Aim To study the inhibitory activities of potential new anti-influenza virus agents,3-O-β-chaco-triosyl pentacyclic triterpenoids against the entry of H5N1influenza viruses.Methods Three target com-pounds were designed and synthesized structurally re-lated to the lead compound 3-O-β-chacotriosyl dioscin derivative (1 )with inhibitory activities against H5N1 influenza viruses.The inhibitory activities of these tar-get compounds were tested at a cellular level pseudo vi-rus system targeting H5N1 influenza viruse entry.Re-sults All the compounds 1 a,1 b and 1 c showed po-tent inhibitory activities against the entry of A/Thai-land/Kan353/2004 pseudo virus into the target cells, of which compound 1 b showed the best inhibitory activ-ity with an IC50 value of (1.25 ±0.22)μmol·L-1. Conclusion The SARs analysis of these compounds indicated that replacement of the aglycone moiety of compound 1 with pentacyclic triterpenoids could in-crease antiviral activity.Different types of pentacyclic triterpen as aglycone residue had the significant influ-ence on the inhibitory activity (1 b >1 c >1 a),sug-gesting ursane type of triterpenes was superior to the two other kinds of triterpenes as aglycone residue.

Objective To delineate and measure the left anterior descending coronary artery (LAD) on CT angiography (CTA) and evaluate the dose delivered to LAD by different radiotherapy techniques for left-sided breast cancer.Methods Twenty-nine left-side breast cancer women with mean age of 54.71 years (range:30-80 years) were included.CTA was performed, and LAD was contoured and the distances were measured between LAD and chest wall (posteroanterior diameter,PD), between LAD and internal mammary artery (horizontal diameter,HD), between LAD and interventricular groove (oblique diameter,OD) at the level of T7-T8,T8-T9,T9-T10 and at level of nipple and lower boundary of the breast.The dose delivered to LAD was calculated on three-dimensional plans for two patients with mastectomy whose chest wall and internal mammary chain (IMC) were irradiated and one patient with breast-conserving surgery who received whole breast irradiation.Results The LAD arose at the level of the third rib in 40% of patients and at the fourth rib in 60% of patients.The mean length of LAD was 7.49±0.58 cm.At the level of T7-T8,T8-T9,T9-T10,the mean PD were 2.99±1.11 cm, 1.26±0.65 cm,0.68±0.39 cm, the mean HD were 2.27±0.84 cm, 2.81±0.65 cm, 3.37±1.21 cm, and the mean OD were 0.47±0.25 cm,0.38±0.21 cm,0.42±0.19 cm respectively.At the level of the breast nipple and the lower boundary of the breast, the mean PD were 2.94±1.06 cm, 0.79±0.46 cm, the mean HD were 2.45±0.89 cm, 3.31±1.22 cm,and the mean OD were 0.56±0.30 cm,0.57±0.24 cm respectively.The mean dose to the LAD was 5 Gy and 14 Gy for patients with mastectomy whose IMC was irradiated with 9 MeV electron and whose IMC was irradiated with 6 MV photon tangential beams.The mean dose to the LAD was 26 Gy for patients with breast conserving surgery.Conclusions To contour the LAD, the interventricular groove could be the reference point.Tangential technique can be giving a higher dose of LAD when compared with other radiation techniques

Objective: To detect the bioavailability of 21 types of perfluorochemicals (PFCs) in rat liver and to examine the effect of protein powder. Methods: Twenty-four rats of the SD strain were randomly divided into the control group, the model group, and the protein powder group. Twenty-one types of PFCs were mixed at an equal concentration of 10 ng/mL, and rats in the model group and the protein powder group were given by oral administration of PFCs mixtures at a daily dose of 5 mL/kg. Rats in the protein powder group were given protein powder by gavage at a dose of 15 mL/kg, while animals in the model and control groups were given deionized water at doses of 15 and 20 mL/kg for 28 successive days. The PFCs contents were quantified in rat liver using ultra-high performance liquid chromatography-electrospray tandem mass spectrometry (UPLC-MS/MS), and the bioavailability was estimated. Results: There were no significant differences in rat body weight or liver/body weight ratio in the control, model and protein powder groups (P>0.05). There were no significant differences in the bioavailability of perfluoroalkylated carboxylic acid (PFCA) or sulfonate (PFSA) in the liver of female and male rats between the protein powder group and the model group (P>0.05), and the gross bioavailability of PFCA (t=-22.266, P<0.001) and PFSA (t=-34.312, P<0.001) was significantly higher in the liver of male rats than in that of female rats in the model group, and the bioavailability of PFCA and PFSA increased followed by a reduction in rat livers with the increase of carbon chain length in the model group. In the model group, the highest bioavailability was measured in perfluorododecanoic acid (PFDoA) and sodium perfluorooctylsulfonate (L-PFOS) in the female rat liver [(36.06±2.93)% and (37.11±1.73)%], and the highest bioavailability was measured in perfluorononanoic acid (PFNA) and L-PFOS in the female rat liver [(61.02±2.16)% and (87.16±3.29)%]. Conclusions The bioavailability of PFCs correlates with the carbon chain length and animal gender in rat livers, and protein powder poses no clear-cut effects on the bioavailability of 21 types of PFCs in rat livers.

Objective: To explore the effects of protein powder on the bioavailability of perfluoroalkyl substances (PFASs) in blood and kidneys of rats and renal function change. Methods: Twenty-four rats of the SD strain were randomly divided into the negative control group, PFASs group and protein powder group, with 8 rats (half males and half females) in each group. PFASs included 13 perfluorocarboxylic acids (PFCAs) and 8 perfluorosulfonic acids (PFSAs), and the mixture was used as a test subject for intervention. The rats in the negative control group were given deionized water at doses of 20 mL/kg·bw, in the PFASs group were given 5 mL/kg·bw of PFASs mixtures and 15 mL/kg·bw of deionized water, and in the protein powder group were given 5 mL/kg·bw of PFASs mixtures and 15 mL/kg·bw of protein powder (0.258 g/mL). After intervention for 28 successive days, body weight and kidney mass were weighed, and the kidney volume index was calculated. Serum creatinine and blood urea nitrogen were detected by an automatic biochemical analyzer. The PFCAs, PFSAs and PFASs contents were quantified in blood and kidney using ultra-high performance liquid chromatography-electrospray tandem mass spectrometry, and the bioavailability was estimated. Results: There was no significant differences in kidney mass, kidney volume index, serum creatinine and blood urea nitrogen among the negative control group, PFASs group and protein powder group (all P>0.05). The bioavailability of blood PFCAs, PFSAs and PFASs in the protein powder group was not significantly different from the PFASs group (all P>0.05). Compared with the PFASs group, the bioavailability of PFCAs, PFSAs and PFASs were significantly increased in kidneys of male rats in the protein powder group (all P<0.05), while were not significant different in those of female rats (all P>0.05). Conclusion Protein powder at the dose of this study can significantly improve the bioavailability of PFASs in kidneys of male rats, while there no obvious effects on the bioavailability of blood PFASs and renal function.

Objective:To explore the efficacy and safety of escharectomy and skin grafting combined with negative pressure wound treatment in the treatment of patients with deep burn.Methods:A total of 208 deep burn patients who were treated in Haining People's Hospital from May 2018 to May 2019 were selected in the research.They were randomly divided into observation group and control group according to the random digital table method, with 104 cases in each group.The observation group was treated with escharectomy and skin grafting combined with negative pressure wound treatment.The control group was treated with escharectomy and skin grafting combined with traditional pressure bandaging.The general treatment, wound healing rate, changes of serum inflammatory factors before treatment and after treatment for 7 days, and complications of the two groups were compared.Results:The total excellent and good healing rate of the observation group (92.31%) was higher than that of the control group (79.81%) (χ 2=6.772, P<0.05). The granulation growth time [(8.23±2.16)d], wound healing time [(17.64±2.58)d], postoperative pain score[(3.16±1.24)points] and hospitalization time [(22.61±2.47)d] in the observation group were lower than those in the control group [(12.15±2.33)d, (20.25±3.16)d, (5.33±1.27)points and (26.13±2.55)d] ( t=12.582, 6.525, 12.468, 10.111, all P<0.05). At 7 days after treatment, the levels of CRP[(21.12±2.48) ng/L], TNF-α [(3.27±0.38)ng/L], IL-6 [(5.32±1.46)ng/L] and C3a [(12.13±1.62)μg/L] in the observation group were lower than those in the control group [(28.06±2.62)ng/L, (5.13±0.43)ng/L, (6.68±1.51)ng/L and (16.43±1.26)μg/L] ( t=19.618, 33.055, 6.603, 21.367, all P<0.05). The total incidence of complications in the observation group (7.69%) was lower than that in the control group (22.12%) (χ 2=8.529, P<0.05). Conclusion:Escharectomy and skin grafting combined with negative pressure can improve the wound healing rate, improve the body's inflammatory response, shorten the recovery time, reduce the occurrence of complications and has good safety.

OBJECTIVETo study the inhibitory activities of 3-O-β-chacotriosyl benzyl ursolate and its derivatives as potential new anti-influenza virus agents against the entry of H5N1 influenza viruses into the target cells.

METHODSFour target compounds were designed and synthesized, which were structurally related to the lead compound 3-O-β-chacotriosyl methyl ursolate (1). The inhibitory activities of these compounds were tested at a cellular level psuedovirus system targeting H5N1 influenza viruse entry.

RESULTS AND CONCLUSIONThe compounds 1b, 1c and 1d showed potent inhibitory activities against the entry of A/Thailand/Kan353/2004 pseudovirus into the target cells, and among them compound 1d showed the strongest inhibitory activity with an IC50 value of 0.96 ± 0.10 µmol/L. The structure-activity relationship analysis of these compounds indicated that when 17-COOH of ursolic acid was esterified, introduction of Me groups rather than aryl groups more strongly enhanced the inhibitory activity. Changing 17-COOH of ursolic acid into amide could increase the antiviral activity and decrease the cytotoxicity of the compounds in MDCK cells.

Animals ; Antiviral Agents ; chemistry ; Dogs ; Influenza A Virus, H5N1 Subtype ; drug effects ; physiology ; Madin Darby Canine Kidney Cells ; Structure-Activity Relationship ; Triterpenes ; chemistry ; Virus Internalization ; drug effects

Tumor microenvironment (TME) is comprised of cellular and non-cellular components that exist within and around the tumor mass. The TME is highly dynamic and its importance in different stages of cancer progression has been well recognized. A growing body of evidence suggests that TME also plays pivotal roles in cancer treatment responses. TME is significantly remodeled upon cancer therapies, and such change either enhances the responses or induces drug resistance. Given the importance of TME in tumor progression and therapy resistance, strategies that remodel TME to improve therapeutic responses are under developing. In this review, we provide an overview of the essential components in TME and the remodeling of TME in response to anti-cancer treatments. We also summarize the strategies that aim to enhance therapeutic efficacy by modulating TME.
Antineoplastic Agents ; pharmacology ; Drug Resistance ; Humans ; Neoplasm Staging ; Neoplasms ; drug therapy ; pathology ; Treatment Outcome ; Tumor Microenvironment ; drug effects ; physiology

Objective:To provide a reference for the choice of electronic data capture system used in clinical research, the function and performance of some tool software were expounded and compared.Methods:We selected three freely available systems of REDCap, Commcare, and OpenEDC as research objects, describing and comparing their user license acquisition path, data capture related functions, and information security assurance measures. This article reflected how the three kinds of tool software ensure research data privacy and scientificity, and presented the consideration of system security and accessibility.Results:REDCap was the most mature system of the three, which had a fairly comprehensive design in functional integrity, data security, user friendliness, and system scalability. Commcare system featured in the mobile collection, and supported the most abundant types of collected data, while OpenEDC was characteristic of low threshold and flexible deployment.Conclusions:REDCap system is widely applicable to small and medium scale medical research, including clinical trials, retrospective studies, cohort studies, and translational research. Commcare system is the preferred option for medical investigations represented by epidemiologic surveys, while OpenEDC is particularly suitable for investigator initiated studies.

Objective:To investigate the clinicopathological characteristics of papillary thyroid microcarcinoma in the isthmus (PTMCI) and the independent risk factors of central lymph node metastasis.Methods:58 consecutive patients with PTMCI admitted from Jan. 2016 to Dec. 2018 (isthmus group) were retrospectively analyzed, including 15 males and 43 females,age (42.93±12.69) years old; According to the specific location of papillary thyroid microcarcinoma (PTMC) in isthmus, PTMCI were subdivided into the right PTMCI and the left PT-MCI 67 patients with a single PTMC located in the unilateral lobe were randomly selected as a control (lobe group) , including 13 cases of male and 54 cases of female, age (47.18±11.34) years old. Index included the patient’s age, gender, tumor diameter, TPOAb, aspect ratio, microcalcification, capsular invasion, lymph node metastasis, surgical methods, operation method, and scope of lymph node dissection. SPSS 21.0 software was used for statistical analysis. The quantitative data of normal distribution was expressed as ± s,and the difference between the two groups was compared by chi-square test.The risk factors of CLNM of the isthmus group were analyzed with univariate chi-square test and multivariate Logistic regression analysis.The difference was statistically significant if P<0.05. Results:Compared with PTMC, PTMCI showed a higher rate of capsule invasion ( P=0.003) ,lymph node metastasis ( P=0.049) ,lymph node metastasis in central region ( P=0.033) ,and surgical methods between the two groups were statistically significant ( P<0.05) ;But PTMCI was significantly lower than PTMC in aspect ratio>1 ( P<0.05) . Univariate analysis showed that capsule invasion ( P=0.001) and microcalcification ( P=0.012) were risk factors for PTMCI lymph node metastasis. Multivariate Logistic regression analysis showed that capsule invasion ( P=0.016) and microcalcification ( P=0.046) were independent risk factors for central lymph node metastasis in PTMCI. Conclusions:Compared with PTMC,PTMCI indicates a higher rate of capsular invasion,lymph node metastasis in prelaryngeal and central lymph node;Compared with PTMC, PTMCI indicates a lower rate of aspect ratio>1; Capsule invasion and microcalcification are independent risk factors for central lymph node metastasis in PTMCI. For patients with the right PTMCI or the left PTMCI and also without capsular invasion and calcification,ipsilateral central lymph node dissection should be considered.

Objective Hypothyroidism(HypoPT) is one of the most common complications of thyroid reoperation,and hypocalcemia caused by HypoPT is a difficult problem in clinical practice.This study aims to investigate the risk factors for hypoealcemia after reoperation of thyroid cancer.Methods Data of 106 patients who underwent reoperation for thyroid cancer from 2013 to 2018 were retrospectively analyzed.According to the parathyroid area involved in the reoperation,the reoperation was graded:low-risk group,intermediate-risk group and high-risk group.Parathyroid hormone(PTH) and total calcium(Ca) levels were monitored at 12 to 24 hours after surgery.The follow-up period was at least 6 months.The PTH cut-off values of postoperative hypocalcemia were analyzed by ROC curve.The chi-square test and logistic regression analysis were used to analyze the risk factors of postoperative hypocalcemia.Results The incidence of transient HypoPT after reoperation was 35％,and the permanent HypoPT was 1.9％.The grade of reoperation was positively correlated with postoperative HypoPT.The ROC curve showed that the PTH cut-off values of postoperative hypocalcemia was 15 pg/ml and area under curve(AUC) was 0.636(95％ CI:0.530-0.742,P＜0.017).Univariate and multivariate analysis showed that reoperation grade and postoperative PTH＜15 pg/ml were independent risk factors for postoperative hypocalcemia.Conclusion The grade of reoperation and postoperative PTH value ＜15 pg/ml can predict postoperative hypocalcemia.