Xuesong Li

Peking University, Peping, Beijing, China

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Publications (34)112.56 Total impact

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    ABSTRACT: To investigate the natural history of renal cell carcinoma (RCC) with delayed treatment and to immunohistochemically analyze the correlation between some biomarkers and the growth rate of RCC. We reviewed our institutional databases to identify renal tumors which were confirmed to be RCC by delayed surgical treatment after at least 12 months of active surveillance (AS). Growth rate was defined as the average growth rate of the maximal diameter on computed tomography or magnetic resonance imaging. The clinicopathological characteristics and immunohistochemical biomarkers (Ki-67, p53, bcl-2, and vascular endothelial growth factor) were analyzed the correlation with the growth rate of RCC. We identified 45 RCCs from 45 patients. The mean patient age was 54 years (range, 26-78 years). The mean tumor size increased from 2.39 cm (range, 0.10-6.70 cm) at presentation to 4.54 cm (range, 1.40-11.80 cm) after a mean time of 45.4 months (range, 12-155 months) of AS. The mean growth rate was 0.79 cm/y (range, 0.10-4.74 cm), and 36 (80.0%) tumors presented a growth rate ≤ 1.00 cm/y. Clear cell RCC had a trend of growing faster than other histological subtypes. Pathological grade was significantly correlated with the growth rate of RCC (p = 0.043). High positive ratio of Ki-67 (r = 0.351, p = 0.018) and being p53 positive (p = 0.019) were significantly correlated to the fast growth rate of RCC. In general, RCCs under AS are slow growing with a wide variation of growth rate, with a portion of RCCs presenting rapid growth kinetics. RCC with rapid growth during AS is characterized by a high histological grade, high positive ratio of Ki-67, and being p53 positive. Copyright © 2015. Published by Elsevier B.V.
    Journal of the Formosan Medical Association 06/2015; DOI:10.1016/j.jfma.2015.05.003 · 1.70 Impact Factor
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    ABSTRACT: Background To analyze the expression of karyopherin alpha 2 (KPNA2) in upper tract urothelial carcinoma (UTUC) and to investigate whether the KPNA2 expression provides additional prognostic information following radical nephroureterectomy (RNU). Methods A tissue microarray (TMA) containing samples from 176 patients with UTUC who underwent RNU at our institute was analyzed for KPNA2 expression using immunohistochemistry. KPNA2 expression in normal urothelial cell line and urothelial carcinoma cell lines was evaluated by western blot analysis. Using RNA interference in vitro, the effects of KPNA2 inhibition on cellular viability, migration and apoptosis were determined. Results KPNA2 expression was significantly upregulated in the UTUC samples compared with the adjacent normal urothelial tissues. High KPNA2 immunoreactivity was identified as a predictor of bladder recurrence (hazard ratio [HR]: 2.017, 95% CI 1.13-3.61, p = 0.018), poor disease-free survival (DFS, HR: 2.754, 95% CI 1.68-4.51, p = 0.001) and poor overall survival (OS, HR: 4.480, 95% CI 1.84-10.89, p = 0.001) for patients with UTUC after RNU. Furthermore, high KPNA2 immunoreactivity was independent of the conventional predictive factors in a multivariate analysis. Additional in vitro experiments revealed that KPNA2 expression was higher in urothelial carcinoma cell lines than in normal urothelial cell line. KPNA2 inhibition with a specific siRNA decreased cell viability and migration and increased apoptosis in urothelial carcinoma cell lines. Conclusions KPNA2 is a novel independent prognostic marker for bladder recurrence, DFS and OS of UTUC patients who have undergone RNU. Moreover, these data suggest that KPNA2 may be a promising therapeutic target for UTUC.
    BMC Cancer 05/2015; 15(4). DOI:10.1186/s12885-015-1369-8 · 3.32 Impact Factor
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    ABSTRACT: We conducted this study to identify gene promoter methylation status and clinical predictors for upper tract urothelial carcinoma (UTUC) patients. Using methylation-sensitive polymerase chain reaction, we examined ten genes promoter methylation status in 687 UTUC patients. A methylated promoter of three genes to predict higher tumor stage (T3 and T4), five genes to predict higher tumor grade (G3) and one gene to predict pN+ were certified in this study. Nine factors were significantly associated with poor cancer-specific survival. Six factors were considered as predictors to develop bladder recurrence after surgery. Methylation occurs commonly in UTUCs, may affect carcinogenic mechanisms, and is a well predictive factor for cancer-specific survival and bladder recurrence in UTUCs.
    Epigenomics 04/2015; DOI:10.2217/epi.15.34 · 5.22 Impact Factor
  • Liqun Zhou, Zhongqiang Guo, Xuesong Li
    The Journal of Urology 04/2015; 193(4):e712. DOI:10.1016/j.juro.2015.02.2107 · 3.75 Impact Factor
  • European Urology Supplements 04/2015; 193(4):e11. DOI:10.1016/j.juro.2015.02.126 · 3.37 Impact Factor
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    ABSTRACT: Background Aberrant methylation of genes is one of the most common epigenetic modifications involved in the development of urothelial carcinoma. However, it is unknown the predictive role of methylation to contralateral new upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU). We retrospectively investigated the predictive role of DNA methylation and other clinicopathological factors in the contralateral upper tract urothelial carcinoma (UTUC) recurrence after radical nephroureterectomy (RNU) in a large single-center cohort of patients.Methods In a retrospective design, methylation of 10 genes was analyzed on tumor specimens belonging to 664 consecutive patients treated by RNU for primary UTUC. Median follow-up was 48 mo (range: 3¿144 mo). Gene methylation was accessed by methylation-sensitive polymerase chain reaction, and we calculated the methylation index (MI), a reflection of the extent of methylation. The log-rank test and Cox regression were used to identify the predictor of contralateral UTUC recurrence.ResultsThirty (4.5%) patients developed a subsequent contralateral UTUC after a median follow-up time of 27.5 (range: 2¿139) months. Promoter methylation for at least one gene promoter locus was present in 88.9% of UTUC. Fewer methylation and lower MI (P¿=¿0.001) were seen in the tumors with contralateral UTUC recurrence than the tumors without contralateral recurrence. High MI (P¿=¿0.007) was significantly correlated with poor cancer-specific survival. Multivariate analysis indicated that unmethylated RASSF1A (P¿=¿0.039), lack of bladder recurrence prior to contralateral UTUC (P¿=¿0.009), history of renal transplantation (P¿<¿0.001), and preoperative renal insufficiency (P¿=¿0.002) are independent risk factors for contralateral UTUC recurrence after RNU.Conclusions Our data suggest a potential role of DNA methylation in predicting contralateral UTUC recurrence after RNU. Such information could help identify patients at high risk of new contralateral UTUC recurrence after RNU who need close surveillance during follow up.
    Journal of experimental & clinical cancer research: CR 01/2015; 34(1):5. DOI:10.1186/s13046-015-0120-2 · 3.27 Impact Factor
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    ABSTRACT: Purpose To explore the characteristics, predictive risk factors, and prognostic effect of concomitant non-muscle-invasive bladder cancer (NMIBC) in patients with upper tract urothelial carcinoma (UTUC). Methods We evaluated 727 consecutive UTUC patients treated with radical resection between 2000 and 2012 in a high-volume center of China. Preoperative cystoscopy was performed in all patients. Patients with previous or concomitant total cystectomy were excluded. Results Overall, 73 patients (10.0 %) had NMIBC. Concomitant NMIBC was associated with previous bladder cancer (p = 0.003), tumor located in ureter (p = 0.008), multifocality (p p = 0.023). The presence of concomitant NMIBC was predictive for lower tumor stage (p = 0.019), papillary architecture (p = 0.023), and organ-confined disease (pT p = 0.006). The median follow-up duration was 57 months. The presence of concomitant NMIBC was a risk factor for bladder recurrence (p p = 0.030) and contralateral recurrence (odds ratio, 1.907, p = 0.016). Most concomitant NMIBC were found at the lateral wall or bladder neck, while most intravesical recurrences occurred near the site of surgery or posterior wall. Conclusions The most common site for concomitant NMIBC was lateral wall and bladder neck, and previous bladder cancer, tumor located in ureter, tumor multifocality, and preoperative renal insufficiency were risk factors for concomitant NMIBC. The presence of concomitant NMIBC is predictive for relative better pathologic outcomes but higher rate of bladder recurrence, while the effect on postoperative survival was limited with patients early-stage UTUCs. The potential mechanisms need further investigation.
    Annals of Surgical Oncology 01/2015; DOI:10.1245/s10434-014-4302-5 · 3.94 Impact Factor
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    ABSTRACT: BACKGROUND High Mobility Group N (HMGN) proteins are a family of chromatin structural proteins that specifically bind to nucleosome core particles. HMGN5 is a novel and characteristic member of the HMGN protein family. We have previously found that HMGN5 is upregulated in prostate cancer and its downregulation had been demonstrated to induce apoptosis and G2-M cell cycle arrest.METHODS The radiosensitization effect of HMGN5 knockdown on PC3 and DU145 cells was assessed using clonogenic assay, flow cytometry, and comet assay. The DNA double-strand break (DSB) repair kinetics of HMGN5 knockdown and control cells after radiation exposure was evaluated using immunocytofluorescence. The mitochondrial reactive oxygen species (ROS) levels were estimated using Dihydrorhodamine 123 (DHR 123) probes. Expression of mitochondrial antioxidant MnSOD was measured by real-time PCR and Western blot. The expression of antiapoptotic proteins Bcl-2 and Bcl-xL as well as cleavage of caspase-3, caspase-9, and PARP were also measured using Western blot.RESULTSHMGN5 knockdown cells exhibit decreased clonogenic survival and increased apoptosis rate in response to 2–8 Gy ionizing radiation (IR). Loss of HMGN5 does not affect the DSB repair kinetics after radiation exposure. HMGN5 knockdown cells demonstrated increased mitochondrial ROS level and suppressed induction of MnSOD upon radiation compared with control cells upon radiation. Further, MnSOD knockdown resulted in inhibited cell viability as well as increased mitochondrial ROS level and apoptosis upon radiation in PC3 and DU145 cells. Finally, HMGN5 knockdown cells showed significantly decreased levels of antiapoptotic proteins Bcl-2 and Bcl-xL as well as increased cleavage of caspase-3, caspase-9, and PARP compared with control cells after radiation.CONCLUSIONSHMGN5 knockdown sensitizes prostate cancer cells to ionizing radiation, and the radiosensitization effect may be partially mediated through suppressed induction of MnSOD and enhanced activation of apoptosis pathway in response to IR. Prostate © 2014 Wiley Periodicals, Inc.
    The Prostate 01/2015; 75(1). DOI:10.1002/pros.22888 · 3.57 Impact Factor
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    ABSTRACT: To describe a modified suture technique for transperitoneal laparoscopic dismembered pyeloplasty (TPLDP) that can be consistently replicated. Between June 2010 and April 2014, 21 men and 7 women with primary pelviureteric junction obstruction underwent our modified TPLDP suture technique performed by the same surgeon. In our method, the dismembering should be performed after performing half of anastomosis to achieve the maintenance of correct orientation and the prevention of torsion of anastomosis. We defined the success criteria as complete clinical resolution of flank pain for the patients with flank pain and complete radiologic resolution for the asymptomatic patients. The mean overall operative time for our technique was 137.3 minutes. The mean operative time for procedures on the left side was longer than on the right side (P = .02). The mean suture time was 37.2 minutes. The mean estimated blood loss was 29.4 mL, and the crossing vessel was found in 7 of 28 patients (25.0%). No open conversion was required. The mean follow-up time was 21.0 months. Only 1 patient still had frequent and intolerable flank pain after surgery whose treatment was unsuccessful. The rest of the patients got complete clinical or radiologic resolution. The success rate was 27 of 28 (96.4%). Our modified TPLDP suture technique is feasible and seems to be safe and to allow high success rate for the treatment of pelviureteric junction obstruction. Sizable sample and further analysis about technique will be completed in the future. Copyright © 2015 Elsevier Inc. All rights reserved.
    Urology 01/2015; 85(1):263-7. DOI:10.1016/j.urology.2014.09.031 · 2.13 Impact Factor
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    ABSTRACT: Prostate cancer is a leading cause of cancer-related death among men. Early diagnosis and treatment are successful against prostate cancer, yet the clinical treatment of advanced prostate cancer remains a challenge. Gemcitabine is used to treat a broad spectrum of solid tumors; however, the clinical response of prostate cancer patients to gemcitabine is limited. In the present study, we showed that HMGN5, a nucleosome binding protein that can unfold chromatin by binding to histone (H1), is overexpressed in prostate cancer cells and plays an oncogenic role in prostate cancer tumorigenesis and development by activating the MAPK signaling pathway. We also found that sensitivity of prostate cancer cells to gemcitabine was positively correlated with HMGN5 expression. Knockdown of HMGN5 expression reduced the sensitivity of PC-3 cells to gemcitabine, and ectopic HMGN5 expression in DU145 cells enhanced the sensitivity to gemcitabine. Gemcitabine decreased HMGN5 expression, consequently leading to inactivation of the MAPK signaling pathway and cleavage of the PARP protein. Finally, we showed that PC-3 cells acquire gemcitabine resistance by gradual loss of HMGN5 expression. The present study suggests that HMGN5 is a potential biomarker for treating prostate cancer, and patients with a high level HMGN5 will benefit from gemcitabine treatment.
    Oncology Reports 12/2014; 33(3). DOI:10.3892/or.2014.3696 · 2.19 Impact Factor
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    ABSTRACT: Potassium inwardly rectifying channel, subfamily J, member 1 (KCNJ1), as an ATP-dependent potassium channel, plays an essential role in potassium balance. KCNJ1 variation is associated with multiple diseases, such as antenatal Bartter syndrome and diabetes. However, the role of KCNJ1 in clear cell renal cell carcinoma (ccRCC) is still unknown. Here, we studied the expression and function of KCNJ1 in ccRCC. The expression of KCNJ1 was evaluated in ccRCC tissues and cell lines by quantitative real-time PCR (qRT-PCR), Western blot, and immunohistochemistry analysis. The relationship between KCNJ1 expression and clinicopathological characteristics was analyzed. p3xFLAG-CMV-14 vector containing KCNJ1 was constructed and used for transfecting ccRCC cell lines 786-O and Caki-2. The effects of KCNJ1 on cell proliferation, invasion, and apoptosis were detected in ccRCC cell lines using cell proliferation assay, transwell assay, and flow cytometry, respectively. We found that KCNJ1 was low-expressed in ccRCC tissues samples and cell lines, and its expression level was significantly associated with tumor pathology grade (P = 0.002) and clinical stage (P = 0.023). Furthermore, the KCNJ1 expression was a prognostic factor of ccRCC patient's survival (P = 0.033). The re-expression of KCNJ1 in 786-O and Caki-2 significantly inhibited cancer cell growth and invasion and promoted cancer cell apoptosis. Moreover, knockdown of KCNJ1 in HK-2 cells promoted cell proliferation. Collectively, these data highlight that KCNJ1, low-expressed in ccRCC and associated with poor prognosis, plays an important role in ccRCC cell growth and metastasis.
    Tumor Biology 10/2014; 36(2). DOI:10.1007/s13277-014-2746-7 · 2.84 Impact Factor
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    ABSTRACT: Objectives To investigate the incidence and treatment strategies for bilateral upper tract urothelial carcinoma (UTUC) and to compare the characteristic and oncologic outcomes of bilateral UTUC with those of unilateral tumors. Methods and materials The study included 892 consecutive patients with UTUC. Bilateral UTUC was defined as synchronous bilateral carcinoma on preoperative imaging before confirmation by pathology or positive urine cytology result plus direct visualization. Radical nephroureterectomy (RNU) or nephron-sparing surgery (NSS) or both were carried out. Results A total of 39 patients (4.37%) suffered from bilateral disease. Discordant histological grade of bilateral tumor was found in 39.3% cases. Bilateral tumors were associated with female sex (P<0.001), preoperative renal insufficiency (P<0.001), previous or concomitant bladder tumors (P = 0.013), lower tumor stages (P = 0.020), papillary architecture (P = 0.001), and smaller-sized tumors (P = 0.020). Patients with worse renal function (P<0.001) or large-sized tumors (P = 0.039) tended to be treated with bilateral RNU. Most patients (67.6%) were treated with unilateral RNU plus unilateral NSS, with NSS being performed on tumors that only extended to the ureter (P = 0.003) and had a smaller size (P = 0.005). The median follow-up duration was 56 months. The 5-year cancer-specific survival and bladder recurrence-free survival rates were 81.2% and 64.5%, respectively, similar to those of unilateral tumors. Male sex (hazard ratio = 11.535) and higher tumor stage (hazard ratio = 3.386) were independent worse prognostic factors. Conclusions The prevalence of bilateral UTUC is rare. Female patients, patients with renal insufficiency, and those with bladder tumor tended to suffer from bilateral disease and were less likely to present with worse pathological outcomes in the Chinese population. The tumor characteristics and renal function were informative in treatment selection. The oncologic outcomes were similar to those in unilateral UTUC, and male sex and a higher tumor stage were poor prognostic factors for these patients.
    Urologic Oncology 09/2014; 33(2). DOI:10.1016/j.urolonc.2014.07.001 · 3.36 Impact Factor
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    ABSTRACT: MicroRNAs are endogenous small noncoding RNAs that are functionally involved in numerous critical cellular processes including tumorigenesis. Data mining using a microRNA array database suggested that let-7d microRNA may be associated with renal cell carcinoma (RCC) malignant progression. Here, we performed further analyses to determine whether let-7d is functionally linked to RCC malignancy.
    Molecular Cancer 09/2014; 13(1):206. DOI:10.1186/1476-4598-13-206 · 5.40 Impact Factor
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    ABSTRACT: Objectives. To report the decline of renal function after radical nephroureterectomy (RNU) in upper tract urothelial carcinoma (UTUC) patients and to develop a nomogram to predict ineligibility for cisplatin-based adjuvant chemotherapy (AC). Methods. We retrospectively analyzed 606 consecutive Chinese UTUC patients treated by RNU from 2000 to 2010. We chose an eGFR of 60 and 45 ml/min/1.73 m(2) as cut-offs for full-dose and reduced-dose AC eligibility. Results. Median eGFR for all patients before and after surgery was 64 and 49 ml/min/1.73 m(2) (P < 0.001). The proportion of patients ineligible to receive full-dose and reduced-dose AC changed from 42% to 74% and from 20% to 38.1%. Older age (OR = 1.007), preoperative eGFR (OR = 0.993), absence of hydronephrosis (OR = 0.801), smaller tumor size (OR = 0.962), and tumor without multifocality (OR = 0.876) were predictive for ineligibility for full-dose AC. Preoperative eGFR (OR = 0.991), absence of hydronephrosis (OR = 0.881), tumor located in renal pelvis (OR = 1.164), and smaller tumor size (OR = 0.969) could predict ineligibility for reduced-dose AC. The c-index of the two models was 0.757 and 0.836. Postoperative renal function was not associated with worse survival. Conclusions. Older age, lower preoperative eGFR, smaller tumor size, tumor located in renal pelvis, and absence of hydronephrosis or multifocality were predictors of postoperative renal insufficiency.
    BioMed Research International 08/2014; 2014:529186. DOI:10.1155/2014/529186 · 2.71 Impact Factor
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    ABSTRACT: To evaluate the efficacy of resiniferatoxin in the treatment of patients with lifelong premature ejaculation.
    International Journal of Urology 06/2014; 21(9). DOI:10.1111/iju.12471 · 1.80 Impact Factor
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    ABSTRACT: A 61-year-old male patient presented with intermittent gross hematuria. A right renal mass with infrahepatic vena caval tumor thrombus was found using magnetic resonance imaging. We undertook a novel combined retroperitoneal and transperitoneal pure laparoscopic nephrectomy with vena caval thrombectomy for this patient. The patient recovered well after surgery and discharged on day 6. A clear cell renal cell carcinoma with venous extension was confirmed by pathologic assay. To our knowledge, this is the first report of such a novel hybrid surgical strategy.
    Urology 05/2014; 83(5):e9-e10. DOI:10.1016/j.urology.2014.01.025 · 2.13 Impact Factor
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    ABSTRACT: The advent of targeted therapy has proved a milestone in the history of metastatic renal cell carcinoma treatment, and several guidelines now recommend sunitinib as first- or second-line treatment. But little is known about its efficacy in Asian patients. The aim of this article was to evaluate the efficacy of sunitinib monotherapy in patients with metastatic renal cell carcinoma treated at two Chinese centers. One hundred and forty-one patients with metastatic renal cell carcinoma were included in the study. Of them, 119 patients received single-agent sunitinib as first-line therapy and the remaining 22 patients received it as second-line therapy. One hundred and twenty patients received sunitinib in a dosage of 50 mg orally once daily on a 4-2 schedule (4 weeks on treatment, 2 weeks off), while 21 patients received 37.5 mg/day continuously until either disease progression or unacceptable toxicity occurred. The overall response rate, survival outcomes, and safety were evaluated. Over a median follow-up time of 23 months (16 cycles; range 2-45 months), complete responses, partial responses, and stable disease lasting two cycles or longer were achieved in 2.8%, 24.1%, and 60.3% of patients respectively (objective response rate 26.9%; overall benefit 87.2%). The median progression-free survival was 14.2 months (range 3-39 months). During the study, 53 patients died and the median survival time was 13.5 months (range 7-25 months). Dose modification or treatment interruption due to adverse events was required in 36.9% of the patients. The most common adverse events were hand-foot syndrome (71.4%), thrombocytopenia (68.8%), hypertension (47.1%), and fatigue (46.3%). Sunitinib had a favorable efficacy/tolerability profile in Chinese patients with metastatic renal cell carcinoma.
    Chinese medical journal 04/2014; 127(8):1450-3. · 1.02 Impact Factor
  • The Journal of Urology 04/2014; 191(4):e316-e317. DOI:10.1016/j.juro.2014.02.817 · 3.75 Impact Factor
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    ABSTRACT: Hypoxic stress and hypoxia-inducible factors (HIFs) play important roles in a wide range of tumors. We demonstrate that SPOP, which encodes an E3 ubiquitin ligase component, is a direct transcriptional target of HIFs in clear cell renal cell carcinoma (ccRCC). Furthermore, hypoxia results in cytoplasmic accumulation of SPOP, which is sufficient to induce tumorigenesis. This tumorigenic activity occurs through the ubiquitination and degradation of multiple regulators of cellular proliferation and apoptosis, including the tumor suppressor PTEN, ERK phosphatases, the proapoptotic molecule Daxx, and the Hedgehog pathway transcription factor Gli2. Knockdown of SPOP specifically kills ccRCC cells, indicating that it may be a promising therapeutic target. Collectively, our results indicate that SPOP serves as a regulatory hub to promote ccRCC tumorigenesis.
    Cancer cell 03/2014; DOI:10.1016/j.ccr.2014.02.007 · 23.89 Impact Factor
  • Chinese medical journal 02/2014; 127(4):782-3. · 1.02 Impact Factor

Publication Stats

47 Citations
112.56 Total Impact Points

Institutions

  • 2011–2015
    • Peking University
      • Institute of Urology
      Peping, Beijing, China
  • 2012–2014
    • Beijing Medical University
      Peping, Beijing, China
  • 2013
    • University of California, San Francisco
      San Francisco, California, United States