Evaluation of the FPMC respiratory panel for detection of respiratory tract pathogens in nasopharyngeal swab and sputum specimens.

OBJECTIVES: The performance of the new Respiratory Pathogen panel (fluorescent probe melting curve, FPMC) for the qualitative detection of 12 organisms (chlamydia pneumoniae, mycoplasma pneumoniae, adenovirus, influenza A virus, influenza B virus, parainfluenza virus, rhinovirus, etc.) was assessed. METHODS: Prospectively collected nasopharyngeal swab (NPS) and sputum specimens (n = 635) were detected by using the FPMC panel, with the Sanger sequencing method as the comparative method. RESULTS: The overall percent concordance between the FPMC analysis method and the Sanger sequencing method was 100% and 99.66% for NPS and sputum specimens, respectively. The FPMC testified an overall positive percent concordance of 100% for both NPS and sputum specimens. The FPMC analysis method also testified an overall negative percent concordance of 100% and 99.38% for NPS and sputum specimens, respectively. CONCLUSIONS: The FPMC analysis method is a stable and accurate assay for rapid, comprehensive detecting for respiratory pathogens.

Internally Formed Preferences for Options only Influence Initial Decisions in Gambling Tasks, while the Gambling Outcomes do not Alter these Preferences.

All humans must engage in decision-making. Decision-making processes can be broadly classified into internally guided decision-making (IDM), which is determined by individuals' internal value criteria, such as preference, or externally guided decision-making (EDM), which is determined by environmental external value criteria, such as monetary rewards. However, real-life decisions are never made simply using one kind of decision-making, and the relationship between IDM and EDM remains unclear. This study had individuals perform gambling tasks requiring the EDM using stimuli that formed preferences through the preference judgment task as the IDM. Computational model analysis revealed that strong preferences in the IDM affected initial choice behavior in the EDM. Moreover, through the analysis of the subjective preference evaluation after the gambling tasks, we found that even when stimuli that were preferred in the IDM were perceived as less valuable in the EDM, the preference for IDM was maintained after EDM. These results indicate that although internal criteria, such as preferences, influence EDM, the results show that internal and external criteria differ.

Association analyses of apolipoprotein E genotypes and cognitive performance in patients with Parkinson's disease.

BACKGROUND: Cognitive impairment is a common non-motor symptom of Parkinson's disease (PD). The apolipoprotein E (APOE) ε4 genotype increases the risk of Alzheimer's disease (AD). However, the effect of APOEε4 on cognitive function of PD patients remains unclear. In this study, we aimed to understand whether and how carrying APOEε4 affects cognitive performance in patients with early-stage and advanced PD. METHODS: A total of 119 Chinese early-stage PD patients were recruited. Movement Disorder Society Unified Parkinson's Disease Rating Scale, Hamilton anxiety scale, Hamilton depression scale, non-motor symptoms scale, Mini-mental State Examination, Montreal Cognitive Assessment, and Fazekas scale were evaluated. APOE genotypes were determined by polymerase chain reactions and direct sequencing. Demographic and clinical information of 521 early-stage and 262 advanced PD patients were obtained from Parkinson's Progression Marker Initiative (PPMI). RESULTS: No significant difference in cognitive performance was found between ApoEε4 carriers and non-carriers in early-stage PD patients from our cohort and PPMI. The cerebrospinal fluid (CSF) Amyloid Beta 42 (Aß42) level was significantly lower in ApoEε4 carrier than non-carriers in early-stage PD patients from PPMI. In advanced PD patients from PPMI, the BJLOT, HVLT retention and SDMT scores seem to be lower in ApoEε4 carriers without reach the statistical significance. CONCLUSIONS: APOEε4 carriage does not affect the cognitive performance of early-stage PD patients. However, it may promote the decline of CSF Aß42 level and the associated amyloidopathy, which is likely to further contribute to the cognitive dysfunction of PD patients in the advanced stage.

The UF-5000 Atyp.C parameter is an independent risk factor for bladder cancer.

Bladder carcinoma (BC) accounts for > 90% of all urothelial cancers. Pathological diagnosis through cytoscopic biopsy is the gold standard, whereas non-invasive diagnostic tools remain lacking. The "Atyp.C" parameter of the Sysmex UF-5000 urine particle analyzer represents the ratio of nucleus to cytoplasm and can be employed to detect urinary atypical cells. The present study examined the association between urinary Atyp.C values and BC risk. This two-center, retrospective case-control study identified clinical primary or newly recurrent BC (study period, 2022-2023; n = 473) cases together with controls with urinary tract infection randomly matched by age and sex (1:1). Urinary sediment differences were compared using non-parametric tests. The correlations between urinary Atyp.C levels and BC grade or infiltration were analyzed using Spearman's rank correlation. The BC risk factor odds ratio of Atyp.C was calculated using conditional logistic regression, and potential confounder effects were adjusted using stepwise logistic regression (LR). Primary risk factors were identified by stratified analysis according to pathological histological diagnosis. The mean value of urinary Atyp.C in BC cases (1.30 ± 3.12) was 8.7 times higher than that in the controls (0.15 ± 0.68; P < 0.001). Urinary Atyp.C values were positively correlated with BC pathological grade and invasion (r = 0.360, P < 0.001; r = 0.367, P < 0.001). Urinary Atyp.C was an independent risk factor for BC and closely related with BC pathological grade and invasion. Elevated urinary Atyp.C values was an independent risk factor for BC. Our findings support the use of Atyp.C as a marker that will potentially aid in the early diagnosis and long-term surveillance of new and recurrent BC cases.

Comparison of endoscopic resection therapies for rectal neuroendocrine tumors.

AIMS: This study was to evaluate and compare the efficacy and safety of endoscopic mucosal resection (EMR), clip-and-snare assisted endoscopic mucosal resection (CS-EMR), and endoscopic submucosal dissection (ESD) for the endoscopic resection of rectal NETs. MATERIAL AND METHODS: A retrospective analysis was performed on 47 patients with rectal NETs who underwent endoscopic treatment in The Second Affiliated Hospital of Soochow University. Manifestations of clinic pathological characteristics, complications, procedure time and hospitalization costs were studied. RESULTS: The complete resection rates with CS-EMR and ESD were significantly higher than those with EMR (CS-EMR vs. EMR, p = 0.038; ESD vs. EMR, p = 0.04), but no significant difference was found between the CS-EMR and ESD groups (p = 0.383). The lateral margin was less distant in the CS-EMR group than in the ESD group and there was no difference with regard to vertical margin (lateral margin distance, 1500 ± 3125 vs.3000 ± 3000 µm; vertical margin distance, 400 ± 275 vs.500 ± 500 µm). Compared to ESD, CS-EMR required less operation time (p < 0.01) and money (p < 0.01) and reduced the length of hospital stays (p < 0.01). CONCLUSIONS: The CS-EMR technique is more effective and efficient than EMR for small rectal NETs. In addition, CS-EMR reduces procedure time, duration of post-procedure hospitalization and decreases patients' cost compared to ESD while ensuring sufficient vertical margin distances.

Homochiral light-sensitive metal-organic framework photoelectrochemical gated transistor for enantioselective discrimination of monosaccharides.

As pure antipodes may differ in biological interactions, pharmacology, and toxicity, discrimination of enantiomers is important in the pharmaceutical and agrochemical industries. Two major challenges in enantiomer determination are transducing and amplifying the distinct chiral-recognition signals. In this study, a light-sensitive organic photoelectrochemical transistor (OPECT) with homochiral character is developed for enantiomer discrimination. Demonstrated with the discrimination of glucose enantiomers, the photoelectrochemically active gate electrode is prepared by integrating Au nanoparticles (AuNPs) and a chiral Cu(II)-metal-organic framework (c-CuMOF) onto TiO2 nanotube arrays (TNT). The captured glucose enantiomers are oxidized to hydrogen peroxide (H2O2) by the oxidase-mimicking AuNPs-loaded c-CuMOF. Based on the confinement effect of the mesopocket structure of the c-CuMOF and the remarkable charge transfer ability of the 1D nanotubular architecture, variations in H2O2 yield are translated into significant changes in OPECT drain currents (ID) by inducing a catalytic precipitation reaction. Variations in ID confer a sensitive discrimination of glucose enantiomers with a limit of detection (LOD) of 0.07 µM for L-Glu and 0.05 µM for D-Glu. This enantiomer-driven gate electrode response strategy not only provides a new route for enantiomer identification, but also helps to understand the origin of the high stereoselectivity in living systems.

A modified dual-knife fistulotomy for achieving challenging biliary cannulation in type 3 papilla.

Video 1A modified dual-knife fistulotomy for achieving challenging biliary cannulation in type 3 papilla.

Mas receptor activation facilitates innate hematoma resolution and neurological recovery after hemorrhagic stroke in mice.

BACKGROUND: Intracerebral hemorrhage (ICH) is a devastating neurological disease causing severe sensorimotor dysfunction and cognitive decline, yet there is no effective treatment strategy to alleviate outcomes of these patients. The Mas axis-mediated neuroprotection is involved in the pathology of various neurological diseases, however, the role of the Mas receptor in the setting of ICH remains to be elucidated. METHODS: C57BL/6 mice were used to establish the ICH model by injection of collagenase into mice striatum. The Mas receptor agonist AVE0991 was administered intranasally (0.9 mg/kg) after ICH. Using a combination of behavioral tests, Western blots, immunofluorescence staining, hematoma volume, brain edema, quantitative-PCR, TUNEL staining, Fluoro-Jade C staining, Nissl staining, and pharmacological methods, we examined the impact of intranasal application of AVE0991 on hematoma absorption and neurological outcomes following ICH and investigated the underlying mechanism. RESULTS: Mas receptor was found to be significantly expressed in activated microglia/macrophages, and the peak expression of Mas receptor in microglia/macrophages was observed at approximately 3-5 days, followed by a subsequent decline. Activation of Mas by AVE0991 post-treatment promoted hematoma absorption, reduced brain edema, and improved both short- and long-term neurological functions in ICH mice. Moreover, AVE0991 treatment effectively attenuated neuronal apoptosis, inhibited neutrophil infiltration, and reduced the release of inflammatory cytokines in perihematomal areas after ICH. Mechanistically, AVE0991 post-treatment significantly promoted the transformation of microglia/macrophages towards an anti-inflammatory, phagocytic, and reparative phenotype, and this functional phenotypic transition of microglia/macrophages by Mas activation was abolished by both Mas inhibitor A779 and Nrf2 inhibitor ML385. Furthermore, hematoma clearance and neuroprotective effects of AVE0991 treatment were reversed after microglia depletion in ICH. CONCLUSIONS: Mas activation can promote hematoma absorption, ameliorate neurological deficits, alleviate neuron apoptosis, reduced neuroinflammation, and regulate the function and phenotype of microglia/macrophages via Akt/Nrf2 signaling pathway after ICH. Thus, intranasal application of Mas agonist ACE0991 may provide promising strategy for clinical treatment of ICH patients.

Hemorrhage profile associated with immune checkpoint inhibitors: a systematic review and a real-world study based on the FAERS database.

OBJECTIVES: To investigate the risk of hemorrhage associated with Immune Checkpoint Inhibitors (ICIs) and characterize its clinical features. METHODS: We systematically reviewed randomized clinical trials (RCTs) of hemorrhage related to ICIs and calculated odds ratios (ORs) with 95% confidence intervals (CIs). Pharmacovigilance studies were conducted by collecting ICIs-related hemorrhage cases from the FAERS database and assessing disproportionalities by reporting odds ratios (RORs) and information components (ICs). RESULTS: A total of 79 RCTs involving 45,100 patients were finally included in the systematic review, with four published RCTs (n = 1965) and 75 unpublished RCTs (n = 43135). The primary analysis showed no significant difference in ICIs compared to the control group (OR 1.18 [95% CI 1.00-1.38], p = 0.05). In subgroup analyses, anti-PD-L1 combined with anti-CTLA-4 increased the risk of hemorrhage (OR 1.95, p = 0.03), and anti-CTLA-4 increased the risk of hemorrhage in the gastrointestinal system (OR 2.23, p = 0.04). 3555 cases of hemorrhage from the FAERS database were included in the disproportionate analysis, and the result suggested that ICIs increased the risk of hemorrhage (IC025 = 0.23). CONCLUSION: Our study suggests that ICIs increase the risk of hemorrhage, and in particular, anti-CTLA-4 significantly increases the risk of hemorrhage in the gastrointestinal system.

Comparison of Dosage of Glucocorticoid in Idiopathic Membranous Nephropathy: A Systematic Review and Network Meta-Analysis.

PURPOSE: Idiopathic membranous nephropathy (IMN) with moderate risk or above was recommended to receive immunosuppressive therapy. We attempted to evaluate the optimal dose of glucocorticoid when combined with evidence-proven effective immunosuppressants by network meta-analysis. METHODS: A systematic review of the literature was conducted in PubMed, Embase, Cochrane Library, and ClinicalTrials.gov from inception until January 2022. Randomized controlled trials (RCTs) in IMN limited to supportive care, glucocorticoids, cyclophosphamide, chlorambucil, calcineurin inhibitors (CNIs), and rituximab were screened. RESULTS: Twenty-eight RCTs of 1,830 patients were included. Therapeutic regimens were divided as follows: moderate- to high-dose glucocorticoids plus CNIs (HMSCn), moderate- to high-dose glucocorticoids plus cyclophosphamide (HMSCt), moderate- to high-dose glucocorticoids plus chlorambucil (HMSCh), zero- to low-dose glucocorticoids plus CNIs (LNSCn), zero- to low-dose glucocorticoids plus cyclophosphamide (LNSCt), rituximab alone (R), glucocorticoids alone (SE), and supportive care alone (SP). Compared with SP, HMSCh (risk ratio [RR]: 1.77, 95% confidence interval [CI]: 1, 3.18), HMSCn (RR: 2.5, 95%CI: 1.25, 5.11), HMSCt (RR: 2.15, 95%CI: 1.29, 3.64), LNSCn (RR: 2.16, 95%CI: 1.25, 3.95), and R (RR: 2.07, 95%CI: 1, 4.39) had a higher probability of total remission rate, while HMSCn represented the highest probability depending on the surface under the cumulative ranking area (SUCRA) ranking values. Regarding infection, no significant difference was found between different doses of glucocorticoids plus the same immunosuppressant. HMSCn and HMSCt showed superiority in reducing 24-hour urine total protein compared with HMSCh, LNSCn, SE, and SP, while HMSCn seemed to be the most effective regimen through the ranking of SUCRA value. CONCLUSION: Moderate- to high-dose glucocorticoids showed superiority in proteinuria remission when combined with CNIs in IMN, with no increasing risk of infection.

Facial palsy induced by immune checkpoint blockade: A systematic analysis of clinical trials and a pharmacovigilance study of postmarketing data.

BACKGROUND: To estimate the risk of facial nerve palsy (FP) associated with immune checkpoint inhibitors (ICIs), and to describe its clinical features. METHODS: Data from randomized controlled trials (RCTs) and FDA Adverse Event Reporting System (FAERS) database were included. The primary outcome was the risk of FP events associated with ICIs. For data from RCTs, pooled analysis was performed by using risk ratios (RRs) with 95%CIs. In a separate retrospective pharmacovigilance study of FAERS, disproportionality was analyzed using the proportional reports reporting odds ratio (ROR) and information components (IC). RESULTS: A total of 21 RCTs (193,05 patients) were included, ICIs were associated with increased risk of FP (OR = 3.07, 95%CI:1.43-6.58). Results of subgroup analysis indicated that OR of ICI-related FP did not vary significantly by tumor type, ICIs treatment schedule, case of events, study design, median PFS and publication status. FAERS pharmacovigilance data identified 274 cases of FP related to ICIs therapy. ICIs were significantly associated with over-reporting frequencies of FP (ROR = 3.03, 95%CI:2.69-3.42; IC = 1.56, 95%CI:1.38-1.76). The median onset time of FP was 5.5 weeks, drug interruption was recorded in 78.0% of cases, with a positive dechallenge in 82.8 % of cases, and 71.7% of cases were recovered or recovering. CONCLUSIONS: These data suggest that ICIs were significantly associated with increased risk of FP in both trial settings and in clinical practice.

Comprehensive analysis of serum exosome-derived lncRNAs and mRNAs from patients with rheumatoid arthritis.

BACKGROUND: Serum exosomes play important roles in intercellular communication and are promising biomarkers of several autoimmune diseases. However, the biological functions and potential clinical importance of long non-coding RNAs (lncRNAs) and mRNAs from serum exosomes in rheumatoid arthritis (RA) have not yet been studied. METHODS: Serum exosomal lncRNAs and mRNAs were isolated from patients with RA and osteoarthritis (OA) and healthy controls. The differentially expressed lncRNAs (DE-lncRNAs) and mRNA profiles in the serum exosomes of patients with RA were analysed using high-throughput sequencing, and their functions were predicted using Gene Ontologyenrichment, Kyoto Encyclopedia of Genes and Genomes pathway, and gene set enrichment analysis. We constructed a DE-lncRNA-mRNA network and a protein-protein interaction network of differentially expressed mRNAs (DE-mRNAs) in RA using the Cytoscape software. The expression of several candidate a DE-lncRNAs and DE-mRNAs in the serum of patients with RA, patients with OA, and healthy controls was confirmed by qRT-PCR. We assessed the diagnostic ability of DE-lncRNAs and DE-mRNAs in patients with RA using receiver operating characteristic analysis. Furthermore, we analysed the characteristics of immune cell infiltration in RA by digital cytometry using the CIBERSORT algorithm and determined the correlation between immune cells and several DE-lncRNAs or DE-mRNAs in RA. RESULTS: The profiles of serum exosomal lncRNAs and mRNAs in patients with RA were different from those in healthy controls and patients with OA. The functions of both DE-lncRNAs and DE-mRNAs in RA are associated with the immune response and cellular metabolic processes. The RT-PCR results show that NONHSAT193357.1, CCL5, and MPIG6B were downregulated in patients with RA. The combination of three DE-mRNAs, CCL5, MPIG6B, and PFKP, had an area under the curve of 0.845 for differentiating RA from OA. Digital cytometry using the CIBERSORT algorithm showed that the neutrophil counts were higher in patients with RA than those in healthy controls and patients with OA. CONCLUSIONS: These findings help to elucidate the role of serum exosomal lncRNAs and mRNAs in the specific mechanisms underlying RA.

Factors associated with balance impairments in the community-dwelling elderly in urban China.

BACKGROUND: Identification of factors relevant to balance performance impairments in the elderly population was critical for developing effective interventions and preventions. However, there have been very limited data available based on large scale studies. The present study identified factors that independently contributed to performance impairments in overall balance, domains of static balance, postural stability, and dynamic balance, and individual items. METHODS: A total of 1984 community-dwelling Chinese elderly from urban areas of Shanghai were recruited. Information on demographic characteristic, exercise, and health status were collected with a face-to-face interview. Balance performances were assessed on site by trained investigators based on the X16 balance testing scale. To identify the effectors, ordinal logistic regression analysis was applied for overall balance, static balance, postural stability, and dynamic balance. Binary logistic regression analysis was used for 16 items. RESULTS: The community-dwelling elderly residents were aged from 60 to 97 years old. With increases of age, risks of impairments in overall balance increased gradually (ORs from 1.26 to 3.20, all P < 0.01). In the elderly with overweight and obesity, there was higher proportion of balance impairments compared to the elderly with normal BMI (OR = 1.26, P < 0.001). Regular exercise every week was associated with reduced risks of balance impairments (ORs from 0.63 to 0.73, all P < 0.001). Presences with vision lesion (ORs from 1.28 to 1.59, all P < 0.001), moderate hearing impairment (OR = 1.54, P < 0.001), somesthesis dysfunction (ORs from 1.59 to 13.26, all P < 0.001), and cerebrovascular disease (OR = 1.45, P = 0.001) were related to increased risks of balance impairments. Likewise, age, exercise, vision, hearing, somesthesis, and cerebrovascular disease were significantly associated with static balance, postural stability, and dynamic balance. Both overweight and obesity and underweight were associated with higher proportions of dynamic balance impairments. Regular exercise was significantly related to reduced risks of impairments in 15 out of the 16 items. CONCLUSIONS: In the elderly, age, overweight and obesity, exercise, vision, hearing, somesthesia, and cerebrovascular disease were dominant factors associated with impairments in overall balance, domains of static balance, postural stability, and dynamic balance, and most individual items. TRIAL REGISTRATION: Not applicable.

A binary composite La(OH)3@Ni(OH)2 nanomaterial on carboxyl graphene for an efficient hybrid supercapacitor electrode.

In this work, we present a binary composite of La(OH)3@Ni(OH)2 on carboxyl graphene (La@Ni/CG) as an electrode material. The layered La@Ni/CG double hydroxides (LDHs) were synthesized by a simple electrodeposition method in which La(OH)3 nanoparticles were first adsorbed onto carboxyl graphene and then coated with Ni(OH)2, with different particle shapes due to the large pH change near the cathodic region. Scanning electron microscopy (SEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), cyclic voltammetry (CV) and galvanostatic charge-discharge (GCD) were used to characterise the as-prepared La@Ni/CG composite. These results showed that the La@Ni/CG composite exhibited improved electrochemical properties, including large specific capacitance (1334.7 F g-1 at 1.4 A g-1) and capacity retention of 90.6% even after 3000 cycles, and excellent rate capability. The improved electrochemical performance of the composite can be attributed to the synergistic effect of surface adsorption and conductive pathways provided by the multiple active species (Ni, La and C) in the La@Ni/CG composite. The results presented in this work provide advances in the efficient design of nanomaterial based electrochemical energy storage devices.

Anastomotic stenosis following proximal gastrectomy with single flap valvulopasty successfully managed with endoscopic stricturotomy: a case report.

Background: Due to its nutritional advantages over total gastrectomy, proximal gastrectomy (PG) with anti-reflux techniques has gained significant attention in East Asian countries in recent years. The double flap technique (DFT) and modified side overlap and fundoplication by Yamashita (mSOFY) are two promising anti-reflux interventions following PG. However, anastomotic stenosis after DFT and gastroesophageal reflux after mSOFY have been reported in several patients. To address these concerns, a hybrid reconstruction procedure was designed, namely, right-sided overlap with single flap valvulopasty (ROSF), for proximal gastrectomy, with the aim of reducing anastomotic stricture and reflux. Among the 38 patients who underwent ROSF at our hospital, one developed Stooler grade II anastomotic stenosis. Herein, we present the successful management of this patient through endoscopic stricturotomy (ES). Case summary: A 72-year-old female complaining of "epigastric pain and discomfort for more than 1 month" was diagnosed with adenocarcinoma of the esophagogastric junction (Siewert type II). She underwent laparoscopic-assisted PG and ROSF procedures at our hospital and recovered well after surgery. However, she started experiencing progressive difficulty in eating and vomiting approximately 3 weeks after the intervention. Endoscopy revealed Stooler grade II esophagogastric anastomotic stenosis. ES with insulated tip (IT) Knife nano was eventually performed, and the patient was able to resume a normal diet without experiencing any discomfort during the 5-month follow-up period. Conclusion: Endoscopic stricturotomy using IT Knife nano successfully treated anastomotic stenosis following ROSF with no associated complications. Thus, ES to treat anastomotic stenosis after PG with valvulopasty can be considered a safe option and should be performed in centers with the required expertise.

Apelin-Overexpressing Neural Stem Cells in Conjunction with a Silk Fibroin Nanofiber Scaffold for the Treatment of Traumatic Brain Injury.

Traumatic brain injury (TBI), especially moderate or severe TBI, is one of the most devastating injuries to the nervous system, as the existing therapies for neurological defect repair have difficulty achieving satisfactory results. Neural stem cells (NSCs) therapy is a potentially effective treatment option, especially after specific genetic modifications and when used in combination with biomimetic biological scaffolds. In this study, tussah silk fibroin (TSF) scaffolds with interconnected nanofibrous structures were fabricated using a top-down method. We constructed the apelin-overexpressing NSCs that were cocultured with a TSF nanofiber scaffold (TSFNS) that simulated the extracellular matrix in vitro. To verify the therapeutic efficacy of engineered NSCs in vivo, we constructed TBI models and randomized the C57BL/6 mice into three groups: a control group, an NSC-ctrl group (transplantation of NSCs integrated on TSFNS), and an NSC-apelin group (transplantation of apelin-overexpressing NSCs integrated on TSFNS). The neurological functions of the model mice were evaluated in stages. Specimens were obtained 24 days after transplantation for immunohistochemistry, immunofluorescence, and western blot experiments, and statistical analysis was performed. The results showed that the combination of the TSFNS and apelin overexpression guided extension and elevated the proliferation and differentiation of NSCs both in vivo and in vitro. Moreover, the transplantation of TSFNS-NSCs-Apelin reduced lesion volume, enhanced angiogenesis, inhibited neuronal apoptosis, reduced blood-brain barrier damage, and mitigated neuroinflammation. In summary, TSFNS-NSC-Apelin therapy could build a microenvironment that is more conducive to neural repair to promote the recovery of injured neurological function.

Interstitial lung disease in patients treated with poly (ADP-ribose) polymerase inhibitors (PARPi): analysis of results from clinical trials and the FDA Adverse Events Reporting System database.

OBJECTIVE: To evaluate the risk of interstitial lung disease associated with poly (ADP-ribose) polymerase inhibitors (PARPi) and characterize its clinical features. METHODS: We systematically reviewed phase III randomized clinical trials of interstitial lung disease related to PARPi and calculated Peto odds ratios (ORs) with 95% confidence intervals (CIs). Pharmacovigilance studies were conducted by collecting cases of PARPi-related interstitial lung disease from the FDA Adverse Events Reporting System and assessing disproportionalities by reporting ORs and information components. RESULTS: A total of five randomized clinical trials involving 2980 patients were included. Although PARPi showed a tendency to increase the risk of interstitial lung disease compared with controls, this difference was not significant (Peto OR: 4.92; 95% CI: 0.92 to 26.35). A total of 170 cases of interstitial lung disease related to PARPi were included, with a median latency of 99 days. PARPi had a significantly increased reporting of interstitial lung disease (reporting OR: 2.86; 95% CI: 2.46 to 3.33; information component (IC): 1.49; 95% CI: 1.28 to 1.74). Our sensitivity analyses showed strong robustness of the disproportionalities between PARPi as a class, olaparib, and interstitial lung disease. Some 91.9% of patients experienced discontinuation, 51.6% achieved remission, and no deaths were reported. CONCLUSION: Our pharmacovigilance study suggested increased reporting of interstitial lung disease related to PARPi particularly olaparib.

Risk factors of immune checkpoint inhibitor-associated acute kidney injury: evidence from clinical studies and FDA pharmacovigilance database.

BACKGROUND: Several risk factors of immune checkpoint inhibitors (ICIs)-associated acute kidney injury (AKI) have been reported sporadically. To identify the risk factors of ICIs-associated AKI in a large-scale population, therefore we conducted a systematic review and a real-world retrospective study. METHODS: We search literature concerning risk factors of ICIs-associated AKI in ClinicalTrials.gov and electronic databases (PubMed, Cochrane Library, Embase) up to January 2022. Meta-analysis was performed by using odds ratios (ORs) with 95%CIs. In a separate retrospective pharmacovigilance study by extracting data from US FDA Adverse Event Reporting System (FAERS) database, disproportionality was analyzed using the reporting odds ratio (ROR). RESULTS: A total of 9 studies (5927 patients) were included in the meta-analysis. The following factors were associated with increased risk of ICIs-associated AKI, including proton pump inhibitors(PPIs) (OR = 2.07, 95%CI 1.78-2.42), angiotensin-converting enzyme inhibitors (ACEIs)/ angiotensin receptor blockers (ARBs) (OR = 1.56, 95%CI 1.24-1.95), nonsteroidal anti-inflammatory drugs (NSAIDs) (OR = 1.29, 95%CI 1.01-1.65), diuretics (OR = 2.00, 95%CI 1.38-2.89), diabetes mellitus (OR = 1.28, 95%CI 1.04-1.57), genitourinary cancer (OR = 1.46, 95%CI 1.15-1.85), combination therapy of ICIs (OR = 1.93, 95%CI 1.25-2.97) and extrarenal immune-related adverse events(irAEs) (OR = 2.51, 95%CI 1.96-3.20). Furthermore, analysis from FAERS database verified that concurrent exposures of PPIs (ROR = 2.10, 95%CI 1.91-2.31), ACEIs/ARBs (ROR = 3.25, 95%CI 2.95-3.57), NSAIDs (ROR = 3.06, 95%CI 2.81-3.32) or diuretics (ROR = 2.82, 95%CI 2.50-3.19) were observed significant signals associated with AKI in ICIs-treated patients. CONCLUSIONS: Concurrent exposures of PPIs, ACEIs/ARBs, NSAIDs or diuretics, diabetes mellitus, genitourinary cancer, combination therapy, and extrarenal irAEs seem to increase the risk of AKI in ICIs-treated patients.

Gene Therapy Strategies Targeting Aging-Related Diseases.

Rapid advancements have taken place in gene therapy technology. However, effective methods for treating aging- or age-related chronic diseases, which are often closely related to genes or even multiple genes, are still lacking. The path to developing cures is winding, while gene therapy that targets genes related to aging represents an exciting research direction with tremendous potential. Among aging-related genes, some candidates have been studied at different levels, from cell to organismal levels (e.g., mammalian models) with different methods, from overexpression to gene editing. The TERT and APOE have even entered the stage of clinical trials. Even those displaying only a preliminary association with diseases have potential applications. This article discusses the foundations and recent breakthroughs in the field of gene therapy, providing a summary of current mainstream strategies and gene therapy products with clinical and preclinical applications. Finally, we review representative target genes and their potential for treating aging or age-related diseases.

Transplantation of glutamatergic neuronal precursor cells in the paraventricular thalamus and claustrum facilitates awakening with recovery of consciousness.

BACKGROUND: Stem cells offer a promising therapeutic strategy for patients with disorders of consciousness (DOC) after severe traumatic brain injury (TBI), but the optimal transplantation sites and cells are not clear. Although the paraventricular thalamus (PVT) and claustrum (CLA) are associated with consciousness and are candidate transplantation targets, few studies have been designed to investigate this possibility. METHODS: Controlled cortical injury (CCI) was performed to establish a mouse model of DOC. CCI-DOC paradigm was established to investigate the role of excitatory neurons of PVT and CLA in disorders of consciousness. The role of excitatory neuron transplantation in promoting arousal and recovery of consciousness was determined by optogenetics, chemogenetics, electrophysiology, Western blot, RT-PCR, double immunofluorescence labeling, and neurobehavioral experiments. RESULTS: After CCI-DOC, neuronal apoptosis was found to be concentrated in the PVT and CLA. Prolonged awaking latency and cognitive decline were also seen after destruction of the PVT and CLA, suggesting that the PVT and CLA may be key nuclei in DOC. Awaking latency and cognitive performance could be altered by inhibiting or activating excitatory neurons, implying that excitatory neurons may play an important role in DOC. Furthermore, we found that the PVT and CLA function differently, with the PVT mainly involved in arousal maintenance while the CLA plays a role mainly in the generation of conscious content. Finally, we found that by transplanting excitatory neuron precursor cells in the PVT and CLA, respectively, we could facilitate awakening with recovery of consciousness, which was mainly manifested by shortened awaking latency, reduced duration of loss of consciousness (LOC), enhanced cognitive ability, enhanced memory, and improved limb sensation. CONCLUSION: In this study, we found that the deterioration in the level and content of consciousness after TBI was associated with a large reduction in glutamatergic neurons within the PVT and CLA. Transplantation of glutamatergic neuronal precursor cells could play a beneficial role in promoting arousal and recovery of consciousness. Thus, these findings have the potential to provide a favorable basis for promoting awakening and recovery in patients with DOC.