Effect of Glycyrrhizae Radix et Rhizoma-containing Serum on LPS-induced Inflammation in Caco2 Cells Based on Inhibition of Ferroptosis by Nrf2/HO-1 Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Glycyrrhizae Radix et Rhizoma （GR）-containing serum on lipopolysaccharide （LPS）-induced inflammation in human colon epithelial adenocarcinoma cells （Caco2） based on inhibition of ferroptosis by the nuclear factor erythroid 2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） pathway. MethodCaco2 cells were divided into a normal group， a model group （LPS， 200 μg·L-1）， low-， medium-， and high-dose GR-containing serum groups （5%， 10%， 20%）， and a ferroptosis inhibitor group （3-amino-4-cyclohexylamino-benzoic acid ethyl ester， Fer-1， 10 μmol·L-1）. The cells in the normal group were cultured normally， while those in other groups underwent the induction of an inflammation model. The cells in the low-， medium-， and high-dose GR-containing serum groups were treated with 5%， 10%， and 20% GR-containing serum for 24 hours， respectively， and the cells in the ferroptosis inhibitor group were treated with Fer-1 for 24 hours. Transmission electron microscopy was used to observe mitochondrial morphology in each group. Flow cytometry was used to detect intracellular Fe2+ levels. Microplate assays were performed to measure superoxide dismutase （SOD） activity， malondialdehyde （MDA） and glutathione peroxidase （GSH-Px） levels. Enzyme-linked immunosorbent assay （ELISA） was used to measure interleukin-1β （IL-1β）， IL-6， IL-10， and tumor necrosis factor-α （TNF-α） levels. Western blot was used to measure the expression levels of Nrf2， HO-1， ferritin heavy chain 1 （FTH1）， and glutathione peroxidase 4 （GSH-Px4） proteins. Small interfering RNA （siRNA） was used to investigate the role of Nrf2 in ferroptosis regulation. The cells after interference were divided into a negative control （NC） group， a Si-Nrf2 group， a GR-containing serum （20%） + Si-Nrf2 group， and a GR-containing serum （20%） + NC group. Microplate assays were performed to measure MDA， SOD， and GSH-Px levels， and Western blot was used to measure the expression levels of Nrf2， HO-1， FTH1， and GSH-Px4 proteins. ResultCompared with the normal group， the model group showed mitochondrial contraction， increased mitochondrial membrane thickness， and smaller mitochondrial morphology， increased Fe2+ content （P<0.01）， blunted SOD activity （P<0.01）， decreased GSH-Px expression （P<0.01）， increased MDA content （P<0.01）， reduced expression levels of Nrf2 and HO-1 （P<0.05）， reduced FTH1 expression （P<0.01）， and down-regulated GSH-Px4 expression （P<0.01）. In the GR-containing serum groups， the medium- and high-dose groups showed a significant decrease in Fe2+ content （P<0.01）， potentiated SOD and GSH-Px activities （P<0.01）， and decreased MDA levels （P<0.01）. The high-dose group showed a significant increase in Nrf2 expression （P<0.05）， and the medium-dose group showed increased expression of HO-1 and GSH-Px4 proteins （P<0.05）. The expression levels of FTH1 significantly increased in the low-， medium-， and high-dose groups （P<0.01）. The study on mechanism revealed that compared with the NC group， the cells transfected with Nrf2 siRNA showed increased MDA content （P<0.01）， blunted SOD activity （P<0.01）， decreased GSH-Px activity （P<0.01）， decreased expression of Nrf2 and HO-1 （P<0.01）， and reduced levels of FTH1 and GSH-Px4 proteins （P<0.01）. Compared with the Si-Nrf2 group， the cells treated with GR-containing serum showed a decrease in MDA content （P<0.01）， an increase in SOD activity （P<0.01）， an increase in GSH-Px activity （P<0.01）， increased expression of Nrf2 and FTH1 proteins （P<0.05）， and higher expression levels of HO-1 and GSH-Px4 proteins （P<0.01）. ConclusionGR-containing serum can reduce the inflammatory cytokines and oxidative stress levels in LPS-induced Caco2 cells. Its mechanism is related to the promotion of Nrf2/HO-1 signaling pathway expression， alleviating intracellular lipid peroxidation and inhibiting ferroptosis.

Cardiac amyloidosis: pathological classification and clinical analysis of 48 cases / 中华病理学杂志

Objective: To investigate the histological features and clinical manifestations in different types of cardiac amyloidosis to improve diagnostic accuracy. Methods: The histopathological features and clinical manifestations of 48 patients diagnosed with cardiac amyloidosis by Congo red stain and electron microscopy through endomyocardial biopsy were collected in West China Hospital of Sichuan University from January 2018 to December 2021. Immunohistochemical stains for immunoglobulin light chains (κ and λ) and transthyretin protein were carried out, and a review of literature was made. Results: The patients age ranged from 42 to 79 years (mean 56 years) and the male to female ratio was 1.1 to 1.0. The positive rate of endomyocardial biopsy was 97.9% (47/48), which was significantly higher than that of the abdominal wall fat (7/17). Congo red staining and electron microscopy were positive in 97.9% (47/48) and 93.5% (43/46), respectively. Immunohistochemical stains showed 32 cases (68.1%) were light chain type (AL-CA), including 31 cases of AL-λ type and 1 case of AL-κ type; 9 cases (19.1%) were transthyretin protein type (ATTR-CA); and 6 cases (12.8%) were not classified. There was no significant difference in the deposition pattern of amyloid between different types (P>0.05). Clinical data showed that ATTR-CA patients had less involvement of 2 or more organs and lower N-terminal pro-B-type natriuretic peptide (NT-proBNP) than the other type patients (P<0.05). The left ventricular stroke volume and right ventricular ejection fraction of ATTR-CA patients were better than the other patients (P<0.05). Follow-up data of 45 patients was obtained, and the overall mean survival time was 15.6±2.0 months. Univariate survival analysis showed that ATTR-CA patients had a better prognosis, while cardiac amyloidosis patients with higher cardiac function grade, NT-proBNP >6 000 ng/L, and troponin T >70 ng/L had a worse prognosis (P<0.05). Multivariate survival analysis showed that NT-proBNP and cardiac function grade were independent prognostic factors for cardiac amyloidosis patients. Conclusions: AL-λ is the most common type of cardiac amyloidosis in this group. Congo red staining combined with electron microscopy can significantly improve the diagnosis of cardiac amyloidosis. The clinical manifestations and prognosis of each type are different and can be classified based on immunostaining profile. However, there are still a few cases that cannot be typed; hence mass spectrometry is recommended if feasible.

Preparation of drug loading system of black phosphorus nanosheets and its anti-ischemic brain injury / 药学学报

In this study, black phosphorus nanosheets (BP) were prepared by the ordinary liquid phase method, and resveratrol was loaded on the BP after being modified by polyethylene glycol. The brain targeting of BP was investigated by fluorescent protein labeling, and the effects of black phosphorus on cerebral ischemia/reperfusion injury were studied by 2,3,5-triphenyltetrazolium chloride (TTC) staining, neurobehavioral evaluation, and brain edema. Protein immunoblotting analysis was used to explore the molecular mechanism of the BP drug delivery system on ischemic brain injury. Hemolysis test and hematoxylin-eosin (H&E) staining were used to evaluate its biocompatibility. The results showed that BP had excellent drug loading capacity, uniform drug loading system structure and particle size, stable drug release curve, and excellent photothermal effect. Through the analysis and comparison of fluorescence intensity, it was found that BP can increase the permeability of blood-brain barrier (BBB) under the condition of near-infrared light assisted irradiation, and make drugs more pass through the BBB. In addition, the black phosphorus nano tablet drug delivery system can significantly improve the neurobehavioral disorder of mice after modeling, and the cerebral infarction area and brain edema degree are significantly decreased. Western blot experiments showed that the drug delivery system could play an anti-ischemic brain injury role by activating the expression of antioxidant signaling pathway proteins nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). The hemolysis test and H&E test results of the BP drug carrier system showed that it had no obvious toxicity and high safety. In conclusion, the BP prepared in this study had high drug loading, good photothermal performance, and high safety. Under the near-infrared condition, they also have certain brain targeting ability, which can improve the therapeutic effect of drugs in the brain. Animal welfare and experimental procedures were following the regulations of the Animal Ethics Committee of the First Affiliated Hospital of Shihezi University.

Changes of aqueous cytomegalovirus DNA in patients with cytomegalovirus retinitis after allogeneic bone marrow hematopoietic stem cell transplantation / 中华眼底病杂志

Objective:To observe aqueous cytomegalovirus (CMV) DNA load in patients with cytomegalovirus retinitis (CMVR) after allogeneic hematopoietic stem cell transplantation (Allo-HSCT), and to explore influencing factors for transient elevation of CMV-DNA load during the treatment.Methods:A retrospective study. From January 2016 to July 2020, 28 eyes of 19 patients with CMVR after Allo-HSCT diagnosed in the Department of Ophthalmology of Peking University People's Hospital were included in the study. Among them, there were 8 males with 12 eyes, 11 females with 16 eyes; the mean age was 28 years; 10 patients were unilateral and 9 patients were bilateral. During the course of treatment and follow-up, the blood CMV-DNA remained negative. All patients were treated with intravitreal injection of 60 mg/ml ganciclovir 0.05 ml (containing ganciclovir 3 mg), twice a week for two weeks in induction phase and weekly injection in maintenance phase. Aqueous humor sample was collected during injection of ganciclovir (IVG) and CMV-DNA load was determined by real-time quantitative polymerase chain reaction. Intravitreal treatment was terminated if aqueous CMV-DNA load turned negative after the fourth or later intravitreal injection. The patients were followed up every 2 weeks for at least 6 months. Serum CMV-DNA was negative in all patients during treatment and follow-up. All the eyes were divided into continuous decline group and non-continuous decline group depending on whether there was transient elevation of aqueous CMV-DNA load, and data between two groups were compared. Pearson linear regression analysis was used to analyze the correlation between aqueous CMV-DNA load and injection times or treatment duration.Results:At the end of treatment, the median number of IVG in the affected eye was 7 (4, 9). The results of correlation analysis showed that the aqueous humor CMV-DNA load of the affected eye was related to the number of treatments [ R2=0.385, P<0.000 1, B=-0.237 log 10 copies/(ml·time)], and the duration of treatment [ R2=0.394, P <0.000 1, B=-0.301 log 10 copies/(ml·week)] were negatively correlated. Among the 28 eyes, 13 eyes (46.4%, 13/28) in the continuous decline group and 15 eyes (53.6%, 15/28) in the non-sustained decline group. Baseline visual acuity ( t=-1.223), intraocular pressure ( t=1.538), aqueous humor CMV-DNA load ( t=-0.109), retinitis lesion area ( Z=-0.308) in the continuous decline group and the non-continuous decline group), the number of quadrants involved ( Z=-0.024) and whether the macula was involved ( Z=-1.826), combined with anterior segment inflammation ( Z =-0.499), combined with high intraocular pressure ( Z=-1.342), terminal visual acuity ( t =-0.845), intraocular pressure ( t=-0.068), total IVG times ( Z=0.907), age ( Z=-0.832), gender composition ( Z=-1.074), etc. The difference was not statistically significant ( P>0.05). Conclusion:The CMV-DNA load in aqueous humor decreases by about 50% every week during the treatment of CMVR eyes after Allo-HSCT; the transient increase in the CMV-DNA load in the aqueous humor during treatment does not affect the treatment process and clinical prognosis.

Systemic risk factors and epidemiology of cytomegalovirus retinitis status-post allogeneic bone marrow hematopoietic stem cell transplantation / 中华眼底病杂志

Cytomegalovirus (CMV) retinitis (CMVR) is a common opportunistic infection of the eye after allogeneic hematopoietic stem cell transplantation in patients with hematological diseases. It often occurs within 3 months after the operation, with CMV activation and high blood CMV peaks. It often occurs on patients with long-term CMV viremia, human leukocyte antigen incompatible transplantation, unrelated donor transplantation, haploid transplantation, childhood hematopoietic stem cell transplantation, delayed lymphocyte engraftment, acute and chronic graft-versus-host disease after surgery. The visual prognosis of patients is related to the area of CMVR lesions on the retina, the number of quadrants involved, whether the macula is involved, and the CMV load of the vitreous body is involved, and it is not related to whether the Epstein-Barr virus infection is combined with blood and vitreous humor. The incidence of CMVR is increasing year by year. It is helpful that paying attention to systemic risk factors and epidemiology can provide more effective guidance for ophthalmologists during diagnosis and treatment, help patients improve the prognosis of vision, and reduce or even avoid the occurrence of blindness caused by CMVR.

Diagnostic value of serum cytokines and autoantibodies in children with central diabetes insipidus / 中国综合临床

Objective:To explore the diagnostic value of serum cytokines and autoantibodies in children with central diabetes insipidus.Methods:A retrospective study was used.A total of 52 children diagnosed with central diabetes insipidus who were hospitalized in Qingdao municipal hospital affiliated to Qingdao Universityfrom January 2016 to January 2020 were selected as the study group, and 60 healthy children with similar gender and age were selected as the control group.The general data of the study group and the control group, 24 h urine volume, urine specific gravity and urine osmotic pressure before the start of water deprivation test, the results of pituitary magnetic resonance imaging (MRI), and the concentration of serum cytokines and autoimmune antibodies were compared to evaluate the value of serum cytokines and autoimmune antibodies in the prediction of central diabetes insipidus.Results:The 24 h urine volume in the study group (201.6 ± 9.9 mL/kg)was significantly higher than that in the control group(9.06±12.5 mL/kg). The urine specific gravity(1.006±0.002) and urine osmotic pressure((116.4±23.5) mOsm/L)were significantly lower than those in the control group((1.013±0.004) and (649.6±72.4) mOsm/L)( t=15.378, 13.298, 45.625, all P<0.001). MRI examination showed that the proportion of disappearance of high signal in posterior pituitary (46.1%(24/52)), the proportion of thickening of the pituitary stalk(32.7%(17/52))and abnormal signal in pituitary(7.7%(4/52)) in study group were significantly higher than the control group(0%(0/0)) (all P<0.05); the levels of serum IL-6, TNF-α, IFN-γ, IL-1β ((117.0±7.8), (234±21.4), (178.6±15.1), (87±6.5) ng/L)and autoimmune antibodies ((654.1±194.3) ng/L) in study group were significantly increased compared to the control((12.5±2.3), (32.5±9.7), (37.8±7.3), (22.6±4.7), (98.0±23.7) ng/L) ( t value were 17.031, 27.490, 15.670, 12.360 and 109.984, respectively; all P<0.05). Conclusion:The concentration of serum cytokines and autoimmune antibodies has a significant clinical value in the evaluation of central diabetes insipidus in children.Combined with head MRI examination, it has a certain value in the diagnosis, treatment and prognosis of central diabetes insipidus in children.

Protective Mechanism of Danggui Shaoyaosan on Podocytes of Nephrotic Syndrome Rats Based on AngⅡ-TRPC6 Pathway / 中国实验方剂学杂志

Objective:To explore the protective effect and the mechanism of Danggui Shaoyaosan（DSS） on angiotensin Ⅱ （AngⅡ）/transient receptor potential cation channel 6 （TRPC6） pathway in nephrotic syndrome （NS） rats. Method:In animal experiments， doxorubicin （4 mg·kg^-1 for the 1^st week and 2 mg·kg^-1 for the 2^nd week） was injected twice to the tail vein of rats to induce NS model in 160 rats， which were then randomly divided into model group （normal saline）， losartan group （30 mg·kg^-1·d^-1）， and low-（4.3 g·kg^-1·d^-1）， medium-（8.6 g·kg^-1·d^-1）， and high-dose （17.2 g·kg^-1·d^-1） DSS groups. Besides， a normal group was also set. After intervention for four weeks， ultrastructure changes of the kidney were identified by transmission electron microscopy （TEM）. The 24-hour urine protein was detected by kits. Radioimmunoassay was used to detect the content of AngⅡ and Calcineurin （CaN） in plasma. Western blot was used to detect the protein expression of TRPC6， angiotensin Ⅱ type 1 receptor （AT1R）， podocyte slit diaphragm-specific protein （Nephrin）， and cysteine-aspartic acid protease-3 （Caspase-3） in the renal cortex. Immunohistochemistry was used to detect the expression of TRPC6 and AT1R in the slit diaphragm. In cell experiments， AngⅡ stimulated MPC5 podocytes. The cells were randomly divided into a normal group， an AngⅡ group， an AngⅡ+SAR7334 （TRPC6-specific inhibitor） group， an AngⅡ+5%DSS group， an AngⅡ+10%DSS group， and an AngⅡ+15%DSS group. Western blot was used to detect the protein expression of TRPC6， AT1R， Nephrin， and Caspase-3 in podocytes. Result:Compared with the normal group， the model group showed increased 24-hour urine protein content （<italic>P</italic><0.01） and AngⅡ and CaN in plasma （<italic>P</italic><0.01）， incomplete glomerular structure， the extensive fusion of podocyte process with elevated fusion rate （<italic>P</italic><0.01）， increased expression distribution of AT1R and TRPC6 in the renal cortex， and up-regulated protein expression of AT1R， TRPC6， and Caspase-3 in renal tissues （<italic>P</italic><0.01）， and reduced Nephrin protein expression （<italic>P</italic><0.01）. Compared with model group， the losartan group and the high-dose DSS group exhibited decreased 24-hour urine protein content （<italic>P</italic><0.01） and the content of AngⅡ and CaN in plasma （<italic>P</italic><0.01）， improved glomerular structure， reduced fusion rate of podocyte process （<italic>P</italic><0.01）， diminished expression distribution of TRPC6 and AT1R in the renal cortex， declining protein expression of AT1R， TRPC6 and Caspase-3 in renal tissues （<italic>P</italic><0.01）， and elevated Nephrin protein expression （<italic>P</italic><0.01）. Additionally， compared with the normal podocytes， AngⅡ-stimulated podocytes showed increased protein expression of AT1R， TRPC6 and Caspase-3 （<italic>P</italic><0.01）， and decreased expression of Nephrin （<italic>P</italic><0.01）. Compared with the AngⅡ group， the AngⅡ+SAR7334 group displayed reduced protein expression of AT1R， TRPC6， and Caspase-3 （<italic>P</italic><0.01） and increased protein expression of Nephrin （<italic>P</italic><0.01）. Conclusion:DSS can improve the pathological characteristics of NS presumedly by inhibiting the interaction between AngⅡ and TRPC6 in podocytes and improving the structural integrity of podocytes to repair the damage of glomerular molecular barrier and slow down the progression of NS-induced proteinuria.

Application of Relative Quality Constant in Grade Evaluation of Codonopsis Radix Slices / 中国实验方剂学杂志

Objective:To establish the grade evaluation method for Codonopsis Radix slices based relative quality constants， in order to provide scientific theoretical basis for grading of Codonopsis Radix slices. Method:Through literature and market research，the main production areas of Codonopsis Radix slices were determined，and 67 batches of Ludangshen slices（52 batches） and Baitiaodang slices （15 batches） were collected. The appearance traits （average quality and average thickness of Codonopsis Radix slices） were observed and measured. According to Chinese Pharmacopoeia （2015 edition）， the extract and the content of Codonopsis pilosula polysaccharide was determined by phenol-sulphoacid method. Then the relative quality constant was calculated，and the results of grade evaluation were evaluated through systematic cluster analysis and correlation analysis. Result:Relative quality constants of 67 batches of Codonopsis Radix slices were between 0.32-2.97. If these samples were divided into three grades：the first-grade relative quality constants were greater than or equal to 2.08，the second grade was greater than or equal to 0.89 but less than 2.08，while the third grade was less than 0.89. The results of systematic cluster analysis showed that 67 batches of Codonopsis Radix slices were clustered into 3 categories，and the results were basically consistent with the classification. The correlation analysis showed a positive correlation between the content of the extracts and the polysaccharide content （P<0.05）. Conclusion:This method links the extrinsic characteristics to the intrinsic quality，and objectively grade Codonopsis Radix slices， so as to provide a basis for its grade standards.

Effect of Echinococcus multilocularis infections on mitochondrial functions of macrophages / 中国血吸虫病防治杂志

Objective To investigate the changes of mitochondrial metabolic functions of macrophages following Echinococcus multilocularis infections, so as to provide insights into the pathogenesis of alveolar echinococcosis. Methods Two groups were assigned according to different treatment methods. In the culture group, mouse leukemic monocyte macrophage RAW264.7 cells were cultured with 2 000 E. multilocularis at a ratio of 500∶1, while RAW264.7 cells in the control group were given no treatment. Then, both the culture and control groups were further divided into the 24 h and 72 h subgroups. Mitochondria were stained with MitoTracker® Deep Red FM and the mean fluorescence intensity of macrophage mitochondria was measured with the Cytation 5 Cell Imaging Multi-Mode Reader. The mitochondrial DNA copy number was quantified using the quantitative real-time PCR (qPCR) assay, and the mitochondrial energy metabolism was monitored using the Seahorse XF assay. In addition, the mitochondrial reactive oxygen species and mitochondrial membrane potential were detected using flow cytometry. Results The mean fluorescence intensities of macrophage mitochondria were significantly lower in the 24 h (15 341 ± 2 532 vs. 17 823 ± 3 429; t = 6.379, P < 0.01) and 72 h (18 102 ± 3 505 vs. 21 511 ± 5 144; t = 17.680, P < 0.01) culture subgroups than in the corresponding control subgroups, and lower mitochondrial DNA copy numbers were measured in the 72 h culture subgroup than in the 72 h control group [(3.23 × 109 ± 1.78 × 107) vs. (4.39 × 109 ± 3.70 × 107); t = 8.85, P < 0.001]. The oxygen consumption rates were significantly greater in the 24 h [(241.70 ± 73.13) pmol/min vs. (69.05 ± 52.30) pmol/min; t = 7.89, P < 0.01] and 48 h culture groups [(249.50 ± 42.06) pmol/min vs. (60.28 ± 40.66) pmol/min; t = 8.64, P < 0.01] than in the corresponding control groups, and a higher extracellular acidification rate was seen in the 48 h culture group than in the 48 h control group ([ 111.6 ± 17.49) mpH/min vs. (35.05 ± 7.57) mpH/min; t = 16.90, P < 0.01]. In addition, flow cytometry detected higher mean fluorescence intensity of mitochondrial reactive oxygen species (58 264 ± 10 087 vs. 4 307 ± 97; t = 12.930, P < 0.01) and lower mitochondrial membrane potential (9.833% ± 2.285% vs. 2.667% ± 0.208%; t = 6.645, P < 0.01) in the 72 h culture group than in the control group. Conclusions E. multilocularis infection may impair mitochondrial functions and inhibit oxidative phosphorylation of macrophages, resulting in increased macrophage glycolysis. It is speculated that the alteration of macrophage metabolic states may contribute to the mechanisms underlying the development and progression of alveolar echinococcosis.

Changes of serum nuclear factor κ B and interleukins in pregnant women with subclinical hypothyroid complicated with gestational diabetes mellitus / 中国综合临床

Objective:To explore the clinical significance of serum nuclear factor κ B, interleukin(IL)-4, IL-10, IL-12, interferon(IFN)- γ expression in subclinical hypothyroidism with gestational diabetes mellitus.Methods:Thirty pregnant women with subclinical hypothyroidism combined with gestational diabetes mellitus in Tangshan Maternal and Child Health Hospital from January 2017 to October 2018 were retrospectively analyzed as group A. Thirty three pregnant women with subclinical hypothyroidism were selected as group B, 35 pregnant women with gestational diabetes mellitus as group C and 40 healthy pregnant women as control group.ELISA was used to detect NF-κB, IL-4, IL-10, IL-12 and IFN-γ, and the results were analyzed and compared.Results:The serum levels of NF-κB were (15.91±5.68), (13.22±5.23), (12.97±5.11), (9.74±3.85) μg/L, IL-12 were (28.91±6.84), (21.64±5.72), (22.23±5.91), (13.68±3.76) ng/L, and serum IFN-γ levels were (23.74±5.55), (18.26±4.63), (17.85±4.31), (12.69±3.85) ng/L in A, B, C and the control group respectively.There were statistically significant differences in the three indicators between groups ( F=5.118, 6.821, 7.133, all P<0.05), and group A was higher than group B, C and control, the differences were statistically significant (all P<0.05); the levels of serum IL-4 in group A, B, C and control group were (8.91±3.99), (10.84±4.47), (11.27±4.62), (13.68±5.46) ng/L, respectively.The levels of serum IL-10 were (10.91±3.86), (13.05±4.58), (12.83±4.69), (15.82±5.33) ng/L, respectively.The differences of serum IL-4 and IL-10 between groups were statistically significant ( F=5.075, 5.616, all P<0.05), and serum IL-4 and IL-10 in group A were lower than those in group B, group C and control group.The levels of serum IL-4 and IL-10 in group B and C were lower than those in control group (all P<0.05). Conclusion:The activation of NF-kB signaling pathway and its related cytokines may be the influencing factors for the development of subclinical hypothyroidism with gestational diabetes mellitus.

Celastrus orbiculatus Extracts Inhibit Human Hepatocellular Carcinoma Growth by Targeting mTOR Signaling Pathways / 中国结合医学杂志

OBJECTIVE@#To characterize the molecular mechanism underlying the antineoplastic activity of Celastrus orbiculatus Thunb. extracts (COE).@*METHODS@#The human hepatocellular carcinoma HepG2 cells with mammalian target of rapamycin (mTOR) knockdown expressed (HepG2/mTOR) were constructed using molecular biological technology. In vitro, the HepG2/mTOR cells were treated with COE at various concentrations (10, 20, 40, 80, 160 and 320 µ g/mL). Cell viability was determined using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assays. According to the half-maximal inhibitory concentration (IC) value (140 mg/L), the concentrations of COE in the subsequent experiment was set to alleviate cytotoxicity. The HepG2/mTOR cells were divided into 5 groups: negative control (untreated), COE treatment groups (40, 80, 120 mg/L COE) and positive control group (cisplatin, DDP, 2 mg/L), respectively. Wild-type HepG2 cells were used as a blank control. The effects of COE on the cell apoptosis were analyzed by flow cytometry and transmission electronic microscopy (TEM), respectively. The protein expression levels of mTOR signal pathways were determined by Western blotting. In vivo, HepG2/mTOR cells (2 × 10 cell/mice) were subcutaneously injected into the right flank of nude mice. Thirty-six female nude mice were randomly assigned to 6 groups according to body weight (6 mice per group) as follows: solvent vehicle control, Banmao Capsule treated group (BM, 195 mg/kg), Tegafur, Gimeracil and Oteracil Potassium Capsules (10 mg/kg) treated group, and different dosages of COE (10, 20, 40 mg/kg) groups. Tumor growth was monitored and immunohistochemical staining was used to examine the expression of apoptosis-related proteins in tumor tissues.@*RESULTS@#COE inhibited the proliferation significantly in a concentration-dependent manner in HepG2/mTOR cells (P<0.01). COE significantly induced the apoptosis of HepG2/mTOR cells (P<0.01), and the apoptotic bodies can be observed under TEM. COE significantly inhibits the proteins expression of mTOR-related signal pathways. In vivo, COE significantly inhibited tumor growth in nude mice (P<0.01). Moreover, the results showed that COE down-regulated the expression of Bcl-2 and Bcl-xL, and up-regulated the levels of Bax and caspase-3 protein (P<0.01).@*CONCLUSION@#COE was a potential chemotherapeutic drug in HCC treatments via targeting mTOR signal pathway.

Therapeutic effect analysis of plasma exchange therapy on rhabdomyolysis syndrome patients caused by wasp stings / 中国中西医结合急救杂志

Objective To investigate the efficacy of plasma exchange therapy in the treatment of rhabdomyolysis syndrome (RMS) caused by wasp stings. Methods Sixty patients with RMS caused by wasp stings were enrolled in the Poisoning Treatment Ward of the Affiliated Hospital of Southwest Medical University from January 2015 to June 2019, including 40 patients complicated with acute kidney injury (AKI). After admission, the patients were given local treatment and systemic medication (intravenous infusion of glucocorticoid, calcium gluconate injection, intramuscular injection of isopropazine hydrochloride and other antihistamines). Plasma exchange was performed on the first and second day after admission, and according to the renal function situations, the patients with AKI underwent intermittent hemodialysis. The changes of urea (Ur), creatinine (Cr), hypersensitive troponin T (hs-TnT), myoglobin (MYO), creatine kinase isoenzyme (CK-MB), lactic dehydrogenase (LDH) and pathological changes of kidney were monitored on admission and after twice of plasma exchanges, and the above results of indexes were compared and analyzed. Results With the prolongation of the plasma exchange time, after the first plasma exchange the level of hs-TnT was significantly higher than that before the plasma exchange [μg/L: 1.30 (0.16, 4.37) vs. 0.26 (0.06, 1.26)], and the levels of LDH and CK-MB were lower than those before the exchange [LDH (μmol·s-1·L-1): 14.01 (6.73, 31.52) vs. 20.55 (8.73, 42.46), CK-MB (U/L): 41.25 (21.27, 102.83) vs. 89.92 (35.85, 163.53), both P < 0.05]; after the second plasma exchange, the Ur, Cr, LDH, hs-TnT, MYO and CK-MB were decreased significantly compared with those before the exchange [Ur (mmol/L): 9.77 (6.43, 11.90) vs. 11.58 (7.65, 19.49), Cr (μmol/L): 90.35 (67.10, 336.10) vs. 115.25 (77.50, 288.83), LDH (μmol·s-1·L-1): 7.84 (5.14, 18.68) vs 20.55 (8.73, 42.46), hs-TnT (μg/L): 0.02 (0.01, 0.09) vs. 0.26 (0.06, 1.26), MYO (μg/L): 200.00 (70.39, 1 000.00) vs. >1 000.00 (1 000.00, >1 000.00), CK-MB (U/L): 4.34 (1.86, 23.65) vs. 89.92 (35.85, 163.56), all P < 0.05]. Under light microscope, renal tubular epithelial cells fell off and showed"naked membrane", and infiltration of a small amount of inflammatory cells could be seen. Conclusion Plasma exchange can effectively remove macromolecules such as MYO, hs-TnT, CK-MB and LDH, reduce acute renal damage caused by rhabdomyolysis syndrome, shorten the course of disease and decrease mortality.

Association between intestinal dysbacteriosis and liver diseases / 临床肝胆病杂志

At present,studies have confirmed the closely relationship between liver diseases and intestinal flora,and regulation of intestinal flora has a certain effect on the progression and therapeutic outcome of liver diseases.With reference to the influencing mechanism of intestinal dysbacteriosis on liver diseases such as alcoholic liver disease,non-alcoholic liver disease,and acute liver injury,this article reviews the research advances in China and foreign countries and summarizes the complications of decompensated liver diseases,such as hepatic encephalopathy and spontaneous bacterial peritonitis,in order to provide new strategies for the treatment of liver diseases in future.

Clinical analysis of AIDS-related Kaposi's sarcoma in head and neck / 中国耳鼻咽喉头颈外科

OBJECTIVE To summarize the clinical features of the acquired immunodeficiency syndrome-related Kaposi's sarcoma(AIDS-KS) in head and neck. METHODS The clinical data of 20 inpatients with AIDS-KS in head and neck from June 2009 to September 2016 in Beijing Ditan Hospital were retrospectively analyzed. RESULTS All 20 patients were male, median age 38.50±10.98. One case was Manchu, 1 case was of Uygur, and others were Han nationality. There were 7 cases with homosexuality history, 2 cases with blood transfusion history, and 1 case with prostitution history. Mass in head and face was the first symptom in 10 cases. The head and neck skin and mucosa were involved, including 2 cases with nasal mucosa involvement, 4 cases with auricle skin involvement, 8 cases with oral mucosal involvement, 3 cases with facial skin involvement, 1 case with neck skin involvement, 1 case with eyelid conjunctiva involvement. Four cases had disseminated lesions. When diagnosed, the CD4+T lymphocyte were 52.55±47.87/mm3. The CD4+T were less than 200/mm3 in all of the patients, including CD4+T＜50/mm3 in 15 cases(75％). After treatment with highly active antiretroviral therapy combined with or without chemotherapy, 12 cases were discharged. Eight cases died due to respiratory failure or septic shock or other reasons. CONCLUSION Kaposi's sarcoma of the head and neck might be the first visit of AIDS patients. Some of the patients get partial remission after highly active antiretroviral therapy and the overall prognosis is poor.

Research progress for pathological mechanism and typing of coronary microcirculation dysfunction / 心血管康复医学杂志

Some patients have symptoms and signs of angina pectoris and relevant evidence of ischemia,but coronary angiography suggested no obvious coronary stenosis.Part of them is caused by coronary microcirculation dysfunction (CMD),which cannot be clinically identified early due to current techniques.Microcirculation dysfunction is corre-lated with occurrence of major clinical events,which can be used as strong predictor for prognosis.Therefore,un-derstanding of its pathological mechanism is help to guide the diagnosis and treatment.The present article made a re-view on pathological mechanism and typing of CMD.

Research progress for pathological mechanism and typing of coronary microcirculation dysfunction / 心血管康复医学杂志

Some patients have symptoms and signs of angina pectoris and relevant evidence of ischemia,but coronary angiography suggested no obvious coronary stenosis.Part of them is caused by coronary microcirculation dysfunction (CMD),which cannot be clinically identified early due to current techniques.Microcirculation dysfunction is corre-lated with occurrence of major clinical events,which can be used as strong predictor for prognosis.Therefore,un-derstanding of its pathological mechanism is help to guide the diagnosis and treatment.The present article made a re-view on pathological mechanism and typing of CMD.

Value of IVIM-DWI and DCE-MRI in the assessment of benign and malignant mesorectal lymph nodes in rectal cancer / 实用放射学杂志

Objective To investigate the diagnostic value of intravoxel incoherent motion diffusion weighted imaging (IVIM-DWI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI)in differentiating non-metastatic from metastatic mesorectal lymph nodes in rectal cancer.Methods IVIM-DWI and DCE-MRI were performed preoperatively in 38 patients with histologically proven rectal carcinoma.The short axis diameter,short-to-long axis diameter ratio,four IVIM-based parameters (ADC,D,D? and f) and six DEC-MRI semi-quantitative parameters (Slope,Maxslope,CER,Washout,TTP,iAUC90 and iAUC180 )were compared between the metastatic (n=28)and non-metastatic (n=27)lymph nodes.Results There were significant statistical significances between the metastatic and non-metastatic lymph nodes in mean short axis diameter (8.87 mm±2.829 mm vs 6.83 mm±1.075 mm),D value[(0.824±0.1 13)× 10 -3 mm2/s vs (1.033±0.244)× 10 -3 mm2/s],CER(1.588 ±0.664 vs 1.054 ±0.41 9),iAUC90 (22.89 ± 9.83 vs 13.59 ± 5.34)and iAUC1 80 (49.38±20.1 9 vs 30.31 ± 1 1.67)(P ≤0.001).The short-to-long axis diameter ratio,ADC,D? ,f,Slope,Maxslope,Washout and TTP values did not show significant differences between the two groups(P >0.05).The respectively optimal cut-off value (area under the curve,sensitivity and specificity)for distinguishing metastatic from non-metastatic lymph nodes were as follows:short axis diameter=7.1 mm(0.744,64.2%,85.1%),D=0.906×10 -3 mm2/s (0.821,81.5%,75.0%),CER=1.05(0.749,85.7%,62.9%), iAUC90 =13.42(0.780,85.7%,62.9%),iAUC180 =49.65 (0.770, 50.0%,100%)respecyively.Conclusion Both IVIM-DWI and DCE-MRI are useful for differentiating non-metastatic from metastatic mesorectal lymph nodes in rectal cancer.

Construction of external treatment data mining system for prescriptions of fragrant traditional Chinese medicine covered in ancient books on traditional Chinese medicine / 中华医学图书情报杂志

The effects of prescriptions of fragrant traditional Chinese medicine covered in ancient books on traditional Chinese medicine published in the past dynasties on disease control and treatment were retrieved from the Full-text Database of Ancient Books on Traditional Chinese Medicine developed by Nanjing University of Traditional Chinese Medicine. A fragrant medicinal subject system with unique characteristics was established by analyzing the characteristics of prescribed fragrant traditional Chi-nese medicine and the prescribing rules of fragrant traditional Chinese medicine according to theirprinciples-methods-formulae-medicinal, clarifying the related factors influencing diseases and the related mechanisms of prescriptions, which can not only promote the theoretical and practical development of external treatment with prescriptions of fragrant traditional Chinese medicine but also provide the reliable philological basis for external diseases and pharmacology of traditional Chinese medical formulae.

The role of hypoxia induced factor-1alpha/apelin/APJ pathway in cardiac stem cell proliferation and cardiogenic differentiation after hypoxia preconditioning / 中国组织工程研究

BACKGROUND: Our previous studies demonstrated that cardiac stem cells (CSCs) transplantation could improve cardiac function in rats with myocardial infarction (MI). However, the overall survival and cardiac differentiation of CSCs were low. OBJECTIVE: To investigate the effect of hypoxia preconditioning on CSCs proliferation and cardiogenic differentiation and the role of hypoxia induced factor-1alpha (HIF-1α)/apelin/putative receptor protein related to the angiotensin receptor AT1 (APJ) pathway in the procedure. METHODS: Cells cultured in vitro experienced exposure to hypoxia (1% O2) for 24 hours. Cardiogenic differentiation was induced by using 5-azacytidine for another 24 hours. Then, cells were cultured in normal condition for 2 weeks. Normoxia (20% O2) was used as a negative control during the whole process. Cell proliferation was detected using MTS method and expressions of HIF-1α, apelin, cTnT and APJ were detected using western blot assay after 24 hours of preconditioning and 2 weeks after the induction of differentiation; the percentage of cTnT-positive cardiomyocyte-like cells was observed by immunofluorescence staining. RESULTS AND CONCLUSION: Compared with the normoxia group, the hypoxia group presented a higher proliferation rate and a higher absorbance value at 490 nm (P < 0.01); the protein expressions of HIF-1α, apelin and APJ were all enhanced after hypoxia exposure for 24 hours and 2 weeks after the induction of differentiation (P < 0.01); the percentage of cTnT-positive cells was greatly increased in the hypoxia group (P < 0.01), and the expression of cTnT was also significantly intensified (P < 0.01). To conclude, hypoxia preconditioning could promote the proliferation and cardiogenic differentiation of CSCs, and the activation of HIF-1α/Apelin/APJ pathway might be involved in this process.

Analysis of components in plasma from effective fractions of Inula cappa based on UHPLC/Q-TOF/MS / 中国药理学通报

Aim To analyze the main components of effective fractions of Inula cappa in rat plasma with UHPLC/Q-TOF/MS technology and serum pharmacochemistry theory.Methods After gavage administration with Inula cappa extracts,blood was collected from abdominal aorta,and the protein in plasma sample was precipitated by methanol.Eclipse Plus C18 RRHD (2.1 mm × 100 mm,1.8 μm) was used,with 0.1％ formic acid agueous solution (A)-0.1％ formic acid and acetonitrile (B) as the mobile phase for gradient elution,and the flow rate was 0.3 mL ·min-1 Detected at negative ion mode,and with the help of Metabolite Tools software from Bruker Corporation,components in plasma were defined.Results A total of 16 compounds were identified,including 9 prototypes and 7 metabolites.Main metabolites were isomerization,methylation,glucuronidation and recombination of caffeoylquinic acid.Conclusions Therefore,our study has comprehensively expounded Inula cappa extracts' constituents migrating to rat plasma,and provided a reference for further studies for in vivo metabolic process and effective material base of Inula cappa.