Epigenetics concerns gene regulatory mechanisms beyond DNA sequence，such as DNA methylation，histone modification，chromatin remodeling，and non-coding RNA. Epigenetic mechanisms play a key role in development，cell fate decision and tumorigenesis. Chromatin modifications and its high order structure across our genome are major forms of epigenetic information，and its establishment and maintenance are closely related to cell metabolism. Metabolic changes in cancer cells include aerobic glycolysis，increased glucose uptake，abnormally active glutamine metabolism，and the use of non-conventional energy supply. These changes meet the vigorous energy and matter needs for the development and spread of cancer，and help tumor cells adapt to hypoxia microenvironment for their survival，proliferation，invasion and migration. There is a complex relationship between epigenetic modifications and cell metabolism in tumor. On the one hand，metabolites in tumor cells may act as cofactors，modification donors or antagonists of epigenetic enzymes，thus modulating the epigenetic landscape. On the other hand，epigenetic modifications can directly regulate the expression of metabolic enzymes，transporters，signaling pathway and transcription factors to affect cell metabolism. This article reviews the crosstalk between epigenetics and cancer metabolism，to explore their potential future applications in the treatment of tumors.
The RAS gene is frequently mutated and abnormally activated in many cancers，and plays an important role in cancer development. Metabolic reprogramming occurs in malignant tumors，which can be one of the key targets for anti-tumor therapy. RAS gene can regulate lipid metabolism through AKT-mTORC1 single axis or multiple pathways，such as lipid synthesis pathways and degradation pathways. Similarly，lipid metabolism can also modify and activate RAS protein and its downstream signaling pathways. This article overviews the current research progress on the interaction between lipid metabolism and RAS，to provide insight in therapeutic strategies of lipid metabolism for RAS-driven tumors.
Cholesterol is an important lipid in the body of mammals and an essential component of membrane structures. Cholesterol homeostasis is critical for the maintenance of cellular and body activities, and is mainly regulated by the balance of de novo cholesterol biosynthesis and the exogenous cholesterol uptake. Aberrantly regulated cholesterol metabolism promotes tumor cell proliferation，survival，invasion and metastasis，and their adaptability into the tumor microenvironment. Therefore，targeting cholesterol biosynthesis and reduction of plasma cholesterol levels and cholesterol esterification will provide new strategies for cancer treatment. This review summarizes the current understanding in cholesterol homeostasis regulation and its function in the occurence and development of cancer，as well as current metabolism-targeted cancer treatments.
The metabolic reprogramming of tumor cells is characterized by increased uptake of various nutrients including glutamine. Glutamine metabolism provides the required substances for glycolysis and oxidative phosphorylation and affects the homeostasis of carbohydrate，fat and protein metabolism to induce the chemoresistance of tumor cells. Combination of chemotherapeutic agents with inhibitors specific to different components of glutamine metabolic pathway has obtained favorable clinical results on various tumors. Glutamine metabolic pathway plays a role in drug resistance of tumor cells in various ways. Firstly，the dynamic change of glutamine transporters can directly affect intracellular glutamine content thereby causing drug resistance; secondly，tumor stromal cells including adipocyte，fibroblast and metabolite from tumor microenvironment would give rise to immune-mediated drug resistance; thirdly，the expression and activity of key enzymes in glutamine metabolism also has a critical role in drug resistance of tumors. This article reviews the effects of glutamine metabolic pathway in the development of tumor chemoresistance，in terms of transporters，tumor microenvironment and metabolic enzymes，to provide insight for improving the therapeutic efficacy for drug-resistant tumors.
Objective: To explore early prevention and control of coronavirus disease 2019 （COVID-19） outbreak based on system dynamics model analysis. Methods:The data of early outbreak of COVID-19 were collected from the World Health Organization，covering countries of the China，United States，United Kingdom，Australia，Serbia and Italy. The susceptible-exposed-infected-recovered （SEIR） model was generalized and then its parameters were optimized. According to the parameters in the basic infection number expression，the sensitivity in the system dynamics model was used to quantitatively analyze the influence of the protection rate，infection rate and average quarantine time on the early spread of the outbreak. Based on the analysis results，targeted prevention and control measures for the early outbreak of COVID-19 were proposed. Results:The generalized SEIR model had a good fit for the early prediction and evaluation of COVID-19 outbreaks in six countries. The spread of COVID-19 was mainly affected by the protection rate，infection rate and average quarantine time. The improvement of the protection rate in the first 10?days was the most important:the greater the protection rate，the fewer the number of confirmed cases. The infection rate in the first 5 days was the most critical:the smaller the infection rate，the fewer the number of confirmed cases. The average quarantine time in the first 5 days was very important:the shorter the average quarantine time，the fewer the number of confirmed cases. Through the comparison of key parameters of six countries，Australia and China had implemented strict epidemic prevention policies，which had resulted in good epidemic prevention effects. Conclusion:In the early stage of the outbreak，it is necessary to improve the protection rate，shorten the average quarantine time，and implement strict isolation policies to curb the spread of COVID-19.
Objective:To evaluate the impact of socioeconomic status，population mobility，prevention and control measures on the early-stage coronavirus disease 2019 (COVID-19) development in major cities of China. Methods: The rate of daily new confirmed COVID-19 cases in the 51 cities with the largest number of cumulative confirmed cases as of February 19，2020 (except those in Hubei province) were collected and analyzed using the time series cluster analysis. It was then assessed according to three aspects，that is, socioeconomic status，population mobility，and control measures for the pandemic. Results: According to the analysis on the 51 cities，4 development patterns of COVID-19 were obtained，including a high-incidence pattern (in Xinyu)，a late high-incidence pattern (in Ganzi)，a moderate incidence pattern (in Wenzhou and other 12 cities)，and a low and stable incidence pattern (in Hangzhou and other 35 cities). Cities with different types and within the same type both had different scores on the three aspects. Conclusion: There were relatively large difference on the COVID-19 development among different cities in China，possibly affected by socioeconomic status，population mobility and prevention and control measures that were taken. Therefore，a timely public health emergency response and travel restriction measures inside the city can interfere the development of the pandemic. Population flow from high risk area can largely affect the number of cumulative confirmed cases.
Objective: This study aimed to quantitatively assess the effectiveness of the Wuhan lockdown measure on controlling the spread of coronavirus diesase 2019 (COVID-19). Method: Firstly，estimate the daily new infection rate in Wuhan before January 23 rd，2020 when the city went into lockdown by consulting the data of Wuhan population mobility and the number of cases imported from Wuhan in 217 cities of Mainland China. Then estimate what the daily new infection rate would have been in Wuhan from January 24 th to January 30th if the lockdown measure had been delayed for 7 days，assuming that the daily new infection in Wuhan after January 23 rd increased in a high，moderate and low trend respectively (using exponential, linear and logarithm growth models). Based on that，calculate the number of infection cases imported from Wuhan during this period. Finally，predict the possible impact of 7-day delayed lockdown in Wuhan on the epidemic situation in China using the susceptible-exposed-infectious-removed (SEIR) model. Results: The daily new infection rate in Wuhan was estimated to be 0.021%，0.026%，0.029%，0.033% and 0.070% respectively from January 19 th to January 23 rd. And there were at least 20 066 infection cases in Wuhan by January 23 rd，2020. If Wuhan lockdown measure had been delayed for 7 days，the daily new infection rate on January 30 th would have been 0.335% in the exponential growth model，0.129% in the linear growth model，and 0.070% in the logarithm growth model. Correspondingly，there would have been 32 075，24 819 and 20 334 infection cases travelling from Wuhan to other areas of Mainland China，and the number of cumulative confirmed cases as of March 19 th in Mainland China would have been 3.3-3.9 times of the officially reported number. Conclusions: Timely taking city-level lockdown measure in Wuhan in the early stage of COVID-19 outbreak is essential in containing the spread of the disease in China.
Objective:To predict the epidemiological trend of coronavirus disease 2019 (COVID-19) by mathematical modeling based on the population mobility and the epidemic prevention and control measures. Methods: As of February 8，2020，the information of 151 confirmed cases in Yueqing，Zhejiang province were obtained，including patients’ infection process，population mobility between Yueqing and Wuhan，etc. To simulate and predict the development trend of COVID-19 in Yueqing, the study established two-stage mathematical models，integrating the population mobility data with the date of symptom appearance of confirmed cases and the transmission dynamics of imported and local cases. Results: It was found that in the early stage of the pandemic，the number of daily imported cases from Wuhan (using the date of symptom appearance) was positively associated with the number of population travelling from Wuhan to Yueqing on the same day and 6 and 9 days before that. The study predicted that the final outbreak size in Yueqing would be 170 according to the number of imported cases estimated by consulting the population number travelling from Wuhan to Yueqing and the susceptible-exposed-infectious-recovered (SEIR) model; while the number would be 165 if using the reported daily number of imported cases. These estimates were close to the 170，the actual monitoring number of cases in Yueqing as of April 27，2020. Conclusion: The two-stage modeling approach used in this study can accurately predict COVID-19 epidemiological trend.
Objective:To develop a quality control checklist for the prevention and control of coronavirus disease 2019 （COVID-19） in fever clinic and isolation ward of the general hospital and to assess its application. Methods: Based on the relevant prevention and control plans and technical guidelines for COVID-19，Delphi method was used to identity items for evaluation，and a quality control checklist for the prevention and control of COVID-19 in the fever clinic and isolation ward was developed in Sir Run Run Shaw Hospital. The checklists included 8 dimensions and 32 items for fever clinic，7 dimensions and 27 items for the isolation ward. The appointed inspectors conducted daily quality control for each shift with this checklist. Results:The expert authority coefficient was 0.88，the mean of the importance of each index in the quality control table was not less than 4.8，and the coefficient of variation was not more than 0.07. During the entire February 2020，8 problems were found and rectified on-the-spot with the application of the checklist. Quality inspection rate was 100% in both isolation wards and fever clinic. The compliance rate and accuracy rate of hand hygiene were 100%; the correct rate of wearing and removing protective equipment increased from 96% to 100%. During the same period，a total of 1915 patients were admitted to the fever clinic，including 191 suspected patients （all were isolated in the hospital，3 were confirmed）. There were no medical staff infected with COVID-19，no cross infection of patients and their families in the hospital. Conclusion: A quality control checklist for the prevention and control of COVID-19 has been developed and applied in the isolation wards and fever clinic，which plays an important role in preventing nosocomial infection.
Objective:To establish and verify a risk prediction nomogram for ipsilateral axillary lymph node metastasis in breast cancer stage T1 （mass ≤ 2 cm）. Methods:The clinicopathological data of 907 patients with T1 breast cancer who underwent surgical treatment from January 2010 to June 2015 were collected，including 573 cases from the Second Affiliated Hospital of Zhejiang University School of Medicine （modeling group） and 334 cases from Zhejiang University Lishui Hospital （verification group）. The risk factors of ipsilateral axillary lymph node metastasis were analyzed by univariate and multivariate logistic regression. The influencing factors were used to establish a nomogram for predicting ipsilateral axillary lymph nodes metastasis in T1 breast cancer. The model calibration，predictive ability and clinical benefit in the modeling group and the verification group were analyzed by C index，receiver operating characteristic curve，calibration curve and decision curve analysis （DCA） curve，respectively. Results:Univariate analysis showed that lymph node metastasis was related with primary tumor size，vascular tumor thrombus，Ki-67，histopathological grade，and molecular type （ P<0.05 or P<0.01）. Multivariate logistic regression analysis showed that the primary tumor > 0.5?cm， vascular tumor thrombus，Ki-67 positive，estrogen receptor （ER） positive，and histopathological grade 2-3 were independent risk factors of axillary lymph node metastasis （ P<0.05 or P<0.01）. Based on the independent risk factors，a nomogram prediction model was established. The C indexes of the model group and the validation group were 0.739 （95% CI:0.693-0.785） and 0.736 （95% CI:0.678-0.793），respectively. The calibration curve and DCA curve of the modeling group and the verification group indicated that the model was consistent and had good clinical benefit. Conclusions:Primary tumor size，histopathological grade，vascular tumor thrombus，Ki-67，and ER status are predictors of ipsilateral axillary lymph node metastasis in T1 breast cancer. The established prediction nomogram can effectively predict the risk of ipsilateral axillary lymph node metastasis in T1 breast cancer，which can be used as a reference for individualized axillary management.
Objective:To investigate the expression of xenotropic and polytropic retrovirus receptor 1 （ XPR1） in papillary thyroid cancer （PTC） and its clinical implication. Methods: The HPA and UALCAN databases were used to explore the expression of XPR1 in PTC and normal tissues. The cBioPortal database was used to obtain the clinical data of PTC patients and XPR1 gene expression profile. The correlation of XPR1 expression with gender，age，sub-types，T stage，N stage，M stage and clinical stage of patients were analyzed. Cox regression was conducted to analysis the factors affecting the prognosis of PTC patients. The mutation of XPR1 was assessed through cBioPortal database. GO and KEGG analyses were used to explore the related biological pathway of XPR1 involved in PTC. Results: HPA database analysis showed that XPR1 was highly expressed in PTC tissue compared with normal tissues. UALCAN analysis displayed that XPR1 expression was significantly higher in PTC tissue compared with normal tissues （ P<0.01），and the highest and lowest expressions of XPR1 were observed in tall cell and follicular sub-type of PTC，respectively. The expression of XPR1 was correlated with age，sub-types，T stage，N stage and disease stage of PTC patients （ P<0.05 or P<0.01），but was not correlated with gender and M stage （all P>0.05）. Cox regression analysis showed that XPR1 was an independent prognostic factor of PTC patients （ HR=2.894， P<0.05）. The cBioPortal database indicated that the XPR1mutation appeared in 6% PTC patients; the mutation type mainly was missense and the mutation point was located at the E615K. Enrichment analysis indicated that XPR1 might affect the PTC progression through involvement in metabolic pathway. Conclusions: XPR1 is highly expressed in PTC tissues，which is associated with the prognosis of patients. Metabolic pathway associated with XPR1 might play an important role in PTC progression，indicating that XPR1 might be a novel biomarker for diagnosis and treatment of PTC.
Objective:To explore the value of quantitative perfusion histogram parameters of dynamic contrast-enhanced magnetic resonance imaging （DCE-MRI） in pathological classification of uterine leiomyoma and its correlation with Ki-67 protein expression. Methods: Thirty five patients with uterine leiomyoma confirmed by operation and pathology at Shaoxing People’s Hospital from October 2015 to September 2017 were analyzed retrospectively，including 15 cases of ordinary type，8 cases of cellular type and 12 cases of degenerative type. All patients were examined by pelvic DCE-MRI before operation，and the histogram parameters （median，mean，skewness，kurtosis，energy，entropy） of various quantitative perfusion parameters，including volume transport constant （K trans），rate constant （K ep），extravascular extracellular space distribute volume per unit tissue volume （V e），blood plasma volume per unit volume of tissue （V p） were calculated，and the efficacy of different parameters in pathological classification of uterine leiomyoma was evaluated by ROC curve. The expression of Ki-67 protein in uterine leiomyoma was detected by immunohistochemical method，and the correlation between histogram parameters and Ki-67 protein expression was analyzed by Pearson and Spearman correlation analysis. Results: The median and mean values of K trans，K ep，V e and V p in the cellular group were higher than those in the degenerative group and the ordinary group（ P<0.05 or P<0.01），while the skewness of V e，the skewness and kurtosis of K ep in the cellular group were lower than those in the ordinary group （all P<0.05）. The entropy of K trans in the cellular group was higher than that in the degenerative group and the ordinary group （all P < 0.05）. The entropy of V p in the cellular group was higher than that in the ordinary group （ P<0.01）. The median，mean，skewness of K trans，median and mean of K ep，median and mean of V e，median，mean，energy and entropy of V p were correlated with Ki-67 expression（all P<0.05）. The results of ROC curve analysis showed that the median threshold of K trans was 0.994/min，the sensitivity and specificity for the diagnosis of cellular uterine leiomyoma were 100.0% and 77.8% respectively，and the area under the ROC curve was 0.949. When the mean threshold of K trans was 1.170/min，the sensitivity and specificity for diagnosing cellular uterine leiomyoma were 100.0% and 77.8% respectively，and the area under the ROC curve was 0.958. The area under the ROC curve of K trans （entropy），K ep （median，mean），V p （median，mean，entropy） in the diagnosis of cellular uterine leiomyoma were 0.755–0.907. Conclusion:DCE-MRI quantitative perfusion histogram parameters have high diagnostic value in differentiating pathological types of uterine leiomyoma，especially for cellular uterine leiomyoma.
Objective:To investigate the effect of transient receptor potential melastatin 2 （TRPM2） inhibitor A10 on oxygen glucose deprivation/reperfusion （OGD/R） injury in SH-SY5Y cells． Methods:Human neuroblastoma SH-SY5Y cells were subject to OGD/R injury，and then were divided into blank control group，model control group and A10 group randomly. The cell survival rate was detected by cell counting kit 8 （CCK-8）; the level of cellular reactive oxygen species （ROS） was detected by reactive oxygen detection kit; the mitochondrial membrane potential was detected by tetramethylrhodamine （TMRM） method; the number of apoptotic cells was detected by TUNEL apoptosis assay kit; the protein expression level of cleaved caspase 3 was detected by Western blot． Results:Compared with 3，20，30，50， 100?μmol/L， 10?μmol/L?A10 has lower cytotoxicity and better inhibition effect on channel activity. Compared with the model control group，ROS level was reduced，the mitochondrial membrane potential was improved，the number of apoptosis cells was reduced ，and the expression of cleaved caspase 3 was significantly reduced in the A10 group（all P<0.05）. Conclusion: A10 can alleviate cell damage after OGD/R by inhibiting TRPM2 channel function，reducing extracellular calcium influx，reducing cell ROS levels，stabilizing mitochondrial membrane potential levels，and reducing apoptosis.
The pathogenesis of hepatitis B virus （HBV）-associated hepatocellular carcinoma （HCC） is complicated with the crosstalk of multiple factors and the multi-step processes. The main mechanisms underlying the HBV-induced HCC include:①integration of HBV DNA into the host hepatocyte genome to alter gene function at the insertion site，resulting in host genome instability and expression of carcinogenic truncated proteins;②HBV gene mutations at S，C，and X coding regions in the genome;③HBV X gene-encoded HBx protein activates proto-oncogenes and inhibits tumor suppressor genes，leading to the HCC occurrence. In this article，the recent research progress on the molecular mechanism of HBV-induced HCC is comprehensively reviewed，so as to provide insights into the prevention，early prediction and postoperative adjuvant therapy of HCC.
Bronchial asthma is a chronic respiratory disease，characterized by airway inflammation，airway hyperresponsiveness，reversible airway obstruction and airway remodeling，in which a variety of cells including airway inflammatory cells and structural cells are involved. Previous studies have shown that asthma is mainly driven by Th2 cytokines IL-4，IL-5，and IL-13，leading to airway eosinophil inflammation. With further research，however，it has been found that neutrophils are also closely related to asthma. Numbers of neutrophils are elevated in airway through increased chemotaxis and decreased apoptosis，which is earlier than eosinophils，leading to airway neutrophilic inflammation. Neutrophils can produce elastase，myeloperoxidase，neutrophil extra- cellular traps，chemokines and cytokines，participating in the occurrence and development of asthma. The antagonists against these molecules，such as anti-IL-8 receptor antibody，anti-IL-17 antibody，and DNase，have shown positive effects on neutrophilic asthma，but further studies are needed to support their clinical application. This article mainly reviews the role of neutrophils in asthma and related mechanisms.
Neuroendocrine tumors are a type of heterogeneous tumors originating from neuroendocrine cells derived from the neural crest，which can secrete a variety of amines and peptide hormones.Based on different molecular biomarkers，histologic types and differentiation degrees，individualized nuclear imaging can provide information for the early diagnosis，clinical staging，treatment guidance，and detection of the recurrence and metastasis of neuroendocrine tumor. In this paper，we review the development and application of nuclear medicine molecular imaging probes such as glucose analogs，somatostatin analogues，amine precursors，hormone analogs and enzyme inhibitors in the diagnosis and treatment of neuroendocrine tumors.