DRD4 promotes chemo-resistance and cancer stem cell-like phenotypes by mediating the activation of the Akt/ß-catenin signaling axis in liver cancer.

BACKGROUND: Liver cancer stem cells (LCSCs) significantly impact chemo-resistance and recurrence in liver cancer. Dopamine receptor D4 (DRD4) is known to enhance the cancer stem cell (CSC) phenotype in glioblastoma and correlates with poor prognosis in some non-central nervous system tumors; however, its influence on LCSCs remains uncertain. METHODS: To investigate the gene and protein expression profiles of DRD4 in LCSCs and non-LCSCs, we utilized transcriptome sequencing and Western blotting analysis. Bioinformatics analysis and immunohistochemistry were employed to assess the correlation between DRD4 expression levels and the pathological characteristics of liver cancer patients. The impact of DRD4 on LCSC phenotypes and signaling pathways were explored using pharmacological or gene-editing techniques. Additionally, the effect of DRD4 on the protein expression and intracellular localization of ß-catenin were examined using Western blotting and immunofluorescence. RESULTS: DRD4 expression is significantly elevated in LCSCs and correlates with short survival in liver cancer. The expression and activity of DRD4 are positive to resistance, self renewal and tumorigenicity in HCC. Mechanistically, DRD4 stabilizes ß-catenin and promotes its entry into the nucleus via activating the PI3K/Akt/GSK-3ß pathway, thereby enhancing LCSC phenotypes. CONCLUSIONS: Inhibiting DRD4 expression and activation offers a promising targeted therapy for eradicating LCSCs and relieve chemo-resistance.

Astrocyte PERK and IRE1 Signaling Contributes to Morphine Tolerance and Hyperalgesia through Upregulation of Lipocalin-2 and NLRP3 Inflammasome in the Rodent Spinal Cord.

BACKGROUND: Endoplasmic reticulum stress plays a crucial role in the pathogenesis of neuroinflammation and chronic pain. This study hypothesized that PRKR-like endoplasmic reticulum kinase (PERK) and inositol-requiring enzyme type 1 (IRE1) regulate lipocalin-2 (LCN2) and Nod-like receptor family pyrin domain containing 3 (NLRP3) expression in astrocytes, thereby contributing to morphine tolerance and hyperalgesia. METHODS: The study was performed in Sprague-Dawley rats and C57/Bl6 mice of both sexes. The expression of LCN2 and NLRP3 was assessed by Western blotting. The tail-flick, von Frey, and Hargreaves tests were used to evaluate nociceptive behaviors. Chromatin immunoprecipitation was conducted to analyze the binding of activating transcription factor 4 (ATF4) to the promoters of LCN2 and TXNIP. Whole-cell patch-clamp recordings were used to evaluate neuronal excitability. RESULTS: Pharmacologic inhibition of PERK and IRE1 attenuated the development of morphine tolerance and hyperalgesia in male (tail latency on day 7, 8.0 ± 1.13 s in the morphine + GSK2656157 [10 µg] group vs. 5.8 ± 0.65 s in the morphine group; P = 0.04; n = 6 rats/group) and female (tail latency on day 7, 6.0 ± 0.84 s in the morphine + GSK2656157 [10 µg] group vs. 3.1 ± 1.09 s in the morphine group; P = 0.0005; n = 6 rats/group) rats. Activation of PERK and IRE1 upregulated expression of LCN2 and NLRP3 in vivo and in vitro. Chromatin immunoprecipitation analysis showed that ATF4 directly bound to the promoters of the LCN2 and TXNIP. Lipocalin-2 induced neuronal hyperexcitability in the spinal cord and dorsal root ganglia via melanocortin-4 receptor. CONCLUSIONS: Astrocyte endoplasmic reticulum stress sensors PERK and IRE1 facilitated morphine tolerance and hyperalgesia through upregulation of LCN2 and NLRP3 in the spinal cord.

Towards quantification of doping in gallium arsenide nanostructures by low-energy scanning electron microscopy and conductive atomic force microscopy.

We calculate a universal shift in work function of 59.4 meV per decade of dopant concentration change that applies to all doped semiconductors and from this use Monte Carlo simulations to simulate the resulting change in secondary electron yield for doped GaAs. We then compare experimental images of doped GaAs layers from scanning electron microscopy and conductive atomic force microscopy. Kelvin probe force microscopy allows to directly measure and map local work function changes, but values measured are often smaller, typically only around half, of what theory predicts for perfectly clean surfaces.

Effect of Neutrophil-to-Lymphocyte Ratio on Post-TAVR Mortality and Periprocedural Pulmonary Hypertension.

Aims: To evaluate the impact of neutrophil-to-lymphocyte ratio (NLR) on periprocedural pulmonary hypertension (PH) and 3-month all-cause mortality in patients with aortic stenosis (AS) who underwent transcatheter aortic valve replacement (TAVR) and to develop a nomogram for predicting the mortality for these patients. Methods and Results: 124 patients undergoing TAVR were categorized into three groups according to systolic pulmonary artery pressure (sPAP): Group I (no PH, n = 61) consisted of patients with no pre- and post-TAVR PH; Group II (improved PH, n = 35) consisted of patients with post-TAVR systolic pulmonary artery pressure (sPAP) decreased by more than 10 mmHg compared to pre-TAVR levels; and Group III (persistent PH, n = 28) consisted of patients with post-TAVR sPAP no decrease or less than 10 mmHg, or new-onset PH after the TAVR procedure. The risk of all-cause mortality within 3 months tended to be higher in Group II (11.4%) and Group III (14.3%) compared to Group I (3.3%) (P=0.057). The multinomial logistic regression analysis demonstrated a positive correlation between NLR and both improved PH (OR: 1.182, 95% CI: 1.036-1.350, P=0.013) and persistent PH (OR: 1.181, 95% CI: 1.032-1.352, P=0.016). Kaplan-Meier analysis revealed a significant association between higher NLR and increased 3-month all-cause mortality (16.1% vs. 3.1% in lower NLR group, P=0.021). The multivariable Cox regression analysis confirmed that NLR was an independent predictor for all-cause mortality within 3 months, even after adjusting for clinical confounders. A nomogram incorporating five factors (BNP, heart rate, serum total bilirubin, NLR, and comorbidity with coronary heart disease) was developed. ROC analysis was performed to discriminate the ability of the nomogram, and the AUC was 0.926 (95% CI: 0.850-1.000, P < 0.001). Conclusions: Patients with higher baseline NLR were found to be at an increased risk of periprocedural PH and all-cause mortality within 3 months after TAVR.

K2CO3-Catalyzed (3 + 2) Cycloaddition Reaction of N-2,2,2-Trifluoroethylisatin Ketimines with Azodicarboxylates: Access to Spirooxindoles Containing Trifluoromethyl-1,2,4-triazolines.

Potassium carbonate-catalyzed (3 + 2) cycloaddition reaction between N-2,2,2-trifluoroethylisatin ketimines and azodicarboxylates has been developed, constructing a series of novel N-heterocycle infused spirooxindoles in good to excellent yields (up to 98%) under milder conditions. The presence of both biologically active oxindole and trifluoromethyl-1,2,4-triazoline moieties in these novel spirocyclic compounds would provide new lead structures in the discovery of heterocyclic compounds with potential pharmaceutical activities.

Fabrication of SU-8 polymer micro/nanoscale nozzle by hot embossing method.

Electrohydrodynamic-jet printing (E-jet printing) is a direct-writing technology for manufacturing micro-nano devices. To further reduce the inner diameter of the nozzle to improve the printing resolution, a large-scale manufacturing method of SU-8 polymer micro/nanoscale nozzle by means of a process combining UV exposure and hot embossing was proposed. To improve the adhesive strength between the UV mask and SU-8, the influence of the oxygen plasma treatment parameters on the water contact angles of the UV mask was analyzed. The effect of hot embossing time and temperature on the replication precision was studied. The influence of UV exposure parameters and thermal bonding parameters on the micro and nanochannel pattern was investigated. The SU-8 polymer nozzles with 188 ± 3 nm wide and 104 ± 2 nm deep nanochannels were successfully fabricated, and the replication precision can reach to 98.5%. The proposed manufacturing method of SU-8 polymer nozzles in this study will significantly advance the research on the transport properties of nanoscale channels in E-jet nozzles and facilitate further advancements in E-jet based applications.

Risk of ICU Admission and Related Mortality in Patients With Sodium-Glucose Cotransporter 2 Inhibitors and Dipeptidyl Peptidase-4 Inhibitors: A Territory-Wide Retrospective Cohort Study.

OBJECTIVES: The benefit of sodium-glucose cotransporter 2 (SGLT2) inhibitors in reducing the occurrence rate of adverse cardiac and renal outcomes in patients with type 2 diabetes has been well described in randomized trials. Whether this benefit extends to patients at the most severe end of the disease spectrum requiring admission to the ICU remains to be examined. DESIGN: Retrospective observational study. SETTING: Data were obtained from a territory-wide clinical registry in Hong Kong (Clinical Data Analysis and Reporting System). PATIENTS: All adult patients (age ≥ 18 yr) with type 2 diabetes and newly prescribed SGLT2 inhibitors or dipeptidyl peptidase-4 (DPP-4) inhibitors between January 1, 2015, and December 31, 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: After 1:2 propensity score matching, a total of 27,972 patients (10,308 SGLT2 inhibitors vs 17,664 DPP-4 inhibitors) were included in the final analysis. The mean age was 59 ± 11 years, and 17,416 (62.3%) were male. The median follow-up period was 2.9 years. The use of SGLT2 inhibitors was associated with decreased ICU admission (286 [2.8%] vs 645 [3.7%]; hazard ratio [HR], 0.79; 95% CI, 0.69-0.91; p = 0.001) and lower risks of all-cause mortality (315 [3.1%] vs 1,327 [7.5%]; HR, 0.44; 95% CI, 0.38-0.49; p < 0.001), compared with DPP-4 inhibitors. The severity of illness upon ICU admission by Acute Physiology and Chronic Health Evaluation IV-predicted risk of death was also lower in SGLT2 inhibitors users. Admissions and mortality due to sepsis were lower in SGLT2 inhibitor users compared with DPP-4 inhibitor users (admissions for sepsis: 45 [0.4%] vs 134 [0.8%]; p = 0.001 and mortality: 59 [0.6%] vs 414 [2.3%]; p < 0.001, respectively). CONCLUSIONS: In patients with type 2 diabetes, SGLT2 inhibitors were independently associated with lower rates of ICU admission and all-cause mortality across various disease categories.

RF-induced heating for active implantable medical devices in dual parallel leads configurations at 1.5 T MRI.

PURPOSE: The Radiofrequency (RF)-induced heating for an active implantable medical device (AIMD) with dual parallel leads is evaluated in this paper. The coupling effects between dual parallel leads are studied via simulations and experiments methods. The global transfer function technique is used to assess the RF-induced heating for dual-lead AIMDs inside four human body models. METHODS: RF-induced heating for spinal cord stimulator systems with 60 and 90 cm length leads are studied at three parallel dual-lead configurations (closely spaced, 8 mm spaced, and 40 mm spaced) and a single-lead configuration. The global transfer function method is used to develop the AIMD models of different configurations and is used for lead-tip heating assessments inside human body models. RESULTS: In simulation studies, the peak 1g specific absorption rate/temperatrue rises of dual parallel leads systems is lower than those from the single-lead system. In experimental American Society for Testing and Materials phantom studies, the temperature rises for the single-lead AIMD system can be 2.4 times higher than that from dual-lead AIMD systems. For the spinal cord stimulator systems used in the study, the statistical analysis shows the RF-induced heating of dual-lead configurations are also lower than those from the single-lead configuration inside all four human body models. CONCLUSION: For the AIMD system in this study, it shows that the coupling effects between the dual parallel leads of AIMD systems can reduce RF-induced heating. The global transfer function for different spatial distance dual-lead configurations can potentially provide a method for the RF-induced heating evaluation for dual-lead AIMD systems.

Intrathecal administration of conditioned serum from different species resolves Chemotherapy-Induced neuropathic pain in mice via secretory exosomes.

Chemotherapy-induced peripheral neuropathy (CIPN) is the most prevalent neurological complication of chemotherapy for cancer, and has limited effective treatment options. Autologous conditioned serum (ACS) is an effective biologic therapy used by intra-articular injection for patients with osteoarthritis. However, ACS has not been systematically tested in the treatment of peripheral neuropathies such as CIPN. It has been generally assumed that the analgesic effect of this biologic therapy results from augmented concentrations of anti-inflammatory cytokines and growth factors. Here we report that a single intrathecal injection of human conditioned serum (hCS) produced long-lasting inhibition of paclitaxel chemotherapy-induced neuropathic pain (mechanical allodynia) in mice, without causing motor impairment. Strikingly, the analgesic effect of hCS in our experiments was maintained even 8 weeks after the treatment, compared with non-conditioned human serum (hNCS). Furthermore, the hCS transfer-induced pain relief in mice was fully recapitulated by rat or mouse CS transfer to mice of both sexes, indicating cross-species and cross-sex effectiveness. Mechanistically, CS treatment blocked the chemotherapy-induced glial reaction in the spinal cord and improved nerve conduction. Compared to NCS, CS contained significantly higher concentrations of anti-inflammatory and pro-resolving mediators, including IL-1Ra, TIMP-1, TGF-ß1, and resolvins D1/D2. Intrathecal injection of anti-TGF-ß1 and anti-Il-1Ra antibody transiently reversed the analgesic action of CS. Nanoparticle tracking analysis revealed that rat conditioned serum contained a significantly greater number of exosomes than NCS. Importantly, the removal of exosomes by high-speed centrifugation largely diminished the CS-produced pain relief, suggesting a critical involvement of small vesicles (exosomes) in the beneficial effects of CS. Together, our findings demonstrate that intrathecal CS produces a remarkable resolution of neuropathic pain mediated through a combination of small vesicles/exosomes and neuroimmune/neuroglial modulation.

Suppressing the Surface Amorphization of Ba0.5Sr0.5Co0.8Fe0.2O3-δ Perovskite toward Oxygen Catalytic Reactions by Introducing the Compressive Stress.

Ba0.5Sr0.5Co0.8Fe0.2O3-δ (BSCF) perovskite has been recognized as a promising oxygen evolution reaction (OER) catalyst due to its superior intrinsic catalytic activity. However, BSCF suffers from serious degradation during the OER process due to its surface amorphization caused by the segregation of A-site ions (Ba2+ and Sr2+). Herein, we construct a novel BSCF composite catalyst (BSCF-GDC-NR) by anchoring the gadolinium-doped ceria oxide (GDC) nanoparticles on the surface of a BSCF nanorod by a concentration-difference electrospinning method. Our BSCF-GDC-NR has greatly improved bifunctional oxygen catalytic activity and stability toward both oxygen reduction reaction (ORR) and OER compared with the pristine BSCF. The improvement of the stability can be related to that anchoring GDC on BSCF effectively suppresses the segregation and dissolution of A-site elements in BSCF during the preparation and catalytic processes. The suppression effects are ascribed to the introduction of compressive stress between BSCF and GDC, which greatly inhibits the diffusions of Ba and Sr ions. This work can give a guidance for developing the perovskite oxygen catalysts with high activity and stability.

A new approach to recognizing the correct pattern of cross-peaks from a noisy 2D asynchronous spectrum by detecting intrinsic symmetry via the Kolmogorov-Smirnov test.

The characteristic cluster pattern of cross-peaks in a 2D asynchronous spectrum provides an effective way to reveal the specific physicochemical nature of subtle spectral changes caused by intermolecular interactions. However, the inevitable presence of noise in the 1D spectra used to construct a 2D asynchronous spectrum is significantly amplified, which poses a serious challenge in identifying the correct cluster pattern of the cross-peaks. While mirror symmetry occurs in some types of cross-peaks, it does not occur in other types. The Kolmogorov-Smirnov test provides a statistical means to check whether the mirror symmetry exists or not between a pair of cross-peaks covered by heavy noise. Thus, different types of cross-peak clusters can be distinguished by excavating intrinsic spectral features from the noisy 2D asynchronous spectrum. The effectiveness of this approach in investigating the nature of intermolecular interactions was showcased in both a simulated model system and a real artemisinin/N-methyl pyrrolidone system.

Recent advances of CREKA peptide-based nanoplatforms in biomedical applications.

Nanomedicine technology is a rapidly developing field of research and application that uses nanoparticles as a platform to facilitate the diagnosis and treatment of diseases. Nanoparticles loaded with drugs and imaging contrast agents have already been used in clinically, but they are essentially passive delivery carriers. To make nanoparticles smarter, an important function is the ability to actively locate target tissues. It enables nanoparticles to accumulate in target tissues at higher concentrations, thereby improving therapeutic efficacy and reducing side effects. Among the different ligands, the CREKA peptide (Cys-Arg-Glu-Lys-Ala) is a desirable targeting ligand and has a good targeting ability for overexpressed fibrin in different models, such as cancers, myocardial ischemia-reperfusion, and atherosclerosis. In this review, the characteristic of the CREKA peptide and the latest reports regarding the application of CREKA-based nanoplatforms in different biological tissues are described. In addition, the existing problems and future application perspectives of CREKA-based nanoplatforms are also addressed.

mTOR deletion ameliorates CD4 + T cell apoptosis during sepsis by improving autophagosome-lysosome fusion.

Autophagy dysfunction contributes to CD4 + T cell apoptosis during sepsis leading to impairment of adaptive immunity. However, the underlying mechanism is unclear. The mammalian target of rapamycin (mTOR) pathway modulates CD4 + T cell survival during sepsis through mechanisms that are not fully understood. We developed a mouse model of sepsis through cecal ligation and puncture (CLP) to investigate dynamic changes in autophagy in CD4 + T cells. We used T cell specific-mTOR/tuberous sclerosis complex 1 (TSC1)-knockout mice to explore the roles of the mTOR pathway in modulating autophagy during sepsis. We observed reduced fusion of autophagosomes with lysosomes in the CD4 + T cells of CLP mice, which may represent a characteristic feature of autophagy dysfunction. Deletion of mTOR relieved autophagosome-lysosome fusion dysfunction and ameliorated apoptosis of CD4 + T cells in CLP mice, but this rescued phenotype was abolished by treatment with bafilomycin A1, a specific A-L fusion inhibitor. We further explored the underlying molecular mechanism and found that phosphorylation levels of transcription factor EB were significant higher in CLP mice and that expression of A-L fusion protein SNAREs were restricted, both of which were ameliorated by mTOR deletion. Taken together, these results suggest that the mTOR pathway plays a critical role in regulation of CD4 + T-cell apoptosis during sepsis, partly through regulation of A-L fusion-related protein transcription.

A technique for the reduction of RF-induced heating of active implantable medical devices during MRI.

PURPOSE: The paper presents a novel method to reduce the RF-induced heating of active implantable medical devices during MRI. METHODS: With the addition of an energy decoying and dissipating structure, RF energy can be redirected toward the dissipating rings through the decoying conductor. Three lead groups (45 cm-50 cm) and 4 (50 cm-100 cm) were studied in 1.5 Tesla MR systems by simulation and measurement, respectively. In vivo modeling was performed using human models to estimate the RF-induced heating of an active implantable medical device for spinal cord treatment. RESULT: In the simulation study, it was shown that the peak 1g-averaged specific absorption rate near the lead-tips can be reduced by 70% to 80% compared to those from the control leads. In the experimental measurements during a 2-min exposure test in a 1.5 Telsa MR system, the temperature rises dropped from the original 18.3℃, 25.8℃, 8.1℃, and 16.1℃ (control leads 1-4) to 5.4℃, 6.9℃, 1.6℃, and 3.3℃ (leads 1-4 with the energy decoying and dissipation structure). The in vivo calculation results show that the maximum induced temperature rise among all cases can be substantially reduced (up to 80%) when the energy decoying and dissipating structures were used. CONCLUSION: Our studies confirm the effectiveness of the novel technique for a variety of scanning scenarios. The results also indicate that the decoying conductor length, number of rings, and ring area must be carefully chosen and validated.

Magnetic resonance conditionality of abandoned leads from active implantable medical devices at 1.5 T.

PURPOSE: During MR scans, abandoned leads from active implantable medical devices (AIMDs) can experience excessive heating at the lead tip, depending on the type of termination applied to the proximal contacts (proximal end treatment). The influence of different proximal end treatments (ie, [1] freely exposed in the tissue, [2] terminated with metal in contact with the tissue, or [3] capped with plastic, and thereby fully insulated, on the RF-induced lead-tip heating) are studied. A technique to ensure that MR Conditional AIMD leads remain MR Conditional even when abandoned is recommended. METHODS: Abandoned leads from three MR Conditional AIMDs ([1] a sacral neuromodulation system, [2] a cardiac rhythm management pacemaker system, and [3] a deep brain stimulator system) were investigated in this study. The computational lead models (ie, the transfer functions) for different proximal end treatments were measured and used to assess the in vivo lead-tip heating for four virtual human models (FATS, Duke, Ella, and Billie) and compared with the lead-tip heating of the complete MR Conditional AIMD system. RESULT: The average and maximum lead-tip heating for abandoned leads proximally capped with metal is always lower than that from the complete AIMD system. Abandoned leads proximally insulated could lead to an average in vivo temperature rise up to 3.5 times higher than that from the complete AIMD system. CONCLUSION: For the three investigated AIMDs under 1.5T MR scanning, our results indicate that RF-induced lead-tip heating of abandoned leads strongly depends on the proximal lead termination. A metallic cap applied to the proximal termination of the tested leads could significantly reduce the RF-induced lead-tip heating.

Computed tomography-guided radiofrequency ablation of cervical intervertebral discs for the treatment of refractory cervicogenic headache: A retrospective chart review.

OBJECTIVE: To evaluate the feasibility and efficacy of computed tomography (CT)-guided radiofrequency ablation (RFA) of cervical intervertebral discs for the treatment of discogenic cervicogenic headache (CEH). BACKGROUND: Some patients with CEH experience no obvious therapeutic effect after conventional therapy, particularly patients with refractory CEH originating from abnormal cervical intervertebral discs. Treatment for this type of CEH remains poorly characterized. METHODS: Using a single intervention arm, pretest/posttest design, we retrospectively analyzed the data of patients who underwent CT-guided RFA of cervical intervertebral discs for CEH at the Pain Medicine Center of Zhejiang Provincial People's Hospital from January 2017 to April 2021. If conservative treatment failed in patients with discogenic CEH, we classified the patients as having refractory CEH and performed RFA of cervical intervertebral discs. We used a numeric rating scale (NRS) to assess pain intensity for 6 months. We also compared therapeutic outcome of patients with different characteristics. RESULTS: A total of 44 patients who underwent CT-guided RFA of cervical intervertebral discs were enrolled and 41 of them were analyzed in the present study. The preoperative median (25th, 75th) NRS score was 4 (4, 5), and it was significantly reduced to 1 (0, 4) 6 months after RFA (p < 0.001). The number of patients with ≥50% of their pain relieved after 6 months was 28 of 41 (68%). No serious treatment-related complications occurred in this study. Compared with single-level RFA, multi-level RFA shows greater effects on pain intensity reduction (p = 0.032) and pain relief rate (p = 0.047) of patients. CONCLUSION: In patients who have discogenic CEH, CT-guided RFA of the cervical intervertebral discs appears to be a promising treatment with no serious complications.

Erratum: CD8+ T cell survival in lethal fungal sepsis was ameliorated by T-cell-specific mTOR deletion: Erratum.

[This corrects the article DOI: 10.7150/ijms.55592.].

Arginine replacement of histidine on temporin-GHa enhances the antimicrobial and antibiofilm efficacy against Staphylococcus aureus.

Antimicrobial peptides (AMPs) show broad-spectrum microbicidal activity against bacteria, fungi, and viruses, and have been considered as one of the most promising candidates to overcome bacterial antimicrobial resistance. Structural modification of AMPs is an effective strategy to develop high-efficiency and low-toxicity antibacterial agents. A series of peptides GHaR6R, GHaR7R, GHaR8R, and GHaR9W with arginine replacement of histidine (His) derived from temporin-GHa of Hylarana guentheri were designed and synthesized. These derived peptides exhibit antibacterial activity against Staphylococcus aureus, and GHaR8R exerts bactericidal effect within 15 min at 4 × MIC (25 µm). The derived peptides caused rapid depolarization of bacteria, and the cell membrane damage was monitored using quartz crystal microbalance with dissipation assay, which suggests that they target cell membranes to exert antibacterial effects. The derived peptides can effectively eradicate mature biofilms of S. aureus. Taken together, the derived peptides are promising antibacterial agent candidates against S. aureus.

mTOR Modulates the Endoplasmic Reticulum Stress-Induced CD4+ T Cell Apoptosis Mediated by ROS in Septic Immunosuppression.

Introduction: When sepsis attacks the body, the excessive reactive oxygen species (ROS) production can result to endoplasmic reticulum stress (ERS) and eventually cause lymphocyte apoptosis. The mammalian target of rapamycin (mTOR) is essential for regulating lymphocyte apoptosis; we hypothesized that it mediates CD4+ T cell apoptosis during ROS-related ERS. Method: We, respectively, used ROS and ERS blockers to intervene septic mice and then detected ERS protein expression levels to verify the relationship between them. Additionally, we constructed T cell-specific mTOR and TSC1 gene knockout mice to determine the role of mTOR in ROS-mediated, ERS-induced CD4+ T cell apoptosis. Results: Blocking ROS significantly suppressed the CD4+ T cell apoptosis associated with the reduction in ERS, as revealed by lower levels of GRP78 and CHOP. ERS rapidly induced mTOR activation, leading to the induction of CD4+ T cell apoptosis. However, mTOR knockout mice displayed reduced expression of apoptotic proteins and less ER vesiculation and expansion than what was observed in the wild-type sepsis controls. Conclusion: By working to alleviate ROS-mediated, ERS-induced CD4+ T cell apoptosis, the mTOR pathway is vital for CD4+ T cell survival in sepsis mouse model.

Patient satisfaction with non-clinical nursing care provided by the nursing assistant under different management models in Chinese public tertiary hospital.

BACKGROUND: There are disparities of in-hospital non-clinical nursing care delivered by the nursing assistant under different management models in China. This study aimed to identify the best management model of the nursing assistant from the patient perspective. METHODS: This is a cross-sectional study. The inpatient satisfaction with in-hospital non-clinical nursing care delivered by the nursing assistant under different management models was measured and analyzed based on a national inpatient survey Likert the 5-point scale questionnaire conducted in 144 public tertiary hospitals across 31 provinces of China. The study conducted univariate analysis and binary Logistic regression analysis to examine which management model of the nursing assistant and any other key determinants would lead to a positive satisfaction rating by the inpatient who experienced non-clinical nursing care. FINDINGS: The overall satisfaction rating of 6211 inpatients received non-clinical nursing care was 4.73 out of 5, among which 96.09% of the responded inpatients had a positive satisfaction rating. By controlling of the other variables, the likelihood of having a positive inpatient satisfaction rating of non-clinical nursing care delivered by the nursing assistant under the direct commercial company management model, the self-employed model, the commercial company and hospital joint management model accounted for only 14.8%, 20.3% and 35.7% of the nursing assistant under the direct hospital management model. CONCLUSIONS: The direct hospital management model of the nursing assistant might be the best one to deliver the non-clinical nursing care that mostly satisfied the inpatient of Chinese public hospitals.