Primary Urothelial Carcinoma of the Ureter: 11-Year Experience in Taipei Veterans General Hospital

BackgroundUrothelial carcinoma of the upper urinary tract is relatively rare, occurring in 5% of all urothelial tumors. Ureteral urothelial carcinoma is even less common than that of the renal pelvis, accounting for about 25% of all upper urinary tract tumors. The aim of this study was to evaluate the clinical behavior, survival, recurrence and prognostic information of primary ureteral urothelial carcinoma from our 11 years of experience at the Taipei Veterans General Hospital.MethodsWe retrospectively reviewed 111 patients with ureteral urothelial carcinoma who had been treated in our hospital between January 1993 and December 2003. Tumor staging was according to the 2002 AJCC TNM classification and stage groupings. Patients with stage 0a and stage 0is were categorized as stage 0a/is, and patients with pathologic T stage pTa and pTis were categorized as pTa/is for statistical analysis. The Kaplan-Meier method was used for survival analysis.ResultsThere were 69 males and 42 females, with a mean age of 70.5 ± 9.4 years at diagnosis. Of the 111 patients, 5 presented with stage 0a/is, 38 with stage I, 23 with stage II, 21 with stage III, and 24 with stage IV. Nephroureterectomy with bladder cuff excision was performed in 78 patients, 12 patients received segmental resection of the ureter, 4 received ureteroscopic laser coagulation, and 17 underwent chemotherapy or radiotherapy or both. Tumors were located on the left side in 53 patients, on the right in 53, and bilaterally in 5. The most frequent initial presenting symptom was gross hematuria (65%). The mean postoperative follow-up period was 49.3 months. Disease recurrence in the nephroureterectomy group occurred in 36 patients (46.2%), with 17 (21.8%) at the urinary bladder, 2 (2.6%) at the retroperitoneum, 1 (1.3%) at the contralateral ureter, 6 (7.7%) with distant metastases to the lung, bone, distant lymph nodes or liver, and 10 (12.8%) at multiple sites. The 5-year cancer-specific survival rate was 100% for pTa/is, 95.2% for pT1, 69.4% for pT2, and 43.8% for pT3. All 3 pT4 cases died of cancer in a median of 12 months. Significant prognostic factors for cancer-specific survival by univariate analysis were pT (p = 0.00001), stage (p = 0.00001), type of treatment (p = 0.00001) and grade (p = 0.0001). On multivariate analysis, only stage (p = 0.0001) and grade (p = 0.014) were significant for cancer-specific and overall survival. Stage (p = 0.0001), pT (p =0.0001) and grade (p = 0.026) were also significant prognostic factors of recurrence in multivariate analysis.ConclusionOur experience showed that patients with pTa/is and pT1 tumors treated with radical surgery have excellent prognoses. Tumor stage and grade are the only significant prognostic factors for both cancer-specific and overall survival

Towards Building the Federated GPT: Federated Instruction Tuning

While "instruction-tuned" generative large language models (LLMs) have demonstrated an impressive ability to generalize to new tasks, the training phases heavily rely on large amounts of diverse and high-quality instruction data (such as ChatGPT and GPT-4). Unfortunately, acquiring high-quality data, especially when it comes to human-written data, can pose significant challenges both in terms of cost and accessibility. Moreover, concerns related to privacy can further limit access to such data, making the process of obtaining it a complex and nuanced undertaking. Consequently, this hinders the generality of the tuned models and may restrict their effectiveness in certain contexts. To tackle this issue, our study introduces a new approach called Federated Instruction Tuning (FedIT), which leverages federated learning (FL) as the learning framework for the instruction tuning of LLMs. This marks the first exploration of FL-based instruction tuning for LLMs. This is especially important since text data is predominantly generated by end users. Therefore, it is imperative to design and adapt FL approaches to effectively leverage these users' diverse instructions stored on local devices, while preserving privacy and ensuring data security. In the current paper, by conducting widely used GPT-4 auto-evaluation, we demonstrate that by exploiting the heterogeneous and diverse sets of instructions on the client's end with the proposed framework FedIT, we improved the performance of LLMs compared to centralized training with only limited local instructions. Further, in this paper, we developed a Github repository named Shepherd. This repository offers a foundational framework for exploring federated fine-tuning of LLMs using heterogeneous instructions across diverse categories.Comment: Project page: https://github.com/JayZhang42/FederatedGPT-Shepher

An expert consensus for the management of chronic hepatitis B in Asian Americans.

BACKGROUND: Hepatitis B virus (HBV) infection is common with major clinical consequences. In Asian Americans, the HBsAg carrier rate ranges from 2% to 16% which approximates the rates from their countries of origin. Similarly, HBV is the most important cause of cirrhosis, hepatocellular carcinoma (HCC) and liver related deaths in HBsAg positive Asians worldwide. AIM: To generate recommendations for the management of Asian Americans infected with HBV. METHODS: These guidelines are based on relevant data derived from medical reports on HBV from Asian countries as well as from studies in the HBsAg positive Asian Americans. The guidelines herein differ from other recommendations in the treatment of both HBeAg positive and negative chronic hepatitis B (CHB), in the approach to HCC surveillance, and in the management of HBV in pregnant women. RESULTS: Asian American patients, HBeAg positive or negative, with HBV DNA levels \u3e2000 IU/mL (\u3e10 CONCLUSIONS: Application of the recommendations made based on a review of the relevant literature and the opinion of a panel of Asian American physicians with expertise in HBV treatment will inform physicians and improve patient outcomes

RSC96 Schwann Cell Proliferation and Survival Induced by Dilong through PI3K/Akt Signaling Mediated by IGF-I

Schwann cell proliferation is critical for the regeneration of injured nerves. Dilongs are widely used in Chinese herbal medicine to remove stasis and stimulate wound-healing functions. Exactly how this Chinese herbal medicine promotes tissue survival remains unclear. The aim of the present study was to investigate the molecular mechanisms by which Dilong promote neuron regeneration. Our results show that treatment with extract of Dilong induces the phosphorylation of the insulin-like growth factor-I (IGF-I)-mediated phosphatidylinositol 3-kinase/serine-threonine kinase (PI3K/Akt) pathway, and activates protein expression of cell nuclear antigen (PCNA) in a time-dependent manner. Cell cycle analysis showed that G1 transits into the S phase in 12–16 h, and S transits into the G2 phase 20 h after exposure to earthworm extract. Strong expression of cyclin D1, cyclin E and cyclin A occurs in a time-dependent manner. Small interfering RNA (siRNA)-mediated knockdown of PI3K significantly reduced PI3K protein expression levels, resulting in Bcl2 survival factor reduction and a marked blockage of G1 to S transition in proliferating cells. These results demonstrate that Dilong promotes the proliferation and survival of RSC96 cells via IGF-I signaling. The mechanism is mainly dependent on the PI3K protein

Investigation of a Potential Scintigraphic Tracer for Imaging Apoptosis: Radioiodinated Annexin V-Kunitz Protease Inhibitor Fusion Protein

Radiolabeled annexin V (ANV) has been widely used for imaging cell apoptosis. Recently, a novel ANV-Kunitz-type protease inhibitor fusion protein, ANV-6L15, was found to be a promising probe for improved apoptosis detection based on its higher affinity to phosphatidylserine (PS) compared to native ANV. The present paper investigates the feasibility of apoptosis detection using radioiodinated ANV-6L15. Native ANV and ANV-6L15 were labeled with iodine-123 and iodine-125 using Iodogen method. The binding between the radioiodinated proteins and erythrocyte ghosts or chemical-induced apoptotic cells was examined. ANV-6L15 can be radioiodinated with high yield (40%−60%) and excellent radiochemical purity (>95%). 123I-ANV-6L15 exhibited a higher binding ratio to erythrocyte ghosts and apoptotic cells compared to 123I-ANV. The biodistribution of 123I-ANV-6L15 in mice was also characterized. 123I-ANV-6L15 was rapidly cleared from the blood. High uptake in the liver and the kidneys may limit the evaluation of apoptosis in abdominal regions. Our data suggest that radiolabled ANV-6L15 may be a better scintigraphic tracer than native ANV for apoptosis detection

Effects of Dipeptidyl Peptidase-4 Inhibition with MK-0431 on Syngeneic Mouse Islet Transplantation

Dipeptidyl peptidase (DPP)-4 inhibitors increase circulating levels of glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide which may promote β-cell proliferation and survival. This study tested if DPP-4 inhibition with MK-0431 is beneficial for diabetic mice syngeneically transplanted with a marginal number of islets. We syngeneically transplanted 150 C57BL/6 mouse islets under the kidney capsule of each streptozotocin-diabetic mouse and then treated recipients with (n=21) or without (n=17) MK-0431 (30 mg/kg/day, po) for 6 weeks. After islet transplantation, blood glucose levels decreased in both MK-0431-treated and control groups. However, the blood glucose and area under the curve of the intraperitoneal glucose tolerance test at 2, 4, and 6 weeks were not significantly different between MK-0431-treated mice and controls. During 6 weeks, both groups exhibited increased body weights over time. However, the weight between two groups did not differ throughout the study period. At 6 weeks after transplantation, the graft beta-cell mass (0.024 ± 0.005 versus 0.023 ± 0.007 mg, P=0.8793) and insulin content (140 ± 48 versus 231 ± 63 ng, P=0.2939) were comparable in the MK-0431-treated group and controls. Our results indicate posttransplant DPP-4 inhibition with MK-0431 in the diabetic recipient with a marginal number of islets is not beneficial to transplantation outcome or islet grafts