Analysis of disulfidptosis- and cuproptosis-related LncRNAs in modulating the immune microenvironment and chemosensitivity in colon adenocarcinoma.

The main objective was to establish a prognostic model utilising long non-coding RNAs associated with disulfidptosis and cuproptosis. The data for RNA-Sequence and clinicopathological information of Colon adenocarcinoma (COAD) were acquired from The Cancer Genome Atlas. A prognostic model was constructed using Cox regression and the Least Absolute Shrinkage and Selection Operator method. The model's predictive ability was assessed through principal component analysis, Kaplan-Meier analysis, nomogram etc. The ability of identifying the rates of overall survival, infiltration of immune cells, and chemosensitivity was also explored. In vitro experiments were conducted for the validation of differential expression and function of lncRNAs. A disulfidptosis and cuproptosis-related lncRNA prognostic model was constructed. The prognostic model exhibits excellent independent predictive capability for patient outcomes. Based on the authors' model, the high-risk group exhibited higher tumour mutation burdened worse survival. Besides, differences in immune cell infiltration and responsiveness to chemotherapeutic medications exist among patients with different risk scores. Furthermore, aberrant expressions in certain lncRNAs have been validated in HCT116 cells. In particular, FENDRR and SNHG7 could affect the proliferation and migration of colorectal cancer cells. Our study developed a novel prognostic signature, providing valuable insights into prognosis, immune infiltration, and chemosensitivity in COAD patients.

Postoperative pain after different doses of remifentanil infusion during anaesthesia: a meta-analysis.

BACKGROUND: This meta-analysis aimed to explore the correlation between the different doses of remifentanil-based anaesthesia and postoperative pain in randomised trials. METHODS: The electronic databases including PubMed, Cochrane, clinical trial registries, and Google Scholar were searched up to November 2022 for randomised controlled trials (RCTs) that assessed the dose dependent efficacy of remifentanil for postoperative pain intensity and hyperalgesia. RESULTS: 31 studies involving 2019 patients were included for analysis. Compared with the high remifentanil dose administration, patients in low doses showed less postoperative pain intensity at 1-2 h (weighted mean differences (WMD): 0.60, 95% CI, 0.05 to 1.15), 3-8 h (WMD: 0.38, 95% CI, 0.00 to 0.75), 24 h (WMD: 0.26, 95% CI, 0.04 to 0.48) and 48 h (WMD: 0.32, 95% CI, 0.09 to 0.55). Remifentanil-free regimen failed to decrease the pain score at 24 h (WMD: 0.10, 95% CI, -0.10 to 0.30) and 48 h (WMD: 0.15, 95% CI, -0.22 to 0.52) in comparison with remifentanil-based anaesthesia. After excluding trials with high heterogeneity, the dose of the remifentanil regimen was closely correlated with the postoperative pain score (P=0.03). In addition, the dose of the remifentanil regimen was not associated with the incidence of postoperative nausea and vomiting (PONV) (P=0.37). CONCLUSIONS: Our meta-analysis reveals that the low dose of remifentanil infusion is recommendable for general anaesthesia maintenance. No evidence suggests that remifentanil-free regimen has superiority in reducing postoperative pain. Moreover, remifentanil doesn't have a dose dependent effect in initiating PONV. TRIAL REGISTRATION: The protocol of present study was registered with PROSPERO (CRD42022378360).

Effect of superior laryngeal nerve block in alleviating sore throat after application of i-gel supraglottic airway: a randomized controlled trial.

BACKGROUND: Postoperative sore throat (POST) is a common complaint after supraglottic airway device (SAD) application. Internal branch of the superior laryngeal nerve (iSLN) block has the potential to alleviate POST. The aim of this trial was to explore the effect of iSLN block in alleviating sore throat, as well as to identify the potential risk factors for POST after SAD insertion. METHODS: One hundred thirty-four patients scheduled for elective gynecological surgery were randomized to either group T: tetracaine syrup (1%) for local lubrication on i-gel supraglottic device (n = 67) or group B: i-gel insertion with water based lubricant on it and followed by bilateral iSLN block (ropivacaine, 0.375%, 2 ml for each side) (n = 67). Under ultrasound guidance, iSLN was exposed below thyrohyoid membrane. The primary outcome was the intensity of sore throat at 6 h after surgery. In addition, POST score at 0.5 h and 24 h, the severity of postoperative swallowing discomfort, acoustic analysis and complications were measured. RESULTS: Compared with tetracaine syrup for local lubrication, iSLN block resulted in a reduced intensity of POST at 0.5 h (P = 0.044, OR = 1.99, 95%CI 1.02 to 3.88) and 6 h (P < 0.001, OR = 5.07, 95%CI 2.53 to 10.14) after surgery, as well as less severity of swallowing discomfort (P < 0.001, OR = 2.21, 95%CI 1.63 to 2.99) and cough (P = 0.039, OR = 1.97, 95%CI 1.04 to 3.73). The patients after iSLN block presented lower jitter and shimmer value in acoustic analysis at 6 h after surgery (P < 0.001). CONCLUSIONS: iSLN block was effective in alleviating POST, improving voice function, as well as reducing postoperative swallowing discomfort and coughing. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2000037974) on 8th Sept 2020.

Retrospective Study of Three Cases of Congenital Leukemia with Clinical Presentations and Particular Cytogenetic Abnormality.

BACKGROUND: The goal is to assess the prognosis of cytogenetic abnormality, because cytogenetic abnormality is rarely encountered in clinical practice. METHODS: We retrospectively report three cytogenetic abnormality cases with clinical, cytogenetic, and genetic characteristic. RESULTS: All cases occurred within one month of birth and had prominent hepatosplenomegaly, including acute myeloid leukemia (case 1, case 2) and acute leukemia (case 3). Moreover, case 1 appeared as leukemia cutis at birth, case 2 was born with respiratory distress, and both showed hyperleukocytosis. The R-banded karyotype detected cytogenetic abnormality in three cases, case 1 with 46,XY,t(8;12)(q21;p13), case 2 with 47,XX,+21 and case 3 with 46,XY,t(6;X)(q22:p12), respectively. Especially in case 1, reverse transcription-polymerase chain reaction analysis showed MLL-AF10 rearranged. CONCLUSIONS: In our studies, all cases had not received chemotherapy and survived about 1 - 2 months. It suggests that cytogenetic disorders are closely related to disease development and likely result in fatal outcome if untreated. Thus, we proposed that a proper treatment decision is urgently needed in congenital leukemia.

Comparison of efficacy, safety, and patient satisfaction between thermal ablation, conventional/open thyroidectomy, and endoscopic thyroidectomy for symptomatic benign thyroid nodules.

PURPOSE: Thermal ablation (TA) is a minimally invasive treatment method for symptomatic benign thyroid nodules (BTNs). This study aimed to evaluate the value of TA by comparing the efficacy, safety, and patient satisfaction with conventional/open thyroidectomy (ConT) and endoscopic thyroidectomy (ET) for symptomatic BTNs. METHODS: Patients with symptomatic BTNs who underwent ConT, ET, or TA therapy between January 2018 and January 2020 were included. Pre-operation data of the two comparisons (TA vs. ConT and TA vs. ET) was balanced using propensity score matching. The technique efficacy (volume reduction ratio ≥50%), nodule disappearance, and regrowth rate were calculated after ablation. The operation and hospitalization time, medical cost, complications, post-operative symptoms, and cosmetic scores were recorded and compared. Patient satisfaction was evaluated using a telephone survey. RESULTS: After a median 19-month follow-up (range, 12-36 months), the technique efficacy rate, nodule disappearance, and regrowth rate were 93.2% (119/129), 6.8% (10/129), and 0.8% (1/129), respectively. Operation time, hospitalization time, and medical costs were less for patients in the TA group than for patients in the ConT and ET groups (all p < 0.001). The incidence of complications, post-operative symptoms, cosmetic scores, and overall satisfaction were not significantly different among groups (all p > 0.05). Post-operative hypothyroidism was less frequent in the TA group than in the ConT and ET groups (all p < 0.05). CONCLUSIONS: Compared to ConT and ET, TA has comparable efficacy, safety, and patient satisfaction and exhibits greater protection of thyroid function for the treatment of symptomatic BTNs.

Characterization of the Composition and Biological Activity of the Venom from Vespa bicolor Fabricius, a Wasp from South China.

We analyzed, for the first time, the major components and biological properties of the venom of Vespa bicolor, a wasp from South China. Using HPLC and SDS-PAGE, combined with LC-MS/MS, MALDI-TOF-MS, and NMR data to analyze V. bicolor venom (VBV), we found that VBV contains three proteins (hyaluronidase A, phospholipase A1 (two isoforms), and antigen 5 protein) with allergenic activity, two unreported proteins (proteins 5 and 6), and two active substances with large quantities (mastoparan-like peptide 12a (Vb-MLP 12a), and 5-hydroxytryptamine (5-HT)). In addition, the antimicrobial activity of VBV was determined, and results showed that it had a significant effect against anaerobic bacteria. The minimum inhibitory concentration and minimum bactericidal concentration for Propionibacterium acnes were 12.5 µg/mL. Unsurprisingly, VBV had strong antioxidant activity because of the abundance of 5-HT. Contrary to other Vespa venom, VBV showed significant anti-inflammatory activity, even at low concentrations (1 µg/mL), and we found that Vb-MLP 12a showed pro-inflammatory activity by promoting the proliferation of RAW 264.7 cells. Cytotoxicity studies showed that VBV had similar antiproliferative effects against all tested tumor cell lines (HepG2, Hela, MCF-7, A549, and SASJ-1), with HepG2 being the most susceptible. Overall, this study on VBV has high clinical importance and promotes the development of Vespa bicolor resources.

Chemical approach to generating long-term self-renewing pMN progenitors from human embryonic stem cells.

Spinal cord impairment involving motor neuron degeneration and demyelination can cause lifelong disabilities, but effective clinical interventions for restoring neurological functions have yet to be developed. In early spinal cord development, neural progenitors of the motor neuron (pMN) domain, defined by the expression of oligodendrocyte transcription factor 2 (OLIG2), in the ventral spinal cord first generate motor neurons and then switch the fate to produce myelin-forming oligodendrocytes. Given their differentiation potential, pMN progenitors could be a valuable cell source for cell therapy in relevant neurological conditions such as spinal cord injury. However, fast generation and expansion of pMN progenitors in vitro while conserving their differentiation potential has so far been technically challenging. In this study, based on chemical screening, we have developed a new recipe for efficient induction of pMN progenitors from human embryonic stem cells. More importantly, these OLIG2+ pMN progenitors can be stably maintained for multiple passages without losing their ability to produce spinal motor neurons and oligodendrocytes rapidly. Our results suggest that these self-renewing pMN progenitors could potentially be useful as a renewable source of cell transplants for spinal cord injury and demyelinating disorders.

Semi-solid extrusion 3D printing ODFs: an individual drug delivery system for small scale pharmacy.

Orodispersible films (ODFs) are promising drug delivery systems for customized medicines as it provide an alternative approach to increase consumer acceptance by advantages of rapid dissolution and administration without water. The aim of this study was to develop a platform to support the realization of tailored treatments suitable for the extemporaneous production of ODFs by semi-solid extrusion (SSE) 3D printing (3DP). Hydroxypropyl methyl cellulose (HPMC) was used as the polymer of ODFs, and levocetirizine hydrochloride was used as the model drug. The optimal formulation was HPMC:API:PS:maltitol:sucralose at a ratio of 64:10:10:15:1. Seventeen percent HPMC solution and optimal formulation were used to prepare film precursors. The impact of dynamic viscosities and fluid mechanics difference on printing applicability was discussed. The ODFs of cube designs with aimed dose of 1.25 mg, 2.5 mg, and 5 mg were printed by SSE 3DP. Good linear relationship between theoretical model volume and drug content (R2 = 0.999) and good dose accuracy indicate that 3DP is a suitable method for preparing individualized ODFs.

Applications of excipients in the field of 3D printed pharmaceuticals.

The aim of this study was to determine the effect of varying excipient content on the formation and physical properties of 3 D printed tablets. Fifteen different excipient preparations were formed into tablets with radii of 5 mm and thickness of 2 mm, using binder jetting (BJ). The tablets were analyzed by assessing visual and microstructural appearance, friability, hardness, and disintegration time. We found that filling agents with high water solubility (e.g. D-sucrose), binding agents with a high viscosity in solution (e.g. polyethylene glycol 4000) and moistening agent with higher water content can increase the bonding strength and hardness of the 3 D printed tablets and prolonged their disintegration time. This work has demonstrated that the type of excipient and its concentration affects the properties of the 3 D printed tablet. This article may be used as a guide for elucidation of the effects of using conventional tablet excipients in the field of 3 D printed pharmaceuticals. The present work should enable the identification of excipients that satisfy requirements, reduce analysis time, and improve efficiency.

Expression of DCX and Transcription Factor Profiling in Photothrombosis-Induced Focal Ischemia in Mice.

Adult neurogenesis is present in the dentate gyrus and the subventricular zone in mammalian brain under physiological conditions. Recently, adult neurogenesis has also been reported in other brain regions after brain injury. In this study, we established a focal striatal ischemic model in adult mice via photothrombosis (PT) and investigated how focal ischemia elicits neurogenesis in the striatum. We found that astrocytes and microglia increased in early post-ischemic stage, followed by a 1-week late-onset of doublecortin (DCX) expression in the striatum. The number of DCX-positive neurons reached the peak level at day 7, but they were still observed at day 28 post-ischemia. Moreover, Rbp-J (a key effector of Notch signaling) deletion in astrocytes has been reported to promote the neuron regeneration after brain ischemia, and we provided the change of gene expression profile in the striatum of astrocyte-specific Rbp-J knockout (KO) mice glial fibrillary acidic protein (GFAP-CreER:Rbp-Jfl/fl), which may help to clarify detailed potential mechanisms for the post-ischemic neurogenesis in the striatum.

Oral disintegrating patient-tailored tablets of warfarin sodium produced by 3D printing.

Individualized medicine is a new direction in the field of modern pharmacy. In this study, we assessed the feasibility and accuracy of 3D printing techniques for the preparation of individualized doses of mouth-disintegrating tablets of warfarin. Warfarin sodium, D-sucrose, pregelatinized starch, povidone K30, microcrystalline cellulose, and silicon dioxide (at a ratio of 1:42.45:46.15:5.1:4.9:0.4) were mixed and used as the printing powder in the 3D printer; preset parameters were used. The dosage of the tablet was controlled by the number of printing layers. The content, dose uniformity, dose accuracy, hardness, friability, disintegration time, dissolution, and the microstructural and overall appearance were determined to evaluate the printed tablets. For the doses of 3, 2, and 1 mg that were produced in the experiment, the disintegration times were 50.0 ± 5.2, 35.7 ± 4.3, and 11.0 ± 2.2 s, respectively, and the relative errors of the dose were -2.33, -1.50, and 0%, respectively. The other indicators were consistent with the preparation requirements of pharmaceutical tablets. It is possible to prepare tablets with excellent properties and controlled drug doses by using 3D printing techniques. This technology will be an important means to achieve individualized medicine.

Novel histone deacetylase inhibitor N25 exerts anti-tumor effects and induces autophagy in human glioma cells by inhibiting HDAC3.

N25, a novel histone deacetylase inhibitor, was created through structural modification of suberoylanilide hydroxamic acid. To evaluate the anti-tumor activity of N25 and clarify its molecular mechanism of inducing autophagy in glioma cells, we investigated its in vitro anti-proliferative effect and in vivo anticancer effect. Moreover, we detected whether N25 induces autophagy in glioma cells by transmission electron microscope and analyzed the protein expression level of HDAC3, Tip60, LC3 in glioma samples by western blot. We additionally analyzed the protein expression level of HDAC3, Tip60, ULK1 (Atg1), and Beclin-1 (Atg6) after treatment with N25 in glioma cells. Our results showed that the anti-tumor activity of N25 in glioma cells is slightly stronger than SAHA both in vitro and in vivo. We found that N25 induced autophagy, and HDAC3 was significantly elevated and Tip60 and LC3 significantly decreased in glioma samples compared with normal brain tissues. Nevertheless, N25 inhibited HDAC3 and up-regulated the protein expression of Tip60, ULK1 (Atg1), and Beclin-1 (Atg6) after treatment of glioma cells with N25. In conclusion, these data suggest that N25 has striking anti-tumor activity in part due to inhibition of HDAC3. Additionally, N25 may induce autophagy through inhibiting HDAC3.

Efficacy and Safety of an Herbal Therapy in Patients with Amnestic Mild Cognitive Impairment: A 24-Week Randomized Phase III Trial.

OBJECTIVE: In the 24-week randomized, double-blind, double-placebo, parallel-controlled trial, we aimed to test the effects of herbal therapy with amnestic mild cognitive impairment (aMCI). METHODS: A total of 324 patients with aMCI entered a 2-week placebo run-in period followed by 24 weeks' treatment of either (a) herbal capsule (5 shenwu capsules/administration, 3 times/day) and placebo identical to donepezil tablets (n = 216) or (b) donepezil (5 mg/day) and placebo identical to herbal capsule (n = 108). RESULTS: Herbal therapy showed a significant improvement on the primary efficacy measure, measured by Alzheimer Disease Assessment Scale-cognitive subscale (ADAS-cog), and showed a mean decrease from baseline of 4.23 points at the endpoint, without a significant difference from the donepezil group. Secondary efficacy measurement of the Logical Memory II Delayed Story Recall subtest (DSR) showed modest improvement in those taking herbal capsule compared to baseline, and there was no significant difference from donepezil group. The frequency of adverse events was much less in the herbal therapy group than the donepezil. CONCLUSION: Herbal therapy demonstrated a significant improvement in cognition and memory, which were similar to the donepezil in patients with aMCI. Herbal therapy was safe and well tolerated. TRIAL REGISTRATION: This study is registered with clinicaltrials.gov NCT01451749.

Oxytocin is implicated in social memory deficits induced by early sensory deprivation in mice.

Early-life sensory input plays a crucial role in brain development. Although deprivation of orofacial sensory input at perinatal stages disrupts the establishment of the barrel cortex and relevant callosal connections, its long-term effect on adult behavior remains elusive. In this study, we investigated the behavioral phenotypes in adult mice with unilateral transection of the infraorbital nerve (ION) at postnatal day 3 (P3). Although ION-transected mice had normal locomotor activity, motor coordination, olfaction, anxiety-like behaviors, novel object memory, preference for social novelty and sociability, they presented deficits in social memory and spatial memory compared with control mice. In addition, the social memory deficit was associated with reduced oxytocin (OXT) levels in the hypothalamus and could be partially restored by intranasal administration of OXT. Thus, early sensory deprivation does result in behavioral alterations in mice, some of which may be associated with the disruption of oxytocin signaling.

[Study on formulation of naoxuekang dispersible tablets].

OBJECTIVE: To study the formulation of Naoxuekang dispersible tablets. METHODS: The formulation was determined by pre-processing leech extractum prior to a series of experiments used to screen excipients like bulking agents and disintegrants and so on, and by adding disintegrants within and without. RESULTS: Microcrystalline cellulose was determined as the bulking agent, and carboxymethyl cellulose and low-substituted hydroxypropyl cellulose were determined as the disintegrants of Naoxuekang dispersible tablet formula. The average disintegration time and nitrogen content of one tablet were 52 seconds and 5.47 milligrams, respectively. Also disperse homogeneity, weight variation and microbial limit all met the requirements in Ch. P. CONCLUSION: The prepared Naoxuekang dispersible tablet is reasonable in formula, feasible in technology, which meets the quality standards.

Efficacy evaluation of oral liquid of bambuterol hydrochloride in treatment children with asthma / 实用儿科临床杂志

Objective To evaluate the efficacy and safety of oral liquid of bambuterol hydrochloride in treatment children with asthma. Methods One hundred and fifty cases as study group treated with oral liquid of bambuterol hydrochloride,50.cases as control group treated with etinoline. Results Two groups had good efficacy, however, gasp and lung wheezing were better improved in study group compared with control group after 1 week treatment(P