Metastasis to the bladder from primary breast cancer: A case report and literature review.

Breast cancer is the most prevalent malignant tumor affecting women and represents the leading cause of female cancer-related mortality worldwide. Although distant organ metastasis accounts for the majority of breast cancer-related deaths, reports on bladder metastasis are limited in the existing literature. The present study describes the case of a patient with bladder metastasis originating from breast cancer. In addition, the present study also provides a review of 54 cases of similar disease that have been documented in the currently available literature. The literature review aims to elucidate the clinicopathological characteristics and therapeutic approaches for such conditions. The median time from breast cancer diagnosis to bladder metastasis was found to be 5.6 years (range, 0-28 years). The origin of the bladder metastases was predominantly invasive ductal carcinoma (IDC) accounting for 52.3% of cases, followed by invasive lobular carcinoma, accounting for 40.9% of cases. The pathology in the primary tumor was the same as the pathology of the bladder metastases in all cases. There was an 88.9% concordance rate for estrogen receptor status, while the progesterone receptor status was 83.3% and the human epidermal growth factor receptor 2 expression status was 100%. The primary initial symptoms included urinary system manifestations, such as increased frequency, urgency, dysuria, urinary incontinence, nocturia and gross hematuria. For the cystoscopic examination, the predominant findings were bladder wall thickening or masses, along with ureteral orifice masses. Overall, the present study demonstrated that the occurrence of bladder metastasis often follows the metastasis of other organs, with IDC being the most prevalent subtype. The pathological characteristics between the primary tumor and bladder metastasis exhibit a high degree of concordance.

Anlotinib succeeded in rescue therapy for hyperprogression induced by immune checkpoint inhibitors: a case report.

Immune checkpoint inhibitors are important therapeutic agents for advanced non-small-cell lung cancer. Nevertheless, these new therapies can lead to unexpected serious complications, such as hyperprogressive disease (HPD). Once HPD occurs, most patients die within 1-3 months due to the lack of effective treatments. This paper reports a patient with advanced lung cancer who experienced HPD after two cycles of third-line sintilimab treatment. Sintilimab was stopped, and rescue anlotinib treatment was started. A partial response was achieved, and the clinical signs and symptoms were relieved. The patient died 7 months later from a lung infection. Although the mechanisms are unknown, anlotinib might be effective in managing non-small-cell lung cancer with HPD after sintilimab.

Immune checkpoint inhibitors (ICIs) are important drugs against advanced lung cancer, but these new drugs can lead to some unexpected serious complications, such as an uncontrolled progression of the disease (termed hyperprogressive disease [HPD]). Once HPD occurs, most patients die within 1­3 months because of the lack of effective treatments for HPD. This article presents a patient with advanced lung cancer who experienced HPD during treatment with an ICI. The ICI treatment was stopped, and anlotinib, another drug against cancer, was started. A partial response was achieved, and the symptoms were relieved. The patient died 7 months later from a lung infection but not of his lung cancer.

Safety level assessment of shield tunneling in water rich sandy pebble strata with large particle size.

Shield tunneling method is widely used in urban metro construction. The construction stability is closely related to the engineering geological conditions. Sandy pebble strata have a loose structure and low cohesion, resulting in great engineering-induced stratigraphic disturbance. Meanwhile, the high water-abundance and strong permeability are extremely detrimental to construction safety. It is of great significance to evaluate the dangerousness of shield tunneling in water-rich pebble strata with large particle size. In this paper, risk assessment of engineering practice is carried through with Chengdu metro project in China as a case study. Referring to the special engineering situations and assessment workload, seven evaluation indices, including compressive strength of pebble layer, boulder volume content, permeability coefficient, groundwater depth, grouting pressure, tunneling speed and tunnel buried depth are selected to establish an evaluation system. A complete risk assessment framework is established based on the cloud model, AHP and entropy weight method. Further, the measured surface settlement is taken as the risk degree characterization to verify the results. This study can provide reference for method selection and evaluation system establishment in the risk assessment of shield tunnel construction in water-rich sandy pebble strata, and contribute to proposing safety management in similar engineering projects.

Safety and efficacy of anlotinib in combination with standard chemotherapy as first-line treatment for extensive-stage small cell lung cancer: A multi-center, prospective study (ACTION-2).

INTRODUCTION: Extensive stage small cell lung cancer (ES-SCLC) is associated with poor prognosis. Recently, anlotinib has demonstrated significant clinical activity as a third-line or further on treatment. This study aimed to evaluate the safety and efficacy of a combination of anlotinib and platinum-etoposide as first-line treatment in patients with ES-SCLC. METHODS: The present multi-center, single-arm, prospective study (NCT04684017) was conducted at three Chinese sites, and included patients with asymptomatic metastasis in the central nervous system. Patients were treated with up to six cycles of chemotherapy comprising etoposide with either carboplatin or cisplatin on day 1 of each cycle. Anlotinib was administered orally once daily on days 1-14 per cycle. The primary end points of the study were safety and investigator assessed objective response rate (ORR). RESULTS: A total of 101 patients were screened from August 2018 to September 2021, of which 86 who had received at least one dose of the treatment were included in the formal analysis. The median follow-up duration was 27.9 months. Complete response and partial response were observed in 2 and 73 patients, respectively, with an ORR of 87.2 % and a disease control rate of 97.7 %. Progression-free survival (PFS) and overall survival (OS) events occurred in 78 and 47 patients, respectively. The median PFS and OS were 9.0 (95 % confidence interval [CI]: 7.5-10.5) and 19 (95 % CI: 16.7-21.3) months, respectively. The incidence of grade 3 or higher adverse events (AEs) was 58.1 % and 24 patients (27.9 %) experienced serious treatment-related AEs. No fatalities consequent to AEs were recorded. CONCLUSION: Given its promising efficacy, safety profile and durability, anlotinib combined with chemotherapy deserves further investigation as first-line anticancer therapy in ES-SCLC (NCT: 04684017).

Anlotinib plus etoposide and cisplatin/carboplatin as first-line therapy for extensive-stage small cell lung cancer (ES-SCLC): a single-arm, phase II study.

Patients with extensive-stage small-cell lung cancer (ES-SCLC) have high relapse rates and poor prognosis. Anlotinib monotherapy has shown promising efficacy for patients with ES-SCLC and has a non-overlapping toxicity profile with chemotherapy. Therefore, the study aims to assess the efficacy and safety of the addition of anlotinib to platinum-chemotherapy as first-line therapy for patients with ES-SCLC. ES-SCLC patients without systemic chemotherapy and immunotherapy were recruited. Eligible patients received anlotinib (12 mg/day, on day 1-14) of a 21-day cycle, with concomitant etoposide (100 mg/m2, on day 1-3) plus cisplatin (75 mg/m2, on day 1) or carboplatin (AUC = 4-5, on day 1) for 4-6 cycles, followed by indefinite anlotinib maintenance therapy. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS). Between Jan 15, 2019 and Dec 31, 2020, 25 patients were enrolled. At the data cut-off time (November 3, 2021), the median follow-up was 14.3 months. Median PFS was 10.3 months (95% CI: 6.0-14.5) and median OS was 17.1 months (95% CI: 11.1-19.3). The ORR and DCR were 90% and 100%, respectively. The most common grade 3 or worse treatment-related adverse events were neutropenia (50%), leukopenia (35%), thrombocytopenia (25%), fatigue (10%), nausea (10%), hyponatremia (10%), anemia (10%). One patient discontinued treatment due to treatment-related adverse events. No treatment-related death occurred. Anlotinib plus platinum-chemotherapy as first-line therapy for ES-SCLC has anti-tumor activity, and showed acceptable tolerability. These results provide a basis for future randomized controlled trials.

Two-frequency chimera state in a ring of nonlocally coupled Brusselators.

Chimera states, which consist of coexisting domains of spatially coherent and incoherent dynamics, have been intensively investigated in the past decade. In this work, we report a special chimera state, 2-frequency chimera state, in one-dimensional ring of nonlocally coupled Brusselators. In a 2-frequency chimera state, there exist two types of coherent domains and oscillators in different types of coherent domains have different mean phase velocities. We present the stability diagram of 2-frequency chimera state and study the transition between the 2-frequency chimera state and an ordinary 2-cluster chimera state.

Aminopyridine derivatives controlled the assembly and various properties of Cu-BTC metal-organic frameworks.

Three Cu(ii) metal-organic frameworks (MOFs) based on 1,3,5-benzenetricarboxylic acid (H3BTC) and three aminopyridine derivatives with different lengths and coordination groups, namely [Cu2(3-azpy)(HBTC)(H2BTC)(µ3-OH)(H2O)2] (), [Cu2(3-ppca)(BTC)(H2O)3]·H2O (), [Cu2(3-ebpba)(BTC)(µ3-OH)] () [3-azpy = 3,3'-azopyridine, 3-ppca = N-(pyridin-3-yl)pyrazine-2-carboxamide, 3-ebpba = (E)-4,4'-(ethene-1,2-diyl)bis(N-pyridin-3-yl)benzamide)], have been hydrothermally synthesized and structurally characterized by elemental analyses, IR, PXRD, TG and single crystal X-ray diffraction analyses. The title MOFs display versatile structural features with 2D and 3D frameworks. Complex exhibits a 2D layer, which is constructed from the 3-azpy bridging ligands and a 1D ladder-like Cu-BTC chain with tetranuclear copper clusters. The 3-azpy was in situ transformed from 3-aminopyridine under the hydrothermal conditions. Complex shows a rare 3D framework, which features a (3,3,3,3)-connected topology with a Schläfli symbol of {8·10·12}2{8(2)·10}2. Complex exhibits a (3,8)-connected {4·6(2)}2{4(2)·6(22)·7·8(3)} topology based on tetranuclear copper clusters. The influence of aminopyridine-based ligands on the structures and properties of the title complexes has been discussed. The electrocatalytic and photocatalytic properties of complexes have also been investigated in detail.

A very rare case of trisomy 4q32.3-4q35.2 and trisomy 21q11.2-21q22.11 in a patient with recombinant chromosomes 4 and 21.

We report the case of a patient with a clinical phenotype consistent with Down Syndrome (DS) who has a novel karyotypic abnormality. Karyotypic analyses were performed to investigate the cause of two spontaneous abortions. A balanced translocation between chromosomes 4 and 21 was identified, along with an additional abnormal chromosome 21. We performed high-resolution banding, comparative genomic hybridization (CGH), and FISH studies in both the patient and her mother to define the abnormality and determine its origin. CGH revealed a gain in copy number on the long arm of chromosome 4, spanning at least 24.4 Mb, and a gain in copy number on the long arm of chromosome 21, spanning at least 16.2 Mb. FISH analysis using a chromosome 21 centromere probe and chromosome 4 long arm telomere (4pter) probe confirmed the origin of the marker chromosome. It has been confirmed by the State Key Laboratory of Medical Genetics of China that this is the first reported instance of the karyotype 47,XX,t(4;21)(q31.3;q11.2),+der(21)t(4;21)mat reported in the world.

Antinociceptive effects of systemic paeoniflorin on bee venom-induced various 'phenotypes' of nociception and hypersensitivity.

Paeoniflorin (PF), one of the active chemical compounds identified from the root of Paeonia lactiflora Pall, has been well-established to exhibit various neuroprotective actions in the central nervous system (CNS) after long-term daily administration. In the present study, by using the bee venom (BV) model of nociception and hypersensitivity, antinociceptive effects of PF were evaluated by intraperitoneal administration in conscious rats. When compared with saline control, systemic pre- and post-treatment with PF resulted in an apparent antinociception against both persistent spontaneous nociception and primary heat hypersensitivity, while for the primary mechanical hypersensitivity only pre-treatment was effective. Moreover, pre- and early post-treatment with PF (5 min after BV injection) could successfully suppress the occurrence and maintenance of the mirror-image heat hypersensitivity, whereas late post-treatment (3 h after BV) did not exert any significant impact. In the Rota-Rod treadmill test, PF administration did not affect the motor coordinating performance of rats. Furthermore, systemic PF application produced no significant influence upon BV-induced paw edema and swelling. Finally, the PF-produced antinociception was likely to be mediated by endogenous opioid receptors because of its naloxone-reversibility. Taken together, these results provide a new line of evidence showing that PF, besides its well-established neuroprotective actions in the CNS, is also able to produce analgesia against various 'phenotypes' of nociception and hypersensitivity via opioid receptor mediation.

Nociceptive stimulus modality-related difference in pharmacokinetic-pharmacodynamic modeling of morphine in the rat.

Pharmacokinetics (PK)-pharmacodynamics (PD) modeling, the mathematical description of the relationship between PK and PD, can estimate and predict relevant parameters associated with onset, magnitude and time courses of dose-concentration-effect of a drug. In this report, we introduce a new nonsteady-state and time-dependent PK-PD modeling of a single dose of morphine in which time courses of concentration of unconjugated and estimated conjugated morphine in compartments of either plasma or biophase (cerebrospinal fluid, CSF) and multiple anti-nociceptive effects across thermal and mechanical stimulus modalities in rats were studied. The results showed that: (1) both intragastric and intraperitoneal administration of a single dose of morphine resulted in a differential anti-nociceptive effect in both magnitude and time course of the drug between thermal and mechanical painful stimuli (anti-mechanical pain effect was 2-3 fold stronger than anti-thermal pain effect, P < 0.01); (2) the PK data showed that the area under concentration-time curves of conjugated morphine was 4.5 and 2.0 fold bigger than unconjugated morphine in either plasma and biophase compartments, suggesting that the PK processes of unconjugated morphine are different from that of conjugated morphine; (3) the PD data also showed a change in PD characteristics of unconjugated and conjugated morphine across systemic and biophasic compartments for anti-mechanical pain effect, while there was no change at all for anti-thermal pain effect; (4) the difference in analgesia of a single dose of morphine across thermal and mechanical stimulus modalities was well reflected by the difference in the nonsteady-state and time-dependent PK-PD modeling, namely, the clockwise hysteresis loop model well represents the relationship of the time course between unconjugated/conjugated morphine concentration (both plasma and biophase) and anti-thermal pain effect, while the counter-clockwise hysteresis loop model well represents that between conjugated morphine concentration (mainly in biophase) and anti-mechanical pain effect. Taken together, the multiple PD-PK modeling is more useful in estimation and prediction of onset, magnitude and time courses of concentration-multiple pharmacological effects of morphine than simple PK or PD models, and establishment of various multiple PD-PK modeling might also be more useful in optimizing clinical use of existing drugs as well as new drugs for analgesia or treatment of other diseases.