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Radical nephroureterectomy (RNU) with bladder sleeve resection is currently the gold standard for the treatment of high-risk ureteral cancer. However, in certain special cases, such as bilateral upper tract urothelial carcinoma(UTUC), isolated and chronic kidney disease, and low-risk UTUC, kidney sparing surgery(KSS) may represent a viable alternative, though it remains highly challenging. The current KSS options for ureteral cancer include endoscopic treatment, segmental ureterectomy, total ureterectomy combined with kidney autotransplantation and nephrostomy. These methods are associated with significant disadvantages, such as a high risk of recurrence and vascular-related complications. On the basis of previous studies, we creatively proposed a surgical method of long segment ureterectomy with tapered demucosalized ileum(TDI) replacement of the ureter for ureteral cancer, and successfully performed this operation on a patient with ureteral cancer. The follow-up results showed that this surgical method provides good tumor control while preserving the patient's renal function and improves the inherent defect of the ileal replacement of the ureter, which is a feasible choice for patients with ureteral cancer and kidney preservation.

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Prostate cancer (PCa) is a prevalent male malignancy that originates in the epithelial cells of the prostate. In terms of incidence and mortality of malignant tumors in men, PCa ranks second and fifth globally and first and third among men in Europe and the United States, respectively. These figures have gradually increased in recent years. The primary modalities used to diagnose PCa include prostate-specific antigen (PSA), multiparametric magnetic resonance imaging (mpMRI), and prostate puncture biopsy. Among these techniques, prostate puncture biopsy is considered the gold standard for the diagnosis of PCa; however, this method carries the potential for missed diagnoses. The preoperative evaluation of the patient in this study suggested advanced PCa. However, the initial prostate puncture biopsy was inconsistent with the preoperative diagnosis, and instead of waiting for a repeat puncture of the prostate primary, we performed a biopsy of the rib metastasis, which was later diagnosed as advanced PCa.

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Renal cell carcinoma (RCC) associated with Xp11.2 translocation/transcription factor E3 (TFE3) gene fusion is a rare subtype of RCC. A 31-year-old male patient was admitted to The Affiliated Hospital of Zunyi Medical University (Zunyi, China) with a solid mass in the left kidney during a routine health examination. After ruling out surgical contraindications, the patient underwent a laparoscopic left partial nephrectomy under general anesthesia. Postoperative pathology and fluorescence in situ hybridization (FISH) identified Xp11.2 translocation RCC. There was no tumor recurrence or metastasis during the 1-year follow-up. Xp11.2 translocation RCC is unusual, its clinical and imaging findings are not specific, and the diagnosis depends on TFE3-immunohistochemical assay and FISH analysis. Surgical resection is the first choice of treatment and its prognosis is worse than that of clear cell RCC, thus regular follow-ups are necessary.

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BACKGROUND: Uroseptic shock secondary to ureteral calculi during pregnancy is rare. It is characterized by rapid onset, rapid progression, aggressive disease, limited treatment, poor prognosis, and a mortality rate higher than 20% with improper or delayed management. A clear diagnosis is made based on typical clinical symptoms and abdominal ultrasound, often requiring combined multidisciplinary treatment and the simultaneous release of the obstruction. The high mortality rate is mainly related to inappropriate early treatment of stones and infections or failure to intervene in a timely manner. CASE PRESENTATION: A 21-year-old first-time pregnant patient with uroseptic shock was admitted to our intensive care unit. The patient was successfully treated at our hospital with multidisciplinary cooperation, high-dose vasoactive drugs, IABP, CRRT, VA-ECMO, and termination of pregnancy. CONCLUSIONS: Timely relief of obstructions, termination of pregnancy, and the provision of IABP, CRRT, and VA-ECMO when necessary in critically ill patients with uroseptic shock during pregnancy can improve the success rate of resuscitation.

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BACKGROUND AND AIMS: Lacto-ghrestatin is abovine milk-derived peptide with the sequence of LIVTQTMKG, named LGP9 here. This study aimed to investigate protective effects of LGP9 on diabetic ß cells in vivo and in vitro. METHODS AND RESULTS: Type-1-diabetic (T1D) mice were generated by alloxan (ALX; 50 mg/kg, i.v.) and received a four-week treatment schedule of LGP9 at 0.3 mg/kg and 1 mg/kg. Related biochemical parameters were analyzed, and the protein expression was evaluated by Western blotting. The results showed that LGP9 decreased body weight, water consumption and blood glucose, improved oxygen stress and upregulated IRS2/PI3K/Akt signaling in the pancreas of T1D mice. To further investigate the mechanism of LGP9 on the preventive effect of the pancreas, Rin-m5f cells were treated with 15 mM alloxan and followed with LGP9 at 30 µM and 90 µM. The results indicated that LGP9 rebalanced oxygen stress levels, increased cell proliferation, decreased cell apoptosis and activated IRS2/PI3K/Akt signaling. CONCLUSION: LGP9 ameliorated alloxan-injured pancreatic ß cells through IRS2/PI3K/Akt signaling. The finding provides important help for the research and development of LGP9 in therapeutics of diabetes.

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One of the challenges in response to population aging is to meet needs for elderly care among older people especially for those who want to age in their homes or communities. However, disabled older people have more challenges due to their restricted mobility to access care resources than non-disabled ones. We propose a new framework based on the changing relationship between older people and their environment, in which resource linkage in elderly care utilization is emphasized. We conducted a survey with 139 participants (i.e., older people age 60 years or over with different level of disabilities) in three types of neighborhoods in Beijing, China. By conducting a decision tree analysis under the Person-Environment Link (P-E Link) model, we (1) characterized unmet needs for elderly care (activities of daily living (ADL) and instrumental activities of daily living (IADL) assistance) among community-dwelling disabled older people; (2) found disabled older people had more unmet needs for both ADL and IADL assistance because of a lack in linkages to care resources than non-disabled ones; and (3) characterized the linkages to care resources for better supporting disabled older people to age in place, including family support, social connection, and spatial environment. Our findings help improve the Anderson behavioral model by characterizing enabling environments, which highlights that not only the availability of enabling resources but also linkages to these enabling resources play an important role in meeting needs for care among disabled older people. Our findings can also inform improvements in policy design that are targeted to reduce elderly care inequalities.

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Cannabidiol (CBD) is a non-psychotomimetic compound derived from Cannabis sativa. Preclinical and clinical studies have shown therapeutic potential of CBD in a variety of disorders. Despite several research efforts on CBD, its antidepressant activity has been poorly investigated and the exact mechanism of action remains unclear. Thus, this study aimed to further explore the mechanism of CBD after chronic administration (7 days). First, the dose level of CBD that is enough to produce antidepressant effects after chronic administration was explored. Second, the changes in key proteins and neurotransmitters through such methods as real-time polymerase chain reaction (RT-PCR), western blotting, and high-performance liquid chromatography-electrochemical detection (HPLC-ECD) were critically studied. Furthermore, correlation between behavioral phenotypes with protein and neurotransmitters was established and the possible mechanism was herein postulated. The results showed that only the high dose CBD 100 mg/kg chronic administration induced antidepressant-like effects in mice subjected to forced swim test. Chronic CBD 100 mg/kg administration resulted in significant increases in serotonin (5-HT) and noradrenaline (NA) levels in the hippocampus (HPC). Similarly, the chronic administration of CBD 30 mg/kg and CBD 100 mg/kg significantly decreased nuclear factor kappa B (NF-κB) expression in the HPC. Moreover, none of the treatments were observed to induce locomotor effects. Thus, we concluded that chronic administration of CBD (100 mg/kg) induced antidepressant-like effects by increasing 5-HT and NA levels in the HPC. These results shed new light on further discovery of the antidepressant effect of CBD.

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Clinical and preclinical researches have shown that sub-anesthetic ketamine elicits sustained antidepressant effects for up to 1-2 weeks. Pharmacokinetics studies (t1/2 = 23 min) in mice showed no ketamine residue at 24 h after sub-anesthetic or anesthetic ketamine administration. Therefore, this study aims to reveal the mechanism underlying these different biological functions at 24 h after sub-anesthetic and anesthetic ketamine treatment. First, at the animal behavioral level, we found that sub-anesthetic ketamine induced antidepressant and anxiolytic effects while anesthetic ketamine induced depressive-like phenotypes and cognitive impairment. Second, we examined the correlation between behavior phenotype and protein expression, and found that the Brain-derived neurotrophic factor (BDNF) level is oppositely regulated by sub-anesthetic and anesthetic ketamine. Sub-anesthetic ketamine significantly increased the BDNF level, correlating to antidepressant effects; whereas anesthetic dose reduced BDNF expression in the hippocampus, correlating to depressive-like behaviors, anxiety-like behaviors and cognitive impairment. Third, the antidepressant effects of sub-anesthetic ketamine were prevented by pre-treatment of ANA-12, a Tropomyosin receptor kinase B (TrkB) inhibitor. Thus, we conclude that BDNF may be the key factor underlying antidepressant and anxiolytic effects of sub-anesthetic ketamine at 24 h after treatment. These results may shed light on future studies and the development of long-lasting anti-depressant drugs and therapies.

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C-Phycocyanin (C-PC), a kind of blue protein isolated from Spirulina platensis, can ameliorate hyperglycemia, but its effects on gluconeogenesis and glycogenesis are unknown. In the present study, we investigated the effects and underlying mechanisms of C-PC on gluconeogenesis and glycogenesis in insulin resistant hepatocytes. Insulin resistance was induced by high glucose (HG) in human hepatocellular carcinoma (HepG2) cells. C-PC ameliorated glucose production and phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) expression in HG-induced insulin resistant HepG2 cells. It also increased glucose uptake, glycogen content and glycogen synthase (GS) activation in HG-induced insulin resistant HepG2 cells. The data revealed the mechanism of C-PC in improving glucose homoeostasis via activating the IRS/PI3 K/Akt and SIRT1/LKB1/AMPK signaling pathway in insulin resistant hepatocytes. C-PC could be a promising leading compound for the development of a hypoglycemic agent.

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In this paper, a novel drug-loaded material (MSNs-SS-PEG) was obtained by grafting the thiol-linked methoxy polyethylene glycol (MeOPEG-SH) onto the thiol-functionalized mesoporous silica nanoparticles (MSNs-SH) via the disulfide bond linker. In our designed experiment, three different chain lengths of PEG (PEG(1000), PEG(5000), and PEG(1000)-PEG(5000)) were used. The silica materials were characterized by Fourier transform infrared spectroscopy (FT-IR), dynamic light scattering, field emission scanning electron microscopy, transmission electron microscopy, nitrogen adsorption-desorption measurements, and X-ray diffraction. The morphology of the MSNs-SS-PEG was spherical with an average diameter of about 150 nm. Due to the covalent modification of hydrophilic MeOPEG, the MSNs-SS-PEG was coated by a thin polymer shell, showing stable and inerratic MCM-41 type mesoporous structure as well as high specific surface areas and large pore volumes. Moreover, the releases of doxorubicin hydrochloride (DOX) from these materials at 10 mM of glutathione were investigated. The PEG functionalization could effectively cap drugs in the mesoporous channels. The release of DOX from the MSNs-SS-PEG(n) revealed redox-responsive characteristic. The obtained results showed that the MSNs-SS-PEG might be promising drug delivery carrier materials, which could play an important role in the development of drug delivery.

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