Clinical study on effect of Shumu Peitu herb-partitioned moxibustion on diarrhea-predominant irritable bowel syndrome and negative emotions / 中国实用护理杂志

Objective:To explore the intervention effect of Shumu Peitu herb-partitioned moxibustion on clinical signs and symptoms and negative emotions of diarrhea-predominant irritable bowel syndrome (IBS-D) patients with liver-stagnation and spleen-deficiency pattern.Methods:A total of 72 patients with IBS-D of liver-stagnation and spleen-deficiency pattern treated in the Department of Gastroenterology of Nanjing Vniversity of Chinese Medicine from September 2021 to June 2022 were selected for randomized controlled trial. The patients were randomly divided into the observation group (2 cases dropped off, 34 cases in total) and control group (1 case dropped off, 35 cases in total) by random number table method. The patients in control group were treated with Tongxieyaofang (TXYF). The patients in observation group were treated with oral administration of TXYF and Shumu Peitu herb-partitioned moxibustion, and both groups were treated for 4 weeks. The clinical efficacy, Traditional Chinese Medicine (TCM) syndrome integral, IBS Quality of Life Questionnaire (IBS-QOL), IBS Symptom Severity Scale (IBS-SSS), Bristol Stool Form Scale and Hospital Anxiety and Depression Scale (HADS) were compared before and after treatment.Results:After treatment, the total effective rate of the observation group was 94.12%(32/34), which was higher than the 71.43%(25/35) in the control group, the difference was significant ( χ2 = 6.18, P<0.05). After treatment, the TCM syndrome integral in the observation group was (7.62 ± 4.08), which was lower than the (9.89 ± 4.71) in the control group, the difference was significant ( t = 2.14, P<0.05). After treatment of 3 days, the scores of quality of life in the five dimensions of dysthymia, behavior disorder, health worry, avoidance of eating and social function in the observation group were (82.44 ± 11.46), (80.25 ± 11.67), (76.23 ± 12.67), (59.80 ± 15.14) and (79.23 ± 11.59) points, which were different with the (73.57 ± 12.39), (72.35 ± 15.48), (69.76 ± 13.11), (50.00 ± 16.17) and (73.04 ± 13.11) points in the control group, the difference were significant ( t values were -3.09 - -2.08, all P<0.05). Three days after treatment, the score of IBS-SSS and Bristol fecal character in the observation group were (118.24 ± 40.64) and (5.09 ± 0.62) points, which were lower than the (146.86 ± 60.09) and (5.51 ± 0.66) points in the control group, the difference were significant ( t = 2.31 and 2.76, both P<0.05). After treatment, the score of HADS-A and HADS-D in the observation group were (6.26 ± 1.75) and (5.29 ± 1.47), which were different with the (7.26 ± 2.19) and (6.17 ± 2.11) in the control group, the difference were significant ( t = 2.08 and 2.00, both P<0.05). Conclusions:Shumu Peitu herb-partitioned moxibustion can effectively improve IBS-D patients with liver-stagnation and spleen-deficiency pattern, relieve clinical symptoms, reduce negative emotions, and improve quality of life.

Study on the mechanism of Kangmin Zhisou Granules in the treatment of bronchial asthma based on network pharmacology and animal experiments / 国际中医中药杂志

Objective:To deeply explore the potential mechanism of Kangmin Zhisou Granules in the treatment of bronchial asthma through network pharmacology method; To verify it with animal experiments.Methods:The active components and corresponding target information of Kangmin Zhisou Granules were screened with the help of BATMAN-TCM database, and the related disease targets of bronchial asthma were obtained through GeneCards and OMIM databases. The drug targets and bronchial asthma targets were intersected and imported String database was used to establish PPI network. Cytoscape 3.9.1 software was used to draw the network diagram of "Chinese materia medica-active components-intersection targets" and the core targets were screened. GO and KEGG enrichment analysis was performed on the core targets using DAVID database. A mouse model of asthma induced by ovalbumin was prepared. After the intervention of Kangmin Zhisou Granules, the pathological changes of mouse lung tissue were observed, and the contents of serum TNF-α, IL-6, IL-1 β were detected by ELISA.Results:Totally 240 active components and 1 364 potential targets were obtained from Kangmin Zhisou Granules. Tumor necrosis factor (TNF), interleukin-6 (IL-6), protein kinase B (AKT1), albumin (ALB), interleukin 1-beta (IL-1β) and other 11 core targets were obtained after screening. The results of GO enrichment analysis showed that the treatment of bronchial asthma by Kangmin Zhisou Granules mainly involved the positive regulation of protein phosphorylation, the regulation of inflammatory response, lipopolysaccharide response and other biological processes, as well as TNF, activated protein kinase (MAPK), interleukin-17 (IL-17) and other signaling pathways. Animal experiments confirmed that Kangmin Zhisou Granules could reduce the expression levels of TNF-α, IL-6 and IL-1β in serum ( P<0.05), and reduce the infiltration of inflammatory cells in the lung tissue of mice, thereby relieving asthma symptoms. Conclusion:Kangmin Zhisou Granules may exert anti-inflammatory effects by acting on TNF-α, IL-6, IL-1β and other targets to alleviate asthma symptoms.

Research progress of autophagy in retinal and eye diseases / 国际眼科杂志(Guoji Yanke Zazhi)

Maintaining the homeostasis of intracellular components degradation and recycling, autophagy is a critical control mechanism of cellular quality. It promotes the degradation of cell components to provide nutrients and energy for cellular metabolism in stress response. The retina is a light-sensitive tissue that transduces and processes visual images in the eye, and it has a high demand for substances and energy. Basal autophagy is essential for holding retinal homeostasis and the normal function of the visual system. Therefore, the latest studies that investigating the participation of autophagy in eye diseases such as glaucoma, age-related macular degeneration, diabetic retinopathy, retinal dystrophies, and retinal detachment were summarized, providing a theoretical basis for the future treatment of eye diseases by regulating autophagy.

Analysis of high risk factors and establishment of risk score model for postpartum massive blood transfusion / 中国输血杂志

【Objective】 To screen the risk factors of severe postpartum hemorrhage that can be found at 32 weeks of pregnancy through univariate and multivariate analysis and establish the risk prediction diagram. 【Methods】 A retrospective analysis was performed on pregnant women who gave birth and received blood transfusion in Women's Hospital of Nanjing Medical University from 2019 to 2021. According to the blood transfusion volume during and after operation, the patients were divided into low/moderate transfusion group (transfusion volume <2 000 mL) and massive-transfusion group (transfusion volume ≥2 000 mL), and the basic information of puerperal, single high risk factor, measures of operation and use of blood preparations were recorded. The differences of physiological and pathological factors between the low/moderate transfusion group and the massive transfusion group were analyzed by univariate analysis. Multivariate analysis and nomogram were performed on the statistically significant factors to calculate the consumption of blood components and hemostatic measures in the massive transfusion group. 【Results】 There were significant differences in age, number of pregnancies, advanced age at first delivery, history of abortion, scar uterus, pernicious placenta previa, placenta accreta, eclampsia/pre-eclampsia and acquired coagulopathy between the low/moderate transfusion group (n=930) and the massive transfusion group (n=108) (P<0.05), among which the number of pregnancies, advanced age for the first delivery, pernicious placenta previa, placenta accreta, and eclampsia/pre-eclampsia were independent risk factors for severe postpartum hemorrhage at 32 weeks of gestation. The scores of risk factors for massive blood transfusion from high to low were placenta accreta, primiparity at advanced age, eclampsia/pre-eclampsia, pernicious placenta previa, number of pregnancies≥4 and scar uterus. 【Conclusion】 The possibility of severe postpartum hemorrhage can be accurately evaluated in the third trimester (around 32 weeks) by univariate analysis, multivariate analysis and nomogram drawing. Among the puerpera underwent blood transfusion, the risk factors for massive hemorrhage included pregnancies ≥4 times, primiparity at advanced age, pernicious placenta previa, placenta accreta, and eclampsia/pre-eclampsia. The model based on these factors has a good prediction effect on massive hemorrhage.

The effect of platelet infusion on the repair of bone marrow hematopoietic niche damage in mice induced by (60)Co radiation and hematopoietic reconstruction after bone marrow transplantation / 中华血液学杂志

Objective: To observe the effect of platelets on hematopoietic stem cell (HSCs) implantation in mice with radiation-induced bone marrow injury and bone marrow transplantation models. Methods: ①Male C57BL/6 mice were divided into a single irradiation group and a radiation infusion group after receiving (60)Co semimyeloablative irradiation for 18-10 weeks. The irradiation infusion group received 1×10(8) platelets expressing GFP fluorescent protein. ② The allogeneic bone marrow transplantation model was established. The experimental groups included the simple transplantation group (BMT) and the transplantation infusion group (BMT+PLT). The BMT group was infused through the tail vein only 5 × 10(6) bone marrow cells, the BMT+PLT group needs to be infused with bone marrow cells at the same time 1× 10(8) platelets. ③ Test indicators included peripheral blood cell and bone marrow cell counts, flow cytometry to detect the proportion of hematopoietic stem cell (HSC) and hematopoietic progenitor cells, bone marrow cell proliferation and apoptosis, and pathological observation of vascular niche damage and repair. Results: ①On the 3rd, 7th, 14(th), and 21st days after irradiation, the bone marrow cell count of the infusion group was higher than that in the single irradiation group (P<0.05), and the peripheral blood cell count was also higher. A statistically significant difference was found between the white blood cell count on the 21st day and the platelet count on the 7th day (P<0.05). In the observation cycle, the percentage of bone marrow cell proliferation in the infusion group was higher, while the percentage of apoptosis was lower. ② The results of bone tissue immunofluorescence after irradiation showed that the continuity of hematopoietic niche with red fluorescence was better in the irradiation infusion group. ③The chimerism percentage in the BMT+PLT group was always higher than that in the BMT group after transplantation.④ The BMT+PLT group had higher bone marrow cell count and percentage of bone marrow cell proliferation on the 7th and 28th day after transplantation than that in the BMT group, and the percentage of bone marrow cell apoptosis on the 14th day was lower than that in the BMT group (P<0.05). After the 14th day, the percentage of stem progenitor cells in the bone marrow cells of mice was higher than that in the BMT group (P<0.05). ⑤The immunohistochemical results of bone marrow tissue showed that the continuity of vascular endothelium in the BMT+PLT group was better than that in the BMT group. Conclusion: Platelet transfusion can alleviate the injury of vascular niche, promotes HSC homing, and is beneficial to hematopoietic reconstruction.

Research progress of m6A methylation in prostate cancer / 亚洲男科学杂志(英文版)

N6-methyladenosine (m6A) is a ubiquitous RNA modification in mammals. This modification is "written" by methyltransferases and then "read" by m6A-binding proteins, followed by a series of regulation, such as alternative splicing, translation, RNA stability, and RNA translocation. At last, the modification is "erased" by demethylases. m6A modification is essential for normal physiological processes in mammals and is also a very important epigenetic modification in the development of cancer. In recent years, cancer-related m6A regulation has been widely studied, and various mechanisms of m6A regulation in cancer have also been recognized. In this review, we summarize the changes of m6A modification in prostate cancer and discuss the effect of m6A regulation on prostate cancer progression, aiming to profile the potential relevance between m6A regulation and prostate cancer development. Intensive studies on m6A regulation in prostate cancer may uncover the potential role of m6A methylation in the cancer diagnosis and cancer therapy.

Value of albumin-related ratios in predicting the risk of death in patients with hepatitis B virus-related acute-on-chronic liver failure / 临床肝胆病杂志

‍ ObjectiveTo investigate and compare the value of albumin-related ratios ［total bilirubin-to-albumin ratio （TAR）， creatinine-to-albumin ratio （CAR）， prothrombin time-international normalized ratio-to-albumin ratio （IAR）， neutrophil count-to-albumin ratio （NAR）， and red blood cell distribution width-to-albumin ratio （RAR）］ in predicting the short-term prognosis of patients with hepatitis B virus-related acute-on-chronic liver failure （HBV-ACLF）. MethodsA retrospective analysis was performed for 354 patients with HBV-ACLF who were admitted to Department of Infectious Diseases， The Affiliated Hospital of Southwest Medical University， from June 2017 to February 2022， and according to their prognosis at 3 months of follow-up， they were divided into survival group （n=272） and death group （n=82）. Related indices were recorded for all patients， including age， sex， complications， and the results of routine blood test， liver function， and coagulation for the first time after admission， and albumin-related ratios and Model for End-Stage Liver Disease （MELD） score were calculated. The t-test was used for comparison of normally distributed continuous data between groups， and the Mann-Whitney U test was used for comparison of non-normally distribution continuous data between groups； the chi-square test was used for comparison of categorical data between groups. The Spearman correlation test was used to investigate the correlation between albumin-related ratios and MELD score. The Logistic regression analysis was used to explore the association of MELD score， TAR， CAR， IAR， NAR， and RAR with poor prognosis. The area under the ROC curve （AUC） was used to as sess the accuracy of albumin-related ratios and MELD score in predicting the short-term prognosis of HBV-ACLF patients， and the De-Long test was used for the comparison of AUC. ResultsCompared with the death group， the survival group had significantly lower MELD score （Z=-8.071， P<0.001）， TAR （Z=-6.695， P<0.001）， CAR （Z=-4.463， P<0.001）， IAR （Z=-7.912， P<0.001）， NAR （Z=-4.061， P<0.001）， and RAR （Z=-4.788， P<0.001）. MELD score was positively correlated with CAR （r=0.616， P<0.001）， IAR （r=0.733， P<0.001）， TAR （r=0.657， P<0.001）， NAR （r=0.392， P<0.001）， and RAR （r=0.380， P<0.001）. The multivariate regression analysis of MELD score and albumin-related ratios showed that high TAR （odds ratio ［OR］=1.014， 95% confidence interval ［CI］： 1.008 — 1.020， P<0.001） and high IAR （OR=22.052， 95%CI： 6.937 — 70.103， P<0.001） were independent risk factors for death. The ROC curves were plotted for albumin-related ratios and MELD score to evaluate their discriminatory ability for mortality， and the results showed that MELD score， TAR， CAR， IAR， NAR， and RAR had an AUC of 0.794， 0.744， 0.663， 0.788， 0.648， and 0.674， respectively， among which MELD score had the highest sensitivity of 86.59% and CAR had the highest specificity of 77.57%. TAR combined with IAR had an AUC of 0.809， with a sensitivity of 76.8% and a specificity of 71.3%. Subgroup analysis of HBV-ACLF showed that TAR combined with IAR had the highest AUC values of 0.884 and 0.733， respectively， in patients with type A or type C HBV-ACLF. ConclusionTAR and IAR can be used as simple and effective prognostic tools to predict the 90-day mortality of HBV-ACLF patients.

The effect of swallowing intervention on improving the esophageal examination by magnetically controlled capsule endoscopy: a cohort study / 中华消化杂志

Objective:To investigate the effect and feasibility of swallowing intervention on esophageal examination by magnetically controlled gastric capsule endoscope (MCE), and to provide theoretical evidence for clinical application.Methods:From January 2021 to May 2022, 196 subjects who underwent MCE examination at West China Hospital, Sichuan University were prospectively enrolled. According to the swallowing action during MCE procedure, the subjects were divided into routine examination control group and swallowing-controlled intervention group with 98 cases in each group. The data of gender, age, history of smoking and drinking, body mass index, clinical symptoms (abdominal pain or abdominal distension, hematochezia, melena or positive fecal occult-bloodtest), esophageal transit time of MCE and detection rate of esophageal lesions were compared between the 2 groups. Wilcoxon rank sum test and chi-square test were used for statistical analysis.Results:There were no significant differences in age, gender, smoking history, drinking history, body mass index, history of diabetes, history of hypertension, and indication of MCE examination between the routine examination control group and swallowing-controlled intervention group (all P>0.05). All the subjects successfully completed the examination, and the capsules were excreted from the body. The median esophageal transit time of swallowing-controlled intervention group was longer than that of the routine examination control group (44.50 s (26.75 s, 101.25 s) vs. 11.00 s (5.00 s, 29.00 s)), and the difference was statistically significant ( Z=-8.13, P<0.001). The esophageal transit time of the patients aged 40 to 59 years old was longer than that of the patients aged <40 years old, but shorter than that of the patients aged ≥60 years old (54.00 s (36.25 s, 64.75 s) vs. 28.00 s (23.00 s, 35.00 s) and 69.50 s (64.75 s, 73.00 s)), and the differences were statistically significant ( Z=-6.72 and -6.91, both P<0.001). The detection rate of esophageal lesions of swallowing-controlled intervention group was higher than that of routine examination control group (22.4%, 22/98 vs. 11.2%, 11/98), and the difference was statistically significant ( χ2=4.41, P=0.036). Conclusion:Command-controlled swallowing can effectively prolong the time of esophagus examination by MCE, and improve the detection rate of esophageal lesions by MCE.

Effect and mechanism of bromodomain-containing protein 4 inhibitor JQl on formaldehyde solution induced inflammatory pain in mice / 解剖学报

Objective To explore the expression and role of bromodomain-containing protein 4(BRD4) in spinal cord of mice which suffered inflammatory pain induced by formaldelryde solution. Methods Thirty-two ICR mice were randomly divided into normal saline group and formaldehyde injection 5 minutes, 30 minutes and 60 minutes groups, with 8 mice in each group. The expression of BRD4 protein and mRNA in spinal cord of mice in each group were detected by Western blotting (n = 4/group) and Real-time PCR (n = 4/group); 66 mice were randomly divided into formaldelryde injection group, vehicle (DMSO) plus formaldelryde injection group and 6. 25, 12. 5, 25 and 50 mg/kg JQl injection plus formaldelryde solution group, with 11 mice in each group. The effect of BRD4 inhibitor JQl on spontaneous pain in each group was observed (n= 11/group); Immunohistochemistry (n= 3/group), Real-time PCR (n = 4/group) or Western blotting (n= 4/group) were used to detect the effects of 25 mg/kg JQ1 on the expression of c-fos and glutamate receptor 2 (GluR2) in the spinal cord of model mice. Results The result showed that levels of BRD4 protein (P<0. 01) and mRNA in spinal cord increased significantly 30 min and 60 min after formaldehyde solution injection (P<0. 05). The behavioral test showed that both 25 mg/kg and 50 mg/kg JQf administration could reduce the second phase spontaneous pain compared with the solvent (DMSO) group (P < 0 . 05). Furthennore, immunohistochemistry and Real-time PCR result showed that 25 mg/kg JQf injection could significantly reduce positive numbers (P<0. 01) and high mRNA expression of c-fos in mouse spinal cord induced by formaldehyde solution (P < 0 . 05), and the Western blotting result showed that 25 mg/kg JQf administration could significantly reduce the expression of glutamate receptor GluR2 (P < 0. OOf). Conclusion BRD4 may play an important role in the induction of central sensitization of inflammatory pain, and JQf may alleviate inflammatory pain behavior by inhibiting the formation of central sensitization of pain.

Rapid identification of homology of carbapenem-resistant Escherichia coli by FTIR / 中华检验医学杂志

Objective:Evaluate the application of Fourier transform infrared spectroscopy in the identification of homology of carbapenem-resistant Escherichia coli(CREC). Methods:A total of 26 carbapenem-resistant Escherichia coli strains were isolated from 9 provinces in China in 2018. The 900-1 200 cm -1 was selected as a spectral region for the Euclidean distance calculating and average linkage clustering between all isolates.The single nucleotide polymorphism (SNP) was analyzed by whole genome sequencing (WGS). Results:Twenty-six CREC strains were divided into 14 infrared spectros copy(IR) types by FTIR. The same IR type belonged to the same sequence type type.Compared with cluster analysis based on WGS, the consistency of FTIR cluster analysis was 92.3% (24/26).Conclusions:FTIR presented excellent performance in identification of homology of CREC.Besides, with the advantages of simple operation and rapid acquisition of results, FTIR may be a useful tool in clinical labs.

Mechanism of Tanreqing Injection in treatment of acute lung injury based on network pharmacology and molecular docking / 中国中药杂志

This study aimed to explore the mechanism of Tanreqing Injection in the treatment of acute lung injury(ALI) based on network pharmacology and molecular docking. The active components and action targets of Tanreqing Injection were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), PubChem, and SwissTargetPrediction databases, as well as available literature reports. The ALI-related targets were obtained from the GeneCards database and then mapped with Tanreqing Injection targets. Following the construction of "drug-component-potential target" network with Cytoscape 3.6.1, the potential targets were input into STRING to yield the protein-protein interaction(PPI) network, which was plotted using Cytoscape 3.6.1. Then the screened key targets were subjected to gene ontology(GO) and Kyoto encyclopedia of genes and genomes(KEGG) enrichment analysis based on DAVID database. The top three key targets RAC-alpha serine/threonine-protein kinase(AKT1), albumin(ALB) and interleukin-6(IL6) were docked to the top three key compounds by PyMOL and AutoDock vina. A total of 58 active components of Tanreqing Injection, 597 corresponding targets and 503 common targets shared by Tanreqing Injection and ALI were fi-gured out, with the key targets AKT1, ALB and IL6 involved. GO and KEGG enrichment analysis yielded 1 445 biological processes and 148 signaling pathways, respectively. Molecular docking verified a good binding ability of the top three key targets to the top three key compounds. The analysis based on network pharmacology and molecular docking uncovered that Tanreqing Injection directly or indirectly regulated the pulmonary capillary endothelial cells and alveolar epithelial cells via anti-inflammation, thus alleviating ALI.

Immunogenicity and safety of a recombinant fusion protein vaccine (V-01) against coronavirus disease 2019 in healthy adults: a randomized, double-blind, placebo-controlled, phase II trial / 中华医学杂志(英文版)

BACKGROUND@#Innovative coronavirus disease 2019 (COVID-19) vaccines, with elevated global manufacturing capacity, enhanced safety and efficacy, simplified dosing regimens, and distribution that is less cold chain-dependent, are still global imperatives for tackling the ongoing pandemic. A previous phase I trial indicated that the recombinant COVID-19 vaccine (V-01), which contains a fusion protein (IFN-PADRE-RBD-Fc dimer) as its antigen, is safe and well tolerated, capable of inducing rapid and robust immune responses, and warranted further testing in additional clinical trials. Herein, we aimed to assess the immunogenicity and safety of V-01, providing rationales of appropriate dose regimen for further efficacy study.@*METHODS@#A randomized, double-blind, placebo-controlled phase II clinical trial was initiated at the Gaozhou Municipal Centre for Disease Control and Prevention (Guangdong, China) in March 2021. Both younger (n = 440; 18-59 years of age) and older (n = 440; ≥60 years of age) adult participants in this trial were sequentially recruited into two distinct groups: two-dose regimen group in which participants were randomized either to follow a 10 or 25 μg of V-01 or placebo given intramuscularly 21 days apart (allocation ratio, 3:3:1, n = 120, 120, 40 for each regimen, respectively), or one-dose regimen groups in which participants were randomized either to receive a single injection of 50 μg of V-01 or placebo (allocation ratio, 3:1, n = 120, 40, respectively). The primary immunogenicity endpoints were the geometric mean titers of neutralizing antibodies against live severe acute respiratory syndrome coronavirus 2, and specific binding antibodies to the receptor binding domain (RBD). The primary safety endpoint evaluation was the frequencies and percentages of overall adverse events (AEs) within 30 days after full immunization.@*RESULTS@#V-01 provoked substantial immune responses in the two-dose group, achieving encouragingly high titers of neutralizing antibody and anti-RBD immunoglobulin, which peaked at day 35 (161.9 [95% confidence interval [CI]: 133.3-196.7] and 149.3 [95%CI: 123.9-179.9] in 10 and 25 μg V-01 group of younger adults, respectively; 111.6 [95%CI: 89.6-139.1] and 111.1 [95%CI: 89.2-138.4] in 10 and 25 μg V-01 group of older adults, respectively), and remained high at day 49 after a day-21 second dose; these levels significantly exceed those in convalescent serum from symptomatic COVID-19 patients (53.6, 95%CI: 31.3-91.7). Our preliminary data show that V-01 is safe and well tolerated, with reactogenicity predominantly being absent or mild in severity and only one vaccine-related grade 3 or worse AE being observed within 30 days. The older adult participants demonstrated a more favorable safety profile compared with those in the younger adult group: with AEs percentages of 19.2%, 25.8%, 17.5% in older adults vs. 34.2%, 23.3%, 26.7% in younger adults at the 10, 25 μg V-01 two-dose group, and 50 μg V-01 one-dose group, respectively.@*CONCLUSIONS@#The vaccine candidate V-01 appears to be safe and immunogenic. The preliminary findings support the advancement of the two-dose, 10 μg V-01 regimen to a phase III trial for a large-scale population-based evaluation of safety and efficacy.@*TRIAL REGISTRATION@#http://www.chictr.org.cn/index.aspx (No. ChiCTR2100045107, http://www.chictr.org.cn/showproj.aspx?proj=124702).

Clinicopathological characteristics and prognosis of patients with sporadic multiple primary gastrointestinal stromal tumors / 中华胃肠外科杂志

Objective: To investigate the clinicopathological characteristics and prognosis of sporadic multiple primary gastrointestinal stromal tumor (GIST). Methods: A retrospective cohort study was conducted. Case inclusion criteria: (1) postoperative pathological diagnosis of GIST; (2) primary GIST with single lesion or sporadic multiple primary GIST (sporadic GIST was defined as primary GIST other than familial and syndrome-related GIST, and multiple primary GIST was defined as the number of primary GISTs in the same patient ≥ 2); (3) patients with complete clinicopathological data. Those with tumor recurrence or distant metastasis, and with other malignancies were excluded. Medical records of patients with primary GIST who underwent surgical resection in the Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from January 2010 to December 2020 were collected. Patients were divided into sporadic multiple primary GIST group and single primary GIST group according to the number of primary GIST lesions. The clinicopathological data and prognosis of the two groups were observed and compared. Results: A total of 1200 patients with primary GIST were enrolled in this study, including 628 males (52.3%) and 572 females (47.7%), with a median onset age of 58 (19-93) years. Among them, 1165 cases (97.1%) were sporadic primary GIST with single lesion; 35 cases (2.9%) were sporadic multiple primary GIST. Among 35 cases of sporadic multiple primary GIST, 3 cases (8.6%) had acid reflux as the first symptom, which was higher than the single primary GIST group (22/1165, 1.9%) (χ(2)=7.437, P=0.006). There were no significant differences in other clinical characteristics between the two groups (all P>0.05). Patients in the sporadic multiple primary GIST group contained a total of 80 primary tumors. Compared with the single primary GIST group, the sporadic multiple primary GIST group had a higher proportion of tumors originating in the stomach [87.5% (70/80) vs. 59.1% (689/1165)], lower proportion of spindle cell in histology [85.0% (68/80) vs. 93.7% (1092/1165)], higher proportion of positive CD34 [97.5% (78/80) vs. 87.6% (1021/1165)], smaller maximum diameter [maximum diameter ≤2.0 cm: 61.2% (49/80) vs. 28.8% (335/1165)], lower mitotic rate [≤5/50 high-power fields (HPF): 93.8% (75/80) vs. 74.5% (868/1165)], lower risk of recurrence [60.0% (48/80) vs. 23.3% (271/1165)], and the differences were all statistically significant (all P<0.05). The 3-year recurrence-free survival rate in the sporadic multiple primary group and the single primary GIST group was 96.6% and 89.3% respectively (P=0.160), and the 3-year overall survival rate was 100.0% and 92.8%, respectively (P=0.088). Conclusions: The most common type of sporadic multiple primary GIST is multiple tumors originating in the stomach at the same time. Compared with primary GIST with single lesion, sporadic multiple primary GIST presents smaller maximum diameter and lower mitotic rate. The prognosis of patients between two groups is not significantly different.

Effect of AT-rich interactive domain 1A gene overexpression on glioblastoma cell invasion / 中国医师杂志

Objective:To investigate the role and mechanism of AT-rich interactive domain 1A gene (ARID1A) in glioblastoma invasion.Methods:Human glioblastoma cell line U87 was cultured in vitro. U87 cells transfected with recombinant pcDNA3.1 (+ )-ARID1A by lipofectamine liposome method as ARID1A overexpression group, and U87 cells transfected with empty plasmid as vector group. Untreated U87 cells were as blank control group. The transfection efficiency was verified by real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) and Western blot. Transwell invasion test was used to detect the invasion ability of cells, and Western blot was used to detect the protein expression of c-myc, matrix metalloproteinases (MMP)-2 and MMP-9. Results:48 hours after transfection with ARID1A eukaryotic expression plasmid, the cell invasion ability of ARID1A overexpression group, vector group and blank control group were (42.2±11.5)%, (98.6±4.8)%, (100.0±5.1)%. There was significant difference between ARID1A overexpression group and the other two groups ( P<0.01); The expressions of c-myc, MMP-2 and MMP-9 in ARID1A overexpression group were lower than those in vector group and blank control group ( P<0.01). Conclusions:ARID1A can inhibit the invasion of glioblastoma by inhibiting the expression of MMP-2/MMP-9, and can be used as a potential therapeutic target for glioblastoma.

Voluntary wheel running prevents the formaldehyde induced negative emotion through up-regulation of hippocampal neurogenesis in mice / 解剖学报

Objective To investigate the effect of voluntary wheel running on negative affective of mice induced by formaldehyde. Methods Thirty male Kunming mice were randomly divided into three groups, including normal saline control group (NS), formaldehyde model group (F), and voluntary wheel running with formaldehyde injection group ( R+ F). The pain model was established by right hindpaw intraplantar formalin injection, the mice of R+F group experienced voluntary wheel running for three weeks before intraplantar formaldehyde injection. The spontaneous pain behavior was determined by the cumulative time of licking paw. The anxiety-like behavior of each group was determined by open field test (OFT) and elevated plus-maze test (EPM) while the depression-like behavior of each group was determined by forced swimming test (FST). The expression of doublecortin ( DCX ) in the hippocampus was determined by immunohistochemistry. Results Compared with the NS group, the typical two-phase pain response was observed in the F group, and compared with the F group, the second phase pain duration was significantly reduced in the R+F group (P<0. 01). In the open field test, the F group showed remarkably reduced time in the inner area(P<0. 001) compared with the NS group, while the R+F group increased time in the inner area (P<0. 05) compared with the F group. In the elevated plus-maze test, the F group showed remarkably reduced time (P< 0. 001) spent in the open arm compared with the NS group, however, compared with the F group, R+F group increased time spent in the open arm (P<0. 05). In the forced swimming test, the immobility time of the F group significant increased (P<0. 01) compared with the NS group, which was decreased in the R+F group (P<0. 05). The Immunohistochemistry showed that the area of DCX positive cells in the hippocampus of the F group was downregulated compared with the NS group, which was upregulated in the R+F group. Conclusion Our findings indicate that voluntary wheel running can improve anxiety and depression-like in mice induced by formaldehyde injection, which may be related to enhanced neurogenesis in the hippocampus.

Influence of marginal bone resorption on two mini implant-retained mandibular overdenture: An in vitro study

PURPOSE@#To investigate the biomechanical effect of marginal bone resorption (MBR) on the mandibular mini implant (MI)-retained overdenture (MI-OD) on the edentulous model. @*MATERIALS AND METHODS@# The experimental mandibular edentulous model was modified from a commercial model with 2 mm thick artificial soft tissue under denture base. Two MIs (Φ2.6 mm x 10 mm) were bilaterally placed between the lateral incisor and the canine area and attached with magnetic attachments. Three groups were set up as follows: 1) alveolar bone around the MI without MBR (normal group), 2) with MBR to 1/2 the length of the implant (resorption group), and 3) complete denture (CD) without MI (CD group). Strain around the MI, pressure near the first molar area, and displacement of denture were simultaneously measured, loading up to 50 N under bilateral/ unilateral loading. Statistical analysis was performed using independent-samples t test and one-way ANOVA (α=.05). @*RESULTS@#The strain around the MI with MBR was approximately 1.5 times higher than that without MBR. The pressure in CD was higher than in MI-ODs (P .05). Similarly, the CD demonstrated a greater displacement of the denture base than did the MI-ODs during bilateral and unilateral loadings (P <.05). @*CONCLUSION@#The strain around the MI with MBR was approximately 1.5 times higher than that without MBR. The pressure on posterior alveolar ridge and denture displacement of MI-ODs significantly decreased compared to CDs, even when MBR occurs. Bilateral balanced occlusion was recommended for MI-ODs, especially when MBR occurred.

Effect of different corneal protective agents on ocular surface in vitrectomy in patients with diabetes / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To investigate effects of different corneal protective agents on ocular surface in vitrectomy in patients with diabetes.<p>METHODS: Totally 90 patients(90 eyes)with diabetes who received vitrectomy were randomly divided into HPMC group(30 eyes), SHSCS group(30 eyes)and BSS group(30 eyes). Hydroxypropyl methyl cellulose(HPMC)and sodium hyaluronate sodium chondroitin sulfate(SHSCS)were used to cover the corneal surface to avoid the cornea drying in HPMC group and SHSCS group, respectively. Balanced salt solution(BSS)was continuously dripped on the cornea to keep the cornea moist in BSS group. Schirmer Ⅰ test(SⅠt), breaking up time(BUT)and central corneal thickness were performed before and after operation. Their changes were observed and compared.<p>RESULTS: At 1wk and 1mo after operation, compared with HPMC group and SHSCS group, SⅠt was significantly increased and BUT was significantly shortened in BSS group(<i>P</i><0.05). At 1wk after operation, BUT of HPMC group was significantly shortened compared with SHSCS group(<i>P</i><0.05). At 3mo after operation: SⅠt and BUT of the three groups were no significant difference compared with before operation(<i>P</i>>0.05). At 1d after operation, the corneal thickness of BSS group was significantly increased compared with HPMC group and SHSCS group(<i>P</i><0.05). At 1wk after operation, the corneal thickness of the three groups were no significant difference compared with before operation(<i>P</i>>0.05).<p>CONCLUSION:The patients with diabetes use HPMC and SHSCS can protect the cornea and maintain the stability of tear film in vitrectomy. Different corneal protectors can be selected according to the clinical practice.

Chimeric antigen receptor T-cell therapy: a promising treatment modality for relapsed/refractory mantle cell lymphoma / 医学前沿

Mantle cell lymphoma (MCL) is a distinct histological type of B-cell lymphoma with a poor prognosis. Several agents, such as proteasome inhibitors, immunomodulatory drugs, and inhibitors of B cell lymphoma-2 and Bruton's tyrosine kinase have shown efficacy for relapsed or refractory (r/r) MCL but often have short-term responses. Chimeric antigen receptor (CAR) T-cell therapy has emerged as a novel treatment modality for r/r non-Hodgkin's lymphoma. However, long-term safety and tolerability associated with CAR T-cell therapy are not defined well, especially in MCL. In this report, we described a 70-year-old patient with r/r MCL with 48-month duration of follow-up who achieved long-term remission after CAR T-cell therapy. CAR T-cell-related toxicities were also mild and tolerated well even in this elderly patient. This report suggested that CAR T-cell therapy is a promising treatment modality for patients with MCL, who are generally elderly and have comorbid conditions.

Potential active compounds of Liupao tea for prevention and treatment of COVID-19 based on network pharmacology and molecular docking / 中国药科大学学报

@#To investigate the material basis and mechanism of Liupao tea on preventing COVID-19 by network pharmacology and molecular docking.The active ingredients and targets of Liupao tea were searched through the literature and the TCMSP databases and the network between the two was built by Cytoscape 3.7.1.Then using GenCards platform to predict the disease targets,mapping the common targets between Liupao tea and disease.The common targets were imported into the STRING database for exploring the protein-protein interaction.Core targets were enriched by gene ontology (GO) enrichment analysis and KEGG (kyoto encyclopedia of genes and genomes) pathway enrichment analysis using DAVID database etc..Finally,the screened active components were docked with the receptor protein SARS-CoV-2 3CL hydrolase (Mpro).Six active ingredients of Liupao tea were screened,such as (-)-epigallocatechin gallate (EGCG),(+)-catechin,(-)-catechin gallate,α-spinasterol,pelargonidin chloride and squalene,and 156 targets were identified.Among them,there were 112 common targets and 38 core targets with COVID-19.GO enrichment analysis (P<0.01) involved lipopolysaccharide,cell response to hypoxia,etc..And the KEGG pathway enrichment analysis (P<0.01)was conducted to obtain the HIF-1,IL-17,T cell receptor and other signaling pathways associated with COVID-19.The results of molecular docking showed that the active ingredients of Liupao tea were well bound to the receptor protein Mpro.The active ingredients of Liupao tea may control HIF-1,IL-17,T cell receptors signaling pathways by binding Mpro hydrolase and acting on inflammation and immune related targets such as MAPK1,TNF to prevent COVID-19.The EGCG of Mpro activity was determined ,and the IC50 was 3.4 μmol/L,which confirmed that EGCG was a certain inhibition effect on Mpro.

Screening of G-quadruplex ligands from Macleaya cordata extract by contrast ultrafiltration with liquid chromatography-mass spectrometry and molecular docking / 中国中药杂志

G-quadruplex DNA has become an important target for tumor therapy and anti-tumor development. Modern pharmacology has proved that Macleaya cordata has anti-inflammatory, antibacterial, anti-tumor and other pharmacological effects. Affinity ultrafiltration method can screen active ingredients from compounds rapidly, but G-quadruplex DNA ligands are difficult to dissociate, which is a key step in conventional ultrafiltration method. In this paper, the filtrates after ultrafiltration were determined by HPLC-MS in substitution. The peaks with 20% reduction of MS response from the incubation vs control were considered to be ligand components to G-quadruplex. Two of the peaks with the relative abundance above 30% were identified as sanguinarine(SAN) and chelerine(CHE). Their circular dichroism conformations further proved that SAN and CHE are active ligands of HT4. In addition, another two gradients with high relative abundance were identified as protopine(PRO) and allpcryprotopine(ALL). The binding rate of SAN, CHE, PRO and ALL was calculated according to the HPLC-MS results, and the results showed a consistency with that of the molecular docking method. The proposed method can be used to screen active components from mixture.