Risk factors of transient and permanent hypoparathyroidism after thyroidectomy: a systematic review and meta-analysis.

BACKGROUND: Postoperative hypoparathyroidism (hypoPT) is a common complication following thyroid surgery. However, current research findings on the risk factors for post-thyroid surgery hypoPT are not entirely consistent, and the same risk factors may have different impacts on transient and permanent hypoPT. Therefore, there is a need for a comprehensive study to summarize and explore the risk factors for both transient and permanent hypoPT after thyroid surgery. MATERIALS AND METHODS: Two databases (PubMed and Embase) were searched from inception to 2024. The Newcastle-Ottawa Scale was used to rate study quality. Pooled odds ratios (OR) were used to calculate the relationship of each risk factor with transient and permanent hypoPT. Subgroup analyses were conducted for hypoPT with different definition-time (6 or 12 mo). Publication bias was assessed using Begg's test, and Egger's test. RESULTS: A total of 19 risk factors from the 93 studies were included in the analysis. Among them, sex and parathyroid autotransplantation were the most frequently reported risk factors. Meta-analysis demonstrated that sex (female vs. male), cN stage, central neck dissection, lateral neck dissection, extent of central neck dissection (bilateral vs. unilateral), surgery (total thyroidectomy (TT) vs. lobectomy), surgery type (TT vs. sub-TT), incidental parathyroidectomy, and pathology (cancer vs. benign) were significantly associated with transient and permanent hypoPT. Preoperative calcium and parathyroid autotransplantation were only identified as risk factors for transient hypoPT. Additionally, node metastasis and parathyroid in specimen were associated with permanent hypoPT. CONCLUSION: The highest risk of hypoPT occurs in female thyroid cancer patients with lymph node metastasis undergoing TT combined with neck dissection. The key to preventing postoperative hypoPT lies in the selection of surgical approach and intraoperative protection.

Astaxanthin Inhibits H2O2-Induced Excessive Mitophagy and Apoptosis in SH-SY5Y Cells by Regulation of Akt/mTOR Activation.

Oxidative stress, which damages cellular components and causes mitochondrial dysfunction, occurs in a variety of human diseases, including neurological disorders. The clearance of damaged mitochondria via mitophagy maintains the normal function of mitochondria and facilitates cell survival. Astaxanthin is an antioxidant known to have neuroprotective effects, but the underlying mechanisms remain unclear. This study demonstrated that astaxanthin inhibited H2O2-induced apoptosis in SH-SY5Y cells by ameliorating mitochondrial damage and enhancing cell survival. H2O2 treatment significantly reduced the levels of activated Akt and mTOR and induced mitophagy, while pretreatment with astaxanthin prevented H2O2-induced inhibition of Akt and mTOR and attenuated H2O2-induced mitophagy. Moreover, the inhibition of Akt attenuated the protective effect of astaxanthin against H2O2-induced cytotoxicity. Taken together, astaxanthin might inhibit H2O2-induced apoptosis by protecting mitochondrial function and reducing mitophagy. The results also indicate that the Akt/mTOR signaling pathway was critical for the protection of astaxanthin against H2O2-induced cytotoxicity. The results from the present study suggest that astaxanthin can reduce neuronal oxidative injury and may have the potential to be used for preventing neurotoxicity associated with neurodegenerative diseases.

Imaging-based adipose biomarkers for predicting clinical outcomes of cancer patients treated with immune checkpoint inhibitors: a systematic review.

Background: Since the application of Immune checkpoint inhibitors (ICI), the clinical outcome for metastatic cancer has been greatly improved. Nevertheless, treatment response varies in patients, making it urgent to identify patients who will receive clinical benefits after ICI therapy. Adipose body composition has proved to be associated with tumor response. In this systematic review, we aimed to summarize the current evidence on imaging adipose biomarkers that predict clinical outcomes in patients treated with ICI in various cancer types. Methods: Embase and PubMed were searched from database inception to 1st February 2023. Articles included investigated the association between imaging-based adipose biomarkers and the clinical outcomes of patients treated with ICI. The methodological quality of included studies was evaluated through Newcastle- Ottawa Quality Assessment Scale and Radiomics Quality Score tools. Results: Totally, 22 studies including 2256 patients were selected. Non-small cell lung cancer (NSCLC) had the most articles (6 studies), followed by melanoma (5 studies), renal cell carcinoma (RCC) (3 studies), urothelial carcinoma (UC) (2 studies), head and neck squamous cell carcinoma (HNSCC) (1 study), gastric cancer (1 study) and liver cancer (1 study). The remaining 3 studies investigated metastatic solid tumors including various types of cancers. Adipose biomarkers can be summarized into 5 categories, including total fat, visceral fat, subcutaneous fat, intramuscular fat and others, which exerted diverse correlations with patients' prognosis after being treated with ICI in different cancers. Most biomarkers of body fat were positively associated with survival benefits. Nevertheless, more total fat was predictable of worse outcomes in NSCLC, while inter-muscular fat was associated with poor clinical benefits in UC. Conclusion: There is relatively well-supported evidence for imaging-based adipose biomarkers to predict the clinical outcome of ICI. In general, most of the studies show that adipose tissue is positively correlated with clinical outcomes. This review summarizes the significant biomarkers proven by researches for each cancer type. Further validation and large independent prospective cohorts are needed in the future. The protocol of this systematic review has been registered at the International Prospective Register of Systematic Reviews (http://www.crd.york.ac.uk/PROSPERO, registration no: CRD42023401986).

Loss of MIR503HG facilitates papillary renal cell carcinoma associated lymphatic metastasis by triggering NOTCH1/VEGFC signaling.

Clinical lymphatic metastasis indicates an extremely poor prognosis. Patients with papillary renal cell carcinoma (pRCC) have a high probability of progressing to lymphatic metastasis. However, the molecular mechanism of pRCC-associated lymphatic metastasis has not been elucidated. In this study, we found a downregulated long non-coding RNA (lncRNA) MIR503HG in pRCC primary tumor tissues due to hypermethylation at the CpG islands within its transcriptional start site. Decreased MIR503HG expression could stimulate tube formation and migration of human lymphatic endothelial cell (HLEC) and play a central role to promote lymphatic metastasis in vivo by enhancing tumor lymphangiogenesis. MIR503HG, located in the nucleus, bound with histone variant H2A.Z and affected the recruitment of histone variant H2A.Z to chromatin. Subsequently, increasing the H3K27 trimethylation caused by MIR503HG-overexpression epigenetically downregulated the NOTCH1 expression, which ultimately resulted in decreasing VEGFC secretion and lymphangiogenesis. Additionally, downregulated MIR503HG facilitated the HNRNPC expression, which ultimately promoted the maturation of NOTCH1 mRNA. Notably, upregulating MIR503HG expression might decrease pRCC resistance to the mTOR inhibitor. Together, these findings highlighted a VEGFC-independent mechanism of MIR503HG-mediated lymphatic metastasis. MIR503HG, identified as a novel pRCC-suppressor, would serve as the potentially biomarker for lymphatic metastasis.

Development and internal validation of a novel nomogram for predicting lymph node invasion for prostate cancer patients undergoing extended pelvic lymph node dissection.

Background: Few studies have focused on the performance of Briganti 2012, Briganti 2017 and MSKCC nomograms in the Chinese population in assessing the risk of lymph node invasion(LNI) in prostate cancer(PCa) patients and identifying patients suitable for extended pelvic lymph node dissection(ePLND). We aimed to develop and validate a novel nomogram based on Chinese PCa patients treated with radical prostatectomy(RP) and ePLND for predicting LNI. Methods: We retrospectively retrieved clinical data of 631 patients with localized PCa receiving RP and ePLND at a Chinese single tertiary referral center. All patients had detailed biopsy information from experienced uropathologist. Multivariate logistic-regression analyses were performed to identify independent factors associated with LNI. The discrimination accuracy and net-benefit of models were quantified using the area under curve(AUC) and Decision curve analysis(DCA).The nonparametric bootstrapping were used to internal validation. Results: A total of 194(30.7%) patients had LNI. The median number of removed lymph nodes was 13(range, 11-18). In univariable analysis, preoperative prostate-specific antigen(PSA), clinical stage, biopsy Gleason grade group, maximum percentage of single core involvement with highest-grade PCa, percentage of positive cores, percentage of positive cores with highest-grade PCa and percentage of cores with clinically significant cancer on systematic biopsy differed significantly. The multivariable model that included preoperative PSA, clinical stage, biopsy Gleason grade group, maximum percentage of single core involvement with highest-grade PCa and percentage of cores with clinically significant cancer on systematic biopsy represented the basis for the novel nomogram. Based on a 12% cutoff, our results showed that 189(30%) patients could have avoided ePLND while only 9(4.8%) had LNI missing ePLND. Our proposed model achieved the highest AUC (proposed model vs Briganti 2012 vs Briganti 2017 vs MSKCC model: 0.83 vs 0.8 vs 0.8 vs 0.8, respectively) and highest net-benefit via DCA in the Chinese cohort compared with previous nomograms. In internal validation of proposed nomogram, all variables had a percent inclusion greater than 50%. Conclusion: We developed and validated a nomogram predicting the risk of LNI based on Chinese PCa patients, which demonstrated superior performance compared with previous nomograms.

Corrigendum: Development of a phagocytosis- dependent gene signature to predict prognosis and response to checkpoint inhibition in clear-cell renal cell carcinoma.

[This corrects the article DOI: 10.3389/fimmu.2022.853088.].

Cuproptosis identifies respiratory subtype of renal cancer that confers favorable prognosis.

Cuproptosis is a newly discovered cell death induced by excessive copper in mitochondria distinct from any known forms of apoptosis. Role of cuproptosis has not been well-reported in cancer, especially in clear-cell renal cell carcinoma (ccRCC). We comprehensively interrogated cuproptotic gene signature in ccRCC by reproducing multi-omics datasets and found cuproptosis was decreased in ccRCC compared with normal kidney. Cuproptosis identified a subgroup with significantly better prognosis. Functional annotation supported increased tricarboxylic acid cycle activity and decreased hypoxia signaling corroborated by metabolomics. Cuproptotic tumors showed decreased angiogenesis but were sensitive to Sunitinib and Sorafenib. Cuproptotic level in ccRCC cell lines showed robust negative correlation with copper ionophore Elesclomol. All findings support a respiratory subtype of ccRCC identified by cuproptosis.

Development of a Phagocytosis-Dependent Gene Signature to Predict Prognosis and Response to Checkpoint Inhibition in Clear-Cell Renal Cell Carcinoma.

Aim: The action of immune checkpoint inhibition (ICI) largely depends on antibody-dependent cellular phagocytosis (ADCP). We thus aim to develop ADCP-based ccRCC risk stratification as both prognostic and therapeutic markers of ICI. Method: Genomic data from multiple public datasets (TCGA, etc.) were integrated. A cancer-intrinsic ADCP gene set for ccRCC tailored from a recent report was constructed based on the association with prognosis, immune infiltrates, and response to ICI. Therapeutic potential was profiled using genome-drug sensitivity datasets. Results: ADCP genes were selected from a recent CRISPR/Cas9 screen report. Following a four-module panel based on clinical traits, we generated a six-gene signature (ARPC3, PHF19, FKBP11, MS4A14, KDELR3, and CD1C), which showed a strong correlation with advanced grade and stage and worsened prognosis, with a nomogram showing predictive efficacies of 0.911, 0.845, and 0.867 (AUC) at 1, 3, and 5 years, respectively. Signatures were further dichotomized, and groups with a higher risk score showed a positive correlation with tumor mutation burden, higher expressions of inhibitory checkpoint molecules, and increased antitumor immune infiltrates and were enriched for antitumor immune pathways. The high risk-score group showed better response to ICI and could benefit from TKIs of axitinib, tivozanib, or sorafenib, preferentially in combination, whereas sunitinib and pazopanib would better fit the low risk-score group. Conclusion: Here we showed a six-gene ADCP signature that correlated with prognosis and immune modulation in ccRCC. The signature-based risk stratification was associated with response to both ICI and tyrosine kinase inhibition in ccRCC.

Epidemiological Features, Risk Factors, and Disease Burden of Respiratory Viruses among Hospitalized Children with Acute Respiratory Tract Infections in Xiamen, China.

Well-established surveillance and monitoring systems for respiratory viruses need to be improved, and epidemiological data on respiratory viruses in China are scarce. This study aimed to investigate the epidemiological characteristics of respiratory viruses among hospitalized children aged ≤2 years with acute respiratory tract infections (ARTIs) in Xiamen, China, from October 2014 to September 2017. The clinical records of 7,248 children hospitalized for ARTIs were retrospectively analyzed. Respiratory syncytial virus (RSV) (22.3%) was the most common virus among hospitalized children aged ≤2 years, followed by parainfluenza (5.0%), adenovirus (3.5%), and influenza (1.7%). RSV-infected children had a higher disease burden, including a higher intensive care unit (ICU) admission rate (12.7%) and higher hospital charges ($635.36). Particularly, infants aged <6 months had the highest risk of RSV infection (odds ratio = 2.4; 95% CI, 1.9-2.9) and a higher ICU admission rate (12.1% vs. 4.5%, 4.6%) and hospital cost ($923.3 vs. $785.5, $811.7) than the other age groups. Therefore, infants aged 0-6 months, particularly premature infants and children with congenital diseases, should receive more attention. There is an urgent need to develop effective immunization strategies to protect these infants during the first 6 months of life and in the RSV season.

Comprehensive Characterization of Metabolism-Associated Subtypes of Renal Cell Carcinoma to Aid Clinical Therapy.

Renal cell carcinoma (RCC) is a disease characterized by excessive administration complexity because it exhibits extraordinary nonuniformity among distinct molecular subtypes. We herein intended to delineate the metabolic aspects of clear cell RCC (ccRCC) in terms of the gene expression profile. Recent studies have revealed that metabolic variations within tumors are related to the responsiveness to immune checkpoint inhibitor (ICI) therapy and patient prognosis. We used 100 previously reported metabolic (MTB) pathways to quantify the metabolic landscape of the 729 ccRCC patients. Three MTB subtypes were established, and the MTB scores were calculated using principal component analysis (PCA). The high MTB score group had better overall survival (OS) and was associated with higher expression of immune-checkpoint and immune-activity signatures. The opposite was true of the low MTB score group, which may explain the poor prognosis of these patients. Three ICI-treated cohorts or tyrosine kinase inhibitor (TKI) treated cohort proved that patients with higher MTB scores exhibited notable therapeutic benefits and clinical gains. This research explained that the MTB score could be applied as a powerful prognostic indicator and predictive of ICI or TKI therapy. Assessing the MTB scores in a more extended group will facilitate our perception of tumor metabolism and provide guidance for studies on targeted approaches for ccRCC patients.

Diagnosis and genotype-phenotype correlation in patients with PKD1/TSC2 contiguous gene deletion syndrome.

Deletions involving the TSC2 and PKD1 genes lead to tuberous sclerosis complex (TSC) and autosomal dominant polycystic kidney disease (ADPKD), which is known as TSC2-PKD1 contiguous gene deletion syndrome (PKDTS). PKDTS leads to severe symptoms and death. There are few reported cases of PKDTS, the phenotypic descriptions are poor, and detailed statistics and descriptions of the time of onset and prognosis of PKDTS are lacking. This is the first study to report on the clinical data of PKDTS patients in China. We analyzed all cases including Chinese individuals and summarized the clinical manifestations and genetic characteristics. Our study was the first to use a combination of exome sequencing and multiplex ligation-dependent probe amplification (MLPA) to screen and diagnose PKDTS. We found that many PKDTS patients have the following: multiple renal cysts; angiofibromas (≥ 3) or fibrous cephalic plaque; subependymal nodules; seizures; intellectual disability. PKDTS develops into polycystic kidney disease from before birth to 17 years old and the time of occurrence of end-stage renal disease or dialysis was 21.62 ± 12.87 years of age, which was significantly earlier than in ADPKD caused by PKD1 mutation. Compared with non-Chinese individuals of diverse ancestry, Chinese people have significant differences in the clinical characteristics, including ungual fibromas (≥ 2), and shagreen patch. Five novel large deletions were identified in Chinese. We found no relationship between the clinical phenotype and the genotype. We combined exome sequencing with MLPA to develop a diagnostic method for PKDTS.

Safety and efficacy of the pan-FGFR inhibitor erdafitinib in advanced urothelial carcinoma and other solid tumors: A systematic review and meta-analysis.

Objective: This review aimed to comprehensively analyze the safety and efficacy of erdafitinib in treating advanced and metastatic urothelial carcinoma and other solid tumors. Methods: PubMed, Embase, and ClinicalTrials.gov were searched until 10 February 2022. The safety outcome as adverse events and efficacy outcomes, including objective response rate, stable disease rates, and progressive disease rates, were selected and analyzed by comprehensive meta-analysis version 3.0 and STATA 15.0. Results: The most common all-grade adverse events were hyperphosphatemia, dry mouth, stomatitis, diarrhea, and dysgeusia. The occurrence of ≥3 adverse events was relatively low, and stomatitis and hyponatremia were the most common. Moreover, eye disorders could not be ignored. Efficacy in urothelial carcinoma patients was obviously better than in other solid tumor patients, with a higher objective response rate (0.38 versus 0.10) and lower progressive disease rate (0.26 versus 0.68). All responses occurred in patients with fibroblast growth factor receptor (FGFR) alteration. In those patients, a specific FGFR alteration (FGFR3-TACC3) was observed to have a maximum response. Conclusion: Erdafitinib has satisfactory clinical activity for metastatic urothelial carcinoma and other solid tumors, while the toxicity is acceptable. With more RCTs and combination therapy trials published, erdafitinib will be applied widely.

The ceRNA PVT1 inhibits proliferation of ccRCC cells by sponging miR-328-3p to elevate FAM193B expression.

Clear cell renal cell carcinoma (ccRCC) is a common and fatal malignancy. Long noncoding RNAs (lncRNAs) have emerged as crucial biomarkers and regulators in many cancers, warranting the detailed investigation of their biological functions and molecular mechanisms. In this study, we explored the role and mechanism of plasmacytoma variant translocation 1 (PVT1), a competitive endogenous RNA (ceRNA) in ccRCC tissues in vitro and in vivo. We found that PVT1 is upregulated in ccRCC cells and promoted cell proliferation. Bioinformatic analysis, dual-luciferase reporter assays, argonaute 2-RNA immunoprecipitation (AGO2-RIP), quantitative PCR arrays, western blot assay, and rescue experiments were conducted to explore the underlying mechanisms of PVT1. Our analyses revealed that miR-328-3p was a direct target of PVT1 and that FAM193B was a direct target of miR-328-3p. FAM193B is upregulated in ccRCC tissues and promotes cell proliferation by activating the MAPK/ERK and PI3K/AKT pathways. Our results indicated that PVT1 promotes ccRCC cells proliferation by sponging miR-328-3p to upregulate FAM193B and activate the MAPK/ERK and PI3K/AKT pathways. Collectively, these results suggest that PVT1- miR-328-3p-FAM193B loop could serve as a potential biomarker and therapeutic target for ccRCC.

Epidemiology of Respiratory Pathogens Among Children Hospitalized for Pneumonia in Xiamen: A Retrospective Study.

OBJECTIVES: To investigate the etiology of common respiratory pathogens in children < 2 years of age hospitalized with pneumonia in Xiamen from 2014 to 2017. METHODS: The medical records of 5581 children with pneumonia were retrospectively reviewed. Direct immunofluorescent test was used for respiratory virus testing. Bacteria were detected by conventional culture method. The results of pathogen detection at admission were analyzed as well as the clinical outcomes of children. RESULTS: The burden of hospitalized children with pneumonia was highest among infants < 6 months old (58.2%). Respiratory syncytial virus (RSV) was the most common respiratory virus (26.0%) followed by parainfluenza (4.8%) and adenovirus (3.2%). Haemophilus influenzae was the most common bacteria detected (16.6%) followed by Moraxella catarrhalis (13.4%), Staphylococcus aureus (13.0%), Streptococcus pneumoniae (12.3%), Escherichia coli (5.1%) and Klebsiella pneumoniae (4.8%). Notably, RSV and K. pneumoniae were detected more frequently in severe pneumonia (35.0% and 10.9%) versus mild pneumonia (25.6% and 4.6%), with higher rates of ICU admissions, longer hospital stays and higher hospital costs compared to those infected with other respiratory pathogens. CONCLUSIONS: Among children < 2 years of age hospitalized with pneumonia in Xiamen, RSV was the most common respiratory virus, while H. influenzae and S. pneumoniae remained the predominant bacterial pathogens detected. Considering the low implementation rate of vaccines against pneumococcal and Hib pneumonia in China, there is an urgent need to increase both vaccination rates to reduce pneumococcal and Hib disease burden.

IL-6 Promotes the Proliferation and Immunosuppressive Function of Myeloid-Derived Suppressor Cells via the MAPK Signaling Pathway in Bladder Cancer.

Muscle-invasive bladder cancer (MIBC) is characterized by a highly complex immune environment, which is not well understood. Interleukin-6 (IL-6) is generated and secreted by multifarious types of cells, including tumor cells. This study was aimed at demonstrating that the levels of IL-6 and the number of myeloid-derived suppressor cells (MDSCs), with a positive correlation between them, increased in MIBC tissues, promoting MIBC cell proliferation, especially in patients with recurrence. In coculture analysis, MDSCs, with the stimulation of IL-6, could significantly lower the proliferation ability of CD4+ or CD8+ T lymphocytes. Further, this study demonstrated that IL-6 could upregulate the mitogen-activated protein kinase (MAPK) signaling pathway in MDSCs. The MAPK signaling inhibitor, aloesin, partially reversed the effects of IL-6 on MDSCs. These data suggested that IL-6 promoted MIBC progression by not only accelerating proliferation but also improving the immune suppression ability of MDSCs through activating the MAPK signaling pathway.

Accumulation of CD45RO+CD8+ T cells is a diagnostic and prognostic biomarker for clear cell renal cell carcinoma.

Renal cell carcinoma is characterized by high immunogenicity and infiltration of immune cells. CD45RO+CD8+ T cells are well known as a critical role in host defense of the immune environment. However, their role in clear cell renal carcinoma (ccRCC) remains unknown. To elucidate the clinical importance of CD45RO+CD8+ T cells in ccRCC as well as its underlying mechanism, we analyzed several types of peripheral immune cells from 274 patients with ccRCC who have received radical or partial nephrectomy and 350 healthy people. Flow cytomety assays showed there was no significant difference in the proportions of CD8+ T cells and its subtypes other than CD45RO+/CD45RA+CD8+ cells. Both gene and protein expression levels of CD45RO in ccRCC tissues were decreased. CD45RO+CD8+ T cells showed increased proliferative abilities but decreased apoptotic abilities through MAPK signaling activation in ccRCC. High expression level of CD45RO+CD8+ T cells inhibited ccRCC progression, including proliferation, invasion, as well as autophagy of ccRCC through many signaling pathways. Bioinformatics and immunohistochemical chip analysis measured gene and protein levels of CD45RO and other related proteins. The combination of UCHL1, HMGB3, and CD36 has diagnostic value in ccRCC and is able to predict prognosis. Collectively, CD45RO+CD8+ T cells play a critical role in ccRCC progression and may be regarded as clinical indicators.

Clinical use of machine learning-based pathomics signature for diagnosis and survival prediction of bladder cancer.

Traditional histopathology performed by pathologists by the naked eye is insufficient for accurate and efficient diagnosis of bladder cancer (BCa). We collected 643 H&E-stained BCa images from Shanghai General Hospital and The Cancer Genome Atlas (TCGA). We constructed and cross-verified automatic diagnosis and prognosis models by performing a machine learning algorithm based on pathomics data. Our study indicated that high diagnostic efficiency of the machine learning-based diagnosis model was observed in patients with BCa, with area under the curve (AUC) values of 96.3%, 89.2%, and 94.1% in the training cohort, test cohort, and external validation cohort, respectively. Our diagnosis model also performed well in distinguishing patients with BCa from patients with glandular cystitis, with an AUC value of 93.4% in the General cohort. Significant differences were found in overall survival in TCGA cohort (hazard ratio (HR) = 2.09, 95% confidence interval (CI): 1.56-2.81, P < .0001) and the General cohort (HR = 5.32, 95% CI: 2.95-9.59, P < .0001) comparing patients with BCa of high risk vs low risk stratified by risk score, which was proved to be an independent prognostic factor for BCa. The integration nomogram based on our risk score and clinicopathologic characters displayed higher prediction accuracy than current tumor stage/grade systems, with AUC values of 77.7%, 83.8%, and 81.3% for 1-, 3-, and 5-y overall survival prediction of patients with BCa. However, prospective studies are still needed for further verifications.

A systematic review and meta-analysis of the effects of early mobilization therapy in patients after cardiac surgery.

BACKGROUND: Prolonged hospitalization and immobility of critical care patients elevate the risk of long-term physical and cognitive impairments. However, the therapeutic effects of early mobilization have been difficult to interpret due to variations in study populations, interventions, and outcome measures. We conducted a meta-analysis to assess the effects of early mobilization therapy on cardiac surgery patients in the intensive care unit (ICU). METHODS: PubMed, Excerpta Medica database (EMBASE), Cumulative Index of Nursing and Allied Health Literature (CINAHL), Physiotherapy Evidence Database (PEDro), and the Cochrane Library were comprehensively searched from their inception to September 2018. Randomized controlled trials were included if patients were adults (≥18 years) admitted to any ICU for cardiac surgery due to cardiovascular disease and who were treated with experimental physiotherapy initiated in the ICU (pre, post, or peri-operative). Data were extracted by 2 reviewers independently using a pre-constructed data extraction form. Length of ICU and hospital stay was evaluated as the primary outcomes. Physical function and adverse events were assessed as the secondary outcomes. Review Manager 5.3 (RevMan 5.3) was used for statistical analysis. For all dichotomous variables, relative risks or odds ratios with 95% confidence intervals (CI) were presented. For all continuous variables, mean differences (MDs) or standard MDs with 95% CIs were calculated. RESULTS: The 5 studies with a total of 652 patients were included in the data synthesis final meta-analysis. While a slight favorable effect was detected in 3 out of the 5 studies, the overall effects were not significant, even after adjusting for heterogeneity. CONCLUSIONS: This population-specific evaluation of the efficacy of early mobilization to reduce hospitalization duration suggests that intervention may not universally justify the labor barriers and resource costs in patients undergoing non-emergency cardiac surgery. PROSPERO RESEARCH REGISTRATION IDENTIFYING NUMBER: CRD42019135338.

Different inactivation behaviors and mechanisms of representative pathogens (Escherichia coli bacteria, human adenoviruses and Bacillus subtilis spores) in g-C3N4-based metal-free visible-light-enabled photocatalytic disinfection.

Continuous economic loss and even human death caused by various microbial pathogens in drinking water call for the development of water disinfection systems with the features of environmentally friendly nature, high inactivation efficacy without pathogen regrowth, facile disinfection operation and low energy consumption. Alternatively, g-C3N4-based visible-light-enabled photocatalytic disinfection can meet the above requirements and thus has attracted increasing interest in recent years. Here, we explored for the first time the antimicrobial ability and mechanisms of a wide spectrum of representative pathogens ranging from bacteria (Escherichia coli), to viruses (human adenoviruses) and spores (Bacillus subtilis spores) by g-C3N4/Vis system with the assistance of two common oxidants (H2O2 and PMS), especially in a comparative perspective. Pristine g-C3N4 could achieve a complete inactivation of bacteria (5-log) within 150 min, but displayed negligible antimicrobial activity against human viruses and spores (< 0.5-log). Fortunately, simple addition of oxidants into the system could greatly enhance the inactivation of bacteria (5-log with PMS within 120 min) and human viruses (2.6-log with H2O2 within 150 min). Roles of reactive oxygen species were found to be quite different in the disinfection processes, depending on both types of chemical oxidants and microbial pathogens. Additionally, disinfection efficiency could be facilely and effectively improved by statistical optimization of two important operating factors (i.e., catalyst loading and oxidant addition). Selection of added oxidants was determined by not only the target pathogen but also the water matrix. As a proof of concept, this work can provide some meaningful and useful information for advancing the field of green and sustainable water disinfection.

FKBP-CaN-NFAT pathway polymorphisms selected by in silico biological function prediction are associated with tacrolimus efficacy in renal transplant patients.

AIM: The aim of the present study was to investigate the potential effects of genetic variations in the FKBP-CaN-NFAT pathway on clinical events associated with tacrolimus efficacy in Chinese renal transplant patients. METHODS: One hundred and forty Chinese renal transplant patients of Han ethnicity with over five years of follow-up were enrolled in our study. A pool of single nucleotide polymorphisms (SNPs) (1284 SNPs) was extracted from the Ensembl database according to chromosomal regions of the candidate genes. Next, 109 SNPs were screened out from this pool using multiple bioinformatics tools for subsequent genotyping using the MALDI-TOF-MS method. The associations of these candidate SNPs with acute rejection, nephrotoxicity, pneumonia and post-transplant estimated glomerular filtration rate (eGFR) were explored. RESULTS: Fourty-four SNPs were found to be associated with tacrolimus-related clinical drug response. Specifically, eight SNPs were associated with the incidence of biopsy-proven acute rejection, four SNPs were associated with the rate of nephrotoxicity, 16 SNPs were correlated with the onset of pneumonia, and 26 SNPs were found to significantly influence post-transplant eGFR trend. An elaborate scoring system was implemented to prioritize the validation of these potentially causal SNPs. In particular, NFATC2 rs150348438 (G>T) performed well during integrative scoring (Ptotal=23.8) and was significantly associated with the occurrence of pneumonia (P = 0.0035, HR=0.91, 95% CI=0.85-0.97) and post-transplant eGFR levels (P = 0.000003). CONCLUSIONS: NFATC2 rs150348438, rs6013219, rs1052653, and NFATC1 rs754093, ranking high in scoring, significantly affected the post-transplant eGFR and the incidence of pneumonia, acute rejection, and nephrotoxicity in renal transplant patients taking tacrolimus. Those SNPs may alter the expression and regulation of FKBP-CaN-NFAT pathway by influencing transcription regulation, mature mRNA degradation and RNA splicing, or protein coding. Critical SNPs of high ranking may serve as PD-associated pharmacogenetic biomarkers indicating individual response variability of TAC, and thus aid the clinical management of renal transplant patients.