Comparative efficacy and safety of intelligent pressure-controlled versus flexible vacuum-assisted ureteral access sheath for 2-4 cm renal calculi.

BACKGROUND: Retrograde intrarenal surgery (RIRS) is being increasingly used to treat 2-4 cm renal stones, which can be attributed to advances in flexible ureteroscopes and ureteral access sheaths (UASs). Despite the improvement and application of flexible vacuum-assisted (FV) and intelligent pressure-controlled (IPC) UASs, no studies have compared their therapeutic efficacy and safety. Therefore, this study aimed to compare the therapeutic efficacy and safety of IPC-UAS and FV-UAS in RIRS 2-4 cm renal stones. METHODS: We included 96 and 103 patients who underwent IPC-UAS and FV-UAS RIRS, respectively, for 2-4 cm renal stones. Stone-free rate (SFR), operative time, and complications were compared between the two groups. RESULTS: The immediate SFR was 69.8% and 82.5% in the IPC-UAS and FV-UAS groups, respectively (P<0.05). There were no significant between-group differences in the 1-month SFR (84.4% vs. 84.5%, P>0.05). The IPC-UAS group had a shorter hospital stay (5.2±2.4 vs. 6.2±3.2 days, P=0.018) and lower cost (CNY13014.7±3240.7 vs. CNY14022.5±2301.6, P=0.012) than the FV-UAS group. There were no significant between-group differences in operative time or complications. CONCLUSIONS: Regarding RIRS for 2-4 cm renal stones, the IPC-UAS group can achieve a 1-month SFR similar to that of the FV-UAS group, with shorter hospitalization and lower cost. Additionally, the IPC-UAS is a promising device for efficient and safe RIRS, considering its intelligent pressure regulation. Our findings could inform optimal UAS selection for managing large renal calculi and demonstrate the utility of the novel IPC-UAS in improving outcomes of RIRS for 2-4 cm renal stones.

Integrated analysis of multiple transcriptomic approaches and machine learning integration algorithms reveals high endothelial venules as a prognostic immune-related biomarker in bladder cancer.

BACKGROUND: Despite the availability of established surgical and chemotherapy options, the treatment of bladder cancer (BCa) patients remains challenging. While immunotherapy has emerged as a promising approach, its benefits are limited to a subset of patients. The exploration of additional targets to enhance the efficacy of immunotherapy is a valuable research direction. METHOD: High endothelial venules (HEV) ssGSEA analysis was conducted using BEST. Through the utilization of R packages Limma, Seurat, SingleR, and Harmony, analyses were performed on spatial transcriptomics, bulk RNA-sequencing (bulk RNA-seq), and single-cell RNA sequencing (scRNA-seq) data, yielding HEV-related genes (HEV.RGs). Molecular subtyping analysis based on HEV.RGs was conducted using R package MOVICS, and various machine learning-integrated algorithm was employed to construct prognostic model. LDLRAD3 was validated through subcutaneous tumor formation in mice, HEV induction, Western blot, and qPCR. RESULTS: A correlation between higher HEV levels and improved immune response and prognosis was revealed by HEV ssGSEA analysis in BCa patients receiving immunotherapy. HEV.RGs were identified in subsequent transcriptomic analyses. Based on these genes, BCa patients were stratified into two molecular clusters with distinct survival and immune infiltration patterns using various clustering-integrated algorithm. Prognostic model was developed using multiple machine learning-integrated algorithm. Low LDLRAD3 expression may promote HEV generation, leading to enhanced immunotherapy efficacy, as suggested by bulk RNA-seq, scRNA-seq analyses, and experimental validation of LDLRAD3. CONCLUSIONS: HEV served as a predictive factor for immune response and prognosis in BCa patients receiving immunotherapy. LDLRAD3 represented a potential target for HEV induction and enhancing the efficacy of immunotherapy.

Differentiation between viral and autoimmune limbic encephalitis: a prospective cohort study with development and validation of a diagnostic model.

BACKGROUND: Distinguishing between viral encephalitis (VE) and autoimmune limbic encephalitis (ALE) presents a clinical challenge due to the overlap in symptoms. We aimed to develop and validate a diagnostic prediction model to differentiate VE and ALE. METHODS: A prospective observational multicentre cohort study, which continuously enrolled patients diagnosed with either ALE or VE from October 2011 to April 2023. The demographic data, clinical features, and laboratory test results were collected and subjected to logistic regression analyses. The model was displayed as a web-based nomogram and then modified into a scored prediction tool. Model performance was assessed in both derivation and external validation cohorts. RESULTS: A total of 2423 individuals were recruited, and 1001 (496 VE, 505 ALE) patients were included. Based on the derivation cohort (389 VE, 388 ALE), the model was developed with eight variables including age at onset, acuity, fever, headache, nausea/vomiting, psychiatric or memory complaints, status epilepticus, and CSF white blood cell count. The model showed good discrimination and calibration in both derivation (AUC 0.890; 0.868-0.913) and external validation (107 VE, 117 ALE, AUC 0.872; 0.827-0.917) cohorts. The scored prediction tool had a total point that ranged from - 4 to 10 also showing good discrimination and calibration in both derivation (AUC 0.885, 0.863-0.908) and external validation (AUC 0.868, 0.823-0.913) cohorts. CONCLUSIONS: The prediction model provides a reliable and user-friendly tool for differentiating between the VE and ALE, which would benefit early diagnosis and appropriate treatment and alleviate economic burdens on both patients and society.

Flexible Ureteroscopy with a Tip-Flexible Pressure-Controlling Ureteral Access Sheath for Renal Stones in Children.

INTRODUCTION: The aim of this study was to evaluate the safety and efficacy of flexible ureteroscopy using a tip-flexible pressure-controlling ureteral access sheath (TFPC-UAS) for renal stones in children. METHODS: Consecutive patients aged 5-18 years with renal stones of diameter 1-3 cm were enrolled between January 2022 and November 2023 at Ganzhou People's Hospital. The patients were treated with flexible ureteroscopy using the TFPC-UAS. The renal pelvic pressure (RPP) parameters were set as follows: control value at -10 mm Hg to 5 mm Hg, warning value at 20 mm Hg, and limit value at 30 mm Hg. The infusion flow rate was set to 100-120 mL/min. A holmium laser (276 µm) was used to fragment the stone at 2.0-2.5 J/pulse with a frequency of 20-30 pulses/s. The cases were analyzed for RPP, operative time, stone-free rate, and complications. RESULTS: A total of 21 consecutive patients were included. Two patients were switched to percutaneous nephrolithotomy owing to sheath placement failure. The RPP was -4.6 ± 2.1 mm Hg. The mean operative time was 56.5 ± 17.1 min. The postoperative hospitalization time was 1.5 ± 0.3 days. The stone-free rates at 1 day and 1 month after surgery were 81.0% and 85.7%, respectively. Residual stones in 2 patients were cleared after extracorporeal shockwave lithotripsy. Three cases of Clavien I complications and one case of Clavien II complications occurred. No major complications (Clavien grade III-V) were observed. CONCLUSIONS: Flexible ureteroscopy with a TFPC-UAS is safe and effective for renal stones in children.

Fluid absorption during flexible ureteroscopy with intelligent control of renal pelvic pressure: a randomized controlled trial.

PURPOSE: To investigate fluid absorption and its influencing factors during flexible ureteroscopy with intelligent control of renal pelvic pressure (RPP). METHODS: A total of 80 patients with upper urinary tract calculi underwent flexible ureteroscopy with intelligent control of RPP by pressure-measuring ureteral access sheath and were randomly divided into four groups. The RPP of Groups A, B, and C were set at - 5, 0 and 5 mmHg, respectively. Conventional flexible ureteroscopy with uncontrolled pressure served as control Group D. The perfusion flow rate was set at 100 ml/min in the four groups, with 20 patients in each group. The fluid absorption was measured by 1% ethanol every 10 min. Operation time, stone-free rate, and complications were recorded. RESULT: Seventy-three patients were finally included in the RCT. The general and preoperative data of the patients were comparable between the groups. The fluid absorption of Groups A, B, and C was significantly less than that of Group D (P < 0.01). Fluid absorption and operation time were positively correlated, and the correlation coefficients R were 0.864, 0.896, 0.918, and 0.947, respectively (P < 0.01). The fluid absorption of patients with vomiting, fever and ureteral injury was greater than that of patients without complications in the four groups (P < 0.01). In different groups, fluid absorption was greater in patients with ureteral injury Post-Ureteroscopic Lesion Scale (PULS) 1-3 than in noninjured patients (P < 0.01). CONCLUSION: Flexible ureteroscopy with intelligent control of RPP effectively reduces the absorption of perfusion fluid. Operation time and ureteral injury are also key factors affecting perfusion fluid absorption. REGISTRATION NUMBER AND DATE: NCT05201599; August 11, 2021.

Retrograde intrarenal surgery with intelligent control of renal pelvic pressure for staghorn calculi: a case report.

Percutaneous nephrolithotomy is the gold standard treatment for staghorn calculi. However, this study reviews a case of an almost complete removal of staghorn calculi following one session of retrograde intrarenal surgery with intelligent control of renal pelvic pressure (RIRS-ICP). A 45 years-old female patient with an 8.3 × 4.5 cm complete staghorn stone was infected with Proteus mirabilis. Two sensitive antibiotics, piperacillin tazobactam and etimicin, were administered for 3 days. Semirigid 7/8.4 Fr ureteroscope was used to treat the renal pelvis and upper calyceal calculi for 57 min. A 550 µm holmium laser fiber with 2.0 J × 30 Hz was set. Next, a disposable flexible ureteroscope of 8.4 Fr was used to address residual middle and lower calyx stones for 94 min. A 200 µm holmium laser fiber with 1.0 J × 30 Hz was set. The renal pelvis pressure was controlled within 15 mmHg. A 2 mm CT scan on the first postoperative day showed inferior caliceal residue of approximately 1.0 × 0.6 cm. No complications occurred. This suggests that RIRS-ICP is a safe and effective treatment for staghorn calculi.

Ureteroscopic lithotripsy with pressure-measuring ureteral access sheath for large ureteral stones.

INTRODUCTION: To evaluate the safety and efficacy of ureteroscopic lithotripsy with pressure-measuring ureteral access sheath (PM-UAS) for large ureteral stones. MATERIAL AND METHODS: A total of 258 consecutive patients with large ureteral stones ≥15 mm was enrolled. They were treated by ureteroscopic lithotripsy with PM-UAS in the oblique supine lithotomy position. The technology can precisely monitor and automatically control cavity pressure. The cavity pressure control value was set at -15 mmHg∼-5 mmHg. The cavity pressure limit value was set at 30 mmHg. Infusion flow rate was set at 100-200 ml/min. Postoperative data such as stone-free rate and complications were analyzed. RESULTS: PM-UAS was successfully implanted in 225 patients at one stage. Eighteen cases of patients who had failed the first surgery were successfully treated with a second operation. Fifty-one cases with stones migrating up to the kidney were converted to flexible lithotripsy. The other 15 cases were converted to percutaneous nephrolithotomy due to significant ureteral stenosis. The operative time was 49.5 ± 11.2 min. The stone-free rates after one month and three months were 87.2% (212/243) and 94.2% (229/243), respectively. Complications from grade I to II were observed in 25(10.3%) patients. No other complications from grade III to V were noted. CONCLUSION: The ureteroscopic lithotripsy with PM-UAS is safe and efficacious for large ureteral stones.

Crushing performance of a novel tetra-missing rib honeycomb: Experimental and numerical studies.

Based on the unique monoclinic characteristics of the plastic deformation of the tetra-missing rib honeycomb, the symmetrical design of the whole and subunits of the tetra-missing rib honeycomb was carried out in this paper, and two new types of tetra-missing rib honeycomb with symmetrical structural characteristics were obtained. First, quasi-static compression was performed on three structures, including a conventional tetra-missing rib honeycomb, and the experimental results showed that both symmetrical designs could effectively improve the plastic deformation of the conventional tetra-missing rib honeycomb. At the same time, round holes were introduced into the three honeycomb structures, and the mechanical properties and deformation modes of the three structures under quasi-static loads were explored. The results of two sets of experiments were compared, and it was found that the introduction of round holes could improve the structural stiffness of the honeycomb. Second, Abaqus/Explicit was used to construct a finite element numerical model in the later stage, and the accuracy of the model was verified. The number of honeycomb cells was determined for the three honeycomb structures, and finally, the dynamic Poisson's ratio of the honeycomb structure in plastic deformation was determined, and the negative Poisson's ratio (NPR) effect of the three honeycombs was compared.

Single-cell transcriptome analysis reveals the association between histone lactylation and cisplatin resistance in bladder cancer.

Patients with bladder cancer (BCa) frequently acquires resistance to platinum-based chemotherapy, particularly cisplatin. This study centered on the mechanism of cisplatin resistance in BCa and highlighted the pivotal role of lactylation in driving this phenomenon. Utilizing single-cell RNA sequencing, we delineated the single-cell landscape of Bca, pinpointing a distinctive subset of BCa cells that exhibit marked resistance to cisplatin with association with glycolysis metabolism. Notably, we observed that H3 lysine 18 lactylation (H3K18la) plays a crucial role in activating the transcription of target genes by enriching in their promoter regions. Targeted inhibition of H3K18la effectively restored cisplatin sensitivity in these cisplatin-resistant epithelial cells. Furthermore, H3K18la-driven key transcription factors YBX1 and YY1 promote cisplatin resistance in BCa. These findings enhance our understanding of the mechanisms underlying cisplatin resistance, offering valuable insights for identifying novel intervention targets to overcome drug resistance in Bca.

The effect and safety assessment of monitoring ethanol concentration in exhaled breath combined with intelligent control of renal pelvic pressure on the absorption of perfusion fluid during flexible ureteroscopic lithotripsy.

PURPOSE: Previously, we designed a ureteral access sheath with the capability of renal pelvic pressure (RPP) measurement and a medical perfusion and aspiration platform, allowing for the intelligent control of RPP. However, the effect of different RPP levels on perfusion fluid absorption remains unclear. This randomized controlled trial aimed to investigate the effects of exhaled ethanol concentration monitoring and intelligent pressure control on perfusion fluid absorption during flexible ureteroscopic lithotripsy. METHODS: Eighty patients scheduled for flexible ureteroscopic lithotripsy were randomly divided into four groups. In groups A, B, and C, the RPPs were set at 0, - 5, and - 10 mmHg, respectively. Group D was regarded as the controls with unfixed RPP. Isotonic saline containing 1% ethanol was used as the irrigation fluid, with an average irrigation flow rate of 100 mL/min. The primary outcome of this study was the absorption of perfusion fluid that was calculated based on the exhaled ethanol concentration. The secondary outcomes included duration of operation and amounts of perfusion fluid used. Postoperative complications, pre- and postoperative renal function, infection markers, and blood gas analysis were also recorded for safety assessment. RESULTS: In all, 76 patients were involved in this study, whose demographic characteristics and preoperative conditions were comparable among groups. Under the same perfusion flow rate, the groups with fixed RPP exhibited reduced absorption of perfusion fluid, duration of operation, and perfusion volume. In particular, the lowest values were observed in group C (RPP = - 10 mmHg). In contrast to the unfixed RPP group, no considerable difference were observed in levels of BUN, Scr, WBC, CRP, and blood gas values among the fixed RPP groups. Moreover, postoperative complications showed no significant difference among groups. CONCLUSION: In flexible ureteroscopic lithotripsy, the groups with fixed RPP had less absorption of perfusion fluid and perfusion volume, shorter duration of surgery, and higher safety than the unfixed group.

Intestinal dysbiosis exacerbates susceptibility to the anti-NMDA receptor encephalitis-like phenotype by changing blood brain barrier permeability and immune homeostasis.

Changes in the intestinal microbiota have been observed in patients with anti-N-methyl-D-aspartate receptor encephalitis (NMDARE). However, whether and how the intestinal microbiota is involved in the pathogenesis of NMDARE susceptibility needs to be demonstrated. Here, we first showed that germ-free (GF) mice that underwent fecal microbiota transplantation (FMT) from NMDARE patients, whose fecal microbiota exhibited low short-chain fatty acid content, decreased abundance of Lachnospiraceae, and increased abundance of Verrucomicrobiota, Akkermansia, Parabacteroides, Oscillospirales, showed significant behavioral deficits. Then, these FMT mice were actively immunized with an amino terminal domain peptide from the GluN1 subunit (GluN1356-385) to mimic the pathogenic process of NMDARE. We found that FMT mice showed an increased susceptibility to an encephalitis-like phenotype characterized by more clinical symptoms, greater pentazole (PTZ)-induced susceptibility to seizures, and higher levels of T2 weighted image (T2WI) hyperintensities following immunization. Furthermore, mice with dysbiotic microbiota had impaired blood-brain barrier integrity and a proinflammatory condition. In NMDARE-microbiota recipient mice, the levels of Evan's blue (EB) dye extravasation increased, ZO-1 and claudin-5 expression decreased, and the levels of proinflammatory cytokines (IL-1, IL-6, IL-17, TNF-α and LPS) increased. Finally, significant brain inflammation, mainly in hippocampal and cortical regions, with modest neuroinflammation, immune cell infiltration, and reduced expression of NMDA receptors were observed in NMDARE microbiota recipient mice following immunization. Overall, our findings demonstrated that intestinal dysbiosis increased NMDARE susceptibility, suggesting a new target for limiting the occurrence of the severe phenotype of NMDARE.

Association of white matter hyperintensities with long-term EGFR-TKI treatment and prediction of progression risk.

PURPOSE: The purpose of this study was to test the hypothesis that brain white matter hyperintensities (WMH) are more common in patients receiving epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) and identify clinical risk factors associated with WMH. EXPERIMENTAL DESIGN: This multiple-center, prospective cohort study was conducted from March 2017 to July 2020. Two groups of patients with non-small cell lung cancer (NSCLC) who received or did not receive EGFR-TKI were included and followed up for more than 24 months. The progression of WMH was defined as an increase of ≥1 point on the Fazekas visual rating scale between the baseline and at the 2-year follow-up. A modified Poisson regression model was performed to evaluate risk factors on increased WMH load. RESULTS: Among 286 patients with NSCLC, 194 (68%) patients with NSCLC who received EGFR-TKI and 92 (32%) patients with NSCLC without EGFR-TKI treatment were analyzed. Modified Poisson regression analysis showed that EGFR-TKI treatment was independently associated with the WMH progression (EGFR-TKI: aRR 2.72, 95% confidence interval [CI] 1.46-5.06, p = .002). Interleukin (IL)-2, IL-4, and IL-10 were associated with increased WMH in the adjusted model (IL-2: aRR 1.55 [95% CI 1.06-2.25], p = .023; IL-4: aRR 1.66 [95% CI 1.13-2.43], p = .010; IL-10: aRR 1.48 [95% CI 1.06-2.06], p = .020). CONCLUSION: Patients with NSCLC who received EGFR-TKI may be at higher risk of developing WMH or worsening of WMH burden. The impact of increased WMH lesions in these patients is to be further assessed. IL-2, IL-4, and IL-10 may be used as potential biomarkers to monitor the risk of increased WMH burden.

[Evaluation of red and white aesthetic effects of porcelain veneers in the restoration of developmental anterior dental gaps].

PURPOSE: To evaluate the red and white aesthetic effect of porcelain veneer in the restoration of developmental anterior interdental spaces. METHODS: A total of 152 anterior teeth in 64 patients with developmental anterior dental gaps were restored using porcelain veneers, the aesthetic effects before and after restoration were evaluated by pink aesthetic index (PES) and white aesthetic index(WES), the aesthetic effect of gingival papilla filling and reconstruction was evaluated by interdental gingival papilla index (PIS), and visual analogue score (VAS) was used to compare the satisfaction of patients before and after restoration. SPSS 203.0 software package was used for statistical analysis. RESULTS: The overall mean scores of PES before and after restoration of 152 developmental anterior interdental teeth were 9.63±2.23 and 13.64±0.88, respectively. The average scores of WES before and after restoration were 6.85±1.87 and 9.81±0.58, respectively. There were significant differences of PES and WES scores before and after restoration(P＜0.01). According to the requirements of "near" perfect restoration(PES≥13 points, WES≥9 points), the red and white aesthetic effect after restoration was near the standard. The scores of PIS before and after restoration were 1.86±0.67 and 2.97±0.18, the interdental gingival papilla was completely filled with space, and the shape was ideal, there were significant statistical differences before and after restoration(P＜0.01). Patients were more satisfied with the smile curve and morphology of the restored anterior teeth than other parameters. CONCLUSIONS: The aesthetic effect of using porcelain veneers to repair developmental anterior interdental gaps is ideal, among which the filling of the papillae between the teeth can meet the expectations of patients, and the aesthetic effect evaluation of PIS and PES/WES applied to porcelain veneers to repair developmental anterior interdental spaces has practical guiding significance in clinical practice.

Insights into the phylogenetic diversity, biological activities, and biosynthetic potential of mangrove rhizosphere Actinobacteria from Hainan Island.

Mangrove rhizosphere soils host diverse Actinobacteria tolerant to numerous stresses and are inevitably capable of exhibiting excellent biological activity by producing impressive numbers of bioactive natural products, including those with potential medicinal applications. In this study, we applied an integrated strategy of combining phylogenetic diversity, biological activities, and biosynthetic gene clusters (BGCs) screening approach to investigate the biotechnological importance of Actinobacteria isolated from mangrove rhizosphere soils from Hainan Island. The actinobacterial isolates were identifified using a combination of colony morphological characteristics and 16S rRNA gene sequence analysis. Based on the results of PCR-detected BGCs screening, type I and II polyketide synthase (PKS) and non-ribosomal synthetase (NRPS) genes were detected. Crude extracts of 87 representative isolates were subjected to antimicrobial evaluation by determining the minimum inhibitory concentration of each strain against six indicator microorganisms, anticancer activities were determined on human cancer cell lines HepG2, HeLa, and HCT-116 using an MTT colorimetric assay, and immunosuppressive activities against the proliferation of Con A-induced T murine splenic lymphocytes in vitro. A total of 287 actinobacterial isolates affiliated to 10 genera in eight families of six orders were isolated from five different mangrove rhizosphere soil samples, specififically, Streptomyces (68.29%) and Micromonospora (16.03%), of which 87 representative strains were selected for phylogenetic analysis. The crude extracts of 39 isolates (44.83%) showed antimicrobial activity against at least one of the six tested indicator pathogens, especially ethyl acetate extracts of A-30 (Streptomyces parvulus), which could inhibit the growth of six microbes with MIC values reaching 7.8 µg/mL against Staphylococcus aureus and its resistant strain, compared to the clinical antibiotic ciproflfloxacin. Furthermore, 79 crude extracts (90.80%) and 48 (55.17%) of the isolates displayed anticancer and immunosuppressive activities, respectively. Besides, four rare strains exhibited potent immunosuppressive activity against the proliferation of Con A-induced T murine splenic lymphocyte in vitro with an inhibition rate over 60% at 10 µg/mL. Type I and II polyketide synthase (PKS) and non-ribosomal synthetase (NRPS) genes were detected in 49.43, 66.67, and 88.51% of the 87 Actinobacteria, respectively. Signifificantly, these strains (26 isolates, 29.89%) harbored PKS I, PKS II, and NRPS genes in their genomes. Nevertheless, their bioactivity is independent of BGCs in this study. Our findings highlighted the antimicrobial, immunosuppressive, and anticancer potential of mangrove rhizosphere Actinobacteria from Hainan Island and the biosynthetic prospects of exploiting the corresponding bioactive natural product.

Crushing analysis of hierarchical multicellular tubes with gradient character along axial and radial directions under oblique loads.

To overcome the disadvantage of high initial peak crush force (IPCF) in hierarchical and gradient structures, the hierarchical multicellular tubes (HMTs) with gradient character along axial and radial directions are proposed based on the bidirectional structural characters of bamboo stem. Crashworthiness performances of HMTs under oblique loads are systematically studied by using numerical simulation. Results show that compared with the square tube with the same mass, HMTs have higher energy absorption capability under different impact angles. The maximum increases of specific energy absorption (SEA) and crush force efficiency (CFE) reach up to 67.02% and 806%, respectively. Whereas, the maximum decrease of IPCF reaches up to 79.92%. Effects of structural parameters, including hierarchical level, wall thickness and internode space, on the crashworthiness performances of HMTs are also fully investigated.

Epigenetic Manipulation Induced Production of Immunosuppressive Chromones and Cytochalasins from the Mangrove Endophytic Fungus Phomopsis asparagi DHS-48.

A mangrove endophytic fungus Phomopsis asparagi DHS-48 was found to be particularly productive with regard to the accumulation of substantial new compounds in our previous study. In order to explore its potential to produce more unobserved secondary metabolites, epigenetic manipulation was used on this fungus to activate cryptic or silent genes by using the histone deacetylase (HDAC) inhibitor sodium butyrate and the DNA methyltransferase (DNMT) inhibitor 5-azacytidine (5-Aza). Based on colony growth, dry biomass, HPLC, and 1H NMR analyses, the fungal chemical diversity profile was significantly changed compared with the control. Two new compounds, named phaseolorin J (1) and phomoparagin D (5), along with three known chromones (2-4) and six known cytochalasins (6-11), were isolated from the culture treated with sodium butyrate. Their structures, including their absolute configurations, were elucidated using a combination of detailed HRESIMS, NMR, and ECD and 13C NMR calculations. The immunosuppressive and cytotoxic activities of all isolated compounds were evaluated. Compounds 1 and 8 moderately inhibited the proliferation of ConA (concanavalin A)-induced T and LPS (lipopolysaccharide)-induced B murine spleen lymphocytes. Compound 5 exhibited significant in vitro cytotoxicity against the tested human cancer cell lines Hela and HepG2, which was comparative to the positive control adriamycin and fluorouracil. Our finding demonstrated that epigenetic manipulation should be an efficient strategy for the induction of new metabolites from mangrove endophytic fungi.

Long non-coding RNA H19 alleviates hippocampal damage in convulsive status epilepticus rats through the nuclear factor-kappaB signaling pathway.

Previous studies have demonstrated that inflammation plays a critical role in hippocampcal damage and cognitive dysfunction induced by convulsive status epilepticus (CSE). Emerging evidence indicated that the long non-coding RNA (lncRNA) H19 acts as an important regulator of inflammation in various diseases. However, the role of H19 in CSE is still unkonwn. In the present study, pilocarpine-induced SE rat model was used to explore the role of H19 in hippocampal neuron damage in CSE. Our results indicated that the increased level of H19 is positively correlated with the expression of inflammatory cytokines (TNF-α and IL-1ß) in hippocampus of SE rats. Moreover, knockdown of H19 could inhibit the activation of microglia and suppress the expression of inflammatory cytokines via nuclear factor-kappaB (NF-κB) signaling pathway. It was further revealed that downregulation of H19 could alleviate hippocampal neuron damage induced by CSE. These findings indicated that H19 modulates inflammatory response and hippocampal damage through the NF-κB signaling pathway in the CSE rats, which provides a promising target to alleviate hippocampcal damage of CSE.

Clinical evaluation and management of a 45-year-old man with confusion, psychosis, agitation, stereotyped behavior, and impaired speech.

Our patient Mr. A is a mentally and physically disabled gentleman. He was first diagnosed with bipolar disorder as a teenager. He incurred a lumbar spinal injury due to a motor vehicle incident in his 20s which led to weakness, numbness, and frequent infection over both of his lower extremities. He also developed alcohol addiction over the course of his life. Mr. A presented to our facility with complicated neuropsychiatric symptoms. By adopting various clinical strategies, we were able to control his symptoms of agitation, self-harm, mood swings, and stereotyped behavior. However, we were not able to improve his neurocognitive functioning or speech impairment which seemed to become severe and irreversible in a period of a few months. We felt disappointed and perplexed by the mixed treatment responses. To understand Mr. A's clinical presentation, various laboratory tests and imaging studies were performed. Different psychotropic medications were used to manage his symptoms. Gradually, we felt that we were able to understand this case better clinically and etiologically. His bipolar disorder, alcohol addiction, and physical injury had likely all contributed to his neuropsychiatric symptoms, directly or indirectly. It is highly possible that an alcohol-related progressive dementia along with his chronic bipolar disorder played a key role in the progression of his brain neurodegeneration. Also, Wernicke-Korsakoff syndrome could reasonably be considered having developed during his clinical course. Moreover, the fluctuation of the patient's neuropsychiatric symptoms we observed during his hospitalization reflects the increased vulnerability of the human brain under sustained neurodegeneration.

Suctioning Flexible Ureteroscopy with Automatic Control of Renal Pelvic Pressure versus Mini PCNL for the Treatment of 2-3-cm Kidney Stones in Patients with a Solitary Kidney.

OBJECTIVE: The aim of the study was to compare the treatment outcomes between suctioning flexible ureteroscopic lithotomy (SF-URL) with automatic control of renal pelvic pressure and minimally invasive percutaneous nephrolithotomy (MPCNL) for the management of 2-3-cm renal stones in patients with a solitary kidney. MATERIALS AND METHODS: A total of 127 patients with a solitary kidney who underwent SF-URL (n = 57) or MPCNL (n = 70) for large renal stones (>2 cm) between June 2015 and October 2020 were consecutively analyzed. The stone characteristics, operative times, stone-free rate (SFR), hospital stays, and incidences of complications were compared. RESULTS: There was a significantly shorter operative time with MPCNL than with SF-URL (43.4 ± 18.9 min vs. 61.8 ± 21.1 min, p = 0.012). SFR at 30 days were 80.7% (46/57) and 90.0% (63/70) for SF-URL and MPCNL, respectively (p > 0.05). The SFR at the 3-month follow-up was comparable in both groups (91.2% vs. 95.7%, p > 0.05). The hemoglobin decline value, hospital stay, serum cystatin C, and percentage of patients requiring blood transfusions in the SF-URL group were obviously better than those in the MPCNL group: (0.8 ± 0.4) versus (3.9 ± 2.7) g/dL (p = 0.007), (3.6 ± 1.5) versus (6.9 ± 3.1) days (p = 0.013), (1.02 ± 0.48) versus (2.54 ± 0.69) mg/L (p = 0.011), and 0 (0.0%) versus 7 (10.0%) (p = 0.016), respectively. The percentages of patients with thrombosis and perirenal hematoma in the MPCNL group were higher than those in the SF-URL group, but the difference was not statistically significant (p > 0.05). CONCLUSION: For the treatment of 2-3-cm renal stones in patients with a solitary kidney, both SF-URL and MPCNL are effective. MPCNL has the advantage of a shorter operation time. However, SF-URL is characterized by less bleeding, shorter hospital stay, and less damage to kidney function.

Betulinic acid promotes the osteogenic differentiation of human periodontal ligament stem cells by upregulating EGR1.

Periodontitis is one of the most common chronic inflammations of the oral cavity, which eventually leads to tooth loss. Betulinic acid (BetA) is an organic acid that has anti-inflammatory effects and is derived from fruits and plants, but its effect on the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) is still unclear. This study aimed to explore the effect of BetA on the osteogenic differentiation of hPDLSCs and its mechanism. Our results revealed that BetA not only promoted the viability of hPDLSCs but also induced their osteogenic differentiation in a dose-dependent manner. In addition, RNA sequencing was used to screen the differentially expressed genes (DEGs) after hPDLSCs were treated with BetA, and 127 upregulated and 138 downregulated genes were identified. Gene Ontology enrichment analysis showed that DEGs were mainly involved in the response to lithium ions and the positive regulation of macrophage-derived foam cell differentiation. The Kyoto Encyclopedia of Genes and Genomes analysis results revealed that DEGs were enriched in the nuclear factor-κB and interleukin-17 signaling pathways. More importantly, we confirmed that early growth response gene 1 (EGR1), one of the three DEGs involved in bone formation, significantly promoted the expression of osteogenic markers and the mineralization of hPDLSCs. Knockdown of EGR1 obviously limited the effect of BetA on the osteogenic differentiation of hPDLSCs. In conclusion, BetA promoted the osteogenic differentiation of hPDLSCs through upregulating EGR1, and BetA might be a promising candidate in the clinical application of periodontal tissue regeneration.