Predictive value of lactate dehydrogenase for Mycoplasma pneumoniae necrotizing pneumonia in children based on decision curve analysis and dose-response analysis.

Mycoplasma pneumoniae necrotizing pneumonia (MPNP) has a long and severe disease course, which seriously threatens to jeopardize patients' lives and health. Early prediction is essential for good recovery and prognosis. In the present study, we retrospect 128 children with MPNP and 118 children with Mycoplasma pneumoniae pneumonia combined with pulmonary consolidation to explore the predictive value of lactate dehydrogenase (LDH) in children with MPNP by propensity score matching method, multiple logistic regression analysis, dose-response analysis and decision curve analysis. The WBC count, PLT count and percentage of neutrophils were significantly higher in necrosis group than consolidation group. The serum CRP, PCT, ESR, D-D, FIB, ALT, LDH, IgG and IgM were significantly higher in necrosis group. Compared to consolidation group, necrosis group is more severe in chest pain and dyspnea. Multivariate logistic regression analysis showed that duration of LDH levels, high fever, D-dimer, and fibrinogen were independent predictive factors for the incidence of MPNP. Restricted cubic spline analysis showed that a non-linear dose-response relationship between the continuous changes of LDH level and the incidence of MPNP. Decision curve analysis revealed that LDH had an important clinical value in predicting MPNP. This study provides a potential serologic indicator for early diagnosis of MPNP.

Gouqizi () seed oil reduces D-galactose induced inflammation in testis of rats Janus kinase 1/signal transducerand activator of transcription 1/nuclear factor-κB and.

OBJECTIVE: To investigate the efficacy of Gouqizi () seed oil (FLSO) on D-gal induced inflammation in testis of rats and . METHODS: In aging Sertoli cells (TM4 cells) induced by D-galactose (D-gal), the expression of upregulated aging-related proteins. The number of cells counted by cell counting kit (CCK)-8 assay showed a high number of cells disposed with FLSO at 50, 100 and 150 µg/mL compared to that for the aging model. , male Sprague-Dawley rats ( = 50, 8-week-old, 230-255 g) were randomly categorized into control, aging model, and FLSO (low-, medium-, and high-dose) groups. The expression of nuclear factor-κB (NF-κB) and its upstream factors [Janus kinase 1 (JAK1) and signal transducerand activator of transcription 1 (STAT1)] was detected by Western blot and immunofluorescence, related inflammatory factors quantified by enzyme-linked immunosorbent assay. Evaluation of testicular tissue by Johnsen score, the spermatogenic function was explored. RESULTS: The expression of interleukin-1ß (IL-1ß) ( < 0.05), IL-6 ( < 0.001), and tumor necrosis factor α (TNF-α) ( < 0.05) was decreased significantly, while that of heme oxygenase-1 (HO-1) ( < 0.001) and IL-10 ( < 0.05) was increased in cells disposed with FLSO 100 µg/mL. FLSO inhibited the expression of NF-B and declined p-p65/p65 ( < 0.01), as detected by Western blotting. In, the levels in serum of IL-1ß ( < 0.001), IL-6 ( < 0.05), and TNF-( < 0.01) declined while IL-10 ( < 0.05) was upregulated post-FLSO treatment. In addition, the expression of JAK-1 and STAT1 increased significantly in testicular tissue of rats treated with FLSO as compared to the aging model of rats ( < 0.001), while the expression of NF-κB ( < 0.001) declined in the testis in the FLSO group, as assessed by immunofluorescence. The levels of inhibor B and testosterone in serum both increased (< 0.05). CONCLUSIONS: In conclusion, this study determined the protective effects of FLSO to tolerate inflammatory injury in the testis, indicating that FLSO alleviates inflammation JAK-1/STAT1/NF-κB pathway.

Study on mechanism of Yangxue Qingnao Granule for the treatment of vascular dementia disease based on network pharmacology and bioinformatics / 国际中医中药杂志

Objective:To explore the possible mechanism of Yangxue Qingnao Granule for the treatment of vascular dementia (VaD) based on network pharmacology and bioinformatics.Methods:The active components and potential targets of Yangxue Qingnao Granule in the treatment of VaD were obtained from TCMSP database, BATMAN-TCM database, GEO database and OMIM database, etc. The heatmap was visualized by using the pheatmap packages in R. Cytoscape 3.8.2 software and the CytoNCA plugin were utilized to build a network of "Chinese materia medica-active component-potential target". CytoNCA plug-in was used to analyze PPI network topology. Metascape was used for GO and KEGG pathway enrichment analyses. Finally, AutoDock Vina 1.5.6 software was applied to construct molecular docking between the active components and potential core targets. Resuls A total of 135 active components of Yangxue Qingnao Granule were screened and 186 potential targets of Yangxue Qingnao Granule against VaD were obtained. GO function enrichment analysis found protein kinase binding, transcription factor binding and other biological functions. KEGG pathway enrichment analysis identified PI3K-Akt signaling pathway, AGE-RAGE signaling pathway, TNF signaling pathway, etc. Molecular docking showed that the main active components of Yangxue Qingnao Granule had good binding activity with the potential targets. Conclusion:Yangxue Qingnao Granule has the characteristics of multi-targets and multi- pathways in the treatment of VaD. It may play a therapeutic role in VaD by inhibiting neuronal apoptosis and reducing inflammatory response.

Electroacupuncture alleviates postoperative pain through inhibiting neuroinflammation via stimulator of interferon genes/type-1 interferon pathway / 中西医结合学报

OBJECTIVE@#This work explores the impact of electroacupuncture (EA) on acute postoperative pain (APP) and the role of stimulator of interferon genes/type-1 interferon (STING/IFN-1) signaling pathway modulation in the analgesic effect of EA in APP rats.@*METHODS@#The APP rat model was initiated through abdominal surgery and the animals received two 30 min sessions of EA at bilateral ST36 (Zusanli) and SP6 (Sanyinjiao) acupoints. Mechanical, thermal and cold sensitivity tests were performed to measure the pain threshold, and electroencephalograms were recorded in the primary somatosensory cortex to identify the effects of EA treatment on APP. Western blotting and immunofluorescence were used to examine the expression and distribution of proteins in the STING/IFN-1 pathway as well as neuroinflammation. A STING inhibitor (C-176) was administered intrathecally to verify its role in EA.@*RESULTS@#APP rats displayed mechanical and thermal hypersensitivities compared to the control group (P < 0.05). APP significantly reduced the amplitude of θ, α and γ oscillations compared to their baseline values (P < 0.05). Interestingly, expression levels of proteins in the STING/IFN-1 pathway were downregulated after inducing APP (P < 0.05). Further, APP increased pro-inflammatory factors, including interleukin-6, tumor necrosis factor-α and inducible nitric oxide synthase, and downregulated anti-inflammatory factors, including interleukin-10 and arginase-1 (P < 0.05). EA effectively attenuated APP-induced painful hypersensitivities (P < 0.05) and restored the θ, α and γ power in APP rats (P < 0.05). Meanwhile, EA distinctly activated the STING/IFN-1 pathway and mitigated the neuroinflammatory response (P < 0.05). Furthermore, STING/IFN-1 was predominantly expressed in isolectin-B4- or calcitonin-gene-related-peptide-labeled dorsal root ganglion neurons and superficial laminae of the spinal dorsal horn. Inhibition of the STING/IFN-1 pathway by intrathecal injection of C-176 weakened the analgesic and anti-inflammatory effects of EA on APP (P < 0.05).@*CONCLUSION@#EA can generate robust analgesic and anti-inflammatory effects on APP, and these effects may be linked to activating the STING/IFN-1 pathway, suggesting that STING/IFN-1 may be a target for relieving APP. Please cite this article as: Ding YY, Xu F, Wang YF, Han LL, Huang SQ, Zhao S, Ma LL, Zhang TH, Zhao WJ, Chen XD. Electroacupuncture alleviates postoperative pain through inhibiting neuroinflammation via stimulator of interferon genes/type-1 interferon pathway. J Integr Med. 2023; 21(5): 496-508.

Effect of wheat-grain moxibustion on Wnt/β-catenin signaling pathway in bone marrow cell in mice with bone marrow inhibition / 中国针灸

OBJECTIVE@#To observe the effect of wheat-grain moxibustion at "Dazhui" (GV 14), "Zusanli" (ST 36) and "Sanyinjiao" (SP 6) on Wnt/β-catenin signaling pathway in bone marrow cell in mice with bone marrow inhibition, and to explore the possible mechanism of wheat-grain moxibustion in treating bone marrow inhibition.@*METHODS@#Forty-five SPF male CD1(ICR) mice were randomly divided into a blank group, a model group and a wheat-grain moxibustion group, 15 mice in each group. The bone marrow inhibition model was established by intraperitoneal injection of 80 mg/kg of cyclophosphamide (CTX). The mice in the wheat-grain moxibustion group were treated with wheat-grain moxibustion at "Dazhui" (GV 14), "Zusanli" (ST 36) and "Sanyinjiao" (SP 6), 3 moxa cones per acupoint, 30 s per moxa cone, once a day, for 7 consecutive days. The white blood cell count (WBC) was measured before modeling, before intervention and 3, 5 d and 7 d into intervention. After intervention, the general situation of mice was observed; the number of nucleated cells in bone marrow was detected; the serum levels of interleukin-3 (IL-3), interleukin-6 (IL-6) and granulocyte macrophage colony stimulating factor (GM-CSF) were measured by ELISA; the protein and mRNA expression of β-catenin, cyclinD1 and C-Myc in bone marrow cells was measured by Western blot and real-time PCR method.@*RESULTS@#Compared with the blank group, the mice in the model group showed sluggish reaction, unstable gait, decreased body weight, and the WBC, number of nucleated cells in bone marrow as well as serum levels of IL-3, IL-6, GM-CSF were decreased (P<0.01), and the protein and mRNA expression of β-catenin, cyclinD1 and C-Myc was decreased (P<0.01). Compared with the model group, the mice in the wheat-grain moxibustion group showed better general condition, and WBC, the number of nucleated cells in bone marrow as well as serum levels of IL-3, IL-6, GM-CSF were increased (P<0.01, P<0.05), and the protein and mRNA expression of β-catenin, cyclinD1 and C-Myc was increased (P<0.05).@*CONCLUSION@#Wheat-grain moxibustion shows therapeutic effect on bone marrow inhibition, and its mechanism may be related to activating Wnt/β-catenin signaling pathway in bone marrow cells, improving bone medullary hematopoiesis microenvironment and promoting bone marrow cell proliferation.

Differences in clinicopathological features, gene mutations, and prognosis between primary gastric and intestinal gastrointestinal stromal tumors in 1061 patients / 中华胃肠外科杂志

Objective: To analyze the clinicopathological features and gene mutations of primary gastrointestinal stromal tumors (GISTs) of the stomach and intestine and the prognosis of intermediate- and high-risk GISTs. Methods: This was a retrospective cohort study. Data of patients with GISTs admitted to Tianjin Medical University Cancer Institute and Hospital from January 2011 to December 2019 were collected retrospectively. Patients with primary gastric or intestinal disease who had undergone endoscopic or surgical resection of the primary lesion and were confirmed pathologically as GIST were included. Patients treated with targeted therapy preoperatively were excluded. The above criteria were met by 1061 patients with primary GISTs, 794 of whom had gastric GISTs and 267 intestinal GISTs. Genetic testing had been performed in 360 of these patients since implementation of Sanger sequencing in our hospital in October 2014. Gene mutations in KIT exons 9, 11, 13, and 17 and PDGFRA exons 12 and 18 were detected by Sanger sequencing. The factors investigated in this study included: (1) clinicopathological data, such as sex, age, primary tumor location, maximum tumor diameter, histological type, mitotic index (/5 mm2), and risk classification; (2) gene mutation; (3) follow-up, survival, and postoperative treatment; and (4) prognostic factors of progression-free survival (PFS) and overall survival (OS) for intermediate- and high-risk GIST. Results: (1) Clinicopathological features: The median ages of patients with primary gastric and intestinal GIST were 61 (8-85) years and 60 (26-80) years, respectively; The median maximum tumor diameters were 4.0 (0.3-32.0) cm and 6.0 (0.3-35.0) cm, respectively; The median mitotic indexes were 3 (0-113)/5 mm² and 3 (0-50)/5 mm², respectively; The median Ki-67 proliferation indexes were 5% (1%-80%) and 5% (1%-50%), respectively. The rates of positivity for CD117, DOG-1, and CD34 were 99.7% (792/794), 99.9% (731/732), 95.6% (753/788), and 100.0% (267/267), 100.0% (238/238), 61.5% (163/265), respectively. There were higher proportions of male patients (χ²=6.390, P=0.011), tumors of maximum diameter > 5.0 cm (χ²=33.593, P<0.001), high-risk (χ²=94.957, P<0.001), and CD34-negativity (χ²=203.138, P<0.001) among patients with intestinal GISTs than among those with gastric GISTs. (2) Gene mutations: Gene mutations were investigated in 286/360 patients (79.4%) with primary gastric GISTs and 74/360 (20.6%) with primary intestinal GISTs. Among the 286 patients with gastric primary GISTs, 79.4% (227/286), 8.4% (24/286), and 12.2% (35/286), had KIT mutations, PDGFRA mutations, and wild-type, respectively. Among the 74 patients with primary intestinal GISTs, 85.1% (63/74) had KIT mutations and 14.9% (11/74) were wild-type. The PDGFRA mutation rate was lower in patients with intestinal GISTs than in those with gastric GISTs[ 0% vs. 8.4%(24/286), χ²=6.770, P=0.034], whereas KIT exon 9 mutations occurred more often in those with intestinal GISTs [22.2% (14/63) vs. 1.8% (4/227), P<0.001]. There were no significant differences between gastric and intestinal GISTs in the rates of KIT exon 11 mutation type and KIT exon 11 deletion mutation type (both P>0.05). (3) Follow-up, survival, and postoperative treatment: After excluding 228 patients with synchronous and metachronous other malignant tumors, the remaining 833 patients were followed up for 6-124 (median 53) months with a follow-up rate of 88.6% (738/833). None of the patients with very low or low-risk gastric (n=239) or intestinal GISTs (n=56) had received targeted therapy postoperatively. Among 179 patients with moderate-risk GISTs, postoperative targeted therapy had been administered to 88/155 with gastric and 11/24 with intestinal GISTs. Among 264 patients with high-risk GISTs, postoperative targeted therapy had been administered to 106/153 with gastric and 62/111 with intestinal GISTs. The 3-, 5-, and 10-year PFS of patients with gastric or intestinal GISTs were 96.5%, 93.8%, and 87.6% and 85.7%, 80.1% and 63.3%, respectively (P<0.001). The 3-, 5-, and 10-year OS were 99.2%, 98.8%, 97.5% and 94.8%, 92.1%, 85.0%, respectively (P<0.001). (4) Analysis of predictors of intermediate- and high-risk GISTs: The 5-year PFS of patients with gastric and intestinal GISTs were 89.5% and 73.2%, respectively (P<0.001); The 5-year OS were 97.9% and 89.3%, respectively (P<0.001). Multivariate analysis showed that high risk (HR=2.918, 95%CI: 1.076-7.911, P=0.035) and Ki-67 proliferation index > 5% (HR=2.778, 95%CI: 1.389-5.558, P=0.004) were independent risk factors for PFS in patients with intermediate- and high-risk GISTs (both P<0.05). Intestinal GISTs (HR=3.485, 95%CI: 1.407-8.634, P=0.007) and high risk (HR=3.753,95%CI:1.079-13.056, P=0.038) were independent risk factors for OS in patients with intermediate- and high-risk GISTs (both P<0.05). Postoperative targeted therapy was independent protective factor for PFS and OS (HR=0.103, 95%CI: 0.049-0.213, P<0.001; HR=0.210, 95%CI:0.078-0.564,P=0.002). Conclusions: Primary intestinal GIST behaves more aggressively than gastric GISTs and more frequently progress after surgery. Moreover, CD34 negativity and KIT exon 9 mutations occur more frequently in patients with intestinal GISTs than in those with gastric GISTs.

Effects of 3, 4-divanillyltetrahydrofuran from Urtica fissa on sexual dysfunction in diabetic mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Urtica fissa E. Pritz. are important herbs and have been traditionally used as ethnic medicine to treat rheumatism, inflammation, diabetes, and benign prostatic hyperplasia by the Han, Uighur, and other minorities in China, and also as an aphrodisiac in Uighur medicine. AIMS OF THE STUDY: To determine the effect and potential mechanism of 3, 4-divanillyltetrahydrofuran (DVTF), one of the main active components isolated from U. fissa on hypogonadism in diabetic mice. MATERIALS AND METHODS: The active compound DVTF was extracted and separated from the roots of U. fissa and identified using mass spectrometry and nuclear magnetic resonance spectroscopy. A mouse model of diabetes was established using high fat and sugar diet combined with streptozotocin. In the treatment groups, mice were received different doses of DVTF for 4 weeks. Fasting blood glucose levels, physiological and biochemical indices, and the mating behavior of DM mice were analyzed. Changes in testicular morphology were assessed using light microscopy and transmission electron microscopy. The expression of testosterone synthesis-related signaling proteins was detected using western blotting. Molecular docking was used to determine the binding ability of DVTF to Nur77. RESULTS: In diabetic mice, body weight and fasting blood glucose levels decreased. Mating behavior, including mount latency, mount number, and intromission number, was improved following DVTF treatment. Plasma total testosterone, free testosterone, and insulin resistance were positively associated with the recovery of testicular pathological structures in diabetic mice. DVTF treatment increased the expression of Nur77, StAR, and P450scc in the testes of diabetic mice. DVTF and Nur77 formed chemical bonds at five sites. CONCLUSION: As one of the main active components of U. fissa, DVTF exert potential therapeutic effects on testicular injury and hypogonadism caused by diabetes through activating the expression of Nur77 and testosterone synthesis related proteins. Our result will provide new insight for the clinical application of Urtica fissa E. Pritz., especially DVTF, as a potential drug candidate in the treatment of hypogonadism in diabetes.

Comparison of different feature extraction methods for applicable automated ICD coding.

BACKGROUND: Automated ICD coding on medical texts via machine learning has been a hot topic. Related studies from medical field heavily relies on conventional bag-of-words (BoW) as the feature extraction method, and do not commonly use more complicated methods, such as word2vec (W2V) and large pretrained models like BERT. This study aimed at uncovering the most effective feature extraction methods for coding models by comparing BoW, W2V and BERT variants. METHODS: We experimented with a Chinese dataset from Fuwai Hospital, which contains 6947 records and 1532 unique ICD codes, and a public Spanish dataset, which contains 1000 records and 2557 unique ICD codes. We designed coding tasks with different code frequency thresholds (denoted as [Formula: see text]), with a lower threshold indicating a more complex task. Using traditional classifiers, we compared BoW, W2V and BERT variants on accomplishing these coding tasks. RESULTS: When [Formula: see text] was equal to or greater than 140 for Fuwai dataset, and 60 for the Spanish dataset, the BERT variants with the whole network fine-tuned was the best method, leading to a Micro-F1 of 93.9% for Fuwai data when [Formula: see text], and a Micro-F1 of 85.41% for the Spanish dataset when [Formula: see text]. When [Formula: see text] fell below 140 for Fuwai dataset, and 60 for the Spanish dataset, BoW turned out to be the best, leading to a Micro-F1 of 83% for Fuwai dataset when [Formula: see text], and a Micro-F1 of 39.1% for the Spanish dataset when [Formula: see text]. Our experiments also showed that both the BERT variants and BoW possessed good interpretability, which is important for medical applications of coding models. CONCLUSIONS: This study shed light on building promising machine learning models for automated ICD coding by revealing the most effective feature extraction methods. Concretely, our results indicated that fine-tuning the whole network of the BERT variants was the optimal method for tasks covering only frequent codes, especially codes that represented unspecified diseases, while BoW was the best for tasks involving both frequent and infrequent codes. The frequency threshold where the best-performing method varied differed between different datasets due to factors like language and codeset.

Analysis of clinicopathological features, gene mutation characteristics and prognosis of 228 cases of primary gastrointestinal stromal tumor of small intestine / 中华消化杂志

Objective:To analyze the clinicopathological features, gene mutation characteristics, and prognostic related factors of patients with primary gastrointestinal stromal tumor (GIST) of small intestine.Methods:From January 1, 2011 to December 30, 2019, surgical resected and pathological diagnosed small intestinal GIST without preoperative adjuvant therapy, at Tianjin Medical University Cancer Institute & Hospital were retrospectively collected. The mutational status of KIT exons 9, 11, 13, and 17 and platelet-derived growth factor receptor alpha ( PDGFRA) exons 12 and 18 were detected by polymerase chain reaction and Sanger direct sequencing. Clinicopathological features and gene mutation characteristics were analyzed. Pearson chi-square test and Bonferroni continuous correction test were used to compare the categorical variables among groups. Kaplan-Meier method and log-rank test were used for univariate survival analysis. The multivariate Cox proportional hazards regression model was used for multivariate survival analysis. Results:The proportions of patients with maximum tumor diameter> 10.0 cm and high-risk GIST located in the jejunum and ileum were higher than those of patients with primary GIST located in the duodenum (18.7%, 28/150 vs. 6.4%, 5/78; 56.7%, 85/150 vs. 43.6%, 34/78), and the differences were statistically significant ( χ2=14.67 and 12.46, P=0.002 and 0.006). The results of gene detection of 58 cases of small intestinal GIST indicated that the percentage of KIT gene mutant and wild type accounted for 84.5% (49/58) and 15.5% (9/58), among which 34 cases (69.4%), 12 cases (24.5%), 2 cases (4.1%) and 1 case (2.0%) were KIT gene exons 11, 9, 13 and 17 mutations, respectively, and none of the case with PDGFRA mutation. The 3-, 5-, and 10-year progression-free survival rates of the patients with small intestinal GIST were 88.1%, 85.0%, and 68.3%, respectively, and the 3-, 5-, and 10-year overall survival rates were 96.6%, 94.5%, and 86.1%, respectively. The results of univariate survival analysis showed that the progression-free survival rate and overall survival rate of patients with very low-risk and low-risk GIST were higher than those of patients with intermediate-risk and high-risk GIST (100.0%, 49/49 vs. 72.3%, 81/112; 100.0%, 49/49 vs. 89.3%, 100/112, respectively), and the differences were statistically significant ( χ2=14.07 and 4.92, P<0.001、=0.027). The results of univariate survival analysis of patients with intermediate-risk and high-risk GIST showed that the epithelioid cell type, mitotic index >5/5 mm 2, Ki-67 proliferation index >5%, and without postoperative adjuvant therapy were all related with progression-free survival time, and the differences were statistically significant ( χ2=8.39, 5.53, 13.73 and 15.44, P=0.004、0.019、<0.001、<0.001). Without postoperative adjuvant therapy was related with poor overall survival time ( χ2=7.06, P=0.008). The results of univariate analysis in patients with intermediate-risk and high-risk GIST and without postoperative adjuvant therapy showed that the epithelioid cell type, high-risk, mitotic index >5/5 mm 2 and Ki-67 proliferation index >10% were all related with progression-free survival time, and the differences were statistically significant ( χ2=10.08, 6.51, 10.37 and 15.72, P=0.001、0.011、0.001、<0.001). The results of multivariate analysis indicated that Ki-67 proliferation index >5% ( HR=5.018, 95% confidence interval(95% CI) 1.745 to 14.430, P=0.003) and without postoperative adjuvant treatment ( HR=0.145, 95% CI 0.051 to 0.414, P<0.001) were independent risk factors of postoperative tumor progression in patients with small intestinal intermediate-risk and high-risk GIST. Ki-67 proliferation index>10% ( HR=8.381, 95% CI 1.364 to 51.487, P=0.022) was an independent risk factor of postoperative tumor progression in patients with small intestinal intermediate-risk and high-risk GIST and without postoperative adjuvant treatment. Conclusions:The most common mutation in small intestinal primary GIST is KIT mutation, followed by wild type, no case of PDGFRA gene mutation has been found. High Ki-67 proliferation index can predict poor prognosis of patients with moderate-risk and high-risk small intestinal primary GIST. Postoperative adjuvant therapy can significantly improve the prognosis of patients with small intestinal intermediate-risk and high-risk primary GIST.

Inhibition of Metformin Combined with Cisplatin on Proliferation of Human Osteosarcoma MG-63 Cells / 中国生物化学与分子生物学报

In order to study the effect and its potential mechanism of metformin combined with cisplatin treatment on human osteosarcoma MG-63 cells, MG-63 cells were treated with metformin and cisplatin and the cell proliferation and apoptosis were detected using CCK8 and flow cytometry; Cell clone formation experiment was performed to detect clone formation rate in each group; Trans well experiment was used to detect the migration and invasion ability of osteosarcoma MG-63 cells, and qPCR and Western blot were used to detect the expression of RNA and protein of apoptosis-related genes. The results showed that metformin combined with cisplatin inhibited the proliferation of human osteosarcoma MG-63 cells and promoted their apoptosis significantly (P < 0. 01); Metformin combined with cisplatin inhibited the clone formation (P < 0. 01), and the migration and invasion of human osteosarcoma MG-63 cells (P < 0. 01); Furthermore, metformin combined with cisplatin down-regulated the expression of apoptosis-related genes MCl￣1and XIAP (P <0. 01), but up-regulated the expression of apoptosis-related genes CASPASE￣3 and Cyto C (P <0. 01) and migration and invasion related genes MMP￣2 and MMP￣9 (P <0. 01). Our study indicated that metformin combined with cisplatin inhibited proliferation, promoted cell apoptosis through MCl￣1 and XIAP, and inhibited cell migration and invasion by regulating the MMP￣2 and MMP￣9 pathways in human osteosarcoma MG-63 cells.

Interaction of smoking and being bullied on suicidal behaviors: a school-based cross-sectional survey in China

BACKGROUND@#Suicidal behaviors are seriously social issues among adolescents in the world. Exposed to smoking and being bullied are risk factors of suicidal behaviors. The present study was aimed to examine the interaction of smoking and being bullied on suicidal behaviors among Chinese adolescents.@*METHODS@#A total of 18,900 students were involved in the questionnaire study, in four cities of China from November 2017 to January 2018. Suicidal behaviors, smoking, and being bullied were measured by self-reported validated instruments. Chi-square tests and logistic regression were used to analyze the associations of suicidal ideation (SI)/suicidal plan (SP)/suicidal attempt (SA), smoking, and being bullied.@*RESULTS@#The prevalence of smoking, being bullied, SI/SP/SA, were 3.1%, 20.6%, 26.4%, 13.2%, and 5.2% respectively. Interaction analysis indicated that being bullied was associated with a greater increase in the likelihood of suicidal behaviors for adolescents with smoking than for those without smoking.@*CONCLUSIONS@#These finding suggest that smoking exacerbates the association between being bullied and suicidal behaviors. Future research should explore how and why smoking appears to more bully-victims than for those without smoking and how to mitigate it.

Association of status of mismatch repair protein expression and EB virus infection with clinicopathological parameters in 886 gastric adenocarcinoma patients / 中华胃肠外科杂志

Objective: To analyze the expression of mismatch repair (MMR) protein and the EB virus infection in gastric adenocarcinoma, and to examine the association of MMR expression and EB virus infection with clinicopathological parameters. Methods: A case-control study was performed. Clinicopathological data of patients who was pathologically diagnosed as gastric adenocarcinoma, received radical gastrectomy and had complete clinicopathological data from August 2017 to April 2020 in Tianjin Medical University Cancer Institute and Hospital were retrospectively collected and analyzed. The immunohistochemistry (IHC) of MMR proteins and in situ hybridization (ISH) of Epstein-Barr virus encoded RNA (EBER) were reviewed. The associations of MMR and EBER results with clinicopathological parameters were analyzed. The main observations of the study were MMR and EBER expression, and association of MMR and EBER results with clinicopathological parameters. Results: Eight hundred and eighty-six patients were enrolled, including 98 patients who received preoperative neoadjuvant chemoradiotherapy. Of 886 patients, 613 (69.2%) were males and the median age was 60 (22-83) years; 831 (93.8%) were mismatch repair proficiency (pMMR), and 55 (6.2%) were mismatch repair deficiency (dMMR). In dMMR group, 47 cases (85.5%) had the deficiency of both MLH1 and PMS2, 1 case (1.8%) had the deficiency of both MSH2 and MSH6, 4 cases (7.3%) had the deficiency only in PMS2, 2 cases (3.6%) had the deficiency only in MSH6, and 1 case (1.8%) had the deficiency only in MSH2. The deficiency rates of PMS2, MLH1, MSH6 and MSH2 were 5.8% (51/886), 5.3% (47/886), 0.3% (3/886) and 0.2% (2/886), respectively. Among the 871 cases with EBER results, 4.9% (43/871) were positive EBER. Univariate analysis showed that dMMR was more frequently detected in female patients (χ(2)=10.962, P=0.001), cancer locating in the antrum (χ(2)=9.336,P=0.020), Lauren intestinal type (χ(2)=9.718, P=0.018), stage T3 (χ(2)=25.866, P<0.001) and TNM stage II (χ(2)=15.470, P=0.002). The ratio of dMMR was not significantly associated with age, tumor differentiation, histological type, lymph node metastasis, distant metastasis or Her-2 immunohistochemical score (all P>0.05). Compared with negative EBER, positive EBER was more frequent in male patients (χ(2)=9.701, P=0.002), cancer locating in gastric fundus and corpus (χ(2)=17.964, P<0.001), gastric cancer with lymphoid stroma (χ(2)=744.073, P<0.001) and poorly differentiated cancer (χ(2)=13.739, P=0.010). Positive EBER was not significantly associated with age, depth of invasion, lymph node metastasis, distant metastasis, TNM stage or Her-2 immunohistochemical score (all P>0.05). In addition, all dMMR cases were EBER negative, and all cases of positive EBER were pMMR. Conclusions: The positive EB virus status is mutually exclusive with dMMR, indicating that different molecular subtypes of gastric adenocarcinoma are involved in different molecular pathways in tumorigenesis and progression. The overlapping of dMMR or positive EBER status and positive Her-2 expression is found in some cases of gastric adenocarcinoma. Patients with gastric adenocarcinoma after radical surgery should be tested for MMR status if they are female, the tumor locates in gastric antrum, the TNM staging is stage II or T3, or if the Lauren classification is intestinal type. And if patients are male, the tumor locates in the gastric fundus and corpus, the cancer is lymphoid stroma, or poor differentiated, the expression of EBER should be detected. Results of our study may provide evidence for further decision-making of clinical treatment.

The clinical value of combined 68Ga-SSA/18F-FDG PET/CT imaging in neuroendocrine neoplasms / 中华核医学与分子影像杂志

Neuroendocrine neoplasms (NEN) are tumors that originate from neuroendocrine cells or peptidergic neurons.NEN can be found in a variety of organs with high heterogeneity in pathology and large difference in prognosis.Conventional imaging methods and pathological biopsy have important roles in the diagnosis of NEN,while both of them have limitations.Most NEN cells highly express several peptide receptors,especially somatostatin receptors (SSTR).Moreover,some of them have high glycolysis activity because of high proliferative activity.68Ga-somatostatin analogs (68Ga-SSA) combined with 18F-fluorodeoxyglucose (18F-FDG) PET/CT imaging can comprehensively evaluate both the expression of SSTR and the activity of glycolysis in NEN,providing effective information for diagnosis,treatment,monitoring and prognosis.This review summarizes the current studies of combined 68Ga-SSA/18F-FDG PET/CT imaging in patients with NEN.

Characteristics of amplitude of low frequency fluctuations in the frontal lobe in depression patients with different sleep quality and its relationship with memory function / 中华行为医学与脑科学杂志

Objective:To explore the association between the spontaneous neural activity and memory function in depressive patients with different sleep quality.Methods:Totally 58 patients with depressive disorder and 58 gender-, age-, education-matched healthy controls (HC) completed 3.0 T MRI Scanning and clinical assessment including Wechsler memory scale (WMS), 24 Hamilton depression scale(HAMD-24) and Pittsburgh sleep quality index (PSQI). According to the score of PSQI, patients were divided into poor sleep quality group (PS, n=38) and good sleep quality group (GS, n=20). Amplitude of low frequency fluctuations (ALFF) were calculated and compared among three groups.Correlation analyses between the brain activity and the score of WMS were conducted as well. Results:Memory quotient of WMS showed differences among three groups( F=14.163, P<0.01), and the lowest score was found in patients with low sleep quality.The brain areas showed significant differences among three groups located in the left medial superior frontal gyrus (lmSFG, MNI: x=-10, y=30, z=58; K=56), right orbital inferior frontal gyrus (roIFG, MNI: x=26, y=20, z=-26; K=24) and left middle frontal gyrus (lMFG, MNI: x=-40 y=32, z=42; K=25) (voxel size P<0.001, cluster size P<0.05, GRF corrected). Compared with GS group, the ALFF of PS group showed significantly increased in the lmSFG, which was negatively correlated with memory quotient ( r=-0.327, P=0.045) and short term memory( r=-0.388, P=0.016). Compared with HC group, the ALFF of PS group showed increased in the lmSFG and lMFG, GS group showed increased ALFF in the roIFG. Conclusion:The impairment of memory function is more serious in patients with depression of low sleep quality, and the activity of frontal lobe is abnormally increased, which is related to memory function.Their association suggests that poor sleep quality in depressive patients may impair memory function by disrupting neural plasticity and synaptic pruning in the frontal lobes.

Mathematical model construction and analysis of the effect of estradiol on the electrical activity of gastric antrum in female rabbits / 解剖学报

Objective To investigate the expression of estrogen receptor in gastric antrum and the effect of estrogen on electrical activity of gastric antrum smooth muscle in female rabbits in virtue of the constructed mathematical model in order to explore the regulation of estrogen on gastric motility. Methods Using immunofluorescence to observe the expression of estrogen receptor in gastric antrum. Using BL-420F bio monitor to monitor: Comparing the difference of antral electromyography index between rabbits in ovariectomized group and rabbits in sham operating group; Observing the dose-response relationship between doses of estradiol (0,0. 1,0. 15,0. 2,0. 25 and 0. 3 mg/ kg). To construct the mathematical model, and to analyze the dose-response relationship and mechanism of action. Rresult The expression of estrogen receptor in the antral wall of the stomach was negative. The activity index of gastric antrum myoelectric activity was significantly decreased after ovarian ablation (P<0. 01). With the increase of estradiol dose, the activity index of gastric antrum muscle increased and then decreased. Analysis of variance showed that the difference of antral electromyographic activity index between adjacent groups was significant (P<0. 05) or extremely significant (P<0. 01). Taking the estradiol dose as the independent variable x, the antral electromyography activity index was the dependent variable y, and the fitting wass obtained: y= 2. 80 + 5. 65 × exp{ -0. 5 × [(x-0. 159) / 0. 038 ]

Improved Research of Adjustable External Fixation Device for Lower Limbs Based on Semiconductor Refrigeration Sheet / 中国医疗器械杂志

A kind of adjustable external fixation device for lower extremity is designed. The circuit is mainly composed of TEC1-00703 semiconductor refrigeration chip, HZC-30A pressure sensor, STC89C52RC single chip microcomputer and other electrical components. It can realize the timing intelligent temperature control and meet the local fixed-point refrigeration. The design of adjustable structure and the application of intelligent air cushion can satisfy the full fixation of lower limbs of different individuals. Its operation does not need much medical knowledge. It can solve the problem of emergency transportation and follow-up treatment of lower limb injury in ice and snow sports. It has a good application prospect and universality.

The clinical value of combined 68Ga-SSA/18F-FDG PET/CT imaging in neuroendocrine neoplasms / 中华核医学与分子影像杂志

Neuroendocrine neoplasms (NEN) are tumors that originate from neuroendocrine cells or peptidergic neurons. NEN can be found in a variety of organs with high heterogeneity in pathology and large difference in prognosis. Conventional imaging methods and pathological biopsy have important roles in the diagnosis of NEN, while both of them have limitations. Most NEN cells highly express several peptide receptors, especially somatostatin receptors (SSTR). Moreover, some of them have high glycolysis activity because of high proliferative activity. 68Ga-somatostatin analogs (68Ga-SSA) combined with 18F-fluorodeoxyglucose (18F-FDG) PET/CT imaging can comprehensively evaluate both the expression of SSTR and the activity of glycolysis in NEN, providing effective information for diagnosis, treatment, monitoring and prognosis. This review summarizes the current studies of combined 68Ga-SSA/18F-FDG PET/CT imaging in patients with NEN.

Meta-analysis of the Correlation Between Schizophrenia and Breast Cancer.

PURPOSE: To determine the correlation between schizophrenia and breast cancer (BC). METHODS: We searched relevant articles indexed in the PubMed, Embase, and Cochrane Library databases; managed the data in Endnote X7 software; evaluated literature quality by Newcastle-Ottawa quality evaluation criteria; designed tables; and extracted relevant data. The main outcome measure was BC incidence. Effect values were risk ratio and 95% confidence intervals. We used Stata 13.1 software to perform the meta-analysis, choosing a corresponding combination model according to heterogeneity test results and carrying out subgroup analyses in order to better understand the stability of results through sensitivity analysis. RESULTS: On the basis of 15 studies that assessed patients in different geographic regions, meta-analysis results showed that BC incidence between the exposure group (patients with schizophrenia) and the control group (nonschizophrenia population or general population) had statistical difference (risk ratio = 1.18; 95% confidence interval, 1.05, 1.32), thus showing that BC incidence in patients with schizophrenia is higher than in the nonschizophrenia or general population. Subgroup analysis indicated that gender and geographic region may be sources of the assessed studies' heterogeneity. CONCLUSION: The incidence of schizophrenia is positively correlated with BC, and the incidence of BC in patients with schizophrenia is increased to a certain degree. Because of the effects of potential and publication bias, this conclusion needs more high-quality studies to increase the strength of evidence.

HIV-1 drug resistance and influencing factors among people living with HIV/AIDS before antiretroviral therapy in Liangshan Yi Autonomous Prefecture / 中华流行病学杂志

Objective@#To explore HIV-1 drug resistance and influencing factors among people living with HIV/AIDS before antiretroviral therapy in Liangshan Yi Autonomous Prefecture (Liangshan).@*Methods@#Between January 1 and June 30, in both 2017 and 2018, a cross-sectional survey was conducted in Liangshan HIV-1 pol sequences were gathered and analyzed according to WHO Guidelines on HIV drug resistance surveillance of 2014. Both HyPhy 2.2.4 and Cytoscape 3.6.1 software were used to analyze the drug resistant strains of HIV-1 transmission network.@*Results@#A total of 464 people living with HIV/AIDS was recruited. The proportion of HIV-1 CRF07_BC subtype was 88.6% (411/464), with HIV-1 drug resistance rate was 9.9% (46/464). The HIV-1 drug resistance rates of non-nucleoside reverse transcriptase inhibitors (NNRTI), nucleoside reverse transcriptase inhibitors(NRTI) and protease inhibitors (PI) were 6.7% (31/464), 1.9% (9/464) and 0.4% (2/464) respectively. New recombinant strains of HIV-1 URF_01BC subtype was independently clustered according to the drug resistant mutation sites. Results from the multivariate logistic analysis showed that injected drug users group had higher risk on HIV-1 drug resistance (aOR=3.03, 95%CI:1.40-6.54) than heterosexual group among people living with HIV/AIDS.@*Conclusions@#HIV-1 drug resistance rate had already been in a high level before antiretroviral therapy was in place. The newly identified recombinant strains of HIV-1 URF_01BC subtype were independently clustered according to the drug resistant mutation sites. It was necessary to strengthen the prevention of the HIV-1 drug resistant strains transmission.

Effect of Shugan Wendan Decoction on LXRα, NF-кB and Endothelial Function in Atherosclerosis Rabbits / 中国实验方剂学杂志

Objective:To investigate the mechanism of Shugan Wendan decoction in treating atherosclerosis based on liver X receptor α(LXRα)/nuclear factor-κB(NF-κB) signal. Method:A New Zealand rabbit model of atherosclerosis with liver-Qi stagnation was established by using calf serum albumin immune injury, high fat feeding and bondage emotional stress method. Theses rabbits are randomly divided into 6 groups, control group,model group, atorvastatin group, Shugan Wendan decoction low, medium and high dose group(2.18,6.54,19.62 g·kg-1·d-1). After successful modeling, the rabbits were treated by injecting drugs with Atorvastatin and low, middle and high dose Shugan Wendan decoction to gastric.The control group and the model group were given intragastric administration of saline in the same volume. The period of gavage is 6 weeks. The pathological changes of the rabbits were detected by hematoxylin-eosin(HE) staining.Serum levels of totalcholesterol(TC), triglyceride(TG),low density extremityprotein(LDL-C), high density extremity protein(HDL-C), nitric oxide(NO), and endothelin-1(ET-1) of the rabbits were detected by enzyme method, nitrate reductase method, and enzyme-linked immunosorbent assay(ELISA), respectively.The gene expression of CRP, IL-1β, IL-6 and MMP-9 in the aorta was detected by Real-time fluorescent quantitative polymerase chain reaction(Real-time PCR) method.The protein expression of LXRα/NF-κB signaling pathway wasdetected by Western blot. Result:Compared with normal control group, in model group, the lumen of the blood vessels was significantly narrowed, atheromatous plaques were formed, and a large number of intracellular foam-like changes were seen. In atorvastatin group and Shugan Wendan decoction group, the blood vessels in high, middle, and low concentration groups were narrowed. Atherosclerotic plaques and foam-like changes were all lower than the model group.Compared with the normal control group, the TG, TC, and LDL-C levels in the model groupincreased(PPPPβ, IL-6 and MMP-9 all increased(Pα protein in the model group was decreased(PκB was increased(PPPβ, IL-6 and MMP-9 in the atorvastatin group,the low, middle and high dose Shugan Wendan decoction groups all decreased(Pα protein in the group was increased(PκB was decreased(PConclusion:Shugan Wendan decoction can inhance the function of vascular endothelial cells and the stability of atherosclerotic plaque by regulating LXRα/NF-κB signaling pathway.