2018年 · 第131卷第10期

The microcirculation is attracting more and more attention due to its central role in prognosis of critically ill patients. Monitoring perfusion of patients on intensive care units is of highest priority to guide diagnostic and treatment strategies to optimize organ perfusion, subsequently leading to an individualized therapy. The most often used parameter to detect alterations in the microcirculation is serum lactate; there is still lack of bedside monitoring methods for direct observation of microcirculation. With the noninvasive, convenient, and unique value in the quick diagnosis and dynamic monitoring during the course of treatment, bedside critical ultrasonography has been widely used, regarded as the "visual stethoscope." Contrast-enhanced ultrasonography (CEUS) is a competing technology that enables real-time observation of vascular perfusion; the basic composition of the contrast agents is microbubbles made of gases embedded within a shell characterized by safety, high tolerance, and lack of radiation, which can reflect ultrasound and avoid destruction during circulation and allow for continuous imaging of the vasculature and microcirculation. Therefore, CEUS can be used for the assess tissue microcirculation of critically ill patients, particularly in visceral organs.^[1]

Acute respiratory distress syndrome (ARDS) is one of the leading death reasons in Intensive Care Unit (ICU).^[1]It is frustrating that there is no pharmacotherapy effective enough to reduce the mortality of ARDS. The most important treatment of ARDS nowadays is supportive treatment, including mechanical ventilation (MV), fluid management, and sedation.^[2]Successful trials of ARDS treatments usually aim to avoid further lung injury of ARDS patients, such as low tidal volume of MV and conservative fluid strategy. These strategies can only maintain the mortality around 40%.^[1]

Gastrointestinal dysfunction plays a critical role in the prognosis of critically ill patients. Previous studies showed rhubarb, a traditional Chinese herb, can protect the intestinal barrier function, prevent intestinal bacterial translocation, and promote gastrointestinal peristalsis, but the clinical studies are less. The aim of this study was to evaluate the effects of rhubarb on gastrointestinal dysfunction in critically ill patients.

From June 2015 to May 2017, a total of 368 critically ill patients with Grade I–III acute gastrointestinal injury (AGI) were enrolled in this study. Patients were divided into two groups according to the exposure factors (whether the patients received rhubarb treatment): the rhubarb group and the usual treatment group. Clinical data were collected within the first 24 h of the Intensive Care Unit (ICU) admission and 7 days after treatment. Survival data on day 28 after ICU admission and the durations of ICU and total hospitalization were also collected. Propensity score matching (PSM) was conducted to reduce confounding bias between the groups. The logistic regression was conducted to screen the influence factors.

The eligible patients were divided into rhubarb group (n = 219, 59.5%) and usual treatment group (n = 149, 40.5%). Before PSM, the remission rate of feeding intolerance in rhubarb group and usual treatment group were 59.8% and 39.6%, respectively. After PSM, the remission rate of feeding intolerance in rhubarb group and usual treatment group was 77.9% and 30.9%, respectively. The remission rates of feeding intolerance in rhubarb group were significantly higher than those in the usual treatment group (all P< 0.05). Compared with the usual treatment group, the rhubarb group had a higher rate of AGI improvement, lower level of C-reactive protein, shorter stay in ICU before and after PSM (P < 0.05). There was no significant difference in 28-day mortality between rhubarb and usual treatment groups before and after PSM (48 vs. 33, P= 0.959; and 16 vs. 21, P= 0.335). The logistic regression analysis showed that the single factor, whether receiving rhubarb therapy, affected the proportion of patients whose enteral nutrition needs ≥83.7 kJ·kg⁻¹·d⁻¹ after 7 days of treatment (odds ratio: 7.908, 95% confidence interval: 3.661–17.083, P< 0.001). No serious adverse effects were found in two groups.

The rhubarb might significantly improve feeding tolerance and relieve gastrointestinal dysfunction in critically ill patients, without serious adverse reactions. It provided proof for the treatment of gastrointestinal dysfunction with rhubarb during clinical practice.

Antimicrobial de-escalation refers to starting the antimicrobial treatment with broad-spectrum antibiotics, followed by narrowing the drug spectrum according to culture results. The present study evaluated the effect of de-escalation on ventilator-associated pneumonia (VAP) in trauma patients.

This retrospective study was conducted on trauma patients with VAP, who received de-escalation therapy (de-escalation group) or non-de-escalation therapy (non-de-escalation group). Propensity score matching method was used to balance the baseline characteristics between both groups. The 28-day mortality, length of hospitalization and Intensive Care Unit stay, and expense of antibiotics and hospitalization between both groups were compared. Multivariable analysis explored the factors that influenced the 28-day mortality and implementation of de-escalation.

Among the 156 patients, 62 patients received de-escalation therapy and 94 patients received non-de-escalation therapy. No significant difference was observed in 28-day mortality between both groups (28.6% vs. 23.8%, P = 0.620). The duration of antibiotics treatment in the de-escalation group was shorter than that in the non-de-escalation group(11 [8–13] vs. 14 [8–19] days, P = 0.045). The expenses of antibiotics and hospitalization in de-escalation group were significantly lower than that in the non-de-escalation group (6430 ± 2730 vs. 7618 ± 2568 RMB Yuan, P = 0.043 and 19,173 ± 16,861 vs. 24,184 ± 12,039 RMB Yuan, P = 0.024, respectively). Multivariate analysis showed that high Acute Physiology and Chronic Health Evaluation II (APACHE II) score, high injury severity score, multi-drug resistant (MDR) infection, and inappropriate initial antibiotics were associated with patients’ 28-day mortality, while high APACHE II score, MDR infection and inappropriate initial antibiotics were independent factors that prevented the implementation of de-escalation.

De-escalation strategy in the treatment of trauma patients with VAP could reduce the duration of antibiotics treatments and expense of hospitalization, without increasing the 28-day mortality and MDR infection.

Measurement of general microcirculation remains difficult in septic shock patients. The peripheral perfusion index (PI) and sublingual microcirculation monitoring are thought to be possible methods. This study was performed to determine whether assessing microcirculation by PI and a new parameter, proportion of perfusion vessel change rate (∆PPV) from sublingual microcirculation monitoring, can be associated with patients’ outcome.

A prospective observational study was carried out, including 74 patients with septic shock in a mixed intensive care unit. Systemic hemodynamic variables were obtained at T0 and 6 h after (T6). PI and sublingual microcirculation indicators were obtained using a bedside monitor and a sidestream dark-field device, respectively. The t-test, analysis of variance, Mann-Whitney U-test, Kruskal- Wallis test, receiver operating characteristic curve analysis with the Hanley-McNeil test, survival curves using the Kaplan-Meier method, and the log-rank (Mantel-Cox) test were used to statistical analysis.

Systemic hemodynamics and microcirculation data were obtained and analyzed. Patients were divided into two groups based on whether the first 6 h lactate clearance (LC) was ≥20%; PI and ∆PPV were lower at T6 in the LC <20% group compared with LC ≥20% (PI: 1.52 [0.89, 1.98] vs. 0.79 [0.44, 1,81], Z= −2.514, P = 0.012; ∆PPV: 5.9 ± 15.2 vs. 17.9 ± 20.0, t= −2.914, P = 0.005). The cutoff values of PI and ∆PPV were 1.41% and 12.1 %, respectively. The cutoff value of the combined indicators was 1.379 according to logistic regression. Area under the curve demonstrated 0.709 (P < 0.05), and the sensitivity and specificity of using combined indicators were 0.622 and 0.757, respectively. Based on the PI and ∆PPV cutoff, all the participants were divided into the following groups: (1) high PI and high ∆PPV group, (2) high PI and low ∆PPV group, (3) low PI and high ∆PPV group, and (4) low PI and low ∆PPV group. The highest Sequential Organ Failure Assessment score (14.5 ± 2.9) was in the low PI and low ∆PPV group (F= 13.7, P < 0.001). Post hoc tests showed significant differences in 28-day survival rates among these four groups (log rank [Mantel-Cox], 20.931; P< 0.05).

PI and ∆PPV in septic shock patients are related to 6 h LC, and combining these two parameters to assess microcirculation can predict organ dysfunction and 28-day mortality in patients with septic shock.

Acute lung injury (ALI) is a severe disease with high mortality and poor prognosis. Protectin DX (PDX), a pro-resolving lipid mediator, exhibits protective effects in ALI. Our experiment aimed to explore the effects and related mechanisms of PDX in mice with ALI induced by lipopolysaccharide (LPS).

BALB/c mice were randomly divided into five groups: sham, LPS, LPS plus 1 ng of PDX (LPS + PDX-1 ng), LPS plus 10 ng of PDX (LPS + PDX-10 ng), and LPS plus 100 ng of PDX (LPS + PDX-100 ng). Bronchoalveolar lavage fluids (BALFs) were collected after 24 h, and total cells, polymorphonuclear leukocytes, monocyte-macrophages, and lymphocytes in BALF were enumerated. The concentration of interleukin (IL)-1β, IL-6, IL-10, tumor necrosis factor-alpha (TNF-α), macrophage inflammatory protein (MIP)-1α, and MIP-2 in BALF was determined, and histopathological changes of the lung were observed. The concentration of protein in BALF and lung wet/dry weight ratios were detected to evaluate pulmonary edema. After determining the optimal dose of PDX, neutrophil–platelet interactions in whole blood were evaluated by flow cytometry.

The highest dose of PDX (100 ng/mouse) failed to provide pulmonary protective effects, whereas lower doses of PDX (1 ng/mouse and 10 ng/mouse), especially 1 ng PDX, alleviated pulmonary histopathological changes, mitigated LPS-induced ALI and pulmonary edema, inhibited neutrophil infiltration, and reduced pro-inflammatory mediator (IL-1β, IL-6, TNF-α, and MIP-1α) levels. Meanwhile, 1 ng PDX exhibited pro-resolving functions in ALI including upregulation of monocyte-macrophage numbers and anti-inflammatory mediator IL-10 levels. The flow cytometry results showed that PDX could inhibit neutrophil–platelet interactions in ALI.

PDX exerts protective effects in LPS-induced ALI by mitigating pulmonary inflammation and abrogating neutrophil–platelet interactions.

The incidence of cancer, diabetes, and autoimmune diseases has been increasing. Furthermore, there are more and more patients with solid organ transplants. The survival rate of these immunocompromised individuals is extremely low when they are severely hit-on. In this study, we established cardiac arrest cardiopulmonary resuscitation (CPR) model in severe combined immunodeficient (SCID) mice, analyzed the expression and activation of mitochondrial autophagy and NLRP3 inflammasome/caspase-1, and explored mitochondrial repair and inflammatory injury in immunodeficiency individual during systemic ischemia-reperfusion injury.

A potassium chloride-induced cardiac arrest model was established in C57BL/6 and nonobese diabetic/SCID (NOD/SCID) mice. One hundred male C57BL/6 mice and 100 male NOD/SCID mice were randomly divided into five groups (control, 2 h post-CPR, 12 h post-CPR, 24 h post-CPR, and 48 h post-CPR). A temporal dynamic view of alveolar epithelial cells, macrophages, and neutrophils from bronchoalveolar lavage fluid (BALF) was obtained using Giemsa staining. Spatial characterization of phenotypic analysis of macrophages in the lung interstitial tissue was analyzed by flow cytometry. The morphological changes of mitochondria 48 h after CPR were studied by transmission electron microscopy and quantified according to the Flameng grading system. Western blotting analysis was used to detect the expression and activation of the markers of mitochondrial autophagy, NLRP3 inflammasome, and caspase-1.

(1) In NOD/SCID mice, macrophages were disintegrated in BALF, and many alveolar epithelial cells were shed at 48 h after resuscitation. Compared with C57BL/6 mice, the ratio of macrophages/total cells peaked at 12 h and was significantly higher in NOD/SCID mice (31.17 ± 4.13 vs. 49.69 ± 2.43, t = 14.46, P= 0.001). After 24 h, the results showed a downward trend. Furthermore, a large number of macrophages were disintegrated in the BALF. (2) Mitochondrial autophagy was present in both C57BL/6 and NOD/SCID mice after CPR, but it began late in the NOD/SCID mice. Compared with C57BL/6 mice, phos-ULK1 (Ser³²⁷) expression was significantly lower at 2 h and 12 h after CPR (2 h after CPR: 1.88 ± 0.36 vs. 1.12 ± 0.11, t= −1.36, P< 0.01 and 12 h after CPR: 1.52 ± 0.16 vs. 1.05 ± 0.12, t= −0.33, P< 0.01), whereas phos-ULK1 (Ser⁷⁵⁷) expression was significantly higher at 2 h and 12 h after CPR in NOD/SCID mice (2 h after CPR: 1.28 ± 0.12 vs. 1.69 ± 0.14, t = 1.7, P< 0.01 and 12 h after CPR: 1.33 ± 0.10 vs. 1.94 ± 0.13, t = 2.75, P< 0.01). (3) Furthermore, NLRP3 inflammasome/caspase-1 activation in the pulmonary tissues occurred early and for only a short time in C57BL/6 mice, but this phenomenon was sustained in NOD/SCID mice. The expression of the NLRP3 inflammasome increased modestly in the C57 mice, but the increase was higher in the NOD/SCID mice than in the C57BL/6 mice, especially at 12, 24, 48 h after CPR (48 h after CPR: 1.46 ± 0.13 vs. 2.97 ± 0.19, t = 5.34, P= 0.001). The expression of caspase-1-20 generally followed the same pattern as the NLRP3 inflammasome.

There is a regulatory relationship between the NLRP3 inflammasome and mitochondrial autophagy after CPR in the healthy mice. This regulatory relationship was disturbed in the NOD/SCID mice because the signals for mitochondrial autophagy occurred late, and NLRP3 inflammasome- and caspase-1-dependent cell injury was sustained.

Recent studies have indicated that autophagy is involved in sepsis-induced myocardial dysfunction. This study aimed to investigate the change of autophagy in cecal ligation and puncture (CLP)-induced myocardium dysfunction and its relationship with mammalian target of rapamycin (mTOR) pathway.

Totally, 12 rats were randomly divided into CLP group or sham-operated (SHAM) group. Cardiac tissues were harvested 18 h after CLP or sham operation. Pathology was detected by hematoxylin and eosin staining, cardiac functions by echocardiography, distribution of microtubule-associated protein light chain 3 type II (LC3II) by immunohistochemical staining, and autophagic vacuoles by transmission electron microscopy. Moreover, phosphorylation of mTOR (p-mTOR), phosphorylation of S6 kinase-1 (PS6K1), and LC3II and p62 expression were measured by western blotting. Pearson’s correlation coefficient was used to analyze the correlation of two parameters.

The results by pathology and echocardiography revealed that there was obvious myocardial injury in CLP rats (left ventricle ejection fraction: SHAM 0.76 ± 0.06 vs. CLP 0.59 ± 0.11, P < 0.01; fractional shortening: SHAM 0.51 ± 0.09 vs. CLP 0.37 ± 0.06, P < 0.05). We also found that the autophagy process was elevated by CLP, the ratio of LC3II/LC3I was increased (P < 0.05) while the expression of p62 was decreased (P < 0.05) in the CLP rats, and there were also more autophagosomes and autolysosomes in the CLP rats. Furthermore, the mTOR pathway in CLP myocardium was inhibited when compared with the sham-operated rats; p-mTOR (P < 0.01) and PS6K1 (P < 0.05) were both significantly suppressed following CLP challenge. Interestingly, we found that the mTOR pathway was closely correlated with the autophagy processes. In our study, while p-mTOR in the myocardium was significantly correlated with p62 (r = 0.66, P= 0.02), PS6K1 was significantly positively correlated with p62 (r = 0.70, P= 0.01) and negatively correlated with LC3II (r= −0.71, P= 0.01).

The autophagy process in the myocardium was accelerated in CLP rats, which was closely correlated with the inhibition of the mTOR pathway.

The hedgehog signaling system (HHS) plays an important role in the regulation of cell proliferation and differentiation during the embryonic phases. However, little is known about the involvement of HHS in the malignant transformation of cells. This study aimed to detect the role of HHS in the malignant transformation of human bronchial epithelial (16HBE) cells.

In this study, two microfluidic chips were designed to investigate cigarette smoke extract (CSE)-induced malignant transformation of cells. Chip A contained a concentration gradient generator, while chip B had four cell chambers with a central channel. The 16HBE cells cultured in chip A were used to determine the optimal concentration of CSE for inducing malignant transformation. The 16HBE cells in chip B were cultured with 12.25% CSE (Group A), 12.25% CSE + 5 μmol/L cyclopamine (Group B), or normal complete medium as control for 8 months (Group C), to establish the in vitro lung inflammatory-cancer transformation model. The transformed cells were inoculated into 20 nude mice as cells alone (Group 1) or cells with cyclopamine (Group 2) for tumorigenesis testing. Expression of HHS proteins was detected by Western blot. Data were expressed as mean ± standard deviation. The t-test was used for paired samples, and the difference among groups was analyzed using a one-way analysis of variance.

The optimal concentration of CSE was 12.25%. Expression of HHS proteins increased during the process of malignant transformation (Group B vs. Group A, F = 7.65, P< 0.05). After CSE exposure for 8 months, there were significant changes in cellular morphology, which allowed the transformed cells to grow into tumors in 40 days after being inoculated into nude mice. Cyclopamine could effectively depress the expression of HHS proteins (Group C vs. Group B, F = 6.47, P< 0.05) and prevent tumor growth in nude mice (Group 2 vs. Group 1, t = 31.59, P< 0.01).

The activity of HHS is upregulated during the CSE-induced malignant transformation of 16HBE cells. Cyclopamine can effectively depress expression of HHS proteins in vitro and prevent tumor growth of the transformed cells in vivo.

Previous studies have shown that hypertension is an important factor contributing to the occurrence and progression of diabetic kidney damage. However, the relationship between the patterns of blood pressure (BP) trajectory and kidney damage in the diabetic population remains unclear. This prospective study investigated the effect of long-term systolic BP (SBP) trajectory on kidney damage in the diabetic population based on an 8-year follow-up community-based cohort.

This study included 4556 diabetic participants among 101,510 participants. BP, estimated glomerular filtration rate (eGFR), and urinary protein were measured every 2 years from 2006 to 2014. SBP trajectory was identified by the censored normal modeling. Five discrete SBP trajectories were identified according to SBP range and the changing pattern over time. Kidney damage was evaluated through eGFR and urinary protein value. A multivariate logistic regression model was used to analyze the influence of different SBP trajectory groups on kidney damage.

We identified five discrete SBP trajectories: low-stable group (n = 864), moderate-stable group (n = 1980), moderate increasing group (n = 609), elevated decreasing group, (n = 679), and elevated stable group (n = 424). The detection rate of kidney damage in the low-stable group (SBP: 118–124 mmHg) was the lowest among the five groups. The detection rate of each kidney damage index was higher in the elevated stable group (SBP: 159–172 mmHg) compared with the low-stable group. For details, the gap was 4.14 (11.6% vs. 2.8%) in eGFR <60 ml·min⁻¹·1.73 m⁻² and 3.66 (17.2% vs. 4.7%), 3.38 (25.0% vs. 7.4%), and 1.8 (10.6% vs. 5.9%) times in positive urinary protein, eGFR <60 ml·min⁻¹·1.73 m⁻² and/or positive urinary protein, and eGFR decline ≥30%, respectively (P < 0.01).

An elevated stable SBP trajectory is an independent risk factor for kidney damage in the diabetic population.

The role of postradiation systemic therapy in non-small cell lung cancer (NSCLC) patients with brain metastasis (BM) was controversial. Thus, we explored the role of Radiation Therapy Oncology Group recursive partitioning analysis (RTOG-RPA) and graded prognostic assessment (GPA) in identifying population who may benefit from postradiation systemic therapy.

The clinical data of NSCLC patients with documented BM from August 2007 to April 2015 of two hospitals were studied retrospectively. Cox regression was used for multivariate analysis. Survival of patients with or without postradiation systemic therapy was compared in subgroups stratified according to RTOG-RPA or GPA.

Of 216 included patients, 67.1% received stereotactic radiosurgery (SRS), 24.1% received whole-brain radiation therapy (WBRT), and 8.8% received both. After radiotherapy, systemic therapy was administered in 58.3% of patients. Multivariate analysis found that postradiation systemic therapy (yes vs. no) (hazard ratio [HR] = 0.361, 95% confidence interval [CI] = 0.202- 0.648, P= 0.001), radiation technique (SRS vs. WBRT) (HR = 0.462, 95% CI = 0.238- 0.849, P= 0.022), extracranial metastasis (yes vs. no) (HR= 3.970, 95% CI = 1.757–8.970, P= 0.001), and Karnofsky performance status (<70 vs. ≥70) (HR = 5.338, 95% CI = 2.829–10.072, P< 0.001) were independent factors for survival. Further analysis found that subsequent tyrosine kinase inhibitor (TKI) therapy could significantly reduce the risk of mortality of patients in RTOG-RPA Class II (HR = 0.411, 95% CI = 0.183- 0.923, P= 0.031) or with a GPA score of 1.5- 2.5 (HR = 0.420, 95% CI = 0.182- 0.968, P= 0.042). However, none of the subgroups stratified according to RTOG-RPA or GPA benefited from the additional conventional chemotherapy.

RTOG-RPA and GPA may be useful to identify beneficial populations in NSCLC patients with BM if TKIs were chosen as postradiation systemic therapy.

Exposure to halogens, such as chlorine or bromine, results in environmental and occupational hazard to the lung and other organs. Chlorine is highly toxic by inhalation, leading to dyspnea, hypoxemia, airway obstruction, pneumonitis, pulmonary edema, and acute respiratory distress syndrome (ARDS). Although bromine is less reactive and oxidative than chlorine, inhalation also results in bronchospasm, airway hyperresponsiveness, ARDS, and even death. Both halogens have been shown to damage the systemic circulation and result in cardiac injury as well. There is no specific antidote for these injuries since the mechanisms are largely unknown.

This review was based on articles published in PubMed databases up to January, 2018, with the following keywords: "chlorine," "bromine," "lung injury," and "ARDS."

The original articles and reviews including the topics were the primary references.

Based on animal studies, it is found that inhaled chlorine will form chlorine-derived oxidative products that mediate postexposure toxicity; thus, potential treatments will target the oxidative stress and inflammation induced by chlorine. Antioxidants, cAMP-elevating agents, anti-inflammatory agents, nitric oxide-modulating agents, and high-molecular-weight hyaluronan have shown promising effects in treating acute chlorine injury. Elevated free heme level is involved in acute lung injury caused by bromine inhalation. Hemopexin, a heme-scavenging protein, when administered postexposure, decreases lung injury and improves survival.

At present, there is an urgent need for additional research to develop specific therapies that target the basic mechanisms by which halogens damage the lungs and systemic organs.

Acute respiratory distress syndrome (ARDS) is a devastating clinical syndrome whose diagnosis and therapy are still in question. The aim of this review was to discuss the current challenge for the diagnosis and treatment of ARDS.

Data sources were the published articles in English through December 2017 in PubMed using the following key words: "acute respiratory distress syndrome," "definition", "diagnosis," "therapy," "lung protective strategy," "right ventricular dysfunction," and "molecular mechanism."

The selection of studies focused on both preclinical studies and clinical studies of therapy of ARDS.

The incidence of ARDS is still high, and ARDS causes high intensive care units admissions and high mortality. The Berlin Definition proposed in 2012 is still controversial owing to lack of sensitivity and specificity. ARDS is still under recognition and it is associated with high mortality. Lung protective strategies with low tidal volume (VT) and lung recruitment should consider the physiology of ARDS because ARDS presents lung inhomogeneity; the same low VT might increase local stress and strain in some patients with low compliance, and lung recruitment could injure lungs in ARDS patients with low recruitability and hemodynamic instability. Acute cor pulmonale is common in severe ARDS. ARDS itself and some treatments could worsen acute cor pulmonale. Molecular understanding of the pathogenic contributors to ARDS has improved, but the molecular-associated treatments are still under development.

ARDS is a devastating clinical syndrome whose incidence and mortality has remained high over the past 50 years. Its definition and treatments are still confronted with challenges, and early recognition and intervention are crucial for improving the outcomes of ARDS. More clinical studies are needed to improve early diagnosis and appropriate therapy.

Mechanical ventilation (MV) has long been used as a life-sustaining approach for several decades. However, researchers realized that MV not only brings benefits to patients but also cause lung injury if used improperly, which is termed as ventilator-induced lung injury (VILI). This review aimed to discuss the pathogenesis of VILI and the underlying molecular mechanisms.

This review was based on articles in the PubMed database up to December 2017 using the following keywords: "ventilator-induced lung injury" , "pathogenesis" , "mechanism" , and "biotrauma" .

Original articles and reviews pertaining to mechanisms of VILI were included and reviewed.

The pathogenesis of VILI was defined gradually, from traditional pathological mechanisms (barotrauma, volutrauma, and atelectrauma) to biotrauma. High airway pressure and transpulmonary pressure or cyclic opening and collapse of alveoli were thought to be the mechanisms of barotraumas, volutrauma, and atelectrauma. In the past two decades, accumulating evidence have addressed the importance of biotrauma during VILI, the molecular mechanism underlying biotrauma included but not limited to proinflammatory cytokines release, reactive oxygen species production, complement activation as well as mechanotransduction.

Barotrauma, volutrauma, atelectrauma, and biotrauma contribute to VILI, and the molecular mechanisms are being clarified gradually. More studies are warranted to figure out how to minimize lung injury induced by MV .

Gastroscopy combined with gastric mucosa biopsies is currently regarded as a gold standard for diagnosis of gastric cancer. However, its application is restricted in clinical practice due to its invasive property. A new noninvasive population screening process combining the assay of anti-Helicobacter pylori antibody and serum pepsinogen (PG) (ABC method) is adopted to recognize the high-risk patients for further endoscopy examination, avoiding the unnecessary gastroscopy for most population and saving the cost consumption for mass screening annually. Nevertheless, controversies exist for the grouping of ABC method and the intervals of gastroscopy surveillance for each group. In this review, we summarized these popular concerned topics for providing useful references to the healthcare practitioner in clinical practice.

The PubMed databases were systematically searched from the inception dates to November 22, 2017, using the keywords "Helicobacter pylori," "Pepsinogens," and "Stomach Neoplasms."

Original articles and reviews on the topics were selected.

Anti-H. pylori antibody and serum PG concentration showed significant changes under the different status of H. pylori infection and the progression of atrophic gastritis, which can be used for risk stratification of gastric cancer in clinic. In addition, anti-H. pylori antibody titer can be used for further risk stratification of gastric cancer contributing to determine better endoscopy surveillance interval.

The early detection and diagnosis of gastric cancer benefit from the risk stratification, but the cutoff values for H. pylori antibody and serum PG concentration require further modification.

Early goal-directed therapy (EGDT) has been used in clinics as a standard procedure in sepsis resuscitation for a long period. However, the ProCESS, ARISE, and ProMISe trials did not find any benefits from EGDT on sepsis mortality, triggering considerable doubt, and reassessment in the field of intensive care medicine. The heterogeneity of the studied patients, the differences of trial designs and interventions may have led to these disappointing results; however, improving oxygenation and tissue perfusion as early as possible is the core issue at hand. Personalized critical hemodynamic treatment (PCHT) should be proposed and applied for shock cases.

To the Editor: Influenza-associated acute respiratory distress syndrome (ARDS) remains a devastating clinical picture.^[1]From December 2017 to January 2018, ten patients with influenza-associated ARDS were admitted to three different hospital’s Intensive Care Units (ICUs) in Chongqing, with all cases resulting in demise. The main documented reasons for their admission to the ICU were due to progressive dyspnea and worsening hypoxemia which lead to endotracheal intubation and mechanical ventilation in these patients. Identification of influenza viruses was achieved using nucleic-acid testing from venous blood. This study was approved by the Institutional Review Board of Daping Hospital, Army Medical University.

To the Editor: The t(9;22)(q34;q11) (Philadelphia chromosome [Ph] ) balanced translocation results in fusion of theBCRgene at 22q11 with cytoplasmic tyrosine kinase geneABL1and plays an essential role in leukemic transformation. The Ph is an infrequent finding inde novoacute myeloid leukemia (AML), approximately 0.5–3% of newly diagnosed patients.^[1]The World Health Organization (WHO) recently released a revised version of the Classification of Hematopoietic and Lymphoid Malignancies, a new provisional category of AML withBCR-ABL1was added to recognize these rare Ph⁺AML cases that could benefit from tyrosine-kinase inhibitor (TKI) therapy.^[2]It is required to enlarge the sample size and research the molecular or genomic features to increase the argument in favor of Ph⁺AML as a real entity.

To the Editor: In the past 10 years, remarkable progress has been made in the treatment of multiple myeloma (MM). In clinical practice, we used Durie-Salmon Staging System (DSS), International Staging System (ISS), and revised ISS to judge the prognosis of myeloma patients. MM is divided into eight types, the type of IgA is considered to be poor prognosis, but so far there is no evidence basis of literature. We analyzed the clinical features and living conditions of IgA type MM patients in the real world.

To the Editor: A 65-year-old male patient was admitted to our hospital on September 9^th, 2016, because of wheals involving the whole body 1 h after ingesting bread and milk. His coexisting symptoms included itchiness, chest discomfort, dyspnea, wheezing, abdominal pain, nausea, vomiting, palpitation, sweating, pale complexion, dizziness, and syncope. His consciousness recovered after taking the Suxiao Jiuxin pill, and then he was sent to our hospital.

To the Editor: A 61-year-old diabetic male presented with a growing hyperplastic plaque measured 1.5 cm × 1.0 cm on the glans of his penis for 2 months [Figure 1a]. The plaque was pruritic burning. Polarized dermoscopy revealed multiple red papules with whitish areas of erosions [Figure 1b]. The patient was diagnosed as vascular neoplasm at other hospitals and he came to the Department of Dermatology, Peking University People’s Hospital for further consultation before an excision surgery.

To the Editor: Gestational diabetes mellitus (GDM) is defined as glucose intolerance with the onset of pregnancy and is related to increased maternal and fetal risks. Incidence of GDM varies in different countries and the prevalence ranges between 4% and 17%.^[1]GDM is one of the most common medical complications of pregnancy, negatively affecting fetal development and metabolic balance. If untreated, GDM can cause fetal malformation, macrosomia, fetal growth retardation, and even intrauterine fetal death. Recent studies have shown correlations between GDM and postpartum insulin resistance, pregnancy-induced hypertension, and dyslipidemia. GDM has also been shown to be associated with placental abnormalities including altered placental function, oxidative stress, and vascular dysfunction.

To the Editor: In a retrospective study by Zhenget al.^[1]assessing the influences of perioperative single-donor platelet apheresis and red blood cell transfusion on 90-day and overall survival in 126 recipients who underwent their first adult-to-adult living donor liver transplantation (LDLT), multivariate regression analysis showed that platelet transfusion was only associated with postoperative early-term mortality, but had no significant impact on postoperative overall long-term mortality. Furthermore, units of red blood cell transfusion were independent predictors of postoperative long-term outcomes. Given that perioperative blood transfusion has been associated with postoperative outcomes of LDLT patients, their findings have potential implications. However, this is a retrospective study, which can introduce a number of potential confounders. Although they have done a valuable job, some methodological issues seem important to avoid any optimistic interpretation or misinterpretation of their results.