[A retrospective analysis of clinical characteristics and mortality risks in elderly patients with acute cholecystitis and cholangitis].

Objective: To analyze the clinical characteristics and explore the risk predictors on mortality in elderly patients with acute cholecystitis and cholangitis. Methods: We conducted a retrospective analysis of elderly patients hospitalized in the Second Medical Center of General Liberation Army Hospital for acute cholecystitis and cholangitis during 2000 to 2018. Clinical data and risk predictors on mortality were assessed. The patients were stratified into three groups based on age:Ⅰ (65-74 years old),Ⅱ (75-84 years old), and Ⅲ (≥85 years old). Logistic regression analysis was used to identify the predictors of mortality. Results: A total of 574 patients were finally enrolled with the mean age 87.6 years including 191 in group Ⅰ, 167 in group Ⅱ, and 216 in group Ⅲ. The main cause of acute cholecystitis and cholangitis was gallstone (76.3%),and the main symptom was abdominal pain (62.9%),followed by chills(62.5%),fever(59.8%),jaundice (47.2%) and septic shock(26.3%). Cholecystitis was the most common diagnosis in groups Ⅰ and Ⅱ,whereas it was cholangitis in group Ⅲ. Percutaneous transhepatic biliary/gallbladder drainage (PTBD/PTGD) and endoscopic retrograde cholangiopancreatography (ERCP) were administrated more frequently in groups Ⅲ. A total of 35 patients (6.1%) died during follow-up. Senior in age (OR=11.1),the Charlson comorbidity index (OR=19.5),cancers (OR=9.6),blood stream infections (OR=7.4),severity of cholecystitis and cholangitis (OR=4.2) were risk factors associated with mortality. Conclusions: Even in the elderly patients with acute cholecystitis and cholangitis,comorbidity is one of the main factors affecting clinical outcomes. Due to the poor performance, this group of population presents more severe disease and undergoes conservative treatment strategies.

Attenuating effect of casein glycomacropeptide on proliferation, differentiation, and lipid accumulation of in vitro Sprague-Dawley rat preadipocytes.

Food components with the ability to suppress preadipocyte proliferation and intracellular lipid accumulation may be helpful in the prevention of obesity, which is a worldwide health concern. Casein glycomacropeptide (GMP), which has pronounced gastric inhibitory activity, could potentially possess fat synthesis inhibition properties and an obesity-alleviating capacity. The objective of the present study was to investigate the effect of GMP on the proliferation and differentiation of preadipocytes as well as triglyceride accumulation and glycerol-3-phosphate dehydrogenase activity in preadipocytes isolated from Sprague-Dawley rats. Different dosages (0, 0.31, 0.625, 1.25, 2.5, and 5.0 mg/mL) of GMP were co-incubated with preadipocytes. The proliferation activity of preadipocytes significantly decreased in the GMP-treated group compared with that of the control group without GMP supplementation. The GMP exhibited an inhibitory effect against preadipocyte proliferation in a dose-dependent manner; the maximal antiproliferative effect was obtained with 2.5 mg/mL. The GMP also attenuated differentiation, as revealed by decreased lipid content, and the effect was more pronounced when cells were treated with GMP before or at the beginning of differentiation induction than at later stages of cell differentiation. Cultured preadipocytes treated with GMP accumulated fewer triglycerides and had lower glycerol-3-phosphate dehydrogenase activity than did the control cells without GMP supplementation. In conclusion, GMP can inhibit the proliferation, differentiation, and lipid accumulation of preadipocytes in vitro.

Antiproliferation and apoptosis induction of paeonol in human esophageal cancer cell lines.

The incidence of esophageal cancer (EC), especially adenocarcinoma, has increased tremendously in Western countries and the prognosis of EC remains poor. Paeonol (Pae), a phenolic component from the root bark of Paeonia moutan, possesses antitumor effects in vitro and in vivo. The present study showed that Pae had an antiproliferative effect on the two human EC cell lines (SEG-1 and Eca-109), with different sensitivities to Pae. Acridine orange staining and flow cytometry assays showed that Pae induced apoptosis on the two cell lines. Further analyses indicated that Pae resulted in a cell cycle arrest at S-phase. Immunohistochemical staining showed the expression of Bcl-2 was decreased and that of Bax was increased in treatment groups, with the ratio of Bcl-2/Bax decreased correspondingly. The results show that Pae shows growth inhibitory and apoptosis induction property and may be a promising agent for the EC treatment.

Primary antibiotic resistance of Helicobacter pylori in Chinese patients: a multiregion prospective 7-year study.

OBJECTIVES: To explore the characteristics of Helicobacter pylori resistance in China and the association between antibiotic resistance and several clinical factors. METHODS: H. pylori strains were collected from patients in 13 provinces or cities in China between 2010 and 2016. Demographic data including type of disease, geographic area, age, gender and isolation year were collected to analyse their association with antibiotic resistance. Antibiotic resistance was detected using the Etest test and the Kirby-Bauer disc diffusion method. RESULTS: H. pylori were successfully cultured from 1117 patients. The prevalence of metronidazole, clarithromycin (CLA), azithromycin, levofloxacin (LEV), moxifloxacin, amoxicillin (AMO), tetracycline and rifampicin resistance was 78.2, 22.1, 23.3, 19.2, 17.2, 3.4, 1.9 and 1.5%, respectively. No resistance to furazolidone was observed. The resistance rates to LEV and moxifloxacin were higher in strains isolated from patients with gastritis compared to those with duodenal ulcer and among women. Compared to patients ≥40 years old, younger patients exhibited lower resistance rates to CLA, azithromycin, LEV and moxifloxacin. The resistance rates to CLA and AMO were higher in strains isolated more recently, and we also found that the prevalence of resistance to metronidazole, CLA, azithromycin and AMO were significantly different among different regions of China. CONCLUSIONS: The resistance rates to metronidazole, CLA and LEV were high in China. Patient age, gender, disease and location were associated with the resistance of H. pylori to some antibiotics. Furazolidone, AMO and tetracycline are better choices for H. pylori treatment in China.

Synthesis and antimalarial activity of 2-aziridinyl- and 2,3-bis(aziridinyl)-1,4-naphthoquinonyl sulfonate and acylate derivatives.

A series of 2-aziridinyl- and 2,3-bis(aziridinyl)-1,4-naphthoquinonyl sulfonate and acylate derivatives has been synthesized and evaluated for antimalarial activity in vitro against the human malaria parasite, Plasmodium falciparum (Vietnam Smith strain, chloroquine-resistant at the R3 level). The most active compounds, 2-aziridinyl-1,4-naphthoquinon-5-yl p-ethylbenzenesulfonate (13), 2-aziridinyl-1,4-naphthoquinon-5-yl p-tert-butylbenzenesulfonate (48), and 2-aziridinyl-5-hydroxy-1,4-naphthoquinone (5) produced 50% inhibition of the growth of P. falciparum at 9.6 x 10(-8), 2.4 x 10(-8), and 8.8 x 10(-8) M, respectively.

Synthesis of 2,3-diaziridinyl-1,4-naphthoquinone sulfonate derivatives as potential antineoplastic agents.

A new class of 2,3-diaziridinyl-1,4-naphthoquinone sulfonates (27 compounds) has been synthesized and evaluated as potential antineoplastic agents. The most active compounds, benzenesulfonate 4, p-toluenesulfonate 5, p-methoxybenzenesulfonate 7,8-quinolinesulfonate 17, and 2-thiophenesulfonate 20, in the aromatic sulfonate series, at their optimum daily dosage level of 25 mg/kg X 6, produced 100%, 90%, 75%, 80%, and 100% 50-day survivors, respectively, of L1210 tumor-bearing mice. At a lower optimum daily dosage level of 20 mg/kg X 6, treatments with p-fluorobenzenesulfonate 11 and p-nitrobenzenesulfonate 15 resulted in 100% and 80% 50-day survivors. In the aliphatic sulfonate series, methanesulfonate 21 produced 80% 50-day survivors at a 10 mg/kg daily dosage level X 6. Benzenesulfonate 4, p-fluorobenzenesulfonate 11, 8-quinolinesulfonate 17, and 2-thiophenesulfonate 20 derivatives were also tested in mice bearing the B16 melanoma; these agents gave T/C X 100 values of 180, 182, 219, and 161, respectively, in this neoplastic cell system. Structure-activity relationships of compounds of this class are discussed.

[Studies on compounds of cancer chemoprevention: synthesis of some amides].

In search for cancer chemoprevention agents, seven new amide compounds have been synthesized. The structures have been determined based on spectral and chemical data. N-4-(ethoxycarbophenyl)-alpha-naphthamide and N-4-(ethoxycarbophenyl)-beta-naphthamide were shown to be 81% and 79% effective, respectively, for inducing different in HL-60 human promyelocytic leukemia cells at the concentration of 10(-5) mol/L in NBT tests.

[Synthesis and biological activity of 2-[(substituted phenyl)vinyl] indole derivatives].

AIM: To synthesize derivatives of 2-[substituted phenyl)vinyl] indole and find compounds with biological activities by screening in vitro. METHODS: Twenty-one compounds of 2-[(substituted phenyl) vinyl] indole were synthesized by reduction, oxidation and Witting reaction. MS, 1HNMR and elemental analysis were used to determine the structures of the new compounds. RESULTS: These compounds are new ones. CONCLUSION: Six compounds (3, 9, 11, 13, 18 and 20) showed effects on some different receptors, such as alpha 2, D2 and H1, and is worth further studying.

[Synthesis and anticancer activity of 3-[(3'-methyl-4'-(substituted phenyl)-1',3'-butadienyl] indole derivatives].

AIM: To study the synthesis and anticancer activity of 3-[(3'-methyl-4'-(substituted phenyl)-1',3'-butadienyl] indole derivatives. METHODS: Electrophilic-substitution, aldol-condensation, selective-reduction, phase-transfer Wittig reaction and hydrolysis reaction were used in the synthesis of the title compounds. RESULTS: Eleven compounds of 3-[(3'-methyl-4'-(substituted phenyl)-1',3'-butadienyl] indole were synthesized. They are new compounds. Compound 8 showed different inhibitory effects on HL-60, HCT-8 and Bel7402 cell lines in vitro, and its inhibitory rate of antiinflammation was 100% at 10(-5) mol.L-1 concentration. CONCLUSION: Compound 8 showed high anticancer and antiinflammatory activities, and is worth further studying.

[Synthesis of substituted 4-styrylcoumarin and their antitumor activities].

AIM: A series of 4-styrylcoumarin derivatives had been designed and synthesized in order to find compounds of antitumor activities by screening. METHODS: Title compounds (1-20) were synthesized by Phase-Transfer Wittig-Horner reaction, and screened by several antitumor models in vitro. Their structures were determined by 1HNMR, MS and elemental analysis. RESULTS: Twenty compounds (1-20) are new compounds. Compound 18 had effects on KB cell lines in vitro. CONCLUSION: It was seen that compound 18 had certain antitumor activities, and it was worth further studying.

[Studies of chemopreventive agents against neoplasma: synthesis of 3-acetyl coumarin derivatives and relationship between antimutagenic activity and structure].

Twenty-five 3-acetylcoumarin derivatives were synthesized among which twenty-two were not reported before. Antimutagenic activity screen in vitro has shown that some of these compounds have various activities. The structure and activity relationship for 5-, 7-, 8-substituents has been studied. Pharmacological data showed that: the substituent on position 8 has important effect on its activity. When there is only a hydroxy group on position 7, its activity is the highest among those with other substituents, but when a methyl is on position 8, the order of the activity is reversed. Other trends have also been found which provided some clues for further structural modification.

[Interaction between protein and ciprofloxacin].

AIM: To study the interaction between ciprofloxacin and BSA in physiological condition by fluorescence spectroscopy. METHODS: The affection of drug to the protein conformation was investigated. The binding constant between drug and BSA from a double reciprocal Lineweaver-Burk plot was determined and the main sort of binding force was found according to the thermodynamic parameters. RESULTS: The binding constants between BSA and ciprofloxacin at 26 degrees C and 45 degrees C are about 10(4). At 26 degrees C, the thermodynamic parameters of reaction between BSA and ciprofloxacin are delta H = -49.13 kJ.mol-1, delta G = -26.45 kJ.mol-1, delta S = -75 kJ.mol-1. The maximum wavelength of the synchronous fluorescence spectra of BSA moved from 279 nm to 289 nm with the increasing of the amount of ciprofloxacin. CONCLUSION: There exists fluorescence energy transfer between BSA and ciprofloxacin. The main sort of binding force between BSA and ciprofloxacin is Van der Waals' interaction. Ciprofloxacin can be deposited and be transported by serum protein in vivo. Ciprofloxacin affects the protein conformation.

[Inhibition of tumor invasion and metastasis by retinoid 4-APR].

The anti-invasive and anti-metastatic effects with new retinoid 4-acetamidophenyl retinoate (4-APR) were studied using in vitro and in vivo experiments. 4-APR, at the dose of 43.3 mg.kg-1.day-1 p.o., was shown to reduce the spontaneous lung metastatic foci of Lewis lung carcinoma. 4-APR was also found to inhibit the artificial lung metastasis of B16-F10 cells by 67.9% and 36.6% and suppress the reconstituted basement membrane invasion of B16-F10 cells by 54.2% and 41.9% at the concentrations of 10(-5) mol.L-1 and 10(-6) mol.L-1, respectively.

[Studies of antitumor and chemopreventive agents against neoplasm: synthesis of coumarin 3-glyoxal derivatives and relationship between structure and antimutagenic activity].

It has been shown that alpha-glyoxal and its derivatives possess antivirus and antitumor activities. Eighteen new coumarin 3-glyoxal derivatives were synthesized in our laboratory. The fragmentation pattern of MS and the characteristic signals of 1HNMR of these compounds have also been studied. In pharmacological test in vitro most of these analogues showed antimutagenic activities, among them, compound 9 exhibited very strong antimutagenic activity and eight compounds showed strong effects. The struture-activity relationship and the possible active substructure responsible for the activity of these compounds were discussed. As expected, coumarin 3-glyoxals showed higher antimutagenic activities than their 3-acetyl coumarin counterparts. We also found that alkylation or esterification of 7-hydroxy were favorable to their activities.

[Preparation of diclofenac sodium controlled release pellets and multiple-dose evaluation in healthy volunteers].

The yield of pellets obtained in preparing diclofenac sodium (DC-Na) controlled release pellets was affected by the lactose/starch ratio of the feed granules, viscosity of the binding solution and residence time in the rolling pot. The pellet shape was found to be correlated with surface tension of the binding solution. The concentration and composition of the coating solution and pellet size distribution were responsible for the agglutination in coating. The controlled release pellets (CRP) and commercial tablets (CT) of DC-Na were administrated orally to healthy volunteers by multiple-dose. The steady-state condition, based on trough plasma concentration on day 3-5, was achieved on day 3. A great difference in plasma drug concentration fluctuation index (FI) between CRP (0.476 +/- 0.0484) and CT (0.935 +/- 0.092) was observed (P < 0.05) during steady-state. The area under the plasma drug concentration-time curve for a 0-12 h interval (AUC) on day 5 of CRP (6.493 +/- 0.4169 micrograms.h.ml-1) and CT (7.551 +/- 0.4745 micrograms.h.ml-1) was shown to be not significantly different (P > 0.05). The relative bioavailability in the human was about 86%.

Clinical dosimetric study of three radiotherapy techniques for postoperative breast cancer: Helical Tomotherapy, IMRT, and 3D-CRT.

This paper is to investigate the dosimetric characteristics of Helical Tomotherapy (HT), step-and-shoot intensity-modulated radiation therapy (SaS-IMRT) and three-dimensional conformal radiation therapy (3D-CRT) for the postoperative breast cancer as well as their dosimetric comparison of the normal tissues. CT images of 10 postoperative patients with early stage breast cancer were transferred into HT, SaS-IMRT and 3D-CRT planning systems respectively after the target region and normal tissues were outlined by the same physician to assure the contour consistency. Each prescribed dose for three different modalities of plans was given to a total of 50 Gy in 25 fractions. Doses and irradiated volumes in heart, lungs, as well as conformity index (CI) and homogeneity index (HI) were evaluated for detailed comparison. All three plans showed appropriate coverage for the prescribed target dose in the dosimetric comparison. The CI in HT and SaS-IMRT as well as 3D-CRT was 0.68 ± 0.12, 0.58 ± 0.08 and 0.40 ± 0.08, respectively. The HI were 1.10 ± 0.03, 1.14 ± 0.02 and 1.17 ± 0.04, which appeared intergroup significant differences (p < 0.05). V5, V10, as well as V20 of the heart were smallest in 3D-CRT than HT and SaS-IMRT. V5 of the ipsilateral lung was the smallest in 3D-CRT than HT and SaS-IMRT (p < 0.05); However, V20 and V30 were smaller in HT and SaS-IMRT than 3D-CRT (p < 0.05). V5 of the contralateral lung was the smallest in 3D-CRT than other groups, with V10~V30 were basically similar in numeric values with not obvious discrepancy. Comparing with SaS-IMRT and 3D-CRT, HT technique in treating breast cancer had the best conformity and homogeneity index as well as steepest dose gradient due to its highly modulated beamlets with rotational technique. The heart volume irradiated was the smallest in conventional 3D-CRT, with SaS-IMRT was the largest among the three techniques, as expected. The volume of the contralateral lung irradiated was the smallest in 3D-CRT than other groups. V5 of the ipsilateral lung was the smallest in 3D-CRT than other two groups. V10~V30 in HT and SaS-IMRT were similar and better than 3D-CRT dosimetrically. We conclude that HT technique had advantages over SaS-IMRT and 3D-CRT based on the dosimetric comparison in this study, especially in the high dose region of ipsilateral lung, target homogeneity and dose uniformity.