONCLUSION: Genetic testing by next-generation sequencing technology showed that the patient carried the homozygous nonsense mutation c.1113 C> A (p.Tyr371*) in the SLC3A1 gene, which was judged to be a functionally pathogenic variant. Sanger sequencing revealed that the patient's parents carried this heterozygous mutation, which is a pathogenic variant that can cause cystinuria. The 24-h urine metabolism analysis showed that the cystine content was 644 mg (<320 mg/24 h), indicating that the patient had cystinuria, consistent with the genetic test results. This case shows that cystinuria and xanthine stones can occur simultaneously, and provides evidence of a possible connection between the two conditions. Furthermore, our findings demonstrate the potential value of genetic testing using next-generation sequencing to effectively assist in the clinical diagnosis and treatment of patients with urinary calculi.

Predicting the storage time of green tea by myricetin based on surface-enhanced Raman spectroscopy.

The quality of green tea changes rapidly due to the oxidation and degradation of polyphenols during storage. Herein, a simple and fast Surface-enhanced Raman spectroscopy (SERS) strategy was established to predict changes in green tea during storage. Raman spectra of green tea with different storage times (2020-2015) were acquired by SERS with silver nanoparticles. The PCA-SVM model was established based on SERS to quickly predict the storage time of green tea, and the accuracy of the prediction set was 97.22%. The Raman peak at 730 cm-1 caused by myricetin was identified as a characteristic peak, which increased with prolonged storage time and exhibited a linear positive correlation with myricetin concentration. Therefore, SERS provides a convenient method for identifying the concentration of myricetin in green tea, and myricetin can function as an indicator to predict the storage time of green tea.

Omicsynin B4 potently blocks coronavirus infection by inhibiting host proteases cathepsin L and TMPRSS2.

The emergence of SARS-CoV-2 variants represents a major threat to public health and requires identification of novel therapeutic agents to address the unmet medical needs. Small molecules impeding viral entry through inhibition of spike protein priming proteases could have potent antiviral effects against SARS-CoV-2 infection. Omicsynin B4, a pseudo-tetrapeptides identified from Streptomyces sp. 1647, has potent antiviral activity against influenza A viruses in our previous study. Here, we found omicsynin B4 exhibited broad-spectrum anti-coronavirus activity against HCoV-229E, HCoV-OC43 and SARS-CoV-2 prototype and its variants in multiple cell lines. Further investigations revealed omicsynin B4 blocked the viral entry and might be related to the inhibition of host proteases. SARS-CoV-2 spike protein mediated pseudovirus assay supported the inhibitory activity on viral entry of omicsynin B4 with a more potent inhibition of Omicron variant, especially when overexpression of human TMPRSS2. Moreover, omicsynin B4 exhibited superior inhibitory activity in the sub-nanomolar range against CTSL, and a sub-micromolar inhibition against TMPRSS2 in biochemical assays. The molecular docking analysis confirmed that omicsynin B4 fits well in the substrate binding sites and forms a covalent bond to Cys25 and Ser441 in CTSL and TMPRSS2, respectively. In conclusion, we found that omicsynin B4 may serve as a natural protease inhibitor for CTSL and TMPRSS2, blocking various coronavirus S protein-driven entry into cells. These results further highlight the potential of omicsynin B4 as an attractive candidate for broad-spectrum antiviral therapy that could rapidly respond to emerging variants of SARS-CoV-2.

High perirenal fat thickness predicts a greater risk of recurrence in Chinese patients with unilateral nephrolithiasis.

INTRODUCTION: The aim of this study was to evaluate the association between recurrence-free survival (RFS) and perirenal fat thickness (PFT) in a cohort of Chinese population with unilateral nephrolithiasis. METHODS: We retrospectively reviewed the medical records of 81 patients with unilateral nephrolithiasis in our center from January 2019 to June 2019. PFT measured on computed tomography (CT) scans was evaluated. Kaplan-Meier curves and log-rank tests were used to assess significant differences in RSF between high-PFT and low-PFT groups within sexes. Univariable and multivariable Cox regression analyses were used to evaluate the potential risk factors for renal stone recurrence. RESULTS: High PFT was significantly associated with high BMI and hyperlipidemia (p = .003 and.047, respectively). The PFT of stone-bearing kidney was significantly greater than PFT of non-stone-bearing kidney (0.77 ± 0.60 cm vs. 0.67 ± 0.58 cm, p = .002) . During the follow-up periods (median 31 months), 21 (25.9%) patients experienced ipsilateral renal stone recurrence. In addition, Kaplan-Meier survival curves showed that patients with low PFT had a significant better RFS than those with high PFT (p = .012). In the univariable Cox analyses, male sex and high PFT were significantly associated with a poor RFS (p = .042 and .018, respectively). Moreover, both male sex and high PFT retained significance in the multivariable analyses (p = .045 and .020, respectively). CONCLUSIONS: Our findings suggested that PFT is a noninvasive and feasible parameter, which may help in the risk stratification of renal stone recurrence in the follow-up periods.

Targeting 7-dehydrocholesterol reductase against EV-A71 replication by upregulating interferon response.

Recent studies have shown a close link between viral infections and cholesterol metabolism. Here, we reported that 7-dehydrocholesterol reductase (DHCR7), a terminal enzyme for catalyzing cholesterol synthesis in the Kandutsch-Russell pathway, is harnessed by enterovirus A71 (EV-A71) benefitting for its replication. Overexpression of DHCR7 resulted in upregulating of EV-A71 replication, while the S14A mutation, which reduces DHCR7 enzyme activity, has no effect on EV-A71 replication. Knockdown of DHCR7 expression with small interfering RNA (siRNA) or enzyme activity inhibition with pharmacological inhibitor AY9944 could significantly inhibit EV-A71 replication. Adding cholesterol to DHCR7 knockdown cells or AY9944-treated cells could rescue EV-A71 replication. More importantly, prophylactic administration of AY9944 effectively protected mice from lethal EV-A71 infection. In addition, the natural cholesterol precursor 7-dehydrocholesterol (7-DHC), which is converted to cholesterol by DHCR7, has a similar effect against EV-A71 infection. Mechanistically, AY9944 or 7-DHC treatment can specifically promote IRF3 phosphorylation to activate interferon response. Moreover, AY9944 effectively cleared coxsackievirus B3 (CVB3) and coxsackievirus A16 (CVA16) infections in vitro. In conclusion, pharmacological modulation of DHCR7 might provide a chance for treatment of enterovirus infection, including EV-A71.

Compound IMB-Z inhibits hepatitis B virus replication through increasing APOBEC3G expression and incorporation into viral nucleocapsids.

OBJECTIVES: As a host restriction factor, apolipoprotein B messenger RNA-editing enzyme catalytic polypeptide-like 3G (APOBEC3G or A3G) has been shown to suppress the replication of several viruses including hepatitis B virus (HBV). Recently, we reported that IMB-Z, a N-phenylbenzamide derivative, could inhibit Enterovirus 71 replication, and A3G mediated its antiviral activity. Whether IMB-Z exhibits an inhibitory effect on HBV replication has not been investigated. MATERIAL AND METHODS: HBV DNA, pregenomic RNA (pgRNA), core protein, and capsid levels were determined by a qPCR assay or Southern blot, Northern blot, Western blot, and particle gel assay, respectively. Mutation analysis of HBV DNAs was conducted by a differential DNA denaturation PCR assay. A3G encapsidation into HBV nucleocapsids was examined by Western blot analysis after ultracentrifugation and a co-immunoprecipitation (IP) assay between HBV core and A3G proteins. RESULTS: In the present study, we found that IMB-Z could considerably inhibit HBV replication in HepAD38 cells. Interestingly, IMB-Z did not alter the HBV pgRNA production but could reduce the level of core protein, viral nucleocapsids, and core-associated DNA, as well as cccDNA intracellular amplification. Similar to the action of IMB-Z's inhibition of Enterovirus 71 replication, we found that IMB-Z's inhibition of HBV replication was associated with increased level of A3G. Mechanistically, we demonstrated that the inhibitory effect of IMB-Z is independent of the cytidine deaminase activity of A3G and is exerted by increasing its incorporation into viral nucleocapsids. CONCLUSIONS: Our results indicate that IMB-Z inhibits HBV through pharmacological induction A3G expression and incorporation into HBV nucleocapsids.

Effects and mechanism of Aß1-42 on EV-A71 replication.

BACKGROUND: ß-Amyloid (Aß) protein is a pivotal pathogenetic factor in Alzheimer's disease (AD). However, increasing evidence suggests that the brain has to continuously produce excessive Aß to efficaciously prevent pathogenic micro-organism infections, which induces and accelerates the disease process of AD. Meanwhile, Aß exhibits activity against herpes simplex virus type 1 (HSV-1) and influenza A virus (IAV) replication, but not against other neurotropic viruses. Enterovirus A71 (EV-A71) is the most important neurotropic enterovirus in the post-polio era. Given the limitation of existing research on the relationship between Aß and other virus infections, this study aimed to investigate the potent activity of Aß on EV-A71 infection and extended the potential function of Aß in other unenveloped viruses may be linked to Alzheimer's disease or infectious neurological diseases. METHODS: Aß peptides 1-42 are a major pathological factor of senile plaques in Alzheimer's disease (AD). Thus, we utilized Aß1-42 as a test subject to perform our study. The production of monomer Aß1-42 and their high-molecular oligomer accumulations in neural cells were detected by immunofluorescence assay, ELISA, or Western blot assay. The inhibitory activity of Aß1-42 peptides against EV-A71 in vitro was detected by Western blot analysis or qRT-PCR. The mechanism of Aß1-42 against EV-A71 replication was analyzed by time-of-addition assay, attachment inhibition assay, pre-attachment inhibition analysis, viral-penetration inhibition assay, TEM analysis of virus agglutination, and pull-down assay. RESULTS: We found that EV-A71 infection induced Aß production and accumulation in SH-SY5Y cells. We also revealed for the first time that Aß1-42 efficiently inhibited the RNA level of EV-A71 VP1, and the protein levels of VP1, VP2, and nonstructural protein 3AB in SH-SY5Y, Vero, and human rhabdomyosarcoma (RD) cells. Mechanistically, we demonstrated that Aß1-42 primarily targeted the early stage of EV-A71 entry to inhibit virus replication by binding virus capsid protein VP1 or scavenger receptor class B member 2. Moreover, Aß1-42 formed non-enveloped EV-A71 particle aggregates within a certain period and bound to the capsid protein VP1, which partially caused Aß1-42 to prevent viruses from infecting cells. CONCLUSIONS: Our findings unveiled that Aß1-42 effectively inhibited nonenveloped EV-A71 by targeting the early phase of an EV-A71 life cycle, thereby extending the potential function of Aß in other non-envelope viruses linked to infectious neurological diseases.

(-)-Lariciresinol Isolated from the Roots of Isatis indigotica Fortune ex Lindl. Inhibits Hepatitis B Virus by Regulating Viral Transcription.

Chronic hepatitis induced by hepatitis B virus (HBV) infection is a serious public health problem, leading to hepatic cirrhosis and liver cancer. Although the currently approved medications can reliably decrease the virus load and prevent the development of hepatic diseases, they fail to induce durable off-drug control of HBV replication in the majority of patients. The roots of Isatis indigotica Fortune ex Lindl., a traditional Chinese medicine, were frequently used for the prevention of viral disease in China. In the present study, (-)-lariciresinol ((-)-LRSL), isolated from the roots of Isatis indigotica Fortune ex Lindl., was found to inhibit HBV DNA replication of both wild-type and nucleos(t)ide analogues (NUCs)-resistant strains in vitro. Mechanism studies revealed that (-)-LRSL could block RNA production after treatment, followed by viral proteins, and then viral particles and DNA. Promoter reporter assays and RNA decaying dynamic experiments indicated that (-)-LRSL mediated HBV RNA reduction was mainly due to transcriptional inhibition rather than degradation. Moreover, (-)-LRSL in a dose-dependent manner also inhibited other animal hepadnaviruses, including woodchuck hepatitis virus (WHV) and duck hepatitis B virus (DHBV). Combining the analysis of RNA-seq, we further found that the decrease in HBV transcriptional activity by (-)-LRSL may be related to hepatocyte nuclear factor 1α (HNF1α). Taken together, (-)-LRSL represents a novel chemical entity that inhibits HBV replication by regulating HNF1α mediated HBV transcription, which may provide a new perspective for HBV therapeutics.

Down-Regulating the High Level of 17-Beta-Hydroxysteroid Dehydrogenase 13 Plays a Therapeutic Role for Non-Alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, and there is no specific drug to treat it. Recent results showed that 17-beta-hydroxysteroid dehydrogenase type 13 (HSD17B13) is associated with liver diseases, but these conclusions are controversial. Here, we showed that HSD17B13 was more highly expressed in the livers of NAFLD patients, and high expression was induced in the livers of murine NAFLD models and cultural hepatocytes treated using various etiologies. The high HSD17B13 expression in the hepatocytes facilitated the progression of NAFLD by directly stabilizing the intracellular lipid drops and by indirectly activating hepatic stellate cells. When HSD17B13 was overexpressed in the liver, it aggravated liver steatosis and fibrosis in mice fed with a high-fat diet, while down-regulated the high expression of HSD17B13 by short hairpin RNAs produced a therapeutic effect in the NAFLD mice. We concluded that high HSD17B13 expression is a good target for the development of drugs to treat NAFLD.

Neddylation of Enterovirus 71 VP2 Protein Reduces Its Stability and Restricts Viral Replication.

Posttranslational modifications (PTMs) of viral proteins play critical roles in virus infection. The role of neddylation in enterovirus 71 (EV71) replication remains poorly defined. Here, we showed that the structural protein VP2 of EV71 can be modified by neural precursor cell-expressed developmentally downregulated protein 8 (NEDD8) in an E3 ligase X-linked inhibitor of apoptosis protein (XIAP)-dependent manner. Mutagenesis and biochemical analyses mapped the neddylation site at lysine 69 (K69) of VP2 and demonstrated that neddylation reduced the stability of VP2. In agreement with the essential role of VP2 in viral replication, studies with EV71 reporter viruses with wild-type VP2 (enhanced green fluorescent protein [EGFP]-EV71) and a K69R mutant VP2 (EGFP-EV71-VP2 K69R) showed that abolishment of VP2 neddylation increased EV71 replication. In support of this finding, overexpression of NEDD8 significantly inhibited the replication of wild-type EV71 and EGFP-EV71, but not EGFP-EV71-VP2 K69R, whereas pharmacologic inhibition of neddylation with the NEDD8-activating enzyme inhibitor MLN4924 promoted the replication of EV71 in biologically relevant cell types. Our results thus support the notion that EV71 replication can be negatively regulated by host cellular and pathobiological cues through neddylation of VP2 protein. IMPORTANCE Neddylation is a ubiquitin-like posttranslational modification by conjugation of neural precursor cell-expressed developmentally downregulated protein 8 (NEDD8) to specific proteins for regulation of their metabolism and biological activities. In this study, we demonstrated for the first time that EV71 VP2 protein is neddylated at K69 residue to promote viral protein degradation and consequentially suppress multiplication of the virus. Our findings advance knowledge related to the roles of VP2 in EV71 virulence and the neddylation pathway in the host restriction of EV71 infection.

Naphthoquine: A Potent Broad-Spectrum Anti-Coronavirus Drug In Vitro.

COVID-19 has spread around the world and caused serious public health and social problems. Although several vaccines have been authorized for emergency use, new effective antiviral drugs are still needed. Some repurposed drugs including Chloroquine, Hydroxychloroquine and Remdesivir were immediately used to treat COVID-19 after the pandemic. However, the therapeutic effects of these drugs have not been fully demonstrated in clinical studies. In this paper, we found an antimalarial drug, Naphthoquine, showed good broad-spectrum anti-coronavirus activity. Naphthoquineinhibited HCoV-229E, HCoV-OC43 and SARS-CoV-2 replication in vitro, with IC50 = 2.05 ± 1.44 µM, 5.83 ± 0.74 µM, and 2.01 ± 0.38 µM, respectively. Time-of-addition assay was also performed to explore at which stage Naphthoquine functions during SARS-CoV-2 replication. The results suggested that Naphthoquine may influence virus entry and post-entry replication. Considering the safety of Naphthoquine was even better than that of Chloroquine, we think Naphthoquine has the potential to be used as a broad-spectrum drug for coronavirus infection.

Stretchable, freezing-tolerant conductive hydrogel for wearable electronics reinforced by cellulose nanocrystals toward multiple hydrogen bonding.

Conductive hydrogels have the mechanical properties and the electronic transport properties of conductive polymers, which have been widely used in the fields of energy storage and bioelectronics. However, the rigidity and brittleness of conductive polymers hinder the long-term stability of hydrogels and limit its application in new flexible electronic devices. It is a high challenging task to prepare ion-conductive hydrogels with excellent mechanical properties, anti-freeze and electrical conductivity through a simple preparation process under the action of hydrogen bonds. We present a facile strategy to prepare mechanically tough, swelling ability hydrogels reinforced by cellulose nanocrystals (CNCs). Herein, CNCs were produced by high pressure homogeneous and pretreated with deep eutectic solvent (DES). The conductivity of the hydrogel is 0.021 S/cm at room temperature. Due to the function of DMSO/H2O in organic solvent system, the ion-conducting hydrogel remains flexible and conductive (0.014 S/cm) at -70 °C. Hydrogel has excellent mechanical properties (stress about 1.4 MPa, strain about 1018%), excellent transparency, freezing resistance (-70 °C) and other comprehensive characteristics. The hydrogel can be assembled into a sensor for use in monitoring large and small movements of the human body, showing good responsiveness and stability.

Evaluating the Effects of Non-Isomorphic Rotation on 3D Manipulation Tasks in Mixed Reality Simulation.

As a hyper-natural interaction technique in 3D user interfaces, non-isomorphic rotation has been considered an effective approach for rotation tasks, where a static or dynamic control-display gain can be applied to amplify or attenuate a rotation. However, it is not clear whether non-isomorphic rotation can benefit 6-degree-of-freedom (6-DOF) manipulation tasks in AR and VR. In this article, we extended the usability studies of non-isomorphic rotation from rotation-only tasks to 6-DOF manipulation tasks and analyzed the collected data using a 2-component model. Using a mixed reality (MR) simulation approach, we also investigated whether environment (AR or VR) had an impact on 3D manipulation tasks. The results reveal that although both static and dynamic non-isomorphic rotation techniques could save time and effort in ballistic phases, only dynamic non-isomorphic rotation was significantly faster than isomorphic rotation. Interestingly, while environment had no significant impact on overall user performance, we found evidence that it could affect fine-tuning in correction phases. We also found that most participants preferred AR over VR, indicating that environmental visual realism could be helpful to improve user experience.

Comparison of the Efficacy of ShuoTong Ureteroscopy and Simple Flexible Ureteroscopy in the Treatment of Unilateral Upper Ureteral Calculi.

Background: ShuoTong ureteroscopy (Sotn-ureteroscopy, ST-URS), a new lithotripsy operation method developed on the basis of ureteroscopy, is widely used to treat ureteral stones in China. Its composition includes rigid ureteral access sheath, standard mirror, lithotripsy mirror, and ShuoTong perfusion aspirator (ST-APM). Here, we compared the efficacy and safety of the ST-URS and the flexible ureteroscope (F-URS) holmium laser lithotripsy in the treatment of unilateral upper ureteral calculi. Methods: Retrospective analysis was conducted on the clinical data of 280 patients who met the inclusion 1) urinary tract CT was diagnosed with unilateral single upper ureteral calculi above the L4 lumbar spine; 2) patient age was from 18 to 80 years old; 3) patients were informed and consented to this study; and 4) patients were approved by the hospital ethics committee (proof number: KY-2019-020) and the exclusion criteria for unilateral upper ureteral calculi in the First Affiliated Hospital of Xiamen University from January 2018 to November 2020, and they were divided into the ST-URS group and the flexible ureteroscopy (F-URS) group. Results: The stone-free rate of 1 day after operation of the ST-URS group was significantly higher than the F-URS group (63.71 vs. 34.62%, P < 0.0001). The operative time (38.45 vs. 46.18 min, P = 0.005) and hospitalization cost (27,203 vs. 33,220 Yuan, P < 0.0001) of the ST-URS group were significantly lower than the F-URS group. There were no significant differences in the success rate of ureteral access sheath placement, operative blood loss, stone-free rate of 1 month after operation, postoperative complications, postoperative hospital stay, and postoperative visual analog scale (VAS) pain score between the two groups (P > 0.05). In subgroups of a diameter of calculi ≥ 1.5 cm, calculi CT numerical value ≥ 1,000 Hounsfield unit and the preoperative hydronephrosis range ≥ 3.0 cm, ST-URS shows more advantages in the operative time, stone-free rate of 1 day after the operation, the hospitalization cost, and the incidence of postoperative complications. Conclusion: In unilateral upper ureteral stones treated with a holmium laser, compared with the simple F-URS, the ST-URS has a shorter operative time, lower hospitalization cost, and a higher stone-free rate of 1 day after the operation, suggesting that the ST-URS could be more widely applied in clinics.

PML Suppresses Influenza Virus Replication by Promoting FBXW7 Expression.

Influenza A viruses (IAV) are responsible for seasonal flu epidemics, which can lead to high morbidity and mortality each year. Like other viruses, influenza virus can hijack host cellular machinery for its replication. Host cells have evolved diverse cellular defense to resist the invasion of viruses. As the main components of promyelocytic leukemia protein nuclear bodies (PML-NBs), PML can inhibit the replication of many medically important viruses including IAV. However, the mechanism of PML against IAV is unclear. In the present study, we found PML was induced in response to IAV infection and ectopic expression of PML could inhibit IAV replication, whereas knockdown of endogenous PML expression could enhance IAV replication. Further studies showed that PML increased the expression of FBXW7 by inhibiting its K48-linked ubiquitination and enhanced the interaction between FBXW7 and SHP2, which negatively regulated IAV replication during infection. Moreover, PML stabilized RIG-I to promote the production of type I IFN. Collectively, these data indicated that PML inhibited IAV replication by enhancing FBXW7 expression in the antiviral immunity against influenza virus and extended the mechanism of PML in antiviral immunity.

Repurposing carrimycin as an antiviral agent against human coronaviruses, including the currently pandemic SARS-CoV-2.

COVID-19 pandemic caused by SARS-CoV-2 infection severely threatens global health and economic development. No effective antiviral drug is currently available to treat COVID-19 and any other human coronavirus infections. We report herein that a macrolide antibiotic, carrimycin, potently inhibited the cytopathic effects (CPE) and reduced the levels of viral protein and RNA in multiple cell types infected by human coronavirus 229E, OC43, and SARS-CoV-2. Time-of-addition and pseudotype virus infection studies indicated that carrimycin inhibited one or multiple post-entry replication events of human coronavirus infection. In support of this notion, metabolic labelling studies showed that carrimycin significantly inhibited the synthesis of viral RNA. Our studies thus strongly suggest that carrimycin is an antiviral agent against a broad-spectrum of human coronaviruses and its therapeutic efficacy to COVID-19 is currently under clinical investigation.

Effect of Preoperative Double-J Ureteral Stenting before Flexible Ureterorenoscopy on Stone-free Rates and Complications.

The effect of preoperative Double-J (DJ) ureteral stenting before flexible ureterorenoscopy (FURS) in the treatment for urinary stones was evaluated. We retrospectively enrolled 306 consecutive patients who underwent FURS from Jan. 2014 to Dec. 2017. All the patients were classified into two groups according to whether they had DJ ureteral stenting before FURS. Baseline characteristics (age, sex, stone location, stone size, surgical success rate, operation time, stone-free rate of the first day after surgery, stone-free rate of the first month after surgery, total complication rate) were compared using Chi-square test for categorical variables and Kruskal-Wallis test for continuous variables. In total, 306 patients were included in this study. The group of DJ stenting before FURS included 203 (66.3%) patients, and non-DJ stenting before FURS was observed in 103 (33.7%) patients. The group of DJ stenting before FURS was significantly associated with a shorter operation time (53.8 vs. 59.3 min, P<0.001), a higher stone-free rate of the first day after surgery (69.0% vs. 51.5%, P=0.003). However, statistical significant differences were not found in the age, sex, stone location, stone size, surgical success rate, stone-free rate of the first month after surgery (89.2% vs. 81.6%, P=0.065) and total complication rate (5.4% vs. 9.7%, P=0.161) between the two groups. Preoperative DJ ureteral stenting before FURS could reduce the operation time and increase stone-free rate of the first day after surgery. However, it might not benefit the stone-free rate of the first month after surgery and reduce the complication rate. Preoperative DJ stenting should be not routinely performed.