Landscape of targeted therapies for advanced urothelial carcinoma.

Bladder cancer (BC) is the tenth most common malignancy globally. Urothelial carcinoma (UC) is a major type of BC, and advanced UC (aUC) is associated with poor clinical outcomes and limited survival rates. Current options for aUC treatment mainly include chemotherapy and immunotherapy. These options have moderate efficacy and modest impact on overall survival and thus highlight the need for novel therapeutic approaches. aUC patients harbor a high tumor mutation burden and abundant molecular alterations, which are the basis for targeted therapies. Erdafitinib is currently the only Food and Drug Administration (FDA)-approved targeted therapy for aUC. Many potential targeted therapeutics aiming at other molecular alterations are under investigation. This review summarizes the current understanding of molecular alterations associated with aUC targeted therapy. It also comprehensively discusses the related interventions for treatment in clinical research and the potential of using novel targeted drugs in combination therapy.

Intensive Surveillance of Porcine-Rhesus Kidney Xenotransplant Using Different Ultrasound Techniques.

BACKGROUND: Significant progress has been made in kidney xenotransplantation in the past few years, and this field is accelerating towards clinical translation. Therefore, surveillance of the xenograft with appropriate tools is of great importance. Ultrasonography has been widely used in kidney allotransplantation and served as an economical and non-invasive method to monitor the allograft. However, questions remain whether the ultrasonographic criteria established for human kidney allograft could also be applied in xenotransplantation. METHODS: In the current study, we established a porcine-rhesus life sustaining kidney xenotransplantation model. The xenograft underwent intensive surveillance using gray-scale, colorful Doppler ultrasound as well as 2D shear wave elastography. The kidney growth, blood perfusion, and cortical stiffness were measured twice a day. These parameters were compared with the clinical data including urine output, chemistry, and pathological findings. RESULTS: The observation continued for 16 days after transplantation. Decline of urine output and elevated serum creatinine were observed on POD9 and biopsy proven antibody-mediated rejection was seen on the same day. The xenograft underwent substantial growth, with the long axis length increased by 32% and the volume increased by threefold at the end of observation. The resistive index of the xenograft arteries elevated in response to rejection, together with impaired cortical perfusion, while the peak systolic velocity (PSV) was not compromised. The cortical stiffness also increased along with rejection. CONCLUSION: In summary, the ultrasound findings of kidney xenograft shared similarities with those in allograft but possessed some unique features. A modified criteria needs to be established for further application of ultrasound in kidney xenotransplantation.

Predicting estimated glomerular filtration rate after partial and radical nephrectomy based on split renal function measured by radionuclide: a large-scale retrospective study.

PURPOSE: The purpose of this study was to develop predictive models for postoperative estimated glomerular filtration rate (eGFR) based on the split glomerular filtration rate measured by radionuclide (rGFR), as choosing radical nephrectomy (RN) or partial nephrectomy (PN) for complex renal masses requires accurate prediction of postoperative eGFR. METHODS: Patients who underwent RN or PN for a single renal mass at Xijing Hospital between 2008 and 2022 were retrospectively included. Preoperative split rGFR was evaluated using technetium-99 m-diethylenetriaminepentaacetic acid (Tc-99 m DTPA) renal dynamic imaging, and the postoperative short-term (< 7 days) and long-term (3 months to 5 years) eGFRs were assessed. Linear mixed-effect models were used to predict eGFRs, with marginal R2 reflecting predictive ability. RESULTS: After excluding patients with missing follow-up eGFRs, the data of 2251 (RN: 1286, PN: 965) and 2447 (RN: 1417, PN: 1030) patients were respectively included in the long-term and short-term models. Two models were established to predict long-term eGFRs after RN (marginal R2 = 0.554) and PN (marginal R2 = 0.630), respectively. Two other models were established to predict short-term eGFRs after RN (marginal R2 = 0.692) and PN (marginal R2 = 0.656), respectively. In terms of long-term eGFRs, laparoscopic and robotic surgery were superior to open surgery in both PN and RN. CONCLUSIONS: We developed novel tools for predicting short-term and long-term eGFRs after RN and PN based on split rGFR that can help in preoperative decision-making.

No Difference Between Tacrolimus and Cyclosporine A on Depression Among Kidney Transplantation Recipients.

BACKGROUND: The 2 main types of calcineurin inhibitors (CNI) are tacrolimus (TAC) and cyclosporine A (CsA); both are needed by patients who receive kidney transplants. A common adverse reaction of TAC is depression, which is listed in its instructions. However, depression occurred rarely, according to the instructions manual for CsA. METHODS: Scales measuring depression were sent to recipients who had taken TAC or CsA to observe whether there was a difference in depression between patients who consumed the 2 drugs. From September 23rd-December 8th 2022, a questionnaire was sent to kidney transplant recipients online to investigate depression by PHQ-9 score. Then, the questionnaires returned were divided into 2 groups: TAC group and CsA group. The difference of basic characteristics was made to equal by means of propensity score matching (PSM). The scores, degrees of depression, and prevalence of major depression between the 2 groups were compared. RESULTS: Of 259 questionnaires returned, 220 questionnaires were valid. Among them, 170 recipients used TAC and 50 recipients used CsA. There were no significant differences in baseline characteristics after PSM. After PSM, there was no statistically significant difference in PHQ-9 (0.8) score, degree of depression (P = .7), or rate of major depression between the 2 groups. CONCLUSIONS: There was no significant difference between kidney transplant recipients taking TAC or CsA in PHQ-9 score, degree of depression, or prevalence of major depression.

Lactobacillus johnsonii 6084 alleviated sepsis-induced organ injury by modulating gut microbiota.

Sepsis is a public cause of death in intensive care unit patients. Probiotics were widely used to increase the survival rate of sepsis by a series of clinical research. The purpose of this research was to investigate the therapeutic effects of Lactobacillus johnsonii 6084 in septic mice. Sepsis mouse model was induced by LPS treatment. The influence of L. johnsonii 6084 on the protection of organ injury induced by sepsis was explored. Moreover, the composition of gut microbiota was studied to clarify the mechanism of L. johnsonii 6084 therapeutic effect on sepsis. L. johnsonii 6084 treatment could conspicuously decrease the mortality and organ injury of sepsis. The reduction of gut microbial diversity and richness in septic mice were moderated by the administration of 6084. The abundance of Bacteroidetes and Proteobacteria were change by LPS treatment while restored by L. johnsonii 6084. To conclude, probiotic 6084 may has optimistic result on reducing mortality of sepsis through rebalancing gut microbiota.

Prevalence and Risk Factors for Allergic Rhinitis in China: A Systematic Review and Meta-Analysis.

The prevalence of allergic rhinitis (AR) has increased tremendously in the recent year in China. Evidence-based medicine to objectively evaluate the prevalence and risk factors for AR in China is urgently required. Toward this, we systematically searched four English and four Chinese databases to identify the literature on the same, from the year of website establishment until November 2021. A total of 51 studies were evaluated, and data were obtained through Stata 16 analysis. Overall pooled risk factors for adult AR were smoking (odds ratio [OR] = 1.89, 95% confidence interval [CI]: 1.25, 2.87), asthma (OR = 3.30, 95% CI: 1.48, 7.39), a family history of AR (OR = 3.17, 95% CI: 2.31, 4.34), a family history of asthma (OR = 3.99, 95% CI: 2.58, 6.16), drug allergy (OR = 1.62, 95% CI: 1.38, 1.89), food allergy (OR = 2.29, 95% CI: 1.39, 3.78), pollen allergy history (OR = 2.41, 95% CI: 1.67, 3.46), antibiotic use (OR = 2.08, 95% CI: 1.28, 3.36), occupational dust exposure (OR = 2.05, 95% CI: 1.70, 2.47), home renovation (OR = 1.73, 95% CI: 0.99, 3.02), and middle school education (OR = 1.99, 95% CI: 1.29, 3.06). Overall pooled risk factors for AR in children were passive smoking (OR = 1.70, 95% CI: 1.02, 2.82), asthma (OR = 3.26, 95% CI: 2.42, 4.39), a family history of AR (OR = 2.59, 95% CI: 2.07, 3.24), a family history of allergy (OR = 4.84, 95% CI: 3.22, 7.26), a history of allergic diseases (OR = 2.11, 95% CI: 1.52, 2.94), eczema(OR = 2.29, 95% CI: 1.36, 3.85), owning pets (OR = 1.56, 95% CI: 1.37, 1.77), eating seafood (OR = 1.30, 95% CI: 1.10, 1.55), boys (OR = 1.58, 95% CI: 1.43, 1.74), and breastfeeding (OR = 0.82, 95% CI: 0.55, 1.22). The results of our meta-analysis showed that the prevalence of allergy rhinitis was 19% (95% CI 14-25) among adults and 22% (95% CI 17-27) among children, with boys showing a higher prevalence than girls. The development of AR in China is associated with several factors, including allergic diseases (eczema, asthma, pollen allergy, and food allergy), a family history of allergy (AR, asthma, and other allergies), and dwelling and working environment (smoking or passive smoking, occupational dust exposure, and owning pets); conversely, breastfeeding can reduce the risk.

Systematic Investigation of Immune-Related lncRNA Landscape Reveals a Potential Long Non-Coding RNA Signature for Predicting Prognosis in Renal Cell Carcinoma.

Background: Renal cell carcinoma (RCC) is the predominant type of malignant tumor in kidney cancer. Finding effective biomarkers, particularly those based on the tumor immune microenvironments (TIME), is critical for the prognosis and diagnosis of RCC. Increasing evidence has revealed that long non-coding RNAs (lncRNAs) play a crucial role in cancer immunity. However, the comprehensive landscape of immune infiltration-associated lncRNAs and their potential roles in the prognosis and diagnosis of RCC remain largely unexplored. Methods: Based on transcriptomic data of 261 RCC samples, novel lncRNAs were identified using a custom pipeline. RCC patients were classified into different immune groups using unsupervised clustering algorithms. Immune-related lncRNAs were obtained according to the immune status of RCC. Competing endogenous RNAs (ceRNA) regulation network was constructed to reveal their functions. Expression patterns and several tools such as miRanda, RNAhybrid, miRWalk were used to define lncRNAs-miRNAs-mRNAs interactions. Univariate Cox, LASSO, and multivariate Cox regression analyses were performed on the training set to construct a tumorigenesis-immune-infiltration-related (TIR)-lncRNA signature for predicting the prognosis of RCC. Independent datasets involving 531 RCC samples were used to validate the TIR-lncRNA signature. Results: Tens of thousands of novel lncRNAs were identified in RCC samples. Comparing tumors with controls, 1,400 tumorigenesis-related (TR)-lncRNAs, 1269 TR-mRNAs, and 192 TR-miRNAs were obtained. Based on the infiltration of immune cells, RCC patients were classified into three immune clusters. By comparing immune-high with immune-low groups, 241 TIR-lncRNAs were identified, many of which were detected in urinary samples. Based on lncRNA-miRNA-mRNA interactions, we constructed a ceRNA network, which included 25 TR-miRNAs, 28 TIR-lncRNAs, and 66 TIR-mRNAs. Three TIR lncRNAs were identified as a prognostic signature for RCC. RCC patients in the high-risk group exhibited worse OS than those in the low-risk group in the training and testing sets (p < 0.01). The AUC was 0.9 in the training set. Univariate and multivariate Cox analyses confirmed that the TIR-lncRNA signature was an independent prognostic factor in the training and testing sets. Conclusion: Based on the constructed immune-related lncRNA landscape, 241 TIR-lncRNAs were functionally characterized, three of which were identified as a novel TIR-lncRNA signature for predicting the prognosis of RCC.