Extracellular vesicles (EVs) are anuclear particles composed of lipid bilayers that contain nucleic acids, proteins, lipids, and organelles. EVs act as an important mediator of cell-to-cell communication by transmitting biological signals or components, including lipids, proteins, messenger RNAs, DNA, microRNAs, organelles, etc, to nearby or distant target cells to activate and regulate the function and phenotype of target cells. Under physiological conditions, EVs play an essential role in maintaining the homeostasis of the pulmonary milieu but they can also be involved in promoting the pathogenesis and progression of various respiratory diseases including chronic obstructive pulmonary disease, asthma, acute lung injury/acute respiratory distress syndrome, idiopathic pulmonary fibrosis (IPF), and pulmonary artery hypertension. In addition, in multiple preclinical studies, EVs derived from mesenchymal stem cells (EVs) have shown promising therapeutic effects on reducing and repairing lung injuries. Furthermore, in recent years, researchers have explored different methods for modifying EVs or enhancing EVs-mediated drug delivery to produce more targeted and beneficial effects. This article will review the characteristics and biogenesis of EVs and their role in lung homeostasis and various acute and chronic lung diseases and the potential therapeutic application of EVs in the field of clinical medicine.
Brain metastasis (BM) is the leading cause of mortality in lung cancer patients. The process of BM (from initial primary tumor development, migration and intravasation, dissemination and survival in the bloodstream, extravasation, to colonization and growth to metastases) is a complex process for which few tumor cells complete the entire process. Recent research on BM of lung cancer has recently stressed the essential role of tumor microenvironment (TME) in assisting tumor cells in the completion of each BM step. This review summarizes recent studies regarding the effects of TME on tumor cells in the entire process of BM derived from lung cancer. The identification of vulnerable targets in the TME and their prospects to provide novel therapeutic opportunities are also discussed.
Mir Ibrahim Sajid, Shaheer Ahmed, Usama Waqar, Javeria Tariq, Mohsin Chundrigarh, Samira Shabbir Balouch, Sajid Abaidullah
中华医学杂志英文版2022年 135卷 15期
DOI: 10.1097/CM9.00000000000020S8
摘要
Artificial intelligence (AI) has proven time and time again to be a game-changer innovation in every walk of life, including medicine. Introduced by Dr. Gunn in 1976 to accurately diagnose acute abdominal pain and list potential differentials, AI has since come a long way. In particular, AI has been aiding in radiological diagnoses with good sensitivity and specificity by using machine learning algorithms. With the coronavirus disease 2019 pandemic, AI has proven to be more than just a tool to facilitate healthcare workers in decision making and limiting physician-patient contact during the pandemic. It has guided governments and key policymakers in formulating and implementing laws, such as lockdowns and travel restrictions, to curb the spread of this viral disease. This has been made possible by the use of social media to map severe acute respiratory syndrome coronavirus 2 hotspots, laying the basis of the "smart lockdown" strategy that has been adopted globally. However, these benefits might be accompanied with concerns regarding privacy and unconsented surveillance, necessitating authorities to develop sincere and ethical government–public relations.
Wenjun Zhu, Yuchen Zhang, Jingyu Shi, Xiaoqin Wang, Renjiao Li, Jia Liu, Ping Li, Dan Liu, Fengming Luo
中华医学杂志英文版2022年 135卷 15期
DOI: 10.1097/CM9.0000000000002006
摘要
Background:
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.
Methods:
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.
Results:
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.
Conclusions:
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.
Trial registration:
Chinese Clinical Trial Registry (ChiCTR), ChiCTR2000032668; http://www.chictr.org.cn/showprojen.aspx?proj=53321.
Kunrong Yu, Na Guo, Dingding Zhang, Ying Xia, Yanling Meng, Li Weng, Bin Du
中华医学杂志英文版2022年 135卷 15期
DOI: 10.1097/CM9.0000000000001974
摘要
Background:
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.
Methods:
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.
Results:
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.
Conclusions:
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.
Background:
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.
Methods:
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.
Results:
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.
Conclusions:
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.
Sumaira Sarwar, Mushir Mulla, Munaz Mulla, Rida Tanveer, Maimoona Sabir, Aneesa Sultan, Salman A. Malik
中华医学杂志英文版2022年 135卷 15期
DOI: 10.1097/CM9.0000000000001970
摘要
Background:
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.
Methods:
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.
Results:
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).
Conclusions:
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.
Li Huang, Lingpin Pang, Qing Gu, Tao Yang, Wen Li, Ruilin Quan, Weiqing Su, Weifeng Wu, Fangming Tang, Xiulong Zhu 等
中华医学杂志英文版2022年 135卷 15期
DOI: 10.1097/CM9.0000000000002112
摘要
Background:
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.
Methods:
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.
Results:
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.
Conclusions:
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.
Trial Registration:
ClinicalTrials.gov, NCT02164526.
Zichen Feng, Ning An, Fangfang Yu, Jun Ma, Na Li, Yuhui Du, Meng Guo, Kaihong Xu, Xiangbo Hou, Zhiyuan Li 等
中华医学杂志英文版2022年 135卷 15期
DOI: 10.1097/CM9.0000000000002062
摘要
Background:
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.
Methods:
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 (UFCr) 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 UFCr level, MTHFD1 polymorphisms, and intelligence. The general linear model was used to explore the effects of gene-environment and gene-gene interaction on intelligence.
Results:
In the high fluoride group, children’s IQ scores decreased by 2.502 when the UFCr 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).
Conclusion:
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.