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Objective: Idiopathic infantile hypercalcemia (IIH) is a rare disorder of PTH-independent hypercalcemia. CYP24A1 and SLC34A1 gene mutations cause two forms of hereditary IIH. In this study, the clinical manifestations and molecular aspects of six new Chinese patients were investigated. Methods: The clinical manifestations and laboratory study of six patients with idiopathic infantile hypercalcemia were analyzed retrospectively. Results: Five of the patients were diagnosed with hypercalcemia, hypercalciuria, and bilateral medullary nephrocalcinosis. Their clinical symptoms and biochemical abnormalities improved after treatment. One patient presented at age 11 years old with arterial hypertension, hypercalciuria and nephrocalcinosis, but normal serum calcium. Gene analysis showed that two patients had compound heterozygous mutations of CYP24A1, one patient had a monoallelic CYP24A1 variant, and three patients had a monoallelic SLC34A1 variant. Four novel CYP24A1 variants (c.116G > C, c.287T > A, c.476G > A and c.1349T > C) and three novel SLC34A1 variants (c.1322 A > G, c.1697_1698insT and c.1726T > C) were found in these patients. Conclusions: A monoallelic variant of CYP24A1 or SLC34A1 gene contributes to symptomatic hypercalcemia, hypercalciuria and nephrocalcinosis. Manifestations of IIH vary with onset age. Hypercalcemia may not necessarily present after infancy and IIH should be considered in patients with nephrolithiasis either in older children or adults. [ABSTRACT FROM AUTHOR]

Aims: Anxiety disorders associated with pain are a common health problem. However, the underlying mechanisms remain poorly understood. We aimed to investigate the role of paraventricular nucleus (PVN)‐central nucleus of the amygdala (CeA) oxytocinergic projections in anxiety‐like behaviors induced by inflammatory pain. Methods: After inflammatory pain induction by complete Freund's adjuvant (CFA), mice underwent elevated plus maze, light–dark transition test, and marble burying test to examine the anxiety‐like behaviors. Chemogenetic, optogenetic, and fiber photometry recordings were used to modulate and record the activity of the oxytocinergic projections of the PVN‐CeA. Results: The key results are as follows: inflammatory pain‐induced anxiety‐like behaviors in mice accompanied by decreased activity of PVN oxytocin neurons. Chemogenetic activation of PVN oxytocin neurons prevented pain‐related anxiety‐like behaviors, whereas inhibition of PVN oxytocin neurons induced anxiety‐like behaviors in naïve mice. PVN oxytocin neurons projected directly to the CeA, and microinjection of oxytocin into the CeA blocked anxiety‐like behaviors. Inflammatory pain also decreased the activity of CeA neurons, and optogenetic activation of PVNoxytocin‐CeA circuit prevented anxiety‐like behavior in response to inflammatory pain. Conclusion: The results of our study suggest that oxytocin has anti‐anxiety effects and provide novel insights into the role of PVNoxytocin‐CeA projections in the regulation of anxiety‐like behaviors induced by inflammatory pain. [ABSTRACT FROM AUTHOR]

Background: To analysis the clinical outcomes of concurrent chemoradiotherapy (CCRT) alone based on 10-year results for loco-regionally advanced nasopharyngeal carcinoma (LANPC), so as to provide evidence for individualized treatment strategy and designing appropriate clinical trial for different risk LANPC patients. Methods: Consecutive patients with stage III-IVa (AJCC/UICC 8th) were enrolled in this study. All patients received radical intensity-modulated radiotherapy (IMRT) and concurrent cisplatin chemotherapy (CDDP). The hazard ratios (HRs) of death risk in patients with T3N0 was used as baseline, relative HRs were calculated by a Cox proportional hazard model to classify different death risk patients. Survival curves for the time-to-event endpoints were analyzed by the Kaplan–Meier method and compared using the log-rank test. All statistical tests were conducted at a two-sided level of significance of 0.05. Results: A total of 456 eligible patients were included. With 12-year median follow-up, 10-year overall survival (OS) was 76%. 10-year loco-regionally failure-free survival (LR-FFS), distant failure-free survival (D-FFS) and failure-free survival (FFS) were 72%, 73% and 70%, respectively. Based on the relative hazard ratios (HRs) of death risk, LANPC patients were classified into 3 subgroups, low-risk group (T1-2N2 and T3N0-1) contained 244 patients with HR < 2; medium-risk group (T3N2 and T4N0-1) contained 140 patients with HR of 2 – 5; high-risk group (T4N2 and T1-4N3) contained 72 patients with HR > 5. The 10-year OS for patients in low-, medium-, and high-risk group were 86%, 71% and 52%, respectively. Significantly differences of OS rates were found between each of the two groups (low-risk group vs. medium-risk group, P < 0.001; low-risk group vs. high-risk group, P < 0.001; and medium-risk group vs. high-risk group, P = 0.002, respectively). Grade 3–4 late toxicities included deafness/otitis (9%), xerostomia (4%), temporal lobe injury (5%), cranial neuropathy (4%), peripheral neuropathy (2%), soft tissue damage (2%) and trismus (1%). Conclusions: Our classification criteria demonstrated that significant heterogeneity in death risk among TN substages for LANPC patients. IMRT plus CDDP alone maybe suitable for low-risk LANPC (T1-2N2 or T3N0-1), but not for medium- and high-risk patients. These prognostic groupings provide a practicable anatomic foundation to guide individualized treatment and select optimal targeting in the future clinical trials. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to explore the clinical value of adjuvant chemotherapy (ACT) following concurrent chemo-radiotherapy (CCRT) and induction chemotherapy (ICT) in loco-regionally advanced nasopharyngeal carcinoma (LANC). Methods: We included 839 newly diagnosed LANC patients in this study. ICT plus CCRT (ICT + CCRT group) was administered to 443 patients, and 396 patients received ACT after ICT plus CCRT (ICT + CCRT + ACT group). Univariate and multivariate Cox regression analyses were carried out. Furthermore, propensity score matching (PSM) was applied to balance the study and control groups. Results: A total of 373 pairs of LANC patients were obtained after PSM analysis. We found that ACT following ICT + CCRT has no significant effect on improving the survival of LANC patients. By further exploring the ICT + CCRT + ACT treatment protocol, we excluded N0–1-positive patients and re-performed PSM in the ICT + CCRT and ICT + CCRT + ACT groups. Each group consisted of 237 patients. Kaplan–Meier analysis revealed that there were differences between the ICT + CCRT and ICT + CCRT + ACT groups in terms of the 5-year overall survival (OS) (78.9% vs. 85.0%, P = 0.034), disease-free survival (DFS) (73.4% vs. 81.7%, P = 0.029), and distant metastasis-free survival (DMFS) (84.9% vs. 76.0%, P = 0.019). In addition, the ICT + CCRT + ACT group had a higher incidence of grade 3/4 acute leukocytopenia/neutropenia. Conclusion: Compared with ICT + CCRT, ACT following ICT plus CCRT can reduce distant metastasis of N2–3-positive LANC and improve the OS and DFS. The results demonstrated the feasibility and clinical utility of ACT following ICT plus CCRT. [ABSTRACT FROM AUTHOR]

Purpose: To investigate whether the addition of fluorouracil to docetaxel and cisplatin induction chemotherapy (IC) can truly improve the prognosis of patients with locoregionally advanced nasopharyngeal carcinoma (NPC). Methods: A total of 801 patients newly diagnosed with non‐metastatic locoregionally advanced NPC were included as the subjects. In this study, propensity score matching (PSM) was used for analysis of overall survival (OS), distant metastasis‐free survival (DMFS), progression‐free survival (PFS) and locoregional relapse‐free survival (LRRFS), and the chi‐squared test or Fisher's exact test was used to investigate toxic reactions. Results: Patients received treatment with docetaxel and cisplatin (TP) or docetaxel, cisplatin and fluorouracil (TPF). With a median follow‐up time of 60 months (range: 5–124 months), the TPF group had better 5‐year OS (84.7% vs 79.0%; P = 0.037), PFS (84.6% vs 76.8%; P = 0.008) and DMFS (89.5% vs 82.3%; P = 0.004) than the TP group. After PSM, 258 patients were matched in each cohort. The Kaplan–Meier analysis showed that the 5‐year OS, PFS and DMFS were 85.5%, 84.2% and 89.2%, respectively, in the TPF group, higher than the 80.8%, 75.0% and 81.4%, respectively, in the TP group (P = 0.048, 0.009 and 0.006, respectively). Moreover, the multivariate analysis revealed that different IC regimens were independent prognostic factors for PFS and DMFS (P = 0.014 and 0.010, respectively). Conclusion: This study found that compared with the TP regimen, TPF induction chemotherapy is associated with improved survival in patients with locoregionally advanced NPC. TPF can produce more mucosal and nausea/vomiting adverse reactions than TP. [ABSTRACT FROM AUTHOR]