Tuina therapy for temporomandibular joint disorder syndrome: A protocol for systematic review and meta-analysis

Background:Temporomandibular joint disorders (TMD) is common in clinic at present, which seriously affects the mental health and quality of life of patients. With the development of society, the incidence of TMD is gradually increasing. At present, there are many treatment methods, Tuina as a characteristic traditional Chinese medicine therapy, clinical treatment of TMD has a significant effect. In recent years, there are many clinical studies on Tuina in the treatment of TMD, but the clinical efficacy of Tuina in the treatment of TMD has not been systematically evaluated. In this study, we systematically evaluated the relevant literature of Tuina in the treatment of TMD by using the method of evidence-based medicine, in order to provide reference for clinical research in this direction in the future.Methods:VIP Chinese database, China knowledge Network, Wanfang, China Biomedical Database, PubMed, Embase, Cochrane Library and Web of Science were searched for clinical randomized controlled trials of Tuina in the treatment of TMD from the establishment of the database to December 2020. The 2 researchers independently screened the literature and carried out quality assessment and data extraction for the included study, and used RevMan5.3 software for risk assessment and Meta analysis.Results:In this study, the efficacy and safety of Tuina in the treatment of TMD were evaluated by effective rate, visual analog score (VAS) of temporomandibular joint pain, dysfunction index ((DI), palpation index (PI), craniomandibular index (CMI), maximum mouth opening (MMO), incidence of adverse reactions and so on.Conclusion:This protocol can provide evidence-based basis for the treatment of TMD, with Tuina to significantly improve the symptoms and function of patients with TMD.OSF Registration number:DOI 10.17605/OSF.IO/J75A8.     

Acute Nicotine Administration Increases BOLD fMRI Signal in Brain Regions Involved in Reward Signaling and Compulsive Drug Intake in Rats

Background:

Acute nicotine administration potentiates brain reward function and enhances motor and cognitive function. These studies investigated which brain areas are being activated by a wide range of doses of nicotine, and if this is diminished by pretreatment with the nonselective nicotinic receptor antagonist mecamylamine.

Methods:

Drug-induced changes in brain activity were assessed by measuring changes in the blood oxygen level dependent (BOLD) signal using an 11.1-Tesla magnetic resonance scanner. In the first experiment, nicotine naïve rats were mildly anesthetized and the effect of nicotine (0.03–0.6mg/kg) on the BOLD signal was investigated for 10min. In the second experiment, the effect of mecamylamine on nicotine-induced brain activity was investigated.

Results:

A high dose of nicotine increased the BOLD signal in brain areas implicated in reward signaling, such as the nucleus accumbens shell and the prelimbic area. Nicotine also induced a dose-dependent increase in the BOLD signal in the striato-thalamo-orbitofrontal circuit, which plays a role in compulsive drug intake, and in the insular cortex, which contributes to nicotine craving and relapse. In addition, nicotine induced a large increase in the BOLD signal in motor and somatosensory cortices. Mecamylamine alone did not affect the BOLD signal in most brain areas, but induced a negative BOLD response in cortical areas, including insular, motor, and somatosensory cortices. Pretreatment with mecamylamine completely blocked the nicotine-induced increase in the BOLD signal.

Conclusions:

These studies demonstrate that acute nicotine administration activates brain areas that play a role in reward signaling, compulsive behavior, and motor and cognitive function.     

Hyperparathyroidism presenting as hyperemesis and acute pancreatitis in pregnancy: A case report

Rationale:Nausea and vomiting are common in the early period of pregnancy and rarely seen as an overture to pancreatitis.Patient concerns:Here, we describe a 31-year-old pregnant woman who presented with progressive nausea and vomiting followed by severe epigastric pain. Biochemical data and sonographic features confirmed the occurrence of acute pancreatitis. Accompanying electrolyte abnormalities included hypercalcemia and hypokalemia. Her condition stabilized following medical treatment, but hypercalcemia persisted despite intravenous fluids and furosemide administration.Diagnoses:A diagnosis of primary hyperparathyroidism was made based on the elevated parathyroid hormone level and urinary calcium-to-creatinine clearance ratio.Interventions:Localization study with neck ultrasonography indicated left inferior parathyroid adenoma. She underwent parathyroidectomy successfully and made an uneventful recovery.Outcomes:At 37 weeks of gestation, she had a serum calcium level of 8.8 mg/dL and normal parathyroid hormone of 28.55 pg/mL. A healthy baby weighing 3180 g was delivered smoothly with no clinical nor biochemical evidence of hypocalcemia.Lessons:Although primary hyperparathyroidism during pregnancy is usually asymptomatic, patients may present with atypical manifestations such as hyperemesis and pancreatitis. Proper diagnosis and timely intervention are crucial to minimizing potential hazards to both mother and fetus.     

Liquid Chromatography-High Resolution Mass Spectrometry for Peptide Drug Quality Control

A liquid chromatography-high resolution mass spectrometry (LC-HRMS) method was developed using three peptide drugs: salmon calcitonin, bivalirudin, and exenatide as model systems to assess the suitability of this approach for monitoring peptide drug product quality. Calcitonin and its related impurities displayed linear responses over the range from 0.1 to 10 μM (R² values for calcitonin salmon, Glu¹⁴-calcitonin, and acetyl-calcitonin were 0.995, 0.996, and 0.993, respectively). Intra-assay precision in terms of relative standard deviation (%RSD) was less than 10% at all tested concentrations. The accuracy of the method was greater than 85% as measured by spiking 0.1, 0.3, and 1% of Glu¹⁴-calcitonin and acetyl-calcitonin into a stock calcitonin solution. Limits of detection for calcitonin, Glu¹⁴-calcitonin, and acetyl-calcitonin were 0.02, 0.03, and 0.04 μM, respectively, indicating that an impurity present at less than 0.1% (0.1 μM) of the drug product API concentration (107 μM) could be detected. Method validation studies analyzing bivalirudin and exenatide drug products exhibited similar results to calcitonin salmon in regard to high selectivity, sensitivity, precision, and linearity. Added benefits of using LC-HRMS-based methods are the ability to also determine amino acid composition, confirm peptide sequence, and quantify impurities, even when they are co-eluting, within a single experiment. LC-HRMS represents a promising approach for the quality control of peptides including the measurement of any peptide-related impurities. While the development work performed here is focus on peptide drug products, the principles could be adapted to peptide drug substance.KEY WORDS: High resolution mass spectrometry, impurity profiling, LC-HRMS, peptide drug     

Phenotype-dependent alteration of pathways and networks reveals a pure synergistic mechanism for compounds treating mouse cerebral ischemia

Aim:

Our previous studies have showed that ursodeoxycholic acid (UA) and jasminoidin (JA) effectively reduce cerebral infarct volume in mice. In this study we explored the pure synergistic mechanism of these compounds in treatment of mouse cerebral ischemia, which was defined as synergistic actions specific for phenotype variations after excluding interference from ineffective compounds.

Methods:

Mice with focal cerebral ischemia were treated with UA, JA or a combination JA and UA (JU). Concha margaritifera (CM) was taken as ineffective compound. Cerebral infarct volume of the mice was determined, and the hippocampi were taken for microarray analysis. Particular signaling pathways and biological functions were enriched based on differentially expressed genes, and corresponding networks were constructed through Ingenuity Pathway Analysis.

Results:

In phenotype analysis, UA, JA, and JU significantly reduced the ischemic infarct volume with JU being superior to UA or JA alone, while CM was ineffective. As a result, 4 pathways enriched in CM were excluded. Core pathways in the phenotype-positive groups (UA or JA) were involved in neuronal homeostasis and neuropathology. JU-contributing pathways included all UA-contributing and the majority (71.7%) of JA-contributing pathways, and 10 new core pathways whose effects included inflammatory immunity, apoptosis and nervous system development. The functions of JU group included all functions of JA group, the majority (93.1%) of UA-contributing functions, and 3 new core functions, which focused on physiological system development and function.

Conclusion:

The pure synergism between UA and JA underlies 10 new core pathways and 3 new core functions, which are involved in inflammation, immune responses, apoptosis and nervous system development.     

GSK-3β suppresses the proliferation of rat hepatic oval cells through modulating Wnt/β-catenin signaling pathway

Aim:

Glycogen synthase kinase 3β (GSK-3β) plays a crucial role in hepatic biology, including liver development, regeneration, proliferation and carcinogenesis. In this study we investigated the role of GSK-3β in regulation of growth of hepatic oval cells in vitro and in liver regeneration in partially hepatectomized rats.

Methods:

WB-F344 cells, the rat hepatic stem-like epithelial cells, were used as representative of oval cells. Cell viability was examined using a WST-8 assay. The cells were transfected with a recombinant lentivirus expressing siRNA against GSK-3β (GSK-3βRNAiLV) or a lentivirus that overexpressed GSK-3β (GC-GSK-3βLV). Adult rats underwent partial (70%) hepatectomy, and liver weight and femur length were measured at d 7 after the surgery. The expression of GSK-3β, phospho-Ser⁹-GSK-3β, β-catenin and cyclin D1 was examined with immunoblotting assays or immunohistochemistry.

Results:

Treatment of WB-F344 cells with the GSK-3β inhibitor SB216763 (5 and 10 μmol/L) dose-dependently increased the levels of phospho-Ser⁹-GSK-3β, but not the levels of total GSK-3β, and promoted the cell proliferation. Knockout of GSK-3β with GSK-3βRNAiLV increased the cell proliferation, whereas overexpression of GSK-3β with GC-GSK-3βLV decreased the proliferation. Both SB216763 and GSK-3βRNAiLV significantly increased the levels of β-catenin and cyclin D1 in the cells, whereas GSK-3β overexpression decreased their levels. In rats with a partial hepatectomy, administration of SB216763 (2 mg/kg, ip) significantly increased the number of oval cells, the levels of phospho-Ser⁹-GSK-3β, β-catenin and cyclin D1 in liver, as well as the ratio of liver weight to femur length at d 7 after the surgery.

Conclusion:

GSK-3β suppresses the proliferation of hepatic oval cells by modulating the Wnt/β-catenin signaling pathway.