Advance in renal cell carcinoma in 2022 ASCO-GU / 中华泌尿外科杂志

ASCO-GU is one of the landmark meetings of urogenital cancer. Within 2022 meeting, the extended follow up result of adjuvant pembrolizumab after nephrectomy in renal cell carcinoma as well as the efficacy and safety of neoadjuvant Axitinib and avelumab for local advanced renal cell carcinoma have been released. There were also explorations in local therapy for oligometastasis, novel combination system therapy and regiments alterations. The further research protocol of immunostimulatory IL-2 cytokine prodrug and PARP inhibitor for metastatic RCC were also disclosed.

Monitoring of sunitinib blood concentration and analysis of its safety and efficacy in Chinese patients with metastatic renal cell carcinoma / 中华泌尿外科杂志

Objective:To investigate the safety and efficacy of individualized sunitinib schedule for patients with metastatic renal cell carcinoma (mRCC) according to the monitoring results of plasma drug concentration.Methods:The clinical data of patients with mRCC who received sunitinib treatment in our center from January 2014 to December 2020 were retrospectively analyzed, including 20 patients who underwent monitoring of plasma drug concentration (monitoring group), and 45 patients, matched by propensity score matching, received sunitinib but did not undergo monitoring of plasma drug concentration during the same period (unmonitored group). In the monitoring group, there were 12 males and 8 females. The mean age was 52.9 years, and ECOG score ≤1 in 16 cases (80%). Three patients were in the IMDC favorable-risk group, 15 patients were in the intermediate-risk group, and 2 patients were in the high-risk group. There were 18 cases of clear cell carcinoma and 2 cases of non-clear cell carcinoma, 5 cases of ISUP grade 1-2 and 11 cases of grade 3-4. In the unmonitored group, there were 31 males and 14 females. The mean age was 57.7 years, and 30 patients had ECOG score ≤1, 15 cases ≥2. There were 10 cases in IMDC favorable-risk group, 23 cases in intermediate-risk group, and 12 cases in high-risk group. Thirty-seven cases were clear cell carcinoma and 8 cases were non-clear cell carcinoma, 8 cases were in ISUP grade 1-2 and 28 cases in grade 3-4. There were no statistically significant differences between the two groups in the above parameters ( P>0.05). The monitoring group used the regimen of taking sunitinib for 4 weeks and stopping for 2 weeks (4/2 week) in the first cycle. The blood concentration of sunitinib was monitored before the first cycle and on days 4, 7, 10, 14, 21 and 28, and personalized medication plan was formulated according to the curve of the blood concentration. The 4/2 week scheme was adopted in the undetected monitoring group.The two groups were compared in the incidence of adverse events (AEs), progression-free survival (PFS), overall survival (OS), tumor treatment response and other clinical outcomes. Results:In the monitoring group, 90% (18/20) of patients receiving sunitinib had a steady-state plasma concentration of more than 150ng/ml, of which 10 patients (50%) had a plasma concentration of 150-200 ng/ml and 8 patients (40%) had a plasma concentration of more than 200 ng/ml. Meanwhile, all patients with plasma concentration higher than 150 ng/ml developed severe AEs (grade 3 and above) after treatment. The other two patients' plasma concentration were 100-150 ng/ml, and did not have severe AEs.All patients in the monitoring group received individualized medication schedule adjustment according to the plasma drug concentration and the occurrence point of severe AEs, ensuring that the peak plasma drug concentration was maintained at about 100-150 ng/ml. Among them, 6 patients were changed to take 2 weeks and stop for 1 week (2/1 week schedule), 4 patients were changed to take 10 days and stop for 5 days (10/5 d schedule), 7 patients were changed to take 7 days and stop for 3 days (7/3 d schedule), and 3 patients were changed to take 5 days and stop for 2 days (5/2 d schedule). The incidence of severe AEs significantly decreased from 90% (18/20) to 35% (7/20), and the difference was statistically significant ( P=0.003), while the incidence of grade 3 and higher AEs was 55.6% (25/45) in the standard group, which was statistically significant compared with the incidence of severe AEs before adjustment in the monitoring group ( P=0.006). Further analysis of the efficacy difference between the two groups showed that the overall objective response rate in the monitoring group (40%, 8/20) was higher than that in the standard group (20%, 9/45), although the difference was not statistically significant ( P=0.09). Median PFS and OS were significantly longer in the monitored group than in the standard group (PFS: 23 vs. 10 months, P=0.002; OS: not reached vs.25 months, P=0.005). Conclusions:The bioavailability of sunitinib is high in mRCC patients, which may lead to higher plasma drug concentration, adjustment of medication regimen based on blood concentration monitoring significantly improved patient safety and clinical outcomes. However, further validation by larger-scale, multi-center and prospective studies is needed.

Pathogenesis of Gouty Arthritis and Intervention with Chinese Medicines： A Review / 中国实验方剂学杂志

Gouty arthritis （GA） is the metabolic rheumatism caused by purine metabolism disorder， which can be acute or chronic. The main manifestations of GA include recurrent redness， swelling， heat pain， and dysfunction of the affected joints. According to the theory of modern medicine， GA is closely associated with the increase in uric acid， the participation of inflammatory cytokines， the weakening of antioxidant response， apoptosis， and the imbalance of intestinal flora and bone metabolism， whereas the specific pathogenesis remains unclear. GA is characterized by easy diagnosis， difficult treatment， and high recurrence rate， which seriously affects the life quality of patients. Colchicine， corticosteroids， non-steroidal anti-inflammatory drugs， and selective cyclooxygenase-2 inhibitors are the commonly used western medicines for this disease， which demonstrate remarkable short-term therapeutic effect. However， long-term use of these medicines will bring serious adverse reactions. Chinese medicines， with high safety and causing few adverse reactions， have a variety of active components which can act on multiple pathways and targets to exert synergistic effects， thus attracting wide attention. This paper systematically reviews the literature reporting the Chinese medicines in improving antioxidant response， reducing chondrocyte apoptosis， and regulating intestinal flora and bone metabolism， aiming to further clarify the pathogenesis of GA and provide a scientific basis for the clinical application of Chinese medicines in the prevention and treatment of GA.

Predictors of efficacy of corticosteroid switching from abiraterone plus prednisone to dexamethasone in patients with metastatic castration-resistant prostate cancer / 亚洲男科学杂志(英文版)

Corticosteroid switching can reverse abiraterone resistance in some patients with metastatic castration-resistant prostate cancer (mCRPC). Here, we investigated the potential biomarkers for predicting the efficacy of corticosteroid switching during treatment with abiraterone acetate (AA). We retrospectively analyzed 101 mCRPC patients receiving corticosteroid switching from West China Hospital and Sun Yat-Sen University Cancer Center between January 2016 and December 2018. All cases received AA plus prednisone as first-line therapy during mCRPC. Primary end points were biochemical progression-free survival (bPFS) and overall survival (OS). The risk groups were defined based on multivariate analysis. A total of 42 (41.6%) and 25 (24.8%) patients achieved 30% and 50% decline in prostate-specific antigen (PSA), respectively, after corticosteroid switching. The median bPFS and median OS on AA plus dexamethasone were 4.9 (95% confidence interval [CI]: 3.7-6.0) months and 18.8 (95% CI: 16.2-30.2) months, respectively. Aldo-keto reductase family 1 member C3 (AKR1C3) expression (hazard ratio [HR]: 2.15, 95% Cl: 1.22-3.80, P = 0.008) and baseline serum alkaline phosphatase (ALP; HR: 4.95, 95% Cl: 2.40-10.19, P < 0.001) were independent predictors of efficacy before corticosteroid switching in the multivariate analysis of bPFS. Only baseline serum ALP >160 IU l-1 (HR: 3.41, 95% Cl: 1.57-7.38, P = 0.002) together with PSA level at switch ≥50 ng ml-1 (HR: 2.59, 95% Cl: 1.22-5.47, P = 0.013) independently predicted poorer OS. Based on the predictive factors in multivariate analysis, we developed two risk stratification tools to select candidates for corticosteroid switching. Detection of serum ALP level, PSA level, and tissue AKR1C3 expression in mCRPC patients could help make clinical decisions for corticosteroid switching.

The clinical exploration of corticosteroid switch of abiraterone acetate in patients with metastatic castration-resistant prostate cancer / 中华泌尿外科杂志

The terminal stage of prostate cancer is metastatic castration-resistant prostate cancer (mCRPC) with poor prognosis and high mortality. Abiraterone acetate (AA), as a new generation drug for endocrine therapy, has been demonstrated to prolonged overall survival signicantly in mCRPC patients. In addition, a corticosteroid drug must be administered during treatment to avoid side effects of abiraterone. It has been found that a corticosteroid switch from prednisone to dexamethasone could delay the development of resistance, significantly prolong the progression-free survival rate of patients, with well tolerance. But the specific mechanism and long-term clinical benefit still need further study. This emerging treatment paradigm provides new ideas for treatment options for patients with mCRPC, however, caution is still needed in clinical practice, and it is recommended to determine the treatment plan after considering all aspects of the patients.

Prognostic factors of salvage radiotherapy after radical prostatectomy / 中华泌尿外科杂志

Objective:To investigate the prognosis after salvage radiotherapy with or without hormone therapy for prostate cancer.Methods:From May 2014 to December 2020, 248 patients undergoing salvage radiotherapy due to prostate-specific antigen (PSA)persistence or biochemical progression after radical prostatectomy at Sun Yat-sen University Cancer Center (n=157) and West China Hospital, Sichuan University (n=91) were analyzed. Median age was 66 (45-78) years old. Median PSA was 23.50 (0.18-845.00) ng/ml. The number of PSA persistence and biochemical progression were 143 (59%) and 105 (42%). The number of pT 2, pT 3a, pT 3b, pT 4, and unknown T stage was 99, 49, 78, 15 and 7 cases.The number of N 0, N 1 and unknown N stage was 153, 44 and 51 cases. 165 cases had positive surgical margin. Gleason score of 6, 7, 8, >8 score and unknown was in 12, 104, 34, 90 and 8 patients. Early and late salvage radiotherapy was performed in 117 and 131 patients, and 70 patients (28%) were CRPC. Hormone therapy was used combined with radiotherapy in 182 patients (73%). PSA decline after radiotherapy was compared with Chi-squre test. Kaplan-Meier method and log-rank test were used to compare progression free-survival (PFS)after radiotherapy. Univariate and multivariate analyses of PFS were performed using Cox proportional hazards model. Early salvage radiotherapy was defined as PSA≤0.5 ng/ml before radiotherapy, and late salvage radiotherapy was defined as PSA>0.5ng/ml. Results:PSA response (PSA decline ≥50%) rate was 94% (233/248), and 82% (203/248) patients had PSA decline ≥ 90%. Twelve (5%) patients had rising PSA after completing radiotherapy, but only 4 (2%) had real progression. The median PFS was 69 months (95% CI 68-70), and 3-year and 5-year PFS rate were 80% and 67%. PFS of PSA persistence and biochemical progression were similar ( HR =0.71, 95% CI 0.37-1.37, P=0.311). Compared with late salvage radiotherapy, early salvage radiotherapy had better PFS [69 (95% CI 68-70) vs. 59 (95% CI 44-74) months, P<0.001]. Compared with hormone sensitive, castration-resistant was associated with worse PFS (5-year PFS rate 74% vs. 51%, P<0.001). In multivariate analysis, Gleason score>8, castration-resistant and late salvage radiotherapy were unfavorable prognostic factors. Conclusions:In patients receiving salvage radiotherapy with or without hormone therapy for PSA persistence and biochemical progression after radical prostatectomy, high PSA level before radiotherapy and castration resistant is associated with poor prognosis.

Explore Mechanism of Modified Si Junzitang in Improving Acidic Microenvironment and Reversing Gastric Precancerous Lesions Based on MCT4/CD147 / 中国实验方剂学杂志

Objective:To observe the effect of modified Si Junzitang on the level of lactic acid in gastric mucosa and the expression of Carboxylic acid transporter 1（MCT1）， monocarboxylic acid transporter 4（MCT4）， and extracellular matrix metalloproteinase inducer （CD147）in rats with gastric precancerous lesions（GPL）. Method:Seventy-four SD male rats were randomly divided into normal group （12 rats） and model group （62 rats）. <italic>N</italic>-methyl-<italic>N'</italic>-nitro-<italic>N</italic>-nitrosoguanidine（MNNG）-ammonia compound method was used to establish GPL rat models， and at the 9^th week， the model rats were randomly divided into model group， folic acid group（2.7 mg·kg^-1）， modified Si Junzitang high， medium and low dose groups（12.6， 6.3， 3.15 g·kg^-1）， with 12 rats in each group. After intragastric administration for 12 weeks， the general conditions of the rats were observed. Hematoxylin-eosin（HE）staining was used to observe the histopathological changes of gastric mucosa in rats， chemical colorimetry was used to detect the content of lactic acid in gastric mucosa； immunohistochemistry and real-time polymerase chain reaction（Real-time PCR）were used to detect MCT1， MCT4， CD147 protein and mRNA expression in gastric mucosal tissues. Result:Modified Si Junzitang significantly improved the pathological manifestations in GPL rats such as gastric mucosal epithelial gland structure， disorder of arrangement and cell atypia. Compared with the normal group， the lactic acid content of the gastric mucosa tissue in the model group increased significantly（<italic>P</italic><0.01）， and the protein and mRNA expressions of MCT1， MCT4， CD147 significantly increased（<italic>P</italic><0.05， <italic>P</italic><0.01）. Compared with the model group， the lactic acid content in each dose group of modified Si Junzitang was significantly reduced（<italic>P</italic><0.05， <italic>P</italic><0.01）， and the protein expression levels of MCT4 and CD147 were also significantly reduced in each dose group of modified Si Junzitang（<italic>P</italic><0.05， <italic>P</italic><0.01）. The mRNA expression of MCT4 was significantly reduced in the middle and high dose groups（<italic>P</italic><0.05， <italic>P</italic><0.01）， and the mRNA expression of CD147 was significantly reduced in the high dose group（<italic>P</italic><0.05）. Modified Si Junzitang showed no significant regulatory effect on MCT1. Conclusion:Modified Si Junzitang can significantly improve the abnormal histopathology of gastric mucosal epithelium in GPL model rats. Its mechanism may be related to down-regulating the overexpression of MCT4 and CD147， inhibiting lactic acid outflow， and improving the acidic microenvironment of gastric mucosal epithelium.

Comparison of the prognosis of subgroup of renal cell carcinoma of different pathological types / 中华泌尿外科杂志

Objective:To study and compare the prognosis of different pathological subtypes of renal cell carcinoma (RCC).Methods:Clinicopathological and prognostic data of 1 346 cases of postoperative renal cell carcinoma during July 2002 to June 2014 in West China Hospital were collected retrospectively.There were 839 males and 507 females, aged (55.1±13.4)years, including 1 120 cases of clear cell RCC, 62 cases of papillary RCC, 79 cases of chromophobe RCC and 85 cases of the other pathological types respectively. ECOG 0 and ≥1 were 911 and 435 cases, with; T 1, T 2, T 3 and T 4 of 1 019, 177, 102 and 48 cases respectively; WHO nuclear grade for well, intermediate, poor differentiation and unknown were 587, 530, 85 and 144 cases separately.Tumor size <5cm, 5-10cm, ≥10cm and unknown were 685, 541, 104 and 16 cases.Combined with necrosis or sacromatoid differentiation were 200/1 146 and 27/1 319 cases separately. Meanwhile, data of 80 439 cases from Surveillance, Epidemiology, and End Results Program (SEER) were also collected.There were 51 371 males and 29 068 females, aged (60.9±12.4) years; , with 66 261, 8 680, 5 022 and 476 cases of White, Black, Asian, American native, or unknown race separately. There were 62 600 of clear cell RCC, 12 170 of papillary RCC, 4 354 of chromophobe RCC and 1 315 of other pathological types, with T 1, T 2, T 3 and T 4 of 55 332, 8 687, 15 516 and 904 cases respectively; WHO nuclear grade for well, intermediate and poor differentiation were 52 323, 22 700 and 5 416 cases separately.Tumor size <5cm, 5-10cm, ≥10cm were 46 741, 25 760 and 7 938 cases respectively. Kaplan-Meier survival analysis were performed on these two group of cases, with different factors between subgroups (gender, age, pathological types, tumor stage, size and nuclear grade) evaluated by log-rank test. To evaluate accuracy of outcome prediction models of SSIGN, Leibovich and UISS score, concordance index of these models were evaluated. Results:In 1 346 cases of our cohort, those with chromophobe RCC were well prognostic, survival were relatively better in clear cell RCC than that of papillary RCC, and worst prognosis were demonstrated in those with other types of RCC (5 year overall survival rate: 97.5%, 87.9%, 79.7% and 68.4% separately). Poor prognosis were seen in those older than 50 years, with poor T stage or nuclear grade, large tumor size and tumors with necrosis or sacromatoid differentiation ( P<0.05). In 80 439 seer cases, the best prognosis was also seen in chromophobe RCC and the worst in other type of RCC separately (5 year overall survival rate: 96.3% and 85.3%). In addition, longer survival was seen in papillary RCC than clear cell RCC (5 year overall survival rate: 92.5% and 88.9%). However, similar results with our cohort were seen in Asian and American native subgroup of SEER cases (95.1%, 88.6%, 86.7%, 80.2% for chromophobe, clear cell, papillary and other types of RCC respectively). Poor prognosis were seen in those older than 50 years, males, Asian/ American Indian, poor T stage or nuclear grade and large tumor size ( P<0.05). Concordance index for SSIGN, Leibovich and UISS models in our cohort were 0.763-0.781, 0.725-0.752 and 0.641-0.660, respectively. The chromophobe RCC subgroup was relative better based on predictive value of prognosis models(c-index of UISS of 0.670-0.781, SSIGN and Leibovich of 0.733-0.903). Conclusions:In Asian RCC population, prognosis of chromophobe RCC is best, clear cell RCC is slightly better than papillary RCC, and the prognosis of other types of RCC is the worst. Concordance index of SSIGN and Leibovich in our cohort were higher than that of UISS, and the use value for predictive model was better in the chromophobe RCC subgroup.

Study on the effect of changing operator on the detection rate of colorectal polyps during surgery / 中国医师进修杂志

Objective:To study the effect of changing operator on the detection rate of colorectal polyps during surgery in patients who had been diagnosed with colorectal polyps by electronic colonoscopy for the first time.Methods:From June 2016 to June 2019, the patients who had been diagnosed with colorectal polyps by electronic colonoscopy for the first time, they were performed by electronic colonoscopy for the second time after 3 months by 5 doctors in the No.946 Hospital of PLA who had engaged in endoscopic work longer and been with rich experience. The results of the electronic colonoscopy were recorded and compared.Results:Fived hundred and seventy-six patients were found have colorectal polyps through electronic colonoscopy for the first time. Among them, 423 patients came to the hospital within 3 months and were eligibled for the research. The detection rate of newly detected polyps by the same operator was 22.7%(96/423), after changing the operator, the detection rate became 24.3% (103/423), but there was no significant difference ( P>0.05). The detection rates of newly detected polyps were respectively 20.8% (220/1 059) and 25.9%(294/1 133), the proportion of newly detected polyps with diameter ≤ 5 mm was respectively 73.6%(162/220) and 82.0%(241/294), the ratio of flat polyps to total newly detected polyps was 71.8%(158/220) and 79.9%(235/294), and there were significant differences ( P<0.05). The proportion of polyps in sigmoid colon was respectively 35.0% (77/220) and 39.1%(115/294), and there was no significant difference ( P>0.05). Conclusions:For patients with colorectal polyps detected by electronic colonoscopy, the operator should be changed during surgery, so that more missed polyps can be detected during surgery, especially flat polyps with diameter ≤ 5 mm. The operator should be changed to improve the detection rate and reduce the probability of missed diagnosis.

Activated PKB/GSK-3β synergizes with PKC-δ signaling in attenuating myocardial ischemia/reperfusion injury via potentiation of NRF2 activity: Therapeutic efficacy of dihydrotanshinone-I

@#Disrupted redox status primarily contributes to myocardial ischemia/reperfusion injury (MIRI). NRF2, the endogenous antioxidant regulator, might provide therapeutic benefits. Dihydrotanshinone-I (DT) is an active component in Salvia miltiorrhiza with NRF2 induction potency. This study seeks to validate functional links between NRF2 and cardioprotection of DT and to investigate the molecular mechanism particularly emphasizing on NRF2 cytoplasmic/nuclear translocation. DT potently induced NRF2 nuclear accumulation, ameliorating post-reperfusion injuries via redox alterations. Abrogated cardioprotection in NRF2-deficient mice and cardiomyocytes strongly supports NRF2-dependent cardioprotection of DT. Mechanistically, DT phosphorylated NRF2 at Ser40, rendering its nuclear-import by dissociating from KEAP1 and inhibiting degradation. Importantly, we identified PKC-δ-(Thr505) phosphorylation as primary upstream event triggering NRF2-(Ser40) phosphorylation. Knockdown of PKC-δ dramatically retained NRF2 in cytoplasm, convincing its pivotal role in mediating NRF2 nuclear-import. NRF2 activity was further enhanced by activated PKB/GSK-3β signaling via nuclear-export signal blockage independent of PKC-δ activation. By demonstrating independent modulation of PKC-δ and PKB/GSK-3β/Fyn signaling, we highlight the ability of DT to exploit both nuclear import and export regulation of NRF2 in treating reperfusion injury harboring redox homeostasis alterations. Coactivation of PKC and PKB phenocopied cardioprotection of DT in vitro and in vivo, further supporting the potential applicability of this rationale. Graphical abstract

Progress of Liquid Biopsy in the Diagnosis and Treatment of Lung Cancer with Malignant Pleural Effusion / 中国肺癌杂志

Lung cancer is the malignancy with the highest mortality rate worldwide. Malignant pleural effusion (MPE) caused by advanced lung cancer severely affects the quality of life and prognosis of patients. Tumor-associated genetic testing is the basis for making precise treatment decisions. There are some risks of tissue biopsy, and it is difficult to sample repeatedly. Due to its non-invasive and can reflect the full profile of tumor gene characteristics, liquid biopsy is increasingly used in the diagnosis and treatment of lung cancer. Because of the extremely low DNA level of circulating tumor, the sensitivity and specificity of liquid biopsy based on blood samples are limited. Tumor cells is enriched in MPE. The detection of cell-free DNA, extracellular vesicles and microRNA in MPE will be helpful to the diagnose, treatment and assess prognosis of patients with lung cancer. This review aims to discuss the research progress of liquid biopsy based on MPE in the diagnosis and treatment of lung cancer patients.
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Exploring Mechanism of Modified Fuzi Lizhongtang in Intervening Inflammatory Response of Intestinal Mucosa in Rats with Ulcerative Colitis Based on mTOR/p-S6K1 / 中国实验方剂学杂志

Objectives:To investigate the therapeutic effect and mechanism of modified Fuzi Lizhongtang on ulcerative colitis （UC） model rats. Method:The 72 male SD rats were randomly divided into normal group，model group，sulfasalazine group（0.5 g·kg-1），modified Fuzi Lizhongtang high，medium and low-dose group （23.62，11.81，5.91 g·kg-1）. These rats were used to replicate the UC rat model by 2，4，6-trinitrobenzene sulfonic acid （TNBS）-ethanol composite modeling and treated by gavage for 2 weeks. The general condition of rats in each group was observed. After anesthesia，blood was collected from abdominal aorta and colonic tissue was taken. Semi quantitative evaluation by the colon mucosa damage index （CMDI），the pathological changes of colonic tissue were observed by the hematoxylin and eosin （HE） staining. The contents of serum interleukin-4 （IL-4），IL-6，IL-10 and tumor necrosis factor-α （TNF-α） were detected by enzyme-linked immunosorbent assay （ELISA）. The expressions of mammalian target of rapamycin（mTOR） and phosphorylated ribosomal protein S6 kinase 1 （p-S6K1） in colonic mucosa were detected by immunohistochemistry （IHC） and Western blot. Result:Compared with normal group，the CMDI score of the model group rats was significantly increased （P<0.01）. The contents of IL-4 and IL-10 in serum were significantly decreased，the contents of IL-6 and TNF-α were significantly increased （P<0.01）. The expression levels of mTOR and p-S6K1 in colonic mucosa were up-regulated （P<0.01）. Compared with model group，the CMDI score of the modified Fuzi Lizhongtang high dose group was significantly decreased （P<0.05）. In modified Fuzi Lizhongtang high and medium dose group，the contents of IL-6 and TNF-α were significantly decreased （P<0.01） and the contents of IL-4 and IL-10 in serum were significantly increased （P<0.05，P<0.01）. In the modified Fuzi Lizhongtang high dose group，the expression level of mTOR and p-S6K1 protein was down-regulated significantly （P<0.05，P<0.01）. Conclusion:Modified Fuzi Lizhongtang high dose group can significantly reduce the congestion and edema，inflammatory cell infiltration，gland distortion，disorder of arrangement and other pathological manifestations of UC colon mucosa，and its mechanism may be related to its down-regulation of mTOR/p-S6K1 signal and the regulation of inflammatory factors secretion.

Effect of Danggui Yinzi on Relieving Allergic Reaction in CU Model Mice by Autophagy Pathway / 中国实验方剂学杂志

Objective:To investigate the effect of Danggui Yinzi on allergic reaction in chronic urticaria (CU) mice model and the mechanism of autophagy intervention. Method:The SPF BALB/c mice were used to replicate the CU mice model by intraperitoneal injection of ovalbumin and aluminum hydroxide suspension. The animals were randomly allocated into six groups: a normal group (normal saline 20 mL·kg-1·d-1), a model group (normal saline 20 mL·kg-1·d-1), a loratadine group(0.001 3 g·kg-1·d-1), a Danggui Yinzi high，medium and low-dose group（39.3，19.6，9.8 g·kg-1·d-1）. The pathological changes of skin tissues were observed by hematoxylin-eosin (HE) staining. Morphological changes of autophagy in skin tissues epithelial cells were observed by transmission electron microscope. The mRNA levels of microtubule-associated protein 1 light chain 3B(LC3B) and ubiquitin-binding protein p62 mRNA in skin tissues were detected by real-time quantitative polymerase chain reaction (Real-time PCR). The expressions of LC3B and p62 in skin tissues were detected by immunohistochemistry (IHC). Result:Danggui Yinzi can significantly improve the pathological manifestations of dermal edema, collagen bundles separation, telangiectasia in CU mice， it can also improve autophagosomes formation and abnormal cell ultrastructure such as nuclear chromatin condensation, mitochondrial swelling, endoplasmic reticulum expansion, etc. Compared with the normal group, the protein expressions of LC3B in skin tissues of the model group was significantly increased (P<0.01), LC3B mRNA level was increased too, while p62 mRNA levels and its protein expressions were decreased-regulated (P<0.01). Compared with the model group, levels of LC3B mRNA and protein expressions of the Danggui Yinzi groups were significantly increased (P<0.05,P<0.01), while p62 mRNA levels and its protein expressions were significantly decreased-regulated (P<0.05,P<0.01). Conclusion:Danggui Yinzi can regulate the expression of LC3B, p62 mRNA and protein expressions, enhance the level of autophagy, and improve the pathological state of CU mice.

Reasons and endoscopic management for proximally migrated pancreatic stents / 中华消化内镜杂志

Objective:To explore the reasons of the proximal migration of pancreatic stents and the endoscopic management.Methods:From April 2007 to January 2015, of all 967 patients with biliopancreatic diseases implanted with pancreatic duct plastic stents at the First Affiliated Hospital of Nanchang University, proximal migration occurred in 10 cases. Migrated rates and endoscopic retrieval methods of pancreatic straight stents and single pigtail stents were compared.Results:Pancreatic straight stents showed a higher migration rate than those single pigtail ones [3.23% (7/217) VS 0.40% (3/750)]. For 3 migrated single pigtail pancreatic stents: 2 were directly removed with biopsy forceps. Another failed in retrieval, and the same stent then was implanted. There was no discomfort after the operation. For 7 migrated pancreatic straight stents: 2 were pulled out of duodenum papilla incision under wire-guided balloon and basket. Five others were pulled out of papilla under wire-guided balloon, and then the stents were removed by a snare.Conclusion:Pancreatic straight stents are more likely to migrate compared with single pigtail stents. Migrated pancreatic straight stents can be removed with wire-guided balloon or basket and snare, while migrated single pigtail stents can be directly retrieved with biopsy forceps.

The update interpretation of 2020 EAU prostate cancer guideline (Part Ⅲ) / 中华泌尿外科杂志

The Chapter "Radical prostatectomy" has been completely update in the 2020 EAU prostate cancer guideline. Recommendation level of "No surgical approach has shown superiority in terms of functional or oncological results" and "Nerve-sparing surgery is not recommended when there is a risk of ipsilateral extracapsular extension" has been adjusted to "weak" . Various surgical techniques could further improve functional outcomes when performed appropriately based on the updated guideline.

The impact of different metastatic sites on the prognosis of mRCC patients and its value for modification of International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model / 中华泌尿外科杂志

Objective:To evaluate the impact of metastatic site on the prognosis in patients with metastatic renal cell carcinoma (mRCC), and it′s value for modifying the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria.Methods:The data of 218 patients pathologically diagnosed with mRCC were analyzed retrospectively in West China Hospital from Jan. 2009 to Dec. 2019. Among all patients, 71.6%(156/218) were male, and 89.0% (194/218) underwent nephrectomy. Most of the patients were pathologically diagnosed with renal clear cell carcinoma (176 patients, 80.7%). Lung (137/218, 62.8%) was the most observed metastatic site, following by bone (47/218, 26.1%), lymph node (37/218, 17.0%) and liver (23/218, 10.6%). All patients were classified into favorable (26 patients, 11.9%), intermediate (126 patients, 57.8%) or poor (37 patients, 17.0%) risk group according to IMDC criteria. Endpoints of this study were progression-free survival (PFS), overall survival (OS) and tumor response. The impact of metastatic sites on patients’ prognosis was analyzed, and those that had significant relationship with prognosis were then added into IMDC criteria and a modifying IMDC model was established. Predictive value of this model was further evaluated by calculating concordance index (C-index).Results:In the whole cohort, median PFS and OS were 13.0 and 33.0 months. Survival analysis suggested that patients with bone ( P=0.004), brain ( P=0.042) and liver ( P=0.046) had significantly shorter OS. Thus, patients were divided into two groups: patients with bone/brain/liver metastasis (82 patients, 37.6%) and patients with other metastatic sites (136 patients, 62.4%). Compared with patients with other metastatic sites, those who with bone/brain/liver metastasis had inferior tumor response by TKIs treatment (disease control rate: 51.2% vs. 73.5%, P=0.004). Multivariate analysis suggested that bone/brain/liver metastasis had negative impact on OS (25.0 vs. 47.0 mo, P=0.039). Furthermore, bone/brain/liver metastasis also showed significant relationship with shorter OS in IMDC low (30.0 vs. 62.0 months, P=0.036), intermediate (31.0 vs. 48.0 months, P=0.048) or high (7.0 vs. 18.0 months, P=0.037) risk group, indicating that metastatic site had predictive value for prognosis of mRCC patients. Based on that, bone/brain/liver metastasis were added into the IMDC criteria, and weighting each parameter was weighted according to its coefficient to patients’ OS. Finally, a modified IMDC scoring system were established. C-index of this modified model was 0.669 (0.599 for current IMDC criteria). Conclusions:Bone/brain/liver metastasis in mRCC patients indicated a shorter OS duration. When adding bone/brain/liver metastasis as a predictive parameter for prognosis of mRCC patients into IMDC criteria, the modified IMDC criteria could offer more accurate prediction for patients’ survival.

Recent progress of virtual reality simulation in endoscopy training / 中华医学教育探索杂志

There are two methods of endoscopic teaching including traditional apprenticeship mode and simulation training. Although the apprenticeship model has some advantages in the docking of experience, there are many shortcomings. Virtual reality simulation training is learner-centered in endoscopic teaching, which is a safe and effective training method and an important supplement to the apprenticeship model. In the process of simulation training, paying attention to feedback, obtaining non-technical ability, dealing with emergencies in endoscopic operation and optimizing ergonomics are the directions of future research. This paper will briefly summarize the research progress of virtual reality simulation training in endoscope teaching.

Mechanism of Yupingfeng Granule on CU Rats Based on IL-23/IL-17 Inflammation Axis / 中国实验方剂学杂志

Objective::To study the effect of Yupingfeng granule on the degranulation of skin mast cells in chronic urticaria (CU) rats and the intervention mechanism of interleukin-23(IL-23), interleukin-17(IL-17) inflammation axis. Method::Totally 60 SPF SD rats were selected and randomly divided into normal group (normal saline), model group (normal saline), and loratadine group (0.9 mg·kg-1·d-1), high-dose Yupingfeng granules group (4.05 g·kg-1·d-1), middle-dose group (2.7 g·kg-1·d-1), low-dose group (1.35 g·kg-1·d-1). The CU rat model was reproduced through intraperitoneal injection of ovalbumin with aluminum hydroxide suspension and DTP vaccine. Histopathological changes of rat skin were observed by hematoxylin-eosin (HE) staining. Degranulation of mast cells in rat skin was determined by toluidine blue staining. IL-23 and IL-17 protein expressions in skin tissue were determined by immunohistochemistry (IHC). IL-23 and IL-17 mRNA transcription levels in skin tissue were determined by real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). Result::Yupingfeng granules can significantly alleviate the pathological manifestations of dermal edema, collagen beam distance, inflammatory cell infiltration of CU rats, and reduce the degranulation reaction of skin tissue mast cells in CU rats. The IL-23, IL-17 mRNA and protein expressions of the skin of model group were significantly increased compared with the normal group (P<0.05, P<0.01). Compared with the model group, Yupingfeng granules can significantly down-regulate IL-23 mRNA and protein expressions of CU rats (P<0.05, P<0.01). Yupingfeng granules had no significant regulatory effect on IL-17. Conclusion::Yupingfeng granule can significantly reduce the degranulation of mast cells in skin tissue of CU rats, and improve the pathological manifestations, such as dermal edema, serous exudation and inflammatory cell infiltration. The mechanism may be related to inhibiting the secretion of IL-23 pro-inflammatory cytokines and improving CU lesions.

The subgroup analysis of the prognostic value of the intraductal carcinoma of the prostate in patients with metastatic prostate cancer / 中华外科杂志

Objective@#To determine the prognostic value of the intraductal carcinoma of the prostate IDC-P in metastatic prostate cancer (mPCa) patients of different subgroups.@*Methods@#Data of 582 de novo mPCa patients between January 2011 and December 2017 diagnosed at Departments of Urology, West China Hospital, Sichuan University were retrospectively analyzed. The age was (70±8) years (range: 45 to 89 years). IDC-P was identified from 12-core prostate biopsy. The prognostic role of IDC-P was assessed by Kaplan-Meier curves and Cox regression. Subgroup analysis was conducted by the forest plot. The endpoints were castration-resistant prostate cancer free survival (CFS) and overall survival (OS).@*Results@#In total, 177/582 (30.4%) patients harbored IDC-P. Patients with IDC-P had poorer CFS and OS than those without IDC-P (mCFS: 12.1 months vs. 16.9 months, P=0.000; mOS: 39.7 months vs. not reached, P=0.000). Multivariate Cox regression analysis indicated that, the existence of IDC-P was an independent prognosticator of both CFS (HR=1.40, 95% CI: 1.10 to 1.79, P=0.006) and OS (HR=1.51, 95% CI: 1.02 to 2.25, P=0.041). Subanalysis indicated that, in most subgroups, IDC-P was an adverse prognosticator of both CFS and OS. Even in subgroups with adverse clinicopathological features, e.g. Gleason score 9 to 10 (CFS: HR=1.467, P=0.007; OS: HR=1.807, P=0.013), baseline prostate specific antigen≥50 μg/L (CFS: HR=1.616, P=0.000; OS: HR=1.749, P=0.006), anemia (CFS: HR=1.653, P=0.036; OS: HR=2.100, P=0.038), alkaline phosphatase≥160 U/L (CFS: HR=1.326, P=0.038; OS: HR=1.725, P=0.010) or abnormal lactate dehydrogenase level (CFS: HR=1.614, P=0.001; OS: HR=1.900, P=0.003), IDC-P was still closely associated with shorter CFS and OS.@*Conclusions@#The presence of IDC-P was closely related to poor survival outcomes for patients with mPCa. IDC-P was an adverse prognosticator in most subgroup patients. The description of IDC-P in the pathological report of prostate biopsy would help clinicians to evaluate the prognosis of mPCa patients more accurately and make better treatment choices.

Clinical analysis of retroperitoneal and transperitoneal laparoscopic radical nephroure-terectomy for upper urinary tract urothelial carcinoma / 中国肿瘤临床

Objective: To evaluate the clinical effects of retroperitoneal and transperitoneal laparoscopic radical nephroureterectomy for upper urinary tract urothelial carcinoma. Methods: We trospectively analyzed the clinical data of 85 patients with upper urinary tract urothelial carcinoma (UTUC) who underwent laparoscopic radical nephroureterectomy in West China Hospital, Sichuan Universi-ty, from January 2012 to December 2016. Forty-nine patients (Group A) underwent retroperitoneal laparoscopic radical nephroureter-ectomy while 36 (Group B) underwent transperitoneal laparoscopic radical nephroureterectomy. Operative time, blood loss volume, time of incision drainage, catheterization time, recovery time of postoperative intestinal function, postoperative hospitalization time, operative complications, postoperative local recurrence, and distant metastasis were compared between the two groups. Results: All operations were successfully performed. Mean operative time was (126.9 ± 11.6) min in Group A, while it was (109.9 ± 14.7) min in Group B; thus, mean operative time was significantly shorter in Group B than in Group A (P<0.05). Mean blood loss volume was (108.5±24.1) mL in Group A, while it was (95.1±19.9) mL in Group B; thus, mean blood loss volume was significantly lower in Group B than in Group A (P<0.05). Mean recovery time of postoperative intestinal function was (1.8±0.5) days in Group A, while it was (2.3± 0.4) days in Group B; thus, mean recovery time of postoperative intestinal function was significantly longer in Group B than in Group A (P<0.05). The other evaluated indicators did not differ significantly between the two groups. Conclusions: Both retroperitoneal and transperitoneal laparoscopic radical nephroureterectomy are safe and effective as minimally invasive treatment for upper UTUC.