Effect of Flexible Ureteroscopic Lithotripsy on Surgical Outcomes, Renal Function and Quality of Life of Patients with 2-3 cm Renal Calculi.

AIM: This retrospective study aims to analyse the effect of flexible ureteroscopic lithotripsy (FURSL) on the surgical outcome, renal function (RF) and quality of life (QoL) of patients with 2-3 cm renal calculi. METHODS: A total of 111 patients with renal calculi (2-3 cm) admitted from January 2019 to May 2022 were selected. Among them, 55 patients who underwent minimally invasive percutaneous nephrolithotomy (PCNL) were set as the control group and 56 patients treated with FURSL served as the research group. The control group consisted of 29 males and 26 females aged (43.31 ± 6.49) years on average. The research group consisted of 31 males and 25 females, with a mean age of (42.46 ± 7.44) years. Parameters such as surgical outcomes (stone clearance rate, bleeding volume, operation time and postoperative recovery time), incidence of adverse reactions (ARs: Gross hematuria, fever, urinary tract infection (UTI) and urinary tract injury), RF (blood urea nitrogen (BUN) and serum creatinine (Scr)), pain degree and QoL were compared. RESULTS: No significant difference in the stone clearance rate was found between the groups. Compared with the control group, the research group had statistically longer operation time, less bleeding, postoperative recovery time, and incidence of ARs and pain and obviously higher QoL. BUN and Scr differed insignificantly between the groups before and after surgery. CONCLUSIONS: FURSL can accelerate postoperative recovery in patients with 2-3 cm renal calculi, lower the risk of postoperative ARs, mitigate pain and improve QoL without significantly affecting RF.

Effect of Flexible Ureteroscopic Lithotripsy on Surgical Outcomes, Renal Function and Quality of Life of Patients with 2–3 cm Renal Calculi

Aim: This retrospective study aims to analyse the effect of flexible ureteroscopic lithotripsy (FURSL) on the surgical outcome, renal function (RF) and quality of life (QoL) of patients with 2–3 cm renal calculi. Methods: A total of 111 patients with renal calculi (2–3 cm) admitted from January 2019 to May 2022 were selected. Among them, 55 patients who underwent minimally invasive percutaneous nephrolithotomy (PCNL) were set as the control group and 56 patients treated with FURSL served as the research group. The control group consisted of 29 males and 26 females aged (43.31 ± 6.49) years on average. The research group consisted of 31 males and 25 females, with a mean age of (42.46 ± 7.44) years. Parameters such as surgical outcomes (stone clearance rate, bleeding volume, operation time and postoperative recovery time), incidence of adverse reactions (ARs: Gross hematuria, fever, urinary tract infection (UTI) and urinary tract injury), RF (blood urea nitrogen (BUN) and serum creatinine (Scr)), pain degree and QoL were compared. Results: No significant difference in the stone clearance rate was found between the groups. Compared with the control group, the research group had statistically longer operation time, less bleeding, postoperative recovery time, and incidence of ARs and pain and obviously higher QoL. BUN and Scr differed insignificantly between the groups before and after surgery. Conclusions: FURSL can accelerate postoperative recovery in patients with 2–3 cm renal calculi, lower the risk of postoperative ARs, mitigate pain and improve QoL without significantly affecting RF (AU)

Synergism of rMV-Hu191 with cisplatin to treat gastric cancer by acid sphingomyelinase-mediated apoptosis requiring integrity of lipid raft microdomains.

BACKGROUND: DDP-based chemotherapy is one of the first-line treatment in GC. However, the therapeutic efficacy of DDP is limited due to side effects. Therefore, it is of great significance to develop novel adjuvants to synergize with DDP. We had demonstrated previously that rMV-Hu191 had antitumor activity in GC. Here we examined the synergism of rMV-Hu191 with DDP in vitro and in vivo. METHODS: Cellular proliferation, the synergistic effect and cell apoptosis were evaluated by CCK-8 assay, ZIP analysis and flow cytometry, respectively. The protein levels and location of ASMase were monitored by western blot and immunofluorescence assay. shRNA and imipramine were used to regulate the expression and activity of ASMase. MßCD was administrated to disrupt lipid rafts. Mice bearing GC xenografts were used to confirm the synergism in vivo. RESULTS: From our data, combinational therapy demonstrated synergistic cytotoxicity both in resistant GC cell lines from a Chinese patient and drug-nonresistant GC cell lines, and increased cell apoptosis, instead of viral replication. Integrity of lipid rafts and ASMase were required for rMV-Hu191- and combination-induced apoptosis. The ASMase was delivered to the lipid raft microdomains at the initial stage of rMV-Hu191 treatment. In vivo GC mice xenografts confirmed the synergism of combinational treatment, together with increased apoptosis and trivial side-effects. CONCLUSIONS: This is the first study to demonstrate that rMV-Hu191 combined with DDP could be used as a potential therapeutic strategy in GC treatment and the ASMase and the integrity of lipid rafts are required for the synergistic effects.

A recombinant Chinese measles virus vaccine strain rMV-Hu191 inhibits human colorectal cancer growth through inducing autophagy and apoptosis regulating by PI3K/AKT pathway.

The potential therapeutic effects of oncolytic measles virotherapy have been verified against plenty of malignancies. However, the oncolytic effects and underlying mechanisms of the recombinant Chinese measles virus vaccine strain Hu191 (rMV-Hu191) against human colorectal cancer (CRC) remain elusive. In this study, the antitumor effects of rMV-Hu191 were evaluated in CRC both in vitro and in vivo. From our data, rMV-Hu191 induced remarkably caspase-dependent apoptosis and complete autophagy in vitro. In mice bearing CRC xenografts, tumor volume was remarkably suppressed and median survival was prolonged significantly with intratumoral treatment of rMV-Hu191. To gain further insight into the relationship of rMV-Hu191-induced apoptosis and autophagy, we utilized Rapa and shATG7 to regulate autophagy. Our data suggested that autophagy was served as a protective role in rMV-Hu191-induced apoptosis in CRC. PI3K/AKT signaling pathway as one of the common upstream pathways of apoptosis and autophagy was activated in CRC after treatment with rMV-Hu191. And inhibition of PI3K/AKT pathway using LY294002 was accompanied by enhanced apoptosis and decreased autophagy which suggested that PI3K/AKT pathway promoted rMV-Hu191-induced autophagy and inhibited rMV-Hu191-induced apoptosis. This is the first study to demonstrate that rMV-Hu191 could be used as a potentially effective therapeutic agent in CRC treatment. As part of the underlying cellular mechanisms, apoptosis and autophagy were involved in the oncolytic effects generated by rMV-Hu191. And the cross-talk between these two processes and the PI3K/AKT signaling pathway was well identified.

A three-dimensional nanostructure of NiFe(OH) X nanoparticles/nickel foam as an efficient electrocatalyst for urea oxidation.

Developing high-performance electrocatalysts for urea oxidation reaction (UOR) can not only solve the problem of environmental pollution, but also solve the problem of the energy crisis by producing hydrogen for electrodes. The preparation of porous three-dimensional nanostructures as efficient electrocatalysts has become important work. Here, we developed a novel three-dimensional (3D) nanostructure of NiFe(OH) X nanoparticles/nickel foam with a high active area by a simple electroplating method and a subsequent treatment with ferric ion solution. This structure shows much greater UOR activity than the control sample (Ni/Ni foam) with the potential of 1.395 V (vs. RHE) (with an overpotential of 1.025 V) for driving the current density of 100 mA cm-2 in 1.0 M KOH electrolyte with 0.33 M urea. This work not only provides rapid and large-scale preparation of a three-dimensional nanostructure, but also gives a new way to design and obtain high-performance electrocatalysts.

Development of Improved Mumps Vaccine Candidates by Mutating Viral mRNA Cap Methyltransferase Sites in the Large Polymerase Protein.

Although a live attenuated vaccine is available for controlling mumps virus (MuV), mumps still outbreaks frequently worldwide. The attenuated MuV vaccine strain S79 is widely used in mumps vaccination in China, but still with many shortcomings, among which the most prominent are the side effects and decreased immunity. Therefore, there is a need to further improve the safety and efficacy of the current MuV vaccine. In the present study, we further attenuated MuV S79 vaccine strain by inhibiting viral mRNA methyltransferase (MTase). We generated a panel of eight recombinant MuVs (rMuVs) carrying mutations in the MTase catalytic site or S-adenosylmethionine (SAM) binding site in the large (L) polymerase protein. These rMuVs are genetically stable and seven rMuVs are more attenuated in replication in cell culture and five rMuVs are more attenuated in replication in lungs of cotton rats compared with the parental vaccine strain S79. Importantly, cotton rats vaccinated with these seven rMuV mutants produced high levels of serum neutralizing antibodies and were completely protected against challenge with a wild-type MuV strain (genotype F). Therefore, our results demonstrate that alteration in the MTase catalytic site or SAM binding site in MuV L protein improves the safety or the immunogenicity of the MuV vaccine and thus mRNA cap MTase may be an effective target for the development of new vaccine candidates for MuV.

Establishment of an efficient reverse genetic system of Mumps virus S79 from cloned DNA.

BACKGROUND: Mumps is a common type of respiratory infectious disease caused by mumps virus (MuV), and can be effectively prevented by vaccination. In this study, a reverse genetic system of MuV that can facilitate the rational design of safer, more efficient mumps vaccine candidates is established. METHODS: MuV-S79 cDNA clone was assembled into a full-length plasmid by means of the GeneArt™ High-Order Genetic Assembly System, and was rescued via reverse genetic technology. RT-PCR, sequencing, and immunofluorescence assays were used for rMuV-S79 authentication. Viral replication kinetics and in vivo experimental models were used to evaluate the replication, safety, and immunogenicity of rMuV-S79. RESULTS: A full-length cDNA clone of MuV-S79 in the assembly process was generated by a novel plasmid assemble strategy, and a robust reverse genetic system of MuV-S79 was successfully established. The established rMuV-S79 strain could reach a high virus titer in vitro. The average viral titer of rMuV-S79 in the lung tissues was 2.68 ± 0.14 log10PFU/g lung tissue, and rMuV-S79 group did not induce inflammation in the lung tissues in cotton rats. Neutralizing antibody titers induced by rMuV-S79 were high, long-lasting and could provide complete protection against MuV wild strain challenge. CONCLUSION: We have established a robust reverse genetic system of MuV-S79 which can facilitate the optimization of mumps vaccines. rMuV-S79 rescued could reach a high virus titer and the safety was proven in vivo. It could also provide complete protection against MuV wild strain challenge.

Attenuated MuV-S79 as vector stably expressing foreign gene.

BACKGROUND: To describe mumps virus (MuV) used as a vector to express enhanced green fluorescent protein (EGFP) or red fluorescent protein (RFP) genes. METHODS: Molecular cloning technique was applied to establish the cDNA clones of recombinant mumps viruses (rMuVs). rMuVs were recovered based on our reverse genetic system of MuV-S79. The properties of rMuVs were determined by growth curve, plaque assay, fluorescent microscopy and determination of fluorescent intensity. RESULTS: Three recombinant viruses replicated well in Vero cells and similarly as parental rMuV-S79, expressed heterologous genes in high levels, and were genetically stable in at least 15 passages. CONCLUSION: rMuV-S79 is a promising platform to accommodate foreign genes like marker genes, other antigens and immunomodulators for addressing various diseases.

A recombinant measles virus vaccine strain rMV-Hu191 has oncolytic effect against human gastric cancer by inducing apoptotic cell death requiring integrity of lipid raft microdomains.

Live-attenuated strain of measles virus (MV) has oncolytic effect. In this study, the antitumor effect of rMV-Hu191, a recombinant Chinese Hu191 MV generated in our laboratory by efficient reverse genetics system, was evaluated in gastric cancer (GC). From our data, rMV-Hu191 induced cytopathic effects and inhibited tumor proliferation both in vitro and in vivo by inducing caspase-dependent apoptosis. In mice bearing GC xenografts, tumor size was reduced and survival was prolonged significantly after intratumoral injections of rMV-Hu191. Furthermore, lipid rafts, a type of membrane microdomain with specific lipid compositions, played an important role in facilitating entry of rMV-Hu191. Integrity of lipid rafts was required for successful viral infection as well as subsequent cell apoptosis, but was not required for viral binding and replication. CD46, a MV membrane receptor, was found to be partially localized in lipid rafts microdomains. This is the first study to demonstrate that Chinese Hu191 MV vaccine strain could be used as a potentially effective therapeutic agent in GC treatment. As part of the underlying cellular mechanism, the integrity of lipid rafts is required for viral entry and to exercise the oncolytic effect.

Application of a Self-Made Equipment for Patient Positioning during Percutaneous Nephroscopy in the Oblique-Supine Position.

BACKGROUND: The oblique-supine position for percutaneous nephrolithotomy (PCNL) has advantages, but the position fixation methods are inadequate. This study aimed to analyze the PCNL outcomes using a patented self-made frame for oblique-supine position. METHODS: This was a prospective study of patients scheduled to undergo PCNL at 2 hospitals in China between November 2009 and December 2016. The patients underwent PCNL in the oblique-supine position using the self-made position frame (n = 94). Operative time, stone clearance rate, intraoperative average systolic pressure, intraoperative average heart rate, intraoperative average airway pressure, intraoperative average intrapelvic pressure, and complications were observed. RESULTS: The patients were 45.3 ± 19.7 years old and 71% were male. Stones were of the size 2.5 ± 1.1 cm. The operative time was 95.6 min and the stone clearance rate was 81.9%. Intraoperative systolic blood pressure was 15.13 ± 1.68 kPa. Intraoperative airway pressure was 15.5 ± 2.3 cm H2O. Postoperative fever was observed in 3.2% of the patients. None had organ injury. Postoperative stay was 4.8 ± 0.6 days. The nephrostomy tube was routinely removed on the 5th day after surgery and the patients were discharged on the following day. CONCLUSION: The self-made surgical position frame met the position requirements for the oblique-supine PCNL operation. This surgical position frame deserves clinical application and promotion.

Enhancement of safety and immunogenicity of the Chinese Hu191 measles virus vaccine by alteration of the S-adenosylmethionine (SAM) binding site in the large polymerase protein.

The live-attenuated measles virus (MV) vaccine based on the Hu191 strain has played a significant role in controlling measles in China. However, it has considerable adverse effects that may cause public health burden. We hypothesize that the safety and efficacy of MV vaccine can be improved by altering the S-adenosylmethionine (SAM) binding site in the conserved region VI of the large polymerase protein. To test this hypothesis, we established an efficient reverse genetics system for the rMV-Hu191 strain and generated two recombinant MV-Hu191 carrying mutations in the SAM binding site. These two mutants grew to high titer in Vero cells, were genetically stable, and were significantly more attenuated in vitro and in vivo compared to the parental rMV-Hu191 vaccine strain. Importantly, both MV-Hu191 mutants triggered a higher neutralizing antibody than rMV-Hu191 vaccine and provided complete protection against MV challenge. These results demonstrate its potential for an improved MV vaccine candidate.