2020年 · 第133卷第07期

In the past decade, artificial intelligence (AI) has been applied in several clinical studies to improve the medical care of patients with gastroenterological diseases, to accurately detect polyps and early cancer lesions, to facilitate the analysis of inflammatory lesions, to assess liver fibrosis, and to predict the response and clinical outcomes of medications.^[1,2]

Organ donation and transplantation in China has shown remarkable improvement through untiring efforts of several generations of transplant surgeons. Our work has been appreciated and recognized by the international community. However, misunderstandings and criticisms, even misinterpretations, and denigrations, have occurred. Therefore, this paper introduces the three evolutionary phases of development of organ transplantation in China: the initial exploration phase, development and construction phase, and scientific standardization phase.

Various experimental and clinical studies have reported on coronary microcirculatory dysfunction ( "no-reflow" phenomenon). Nevertheless, pathogenesis and effective treatment are yet to be fully elucidated. This study aimed to measure the intracoronary pressure gradient in the no-reflow artery during emergent percutaneous coronary intervention and explore the potential mechanism of no-reflow.

From September 1st, 2018 to June 30th, 2019, intracoronary pressure in acute myocardial infarction patient was continuously measured by aspiration catheter from distal to proximal segment in the Department of Coronary Care Unit, Tianjin Chest Hospital, respectively in no-reflow arteries (no-reflow group) and arteries with thrombolysis in myocardial infarction-3 flow (control group). At least 12 cardiac cycles were consecutively recorded when the catheter was pulled back. The forward systolic pressure gradient was calculated as proximal systolic pressure minus distal systolic pressure. Comparison between groups was made using the Student t test, Mann-Whitney U-test or Chi-square test, as appropriate.

Intracoronary pressure in 33 no-reflow group and 26 in control group were measured. The intracoronary forward systolic pressure gradient was －1.3 (－4.8, 0.7) and 3.8 (0.8, 8.8) mmHg in no-reflow group and control group (Z = －3.989, P < 0.001), respectively, while the forward diastolic pressure gradient was －1.0 (－3.2, 0) and 4.6 (0, 16.5) mmHg in respective groups (Z = －3.851, P < 0.001). Moreover, the intracoronary forward pressure gradient showed significant difference between that before and after nicorandil medication (Z=－3.668, P < 0.001 in systolic pressure gradient and Z =－3.530, P < 0.001 in diastolic pressure gradient).

No reflow during emergent coronary revascularization is significantly associated with local hemodynamic abnormalities in the coronary arteries. Intracoronary nicorandil administration at the distal segment of a coronary artery with an aspiration catheter could improve the microcirculatory dysfunction and resume normal coronary pressure gradient.

www.ClinicalTrials.gov (No. NCT 03600259).

Diabetes mellitus (DM) is considered a cardiovascular risk factor. The aim of this study was to analyze the prevalence and volume of coronary artery plaque in patients with diabetes mellitus (DM) vs. those without DM.

This study recruited consecutive patients who underwent coronary computed tomography (CT) angiography (CCTA) between October 2016 and November 2017. Personal information including conventional cardiovascular risk factors was collected. Plaque phenotypes were automatically calculated for volume of different component. The volume of different plaque was compared between DM patients and those without DM.

Among 6381 patients, 931 (14.59%) were diagnosed with DM. The prevalence of plaque in DM subjects was higher compared with nondiabetic group significantly (48.34% vs. 33.01%, χ² = 81.84, P < 0.001). DM was a significant risk factor for the prevalence of plaque in a multivariate model (odds ratio [OR] = 1.465, 95% CI: 1.258-1.706, P < 0.001). The volume of total plaque and any plaque subtypes in the DM subjects was greater than those in nondiabetic patients significantly (P < 0.001).

The coronary artery atherosclerotic plaques were significantly higher in diabetic patients than those in non-diabetic patients.

Ophthalmic ambulatory surgery is preferred to be performed under general anesthesia either by total intravenous anesthesia (TIVA) or by inhalational anesthesia to increase the patient comfort. However, anesthesia-controlled time (ACT) can cause increased non-operative operating room (OR) time which may adversely affect the ORs efficiency. This study was aimed to compare the ACT of desflurane with that of propofol-remifentanil in strabismus ambulatory surgery.

From November 2016 to December 2017, a total of 200 strabismus patients (aged 18-60 years old, and scheduled for elective ambulatory surgery at Zhongshan Ophthalmic Center) were randomly assigned to receive either propofol-based TIVA (group TIVA) or desflurane anesthesia (group DES) for maintenance of anesthesia. The primary outcome was the extubation time. Secondary outcomes included surgical time, anesthetic time, OR exit time, and Phase I and II recovery time. The intraoperative incidences of hypotension, bradycardia and oculocardiac reflex (OCR), and the incidences of any post-operative complications were recorded. Mann-Whitney U test and Chi-square or Fisher exact tests were used to compare the two groups.

We found that the extubation time (5.5 [3.9-7.0] vs. 9.7 [8.5-11.4] min, P < 0.001) and the incidence of prolonged time to extubation (0 vs. 6%, P = 0.029) in the DES group were significantly decreased compared with those in the TIVA group. The patients in the DES group displayed shorter OR exit time as compared with that in the TIVA group (7.3 [5.5-8.7] vs. 10.8 [9.3-12.3] min, P < 0.001). The patients using desflurane exhibited more stable hemodynamics during surgery than the patients using propofol-based TIVA, as demonstrated by lower incidences of hypotension (1% vs. 22%, P < 0.001), bradycardia (2% vs. 13%, P = 0.002), and OCR (17% vs. 44%, P < 0.001).

DES enhanced the ophthalmic OR efficiency by reducing the extubation time and OR exit time, and provided more stable hemodynamics intra-operatively than TIVA in patients undergoing strabismus ambulatory surgery.

ClinicalTrials.gov, No. NCT02922660; https://clinicaltrials.gov/ct2/show/NCT02922660?id=NCT02922660&draw=2&rank=1

Previous studies have provided conflicting evidence about the increased overall survival (OS) in lung cancer patients with diabetes mellitus (DM) compared with those without DM. This study assessed progression-free survival (PFS)/OS in lung cancer patients with or without DM and tentatively analyzed the impact of blood glucose levels on PFS/OS in lung cancer patients.

Data were collected from lung cancer patients based upon admission records from January 2010 to January 2012 and follow-up records from January 2010 to January 2015 in the Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai. The data included patient sex, age, body mass index (BMI), smoking status, history of DM, level of blood glucose, pathological type, clinical stage of cancer, chemotherapy regimen, and history of anti-DM drugs. The Cox regression model and Kaplan-Meier method were used for the analysis of hazard factors and PFS/OS. For comparison of PFS/OS in lung cancer with or without DM, patients were divided into three groups: lung cancer with DM, lung cancer without DM but with elevated level of blood glucose, lung cancer without DM or elevated level of blood glucose.

In total, the data from 200 lung cancer patients (138 males/62 females, aged 29.0 to 78.0 years, mean 60.0 ± 8.6 years) were collected. For the comparison of PFS/OS in lung cancer patients with or without DM, patients were divided into three groups: lung cancer with DM (n = 31); lung cancer without DM but with elevated levels of blood glucose (n = 40); and lung cancer without both DM and elevated levels of blood glucose (n = 128), whereas 1 patient dropped out of the study. All the patients underwent complete chemotherapy and were followed up for 36.0 to 60.0 months. Kaplan-Meier survival analysis showed that lung cancer patients with DM had increased PFS and OS compared with those without DM (log-rank, P < 0.05, P < 0.01); the median PFS in lung cancer with DM was 12.0 months (95% confidence interval [CI], 4.0-16.0) vs. 6.0 months in those without DM (95% CI, 5.8-6.3); and the median OS in lung cancer patients with DM was 37.0 months (95% CI, 29.0-46.6) vs. 12.0 months in those without DM (95% CI, 10.9-13.1). For the other two groups of patients without DM, there was a trend toward a shorter PFS and OS in patients with elevated blood glucose compared with those without elevated blood glucose. Cox regression showed that PFS in lung cancer patients was favorably associated with the usage of anti-DM drugs, BMI, clinical stage of cancer, and chemotherapy regimen (all P < 0.05) but was inversely associated with the level of blood glucose (P < 0.05).

Lung cancer patients with DM have prolonged PFS and OS compared with those without DM, and the level of blood glucose was inversely associated with PFS. The current results indicate that PFS may be a meaningful intermediate endpoint for OS and that the levels of blood glucose hopefully represent a prognostic factor in lung cancer patients.

Regulatory policy (RP) is known as a major factor to improve health care system performance. A significant difference in maternal mortality rates (MMRs) was observed between New York city (NYC) and Shanghai (SH), both first-class international metropolises. This study aims to adopt a quantitative evaluation model to analyze whether RP differences contribute to the different MMRs of the two cities.

Based on collection of all publicly released policy documents regarding maternal health in the two cities, we assessed and compared the status of their maternal health care RPs from 2006 to 2017 through a series of quantitative indicators as regulatory elements coverage rate (RECR), departmental responsibility clarity rate (DRCR), and accountability mechanism clarity rate (AMCR), based on two characteristics of comprehensiveness and effectiveness of RPs. Pearson correlation analysis, principal component analysis, and linear regression analysis were used to test the relationships between the indicators and MMR in SH and NYC.

By 2017, disparities of maternal health care RP are found between SH and NYC, from the indicators of RECR (100% vs. 77.0%), DRCR (38.9% vs. 45.1%), and AMCR (29.2% vs. 22.5%). From 2006 to 2017, RECR, DRCR, and AMCR in SH have shown a higher growth of 8.7%, 53.2%, and 45.2%, compared with growth of 25.0%, 12.5%, and 2.9% in NYC. The three indicators were found all negatively correlated with MMR in SH (Coefficients = －0.831, －0.833, and －0.909, and P < 0.01), while only RECR and DRCR had negative correlation with MMR in NYC (Coefficients = －0.736 and －0.683, and P < 0.05). Linear regression showed that the principal components of the three indicators were found with significant impact on MMRs both in SH (R = 0.914, R² = 0.836, P < 0.001) and NYC (R = 0.854, R² = 0.357, P = 0.04).

Compared with NYC, the more comprehensive and effective maternal health care RPs in SH had a stronger impact on MMR control, which contributed to the differences between the two cities’ MMRs to some extent. The methods and indicators we adopted for assessment are reasonable and comparable.

The use of microRNAs in the therapy of kidney disease is hampered by the difficulties in their effective delivery. Microvesicles (MVs) are known as natural carriers of small RNAs. Our prior research has demonstrated that MVs isolated from mesenchymal stem cells (MSCs) are capable of attenuating kidney injuries induced by unilateral ureteral obstruction and 5/6 sub-total nephrectomy in mice. The present study aimed to evaluate the effects of miR-34a-5p (miR-34a)-modified MSC-MVs on transforming growth factor (TGF)-β1-induced fibrosis and apoptosis in vitro.

Bone marrow MSCs were modified by lentiviruses over-expressing miR-34a, from which MVs were collected for the treatment of human Kidney-2 (HK-2) renal tubular cells exposed to TGF-β1 (6 ng/mL). The survival of HK-2 cells was determined using 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) and Annexin V-Light 650/propidium iodide (PI) assays. The expression levels of epithelial markers (tight junction protein 1 [TJP1] and E-cadherin) and mesenchymal markers (smooth muscle actin alpha (α-SMA) and fibronectin) in HK-2 cells were measured using Western blot analysis and an immunofluorescence assay. In addition, changes in Notch-1/Jagged-1 signaling were analyzed using Western blotting. Data were analyzed using a Student’s t test or one-way analysis of variance.

MiR-34a expression increased three-fold in MVs generated by miR-34a-modified MSCs compared with that expressed in control MVs (P < 0.01, t= 16.55). In HK-2 cells, TJP1 and E-cadherin levels decreased to 31% and 37% after treatment with TGF-β1, respectively, and were restored to 62% and 70% by miR-34a-enriched MSC-MVs, respectively. The expression of α-SMA and fibronectin increased by 3.9- and 5.0-fold following TGF-β1 treatment, and decreased to 2.0- and 1.7-fold after treatment of HK-2 cells with miR-34a-enriched MSC-MVs. The effects of miR-34a-enriched MSC-MVs on epithelial-mesenchymal transition (EMT) markers were stronger than control MSC-MVs. The effects of miR-34a-enriched MSC-MVs on these EMT markers were stronger than control MSC-MVs. Notch-1 receptor and Jagged-1 ligand, two major molecules of Notch signaling pathway, are predicted targets of miR-34a. It was further observed that elevation of Notch-1 and Jagged-1 induced by TGF-β1 was inhibited by miR-34a-enriched MSC-MVs. In addition, TGF-β1 exposure also induced apoptosis in HK-2 cells. Although miR-34a-mofidied MSC-MVs were able to inhibit TGF-β1-triggered apoptosis in HK-2 cells, the effects were less significant than control MSC-MVs (control:TGF-β1 :miR-nc-MV:miR-34a-MV = 1.3:0.6:1.1:0.9 for MTT assay, 1.8%:23.3%:9.4%:17.4% for apoptosis assay). This phenomenon may be the result of the pro-apoptotic effects of miR-34a.

The present study demonstrated that miR-34a-over-expressing MSC-MVs inhibit EMT induced by pro-fibrotic TGF-β1 in renal tubular epithelial cells, possibly through inhibition of the Jagged-1/Notch-1 pathway. Genetic modification of MSC-MVs with an anti-fibrotic molecule may represent a novel strategy for the treatment of renal injuries.

Metabolic syndrome (MetS) describes a set of risk factors that can eventually lead to the occurrence of cardiovascular and cerebrovascular disease. A detailed understanding of the MetS mechanism will be helpful in developing effective prevention strategies and appropriate intervention tools. In this article, we discuss the relationship between the clinical symptoms of MetS and differences in the gut microbial community compared with healthy individuals, characterized by the proliferation of potentially harmful bacteria and the inhibition of beneficial ones. Interactions between gut microbiota and host metabolism have been shown to be mediated by a number of factors, including inflammation caused by gut barrier defects, short-chain fatty acids metabolism, and bile acid metabolism. However, although we can clearly establish a causal relationship between gut microbial profiles and MetS in animal experiments, the relationship between them is still controversial in humans. Therefore, we need more clinical studies to augment our understanding of how we can manipulate the gut microbiota and address the role of the gut microbiota in the prevention and treatment of MetS.

Type 2 diabetes mellitus (T2DM), a worldwide epidemic disease, has caused tremendous economic and social burden, but the pathogenesis remains uncertain. Nowadays, the impact of unrhythmic circadian clock caused by irregular sleep and unhealthy diet on T2DM has be increasingly studied. However, the contribution of the endogenous circadian clock system to the development of T2DM has not yet been satisfactorily explored. It is now becoming clear that the gut microbiota and the circadian clock interact with each other to regulate the host metabolism. Considering all these above, we reviewed the literature related to the gut microbiota, circadian clock, and T2DM to elucidate the idea that the gut microbiota is closely tied to the regulation of the circadian clock in the development of T2DM, which provides potential for gut microbiota-directed therapies to ameliorate the effects of circadian disruptions linked to the occurrence and development of T2DM.

The homeostasis of the gut-brain axis has been shown to exert several effects on physiological and psychological health. The gut hormones released by enteroendocrine cells scattered throughout the gastrointestinal tract are important signaling molecules within the gut-brain axis. The interaction between gut microbiota and gut hormones has been greatly appreciated in gut-brain cross-talk. The microbiota plays an essential role in modulating many gut-brain axis-related diseases, ranging from gastrointestinal disorders to psychiatric diseases. Similarly, gut hormones also play pleiotropic and important roles in maintaining health, and are key signals involved in gut-brain axis. More importantly, gut microbiota can affect the release and functions of gut hormones. This review highlights the role of gut microbiota in the gut-brain axis and focuses on how microbiota-related gut hormones modulate various physiological functions. Future studies could target the microbiota-hormones-gut brain axis to develop novel therapeutics for different psychiatric and gastrointestinal disorders, such as obesity, anxiety, and depression.

The human gastrointestinal tract accommodates an entire micro-environment for divergent physiologic processes, the dysbiosis of this micro-ecology has a strong inter-action with the pathogenesis of inflammatory bowel disease (IBD). In the past few years, with the advances in the understanding of microbiome, its metabolites and further application of next generation sequencing, analysis of dynamic alteration of gut micro-environment was realized, which provides numerous information beyond simple microbiota structure or metabolites differences under chronic colitis status. The subsequent intervention strategies targeting the modulation of intestinal micro-environment have been explored as a potential therapy. In this review, we will summarize the recent knowledge about multi-dimensional dysbiosis, the inter-action between fungus and bacteria under inflamed mucosa, and the clinical application of probiotics and fecal microbiota transplantation as a promising therapeutic approach in IBD.

The incidence of septic acute kidney injury (AKI) is increasing, it has become a major threat to human health because of its acute onset, poor prognosis, and high hospital costs. The most common cause of AKI in critical-care units is sepsis. Septic AKI is a complex and multi-factorial process; its pathogenesis is not fully understood. In sepsis, the destruction of mucosal barriers, intestinal flora disorders, intestinal ischemia/reperfusion injury, use of antibiotics, and lack of intestinal nutrients lead to an inflammatory reactions that in turn affects the metabolism and immunity of the host. Such changes further influence the occurrence and development of AKI. New technology is enabling various detection methods for intestinal flora. Clinical application of these methods in septic renal injury is expected to clarify the relationship among pathogenesis, disease progression mechanism, and intestinal flora.

A pancreatic cystic neoplasm (PCN) is a rare pancreatic disease. Malignant PCNs are usually identified incidentally while evaluating other lesions. However, PCNs are being identified more frequently owing to the increased use of abdominal imaging. Malignant PCNs have complicated and diverse biological behaviors, including various malignant risk factors, diverse molecular features, natural history, and complex pathological classifications. Although many diagnostic methods, such as cross-sectional imaging and endoscopic evaluation, have been developed, malignant PCNs are still difficult to differentiate from benign tumors. On searching for related articles in the recent decade, we found that some molecular biomarkers such as carcinoembryonic antigen could be useful for discriminating between malignant tumors and benign tumors. However, cytopathologic evaluation is the most useful method for differentiating between benign and malignant lesions. Although cytopathologic evaluation has a specificity of 100% for identifying malignancies, its accuracy is often hampered by the low cellularity of PCN cells in the cystic fluid. Herein, we review the progress in the use of cellular and molecular markers for the accurate identification of PCNs.

Historically, breast cancer has been regarded as an immunogenic "cold" tumor. However, the discovery of immune checkpoint inhibitors has made immunotherapy becoming an emerging new treatment modality for breast cancer. This review discusses the immune system, immune features of breast cancer, and the programmed cell death protein-1/programmed cell death protein ligand-1 (PD-1/PD-L1) inhibitors used in the treatment of breast cancer. High T lymphocyte infiltration and mutation burden were observed in triple-negative breast cancer and human epidermal growth factor receptor 2 positive breast cancer. Increasing breast cancer immunogenicity and modulating the tumor microenvironment has been reported to improve the therapeutic efficacy of immunotherapy. Recent clinical trials involving PD-1/PD-L1 inhibitors monotherapy in breast cancer has revealed little efficacy, which highlights the need to develop combinations of PD-1/PD-L1 inhibitors with chemotherapy, molecularly targeted therapies, and other immunotherapies to maximize the clinical efficacy. Collectively, the immunotherapy might be a promising therapeutic strategy for breast cancer and several clinical trials are still on-going.

It shows that detrimental exposures and conditions in mothers can lead to the development of obesity and type 2 diabetes in offspring. This can lead to a vicious cycle of metabolic dysfunction, where rising rates of obesity, pre-diabetes, and diabetes in individuals of reproductive age, propagating risks to subsequent generations. It is well established that regular exercise has important health benefits for people with obesity and type 2 diabetes. Recently, increasing studies aim to examine the effects of maternal exercise on metabolic health in offspring. This review aims to demonstrate the evidence linking maternal exercise during critical periods of development and its implications for glucose metabolism in offspring, including intervention timing, sexual dimorphism, different exercise type, and intensity. Then we further examine the potential role of epigenetic modifications in this process.

Hemodialysis (HD) is a crucial renal replacement therapy for patients with end-stage renal disease. Despite improvements in dialysis technology, mortality for maintenance HD (MHD) patients remains high. To improve the quality of life among MHD patients, it is necessary to examine the risk factors associated with mortality. In this study, we retrospectively analyzed patients’ conditions at the beginning of dialysis and assessed the risk factors for mortality in MHD patients treated at the Center for Hemodialysis in West China Hospital, Sichuan University, China. The aim of this study was to identify significant risk factors to guide the treatment of MHD patients and targeted early preventions to improve prognosis.

To the Editor:Ovarian cancer is the leading cause of death from gynecologic malignancies. The major limitation to the successful long-term treatment of ovarian cancer is the development of chemotherapeutic resistance, which involves thousands of genes. In this study, a single-channel low-density custom microarray was designed to compare gene expression profiles between chemotherapy-resistant and chemotherapy-sensitive ovarian cancer. The 87 genes were identified to be differentially expressed in resistant and sensitive specimens that can be used to fairly accurately predict drug resistance in serous ovarian cancer.

To the Editor:Central pontine myelinolysis (CPM), a form of osmotic demyelination syndrome (ODS) typically occurring in the central pons, was first described in alcoholic and malnourished individuals by Adamset al^[1]in 1959. ODS is frequently associated with alcohol abuse, liver transplantation, and rapid correction of hyponatremia.^[2]The clinical manifestations of CPM are variable, including dysarthria, dysphagia, oculomotor dysfunction, variable degrees of quadriparesis and even locked-in syndrome. In addition, some patients may be asymptomatic. The size of myelinolysis in the central pons on brain magnetic resonance imaging (MRI) is not always matched with the severity of clinical symptoms. Previously, a limited number of case reports focued on the magnetic resonance spectroscopy (MRS) findings of CPM. Here, we report a case of CPM and emphasize the importance of MRS.

To the Editor:Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder characterized by insulin resistance (IR) and β-cell dysfunction,^[1]and the development of microvascular (including nephropathy and retinopathy) and macrovascular complications if not well managed. Diabetic nephropathy (DN) is a form of chronic kidney disease that is caused by diabetes.^[2]The incidence of chronic kidney disease in Chinese patients with T2DM is gradually increasing.^[3]The early stage of DN is characterized by a rise in urine albumin concentration and renal hyper-filtration.

To the Editor: Chest pain is one of the most common complaints for patients attending emergency departments (EDs) globally. It is important to accurately stratify risk of possible acute coronary syndrome (ACS) for these patients.^[1]Several risk stratification scores such as thrombolysis in myocardial infarction (TIMI), global registry for acute coronary events (GRACE), Banach and HEART are helpful.^[2]Previous research in our setting compared these four scores and found that the HEART score, with a C-statistic of 0.731, was the best for predicting 7-day major adverse cardiac events (MACE).^[3]

To the Editor:Squamous cell carcinoma (SCC) in the ungual apparatus is a rare neoplasm. Although it is the most prevalent malignant tumor in this region, it often presents with non-specific features that lead to misdiagnosis and delayed treatment.^[1]Various treatments have been proposed, including Mohs micrographic surgery, wide local excision with skin grafting, and amputation of the digit. Given the rarity of the condition, there is no consensus on the optimal treatment.^[2]Photodynamic therapy (PDT) has been extensively used to treat non-melanoma skin cancers, such as actinic keratosis, basal cell carcinoma, and SCCin situ.^[3]The difficult treatment of subungual SCC and the success rates of PDT for early SCC suggested that this treatment would be useful for treating the following patient, who was diagnosed with subungual SCC but refused surgery and was ultimately successfully treated with topical PDT.