Objective To investigate whether chemokine CCL2(also known as monocyte chemotactic protein 1 or MCP-1)has a causal relationship with lung cancer.Methods Genetic data of chemokine CCL2 and different pathological subtypes of lung cancer were extracted from genome-wide association studies(GWAS),and inverse-variance weighted(IVW)analysis was used as main analysis,while weighted median,simple model,MR-Egger regression,and weighted model were chosen as supplementary analyses.Sensitivity analyses were performed to verify the reliability of the data.Results The result of IVW analysis on chemokine CCL2 to lung adenocarcinoma was OR = 1.065,95%CI(0.919～1.234),P = 0.401.The result of IVW analysis on chemokine CCL2 to squamous cell lung carcinoma was OR = 1.059,95%CI(0.931～1.205),P = 0.381.The result of IVW analysis on chemokine CCL2 to small cell lung carcinoma was OR = 0.959,95%CI(0.760～1.208),P = 0.720.Conclusions There is no direct causal relationship between chemokine CCL2 and lung cancer.

Cardiovascular disease is a health hazard to humans and systolic heart failure due to myocardial infarction is a major cause of death.It was previously thought that myocardial cells of the adult mammalian heart possess a limited ability to proliferate and self-renew.However,it has been widely reported that mammals have the ability to regenerate the myocardium,which is restricted to early postnatal life,and that it is strong enough to repair damaged heart tissue.The discovery of myocardial regeneration in neonatal hearts has provided an ideal animal model to investigate the mechanisms that affect myocardial regeneration,and many mechanisms that reverse myocardial cell cycle arrest and promote myocardial regeneration have been revealed.In this article,we review the factors affecting gene expression for myocardial regeneration(e.g.,ncRNAs and transcription factors),myocardial regeneration-related signaling pathways,and the regulation of myocardial regeneration by non-myocardial cells(e.g.,extracellular matrix,immune response,and epicardium)to provide directions for achieving myocardial regeneration after myocardial injury in adult mammals.

Objective:To evaluate the value of contrast-enhanced ultrasound (CEUS) in the diagnosis of solid intraductal papilloma (sIDP) of breast by comparing with fibronenoma of breast (FA).Methods:The CEUS data of 62 cases of sIDP patients and 94 cases of FA patients that confirmed by pathology in the First Affiliated Hospital of Soochow University from October 2016 to January 2021 were retrospectively analyzed. The patients were divided into sIDP group and FA group according to the pathological results. The enhancement speed, enhancement degree, enhancement uniformity, whether the edge after enhancement was polished, whether the enhancement range was enlarged, whether there was a ring unenhanced area in the inner edge of the lesion and whether the inner edge of the unenhanced area was polished were observed in the two groups. SonoLiver software was used to perform offline analysis of the dynamic process of CEUS in the two groups respectively, the enhancement sequence diagram of the lesions was obtained. The pathological result was taken as the gold standard, univariate analysis was applied, and the parameters with statistical significance between the two groups were included in multivariate Logistic regression analysis to establish a differential diagnosis model. The diagnostic efficiency of sIDP was analyzed by ROC curve and diagnostic model.Results:Compared with the FA group, CEUS in the sIDP group mostly showed fast forward, high enhancement, and the enhancement sequence was mostly centrifugal. After CEUS, the lesion edges in the sIDP group were mostly accompanied by unenhanced areas and the inner edges of the unenhanced areas were not intact, and the differences between the two groups were statistically significant (all P<0.05). Binary Logistic regression showed that age, enhancement degree and enhancement order were independent risk factors for sIDP diagnosis. The ROC curve showed that the area under the ROC curve of age, enhancement degree and enhancement sequence combined for the diagnosis of sIDP was 0.874 (95% CI=0.812-0.922), the accuracy was 76.9%, the sensitivity was 67.7%, the specificity was 83.0%, the positive predictive value was 72.4%, and the negative predictive value was 79.6%. Conclusions:There are significant differences in age, enhancement degree and enhancement sequence between sIDP and FA patients. The three-parameter combination can improve the diagnostic efficiency of sIDP.

Objective:To explore the difference of the vessel and plaque characteristics, myocardial perfusion and cardiac function between patients with ischemia with non-obstructive coronary artery disease (INOCA) and obstructive coronary artery disease (CAD).Methods:From July 2021 to June 2022, 101 patients with angina were referred to dynamic computed tomography myocardial perfusion (CTP) and coronary computed tomography angiography (CCTA) and retrospectively included in our hospital. Based on the results of CTP and CCTA, patients were divided into INOCA (27 cases), moderate obstructive CAD (26 cases) and severe obstructive CAD (48 cases). The anatomical coronary artery stenosis, plaque characteristics and myocardial perfusion features of all patients were analyzed. Furthermore, left ventricular global longitudinal strain (GLS), global circumferential strain (GCS), and global radial strain (GRS) were obtained on full-phase reconstruction CCTA image by using Medis Suite 3.2 postprocessing software. Multigroup analysis used one way ANOVA or Kruskal Wallis H test. Results:Patients with INOCA were younger than patients with moderate and severe obstructive CAD ( P<0.001). INOCA patients (7.4%, 2/27) had lower rate of positive remodeling than both moderate (57.7%, 15/26, P<0.001) and severe obstructive CAD patients (33.3%, 16/48, P=0.017). The percentage of ischemic myocardium volume in patients with INOCA were similar with those in patients with severe CAD (all P>0.05), but significantly higher than those in patients with moderate CAD (all P<0.05). No significant difference in terms of GLS was detected between patients with INOCA [-17.4% (-21.6%, -11.6%)] and severe CAD [-17.6% (-21.9%, -14.8%), P=0.536], however, patients both with INOCA and severe CAD also had higher GLS than patients with moderate obstructive CAD [-22.3% (-29.8%, -19.0%), all P<0.05]. Conclusions:Based on"one-stop-shop"CTP combined with CCTA imaging, early cardiac functional changes including abnormal myocardial perfusion and myocardial strain in INOCA patients were similar to those in patients with severe obstructive CAD and more severe than those in patients with moderate obstructive CAD.

OBJECTIVE To establish the quality evaluation method of Polyporus formula granules, and to comprehensive evaluate the quality uniformity and stability of products from different manufacturers. METHODS The fingerprint of Polyporus formula granules was determined by HPLC. Shim-pack GIST C18-AQ(4.6 mm×150 mm, 3 μm) was used, mobile phase was acetonitrile-water with gradient elution, volume flow rate was 1.0 mL·min-1, detection wavelength was 350 nm (0-3 min) and 250 nm(3-35 min), column temperature was 30℃. HPLC fingerprints of Polyporus formula granules from different manufacturers were established, common peaks were identified, similarities were evaluated and cluster analysis were performed. HPLC was used to determine the contents of 4 active ingredients, and the quality of 16 batches of samples was analyzed and evaluated. RESULTS The established HPLC fingerprint of Polyporus formula granules defined 14 common peaks and identified 6 common components. They were peak 2(uridine), peak 4(guanosine), peak 6(adenosine), peak 12(polyporusteron B), peak 13(polyporusteron A), peak 14(polyporusteron C). The similarity of 16 batches of samples were 0.609-0.982, and could be clustered into 2 categories by cluster analysis. Guanosine, adenosine, polyporusteron B and polyporusteron A all showed good linear relationships(r ≥ 0.999 7), RSDs of instrument precision, stability and reproducibility tests were <3%. The average recoveries were 98.22%, 99.32%, 99.56%, 99.15%, RSD<3%(n=6). The contents of guanosine, adenosine, polyporusteron B, polyporusteron A in 16 batches of samples were 6.326-28.006, 13.392-44.058, 10.324-30.335, 9.270-26.964 μg·g-1.CONCLUSION There is considerable quality difference among different manufacturers. The established fingerprint combine with the compound determination can comprehensively and accurately evaluate the internal quality of Polyporus formula granules, and provide a basis for the overall improvement of the quality.

Malignancies are diseases resulting from an imbalance of cell growth and proliferation， endangering human health and life. Currently， there is no clinically effective treatment for tumors. Tumor cells may alter cell adhesion and tumor cell migration and movement by degrading the extracellular matrix， generating vascular factors， affecting epithelial-mesenchymal transformation， or altering the tumor microenvironment. The mechanisms which lead to multidrug resistance （MDR） are the regulation of membrane proteins， apoptosis-regulated gene expression， enzyme-mediated multidrug resistance， DNA damage repair， and epithelial-stromal transformation， resulting in ineffective treatment of tumors. Therefore， the search for natural， safe， and effective chemosensitizers has become a critical part in tumor research. Due to the increasing use of Chinese medicine in cancer treatment， researchers have conducted more extensive studies on its monomers and compounds. In addition， the mechanisms of Chinese medicine in inhibiting tumor invasion and metastasis and reversing drug resistance are gradually unraveled. The monomers and compounds of Chinese medicine may inhibit tumor invasion， metastasis， and drug resistance by enhancing the sensitivity of chemotherapy drugs and adjuvant properties. Furthermore， they can also improve the tolerance of patients to chemotherapy drugs， relieve side effects of chemotherapy， reduce the chance of recurrence， and prolong the life of patients. The development of traditional Chinese medicine plays an important role in reducing tumor recurrence and metastasis， reversing drug resistance， prolonging the prognosis of cancer patients， improving their quality of life， and prolonging their survival time. Currently， various types of Chinese medicines have been proven to be capable of reducing tumor invasion and metastasis， and reversing drug resistance. The present article reviewed development and findings of Chinese medicine as an anti-tumor invasion， anti-metastasis， and anti-tumor resistance therapy in recent years， in order to provide ideas for future research on anti-tumor effect of active components in Chinese medicine.

Glycosphingolipids (GSLs) are widely distributed in the phospholipid bilayer of various cell membranes, which play an important role in maintaining cell membrane stability, and regulate various cellular processes including adhesion, proliferation, apoptosis and recognition, as well as participate in various cellular activities. In addition, GSLs are not only involved in the process of apoptosis, but also regulate multiple signals in tumorigenesis and tumor development. The tumor-associated GSLs are expected to be used as diagnostic markers and immunotherapeutic targets for malignant tumors. These findings have important implications for the study of apoptosis and provide the new direction of tumor therapy. This review summarized the latest research progress of GSLs-mediated apoptosis and its effect on the genesis, development and metastasis of tumor cells. Moreover, we discussed the metabolic pathway of GSLs-mediated apoptosis and its application in tumor therapy, as well as the development prospect of targeted therapy strategies based on GSLs.
Humans ; Glycosphingolipids/metabolism* ; Apoptosis ; Cell Membrane ; Neoplasms/metabolism*

Objective:To investigate the safety and feasibility of minimally invasive pancreatic tumor enucleation.Methods:The clinicopathological data of 60 patients with minimally invasive pancreatic tumor enucleation admitted to the Department of Pancreatic Surgery of Fudan University Cancer Center from November 2019 to August 2021 were retrospectively analyzed. There were 17 males and 43 females,with age of (50.0±13.2)years(range: 23 to 73 years). Tumors were located in the head of pancreas in 40 cases(66.7%),neck and tail of pancreas in 20 cases(33.3%). Patients were divided into robotic group( n=25) and laparoscopic group( n=35) according to surgical methods. The measurement data were compared by t-test or Mann-Whitney U test, and the categorical data were compared by χ 2 test or Fisher exact probability method. The influencing factors of postoperative pancreatic fistula were analyzed by univariate and multivariate Logistic regression. Results:All patients successfully completed tumor enucleation without conversion to laparotomy. The operation time was (183.5±67.3)minutes(range:90 to 410 minutes). Twelve patients(20.0%) underwent stent placement and pancreatic duct repair during operation. The removal time of abdominal drainage tube after operation was (24.7±22.9)days(range:2 to 113 days). The tumor diameter in the robotic group was larger than that in the laparoscopic group((3.5±0.9)cm vs. (2.9±0.7)cm, t=-2.825, P=0.006). The incidences of postoperative biochemical fistula and grade B pancreatic fistula were 20.0%,22.9% and 36.0%,51.4%,respectively(χ2=2.289, P=0.318). There were no grade C pancreatic fistula,lymphatic fistula,biliary fistula,delayed gastric emptying,secondary operation and perioperative death in both groups. Multivariate logistic regression analysis was performed on the occurrence of clinically related pancreatic fistula(above grade B). The results showed that the increase of body mass index( OR=1.285,95% CI:1.053 to 1.569, P=0.014),the larger diameter of the tumor( OR=3.703,95% CI:1.465 to 9.360, P=0.006) and intraoperative pancreatic duct repair( OR=7.889,95% CI:1.471 to 42.296, P=0.016) were independent risk factors,whereas robotic surgery( OR=0.168,95% CI:0.036 to 0.796, P=0.025) was a protective factor. No case of pancreatin dependent dyspepsia and new onset diabetes mellitus was observed. Conclusions:Minimally invasive tumor enucleation is feasible in the treatment of benign and low-grade pancreatic tumors. The incidence of pancreatic fistula is high in the short term after operation,but serious complications are rare. The robot assisted system can reduce the risk of postoperative pancreatic fistula and has more advantages in dealing with larger diameter tumors because of clearer surgical vision and more accurate operation.

Objective:To investigate the safety and feasibility of minimally invasive pancreatic tumor enucleation.Methods:The clinicopathological data of 60 patients with minimally invasive pancreatic tumor enucleation admitted to the Department of Pancreatic Surgery of Fudan University Cancer Center from November 2019 to August 2021 were retrospectively analyzed. There were 17 males and 43 females,with age of (50.0±13.2)years(range: 23 to 73 years). Tumors were located in the head of pancreas in 40 cases(66.7%),neck and tail of pancreas in 20 cases(33.3%). Patients were divided into robotic group( n=25) and laparoscopic group( n=35) according to surgical methods. The measurement data were compared by t-test or Mann-Whitney U test, and the categorical data were compared by χ 2 test or Fisher exact probability method. The influencing factors of postoperative pancreatic fistula were analyzed by univariate and multivariate Logistic regression. Results:All patients successfully completed tumor enucleation without conversion to laparotomy. The operation time was (183.5±67.3)minutes(range:90 to 410 minutes). Twelve patients(20.0%) underwent stent placement and pancreatic duct repair during operation. The removal time of abdominal drainage tube after operation was (24.7±22.9)days(range:2 to 113 days). The tumor diameter in the robotic group was larger than that in the laparoscopic group((3.5±0.9)cm vs. (2.9±0.7)cm, t=-2.825, P=0.006). The incidences of postoperative biochemical fistula and grade B pancreatic fistula were 20.0%,22.9% and 36.0%,51.4%,respectively(χ2=2.289, P=0.318). There were no grade C pancreatic fistula,lymphatic fistula,biliary fistula,delayed gastric emptying,secondary operation and perioperative death in both groups. Multivariate logistic regression analysis was performed on the occurrence of clinically related pancreatic fistula(above grade B). The results showed that the increase of body mass index( OR=1.285,95% CI:1.053 to 1.569, P=0.014),the larger diameter of the tumor( OR=3.703,95% CI:1.465 to 9.360, P=0.006) and intraoperative pancreatic duct repair( OR=7.889,95% CI:1.471 to 42.296, P=0.016) were independent risk factors,whereas robotic surgery( OR=0.168,95% CI:0.036 to 0.796, P=0.025) was a protective factor. No case of pancreatin dependent dyspepsia and new onset diabetes mellitus was observed. Conclusions:Minimally invasive tumor enucleation is feasible in the treatment of benign and low-grade pancreatic tumors. The incidence of pancreatic fistula is high in the short term after operation,but serious complications are rare. The robot assisted system can reduce the risk of postoperative pancreatic fistula and has more advantages in dealing with larger diameter tumors because of clearer surgical vision and more accurate operation.

The autolysis of brewer's yeast seriously affects the quality of beer and the quality of yeast is considered as one of the key factors in beer brewing. Previous studies on brewer's yeast autolysis showed that RLM1 gene, an important transcription factor in cell integrity pathway, is closely related to the autolysis of yeast. In this study, RLM1 was knocked out and overexpressed in a haploid brewer's yeast. RLM1 disruption resulted in poor anti-autolysis performance of yeast, whereas overexpression of RLM1 contributed to the anti-autolytic ability of yeast. In addition, RLM1 gene knockout affected the osmotic stress resistance, cell wall damage resistance, nitrogen starvation resistance and temperature tolerance of yeast strain. The transcriptional level of GAS1 involved in cell wall assembly and DNA damage response was regulated along with the expression of RLM1, whereas other genes in CWI pathway did not show apparent regularity. RLM1 might mainly affect the expression of GAS1 so as to improve the stress resistance of lager yeast in harsh environment. The result from this study help further understand the mechanism of yeast autolysis and lay a foundation for breeding brewer's yeast strain with better anti-autolytic ability.
Autolysis ; Beer ; Cell Wall ; Humans ; MADS Domain Proteins ; Saccharomyces cerevisiae ; Saccharomyces cerevisiae Proteins