Myocardial ischemia/reperfusion injury(MIRI)occurs after cardiopulmonary bypass open heart surgery,cardiovascular intervention and thrombolytic therapy,which is the most important cause of cardiac insufficiency,heart fail-ure,and even death in patients after treatment.In recent years,studies have found that the release of endogenous active peptides can alleviate the production of MIRI,and regulating the function and action of endogenous peptides may be one of the most effective ways to treat MIRI.Dipeptidyl peptidase 4(DPP4)is an important serine protease in mammals,with enzymatic activity to hydrolyze endogenous peptides.Its primary physiological function is to metabolize short peptides,in-cluding growth factors,hormones,etc.This review aims to better understand and search for effective therapeutic targets by elucidating the impact of DPP4 on the hydrolysis of endogenous peptides in MIRI,and ultimately provide new ideas for the therapeutic effects of MIRI.

Traditionally, Tripterygium hypoglaucum (Levl.) Hutch (THH) are widely used in Chinese folk to treat rheumatoid arthritis (RA). This study aimed to investigate whether the anti-RA effect of THH is related with the gut microbiota. The main components of prepared THH extract were identified by HPLC-MS. C57BL/6 mice with adjuvant-induced arthritis (AIA) were treated with THH extract by gavage for one month. THH extract significantly alleviated swollen ankle, joint cavity exudation, and articular cartilage destruction in AIA mice. The mRNA and protein levels of inflammatory mediators in muscles and plasma indicated that THH extract attenuated inflammatory responses in the joint by blocking TLR4/MyD88/MAPK signaling pathways. THH extract remarkably restored the dysbiosis of the gut microbiota in AIA mice, featuring the increases of Bifidobacterium, Akkermansia, and Lactobacillus and the decreases of Butyricimonas, Parabacteroides, and Anaeroplasma. Furthermore, the altered bacteria were closely correlated with physiological indices and drove metabolic changes of the intestinal microbiota. In addition, antibiotic-induced pseudo germ-free mice were employed to verify the role of the intestinal flora. Strikingly, THH treatment failed to ameliorate the arthritis symptoms and signaling pathways in pseudo germ-free mice, which validates the indispensable role of the intestinal flora. For the first time, we demonstrated that THH extract protects joint inflammation by manipulating the intestinal flora and regulating the TLR4/MyD88/MAPK signaling pathway. Therefore, THH extract may serve as a microbial modulator to recover RA in clincial practice.ver RA in clincial practice.
Mice ; Animals ; Gastrointestinal Microbiome ; Tripterygium ; Myeloid Differentiation Factor 88/genetics* ; Toll-Like Receptor 4/genetics* ; Mice, Inbred C57BL ; Arthritis, Experimental/drug therapy*

OBJECTIVE：To prov ide referen ce for clinical safe and rational use of belimumab by mining the risk signals of adverse drug event （ADE）. METHODS ：ADE reports related to belimumab were collected from FDA adverse event reporting system（FAERS）from the first quarter of 2015 to the first quarter of 2021. The reporting odds ratio （ROR）method and the Medicines and Healthcare Products Regulatory Agency （MHRA）method were adopted to mine the ADE risk signals related to belimumab，setting the threshold as the number of reports ＞3 and the lower limit of 95％ CI ＞1（ROR method ）and the proportional reporting ratio （PRR）＞2，and χ2 ＞4（MHRA method ）. ADEs were counted and classified by using the preferred system organ class （SOC）and preferred term （PT）of Medical Dictionary for Regulatory Activities （MedDRA）. RESULTS & CONCLUSIONS：A total of 3 529 ADE reports with belimumab as the primary suspicious drug were screened ，in which female patients（90.31％）were much more than male patients （6.15％）；age distribution was concentrated in 18-59 years old （41.80％）. There were 1 234 cases（34.97％）of severe ADE reports ，mainly involving hospital or prolonged hospital stay. Most of the reporters were consumers or other non-medical professionals （81.84％）. North America reported the most （70.39％）and the main reporting country was the United States （2 029 reports）. A total of 180 PTs were mined from 3 529 reports，in addition to PTs associated with primary disease （systemic lupus erythematosus ，pain，arthralgia，pyrexia，weight decreased ，swelling，oropharyngeal pain ， etc.），PTs related to medication error （product dose omission ，inappropriate schedule of product administration ，underdose， product availability issue ，etc.）and PTs related to infection （influenza，urinary tract infection ，infection，sinusitis，etc.）were reported in a large number of cases. Twenty-six SOCs were involved ，the top 10 SOC in ADE reports were all kinds of injuries ， poisoning and surgical complications （2 225 reports），infections and infectious diseases （1 247 reports），general disorders and administration site conditions （1 196 reports），musculoskeletal and connective tissue disorders （1 195 reports），surgical and medical procedures（515 reports），etc. PTs in SOC in the first place （all kinds of injuries ，poisoning and surgical complications ）of ADE reports were all related to medication error ；herpes zoster ，kidney infection and cellulitis in SOC in the second place （infections and infectious diseases ）of ADE reports were not included in the drug instruction of belimumab ；most PTs in SOCs such as various nervous system diseases ，immune system diseases ，mental diseases ，benign，malignant and unknown tumors （including cystic and polypoid）which were taken attention in clinic were not included in the drug instruction of belimumab. It is suggested to avoid medication errors as far as possible in clinical use of belimumab ，and to guard against adverse reactions such as herpes zoster ， kidney infection ，cellulitis and various nervous system diseases ，immune system diseases and mental diseases. In addition ，the patients with malignant tumor or related history should use belizumab carefully.

Objective:To test whether the constructed intervention model of advance care planning (ACP) for patients with advanced cancer can be successfully implemented and the preliminary intervention effect, which provides reference for empirical research.Methods:32 cases of advanced cancer patients and 25 cases of their families at the Fifth Affiliated Hospital of Zunyi Medical University, Zhuhai were selected. The patients were subdivided into the experimental group and the control group by random number table method. The control group received routine nursing, while the experimental group adopted the intervention model of "VIP for future care" on the basis of customary nursing. We measured the main outcome indicators: enrollment rate, consent rate, completion rate and loss of follow-up rate and secondary outcome indicators: decision-making certainty, end-of-life care preference and post-intervention satisfaction of patients and their families, within 1 week and 1 month after intervention.Results:The enrollment rate, consent rate and loss of follow-up rate were 74.6% (206/276), 36.9% (76/151)and 15.6% (5/32), respectively. After intervention, the completion rates of the experimental group and the control group were 16/16 and 15/16 within one week, and 14/16 and 13/16 within one month. All of the family members were conducted during the follow-up period. The intervention mode of "VIP for future care" had a statistically significant difference in decision-making certainty between the two groups of patients ( β=0.63, 95% CI 0.08-1.18, P<0.05), no statistically significant difference in end-of-life care preference between the two groups of patients and their families ( P>0.05), and had a statistically significant difference in "whether to recommend this project to others" between the two groups ( χ2 value was 4.167 , P<0.05). Conclusions:On the premise of sufficient preparation, the "VIP for future care" intervention mode can be successfully implemented in advanced cancer patients in mainland China, can improve the decision-making certainty of patients and the satisfaction of patients and their families, and it is recommended. And should be applied to ACP intervention for patients with advanced cancer.

Objective To evaluate the feasibility of anticoagulant therapy for acute proximal deep vein thrombosis without inferior vena cava filter placement for femoral neck patients before hip arthroplasty.Methods From January 2013 to August 2017,9 femoral neck fractures patients with acute proximal deep vein thrombosis before hip arthroplasty were enrolled into this study.There were 3 men and 6 women.The average age was 76.44±5.39 years old (range,69 to 83 years old).The average injured time before admission was 4.00±4.06 days.All patients received anticoagulant therapy without placement of inferior vena cava filter before hip arthroplasty.Four patients received Rivaroxaban 10mg,two times per day,while two patients received Enoxaparin 0.4 ml,two times per day;3 cases received Batroxobin 0.5 ml,every other day combined with Rivaroxaban 10 mg one time per day or Enoxaparin 0.4 ml,one time per day.The size of thrombus before and after treatment,changes of coagulation markers,the outcome of thrombosis before surgery,during surgery,postoperatively and during follow-up,the related complications were recorded.Results The diagnosis time for proximal DVT was 3.89±3.01 days after admission.8 patients showed proximal DVT combined with distal thrombus and 1 patient showed isolated proximal DVT.The average length of proximal thrombus was 10.78±6.10 cm (range,4.0-20.0 cm).The mean duration of treatment was 14.22±7.03 days.The results showed 5 proximal DVTs have complete disappeared,3 cases significantly improved,and 1 case had no change but showed stable.After treatment,the length of the proximal thrombus was significantly decreased (10.77±6.10 cm vs.4.39±6.50 cm),there were statistically significant between two groups (t=3.429,P=0.009);D-dimer was significantly lower after treatment (10.47±4.87 μg/ml vs.2.59± 1.60 μg/ml) with statistical difference (t=4.970,P=O.O01).However,no statistical significance was found in other coagulation parameters such as plasma prothrombin time,the international normalized ratio,activated partial thromboplastin time,thrombin time,fibrinogen.Incision exudate occurred in one patient and anticoagulant therapy was paused,however,two days later,DVT recurred and then the patient received continuous therapy with drug anticoagulation.The average time for postoperative follow-up was 8.3±7.6 months.At the latest follow-up,4 cases had thoroughly recovered with the thrombi fully resolved;4 cases had significantly improved including three thrombi partly locating in the muscular veins and one partly locating in the infra-popliteal vein.One case became more severe after discharge and received continuous anticoagulant therapy.No death,symptomatic pulmonary embolism,bleeding and other adverse events occurred.Conclusion Inferior vena cava filter placement for femoral neck fracture patients with acute proximal venous thrombosis before hip arthroplasty may not be potent.Anticoagulant therapy which make the proximal thrombus completely dissolved or stabilized before surgery may be effective.

BACKGROUND: China has the world's largest tea plantation area in the world. To sustain high yields of the tea, multiple pesticides are used on tea crops to control pests. Organophosphorus (OP) pesticides are among the most widely used types of agricultural pesticides in China. As tea is a significant potential source of exposure to pesticide residues, the public concern has increased in relation to pesticide residues found in tea in China. The aim of the study was to estimate cumulative dietary exposure to OP residues from tea infusion for Chinese tea consumers to determine whether exposure to OP residues from tea infusion is a cause of health concern for tea consumers in China. METHODS: OP residue data were obtained from the China National Monitoring Program on Food Safety (2013-2014), encompassing 1687 tea samples from 12 provinces. Tea consumption data were obtained from the China National Nutrient and Health Survey (2002), comprising 506 tea consumers aged 15-82 years. The transfer rates of residues from tea leaves into tea infusions were obtained from the literature. The relative potency factor (RPF) approach was used to estimate acute cumulative exposure to 20 OP residues from tea infusion using methamidophos as the index compound. Dietary exposure was calculated in a probabilistic way. RESULTS: For tea consumers, the mean and the 99.9th percentile (P99.9) of cumulative dietary exposure to OP residues from tea infusion equalled 0.08 and 1.08 μg/kg bw/d. When compared with the acute reference dose (ARfD), 10 μg/kg bw/d for methamidophos, this accounts for 0.8 and 10.8% of the ARfD. CONCLUSIONS Even when considering OP residues from vegetables, fruits and other foods, there are no health concerns based on acute dietary exposure to OP residues from tea infusion. However, it is necessary to strengthen the management of the OP pesticides used on tea in China to reduce the risk of chronic dietary exposure to OPs from tea infusion.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; China ; Dietary Exposure ; analysis ; Female ; Humans ; Male ; Middle Aged ; Organophosphorus Compounds ; analysis ; Pesticide Residues ; analysis ; Risk Assessment ; methods ; Tea ; chemistry ; Young Adult

Objective To observe the expression of PAX-2 and PTEN in different types of endometrial lesions, and to study their relationship with endometrial intraepithelial neoplasia (EIN). Methods 60 cases of endometrial hyperplasic lesions and 70 cases of endometrial carcinoma were enrolled. All cases were reclassified by using the diagnostic criteria of EIN, and PAX-2 and PTEN were stained to compare the difference among them. Results The deletion rates of PAX-2 in benign hyperplasia, EIN and endometrial carcinoma were 39.5 % (15/38), 72.7 % (16/22) and 78.6 % (55/70), respectively, and there was a statistical difference (χ2= 21.664, P= 0.000). The deletion rates of PTEN in benign hyperplasia, EIN and endometrial carcinoma were 47.4%(18/38), 54.5%(12/22) and 75.7%(53/70), respectively, and there was no statistical difference (χ2=2.878, P=0.411). Conclusion The staining of PAX-2 could be considered as a reliable adjuvant diagnostic method in the diagnostic criteria of EIN, however, the loss of PTEN just should be regarded as a suggestion of EIN, not a confirmed diagnostic basis.

Objective:To investigate the effect of the extract of Schisandra chinensis on the matrix metalloproteinases(MMPs) system in kidney tissue of the diabetic rats,and to explore its protective effect on the kidney tissue from the matrix degradation perspective.Methods:STZ was used to establish rat models of diabetes mellitus.A total of 45 diabetic rats were randomly divided into model group,extract of Schisandra chinensis group and Benazepril group,and there were 15 rats in each group.Another 15 rats were selected and used as normal control group.12 weeks after administration,the routine blood and urine biochemical indexes,the histological changes,blood glucose (BG),blood urea nitrogen(BUN),serum creatinine(Scr),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterin(LDL-C),total cholesterol(T-CHO),and triglyceride(TG) levels,excretion rates of albuminuria and proteinuria of the rats in various groups were detected;the expression amounts of fibronectin (FN),type Ⅳ collagen (Col Ⅳ),and matrix metalloproteinase inhibitor metalloproteinase-2 (TIMP-2) in kidney tissue of the rats were detected by immunohistochemical method;the activity of matrix metalloproteinase-2 (MMP-2) was detected by zymography.Results:Compared with model group,the glomeruli matrix accumulation of the rats in extract of Schisandra chinensis group was significantly improved,the excretion rate of albuminuria,LDL-C level and serum MDA level were decreased(P<0.05),the activities of CAT(P<0.01)and SOD(P<0.05)in kidney tissue were increased,and the level of MDA in kidney tissue was decreased(P<0.05).The immunohistochemistry results showed that compared with model group,the expression amounts of FN,Col Ⅳ,and TIMP-2 in kidney tissue of the rats in extract of Schisandra chinensis group were significantly decreased.The zymography results showed that compared with model group,the activity of MMP-2 in kidney tissue of the rats in extract of Schisandra chinensis group was significantly increased(P<0.05).Conclusion:Extract of Schisandra chinensis has protective effect on the kidney tissue of the diabetic rats induced by STZ,and the mechanism may be related to the inhibition of oxidative stress and the improvement of MMP-2 activity as well as the inhibition of TIMP-2 expression which could improve the matrix degradation.

Objective:To investigate the value of 3D printing technology in sphenoid ridge meningioma dissection. Methods:By using craniocerebral spiral enhanced CT scan DICOM images, the skull, vessels, and tumor were extracted, reconstructed, and assembled and integrated in the same coordinate system. Then, we constructed a 3D virtual model and a 3D-printed entity model, which was ap-plied for preoperation and postoperation. Results:Virtual models of the brains of five patients were reconstructed successfully and 3D entity models were produced. The models expressed the relationship among tumors, adjacent blood vessels, and the important posi-tion of the nerve tissue. Then, the models were applied to the reference before surgery planning and after surgery. Five cases were successfully performed. Conclusion:The use of the entity model of sphenoid ridge meningioma is important in optimizing operation plans, improving tumor resection, and reducing intraoperative bleeding.

Objective To investigate the effects of periplocin from Cortex Periplocae (CPP) on apoptosis of human lung cancer A549 cells and expression of survivin, and demonstrate its anti-tumor effect and the possible mechanism. Methods Inhibitory effect of CPP at different concentrations (1. 25, 2. 50, 5. 00, 10. 00, 20. 00 ng·mL-1 ) and for different time length (24, 48, 72 h) on A549 cell proliferation was tested by MTT method. Apoptosis rate of A549 cells treated with CPP at different concentrations (2. 50, 5. 00, 10. 00 ng·mL-1 ) were measured using flow cytometry (FCM) for 6, 12, 24, 48, 72 h, respectively. The morphological and ultrastructural changes of the apoptosis cells were observed by acridine orange/ ethidium bromide (AO/ EB) staining and transmission electron microscopy (TEM). The effects of CPP on mRNA and protein expression of apoptosis associated gene survivin were assessed by RT-PCR and Western blotting. Results CPP could significantly inhibit the growth of A549, and the inhibition rate reached (93. 46±2. 35)% . The results of FCM showed that the apoptosis rate of A549 cells treated with CPP was increased significantly as compared to the control group ( P<0. 05). Meanwhile, typical apoptotic peaks were detected. The characteristic morphological changes of apoptosis were observed in A549 exposed to CPP, including cell shrinkage, the nuclei became yellow-red by AO/ EB staining, and typical ultrastructural changes, including nuclear chromatin condensation along the nuclear membrane, vacuolar degeneration of cytoplasm observed by TEM. The result of RT-PCR indicated that survivin mRNA expression decreased obviously in A549 cells exposed to CPP. The protein expression of survivin in A549 cells treated with 10. 0 ng·mL-1 CPP(0. 251±0. 012)was weaker than that in control group(0. 928±0. 016). Conclusion CPP can induce apoptosis in human lung cancer cell lines A549, and the probable mechanism is related to the down-regulation of survivin mRNA and protein.