Potential low toxic alternative for Na-Cl cotransporter inhibition: A diuretic effect and mechanism study of Pyrrosia petiolosa.

BACKGROUND: Hydrochlorothiazide, a diuretic commonly used for the treatment of hypertension, is often associated with serious metabolic side effects. Pyrrosia petiolosa (Christ) Ching is a traditional Chinese medicine that possesses diuretic properties, without any obvious side effects. AIM: To evaluate the diuretic effect of P. petiolosa (Christ) Ching and to elucidate its underlying mechanism of action. METHODS: Extracts obtained from different polar components of P. petiolosa (Christ) Ching were analyzed for toxicity in a Kunming mouse model. The diuretic effects of the extracts were compared to that of hydrochlorothiazide in rats. In addition, compound isolation procedures, cell assays of Na-Cl cotransporter inhibition and rat diuretic test of monomeric compounds were conducted to identify the active ingredients in the extract. Subsequently, homology modeling and molecular docking were performed to explain the reason behind the diuretic activity observed. Finally, LC-MS analysis was used to elucidate the underlying mechanism of action of P. petiolosa (Christ) Ching. RESULTS: No toxicity was observed in mice administered P. petiolosa (Christ) Ching extracts. The ethyl acetate fraction showed the most significant diuretic effect. Similar results were obtained during the analysis for Na+ content in rat urine. Further separation of P. petiolosa (Christ) Ching components led to the isolation of methyl chlorogenate, 2',3'-dihydroxy propyl pentadecanoate, and ß-carotene. Results from cell assays showed that the Na-Cl cotransporter inhibitory activity of methyl chlorogenate was greater than that of hydrochlorothiazide. This result was again confirmed by the diuresis tests of monomeric compounds in rats. The molecular simulations explain the stronger interactions between the methyl chlorogenate and Na-Cl cotransporter. Of the compounds determined using LC-MS analysis, 185 were identified to be mostly organic acids. CONCLUSIONS: P. petiolosa possesses significant diuretic activities without any obvious toxicity, with least two possible mechanisms of action. Further study on this herb is warranted.

[Spinal endoscopic technique in the surgical treatment of thoracic ossification of the ligamentum flavum].

Thoracic ossification of the ligamentum flavum (TOLF) is a pathological heterotopic ossification disease in which the fibrous tissue of the ligamentum flavum of the thoracic spine converts into bony tissue, often leading to thoracic spinal stenosis and compression of the thoracic spinal cord nerve. When TOLF patients present with symptoms of spinal cord nerve compression, surgical treatment is usually required, and traditional open surgery is more invasive and carries a higher risk of spinal cord nerve injury. In recent years, domestic and foreign researchers have tried to apply spinal endoscopic techniques such as microendoscopy, percutaneous foraminoscopy, and unilateral biportal endoscopy for the treatment of TOLF, which can maximize the preservation of normal bone while achieving adequate decompression of the spinal cord nerve, with less damage to spinal stability, and have the advantages of less surgical trauma, less bleeding, and faster postoperative recovery. Due to the special anatomical structure of the thoracic vertebra, spinal endoscopic techniques should focus on safety and it is recommended that they are performed in experienced centers, and surgical indications should be strictly controlled.

[Feasibility and safety of remote programming in postoperative follow-up of cardiovascular implantable electronic devices].

Objective: To explore the feasibility and safety of remote programming technology based on 5G cloud technology support platform in postoperative follow-up of cardiovascular implantable electronic devices(CIED). Methods: This study was a multicenter cross-sectional study. CIED patients from 12 hospitals lacking full-time follow-up specialists in Sichuan Province were enrolled from June 2021 to October 2021. All patients' devices received remote inspecting and programming by the follow-up specialist of the remote follow-up center of the Third People's Hospital of Chengdu through 5G cloud technology support platform. The baseline data, device alarm events, device reprogramming events, adverse reactions and satisfaction questionnaire survey results were collected. Results: A total of 195 CIED implantation patients were included, with an age of (72.5±11.3) years, including 103 males (52.6%). All patients completed remote inspecting and programming successfully, with a duration of (5.8±4.0) min. Ninety-one patients' CIED were reprogrammed, with a total of 104 parameter adjustments. No abnormal communication or adverse events occurred. The satisfaction questionnaire showed that 97.9%(191/195) of the patients trusted or relatively trusted remote follow-up and 86.7%(169/195) of the patients were willing to choose remote follow-up mode for device management. Conclusion: The remote programming based on 5G cloud technology support platform may be feasible and safe for postoperative follow-up of CIED patients.

Octahedral Distortion and Displacement-Type Ferroelectricity with Switchable Photovoltaic Effect in a 3d

Because of the half-filled t_{2g}-electron configuration, the BO_{6} octahedral distortion in a 3d^{3} perovskite system is usually very limited. In this Letter, a perovskitelike oxide Hg_{0.75}Pb_{0.25}MnO_{3} (HPMO) with a 3d^{3} Mn^{4+} state was synthesized by using high pressure and high temperature methods. This compound exhibits an unusually large octahedral distortion enhanced by approximately 2 orders of magnitude compared with that observed in other 3d^{3} perovskite systems like RCr^{3+}O_{3} (R=rare earth). Essentially different from centrosymmetric HgMnO_{3} and PbMnO_{3}, the A-site doped HPMO presents a polar crystal structure with the space group Ama2 and a substantial spontaneous electric polarization (26.5 µC/cm^{2} in theory) arising from the off-center displacements of A- and B-site ions. More interestingly, a prominent net photocurrent and switchable photovoltaic effect with a sustainable photoresponse were observed in the current polycrystalline HPMO. This Letter provides an exceptional d^{3} material system which shows unusually large octahedral distortion and displacement-type ferroelectricity violating the "d^{0}-ness" rule.

[Effects of novel bioactive glasses on promoting remineralization of artificial dentin caries].

OBJECTIVE: To investigate the effects of novel bioactive glasses (BG) including PSC with high phosphorus component and FBG with fluorine-doped element on promoting remineralization of artificial dentin caries. METHODS: (1) BGs were used in this study as follows: PSC (10.8%P2O5-54.2%SiO2-35.0%CaO, mol.%) were synthesized using phytic acid as the phosphorus precursor through sol-gel method. FBG (6.1%P2O5-37.0%SiO2-53.9%CaO-3.0%CaF2, mol.%) and 45S5(6.0%P2O5-45.0%SiO2-24.5%CaO-24.5%Na2O, mol.%) were synthesized by traditional melt method. (2) The above BGs were soaked in simulated body fluid (SBF) for 24 hours. Then X-ray diffraction (XRD) was used to analyze the formation of hydroxyapatite (HA) crystals. (3) Prepared 1 mm thick dentin slices were soaked in 17% ethylene diamine tetraacetic acid (EDTA) for 1 week to demineralize the dentin. Then the dentin slices treated by BG were soaked in SBF for 1 week. Field emission scanning electron micro-scopy (FE-SEM) was used to observe the surface morphology of the dentin slices. (4) Four cavities were prepared to 1 mm depth in each 2 mm thick dentin slice, then were treated with lactic acid for 2 weeks to form the artificial dentin caries. Wax, mineral trioxide aggregate (MTA), PSC and FBG were used to fill four cavities as blank control group, MTA group, PSC group and FBG group respectively. Then the spe-cimens were soaked in SBF for 4 weeks. The changes of depth and density of demineralized dentin were analyzed using Micro-CT before filling and after 2 and 4 weeks filling. RESULTS: (1) PSC and FBG promoted mineral formation on the surfaces of the demineralized dentin. And the speed was faster and crystallinity was higher in PSC group than the FBG and 45S5 groups. (2) The increased mineral density of artificial dentin caries in PSC group were (185.98 ± 55.66) mg/cm3 and (213.64 ± 36.01) mg/cm3 2 and 4 weeks after filling respectively, which were significantly higher than the control group [(20.38 ± 7.55) mg/cm3, P=0.006; (36.46 ± 10.79) mg/cm3, P=0.001]. At meanwhile, PSC group was also higher than MTA group [(57.29 ± 10.09) mg/cm3; (111.02 ± 22.06) mg/cm3], and it had statistical difference (P=0.015; P=0.006). The depth of remineralized dentin in PSC group were (40.0 ± 16.9) µm and (54.5 ± 17.8) µm 2 and 4 weeks respectively, which were also statistically different from the control group (P =0.010;P=0.001). There were no statistical differences between the control group and MTA group. The above effects of FBG group were between PSC and MTA. CONCLUSION: PSC has advantages in the speed, quality and depth of mineral deposition in the demineralized layer of artificial dentin caries. It would be expected to be an ideal material to promote the remineralization of dentin caries.

[Applications and challenges of large language models in critical care medicine].

The rapid development of big data methods and technologies has provided more and more new ideas and methods for clinical diagnosis and treatment. The emergence of large language models (LLM) has made it possible for human-computer interactive dialogues and applications in complex medical scenarios. Critical care medicine is a process of continuous dynamic targeted treatment. The huge data generated in this process needs to be integrated and optimized through models for clinical application, interaction in teaching simulation, and assistance in scientific research. Using the LLM represented by generative pre-trained transformer ChatGPT can initially realize the application in the diagnosis of severe diseases, the prediction of death risk and the management of medical records. At the same time, the time and space limitations, illusions and ethical and moral issues of ChatGPT emerged as the times require. In the future, it is undeniable that it may play a huge role in the diagnosis and treatment of critical care medicine, but the current application should be combined with more clinical knowledge reserves of critical care medicine to carefully judge its conclusions.

[Effect of hemoperfusion on protein energy wasting and long-term prognosis in patients on maintenance hemodialysis].

Objective: To explore the effect of hemoperfusion (HP) combined with hemodialysis (HD) (HD+HP) on protein energy wasting (PEW) and long-term prognosis in patients on maintenance HD (MHD). Methods: A prospective multicenter cohort study was conducted. Adult MHD patients who completed PEW assessment and underwent regular dialysis between July 2015 and July 2021 at 23 hemodialysis centers in Guizhou Province were selected. Demographic characteristics, physical indicators, laboratory indicators, 3-day diet diary and HP treatment data of the subjects were collected. The patients were divided into different groups according to the presence or absence of HP, the frequency of HP treatment and the type of cartridge, and then relevant indicators were compared. Multivariate logistic regression model and Cox proportional regression model were used to analyze the influence of HP treatment on PEW risk in MHD patients. Meanwhile, Kaplan-Meier method was used to plot the survival curve. Results: A total of 4 623 MHD patients (2 789 males and 1 834 females) aged (53.7±15.9) years were included in the study, with a median dialysis age of 64.3 (44.3, 92.3) months. There were 3 429 (74.2%) MHD patients treated with HD+HP, and 1 194 patients (25.8%) were not treated with HP. According to the 2008 diagnostic criteria of the International Society for Renal Nutrition and Metabolism (ISRNM), the incidence of PEW was 26.0% (1 204/4 623). Multivariate logistic regression analysis showed that female (OR=2.48, 95%CI: 1.55-3.95, P<0.001), diabetes (OR=1.75, 95%CI: 1.08-2.83, P=0.024) and high-sensitivity C-reactive protein (hs-CRP) (OR=1.02, 95%CI: 1.01-1.03, P=0.003) were risk factors for PEW, while treatment with HD+HP (OR=0.51, 95%CI: 0.31-0.87, P=0.012) and elevated triglyceride levels (OR=0.62, 95%CI: 0.48-0.80, P<0.001) were protective factors. Cox hazard ratio regression showed that among different HP treatment frequencies and cartridge types, 2 times/month (HR=0.40, 95%CI: 0.17-0.95, P=0.037), 3 times/month (HR=0.44, 95%CI: 0.23-0.85, P=0.014), 4 times/month (HR=0.54, 95%CI: 0.34-0.85, P=0.008), HA130 (HR=0.57, 95%CI: 0.36-0.89, P=0.014) and HA230 (HR=0.30, 95%CI: 0.15-0.63, P=0.001) had protective effects on the occurrence of PEW in MHD patients. The all-cause mortality rate was 11.3% (521/4 623) at 33 (24, 48) months of follow-up. Kaplan-Meier analysis showed that patients undergoing 4 times/month HP treatment (χ2=36.78, P<0.001) and using HA230 (χ2=9.46, P=0.002) had the highest survival rate. Conclusion: Treatment with HD+HP is a protective factor for PEW in patients with MHD, and 4 times/month HP treatment or HA230 significantly reduces the risk of PEW and all-cause mortality in patients with MHD.

[Establishment of a digital remote platform for respiratory support and intelligent early warning in intensive care units].

During the disease progression or treatment of critically ill patients with lung injury, the changes in respiratory mechanics are continuous and dynamic. Establishing a digital platform for respiratory support in the ICU, which enables the continuous recording, dynamic analysis, and real-time alerting of numerical and waveform data from mechanical ventilation, can help intensivists improve their understanding of "dynamic respiratory mechanics", improve respiratory therapy and patient outcomes, as well as reduce workload and increase work efficiency. The construction of a dedicated database for mechanical ventilation, based on ventilator waveforms provides essential data support for projects such as respiratory mechanics data algorithm models. This will facilitate the establishment of an auxiliary decision-making system, enable the realization of intelligent mechanical ventilation, and create a new era of dynamic respiratory mechanics.

Superconductivity in a unique type of copper oxide.

The mechanism of superconductivity in cuprates remains one of the big challenges of condensed matter physics. High-T c cuprates crystallize into a layered perovskite structure featuring copper oxygen octahedral coordination. Due to the Jahn Teller effect in combination with the strong static Coulomb interaction, the octahedra in high-T c cuprates are elongated along the c axis, leading to a 3dx 2-y 2 orbital at the top of the band structure wherein the doped holes reside. This scenario gives rise to 2D characteristics in high-T c cuprates that favor d-wave pairing symmetry. Here, we report superconductivity in a cuprate Ba2CuO4-y , wherein the local octahedron is in a very exceptional compressed version. The Ba2CuO4-y compound was synthesized at high pressure at high temperatures and shows bulk superconductivity with critical temperature (T c ) above 70 K at ambient conditions. This superconducting transition temperature is more than 30 K higher than the T c for the isostructural counterparts based on classical La2CuO4 X-ray absorption measurements indicate the heavily doped nature of the Ba2CuO4-y superconductor. In compressed octahedron, the 3d3z 2-r 2 orbital will be lifted above the 3dx 2-y 2 orbital, leading to significant 3D nature in addition to the conventional 3dx 2-y 2 orbital. This work sheds important light on advancing our comprehensive understanding of the superconducting mechanism of high T c in cuprate materials.

[A case of ocular albinism with an abnormal visual evoked potential].

A 16-year-old male patient had poor binocular vision, alternating exotropia, horizontal nystagmus, and no obvious pigmentation loss in the eyes and other parts of the body. Optical coherence tomographic examination showed no normal central macular depression. The three-channel flash visual evoked potential method was used to examine each eye. The left and right channel reactions were found to be significantly asymmetric, and the clinical diagnosis was ocular albinism.

[Efficacy of fenestrated atrial septal defect occulders on pulmonary hypertension dogs].

Objective: To explore the short-term efficacy of fenestrated atrial septal defect (ASD) occulders in the treatment of pulmonary arterial hypertension (PAH). Methods: Thirty-six healthy dogs were divided into the balloon atrial septostomy (BAS)+fenestrated ASD occulders group (n=12), BAS group (n=12) and non-septostomy group (n=12). PAH was induced by intra-atrial injection of dehydrogenized monocrotaline (1.5 mg/kg) in all dogs. Animals in the BAS+fenestrated ASD occulders group underwent atrial septal puncture and fenestrated ASD occulders implantation. Animals in the BAS group underwent balloon atrial septostomy. The non-septostomy group received no surgical intervention. The hemodynamic indexes and blood N-terminal pro-B-type natriuretic peptide (NT-proBNP) of dogs were measured before modeling, 2 months after modeling, 1, 3, and 6 months after surgery, respectively. Echocardiography was performed to observe the patency of the shunt and atrial septostomy of the dogs in the BAS+fenestrated ASD occulders group and BAS group at 1, 3, and 6 months after surgery. Three dogs were sacrificed in each group at 1, 3, and 6 months after surgery, respectively. Atrial septal tissue and fenestrated ASD occulders were removed to observe the patency and endothelialization of the device. Lung tissues were obtained for hematoxylin-eosin (HE) staining to observe the inflammatory cells infiltration and the thickening and narrowing of the pulmonary arterials. Results: Among 36 dogs, 2 dogs died within 24 hours after modeling, and 34 dogs were assigned to BAS+fenestrated ASD occulders group (n=12), BAS group (n=11), and non-septostomy group (n=11). Compared with BAS group, the average right atrial pressure (mRAP) and NT-proBNP of dogs in the BAS+fenestrated ASD occulders group were significantly reduced at 3 months after surgery (P<0.05), and the cardiac output (CO) was significantly increased at 6 months after surgery, arterial oxygen saturation (SaO2) was also significantly reduced (P<0.05). Compared with non-septostomy group, dogs in the BAS+fenestrated ASD occulders group had significantly lower mRAP and NT-proBNP at 1, 3, and 6 months after surgery (P<0.05), and higher CO and lower SaO2 at 6 months after surgery (P<0.05). Compared with the non-septostomy group, the dogs in the BAS group had significantly lower mRAP and NT-proBNP at 1 month after surgery (P<0.05), and there was no significant difference on mRAP and NT-proBNP at 3 and 6 months after surgery (P>0.05). Echocardiography showed that there was a minimal right-to-left shunt in the atrial septum in the BAS group at 1 month after the surgery, and the ostomy was closed in all the dogs in the BAS group at 3 months after the surgery. There was still a clear right-to-left shunt in the dogs of BAS+fenestrated ASD occulders group. The shunt was well formed and satisfactory endothelialization was observed at 1, 3 and 6 months after surgery. The results of HE staining showed that the pulmonary arterials were significantly thickened, stenosis and collapse occurred in the non-septostomy group. Pulmonary microvascular stenosis and inflammatory cell infiltration in the pulmonary arterials were observed in the non-septostomy group. Pulmonary arterial histological results were comparable between BAS+fenestrated ASD occulders group and non-septostomy group at 6 months after surgery. Conclusions: The fenestrated ASD occulder has the advantage of maintaining the open fistula hole for a longer time compared with simple balloon dilation. The fenestrated ASD occulder can improve cardiac function, and it is safe and feasible to treat PAH in this animal model.

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is associated with IRF7, BANK1 and TBX21 polymorphisms in two populations.

BACKGROUND AND PURPOSE: Autoantibodies targeting the GluN1(NR1) subunit of the anti-N-methyl-D-aspartate receptor (NMDAR) cause encephalitis. Although it has been shown that anti-NMDAR encephalitis is associated with human leukocyte antigen (HLA) loci, susceptibility genes for the disease outside the HLA loci remain unidentified. In this study, we aimed to explore the association of anti-NMDAR encephalitis with non-HLA genes. METHODS: Two Chinese anti-NMDAR encephalitis cohorts from Han populations were recruited for this study. The North Chinese case-control set consisted of 98 patients and 460 controls, while the South Chinese case-control set included 78 patients and 541 controls. All participants were genotyped for 28 single nucleotide polymorphisms that are associated with autoimmune disorders or infectious diseases. RESULTS: In two independent case-control sets, we identified significant associations of anti-NMDAR encephalitis with IRF7 rs1131665 (odds ratio [OR] 3.34, 95% confidence interval [CI] 1.99-5.63; P < 0.000001, Padjusted  = 0.00004), BANK1 rs4522865 (OR 1.44, 95% CI 1.15-1.82; P = 0.0017, Padjusted  = 0.0149), and TBX21 rs17244587 (OR 2.03, 95% CI 1.35-3.05; P = 0.00051, Padjusted  = 0.0066). Furthermore, analysis of the three polymorphisms with clinical features of the disease revealed that the IRF7 rs1131665 was associated with tumor status. CONCLUSION: The present study has for the first time identified non-HLA susceptibility genes for anti-NMDAR encephalitis. The association of IRF7, BANK1 and TBX21 with anti-NMDAR encephalitis suggests that B-cell activation, Th1 responses, virus infection and the type I interferon signaling pathway are involved in the pathogenesis of the disease.

[Association of systemic immune-inflammation index with protein-energy wasting and prognosis in patients on maintenance hemodialysis].

Objective: To explore the association of systemic immune-inflammation index (SII) with protein-energy wasting (PEW) and prognosis in maintenance hemodialysis (MHD) patients. Methods: A multicenter cohort study was conducted in 11 hemodialysis centers of Guizhou province from July to September 2019. The patients were divided into the PEW group and non-PEW group. After 12 months of follow-up, death was the endpoint event. Multivariate logistic regression analysis was used to assess the independent risk factors of PEW in MHD patients. The receiver operating characteristic (ROC) curve analysis was performed to evaluate the predictive value of SII for PEW, and the optimal cut-off value of SII was calculated. The Kaplan-Meier method was used to draw the survival curve, and log-rank test was employed to compare the difference of survival rate between the two groups. Results: A total of 859 patients were included [540 males and 319 females, aged (54±15) years], and there were 220 cases (25.6%) and 639 cases (74.4%) in PEW and non-PEW groups, respectively. SII was higher in the PEW group than that of the non-PEW group [600 (440, 915) vs 475 (353, 633), P<0.01]. Multivariate logistic regression analysis showed that SII was an independent predictor for PEW (OR=1.001, 95%CI: 1.000-1.002, P=0.02). ROC curve analysis showed that the area under the curve for SII to predict PEW in MHD patients was 0.725 (95%CI: 0.683-0.766), with the sensitivity and specificity of 69% and 70%, respectively. All patients were followed up for 12 months, and 45 died (with a mortality rate of 5.24%). Patients were divided into SII>520 group and SII≤520 group according to the optimal cut-off value, and subsequent Kaplan-Meier survival analysis showed that the 1-year cumulative survival rate of the SII>520 group (92.3%) was lower than that of SII≤520 group (97.1%) (χ2log-rank=9.707, P=0.002). Further subgroup analysis revealed that, in PEW patients with MHD, the 1-year cumulative survival rate of the SII>520 group (88.5%) was also lower than that of SII≤520 group (92.3%) (χ2log-rank=7.226, P=0.007). Conclusion: SII is an independent risk factor for PEW in MHD patients, and the higher the SII level, the lower the long-term survival rate and the prognosis.

[Technology specification of bedside hypertonic saline-contrast electrical impedance tomography of lung perfusion and clinical application].

Bedside hypertonic saline-contrast electrical impedance tomography (EIT) method for lung perfusion evaluation has several advantages of bedside, simple, noninvasive and radiation-free. For a long time, EIT perfusion image of hypertonic saline was mostly limited to animal experiments, and related clinical research is in the ascendant. This technical specification for clinical application is reached based on our previous researches, review of literatures in this field. The purpose of this technical specification is to facilitate the unified and standardized use of hypertonic saline-contrast EIT technology for regional lung perfusion, to evaluate the safety and quality control of the technology, and to unify the results.

Activated inducible co-stimulator-positive programmed cell death 1-positive follicular helper T cells indicate disease activity and severity in ulcerative colitis patients.

Inducible co-stimulator-positive (ICOS) and programmed cell death 1-positive (PD-1) are important markers for follicular helper T cells (Tfh); however, their roles and clinical values in ulcerative colitis (UC) remain unknown. In this study, we recruited 68 UC patients and 34 healthy controls. Circulating ICOS+ , PD-1+ and ICOS+ PD-1+ Tfh subsets were analyzed by flow cytometry. Twelve active UC patients achieving remission after treatment with 5-aminosalicylic acid were followed-up and Tfh subset changes were analyzed. Serum immunoglobulin (Ig)G, C-reactive protein (CRP), interleukin (IL)-4 and IL-21 levels and B cell subsets were analyzed and Mayo scores were calculated. Correlation analyses were performed between Tfh subsets and the clinical indicators. Receiver operating characteristic (ROC) curves were generated to evaluate the efficiency of Tfh subsets for disease monitoring. We found that levels of ICOS+ , PD-1+ and ICOS+ PD-1+ Tfh cells were significantly increased in active UC and significantly decreased when achieving clinical remission. Activated ICOS+ PD-1+ Tfh cells were positively correlated with serum CRP and Mayo scores. Furthermore, ICOS+ PD-1+ Tfh cells were significantly correlated with circulating new memory B cells and plasmablasts, as well as serum IgG, IL-4 and IL-21. ROC analyses showed that when ICOS+ PD-1+ Tfh cells were used in combination with PD-1+ Tfh cells, the diagnostic efficacy in distinguishing active UC from stable remission patients was higher than that of any one used alone, with area under curve (AUC) value 0·931. Our findings suggest that increased ICOS+ PD-1+ Tfh cells are associated with the activation of B cells in the pathogenesis of UC, and may be a potential biomarker for UC disease monitoring.

[Diagnostic and prognostic value of peripheral lymphocyte subtyping for invasive candidiasis infection in critically ill patients with non-neutropenic sepsis].

Objective: To assess the diagnostic and prognostic value of lymphocyte subtyping for invasive candidiasis infection (ICI) in critically ill patients with non-neutropenic sepsis. Methods: A prospective observational cohort study was performed at Peking Union Medical College Hospital (PUMCH), 377 patients with non-neutropenic sepsis admitted to Department of Critical Care Medicine from January 2017 to November 2019 were enrolled. There were 9.0% (34/377) patients diagnosed as ICI. Vital signs, supportive care therapy and microbiological specimens were collected. Peripheral blood lymphocyte subtypes, serum globulin, complements, inflammatory factors such as interleukin(IL)-6, IL-8, IL-10 and tumor necrosis factor were detected within 24 hours after sepsis was diagnosed. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value and prognostic significance of immunological indicators for ICI. Multiple logistic regression was used to analyze the independent risk factors for ICI. Kaplan-Meier analysis was used to analyze survival. Results: The acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score was 17.0 (13.0, 21.0) in all 377 patients. The sequential organ failure score (SOFA) was 11.0 (8.0, 13.0), and the 28-day mortality rate was 27.6% (104/377). Peripheral blood CD8+absolute T lymphocyte count≤177 cells/µl, CD28+CD8+T-cell count≤81 cells/µl and 1, 3-ß-D-glucan (BDG) ≥88.20 ng/L were closely correlated with the diagnosis of ICI (AUC=0.793,95%CI 0.749-0.833,P<0.000 1;AUC=0.892,95%CI 0.856-0.921, P<0.000 1;AUC=0.761, 95%CI 0.715-0.803,P<0.000 1, respectively), with sensitivity of diagnosis 94.12%, 100.00%, and 88.24%; the specificity of diagnosis 81.34%, 62.39%, 63.56% respectively. Multivariate logistic regression analysis identified CD8+T-cell count≤139 cells/µl (OR=7.463, 95%CI 1.300-42.831, P=0.024) and CD28+CD8+T-cell counts≤52 cells/µl (OR=57.494, 95%CI 3.986-829.359, P=0.003) as independent risk factors for higher mortality. Kaplan-Meier survival analysis suggested that CD8+T-cell count ≤139 cells/µl (P=0.0159) and CD28+CD8+T-cell count≤52 cells/µl (P=0.000 1) were associated with higher mortality within 28 days (68.8%, 91.7%). Conclusions: Low CD28+CD8+T cell count in peripheral blood is closely related to the development and clinical outcome of ICI in sepsis patients, which could be used as an effective indicator for the diagnosis and prognosis prediction of ICI.

[Relationship between social support, resilience, self-esteem and post-traumatic stress disorder in intensive care unit nurses].

Objective: To investigate the correlation between social support, resilience, self-esteem and post-traumatic stress disorder (PTSD) in intensive care unit (ICU) nurses. Methods: A total of 717 ICU nurses from 24 provinces conducted these questionnaires (Chinese version of Impact of Event Scale-Revised(IES-R), Social Support Rate Score(SSRS), Cannor-Davidson Resilience(CD-RISC) and Self-Esteem Scale(SES)). There were 101 males and 616 females, with an average age of (30±5) years. With the aim to investigate PTSD impact factors, the ICU nurses were divided into the PTSD positive group (IES-R>35) and PTSD negative group (IES-R<35). The correlation between IES-R and other scales were analyzed with linear regression analysis. Results: In this investigation, 414 nurses were screened with PTSD and 303 nurses without. IES-R score was negatively correlated with SSRS, CD-RISC and SES (r=-0.275, -0.202, -0.709, all P<0.05). Multivariate regression analysis showed that ICU clinical experience was an independent risk factor for PTSD, and SES Score, SSRS Score and physical health status were protective factors. SES partially mediated the association of SSRS with IES-R, and the mediating effect were 51.5%. The area under characteristic curve (ROC) showed that SSRS score, CD-RISC score, SES score and PTSD risk score Logit (P) for prediction of PTSD was 0.629, 0.604, 0.831 and 0.848, respectively. Conclusions: Social support, physical health and self-esteem are protective factors of PTSD, while ICU clinical experience is a risk factor. SES partially mediated the association of SSRS with IES-R.

[Clinical value of early bedside ultrasound measurement of quadriceps femoris in diagnosis of ICU-acquired weakness].

Objective: To explore the correlation between quadriceps thickness (thickness of rectus femoris and vastus intermedius), cross-sectional area (cross-sectional area of the rectus femoris) and the strength score of the Medical Research Council (MRC) in critically ill patients, and to explore the changes in the length of hospital stay in the intensive care unit (ICU), and to determine the diagnostic value of muscle changes in the ICU-acquired weakness (ICU-AW). Methods: Patients admitted to the Department of Critical Care Medicine from March to October in 2019 who were expected to stay for more than five days were enrolled in this study. The cross-sectional area of the rectus femoris, the thickness of the rectus femoris, the thickness of the vastus intermedius on the first day of the ICU (D(1)), day 3 (D(3)), and day 5 (D(5)), day 7 (D(7)), out of ICU (D(ICU)), and the MRC muscle strength scores on the day of out of ICU prospectively were collected in all the patients, and the correlation and the regularity of quadriceps changes were analyzed. MRC>48 points on the day of dismiss of ICU were used as the standard for the diagnosis of ICU-AW, and the relationship between muscle changes of the quadriceps and ICU-AW was analyzed. The t test or the Mann-Whitney U test was used for data analysis. Results: A total of 45 patients were included, including 25 males and 20 females, aged (58±10) years. The rectus femoris cross-sectional area, rectus femoris thickness, and vastus intermedius thickness decreased with the length of ICU hospital stay. The cross-sectional area, thickness of the rectus femoris muscle, and the vastus intermedius thickness were positively correlated with the MRC score (r=0.452, 0.411, 0.402, all P<0.05), and the changes were all negatively correlated with the MRC score (r=-0.682, -0.740, -0.734, all P<0.05). On the 3rd day after ICU admission, the best cutoff value of rectus muscle cross-sectional area atrophy rate for discrimination of ICU-AW was 6.0%, with a sensitivity of 66.7% and a specificity of 77.8%; on the 5th day, the best cutoff value of rectus femoris thickness atrophy rate was 14.5%, with a sensitivity of 77.8% and a specificity of 66.7%; on the 7th day, the best cutoff value of vastus intermedius thickness atrophy rate was 19.9%, with a sensitivity of 70.6% and a specificity of 87.5%. Conclusion: Bedside ultrasound measurement of the quadriceps femoris cross-sectional area and thickness has certain diagnostic value for ICU-AW, and can identify patients with ICU-AW early.

[Reversal effect of peptide-modified chitosan tetramethylpyrazine nanoparticles on multidrug resistance in tumor cells].

To prepare peptide-modified chitosan tetramethylprazine nanoparticles(FGF-CS-TMP-NPS) and investigate its reversal effect on multidrug resistance in tumor cells. The pEGF-CS-TMP-NPs were prepared by ion crosslinking method, and their physicochemical properties were investigated. Western blot was used to detect the expression levels of epidermal growth factor receptor(EGFR)(MCF-7, MCF-7/ADR, K562 and K562/ADR) and drug-resistant related protein P-gp. MCF-7/ADR and K562/ADR were selected as cell models. The cytotoxicity of pEGF-CS-TMP-NPs, the multiple of cell resistance to adriamycin, the reversal resistance index of pEGF-CS-TMP-NPs to doxorubicin and the sensitization of pEGF-CS-TMP-NPs to doxorubicin were detected by MTT assay. After MCF-7/ADR and K562/ADR were treated with pEGF-CS-TMP-NPs, the expression changes of P-gp were detected by Western blot. The encapsulation efficiency and drug loading of pEGF-CS-TMP-NPs were 37.66%± 0.53% and 3.25%± 0.34% respectively in HPLC. The nanoparticles showed an average particle size of(150.50±9.3) nm, polymer dispersity index of(0.059±0.007) and Zeta potential of(19.30±2.02) mV as detected by laser particle size analyzer. The nanoparticles were spherical and well dispersed under transmission electron microscope. Western blot results showed that EGFR was positively expressed in MCF-7 and MCF-7/ADR cells, while negatively expressed in K562 and K562/ADR cells. P-gp was highly expressed in MCF-7/ADR and K562/ADR, while negatively expressed in MCF-7 and K562. pEGF-CS-TMP-NPs had a weak effect on MCF-7/ADR and K562/ADR. The adriamycin resistance of MCF-7/ADR cells was 108.36 times, and that of K562/ADR cells was more than 100 times. When IC_(85) of pEGF-CS-TMP-NPs was used as the administration concentration, the reversion index of MCF-7/ADR and K562/ADR cells was 3.68 and 1.87, respectively. pEGF-CS-TMP-NPs could enhance the sensitivity of adriamycin to MCF-7/ADR cells in a positive correlation with the concentration, and the sensitivity was significantly higher than that of K562/ADR cells. Western blot results showed that the expression level of P-gp in MCF-7/ADR cells decreased significantly after treatment with pEGF-CS-TMP-NPs, while the expression level of P-gp in K562/ADR cells did not change significantly. Experimental results show that pEGF-CS-TMP-NPs have an active targeting effect on MCF-7/ADR cells with high EGFR expression, and can effectively reverse the multidrug resistance of MCF-7/ADR cells. Active targeting effect is related to the peptides modification of nanoparticles, and the mechanism of reversing tumor MDR may be achieved by down-regulating the expression level of P-gp.

Sodium nitrite potentiates antimicrobial photodynamic inactivation: possible involvement of peroxynitrate.

We have recently shown that a wide range of different inorganic salts can potentiate antimicrobial photodynamic inactivation (aPDI) and TiO2-mediated antimicrobial photocatalysis. Potentiation has been shown with azide, bromide, thiocyanate, selenocyanate, and most strongly, with iodide. Here we show that sodium nitrite can also potentiate broad-spectrum aPDI killing of Gram-positive MRSA and Gram-negative Escherichia coli bacteria. Literature reports have previously shown that two photosensitizers (PS), methylene blue (MB) and riboflavin, when excited by broad-band light in the presence of nitrite could lead to tyrosine nitration. Addition of up to 100 mM nitrite gave 6 logs of extra killing in the case of Rose Bengal excited by green light against E. coli, and 2 logs of extra killing against MRSA (eradication in both cases). Comparable results were obtained for other PS (TPPS4 + blue light and MB + red light). Some bacterial killing was obtained when bacteria were added after light using a functionalized fullerene (LC15) + nitrite + blue light, and tyrosine ester amide was nitrated using both "in" and "after" modes with all four PS. The mechanism could involve formation of peroxynitrate by a reaction between superoxide radicals and nitrogen dioxide radicals; formation of the latter species was demonstrated by spin trapping with nitromethane.