RT-PCR and immunohistochemistry were used to measure the mRNA and protein expression of insulin receptor substrate 2 (IRS-2) in the muscle of smoking rats. The mRNA and protein expressions of IRS-2 in the smoking subgroups fed with normal diet or high-fat diet were significantly lower than those in corrsponding control groups (0.27±0.02 vs 0.41±0.25, 0.40±0.04 vs 0.51±0.02 for mRNA; 2.91±0.42 vs 4.90±0.29, 2.43±0.36 vs 3.80±0.30 for protein, all P<0.01). There were no differences in mRNA and protein expressions of IRS-2 between the smoking group of diabetic rats and the matched control rats (P>0.05). The variation of gene expression of IRS-2 may be involved in the mechanism of insulin resistance caused by smoking.

Objective To investigate the differences of measurement of gross target volume (GTV)between endoscopic ultrasonography ( EUS )-based ( GTVEUS ) and computed tomography ( CT ) -based (GTVCT) method for thoracic esophageal squamous cell carcinoma. Methods EUS was performed on 36consecutive patients with thoracic squamous cell carcinoma, and the superior and inferior boarders of the tumor defined by EUS were marked with hemoclips. The CT planning scan was then performed with the patient in supine position, and the GTVCT and GTVEUS were contoured respectively. The lengths ( LCT and LEUS) and spatial locations of longitudinal GTVCT and GTVEUS were compared. Results The mean LCT and LEUS were (7. 79 ± 3. 15 ) cm and (7. 42 ± 2. 72) cm, respectively ( t = 0. 82, P ＞ 0. 05 ), with a correlation coefficient of 0. 61 (P ＜0. 001 ). Locations of longitudinal GTVCT and GTVEUS were compared in 34cases, with 2 excluded for invisualization on CT. The mean conformal index (CI) was (0. 79 ± 0. 18 ), and spatial variations were found in 71% patients, with 8 patients at proximal end and 21 others at distal end.There was no clip placement associated complication. Conclusion Endoscopic hemoclips placement is safe and reliable. EUS can provide additional information to CT in defining longitudinal GTV in thoracic esophageal squamous cell carcinoma, especially in superficial and submucosal carcinomas.

Objective To investigate the methylation status of PCDH8 gene in pancreatic carcinoma.Methods Methylation of PCDH8 gene in 2 samples of normal pancreatic tissues and 6 pancreatic carcinoma cell lines (PANC1, ASPC1, BxPC3, CFPAC, PaTu8988 and SW1990) was detected by the methylationspecific PCR (MSP) method. The expression of PCDH8 mRNA was detected with 5-Aza-2-deoxycytidine (5-Aza-dC) treatment, a kind of DNA methyltransferase (DNMT) inhibitor in 6 pancreatic carcinoma cell lines by real-time-PCR. Results The methylation of PCDH8 gene was not detected in normal tissues, while it was partially methylated in PANC1, BxPC3, CFPAC and it was totally methylated in PaTu8988, ASPC1, SW1990.PCDH8 mRNA was expressed in PANC1, SW1990, PaTu8988 and the relative quantities of mRNA expression (RQ) were 1.576 ± 0.648, 0.013 ± 0.008, 0.002 ± 0.001; PCDH8 mRNA was not expressed in BxPC3,CFPAC, ASPC1. After 5-Aza-dC treatment, PCDH8 mRNA was expressed in PANC1, ASPC1, BxPC3,CFPAC, PaTu8988, SW1990 and the relative quantities of mRNA expression all significantly increased, and they were 7. 463 ± 2.628, 10. 696 ± 1.539, 7.852 ± 2.762,421.815 ± 1.493, 118.595 ± 4.089, 6.690 ±1.884. Conclusions The methylation of PCDH8 gene may be the major mechanism of down-regulated expression of PCDH8 gene in pancreatic carcinoma.

Objective To investigate the RADIL mRNA expression in pancreatic carcinoma and to evaluate its clinical significance.Methods Fluoesecent quantitative PCR (FQ-PCR) was used to detect the RADIL mRNA expression in 40 patients with pancreatic carcinoma and adjacent tissue and in 5 healthy adult with normal pancreatic tissue and to observe its relationship with clinicopathologic parameters.Results RADIL mRNA was expressed in pancreatic carcinoma and adjacent tissue, as well as normal pancreatic tissue, and the relative expression was 2.263 ± 3.826, 5.425 ± 8.858 and 8.559 ± 4.214, respectively.There was statistically significant difference among the three groups (P ＜0.05 ).RADIL mRNA expression was closely related with the metastasis and differentiation grade ( r = -0.312 and -0.294, P ＜ 0.05 ), however, it was not significantly related to tumor site, tumor size, CA19-9, TNM staging, sex and age.Conclusions RADIL gene may have an inhibitory effect on the pancreatic cancer.

Objective To investigate the diagnostic value of the K-ras mutations in FNA samples for early detection of pancreatic cancer. Methods FNA samples of 27 patients with pancreatic cancers, 9 patients with other malignant tumors and 14 patients with non malignant pancreatic mass (NMPM) were collected. DNA was extracted, and K-ras gene was amplified through PNA-mediated PGR clamping, the products were sequenced to determine the mutation type. Results The positive rate of K-ras mutations in pancreatic cancers,other malignant tumors and NMPM were 88.9%, 44.4%, 35.7%. There was significant difference in K-ras gene mutations in FNA samples between pancreatic cancer and other malignant tumors ( P = 0. 013 ) and NMPM ( P = 0. 001 ). The sensitivity, specificity, positive predictive value, negative predictive value,accuracy of K-ras mutations in FNA samples of pancreatic cancers were 88.9%, 55.6%, 85.7%, 62.5%,80.6% when compared with other malignant tumors, and the difference between the two groups was significant (P =0. 013) ;Those were 88.9%, 64.3%, 82.8%, 75.0%, 80. 5% when compared with NMPM, and the difference between the two groups was significant ( P = 0. 001 ). When cytology of FNA samples and K-ras mutations was combined, the positive rate of pancreatic cancer was up to 96.3%. Conclusions The detection of K-ras mutations in EUS-FNA samples helped improve the positive diagnostic rate of pancreatic cancer.

Objective:To explore the diagnostic value of endoscopic ultrasonography (EUS) for duodenal accessory papilla.Methods:Data of 122 cases of duodenal accessory papilla diagnosed by EUS at the endoscopy center of the First Affiliated Hospital of Zhejiang University School of Medicine from February 28, 2006 to February 28, 2018 were analyzed and summarized.Results:Of the 122 duodenal accessory papilla cases, the age was 52.1±12.9, with more males than females. The most common site of duodenal accessory papillae was the descending part above the papilla (88/122, 72.13%), followed by the junction of duodenal bulb and descending part (29/122, 23.77%), and a small proportion of lesions located in the duodenal bulb (5/122, 4.10%). Duodenal accessory papillae were all solitary, whose diameter mostly ranged 0.5-1.0 cm (88/122, 72.13%), a smaller proportion of diameter larger than 1.0 cm (23/122, 18.85%), and only a few with diameter less than 0.5 cm (11/122, 9.02%). Most duodenal accessory papillae were hypoechoic (71/122, 58.20%) or moderate to low echogenic (35/122, 28.68%), and the echoes were mostly homogeneous. The mucosa layer was smooth, with a sphincteroid structure in the submucosa and below. The boundary of the duodenal accessory papillae was mostly clear (121/122, 99.18%) and characteristic lacunar cavity structures were often seen in the center (83/122, 68.03%). The surrounding intestinal wall was normal and no associated enlarged lymph nodes were found around the intestine.Conclusion:EUS can clearly show the structure of duodenal accessory papilla and adjacent organs, and is of high value for the diagnosis of duodenal accessory papilla.

Objective:To investigate the consistency between the iodine-unstained area and the pathological size of endoscopic submucosal dissection (ESD) specimens of superficial esophageal cancer.Methods:A retrospective study was performed on data of 32 patients with superficial esophageal cancer who accepted ESD from May 2019 to April 2020 in the First Affiliated Hospital, Zhejiang University School of Medicine. The maximum transverse diameter and maximum longitudinal diameter of the iodine-unstained area were compared with the tumor pathological area. A size difference no more than 0.5 cm was considered as conformity, any difference between 0.5 and 1.0 cm was considered as non-conformity, and any difference no less than 1.0 cm was considered as serious non-conformity. At the same time, pink sign after spraying Lugo solution and the consistency of pink sign area with the iodine free area were observed.Results:A total of 32 patients with 33 lesions were enrolled in this study, including 23 males and 9 females and the age of the patients was 59.5±7.3 years. There were 19 (57.6%) lesions whose size of iodine-unstained area was consistent with the tumor pathological area. These 19 lesions were all positive for the pink sign, and the pink sign area overlapped with the iodine-unstained area. In addition, 4 (12.1%) iodine-unstained areas of the lesions did not match the size of the pathological area, and 10 (30.3%) iodine-unstained areas of the lesions were seriously inconsistent with the size of the pathological area. These 14 (42.4%) lesions were all positive for pink sign, and the pink sign area was significantly smaller than the iodine-unstained area. Among the 14 discordant lesions, 2 lesions underwent ESD according to the iodine-unstained area, which resulted in excessive resection and postoperative stenosis.Conclusion:Determining the extent of superficial esophageal cancer by iodine-unstained areas before ESD may lead to excessive resection of the lesions, which is related to the fact that the iodine-unstained areas of the lesions are sometimes significantly larger than the pink sign areas. Therefore, in order to achieve precise treatment, endoscopists can choose the iodine-unstained area with positive pink sign as the first choice for resection.

ObjectiveTo observe the differences of brain functioning between dominant and non-dominant hemispheres during rehabilitation for subacute stroke based on functional near-infrared spectroscopy (fNIRS). MethodsFrom September, 2019 to June, 2020, ten subacute stroke inpatients with left hemiplegia (non-dominant hemisphere group) and 16 with right hemiplegia (dominant hemisphere group) from Beijing Bo'ai Hospital received the same unilateral task-oriented occupational therapy for upper limbs, for four weeks. They were assessed with Action Research Arm Test, Fugl-Meyer Assessment-Upper Extremities and grip strength before and after treatment, and scanned with fNIRS to the β value of bilateral sensorimotor cortex, premotor cortex and prefrontal cortex according to the changes of oxyhemoglobin concentration. ResultsAll the indexes of assessment improved in the both groups after treatment (|t| > 3.253, P < 0.05), while the scores of Action Research Arm Test and grip strength improved more in the dominant hemisphere group than in the non-dominant hemisphere group (|t| > 2.154, P < 0.05). For the β value of fNIRS, there was no main effect on time, region and groups (F < 0.542, P > 0.05), and the interactive effect between region and group was significant (F = 4.226, P < 0.01): In the dominant hemisphere group, the β value was higher in the ipsilateral premotor cortex than in the contralateral cortex (P = 0.030), and it was less in the contralateral prefrontal cortex than in the ipsilateral sensorimotor cortex (P = 0.024), ipsilateral premotor cortex (P = 0.003) and ipsilateral prefrontal cortex (P = 0.018). ConclusionFor the subacute stroke patients with right hemiplegia, the activation of brain regions is different between dominant and non-dominant hemispheres during the rehabilitation of upper limb and hand.

Macrophages are important immune effector cells with significant plasticity and heterogeneity in the body immune system, and play an important role in normal physiological conditions and in the process of inflammation. It has been found that macrophage polarization involves a variety of cytokines and is a key link in immune regulation. Targeting macrophages by nanoparticles has a certain impact on the occurrence and development of a variety of diseases. Due to its characteristics, iron oxide nanoparticles have been used as the medium and carrier for cancer diagnosis and treatment, making full use of the special microenvironment of tumors to actively or passively aggregate drugs in tumor tissues, which has a good application prospect. However, the specific regulatory mechanism of reprogramming macrophages using iron oxide nanoparticles remains to be further explored. In this paper, the classification, polarization effect and metabolic mechanism of macrophages were firstly described. Secondly, the application of iron oxide nanoparticles and the induction of macrophage reprogramming were reviewed. Finally, the research prospect and difficulties and challenges of iron oxide nanoparticles were discussed to provide basic data and theoretical support for further research on the mechanism of the polarization effect of nanoparticles on macrophages.
Humans ; Macrophages/metabolism* ; Cytokines ; Inflammation ; Neoplasms/metabolism* ; Nanoparticles ; Magnetic Iron Oxide Nanoparticles ; Tumor Microenvironment

Natural products, and especially the active ingredients found in traditional Chinese medicine (TCM), have a thousand-year-long history of clinical use and a strong theoretical basis in TCM. As such, traditional remedies provide shortcuts for the development of original new drugs in China, and increasing numbers of natural products are showing great therapeutic potential in various diseases. This paper reviews the molecular mechanisms of action of natural products from different sources used in the treatment of inflammatory diseases and cancer, introduces the methods and newly emerging technologies used to identify and validate the targets of natural active ingredients, enumerates the expansive list of TCM used to treat inflammatory diseases and cancer, and summarizes the patterns of action of emerging technologies such as single-cell multiomics, network pharmacology, and artificial intelligence in the pharmacological studies of natural products to provide insights for the development of innovative natural product-based drugs. Our hope is that we can make use of advances in target identification and single-cell multiomics to obtain a deeper understanding of actions of mechanisms of natural products that will allow innovation and revitalization of TCM and its swift industrialization and internationalization.