Cuproptosis-Related Gene FDX1 Suppresses the Growth and Progression of Colorectal Cancer by Retarding EMT Progress.

Colorectal cancer (CRC) is a usual cancer and a kind of lethiferous cancer. Cuproptosis-related gene ferredoxin 1 (FDX1) has been discovered to act as a suppressor, thereby suppressing some cancers' progression. But, the regulatory functions of FDX1 in CRC progression keep vague. In this work, at first, through TCGA database, it was revealed that FDX1 exhibited lower expression in COAD (colon adenocarcinoma) tissues, and CRC patients with lower FDX1 expression had worse prognosis. Furthermore, FDX1 expression was verified to be down-regulated in CRC tissues (n = 30) and cells. It was further uncovered that FDX1 expression was positively correlated with CDH1 and TJP1 (epithelial marker), and negatively correlated with CDH2, TWIST1, and FN1 (stromal marker), suggesting that FDX1 was closely associated with the epithelial-mesenchymal transition (EMT) progress. Next, it was demonstrated that overexpression of FDX1 suppressed cell viability, invasion, and migration in CRC. Furthermore, it was verified that FDX1 retarded the EMT progress in CRC. Lastly, through rescue assays, the inhibited CRC progression mediated by FDX1 overexpression was rescued by EGF (EMT inducer) treatment. At last, it was uncovered that the tumor growth and metastasis were relieved after FDX1 overexpression, but these changes were reversed after EGF treatment. In conclusion, FDX1 inhibited the growth and progression of CRC by inhibiting EMT progress. This discovery hinted that FDX1 may act as an effective candidate for CRC treatment.

Initial clinical features of suspected coronavirus disease 2019 in two emergency departments outside of Hubei, China.

With an increasing number of Coronavirus Disease 2019 (COVID-19) cases outside of Hubei, emergency departments (EDs) and fever clinics are facing challenges posed by the large number of admissions of patients suspected to have COVID-19. Therefore, it is of crucial importance to study the initial clinical features of patients, to better differentiate between infected and uninfected patients outside Hubei. A total of 116 patients suspected of having COVID-19 who presented to two emergency departments in Anhui for the first time between 24 January 2020 and 20 February 2020 were enrolled in the study. The initial clinical data of these patients, such as epidemiological features, symptoms, laboratory results, and chest computed tomography (CT) findings were collected using a standard case report form on admission. Thirty-two patients were diagnosed with COVID-19; the remaining 84 patients were referred to as negative cases. The median age of the diagnosed patients was 46 years, but only 35 years for negative cases. History of exposure to Wuhan or COVID-19 patients in the previous 2 weeks was observed in 63% of the diagnosed and 44% of negative cases. Median time from illness onset to ED admission was 5 days for all patients, diagnosed patients, and negative cases, respectively. Fever was observed in 27 (84%) and 57 (68%) diagnosed and negative cases, respectively. Nineteen (59%) diagnosed and 24 (29%) negative cases had lymphopenia on admission in ED. A chest CT scan on admission revealed the presence of pneumonia in the majority of the diagnosed patients (30 out of 32, 94%) and in 56 (67%) negative cases. Bilateral involvement and ground-glass opacity (GGO) were present in 91% and 47% of the diagnosed patients. Thirty-two patients were diagnosed with COVID-19; the remaining 84 patients were referred to as negative cases. The median age of the diagnosed patients was 46 years, but only 35 years for negative cases. History of exposure to Wuhan or COVID-19 patients in the previous 2 weeks was observed in 63% of the diagnosed and 44% of negative cases. Median time from illness onset to ED admission was 5 days for all patients, diagnosed patients, and negative cases, respectively. Fever was observed in 27 (84%) and 57 (68%) diagnosed and negative cases, respectively. Nineteen (59%) diagnosed and 24 (29%) negative cases had lymphopenia on admission in ED. A chest CT scan on admission revealed the presence of pneumonia in the majority of the diagnosed patients (30 out of 32, 94%) and in 56 (67%) negative cases. Bilateral involvement and GGO were present in 91% and 47% of the diagnosed patients.

A modified PLASMIC score including the lactate dehydrogenase/the upper limit of normal ratio more accurately identifies Chinese thrombotic thrombocytopenic purpura patients than the original PLASMIC score.

BACKGROUND: The PLASMIC score was recently published to aid in the early identification of thrombotic thrombocytopenic purpura (TTP) patients. This study aims to evaluate whether this score is suitable for Chinese suspected TTP patients and find the utility of patients' other characteristics in predicting severe ADAMTS13 deficiency. METHODS: We retrospectively studied a Chinese cohort of 38 consecutive hospitalized patients with suspected TTP, ADAMTS13 test results, and other clinical data from September 2016 to May 2018. The predictive power of PLASMIC score in our cohort was evaluated, and patients' other characteristics, especially the high lactate dehydrogenase/the upper limit of normal (LDH/ULN), were studied to determine their distinguishing ability for TTP patients. RESULTS: In this Chinese cohort, 17 patients were diagnosed with TTP according to ADAMTS13 activity results. When dichotomized at intermediate-high risk (scores 5-7) vs low risk (scores 0-4), the PLASMIC score predicted TTP with a sensitivity of 100%, a specificity of 9.52%, and a misdiagnosis rate of 90.48%. And the LDH/ULN alone, or plus platelet count, reticulocyte percentage and indirect bilirubin (IBIL) both had excellent predictive power (area under the curve [AUC] 0.937, 95% confidence interval [CI] 0.863-1.000, P = .000, and AUC 0.994, 95% CI 0.980-1.000, P = .000, respectively). The model including platelet count, reticulocyte percentage, IBIL, and LDH/ULN ratio had a sensitivity of 100%, a specificity of 95.2%, and a misdiagnosis rate of 4.8%. CONCLUSIONS: A modified PLASMIC score plus LDH/ULN ratio might be more suitable for identifying ADAMTS13 deficiency patients, especially for making an earlier diagnosis, guiding the immediate and reasonable plasma exchange, and also avoiding unnecessary allocation of plasma.

VraR Binding to the Promoter Region of agr Inhibits Its Function in Vancomycin-Intermediate Staphylococcus aureus (VISA) and Heterogeneous VISA.

Acquisition of vancomycin resistance in Staphylococcus aureus is often accompanied by a reduction in virulence, but the mechanisms underlying this change remain unclear. The present study was undertaken to investigate this process in a clinical heterogeneous vancomycin-intermediate S. aureus (hVISA) strain, 10827; an hVISA reference strain, Mu3; and a VISA reference strain, Mu50, along with their respective series of vancomycin-induced resistant strains. In these strains, increasing MICs of vancomycin were associated with increased expression of the vancomycin resistance-associated regulator gene (vraR) and decreased expression of virulence genes (hla, hlb, and coa) and virulence-regulated genes (RNAIII, agrA, and saeR). These results suggested that VraR might have a direct or indirect effect on virulence in S. aureus In electrophoretic mobility shift assays, VraR did not bind to promoter sequences of hla, hlb, and coa genes, but it did bind to the agr promoter region. In DNase I footprinting assays, VraR protected a 15-nucleotide (nt) sequence in the intergenic region between the agr P2 and P3 promoters. These results indicated that when S. aureus is subject to induction by vancomycin, expression of vraR is upregulated, and VraR binding inhibits the function of the Agr quorum-sensing system, causing reductions in the virulence of VISA/hVISA strains. Our results suggested that VraR in S. aureus is involved not only in the regulation of vancomycin resistance but also in the regulation of virulence.

A 10-second fluid challenge guided by transthoracic echocardiography can predict fluid responsiveness.

INTRODUCTION: The accurate assessment of intravascular volume status for the therapy of severe hypovolemia and shock is difficult and critical to critically ill patients. Non-invasive evaluation of fluid responsiveness by the rapid infusion of a very limited amount of volume is an important clinical goal. This study aimed to test whether echocardiographic parameters could predict fluid responsiveness in critically ill patients following a low-volume (50-ml crystalloid solution) infusion over 10 seconds. METHODS: We prospectively studied 55 mechanically ventilated patients. Echocardiography was performed during a 50-ml infusion of crystalloid solution over 10 seconds and a further 450 ml over 15 minutes. Cardiac output (CO), stroke volume (SV), aortic velocity time index (VTI), and left ventricular ejection fraction (LVEF) were recorded. Patients were classified as responders (Rs) if CO increased by at least 15% following the 500-ml volume expansion or were classified as non-responders (NRs) if CO increased by less than 15%. Area under the receiver operating characteristic curves (AUC) compared CO variations after 50 ml over 10 seconds (∆CO50) and 500 ml over 15 minutes (∆CO500) and the variation of VTI after infusion of 50 ml of fluid over 10 seconds (∆VTI50). RESULTS: In total, 50 patients were enrolled, and 27 (54%) of them were Rs. General characteristics, LVEF, heart rate, and central venous pressure were similar between Rs and NRs. In the Rs group, the AUC for ∆CO50 was 0.95 ± 0.03 (P <0.01; best cutoff value, 6%; sensitivity, 93%; specificity, 91%). Moreover, ∆CO50 and ∆CO500 were strongly correlated (r = 0.87; P <0.01). The AUC for ∆VTI50 was 0.91 ± 0.04 (P <0.01; best cutoff value, 9%; sensitivity, 74%; specificity, 95%). ∆VTI50 and ∆CO500 were positively correlated (r = 0.72; P <0.01). CONCLUSION: In critically ill patients, the variation of CO and VTI after the administration of 50-ml crystalloid solution over 10 seconds (∆CO50 and ∆VTI50) can accurately predict fluid responsiveness. TRIAL REGISTRATION: Current Controlled Trials ISRCTN10524328. Registered 12 December 2013.

Luteolin regulating synthesis and catabolism of osteoarthritis chondrocytes via activating autophagy.

Osteoarthritis (OA) is a prevalent bone and joint disease characterized by degeneration. The dysregulation between chondrocyte synthesis and breakdown is a key factor in OA development. Targeting the degenerative changes in cartilage tissue degradation could be a potential treatment approach for OA. Previous research has established a strong link between autophagy and the regulation of chondrocyte functions. Activating autophagy has shown promise in mitigating cartilage tissue degeneration. Currently, osteoarthritis treatment primarily focuses on symptom management, as there is no definitive medication to stop disease progression. Previous studies have demonstrated that luteolin, a flavonoid present in Chinese herbal medicine, can activate autophagy and reduce the expression of MMP1 and ADAMTS-5. This study utilized an in vitro osteoarthritis model with chondrocytes stimulated by IL-1ß, treated with varying concentrations of luteolin. Treatment with luteolin notably increased the levels of synthesis factors Aggrecan and Collagen II, while decreasing the levels of decomposition factors MMP-1 and ADAMTS-5. Moreover, inhibition of autophagy by Chloroquine reversed the imbalances in chondrocyte activities induced by IL-1ß. In an in vivo model of knee osteoarthritis induced by medial meniscal instability (DMM), luteolin was administered as a therapeutic regimen. After 12 weeks, knee cartilage tissues from mice were analyzed. Immunofluorescence and immunohistochemical staining revealed a decrease in P62 expression and an increase in Beclin-1 in the cartilage tissues. Additionally, cartilage wear in the knee joints of mice was alleviated by safranin O and fast green staining. Our study findings underscore the significant role of luteolin in effectively rebalancing chondrocyte activities disrupted by IL-1ß. Our results strongly indicate that luteolin has the potential to be developed as a novel therapeutic agent for the treatment of osteoarthritis, offering promising prospects for future drug development.

Analysis of S. Epidermidis icaA and icaD genes by polymerase chain reaction and slime production: a case control study.

BACKGROUND: Staphylococcus epidermidis is a common pathogen in medical device-associated infections and have an ability to form adherent slime. We aimed to study the effects of icaA and icaD genes on the slime formation of Staphylococcus epidermidis associated with catheter-associated infections. METHODS: S. epidermidis isolates from the central venous catheter blood of patients with catheter-associated infections, and from the nasal vestibules of healthy volunteers, intensive care unit hospital staff, and patients, were collected. Slime phenotype was determined by Congo red agar test. The icaA/D was detected by polymerase chain reaction. Slime was examined using scanning electron microscopy. RESULTS: A total of 82 S. epidermidis isolates were collected. We found a statistically significant difference with regards to slime production between the clinical isolates from the catheter blood specimens and those from the nasal vestibules (p<0.05). All S. epidermidis slime positive strains isolated were icaA positive. There was a greater correlation between the presence of both icaA and icaD and the slime production than the single expression of icaA or icaD and the presence of slime in all groups. The co-expression of mecA and icaD was associated with enhanced resistance to antibiotics. CONCLUSION: S. epidermidis bacteria are significant nosocomial pathogens, and icaA/D can clarify the adhesion mechanism in the pathogenesis of infections associated with medical devices. This study result could be useful for the development of rapid diagnosis for slime producing and methicillin resistant S. epidermidis strains.

[A study of the clinical features and the effect of therapy on acute respiratory distress syndrome patients as a result of severe triphosgene poisoning].

OBJECTIVE: To investigate the clinical features and treatment strategy for acute respiratory distress syndrome (ARDS) caused by phosgene. METHODS: Individualized therapy was carried out in 17 cases of severe phosgene poison patients. Blood routine, electrolytes, blood gas analysis, hepatic and renal function tests and cardiac enzymes were examined before and after treatment. RESULTS: Vital signs, fluid, electrolytes and acid-base disturbances were improved after treatment. As compared to that of pre-treatment period, white blood cells [WBC, ×10(9)/L: 12.18 ± 4.76 vs. 21.93 ± 6.21], neutrophil percentage (0.87 ± 0.05 vs. 0.92 ± 0.03), hemoglobin (Hb, g/L: 128.12 ± 25.65 vs. 173.71 ± 23.53), blood platelet count [PLT,×10(9)/L:165.12 ± 31.70 vs. 254.47 ± 70.80], alanine transaminase (ALT, U/L: 70.71 ± 46.70 vs. 212.71 ± 141.34), aspartate aminotransferase (AST, U/L: 52.47 ± 34.68 vs. 82.41 ± 34.60), blood urea nitrogen (BUN, mmol/L: 5.83 ± 4.09 vs. 7.89 ± 5.96), serum creatinine (SCr, µmol/L: 48.13 ± 14.97 vs. 67.25 ± 24.29), lactate dehydrogenase (LDH, U/L: 280.10 ± 81.77 vs. 586.35 ± 186.71), creatine kinase (CK, U/L: 199.12 ± 106.75 vs. 683.00 ± 323.21), MB isoenzyme of creatine kinase (CK-MB, U/L: 26.94 ± 9.13 vs. 45.59 ± 11.21), serum chlorine anion [Cl(-), mmol/L: 95.88 ± 6.06 vs. 102.29 ± 7.28], respiratory rate (RR, beats/min: 20.88 ± 4.30 vs. 30.06 ± 5.78), heart rate (HR, beats/min: 82.76 ± 17.16 vs. 113.35 ± 16.90), blood pH value (7.34 ± 0.44 vs. 7.39 ± 0.03) were all decreased (P < 0.05 or P < 0.01). Serum sodium ion [Na(+),mmol/L:140.61 ± 6.69 vs. 134.06 ± 4.80], arterial partial pressure of oxygen [PO(2), mm Hg, 1 mm Hg = 0.133 kPa: 84.41 ± 30.58 vs. 59.88 ± 15.19] and pulse oxygen saturation [SpO(2): 0.91 ± 0.08 vs. 0.78 ± 0.15] were increased (P < 0.05 or P < 0.01). Sixteen patients totally recovered, 1 patient died, and the cure rate was 94.12%. CONCLUSIONS: Respiratory system could be mainly injured as the result of exposure to phosgene and leading to ARDS. Early initial combination therapies with corticosteroids and respiratory support should be addressed.

Study of a High-Temperature and High-Density Water-Based Drilling Fluid System Based on Non-sulfonated Plant Polymers.

The environment-friendly water-based drilling fluid system developed for the petroleum development industry cannot successfully withstand temperatures up to 180 °C, and most high temperature-resistant additives with sulfonic acid groups that have been successfully applied to water-based drilling fluid are not good for environmental protection. In order to solve the above technical problems, a non-sulfonated filtrate reducer and viscosity reducer with resistance to high temperature were prepared by using humic acid, lignin and a multifunctional monomer as raw materials. In laboratory experiments, the molecular weights of the FLO-H filtrate reducer and the VR-H viscosity reducer were 5.45 × 105 g/mol and 8.51 × 103 g/mol, respectively, and all of them showed good high-temperature resistance. The API filtration loss of the bentonite-base slurry with 3.0 wt% FLO-H was only 6.2 mL, which indicated that FLO-H had a prominent reduction in filtration loss after aging at high temperature. When the dosage of VR-H was 1.0 wt%, the plastic viscosity of the water-based drilling fluid after aging at 200 °C decreased from 71 mPa·s to 55 mPa·s, which provided excellent dispersion and dilution. The high-temperature and high-density water-based drilling fluid containing the FLO-H filtrate reducer and the VR-H viscosity reducer had good suspension stability and low filtration performance at the high temperature of 200 °C, which can meet the requirements of high-temperature deep well drilling.

Induction chemotherapy increases efficacy and survival rate of patients with locally advanced esophageal squamous cell carcinoma.

Objective: The efficacy of concurrent chemoradiotherapy (CRT) after induction chemotherapy (IC) in the treatment of esophageal squamous cell carcinoma (ESCC) remains unclear. The purpose of this study was to explore the efficacy of IC in patients with ESCC. Methods: 124 patients with ESCC receiving CRT were included. Patients were divided into IC+CRT group and CRT group. Short-term and long-term efficacy as well as survival time of the two groups were compared, influencing factors of IC efficacy were investigated, and overall survival (OS) and progression-free survival (PFS) between the two groups were compared in different subgroups. Results: There was no significant difference in the objective response rate (ORR) between the two groups. After IC, the ORR was higher in patients with single-drug concurrent chemotherapy weekly and patients with effective IC. In the long-term efficacy, advanced clinical stage patients had a shorter PFS compared to early-stage patients, and chemoradiotherapy mode ameliorates patients' PFS. OS and PFS of IC+CRT group were longer than that of CRT group in both tumor diameter <5cm and single-drug chemotherapy weekly subgroups. In addition, OS of IC+CRT group was longer than that of CRT group in pathological grade G1-2 subgroup. Conclusions: IC improve the efficacy and survival rate of patients with locally advanced ESCC, and the benefits are more advantageous in subgroups of effective IC, pathological grade G1-2, tumor diameter < 5cm, single-drug concurrent chemotherapy weekly.

The diagnostic value of next-generation sequencing technology in sepsis.

Objective: This study aims to assess the clinical utility of next-generation sequencing (NGS) in sepsis diagnosis. Methods: A prospective study was conducted on patients with a high suspicion of sepsis by unknown pathogens from January 2017 to December 2021. Blood samples were taken from patients to perform NGS, blood culture (BC), leucocyte (WBC), procalcitonin (PCT), creatinine (CREA), Albumin (ALB) and C-reactive protein (CRP) tests. Results: The feedback time for BC was 3~5 days for bacteria and 5~7 days for fungi, while the turnover time for NGS was only 24 h. The clinical diagnosis was considered the "gold standard". 83 patients passed our inclusion criteria and were separated into two groups by clinical diagnosis. 62 met the clinical diagnosis criteria for sepsis and 21 were non-sepsis. The data from the two groups were retrospectively compared and analyzed. Of 62 sepsis in 83 patients, 8(9.64%) were diagnosed by both BC and NGS, 51 (61.45%) by NGS only, 1(1.20%) by BC and 2 (2.41%) by conventional testing only; PCT, CREA, CRP levels and the detection rate of NGS and BC were higher in the sepsis group than in the non-sepsis group, while ALB levels were lower (p<0.05). The logistic regression results in our study revealed that NGS and ALB were independent prediction factors for sepsis (p<0.05), the area under the receiver operating characteristic curve (AUC), sensitivity and specificity of NGS for diagnosing sepsis was 0.857, 95.16% and 76.19%, while ALB was 0.728, 58.06%, 80.95%, respectively. The combination's sensitivity, specificity and AUC of NGS and ALB were 93.55%, 85.71% and 0.935, greater than that of Albumin or NGS only (both p<0.05). Conclusion: NGS can effectively and quickly identify pathogens, thereby emerges as a promising technology for sepsis diagnosis. Combination of NGS and ALB can be used for early screening and is more powerful than NGS or ALB only.

Acute respiratory distress syndrome following multiple wasp stings treated with extracorporeal membrane oxygenation: A case report.

BACKGROUND: It is necessary for clinicians to be aware of a rare but possible acute respiratory distress syndrome (ARDS) complication caused by multiple wasp stings. Severe ARDS has a high mortality rate but no specific pharmacotherapies have been identified to date. This case study presents the first case of severe ARDS caused by multiple wasp stings, treated successfully with extracorporeal membrane oxygenation (ECMO). It also emphasizes the effectiveness of early ECMO treatment for severe ARDS with persistent hypoxemia. CASE SUMMARY: A 24-year-old woman was admitted to the emergency department after being stung by more than 10 wasps within a 30-min period, with clinical symptoms of multiple rashes, dizziness, chest tightness, nausea, and vomiting. On the 2nd day of admission, the patient developed progressive dyspnea. The patient was diagnosed with ARDS based on clinical manifestations and lung computed tomography (CT) scan. Because of the progressive dyspnea, the intensive care unit physician performed endotracheal intubation and continued to provide ventilator support, but the patient's respiratory distress worsened, as indicated by the ratio of arterial partial pressure of oxygen to fraction of inspired oxygen. Veno-venous ECMO was initiated for 6 d. On day 7 of admission, ECMO was stopped. On the 11th day of admission, CT scan of the lungs revealed significant reduction of ground-glass opacities and consolidations. After about 2 wk, the patient recovered completely from ARDS and was discharged to home. At the 2-mo follow-up, the patient was in good health with no recurrence of dyspnea nor chest tightness. CONCLUSION: ARDS complication caused by multiple wasp stings may be fatal when mechanical ventilation becomes dangerous due to persistent hypoxemia and despite optimization of ARDS management. We propose that the early implementation of ECMO is a relatively effective treatment, although the evidence is relatively limited.

Poldip2 knockdown protects against lipopolysaccharide-induced acute lung injury via Nox4/Nrf2/NF-κB signaling pathway.

Polymerase δ-interacting protein 2 (Poldip2) has been reported to mediate acute lung injury (ALI); however, the underlying mechanism is not fully explored. Male C57BL/6 mice and A549 cells were used to establish the lipopolysaccharide (LPS)-induced ALI model, then the expression of Poldip2 and its effect on oxidative stress and the resulting inflammation were detected. Adeno-associated virus serotype 6 (AAV6) mediated Poldip2 knockdown was transfected into mice via intratracheal atomization. And A549 cells stimulated with LPS was used to further confirm our hypothesis in vitro. ML385, specifically inhibited the activation of the Nrf2 signaling pathway. Our data suggested that LPS stimulation remarkably increased protein levels of Nox4 and p-P65, activities of NADPH and MPO, and generation of ROS, TNF-α, and IL-1ß while decreased protein levels of Nrf2 and HO-1 compared with those in NC shRNA + Saline group, which were obviously reversed by Poldip2 knockdown. Concomitantly, Poldip2 knockdown dramatically reduced contents of MDA and enhanced activities of SOD and GSH-Px compared to NC shRNA + LPS group. In vitro, we found that knockdown of Poldip2 significantly reversed LPS-induced increase protein levels of Nox4 and p-P65, activity of NADPH, and generation of ROS, TNF-α, and IL-1ß, and decrease protein levels of Nrf2 and HO-1, ML385 pretreatment reversed the effects of Poldip2 knockdown mentioned above. Our study indicated that Poldip2 knockdown alleviates LPS-induced ALI via inhibiting Nox4/Nrf2/NF-κB signaling pathway.

[Effect of Xuebijing injection on T helper 17 and CD4+ CD25+ regulatory T cells in patients with sepsis].

OBJECTIVE: To study the level and significance of T helper 17 (Th17) and CD4(+) CD25(+) regulatory T cells (Treg) in peripheral blood of patients with sepsis and to evaluate the effects of Xuebijing injection on them. METHODS: ¹ Sixty-four patients with sepsis in intensive care unit (ICU) of Anhui Provincial Hospital were divided into three groups: sepsis group (n=26), severe sepsis group (n=21), and septic shock group (n=17). Eighteen healthy individuals served as controls. The comparison in the expression of Th17 and CD4(+)CD25(+) Treg within groups and the correlation between their levels and the severity of sepsis was made. ² Sixty-four patients were also randomly divided into two groups: routine group (n=25, received routine bundle treatment) and Xuebijing treatment group (n=39, received bundle treatment + Xuebijing treatment). Patients in Xuebijing treated group were given 50 ml Xuebijing injection two times per day in addition to routine bundle treatment. Seven days constituted one course of treatment. The expressions of Th17 and CD4(+) CD25(+) Treg of 64 patients on the 1 day and 7 days after treatment were detected by flow cytometry. The effects of Xuebijing injection on the patients were evaluated. RESULTS: ¹ The expression rate of Th17 and CD4(+)CD25(+) Treg was (0.84 ± 0.29)% and (0.43 ± 0.20)% respectively in control group, and they were lower than that of patients with sepsis (P<0.05). The expression rate of Th17 was higher in severe sepsis group [(3.18 ± 0.84)%] than that of other two groups (P <0.05). Moreover , The expression rate of CD4(+)CD25(+) Treg was highest [(3.28 ± 0.76)%] in septic shock group (P<0.05) , and it was positive correlated with acute physiology and chronic health evaluation II (APACHEII) score and blood lactate (r(1)=0.519, r(2)=0.451, both P =0.01) in all 64 patients. ² Compared with routine group, our study indicated that Xuebijing injection could reduce the abnormal expression of Th17 [(1.72 ± 0.69)% vs. (2.35 ± 0.81)%,P<0.05] and CD4(+)CD25(+) Treg [(1.78 ± 1.00)% vs. (2.30 ± 0.85)%,P<0.05] and decrease length of stay in ICU [(4.7 ± 2.6) days vs. (7.5 ± 4.3) days,P=0.002]. It also lowered 28-day mortality of patients with sepsis, but the difference between two groups was not significant (20.5% vs. 28.0%,P>0.05). CONCLUSION: The expression of Th17 and CD4(+)CD25(+) Treg was increased in sepsis patients and was positively correlated with severity of sepsis, suggesting that they may play an important role in pathogenesis of sepsis. Xuebijing injection could decrease the abnormal expression of Th17 and CD4(+) CD25(+) Treg and tend to decrease the fatality rate of sepsis.

Knowledge, attitudes, and practices related to augmented renal clearance among pediatricians in China: A cross-sectional study.

ABSTRACT: Our purpose was to assess pediatricians' knowledge of augmented renal clearance (ARC).We conducted cross-sectional analyses of 500 pediatricians from 16 tertiary hospitals in Anhui Province, China. Pediatricians provided demographic information and were asked questions about their knowledge of ARC, including risk factors, evaluation tools, and the impact on patient prognosis, with a focus on the attitude and practice of pediatricians related to adjusting vancomycin regimens when ARC occurs.A total of 491 valid questionnaires were finally included, only 276 pediatricians stated that they "know about ARC." Compared with the "do not know about ARC" group, the "know about ARC" group was younger (43.7 ±â€Š8.0 vs 48.0 ±â€Š7.9, P < .001), and their main source of ARC knowledge was from social networking platforms. A total of 193 (70%) chose at least 4 of the following factors as risk factors for children with ARC: severe trauma, sepsis, burns, major surgery, lower disease severity, and hematological malignancies. A total of 110 (40%) and 105 (38%) pediatricians chose the Schwartz formula and cystatin C, respectively, as the indicators to evaluate the renal function of ARC children. Concerning the estimated glomerular filtration rate threshold to identify ARC children, 201 (73%) pediatricians chose 130 mL/min/1.73 m2, while 55 (20%) chose "age-dependent ARC thresholds." Overall, 220 (80%) respondents indicated that ARC would impact the treatment effect of vancomycin, but 149/220 (68%) were willing to adjust the vancomycin regimen; only 22/149 (8%) considered that the dose should be increased, but no one knew how to increase. Regarding the prognosis of ARC children, all respondents chose "unclear."ARC is relatively common in critically ill children, but pediatricians do not know much about it, as most of the current knowledge is based on adult studies. Furthermore, ARC is often confused with acute kidney injury, which would lead to very serious treatment errors. Therefore, more pediatric studies about ARC are needed, and ARC should be written into official pediatric guidelines as soon as possible to provide reference for pediatricians.

Case Report: A Candida Meningitis in an Immunocompetent Patient Detected Through the Next-Generation Sequencing.

Background: Fungal infections of the central nervous system (CNS) are not commonly seen clinically. Clinical diagnosis of fungal infections often depend on the pathogen culture and the clinical features. This method is time-consuming and insensitive, which can lead to misdiagnosis. The authors introduce an adult patient with fungal infections diagnosed by next-generation sequencing (NGS). Case: The patient was a 60-year-old male Chinese who had both hypermyotonia of the lower extremities and fever. The auxiliary examinations such as MRI, CT, and cerebrospinal fluid (CSF) analysis showed obvious abnormalities. Because of the difficulties in diagnosis, it was hard to determine the treatment plan. The NGS detected specific sequences of Candida albicans in 3 days. The patient was then treated with liposomal amphotericin B and fluconazole. About 3 weeks later, the symptoms of the patient improved significantly and he was discharged from the hospital. Conclusion: Compared with the routine cultural method, NGS has made a huge advancement in infection diagnosis and targeting antimicrobial therapy for CNS infection.

[Effects of hyperbaric oxygen on T lymphocyte subpopulation and its electron microscopic changes in rats with acute pancreatitis].

OBJECTIVE: To investigate the effect of hyperbaric oxygen (HBO) therapy on T lymphocyte subpopulations in rats with acute pancreatitis (AP). METHODS: According to random number table, 56 Sprague Dawley (SD) rats were divided into three groups: the sham group, model group, and HBO therapy group. The rats of model and HBO groups underwent pancreatic duct ligation to induce pancreatitis, then they were divided into three subgroups of 8 rats each. The HBO group was treated with a daily exposure to HBO [2.5 atm (1 atm=101.325 kPa)]. The rats in each subgroup were euthanased on days 1, 3, 7, and the subpopulations of T lymphocytes in peripheral blood were detected respectively using flow cytometry. The nuclei, mitochondrion, rough and smooth endoplasmic reticulum of the pancreatic cells were examined using electron microscopy. RESULTS: The serum level of amylase on day 1 in model and HBO groups was significantly lower than that in sham group. In the model group the CD4(+)CD8(+) cells and the CD4(+)/CD8(+) ratio in AP rats was significantly decreased, indicating the presence of immune suppression. After 7 days of HBO therapy, compared with the model group, the CD4(+) lymphocytes in the HBO group were markedly increased on day 3 and day 7 [(27.92±2.10)% vs. (20.79±2.80)%, (26.58±4.50)% vs. (17.76±4.40)%]. The number of CD8(+) lymphocytes were also increased to a certain extent on day 7 [(25.32±3.70)% vs. (22.46±3.10)%]. The CD4(+)/CD8(+) ratio was obviously increased on day 3 and day 7 (1.07±0.14 vs. 0.86±0.15, 1.04±0.11 vs. 0.79±0.12, P<0.05 or P <0.01). Also beneficial effects as evaluated on the nuclei, mitochondrion, rough and smooth endoplasmic reticulum were found in the HBO group (10.8±1.6 vs. 17.9±1.7, 22.1±1.6 vs. 27.5±1.3, 16.8±1.0 vs. 29.3±0.8, 21.2±1.4 vs. 28.7±1.2, all P <0.01). CONCLUSION: This study shows that 7-day HBO therapy can promote a more balanced profile of T lymphocyte subpopulations, resulting in improvement of cellular immune function, and it can ameliorate pathological changes as shown by electron microscopic examination.

[Effects of hyperbaric oxygen on the acute lung injury induced by oleic acid in rats].

OBJECTIVE: To explore the effect of hyperbaric oxygen (HBO) on acute lung injury (ALI) induced by oleic acid (OA) in rats. METHODS: Eighty healthy Sprague-Dawley (SD) rats were randomly divided into four groups. In OA group (n=30), ALI was produced by injection of OA 0.15 ml/kg through tail vein. Ten rats were randomly selected and sacrificed after injection of OA at the time of 4 hours, 3 days, and 7 days, respectively. In OA plus HBO group (n=20), rats received HBO intervention in a special box with oxygen of 2.5 atm (1 atm=101.325 kPa) for 90 minutes. Ten rats were randomly respectively sacrificed at 3 days and 7 days. In simple HBO group, 20 rats were sacrificed at 3 days and 7 days of HBO intervention, respectively. Other 10 rats were assigned as control group. Blood, lung specimens were collected after sacrifice. Serum contents of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and IL-6 were measured. Gross changes and pathological findings of the left lung were recorded. The wet to the dry weigh (W/D) of the right lung was determined. RESULTS: Partial pressure of oxygen in arterial blood (PaO2, mm Hg, 1 mm Hg=0.133 kPa) fell from 107.70+/-5.37 to 57.40+/-2.63 in OA group. Congestion, bleeding and edema could be seen grossly. They could also be found under microscope with disappearance of normal structure, and accumulation of fluid in interstitium with inflammatory cell infiltration and hyaline membrane formation were also found. Lung W/D ratio was increased as compared with the control group (6.94+/-0.44 vs. 4.59+/-0.44, P<0.05). A marked increase was found in serum TNF-alpha, IL-1 beta, IL-6 levels [TNF-alpha (microg/L): 18.52+/-1.20 vs. 5.27+/-0.61, IL-1 beta (microg/L): 13.73+/-1.37 vs. 6.13+/-1.51, IL-6 (microg/L): 14.51+/-1.21 vs. 11.14+/-0.89]. After HBO therapy for 3 days and 7 days, PaO2 (mm Hg, 3 days: 79.20+/-1.68 vs. 59.00+/-2.70, 7 days: 94.30+/-3.77 vs. 74.00+/-3.85) and lung W/D (3 day: 7.43+/-0.73 vs. 9.82+/-0.99, 7 days : 6.75+/-1.14 vs. 8.77+/-1.60) of HBO group were ameliorated to varying degrees compared with OA model group (P<0.05 or P<0.01). HBO therapy for 3 days could lower levels of IL-1 beta (microg/L) in the serum (6.46+/-1.99 vs. 9.09+/-1.09, P<0.05). CONCLUSION: It is suggested that HBO treatment for ALI in rats had effects of improving arterial blood gases and the lung water transport, and inhibiting inflammatory mediators production.

[A study on the active efflux system in methicillin-resistant Staphylococcus aureus].

OBJECTIVE: To explore the status of methicillin-resistant Staphylococcus aureus (MRSA) infection in an intensive care unit (ICU), and investigate the active efflux mechanism of MRSA. METHODS: Eighty isolates were identified as MRSA among 102 strains of Staphylococcus aureus collected, and then the minimal inhibitory concentration (MIC) were determined. The 4 primers of active efflux gene were designed to amplify the 80 clinical isolates respectively by polymerase chain reaction (PCR). The PCR products were analyzed by electrophoresis in order to grasp the situation of the existence of the four genes (norA, qacA, qacB and qacJ). Omeprazole inhibition test was used to observe the changes in the susceptibility of MRSA to antibiotics. RESULTS: The detection rate of MRSA was 78.4%. The sensitivity rate of MRSA to both vancomycin and teicoplanin was 100.0%, while to other antibiotics (oxacillin, benzylpenicillin, cefuroxime, cefotaxime, ceftazidime, ceftiaxone, cefepime, cefoxitin, imipenem, piperacillin and tazobactam, azithromycin, erythromycin, chloramphenicol, clindamycin, amikacin, gentamicin, levofloxacin, gatifloxacin, ciprofloxacin) MRSA was multi-drug resistant. The detection rates of norA, qacA, qacB and qacJ were 67.5% (54/80), 15.0% (12/80), 21.2% (17/80) and 11.2% (9/80), respectively. Combined use of omeprazole and levofloxacin could lower MIC value. CONCLUSION: The infection of MRSA in ICU is serious. MRSA is multi-drug resistant and possesses active efflux genes norA, qacA, qacB and qacJ. Omeprazole can inhibit the activity of the active efflux genes.

Therapeutic role of melatonin in migraine prophylaxis: A systematic review.

BACKGROUND: Melatonin is the "clock factor" generated from pineal gland dominating regular circadian rhythm in humans. Migraine is one of the most severe and debilitating primary headache disorders. Thus far, many diseases have been found to associate with melatonin, including the migraine. Therefore, melatonin's therapeutic potential for migraine is drawing attention. OBJECTIVES: The aim of this study is to offer a systematic review of extant data of melatonin in migraine prophylaxis and to provide clinical implications and specific recommendations for future studies. DATA SOURCES AND STUDY METHODS: A systematic research was conducted in September 2018 by using PubMed and Google Scholar databases to search for science literature published after 1988. RESULTS: In all, 7 eligible articles were identified, including 4 randomized controlled studies and 3 observational studies. Due to high heterogeneities and limited number of studies, meta-analysis was not feasible, and only systematic review was performed. The results show that present evidence cannot claim melatonin's effectiveness according to the conflicting outcomes; however, the two negative outcomes of melatonin not different from placebo and melatonin inferior to amitriptyline are possible under-powering because of methodological, pharmacological, and therapeutic shortcomings. Observational studies also support melatonin's efficacy in migraine. As a result, melatonin is very likely to benefit migraine in prophylaxis and may have a similar effectiveness to other main preventive medications. Immediate-release melatonin 3 mg was established as effective, melatonin receptor agonist (Agomelatine) 25 mg and prolonged-release melatonin 4 mg were observed efficacious in observational studies. Melatonin displayed ineffective in the 2-month trial; thus, 3 months or more may be an enough duration for migraine therapy. Despite melatonin being generally safe, emerging literature is illustrating that a few severe adverse effects can be caused by melatonin, for example, liver injuries, reproductive system dysfunctions, and detrimental immunostimulation. CONCLUSIONS: Melatonin is very likely to be a promising alternative for migraine prophylaxis. Current literature examining melatonin's efficacy in migraine prevention is growing, but still limited. Future studies of perfect design in methodology, pharmacology, and therapeutics are needed to achieve a deeper awareness of melatonin's role in migraine as well as more studies to explore the safety issues of melatonin medicine.