Abstract: Our previous work revealed berberine can significantly enhance the susceptibility of fluconazole against fluconazole-resistant Candida albicans, which suggested that berberine has synergistic antifungal activity with fluconazole. Preliminary SAR of berberine needs to be studied for the possibility of investigating its target and SAR, improving its drug-likeness, and exploring new scaffold. In this work, 13-substitutited benzyl berberine derivatives and N-benzyl isoquinoline analogues were synthesized and characterized by 1H NMR and MS. Their synergetic activity with fluconazole against fluconazole-resistant Candida albicans was evaluated in vitro. The 13-substitutited benzyl berberine derivatives 1a-1e exhibited comparable activity to berberine, which suggested that the introduction of functional groups to C-13 can maintain its activity. The N-benzyl isoquinolines, which were designed as analogues of berberine with its D ring opened, exhibited lower activity than berberine. However, compound 2b, 2c, and 4b showed moderate activity, which indicated that berberine may be deconstructed to new scaffold with synergistic antifungal activity with fluconazole. The results of our research may be helpful to the SAR studies on its other biological activities.
Antifungal Agents ; pharmacology ; Berberine ; pharmacology ; Candida albicans ; drug effects ; Drug Resistance, Fungal ; Drug Synergism ; Fluconazole ; pharmacology ; Isoquinolines ; pharmacology ; Microbial Sensitivity Tests

Objective: To evaluate the effect of preservation of left colic artery (LCA) on postoperative anastomotic leakage in patients with rectal cancer after neoadjuvant therapy. Methods: A retrospective cohort study was conducted to collect data of rectal cancer patients at Department of Gastrointestinal Surgery of Fujian Cancer Hospital from September 2014 to August 2017. Inclusion criteria: (1) age of 18 to 79 years; (2) rectal adenocarcinoma confirmed by postoperative pathology; (3) patients without preoperative serious cardiovascular and cerebrovascular disease receiving preoperative neoadjuvant radiotherapy or chemoradiotherapy; (4) laparoscopic-assisted anterior rectal resection and distal ileostomy were performed simultaneously; (5) complete clinical data. Exclusion criteria: patients with extensive abdominal metastasis, or distant organ metastasis during operation, and combined organ resection. According to whether LCA was retained during operation, the patients were divided into two groups, then the intraoperative and postoperative clinical outcomes were compared. Moreover, univariate analysis and multivariate logistic regression were used to analyze risk factors of postoperative anastomotic leakage. Results: A total of 125 patients were included in this study, including 56 patients in the retained LCA group and 69 patients in the non-retained LCA group. Differences in baseline data, such as gender, age, diabetes mellitus, body mass index, hemoglobin, distance between tumor and anal margin, maximum diameter of tumor, preoperative neoadjuvant therapy, and ypTNM stage, between retained LCA group and non-retained LCA group were not statistically significant (all P>0.05), indicating that two groups were comparable. Meanwhile there were no significant differences in operation time, intraoperative blood loss, total number of lymph node harvested, number of harvested lymph node at the root of inferior mesenteric artery, circumferential margin, anastomotic bleeding, or postoperative hospital stay between two groups (all P>0.05). Thirteen patients in the non-retained LCA group (18.8%) developed postoperative anastomotic leakage, including 7 cases of grade A, 5 cases of grade B and 1 case of grade C, while in the retained LCA group, only 5.4% (3/56) of patients developed postoperative anastomotic leakage, including 1 case of grade A and 2 cases of grade B without case of grade C, whose difference was statistically significant (U=1674.500, P=0.028). Univariate analysis showed that preoperative hemoglobin <120 g/L and non-retained LCA were associated with postoperative anastomotic leakage (both P<0.05). Multivariate analysis cofirmed that preoperative hemoglobin < 120 g/L (OR=3.508, 95% CI: 1.158 to 10.628, P=0.017) and non-retained LCA (OR=4.065, 95%CI: 1.074 to 15.388, P=0.031) were independent risk factors for postoperative anastomotic leakage. Median follow-up time was 31 months (16 to 51 months), and no long-term complication was found. Local recurrence and distant metastasis were found in 1 case (1.8%) and 7 case (12.5%) in the retained LCA group, while those were found in 2 cases (2.9%) and 5 cases (7.2%) respectively, in the non-retained LCA group, whose differences were not statistically significant (P=1.000, P=0.321 respectively). Conclusion Preservation of left colic artery not only can ensure radical lymph node dissection efficacy under the condition of similar operation time and blood loss, but also can effectively reduce the incidence of postoperative anastomotic leakage for rectal cancer patients after neoadjuvant therapy.

Objective To assess the changes in iodine status and dietary iodine intake among Shanghai residents since common salt was iodized 20 years ago.Methods As-CE Catalysis spectrophotometry was used to determinate the urine iodine level in school-age children,pregnant women,wet nurse and adults of Shanghai between 1995 and 2015.B ultrasonic was used to determinate the thyroid volume of school-age children.And then the goiter rate was calculated.Direct titration or arbitration methods were applied to detect the household salt iodine level quantitatively.The survey was conducted by using 3 days 24-hour dietary questionnaire and condiment weighing methods to analyze the level of iodine intake and sources for the cases of all iodized salt consumption and all consumption of non-iodized salt.Results The median urine iodine concentration (UIC) of school age children was 72.3 μg/L in 1995,rose to 214-231 μg/L from 1997-1999,and then became stable between 100 μg/L and 200 μg/L since 2002.The goiter rate was below 5% among children aged 8-10 from 1995-2015 in Shanghai.The median urine iodine of pregnant women was between 126.5 μg/L and 139.8 μg/L.The median UIC of other populations were all between 100 μg/L and 200 μg/L: with adults,lactating women,infants and young children and women of childbearing age,the median urinary iodine was 138.4,123.1-131.1,150.1 and 125.6 μg/L.The qualified iodized salt at household consumption rate was 90% from 2001 to 2009,the percentage declined year by year from 2010.In the cases of all taking iodine salt,the median iodine intake volume for male aged 7-10,11-13,14-18 and over 18 was 200.3,235.5,252.7 and 215.4 μg/L;women aged 7-10,11-13,14-18 and over 18 was 193.0,213.8,208.3 and 186.1 μg/L.The contribution rate of iodine salt in the diet were 51.6%-54.1% and 49.1%-53% in men and women.Kelp,seaweed and fish and shrimp on the contribution of iodine are 7.6%-16.6% and 4.5%-7.4%.Conclusion In the past about 20 years,iodine nutritional status of residents in Shanghai has stabilized totally in a appropriate and safe level.However,the iodine nutrition of pregnant women was insufficient.As iodized salt is the major source of dietary iodine in coastal areas,it is still necessary to continue the policy of universal salt iodized in Shanghai to ensure residents'' needs for iodine and control the risk of iodine deficiency.

OBJECTIVETo investigate the level of CD4+ CD25+ Foxp3+ regulatory T cells and observe relation between expression of Foxp3 and CD127 in peripheral blood of chronic HBV infection.

METHODSCD4+ CD25+ Foxp3+ and CD4+ CD25+ CD127low Treg in peripheral blood from 34 patients of immune tolerance stage, 26 patients of immune clearance stage and 31 patients of non-active status were quantitatively analyzed by flow cytometry.

RESULTSImmune tolerance group presented a higher fraction of CD4+ CD25+ Foxp3+ and CD4+ CD25+ CD127low Treg than non-active group in chronic HBV infection (Z = -2.693, P = 0.007 and t = 3.251, P = 0.002), and HBV positive group also presented a higher fraction than non-active group (t = 2.266, P = 0.026 and t = 3.208, P = 0.002), But ALT normal group is similar to ALT abnormal group (P > 0.05). In this study, the relation between expression of CD127low and Foxp3+ from CD4+ CD25+ regulatory T cells was observed, and CD4+ CD25+ CD127low Treg presented a higher fraction than CD4+ CD25+ Foxp3+ Treg.

CONCLUSIONPeripheral Treg in HBV active replication group is higher than HBV negative group of chronic HBV infection. Expression of CD127low is consistent with Foxp3+ in CD4+ CD25+ regulatory T cells, but the former is significantly higher than the latter.

Adolescent ; Adult ; Female ; Forkhead Transcription Factors ; blood ; genetics ; immunology ; Hepatitis B virus ; immunology ; Hepatitis B, Chronic ; genetics ; immunology ; virology ; Humans ; Interleukin-2 Receptor alpha Subunit ; blood ; immunology ; Interleukin-7 Receptor alpha Subunit ; blood ; genetics ; immunology ; Male ; Middle Aged ; T-Lymphocytes, Regulatory ; immunology ; Young Adult

OBJECTIVE: To study the effects of prenatal cold stress on the behavior and mood of offspring in pregnant rats. METHODS: Six SPF-class Wister pregnant rats were randomly divided into normal temperature control group and cold stress group with 3 rats in each group. The pregnant female rats in the normal temperature control group were kept in the environment of (22 ±2)℃, and the pregnant female rats in the cold stress group were placed in the artificial intelligence climate chamber at(4 ±0.1)℃ for 7 days before the birth, and the young rats were divided into normal temperature after the young rats were born. After the young rats were born, they were divided into normal temperature control group of male rats (MR, 22), normal temperature control group of mother rats (FR, 15), cold stress group of male rats (MC, 15), and cold stress group of female rats (FC, 15) .In the fourth generation of the offspring, the open field experiment and the elevated cross maze test were carried out. RESULTS: In the open field experiment, there was no significant difference in spontaneous activity and exploration behavior between the normal temperature control group and the cold stress group (P＞0.05). In the elevated plus maze experiment, the retention time of the open arms, the number of open arms and the distance of the male and female rats in the cold stress group were significantly higher than those in the normal temperature control group (P＜0.05). CONCLUSION Prenatal maternal cold stress has no significant effect on spontaneous activity, exploration behavior and activity level of offspring, but the offspring have obvious abnormal behaviors with reduced anxiety behavior.
Animals ; Anxiety ; Behavior, Animal ; Cold-Shock Response ; Exploratory Behavior ; Female ; Male ; Maze Learning ; Pregnancy ; Prenatal Exposure Delayed Effects ; Random Allocation ; Rats ; Stress, Psychological