Burkholderia semiarida as Cause of Recurrent Pulmonary Infection in Immunocompetent Patient, China.

Burkholderia semiarida was previously identified solely as a plant pathogen within the Burkholderia cepacia complex. We present a case in China involving recurrent pneumonia attributed to B. semiarida infection. Of note, the infection manifested in an immunocompetent patient with no associated primary diseases and endured for >3 years.

Status and influencing factors of work stress among nurse managers in western China: a cross-sectional survey study.

AIMS: Due to the nature of their work, nurses are more prone to experiencing psychological consequences than other healthcare workers. However, evidence on the emotional burden of nurse managers in China is limited. Furthermore, perceived organizational support has been approved that can affect mental health outcomes. Therefore, this study aimed to investigate the status quo and influencing factors of nurse managers' work stress, and their possible relationship with perceived organizational support, which could further provide more countermeasures to safeguard their health. METHODS: A cross-sectional online survey of 21 secondary and tertiary hospitals was conducted in a city in Sichuan province, Southwest China, using a convenience sampling method between October and November 2022. Data were collected using the general information questionnaire, the Chinese version of the Stress Overload Scale (SOS) and the perceived Organizational Support Scale (POSS). SPSS 23.0 was applied to analyze the data. RESULTS: In total, 380 participants completed the survey. The median scores (interquartile range [IQR]) for SOS and POSS were 60.50 (50.00, 70.75) and 51.00 (44.00, 55.00), respectively. The work stress of the nurse managers was negatively correlated with perceived organizational support (P < 0.01). Multiple linear regression analysis showed that age older than 40 years, from secondary hospitals, working in emergency or pediatric wards, and professional qualification of supervisor nurse or deputy supervisor nurse, and the scores of POSS less than 51 significantly influenced the work stress of the nurse managers. CONCLUSIONS: Our study shows that nurse managers are more prone to work stress, and organizational support can effectively reduce this stress. Governments and hospital administrators should pay more attention to providing comprehensive strategies based on various risk factors to protect and promote psychological health.

The relationship between perceived organizational support and burnout in newly graduated nurses from southwest China: the chain mediating roles of psychological capital and work engagement.

BACKGROUND: Burnout affects the quality of work and health, increases the rate of turnover of newly graduated nurses, and leads to a shortage of nurse resources. Perceived organizational support (POS) can mitigate burnout, but the exact mechanism is unclear. The purpose of this study was to explore the mediating roles of psychological capital (PsyCap) and work engagement (WE) in the relationship between POS and burnout. METHODS: This is a cross-sectional study. An anonymous investigation with a convenience sampling of nurses was conducted in Sichuan province, southwest China between October 2023 and November 2023. The Perceived Organizational Support Scale, Maslach's Burnout Inventory General Survey, the Psychological Capital questionnaire, and the Utrecht Work Engagement Scale were used to collect data. SPSS 26.0 and AMOS 26.0 were applied for statistical analysis. RESULTS: A total of 995 newly graduated nurses participated in this study. The average burnout score of the nurses was 2.45 (1.06) and the incidence of burnout was 82.6%. Burnout was negatively correlated with POS (r=-0.624, p < 0.05), PsyCap (r = -0.685, p < 0.05) and WE (r = -0.638, p < 0.05). The total effect of POS on burnout (ß = 0.553) consisted of a direct effect (ß = 0.233) as well as an indirect effect (ß = 0.320) mediated through PsyCap and WE. PsyCap and WE have a chain-mediated effect between the POS of newly graduated nurses and burnout (ß = -0.056, Bootstrap 95% confidence interval (-0.008, -0.003), which represented 10.12% of the total effect. CONCLUSIONS: This study confirms that POS has a significant negative predictive effect on burnout. POS was first associated with a decrease in PsyCap, followed by a sequential decline in WE, which in turn was associated with an increase in burnout symptoms among newly graduated nurses. Hospital managers can reduce the levels of burnout of newly graduated nurses by increasing organizational support and improving PsyCap and WE.

The Prevalence and Risk Factors for Postoperative Thirst: A Systematic Review and Meta-analysis.

PURPOSE: Thirst is a symptom of dehydration and one of the main complications affecting postoperative outcomes and comfort. Persistent water scarcity can have a detrimental effect on the cognitive function and psychology of patients. However, the current evidence about the prevalence and risk factors for postoperative thirst is not fully understood. Therefore, this study aims to investigate the prevalence and risk factors of postoperative thirst and provide guidance for clinical practice. DESIGN: Systematic review and meta-analysis. METHODS: We searched PubMed, Cochrane Library, Web of Science, Embase, Clinicaltrials.gov, China National Knowledge Infrastructure, and Wanfang Database. Eligible studies were evaluated using the Agency for Healthcare Research and Quality. The collected data were pooled and analyzed using Stata15.0. FINDINGS: A total of 11 cross-sectional studies were included involving 20,612 patients. Eight studies reported prevalence and the pooled prevalence of postoperative thirst was 76.8% (95% confidence interval [CI]: 0.664 to 0.858). Five studies contributed to meta-syntheses of risk factors for postoperative thirst. The results indicated that sex (odds ratio [OR] = 1.44, 95% CI = 1.13 to 1.84, I2 = 80.2%, P = .006), anesthesia drug (OR = 1.48, 95% CI = 1.06 to 2.06, I2 = 94.8%, P < .001), surgical type (OR = 0.66, 95% CI = 0.49 to 0.9, I2 = 77.9%, P = .004) were statistically associated with postoperative thirst. CONCLUSIONS: Our study shows a high prevalence of postoperative thirst. Sex, anesthesia drug, and surgical type are risk factors that influence postoperative thirst. Nurses and other health care professionals should routinely assess the postoperative thirst of patients and perform targeted interventions to alleviate their distressing symptoms and improve the quality of care.

A Systematic Review and Meta-Analysis of Risk Factors for Unplanned Intraoperative Hypothermia Among Adult Surgical Patients.

PURPOSE: Unplanned intraoperative hypothermia (UIH) is a frequent but preventable complication of surgery. Accurate identification of UIH risk factors allows nurses to minimize its negative outcomes. This study aimed to investigate the risk factors for UIH in adult surgical patients. DESIGN: Systematic review and meta-analysis METHODS: We comprehensively searched PubMed, Cochrane Central Register of Controlled Trials, Web of Science, Ovid Embase, and ClinicalTrials.gov from their inception until December 31, 2020 to identify available, related studies in English. Two authors independently extracted data from these studies. Data analysis was performed using Review Manager Version 5.3. RESULTS: This meta-analysis included 12 studies involving 15,010 patients. The combined results showed that age [mean difference (MD) = 4.85, P < .0001; I2 = 94%], body mass index (MD = - 0.76, P = .001; I2 = 59%), ambient temperature [odds ratio (OR) = 0.82, P < .001; I2 = 54%], preoperative systolic blood pressure (MD = -14.68, P < .00001; I2 = 30%), preoperative heart rate (MD = - 13.25, P < .00001; I2 = 0%), duration of anesthesia (>2 h; OR = 2.67, P < .001; I2 = 0%), and intravenous fluid administration >1,000 mL (OR = 2.02, P = .01; I2 = 77%) were significantly associated with a higher risk of UIH. CONCLUSIONS: Our study demonstrated that various risk factors contribute to the development of UIH. Perioperative nurses should understand these risk factors in order to apply evidence-based procedures and improve patient outcomes. Due to the substantial clinical heterogeneity across studies, further studies are needed to verify these findings.

Application of ultrasound-guided radial artery cannulation in paediatric patients: A systematic review and meta-analysis.

BACKGROUND: Numerous studies have demonstrated the benefits and safety of ultrasound guidance in comparison with conventional palpation for radial artery cannulation in adult patients. However, the current evidence for paediatric patients is not fully understood. OBJECTIVE: The objective of this study was to compare the efficiency and safety of ultrasound guidance with those of traditional palpation for radial artery cannulation in paediatric patients and provide convincing evidence for clinical practice. METHODS: PubMed, Cochrane Library, ClinicalTrials.gov (Min et al-2019, NCT02795468, Anantasit et al-2017, NCT02668471), China National Knowledge Infrastructure, and Wanfang Data were systematically searched from their inception until December 31, 2019, to identify relevant randomised controlled trials. Data were extracted from the included studies independently by two investigators. The primary outcome of interest was the first-attempt success rate. Review Manager Version 5.3 and trial sequential analysis (beta = 0.9) were applied to analyse the collected data. RESULTS: A total of eight randomised controlled trials involving 680 paediatric patients were included in this study. The pooled findings showed that ultrasound-guided radial artery cannulation, in comparison with traditional palpation, can significantly improve the first-attempt success rate (relative risk [RR] = 1.65, 95% confidence interval [CI] = 1.36-2.01, P < 0.00001). Trial sequential analysis indicated that this available evidence was conclusive. Moreover, ultrasound guidance was associated with an increased total success rate (RR = 1.38, 95% CI = 1.15-1.66, P = 0.0004), a decreased mean procedural time (standardised mean difference = -0.89, 95% CI = -1.52 to -0.25, P = 0.006), and incidence of haematoma (RR = 0.19, 95% CI = 0.10-0.35, P < 0.00001). CONCLUSION: Ultrasound-guided radial arterial cannulation in paediatric patients is associated with improved first-attempt success rates, total success rates, and mean procedural time and decreased incidence of haematoma. The current evidence suggests that ultrasound guidance should be the standard of care for radial artery cannulation in clinical practice.

Effect of mild hypothermia on prognosis of patients with severe traumatic brain injury: A meta-analysis with trial sequential analysis.

BACKGROUND: Severe traumatic brain injury (sTBI) is a leading cause of death and neurologic disability worldwide. Although numerous previous studies have reported a positive effect of mild hypothermia treatment on sTBI, recent randomised controlled trials have not shown consistent benefits. OBJECTIVE: The objective of this study was to explore the effects of mild hypothermia on prognosis in patients with sTBI and provide the best evidence to clinical practice. METHODS: The databases PubMed, Embase, the Cochrane Library, ClinicalTrials.gov, and China National Knowledge Infrastructure (CNKI) were systematically searched from their inception to December 31, 2018, to identify relevant randomised controlled trials. Two authors independently reviewed and extracted data from included studies. The outcomes of interest were mortality and favourable neurological outcome. Review Manager, version 5.3, and trial sequential analysis (TSA) (beta = 0.9) were used to evaluate the collected data. RESULTS: A total of 15 trials involving 2523 patients with sTBI were included. The pooled results showed that there was no significant statistical difference of mortality between two groups (risk ratio [RR] = 0.94, 95% confidence interval [CI] = 0.77-1.14, P = 0.53), and TSA indicated that the current available evidence was conclusive. However, patients receiving mild hypothermia therapy had better neurological outcome than those receiving normothermia therapy (RR = 1.20, 95% CI = 1.01-1.42, P = 0.04), and TSA indicated that more studies should be conducted to clarify this issue. CONCLUSION: Our findings suggest that mild hypothermia can improve long-term neurological recovery for patients with sTBI, but which is not helpful to decrease the mortality. More well-designed rigorous clinical trials are needed to verify these results.

Identification and validation of NOLC1 as a potential target for enhancing sensitivity in multidrug resistant non-small cell lung cancer cells.

Adjuvant chemotherapy has become the frequently adopted standard therapeutic approach for non-small cell lung cancer (NSCLC). However, the development of multidrug resistance (MDR) is a major obstacle contributing to the failure of chemotherapy. This study aimed to identify genes associated with MDR development that predict tumor response to chemotherapy in NSCLC. In the present study, a multidrug-resistant NSCLC cell sub-line, A549/MDR, was established from the A549/DDP cell line and characterized. The resistance index (RI) of this subline was calculated according to the IC50 of A549/MDR relative to the parental A549/DDP cells. The gene expression profiles of A549/DDP and A549/MDR were obtained using an oligonucleotide microarray (Agilent SureHyb microarray chip). The microarray results were validated by qRT-PCR and selected genes were analyzed by in vitro loss-of-function experiments. Gene expression profiling identified 921 differentially expressed genes (DEGs) according to the selection criteria, in which 541 genes were upregulated and 380 genes were downregulated in A549/MDR compared with A549/DDP cells. We found that these DEGs are involved in diverse biological processes, including ribonucleoprotein complex, drug metabolism, the Hippo signaling pathway and transcriptional misregulation. NOLC1, as one of the identified DEGs, was confirmed to be overexpressed in A549/MDR cells and its knockdown significantly enhanced the drug sensitivity of A549/MDR cells in response to multidrug treatment. Furthermore, knockdown of NOLC1 downregulated the expression levels of drug resistance-associated molecules (LRP and MDR1) in A549/MDR cells. These findings provide a new and comprehensive expression profile of MDR in NSCLC cells. Identification and validation of NOLC1 might be a promising therapeutic strategy for the management of MDR of NSCLC patients.

Genotype Distribution and Molecular Epidemiology of Hepatitis C Virus in Guangzhou, China: Predominance of Genotype 1b and Increasing Incidence of Genotype 6a.

BACKGROUND/AIMS: Distribution of Hepatitis C virus (HCV) genotypes vary geographically and may associate with the mode of transmission. Little is known about the molecular epidemiology of HCV infection in Guangzhou, China. METHODS: A cross-sectional survey included 561 subjects with chronic HCV infection registered at Nanfang Hospital, Southern Medical University, was performed. All residents were invited for a questionnaire interview to collect information about their personal status and commercial blood donation history. RESULTS: A total of 463 chronic hepatitis C (CHC) patients were finally enrolled. Among the 463 samples, 426 were characterized by partial core-E1 sequences and classified into 7 subtypes: 1b (n=263, 61.7%), 6a (n=86, 20.2%), 2a (n=26, 6.1%), 3b (n=26, 6.1%), 3a (n=22, 5.2%), 6u (n=2, 0.5%), and 4a (n=1, 0.2%). Analysis of genotype-associated risk factors revealed that blood donation and transfusion were strongly associated with subtypes 1b and 2a, while genotype 3b and 6a were more frequent in intravenous drug users. CONCLUSIONS: Phylogeographic analyses demonstrated that the distribution of HCV genotypes in Guangzhou is complex. Interestingly, 6a has become a local endemic in Guangzhou and may be the second source region to disseminate 6a to other provinces.

A different inhibitor is required for overcoming entecavir resistance: a comparison of four rescue therapies in a retrospective study.

AIMS: Little clinical data are available regarding re-establishing the effective inhibition of entecavir (ETV)-resistant mutants. In this retrospective study, we aimed to compare the efficacies of four treatment regimens as rescue therapy for those chronic hepatitis B (CHB) patients with ETV resistance. METHODS: A total of 65 patients with ETV resistance were assigned either with tenofovir disoproxil fumarate (TDF) monotherapy (n = 21), ETV (0.5 mg) plus adefovir (ADV) combination therapy (n = 19), ETV (1.0 mg) monotherapy (n = 11) or ETV (0.5 mg) plus TDF combination therapy (n = 14). The efficacy and safety of four treatment regimens were compared. RESULTS: There were no significant differences among the four study groups in baseline characteristics, including HBV DNA levels (χ2  = 0.749, P = 0.862) and hepatitis B e antigen-positivity (χ2  = 0.099, P = 0.992). The median reduction in serum HBV DNA level from baseline at week 48 was -2.37 ± 1.07 log10 IU ml-1 , -2.16 ± 0.81 log10 IU ml-1 , -1.17 ± 1.23 log10 IU ml-1 and -2.49 ± 1.10 log10 IU ml-1 , respectively (F = 4.078, P = 0.011). The TDF group and ETV (0.5 mg) + TDF group have the highest undetectable HBV DNA rate (76.19% vs. 78.57%) compared to the ETV (0.5 mg) + ADV group and the ETV (1.0 mg) group (63.16% vs. 18.18%, respectively). Two patients in the ETV (1.0 mg) group experienced virological breakthrough at week 48 and was attributed to poor drug adherence. CONCLUSIONS: TDF monotherapy appeared to deliver the highest undetectable HBV DNA rate in patients with ETV resistance, and ADV plus ETV combination therapy could be another choice for patients with financial restraint.

Cold-inducible RNA binding protein regulates mucin expression induced by cold temperatures in human airway epithelial cells.

Mucus overproduction is an important manifestation of chronic airway inflammatory diseases, however, the mechanisms underlying the association between cold air and mucus overproduction remain unknown. We found that the expression of the cold-inducible RNA binding protein (CIRP) was increased in patients with chronic obstructive pulmonary disease (COPD). In the present study, we tested whether CIRP was involved in inflammatory factors and mucin5AC (MUC5AC) expression after cold stimulation and investigated the potential signaling pathways involved in this process. We found that CIRP was highly expressed in the bronchi of COPD patients. The expression of CIRP, interleukin-1ß (IL-1ß) and tumor necrosis factor α (TNF-α) were increased, and the CIRP was localized in cytoplasm after cold stimulation. MUC5AC mRNA and protein expression levels were elevated in a temperature- and time-dependent manner after cold stimulation and were associated with the phosphorylation of ERK and NF-κB, which reflected their activation. These responses were suppressed by knockdown of CIRP with a specific siRNA or the ERK and NF-κB inhibitors. These results demonstrated that CIRP was expressed in the bronchi of human COPD patients and was involved in inflammatory factors and MUC5AC expression after cold stimulation through the ERK and NF-κB pathways.

[Mediated mechanism of NDRG2 in the regulation of neutrophil nuclear transcription factor-κB signaling pathway through the deubiquitylating enzyme of Zc3h12d].

OBJECTIVE: To explore the role NDRG2/Zc3h12d in the regulation of neutrophil nuclear transcription factor-κB signaling pathway and the underlying mechanisms.
 METHODS: Sixteen HBE cells were incubated with lipopolysaccharide (LPS) to establish airway mucus hypersecretion model, which was transfected with NDRG2 or Zc3h12d siRNA. The cells were divided into 5 groups: a LPS+NDRG2 siRNA (Group A), a LPS+ NDRG2 and Zc3h12d siRNAs (Group B), a LPS+Zc3h12d siRNA (Group C), a LPS+ empty plasmid (Group D), and a negative control group (Group E). The reverse transcription-polymerase chain reaction (RT-PCR) was used to measure the expression level of mucin (MUC) 5AC mRNA. The levels of MUC5AC and the inflammatory factors were examined by the enzyme-linked immunosorbent assay (ELISA). The NF-κB p65 and the Zc3h12d protein levels were measured by Western blot. The MUC5C expression was further examined by laser confocal method.
 RESULTS: Compared with Group B, the levels of MUC5AC mRNA and protein in Group A were decreased (P<0.05), there was no significant difference in the MUC5AC mRNA and MUC5AC protein levels between the Group B and the Group C (P>0.05). Compared with Group D, the MUC5AC (mRNA and protein) and inflammatory factor levels in the Group A were significantly decreased (P<0.05); compared with Group E, after incubation with LPS, the levels of MUC5AC (mRNA and protein) and inflammatory factors in the Group D was increased, with significantly difference (P<0.05).
 CONCLUSION: NDRG2 can regulate the function of NF-κB signaling pathway through the deubiquitylating enzyme of Zc3h12d.

Vitamin E does not decrease the incidence of chemotherapy-induced peripheral neuropathy: a meta-analysis.

AIM OF THIS STUDY: Chemotherapy-induced peripheral neuropathy (CIPN) is a major complication of cancer patients with chemotherapy. Although many interventions have been evaluated in previous studies, findings are controversial. The aim of this meta-analysis is to assess the efficacy of vitamin E supplementation in preventing CIPN. MATERIAL AND METHODS: The electronic databases MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were systematically searched from their inception to December 31, 2013 to identify relevant randomised controlled trials. Two reviewers independently scanned and extracted the data of included studies. Review Manager 5.2 was used to analyse data. RESULTS: Six articles involving 353 patients were included in meta-analysis. The results showed that vitamin E supplementation did not appear to significantly decrease the incidence of CIPN (relative risk (RR), 0.55; 95% confidence interval (CI), 0.29 to 1.05; p = 0.07), with significant heterogeneity (I(2) = 77%). However, Vitamin E supplementation can significantly prevent cisplatin associated neurotoxicity (RR, 0.31; 95%CI, 0.17 to 0.58; p = 0.0002), with no heterogeneity (I(2) = 0%). CONCLUSIONS: Vitamin E administration dose not decrease the incidence of CIPN. However, additional randomised controlled trials using large samples are needed to confirm the role of vitamin E supplementation.

Liberal Preoperative Fasting in Adults Undergoing Elective Surgery: A Scoping Review Protocol.

Background: Prolonged fasting before surgery has negative effects on the physiology and psychology of patients. Preoperative liberal fasting proposes that patients can drink clear liquids before entering the operating theater, challenging the guideline strategy of a two-hour preoperative liquid fast for adults. In recent years, there have been an increasing number of studies on liberal preoperative fasting in adults. However, currently there is no consensus on the safe amount of fluid consumed, adverse effects, or benefits of this new policy. Objective: This scoping review protocol will map the existing evidence of liberal preoperative fasting in adults undergoing elective surgery for clinical practice, to summarize more scientific evidence to healthcare professionals when providing perioperative care. Methods and Analysis. The methodology will follow the six steps of the Arksey and O'Malley methodological framework and be guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Review. A comprehensive search of six databases will be performed from their inception to 31 May 2023 to identify suitable English studies. Two trained investigators will independently screen and extract the data, and any disagreements will be judged by a third investigator. The results of the study will be presented as graphs or tables. Ethics and Dissemination. This scoping review only examines literature in the database, without reference to human or animal studies, and therefore does not require ethical approval. The findings of this scoping review will be published in peer-reviewed journals or presented at conferences. The Registration Number. This scoping review has been registered in the Open Science Framework (https://doi.org/10.17605/OSF.IO/PMW7C).

Research trends related to emergence agitation in the post-anaesthesia care unit from 2001 to 2023: A bibliometric analysis.

Background: Emergence agitation (EA) is a behavioural disturbance encountered during the recovery phase of patients following general anaesthesia. It is characterised by restlessness, involuntary limb movements, and drainage tube withdrawal and may significantly harm patients and medical staff. The mechanism of EA has not been fully understood and is still a challenging subject for researchers. Methods: We extracted relevant publications published between 1 January 2001 and 31 December 2023 on the Web of Science Core Collection platform. VOSviewer software was utilised to analyse the retrieved literature and predict the development trends and hotspots in the field. Results: The results show that the number of publications grew annually, with China contributing the most, followed by the United States and South Korea. The co-occurrence of keywords "children," "propofol," "risk factors" are current research hotspots. Owing to its self-limiting and short-duration characteristics, EA lacks standardised clinical time guidelines and objective assessment tools, which may be the focus of future research in this field. Conclusions: Understanding the research hotspots and the latest progress in this field, this study will help to continuously improve the clinical understanding and management of EA, and help to timely identify environmental risk factors for EA in clinical practice.

Generation of an integration-free induced pluripotent stem cell line, FJMUUHi002-A, from a Rett syndrome patient with a heterozygous mutation p. R133C in MeCP2.

The human iPS cell line, hiPS-RTT (FJMUi002-A), is derived from peripheral blood mononuclear cells (PBMCs) from a 12-year-old female RTT patient carrying a heterozygous p. R133C (c.397C > T) mutation in the MeCP2 gene. The hiPS-RTT cell line was generated by non-integrative reprogramming vectors encoding OCT3/4, SOX2, KLF4, and c-MYC and was free of genomically integrated reprogramming genes. The hiPS-RTT cell line had a normal karyotype, expressed pluripotency markers, and had capacity to form three germ layers in vitro and in vivo, which offering a useful resource to study the pathogenesis and treatment strategies of RTT.

Albumin-based co-loaded sonosensitizer and STING agonist nanodelivery system for enhanced sonodynamic and immune combination antitumor therapy.

STING agonists can activate natural and adaptive immune responses, and are expected to become a new type of immunotherapy drug for tumor therapy. However, how to target deliver STING agonists to tumor tissues is a key factor affecting the efficacy of tumor treatment. Sonodynamic therapy (SDT) has become a research hotspot in the field of cancer treatment due to its non-invasive, spatiotemporally controllable, and high tissue penetration capabilities. Therefore, how to choose the appropriate drug delivery strategy, build a suitable drug delivery system to co-deliver photosensitizers and STING agonists, is a challenge faced in the tumor treatment. In this study, we developed an albumin-based nanodelivery system named FA-ICG&MnOx@HSA that co-loaded the sonosensitizers indocyanine green (ICG) and manganese oxide (MnOx). This approach achieved folate receptor-targeting mediated tumor delivery and tumor microenvironment (TME)-responsive release facilitated by high levels of glutathione (GSH) and hydrogen peroxide (H2O2), which catalyze oxygen generation to potentiate SDT efficacy in killing tumors and inducing immunogenic cell death (ICD). Simultaneously, the released Mn2+ acted as a STING agonist promoting dendritic cell maturation, IFN-ß production, and proliferation of T cells. Ultimately, this albumin based co-loaded sonosensitizer and STING agonist demonstrated promising potential for advancing tumor treatment.

Immune checkpoint reprogramming via sequential nucleic acid delivery strategy optimizes systemic immune responses for gastrointestinal cancer immunotherapy.

Monoclonal antibodies targeting immune checkpoints have been widely applied in gastrointestinal cancer immunotherapy. However, systemic administration of various monoclonal antibodies does not often result in sustained effects in reversing the immunosuppressive tumor microenvironment (TME), which may be due to the spatiotemporal dynamic changes of immune checkpoints. Herein, we reported a novel immune checkpoint reprogramming strategy for gastrointestinal cancer immunotherapy. It was achieved by the sequential delivery of siPD-L1 (siRNA for programmed cell death ligand 1) and pOX40L (plasmid for OX40 ligand), which were complexed with two cationic polymer brush-grafted carbon nanotubes (dense short (DS) and dense long (DL)) designed based on the structural characteristics of nucleic acids and brush architectures. Upon administrating DL/pOX40L for the first three dosages, then followed by DS/siPD-L1 for the next three dosages to the TME, it upregulated the stimulatory checkpoint OX40L on dendritic cells (DCs) and downregulated inhibitory checkpoint PD-L1 on tumor cells and DCs in a sequential reprogramming manner. Compared with other combination treatments, this sequential strategy drastically boosted the DCs maturation, and CD8+ cytotoxic T lymphocytes infiltration in tumor site. Furthermore, it could augment the local antitumor response and improve the T cell infiltration in tumor-draining lymph nodes to reverse the peripheral immunosuppression. Our study demonstrated that sequential nucleic acid delivery strategy via personalized nanoplatforms effectively reversed the immunosuppression status in both tumor microenvironment and peripheral immune landscape, which significantly enhanced the systemic antitumor immune responses and established an optimal immunotherapy strategy against gastrointestinal cancer.

A multicentre, randomised, double-blind, double-dummy, parallel-controlled, phase 3 clinical trial assessing the efficacy and safety of intravenous nemonoxacin malate vs. levofloxacin for community-acquired pneumonia in adult patients.

BACKGROUND: Nemonoxacin malate is a novel non-fluorinated quinolone for oral and intravenous (IV) administration. This phase 3, multicentre, randomised, double-blind, double-dummy, parallel-controlled clinical trial (NCT02205112) evaluated the efficacy and safety of IV nemonoxacin vs. levofloxacin for the treatment of community-acquired pneumonia (CAP) in adult patients. METHODS: Eligible patients were randomised to receive 500 mg nemonoxacin or levofloxacin via IV infusion, once daily for 7-14 days. The primary endpoint was the clinical cure rate at the test-of-cure (TOC) visit in the modified intent-to-treat (mITT) population. Secondary efficacy and safety were also compared between nemonoxacin and levofloxacin. RESULTS: Overall, 525 patients were randomised and treated with nemonoxacin (n = 349) or levofloxacin (n = 176). The clinical cure rate was 91.8% (279/304) for nemonoxacin and 85.7% (138/161) for levofloxacin in the mITT population (P > 0.05). The clinical efficacy of nemonoxacin was non-inferior to levofloxacin for treatment of CAP. Microbiological success rate with nemonoxacin was 88.8% (95/107) and with levofloxacin was 87.8% (43/49) (P > 0.05) at the TOC visit in the bacteriological mITT population. The incidence of drug-related adverse events (AEs) was 37.1% in the nemonoxacin group and 22.2% in the levofloxacin group. These AEs were mostly local reactions at the infusion site, nausea, elevated alanine aminotransferase/aspartate aminotransferase (ALT/AST), and QT interval prolongation. The nemonoxacin-related AEs were mostly mild and resolved after discontinuation of nemonoxacin. CONCLUSIONS: Nemonoxacin 500 mg IV once daily for 7-14 days is effective and safe and non-inferior to levofloxacin for treating CAP in adult patients.

Risk factors associated with lymphoedema among Chinese women after breast cancer surgery.

Lymphoedema is recognized as a major sequela after breast cancer treatment. This study aims to estimate the risk factors of lymphoedema development after breast cancer treatment in Chinese women. A case-control study including 100 women with lymphoedema and 130 without lymphoedema, matched on the type of surgery. Lymphoedema was defined as breast cancer patients who complained of sensations such as swelling or heaviness. The logistic regression analysis was used to examine the relationship between lymphoedema and various factors. Findings from this study show that age, overweight or obesity and radiotherapy were associated with lymphoedema development. Oncologists and nurses should provide adequate information for breast cancer survivors, especially for those who are at high-risk of developing lymphoedema.