Objective 3,4-Methylenedioxyphenethylamine and caffeic acid derivatives have been proven previously in our group to produce activity against drug resistant fungi synergistic with fluconazole (FCZ).The two pharmacophores were cou-pled by amino acids as linkers in this project in order to design and synthesize the novel compounds and investigate the activity against drug resistant fungi in vitro.Methods 3,4-Methylenedioxyphenethylamine initially reacted with Boc-protected amino acids,following deprotection and coupling reaction with caffeic acid,to get nine title compounds.All title compounds as well as four intermediates were subjected to antifungal activity screening for fluconazole resistant Candida albicans in vitro.Results Nine title compounds showed synergistic antifungal activity for drug resistant Candida albicans with fluconazole at a concentra-tion range of 0.5-2.0μg/ml.Among them,compounds 3b,3f,3g and 3i showed the higher activity with the same MIC80 value of 0.5 μg/ml,which is comparable to those of the control compounds 7b and 5.Conclusion Linking 3,4-methylenedioxyphen-ethylamine and caffeic acid with piperidine-4-carboxylic acid (3b),valine (3g),leucine (3f) and isoleucine (3i) led to novel compounds with high synergistic antifungal activity against drug resistant Candida albicans combined with fluconazole.

Objective:To observe the clinical effect and safety of lauryl alcohol injection under the guidance of ultrasound in the treatment of thyroid cyst.Methods:From February 2017 to February 2019, 148 patients with thyroid cyst who had been treated in the First People's Hospital of Huzhou were divided into study group and control group according to the random number table method, with 74 patients in each group.The patients in the study group were treated with ultrasound-guided percutaneous injection of lauryl alcohol, while the patients in the control group were treated with ultrasound-guided percutaneous injection of anhydrous ethanol.The changes of serum free triiodothyronine(FT 3), free tetraiodothyronine(FT 4) and thyroid-stimulating hormone(TSH) were compared before treatment and after treatment for 6 months.The curative effect was evaluated and the adverse reactions were observed after treatment. Results:There were no statistically significant differences in the serum TSH, FT 3 and FT 4 between the two groups before and after treatment( t=-0.514~0.624, P=0.513~0.852). The overall effective rate in the study group(94.59%) was significantly higher than that in the control group(82.43%)(χ 2=5.382, P=0.020). The overall incidence of adverse reactions in the study group(12.16%) was significantly lower than that in the control group(31.08%)(χ 2=7.815, P=0.005). Conclusion:Ultrasound-guided injection of lauryl alcohol and anhydrous ethanol did not affect the thyroid function of patients with thyroid cysts, while ultrasound-guided injection of lauryl alcohol is conducive to improve the efficacy of thyroid cysts, and the safety is higher, which is worthy of clinical application.

OBJECTIVETo observe the effects among aconite cake-separated moxibustion, moxibustion and acupuncture for knee osteoarthritis (KOA) with kidney-marrow deficiency and to explore the feasibility of cake-separated moxibustion as a home remedy solution.

METHODSNinety patients were randomized into an aconite cake-separated moxibustion group, a moxibustion group and an acupuncture group, 30 cases in each one. The acupoints in the three groups were Neixiyan (EX-LE 4), Dubi (ST 35) in the affected side, and bilateral Xuehai (SP 10), Liangqiu (ST 34), Heding (EX-LE 2), Shenshu (BL 23) and Zusanli (ST 36). All the treatment was given for 3 sessions, 10 days as a session with 2 to 3 days between 2 sessions, and once a day. The first 2 courses of aconite cake-separated moxibustion was applied in the hospital and the other 1 session was used at home guided by officer physician. Symptoms and physical signs classification score and life quality scores were recorded before and after treatment and 6 months after treatment, including walking pain, knee pain in stoop and squat, knee discomfort in stair activity and daily discomfort. The effects were evaluated.

RESULTSThe symptoms and physical signs classification scores in the three groups after treatment and at follow-up were lower than those before treatment (<0.01,<0.05), and the scores in the aconite cake-separated moxibustion group were better than those in the moxibustion group and acupuncture group (all<0.01). The scores of walking pain, knee pain in stoop and squat, knee discomfort in stair activity and daily discomfort were lower in the three groups after treatment and 6 months after treatment (<0.01,<0.05), and the scores of walking pain and daily discomfort in the aconite cake-separated moxibustion group were lower than those in the moxibustion group and acupuncture group (<0.01,<0.05). After treatments, the cured and markedly effective rate in the aconite cake-separated moxibustion group was 63.3% (19/30); that in the moxibustion group was 50.0% (15/30) and one in the acupuncture group was 43.3% (13/30). The cured and markedly effective rate of aconite cake-separated moxibustion group was more promising than those in the other two groups (both<0.05). At follow-up, the cured and markedly effective rate in the aconite cake-separated moxibustion group was 56.7% (17/30), which was better than 36.7% (11/30) in the moxibustion group and 40.0% (12/30) in the acupuncture group (both<0.05).

CONCLUSIONAconite cake-separated moxibustion can be used for KOA patients with kidney-marrow deficiency, which can improve patients' life quality and is better than moxibustion and acupuncture. The method is feasible as a home remedy solution.

Objective:To investigate the epidemiological characteristics, diagnosis, treat-ment and prognosis of gallbladder cancer in China from 2010 to 2017.Methods:The single disease retrospective registration cohort study was conducted. Based on the concept of the real world study, the clinicopathological data, from multicenter retrospective clinical data database of gallbladder cancer of Chinese Research Group of Gallbladder Cancer (CRGGC), of 6 159 patients with gallbladder cancer who were admitted to 42 hospitals from January 2010 to December 2017 were collected. Observation indicators: (1) case resources; (2) age and sex distribution; (3) diagnosis; (4) surgical treatment and prognosis; (5) multimodality therapy and prognosis. The follow-up data of the 42 hospitals were collected and analyzed by the CRGGC. The main outcome indicator was the overall survival time from date of operation for surgical patients or date of diagnosis for non-surgical patients to the end of outcome event or the last follow-up. Measurement data with normal distribu-tion were represented as Mean±SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(range), and com-parison between groups was conducted using the U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Univariate analysis was performed using the Logistic forced regression model, and variables with P<0.1 in the univariate analysis were included for multivariate analysis. Multivariate analysis was performed using the Logistic stepwise regression model. The life table method was used to calculate survival rates and the Kaplan-Meier method was used to draw survival curves. Log-rank test was used for survival analysis. Results:(1) Case resources: of the 42 hospitals, there were 35 class A of tertiary hospitals and 7 class B of tertiary hospitals, 16 hospitals with high admission of gallbladder cancer and 26 hospitals with low admission of gallbladder cancer, respectively. Geographical distribution of the 42 hospitals: there were 9 hospitals in central China, 5 hospitals in northeast China, 22 hospitals in eastern China and 6 hospitals in western China. Geographical distribution of the 6 159 patients: there were 2 154 cases(34.973%) from central China, 705 cases(11.447%) from northeast China, 1 969 cases(31.969%) from eastern China and 1 331 cases(21.611%) from western China. The total average number of cases undergoing diagnosis and treatment in hospitals of the 6 159 patients was 18.3±4.5 per year, in which the average number of cases undergoing diagnosis and treatment in hospitals of 4 974 patients(80.760%) from hospitals with high admission of gallbladder cancer was 38.8±8.9 per year and the average number of cases undergoing diagnosis and treatment in hospitals of 1 185 patients(19.240%) from hospitals with low admission of gallbladder cancer was 5.7±1.9 per year. (2) Age and sex distribution: the age of 6 159 patients diagnosed as gallbladder cancer was 64(56,71) years, in which the age of 2 247 male patients(36.483%) diagnosed as gallbladder cancer was 64(58,71)years and the age of 3 912 female patients(63.517%) diagnosed as gallbladder cancer was 63(55,71)years. The sex ratio of female to male was 1.74:1. Of 6 159 patients, 3 886 cases(63.095%) were diagnosed as gallbladder cancer at 56 to 75 years old. There was a significant difference on age at diagnosis between male and female patients ( Z=-3.99, P<0.001). (3) Diagnosis: of 6 159 patients, 2 503 cases(40.640%) were initially diagnosed as gallbladder cancer and 3 656 cases(59.360%) were initially diagnosed as non-gallbladder cancer. There were 2 110 patients(34.259%) not undergoing surgical treatment, of which 200 cases(9.479%) were initially diagnosed as gallbladder cancer and 1 910 cases(90.521%) were initially diagnosed as non-gallbladder cancer. There were 4 049 patients(65.741%) undergoing surgical treatment, of which 2 303 cases(56.878%) were initially diagnosed as gallbladder cancer and 1 746 cases(43.122%) were initial diagnosed as non-gallbladder cancer. Of the 1 746 patients who were initially diagnosed as non-gallbladder cancer, there were 774 cases(19.116%) diagnosed as gallbladder cancer during operation and 972 cases(24.006%) diagnosed as gallbladder cancer after operation. Of 6 159 patients, there were 2 521 cases(40.932%), 2 335 cases(37.912%) and 1 114 cases(18.087%) undergoing ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) examination before initial diagnosis, respec-tively, and there were 3 259 cases(52.914%), 3 172 cases(51.502%) and 4 016 cases(65.205%) undergoing serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis, respectively. One patient may underwent multiple examinations. Results of univariate analysis showed that geographical distribution of hospitals (eastern China or western China), age ≥72 years, gallbladder cancer annual admission of hospitals, whether undergoing ultrasound, CT, MRI, serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis were related factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.45, 1.98, 0.69, 0.68, 2.43, 0.41, 1.63, 0.41, 0.39, 0.42, 95% confidence interval as 1.21-1.74, 1.64-2.40, 0.59-0.80, 0.60-0.78, 2.19-2.70, 0.37-0.45, 1.43-1.86, 0.37-0.45, 0.35-0.43, 0.38-0.47, P<0.05). Results of multivariate analysis showed that geographical distribution of hospitals (eastern China or western China), sex, age ≥72 years, gallbladder cancer annual admission of hospitals and cases undergoing ultrasound, CT, serum CA19-9 examination before initially diagnosis were indepen-dent influencing factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.36, 1.42, 0.89, 0.67, 1.85, 1.56, 1.57, 0.39, 95% confidence interval as 1.13-1.64, 1.16-1.73, 0.79-0.99, 0.57-0.78, 1.60-2.14, 1.38-1.77, 1.38-1.79, 0.35-0.43, P<0.05). (4) Surgical treatment and prognosis. Of the 4 049 patients undergoing surgical treatment, there were 2 447 cases(60.435%) with complete pathological staging data and follow-up data. Cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb were 85(3.474%), 201(8.214%), 71(2.902%), 890(36.371%), 382(15.611%), 33(1.348%) and 785(32.080%), respectively. The median follow-up time and median postoperative overall survival time of the 2 447 cases were 55.75 months (95% confidence interval as 52.78-58.35) and 23.46 months (95% confidence interval as 21.23-25.71), respectively. There was a significant difference in the overall survival between cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb ( χ2=512.47, P<0.001). Of the 4 049 patients undergoing surgical treatment, there were 2 988 cases(73.796%) with resectable tumor, 177 cases(4.371%) with unresectable tumor and 884 cases(21.833%) with tumor unassessable for resectabi-lity. Of the 2 988 cases with resectable tumor, there were 2 036 cases(68.139%) undergoing radical resection, 504 cases(16.867%) undergoing non-radical resection and 448 cases(14.994%) with operation unassessable for curative effect. Of the 2 447 cases with complete pathological staging data and follow-up data who underwent surgical treatment, there were 53 cases(2.166%) with unresectable tumor, 300 cases(12.260%) with resectable tumor and receiving non-radical resection, 1 441 cases(58.888%) with resectable tumor and receiving radical resection, 653 cases(26.686%) with resectable tumor and receiving operation unassessable for curative effect. There were 733 cases not undergoing surgical treatment with complete pathological staging data and follow-up data. There was a significant difference in the overall survival between cases not undergoing surgical treatment, cases undergoing surgical treatment for unresectable tumor, cases undergoing non-radical resection for resectable tumor and cases undergoing radical resection for resectable tumor ( χ2=121.04, P<0.001). (5) Multimodality therapy and prognosis: of 6 159 patients, there were 541 cases(8.784%) under-going postoperative adjuvant chemotherapy and advanced chemotherapy, 76 cases(1.234%) under-going radiotherapy. There were 1 170 advanced gallbladder cancer (pathological staging ≥stage Ⅲa) patients undergoing radical resection, including 126 cases(10.769%) with post-operative adjuvant chemotherapy and 1 044 cases(89.231%) without postoperative adjuvant chemo-therapy. There was no significant difference in the overall survival between cases with post-operative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.23, P=0.629). There were 658 patients with pathological staging as stage Ⅲa who underwent radical resection, including 66 cases(10.030%) with postoperative adjuvant chemotherapy and 592 cases(89.970%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.05, P=0.817). There were 512 patients with pathological staging ≥stage Ⅲb who underwent radical resection, including 60 cases(11.719%) with postoperative adjuvant chemotherapy and 452 cases(88.281%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemo-therapy and cases without post-operative adjuvant chemo-therapy ( χ2=1.50, P=0.220). Conclusions:There are more women than men with gallbladder cancer in China and more than half of patients are diagnosed at the age of 56 to 75 years. Cases undergoing ultrasound, CT, serum CA19-9 examination before initial diagnosis are independent influencing factors influencing initial diagnosis of gallbladder cancer patients. Preoperative resectability evaluation can improve the therapy strategy and patient prognosis. Adjuvant chemotherapy for gallbladder cancer is not standardized and in low proportion in China.