ObjectiveTo explore the therapeutic mechanism of Buchong Tiaojing prescription for rats with diminished ovarian reserve （DOR） from the perspectives of nucleotide-binding oligomerization domain （NOD）-like receptor protein 3 （NLRP3） inflammasome and ferroptosis. MethodsA total of 48 female SD rats were randomly divided into a normal group， a model group， low， medium， and high dose groups of Buchong Tiaojing prescription， and an MCC950 group， with eight rats in each group. Except the normal group， all the other groups were injected subcutaneously on the back of the neck with D-galactose to prepare the DOR rat model. From the 15th day of modeling， the rats in the low， medium， and high dose groups of Buchong Tiaojing prescription were subjected to gavage daily at doses of 14.4， 28.8， 57.6 g·kg^-1， respectively. Rats in the MCC950 group were injected intraperitoneally with MCC950 at a dose of 10 mg·kg^-1， once every other day. The interventions of all the groups lasted for 4 weeks. The estrous cycle of the rats was observed with vaginal exfoliated cell smear. Hematoxylin-eosin （HE） staining was performed to observe the development of follicles and corpus luteum in the ovary. Enzyme-linked immunosorbent assay （ELISA） was performed to detect the levels of serum sex hormones and interleukin-1β （IL-1β）. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot assay were performed to detect the mRNA and protein expression of NLRP3 inflammasome， acyl-CoA synthetase long-chain family member 4 （ACSL4）， transferrin receptor 1 （TFR1）， and glutathione peroxidase 4 （GPX4）， and oxidative stress kits were used to detect ovarian superoxide dismutase （SOD） and malondialdehyde （MDA） levels. ResultsDuring the experiment， one rat died in the high dose group of Buchong Tiaojing prescription， and a total of 47 rats were finally included in the index tests and statistics. Compared with those in the normal group， rats in the model group had significantly disturbed estrous cycles， increased number of atretic follicles， and significant disorder of serum sex hormones. The mRNA and protein expression of NLRP3 inflammasome， ACSL4， and TFR1 in ovarian tissue was up-regulated （P<0.01）， while that of GPX4 was significantly down-regulated （P<0.01）. The SOD content in the ovary was decreased significantly， while the MDA level was increased （P<0.01）. After drug intervention， the estrous cycle of rats was basically resumed， and the follicles at all levels were more structurally intact and significantly increased in number. Additionally， the levels of serum sex hormones and IL-1β were significantly improved. The mRNA and protein expression of NLRP3 inflammasome， ACSL4， and TFR1 were down-regulated， while that of GPX4 was significantly up-regulated， and the ovarian oxidative stress was alleviated （P<0.05， P<0.01）， especially in the high dose group of Buchong Tiaojing prescription and the MCC950 group. ConclusionInflammatory injury and ferroptosis occur in the ovaries of DOR rats， and the Buchong Tiaojing prescription is able to inhibit ovarian NLRP3 inflammasome， alleviate the degree of ovarian ferroptosis， and improve ovarian reserve.

The portable light-weight magnetic resonance imaging system can be deployed in special occasions such as Intensive Care Unit (ICU) and ambulances, making it possible to implement bedside monitoring imaging systems, mobile stroke units and magnetic resonance platforms in remote areas. Compared with medium and high field imaging systems, ultra-low-field magnetic resonance imaging equipment utilizes light-weight permanent magnets, which are compact and easy to move. However, the image quality is highly susceptible to external electromagnetic interference without a shielded room and there are still many key technical problems in hardware design to be solved. In this paper, the system hardware design and environmental electromagnetic interference elimination algorithm were studied. Consequently, some research results were obtained and a prototype of portable shielding-free 50 mT magnetic resonance imaging system was built. The light-weight magnet and its uniformity, coil system and noise elimination algorithm and human brain imaging were verified. Finally, high-quality images of the healthy human brain were obtained. The results of this study would provide reference for the development and application of ultra-low-field magnetic resonance imaging technology.
Humans ; Magnetic Resonance Imaging/methods* ; Magnetic Resonance Spectroscopy/methods* ; Head ; Equipment Design ; Magnets

Objective:To explore the expression and importance of Piezo1, E-cadherin, and Vimentin in nasal polyps patients. Methods:Thirty-five patients undergoing endoscopic sinus surgery under general anesthesia were streamed into 20 cases of nasal polyps（NP group） and 15 cases of simple septoplasty without any sinus disease（Control group）. Immunofluorescence staining and Western Blot were applied to detect the protein level of Piezo1, E-cadherin, and Vimentin in NP tissues and nasal polyp-derived primary human nasal epithelial cells（pHNECs）. Also, BEAS-2B cell lines were treated with human TGF-β1 protein to establish epithelial mesenchymal transition（EMT） model in vitro and quantitative real-time polymerase chain reaction were used to calculate Piezo1 and above biomarkers in the model. Results:Compared with control group, Piezo1 and Vimentin showed higher level while E-cadherin was lower in NP tissues and pHNECs.In EMT model in vitro, Piezo1 and Vimentin were demonstrated higher expression with decreased level of E-cadherin. Conclusion:The tendency of Piezo1 is consistent with the mesenchymal-related biomarker Vimentin, going against with epithelial-related biomarker E-cadherin, implying its involvement with EMT process in nasal polyps.
Humans ; Biomarkers/metabolism* ; Cadherins/metabolism* ; Chronic Disease ; Epithelial-Mesenchymal Transition ; Nasal Polyps/metabolism* ; Rhinosinusitis ; Sinusitis ; Transforming Growth Factor beta1/metabolism* ; Vimentin/metabolism*

Objective To explore cross-talk elimination method in the determination of gross α and gross β activities using a low-background α/β gas-flow proportional counter. Methods A CLB-104 low-background α/β gas-flow proportional counter was used in this study. First, the α threshold was increased to eliminate the cross-talk counting caused by β particles in the α channel. Then, the α-β anticoincidence threshold was reduced to eliminate the cross-talk counting induced by low-energy α particles in the β channel, and β counts were corrected to eliminate the counts induced by internal convention electrons in the β channel. Finally, gross α and gross β activities of non-saline water samples with different activity levels were determined and compared with gross α and gross β activities of the same samples determined on a BH1227 low-background α/β solid scintillation counter, in order to verify effectiveness of the cross-talk elimination method. Results By eliminating the cross-talk counts of β particles in the α channel and the cross-talk counts of α particles in the β channel, and deducting the counts of internal convention electrons in the β channel, the gross α and gross β activities of the same samples determined by CLB-104 were consistent with the values determined by BH1227. Conclusion Cross-talk counts induced by low-energy α particles or β particles can be eliminated by threshold adjustment, and the counts caused by internal convention electrons in the β channel can be eliminated by correction.

To explore the mechanism of tea albino variation and high theanine formation, 'Fuyun 6' and a new theanine-rich tea cultivar 'Fuhuang 2' were as materials in this study, pigment content, metabolome and transcriptome of the two cultivars were analyzed by ultramicroelectron microscopy, widely targeted metabolomics, targeted metabolomics and transcriptomics. The results showed that five catechins, theobromine, caffeine, and 20 free amino acids, including theanine, glutamine, arginine, etc., were identified by targeted metabolomics. The amino acid content of 'Fuhuang 2' was significantly higher than that of 'Fuyun 6', and the theanine content was as high as 57.37 mg/g in 'Fuhuang 2'. The ultrastructure of leaves showed that the chloroplast cell structure of 'Fuhuang 2' was fuzzy, most of the grana lamellae were arranged in disorder, with large gaps, and the thylakoids were filiform. The determination of pigments showed that compared with 'Fuyun 6', the contents of chlorophyll A and B, carotenoids, flavonoids and other pigments of 'Fuhuang 2' decreased significantly, some important pigment-related-genes, such as chlorophyllase (CLH), 9-cis-epoxycarotenoid dioxygenase (NCED), flavonoid 3β-hydroxylase (F3H) and flavonoid 3', 5'-hydroxylase (F3'5'H) were significantly changed. Compared with 'Fuyun 6', 'Fuhuang 2' identified 138 significantly changed metabolites (SCMs) and 658 differentially expressed genes (DEGs). KEGG enrichment analysis showed that SCMs and DEGs were significantly enriched in amino acid biosynthesis, glutathione metabolism and TCA cycle. In general, the albino phenotype of 'Fuhuang 2' may be caused by a deficiency in photosynthetic proteins, chlorophyll metabolism genes and chlorophyll content. The accumulation of high theanine in 'Fuhuang 2' may be due to the low nitrogen consumption in yellowed leaves and the lack of carbon skeleton, amino and nitrogen resources are stored more effectively, resulting in the up regulation of metabolites and related gene expression in the amino acid synthesis pathway, theanine has become a significant accumulation of nitrogen-containing compounds in yellowed leaves.
Camellia sinensis/genetics* ; Chlorophyll A/metabolism* ; Plant Proteins/genetics* ; Plant Leaves/chemistry* ; Chlorophyll/metabolism* ; Transcriptome ; Flavonoids/metabolism* ; Amino Acids/genetics* ; Tea ; Mixed Function Oxygenases/metabolism* ; Nitrogen/metabolism*

Hepatocellular carcinoma （HCC） most often develops in patients with liver disease characterized by chronic non-resolving inflammation. The inflammatory response is mainly derived from innate immune cells， and tumor-associated macrophages （TAMs） play an important role in the development of tumors．It is usually chemotactic from mononuclear progenitor cells in the blood to tumor tissue， then is induced by the tumor microenvironment and further develops into TAMs. They play an important role in promoting tumor growth，angiogenesis and tumor invasion and inducing tumor tissues to form an environment without inhibition mechanisms. As the relationship between TAMs and malignant tumors becomes clearer， TAMs are beginning to be seen as therapeutic targets. The heterogeneity of TAM subtypes and their origin and dynamic phenotype during the initiation and progression of HCC has been partially unraveled. It further forms the base for developing therapeutic agents by decreasing the population of TAMs via blocking recruitment of bone marrow-derived monocytes and functionally reprograms TAMs to anti-tumoral behavior. This review focuses on the preclinical evolution and hitherto clinical trials for TAM-targeted therapy in HCC.

【Objective】 To prepare positron emission computed tomography (PET) molecular probes targeting macrophages using Nb119 and BCⅡ10 labeled with ⁶⁸Ga nuclide. 【Methods】 To explore the labeling conditions of nanobodies with ⁶⁸Ga nuclides, first, the anti-Vsig4 nanobody Nb119 and isotype control antibody BCⅡ10 were incubated with NOTA and then purified to obtain the chelating agent-modified NOTA-Nb119 and NOTA-BCⅡ10. The NOTA-Nb119 and NOTA-BCⅡ10 were further incubated with ⁶⁸Ga. Finally, NOTA-Nb119 was identified by SDS-PAGE and MALDI-TOF methods, and the radiochemical purity was detected by radio-HPLC. 【Results】 The results of SDS-PAGE showed that the lanes of the successfully labeled NOTA-Nb119 had apparent hysteresis than the unlabeled nanobody band, which proved that the molecular weight of the labeled product was increased and NOTA successfully modified the nanobody. Subsequently, ⁶⁸Ga nuclides could successfully label Nb119 and BCⅡ10. According to radio-HPLC detection, the radiochemical purity of NOTA-Nb119 and NOTA-BCⅡ10 labeled with ⁶⁸Ga was greater than 90% and remained stable. 【Conclusion】 ⁶⁸Ga-labeled nanobodies have high radiochemical purity and high stability, indicating that this study can be applied to other nanobodies for modification and labeling and provides a practical and feasible method for the preparation of PET using nanobodies.

Objective:To investigate the application value of hybrid approach in laparoscopic radical resection of left hemicolon cancer.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 96 patients with left hemicolon cancer who were admitted to Henan Provincial People′s Hospital between January 2015 and March 2018 were collected. There were 52 males and 44 females, aged from 29 to 75 years, with an average age of 61 years. Patients underwent laparoscopic radical resection of left hemicolon cancer. Observation indicators: (1) surgical situations and postoperative recovery; (2) postoperative pathological examination; (3) postoperative chemotherapy; (4) follow-up. Follow-up using outpatient examination and telephone interview was performed to detect postoperative survival, tumor recurrence and metastasis of patients up to October 2019. Measurement data with skewed distribution were represented as M (range), and count data were described as absolute numbers. Results:(1) Surgical situations and postoperative recovery: all the 96 patients underwent laparoscopic radical resection of left hemicolon cancer with hybrid approach. Of 96 patients, 5 underwent laparoscopic multiple organ resection including 2 combined with splenectomy, 2 combined with gastric wall wedge resection, 1 combined with splenectomy and distal pancreatectomy; 7 underwent hand-assisted laparoscopic surgery including 5 undergoing multiple organ resection due to tumor invasion, 2 combined with terminal ileostomy due to poor exposure caused by severe obstruction in proximal intestinal canal; 84 underwent laparoscopic-assisted surgery. There was no intraoperative conversion to laparotomy. Of 96 patients, 3 received posterior ileum anastomosis, 2 received rotating ascending colon anastomosis, 91 received in situ anastomosis. Operation time, volume of intraoperative blood loss, and time to first flatus were 140 minutes (range, 70-250 minutes), 50 mL (range, 30-140 mL), 2 days (range, 1-4 days), respectively. Of 96 patients, 5 had postoperative incision infection, 5 had pulmonary infection, 3 had adhesive intestinal obstruction, 1 had anastomotic leakage, and they were cured after conservative treatment. Duration of postoperative hospital stay of the 96 patients was 8 days(range, 5-27 days). (2) Postoperative pathological examination: of the 96 patients, the number of lymph nodes dissected and length of surgical specimen were 19 (range, 13-25) and 35 cm (range, 25-50 cm). All the 96 patients had negative surgical margin. Pathological T staging of 96 patients: 5 patients were in pT1 stage, 46 in pT2 stage, 37 in pT3 stage, 8 in pT4 stage. Pathological N staging of 96 patients: 32 patients were in pN0 stage, 47 in pN1 stage, 17 in pN2 stage. Pathological types of 96 patients: 7 patients had mucinous adenocarcinoma, 16 had poorly differentiated adenocarcinoma, 46 had moderately differentiated adenocarcinoma, and 27 had well differentiated adenocarcinoma. (3) Postoperative chemotherapy: 68 of the 96 patients underwent standard chemotherapy of XELOX regimen, and 28 had no chemotherapy. (4) Follw-up: 86 patients were followed up for 19-58 months, with a median time of 11 months. During the follow-up, all the 86 patients survived, of which 82 had no tumor recurrence, 3 survived with tumor after detection of liver metastasis, and 1 survived with tumor after detection of liver and pulmonary metastasis.Conclusion:The hybrid approach is safe and feasible in the laparoscopic radical resection of left hemicolon cancer.

With the increasing cost of drug development and clinical trials, it is of great value to make full use of all kinds of data to improve the efficiency of drug development and to provide valid information for medication guidelines. Model-based meta-analysis (MBMA) combines mathematical models with meta-analysis to integrate information from multiple sources (preclinical and clinical data, etc.) and multiple dimensions (targets/mechanisms, pharmacokinetics/pharmacodynamics, diseases/indications, populations, regimens, biomarkers/efficacy/safety, etc.), which not only provides decision-making for all key points of drug development, but also provides effective information for rational drug use and cost-effectiveness analysis. The classical meta-analysis requires high homogeneity of the data, while MBMA can combine and analyze the heterogeneous data of different doses, different time courses, and different populations through modeling, so as to quantify the dose-effect relationship, time-effect relationship, and the relevant impact factors, and thus the efficacy or safety features at the level of dose, time and covariable that have not been involved in previous studies. Although the modeling and simulation methods of MBMA are similar to population pharmacokinetics/pharmacodynamics (Pop PK/PD), compared with Pop PK/PD, the advantage of MBMA is that it can make full use of literature data, which not only improves the strength of evidence, but also can answer the questions that have not been proved or can not be answered by a single study. At present, MBMA has become one of the important methods in the strategy of model-informed drug development (MIDD). This paper will focus on the application value, data analysis plan, data acquisition and processing, data analysis and reporting of MBMA, in order to provide reference for the application of MBMA in drug development and clinical practice.

Objective To evaluate the clinical curative effect and prognosis of hand-assisted laparoscopic (HALS) and laparoscopic assisted surgery for Siewert Ⅱ,Ⅲ gastroesophageal junction adenocarcinoma (AEG).Methods A retrospective analysis of 105 patients with advanced Siewert type Ⅱ and Ⅲ AEG between Jan 2012 and Jan 2013 was made on the operation time,amount of blood loss,number of lymph nodes dissected,postoperative complications,postoperative hospital stay and postoperative 5-year survival rate.Results HALS resulted in significantly shorter operation time and the average postoperative hospital stay [(203±54) min比(283±72) min,t=-4.902,P=0;(10±4) d 比(13±3)d,t=-0.939,P =0.002] for advanced Siewert type Ⅱ and Ⅲ AEG.There was no conversion to open surgery in HALS group,while there was 3 cases in laparoscopy assisted surgery group (x2 =4.118,P =0.042).5 year overall survival (OS) in HALS group was 46.7％ (95％ CI39.98-53.88),and it was 60.9％ for stage Ⅱ patients 37.8％ for stage Ⅲ.5 years OS rate was not significantly different between the two groups.Conclusion HALS compared with laparoscopy assisted surgery in the treatment of advanced Siewert type Ⅱ and type Ⅲ AEG has shorter operation time,higher safety operation,shorter postoperative recovery time.The number of patients with postoperative complications and the 5-year survival rate after surgery are not significantly different between the two groups.