The efficacy and safety of different doses of calcitriol combined with neutral phosphate in X-linked hypophosphatemia: a prospective study.

The present study was the first prospective cohort evaluated the efficacy and safety of different doses of calcitriol in XLH children. The results suggested that a dose of 40 ng/kg/day calcitriol, compared with 20 ng/kg/day, was more effective in relieving the rickets, with similar safety outcomes. Further investigations were expected to set more dose groups. INTRODUCTION: Dose recommended for calcitriol in X-linked hypophosphatemia (XLH) varies in different studies. Therefore, we aimed to compare the efficacy as well as the safety of 20 ng/kg/d and 40 ng/kg/d calcitriol in Chinese XLH pediatrics population. METHODS: A 2-year, randomized, open-label, prospective study recruited 68 XLH children, which were randomized to receive either 40 ng/kg/day or 20 ng/kg/day calcitriol. Efficacy endpoints were the total Thacher ricket severity score (RSS) change from baseline to month 12 and 24, the difference in serum TALP level, fasting serum phosphate level, body height Z-score, and frequency of dental abscess. Safety assessments were done using renal ultrasound nephrocalcinosis grades (0-4), fasting serum and 24 h urine calcium level, and the occurrence of hyperparathyroidism. RESULTS: The decrease in the total RSS from baseline was more significant in the high-dose group at 12 (difference 0.87, p = 0.049) and 24 month (difference 1.23, p = 0.011). The serum TALP level was significantly lower in the high-dose group at 6 months. Pi level, height Z-score change, frequency of dental abscess and ratio of de novo nephrocalcinosis were comparable. A lower incidence of secondary hyperparathyroidism was seen in the high-dose group (p < 0.0001). CONCLUSION: For the first time in this prospective cohort, 40 ng/kg/d calcitriol was shown to be the more effective therapy in XLH children than the 20 ng/kg/d. Moreover, 40 ng/kg/d calcitriol was not associated with increasing adverse events. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT 03,820,518.

[Study on the feature of cortical auditory evoked potential under different auditory tasks in cochlear implant children].

Objective: To investigate the variation regularity and influencing factors of cortical auditory evoked potential (CAEP) evoked by pure tone, syllable and tone stimuli in cochlear implant (CI) children. Methods: Cortical auditory evoked potential (CAEP) responses were collected from 46 CI children in the sound field. Pure tones with frequencies of 1 kHz and 2 kHz were used as the standard and the deviant respectively in the pure tone stimulation condition. The Chinese Mandarin tokens/ba/-/pa/and/ba1/-/ba4/pairs were used as the stimuli respectively in the syllable and tone stimulation condition. The latency, amplitude and presence rate of P1 and mismatch negative(MMN) were obtained and the correlation between the difficulty of auditory task, the age of hearing month, the duration of severe-profound hearing loss, the wearing history of hearing aid before CI, the hearing threshold of the better ear before CI and the latency and amplitude of P1 and MMN were analyzed. All statistical analyses and figures were conducted using SPSS 25.0. Results: The P1 presence rate of pure tone, syllable and tone group was 100% (17/17), 100% (13/13) and 75.0% (12/16), respectively, with significant difference (χ²=8.214, P=0.016). There was significant difference between pure tone group and tone group (χ²=4.836, P=0.028), but no significant difference between pure tone group and syllable group, syllable group and tone group. The MMN presence rate of pure tone, syllable and tone group was 94.1% (16/17), 84.6% (11/13) and 62.5% (10/16), respectively, but no significant difference among the three groups with different auditory tasks(χ²=0.066, P=0.066). No significant difference was observed among the three groups of different auditory tasks in the latency and amplitude of P1 and MMN. Multiple linear regression analysis showed that the latency of P1 was positively correlated with the difficulty of auditory task and the hearing threshold of the better ear before CI, and negatively correlated with hearing age and the history of hearing aid before CI. The latency of MMN was positively correlated with the difficulty of auditory task, and negatively correlated with hearing age. Conclusions: The P1 presence rate of pure tone auditory task is significantly higher than that of tone auditory task. The difficulty of auditory task, hearing age, the history of hearing aid before CI, and the hearing threshold of the better ear before CI has significant effects on the P1 latency. The difficulty of auditory task and hearing age has significant effects on the MMN latency.

RN1, a novel galectin-3 inhibitor, inhibits pancreatic cancer cell growth in vitro and in vivo via blocking galectin-3 associated signaling pathways.

Galectin-3 (Gal-3) has been implicated in pancreatic ductal adenocarcinoma (PDAC), and its candidacy as a therapeutic target has been evaluated. Gal-3 is widely upregulated in tumors, and its expression is associated with the development and malignancy of PDAC. In the present study, we demonstrate that a polysaccharide, RN1, purified from the flower of Panax notoginseng binds to Gal-3 and suppresses its expression. In addition, RN1 markedly inhibits PDAC cells growth in vitro, in vivo and in patient-derived xenografts. Mechanistically, RN1 binds to epidermal growth factor receptor (EGFR) and Gal-3, thereby disrupting the interaction between Gal-3 and EGFR and downregulating extracellular-related kinase (ERK) phosphorylation and the transcription factor of Gal-3, Runx1 expression. Inhibiting the expression of Runx1 by RN1, suppresses Gal-3 expression and inactivates Gal-3-associated signaling pathways, including the EGFR/ERK/Runx1, BMP/smad/Id-3 and integrin/FAK/JNK signaling pathways. In addition, RN1 can also bind to bone morphogenetic protein receptors (BMPR1A and BMPR2) and block the interaction between Gal-3 and the BMPRs. Thus, our results suggest that a novel Gal-3 inhibitor RN1 may be a potential candidate for human PDAC treatment via multiple targets and multiple signaling pathways.

[Studies on the chemical constituents of the herba of Cuscuta chinensis].

The chemical constituents of the herb of Cuscuta chinensis Lam. were investigated. Five compounds were isolated from petroleum ether and chloroform fraction. Their structures were identified as beta-sitosterol, d-sesamin, 9(R)-hydroxy-d-sesamin, d-pinoresinol and daucosterol by chemical and spectroscopical methods. All these compounds were isolated from the stem for the first time.

Panax ginseng extract improves the scopolamine-induced disruption of 8-arm radial maze performance in rats.

The effects of Panax ginseng ethanol extract and its water (WSF)- and lipid-soluble (LSF) fractions on the scopolamine-induced disruption of radial maze performance in rats were examined. Ginseng root was refluxed with ethanol, and WSF and LSF were prepared from this ethanol extract. Scopolamine (0.075-0.3 mg/kg, i.p.) dose-dependently impaired the maze performance. However, the oral administration of Panax ginseng ethanol extract and WSF (2-8 g dried root/kg) 90 min before testing improved the maze performance disrupted by scopolamine (0.3 mg/kg) in a dose-dependent manner, but LSF failed to attenuate the disruption. These data suggest that ginseng extract possesses a beneficial effect regarding spatial cognitive impairment and that the water-soluble fraction of ginseng extract mainly contributes to the effect of the ethanol extract.

Panax ginseng extract improves the performance of aged Fischer 344 rats in radial maze task but not in operant brightness discrimination task.

The effect of Panax ginseng extract on the learning performance of aged Fischer 344 rats using the 8-arm radial maze task and the operant discrimination task was examined. Aged rats showed significantly impaired learning performance in both tasks. Daily administration of ginseng extract (8 g/kg/d, p.o. for 12-33 d) ameliorated the impairment of learning performance in the radial maze task but not in the operant discrimination task. These results suggest that subchronic treatment with ginseng extract improves spatial cognitive impairment in aged rats.

[Research on sterilization of pathogens by high electrostatic voltage method].

An experimental research has been carried out on the sterilization of four kinds of pathogens by high electrostatic method along with an inquiry into the influence of voltage waveform and the treated time on sterilization. It is concluded that pathogens can be killed efficiently by corona discharge field.

A kampo prescription, shimotsu-to, improves scopolamine-induced spatial cognitive deficits in rats.

The effect of a Kampo (traditional Chinese medicine) prescription, Shimotsu-to, on spatial cognitive deficits produced by scopolamine was examined using an eight-arm radial maze and a T-maze. Scopolamine (SCOP; 0.075-0.3 mg/kg, ip) dose-dependently disrupted the radial maze performance. Single doses of Shimotsu-to (0.5 and 1.0 g/kg, po) as well as physostigmine (0.15 and 0.3 mg/kg, ip) improved the SCOP (0.3 mg/kg)-induced performance deficits in a dose-dependent manner. Shimotsu-to administered for 1 week in drinking water (0.5 and 1.0 g/kg/day) also exhibited dose-dependent reversal of SCOP-induced impairments in the radial maze performance. The same treatment improved SCOP (0.2 mg/kg)-induced impairments in T-maze delayed alternation performance. These data clearly demonstrated the beneficial effects of Shimotsu-to on spatial cognition.