[Clinical outcomes of simultaneous bilateral endoscopic surgery for bilateral upper urinary tract calculi].

OBJECTIVE: To discuss the efficacy and safety of simultaneous bilateral endoscopic surgery (SBES) for bilateral upper urinary tract calculi, and to summarize the initial experience. METHODS: Patients diagnosed with bilateral upper urinary tract calculi who underwent SBES in the Department of Urology, Beijing Chao-Yang Hospital from January 2019 to January 2020 were enrolled retrospectively. The demographic and clinical data of the patients were recorded, and the operation status, stone free rate (SFR) and peri-operative complications were analyzed. The primary end point was SFR, and second end point was peri-operative complications. RESULTS: A total of 23 patients underwent SBES, of which SBES was completed in 19 patients (12 males, and 7 females). The mean age was (41.3±12.0) years. Fourteen patients underwent modified supine position surgery and 4 patients in prone split-leg position. There was no statistical difference in the demographic and baseline clinical data of the patients in different positions. One patient underwent right percutaneous nephrolithotomy (PCNL) and left endoscopic combined intra-renal surgery (ECIRS) in the prone split-leg position, while 18 patients received simul-taneous surgery with PCNL and contralateral retrograde intra-renal surgery (RIRS). The mean anesthesia and operation time was (128.7±26.5) min and (70.7±20.3) min, respectively, which was significantly longer in the patients with prone split-leg position than in the patients with modified supine position, anesthesia time in the patients with prone split-leg position and modified supine position: (148.4±20.4) min vs. (121.6±25.3) min, respectively, t=－2.121, P=0.049, while the operation time in the patients with prone split-leg position and modified supine position: (86.4±21.1) min vs. (65.1±17.4) min, respectively, t=－2.222, P=0.040. There was no significant difference between the two groups in indwelling of nephrostomy [prone split-leg position and modified supine position: (2.6±0.9) d vs. (2.1±1.0) d, respectively; t=－0.880, P=0.391] and the length of hospital stay [prone split-leg position and modified supine position: (6.0±2.7) d vs. (5.2±1.8) d, respectively; t=－0.731, P=0.475]. One month after the operation, the SFR was 78.9%, and 3 patients had minor peri-operative complications (Clavien-Dindo grades Ⅰ/Ⅱ) without any serious complications (Clavien-Dindo grades Ⅲ/Ⅳ/Ⅴ). CONCLUSION: The simultaneous bilateral endoscopic surgery would decrease the operation time and anesthesia exposure under the premise of ensuring the SFR, which is helpful to reduce the risk of peri-operative complications, especially to the patients who can not tolerate the second-stage or long-time operation.

[Endoscopic combined ultrasound-guided access vs. ultrasound-guided access in endoscopic combined intrarenal surgery].

OBJECTIVE: To compare the outcomes of endoscopic combined ultrasound-guided access (EUGA) with the conventional ultrasound-guided access (UGA) to achieve percutaneous renal access in endoscopic combined intrarenal surgery (ECIRS). METHODS: A retrospective review of 53 patients undergoing ECIRS to treat upper urinary tract calculi between January 2017 and October 2019 was con-ducted. All of the cases were of complex upper urinary tract stones larger than 2 cm in diameter. The com-plex stone situations, such as multiple renal calyces calculi or staghorn calculi necessitated ECIRS. Under general anesthesia, the patients were placed in the galdakao-modified supine valdivia (GMSV) position, thus allowing both antegrade and retrograde accesss. The patients were divided to UGA and EUGA groups according to the protocol of achieving percutaneous renal access. In 28 cases, endoscopic combined ultrasound-guided accesss were obtained. Puncture and dilation were performed under direct flexible ureteroscopic visualization, while percutaneous renal access of 25 cases were performed with the conventional technique employing ultrasound guidance. Demographic and perioperative information, such as stone burden, presence of hydronephrosis and number of calyces involved was compared. Primary outcomes included total operative time, renal access time, repeat puncture, hemoglobin level, perioperative complications, and stone-free rate. RESULTS: No major intra-operative complication was recorded in all the 53 ECRIS. No significant difference was observed between the groups in age and gender. There was no significant difference in body mass index[BMI (29.21±3.14) kg/m2 vs.(28.53±2.56) kg/m2], stone burden (37.68±6.89) mm vs. (35.53±6.52) mm, number of calyces involved 2.72±0.68 vs. 2.86±0.71, presence of hydronephrosis (56.0% vs. 46.4%), total operative time (93.0±12.2) min vs. (96.8±14.2) min, hemoglobin level reduction (6.56±2.16) g/L vs. 97.54±2.64) g/L, stone-free rate (92.0% vs. 92.8%), hospital stay (5.52±0.59) d vs. (5.64±0.62) d, perioperative complication rate (8.0% vs. 7.2%). Two patients in EUGA group experienced perioperative complications (one urinary tract infection and one hematuria) while two patients in UGA group experienced perioperative urinary tract infection. None in both groups received blood transfusion. The patients undergoing EUGA had shorter renal access time [(4.0±0.7) min vs. (6.8±2.6) min, P < 0.01] and less repeat puncture (0 vs. 4 cases, P < 0.05). CONCLUSION: EUGA is an optimal technique to establish percutaneous renal access in ECIRS, which minimizes access time and repeated procedures.

[Oncologic outcomes of high-risk upper tract urothelial carcinoma patients undergoing radical nephroureterectomy combined with adjuvant chemotherapy].

Objective: To assess the oncologic outcomes of radical nephroureterectomy (RUN) combined with adjuvant chemotherapy (ACT) in patients with high risk upper tract urothelial carcinoma (UTUC). Methods: One-hundred-thirty-four individuals with high-risk UTUC who underwent RUN with or without ACT were evaluated. Cox proportional hazard model and Kaplan-Meier analysis were used to determine overall and cancer specific survival in the cohort. Results: The median follow-up duration was 24 months (range: 6-36) in the RUN group (n=61) and 18 months (range: 6-36) in the RUN+ACT group (n=73). Median time of overall survival (OS) and cancer specific survival (CSS) showed much better in RUN+ACT group than in RUN group, but the differences were not reached the significant standard. The further analysis in lymph node positive cohort displayed that median times of oncologic events were prolonged in the RUN+ACT group compared with the RUN group: OS (30.1 mon vs 18.0 mon, P=0.083) and CSS (29.2 mon vs 18.6 mon, P=0.047). Additionally in T3/T4 cohort, the significant growth in the median times of OS (25.2 mon vs 12.6 mon, P=0.038) and CSS (31.3 mon vs 18.9 mon, P=0.044) were observed in combination treatment group. Conclusion: ACT could play the important synergistic role in improving the OS and CSS of RUN treated UTUC patients with lymph node-positive or stage of T3/T4.

[Derepression of CXCR7 indicates resistance to enzalutamide in castration resistant prostate cancer].

Objective: To investigate the effect of the derepression of chemokine receptor-7 (CXCR7) in prostatic tissues from patients with Castration Resistant Prostate Cancer (CRPC) on the resistance to enzalutamide (Enza). Methods: During the period of January 2015 to December 2017 all CRPC cases who underwent radical radiotherapy or androgen deprivation therapy (ADT) were evaluated. After prostatic puncture biopsy, the tissues were treated for immunostaining with CXCR7. Cox proportional hazard modeling and Kaplan-Meier analysis were used to determine PSA Progression-Free Survival (PSAP-FS) and Clinical or Radiographic Progression-Free Survival (CRP-FS) in the cohort. At last, PSA response rates and progression outcomes in CXCR7 negative cases and CXCR7 positive cases were analyzed. Results: Total 39 CRPC patients were enrolled in this study. And 23 cases derepress CXCR7, 16 cases negatively express CXCR7. The median follow-up duration was 12 months (range: 6-18) in the cohort. Chi-square analysis confirmed that PSA response rates after Enza treatment were significantly associated with CXCR7 derepression (χ(2)=22.129, P=0.000 06). Compared with CXCR7 positive expression group, CXCR7 negative expression group displayed improved median PSAP-FS (4.4 mon vs 11.7 mon, P=0.040 8) and CRP-FS (5.2 mon vs 13.1 mon, P=0.036 2) after Enza treatment. Conclusion: Derepression of CXCR7 in CRPC patients may be associated with resistance to enzalutamide. This protein may be novel target for treatment of CRPC.

[Prospective controlled observation ofeffect of adjuvant chemotherapy onsurvival and prognosis ofhigh-risk upper tract urothelial carcinoma patients underwent radical nephroureterectomy].

Objective: To assess the oncologic outcomes of radical nephroureterectomy (RNU) combined with adjuvant chemotherapy (ACT) in patients with high risk upper tract urothelial carcinoma (UTUC). Methods: From January 2014, all high-risk UTUC patients after RNU surgery were enrolled in this prospective comparative trial. And these patients were randomized to ACT group (Gemcitabine+Cisplatin three weeks regimen) and observing group. Cox proportional hazard modeling and Kaplan-Meier analysis were used to determine overall survival (OS), cancer specific survival (CSS) and disease-free survival (PFS) in the cohort. Results: The median follow-up duration was36 months (range: 6-54) in the ACT group (n=94) and 30 months (range: 6-54) in the observing group (n=82). Oncologic outcomes of RNU treated high-risk UTUC patients were improved much significantly by ACT: OS [P=0.0397, HR: 1.39(0.91-1.75)], CSS [P=0.0255, HR: 1.26(1.07-1.45)] and PFS [P=0.0033, HR: 3.78(3.13-4.55)]. The further analysis in lymph node positive cohort displayed that median times of oncologic events were prolonged in the ACT group compared with the observing group: OS (26.8mon vs 36.3mon, P=0.0255), CSS (28.2mon vs39.3mon, P=0.0197) and PFS (11.4mon vs 31.9mon, P=0.0018). Additionally in T3/4 cohort, the significant growth in the median times of OS (20.6mon vs 32.2mon, P=0.0183), CSS (21.9mon vs 38.4mon, P=0.0226) and PFS (13.9mon vs 36.3mon, P=0.0217) were observed in ACT group. Conclusion: ACT could play the important synergistic role in improving the OS, CSS and PFS of high-risk UTUC patients after RNU.

[Environmental chemicals exposure and abnormal expression of non-coding RNAs].

Environmental chemicals exposure is closely related to occurrence and development of diseases. The abnormal expression of non-coding RNAs is a key factor in biological effects of environmental chemicals. Non-coding RNAs play an important role in the normal function of cells and the occurrence and development of diseases. In addition, non-coding RNAs, as a biomarker, could be widely used in the diagnosis, prevention and treatment of diseases. This paper outlines the relationship between environmental chemical exposure and non-coding RNAs and the function and mechanism of non-coding RNAs. It also presents existing issues and future research directions.

[Activation of HIF-1α/ß-catenin signal pathway leads to radioresistance of prostate cancer cells].

Objective: To investigate the role of hypoxia-inducible factor-1α (HIF-1α) and ß-catenin in radioresistance of prostate cancer (PCa) cells. Method: Two PCa cell lines, LNCaP and C4-2B, were grouped as: negative control (no treatment), HIF-1α overexpression group (transfected with HIF-1α plasmids), and ß-catenin silencing group (transfected with HIF-1α plasmids and ß-catenin-shRNA). Cell proliferation, cycle, invasion, and radiosensitivity were measured under normal or hypoxic condition. Radiosensitivity was tested in two mice PCa models (the LNCaP orthotopic BALB/c-nu mice model and the C4-2B subcutaneous SCID mice model). Results: In both LNCaP and C4-2B cells, HIF-1α transfection led to an enhanced ß-catenin nuclear translocation, while ß-catenin silencing inhibited the ß-catenin nuclear translocation. Enhanced ß-catenin nuclear translocation caused by HIF-1α overexpression resulted in enhanced cell proliferation and invasion, altered cell cycle distribution, reduced apoptosis, and improved non-homologous-end-joining (NHEJ) repair under irradiation condition. In vivo imaging of orthotopic models showed that HIF-1α overexpression LNCaP cells produced tumors with 3-fold volume (P=0.003 1) and 2-fold wet weight (P=0.039 4) than those by negative control cells at day 21, and ß-catenin silencing cells aberrantly reduced both tumor volume (P=0.000 3) and wet weight (P=0.017 5) than HIF-1α overexpression cells. In addition, C4-2B subcutaneous models showed similar tumor promotion effects induced by HIF-1α overexpression (tumor volume: P=0.000 1 and wet weight: P=0.047 3) and suppressive effects by ß-catenin silencing (tumor volume: P<0.000 1 and wet weight: P=0.022 1) as LNCaP orthotopic xenograft with regard to tumor volume and wet weight. Conclusions: HIF-1α overexpression enhanced ß-catenin nuclear translocation, which led to the activation of the ß-catenin/NHEJ signaling pathway and increased cell proliferation, invasion, and DNA repair. These results suggest that HIF-1α overexpression led to radioresistance of PCa cells.

Prevalence of kidney stones and associated risk factors in the Shunyi District of Beijing, China.

INTRODUCTION: Kidney stone formation is a multifactorial condition that involves interaction of environmental and genetic factors. Presence of kidney stones is strongly related to other diseases, which may result in a heavy economic and social burden. Clinical data on the prevalence and influencing factors in kidney stone disease in the north of China are scarce. In this study, we explored the prevalence of kidney stone and potentially associated risk factors in the Shunyi District of Beijing, China. METHODS: A population-based cross-sectional study was conducted from December 2011 to November 2012 in a northern area of China. Participants were interviewed in randomly selected towns. Univariate analysis of continuous and categorical variables was first performed by calculation of Spearman's correlation coefficient and Pearson Chi squared value, respectively. Variables with statistical significance were further analysed by multivariate logistic regression to explore the potential influencing factors. RESULTS: A total of 3350 participants (1091 males and 2259 females) completed the survey and the response rate was 99.67%. Among the participants, 3.61% were diagnosed with kidney stone. Univariate analysis showed that significant differences were evident in 31 variables. Blood and urine tests were performed in 100 randomly selected patients with kidney stone and 100 healthy controls. Serum creatinine, calcium, and uric acid were significantly different between the patients with kidney stone and healthy controls. Multivariate logistic regression revealed that being male (odds ratio=102.681; 95% confidence interval, 1.062-9925.797), daily intake of white spirits (6.331; 1.204-33.282), and a history of urolithiasis (1797.775; 24.228-133 396.982) were factors potentially associated with kidney stone prevalence. CONCLUSIONS: Male gender, drinking white spirits, and a history of urolithiasis are potentially associated with kidney stone formation.

[Long-term oncologic outcomes of localized high-risk prostate cancer undergoing brachytherapy combined with external-beam radiation therapy and maximal androgen blockade].

Objective: To investigate the oncologic outcome and PSA kinetics of localized high-risk prostate cancer (PCa) patients treated with combination strategy of radiation therapy (RT) and maximal androgen blockade (MAB). Methods: We retrospectively reviewed the clinical data of 320 localized PCa patients undergoing RT+ MAB from 2001 to 2015. And radiation treatment protocol consisted of permanent prostate brachytherapy (PPB) at 110 Gy and EBRT at 45 Gy/23 fractions. Results: The median follow-up time was 90 (range: 12-186) months. And 117 (36.6%) cases underwent MAB + external-beam radiotherapy (EBRT), and other 203 (63.4%) cases received MAB+ EBRT+ PPB. Multivariate Cox regression analyses showed that PSA kinetics were positive indicators of oncologic outcomes. Furthermore, PSA kinetics were aberrantly improved by supplemental PPB to MAB+ EBRT as following, PSA nadir (1.3±0.7)µg/L vs(0.11±0.06)µg/L, time of PSA decrease to nadir (7.5±1.8)months vs (3.2±2.1)months, PSA doubling time (15.6±4.2)months vs (22.6±6.1)months, PSA decreasing amplitude (84.6±6.2)%vs(95.8±3.4)%. Additionally, the median time of several important oncologic events in MAB+ EBRT+ PPB group were also prolonged than that in MAB+ EBRT group as following, overall survival (12.3 years vs 9.1 years, P<0.001), biochemical recurrence-free survival (9.8 years vs 6.5 years, P<0.001), skeletal-related event (10.4years vs 8.2 years, P<0.001), and cytotoxic chemotherapy (11.6 years vs 8.8 years, P=0.007). Conclusion: MAB+ EBRT+ PPB is extremely effective combination strategy for localized high-risk PCa patients, and PPB plays the important synergistic role in improving PSA kinetics, which are independent predictor for oncologic outcomes.

Recovery of gastrointestinal function with thoracic epidural vs. systemic analgesia following gastrointestinal surgery.

The objective of this review was to systematically assess the effect of thoracic epidural analgesia (TEA) vs. systemic analgesia (SA) on the recovery of gastrointestinal (GI) function in patients following GI surgery. We performed a comprehensive literature search to identify randomized controlled trials of adult patients undergoing GI surgery, comparing the effect of two postoperative analgesia regimens. Patients postoperatively receiving local anesthesia-based TEA with or without opioids were compared to patients receiving opioid-based SA. The outcomes considered were times to GI function recovery, GI complications, and specific side effects. Twelve studies with 331 patients in the TEA group and 319 in the SA group were included. Compared to SA, TEA improved the GI recovery after GI procedures by shortening the time to first passage of flatus by 31.3 h, 95% confidence intervals (CIs): -33.2 to -29.4, P < 0.01; and shortening the time to first passage of stool by 24.1 h, 95% CIs: -27.2 to -20.9, P < 0.001. There was no difference between the groups in the incidence of anastomotic leakage and ileus. The occurrence of postoperative hypotension was relatively higher in the TEA group, risk ratio: 7.9, 95% CIs: 2.4 to 26.5, P = 0.001; other side effects (such as pruritus and vomiting) were similar in the two groups. There is evidence that TEA (compared to SA) improves the recovery of GI function after GI procedures without any increased risk of GI complications. To further confirm these effects, larger, better quality randomized controlled trials with standard outcome measurements are needed.

Expression of breast cancer anti-estrogen resistance 1 in relation to vascular endothelial growth factor, p53, and prognosis in esophageal squamous cell cancer.

The purpose of this study was to clarify the role of breast cancer anti-estrogen resistance 1 (BCAR1) expression in relation to vascular endothelial growth factor (VEGF), p53, and proliferation in esophageal squamous cell cancer (ESCC). Expression of BCAR1, VEGF, p53, and the ki-67 proliferative index were examined by tissue microarray and immunohistochemistry in 106 specimens with ESCC and matched adjacent normal tissues. Among them, 40 cases were simultaneously examined by Western blot. Both Western blot and immunohistochemistry showed that BCAR1 expression was substantially higher in ESCC than in adjacent normal tissues (P < 0.001). BCAR1 expression was significantly connected with degree of tumor differentiation, with poorly differentiated tumors showing higher BCAR1 expression (P < 0.001). BCAR1 expression was significantly and positively correlated with VEGF and p53 expression levels (r= 0.541, P < 0.001; r= 0.374; P < 0.001) but not proliferative index (r= 0.44; P= 0.066). Additionally, a significant relationship was also observed between VEGF and p53 (r= 0.321; P= 0.001). Kaplan-Meier survival analysis revealed that patients with high BCAR1 expression had significantly shorter survival times than those with low BCAR1 expression levels (median survival 40 months vs. 27 months, P= 0.09). Multivariate analysis also revealed that levels of BCAR1 expression (hazard ratio 2.250, P= 0.015) was a significant and independent prognostic indicator. High expression of BCAR1 is associated with elevated VEGF and p53 expression levels, as well as poor prognosis in ESCC. Therefore, BCAR1 may be a potential candidate for predicting prognosis and a new therapy target for ESCC.

[Association between sedentary behavior and force expiratory volume in 1 second reduction in middle-aged and elderly adults in communities].

Objective: To analyze the relationship between sedentary behavior and the force expiratory volume in 1 second (FEV1) reduction in middle-aged and elderly people in communities. Methods: The participants aged ≥40 years were randomly selected from a natural population cohort in Songjiang District, Shanghai, for pulmonary function tests and survey by using international physical activity questionnaire, a generalized additive model was used to analyze the association between sedentary behavior and FEV1 reduction in the study population and different sex-age subgroups. Results: A total of 3 121 study subjects aged ≥40 years were included. The prevalence of FEV1 reduction was 14.8%, which was higher in men than in women. There were 24.8% participants were completely sedentary. The prevalence of FEV1 reduction in women aged <60 years in complete sedentary group was 2.04 (95%CI: 1.11-3.72) times higher than that in non-complete sedentary group. In men aged <60 years, the prevalence of FEV1 reduction increased with daily sedentary time (OR=1.16, 95%CI: 1.04-1.29), and the prevalence of FEV1 reduction was also higher in those with sedentary time >5 hours/day than those with sedentary time ≤5 hours/day (OR=3.02, 95%CI: 1.28-7.16). The sensitivity analysis also found such associations. Conclusions: FEV1 reduction rate in age group <60 years was associated with sedentary behavior. Complete sedentary behavior or absence of moderate to vigorous physical activity played important roles in FEV1 reduction in women, while men were more likely to be affected by increased sedentary time, which had no association with physical activity. Reducing sedentary time to avoid complete sedentary behavior, along with increased physical activity, should be encouraged in middle-aged and elderly adults in communities to improve their pulmonary function.

[Association between metabolism-related chronic disease combination and prevalence of non-alcoholic fatty liver disease in community residents in Shanghai].

Objective: To explore the combination of metabolism-related chronic diseases associated with the prevalence of non-alcoholic fatty liver disease (NAFLD) in community residents in Shanghai. Methods: The baseline data of Shanghai Suburban Adult Cohort and Biobank were used to understand the prevalence of five metabolism-related chronic diseases, including obesity, hypertension, hyperlipidemia, gout and diabetes, based on questionnaire survey, physical examination and blood biochemical detection. NAFLD was diagnosed by B-ultrasound detection and questionnaire. Multivariable logistic regression model was used to analyze the association of 31 metabolism-related chronic diseases combinations with the prevalence of NAFLD. Results: The median age (Q1, Q3) of 65 477 subjects was 60 (51, 66) years, and men accounted for 40.6%. The overall prevalence of NAFLD was 38.2%, and the prevalence of HAFLD in patients without any of the five metabolism-related chronic diseases was 12.0%. The chronic disease combination with the strongest association with NAFLD was obesity + hypertension + hyperlipidemia + gout + diabetes in the total population (OR=37.94, 95%CI: 31.02-46.41), in women (OR=36.99, 95%CI: 28.78-47.54) and in age group ≥60 years (OR=36.19, 95%CI: 28.25-46.36). The chronic disease combination with the strongest association with NAFLD was obesity + hyperlipidemia + gout + diabetes in men (OR=50.70, 95%CI: 24.62-104.40) and in age group <60 years (OR=49.58, 95%CI: 24.22-101.47). Conclusions: The prevalence of NAFLD in community residents in Shanghai was high. Attention needs to be paid to health of obese people and weight loss should be promoted for them. Community health education should be strengthened for patients complicated with gout, diabetes, hyperlipidemia and hypertension and it is necessary to correct abnormal serum uric acid, blood sugar, blood lipids and blood pressure in a timely manner to reduce the risk of NAFLD.

[Advances of hydrogel in early protection of exposed intra-abdominal organs after open abdomen].

The protection of open abdomen (OA) wound is a significant subject in the field of trauma surgery. The key technical challenge in the early stage of OA wound management involves promoting granulation tissue filling between intestinal segments, reducing intestinal wall abrasion, and preventing the development of enteroatmospheric fistulas (EAF). Hydrogels, characterized by their high water content and exceptional biocompatibility, serve as extracellular matrix-mimicking materials, and are extensively employed in various medical and healthcare applications. In this review, we discuss the application of hydrogel developed by natural biomaterials in OA wounds protection, taking into consideration the unique pathophysiological characteristics of the OA wounds. This review aims to provide valuable insights for the development of hydrogel materials for early-stage OA wound protection in future research.

[Expert consensus on the biobank development of oral genetic diseases and rare diseases and storage codes of related biological samples from craniofacial and oral region].

The biological samples of oral genetic diseases and rare diseases are extremely precious. Collecting and preserving these biological samples are helpful to elucidate the mechanisms and improve the level of diagnose and treatment of oral genetic diseases and rare diseases. The standardized construction of biobanks for oral genetic diseases and rare diseases is important for achieving these goals. At present, there is very little information on the construction of these biobanks, and the standards or suggestions for the classification and coding of biological samples from oral and maxillofacial sources, and this is not conducive to the standardization and information construction of biobanks for special oral diseases. This consensus summarizes the background, necessity, principles, and key points of constructing the biobank for oral genetic diseases and rare diseases. On the base of the group standard "Classification and Coding for Human Biomaterial" (GB/T 39768-2021) issued by the National Technical Committee for Standardization of Biological Samples, we suggest 76 new coding numbers for different of biological samples from oral and maxillofacial sources. We hope the consensus may promote the standardization, and smartization on the biobank construction as well as the overall research level of oral genetic diseases and rare diseases in China.

Oral FTY720 administration induces immune tolerance and inhibits early development of atherosclerosis in apolipoprotein E-deficient mice.

Orally administered immunomodulatory drugs have recently demonstrated the ability to induce an oral tolerance via inhibition of effector T cells and induction of certain subsets of regulatory T cells (Tregs) which have the potential to prevent several autoimmune diseases. In the present study, we hypothesized that short-term, low-dose, oral FTY720 administration may induce latency-associated peptide (LAP) Tregs and CD4(+) Foxp3(+) Tregs in atherogenesis, potentially resulting in remission of early development of atherosclerosis in apolipoprotein E-deficient (APOE(-/-)) mice. FTY720 was orally administered to APOE(-/-) mice 4 weeks of age on a high-cholesterol diet and atherosclerosis was assessed at 8 weeks of age. Oral administration of FTY720 significantly reduced atherosclerotic lesion formation compared with control mice. We observed a significant increase in LAP(+) and Foxp3(+) cells in the CD4+T-cell population of FTY720-treated mice in association with increased production of the anti-inflammatory cytokine transforming growth factor-ß (TGF-ß) as well as suppressed T-helper type 1 immune responses. Our findings reveal that short-term, low-dose oral FTY720 treatment had great benefits in inhibiting early development of atherosclerosis in mice via induction of a regulatory T-cell response and inhibition of effector T responses. These findings suggest that oral immune modulation may represent an attractive therapeutic approach to atherosclerosis.

Comparison of urology residency training between the United States and China.

OBJECTIVE: This study compares the present status and traits of urology residency programs in the United States and China. METHODS: The flow path, structure, curriculum, operative experience, scholarly activities, evaluation systems and other aspects of training were comparatively evaluated between China and the United States. RESULTS: Urology residency training programs are different between China and the United States in many aspects. Admission requirements for the United States urology residency program are more rigorous, and the specialty training program in the United States is more concentrated. Furthermore, residency programs in USA have much more practical clinical and research training, and their evaluation process is more diverse, and it has been designed to assess competencies. Moreover, job opportunities after residency substantially differ between these two countries. Becoming an independent urologic surgeon is not the specific goal of the Urology residency training program in China, and it would require more training time than in the United States. CONCLUSION: Urology residency training programs in the United States and China have a unique format and characteristics. The training programs in China are focused on general techniques and procedures, while training programs in USA follow a more standardized curriculum. Both USA and China may complement each other to create training programs that would ultimately provide high-quality patient care.

Reconstruction of hypopharyngeal and cervical esophageal defect after resection of hypopharyngeal carcinoma: a new technique based on the use of bilateral platysma myocutaneous flaps.

Commonly used procedures for reconstructing hypopharyngeal and cervical esophageal defects resulting from total laryngopharyngectomy (TL) are the gastric conduit or colon transposition as well as microvascularized free flaps. Herein we designed an alternative procedure utilizing bilateral platysma myocutaneous flaps (PMCFs) for the reconstruction of hypopharyngeal and cervical esophageal defects. This report summarizes the technical description of this procedure. TL and cervical esophagectomy were performed and bilateral PMCFs were harvested for reconstruction of hypopharyngeal and cervical esophageal defects in 25 patients aged between 46 and 73 years (mean 58.7 ± 16.2 years). All these patients had advanced-stage (IV) cancer with involvement of the cervical esophagus. Operative time ranged from 176 to 382 minutes (average 243 ± 91 minutes) and the mean intraoperative blood loss was 294 ± 119mL. There were six cases of anastomotic leak (24.0%) and two of them (8.0%) developed anastomotic stricture. Neither flap necrosis nor postoperative death was observed. The majority of our patients (68.0%) were restored to a normal unrestricted oral diet after surgery. The 3-year and 5-year actuarial survival rates were approximately 54.7% and 26.1%, respectively. We conclude that reconstruction of the cervical esophagus with bilateral PMCFs is a valuable method for treating advanced hypopharyngeal carcinoma.

[Establishment of mini-guts organoid and research on intestinal disease from the new perspective].

Intestinal organoids, also named "mini-guts", reconstitute sophisticated three-dimensional architecture recapitulating diversified intestinal epithelial cell types and physiology, which is driven by the proliferative and self-assembling characteristics of crypt stem cells. The initiation of organoids study relies on the identification of Lgr5+ crypt stem cells from different intestinal segments and the key role of EGF, Wnt, BMP/TGF-ß, Notch signal pathways within the microenvironment during the cultivation process. Besides constituting polarized crypt-villus structures, these "mini-guts" exhibit various effective functions of intestinal epithelium. Since 2009 when the culture system of small intestinal organoids was established by Sato et al, intestinal organoids excel conventional intestinal models depending on genetical mutation in multiple aspects and thus have become the hotspot among the research on intestinal diseases. Combined with genomics, material science and engineering, "mini-guts" have been widely applied to the research on intestinal development, intestinal transport physiology, epithelial barrier, pathogen-host interaction and the study on cystic fibrosis, infectious diarrhea, ulcerative colitis, Crohn's disease, intestinal cancer, etc. In this review, we summarize the new insights introduced by organoid into the research on intestinal diseases, and related research advances and applications.

[Association of hyperuricemia with risk of incident chronic kidney disease in adult in Songjiang district, Shanghai: a follow-up study].

Objective: To evaluate the association of hyperuricemia with the risk for chronic kidney disease (CKD) in community adults. Methods: A community-based follow-up study comprising of 7 276 adults aged 20-74 years who attended the natural population cohort in Eastern China and had no CKD at baseline survey was performed in the Songjiang district, Shanghai. CKD was diagnosed according to the National Kidney Foundation Practice Guidelines for Chronic Kidney Disease criteria. Hyperuricemia was defined as serum uric acid level >420 µmol/L for men and >360 µmol/L for women. Cox proportional hazards model was used to examine the association of hyperuricemia with the risk for CKD. Results: During a median follow-up period of 2.65 year, 301 participants were newly diagnosed with CKD. The cumulative incidence rate and incidence density of CKD were 4.14%, and 16.01/1 000 person-years (95%CI: 14.20-17.82), respectively. A higher prevalence of hyperuricemia was observed in subjects with CKD compared with those without CKD. Multivariate Cox regression model analysis showed that hyperuricemia was associated with the increased risk for CKD, with an adjusted HR of 1.92 (95%CI: 1.46-2.53). Their positive associations remained in almost all the subgroups, including sex, age (<60, ≥60 years), BMI (<25.0, ≥25.0 kg/m2), type 2 diabetes, and hypertension. A significant synergistic effect of the interaction between age and hyperuricemia on CKD was found, and the synergy index was 1.78 (95%CI: 1.18-2.68). Conclusion: The incidence of CKD in adults in Songjiang district was relatively high. Hyperuricemia is an independent risk factor for the development of CKD.