Fruquintinib-induced renal-limited thrombotic microangiopathy: a case report.

BACKGROUND: Fruquintinib is a highly selective inhibitor of vascular endothelial growth factor receptor (VEGFR). Currently, there are no reported cases of fruquintinib causing kidney-restrictive thrombotic microangiopathy (TMA) in the available Chinese and foreign literature. CASE PRESENTATION: In this case report, we presented a 73-year-old patient receiving fruquintinib for metastatic colon cancer, manifesting abundant proteinuria, in which kidney-restrictive TMA was also diagnosed through renal biopsy. As far as we were concerned, this was the frst reported in terms of fruquintinib-induced kidney-restrictive TMA confrmed by renal biopsy. CONCLUSION: This case indicates that fruquintinib may result in kidney-restrictive TMA, which is a rare but life-threatening complication of cancer treatment drug. Therefore, regular monitoring of proteinuria and blood pressure is imperative for all patients undergoing anti-VEGF drug therapy. And renal biopsy should be promptly conducted to facilitate early detection of thrombotic microangiopathy.

Carboxymethyl cellulose-based hydrogel with high-density crack microstructures inspired from the multi-tentacles of octopus for ultrasensitive flexible sensing microsystem.

Constructing high-density contact-separation sites on conductive materials highly determines the sensitivity of flexible resistance-type sensors relying on the crack microstructures. Herein, inspired from the multiple-tentacle structures on octopus, we demonstrated a sort of novel carbonized ZIF-8@loofah (CZL) as conductive material to develop ultrasensitivity flexible sensor, in which the carbonized ZIF-8 nanoparticles (~100 nm) served as tentacles. Originating from the formation of high-density contact-separation sites, the fabricated CZL-based strain sensor delivered ultrahigh sensitivity of GFmax = 15,901, short response time of 22 ms and excellent durability over 10,000 cycles. These features enable the sensor with efficient monitoring capacity for complex human activities, such as pulse rate and phonation. Moreover, when CZL was assembled into triboelectric nanogenerator (TENG), CZL-based TENG can effectively convert the irregular biomechanical energy into electric energy, providing sustainable power supply for the continuous operation of the sensing micro-system. Our findings established a novel platform to develop high-performance self-powered sensing systems of physiological parameter of human inspired from the nature.

[Comparison of efficacy and safety of immunosuppressive therapy and rituximab targeting therapy in idiopathic membranous nephropathy].

Objective To assess the efficacy and safety of three treatment modalities (rituximab targeted B-cell therapy, calcium-phosphate inhibitor in conjunction with low-dose corticosteroids, and full-dose corticosteroids combined with cyclophosphamide) for patients at intermediate or high risk of idiopathic membranous nephropathy (IMN) and to analyze the factors impacting the remission rates of IMN. Methods A retrospective cohort study was conducted to analyze patients diagnosed with IMN in our nephrology department via renal biopsy, identifying a total of 148 patients at intermediate or high risk. These patients were categorized into three treatment groups: a RTX group with 60 patients receiving rituximab, a CNI group with 42 patients receiving calcineurin inhibitors, and a CTX group with 46 patients received cyclophosphamide. Baseline measurements of 24-hour urine protein, serum albumin, blood creatinine, uric acid, estimated glomerular filtration rate (eGFR), and serum anti-phospholipase A2 receptor antibody levels were recorded at the onset of the follow-up. Subsequently, changes in 24-hour urine protein, eGFR, remission rates, and occurrence of adverse events among the three patient groups were compared at 6, 12, and 18 months post-treatment. Moreover, COX regression analysis was employed to ascertain factors influencing the remission rate of IMN. Results At the outset of the follow-up period, no significant difference existed in baseline characteristics such as gender, age, 24-hour urine protein quantification, serum albumin, serum creatinine, uric acid, eGFR, serum anti-PLA2R antibody levels, body mass index (BMI), and systolic blood pressure among the patients, indicating the comparability of three groups. After 6 months, there were no notable changes in 24-hour urine protein quantification and eGFR among the three groups; however, remission rates in the RTX and CTX groups were lower than those in the CNI group. By the 12-month mark, 24-hour urine protein quantification in the RTX group significantly decreased compared to the CTX group, with overall remission rates showing no significant differences among the three groups. By the 18-month milestone, 24-hour urine protein quantification in the RTX group remained notably lower than that in the CTX group, with significantly higher eGFR levels. Additionally, the CTX group exhibited lower 24-hour urine protein quantification compared to the CNI group, with both RTX and CTX groups displaying higher remission rates than the CNI group. Predominant adverse reactions in the RTX group included infusion reactions and infections, whereas the CNI group were associated with metabolic syndrome and elevated serum creatinine, and the CTX group primarily experienced hepatic dysfunction. Multifactorial COX regression analysis revealed an association between baseline anti-PLA2R antibodies and remission rates of IMN (HR=1.162, 95% CI 1.078-1.249). Conclusion RTX therapy for IMN exhibits a gradual onset of action, boasting a superior disease remission rate at 18 months in comparison to CNI. It demonstrates a similarity to CTX in this aspect and offers prolonged maintenance of remission. Conversely, CNI demonstrates a rapid onset of action but poses a risk of exacerbating renal impairment in patients. Notably, elevated levels of serum anti-PLA2R antibodies emerge as an independent risk factor influencing remission in IMN.

Coactivations of barrel and piriform cortices induce their mutual synapse innervations and recruit associative memory cells.

After associative learning, a signal induces the recall of its associated signal, or the other way around. This reciprocal retrieval of associated signals is essential for associative thinking and logical reasoning. For the cellular mechanism underlying this associative memory, we hypothesized that the formation of synapse innervations among coactivated sensory cortices and the recruitment of associative memory cells were involved in the integrative storage and reciprocal retrieval of associated signals. Our study indicated that the paired whisker and olfaction stimulations led to an odorant-induced whisker motion and a whisker-induced olfaction response, a reciprocal form of associative memory retrieval. In mice that showed the reciprocal retrieval of associated signals, their barrel and piriform cortical neurons became mutually innervated through their axon projection and new synapse formation. These piriform and barrel cortical neurons gained the ability to encode both whisker and olfaction signals based on synapse innervations from the innate input and the newly formed input. Therefore, the associated activation of sensory cortices by pairing input signals initiates their mutual synapse innervations, and the neurons innervated by new and innate synapses are recruited to be associative memory cells that encode these associated signals. Mutual synapse innervations among sensory cortices to recruit associative memory cells may compose the primary foundation for the integrative storage and reciprocal retrieval of associated signals. Our study also reveals that new synapses onto the neurons enable these neurons to encode memories to new specific signals.

[Triperygium wilfordii multiglucoside ameliorates kidney damage in diabetic rats by inhibiting the expressions of MBL and MASP2].

Objective To explore the effect of Triperygium wilfordii multiglucoside (TWM) on the expressions of mannose-binding lectin (MBL) and mannan-binding lectin serine peptidase 2 (MASP2) in the kidney of diabetic rats, and discuss the protective role of TWM in diabetic nephropathy and its possible mechanism. Methods Forty-five male SD rats were randomly assigned into model group (n=35) and normal control group (n=10). Rats in the normal control group were fed with regular diet, while those in the model group were fed with high-fat high-sugar diet and given an intraperitoneal injection of 40 mg/kg streptozotocin (STZ) six weeks later. The successfully induced type 2 diabetic rat models (n=33) were then randomized into DM group (n=16) and TWM treatment group (n=17) treated with TWM [10 mg/(kg.d)] for eight weeks. At the end of 14th week, the levels of blood sugar, 24-hour urine protein, serum creatinine and blood urea nitrogen were measured. Renal pathological changes were examined with PAS staining. MBL-A and MASP2 expressions were detected by immunohistochemistry in the renal tissues. The expressions of MBL1, MASP2, NF-κB and MCP-1 mRNAs were semi-quantified by real-time PCR. The expressions of MBL-A, MASP2, NF-κB and MCP-1 proteins were determined by Western blotting. Results Compared with the diabetic group, the levels of serum creatinine, blood urea nitrogen, 24-hour urine protein decreased, renal histopathology was improved, the expressions of MBL, MASP2, NF-κB and MCP-1 mRNAs and proteins were reduced in the TWM group. Correlation analysis showed that the expression of MBL was positively correlated with MASP2, NF-κB, MCP-1 and 24-hour urine protein. Conclusion MBL and MASP2 are over-expressed in the kidney of diabetic rats. TWM can ameliorate kidney damage in diabetic rats and delay the development of diabetic nephropathy by inhibiting the expressions of MBL and MASP2.

Piriform cortical glutamatergic and GABAergic neurons express coordinated plasticity for whisker-induced odor recall.

Neural plasticity occurs in learning and memory. Coordinated plasticity at glutamatergic and GABAergic neurons during memory formation remains elusive, which we investigate in a mouse model of associative learning by cellular imaging and electrophysiology. Paired odor and whisker stimulations lead to whisker-induced olfaction response. In mice that express this cross-modal memory, the neurons in the piriform cortex are recruited to encode newly acquired whisker signal alongside innate odor signal, and their response patterns to these associated signals are different. There are emerged synaptic innervations from barrel cortical neurons to piriform cortical neurons from these mice. These results indicate the recruitment of associative memory cells in the piriform cortex after associative memory. In terms of the structural and functional plasticity at these associative memory cells in the piriform cortex, glutamatergic neurons and synapses are upregulated, GABAergic neurons and synapses are downregulated as well as their mutual innervations are refined in the coordinated manner. Therefore, the associated activations of sensory cortices triggered by their input signals induce the formation of their mutual synapse innervations, the recruitment of associative memory cells and the coordinated plasticity between the GABAergic and glutamatergic neurons, which work for associative memory cells to encode cross-modal associated signals in their integration, associative storage and distinguishable retrieval.