Randomized clinical trial on D2 lymphadenectomy versus D2 lymphadenectomy plus complete mesogastric excision in patients undergoing gastrectomy for cancer (DCGC01 study).

BACKGROUND: It is unknown whether D2 lymphadenectomy + complete mesogastric excision for gastric cancer improves survival compared with just D2 lymphadenectomy. METHODS: Between September 2014 and June 2018, patients with advanced gastric cancer were randomly assigned (1 : 1) to laparoscopic D2 lymphadenectomy or D2 lymphadenectomy + complete mesogastric excision gastrectomy. The modified intention-to-treat population was defined as patients who had pathologically confirmed gastric adenocarcinoma (pT1 N1-3 M0 and pT2-4 N0-3 M0). The primary endpoint was 3-year disease-free survival. Secondary endpoints were the recurrence pattern and overall survival. RESULTS: The median follow-up of patients in the D2 lymphadenectomy group (169 patients) and patients in the D2 lymphadenectomy +complete mesogastric excision group (169 patients) was 55 (interquartile range 37-60) months and 51 (interquartile range 40-60) months respectively. Recurrence occurred in 50 patients in the D2 lymphadenectomy group (29.6%) versus 33 patients in the D2 lymphadenectomy + complete mesogastric excision group (19.5%) (P = 0.032). The 3-year disease-free survival was 75.5% (95% c.i. 68.3% to 81.3%) in the D2 lymphadenectomy group versus 85.0% (95% c.i. 78.7% to 89.6%) in the D2 lymphadenectomy + complete mesogastric excision group (log rank P = 0.042). The HR for recurrence in the D2 lymphadenectomy + complete mesogastric excision group versus the D2 lymphadenectomy group was 0.64 (95% c.i. 0.41 to 0.99) by Cox regression (P = 0.045). The 3-year overall survival rate was 77.5% (95% c.i. 70.4% to 83.1%) in the D2 lymphadenectomy group versus 85.8% (95% c.i. 79.6% to 90.2%) in the D2 lymphadenectomy + complete mesogastric excision group (log rank P = 0.058). The HR for death in the D2 lymphadenectomy + complete mesogastric excision group versus the D2 lymphadenectomy group was 0.64 (95% c.i. 0.41 to 1.02) (P = 0.058). CONCLUSION: Compared with conventional D2 dissection, D2 lymphadenectomy + complete mesogastric excision is associated with better disease-free survival, but there is no statistically significant difference in overall survival. REGISTRATION NUMBER: NCT01978444 (http://www.clinicaltrials.gov).

SERCA2 protects against cisplatin-induced damage of auditory cells: Possible relation with alleviation of ER stress.

AIMS: SERCA2, one of the P-type pumps encoded by gene ATP2A2, is the only calcium reflux channel of the endoplasmic reticulum (ER) and participates in maintaining calcium homeostasis. The present study was designed to explore SERCA2 expression pattern in auditory hair cells and the possible mechanism underlying the effects of SERCA2 on cisplatin-induced ototoxicity. MAIN METHODS: The SERCA2 expression pattern in cochlea hair cells and HEI-OC1 cells was measured by Western blot (WB) and immunofluorescence staining. The apoptosis and its related factors were detected by TUNEL assay and WB. The expression levels of ER stress-related factors, ATF6, PERK, IRE1α, and GRP78, were measured via WB. As for the determination of SERCA2 overexpression and knockdown, plasmids and lentiviral vectors were constructed, respectively. KEY FINDINGS: We found that SERCA2 was highly expressed in cochlea hair cells and HEI-OC1 cells. Of note, the level of SERCA2 expression in neonatal mice was remarkably higher than that in adult mice. Under the exposure of 30 µM cisplatin, SERCA2 was down-regulated significantly compared with the control group. In addition, cisplatin administration triggered the occurrence of ER stress and apoptosis. Those events were reversed by overexpressing SERCA2. On the contrary, SERCA2 knockdown could aggravate the above processes. SIGNIFICANCE: The findings from the present study disclose, for the first time, that SERCA2 is abundantly expressed in cochlea hair cells, and the suppression of SERCA2 caused by cisplatin could trigger ER homeostasis disruption, thereby implying that SERCA2 might be a promising target to prevent cisplatin-induced cytotoxicity of hair cells.

LDL-C and TC mediate the risk of PNPLA3 inhibition on cardiovascular diseases.

BACKGROUND: PNPLA3 is a promising target for the treatment of Metabolic Dysfunction-Associated Steatotic Liver Disease. ARO-PNPLA3 is a drug that efficiently lowers PNPLA3 expression in hepatocytes at the mRNA level, resulting in a significant reduction in liver fat in Phase I clinical trials. However, the long-term effects and potential side effects of ARO-PNPLA3 are not well understood. METHODS: We conducted a two-sample, two-step Mendelian randomization (MR) analysis to investigate the association between PNPLA3 inhibition and 10 cardiovascular diseases (CVDs), as well as the role of lipid traits as mediators. We identified genetic variants near the PNPLA3 gene, which are linked to liver fat percentage, as instrumental variables for inhibiting PNPLA3. Additionally, positive control analyses on liver diseases were conducted to validate the selection of the genetic instruments. RESULTS: Genetically predicted PNPLA3 inhibition significantly increased the risk of coronary atherosclerosis (1.14, 95% CI 1.06, 1.23), coronary heart disease (1.14, 95% CI 1.08, 1.21), and myocardial infarction (1.16, 95% CI 1.08, 1.26). Suggestive associations were observed for increased risk of heart failure (1.09, 95% CI 1.02, 1.17, P = 0.0143) and atrial fibrillation (1.17, 95% CI 1.00, 1.36, P = 0.0468). Blood low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) mediated approximately 16-25%, 16-30%, and 14-22% of the associations between PNPLA3 inhibition and coronary atherosclerosis, myocardial infarction, and coronary heart disease, respectively. CONCLUSION: This study suggests that PNPLA3 inhibition increases the risk of major CVDs. Moreover, blood LDL-C and TC may mediate a significant proportion of the associations between PNPLA3 inhibition and coronary atherosclerosis, coronary heart disease, or myocardial infarction.

Assessment of Perfusion Volumes by a New Automated Software for Computed Tomography Perfusion.

INTRODUCTION: To compare the perfusion volumes assessed by a new automated CT perfusion (CTP) software iStroke with the circular singular value decomposition software RAPID and determine its predictive value for functional outcome in patients with acute ischaemic stroke (AIS) who underwent endovascular treatment (EVT). METHODS: Data on patients with AIS were collected from four hospitals in China. All patients received CTP followed by EVT with complete recanalisation within 24 hours of symptom onset. We evaluated the agreement of CTP measures between the two softwares by Spearman's rank correlation tests and kappa tests. Bland-Altman plots were used to evaluate the agreement of infarct core volume (ICV) on CTP and ground truth on diffusion-weighted imaging (DWI). Logistic regression models were used to test the association between ICV on these two softwares and functional outcomes. RESULTS: Among 326 patients, 228 had DWI examinations and 40 of them had infarct volume >70 mL. In all patients, the infarct core and hypoperfusion volumes on iStroke had a strong correlation with those on RAPID (ρ=0.68 and 0.66, respectively). The agreement of large infarct core (volume >70 mL) was substantial (kappa=0.73, p<0.001) between these two softwares. The ICV measured by iStroke and RAPID was significantly correlated with independent functional outcome at 90 days (p=0.009 and p<0.001, respectively). In patients with DWI examinations and those with an ICV >70 mL, the ICV of iStroke and RAPID was comparable on individual agreement with ground truth. CONCLUSION: The automatic CTP software iStroke is a reliable tool for assessing infarct core and mismatch volumes, making it clinically useful for selecting patients with AIS for acute reperfusion therapy in the extended time window.

Mediating Effect of Tobacco Dependence on the Association Between Maternal Smoking During Pregnancy and Chronic Obstructive Pulmonary Disease: Case-Control Study.

BACKGROUND: Maternal smoking during pregnancy (MSDP) is a known risk factor for offspring developing chronic obstructive pulmonary disease (COPD), but the underlying mechanism remains unclear. OBJECTIVE: This study aimed to explore whether the increased COPD risk associated with MSDP could be attributed to tobacco dependence (TD). METHODS: This case-control study used data from the nationwide cross-sectional China Pulmonary Health study, with controls matched for age, sex, and smoking status. TD was defined as smoking within 30 minutes of waking, and the severity of TD was assessed using the Fagerstrom Test for Nicotine Dependence. COPD was diagnosed when the ratio of forced expiratory volume in 1 second to forced vital capacity was <0.7 in a postbronchodilator pulmonary function test according to the 2017 Global Initiative for Chronic Obstructive Lung Disease criteria. Logistic regression was used to examine the correlation between MSDP and COPD, adjusting for age, sex, BMI, educational attainment, place of residence, ethnic background, occupation, childhood passive smoking, residential fine particulate matter, history of childhood pneumonia or bronchitis, average annual household income, and medical history (coronary heart disease, hypertension, and diabetes). Mediation analysis examined TD as a potential mediator in the link between MSDP and COPD risk. The significance of the indirect effect was assessed through 1000 iterations of the "bootstrap" method. RESULTS: The study included 5943 participants (2991 with COPD and 2952 controls). Mothers of the COPD group had higher pregnancy smoking rates (COPD: n=305, 10.20%; controls: n=211, 7.10%; P<.001). TD was more prevalent in the COPD group (COPD: n=582, 40.40%; controls: n=478, 33.90%; P<.001). After adjusting for covariates, MSDP had a significant effect on COPD (ß=.097; P<.001). There was an association between MSDP and TD (ß=.074; P<.001) as well as between TD and COPD (ß=.048; P=.007). Mediation analysis of TD in the MSDP-COPD association showed significant direct and indirect effects (direct: ß=.094; P<.001 and indirect: ß=.004; P=.03). The indirect effect remains present in the smoking population (direct: ß=.120; P<.001 and indirect: ß=.002; P=.03). CONCLUSIONS: This study highlighted the potential association between MSDP and the risk of COPD in offspring, revealing the mediating role of TD in this association. These findings contribute to a deeper understanding of the impact of prenatal tobacco exposure on lung health, laying the groundwork for the development of relevant prevention and treatment strategies.

Protocol of a multicenter, single-blind, randomized, parallel controlled trial evaluating the effect of microbiological rapid on-site evaluation (M-ROSE) guiding anti-infection treatment in patients with severe hospital-acquired pneumonia.

INTRODUCTION: The mortality rate of hospitalized patients with severe hospital-acquired pneumonia (SHAP) remains high. Empirical broad-spectrum antibiotic coverage and the misuse of high-grade antibiotics could lead to the emergence of multi-drug and even pandrug-resistant bacteria. In addition to metagenomic next-generation sequencing (mNGS), microbiological rapid on-site evaluation (M-ROSE) might be a useful technique to identify the pathogens in the early stage; however, the effect of M-ROSE guiding anti-infection treatment on prognostic outcomes of SHAP patients is still unclear. METHODS/DESIGN: This is a multicenter, single-blind, prospective, randomized controlled trial to evaluate the effect of M-ROSE guiding anti-infection treatment in SHAP patients, which will provide new strategies for the prevention and control of clinical multi-drug resistance bacteria. A total of 166 patients with SHAP, aged 18 years and over, will be recruited from seven centers in Beijing and randomly assigned to the intervention group (M-ROSE combined with mNGS) or the control group (mNGS only) in a 1:1 ratio using the central randomization system. Patients in the intervention group will accept M-ROSE and mNGS analysis, and the control group will accept mNGS analysis. Individualized anti-infective treatment and routine treatment will be selected according to the analysis results. The primary outcome is the ICU outcome (mortality). The safety of the intervention measures will be evaluated during the entire trial period. This trial will be the first randomized controlled trial to evaluate the effect of M-ROSE guiding treatment on mortality in patients with SHAP and may change the prevalence of multi-drug resistant bacteria. ETHICS AND DISSEMINATION: This trial adheres to the Declaration of Helsinki and guidelines of Good Clinical Practice. Signed informed consent will be obtained from all participants. The trial has been approved by the Chinese PLA General Hospital (Approval Number: 20220322001). TRIAL REGISTRATION: ClinicalTrials.gov NCT05300776. Registered on 25 March 2022.

3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase (HMGCR) protects hair cells from cisplatin-induced ototoxicity in vitro: possible relation to the activities of p38 MAPK signaling pathway.

The 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase (HMGCR) gene encodes rate-limiting enzyme in cholesterol biosynthesis, which is related to cell proliferation and mitochondrial function. The present study was designed to explore the expression of HMGCR in murine cochlear hair cells and HEI-OC1 cells and the possible mechanisms underpinning the actions of HMGCR in cisplatin-induced ototoxicity, with special attention given to p38 mitogen-activated protein kinase (MAPK) activities in vitro. The expressions of HMGCR, p-p38, cleaved caspase-3 and LC3B was measured by immunofluorescence and western blot. JC-1 staining and MitoSOX Red were used to detect mitochondria membrane potential (MMP) and reactive oxygen species (ROS) levels respectively. The apoptosis of auditory cells was assessed by TUNEL staining and flow cytometry. Protein levels of bcl2/bax and beclin1 were examined by western blot. We found that HMGCR was widely expressed in the auditory cells, of both neonatal mice and 2-month-old mice, in cytoplasm, nucleus and stereocilia. Moreover, 30 µM cisplatin elicited the formation of ROS, which, in turn, led to HMGCR reduction, activating p38 kinase-related apoptosis and autophagy in auditory cells. Meanwhile, co-treatment with ROS scavenger at a concentration of 2 mM, N-acetyl-L-cysteine (NAC), could alleviate the aforementioned changes. In addition, HMGCR silencing resulted in higher p38 MAPK-mediated apoptosis and autophagy under cisplatin injury. Taken together, we demonstrate that, for the first time, that HMGCR is expressed in the cochlear. Furthermore, HMGCR exerts protective benefit on auditory cells against cisplatin-mediated injury stimulated by ROS, culminating in regulation of p38 MAPK-dependent apoptosis and autophagy.

Synchronous triple primary gastrointestinal malignant tumors treated with laparoscopic surgery: A case report.

Synchronous gastrointestinal multiple primary tumors including gastric, colonic, and rectal cancers are rare. Moreover, it was a challenge to find an appropriate procedure without negatively impacting the overall outcome. We described the case of a 63-year-old woman who presented with a 4 month history of upper abdominal pain, acid regurgitation, and anemia. Gastroscopy with biopsy suggested early cancer of gastric antrum. Abdominal contrast-enhanced computerized tomography and colonoscopy revealed ascending colon and rectum tumors. She had no family history of malignancy. Endoscopic submucosal dissection was performed for gastric cancer, and the pathological result presented that it was poorly differentiated and invaded into deep submucosa. The laparoscopy-assisted radical surgery combined with distal gastrectomy, right hemicolectomy, and anterior resection of rectum was performed for these three tumors via eight ports and a 7 cm midline upper-abdominal incision. No other perioperative complications were encountered except postoperative ileus. The patient was discharged on the 12th postoperative day. The pathological results revealed gastric cancer (T1N0M0), right colonic cancer (T3N1M0), and rectal cancer (T2N0M0), indicating complete surgical resection. We reported that our laparoscopic approach for synchronous triple primary gastrointestinal malignant tumors was feasible and minimally invasive.

The protective role of Wnt3a in peroxynitrite-induced damage of cochlear hair cells in vitro.

OBJECTIVE: To investigate the effect of peroxynitrite on the cultured cochlear hair cells of C57BL/6 P3 mice in vitro as well as the role of Wnt3a, as an activator of the canonical Wnt signaling pathway, underlying the action of such an oxidative stress. METHODS: The in vitro primary cultured cochlear hair cells were subjected to l00 µM peroxynitrite and l00 µM peroxynitrite +25 ng/mL Wnt3a for 24 h, the cell survival and morphological changes were examined by immunofluorescence and transmission electron microscopy. RESULTS: The number of surviving hair cells was significantly reduced in the 100 µM peroxynitrite group, while it was significantly higher in the Wnt3a + peroxynitrite treated group compared with the peroxynitrite treated group. The transmission electron microscopy showed that exposure to peroxynitrite induced a dramatic decrease in the number of mitochondria and severely disrupted mitochondrial ultrastructure, while Wnt3a clearly diminished the disruption of mitochondrial structure and preserved a higher number of mitochondria. CONCLUSION: These results indicated that peroxynitrite could cause oxidative damage to the cochlear hair cells, and low concentrations of Wnt3a has a protective effect against oxidative damage. LEVEL OF EVIDENCE: Level 2.

Antiplatelet therapy may improve the prognosis of patients with moyamoya disease: a 12-year retrospective study.

OBJECTIVES: The clinical value of antiplatelet therapy (APT) for moyamoya disease (MMD) remains controversial. Our study attempts to clarify the value of APT in this disease. METHODS: We collected basic information, treatment strategies, and prognostic information on patients with MMD from 2010 to 2022 at our center. The data were divided into two groups, depending on whether APT was used or not, and compared by Pearson Chi-Square, Fisher's exact test, or Wilcoxon rank-sum test. We used propensity scores or inverse probability of treatment weighting to balance the covariates. Following this, we performed a meta-analysis of APT use in MMD. RESULTS: 177 patients were enrolled, with a median follow-up of 41.1 months. APT did not affect the prognosis of patients with perioperative MMD, ischemic MMD, or asymptomatic MMD (P > 0.05), without increasing cerebral hemorrhagic risk. In contrast, APT was found to reduce mortality among patients with hemorrhagic MMD (P = 0.019), without affecting functional status, increasing stroke risk, or causing intracerebral hemorrhage (P > 0.05). But the small group cannot show the effect of APT. Our meta-analysis included nine articles involving 28,925 patients with MMD. It showed that APT could reduce stroke risk (odds ratio, OR = 0.57, 95% CI 0.49 to 0.65) and the Modified Rankin Scale (mRS) (weighted mean difference, WMD = - 0.07, 95% CI 0.14-0.00) during follow-up. The cohort study has limited weight (1.97% and 19.29%) in the meta-analysis. CONCLUSION: Although the limited number of included documents, APT could be beneficial to the prognosis of MMD.

NT-proBNP change is useful for predicting weaning failure from invasive mechanical ventilation among postsurgical patients: a retrospective, observational cohort study.

BACKGROUND: To evaluate the predictive value of N-terminal prohormone B-type natriuretic peptide (NTproBNP) for weaning failure among patients undergoing major surgeries during spontaneous breathing trial (SBT), compared to traditional weaning parameters. METHODS: The observational cohort study retrospectively included postsurgical patients who received IMV and underwent a 2 h SBT. According to weaning outcome, NTproBNP level at initiation (NTproBNP1) and at end of 2 h SBT(NTproBNP2), the ΔNTproBNP%, RSBI and MV were compared between weaning failure and weaning success group. Multiple logistical regression and ROC curve were used to evaluate the capability of NTproBNP to predict weaning failure. RESULTS: Out of the 323 included postsurgical patients, 45 (13.9%) patients had failed weaning. The ΔNTproBNP% was a better predictor for weaning failure (AUC 0.744;95%CI,0.693-0.791) than NTproBNP1(AUC 0.639; 95%CI,0.580-0.694)), NTproBNP2(AUC 0.742, 95%CI,0.688-0.792) and other traditional weaning index such as RSBI (AUC 0.651; 95%CI, 0.597-0.703) and MV (AUC 0.552; 95%CI,0.496-0.607). The cutoff value of ΔNTproBNP% for predicting weaning failure was 23.3% with the sensitivity75.76% and specificity73.38%. The multiple logistic regression analysis found that ΔNTproBNP%>23.3% was an independent predictor of weaning failure. CONCLUSION: ΔNTproBNP% may be a useful marker for predict weaning failure for postsurgical patients, and it's better to be more careful to withdraw from invasive mechanical ventilation for those postsurgical patients with ΔNTproBNP% >23.3%. The corresponding interventions to optimize cardiac function should be actively given to these patients.

Potential therapeutic targets for sarcopenia identified by Mendelian randomisation.

BACKGROUND: Identifying sarcopenia's causally associated plasma proteins would provide potential therapeutic targets. METHODS: We screened out sarcopenia-related proteins with genome-wide association studies (GWAS) summary data and cis-protein loci genetic instruments. Summary data of sarcopenia were obtained from a GWAS of 256,523 Europeans aged 60 years and over. The causal effects of the proteins were investigated by cis-Mendelian Randomisation (MR) and multiverse sensitivity analysis. We also explored the robust proteins' causal associations with appendicular lean mass (ALM) and surveyed their druggability and clinical development activities. RESULTS: In sum, 60 proteins from plasma proteome analysis studies and 12 from other studies were enrolled for MR analysis. In the whole population, four proteins (HPT, AT1B2, ISLR2 and TNF12) showed causal associations with the risk of sarcopenia according to the European Working Group on Sarcopenia in Older People (EWGSOP) criterion. In the female population, AT1B2 and TNFSF12 revealed causal associations with sarcopenia risk according to the EWGSOP criterion; HGF revealed a negative association according to the National Institutes of Health criterion. All of them were druggable, and the inhibitors of TNF12 and HGF were evaluated in clinical trials for other diseases. TNF12 also revealed a negative causal association with ALM, whereas HGF was positively causally associated with ALM. CONCLUSIONS: Five druggable plasma proteins revealed causal associations with sarcopenia in the whole or female populations. TNF12 and HGF were the targets of therapeutic agents evaluated in clinical trials, and they were also causally associated with ALM. Our study suggested the potential mechanisms and therapeutic targets for sarcopenia.

CT-determined sarcopenia is associated with neutropenia in patients undergoing hyperthermic intraperitoneal chemotherapy for gastrointestinal cancer.

BACKGROUND: With better patient selection and the increasing experience in patients undergoing hyperthermic intraperitoneal chemotherapy (HIPEC) combined surgery, the rate of severe postoperative complications and mortality decreased significantly. However, leukopenia and neutropenia were still a particular concern, and their relation to sarcopenia was not clarified. METHODS: Data of consecutive patients who underwent HIPEC for gastrointestinal cancer were collected and analyzed retrospectively between September 2020 and August 2022. Sarcopenia was assessed using psoas muscle index (PMI) at the L3 level on preoperative computed tomography (CT). RESULTS: Among 103 patients enrolled, 37 (35.9%) were classified as sarcopenic. Most leukopenia and neutropenia occurred during the hospital leaving period after HIPEC and surgery. Before the first time of postoperative chemotherapy, the blood tests revealed 11 (29.73%) and 6 (9.09%) patients were diagnosed with neutropenia in sarcopenia and no sarcopenia groups, respectively. Logistic regression analysis revealed sarcopenia was independently associated with the increased risk of neutropenia (OR 5.58, 95% CI 1.70-18.29, p = 0.005). An incremental albumin level was protective against the occurrence of leukopenia and neutropenia. CONCLUSIONS: Sarcopenia and low albumin level were significantly associated with an increased rate of delayed neutropenia after HIPEC in that disease setting and could be the preoperative risk predictors.

The protective role of Wnt3a in peroxynitrite-induced damage of cochlear hair cells in vitro

Abstract Objective To investigate the effect of peroxynitrite on the cultured cochlear hair cells of C57BL/6 P3 mice in vitro as well as the role of Wnt3a, as an activator of the canonical Wnt signaling pathway, underlying the action of such an oxidative stress. Methods The in vitro primary cultured cochlear hair cells were subjected to l00 μM peroxynitrite and l00 μM peroxynitrite +25 ng/mL Wnt3a for 24 h, the cell survival and morphological changes were examined by immunofluorescence and transmission electron microscopy. Results The number of surviving hair cells was significantly reduced in the 100 μM peroxynitrite group, while it was significantly higher in the Wnt3a + peroxynitrite treated group compared with the peroxynitrite treated group. The transmission electron microscopy showed that exposure to peroxynitrite induced a dramatic decrease in the number of mitochondria and severely disrupted mitochondrial ultrastructure, while Wnt3a clearly diminished the disruption of mitochondrial structure and preserved a higher number of mitochondria. Conclusion These results indicated that peroxynitrite could cause oxidative damage to the cochlear hair cells, and low concentrations of Wnt3a has a protective effect against oxidative damage. Level of evidence: Level 2.

Immunoglobulin G4-related disease in the sigmoid colon in patient with severe colonic fibrosis and obstruction: A case report.

BACKGROUND: Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated condition characterized by abundant IgG4 positive plasma cells and fibrosis in the affected tissues. It affects most parts of the body; however, there are not many reports on IgG4-RD involving the colon. CASE SUMMARY: A 50-year-old man complaining of intermittent fever for more than two years was referred to our hospital. Based on various investigations before surgery, we diagnosed him with chronic perforation of the sigmoid colon caused by inflammatory change or tumor. IgG blood tests before the operation suggested IgG4-RD, and postoperative pathology confirmed this prediction. CONCLUSION: We present a patient with IgG4-RD with colon involvement, which is an uncommon site. This report will expand the understanding of IgG4-RD in unknown tissues.

Chronic suppurative otitis media causes macrophage-associated sensorineural hearing loss.

BACKGROUND: Chronic suppurative otitis media (CSOM) is the most common cause of permanent hearing loss in children in the developing world. A large component of the permanent hearing loss is sensory in nature and our understanding of the mechanism of this has so far been limited to post-mortem human specimens or acute infection models that are not representative of human CSOM. In this report, we assess cochlear injury in a validated Pseudomonas aeruginosa (PA) CSOM mouse model. METHODS: We generated persisters (PCs) and inoculated them into the mouse middle ear cavity. We tracked infection with IVIS and detected PA using RT-PCR. We assessed cochlear damage and innate immunity by Immunohistochemistry. Finally, we evaluated cytokines with multiplex assay and quantitative real-time PCR. RESULTS: We observed outer hair cell (OHC) loss predominantly in the basal turn of the cochlear at 14 days after bacterial inoculation. Macrophages, not neutrophils are the major immune cells in the cochlea in CSOM displaying increased numbers and a distribution correlated with the observed cochlear injury. The progression of the morphological changes suggests a transition from monocytes into tissue macrophages following infection. We also show that PA do not enter the cochlea and live bacteria are required for cochlear injury. We characterized cytokine activity in the CSOM cochlea. CONCLUSIONS: Taken together, this data shows a critical role for macrophages in CSOM-mediated sensorineural hearing loss (SNHL).

Mean platelet volume as a predictive biomarker for in-hospital mortality in patients receiving invasive mechanical ventilation.

BACKGROUND: Although mean platelet volume (MPV) has been reported to be associated with poor prognosis of various critical illness, the relationship between MPV and in-hospital mortality among patients undergoing invasive mechanical ventilation (IMV) is unclear. METHODS: A retrospective observational study including patients receiving IMV was conducted from January, 2014 to January, 2019. The patients were divided into two groups by MPV cutoff value. The receiver operating characteristics curve was used to evaluate the predictive ability of MPV for in-hospital mortality. Univariate and multivariate Cox regression analysis were conducted to analyze the value of MPV for predicting in-hospital mortality. Kaplan-Meier cumulative incidence curve was employed to observe the incidence of in-hospital mortality. RESULTS: A total of 274 patients were enrolled in the study, and 42 patients (15.3%) died in hospital. MPV > 11.4 fl was a valuable predictor for in-hospital mortality (AUC0.848; 95%CI, 0.800-0.889) with sensitivity 66.7%, and specificity = 86.21%. MPV > 11.4 fl was an independent risk factor for in-hospital mortality (adjusted HR 2.640, 95%CI, 1.208-5.767, P = 0.015). Compared to the group of MPV ≤ 11.4 fl, patients with MPV > 11.4 fl had increased mortality (log-rank test = 40.35, HR = 8.723, P < 0.0001). The relationship between MPV and in-hospital mortality was stronger in female patients than in male patients. CONCLUSION: MPV > 11.4 fl is a more useful marker for predicting in-hospital mortality among critically ill patients receiving IMV, especially in female patients. Attention to the MPV marker is simple and profitable with immediate applicability in daily clinical practice.

Prevalence and burden of chronic cough in China: a national cross-sectional study.

Background: Chronic cough is a common complaint, but there are no population-based data on its burden in China. We determined the prevalence of chronic cough and its impact on health status in adults stratified by sex, age and the diagnosis of COPD or the presence of small airway dysfunction (SAD). Methods: A representative sample of 57 779 Chinese adults aged 20 years or older was recruited and pulmonary function test was measured. Chronic cough was defined as cough lasting for >3 months in each year. Quality of life was assessed by the 12-item Short Form Health Survey (SF-12), and self-reported history of hospital visits was recorded. Results: Chronic cough was found in 3.6% (95% CI 3.1-4.1) of Chinese adults, 2.4% (95% CI 1.9-3.1) of those aged 20-49 years and 6.0% (95% CI 5.3-6.8) of those aged 50 years or older. Individuals with chronic cough had an impaired physical component summary (PCS) score of the SF-12 (p<0.0001) and more emergency visits (p=0.0042) and hospital admissions (p=0.0002). Furthermore, the impact of chronic cough on PCS score was more significant in those aged 50 years or older, or with COPD (p=0.0018 or 0.0002, respectively), with the impact on hospital admission being more significant in those with COPD or with SAD (p=0.0026 or 0.0065, respectively). Conclusions: Chronic cough is prevalent in China and is associated with a poorer health status, especially in individuals aged 50 years or older and those with the diagnosis of COPD or SAD.

Gold nanocluster adjuvant enables the eradication of persister cells by antibiotics and abolishes the emergence of resistance.

Persister cells are responsible for relapses of infections common in cystic fibrosis and chronic suppurative otitis media (CSOM). Yet, there are no Food and Drug Administration (FDA) approved antibiotics to eradicate persister cells. Frustratingly, the global preclinical bacterial pipeline does not contain antibacterial agents targeting persister cells. Therefore, we report a nontraditional antimicrobial chemotherapy strategy based on gold nanoclusters adjuvant to eradicate persister cells by existing antibiotics belonging to that different class. Compared to killing with antibiotics alone, combining antibiotics and AuNC@CPP sterilizes persister cells and biofilms. Enhanced killing of up to 4 orders of magnitude in a validated mouse model of CSOM with Pseudomonas aeruginosa infection was observed when combining antibiotics and AuNC@CPP, informing a potential approach to improve the treatment of CSOM. We established that the mechanism of action of AuNC@CPP is due to disruption of the proton gradient and membrane hyperpolarization. The method presented here could compensate for the lack of new antibiotics to combat persister cells. This method could also benefit the current effort to slow resistance development because AuNC@CPP abolished the emergence of drug-resistant strains induced by antibiotics.