Comparison of perioperative result and complications of robot-assisted radical cystectomy with intracorporeal and extracorporeal urinary diversion / 中华泌尿外科杂志

Objective:To explore and compare the perioperative result and complications of robot-assisted radical cystectomy with intracorporeal and extracorporeal urinary diversion.Methods:Clinical data of bladder cancer patients undergoing robot-assisted radical cystectomy with ileal conduit in Zhejiang Provincial People's Hospital from January 2015 to March 2020 were retrospectively analyzed. Eighty-two patients underwent extracorporeal urinary diversion (ECUD group), and 122 underwent intracorporeal urinary diversion (ICUD group). In the ECUD group, the median age was 70(61, 76)years old, including 67 male (81.7%), the median BMI was 26.1(24.3, 28.5), 67 cases(81.7%) was ASA score 0-2, 15 cases (18.3%)was 3 or higher, 15 cases (18.3%) were high risk non-muscular invasive bladder cancer. 67 cases (81.7%) were muscular invasive bladder cancer. 16 cases (19.5%) received neoadjuvant chemotherapy. Past medical history included smoking in 35 cases (43.2%), hypertension in 31 cases (37.5%), diabetes in 17 cases (21.3%), heart disease in 13 cases (15.7%), and abdominal surgery in 15 cases (17.8%). In the ICUD group, the median age was 68 (62, 75), 95 male (77.9%), the median BMI was 25.6 (23.4, 27.8)kg/m 2, 105 cases(86.1%) was ASA score 0-2, 17 cases (13.9%)was 3 or higher, 29 cases (24.9%) were high risk non-muscular invasive bladder cancer, and 93 cases (75.1%) were muscular invasive bladder cancer. There were 22 cases (18.0%) undergoing neoadjuvant chemotherapy. Past medical history included smoking in 58 cases (47.3%), hypertension in 44 cases (32.6%), diabetes in 33 cases (22.8%), heart disease in 28 cases (26.7%), and abdominal surgery in 17 cases (14.2%). No significance was detected in characteristics between the two groups. For ileal bladder making and ureteral implantation method in ICUD group, 15 cm ileum was taken using stapler at the 15 cm from ileocecum to make ileal conduit and restore the continuity of the ileum. The proximal end of the ileal conduit was closed. The bilateral ureteral were implanted 3 cm apart on the ileal bladder. F6 single J tube was placed into both of the ureters to drain urine. For ECUD group, the subumbilical 5 cm incision was taken to enter the abdominal cavity. The ileocecum was found and the terminal ileum was taken out of the body. A segment of 15 cm in length ileocecum 15 cm away from the cecum was cut off with a linear cutting stapler and the blood vessels of arterial arch were ligated, then a small opening at the same ileum position was cut. The continuity of the ileocecum was restored. The ileal conduit was irrigated, and the bilateral ureters were placed into a single J tube and anastomosed to the ileal conduit 3 cm apart. The operation time, intraoperative blood loss, postoperative exhaust time, postoperative feeding time, postoperative hospital stay, postoperative incision pain score, postoperative readmission rate, peri-operative mortality, postoperative complications and pathology results were compared between the two groups. Results:All cases were successfully performed robotically without conversion or major intraoperative complications. There was no significant difference in operation time between ICUD group and ECUD group [260(230, 310) min and 235(220, 290) min, P=0.078]. The estimated blood loss in ECUD group was more than that in ICUD group [300(200, 400) ml and 150(100, 300), P=0.037], but there was no difference in blood transfusion rate between the two groups [7(8.6%) and 9(7.4%), P=0.196]. The exhaust time [4(2-6) days and 2(1, 3) days] and postoperative solid food feeding time [7(4, 9) days and 4(3, 5) days] in the ECUD group were longer than those in the ICUD group (all P<0 05). The exhaust time[4(2-6)day and 2(1, 3)day] and solid food feeding time[7(4, 9)day and 4(3, 5)day] in ECUD group were longer than those in ICUD group. There was no significant difference in postoperative hospital stay between ECUD group and ICUD group[8(5, 11)day and 6(5, 9)day, P=0.212]. Clavien-Dindo Ⅰ-Ⅱ grade was defined mild complication, Ⅲ grade or above was defined serious complication, early complication was defined within 30 days after operation, and late complication was defined 30-90 days after operation. The overall early postoperative complication rate were 19.6%(24) and 34.2%(28)(ICUD vs.ECUD), the mild complications rate were 13.9%(17) and 25.6%(21)(ICUD vs.ECUD), and the late severe complication rate were 4.1%(5)and 10.1%(8)(ICUD vs.ECUD). ICUD group were significantly lower than those of ECUD group (all P<0.05). There was no difference in the early severe complication rate [5.7%(7) and 8.5%(7)], the total late complication rate [15.6%(19) and 16.1%(13)], and the late mild complication rate [11.5% (14) and 6.0% (5)] (all P>0.05). There was no significant difference between ICUD group and ECUD group, in term of the number of lymph nodes dissected [21(14, 25) and 19(15, 24)], the positive rate of lymph nodes [10.7%(13) and 10.0%(8)], the positive rate of surgical margin [3.3%(4) and 4.8%(4)] and postoperative pathological stage T 1-T is [25(20.3%) and 14(17.1%)], and T 2-T 3 [97(79.7%) and 68(82.9%)]. The number of patients with postoperative incision pain (pain score >5) was 43 (35.6%) in ICUD and 46 (56.5%) in ECUD( P< 0.05). The 30-day and 90-day readmission rates were 1.6% (2/82) and 4.9% (6/82) in ICUD group, and 1.2% (1/122) and 9.8% (8/122) in ECUD group, respectively. There was no peri-operative mortality in both groups. Conclusions:Robot-assisted radical cystectomy with ileal conduit is a safe and repeatable method for the treatment of muscular invasive or high-risk non-muscular invasive bladder cancer. Complete intracorporeal bladder reconstruction is feasible and has the advantages of less intraoperative bleeding, faster postoperative intestinal function recovery and less complications.

Efficacy comparison of robot-assisted partial nephrectomy and laparoscopic partial nephrectomy in the treatment of giant renal angiomyolipoma / 中华泌尿外科杂志

Objective:To evaluate the efficacy of robot-assisted partial nephrectomy (RAPN)and laparoscopic partial nephrectomy(LPN)in the treatment of giant (>7cm) renal angiomyolipoma (RAML).Methods:The clinical data of 43 patients with giant RAML(>7cm) who underwent surgery in Zhejiang People's Hospital from October 2014 to May 2020 was retrospectively analysed, including 23 routine RAPN and 20 routine LPN. The median age of patients in the RAPN group was 45(17-65) years old, with 4 males and 19 females.The median body mass index(BMI) was 20.3(18.0-25.7) kg/m 2. Tumors located on the left side in 11 cases and on the right side in 12 cases. Tumors located on upper pole in 9 cases, middle pole in 5 cases , lower pole in 5 cases. The median R. E.N.A.L. score was 8(4-12) points and the largest tumor diameter was 7.5(7.1-17.0) cm. The median age of patients in the LPN group was 53(27-78) years old, with 1 males and 19 females. The median BMI was 21.4(19.0-25.5) kg/m 2. Tumors located on the left side in 9 cases and right side in 11 cases. Tumors located on the upper pole in 7 cases, middle pole in 4 cases and lower pole in 5 cases. 4 cases were multiple tumors, 2 cases were bilateral, and 2 cases were unilateral. The median R. E.N.A.L. score was 8(4-12) points and the median maximum diameter of tumor was 7.3(7.0-20.0) cm. There was no statistically significant difference in general information between the two groups ( P>0.05). The operation time, warm ischemia time, intraoperative blood loss, postoperative complications, postoperative recovery, renal function and other indicators of the two groups were compared, as well as the follow-up results. Results:The operations in both groups were successfully completed, and none of them were transferred to open surgery. Patients in the RAPN group had markedly lower median operation time [115(90-220) vs.145(120-240) min], and reduced median time of warm ischemia [15(10-25) vs. 23(20-28) min] than those in the LPN group, the difference between the two groups was statistically significant ( P<0.05). There were no significant differences in the median time of eating [1(1-2) vs. 1(1-3)d], time of extubation [4(3-16) vs. 5(3-14)d], postoperative absolute time in bed [4(3-7) vs. 4(2-12)d], hospitalization time [7(5-16) vs. 8(4-14)d], creatinine change[11.3(1.6-44.8) vs. 18.2(1.0-54.8)μmol/L], eGFR change [21.5(1.8-43.5) vs. 22.1(5.6-51.3) ml/(min·1.73m 2)], and hemoglobin change[22.5(11-43) vs. 23.0 (9-62) g/L] between the two groups( P>0.05). The incidence of postoperative complications in the RAPN group and the LPN group were 0 and 15%(3/20), respectively, and the difference was statistically significant ( P<0.05). 3 patients had blood transfusion during the operation, because 2 patients had renal wound hemorrhage. During the operation, ultrasonic scalpel electrocoagulation to halt bleeding and hemostatic cotton padding were performed, which improved after suture. One case had active hemorrhage from the renal wound arteries after surgery, which improved after blood transfusion and embolization. Another 2 patients had postoperative fever, improved after anti-infection and antipyretic treatment. There was no leakage of urine after operation in RAPN group and LPN group. The RAPN group was followed up for 6 months to 45 months with a median time of 12 months, and the LPN group was 8 months to 50 months with a median time of 15 months. No tumor recurrence or delayed renal stump bleeding was identified. Conclusions:Compared with LPN, RAPN therapy of giant RAML can shorten the operation time and warm ischemia time, and decrease postoperative complications, the two have similar short-term follow-up results in terms of tumor control and renal function protection.

Dose-response relationships of resistance exercise intensity in frail elderly: a systematic review / 中国实用护理杂志

Objective:To systematically evaluate the dose-response relationships of resistance exercise intensity in frail elderly.Methods:A comprehensive search of randomized controlled trials on the dose-response relationships of resistance exercise for frail elderly in PubMed, Embase, The Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang Database. The documents that met the conditions were screened out, and after the data were extracted and the quality of the documents were evaluated, the RevMan 5.3 software was used for Meta analysis.Results:A total of 10 eligible randomized controlled trials were included in this study. The subjects of the study were 454 cases of frail and pre-frail elderly. After Meta analysis, there was a dose-response relationships between the training intensity of resistance exercise and the muscle strength, muscle endurance, and physical function of frail elderly. Both low-intensity and high-intensity resistance exercises can significantly increase the leg muscle strength of frail elderly people ( MD=4.58, 95% CI 3.34-5.82, P<0.05) and muscle endurance ( MD=12.27, 95% CI 6.54-17.99, P<0.05). Compared with low-intensity resistance exercise, high-intensity resistance exercise increased leg muscle strength of frail elderly people ( MD=7.97, 95% CI 0.85-15.09, P<0.05) and muscle endurance ( MD=6.94, 95% CI 5.21-8.66, P<0.05) showed more obvious advantages. The analysis of the results of the chair sitting test and the stairs climbing test shows that low-intensity resistance exercise has no obvious advantage in improving the physical function of frail elderly people, while high-intensity resistance exercise can significantly improve the physical function of frail elderly people ( MD=-5.8, 95% CI -7.3--4.29, P<0.05; MD=-1.20, 95% CI-2.17--0.23, P<0.05). Conclusions:Resistance exercise can significantly improve the muscle strength, muscle endurance and physical function of the frail elderly. High-intensity resistance exercise is more effective than low-intensity resistance exercise.

Treatment and prognosis of multiple primary malignant neoplasms complicated with renal cell carcinoma / 北京大学学报(医学版)

OBJECTIVE@#To investigate the treatment and prognosis of multiple primary malignant neoplasms (MPMN) complicated with renal cell carcinoma (RCC), and to make risk stratification.@*METHODS@#A retrospective study of 27 cases of MPMN with RCC in two centers, including the different tumors of MPMN, specific treatment methods, and the interval between primary cancers. At the same time, the survival conditions, including recurrence, metastasis and survival, were followed up for statistical analysis. The interval between the two kinds of primary cancer within 6 months was simultaneous MPMNs, and more than 6 months was metachronous MPMNs. For simple risk stratification of cases, as long as one of the MPMNs had a stage Ⅲ or higher malignancy, which was defined as high risk.@*RESULTS@#Among the 27 patients, 20 were male and 7 were female, with age at the time of diagnosis was 42-82 years, with an average age of (61.3±11.7) years. The age at the diagnosis of renal cancer was 43-87 years, with an average age of (66.0±11.3) years. There were 21 cases with duplex primary malignant neoplasms, 4 cases with triple primary malignant neoplasms, and 2 cases with quadruple primary malignant neoplasms. The interval between first cancer and second cancer was 0-360 months, with a median of 18 months. There were 17 cases of metachronous multiple primary malignant neoplasms and 10 cases of simultaneous multiple primary malignant neoplasms. The most common system of MPMN with comorbid RCC involved urologic system, digestive system and respiratory system. The most common locations of MPMN with comorbid RCC were bladder cancer, lung cancer and colon cancer. Follow-up time calcu- lated from the last cancer was 2-156 months, with a median of 32 months. And 14 cases survived and 13 cases died, with 11 cases being tumor related. Tumor stage was the risk factor of prognosis. Any kind of tumor stage in stage Ⅲ or above had a relatively poor prognosis.@*CONCLUSION@#MPMN complicated with RCC is relatively rare. Standard treatment should be used for each cancer type during the treatment process. The prognosis mainly depends on the highest stage of each tumor. Simple risk stratification shows that the prognosis of the high-risk group is worse. This simple stratification method may be helpful to predict the prognosis.

Preclinical studies of the triazolo1,5-apyrimidine derivative WS-716 as a highly potent, specific and orally active P-glycoprotein (P-gp) inhibitor

Multidrug resistance (MDR) is the main cause of clinical treatment failure and poor prognosis in cancer. Targeting P-glycoprotein (P-gp) has been regarded as an effective strategy to overcome MDR. In this work, we reported our preclinical studies of the triazolo[1,5-a]pyrimidine-based compound WS-716 as a highly potent, specific, and orally active P-gp inhibitor. Through direct binding to P-gp, WS-716 inhibited efflux function of P-gp and specifically reversed P-gp-mediated MDR to paclitaxel (PTX) in multiple resistant cell lines, without changing its expression or subcellular localization. WS-716 and PTX synergistically inhibited formation of colony and 3D spheroid, induced apoptosis and cell cycle arrest at G2/M phase in resistant SW620/Ad300 cells. In addition, WS-716 displayed minimal effect on the drug-metabolizing enzyme cytochrome P4503A4 (CYP3A4). Importantly, WS-716 increased sensitivity of both pre-clinically and clinically derived MDR tumors to PTX in vivo with the T/C value of 29.7% in patient-derived xenograft (PDX) models. Relative to PTX treatment alone, combination of WS-716 and PTX caused no obvious adverse reactions. Taken together, our preclinical studies revealed therapeutic promise of WS-716 against MDR cancer, the promising data warrant its further development for cancer therapy.

Mechanism of Gegen Qinliantang against Vulnerable Plaque of Atherosclerosis： Based on Macrophage Pyroptosis Mediated by NF-κB/NLRP3/Caspase-1 Pathway / 中国实验方剂学杂志

ObjectiveTo explore the effect of Gegen Qinliantang （GQL） on vulnerable plaque of atherosclerosis based on the macrophage pyroptosis mediated by nuclear factor （NF）-κB/NOD-like receptor protein 3 （NLRP3）/cysteine-aspartic acid protease （Caspase）-1 pathway. MethodA total of 12 normal C57BL/6CNC mice were used as the control group， and 60 ApoE-/- mice of the same line were randomized into 5 groups： model group， low-dose， medium-dose， and high-dose GQL groups （GQL-D， GQL-Z， GQL-G groups， respectively）， and western medicine group. The control group and model group were given （ig） equal volume sterile distilled， and GQL-D， GQL-Z， GQL-G and western medicine groups received （ig） corresponding concentration of drugs for 8 weeks. Aortic plaques were observed based on hematoxylin and eosin （HE） staining. Serum levels of interleukin （IL）-1β and IL-18 were detected by enzyme-linked immunosorbent assay （ELISA）， protein levels of macrophage mannose receptor （CD206）/apoptosis-associated speck-like protein containing a CARD （ASC） and CD206/NLRP3 by double-labeling immunofluorescence， and C-terminal gasdermin D （GSDMD）， N-terminal GSDMD， NLRP3， pro-cysteinyl aspartate specific proteinase 1 （pro-Caspase-1） and NF-κB p65 by Western blot. ResultCompared with the control group， model group demonstrated serious pathological changes， rise of the levels of serum IL-1β and IL-18 and tissue ASC， NLRP3， C-terminal GSDMD， N-terminal GSDMD， pro-Caspase-1， and NF-κB p65， and decrease of CD206 level （P<0.05）. As compared with model group， the administration groups showed alleviation of the lesions in aortic wall， decrease in levels of serum IL-1β and IL-18 and tissue ASC， NLRP3， C-terminal GSDMD， N-terminal GSDMD， pro-Caspase-1， and NF-κB p65， and rise of CD206 level， with significant difference between some groups （P<0.05）. ConclusionGegen Qinliantang alleviates vulnerable plaque of atherosclerosis by regulating NF-κB/NLRP3/Caspase-1 pathway and further relieving macrophage pyroptosis.

Gegen Qinliantang Regulates Polarization Tendency of Macrophages to Intervene in Vulnerable Plaque in AS of ApoE-/- Mice / 中国实验方剂学杂志

ObjectiveTo explore the mechanism underlying the intervention of Gegen Qinliantang （GQL） in vulnerable plaques in atherosclerosis （AS） of ApoE-/- mice by regulating the polarization of macrophages. MethodTwelve normal C57BL/6CNC mice were used as the control group， and 60 ApoE-/- mice of the same line were randomized into 5 groups： model group， low-dose， middle-dose， and high-dose GQL groups （GQL-D， GQL-Z， and GQL-G groups， respectively）， and atorvastatin group （western medicine group）. High-fat diet was used for modeling. The control group and the model group were given （ig） equal volume of sterile distilled water， and GQL-D， GQL-Z， GQL-G， and western medicine groups received （ig） corresponding concentration of drugs for 8 weeks. The levels of total cholesterol （TC）， triglyceride （TG）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） were detected with biochemical methods. The distribution of plaques in the aortic region was observed based on oil red O staining and hematoxylin-eosin （HE） staining. Serum levels of M1 pro-inflammatory factors tumor necrosis factor （TNF）-α and interleukin （IL）-6 and M2 anti-inflammatory factors IL-13 and transforming growth factor （TGF）-β were detected by enzyme-linked immunosorbent assay （ELISA）. Protein expression of macrophage mannose receptor CD206/arginase-1 （Arg-1） and CD206/inducible nitric oxide synthase （iNOS） was determined by double-labeling immunofluorescence， and mRNA expression of aortic Arg-1 and iNOS by real-time polymerase chain reaction （PCR）. ResultLevels of TG， TC， and LDL-C were significantly lower and HDL-C level was significantly higher in the GQL-Z， GQL-G， and western medicine groups than in the model group. As the concentration of GQL rose， the area with plaques gradually shrunk and the color became lighter. The staining areas of the GQL-G group and the western medicine group were the most scattered. The administration groups showed significant increase in the protein levels of Arg-1 and CD206， significant decrease in the protein level of iNOS， significant rise of Arg-1 mRNA level， and significant drop of iNOS mRNA level （P<0.05）. ConclusionGQL intervenes in the vulnerable plaques in AS by improving lipid metabolism， inhibiting macrophage M1 polarization， promoting macrophage M2 polarization， and further improving the inflammatory microenvironment.

Effect of peer education on knowledge, attitude and practices towards schistosomiasis among primary school students in endemic foci of Wuhan City / 中国血吸虫病防治杂志

Objective To evaluate the effect of peer education on knowledge, attitude and practices towards schistosomiasis control among primary school students in endemic foci of Wuhan City. Methods Yucai Hankou Primary School in Jiang’ an District, Wuhan City was selected in 2021, and all students at grades 4 and 5 were sampled using a cluster sampling method to receive peer education about schistosomiasis. The changes of knowledge, attitude and practices towards schistosomiasis control were compared before and after peer education to evaluate the effect of peer education on knowledge, attitude and practices towards schistosomiasis control. Results The overall awareness of schistosomiasis control knowledge and the overall proportion of correct attitudes towards schistosomiasis control and correct schistosomiasis-related behaviors increased from 51.50%, 93.70% and 92.99% before peer education to 86.50%, 98.98% and 98.72% after peer education among primary school students, respectively (χ2=149.457, 21.692 and 20.691, all P values < 0.05). The overall awareness of schistosomiasis control knowledge and the overall proportion of correct attitudes towards schistosomiasis control and correct schistosomiasis-related behaviors were 49.19%, 92.20% and 92.72% among Grade 4 primary school students and 53.83%, 95.21% and 93.28% among Grade 5 primary school students prior to peer education (χ2 = 1.214, 2.034 and 0.096, all P values > 0.05), and increased to 75.93%, 98.09% and 97.59% among Grade 4 primary school students and 97.16%, 99.87% and 99.87% among Grade 5 primary school students after peer education, respectively (χ2 = 40.798, 9.572, 7.207, 133.194, 9.678 and 14.926, all P values < 0.05). The overall awareness of schistosomiasis control knowledge and the overall proportion of correct attitudes towards schistosomiasis control and correct schistosomiasis-related behaviors were 51.25%, 76.92% and 77.97% among male primary school students and 51.80%, 94.42% and 95.70% among female primary school students prior to peer education, the differences in the overall proportion of correct attitudes towards schistosomiasis control and correct schistosomiasis-related behaviors between male primary school students and female primary school students were significant (χ2 = 30.462 and 33.416, both P values < 0.05), and increased to 86.23%, 98.25% and 97.79% among male primary school students and 86.83%, 99.85% and 99.85% among female primary school students after peer education (χ2 = 0.081, 3.529 and 3.335, all P values > 0.05), respectively. Conclusions Peer education is effective to improve the knowledge, attitude and practices towards schistosomiasis control among primary school students in endemic foci of Wuhan City, which may be more effective to improve the awareness of schistosomiasis control knowledge and proportion of correct schistosomiasis-related behaviors among primary school students at high grades.

Correlation Analysis Between Color and Content Changes of Five Components of Wine-processed Polygonatum kingianum Rhizoma During Processing / 中国实验方剂学杂志

ObjectiveTo study the correlation between the appearance color of the sample powder and the contents of five non-sugar components of wine-processed Polygonatum kingianum rhizoma during processing， and determine the feasibility of color quantitative value for judging the processing end point of the wine-processed products， and to screen steroidal saponins and flavonoids as markers for the control of the wine-processed products during processing. MethodThe changes of apparent color of the sample powder at different time points of the wine-processed products were measured by colorimeter， and the total color value （E*ab），the total color difference value （ΔE*ab） were calculated. The contents of protodioscin， pseudoprotodioscin， dioscin， diosgenin and narcissoside in the wine-processed products （No. S0-S10） after processing for 0， 5， 10， 14， 16， 18， 20， 22， 24， 26， 28 h were determined simultaneously by ultra-high performance liquid chromatography-tandem mass spectrometry （UHPLC-MS/MS）. Cluster analysis （HCA）， principal component analysis （PCA）， partial least squares discriminant analysis （PLS-DA） and Pearson correlation analysis were used to analyze the chromaticity value of the sample powder and the content of the five components. ResultDuring processing of wine-processed P. kingianum rhizoma， E*ab of the sample powder showed a decreasing trend and the apparent color changed from light yellow to lacquer black. The contents of the five components showed an obvious dynamic change trend with time， and showed different laws. HCA results showed that the processing process of the wine-processed products could be divided into three stages， namely， the early stage （samples S0-S1）， the middle stage （samples S2-S4） and the late stage （samples S5-S10）. PCA results showed that there were significant differences in color and contents of five components between the initial sample and the processing samples， and the difference between samples S8 and S9 was the smallest. PLS-DA results showed that the variable importance in the projection （VIP） values of b*， the contents of pseudoprotodioscin， narcissoside， diosgenin and protodioscin were >1. Pearson correlation analysis showed that the contents of protodioscin， diosgenin and narcissoside had a significant positive correlation with E*ab （P<0.01）， the content of diosgenin had a significant negative correlation with E*ab （P<0.01）， while the content of pseudoprotodioscin had no linear correlation with E*ab. ConclusionIn the process of wine-processed P. kingianum rhizoma， there is a certain linear correlation between color quantitative value and chemical composition， and the processing end point can be determined objectively. It can be considered that protodioscin can be used as a marker for the control of the wine-processed products.

Mechanism of Jiawei Bazhen Yimu Capsule in Treatment of Premature Ovarian Failure Based on Estrogen Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Jiawei Bazhen Yimu capsule on serum sex hormones， sexual organs and estrogen signaling pathway in female rats with premature ovarian failure. MethodThe key target proteins of Jiawei Bazhen Yimu capsule in the treatment of premature ovarian failure were screened out by network pharmacology analysis. Female healthy SD rats were selected, and the rat model of premature ovarian failure was established by ovariectomy. Fifty ovariectomized rats were randomly divided into a model group, an estradiol (E2) valerate group, and Jiawei Bazhen Yimu capsule low, medium, and high-dose groups. Another 10 healthy female rats were set as a sham operation group. The sham operation group and the model group were given distilled water by gavage, and other administration groups were given corresponding doses of drugs by gavage. After 21 d, the serum hormone levels of female rats were measured, including E2, progesterone (P), follicle stimulating hormone (FSH), and luteinizing hormone (LH). Immunofluorescence staining (IF) was used to detect the protein expression levels of estrogen receptor 1 (ESR1), estrogen metabolism P4503A4 enzyme (CYP3A4), and P45019A1 enzyme (CYP19A1) in the uterine tissues of female rats. ResultAs compared with the model group, the serum E2 and P levels of female rats in the Jiawei Bazhen Yimu capsule low, medium, and high-dose groups were significantly increased. Jiawei Bazhen Yimu capsule improved the endometrial status of female rats and increased positive expression of ESR1, CYP3A4, and CYP19A1 in the uterine tissues of female rats (P<0.05). ConclusionThe mechanism of Jiawei Bazhenyimu capsule in the treatment of premature ovarian failure may be related to its hormone-like effect and activation of the estrogen signaling pathway.

A new phloroglucinol from Dryopteris fragrans and its antibacterial activity in vitro / 中国中药杂志

A new phloroglucinol was isolated from 50% ethanol extract of Dryopteris fragrans by silica gel column chromatography, Sephadex LH-20 gel column chromatography, thin-layer chromatography(TLC), and preparative liquid column chromatography. On the basis of MS, ~1H-NMR, ~(13)C-NMR, and reference materials, compound 1 was identified as 2,5-cyclohexadien-1-one, 2-{[2,6-dihydroxy-4-methoxy-3-methyl-5-(1-isobutyl)phenyl]methyl}-3,5-dihydroxy-4,4-dimethyl-6-(1-oxobutyl)(1), and named disaspidin BB. Compound 1 was evaluated for its antibacterial activity. The experimental results showed that compared with the commonly used topical antibiotics erythromycin or mupirocin, disaspidin BB exhibited significant antibacterial activities against Staphylococcus epidermidis(SEP), S. haemolyticus(SHA), and methicillin-resistant S. aureus(MRSA)(P<0.05). Additionally, disaspidin BB was sensitive to ceftazidime-resistant SEP1-SEP4, SHA5-SHA7, MRSA8, and MRSA9. The MIC values of disaspidin BB against SEP and SHA were 1.67-2.71 μg·mL~(-1) and 10.00-33.33 μg·mL~(-1) respectively. Disaspidin BB has good antibacterial activities and deserves development as a new anti-infective drug for external use.

Advances in N-methyl-D-aspartate Receptor Signaling Pathway and Mechanism of the Pathway-mediated Apoptosis / 中国医学科学院学报

N-methyl-D-aspartate receptor (NMDAR),an important ionic glutamate receptor and a ligand and voltage-gated ion channel characterized by complex composition and functions and wide distribution,plays a key role in the pathological and physiological process of diseases or stress states.NMDAR can mediate apoptosis through different pathways such as mitochondrial and endoplasmic reticulum damage,production of reactive oxygen species and peroxynitrite,and activation of mitogen-activated protein kinase and calpain.This paper reviews the structure,distribution,and biological characteristics of NMDAR and the mechanisms of NMDAR-mediated apoptosis.

TRPV4 Regulates Soman-Induced Status Epilepticus and Secondary Brain Injury via NMDA Receptor and NLRP3 Inflammasome / 神经科学通报·英文版

Nerve agents are used in civil wars and terrorist attacks, posing a threat to public safety. Acute exposure to nerve agents such as soman (GD) causes serious brain damage, leading to death due to intense seizures induced by acetylcholinesterase inhibition and neuronal injury resulting from increased excitatory amino-acid levels and neuroinflammation. However, data on the anticonvulsant and neuroprotective efficacies of currently-used countermeasures are limited. Here, we evaluated the potential effects of transient receptor vanilloid 4 (TRPV4) in the treatment of soman-induced status epilepticus (SE) and secondary brain injury. We demonstrated that TRPV4 expression was markedly up-regulated in rat hippocampus after soman-induced seizures. Administration of the TRPV4 antagonist GSK2193874 prior to soman exposure significantly decreased the mortality rate in rats and reduced SE intensity. TRPV4-knockout mice also showed lower incidence of seizures and higher survival rates than wild-type mice following soman exposure. Further in vivo and in vitro experiments demonstrated that blocking TRPV4 prevented NMDA receptor-mediated glutamate excitotoxicity. The protein levels of the NLRP3 inflammasome complex and its downstream cytokines IL-1β and IL-18 increased in soman-exposed rat hippocampus. However, TRPV4 inhibition or deletion markedly reversed the activation of the NLRP3 inflammasome pathway. In conclusion, our study suggests that the blockade of TRPV4 protects against soman exposure and reduces brain injury following SE by decreasing NMDA receptor-mediated excitotoxicity and NLRP3-mediated neuroinflammation. To our knowledge, this is the first study regarding the “dual-switch” function of TRPV4 in the treatment of soman intoxication.

Adrenal cavernous hemangioma: A case report and literature review / 北京大学学报(医学版)

A 57-year-old male patient was referred to our department with complaints of his right adrenal gland occupancy and hypertension about 6 months. When admitted to the hospital, the blood pressure was about 160/100 mmHg, and the heart rate was 110 beats/min. He was no obvious obesity, acne, abnormal mood, without weakness of limbs, acral numbness, palpitation and headache. He presented with type 2 diabetes for more than 3 years, with oral administration of metformin enteric coated tablets and subcutaneous injection of insulin glargine to control blood glucose, and satisfied with blood glucose control. Enhanced CT showed that: the right adrenal gland showed a kind of oval isodense, slightly hypodense shadow, the edge was clear, lobular change, the size was about 5.8 cm×5.4 cm, uneven density, there were nodular and strip calcification, round lipid containing area and strip low density area, and the CT value of solid part was about 34 HU. Enhanced scan showed heterogeneous nodular enhancement in the solid part of the right adrenal gland, nodular enhancement could be seen inside. The CT values of solid part in arterial phase, venous phase and delayed phase were 45 HU, 50 HU and 81 HU, respectively. Considering from the right adrenal gland, cortical cancer was more likely. No obvious abnormality was found in his endocrine examination. After adequate preoperative preparation, retroperitoneal laparoscopic adrenalectomy was performed under general anesthesia. During the operation, the 6 cm adrenal tumor was closely related to the inferior vena cava and liver, and after careful separation, the tumor was completely removed and normal adrenal tissue was preserved. The operation lasted 180 min and the blood loss was 100 mL, and the blood pressure was stable during and after the operation. There was no obvious complication. The results of pathological examinations were as follows: the size of the tumor was 7.5 cm×6.0 cm×3.5 cm, soft, with intact capsule and grayish-red cystic in section. Pathological diagnosis: (right adrenal gland) cavernous hemangioma, secondary intravascular thrombosis, old hemorrhagic infarction with calcification and ossification. After 6 months of observation, no obvious complications and tumor recurrence were found. In summary, cavernous hemangioma of adrenal gland is a rare histopathological change. Its essence is a malformed vascular mass. Blood retention is the cause of thrombosis and calcification in malformed vessels. The imaging findings were inhomogeneous enhancement of soft tissue masses, and the adrenal function examination showed no obvious abnormalities. Retroperitoneal laparoscopic surgery is feasible after adequate preoperative preparation. It is difficult to diagnose the disease preoperatively and needs to be confirmed by postoperative pathology.

Occupational Health Risk Assessment of Benzene, Toluene, and Xylene in Shanghai / 生物医学与环境科学（英文）

Objective@#This study was designed to conduct a retrospective and systematic occupational health risk assessment (OHRA) of enterprises that used benzene, toluene, and xylene (BTX) in Shanghai, China.@*Methods@#All data for the study were obtained from 1,705 occupational health examination and evaluation reports from 2013 to 2017, and a semiquantitative model following Chinese OHRA guidelines (GBZ/T 298-2017) was applied for the assessment.@*Results@#The selected enterprises using BTX were mainly involved in manufacturing of products. Using the exposure level method, health risk levels associated with exposure to BTX were classified as medium, negligible, or low. However, the risk levels associated with benzene and toluene were significantly different according to job types, with gluers and inkers exhibiting greater health risks. For the same job type, the health risk levels assessed using the comprehensive index method were higher than those using the exposure level method.@*Conclusion@#Our OHRA reveals that workers who are exposed to BTX still face excessive health risk. Additionally, the risk level varied depending on job categories and exposure to specific chemicals. Therefore, additional control measures recommended by OHRA guidelines are essential to reduce worker exposure levels.

Surgical strategies and approaches for the management of tumors at cervicothoracic junction / 中华胸心血管外科杂志

Objective:To investigate the surgical treatment of the tumors at cervicothoracic junction.Methods:A retrospective analyses was performed for 63 patients with tumors at the cervicothoracic junction receiving surgery from Mar 2008 to May 2020 in the Department of Thoracic Surgery, Zhongshan Hospital, Fudan University. Clinical data about manifestation, surgical approach, resection degree and pathological types were collected. There were 43 cases of asymptomatic patients and 20 cases of patients with ≥1 clinical manifestations. Twenty two patients receiving radical resection with video-assisted thoracoscopic surgery. Anterior approach was the most popular treatment in open surgery (24 cases, 38.1%), and 8 cases of anterolateral approach(6 cases of Hemiclamshell incisions, 2 cases of trap-door incisions), 1 case of posterior approach, 2 cases of posterolateral approach and 1 case of supraclavicular combined posterolateral approach.Results:Pathological examination suggested 61 cases of radical resection and 2 cases of microscopic residual. Neurilemmoma was the most common pathological type (27 cases, 42.9%), the second common pathological type was tumor originated from fibrous tissues (6 cases, 9.5%). The 3-year overall survival rate of those 63 patients was 88.9%, while the 5-year overall survival rate was 84.1%.Conclusion:Tumors involving the cervicothoracic junction are characterized as special location, complicated anatomy and various histopathological subtypes. Individualized approach and surgery improve safety and normalization of tumors at cervicothoracic junction treatment.

Effect of statins on the progression and prognosis of chronic liver diseases / 临床肝胆病杂志

Chronic liver diseases can progress to liver fibrosis and cirrhosis and may lead to portal hypertension and even hepatocellular carcinoma. In recent years, more and more studies have shown that statins can improve liver histology, delay progression to liver fibrosis, and reduce the risk of decompensation and hepatocellular carcinoma in patients with nonalcoholic fatty liver disease. This article introduces the advances in the application of statins in patients with chronic liver diseases, so as to provide a basis for the prevention and treatment of chronic liver diseases.

Robotic versus laparoscopic total mesorectal excision surgery in rectal cancer: short-mid term oncological outcomes / 中华普通外科杂志

Objective:To investigate the safety and mid-term efficacy of robotic versus laparoscopic total mesorectal excision surgery in rectal cancer.Methods:A total of 240 patients were diagnosed with rectal cancer at the Anorectal Department of Gansu Provincial Hospital from Aug 2015 to Mar 2021, 112 patients underwent laparoscopic total mesorectal excision (L-TME group) and 128 patients did robotic-assisted total mesorectal excision (R-TME group).Results:Compared to the R-TME group, the L-TME group had higher conversion rate (5.4% vs. 0.8%, χ2=4.417, P=0.036), higher incidence of complications (32.1% vs. 17.2%, χ2=7.290, P=0.007), higher circumferential resection margin involvement (7.1% vs. 1.6%, χ2=4.658, P=0.031), lower 3-year DFS and OS(74.1% vs. 85.2%, χ2=4.962, P=0.026) and (81.3% vs. 91.4%, χ2=5.494, P=0.019), lower 3-year DFS and OS in AJCC stage Ⅲ(52.5% vs. 76.1%, χ2=5.799, P=0.016) and (65.0% vs. 84.8%, χ2=4.787, P=0.029). Conclusion:R-TME can achieve better oncological outcomes and is more beneficial for RC patients compared with L-TME, especially for those with stage Ⅲ rectal cancers.

The transvesical approach technique for robot-assisted radical prostatectomy for early stage prostate cancer / 中华泌尿外科杂志

Objective:To investigate the feasibility and safety of the transvesical approach of robot-assisted radical prostatectomy.Methods:From June 2017 to May 2020, 41 patients underwent transvesical approach of robot-assisted radical prostatectomy. The patients’ mean age was 62.5(51-69)years. The mean prostate volume was 36.3(22.0-57.8)ml. The mean preoperative PSA value was 7.3(3.7-12.3)ng/ml. All preoperative Gleason score was less than or equal to 7 points and preoperative TNM stage ranged from T 2a to T 2b . All patients were diagnosed by prostate biopsy before surgery or pathological diagnosis after prostate enucleation. Robot-assisted radical prostatectomy through the longitudinal incision of the bladder neck was used. It was easy to identify and preserve the bladder neck during the operation. The bladder was opened with a small longitudinal incision, and the prostate was removed intrafascial. The pubic prostatic ligament and pudendal artery were fully preserved to achieve complete reduction of the anatomical structure. Results:All the operations were completed by robot-assisted radical prostatectomy with no transition to open surgery. The mean surgery time was 111.3(105-131)min. The mean estimated blood loss was 95.5 (50-220) ml. The mean postoperative hospital stay was 5.2(3-8)d. The time of postoperative catheter removal was 6.3(5-7)d. After 6 to 24 months of follow-up, 35 patients (85.4%, 35/41) received immediate recovery of continence, 4 patients had no urine leakage after 1 week, and 2 patients had no urine leakage after 1 month. All patients had regained continence 6-month postoperatively. No tumor biochemical recurrence (tPSA<0.2 ng/ml).Conclusions:The transvesical approach of robot-assisted radical prostatectomy was a safe and effective surgical technique, which was beneficial in early continence recovery, and also suitable for prostate cancer patients after prostate enucleation.

Treatment of posterior-column dominating three-column tibial plateau fractures using raft-nailing and cannulated screwing via the posteromedian approach / 中华创伤骨科杂志

Objective:To evaluate the outcomes of posterior-column dominating three-column tibial plateau fractures treated by raft-nailing and cannulated screwing via the posteromedian approach.Methods:From October 2017 to June 2019, 15 patients with posterior-column dominating three-column tibial plateau fracture were surgically treated at Department of Orthopedics, The First Affiliated Hospital to Harbin Medical University. They are 11 males and 4 females, aged from 26 to 65 years (average, 41.2 years). All patients were operated on under general anesthesia or spinal anesthesia. After full exposure via the posteromedian approach using a popliteal S-shaped incision, their fractures were treated with raft-nailing and cannulated screwing. Wound healing and neurovascular injury were observed after operation. X-ray films were taken regularly to monitor fracture union and measure the tibial plateau angle (TPA) and posterior slope angle (PA) of the tibial plateau. The knee function was assessed using The Hospital for Special Surgery (HSS) scoring system at 12 months after operation.Results:Incisions healed by the first intention after surgery in 14 patients but the healing was delayed due to fat liquefaction in one patient. No symptoms of neurovascular injury were observed in the 15 patients who were followed up for 12 to 29 months (average, 16.5 months). All fractures united after 12 to 20 weeks (average, 15.4 weeks). At 3 days and 12 months after operation, respectively, their PA was 9.3°±2.1° and 9.7°±1.6° and their TPA 4.3°±1.2° and 4.1°±1.1°, showing no significant difference ( P>0.05). At 12 months after operation, their HSS scores ranged from 84 to 95 (average, 89.3), their knee flexion from 105° to 138° (average, 126.5°) and their knee extension from 0° to 8° (average, 3.4°). Conclusions:In the treatment of posterior-column dominating three-column tibial plateau fractures, raft-nailing combined with cannulated screwing via the posteromedian approach can achieve not only full exposure by a single incision but also stable plateau fixation, reduce operative invasion, and simplify operative procedures, leading to fine surgical outcomes.