2018年 · 第131卷第19期

Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases with a high prevalence in the general population. The association between NAFLD and cardiovascular disease has been well addressed in previous studies. However, whether NAFLD is associated with carotid artery disease in a community-based Chinese population remained unclear. The aim of this study was to investigate the association between NAFLD and carotid artery disease.

A total of 2612 participants (1091 men and 1521 women) aged 40 years and older from Jidong of Tangshan city (China) were selected for this study. NAFLD was diagnosed by abdominal ultrasonography. The presence of carotid stenosis or plaque was evaluated by carotid artery ultrasonography. Logistic regression was used to analyze the association between NAFLD and carotid artery disease.

Participants with NAFLD have a higher prevalence of carotid stenosis (12.9% vs. 4.6%) and carotid plaque (21.9% vs. 15.0%) than those without NAFLD. After adjusting for age, gender, smoking status, income, physical activity, diabetes, hypertension, triglyceride, waist-hip ratio, and high-density lipoprotein, NAFLD is significantly associated with carotid stenosis (odds ratio [OR]: 2.06, 95% confidence interval [CI]: 1.45–2.91), but the association between NAFLD and carotid plaque is not statistically significant (OR: 1.10, 95% CI: 0.86–1.40).

A significant association between NAFLD and carotid stenosis is found in a Chinese population.

Oxygen-glucose deprivation-nutrition resumption (OGD-NR) models on H9c2 cells are commonly used in vitro models of simulated myocardial ischemia-reperfusion injury (MIRI), but no study has assessed whether these methods for establishing in vitro models can effectively imitate the characteristics of MIRI in vivo. This experiment was designed to analyze the feasibility of six OGD-NR models of MIRI.

By searching the PubMed database using the keywords "myocardial reperfusion injury H9c2 cells," we obtained six commonly used OGD-NR in vitro models of MIRI performed on H9c2 cells from more than 400 published papers before January 30, 2017. For each model, control (C), simulated ischemia (SI), and simulated ischemia-reperfusion (SIR) groups were assigned, and cell morphology, lactate dehydrogenase (LDH) release, adenosine triphosphate (ATP) levels, reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and inflammatory cytokines were examined to evaluate the characteristics of cell injury. Subsequently, a coculture system of cardiomyocyte-endothelial-macrophage was constructed. The coculture system was dealt with SI and SIR treatments to test the effect on cardiomyocytes survival.

For models 1, 2, 3, 4, 5, and 6, SI treatment caused morphological damage to cells, and subsequent SIR treatment did not cause further morphological damage. In the models 1, 2, 3, 4, 5 and 6, LDH release was significantly higher in the SI groups than that in the C group (P < 0.05), and was significantly lower in the SIR groups than that in the SI groups (P < 0.05), except for no significant differences in the LDH release between C, SI and SIR groups in model 6 receiving a 3-h SI treatment. In models 1, 2, 3, 4, 5, and 6, compared with the C group, ATP levels of the SI groups significantly decreased (P < 0.05), ROS levels increased (P < 0.05), and MMP levels decreased (P < 0.05). Compared with the SI group, ATP level of the SIR groups was significantly increased (P < 0.05), and there was no significant ROS production, MMP collapse, and over inflammatory response in the SIR groups. In a coculture system of H9c2 cells-endothelial cells-macrophages, the proportion of viable H9c2 cells in the SIR groups was not reduced compared with the SI groups.

All the six OGD-NR models on H9c2 cells in this experiment can not imitate the characteristics of MIRI in vivo and are not suitable for MIRI-related study.

Shensong Yangxin Capsule (SSYX), traditional Chinese medicine, has been used to treat arrhythmias, angina, cardiac remodeling, cardiac fibrosis, and so on, but its effect on cardiac energy metabolism is still not clear. The objective of this study was to investigate the effects of SSYX on myocardium energy metabolism in angiotensin (Ang) II-induced cardiac hypertrophy.

We used 2 µl (10⁻⁶ mol/L) AngII to treat neonatal rat cardiomyocytes (NRCMs) for 48 h. Myocardial α-actinin staining showed that the myocardial cell volume increased. Expression of the cardiac hypertrophic marker-brain natriuretic peptide (BNP) messenger RNA (mRNA) also increased by real-time polymerase chain reaction (PCR). Therefore, it can be assumed that the model of hypertrophic cardiomyocytes was successfully constructed. Then, NRCMs were treated with 1 µl of different concentrations of SSYX (0.25, 0.5, and 1.0 μg/ml) for another 24 h. To explore the time-depend effect of SSYX on energy metabolism, 0.5 μg/ml SSYX was added into cells for 0, 6, 12, 24, and 48 h. Mitochondria was assessed by MitoTracker staining and confocal microscopy. mRNA and protein expression of mitochondrial biogenesis-related genes – Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), energy balance key factor – adenosine monophosphate-activated protein kinase (AMPK), fatty acids oxidation factor – carnitine palmitoyltransferase-1 (CPT-1), and glucose oxidation factor – glucose transporter- 4 (GLUT-4) were measured by PCR and Western blotting analysis.

With the increase in the concentration of SSYX (from 0.25 to 1.0 μg/ml), an increased mitochondrial density in AngII-induced cardiomyocytes was found compared to that of those treated with AngII only (0.25 μg/ml, 18.3300 ± 0.8895 vs. 24.4900 ± 0.9041, t = 10.240, P < 0.0001; 0.5 μg/ml, 18.3300 ± 0.8895 vs. 25.9800 ± 0.8187, t = 12.710, P < 0.0001; and 1.0 μg/ml, 18.3300 ± 0.8895 vs. 24.2900 ± 1.3120, t= 9.902, P < 0.0001; n = 5 per dosage group). SSYX also increased the mRNA and protein expression of PGC-1α (0.25 μg/ml, 0.8892 ± 0.0848 vs. 1.0970 ± 0.0994, t = 4.319, P = 0.0013; 0.5 μg/ml, 0.8892 ± 0.0848 vs. 1.2330 ± 0.0564, t = 7.150, P < 0.0001; and 1.0 μg/ml, 0.8892 ± 0.0848 vs. 1.1640 ± 0.0755, t = 5.720, P < 0.0001; n = 5 per dosage group), AMPK (0.25 μg/ml, 0.8872 ± 0.0779 vs. 1.1500 ± 0.0507, t= 7.239, P < 0.0001; 0.5 μg/ml, 0.8872 ± 0.0779 vs. 1.2280 ± 0.0623, t= 9.379, P < 0.0001; and 1.0 μg/ml, 0.8872 ± 0.0779 vs. 1.3020 ± 0.0450, t = 11.400, P < 0.0001; n = 5 per dosage group), CPT-1 (1.0 μg/ml, 0.7348 ± 0.0594 vs. 0.9880 ± 0.0851, t= 4.994, P = 0.0007, n= 5), and GLUT-4 (0.5 μg/ml, 1.5640 ± 0.0599 vs. 1.7720 ± 0.0660, t= 3.783, P = 0.0117; 1.0 μg/ml, 1.5640 ± 0.0599 vs. 2.0490 ± 0.1280, t = 8.808, P < 0.0001; n = 5 per dosage group). The effect became more obvious with the increasing concentration of SSYX. When 0.5 μg/ml SSYX was added into cells for 0, 6, 12, 24, and 48 h, the expression of AMPK (6 h, 14.6100 ± 0.6205 vs. 16.5200 ± 0.7450, t = 3.456, P = 0.0250; 12 h, 14.6100 ± 0.6205 vs. 18.3200 ± 0.9965, t = 6.720, P < 0.0001; 24 h, 14.6100 ± 0.6205 vs. 21.8800 ± 0.8208, t = 13.160, P < 0.0001; and 48 h, 14.6100 ± 0.6205 vs. 23.7400 ± 1.0970, t = 16.530, P < 0.0001; n = 5 per dosage group), PGC-1α (12 h, 11.4700 ± 0.7252 vs. 16.9000 ± 1.0150, t = 7.910, P < 0.0001; 24 h, 11.4700 ± 0.7252 vs. 20.8800 ± 1.2340, t= 13.710, P < 0.0001; and 48 h, 11.4700 ± 0.7252 vs. 22.0300 ± 1.4180, t= 15.390; n = 5 per dosage group), CPT-1 (24 h, 15.1600 ± 1.0960 vs. 18.5800 ± 0.9049, t= 6.048, P < 0.0001, n = 5), and GLUT-4 (6 h, 10.2100 ± 0.9485 vs. 12.9700 ± 0.8221, t = 4.763, P = 0.0012; 12 h, 10.2100 ± 0.9485 vs. 16.9100 ± 0.8481, t= 11.590, P < 0.0001; 24 h, 10.2100 ± 0.9485 vs. 19.0900 ± 0.9797, t= 15.360, P < 0.0001; and 48 h, 10.2100 ± 0.9485 vs. 14.1900 ± 0.9611, t= 6.877, P < 0.0001; n = 5 per dosage group) mRNA and protein increased gradually with the prolongation of drug action time.

SSYX could increase myocardial energy metabolism in AngII-induced cardiac hypertrophy. Therefore, SSYX might be considered to be an alternative therapeutic remedy for myocardial hypertrophy.

Risperidone and paliperidone have been the mainstay treatment for schizophrenia and their potential role in neuroprotection could be associated with brain-derived neurotrophic factor (BDNF) and N400 (an event-related brain potential component). So far, different effects on both BDNF and N400 were reported in relation to various antipsychotic treatments. However, few studies have been conducted on the mechanism of risperidone and paliperidone on BDNF and N400. This study aimed to compare the effects of risperidone and paliperidone on BDNF and the N400 component of the event-related brain potential in patients with first-episode schizophrenia.

Ninety-eight patients with first-episode schizophrenia were randomly divided into the risperidone and paliperidone groups and treated with risperidone and paliperidone, respectively, for 12 weeks. Serum BDNF level, the latency, and amplitude of the N400 event-related potential before and after the treatment and Positive and Negative Syndrome Scale (PANSS) scores were compared between the two groups.

A total of 94 patients were included in the final analysis (47 patients in each group). After the treatment, the serum BDNF levels in both groups increased (all P < 0.01), while no significant difference in serum BDNF level was found between the groups before and after the treatment (all P > 0.05). After the treatment, N400 amplitudes were increased (from 4.73 ± 2.86 μv and 4.51 ± 4.63 μv to 5.35 ± 4.18 μv and 5.52 ± 3.08 μv, respectively) under congruent condition in both risperidone and paliperidone groups (all P < 0.01). Under incongruent conditions, the N400 latencies were shortened in the paliperidone group (from 424.13 ± 110.42 ms to 4.7.41 ± 154.59 ms, P < 0.05), and the N400 amplitudes were increased in the risperidone group (from 5.80 ± 3.50 μv to 7.17 ± 5.51 μv, P < 0.01). After treatment, the total PANSS score in both groups decreased significantly (all P < 0.01), but the difference between the groups was not significant (P > 0.05). A negative correlation between the reduction rate of the PANSS score and the increase in serum BDNF level after the treatment was found in the paliperidone group but not in the risperidone group.

Both risperidone and paliperidone could increase the serum BDNF levels in patients with first-episode schizophrenia and improve their cognitive function (N400 latency and amplitude), but their antipsychotic mechanisms might differ.

Myocardial ischemia injury is one of the leading causes of death and disability worldwide. Cardiac fibroblasts (CFs) have central roles in modulating cardiac function under pathophysiological conditions. Activating transcription factor 3 (ATF3) plays a self-protective role in counteracting CF dysfunction. However, the precise function of CF-specific ATF3 during myocardial infarction (MI) injury/repair remains incompletely understood. The aim of this study was to determine whether CF-specific ATF3 affected cardiac repair after MI.

Fifteen male C57BL/6 wild-type mice were performed with MI operation to observe the expression of ATF3 at 0, 0.5, 1.0, 3.0, and 7.0 days postoperation. Model for MI was constructed in ATF3TGfl/flCol1a2-Cre+ (CF-specific ATF3 overexpression group, n = 5) and ATF3TGfl/flCol1a2-Cre− male mice (without CF-specific ATF3 overexpression group, n = 5). In addition, five mice of ATF3TGfl/flCol1a2-Cre+ and ATF3TGfl/flCol1a2-Cre− were subjected to sham MI operation. Heart function was detected by ultrasound and left ventricular remodeling was observed by Masson staining (myocardial fibrosis area was detected by blue collagen deposition area) at the 28^th day after MI surgery in ATF3TGfl/flCol1a2-Cre+ and ATF3TGfl/flCol1a2-Cre− mice received sham or MI operation. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect cell proliferation/cell cycle-related gene expression in cardiac tissue. BrdU staining was used to detect fibroblast proliferation.

After establishment of an MI model, we found that ATF3 proteins were increased in the heart of mice after MI surgery and dominantly expressed in CFs. Genetic overexpression of ATF3 in CFs (ATF3TGfl/flCol1a2-Cre+ group) resulted in an improvement in the heart function as indicated by increased cardiac ejection fraction (41.0% vs. 30.5%, t = 8.610, P = 0.001) and increased fractional shortening (26.8% vs. 18.1%, t= 7.173, P = 0.002), which was accompanied by a decrease in cardiac scar area (23.1% vs. 11.0%, t= 8.610, P = 0.001). qRT-PCR analysis of CFs isolated from ATF3TGfl/flCol1a2-Cre+ and ATF3TGfl/flCol1a2-Cre− ischemic hearts revealed a distinct transcriptional profile in ATF3-overexpressing CFs, displaying pro-proliferation properties. BrdU-positive cells significantly increased in ATF3-overexpressing CFs than control CFs under angiotensin II stimuli (11.5% vs. 6.8%, t = 31.599, P = 0.001) or serum stimuli (31.6% vs. 20.1%, t = 31.599, P = 0.001). The 5(6)-carboxyfluorescein N-hydroxysuccinimidyl ester assay showed that the cell numbers of the P2 and P3 generations were higher in the ATF3-overexpressing CFs at 24 h (P2: 91.6% vs. 71.8%, t = 8.465, P = 0.015) and 48 h (P3: 81.6% vs. 51.1%, t = 9.029, P = 0.012) after serum stimulation. Notably, ATF3 overexpression-induced CF proliferation was clearly increased in the heart after MI injury.

We identify that CF-specific ATF3 might contribute to be MI repair through upregulating the expression of cell cycle/proliferation-related genes and enhancing cell proliferation.

A high consumption of fructose leads to hepatic steatosis. About 20–30% of triglycerides are synthesized via de novo lipogenesis. Some studies showed that endoplasmic reticulum stress (ERS) is involved in this process, while others showed that a lipotoxic environment directly influences ER homeostasis. Here, our aim was to investigate the causal relationship between ERS and fatty acid synthesis and the effect of X-box binding protein-1 (XBP-1), one marker of ERS, on hepatic lipid accumulation stimulated by high fructose.

HepG2 cells were incubated with different concentrations of fructose. Upstream regulators of de novo lipogenesis (i.e., carbohydrate response element-binding protein [ChREBP] and sterol regulatory element-binding protein 1c [SREBP-1c]) were measured by polymerase chain reaction and key lipogenic enzymes (acetyl-CoA carboxylase [ACC], fatty acid synthase [FAS], and stearoyl-CoA desaturase-1 [SCD-1]) by Western blotting. The same lipogenesis-associated factors were then evaluated after exposure of HepG2 cells to high fructose followed by the ERS inhibitor tauroursodeoxycholic acid (TUDCA) or the ERS inducer thapsigargin. Finally, the same lipogenesis-associated factors were evaluated in HepG2 cells after XBP-1 upregulation or downregulation through cell transfection.

Exposure to high fructose increased triglyceride levels in a dose- and time-dependent manner and significantly increased mRNA levels of SREBP-1c and ChREBP and protein levels of FAS, ACC, and SCD-1, concomitant with XBP-1 conversion to an active spliced form. Lipogenesis-associated factors induced by high fructose were inhibited by TUDCA and induced by thapsigargin. Triglyceride level in XBP-1-deficient group decreased significantly compared with high-fructose group (4.41 ± 0.54 μmol/g vs. 6.52 ± 0.38 μmol/g, P < 0.001), as mRNA expressions of SREBP-1c (2.92 ± 0.46 vs. 5.08 ± 0.41, P < 0.01) and protein levels of FAS (0.53 ± 0.06 vs. 0.85 ± 0.05, P = 0.01), SCD-1 (0.65 ± 0.06 vs. 0.90 ± 0.04, P = 0.04), and ACC (0.38 ± 0.03 vs. 0.95 ± 0.06, P < 0.01) decreased. Conversely, levels of triglyceride (4.22 ± 0.54 μmol/g vs. 2.41 ± 0.35 μmol/g, P < 0.001), mRNA expression of SREBP-1c (2.70 ± 0.33 vs. 1.00 ± 0.00, P < 0.01), and protein expression of SCD-1 (0.93 ± 0.06 vs. 0.26 ± 0.05, P < 0.01), ACC (0.98 ± 0.09 vs. 0.43 ± 0.03, P < 0.01), and FAS (0.90 ± 0.33 vs. 0.71 ± 0.02, P = 0.04) in XBP-1s-upregulated group increased compared with the untransfected group.

ERS is associated with de novo lipogenesis, and XBP-1 partially mediates high-fructose-induced lipid accumulation in HepG2 cells through augmentation of de novo lipogenesis.

XB130 is a recently discovered adaptor protein that is highly expressed in many malignant tumors, but few studies have investigated its role in hepatocellular carcinoma (HCC). Therefore, this study explored the relationship between this protein and liver cancer and investigated its molecular mechanism of action.

The expression of XB130 between HCC tissues and adjacent nontumor tissues was compared by real-time polymerase chain reaction, immunochemistry, and Western blotting. XB130 silencing was performed using small hairpin RNA. The effect of silencing XB130 was examined using Cell Counting Kit-8, colony assay, wound healing assay, and cell cycle analysis.

We found that XB130 was highly expressed in HCC tissues (cancer tissues vs. adjacent tissues: 0.23 ± 0.02 vs. 0.17 ± 0.02, P < 0.05) and liver cancer cell lines, particularly MHCC97H and HepG2 (MHCC97H and HepG2 vs. normal liver cell line LO-2: 2.35 ± 0.26 and 2.04 ± 0.04 vs. 1.00 ± 0.04, respectively, all P < 0.05). The Cell Counting Kit-8 assay, colony formation assay, and xenograft model in nude mice showed that silencing XB130 inhibited cell proliferative ability both in vivo and in vitro, with flow cytometry demonstrating that the cells were arrested in the G0/G1 phase in HepG2 (HepG2 XB130-silenced group [shA] vs. HepG2 scramble group [NA]: 74.32 ± 5.86% vs. 60.21 ± 3.07%, P < 0.05) and that the number of G2/M phase cells was decreased (HepG2 shA vs. HepG2 NA: 8.06 ± 2.41% vs. 18.36 ± 4.42%, P < 0.05). Furthermore, the cell invasion and migration abilities were impaired, and the levels of the epithelial-mesenchymal transition-related indicators vimentin and N-cadherin were decreased, although the level of E-cadherin was increased after silencing XB130. Western blotting showed that the levels of phosphorylated phosphoinositide 3-kinase (PI3K) and phospho-protein kinase B (p-Akt) also increased, although the level of phosphorylated phosphatase and tensin homolog increased, indicating that XB130 activated the PI3K/Akt pathway. Furthermore, we found that a reduction in XB130 increased liver cancer cell sensitivity to tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis.

Our findings suggest that XB130 might be used as a predictor of liver cancer as well as one of the targets for its treatment.

This study was to review the efficacy of surgical resections in different clinical situations for a better understanding of the meaning of surgery in the treatment of neuroblastoma (NB).

The online database ScienceDirect (2016–2018) was utilized. The search was conducted using the keywords "neuroblastoma," "neuroblastoma resection," "neuroblastoma surgery," and "high-risk neuroblastoma."

We retrospectively analyzed of patients who underwent surgical resections in different clinical situations. The article included findings from selected relevant randomized controlled trials, systematic reviews, and meta-analyses or good-quality observational studies. Abstracts only, letters, and editorial notes were excluded. Full-text articles and abstracts were extracted and reviewed to identify key articles discussing surgery management of NB, which were then selected for critical analysis.

A total of 7800 English language articles were found containing references to NB (2016–2018). The 163 articles were searched which were related to the surgical treatment of NB (2016–2018). Through the analysis of these important articles, we found that the treatments of NB at low- and intermediate-risk groups were basically the same. High-risk patients remained controversial.

NB prognosis varies tremendously based on the stage and biologic features of the tumor. After reviewing the relevant literature, patients with low-risk disease are often managed with surgical resection or observation alone with tumors likely to spontaneously regress that are not causing symptoms. Intermediate patients are treated with chemotherapy with the number of cycles depending on their response as well as surgical resection of the primary tumor. High-risk patients remain controversial. Multidisciplinary intensive treatment is essential, especially for patients who received subtotal tumor resection. Minimally invasive surgery for the treatment of NBs without image-defined risk factors in low- to high-risk patients is safe and feasible and does not compromise the treatment outcome. We conclude that ≥90% resection of the primary tumor is both feasible and safe in most patients with high-risk NB. New targeted therapies are crucial to improve survival.

Endothelial cells (ECs) are important metabolic and endocrinal organs which play a significant role in regulating vascular function. Vascular ECs, located between the blood and vascular tissues, can not only complete the metabolism of blood and interstitial fluid but also synthesize and secrete a variety of biologically active substances to maintain vascular tension and keep a normal flow of blood and long-term patency. Therefore, this article presents a systematic review of common injuries and healing mechanisms for the vascular endothelium.

An extensive search in the PubMed database was undertaken, focusing on research published after 2003 with keywords including endothelium, vascular, wounds and injuries, and wound healing.

Several types of articles, including original studies and literature reviews, were identified and reviewed to summarize common injury and repair processes of the endothelial lining.

Endothelial injury is closely related to the development of multiple cardiovascular and cerebrovascular diseases. However, the mechanism of vascular endothelial injury is not fully understood. Numerous studies have shown that the mechanisms of EC injury mainly involve inflammatory reactions, physical stimulation, chemical poisons, concurrency of related diseases, and molecular changes. Endothelial progenitor cells play an important role during the process of endothelial repair after such injuries. What’s more, a variety of restorative cells, changes in cytokines and molecules, chemical drugs, certain RNAs, regulation of blood pressure, and physical fitness training protect the endothelial lining by reducing the inducing factors, inhibiting inflammation and oxidative stress reactions, and delaying endothelial caducity.

ECs are always in the process of being damaged. Several therapeutic targets and drugs were seeked to protect the endothelium and promote repair.

To the Editor: Endoscopic retrograde cholangiopancreatography (ERCP) plays a vital role in the management of pancreaticobiliary diseases in recent years and it concomitantly carries a risk of complications including post-ERCP pancreatitis, cholangitis, bleeding, and perforation. The incidence of primary post-ERCP complications ranges from 5.4% to 23.0%, and ERCP-induced perforation can occur in 0.3–1.0% of cases, but the associated mortality is high ranging from 8% to 23%.^[1]Because of the confluence of the bile duct and pancreatic duct meet at the papilla in proximity to the site of perforation in the duodenum, there is a potential risk of leakage of bile and pancreatic juice into the retroperitoneal space or peritoneum. Patients with Stapfer’s Type II perforation (perivaterian perforation) generally suffered from systemic inflammatory response syndrome, which could progress rapidly to acute lung injury and acute renal insufficiency and even multiple organ failure. All of these contribute to the significantly high mortality. A timely recognition and appropriate treatment are crucial to the management of ERCP-induced perforation to reduce the overall mortality. Conventionally, surgery remains the primary treatment for iatrogenic perforations. With the improvement in endoscopic technique and development of new accessories, nonsurgical management with endoscopic treatment of perforation is increasingly being reported.^[2]We report a retrospective analysis of ERCP-induced Stapfer’s Type II perforations over a 5-year period managed with nonsurgical approach combined with salvage ERCP.

To the Editor: Recently, with the development of endoscopic therapy technology, the incidence of iatrogenic perforation is also increasing. If the defect was not treated properly, subsequent gastrointestinal fistula and infection could lead to serious complications. This study evaluated a simple method for close gastric defect after endoscopic treatment, with endoloop and metallic clips using single-channel endoscope.

To the Editor: Cataract and age-related macular degeneration (AMD), often develop concurrently, which are two of the leading causes of visual damages associated with aging. Sunlight is reported to contribute to the pathogenesis of both cataract and AMD.^[1]In cases of cataract, less sunlight could possibly access to the ocular fundus. On this basis, lens opacity maybe a protective factor for AMD. Nevertheless, there are still disputes up to now.

To the Editor: Reduced vision impacts not only the individual but also the family, community, and public health. It leads to a significant economic burden, including increased education cost, reduced personal income, and loss of productivity for caregivers, and numerous intangible consequences, such as loss of independence, reduced quality of life, and excess morbidity for individuals. An estimated 19 million of the world’s children are visually impaired, while 1.4 million are blind, according to the World Health Organization (WHO) criteria. Therefore, the control of visual impairment or blindness (VI/BL) in children is still one of the priority areas of the WHO’s "Vision 2020: the Right to Sight" program.

To the Editor: Nonarteritic anterior ischemic optic neuropathy (NAION) is an acute optic neuropathy disease that is common in the elderly. The incidence of NAION is approximately (2.3–10.2)/100,000, and both eyes are involved in many patients. Xuet al.^[1]reported that the incidence in the Chinese population was 1/16,000. Acute visual acuity (VA) damage without any pain and a poor prognosis are the main features of NAION. This study aimed to find the related risk factors for NAION in average individuals to promote the prevention or early diagnosis of NAION.

To the Editor: Several kinds of malignant tumors show perineural invasion (PNI), which can cause locoregional recurrence and reduce the likelihood of survival after surgery. Our previous study has shown that PNI in cervical cancer is associated with other pathology risk features, and other studies have shown that it is a predictor of poor prognosis.^[1,2,3]These findings highlight the importance of clarifying the molecular mechanism of PNI.

To the Editor: A 30-year-old pregnant women at 12⁺²(means 12 weeks and 2 days of gestation) weeks of gestation suffered severe distending pain in the lower abdomen, dizzy, and weakness for over 5 h. The patient had no other medical history except one abortion. Bimanual examination revealed tenderness in the left adnexal region and no hemorrhage in closed cervical os. Ultrasound showed a live fetus of 12⁺²weeks in the uterus, an irregular heterogeneous hypoechoic mass in front of the uterus, and massive fluid in the pelvis [Figure 1]. Culdocentesis revealed ~5-ml blood. The laboratory test showed hemoglobin of 85 g/L, hematocrit of 26.6%, white blood cell count of 19.09 × 10⁹/L, and normal platelet and clotting. Due to unknown intraperitoneal hemorrhage, an emergency laparoscopy was arranged.

To the Editor: A uterine carcinosarcoma (malignant mixed Müllerian tumor [MMMT]) is a rare, aggressive, malignant tumor which demonstrates both malignant epithelial (carcinoma) and mesenchymal (sarcoma) components.^[1]MMMTs account for 2–5% of all uterine malignancies. Metastatic progression is uncommon and occurs through hematologic, lymphatic, and intraperitoneal spread. Risk factors for MMMTs include radiation, excessive estrogen exposure, obesity, and nulliparity. The 2-year survival rate for patients with MMMTs is 53% for Stage I disease and decreases to 8.5% for Stages II and III.^[2]

To the Editor: Hyperhomocysteinemia (HHcy) is an important risk factor for atherothrombotic disease and venous thrombosis.^[1]Normally, homocysteine (Hcy) is either remethylated to methionine (Met) by a Vitamin B12-dependent reaction or betaine as the methyl donor, or trans-sulfurated to cysteine through a pyridoxine-dependent reaction. Based on plasma level of total Hcy, HHcy is typically classified into three groups as follows: mild (tHcy 15–30 µmol/L), moderate (tHcy 30–100 μmol/L), and severe (tHcy >100 μmol/L).^[2]Severe HHcy is rare and most commonly caused by inherited deficiency of cystathionine beta-synthase (CBS), or less frequently, of methylenetetrahydrofolate reductase (MTHFR) genes. The presentations of this metabolic disorder include developmental delay, intellectual disability, epilepsy, ectopia lentis, myopia, hypopigmentation of the skin and hair, marfanoid habitus, and thromboembolic disorders.^[3]These manifestations are often overlooked in the early stage until the occur of thrombotic events like cerebral venous sinus thrombosis (CVST).

To the Editor: Giant axonal neuropathy (GAN) is a rare neurodegenerative disease caused by recessive mutations inGANgene encoding gigaxonin. Nerve pathology of GAN shows typical giant axon with accumulating intermediate filaments. The disease is progressive with impairments in both peripheral and central nervous system. Here, we reported a case presenting gait disturbance, giant axon in nerve biopsy, and abnormalities in brain magnetic resonance imaging (MRI).

As a rare autosomal-recessive metabolic disorder, cystinosis is caused by defective transport of cystine across the lysosomal membrane.^[1]Once the diagnosis of cystinosis is confirmed, specific treatment with cysteamine, an aminothiol, should be applied to the patient as soon as possible in order to preserve renal function and improve growth in affected children.^[2]Cysteamine is the only specific drug approved by the Food and Drug Administration for cystinosis. Although it cannot reverse the existing kidney damage, it was reported that 17 patients treated with cysteamine for 7 years recovered almost normal kidney function and, more importantly, they grew normally.^[3]Another report suggested that cysteamine treatment could postpone end-stage kidney damage for 10–20 years.^[4]However, the immediate challenge lies in the access to the necessary medication in China for the management of cystinosis. Here, we report the case of two sibling boys with cystinosis in order to raise awareness to the international community about the urgent need for worldwide policy and action for such rare diseases.

A 48-year-old woman had a symptom of chest pain a month ago, without obvious inducement, coughing, sputum, hemoptysis, or chest tightness. The pain in the chest was irregular. The patient was admitted to the First Hospital of Jilin University for further treatment. The patient denied the history of hypertension, coronary heart disease, diabetes mellitus, and other diseases. She also denied family history of hereditary disease. However, she has had a smoking history for 20 years, about 10 cigarettes per day, no quit. Physical examination and blood tests did not show apparent abnormality. All tumor markers were negative. The computed tomography (CT) showed a high-density mass of right upper lobe of the lung, which was about 17 mm × 15 mm [Figure 1a]. The boundary was smooth, and the density was uniform. The image of a narrow arc of fluid was seen in the right thoracic cavity and there was no significant lymph node (LN) metastasis in the mediastinum [Figure 1b]. The patient underwent exploration under thoracoscope, and the intraoperative rapid pathology showed suspicious adenocarcinoma, the patient received the resection of the upper lobe of the right lung. However, the final pathology revealed the pulmonary sclerosing hemangioma (PSH). Microscopic findings of the postoperative specimen showed a mixture of papillary and sclerotic patterns with two cell types as follows: cuboidal surface and stromal round cells. The cuboidal surface cells resembling pneumocytes and round stromal cells with well-defined borders were centrally located round to oval vesicular nuclei and rare nucleoli. The round stromal cells mostly had slightly eosinophilic cytoplasm with some showing a more vacuolated or foamy appearance. In other areas, there were large blood-filled spaces lined by flattened cells. Solid sheets of round cells with scattered cuboidal surface cells forming small tubules were also noted [Figure 1c]. The round stromal cells were positive for thyroid transcription factor-1 (TTF-1) and vimentin but negative for epithelial membrane antigen (EMA) and pan-Cytokeratin, and the cuboidal surface cells were positive for TTF-1, vimentin, EMA, Ki-67, and pan-Cytokeratin [Figure 1d-1h].

In the very interesting report published inChinese Medical Journal^[1]concerning a 65-year-old hypertensive and hyperlipidemic male patient, with stent implantation 5 years previously, the patient developed anaphylactic shock accompanied by chest discomfort, palpitation, itchiness, nausea, vomiting, dyspnea, wheezing, abdominal pain, sweating, pale complexion, dizziness, and syncope following bread and milk consumption. The clinical symptomatology was associated with electrocardiographic and laboratory evidence of acute inferolateral myocardial infarction, and the patient recovered with epinephrine, antiallergic, and myocardial infarction protocol therapy including ticagrelor and Clexane. Coronary arteriography demonstrated lesions in the left trunk and the three coronary branches, but the stented areas were unobstructed. The allergen test revealed a Grade 2 (2.11 kUA/L) for wheat and Grade 0 for milk.

As mentioned in our previous article,^[1]a 65-year-old man was admitted to our hospital on September 9, 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. His blood pressure dropped to 51/21 mmHg (1 mmHg= 0.133 kPa). The laboratory tests showed that myocardial enzyme increased and a ST elevation of the electrocardiogram. Coronary angiography revealed that the stent was unobstructed.