Raddeanin A Protects the BRB Through Inhibiting Inflammation and Apoptosis in the Retina of Alzheimer's Disease.

Neuroinflammation and endothelial cell apoptosis are prominent features of blood-brain barrier (BBB) disruption, which have been described in Alzheimer's disease (AD) and can predict cognitive decline. Recent reports revealed vascular ß-amyloid (Aß) deposits, Muller cell degeneration and microglial dysfunction in the retina of AD patients. However, there has been no in-depth research on the roles of inflammation, retinal endothelial cell apoptosis, and blood-retinal barrier (BRB) damage in AD retinopathy. We found that Raddeanin A (RDA) could improve pathological and cognitive deficits in a mouse model of Alzheimer's disease by targeting ß-amyloidosis, However, the effects of RDA on AD retinal function require further study. To clarify whether RDA inhibits inflammation and apoptosis and thus improves BRB function in AD-related retinopathy. In vitro we used Aß-treated HRECs and MIO-M1 cells, and in vivo we used 3×Tg-AD mice to investigate the effect of RDA on BRB in AD-related retinopathy. We found that RDA could improve BRB function in AD-related retinopathy by inhibiting NLRP3-mediated inflammation and suppressing Wnt/ß-catenin pathway-mediated apoptosis, which is expected to improve the pathological changes in AD-related retinopathy and the quality of life of AD patients.

CERS4 predicts positive anti-PD-1 response and promotes immunomodulation through Rhob-mediated suppression of CD8+Tim3+ exhausted T cells in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is one of the main malignant tumors with high mortality and short survival time. Immunotherapy has become the standard treatment for advanced NSCLC, but it has the problems of drug resistance and low response rate. Therefore, obtaining effective biomarkers to predict and enhance immune checkpoint inhibitors (ICIs) efficacy in NSCLC is important. Sphingolipid metabolism is recently found to be closely involved in tumor immunotherapy. CERS4, an important sphingolipid metabolizing enzyme, is positively correlated with the efficacy of anti-PD-1 therapy for NSCLC. Upregulation of CERS4 expression could improve the efficacy of anti-PD-1 therapy for NSCLC. High expression of CERS4 could downregulate the expression of Rhob in tumor. Significantly, the ratio of CD4+/CD8+ T cell increased and the ratio of Tim-3+/CD8+ T cell decreased in spleen and peripheral blood cells. When Rhob was knocked out, the efficacy of PD-1 mAb treatment increased, and the frequency of Tim-3+ CD8+ T cell decreased. This finding further confirmed the role of sphingolipid metabolites in regulating the immunotherapeutic function of NSCLC. These metabolites may improve the efficacy of PD-1 mAb in NSCLC by regulating the CERS4/Rhob/Tim-3 axis. Overall, this study provided a potential and effective target for predicting and improving the efficacy of ICIs for NSCLC. It also provided a new perspective for the study on the mechanisms of ICIs resistance for NSCLC.

The rhizospheric transformation and bioavailability of mercury in pepper plants are influenced by selected Chinese soil types.

Understanding and prediction of mercury (Hg) phytoavailability in vegetable-soil systems is essential for controlling food chain contamination and safe vegetable production as Hg-contaminated soils pose a serious threat to human health. In this study, four typical Chinese soils (Heilongjiang, Chongqing, Yunnan, and Jilin) with varied physicochemical properties were spiked with HgCl2 to grow sweet pepper (Capsicum annuum L.) in a pot experiment under greenhouse condition. The chemical fractionation revealed a significant decrease in exchangeable Hg, while an increase in organically bound Hg in the rhizosphere soil (RS) compared to bulk soil (BS). This observation strongly highlights the vital role of organic matter on the rhizospheric Hg transformation irrespective of contamination levels and soil properties. Stepwise multiple linear regression (SMLR) analysis between Hg concentration in plants, Hg fractions in RS and BS, and soil properties showed that Hg in plant parts was significantly influenced by soil total Hg (THg) (R2 = 0.90), soil clay (R2 = 0.99), amorphous manganese oxides (amorphous Mn) (R2 = 0.97), amorphous iron oxides (amorphous Fe) (R2 = 0.70), and available Hg (R2 = 0.97) in BS. Nevertheless, in the case of RS, Hg accumulation in plants was affected by soil THg (R2 = 0.99), amorphous Mn (R2 = 0.97), amorphous Fe oxides (R2 = 0.66), soil pH, and organically bound Hg fraction (R2 = 0.96). Among all the evaluated soils (n = 04), metal (mercury) concentration in terms of plant uptake was reported highest in the Jilin soil. Based on SMLR analysis, the results suggested that the phytoavailability of Hg was mainly determined by THg and metal oxides regardless of the rhizospheric effect. These findings facilitate the estimation of Hg phytoavailability and ecological risk that may exist from Hg-contaminated areas where pepper is the dominant vegetable.

Mass spectrometry-based proteomic analysis of potential infectious bursal disease virus VP3-interacting proteins in chicken embryo fibroblasts cells.

The structural protein VP3 of infectious bursal disease virus (IBDV) plays a critical role in viral assembly, replication, immune escape, and anti-apoptosis. Interaction between VP3 and host protein factors can affect stages in the viral replication cycle. In this study, 137 host proteins interacting with VP3 protein were screened through liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based proteomics approach. The functions and relevance of the proteins were obtained through bioinformatics analysis. Most VP3-interacting proteins were linked to binding, catalytic activity, and structural molecular activity, and performed functions in cell parts and cells. Biological functions of VP3-interacting proteins were mainly relevant to "Cytoskeleton", "Translation", and "Signal transduction mechanisms", involving ribosomes, "Tight junction", regulation of actin cytoskeleton, and other pathways. Six potential VP3-interacting proteins in host cells were knocked down, and vimentin, myosin-9, and annexin A2 were found to be related to IBDV replication. This study would help explore regulatory pathways and cellular mechanisms in IBDV-infected cells, and also provided clues for the in-depth study of VP3 biological functions and IBDV replication or pathogenesis.

Comparison of three concentrations of ropivacaine in posterior quadratus lumborum block: A randomized clinical trial.

Background: A conclusive evidence regarding the optimal concentration and volume of local anesthetic for quadratus lumborum block is lacking. Methods: In this single-center, prospective, randomized, controlled study, 60 patients scheduled for laparoscopic colorectal surgery were randomly assigned to 3 different combinations of volume and concentration of ropivacaine (3 mg/kg) - Group 0.25%, Group 0.375% and Group 0.5%. All subjects received ultrasound-guided posterior quadratus lumborum block prior to the induction. The primary outcome was the complete sensory block rate of surgical site measured at 30 min after quadratus lumborum block, after extubation, at 12, 24, and 48 h after operation. Secondary outcomes were the changes in hemodynamic parameters before and after incision (ΔSBP, ΔDBP and ΔHR), postoperative pain score, the sufentanil consumption after surgery, length of stay and adverse reactions. Results: The sensory block rate of surgical site at 5 time points differed significantly among the three groups (P < 0.001). Both Group 0.375% (P < 0.001) and Group 0.5% (P < 0.001) had a higher sensory block rate than Group 0.25%, but no significant difference was observed between the former two. Group 0.375% and Group 0.5% had lower postoperative pain scores, lower sufentanil consumption after surgery and shorter length of stay. No statistical difference was observed in ΔSBP, ΔDBP, ΔHR and the incidence of adverse reactions. Conclusions: 0.375% and 0.5% ropivacaine in posterior quadratus lumborum block provide better sensory block of surgical site when compared to 0.25% in laparoscopic colorectal surgery. Trial registration number: Chinese Clinical Trials Registry (ChiCTR2100043949).

[Change and significance of Th22 cells in patients with aplastic anemia].

OBJECTIVE: To explore the proportion of Th22 cells in peripheral blood of patients with aplastic anemia (AA) and evaluate its significance. METHODS: From January 2011 to June 2012, a total of 47 AA patients were recruited and divided into 4 groups: severe aplastic anemia (SAA) pre-therapy (group A, n = 11), non-severe aplastic anemia (NSAA) pre-therapy (group B, n = 12), SAA post-therapy (group C, n = 12), NSAA post-therapy (group D, n = 12) and healthy donor controls (n = 12). The proportion of Th22 cells in peripheral blood of each group was evaluated by flow cytometry. The cytokines interleukin-22 (IL-22), transforming growth factor-ß (TGF-ß), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were measured by ELISA. And the level of IL-22 mRNA was examined by reverse transcription-PCR (RT-PCR). RESULTS: The percentage of Th22 cells and the level of IL-22, TNF-α, IL-6 and IL-22 mRNA in group A (4.3% ± 1.4%, (57 ± 17) ng/L, (497 ± 123) ng/L, (323 ± 88) ng/L, 1.65 ± 0.51) and group C (2.6% ± 0.6%, (34 ± 10) ng/L, (314 ± 79) ng/L, (187 ± 45) ng/L, 0.92 ± 0.28) were significantly higher than that in control group (1.2% ± 0.3%, (19 ± 6) ng/L, (228 ± 50) ng/L, (134 ± 26) ng/L, 0.47 ± 0.09,all P < 0.05). The percentage of Th22 cells and the level of IL-22, TNF-α , IL-6 and IL-22 mRNA in group A were higher than those in group C (all P < 0.05). NSAA patients had similar results. The percentage of Th22 cells and the level of IL-22, TNF-α , IL-6 and IL-22 mRNA in group A were higher than those in group B (all P < 0.05). But the level of TGF-ß in groups A and C were significantly lower than that in control group ((3.4 ± 1.1) and (5.8 ± 1.7) vs (9.7 ± 2.8) ng/L, P < 0.05). And the level of TGF-ß in group A was lower than that of group B (P < 0.05). CONCLUSIONS: The number of Th22 cells is elevated in AA patients. Th22 cells may be positively correlated with the development of AA. And a higher level of TNF-α, IL-6 and a lower level of TGF-ß promote the differentiation of Th22 cells.

Clinical Effect of Lamivudine Combined with Leflunomide and Methylprednisolone Tablets in the Treatment of Hepatitis B Virus-Associated Glomerulonephritis and Its Influence on Renal Function Indicators.

BACKGROUND: In this study, the clinical effect of lamivudine combined with leflunomide and methylprednisolone in the treatment of hepatitis B virus-associated glomerulonephritis (HBV-GN) and their influence on renal function indexes was explored. METHODS: Patients with HBV-GN were selected for retrospective analysis and divided into the group B and group A, with 41 cases in each group. The group B was given leflunomide and methylprednisolone, whereas the group A was supplemented with lamivudine. The level of 24 h proteinuria (PRO), albumin (ALB), beta2-microglobulin (ß2-MG), alanine aminotransferase (ALT), interferon-gamma (IFN-γ) and interleukin-4 (IL-4) in two groups was measured. The clinical efficacy, adverse reactions appetite, spirit, sleep and daily life scores of the two groups were recorded. RESULTS: With the extension of treatment time to end of the treatment, the level of 24 h PRO, ALB and ß2-MG in the group A significantly changed compared with that before treatment (p < 0.05). Moreover, the level of ALT, IFN-γ and IL-4 in the two groups significantly decreased compared with that before treatment, and the level of the three indexes in the group A decreased more significantly (p < 0.05). The total effective rate in the group A was higher than that in the group B (p < 0.05). The occurrence of adverse reactions showed no statistically significant difference between the two groups. After treatment, scores of appetite, spirit, sleep and daily living were increased in the two groups, and the increase in the group A was more significant than that in the group B (p < 0.05). CONCLUSIONS: Lamivudine combined with methylprednisolone and leflunomide treatment is conducive to clearing Hepatitis B virus (HBV) and improving renal function.

Correction: Highly photoluminescent nitrogen-rich carbon dots from melamine and citric acid for the selective detection of iron(iii) ion.

[This corrects the article DOI: 10.1039/C5RA26521E.].

Effect of non-mechanical bowel preparation on postoperative gastrointestinal recovery following surgery on malignant gynecological tumors: A randomized controlled trial.

OBJECTIVE: To investigate the efficacy and safety of non-mechanical bowel preparation (non-MBP) in patients undergoing surgery for malignant gynecological tumors. METHODS: Patients undergoing surgery for a gynecological malignancy (n = 105) were randomized to receive mechanical bowel preparation (MBP) or non-MBP. Parameters indicating postoperative gastrointestinal function recovery were the primary outcomes. The secondary outcomes included the number of postoperative complaints, the plasma levels of D-lactate and diamine oxidase (DAO), ease of visualization of the surgical field, involuntary defecation during surgery, operation time, wound healing, surgical site infection, length of hospital stay, and tolerance to MBP. RESULTS: The participants in the non-MBP group exhibited shorter time intervals until the first postoperative bowel movement (27.87 vs. 29.48 h), first passage of flatus (50.96 vs. 55.08 h), and first passage of stool (75.94 vs. 98.50 h) compared with the MBP group, while they also exhibited fewer postoperative gastrointestinal symptoms, including nausea (18.9% vs. 38.5%), vomiting (26.4% vs. 51.9%), abdominal pain (34.0% vs. 78.9%), and bloating (3.8% vs.26.9%). The plasma D-lactate and DAO levels were significantly increased following bowel preparation compared with the baseline levels in the MBP group (2.93 vs. 5.68 nmol/mL and 20.46 vs. 54.49 ng/mL, respectively), but no such differences were observed in the non-MBP group. Compared with the MBP group, surgical field visualization was superior (92.45% vs. 78.85%), and the operation time was shorter (173.58 vs. 203.88 min) in the non-MBP group. The patients undergoing MBP complained of bloating (182.35%), an unpleasant taste (78.43%), sleep disturbance (70.59%), nausea (68.63%), abdominal pain (64.71%), vomiting (45.10%), polydipsia (33.33%), dizziness (25.49%), and headache (7.84%). CONCLUSIONS: The use of non-MBP in patients undergoing surgery for gynecological malignancies is more conducive to the postoperative recovery of gastrointestinal function.

[Clinical Observation of Venetoclax Combined with Demethylating Agents on the Treatment of Relapsed/Refractory Acute Myeloid Leukemia].

OBJECTIVE: To investigate the efficacy and safety of venetoclax (VEN) combined with demethylating agents (HMA) in the treatment of relapsed/refractory acute myeloid leukemia (R/R AML). METHODS: The clinical data of 26 adult R/R AML patients who received the combination of VEN with azacitidine (AZA) or decitabine (DAC) in Huai'an Second People's Hospital from February 2019 to November 2021 were retrospectively analyzed. The treatment response, adverse events as well as survival were observed, and the factors of influencing the efficacy and survival were explored. RESULTS: The overall response rate (ORR) of 26 patients was 57.7% (15 cases), including 13 cases of complete response (CR) and CR with incomplete count recovery (CRi) and 2 cases of partial response (PR). Among the 13 patients who got CR/CRi, 7 cases achieved CRm (minimal residual disease negative CR) and 6 cases did not, with statistically significant differences in overall survival (OS) and event-free survival (EFS) between the two groups (P=0.044, 0.036). The median OS of all the patients was 6.6 (0.5-15.6) months, and median EFS was 3.4 (0.5-9.9) months. There were 13 patients in the relapse group and refractory group, respectively, with response rate of 84.6% and 30.8% (P=0.015). The survival analysis showed that the relapse group had a better OS than the refractory group (P=0.026), but there was no significant difference in EFS (P=0.069). Sixteen patients who treated for 1-2 cycles and 10 patients who treated for more than 3 cycles achieved response rates of 37.5% and 90.0%, respectively (P=0.014), and patients treated for more cycles had superior OS and EFS (both P<0.01). Adverse effects were mainly bone marrow suppression, complicated by various degrees of infection, bleeding, and gastrointestinal discomfort was common, but these could be all tolerated by patients. CONCLUSION: VEN combined with HMA is an effective salvage therapy for patients with R/R AML and is well tolerated by patients. Achieving minimal residual disease negativity is able to improve long-term survival of patients.

Age-related self-DNA accumulation may accelerate arthritis in rats and in human rheumatoid arthritis.

The incidence of rheumatoid arthritis (RA) is increasing with age. DNA fragments is known to accumulate in certain autoimmune diseases, but the mechanistic relationship among ageing, DNA fragments and RA pathogenesis remain unexplored. Here we show that the accumulation of DNA fragments, increasing with age and regulated by the exonuclease TREX1, promotes abnormal activation of the immune system in an adjuvant-induced arthritis (AIA) rat model. Local overexpression of TREX1 suppresses synovial inflammation in rats, while conditional genomic deletion of TREX1 in AIA rats result in higher levels of circulating free (cf) DNA and hence abnormal immune activation, leading to more severe symptoms. The dysregulation of the heterodimeric transcription factor AP-1, formed by c-Jun and c-Fos, appear to regulate both TREX1 expression and SASP induction. Thus, our results confirm that DNA fragments are inflammatory mediators, and TREX1, downstream of AP-1, may serve as regulator of cellular immunity in health and in RA.

Comparative effects of liensinine and neferine on the human ether-a-go-go-related gene potassium channel and pharmacological activity analysis.

Liensinine and neferine, a kind of isoquinoline alkaloid, can antagonize the ventricular arrhythmias. The human ether-a-go-go-related gene (hERG) is involved in repolarization of cardiac action potential. We investigated the effects of liensinine and neferine on the biophysical properties of hERG channel and the underlying structure-activity relationships. The effects of liensinine and neferine were examined on the hERG channels in the stable transfected HEK293 cells using a whole-cell patch clamp technique, western blot analysis and immunofluorescence experiment. The pharmacokinetics and tissue distribution determination of liensinine and neferine in rats were determined by a validated RP-HPLC method. Liensinine and neferine induced decrease of current amplitude in dose-dependent. Liensinine reduced hERG tail current from 70.3±6.3 pA/pF in control group to 56.7±2.8 pA/pF in the 1 µM group, 53.0±2.3 pA/pF (3 µM) and 17.8±0.7 pA/pF (30 µM); the corresponding current densities of neferine-treated cells were 41.9±3.1 pA/pF, 32.3±3.1 pA/pF and 16.2±0.6 pA/pF, respectively. Neferine had binding affinity for the open and inactivated state of hERG channel, liensinine only bound to the open state. The inhibitory effects of liensinine and neferine on hERG current were attenuated in the F656V or Y652A mutant channels. Neferine distributed more quickly than liensinine in rats, which was found to be in higher concentration than liensinine. Both liensinine and neferine had no effect on the generation and expression of hERG channels. In conclusion, neferine is a more potent blocker of hERG channels than liensinine at low concentration (<10 µM), which may be due to higher hydrophobic nature of neferine compared with liensinine. Neferine may be safety even for long-term treatment as an antiarrhythmic drug.

The key role of sphingolipid metabolism in cancer: New therapeutic targets, diagnostic and prognostic values, and anti-tumor immunotherapy resistance.

Biologically active sphingolipids are closely related to the growth, differentiation, aging, and apoptosis of cancer cells. Some sphingolipids, such as ceramides, are favorable metabolites in the sphingolipid metabolic pathway, usually mediating antiproliferative responses, through inhibiting cancer cell growth and migration, as well as inducing autophagy and apoptosis. However, other sphingolipids, such as S1P, play the opposite role, which induces cancer cell transformation, migration and growth and promotes drug resistance. There are also other sphingolipids, as well as enzymes, played potentially critical roles in cancer physiology and therapeutics. This review aimed to explore the important roles of sphingolipid metabolism in cancer. In this article, we summarized the role and value of sphingolipid metabolism in cancer, including the distribution of sphingolipids, the functions, and their relevance to cancer diagnosis and prognosis. We also summarized the known and potential antitumor targets present in sphingolipid metabolism, analyzed the correlation between sphingolipid metabolism and tumor immunity, and summarize the antitumor effects of natural compounds based on sphingolipids. Through the analysis and summary of sphingolipid antitumor therapeutic targets and immune correlation, we aim to provide ideas for the development of new antitumor drugs, exploration of new therapeutic means for tumors, and study of immunotherapy resistance mechanisms.

The effect of age on the clinical and immune characteristics of critically ill patients with COVID-19: A preliminary report.

BACKGROUND: In December 2019, a new disease named coronavirus disease 2019 (COVID-19) was occurred. Patients who are critically ill with COVID-19 are more likely to die, especially elderly patients. We aimed to describe the effect of age on the clinical and immune characteristics of critically ill patients with COVID-19. METHODS: We retrospectively included 32 patients with COVID-19 who were confirmed to have COVID-19 by the local health authority and who were admitted to the first affiliated hospital of Zhengzhou University in Zhengzhou, China between January 3 and March 20, 2020. Clinical information and experimental test data were retrospectively collected for the patients. The 32 patients in this study were all in a critical condition and were classified as severe, according to the guidelines of 2019-nCoV infection from the National Health Commission of the People's Republic of China. Data were compared between those <60 years old and ≥60 years old. RESULTS: Of 32 patients, 13 were under 60 years old, and 19 patients were ≥60 years old. The most common symptom among all patients upon admission was fever (93.8%, 30/32). Compared to younger patients, older patients exhibited increased comorbidities. Among patients who were 60 years and older, platelet count, direct bilirubin (DBIL), indirect bilirubin(IBIL), lactate dehydrogenase (LDH), B-type natriuretic peptide (BNP), C-reactive protein (CRP), procalcitonin (PCT), and interleukin-10 (IL-10) were significantly higher than in younger patients who were less than 60 years old. CD4+ T lymphocytes, CD8+ T lymphocytes, and NKT lymphocytes were decreased, CD4+/CD8+ T lymphocytes were significantly increased in all 32 patients, while there were no evident differences between younger and older patients. The CURB-65 (confusion, urea, respiratory, rate, blood pressure plus age ≥65 years), Acute Physiology and Chronic Health Evaluation (APACHE) II and pH value were significantly higher in older patients than in patients who were under 60 years old. However, the PaO2 and PaO2:FiO2 were lower in older patients than the younger. Compared to patients under 60 years old, patients who were 60 years and older tended to develop ARDS (15 [78.9%] vs 5 [38.5%]), septic shock (7 [36.8%] vs 0 [0.0%]) and were more likely to receive mechanical ventilation (13 [68.4%] vs 3[23.1%]). Dynamic trajectories of seven laboratory parameters were tracked on days 1, 3, 5 and 7, and significant differences in lymphocyte count (P = 0.026), D-dimer (P = 0.010), lactate dehydrogenase (P = 0.000) and C-reactive protein (P = 0.000) were observed between the two age groups. CONCLUSIONS: A high proportion of critically ill patients were 60 or older. Furthermore, rapid disease progression was noted in elderly patients. Therefore, close monitoring and timely treatment should be performed in elderly COVID-19 patients.

[The Clinical Features of Metabolic Syndrome in Receptors of Hematopoietic Stem Cells].

OBJECTIVE: To evaluate the incidence and clinical characteristics of metabolic syndrome (MS) within one year after hematopoietic stem cell transplantation (HSCT) in order to screen the risk factors for HSCT-MS, provide early intervention and improve the long-term quality of survival of patients. METHODS: The clinical follow-up data of 64 HSCT patients (survival time > 1 year) who received HSCT in our center from January 2007 to August 2018 were collected. Among them, 50 cases were allogeneic hematopoietic stem cell transplantation (allo-HSCT) and 14 cases were autologous hematopoietic stem cell transplantation (auto-HSCT). The changes of MS-related indexes and clinical characteristics before and 1, 3, 6 and 12 months after HSCT were analyzed retrospectively. RESULTS: In allo-HSCT group, 14 cases were diagnosed as MS before operation, including high-density lipoprotein cholesterol (hypo-HDL-C)> hyper triglycerides（hyper-TG）> hyper fasting glucose（hyper-FBG）> abdominal obesity (AO) > hypertension. The preoperative diagnosis of MS in the auto-HSCT group was 5 cases, in the order of hyper-FBG> hyper-TG> AO> hypo-HDL-C> hypertension. Incidence of MS at 1, 3, 6 and 12 months after transplantation: 19, 26, 24 and 20 cases in the allo-HSCT group, respectively; auto-HSCT group were 7, 7, 6 and 6 cases, respectively. Hyper-TG and hypo-HDL-C were prominent in both groups. CONCLUSION: The incidence of HSCT-MS is significantly higher within 1 year after HSCT. Regardless of allo-HSCT and auto-HSCT, the prevention and control of HSCT-MS is emphasized as an important guarantee to improve the long-term survival quality of HSCT patients.

[Clinical characteristics and prognostic factors of adult patients with acute respiratory failure due to influenza infection].

OBJECTIVE: To investigate the clinical characteristics and prognostic predictors of adult patients with acute respiratory failure due to influenza infection. METHODS: A retrospective analysis was performed on adult patients with acute respiratory failure due to confirmed influenza infection admitted to intensive care units (ICU) of the First Affiliated Hospital of Zhengzhou University and the Sixth People's Hospital of Zhengzhou between January 2018 and January 2020. The subjects were divided into survival and death groups according to whether the patients died before discharge. Demographic and clinical data including underlying conditions, laboratory variables, therapy and prognostic factors of hospital mortality between the two groups were analyzed. The risk factors of mortality were evaluated by univariate and multivariate Logistic regression analysis. Then, the correlation between lymphocyte (LYM) count and LYM subsets were analyzed. The survival rates of different acute physiologic and chronic health evaluation II (APACHE II) and LYM level subgroups were compared. RESULTS: A total of 104 patients were enrolled. Among them, 67 cases (64.4%) had underlying conditions, 91.3% of the patients (95 cases) were infected by influenza A virus, and the hospital mortality rate was 39.4% (41 cases). Compared with survival group, the patients of death group had higher respiratory rate (times/min: 26.0±5.6 vs. 23.7±5.0), APACHE II score (18.20±4.88 vs. 12.35±4.58), procalcitonin [PCT (µg/L): 0.82 (0.23, 4.63) vs. 0.39 (0.11, 0.92)], higher percentage of cardiovascular disease [24.4% (10/41) vs. 7.9% (5/63)] and invasive mechanical ventilation [63.4% (26/41) vs. 17.5% (11/63), all P < 0.01], but had lower oxygenation index [PaO2/FiO2 (mmHg, 1 mmHg = 0.133 kPa): 131.8±34.5 vs. 181.7±31.6] at ICU admission, LYM (×109/L: 0.53±0.40 vs. 0.92±0.44), hemoglobin [Hb (g/L): 105.66±28.17 vs. 118.29±28.29], platelet count [PLT (×109/L): 135.12±85.40 vs. 199.81±110.11], T lymphocyte count [cells/µL: 181 (131, 275) vs. 319 (238, 528)], CD4+ count [cells/µL: 110 (71, 161) vs. 190 (120, 311)] and CD8+ count [cells/µL: 71 (33, 100) vs. 121 (81, 188), all P < 0.01]. Patients of death group also had a shorter length of hospital stay [days: 7.0 (4.0, 11.0) vs. 12.0 (8.0, 20.0), P < 0.01]. Univariate analysis showed that APACHE II score [odds ratio (OR) = 1.207, 95% confidence interval (95%CI) was 1.094-1.332, P < 0.001], LYM (OR = 0.070, 95%CI was 0.018-0.271, P < 0.001), Hb (OR = 0.984, 95%CI was 0.970-0.999, P = 0.031), PLT (OR = 0.992, 95%CI was 0.987-0.997, P = 0.003), T lymphocyte count (OR = 0.996, 95%CI was 0.993-0.998, P = 0.001) and PaO2/FiO2 (OR = 0.955, 95%CI was 0.938-0.972, P < 0.001) were the risk factors for the prognosis of influenza patients with acute respiratory failure. Further multivariate Logistic analysis also showed that APACHE II score (OR = 1.195, 95%CI was 1.041-1.372, P = 0.011), LYM (OR = 0.063, 95%CI was 0.011-0.369, P = 0.002) and PaO2/FiO2 (OR = 0.953, 95%CI was 0.933-0.973, P < 0.001) were the predictors of mortality. Moreover, patients with peripheral blood LYM < 0.65×109/L or APACHE II score > 14 had a higher risk of poor outcome. There were significantly positive correlation between LYM and LYM subsets (T lymphocyte, CD4+ and CD8+ lymphocyte, r value was 0.593, 0.563, and 0.500, respectively, all P < 0.001). CONCLUSIONS: Influenza patients with acute respiratory failure were critically ill and had a high mortality rate. APACHE II score, PaO2/FiO2 and LYM at ICU admission were independent risk factors affecting the prognosis of patients.

Association between the gut microbiota and patient responses to cancer immune checkpoint inhibitors.

Studies are increasingly investigating the association between the gut microbiota and the outcomes of immunotherapy in patients with cancer. Notably, certain studies have demonstrated that the gut microbiota serves a key role in regulating a patient's response to immunotherapy. In the present review, the potential associations between the gut microbiota, and cancer, host immunity and cancer immunotherapy are reviewed. Furthermore, the effects of fecal microbiota transplantation, antibiotics, probiotics, prebiotics, synbiotics, components of traditional Chinese medicine and various lifestyle factors on the gut microbiota and cancer immunotherapy outcomes are discussed. Certain dominant bacterial groups in the context of cancer immunotherapy and certain effective methods for optimizing immunotherapy by regulating the gut microbiota have been identified. Further investigation may enable the rapid conversion of these discoveries into practical products and clinically applicable methods.

[Effects of Nitrogen Fertilizer and Straw Returning Methods on N2O Emissions in Wheat-Maize Rotational Soils].

In order to explore the impacts of nitrogen fertilizer and straw returning methods on N2O emissions, a two-factor split-zone design was adopted for experimentation under the winter wheat-summer maize rotation model in the Guanzhong area of Shanxi, China. The main areas of interest were conventional nitrogen (G) and reduced nitrogen (70% G); the sub-areas were straw no return (N), straw return (S), and straw return + biochar (SB); we analyzed their impacts on N2O emissions and crop yield, and the relationships with related impact factors. The results showed that the N2O emissions peaks appeared in the wheat season and maize season treatments within 5-16 days after fertilization, and also appeared after rainfall. The N2O flux was significantly and positively correlated with soil temperature and NH4+-N content. Regardless of the wheat season, maize season, or annual total N2O emissions, the 70% GSB treatment was the lowest and the GS treatment was the highest. At the same level of nitrogen application, S treatment increased N2O emissions, SB treatment could reduce N2O emissions, both S and SB treatments could significantly increase crop yields, and SB production increased more; 70%G-level annual N2O emissions, when compared with the G level, had been reduced by 40% to 48%, while the yield has not decreased significantly. Through comprehensive consideration, a reduction of nitrogen by 30% was achieved through the combination of straw + biochar on the basis of conventional nitrogen application, while ensuring high crop yields and the best N2O emissions reduction.

Intrathoracic infusion therapy with Lentinan and chemical irritants for malignant pleural effusion: a systematic review and meta-analysis of 65 randomized controlled trials.

BACKGROUND: Aderivative of Shiitake mushrooms, Lentinan is used to control malignant pleural effusion (MPE) through intrathoracic infusion. PURPOSE: To determine the clinical response, survival and safety of Lentinan plus chemical irritants, and the optimal combinations with chemical irritants, indication, threshold and optimal regimen for achieving the desired responses. STUDY DESIGN: We performed a new systematic review and meta-analysis following the PRISMA guidelines. METHODS: We collected all randomized controlled trials (RCTs) regarding Lentinan plus chemical irritants from Chinese and English electronic databases (from inception until March 2019). We evaluated their bias risk, synthesized data using meta-analysis, and summarized evidence quality following the Grades of Recommendation Assessment, Development and Evaluation approach. RESULTS: We included 65 RCTs involving 4,080 patients and nine chemical irritants. Most trials had unclear bias risk. Lentinan with cisplatin significantly improved complete response [Risk ratio (RR) = 1.68, 95% confidence intervals (CI) (1.51 to 1.87), p < 0.00001, Fig.3a] and quality of life [RR = 1.51 95% CI (1.41 to 1.62), p < 0.00001, Fig.4], and decreased the risk of treatment failure, myelosuppression, gastrointestinal reaction, and chest pain. For patients with moderate to large volume of the pleural effusion, primary treatment, KPS score ≥ 50-60, or anticipated survival time ≥ 3months, Lentinan (3-4 mg/time, once a week for three to four times) withcisplatin (30-40 mg/m2 or 50-60 mg/m2) significantly improved complete response and decreased failure. Most results were robust and moderate quality. CONCLUSION: The results suggest that Lentinan with chemical irritants, especially cisplatin is beneficial to the patient with MPE, and provide evidence for the indication, threshold, and optimal regimen that may achieve success and decrease failure.

Enhanced electrochemical performance of Li-Co-BTC ternary metal-organic frameworks as cathode materials for lithium-ion batteries.

Metal-organic frameworks (MOFs) with diverse structures have been projected as futuristic electrode materials for lithium-ion batteries (LIBs). In this work, two ternary Li-Co-MOFs of three-dimensional (3D) porous structures were synthesized, inspired by LiCoO2 inorganic metal salts, through a simple solvothermal method and further applied as active cathode materials for the first time in lithium-ion batteries. In these MOF structures, the lithium atoms are located at the same (SNNU-73) or different (SNNU-76) sites as cobalt atoms, and the four-coordinated tetrahedron mode is used to coordinate with the oxygen atoms. The 3D porous frameworks provide a good channel for the embedding and de-embedding of lithium ions. The experimental results suggest that porous Li-Co-MOF ternary composites show excellent cycling stability. Particularly, the discharge capacity and average coulombic efficiency of SNNU-73 reach 155.6 mA h g-1 and nearly 100% for 50 cycles at a rate of 50 mA g-1. This synergistic effect of mixed Li and Co sites demonstrates great potential of MOFs as advanced electrode materials, and provides a promising route to designing porous materials for lithium-ion batteries in the future.