Analysis of natural regression and influencing factors of HSIL in the cervix of childbearing age patients / 中华妇产科杂志

Objective: To investigate the natural regression and related factors of high-grade squamous intraepithelial lesion (HSIL) in the cervix of childbearing age women, and to evaluate the applicability of conservative management for future fertility needs. Methods: This study included 275 patients of reproductive age with fertility needs, who were diagnosed as HSIL by biopsy from April 30, 2015 to April 30, 2022, including 229 cases (83.3%) cervical intraepithelial neoplasia (CIN) Ⅱ and 46 cases (16.7%) CIN Ⅱ-Ⅲ. They were followed-up without immediate surgery in the First Affiliated Hospital of Nanjing Medical University. The median follow-up time was 12 months (range: 3-66 months). The regression, persistence and progression of lesions in patients with HSIL were analyzed during the follow-up period, the influencing factors related to regression and the time of regression were analyzed. Results: (1) Of the 275 HSIL patients, 213 cases (77.5%, 213/275) experienced regression of the lesion during the follow-up period. In 229 CIN Ⅱ patients, 180 cases (78.6%) regressed, 21 cases (9.2%) persisted, and 28 cases (12.2%) progressed. In 46 CIN Ⅱ-Ⅲ patients, 33 cases (71.7%) regressed, 12 cases (26.1%) persisted, and 1 case (2.2%) progressed to invasive squamous cell carcinoma stage Ⅰ a1. There was no significant difference in the regression rate between the two groups (χ2=1.03, P=0.309). (2) The average age at diagnosis, age <25 years old at diagnosis were independent influencing factor of HSIL regression in univariate analysis (all P<0.05). There was no significant difference between HSIL regression and pathological grading, the severity of screening results, human papillomavirus (HPV) genotype, colposcopy image characteristics, number of biopsies during follow-up and pregnancy experience (all P>0.05). (3) The median regression times for patients aged ≥25 years and <25 years at diagnosis were 15 and 12 months, respectively. Kaplan-Meier analysis showed that age ≥25 years at diagnosis significantly increased the median regression time compared to <25 years (χ2=6.02, P=0.014). Conclusions: For HSIL patients of childbearing age, conservative management without immediate surgical intervention is preferred if CINⅡ is fully evaluated through colposcopy examination. Age ≥25 years at diagnosis is a risk factor affecting the prognosis of HSIL patients.

Application of PDX model in the evaluation of nano-delivery systems / 药学学报

Malignant tumor is a major disease affecting human health. The nano-delivery system itself has a unique size effect and it can achieve tumor-targeted distribution of drug molecules, improve the therapeutic effect, and reduce the toxic and side effects on normal tissues and cells after functional modification. Patient-derived xenografts (PDX) models can be established by transplanting patient-derived cancer cells or small tumor tissue into immunodeficient mice directly. Compared with the tumor cell line model, this model can preserve the key features of the primary tumor such as histomorphology, heterogeneity, and genetic abnormalities, and keep them stable between generations. PDX models are widely used in drug evaluation, target discovery and biomarker development, especially providing a reliable research platform for the diagnosis and treatment evaluation of nano-delivery systems. This review summarizes the application of several common cancer PDX models in the evaluation of nano-delivery systems, in order to provide references for researchers to perform related research.

The role of group 3 innate lymphoid cells(ILC3) in the evolution of the immune system: An update / 细胞与分子免疫学杂志

Group 3 innate lymphoid cells (ILC3) are an ILC subset that is characterized by the expression of retinoic acid-related orphan nuclear receptor γt (RORγt) and interleukin 22 (IL-22). This review summarizes the role of ILC3 in coordinating innate immunity and adaptive immunity based on current research and elaborate the significance of ILC3 from the perspective of immune system evolution. In addition, based on immune-related functions, we propose a possible time when ILC3 appears in the evolution of the immune system. And then, the research limitations and prospects are discussed.

Treatment analysis of complex Schatzker type Ⅳ tibial plateau fractures / 中国骨伤

OBJECTIVE@#To explore treatment strategy for complex Schatzker Ⅳ tibial plateau fracture.@*METHODS@#Forty-one patients with complex Schatzker type Ⅳ tibial plateau fractures were treated from January 2016 to January 2021, including 28 males and 13 females, aged from 19 to 65 years old with an average of (35.3±19.8) years old. Individualized treatment plan was developed according to preoperative imaging characteristics, medial surgical approach was mainly combined with other auxiliary incisions. Posteromedial inverted L approach was used in 18 patients, posteromedial approach and anterolateral extended approach in 19 patients, and posteromedial approach with anterolateral and lateral condylar osteotomy in 4 patients. Articular surface and facture healing were observed, range of knee joint motion was measured at 12 months after opertaion, and function of knee joint was evaluated by Lysholm scoring system.@*RESULTS@#Forty-one patients were followed up for 12 to 26 months with an average of (13.3±6.8) months. Twenty-nine patients and 10 patients were obtained complete fracture healing at 6 and 12 months after operation respectively, and fracture healing time was 4 to 13 months with an average of (5.0±3.7) months. Two patients occurred posterior medial internal fixation failure and varus deformity of knee joint, and the fracture healed and varus deformity was corrected after the second operation. Range of knee joint motion was (118±29) °, and Lysholm score was(83.0±16.0) points.@*CONCLUSION@#Individualized treatment should be reasonably selected for complex Schatzker Ⅳ tibial plateau fractures, the characteristics of lateral plateau fractures are an important reference for selecting surgical approaches, the effective fixation of posteromedial bone blocks should be pay full attention, and the overall treatment results are satisfied.

Effects of staged acupuncture on endometrial receptivity and anxiety in patients with recurrent implantation failure of thin endometrium based on "thoroughfare vessel is the sea of blood" theory / 中国针灸

OBJECTIVE@#To compare the clinical efficacy between staged acupuncture based on "thoroughfare vessel is the sea of blood" theory combined with routine hormone replacement cycle treatment and routine hormone replacement cycle treatment for patients with recurrent implantation failure (RIF) of thin endometrium.@*METHODS@#A total of 72 RIF patients with thin endometrium were randomly divided into an observation group and a control group, 36 cases in each group. The patients in the control group were treated with routine hormone replacement cycle treatment. Based on the treatment of the control group, the patients in the observation group were treated with staged acupuncture based on "thoroughfare vessel is the sea of blood" theory. The main acupoints were Neiguan (PC 6) and Gongsun (SP 4), and the supplementary acupoints were selected according to the menstrual cycle and syndrome differentiation; the acupuncture was given once every other day, 3 times a week, for 3 consecutive menstrual cycles. The thickness and shape of endometrium, and Hamilton anxiety scale (HAMA) score were observed at implantation window before and after treatment; the clinical pregnancy rate, live birth rate and cycle cancellation rate were compared between the two groups; the correlation between endometrial thickness and HAMA score was analyzed.@*RESULTS@#Compared before treatment, the endometrial thickness in the two groups and the proportion of type A+B endometrium in the observation group were increased (P<0.05), and the HAMA scores in the two groups were decreased (P<0.05) after treatment. The above indexes in the observation group were superior to those in the control group (P<0.05). The clinical pregnancy rate and live birth rate in the observation group were higher than those in the control group (P<0.05), and the cycle cancellation rate was lower than that in the control group (P<0.05). There was a negative correlation between endometrial thickness and HAMA score (P<0.05).@*CONCLUSION@#Based on the routine hormone replacement cycle treatment, the addition use of staged acupuncture based on "thoroughfare vessel is the sea of blood" theory could improve the thickness and shape of endometrium, relieve anxiety, increase the clinical pregnancy rate and live birth rate, and reduce the cycle cancellation rate in RIF patients with thin endometrium. The curative effect is superior to the routine hormone replacement cycle treatment alone.

Risk analysis and preventive strategies of implant placement in patients with hypertension / 中华口腔医学杂志

Recently, among the edentulous patients who undergo dental implants, the proportion of hypertensive patients remains high, which poses a greater challenge for clinicians to operate and to maintain the therapeutic effect. The present review comprehensively summarized clinical researches about the adverse effects on dental implants, outlined molecular mechanisms of the positive effects of various antihypertensive drugs on bone metabolism, and proposed that clinicians should select preventive strategies during preoperative and intraoperative procedures according to the blood pressure of patients with hypertension.

Determination of paclitaxel prodrug in SD rat plasma by LC-MS/MS and its application in preclinical pharmacokinetic studies / 药学学报

A fast and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of prodrug of paclitaxel (Pro-PTX) and paclitaxel (PTX) in rat plasma was developed. The plasma samples were subjected to protein precipitation with acetonitrile (0.1% formic acid), and then separated by LC with an Ultimate AQ-C18 column (50 mm × 3.0 mm, 3 μm) and acetonitrile-1 mmol·L-1 ammonium formate (containing 0.1% formic acid) as the mobile phase. Multiple reaction monitoring (MRM) scanning mode was used to detect the ion responses m/z 983.4→415.2 (Pro-PTX), m/z 854.4→286.1 (PTX) and m/z 808.3→527.2 (Docetaxel, internal standard) by using a triple quadrupole tandem mass spectrometer with electrospray ionization source and positive ion mode. The method validation results show that the linear ranges of Pro-PTX and PTX in plasma were 2.00-500 ng·mL-1 (r > 0.99) and 4.00-1 000 ng·mL-1 (r > 0.99), the lower limit of quantification was 2.00 ng·mL-1 and 4.00 ng·mL-1, respectively; the quality control samples with low, medium and high concentrations of Pro-PTX and PTX were within the batch, the relative standard deviation (RSD) between batches were all less than 9%; the relative deviation (RE) was within the range of ± 9%; In the stability test, both Pro-PTX and PTX in plasma were stable under various storage conditions. The method was sensitive, specific, and reproducible, and was suitable for the pharmacokinetic study of Pro-PTX in rats. Animal experiments were approved by the Ethics Committee of Laboratory Animal Management and Animal Welfare, Institute of Materia Medica, Chinese Academy of Medical Sciences (No.: 00003552).

Study of mass spectrometry imaging metabolomics of paclitaxel based on esophageal cancer multicellular tumor spheroids cultured in vitro / 药学学报

Multicellular tumor spheroids (MCTS) can simulate the structure and metabolic characteristics of tumors in vivo, which is of great significance to study the metabolic phenotype of tumor cells and the mechanism of drug intervention. In this study, esophageal cancer MCTS were constructed, and MCTS frozen sections were prepared after treated with different formulations of paclitaxel (PTX) including common PTX injection, PTX liposome and albumin bound PTX. MCTS mass spectrometry imaging analysis method was established by using air flow assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI). The visualization of the permeation and enrichment process of PTX in MCTs after PTX treatment was realized, and the spatially resolved metabolomics of PTX injection group was studied. The results showed that the permeation and enrichment behavior of PTX in MCTs model were related to the formulations. The changes of endogenous metabolites in MCTs of esophageal cancer after treated with PTX injection had temporal and spatial characteristics. The metabolic changes of MCTS during the initial 0-4 hours were dominated by the down-regulation of middle-high polarity metabolites and some lipids in the central region of MCTS, while the metabolic changes of MCTS during 8-72 hours were mainly up-regulated by lipid metabolites in the peripheral region of MCTS. The combination of in vivo tumor-associated MCTs model with label free, highly sensitive and high coverage mass spectrometry imaging technology provided a new method and strategy for the study of pharmacometabolomics.

Luteoloside protects the vascular endothelium against iron overload injury via the ROS/ADMA/DDAH II/eNOS/NO pathway / 中国天然药物

Iron overload injury is considered to be a part of blood stasis syndrome of arthralgia in traditional Chinese medicine. Its primary therapies include clearing heat and detoxification, activating blood circulation, and removing blood stasis. Lonicera japonica flos (LJF) has long been known as an excellent antipyretic and antidote. Luteoloside (Lut) is one of the main components of LJF and exhibits antioxidant, anti-inflammatory, and cytoprotective properties. However, the protection of Lut against iron overload injury and its underlying mechanisms remain unclear. Therefore, HUVECs were exposed to 50 μmol·L-1 iron dextran for 48 h to establish an iron overload damage model and the effects of Lut were assessed. Our results showed that 20 μmol·L-1 Lut not only increased cell viability and weakened LDH activity, but also significantly up-regulated DDAHⅡ expression and activity, increased p-eNOS/eNOS ratio and NO content, and reduced ADMA content in HUVECs exposed to iron overload. Furthermore, Lut significantly attenuated intracellular/mitochondrial ROS generation, improved SOD, CAT, and GSH-Px activities, reduced MDA content, maintained MMP, inhibited mPTP opening, prevented cyt c from mitochondria released into cytoplasm, reduced cleaved-caspase3 expression, and ultimately decreased cell apoptosis induced by iron overload. The effects of Lut were similar to those of L-arginine (an ADMA competitive substrate), cyclosporin A (a mPTP blocker agent), and edaravone (a free radical scavenger) as positive controls. However, addition of pAD/DDAH II-shRNA adenovirus reversed the above beneficial effects of Lut. In conclusion, Lut can protect HUVECs against iron overload injury via the ROS/ADMA/DDAH II/eNOS/NO pathway. The mitochondria are the target organelles of Lut's protective effects.

Clinicopathological features and prognosis of fumarate hydratase deficient renal cell carcinoma / 北京大学学报(医学版)

OBJECTIVE@#To investigate the clinicopathological features and prognosis of fumarate hydratase deficient renal cell carcinoma (FH-RCC).@*METHODS@#Immunohistochemical (IHC) staining was used to detect the expression of fumarate hydratase (FH) in tumor tissues of 109 different types of renal cell carcinoma (RCC) patients aged 60 years and younger from the Department of Urology of Peking University First Hospital from January 2013 to December 2019. The clinicopathological data and prognosis of FH-RCC were collected and analyzed.@*RESULTS@#There were eleven patients with FH-negative expression. Seven were males and four females. The age of onset ranged 16-53 years (mean age: 36.7 years), and four female patients all had a history of uterine leiomyoma. Only one first-degree relative of one patient had renal cancer, and none of the patients had a history or family history of cutaneous leiomyomas. The diameter of the tumor was 2.1-12.0 cm (mean: 8.83 cm). Renal sinus or perirenal fat invasion was seen in nine cases, tumor thrombus in renal vein or inferior vena cava in six cases, lymph node metastasis in seven cases, adrenal gland invasion in four cases and splenic capsule invasion in one case. The cases were initially diagnosed as type Ⅱ papillary RCC (7/49, 14.3%), collecting duct carcinoma (2/9, 22.2%) and unclassified RCC (2/51, 3.9%). Tumor histopathology mostly showed a mixture of different structures, such as papillary, tubular cystic, solid, and so on. The most common histological structures were papillary (9/11, 81.8%) and tubular (8/11, 72.7%). Three cases had sarcomatoid areas. At least focal eosinophilic nucleolus (WHO/grades Ⅲ-Ⅳ) and perinuclear halo could be seen in all cases. Immunohistochemical (IHC) stains of most tumors were negative for CA9, CD10 and CK7. The results of fluorescence in situ hybridization (FISH) showed that there was no translocation or amplification of TFE3 gene in two cases with TFE3 IHC expression. All the patients were followed up for 11-82 months. Mean survival was 24 months. Five cases died of distant metastasis 9-31 months after operation (mean: 19 months), and five of the six patients alive had became metastatic.@*CONCLUSION@#Morphologically, FH-RCC overlaps with many types cell RCC. A mixture of papillary and tubular cystic arrangement is the most common growth pattern of FH-RCC. At least focally large and obvious eosinophilic nucleoli are an important histological feature of this tumor. The negative expression of FH can help to confirm the diagnosis. Young female RCC patients with uterine leiomyomas should be suspected of FH-RCC. Some FH-RCC cases lack clinical evidence. The suspicion raised by pathologists based on histological characteristics is often the key step to further genetic testing and the final diagnosis of the tumor.

Therapeutic mechanism of Psammosilene tunicoides extract on rheumatoid arthritis based on NLRP3 inflammasome / 中国中药杂志

In this study, we investigated the mechanism of crude extract of Psammosilene tunicoides(CEPT) in the treatment of rheumatoid arthritis(RA) based on the Nod-like receptor protein 3(NLRP3) inflammasome. The collagen-induced arthritis(CIA) mouse model was established. On day 32 after the primary immunization, according to the arthritis score, the mice were randomly divided into model group, positive control(methotrexate) group, low-and high-dose CEPT groups, and normal group, with 10 mice in each group. According to the administration dose of each group, the mice were continuously administered for 21 days. Every four days during the administration, the paw edema degree, arthritis score, and spleen index of the mice were measured; histopathological examination was performed for the ankles of the mice; the contents of IL-1β and IL-18 in the serum were determined; the protein expression levels of NLRP3, caspase-1, and apoptosis-associated speck-like protein containing a CARD(ASC), as well as the mRNA expression levels of NLRP3 and caspase-1 in the ankle joints of the mice were detected. The results showed that compared with those in the model group, the mice in the positive control group and CEPT groups had significantly decreased the contents of IL-1β and IL-18 in the serum and spleen index(P<0.01), significantly lowered arthritis score and degree of paw edema(P<0.01), alleviated arthritic infiltration of the knee, and down-regulated protein and mRNA levels of NLRP3, ASC, and caspase-1 in the ankle joint(P<0.01). These results suggest that P. tunicoides may reduce the paw edema and arthritis score and alleviate the inflammatory response in CIA mice by inhibiting the expression of NLRP3. This study provides a basis for the study of immune regulation of P. tunicoides in RA.

Analysis of the Predictive Value of EZH2 Expression Level on the Clinical Efficacy and Long-term Prognosis of Patients with Primary Gastrointestinal Diffuse Large B-cell Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To investigate the predictive value of methyltransferase EZH2 expression level on the clinical efficacy and long-term prognosis of patients with primary gastrointestinal diffuse large B-cell lymphoma (PGI-DLBCL).@*METHODS@#161 patients with newly treated PGI-DLBCL in our hospital from August 2013 to July 2019 were selected. The expression level of EZH2 protein was detected by immunohistochemistry, and the short-term efficacy and long-term survival differences of patients with different levels of EZH2 were compared. The predictive values of EZH2 expression level on the short-term efficacy and long-term prognosis of PGI-DLBCL patients were analyzed by Log-rank test and COX risk proportional regression model. Chi-square test and Logistic regression analysis were used to analyze the influencing factors of EZH2 expression level.@*RESULTS@#The complete response (CR) and overal response(OR) rates of those with high EZH2 expression were significantly lower than those with low EZH2 expression (P<0.001). The median OS and PFS of EZH2 high-level and low-level expression group was 37, 31 months and 49, 42 months, respectively. The cumulative OS and PFS rates of the high-level expression group were significantly lower than those of the low-level expression group, and the differences were statistically significant (P<0.05). The high expression levels of H3K27me3, EZH2, BCL-2, BCL-6, c-MYC were closely related to the shortening of OS and PFS, while the high expression level of Ki-67 was closely related to the shortening of OS (P<0.05), of which the high expression levels of H3K27me3, EZH2, BCL-2, and BCL-6 were independent risk factors for shortening of OS and PFS. The expression level of EZH2 was positively correlated with the expression level of H3K27me3, BCL-6, c-MYC and Ki-67 (r=0.741, r=0.837, r=0.809, r=0.772), and the high expression levels of H3K27me3, BCL-6 and Ki-67 were independent factors influencing the high expression of EZH2.@*CONCLUSION@#In patients with PGI-DLBCL, the high expression of EZH2 significantly reduces the short-term CR and OR rates, which is an independent risk factor for the shortening of long-term OS and PFS rates, and it is independently related to the high expression of H3K27me3 and BCL6.

Fermented Cordyceps Powder Combined with ACEI/ARB in Treatment of Diabetic Kidney Disease： A Systematic Review / 中国实验方剂学杂志

［Abstract］Objective:To evaluate the efficacy and safety of fermented cordyceps powder combined with angiotensin-converting enzyme inhibitors （ACEI）/angiotensin Ⅱ receptor blocker （ARB） in the treatment of diabetic kidney disease （DKD）. Method:The randomized controlled trials （RCTs） concerning the treatment of DKD with fermented cordyceps powder plus ACEI/ARB were retrieved from Pubmed， Embase， Cochrane library， China National Knowledge Infrastructure （CNKI）， Chinese BioMedical Literature Database on disc （CBMdisc）， Wanfang Data Knowledge Service Platform， and Chongqing Weipu Database for Chinese Technical Periodicals （VIP）. The quality of the included articles was evaluated by the Cochrane Collaboration's tool， followed by data analysis using RevMan 5.3. Result:A total of 48 RCTs were included， involving 4 562 cases. As revealed by Meta-analysis， the effective rate of fermented cordyceps powder combined with ACEI/ARB was higher than that of ACEI/ARB ［risk ratio （RR）=1.20， 95% confidence interval （CI） （1.15，1.24）， <italic>P</italic><0.000 01］. Moreover， such combination effectively reduced urinary albumin excretion rate ［standardized mean difference （SMD）=-2.61，95%CI （-3.17，-2.05），<italic>P</italic><0.000 01］，24-h proteinuria［SMD=-1.75，95%CI （-2.15，-1.35），<italic>P</italic><0.000 01］， serum creatinine（Scr）［mean difference （MD）=-14.57，95%CI （-17.94，-11.21），<italic>P</italic><0.000 01］， blood urea nitrogen（BUN）［MD=-1.05，95%CI （-1.29，-0.81），<italic>P</italic><0.000 01］， cystatin C （Cys-C） ［MD=-0.52，95%CI （-0.68，-0.36），<italic>P</italic><0.000 01］， fasting blood glucose（FBG）［MD=-0.59，95%CI （-0.93，-0.25），<italic>P</italic>=0.000 6］， hemoglobin A1c（HbA1c）［MD=-0.50，95%CI（-0.75，-0.24），<italic>P</italic>=0.000 1］， tumor necrosis factor-<italic>α</italic>（TNF）-<italic>α </italic>［SMD=-1.68，95%CI （-2.21，-1.15），<italic>P</italic><0.000 01］， C-reactive protein（CRP） ［SMD=-1.35，95%CI （-1.77，-0.93），<italic>P</italic><0.000 01］， and interleukin-6 （IL-6） ［SMD=-1.52，95%CI （-1.98，-1.07），<italic>P</italic><0.000 01］. There was no significant difference in the incidence of adverse events between the two groups ［RR=0.77，95%CI （0.49，1.21），<italic>P</italic>=0.25］. Conclusion:Fermented cordyceps powder combined with ACEI/ARB is more effective than ACEI/ARB in the treatment of DKD， which is worthy of clinical promotion and use. More multi-center RCTs with a large sample size are needed for verification.

Averaging Strategy to Form the Imaging for Routine Reading of Insulinoma from Pancreatic Perfusion Dataset / 中国医学科学院学报

Objective To determine the appropriate averaging strategy for pancreatic perfusion datasets to create images for routine reading of insulinoma.Methods Thirty-nine patients undergoing pancreatic perfusion CT in Peking Union Medical College Hospital and diagnosed as insulinoma by pathology were enrolled in this retrospective study.The time-density curve of abdominal aorta calculated by software dynamic angio was used to decide the timings for averaging.Five strategies,by averaging 3,5,7,9 and 11 dynamic scans in perfusion,all including peak enhancement of the abdominal aorta,were investigated in the study.The image noise,pancreas signal-to-noise ratio(SNR),lesion contrast and lesion contrast-to-noise ratio(CNR)were recorded and compared.Besides,overall image quality and insulinoma depiction were also compared.ANOVA and Friedman's test were performed.Results The image noise decreased and the SNR of pancreas increased with the increase in averaging time points(all P0.99)and were higher than that of the first group(all P<0.05).There was no significant difference in overall image quality among the 5 groups(P=0.977).Conclusions Image averaged from 5 scans showed moderate image noise,pancreas SNR and relatively high lesion contrast and lesion CNR.Therefore,it is advised to be used in image averaging to detect insulinoma.

Correlation of Intravoxel Incoherent Motion-derived Parameters with Computer Tomography Perfusion Parameters in Insulinoma / 中国医学科学院学报

To prospectively evaluate the correlation between intravoxel incoherent motion (IVIM)-derived parameters and CT perfusion parameters as well as the pathological grade in insulinoma. A total of 55 patients with suspected insulinoma undergoing IVIM and CT perfusion scans were prospectively enrolled. The images were post-processed to obtain IVIM parameters including apparent diffusion coefficient (ADC),diffusion (D),perfusion correlated diffusion (D*),and f,and CT perfusion parameters including blood flow (BF),blood volume (BV),and permeability (PM). The pathological specimens were stained to obtain pathological parameters including the grading,ki-67 index,and the mitotic count. The IVIM derived parameters of normal pancreas including head,body,and tail as well as that of the pancreatic insulinoma were compared. The correlation between IVIM parameters and CT perfusion parameters as well as the pathological parameters was analyzed. ADC and D values of pancreatic tail were significantly lower than those of the pancreatic head and neck (all 0.05). IVIM parameters differ at different anatomical parts of normal pancreas. IVIM parameters can distinguish normal pancreatic parenchyma from insulinoma. The ADC value is weakly correlated with BF.

Research progress on the regulation of tumor metabolism, tumor immunotherapy and new analytical methods / 药学学报

In order to achieve rapid proliferation and adapt to the complex microenvironment, tumor cells have dominant characteristics such as unique metabolic patterns and the ability to escape from immunoregulation. Tumor cells reprogram multiple metabolic pathways to promote immune escape, which impacts tumor diagnosis, treatment and prognosis. Based on the effect of metabolic changes on tumor immune escape and its molecular mechanism, metabolic regulation provides new approaches to enhance immunotherapy. We review recent advances in tumor immuno-escape and immunotherapy based on metabolic regulation. Cutting-edge analytical techniques and methods for tumor metabolism research such as metabolomics, mass spectrometry imaging-based spatially-resolved metabolomics and metabolic flow analysis are also discussed.

Resveratrol inhibits hypoxia-induced oxidative stress and proliferation in pulmonary artery smooth muscle cells through the HIF-1α/NOX4/ROS signaling pathway / 生理学报

The purpose of the present study was to determine the effects of resveratrol on hypoxia-induced oxidative stress and proliferation in pulmonary artery smooth muscle cells (PASMCs) and the underlying mechanism. Primary rat PASMCs were isolated and cultured in vitro and pretreated with different concentrations of resveratrol (10, 20, and 40 µmol/L) or the NADPH oxidase (NOX) inhibitor VAS2870 (10 µmol/L) for 0.5 h. The cells were then cultured under normoxia (21% O

Inter- and intra-observer variability for the assessment of coronary artery tree description and lesion EvaluaTion (CatLet©) angiographic scoring system in patients with acute myocardial infarction / 中华医学杂志(英文版)

BACKGROUND@#Previously, we developed a novel Coronary Artery Tree description and Lesion EvaluaTion (CatLet©) angiographic scoring system, which was capable of accounting for the variability in the coronary anatomy and assisting in the risk-stratification of patients with acute myocardial infarction (AMI). Our preliminary study revealed that the CatLet score better predicted clinical outcomes for AMI patients than the Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery score. However, the reproducibility of the CatLet score in both inter- and intra-observer remains to be evaluated.@*METHODS@#A total of 30 consecutive AMI patients, admitted in September of 2015, were independently assessed by two experienced interventional cardiologists to evaluate the inter-observer reproducibility of the CatLet score. Another set of 49 consecutive AMI patients, admitted between September and October in 2014, were assessed by one of the two interventional cardiologists on two occasions 3 months apart to evaluate the intra-observer reproducibility of the CatLet score. The weighted kappa was used to express the degree of agreement.@*RESULTS@#The weighted kappa values (95% confidence interval) for the intra- and inter-observer reproducibility of the CatLet Score were 0.82 (0.59-1.00, Z = 7.23, P 22). Regarding the adverse characteristics pertinent to lesions and dominance parameters, the kappa values for the inter-observer variability were 0.80 (0.56-1.00, Z = 6.47, P < 0.001) for total number of lesions, 0.57 (0.28-0.85, Z = 3.03, P < 0.001) for bifurcation, 0.69 (0.43-0.96, Z = 5.06, P < 0.001) for heavy calcification, 1.00 (0.72-1.00, Z = 6.93, P < 0.001) for tortuosity, 0.54 (0.26-0.82, Z = 3.78, P < 0.001) for thrombus, 0.69 (0.48-0.91, Z = 6.29, P < 0.001) for right coronary artery dominance, 0.69 (0.41-0.96, Z = 4.91, P < 0.001) for left anterior descending artery length, and 0.22 (0.06-0.51, Z = 1.56, P = 0.06) for diagonal size. Equivalent values for the intra-observer variability were moderate to almost perfect (range 0.54-1.00).@*CONCLUSIONS@#The reproducibility of the CatLet angiographic scoring system for evaluation of the coronary angiograms ranged from substantial to excellent. The high reproducibility of the CatLet angiographic scoring system will boost its clinical application to patients with AMI.

Network Pharmacology-based Mechanism of Xiao Xianxiongtang in Treatment of Coronary Heart Disease / 中国实验方剂学杂志

Objective::To predict Xiao Xianxiongtang's treatment of coronary heart disease (CHD) targets and analyze their function by the network pharmacology method, and build ingredients-targets-channel network pharmacological model, in order to reveal potential pathways and mechanisms of Xiao Xianxiongtang for CHD treatment. Method::Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) was used to obtain components, and CHD targets over Xiao Xianxiongtang were predicted by using Swiss Target Prediction reverse pharmacophore matching method. CHD targets which Food and Drug Administration (FDA) approved were collected from Therapeutic Target Database (TTD), Drugbank and Disease-gene Net databases (DisGeNET). Wenn diagram was used to obtain the correlation intersection.Target characteristics were analyzed with GEO2R online, Reactome FI was used to analyze the enrichment of target pathways, and Cytoscape software was used to construct the " component-target-pathway" network. Result::Network analysis showed that Xiao Xianxiongtang treated CHD by regulating 24 target proteins through 25 therapeutic components, and acting on 21 specific pathways and 4 biological processes.According to the multiple gene chip analysis of GEO2R online, there were up-down-regulated differences in the targets, including 11 up targets and 13 down targets. Conclusion::Xiao Xianxiongtang treats CHD by involving the biological processes through berberine and flavonoid groups of Coptidis Rhizoma, nucleosides and organic acids of Arum ternatum Thunb, stigmasterols and flavonoids of Trichosanthes kirilowii Maxim, such as gene expression, metabolism and protein metabolism, adjusting the gene expressions of relevant target proteins, regulating gene transcription pathways, such as biological oxidation reaction and lipid and lipoprotein metabolism, insulin-like growth factor binding protein (IGFBPs) of insulin-like growth factor (IGF) transshipment and intake, and the degradation of extracellular matrix signaling pathways.

Immunotherapy for lung cancer: immunosuppressive cells and intrapulmonary immunity / 上海交通大学学报（医学版）

Immunotherapy is one of the most rapidly developed tumor treatment strategies. Immune checkpoint inhibitors (ICIs) enhance the anti-tumor immune response by inhibiting the inhibitory effect of tumor cells on T cells. At present, antibodies against cytotoxic T-lymphocyte associated protein 4 (CTLA-4), programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) have been approved for clinical therapies. However, those treatments are only effective in the minority of patients. This may be related to the deeper immunosuppression mediated by myeloid-derived suppressor cells (MDSCs) and regulatory cells (Tregs). The microenvironment of the lung affects tumor immunity with its unique physiological function, which can quickly resist pathogens to maintain immune balance in the lung, but also can promote tumor progression. In this paper, the effects of immunosuppressive cells in the treatment of ICIs and the role of them in the lung immune environment are analyzed to explore the strategies to improve the effect of immunotherapy in patients with lung cancer.