Identifying the genetic association between systemic lupus erythematosus and the risk of autoimmune liver diseases.

BACKGROUND: Previous studies on the relationship between systemic lupus erythematosus (SLE) and autoimmune liver diseases (AILDs) are inconclusive. Therefore, we employed Mendelian randomization (MR) to explore the causal associations between SLE and AILDs. METHODS: A two-sample MR analysis was performed using summary-level statistics sourced from genome-wide association study (GWAS) datasets. Inverse-variance weighting (IVW), MR‒Egger, and weighted median (WM) were further supported by several sensitivity analyses. RESULTS: We detected causal genetic associations between SLE and primary biliary cholangitis (PBC) (odds ratio (OR) = 1.31, 95% CI = 1.15-1.51, P < 0.01; adjusted OR = 1.63, 95% CI = 1.39-1.90, P < 0.01) and between SLE and primary sclerosing cholangitis (PSC) (OR = 1.09, 95% CI = 1.01-1.08, P = 0.03; adjusted OR = 1.10, 95% CI = 1.00-1.21, P = 0.04). No causal association was found between SLE and autoimmune hepatitis. CONCLUSIONS: We are the first to use MR analysis to explore the causal relationships between SLE and various AILDs, revealing an increased risk of PBC and PSC in individuals with SLE.

Development and validation of a noninvasive prediction model for significant hepatic liver fibrosis in Chinese patients with autoimmune hepatitis.

INTRODUCTION AND OBJECTIVES: Autoimmune hepatitis (AIH) is a prevalent noninfectious liver disease. However, there is currently a lack of noninvasive tests appropriate for evaluating liver fibrosis in AIH patients. The objective of this study was to develop and validate a predictive model for noninvasive assessment of significant liver fibrosis (S ≥ 2) in patients to provide a reliable method for evaluating liver fibrosis in individuals with AIH. MATERIALS AND METHODS: The clinical data of 374 AIH patients were analyzed. A prediction model was established through logistic regression in the training set, and bootstrap method was used to validate the models internally. In addition, the clinical data of 109 AIH patients were collected for external verification of the model.The model was expressed as a nomogram, and area under the curve (AUC) of the receiver operating characteristic (ROC), calibration curve, and decision curve analysis were used to evaluate the accuracy of the prediction model. RESULTS: Logistic regression analysis revealed that age, platelet count (PLT), and the A/G ratio were identified as independent risk factors for liver fibrosis in AIH patients (P < 0.05). The diagnostic model that was composed of age, PLT and A/G was superior to APRI and FIB-4 in both the internal validation (0.872, 95%CI: 0.819-0.924) and external validation (0.829, 95%CI: 0.753-0.904). CONCLUSIONS: Our predictive model can predict significant liver fibrosis in AIH patients more accurately, simply, and noninvasively.

Psoas abscess: an uncommon disorder.

BACKGROUND: Psoas abscess (PA) is an uncommon disease that has been increasingly reported in the recent years. We reviewed patients with PA and analyzed their clinical characteristics to improve our understanding of this rare disorder. METHODS: We retrospectively reviewed the clinical presentations, microbiology, and outcomes of patients with PA between 2011 and 2022 at the Zhejiang Provincial People's Hospital in China. RESULTS: There were 40 adult patients identified with the discharge diagnosis of PA. The mean age was 60 years, and 67.5% of the patients were male. Primary symptoms were typically nonspecific. In all, 20 abscesses were considered secondary, and the most common was infective spondylitis. The most common causative organism for primary PA was Staphylococcus aureus, followed by Escherichia coli, whereas multiple bacterial species were found in secondary abscesses. The overall in-hospital mortality rate was 5%. Patients with secondary PA had a longer hospital stay. CONCLUSION: PA, as a serious infectious condition, usually presents with nonspecific symptoms and laboratory test results, making early diagnosis difficult. These profiles differed from those reported in the present study. The initial clinical status and subsequent imaging studies can lead to favorable outcomes.

Establishment and evaluation of an early prediction model of hepatorenal syndrome in patients with decompensated hepatitis B cirrhosis.

BACKGROUND AND AIM: In China, hepatorenal syndrome is a serious complication in the decompensated stage of hepatitis B cirrhosis, which requires early clinical intervention, so the early diagnosis of hepatorenal syndrome is crucial. This study establishes a new predictive model based on serum biomarkers for the early diagnosis of hepatorenal syndrome. METHODS: Patients with decompensated hepatitis B cirrhosis who met the inclusion and exclusion criteria were retrospectively enrolled. Patients were randomly assigned to the training dataset and validation dataset at a 7:3 ratio. Univariate and multivariate logistic regression analyses were used to screen the risk factors for hepatorenal syndrome. The identified risk factors were used to establish and verify a model. RESULTS: This study included 255 patients with decompensated hepatitis B cirrhosis, including 184 in the training group and 71 in the validation group. The multivariate logistic regression model was established in the training group and verified in the validation group. Logistic regression showed that hemoglobin (OR 0.938, 95% CI 0.908-0.969), total bilirubin (OR 1.014, 95% CI 1.008-1.021) and creatinine (OR 1.079, 95% CI 1.043-1.117) were independent risk factors for hepatorenal syndrome (P < 0.05). These were used to establish the model. In the training group and the validation group, the area under the ROC curve of the nomogram for the diagnosis of hepatorenal syndrome was 0.968 and 0.980, respectively. CONCLUSION: The three serum biomarkers, including hemoglobin, total bilirubin and creatinine, can be used as independent early predictors of hepatorenal syndrome in patients with decompensated hepatitis B cirrhosis.

Fatty liver is associated with significant liver inflammation and increases the burden of advanced fibrosis in chronic HBV infection.

BACKGROUND: Concurrent non-alcoholic fatty liver disease (NAFLD) is common in patients with chronic HBV infection. But the impact of fatty liver on the histologic progression of HBV infection remains controversial. METHODS: Consecutive HBV-infected patients who underwent liver biopsy between 2016 and 2021 were included. Alcohol consumption and other types of viral hepatitis were excluded. All biopsies were scored for grading and staging by Scheuer's score, and the steatosis was scored as an estimate of the percentage of liver parenchyma replaced by fat. Logistic regression analyses were applied to assess the associated factors for significant liver inflammation (G ≥ 2), significant fibrosis (S ≥ 2) and advanced fibrosis (S ≥ 3). RESULTS: Among the 871 HBV-infected patients, hepatic steatosis was prevalent in 255 patients (29.28%). Significant liver inflammation was present in 461 patients (52.93%). Significant fibrosis was observed in 527 patients (60.51%), while advanced liver fibrosis was observed in 171 patients (19.63%). Patients with concomitant NAFLD were more likely to have significant liver inflammation and advanced fibrosis. Fatty liver was an independent risk factor for significant liver inflammation (OR: 2.117, 95% CI: 1.500-2.988), but it could not predict the development of fibrosis. Especially, in HBV-infected patients with persistent normal ALT (immune tolerant and inactive carrier phase), the presence of significant liver inflammation was higher in NAFLD than those without NAFLD. The prevalence of advanced liver fibrosis was higher in NAFLD than non-NAFLD only in the immune tolerant phase, while NAFLD did not increase fibrosis burden in other stages of HBV infection. We developed a predictive model for significant liver inflammation with the area under receiver operating characteristic curve (AUROC) of 0.825, and a model for significant fibrosis with the AUROC of 0.760. CONCLUSIONS: NAFLD is independently associated with significant liver inflammation, and increases the burden of advanced liver fibrosis in HBV-infected patients. The influence of NAFLD on the degree of liver inflammation and fibrosis is different in distinct clinical phases of chronic HBV infection.

Construction and Application of Chain Management Information System for Cancer Pain.

BACKGROUND: With the rapid development of information technology, hospital information systems (HISs) have been deeply applied in the medical field and have shown broad application prospects. There are still some noninteroperable clinical information systems that pose an obstacle to the effective coordination of care, such as cancer pain management. AIM: To construct a chain management information system for cancer pain and explore its clinical application effect. METHODS: A quasiexperimental study was conducted in the inpatient department of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine. A total of 259 patients were nonrandomly divided into two groups: the experimental group (after the system was applied, n = 123) and the control group (before the system was applied, n = 136). The cancer pain management evaluation form score, patient satisfaction with pain control, pain score at admission and discharge, and the worst pain score during hospitalization were compared between the two groups. RESULTS: Compared with the control group, the score of the cancer pain management evaluation form was significantly higher (p < .05). There were no statistically significant differences in worst pain intensity, pain score at admission and discharge, and patients' satisfaction with pain control between the two groups. CONCLUSIONS: The cancer pain chain management information system can enable nurses to evaluate and record pain in a more standardized way, but it has no significant effect on the pain intensity of cancer patients.

Ethical predicaments and countermeasures in nursing informatics.

With the increasing use of technology in nursing, how nurses perform practice care has changed, inevitably leading to ethical concerns that differ from original ethical norms in nursing. Studies have focused on ethical issues in health informatics from clinicians' or patients' perspectives, while nurses' perspective is needed. This paper conducts a theoretical study on ethical predicaments that arise in nursing informatics from nurses' perspectives. Why and how these predicaments emerge are elaborated. Also, this paper offers countermeasures in realistic contexts from technique, education, and leadership aspects. Collaborations between governments, administrators, educators, technicians, and nurses are needed to step out of these predicaments.

Sulfated modification of hyaluronan tetrasaccharide enhances its antitumor activity on human lung adenocarcinoma A549 cells in vitro and in vivo.

Hyaluronan (HA) is a glycosaminoglycan polymer involved in cell phenotype change, inflammation modulation, and tumor metastasis progression. HA oligosaccharides have a higher solubility and drug-forming ability than polysaccharides. HA tetrasaccharide was reported as the smallest fragment required for inhibiting triple-negative breast cancer, but the anti-tumor activity of HA tetrasaccharide (HA4) and its sulfated derivatives in lung cancer is still unknown. In this study, HA4 was prepared via HA degradation by chondroitinase ABC (CSABC), while its sulfated derivatives were prepared by sulfur pyridine trioxide complex in N, N-dimethylformamide (DMF). Then, the anti-tumor activity was detected via MTT assay and xenograft tumor experiments, while the expression level change of apoptosis genes was analyzed by qRT-PCR. Electrospray mass spectrometry (ESI-MS) analysis showed several HA4 sulfated derivatives, GlcA2GlcNAc2 (SO3H)n contains 0-6 sulfation groups, which mainly contain 3-6, 2-3, and 0-1 sulfation groups were classified as HA4S1, HA4S2, and HA4S3, respectively. After the addition of 1.82 mg/mL HA4, HA4S1, HA4S2, and HA4S3, the cell viability of A549 cells was reduced to 81.2 %, 62.1 %, 50.3 %, and 65.9 %, respectively. Thus, HA4S2 was chosen for further measurement, the qRT-PCR results showed it significantly up-regulated the expression of genes in the apoptosis pathway. Moreover, HA4S2 exhibited stronger antitumor activity than HA4 in vivo and the tumor inhibition rate reached 36.90 %. In summary, this study indicated that the CSABC enzyme could effectively degrade HA into oligosaccharides, and sulfation modification was an effective method to enhance the antitumor activity of HA tetrasaccharides.

An analysis of clinical and imaging features of unilateral impacted maxillary central incisors: A cross-sectional study.

INTRODUCTION: This cross-sectional study sought to assess clinical features and 3-dimensional distribution of unilateral impacted maxillary central incisors and identify factors associated with the root morphology. METHODS: Cone-beam computed tomography (CBCT) images from 94 subjects exhibiting unilateral impacted maxillary incisors were selected and evaluated. Original CBCT data were reconstructed using Mimics software (version 17.0; Materialise, Belgium). Clinical features and 3-dimensional distribution of impacted maxillary central incisors and factors associated with the root morphology were observed and analyzed by 2 orthodontists. RESULTS: This patient cohort included 52 male patients and 42 female patients. Thirty-three incisors (35.11%) with dilacerated roots, 17 incisors (18.09%) with retained deciduous teeth, 15 incisors (15.96%) with supernumerary teeth, and 15 incisors (15.96%) with a history of trauma were identified in the study. Of the 94 impacted incisors, the most common were labially impacted (n = 65; 69.15%), followed by vertically impacted (n = 17; 18.09%) and palatally impacted (n = 12; 12.77%). Chi-square tests revealed that differences in subjects with supernumerary teeth, buccolingual position, sagittal position, and axial position in the upright and dilacerated root groups were statistically significant (P <0.05). Logistic regression analysis indicated that the incidence of dilacerations was higher in the inverted position than in the inclined position and horizontal position (P <0.05). CONCLUSIONS: Labially impacted maxillary incisors were more common than vertically or palatally incisors. Dilaceration was most commonly observed in patients with inverted incisors. In clinical practice, CBCT is a valuable tool for diagnosing impacted maxillary central incisors and for making appropriate treatment plans for patients.

High hepatitis C virus cure rates with approved interferon-free direct-acting antivirals among diverse mainland Chinese patients including genotypes 3a and 3b.

BACKGROUND AND AIM: Globally, China has the highest chronic hepatitis C (CHC) burden, but its real-world direct-acting antiviral (DAA) data are limited. Our aim is to investigate the real-world outcome of China Food and Drug Administration-approved DAA therapies across mainland China including those with genotype (GT) 3. METHODS: The REAL-C is a multinational real-world interferon-free DAA-treated CHC registry of several mainland China and other Asian centers. We evaluated the sustained virological response rate 12 weeks after end of treatment (SVR12), adverse events, and treatment effect on liver function and fibrosis (fibrosis-4 index). RESULTS: We analyzed 859 DAA-treated CHC patients (6/1/2017-5/30/2019) from 12 mainland China centers (three municipalities and nine provinces): median age 52, 49.9% male, 33.1% cirrhosis, 95% treatment naïve, and 2.5% HBsAg+ . The most common GT was GT1b (523, 62.2%), followed by GT2a (156, 18.5%), GT3b (74, 8.8%), GT3a (41, 4.9%), and GT6 (37, 4.4%). SVR12 rates were 98.0% overall (95% confidence interval 96.9-98.8%), 98.1% for GT1b, 96.8% GT2a, 100% GT3a, 97.3% GT3b, and 100% GT6. Baseline cirrhosis and male sex but not prior treatment history, renal dysfunction, age, and GTs were associated with SVR12. For both cirrhotic and non-cirrhotic patients, there were significant improvement in liver function tests, alpha fetoprotein, and fibrosis-4 index with SVR12. Serious adverse events were rare (1.1%) with only nine patients discontinuing therapy prematurely and anemia being the most common adverse event (13.1%, mostly with ribavirin). CONCLUSIONS: In real-world Chinese patients with diverse GTs, Chinese Food and Drug Administration-approved interferon-free DAAs were well tolerated, provided high cure rates (98.0% overall) including GT3a/3b, and led to improvement of liver function.

Impact of Muscle Mass on Survival in Patients with Sepsis: A Systematic Review and Meta-Analysis.

INTRODUCTION: The aim of this study is to investigate the association between loss of muscle mass and prognosis of sepsis. METHODS: Six databases, including PubMed, Embase, Cochrane Library, Web of Science, Scopus, and Ovid, were searched by the deadline of August 18, 2020. A meta-analysis was conducted on the collected data by means of a random-effects model. The quality of each included article was assessed according to the Newcastle-Ottawa Scale. RESULTS: Out of 1,819 references, 6 articles and 1 conference abstract were included. Sepsis patients with a loss of muscle mass or sarcopenia had higher mortality (risk ratio [RR]: 1.94, 95% confidence intervals [CI]: 1.59-2.37; I-squared = 18.7%, p < 0.001). The RR of mortality within 30 days (RR: 2.31, 95% CI: 1.78-2.99, p < 0.001) was higher than that of mortality over 30 days. Loss of psoas muscle mass, as evaluated by CT, showed the highest RR of sepsis mortality. In addition, based on data on overall survival retrieved from 4 trials, the pooled hazard ratio (HR) for patients with a loss of muscle mass or sarcopenia was 3.04. Subgroup analysis showed that survival time was the main source of heterogeneity for the overall HR. Furthermore, the scanning areas of muscle mass in survival patients were 0.33 cm2/m2 higher than those measured in deceased patients. CONCLUSION: A loss of muscle mass, as evaluated by CT scan, was associated with a poor outcome in sepsis.

Development and application of quality checklist for the prevention and control of COVID-19 in fever clinic and isolation ward of the general hospital.

To develop a quality control checklist for the prevention and control of coronavirus disease 2019 （COVID-19） in fever clinic and isolation ward of the general hospital and to assess its application. Based on the relevant prevention and control plans and technical guidelines for COVID-19，Delphi method was used to identity items for evaluation，and a quality control checklist for the prevention and control of COVID-19 in the fever clinic and isolation ward was developed in Sir Run Run Shaw Hospital. The checklists included 8 dimensions and 32 items for fever clinic，7 dimensions and 27 items for the isolation ward. The appointed inspectors conducted daily quality control for each shift with this checklist. The expert authority coefficient was 0.88，the mean of the importance of each index in the quality control table was not less than 4.8，and the coefficient of variation was not more than 0.07. During the entire February 2020，8 problems were found and rectified on-the-spot with the application of the checklist. Quality inspection rate was 100% in both isolation wards and fever clinic. The compliance rate and accuracy rate of hand hygiene were 100%; the correct rate of wearing and removing protective equipment increased from 96% to 100%. During the same period，a total of 1915 patients were admitted to the fever clinic，including 191 suspected patients （all were isolated in the hospital，3 were confirmed）. There were no medical staff infected with COVID-19，no cross infection of patients and their families in the hospital. A quality control checklist for the prevention and control of COVID-19 has been developed and applied in the isolation wards and fever clinic，which plays an important role in preventing nosocomial infection.

The limiting factors of oncolytic virus immunotherapy and the approaches to overcome them.

Oncolytic virus (OV) immunotherapy is characterized by viruses which specifically target cancer cells and cause their cytolysis. They provide a unique and promising new tool for the eradication of cancer as they interact with and affect the tumor microenvironment (TME), vasculature, and immune system. Advancements of genetic engineering have allowed for these viruses to be armed in such a way to have enhanced targeting, strong immunomodulation properties, and an ability to modify the TME. However, there are still major limitations in their use, mostly due to difficulties in delivering the viral particles to the tumors and in ensuring that the immunomodulatory properties are able to stimulate the host immune response to mount a complete response. Using novel delivery systems and using OVs as a complementary therapy in a combinatorial treatment have shown some significant successes. In this review, we discuss the major issues and difficulties in using OVs as anti-tumor agents and some of the strategies put in place so far to overcome these limitations. KEY POINTS: • Oncolytic viruses (OVs) infect cancer cells and cause their cytolysis. • The major limitations in using OVs as anti-tumor therapy were discussed. • The potential strategies to overcome these limitations were summarized.

Low-density lipoprotein decorated and indocyanine green loaded silica nanoparticles for tumor-targeted photothermal therapy of breast cancer.

Photothermal therapy (PTT) is well recognized to be a highly reliable way to treat cancer effectively. Nevertheless, the poor tumor targetability and the inferior stability of PTT agents are two remaining difficulties in PTT. As a result, in this study, the silica nanoparticles (SLN) were coated by low-density lipoprotein (LDL) to develop a multifunctional platform (LDL/SLN) to specifically target the LDL receptor (LDLR) overexpressed breast cancer cells. Furthermore, indocyanine green (ICG) was loaded inside LDL/SLN to establish a drug delivery system (DDS) fit for tumor-specific PTT of breast cancer. According to our results, LDL/SLN/ICG was nano-scaled particles with uniform size and reliable stability under physiological condition. Additionally, LDL/SLN/ICG could smartly target the MCF-7 cells that overexpress LDLR. Most importantly, further studies also demonstrated that LDL/SLN/ICG showed beneficial outcome than SLN/ICG. The high stability as well as the moderate size made it suitable to serve as DDS for cancer therapy. Moreover, the LDL modification was able to enhance the tumor accumulation of LDL/SLN/ICG, which finally achieved elevated PTT benefits than other groups. We therefore suggested that LDL/SLN/ICG could be a future alternative for promising tumor-targeted PTT for breast cancer.

[Standardized sputum collection increases sputum sample collection rate for novel coronavirus nucleic acid detection].

OBJECTIVE: To evaluate the effect of standardized health education on the sputum specimen collection rate for nucleic acid detection of coronavirus disease 2019 (COVID-19). METHODS: Two hundred and twenty-seven patients in fever clinics and isolation wards of Sir Run Run Shaw Hospital of Zhejiang University and 307 migrant workers returning to 5 enterprises in Shanghai from February 3 to March 14, 2020 were enrolled in the study. Through clarifying the procedures of collecting sputum specimens, making graphic/video health education materials, standardizing the contents and methods of health education, we conducted education to the subjects. The subject expectorated spontaneously or with medical assistance. For patients, the number of sampling attempts and sputum acquisition times were documented before and after the implementation of the standardized expectoration method; for the returning migrant employees in the enterprises, only the number of collected samples after the implementation of the standardized expectoration method were recorded. RESULTS: A total of 378 sputum samples were collected from 227 patients. The sputum sampling rates before and after the implementation of health education were 40.9%and 58.4%, respectively (P<0.01). A total of 304 sputum samples were obtained from 307 enterprise returnees, with a sample collection rate of 99.0%. CONCLUSIONS: The education for standardized sputum sample collection method can effectively increase the sputum collection rate.

The molecular differences between human papillomavirus-positive and -negative oropharyngeal squamous cell carcinoma: A bioinformatics study.

OBJECTIVE: To investigate the genetic and epigenetic differences between human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) and HPV-negative OPSCC. METHODS: Microarray data of HPV-positive and -negative OPSCC were retrieved from NCBI GEO datasets. Differentially expressed genes (DEGs) and differentially expressed miRNAs (DE-miRNAs) were identified by performing differential expression analysis. A functional enrichment analysis was performed to explore the biological processes and signaling pathways that DEGs and DE-miRNAs were involved in, respectively. A protein-protein interaction (PPI) network of DEGs was constructed to identify hub genes. miRNA-target network and miRNA-miRNA functional synergistic network were each constructed in order to identify risk-marker miRNAs. An miRNA-target-pathway network was constructed in order to explore the function of identified risk-marker miRNAs. RESULTS: Microarray data from 3 datasets (GSE39366, GSE40774, and GSE55550) was included and analyzed. The PPI network identified 3 hub genes (VCAM1, UBD, and RPA2). MiR-107 and miR-142-3p were found to play the most significant role in both the DE-miRNA-target network as well as in the miRNA-miRNA functional synergistic network. MiR-107 was involved in HPV-induced tumorigenesis by targeting many genes (CAV1, CDK6, MYB, and SERPINB5) and regulating the p53 signaling pathway, the PI3K-Akt signaling pathway, and the autophagy pathway. In addition, miR-142-3p was implicated in HPV-induced tumorigenesis by targeting the PPFIA1 gene and regulating transcriptional dysregulation and other cancerous pathways. CONCLUSION: Three genes (VCAM1, UBD, and RPA2), two miRNAs (miR-107 and miR-142-3p), and four pathways (p53, PI3K-Akt, autophagy, and transcription dysregulation in cancer) were identified to play critical roles in distinguishing HPV-positive OPSCC from HPV-negative OPSCC.

Clinical characteristics and prognostic factors of liver cirrhosis patients with systemic inflammatory response syndrome.

AIM: Our objective is to study the clinical characteristics of cirrhosis patients with SIRS and investigate its prognostic factors. METHODS: We analyzed 285 consecutive patients and their data were evaluated retrospectively. Data were compared in patients with/without SIRS during hospitalization. Univariate and multivariate Cox regression analyses were undertaken separately for cirrhotic patients with SIRS to assess predictive factors for 90-day mortality. RESULTS: The mortality was 38.24% (52/136) in patients with SIRS and 6.04% (9/149) in patients without SIRS for 90-day follow-up (P < 0.001). The univariate analysis showed gastrointestinal hemorrhage (P < 0.001), hepatic encephalopathy (P < 0.001), albumin <30 g/L (P < 0.037), creatinine (Cr) >175 µmol/L (P < 0.001), cholinesterase(ChE) activity <3000 U/L (P = 0.019), white blood cell count ≥10 000 (109/L) (P = 0.018), neutrophils ≥80% (P = 0.018), C-reactive protein (CRP) ≥25 mg/L (P < 0.001), procalcitonin ≥1.0 ng/mL (P = 0.007), Child-Pugh class C (P < 0.001), septicemia (P < 0.001), pulmonary infection (P < 0.001),multi-site infection (P = 0.001), acute-on-chronic liver failure (ACLF) (P < 0.001), and advanced hepatocellular carcinoma (HCC) (P < 0.001). In multivariate analysis, only Cr ≥175 µmol/L (hazard ratio [HR] = 2.768; confidence interval [CI], 1.53-5.04; P = 0.001), C-reactive protein ≥25 mg/L (HR = 3.179; CI, 1.772-7.03; P = 0.004), multi-site infection (HR = 19.427; CI, 7.484-50.431; P < 0.001), ACLF (HR = 7.308; CI, 3.048-17.521; P < 0.001), advanced HCC (HR = 2.523; CI, 1.019-6.248; P = 0.045) were independent predictors of 90-day mortality in cirrhotic patients with SIRS. CONCLUSION: Cr ≥ 175 µmol/L, CRP ≥ 25 mg/L, multi-site infection, ACLF, and advanced HCC independently predicted a higher rate of 90-day mortality in liver cirrhosis with SIRS.

Glycometabolic reprogramming associated with the initiation of human dental pulp stem cell differentiation.

Glycometabolism, particularly mitochondrial oxidative phosphorylation (OXPHOS) and glycolysis, plays a central role in cell life activities. Glycometabolism can be reprogrammed to maintain the stemness or to induce the differentiation of stem cells, thereby regulating tissue repair and regeneration. However, research on the glycometabolism of human dental pulp stem cells (hDPSCs) remains scarce. Here, we investigated the relationship between glycometabolic reprogramming and initiation of hDPSC differentiation. We found the differentiation of hDPSCs commenced on day 3 when cells were cultured in mineralized medium. When cell differentiation commenced, mitochondria became elongated with well-developed cristae, and the oxygen consumption rate of mitochondria was enhanced, manifested as an increase in basal respiration, mitochondrial ATP production, and maximal respiration. Interestingly, glycolytic enzyme activities, glycolysis capacity, and glycolysis reserve were also upregulated at this time to match the powerful bioenergetic demands. More importantly, hDPSCs derived from different donors or cultured in various oxygen environments showed similar glycometabolic changes when they began to differentiate. Thus, glycometabolic reprogramming accompanies initiation of hDPSC differentiation and could potentially play a role in the regulation of dental pulp repair.

Novel role of zonula occludens-1: A tight junction protein closely associated with the odontoblast differentiation of human dental pulp cells.

Zonula occludens-1 (ZO-1), a tight junction protein, contributes to the maintenance of the polarity of odontoblasts and junctional complex formation in odontoblast layer during tooth development. However, expression and possible role of ZO-1 in human dental pulp cells (hDPCs) during repair process remains unknown. Here, we investigated the expression of ZO-1 in hDPCs and the relationship with odontoblast differentiation. We found the processes of two adjacent cells were fused and formed junction-like structure using scanning electron microscopy. Fluorescence immunoassay and Western blot confirmed ZO-1 expression in hDPCs. Especially, ZO-1 was high expressed at the cell-cell junction sites. More interestingly, ZO-1 accumulated at the leading edge of lamellipodia in migrating cells when a scratch assay was performed. Furthermore, ZO-1 gradual increased during odontoblast differentiation and ZO-1 silencing greatly inhibited the differentiation. ZO-1 binds directly to actin filaments and RhoA/ROCK signaling mainly regulates cell cytoskeleton, thus RhoA/ROCK might play a role in regulating ZO-1. Lysophosphatidic acid (LPA) and Y-27632 were used to activate and inhibit RhoA/ROCK signaling, respectively, with or without mineralizing medium. In normal cultured hDPCs, RhoA activation increased ZO-1 expression and especially in intercellular contacts, whereas ROCK inhibition attenuated the effects induced by LPA. However, expression of ZO-1 was upregulated by Y-27632 but not significantly affected by LPA after odontoblast differentiation. Hence, ZO-1 highly expresses in cell-cell junctions and is related to odontoblast differentiation, which may contribute to dental pulp repair or even the formation of an odontoblast layer. RhoA/ROCK signaling is involved in the regulation of ZO-1.