Structure-activity Omics of Anti-inflammatory and Analgesic Effect of Corydalis Rhizoma in Qizhi Weitong Granules / 中国实验方剂学杂志

ObjectiveTo explain the anti-inflammatory and analgesic effects of Corydalis Rhizoma by the means of structure-activity omics. MethodOn the basis of the previous in vitro screening study， we studied the in vivo efficacy of the alkaloids in Corydalis Rhizoma. With the targets as a bridge， the structures of chemical components in Corydalis Rhizoma were connected with the efficacy. The molecular docking of the alkaloids in Corydalis Rhizoma with the targets of inflammation and pain was carried out. According to the docking scores and the differences in the structural nucleus of Corydalis Rhizoma alkaloids， a study of structure-activity omics was carried out to summarize the rules of their connection. ResultThe alkaloids in Corydalis Rhizoma had good anti-inflammatory and analgesic effects in vivo， involving 53 chemical components and 73 targets. There were 3 074 targets associated with inflammation and pain， and 42 targets of direct action were shared by the chemical components and the disease. The protein-protein interaction （PPI） and molecular docking analysis predicted that the main active components of Corydalis Rhizoma were tetrahydropalmatine and palmatine， and the core targets were prostaglandin endoperoxide synthase 2 （PTGS2）， glutamate receptor metabotropic 5 （GRM5）， estrogen receptor 1 （ESR1）， solute carrier family 6 member 4 （SLC6A4）， and fusion oncoproteins （FOS）. According to the differences of mother nucleus， the 53 alkaloid components of Corydalis Rhizoma were classified into 8 categories， including protoberberine， berberine， and aporphine， which had high binding affinities with PTGS2， GRM5 and other targets. The relationship between the structures of Corydalis Rhizoma alkaloids and docking scores in each group showed the same law. In protoberberine， appropriate substituents with hydroxyl， alkoxy or methyl groups on the A and D rings of the parent ring were conducive to enhancing the binding activities with the two targets. In berberine， the structure containing a methyl group on position 13 had strong binding affinities with the two targets. It is hypothesized that the methyl fragment changes the binding mode between the component structure and amino acid residues， which greatly improves the binding affinity. ConclusionThis study employs the method of structure-activity omics to analyze the material basis for the anti-inflammatory and analgesic effects of alkaloids in Corydalis Rhizoma， and the structure-activity omics provides new ideas for revealing the pharmacodynamic substances of traditional Chinese medicine.

CiteSpace-based visual analysis of research progress on intracerebral hemorrhage-related signaling pathways in recent 10 years / 中风与神经疾病杂志

@#Objective To explore the hotspots and trend of research on the signaling pathways of intracerebral hemorrhage in the past 10 years through bibliometrics and visual analysis. Methods We used CiteSpace to perform bibliometrics and visual analysis on relevant articles published in the recent 10 years， which were obtained from the Science Citation Index Expanded database of the Web of Science Core Collection. Results According to visual analysis of 796 pieces of literature on intracerebral hemorrhage-related signaling pathways， there is a growing number of papers published in this field. China was the country with the largest number of papers published. Loma Linda University was the institution with the largest number of papers published. The funding institution sponsoring most in this field was the National Natural Science Foundation of China. The keyword analysis showed that the research focused on inflammatory reactions， oxidative stress， microRNA gene expression， nuclear factor-kappa B signaling pathways， extracellular regulated protein kinase 1/2 signaling pathways， the lipid-signaling molecule sphingosine-1-phosphate， and scalp acupuncture therapy. Conclusion CiteSpace-based visual analysis can directly display the research hotspots and trend of intracerebral hemorrhage-related signaling pathways， providing new insights into the treatment and prevention of intracerebral hemorrhage.

Research advances in the pyroptosis signaling pathway after intracerebral hemorrhage / 中风与神经疾病杂志

@#Pyroptosis is an important mechanism leading to secondary brain injury （SBI） after intracerebral hemorrhage （ICH）， which can be classified into the inflammasome-dependent classical pyroptosis pathway and the caspase-4/5/11-dependent non-classical pyroptosis pathway. GSDMD and GSDME of the gasdermin family are the key effectors of pyroptosis and bind to lipids on cell membrane to induce the formation of membrane pore. Interleukin-1β/-18 is a downstream inflammatory factor that mediates inflammatory injury after pyroptosis. This article reviews the key proteins in the pyroptosis pathway and the mechanism of action of the pyroptosis signaling pathway after ICH.

Research progress on the regulation and mechanism of reactive oxygen species on tumor immune checkpoints / 药学学报

Immune checkpoints (ICs) are immunosuppressive molecules expressed on immune cells, which can regulate immune cells' activation. Immune checkpoint inhibitors (ICIs) which can block the interaction of immune checkpoints and their ligands, improve the cytotoxic effect of the immune system on tumor cells. Immunotherapy such as employing ICIs has gradually become a conventional therapeutic strategy for cancer treatment. However, the low response rate and the emergence of drug resistance have seriously affected the clinical efficacy of ICIs. Reactive oxygen species (ROS) are electronic reduction products of active oxygen, as well as natural by-products of cell metabolism, which can be used as regulators of intercellular signals. Tumor microenvironment (TME) is often in the state of oxidative stress (OS), which is the imbalance between oxidative system and antioxidant system. ROS can affect the interaction with its ligands by regulating the expression and activity of immune checkpoints in TME, thus affecting the anti-tumor effect of immune cells. Accumulating studies have shown that ROS could regulate tumor immune checkpoints through several pathways. Due to different types and stages of tumor, it would be clinical beneficial to understand the mechanistic link of ROS on tumor immune checkpoint, and choose appropriate ROS regulators combined with immune checkpoint inhibitors to maximize anti-tumor effects. This article reviews the common metabolic sources and characteristics of ROS, the regulatory effect and mechanism of ROS on tumor immune checkpoints and its therapeutic application.

The characteristics of non-alcoholic fatty liver disease and its associated factors in patients with rheumatoid arthritis / 中华预防医学杂志

Objective: To investigate the characteristics of non-alcoholic fatty liver disease (NAFLD) and its associated factors in rheumatoid arthritis (RA) patients. Methods: This cross-sectional study recruited 385 RA patients [including 72 (18.7%) male and 313 (81.3%) female] who received abdominal sonographic examination from August 2015 to May 2021 at Department of Rheumatology, Sun Yat-Sen Memorial Hospital. There were 28 RA patients at 16-29 years old and 32, 80, 121, 99, 25 at 30-39, 40-49, 50-59, 60-69, ≥ 70 years old, respectively. Demographic and clinical data were collected including age, gender, history of alcohol consumption, disease duration, body mass index (BMI), waist circumference, blood pressure, RA disease activity indicators and previous medications. Logistic regression analyses were used to identify the associated factors of NAFLD in RA patients. Results: The prevalence of NAFLD was 24.2% (93/385) in RA patients, 26.3% (21/80) in 40-49 age group and 33.1% (40/121) in 50-59 age group. There were 22.1% (85/385) and 3.6% (14/385) RA patients with overweight and obese, in which the prevalence of NAFLD was 45.9% (39/85) and 78.6% (11/14) respectively, which was 2.6 folds and 4.5 folds that of RA patients with normal BMI. Although there was no significant difference of age, gender and RA disease activity indicators between RA patients with or without NAFLD, those with NAFLD had higher proportions of metabolic diseases including obese (11.8% vs. 1.0%), central obesity (47.3% vs. 16.8%), hypertension (45.2% vs. 29.8%) and type 2 diabetes mellitus (24.7% vs. 12.0%), consistent with higher levels of total cholesterol [(5.33±1.31) mmol/L vs. (4.73±1.12) mmol/L], triglyceride [(1.51±1.08) mmol/L vs. (0.98±0.54) mmol/L] and low-density lipoprotein cholesterol [(3.37±0.97) mmol/L vs. (2.97±0.78) mmol/L, all P<0.05]. Multivariate logistic regression analysis showed that BMI (OR=1.314) and triglyceride (OR=1.809) were the independent factors positively associated with NAFLD in RA patients. Conclusion: NAFLD is a common comorbidity in RA patients, especially in those with middle-aged, overweight or obese, which is associated with high BMI or high triglyceride. Screening and management of NAFLD in RA patients especially those with overweight, obese or dyslipidemia should be emphasized.

Progress in replicative senescence of mesenchymal stem cells regulated by microenvironment / 生理学报

Mesenchymal stem cells (MSCs) are a class of pluripotent cells that can self-renew and differentiate. Numerous studies have shown that MSCs have important roles in areas such as regenerative medicine and tissue engineering. However, it is worth noting that MSCs will gradually age during long-term in vitro expansion with decreased stemness such as weakened migration ability, slowed proliferation rate and decreased differentiation potential, which greatly hinders the application of MSCs. Currently, the microenvironment for cell growth is recognized as one of the factors causing senescence in MSCs. Recent studies point out that the latest technologies such as exogenous administration, oxygen concentration regulation and extracellular matrix (ECM) construction can delay stem cell senescence by simulating or regulating the microenvironment. Here, we review the current knowledge of the characteristics and molecular mechanisms of senescent MSCs and microenvironment strategies to maintain MSCs stemness, which can provide a reference for future large-scale application of MSCs preparations in tissue engineering and clinical studies.

The SARS-CoV-2 transcriptome and the dynamics of the S gene furin cleavage site in primary human airway epithelia

The novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) caused the devastating ongoing coronavirus disease-2019 (COVID-19) pandemic which poses a great threat to global public health. The spike (S) polypeptide of SARS-CoV-2 consists of the S1 and S2 subunits and is processed by cellular proteases at the S1/S2 boundary. The inclusion of the 4 amino acids (PRRA) at the S1/S2 boundary forms a furin cleavage site (FCS), 682RRAR{downarrow}S686, distinguishing SARS-CoV-2 from its closest relative, the SARS-CoV. Various deletions surrounding the FCS have been identified in patients. When SARS-CoV-2 propagated in Vero cells, the virus acquired various deletions surrounding the FCS. In the present study, we studied the viral transcriptome in SARS-CoV-2 infected primary human airway epithelia (HAE) cultured at an air-liquid interface (ALI) with an emphasis on the viral genome stability at the S1/S2 boundary using RNA-seq. While we found overall the viral transcriptome is similar to that generated from infected Vero cells, we identified a high percentage of mutated viral genome and transcripts in HAE-ALI. Two highly frequent deletions were found at the S1/S2 boundary of the S gene: one is a deletion of 12 amino acids, 678TNSPRRAR{downarrow}SVAS689, which contains the FCS, another is a deletion of 5 amino acids, 675QTQTN679, which is two amino acids upstream of the FCS. Further studies on the dynamics of the FCS deletions in apically released virions revealed that the selective pressure for the FCS maintains the S gene stability in HAE-ALI but with exceptions, in which the FCS deletions are remained at a high rate. Thus, our study presents evidence for the role of unique properties of human airway epithelia in the dynamics of the FCS region during infection of human airways, which is donor-dependent.

Advances of using microfluidic chips for research and diagnosis of pulmonary inflammatory diseases / 生物工程学报

Microfluidic chip technology integrates the sample preparation, reaction, separation and detection on a chip. It consists a network of microchannels, which controls the whole system through fluid. With the advantages of portability, high throughput, and the ability to simulate the microenvironment in vivo, it has a broad application prospect in the research of disease diagnosis, pathogenesis and drug screening. Pulmonary inflammatory disease is a common disease usually caused by bacterial, viral and fungal infections. Early pneumonia is often difficult to diagnose due to lack of obvious respiratory symptoms or the symptoms are mostly atypical, but the disease progresses rapidly. Recently, microfluidic chip technology has been increasingly used to the study of pulmonary inflammatory diseases. In particular, it has been used to develop a "lung-on-a-chip" model, which can reproduce the key structure, function and mechanical properties of human alveolar capillary interface (i.e., the basic functional unit of a living lung), and well simulate the alveoli in vitro. Compared with the cell and animal models, this multifunctional micro experimental platform has great advantages. This article summarizes the advances of using microfluidic chips for the research and diagnosis of pulmonary inflammatory diseases, with the aim to provide new ideas for researchers in this area.

Advance of synergism of immune checkpoint blockade and anti-angiogenesis in cancer treatment / 中国药理学通报

Immune checkpoint inhibitor ( ICI) activates the host' s anti-tumor immune response by blocking negative regulatory immune signals. A series of clinical trials showed that ICI could effectively induce tumor regression in a subset of advanced cancer patients. Anti-angiogenesis drugs commonly used to block tumor angiogenesis can inhibit the growth of tumors, but they cannot improve the survival of patients with limitations in application such as drug resistance. Tumor immune response is closely related to angiogenesis. In turn, tumor angiogenesis highly depends on immunosuppressive microenvironment. Recent studies have indicated that ICI resistance could be alleviated by combination therapy with anti-angiogenesis treatment, and the efficacy of combination therapy was superior to that of monotherapy. The reciprocal regulation between tumor vascular normalization and immune reprogramming forms a reinforcing loop that reconditions the tumor immune microenvironment to induce durable antitumor immunity. This review clarifies the latest understanding of ICI combined anti-angiogenesis therapy and provides ideas for subsequent research.

Intrinsic and extrinsic mechanisms regulating neuronal dendrite morphogenesis / 浙江大学学报·医学版

Neurons are the structural and functional unit of the nervous system. Precisely regulated dendrite morphogenesis is the basis of neural circuit assembly. Numerous studies have been conducted to explore the regulatory mechanisms of dendritic morphogenesis. According to their action regions, we divide them into two categories: the intrinsic and extrinsic regulators of neuronal dendritic morphogenesis. Intrinsic factors are cell type-specific transcription factors, actin polymerization or depolymerization regulators and regulators of the secretion or endocytic pathways. These intrinsic factors are produced by neuron itself and play an important role in regulating the development of dendrites. The extrinsic regulators are either secreted proteins or transmembrane domain containing cell adhesion molecules. They often form receptor-ligand pairs to mediate attractive or repulsive dendritic guidance. In this review, we summarize recent findings on the intrinsic and external molecular mechanisms of dendrite morphogenesis from multiple model organisms, including , and mice. These studies will provide a better understanding on how defective dendrite development and maintenance are associated with neurological diseases.

Research progress on the role of Ang/Tie axis in angiogenesis and metastasis / 药学学报

The tumor contains abundant new vessels, which are unevenly distributed, irregular, and branch-disordered. Angiopoietin (Ang) and tyrosine kinase receptor Tie mediate stable maturation of angiogenesis. Ang1 mainly plays a role in promoting vascular stabilization, and Ang2 is highly expressed in vessels, which makes the structure and function of vessels abnormal. Leaked vessels provide opportunities for invasion and metastasis of circulating tumor cells. Targeting the Ang/Tie axis to correct the abnormal state of vessels and promote its normalization, combined with chemotherapy drugs or immunotherapy, play a synergistic effect against tumors. This article summarizes the role of Ang/Tie axis in tumor angiogenesis and metastasis, and it aims to provide new ideas and strategies for clinical treatment of tumors.

High salt-induced weakness of anti-oxidative function of natriuretic peptide receptor-C and podocyte damage in the kidneys of Dahl rats / 中华医学杂志(英文版)

BACKGROUND@#Atrial natriuretic peptide (ANP) and its natriuretic peptide receptors A (NPR-A) and C (NPR-C) are involved in the regulation of physiological and pathophysiological process of blood pressure. The present study aimed to determine the role of NPR-C in the development of salt-sensitive hypertension.@*METHODS@#The Dahl salt-sensitive (DS) and salt-resistant (DR) rats were used in this study. Animals were matched according to their age and weight, and then placed on either a high-salt (HS, 8%) or a normal-salt (NS, 0.4%) diet for 6 weeks randomly using random number table. The systolic blood pressure (SBP), plasmatic sodium concentration (PLNa), urinary sodium excretion (UVNa), and serum creatinine concentration (Scr) were measured. The concentration of ANP in blood and tissues (heart and kidney) was detected by enzyme-linked immunosorbent assay. The expression of ANP, NPR-A, and NPR-C in kidney was evaluated with western blot analysis. Regarding renal redox state, the concentration changes in malondialdehyde (MDA), lipofuscin, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox), and nitric oxide synthase (NOS) in kidney were detected by a spectrophotometric method. The kidney damage was evaluated using pathological techniques and the succinodehydrogenase (SDHase) examination. Furthermore, after an intra-peritoneal injection of C-atrial natriuretic peptide (ANP)4-23 (C-ANP4-23), an NPR-C receptor agonist, the SBP, biochemical values in blood and urine, and renal redox state were evaluated. The paired Student's t test and analysis of variance followed by the Bonferroni test were performed for statistical analyses of the comparisons between two groups and multiple groups, respectively.@*RESULTS@#The baseline SBP in all groups was within the normal range. At the end of the 6-week experiment, HS diet significantly increased the SBP in DS rats from 116.63 ± 2.90 mmHg to 162.25 ± 2.15 mmHg (t = -10.213, P  0.05). The significant increase of PLNa, UVNa, and Scr related to an HS diet was found in both DS and DR rats (all P < 0.05). However, significant changes in the concentration (t = -21.915, P < 0.001) and expression of renal ANP (t = -3.566, P = 0.016) and the expression of renal NPR-C (t = 5.864, P = 0.002) were only observed in DS hypertensive rats. The significantly higher desmin immunochemical staining score (t = -5.715, P = 0.005) and mitochondrial injury score (t = -6.325, P = 0.003) accompanied by the lower SDHase concentration (t = 3.972, P = 0.017) revealed mitochondrial pathologic abnormalities in podocytes in DS rats with an HS diet. The distinct increases of MDA (t = -4.685, P = 0.009), lipofuscin (t = -8.195, P = 0.001), and Nox (t = -12.733, P < 0.001) but not NOS (t = -0.328, P = 0.764) in kidneys were also found in DS hypertensive rats. C-ANP4-23 treatment significantly decreased the SBP induced by HS in DS rats (P < 0.05), which was still higher than NS groups with the vehicle or C-ANP4-23 treatment (P < 0.05). Moreover, the HS-induced increase of MDA, lipofuscin, Nox concentrations, and Nox4 expression in DS rats was significantly attenuated by C-ANP4-23 treatment as compared with those with HS diet and vehicle injection (all P < 0.05).@*CONCLUSIONS@#The results indicated that the renal NPR-C might be involved in the salt-sensitive hypertension through the damage of mitochondria in podocytes and the reduction of the anti-oxidative function. Hence, C-ANP4-23 might serve as a therapeutic agent in treating salt-sensitive hypertension.

Mesenchymal stem cells in the treatment of COVID-19-progress and challenges / 生物工程学报

At present, SARS-CoV-2 is raging, and novel coronavirus pneumonia (COVID-19) has caused more than 35 million confirmed patients and more than 500 000 cases death, which seriously endanger human health, socioeconomic development, as well as global medical and public health systems. COVID-19 is highly contagious, has a long incubation period, and causes many death cases due to lack of effective specific treatment. Mesenchymal stem cells have powerful anti-inflammatory and immunoregulatory functions, and can effectively reduce the cytokine storm caused by coronavirus in patients, and improve the pulmonary fibrosis of patients, promote the repair of damaged lung tissue, and reduce the mortality. Currently, a number of related clinical trials of mesenchymal stem cell treatment of COVID-19 have been conducted, and have confirmed the safety and efficacy, suggesting a good clinical application prospect. While progress has been made in mesenchymal stem cell therapy for COVID-19, we should also catch sight of the problems and challenges faced by mesenchymal stem cell clinical trials under severe epidemic situation, including clinical trials design, stem cell quality management, and ethics in treatment. Only by paying attention to these can we guarantee the safe and effective development of mesenchymal stem cell clinical trials in the treatment of COVID-19.

Anti-renal fibrosis effect of asperulosidic acid via TGF-ß1/smad2/smad3 and NF-κB signaling pathways in a rat model of unilateral ureteral obstruction.

BACKGROUND: Renal fibrosis is the most common pathway leading to end-stage renal disease. It is characterized by excess extracellular matrix (ECM) accumulation and renal tissue damage, subsequently leading to kidney failure. Asperulosidic acid (ASPA), a bioactive iridoid glycoside, exerts anti-tumor, anti-oxidant, and anti-inflammatory activities, but its effects on renal fibrosis induced by unilateral ureteral obstruction (UUO) have not yet been investigated. PURPOSE: This study aimed to investigate the protective effect of ASPA on renal fibrosis induced by UUO, and to explore its pharmacological mechanism. METHODS: Thirty-six Sprague-Dawley (SD) rats were randomly divided into six groups: sham group, UUO model group, three ASPA treatment groups (10, 20, and 40 mg/kg), and captopril group (20 mg/kg). Rats were administered vehicle, ASPA or captopril intraperitoneally once a day for 14 consecutive days. Urea nitrogen (BUN), uric acid (UA) and inflammatory factors in serum samples were evaluated on the 7th, 10th, and 14th day after renal fibrosis induction. In addition, the 12 h urine was collected to test the content of urinary protein (upro) on the 14th day. The obstructive renal tissues were collected for pathological analysis (hematoxylin and eosion (H&E) staining and Masson's Trichrome staining) and immunohistochemical analysis on the 14th day after renal fibrosis induction. The mRNA expression of related factors and the protein levels of smad2, smad3, and smad4 were measured in UUO-induced rats by real time PCR and Western blot, respectively. RESULTS: The levels of BUN, UA, and upro were elevated in UUO-induced rats, but ASPA treatment improved renal function by reducing the levels of BUN, UA, and upro. The protein levels of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and IL-6, as well as the mRNA levels of TNF-α, IL-1ß, IL-6, monocyte chemoattractant protein-1 (MCP-1) and interferon-γ (IFN-γ), were decreased after ASPA administration (10, 20 and 40 mg/kg) in a dose-dependent manner. The ASPA exerted an alleviation effect on the inflammatory response through inhibition of nuclear factor-kappa B (NF-κB) pathway. In addition, reductions in α-smooth muscle actin (α-SMA), collagen III, and fibronectin expression were observed after ASPA administration at doses of 20 and 40 mg/kg. Furthermore, the renal expression of transforming growth factor-ß1 (TGF-ß1), smad2, smad3, and smad4 was down-regulated by ASPA treatment at doses of 20 and 40 mg/kg. CONCLUSION: ASPA possessed protective effects on renal interstitial fibrosis in UUO-induced rats. These effects may be through inhibition of the activation of NF-κB and TGF-ß1/smad2/smad3 signaling pathways.

Caveolin-1: oxidative stress target in tumor cells / 生理学报

Aberrant oxidative metabolism in cells is one of the hallmarks of cancer. Overproduction of reactive species promotes carcinogenesis by inducing genetic mutations and activating oncogenic pathways, and thus, antioxidant therapy is considered as an important strategy for cancer prevention and treatment. Caveolin-1 (Cav-1), a constituent protein of caveolae, is involved in not only the formation of the caveolae, vesicular transport, maintaining cholesterol homeostasis directly, but also many cellular physiological and pathological processes including growth, regulation of mitochondrial antioxidant level, apoptosis and carcinomas by interacting with a lot of signaling molecules through caveolin scaffolding domain. Cav-1 has also been shown to mediate tumor genesis and progression through oxidative stress modulation, while Cav-1-targeted treatment could scavenge the reactive species. Intracellular reactive species could modulate the expression, degradation, post-translational modifications and membrane trafficking of Cav-1. More importantly, emerging evidence has indicated that multiple antioxidants could exert antitumor activities in cancer cells by modulating the signaling of Cav-1. This paper reviewed the research progresses on the roles of Cav-1 and oxidative stress in tumorigenesis and development, and would provide new insights on designing strategies for cancer prevention or treatment.

Research progress of Adenosine 5'-monophosphate-activated protein kinase in the regulation of glycolipid metabolism / 生物工程学报

Adenosine 5'-monophosphate-activated protein activated protein kinase (AMPK), a heterotrimeric complex, is an important kinase to regulate glycolipid metabolism and energy balance involved in a variety physiological processes in human body. Many research indicated that the function and activity of AMPK were closely related to inflammation, diabetes and cancers. Recent reports show that inhibition of metformin (a first-line drug) on hepatic glucose in patients with hyperglycemia is associated with AMPK pathway, suggesting that targeting AMPK may be one of the effective strategies for the prevention and treatment of a variety of chronic diseases. Here, we review research progress on the structure, activation and regulation of AMPK in glycolipid metabolism to provide an insight into the basic and clinical research of diabetes therapy.

Determination of methyl ethyl ketone in urine by headspace gas chromatography / 中华劳动卫生职业病杂志

Objective@#To establish a method for determination of methyl ethyl ketone in urine by headspace gas chromatography.@*Methods@#In the urine sample(hereinafter referred to as urine sample), methyl ethyl ketone is pretreated by headspace technology, and a certain amount of head air is injected into the gas chromatograph, separated by capillary column, detected by hydrogen flame ionization detector, and the retention time is qualitative and the peak height is high. Peak area.@*Results@#Good linearity was in the range of 0.01 to 6.0 μg/ml with a regression equation of y=13.316x+0.8497 and γ=0.9997.The minimum detectable concentration of methyl ethyl ketone was 0.01 μg/ml. The range intra-day RSD and inter-day RSD were 2.2%-5.5% and 2.5%-6.1% respectively. Urine samples can be stored for 20 days in the refrigerator at 4 ℃.@*Conclusion@#The method has a high advantage of sensitivity and accuracy, and also easy to operate. Therefore, it is suitable for the determination of methyl ethyl ketone in urine.

Difference in survival between right- versus left-sided colorectal neuroendocrine neoplasms / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Neuroendocrine neoplasms (NENs) are a heterogeneous group of tumors that arise from neuroendocrine cells, and in some cases are capable of producing agents that may cause characteristic hormonal syndromes (Cives and Strosberg, 2018). Such tumors were previously thought to be rare, but the rate of detection of NENs, especially from the gastrointestinal tract, is increasing with the widespread use of colonoscopy, cross-sectional imaging, and biomarkers (Gu et al., 2019). A study based on the Surveillance, Epidemiology, and End Results (SEER) database showed that the age-adjusted incidence of NENs increased 6.4-fold from 1973 (1.09 per 100 000) to 2012 (6.98 per 100 000) (Dasari et al., 2017), while there was a progressive increase in the incidence of colorectal NENs (Starzyńska et al., 2017).

A Clinical Experience of Laparoscopic Nephrectomy in Primary Hospital / 昆明医科大学学报

Objective To investigate the clinical value and the experience of retroperitoneal laparoscopic nephrectomy in primary hospitals. Methods A retrospective analysis of 20 cases of retroperitoneal nephrectomy performed in the people's hospital of Jianshui from July 2014 to December 2017 and 23 cases of open nephrectomy in the same period as the control group, the two groups of surgery and postoperative recovery were analyzed and compared. Results The two groups of patients were operated successfully. The surgery time of the laparoscopic group was (110.14 ±15.63) min and the control group was (100.33 ±10.58) min. There was no statistical difference between the two groups (P＞0.05). No complications occurred during the follow-up period between the two groups, and the difference was not statistically significant. The intraoperative blood loss in the two groups was (40.63 ±22.21) ml and (80.45 ±38.31) m L respectively, and the difference was statistically significant (P＜ 0.05).The indwelling time of drainage tube in the two groups was (2-3) days and (6-7) days respectively. The difference was statistically significant (P＜ 0.05), and the hospitalization time was (3.2 ±2.2) days and (6.4 ± 3.3) days respectively, the difference was statistically significant (P＜0.05). Conclusions Laparoscopic nephrectomy has the advantages of less trauma, faster recovery and shorter hospital stay. With the improvement of operation technique, it will bring more advantages and be worth popularizing.

Clinicopathological characteristics and prognosis of salivary gland secretory carcinoma / 临床与实验病理学杂志

Purpose To investigate the clinicopathological features and prognosis of salivary gland secretory carcinoma(SC). Methods A retrospective study was performed including reviewing the clinical documents and pathological sections of 10 cases of SC. Immunohistochemical EnVision study and histochemical staining were performed in the 10 cases. Fluorescence in situ hybridization (FISH) was used to detect the ETV6-NTRK3 fusion gene. Results There were 8 men and 2 women included in this study. The mean age was 45 years(ranged from 22 to 62 years).9 cases occurred in the parotid and 1 case in submandibular gland. Local painless masses were common first symptoms. Tumor size ranged from 1 cm to 3.5 cm in maximum diameter (average 1.8 cm) and the cut surface of most tumors was solid with dusty red or grayish yellow color, of which 1 case showed cystic degeneration. Histologically, the tumors usually pushed and were invasive to the adjacent tissues. Sometimes, the tumors showed expansive growth pattern. Tumor cells demonstrated microcystic, cystic papillary and alveolar patterns. Eosinophilic secretions could be observed in both microcysts and lumen of alveolus. Immunohistochemically, 10 cases revealed diffuse positivity of cytokeratin, and 9 cases were diffusely and strongly positive for S-100, Mammaglobin, vimentin and CK7, whereas all cases were negative for CD117, Dog-1, p53, p63, SMA, and GATA3. The tumor cells were positive for PAS staining and negative for mucicarmine staining. The detection ETV6-NTRK3 fusion gene was carried out in 4 cases by FISH analysis, among which 3 cases were positive. Follow-up data were available in the 10 patients (ranged from 2 months to35 years), among which 9 patients were alive, except for 1 patient died of tumor recurrence and metastasis 16 years after surgery. Conclusion SC is a newly recognized rare malignant tumor of salivary gland with a lowgrade malignancy, slow growth pattern and favorable prognosis. The histological structures of microcysts and eosinophilic secretions are (he crucial histological characteristics of SC. Diffusely strong positive expression of S-100 and mammaglobin is helpful for the diagnosis and differential diagnosis of the tumor. The diagnosis of SC could be confirmed when ETV6-NTRK3 fusion gene could be identified.