Endomorphins(EMs),two tetrapeptides, were discovered in 1997 and believed to be endogenous ligands of μ-opioide receptor(MOR). They mediated various physiological processes by binding to MOR that couple with G-proteins. Based on our works and literatures, we reviewed the distribution in nerve system, receptor binding properties, analgesis, effects on ion channels, conformation and struction-activity relationship of EMs.

AIM　To analyze the effects of endomorphins (EMs) and their analogs (［D-Pro2］EM-1, ［D-Ala2］EM-1, ［D-Pro2］EM-2 and ［D-Ala2］EM-2) on the cardiovascular system of anesthetized rats and to study its mechanism. METHODS　Responses to EMs and their analogs were investigated in the systemic vascular bed of rats and the mesenteric microarteria of Bufo gargarizans. Responses to EMs were investigated on the hindquarters of the rat vascular bed under constant-flow conditions and on the isolated rabbit thoracic aorta strips. RESULTS　The EMs and their analogs showed dose-related (10-9-10-6 mol*L-1, iv) and naloxone-sensitive (2 mg*kg-1, iv) hypotension in mean arterial pressure of rats with similar duration and vasodilatation in mesenteric microarteria of Bufo gargarizans. The sequence of potencies was EMs > ［D-Pro2］EM-2 > ［D-Ala2］EM-2 > ［D-Ala2］EM-1 > ［D-Pro2］EM-1. EMs were shown not to relax the isolated rabbit thoracic aorta strips without endothelium. EMs, however, relaxed them with endothelium significantly. This action was blocked by Nx (10-5 mol*L-1) and L-NNA (10-4 mol*L-1). CONCLUSION　The significant hypotensive activity of EMs and their analogs is mainly associated with their vasodilatation, which is related to the release of NO from vascular endothelium, and their potency is not completely related to their affinity for μ-opiate receptor.

Objective To investigate the effect of combination therapy by observing the salivary glands function and related organ pathology after given methotrexate (MTX) and cyclophosphamide (CTX) intermittently in induced mice model of Sjogren's syndrome (SS). To further explore the synergistic effect of combination therapy by detecting the immunological regulatory factor B cell activation factor belonging to the TNF family (BAFF) expression. Methods The ingredients of Lewis rat's exocrine glands homogenate were injected into female C57BL/6 mice to set up the mice model of SS. After established the SS mice model successfully, they were randomly divided into six SS model group, including low-dose MTX treatment group (0.02 mg/w), high-dose MTX treatment group (0.06 mg/w), CTX pause treatment group (1.2 mg/3 w), CTX alternate day treatment group (0.6 mg/2 d), MTX+CTX combination treatment group (MTX 0.02 mg/3 w+ CTX 1.2 mg/3 w). Treatment effects were assessed both clinically and histologically. Results Eighteen weeks after the first treatment, the improvement of the salivary secretion of the CTX alternate day treatment group and MTX+CTX combination treatment group were higher than other groups, which showed statistically significant difference (P<0.01). Compared with the SS model control group, HE staining showed that the lymphocytic infiltration of exoerine glands was decreased in the treatment group. In the CTX alternate day treatment group and MTX+CTX combination treatment group, few amount of inflammatory cell infiltration were found, and the expression intensity of BAFF mRNA and protein were decreased markedly in salivary gland than others by RT-PCR and immunohistochemistry assay (P<0.01). Conclusion MTX and CTX can inhibit lymphocytic infiltration of the salivary glands, inhibit BAFF transcriptional level and production of BAFF protein, leading to an increase of fluid production. It suggests that modulation of signaling via BAFF pathways may be a mechanism of action. MTX and CTX combination therapy is more effective than single-agent therapy. The inhibitory effects of MTX and CTX on BAFF-mediated inflammatory pathways are primarily synergistic.

Objective To investigate the lipid profiles of patients with primary Sjogren's syndrome (pSS) and to analyze the correlation between abnormal serum lipids and the inflammationsof SS. Methods One hundred and fourteen pSS patients and 20 gendermatehed healthy controls were studied. Serum lipids were measured in both groups. Results There was statistically significant difference between SS and healthy controls, and the serum HDL-c and apoA<,1 concentrations were significantly lower in patients (P<0.05). The incidence of abnormal serum lipids was 39.5% in these patients. Patients with abnormal lipids had longer course of disease, higher ESR level, lower salivary flow rate and more frequent parotid gland enlargement than those without abnormal lipids(P<0.05). Logistic regression analysis revealed statistically significant association between serum lipids levels and occurrence of parotid gland enlargement. Conclusion Findings from this study suggest that patients with SS have altered lipid profiles and the decrease of apoA, and HDL-c levels may be the correlated factors of SS. The inflammation of SS may cause changes in lipids metabolisms.

A novel series of sorafenib analogs containing 2-picolinyl hydrazide moiety were designed and synthesized. In vitro, most of synthesized compounds have antiproliferation activity on MDA-MB-231, ACHN, HepG2, Mia-PaCa-2 and SW1990 cell lines tested by MTT assay. It is worth noting that the antitumor activities of compounds 2c, 2d and 2f are more potent than that of sorafenib on pancreatic cancer cells Mia-PaCa-2 and SW1990, and the activities of compounds 3f and 3g are 2-3 times than that of sorafenib on human hepatocellular carcinoma HepG2 cell line.

Objective To evaluate the value of IgA and IgG antibodies against α-fodrin in both serum antibodies in SS is also assessed.Methods Samples from 39 patients with SS(25 primary and 14 secondary),8 patients with systemic lupus erythematosus(SLE),and 15 patients with rheumatoid arthritis (RA)as well as 10 healthy blood donors were collected.Anti-α-fodrin antibodies were measured using ELISA.Results The titer of serum anti-α-fodrin was higher in SS than in other connective tissue diseases group and healthy group(P<0.01).IgA type anti-α-fodrin antibodies was detected in 60%.44% of serum and saliva in patients with pSS respectively.IgG antibodies were detected in 43% of sera,and 29% of saliva of patients with pSS.The sensitivity and specificity of serum anti-α-fodrin IgA in SS was 54%and 85%.The level of anti-α-fodrin was positively associated with xerostomia and parotid swelling (P<0.05),and was negatively associated with xeroma,renal tubule acidosis,lung interstitial disease and hepatic damages(P>0.05).Conclusion Saliva and serLlm anti-α-fodrin level may be diagnostic for SS.It may be a useful screening marker.

OBJECTIVETo evaluate the efficacy and safety of meropenem in Chinese patients, we conducted a study for the treatment of patients with lower respiratory tract infections, urinary tract infections and other infections.

METHODSA total of 182 hospitalized patients were enrolled in the study. 90 patients received 500 mg meropenem every 12 hours (or 1 g every 12 hours if necessary) and 92 patients received imipenem/cilastatin 500 mg/500 mg every 12 hours (or 1 g every 12 hours if necessary) by intravenous infusion. The duration of treatment was 7 - 14 days for both groups.

RESULTSSeventy of 90 cases receiving meropenem and 70 of 92 cases receiving imipenem/cilastatin were assessable for clinical efficacy. The overall efficacy rates were 90% for the meropenem group and 87% for the imipenem/cilastatin group, and the bacterial eradication rates were 86% in both groups. 93 (76%) of 123 strains isolated from patients produced beta-lactamases. Adverse drug reactions were evaluated in 72 cases in the meropenem group and 70 cases in the imipenem/cilastatin group. The adverse drug reaction rates were 9.7% and 8.6%, respectively. The results showed that there were no statistical differences between these two groups (P > 0.05).

CONCLUSIONMeropenem is effective and safe for the treatment of bacterial infections caused mainly by beta-lactamase-producing strains.

Adult ; Aged ; Alanine Transaminase ; blood ; Aspartate Aminotransferases ; blood ; Cilastatin ; administration & dosage ; adverse effects ; therapeutic use ; Female ; Humans ; Imipenem ; administration & dosage ; adverse effects ; therapeutic use ; Male ; Middle Aged ; Respiratory Tract Infections ; drug therapy ; Thienamycins ; adverse effects ; therapeutic use ; Urinary Tract Infections ; drug therapy

Zhuye Shigaotang， first recorded in ZHANG Zhongjing's Synopsis of the Golden Chamber （《金匮要略》）， is a commonly used prescription for treating heat syndrome in modern times. However， physicians of the past dynasties have different opinions on the mechanism of Zhuye Shigaotang in disease treatment. Based on HUANG Yuanyu's theory of Qi circulation， this paper holds that the root cause of the diseases treated by Zhuye Shigaotang is the deficiency of spleen and stomach in the middle energizer and the dysfunction of ascending and descending. The failure of Yin ascending leads to the failure of Yang transformation， and the failure of Yang descending causes the failure of Yin generation. As a result， heat and fire become predominant in the heart， lung， and stomach， which causes Qi counterflow and fluid consumption. Based on this pathogenesis， Zhuye Shigaotang is mainly composed of pungent， warm， sweet， and cold herbs. The combination of these herbs can protect the spleen and stomach and recover the Qi movement in the middle energizer， thereby clearing heat and fire， descending Qi， and promoting the generation of Qi and fluid. In clinical practice， this prescription can be applied to treating the syndromes of deficiency in spleen and stomach， dysfunction of middle energizer in transportation， dysfunction of ascending and descending， excessive heat and fire， and Qi counterflow and fluid consumption. The interpretation of Zhuye Shigaotang from the theory of Qi circulation can provide a new idea for differentiating syndromes， seeking causes， and developing prescriptions， which broadens the scope of clinical application of this prescription and provides a reference for interpreting ZHANG Zhongjing's method of compatibility.

Objective:To investigate the kinetic metrics of 68Ga-fibroblast activation protein inhibitor (FAPI)-04 in pancreatic cancers and normal organs by using total-body PET dynamic imaging. Methods:From December 2020 to December 2021, 68Ga-FAPI-04 total-body PET/CT dynamic imaging were performed on 6 pancreatic cancer patients (3 males, 3 females, median age 55.5 years) in Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University. Images were respectively analyzed. Manual delineations of volume of interests (VOIs) on multiple normal organs and pathological lesions were performed and time-to-activity curves (TACs) were generated. A reversible two-tissue compartment model (2TCM) was fitted for each tissue TAC. Rate constants including K1, k2, k3 and k4, and the total volume of distribution ( Vt) were obtained and compared by tissue types. Wilcoxon rank sum test and Spearman correlation analysis were used for data analysis. Results:Kinetic metrics varied significantly among normal organs and pancreatic cancer lesions ( z values: 2.00-1 240.00, all P<0.05). The highest K1 among lesions was observed in primary tumor (0.30 min -1), which was observed in the spleen (1.42 min -1) among normal organs. The highest k2 among lesions was observed in peritoneal metastases (0.24 min -1), which was observed in the spleen (2.59 min -1) among normal organs. Primary tumor showed the highest k3 of 0.17 min -1 among lesions, and the pancreas had the highest k3 of 0.16 min -1 among normal organs. Primary tumor had the highest k4 of 0.03 min -1 among lesions, and the heart, lungs, parotid glands had high k4(0.06 min -1) among normal organs. Vt were higher in pathological lesions compared to normal organs, with the highest in primary tumor (13.78 ml/cm 3). There were correlations between Vt in lesions and SUV mean( rs=0.86, P<0.001) or SUV max ( rs=0.77, P<0.001). Conclusion:The rate constants including K1, k2, k3 and k4, and Vt of 68Ga-FAPI-04 vary among normal organs and lesions.