Tislelizumab combined with sunitinib in the treatment of metastatic clear cell renal cell carcinoma with renal venous tumor thrombus: A case report and literature review.

In recent years, with the in-depth study of PD-1/PD-L1 related pathways, great progress has been made in cancer immunotherapy. However, the immunotherapy regimen for mccRCC is still controversial in clinical practice. A 50-year-old man with mccRCC complicated with renal venous tumor thrombus from 2019 to present, including surgical treatment, targeted therapy and the combined treatment regimen of "Tislelizumab combined with Sunitinib". Although he experienced a roller coaster of adverse reactions during treatment, the patient's prognosis was good. Tislelizumab combined with Sunitinib is safe and effective in the Treatment of mccRCC.

Sulforaphane attenuates irradiation induced testis injury in mice.

OBJECTIVE: The testis is vulnerable to ionizing radiation, sexual dysfunction and male infertility are common problems after local radiation or whole-body exposure. Currently, there are no approved drugs for the prevention or treatment of radiation testicular injury. Sulforaphane (SFN) is an indirect antioxidant that induces phase II detoxification enzymes and antioxidant genes. Herein, we investigated the radiation protective effect of SFN on testicular injury in mice and its potential mechanism. MATERIALS AND METHODS: Mice were randomly divided into blank control group (Ctrl), radiation + no pretreatment group (IR), and radiation + SFN groups (IRS). In the radiation + SFN groups, starting from 72 h before radiation, SFN solution was intraperitoneally injected once a day until they were sacrificed. Mice in the blank control group and the radiation + no pretreatment group were simultaneously injected intraperitoneally with an equal volume of the solvent used to dissolve SFN (PBS with a final concentration of 0.1%DMSO) until they were sacrificed. They were subjected to 6Mev-ray radiation to the lower abdominal testis area (total dose 2Gy). Twenty-four hours after radiation, six mice in each group were randomly sacrificed. Seventy-two hours after radiation, the remaining mice were sacrificed. RESULTS: The results showed that the harmful effects of ionizing radiation on testes were manifested as damage to histoarchitecture, increased oxidative stress, and apoptosis, and thus impaired male fertility. SFN injections can reverse these symptoms. CONCLUSIONS: The results showed that SFN can improve the damage of mouse testis caused by irradiation. Furthermore, SFN prevents spermatogenesis dysfunction caused by ionizing radiation by activating Nrf2 and its downstream antioxidant gene.

Improving effects of telmisartan on spermatogenic disorder induced by fractionated low-dose irradiation in mice.

BACKGROUND: Male infertility is a hot problem worldwide, but there are few treatments, especially male infertility caused by irradiation is difficult to treat. The aim of this study was to investigate and evaluate novel drugs for the treatment of male infertility caused by irradiation. METHODS: we randomly divided 18 male BALB/c mice into 3 groups: control, irradiated, and telmisartan. Both irradiated and telmisartan group completed whole-body 0.5 Gy five times irradiation, and the telmisartan group received intraperitoneal injection of telmisartan (1.2 mg/kg) daily on the next day after irradiation, and all groups were sampled on day 25 after irradiation. RESULTS: Sperm motility results show that total sperm motility of irradiated group was significantly lower compared with control group, and testicular HE results showed that testis in irradiated group were severely damaged. Compared with irradiated group, the total sperm motility, sperm concentration, testicular index, Johnsen score, and the seminiferous tubule layer numbers were higher in telmisartan group (P < 0.05). The immunohistochemical staining showed γ-H2AX expression is higher in telmisartan group compared with irradiated group. And the relative mRNA expression of PLZF, GFRA1, STRA8, DMRT1, SPO11, SYCP2, OVOL2, CCNA1, TJP3, RUNX2, TXNDC2 TNP1, and PRM3 in telmisartan group was all significantly higher than irradiated group (P < 0.05). CONCLUSION: In conclusion, in vivo experiments confirmed that telmisartan ameliorated the spermatogenic disorder in mice caused by fractionated low-dose irradiation via promoting spermatogenesis.

[Differential expressions of seminal plasma piRNAs in men and its significance].

OBJECTIVE: To study the differential expressions of piRNAs in the seminal plasma of men and the role of piRNAs in spermatogenesis. METHODS: We sequenced the seminal plasma samples collected from 187 male infertility patients and 58 normal healthy men, obtained differentially expressed piRNAs, and detected the relative expressions of piRNAs in different types of sperm by RT-qPCR to explore their significance in the diagnosis of male infertility. Using histopathology, RNA-protein pull-down and Western blot, we investigated the action mechanism of piRNAs in spermatogenesis in the mouse model. RESULTS: RT-qPCR of the seminal plasma samples revealed a high expression of hsa_piR_000478 in teratozoospermia and ROC curve analysis showed an auxiliary significance of hsa_piR_000478 in the diagnosis of the disease (AUC = 0.7549). Transfection of hsa_piR_000478 and its homologous sequence piR_mmu_54800729 into the seminiferous tubules of the mouse model significantly decreased sperm motility, increased the percentage of morphologically abnormal sperm and destroyed the testicular structure. Molecular biological experiments exhibited a close correlation between piRNAs and the energy metabolism-related pathway, which elevated the level of cell glycolysis and interfered with normal spermatogenesis. CONCLUSION: hsa_piR_000478 has an auxiliary significance in the diagnosis of male infertility, and piRNAs may interfere with spermatogenesis by affecting the glycolysis-related pathway in the spermatogenic microenvironment of the testis.