2022年 · 第135卷第15期

Adipose stem cells (ADSCs) have been reported to have multidirectional differentiation potential, and can promote cell proliferation and growth, and nerve regeneration function, which has become a promising treatment regimen for wound repair. Exosomes derived from ADSCs (ADSCs-Exos) have excellent tissue repair functions, including high vascular endothelial growth factor A, fibroblast growth factor 2, hepatocyte growth factor, platelet-derived growth factor subunit BB, and other important wound healing factors.^[1]Supplementary Figure 1, http://links.lww.com/CM9/A828 is a simplified diagram of the exosome formation and release model.

Obesity has become a global epidemic, and the prevalence of obesity has increased to pandemic levels over the past 50 years.^[1]According to the statistics of the World Health Organization (WHO), there are >2.1 billion overweight and obese adults worldwide, 1.5 billion of whom are overweight and 640 million of whom are obese.^[2]It is predicted that 57.8% (3.3 billion people) of the world’s adult population will have a body mass index of 25 kg/m²or higher by 2030, which is a huge challenge in both developed and developing countries.^[3,4]In the United States, the prevalence of adult obesity and severe obesity continues to increase; it is estimated that by 2030, nearly one in two adults will have obesity, and nearly one in four adults is projected to have severe obesity.^[5]It has been reported that the occurrence of overweight and obesity in residents aged ≥18 years are 34.3% and 16.4%, those in children and adolescents aged 6 to 17 years are 11.1% and 7.9%, and those in children under 6 years old are 6.8% and 3.6%, respectively.^[6]The problem of overweight and obesity incidence in children and adolescents has increased at an alarming rate, posing a great threat to society as a whole.^[7]Therefore, finding an effective means to control the growth of obesity and explore new approaches in both scientific research and public policy is urgently needed.

Nasal insertion is the preferred method for non-intubated patients in flexible bronchoscopy; however, the relatively narrow nasal cavity results in difficulties related to bronchoscope insertion. This study aimed to investigate whether pre-operative nasal probe tests could reduce the time to pass the glottis, improve the first-pass success rate and patients’ tolerance, and reduce postoperative bleeding.

This three-arm prospective randomized controlled trial was conducted in a tertiary hospital between May and October 2020. Three hundred patients requiring diagnosis and treatment using flexible bronchoscopy were randomly allocated to three groups: control group, simple cotton bud detection group (CD group), and adrenaline + lidocaine detection group (AD group). The primary outcome was the time to pass the glottis. Secondary outcomes included the first-pass success rate, the patients’ tolerance scores, and post-operative bleeding. One-way analysis of variance, Kruskal-Wallis H test, Chi-squared test, Fisher’s exact test, and Bonferroni’s multiple comparison tests were used in this study.

In total, 189 men and 111 women were enrolled in this study, with a mean age of 55.72 ± 12.86 years. The insertion time was significantly shorter in the AD group than in the control group (18.00 s [12.00–26.50 s] vs. 24.00 s [14.50–45.50 s], P = 0.005). Both the AD (99% vs. 83%, χ² = 15.62, P < 0.001) and CD groups (94% vs. 83%, χ² = 5.94, P = 0.015) had a significantly higher first-pass success rate than the control group. Compared with the control group, post-operative bleeding (1% vs. 13%, χ² = 11.06, P < 0.001) was significantly lower in the AD group. However, no significant difference was found in the patients’ tolerance scores.

Pre-operative nasal cavity probe tests especially with adrenaline and lidocaine during flexible bronchoscopy can significantly reduce the time to pass the glottis, improve the first-pass success rate, and reduce post-operative nasal bleeding. Pre-operative nasal probe tests are recommended as a time-saving procedure for patients undergoing flexible bronchoscopy.

Chinese Clinical Trial Registry (ChiCTR), ChiCTR2000032668; http://www.chictr.org.cn/showprojen.aspx?proj=53321.

Feeding intolerance (FI) among intensive care unit (ICU) patients undergoing early continuous enteral nutrition (EN) is related to poor outcomes. This study aimed to explore the prevalence and risk factors of FI in ICU patients.

We retrospectively enrolled 1057 patients who received early continuous EN via a nasogastric tube between January 2014 and August 2019. The prevalence of FI during the first 7 days of ICU stay was calculated, and the risk factors were investigated using multivariate logistic regression analysis.

The prevalence of FI during the first 7 days of ICU stay was 10.95%. FI occurred in 159 of 1057 (15.04%) patients on ICU day 2, 114 of 977 (11.67%) patients on ICU day 3, and 86 of 715 (12.03%) patients on ICU day 7. Mechanical ventilation (MV) (odds ratio [OR]: 1.928, 95% confidence interval [CI]: 1.064–3.493, P = 0.03) was an independent risk factor for FI defined by a gastric residual volume (GRV) of 200 mL and/or vomiting, and acute renal failure (OR: 3.445, 95% CI: 1.115–10.707, P = 0.032) was an independent risk factor of FI defined by a GRV of 500 mL and/or vomiting. Continuous renal replacement therapy (CRRT) was an independent predictor regardless of the FI defined by a GRV of 200 mL (OR: 2.064, 95% CI: 1.233–3.456, P = 0.006) or 500 mL (OR: 6.199, 95% CI: 2.108–18.228, P = 0.001) in the ICU patients.

FI occurs frequently in early ICU days, especially in patients receiving MV and CRRT. However, further investigation of a consensus definition of FI and risk factors is still warranted in future studies.

Previous evidence suggests inflammation may be a double-edged sword with cancer-promoting and cancer suppressing function. In this study, we explore the impact of local and systemic inflammation on cancer growth.

Female BALB/C mice were subcutaneously implanted with foreign body (plastic plates) to build up a local inflammation and intraperitoneally injected with PolyIC or lipopolysaccharides (LPS) to build up a systemic inflammation, followed by subcutaneous injection of 5 × 10⁵ colon cancer cells. Immunohistochemistry and enzyme linked immunosorbent assay were utilized to detect the Ki67 and interleukin (IL) 6, IL-1β, and monocyte chemoattractant protein-1 expression in the tumor tissues and serum, respectively. The distributions of immune cells and expression of toll-like receptors (TLRs) were evaluated by flow cytometry (FCM) and quantitative real time-polymerase chain reaction.

The results showed that local inflammation induced by foreign body implantation suppressed tumor growth with decreased tumor weight (P = 0.001), volume (P = 0.004) and Ki67 index (P < 0.001). Compared with the control group, myeloid-derived suppressive cells sharply decreased (P = 0.040), while CD4⁺ T cells slightly increased in the tumor tissues of the group of foreign body-induced local inflammation (P = 0.035). Moreover, the number of M1 macrophages (P = 0.040) and expression of TLRs, especially TLR3 (P < 0.001) and TLR4 (P < 0.001), were significantly up-regulated in the foreign body group. Contrarily, tumor growth was significantly promoted in LPS or PolyIC-induced systemic inflammation (P = 0.009 and 0.006). FCM results showed M1 type macrophages (P = 0.017 and 0.006) and CD8⁺ T cells (P = 0.031 and 0.023) were decreased, while M2 type macrophages (P = 0.002 and 0.007) were significantly increased in tumor microenvironment of LPS or PolyIC-induced systemic inflammation group. In addition, the decreased expression of TLRs was detected in LPS or PolyIC group.

The foreign body-induced local inflammation inhibited tumor growth, while LPS or PolyIC-induced systemic inflammation promoted tumor growth. The results suggested that the different outcomes of tumor growth might be attributed to the infiltration of anti-tumor or pro-tumor immune cells, especially M1 or M2 type macrophages into tumor microenvironment.

Head and neck cancers (HNCs) are a heterogeneous group of tumors that progress owing to varied enviromental and genetic risk factors. Viral infections are threatening and adept at altering the expression of cellular transcription factors such as nuclear factor kappa B (NF-κB) and deregulation of other cellular proteins like NF kappa B inhibitor alpha (IκBα). The present study was conducted to detect high-risk genotypes of human papillomavirus (HPV) and protein expression of NF-κB signaling pathway in HNC patients with HPV infection.

For HPV detection, genomic DNA from 152 HNC tumors was extracted formalin-fixed paraffin-embedded tissue DNA kit. For genotyping, polymerase chain reaction (PCR) using a general primer, HPV type-specific primers and agarose gel electrophoresis were performed. Immunohistochemistry (IHC) was also performed on 4-μm thick tissue sections using HPV E6 monoclonal antibody. Protein expression analysis of NF-κB signaling pathway including p50, p65, and IκBα was performed using IHC.

PCR analysis showed that 24.3% (37/152) of HNC cases were HPV positive. Among HPV positive, 86.5% (32/37) were tobacco users, while among HPV negative, 66.9% (77/115) were tobacco users. A significant association of HPV positivity and tobacco user was observed by univariate analysis [P < 0.01; odds ratio (OR): 0.310, 95% confidence interval (CI): 0.110 to 0.870]. More HPV positive patients were with poor oral hygiene (78.3%) when compared with patients with good oral hygiene (21.6%) [P < 0.03, OR: 2.440, 95% CI: 1.650 to 3.600]. The results of the logistic regression analysis showed that age, tobacco use and oral hygiene are significant predictors (P < 0.02). PCR and IHC staining results confirmed that HPV16 was predominant among HNC cases (64.8%) when compared with HPV18 (35.2%). Expression of NF-κB proteins (p50, p65, and IκBα inhibitor) were also observed in HPV and non-HPV infected HNC tissues. IHC expression of p50, and p65 showed nuclear staining, while IκBα inhibitor showed cytoplasmic staining. Protein expression in HPV cases was higher as compared to HPV naive cases (P < 0.05).

From the study, it can be established that the use of tobacco, oral hygiene, and HPV infection may be synergistically involved in modulating the expression of NF-κB signaling pathway for the development and progression of HNC in the Pakistani population.

Coronary artery disease (CAD) is the commonest cause of heart failure (HF), whereas pulmonary hypertension (PH) has not been established or reported in this patient population. Therefore, we assessed the prevalence, risk factors, and survival in CAD-associated HF (CAD-HF) complicated with PH.

Symptomatic CAD-HF patients were continuously enrolled in this prospective, multicenter registry study. Echocardiography, coronary arteriography, left and right heart catheterization (RHC), and other baseline clinical data were recorded. Patients were followed up and their survival was recorded.

One hundred and eighty-two CAD-HF patients were enrolled, including 142 with HF with a preserved ejection fraction (heart failure with preserved ejection fraction [HFpEF]; left ventricular ejection fraction [LVEF] ≥50%) and 40 with a reduced ejection fraction (heart failure with reduced ejection fraction [HFrEF]; LVEF < 50%). PH was diagnosed with RHC in 77.5% of patients. Patients with PH showed worse hemodynamic parameters and higher mortality. HFrEF-PH patients had worse survival than HFpEF-PH patients. CAD-HF patients with an enlarged left ventricular end-diastolic diameter and reduced hemoglobin were at higher risk of PH. Nitrate treatment reduced the risk of PH. Elevated creatinine and mean pulmonary arterial pressure (mPAP), diastolic pressure gradient (DPG) ≥7 mmHg, and previous myocardial infarction (MI) entailed a higher risk of mortality in CAD-HF patients with PH.

PH is common in CAD-HF and worsens the hemodynamics and survival in these patients. Left ventricle enlargement and anemia increase the risk of PH in CAD-HF. Patients may benefit from nitrate medications. Renal impairment, elevated mPAP, DPG ≥7 mmHg, and previous MI are strong predictors of mortality in CAD-HF-PH patients.

ClinicalTrials.gov, NCT02164526.

Excessive exposure to fluoride can reduce intelligence. Methylenetetrahydrofolate dehydrogenase, cyclohydrolase, and formyltetrahydrofolate synthetase 1 (MTHFD1) polymorphisms have important roles in neurodevelopment. However, the association of MTHFD1 polymorphisms with children’s intelligence changes in endemic fluorosis areas has been rarely explored.

A cross-sectional study was conducted in four randomly selected primary schools in Tongxu County, Henan Province, from April to May in 2017. A total of 694 children aged 8 to 12 years were included in the study with the recruitment by the cluster sampling method. Urinary fluoride (UF) and urinary creatinine were separately determined using the fluoride ion-selective electrode and creatinine assay kit. Children were classified as the high fluoride group and control group according to the median of urinary creatinine-adjusted urinary fluoride (UF_Cr) level. Four loci of MTHFD1 were genotyped, and the Combined Raven’s Test was used to evaluate children’s intelligence quotient (IQ). Generalized linear model and multinomial logistic regression model were performed to analyze the associations between children’s UF_Cr level, MTHFD1 polymorphisms, and intelligence. The general linear model was used to explore the effects of gene-environment and gene-gene interaction on intelligence.

In the high fluoride group, children’s IQ scores decreased by 2.502 when the UF_Cr level increased by 1.0 mg/L (β= –2.502, 95% confidence interval [CI]: –4.411, –0.593), and the possibility for having "excellent" intelligence decreased by 46.3% (odds ratio = 0.537, 95% CI: 0.290, 0.994). Children with the GG genotype showed increased IQ scores than those with the AA genotype of rs11627387 locus in the high fluoride group (P < 0.05). Interactions between fluoride exposure and MTHFD1 polymorphisms on intelligence were observed (Pinteraction < 0.05).

Our findings suggest that excessive fluoride exposure may have adverse effects on children’s intelligence, and changes in children’s intelligence may be associated with the interaction between fluoride and MTHFD1 polymorphisms.

Earlier, the major surgical treatments for ventral hernia were open sublay repair and laparoscopic intraperitoneal onlay mesh (Lap-IPOM) repair. Sublay is an effective and safe plane.^[1]Recently, some surgeons successfully transferred open sublay repair to endoscopic sublay repair (ESR), which may avoid the wound events after open procedure and potential risks of intra-abdominal injury and mesh complications from Lap-IPOM repair.^[1,2,3]

To the Editor:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus causing coronavirus disease 2019 (COVID-19).^[1]As a new evolutionary branch within coronaviruses, SARS-CoV-2 contains around 29.8 kilobase and shows 79.2% identity with SARS-CoV-1.^[2]As the successor to SARS-CoV-1, SARS-CoV-2 shares a highly similar sequence and behavior pattern with SARS-CoV-1.^[3]Recent study found that SARS-CoV-1 encoded 18 to 22 nt small viral RNAs (svRNAs), which were independent of RNase III, cell type, and host species but relies on the extent of viral replication.^[3]Evidence has supported that svRNAs could be generated from cytoplasmic RNA viruses, relevant to viral pathogenicity.^[3]As shown in SARS-CoV-1, inhibiting one of the svRNAs named svRNA-N reducedin vivolung pathology and inflammation.^[4]We verified the existence of two SARS-CoV-2-encoded small RNAs and investigated the pro-inflammatory effects during their maturation in human bronchial epithelial cell line (16HBE), which might provide new insight into the pathogenesis and possible treatment options for COVID-19.

To the Editor:Esophageal squamous cell carcinoma (ESCC) is the seventh most common malignant cancer worldwide.^[1]There is an urgent need to find sensitive and specific biomarkers to improve ESCC diagnosis and prognosis.^[2]Tumor-specific long non-coding RNA (lncRNA) seems to be potential biomarkers for the diagnosis and treatment of cancer.^[3]Our previous study has performed data mining analyses for ESCC and identification of the dysregulated lncRNAs from the Gene Expression Omnibus database (GEO, https://www.ncbi. nlm.nih.gov/sites/GDSbrowser).^[4]The results demonstrated that lncRNA plasmacytoma variant translocation 1 (PVT1) gene expression is significantly up-regulated in ESCC tumor tissues. In the present study, we analyze the feasibility of using PVT1 as a tumor molecular marker and discuss its potential clinical applications.

To the Editor:Systemic lupus erythematosus (SLE) is a chronic autoimmune disease of unknown cause that can affect any organ of the body. Human papillomavirus (HPV) infection is associated with the development of cervical dysplasia and cancer in SLE patients. HPV vaccines can effectively prevent HPV infection and subsequent HPV-related diseases. HPV vaccination is effective, immunogenic, and safe for SLE patients.^[1]However, concerns about the safety of HPV vaccine have been raised by case reports of the onset of SLE following HPV vaccination.^[1,2,3]

To the Editor:Allergic asthma and allergic rhinitis (AR) are common diseases that often occur concomitantly. Approximately 80% of allergic asthmas suffer from AR symptoms, as the two diseases share common immunopathological mechanisms. Sensitization and exposure to allergens are the risk factors that induce and aggravate allergic airway diseases such as allergic asthma and AR. With climate change, the distribution of allergens during different seasons has become very heterogeneous. Therefore, the identification of specific allergens prevalent during different seasons and in various population subsets would be useful for formulating strategies that would help to prevent and treat respiratory allergic diseases, including allergic asthma and AR. The main purpose of this study was to investigate that whether the distribution of inhaled allergens among allergic asthma patients with or without AR who visited the hospital for the first time in different seasons had seasonal specificity.

To the Editor:Left ventricular diastolic dysfunction (LVDD) is an unrecognized subclinical presentation of autoimmune diseases (AD) and carries a worse prognosis. Elevated serum uric acid (SUA), as a proinflammatory factor, is associated with changes in cardiac function in the general population as well as in those with cardiac diseases; however, it has never been investigated in patients with AD. Therefore, we conducted this retrospective study in a large population of patients with a wide spectrum of AD to explore the burden of LVDD and its relationship with quartiles of SUA level.

To the Editor:Diabetes mellitus (DM) is a chronic disease that endangers human health and can lead to different complications.^[1]Coronary artery disease is one of the most serious complications in DM patients. Recently, increasing evidence has shown that the pathophysiology of diabetic coronary diseases is related to ion channels dysfunction in coronary artery smooth muscle cells (SMCs).^[2]Therefore, a better understanding of the ionic mechanism underlying diabetic coronary artery dysfunction is of clinical importance.

To the Editor:A 71-year-old male patient was referred for incidentally delayed type Ib endoleak on computed tomographic angiography (CTA). He had been performed endovascular abdominal aortic aneurysm repair (EVAR) with the Zenith (Cook Inc, Bloomington, IN, USA) stent-grafts for right common iliac artery (CIA) aneurysm with a diameter of 4.4 cm at 17 months ago. The vital sign was stable, and there was no related symptom. On CTA at 8 months after EVAR, there was no endoleak [Figure 1A]. On this visit, CTA showed that there was a newly developed type Ib endoleak at the left iliac limb [Figure 1B]. So, we tried reintervention via left femoral artery puncture, but it failed because of severe calcific stenosis and tortuosity of the external iliac artery (EIA). Therefore, we performed a left axillary artery puncture. A guidewire was passed into the main body and left limb and was captured by snaring through the left femoral artery. We tried to insert a stent-graft into the distal end of preexisting stent-graft, but could not do it. An angiography showed that the guidewire was passed through a tiny space between the stent and graft, and then came out toward the iliac artery lumen [Figure 1C]. Therefore, another Zenith (Cook Inc, Bloomington, IN, USA) stent-graft with 12 mm in diameter was inserted into EIA to make EIA to be less tortuous. Fortunately, the guidewire was passed through pre-existing stent-graft into the proximal aorta. Finally, a stent-graft with 12 mm in diameter was additionally inserted to manage type Ib endoleak. At the 7th day postoperatively, CTA showed that there was no endoleak [Figure 1D]. The patient was uneventfully discharged.

To the Editor:Systemic sclerosis (SSc) is an autoimmune disease characterized by progressive skin and visceral fibrosis, microvasculopathy, and autoimmunity. Circulating auto-antibodies (AAbs) are detectable in 90% to 95% of patients with SSc.^[1]It is reported that 60% to 80% of SSc patients are positive for anti-topoisomerase I antibody (ATA), anti-centromere antibody (ACA), and anti-RNA polymerase III antibody (ARA).^[2]These three AAbs are the most prevalent SSc-associated AAbs, with high specificity for the diagnosis of SSc; so they have been included in the classification criteria for SSc defined by the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) in 2013. Currently, SSc-associated AAbs have been widely used in clinical practice, and the research on the clinical significance of AAbs is still in progress. In our present study, we analyzed the correlations between the SSc-associated auto-antibody profile and clinical manifestations in a well-characterized Chinese SSc cohort.

To the Editor:Epidemiological studies have shown that fine particulate matter 2.5 (PM2.5) exposure increases the risk of skin hyperpigmentation.^[1]A recent study proved that PM2.5 could induce melanogenesis by regulating tyrosinase (TYR), and tyrosinase-related protein 1 (TYRP1) and 2 (TYRP2) expression via aryl hydrocarbon receptor (AhR)/mitogen-activated protein kinase signaling activation.^[2]The AhR is widespread in skin cells and its ligation controls oxidation/anti-oxidation, epidermal barrier function, photo-induced response, innate immunity, and melanogenesis. It can be activated by dioxin and polycyclic aromatic hydrocarbons (the constituents of PM2.5) and its activation induces the transcription of genes encoding both phase I and phase II xenobiotic metabolism enzymes (cytochromes P450 [CYP] 1A1, CYP1A2, and CYP1B1).^[3,4]BaP and hazardous dioxins activate AhR with a robust reactive oxygen species (ROS) generation, which is at least partly mediated by CYP1A1. Moreover, CYP1A1-mediated oxidative stress is responsible for the production of pro-inflammatory cytokines, such as interleukin (IL)-1, IL-6, and IL-8 in environmental contaminant-treated human keratinocytes.^[3,5]However, there are very few studies on the toxic effects of PM2.5 on melanogenetic cells. Herein, we treated human melanoma cells A375 with various concentrations of PM2.5 to investigate whether PM2.5 can promote melanogenesis, and its relationship with AhR signaling, oxidative stress, and inflammatory response.

Tothe Editor:Anthracycline antibiotics are the core treatment strategy for breast cancer, hematological malignancies, and sarcomas. The main clinical drugs are daunorubicin and doxorubicin. Unfortunately, cumulative doses of anthracyclines can induce cardiac dysfunction in patients with tumors, such as cardiotoxicity, myocardial ischemia, or infarction, which in turn affects the tumor treatment.^[1,2]Researchers found that anthracycline-in-duced cardiotoxicity (AIC) develops during or after treatment; however, the exact mechanism is unclear. Therefore, the optimal use of non-invasive cardiac examinations is necessary to control the drug side effects. Medical imaging technology has been reckoned to be the most effective method for the non-invasive detection of AIC. Therefore, to minimize the cardiac risk, a brief overview of the latest advances in medical imaging technology has been provided in this article.