Objective To investigate the coagulant function of Thrombomodulin-Protein C-EPCR System in rats with hemorrhagic shock in virto study.Methods In this study,30 rats were divided into three groups,with each group 10 rats:control group,the sham shock group,hemorrhagic shock group.Hemorrhagic shock model was subjected to computer-controlled arterial hemorrhage to 40 mm Hg for 60 min The rat blood serum samples were obtained from rats in sham shock group and shock group after maintaining 3 hours,and fetal bovine serum (FBS) was used as control group.Then medium contained fore-mentioned serums cultured with SV40-transformed aortic rat endothelial cells for 6 hours,12 hours and 18hours.The messenger RNA (mRNA) expression of thrombmodulin (TM),Endothelial cell protein C receptor in the SV40-transformed aortic rat endothelial cells which were treated with serums were detected by reverse-transcription polymerase chain reaction.Results Compared to control group,SVARECs were incubated for 6hrs with shock serum,the mRNA expression of TF,TM and t-PA was significantly higher,and continued elevating at the time of 18 hours (P ＜ 0.01).Conclusions Serums from hemorrhagic shock rats upregulate TMmRNA EPCRmRNA expression on the endothelial cells surface.It is suggested that Thrombomodulin-Protein C-EPCR System pay a key role of anticoagulation,the protection of endothelial function.

This study was aimed to observe the effects on glucolipid metabolism of aqueous extract of traditional South African herb Sutherlandia. Intraperitoneal injection of streptozotocin (STZ) combined with high fat feed method was used in the establishment of type 2 diabetes rat model. Then, rats were randomly divided into the normal group, model group, pioglitazone group, and the Sutherlandia group. Observation was made on changes of body weight, oral glucose tolerance test (OGTT), blood triglycerides (TG), total cholesterol (TC), low density lipoprotein (LDL-C), high density lipoprotein (HDL-C). Western blot method was used to detect IRS-1 expression of skeletal muscle in rats of each group. The results showed that compared with the normal group, body weight in the model group was decreased, and indicators of OGTT, TG, TC, LDL-C were significantly increased (P< 0.05). Symptoms such as increased drink-ing, eating and urine were obvious; and the IRS-1 expression was obviously decreased (P< 0.05). After treatment, compared with the model group, there was no significant body weight increase in the Sutherlandia group or the pi-oglitazone group. Indicators of blood glucose, TG, TC in the Sutherlandia group and the pioglitazone group were ob-viously decreased with no statistical difference (P< 0.05 or P< 0.01). In the Sutherlandia group and the pioglitazone group, IRS-1 expression of skeletal muscle in rats was obviously increased with no statistical difference (P< 0.05). It was concluded that type 2 diabetes rats induced by intraperitoneal injection of STZ combined with high fat feed method can induce glucolipid metabolism disorders. Traditional South African herb Sutherlandia can obviously reduce the blood sugar level, improve blood lipid metabolism, and improve the level of insulin. Sutherlandia can improve the IRS-1 expression of skeletal muscle in rats, relief the insulin resistance, and lower blood sugar. However, the effect of its exact ways required further in-depth study.

BACKGROUNDMethylenetetrahydrofolate reductase (MTHFR) plays an important role in metabolism of folate and DNA methylation. In vitro, many studies have demonstrated that abnormal methylation of some genes may affect the sensitivity of tumor cells to cytotoxic drugs and agents interfering with DNA synthesis. The aim of this study is to investigate the relationship between genetic polymorphisms of MTHFR C677T or A1298C and the response to platinum-based chemotherapy in non-small cell lung cancer (NSCLC).

METHODSA total of 97 patients with NSCLC were analyzed. MTHFR genotypes were detected in all the patients by PCR-RFLP method. All the patients were treated with platinum-based chemotherapy.

RESULTS(1) Out of all the cases, the frequencies of MTHFR C677T C/C, C/T and T/T genotypes were 34.0%, 50.5% and 15.5%, respectively, while the frequencies of MTHFR A1298C A/A, A/C and C/C genotypes were 64.6%, 29.2% and 6.3%, respectively. The overall response rate (complete and partial response) to platinum-based chemotherapy was 39.2%. (2) No significant difference in response rate to chemotherapy was observed according to the MTHFR C677T or A1298C genotypes. However, MTHFR C677T and A1298C polymorphisms showed a synergic effect on chemotherapeutic efficacy, the response rate of patients with MTHFR C677T T allele and A1298C A/A genotype (51.1%) was significantly higher than those with MTHFR C677T C/T and A1298C C allele (12.5%)(P=0.007, OR=7.30, 95% CI: 1.34-52.47).

CONCLUSIONSThe results suggest that the synergic effect between MTHFR C677T and A1298C polymorphisms is associated with clinical response to platinum-based chemotherapy. Detection of MTHFR genotypes may indicate the sensitivity of NSCLC patients to platinum-based chemotherapy.

Objective To observe the effects of electroacupuncture(EA)on glutamate(Glu),metabotropic glutamate receptor 2/3(mGluR2/3)and apoptosis related proteins expression in hippocampus in rats with acute myocardial ischemia(AMI);To explore the mechanism of EA against AMI.Methods Totally 50 SD rats were randomly divided into sham-operation group,model group,EA group and inhibitor group,with 10 rats in each group.Except for the sham-operation group,the rats were treated with ligation at the left anterior descending coronary artery to establish AMI model.The rats in the EA group was treated with EA at"Shenmen"and"Tongli",30 minutes each time,once a day for 3 consecutive days.The rats in the inhibitor group were treated with injection of LY341459 via the lateral ventricle 30 min after modeling.HE staining was used to observe myocardial tissue morphology,and ELISA was used to detect Caspase-3 activity in myocardial tissue and Glu content in hippocampal tissue,immunofluorescence staining was used to detect mGluR2/3 expression in hippocampal tissue,TUNEL staining was used to detect apoptosis in hippocampal tissue cells,Western blot was used to detect the expressions of PI3K,Akt,and Caspase-3 protein in hippocampal tissue.Results Compared with the sham-operation group,the myocardial cells of the model group rats showed sparse and swelling with severe infiltration of inflammatory cells;the activity of Caspase-3 in myocardial tissue significantly increased,and the Glu content,positive expression of mGluR2/3,number of apoptotic cells in hippocampal tissue significantly increased(P<0.01),and the expressions of PI3K and Akt proteins in hippocampal tissue were significantly decreased,while the expression of Caspase-3 protein significantly increased(P<0.01).Compared with the model group,myocardial cell edema and inflammatory cell infiltration were reduced in the EA group and inhibitor group,the activity of Caspase-3 in myocardial tissue was significantly decreased,the Glu content,positive expression of mGluR2/3,and number of apoptotic cells in hippocampal tissue were significantly reduced(P<0.01),the expressions of PI3K and Akt proteins in hippocampal tissue significantly increased,while the expression of Caspase-3 protein significantly decreased(P<0.01).Conclusion EA can improve myocardial injury in AMI rats,and its mechanism may be related to activation of PI3K/Akt signaling pathway,inhibition of hippocampal mGluR2/3 overexpression,reduction of Glu accumulation,inhibition of apoptosis of hippocampal neurons and reduction of neurotoxicity.

Objective:To screen the optimal process of ambi-extracting of Xinyi Powder and inclusion of volatile oil.Methods:Single factor experiment was used to optimize the extraction process of Xinyi Powder by taking crushing particle size, extraction times, the amount of water added and extraction time as the investigation factors. L 9(3 4) orthogonal test was used to optimize the inclusion process of volatile oil in Xinyi Powder. Results:The optimal extraction process of ambi-extracting of Xinyi Powder was as follows: the slices were not crushed, 10 times the amount of water was added, and extracted for 3 hours; the best inclusion process of volatile oil as follows: β-cyclodextrin:water=1:25, β-cyclodextrin:volatile oil=6:1, inclusion temperature 35 ℃, inclusion time 3 hours.Conclusion:The ambi-extracting process and volatile oil inclusion process are simple, stable and feasible.

Objective: This study aimed to evaluate the consistency or stability of mental disorders diagnosed in the psychiatry ward setting, investigate factors associated with consistency, and observe the disease distribution over the decade. Methods: A total of 20,359 psychiatric inpatients were included in this retrospective study from June 2011 to December 2020. Diagnoses from the first admission to discharge were evaluated to determine the diagnostic consistency during hospitalization. Readmissions were selected as the subgroup, whose first and last discharge diagnoses were compared to analyze the relatively long-term diagnostic stability. Demographic and clinical characteristics were collected to identify predictors of diagnostic discrepancy. Results: From 2011–2020, the hospitalization rate decreased from 42.7% to 20.7% for schizophrenia and grew from 13.3% to 23.8% for depression. Diagnoses were retained by 92.6% of patients at their first discharge diagnosis, ranging from 100% for disorders of psychological development to 16.3% for unspecified mental disorders. About 33.9% of diagnostic conversions were to bipolar disorder in patients having inconsistent diagnoses. However, among rehospitalizations, the diagnostic stability notably dropped to 71.3%. For rehospitalizations, mood disorders and schizophrenia spectrum disorders were relatively stable diagnoses categories, with 72.6% to 76.7% of patients receiving the same diagnosis, although results of specified diagnoses within these categories ranged from 5.9% to 91.0%. Except for mood disorders and schizophrenia spectrum disorders, the diagnoses of all other categories were below 70%. Long lengths of hospitalization and old age were associated with short-term diagnosis alterations. Conclusion Longitudinal follow-up and integration of multiple aspects of information are essential for accurate diagnosis.

Objective:To explore the effect of tanshinone ⅡA on myocardial remodeling in ischemia/reperfusion (I/R)-induced heart failure of rodent model.Methods:① In vivo, 30 SD rats were randomly divided into sham operation, heart failure and tanshinone ⅡA treatment group, with 10 rats in each group. The I/R model was established by ligating the left coronary artery until ST segment elevation for 30 minutes, then the ligation was removed for 2 hours as reperfusion. In the sham operation group, the rat chest was opened without artery ligation. Three days after model establishment, tanshinone ⅡA (10 mg/kg) were given intraperitoneal injected in tanshinone ⅡA group for 9 weeks. In the other two groups, normal saline was administrated in the same way. The behavioral manifestations of the rats in each group were observed; hemodynamic indexes were evaluated; Masson staining was performed to observe the degree of myocardial fibrosis; enzyme linked immunosorbent assay (ELISA) was used to detect the content of Galectin-3 in myocardial tissue; quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to detect the expressions of collagenⅢ, collagenⅠ, matrix metalloproteinase 2 (MMP-2) and tissue inhibitor of metalloproteinase (TIMP-1). ② In vitro, rats primary cardiac fibroblasts were extracted and isolated, and divided into blank control group, angiotensinⅡ group (7-10 mmol/L angiotensinⅡ) and angiotensinⅡ+ tanshinoneⅡA group (7-10 mmol/L angiotensinⅡ+ 5-10 mmol/L tanshinone ⅡA). At 24 hours and 48 hours of culture, the cell proliferation in each group was detected by methyl thiazolyl tetrazolium (MTT); the expressions of collagenⅢ, collagenⅠ, MMP-2 and TIMP-1 were detected by qRT-PCR; the content of Galectin-3 in cardiac fibroblasts was detected by ELSIA. Results:① In vivo, the rats' activity status, hair conformity and food intake were ranked from good to bad in order of sham operation group, tanshinone ⅡA group and heart failure model group. Compared with the sham-operated group, the heart rate (HR) of the rats in the heart failure model group was significantly decreased and the heart function was significantly impaired. The mRNA and protein expression of collagenⅠ, collagenⅢ, TIMP-1 and Galectin-3 content were significantly increased, while the mRNA and protein expression of MMP-2 were significantly decreased. Compared with the heart failure model group, rats in the tanshinone ⅡA group showed significantly higher HR and improved cardiac function, significantly lower mRNA expression of collagenⅠ and collagenⅢ, significantly lower mRNA and protein expression of TIMP-1 and Galectin-3, and significantly higher mRNA and protein expression of MMP-2, and the most obvious changes were in the 9th weeks of modeling [collagenⅠ mRNA (2 -ΔΔCt): 4.70±1.19 vs. 10.21±1.62, collagenⅢ mRNA (2 -ΔΔCt): 3.03±0.46 vs. 13.84±1.93, TIMP-1 mRNA (2 -ΔΔCt): 1.90±0.19 vs. 4.55±0.43, TIMP-1/GAPDH: 0.33±0.04 vs. 0.67±0.05, Galectin-3 (ng/L): 489.93±79.30 vs. 821.72±94.09, MMP-2 mRNA (2 -ΔΔCt): 0.37±0.07 vs. 0.03±0.01, MMP-2/GAPDH: 0.69±0.09 vs. 0.21±0.04, all P < 0.05]. Masson staining showed that myocardial tissue fibrosis was obvious in the heart failure group, and the degree of fibrosis in the tanshinoneⅡA group was reduced. ② In vitro, compared with the blank control group, the proliferation rate, collagenⅠ, collagen Ⅲ and TIMP-1 expression and Galectin-3 content of myocardial fibroblasts were significantly increased, and MMP-2 expression was significantly decreased in the angiotensin group at 24 h and 48 h of culture. Compared with the angiotensin group, the proliferation rate of cardiac fibroblasts and the expression of collagenⅠ, collagen Ⅲ and TIMP-1 and the content of Galectin-3 were significantly decreased, and the expression of MMP-2 mRNA was significantly increased in the angiotensin + tanshinone ⅡA group, and the most significant changes were at 48 hours of culture [proliferation rate: (57.0±3.7)% vs. (67.0±2.4)%, collagenⅠmRNA (2 -ΔΔCt): 551.43±67.10 vs. 871.48±12.25, collagenⅢ mRNA (2 -ΔΔCt): 233.76±18.73 vs. 385.51±31.35, TIMP-1 mRNA (2 -ΔΔCt): 238.69±17.37 vs. 351.84±26.17, Galectin-3 (ng/L): 283.76±28.73 vs. 415.51±31.35, MMP-2 mRNA (2 -ΔΔCt): 108.54±12.10 vs. 51.47±6.25, all P < 0.05]. Conclusion:Tanshinone ⅡA can improve cardiac function, inhibit myocardial fibrosis and improve myocardial remodeling in rats with I/R-induced heart failure.

Objective:To investigate the radiation dosimetry and biodistribution of 68Ga-FAPI-04 PET/CT in patients with hepatobiliary tumor. Methods:A total of six patients with hepatic lesions who underwent PET/CT examination in Peking Union Medical College Hospital were enrolled. After intravenous injection of radiotracer 68Ga-FAPI-04 at (170.57 ± 14.43) MBq, whole-body imaging were performed at the time points of 3, 10, 15, 20, 30 and 60 min, respectively. Biodistribution pattern was observed. Regions of interest were manually delineated. Radiation dosimetry of all target organs were calculated by Olinda/EXM software. Results:The radioactive uptake dissipated gradually in liver whereas it was relatively stable in tumor lesions. The average SUV max of tumor lesions reached the maximum value (13.87± 2.55) at 20 min after injection. The target-to-background ratio increased with time, reaching the maximum value (10.09 ± 8.17) at 30 min after injection. The average effective dose in total body was (0.020 ± 0.002) mSv/MBq and organ with the highest effective dose was bladder wall at (0.146 ± 0.035) mSv/MBq. Conclusions:The effective dose in total body of 68Ga-FAPI-04 was similar to that of 18F-FDG. 68Ga-FAPI-04 is expected to be a PET/CT radiotracer for hepatobiliary tumors in consideration of rapid tumor uptake, low accumulation of liver background, and no influence of blood sugar levels.

Stress cardiomyopathy (SC) is an acute cardiomyopathy caused by intense mental stimulation or physical stress. Currently, few interventions are effective in reducing mortality, improving prognosis, or preventing recurrence in acute or chronic stages of SC. Therefore, it is particularly important to establish a reliable and effective SC animal model to study the pathogenesis and prevention of SC. In this paper, the preparation methods and evaluation indexes of SC models at home and abroad were reviewed, including the operation details of catecholamine hormone injection method, binding method, binding combined with electroshock method, binding combined with dehydration method, vagus nerve electrical stimulation and other modeling methods, as well as evaluation indexes such as open field test, cardiac ultrasound, electrocardiogram and ELISA, striving to provide useful reference for model selection and establishment of SC research.

ObjectiveTo reveal the influence of Jianchangbang characteristic processing method on the change process of volatile components and the processing mechanism of reducing toxicity and increasing efficiency of Magnoliae Officinalis Cortex（MOC） by studying the changes in the composition and content of volatile components during the processing of ginger processed Xingpo pieces. MethodSamples of raw products， ginger juice moisturized products and stir-fried and heap moisturized products of MOC were taken according to the set time points， and headspace gas chromatography-mass spectrometry（HS-GC-MS） was used to determine the contents of volatile components in the samples， and the relative content of each component was obtained by peak area normalization. Principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA） were performed on the sample data using SIMCA 14.1 software， and the differential components during the processing were screened with variable importance in the projection（VIP） value>1 as the indicator. ResultA total of 68 volatile components were identified in the samples， among which some of the chemical components with similar structures showed similar trends of changes， and there was also the phenomenon of interconversion between compounds. Compared with the raw products， the contents of 42 components in ginger juice moisturized products increased， while the contents of 25 components decreased， 19 components were unique， and 4 components were unique to the raw products. Compared with ginger juice moisturized products， MOC in the early stage of piling had three unique components， and the contents of 11 components such as cyclosativene and （+）-α-pinene increased， and the contents of 5 components such as tricyclic terpene and α-curcumene decreased， and ginger juice moisturized products had four unique components. Compared with the early stage of piling， in the later stage， the contents of 8 components such as （+）-α-pinene and camphene significantly increased， while the contents of 6 components such as linalool and α-selinene significantly decreased. During the processing of MOC， there were significant changes in the chemical composition of the samples before and after 20 days. The differences between ginger juice moistening and the early stage of piling， the early stage and the later stage of piling could be clearly distinguished. ConclusionDuring the preparation process of ginger processed Xingpo pieces， the addition of ginger juice can reduce the contents of stimulating components， and the contents of active components continue to increase in several stages， such as the addition of ginger juice， frying and heap moisturizing， the quality of the decoction pieces may change significantly at about 20 d of processing. This study can provide a research basis for exploring the processing mechanism of ginger processed Xingpo pieces.