Development and validation of a LC–MS/MS assay for tenofovir and tenofovir alafenamide in human plasma: Application in a bioequivalence study

Original Research

Abstract

Introduction: Tenofovir alafenamide (TAF), a prodrug of tenofovir (TFV), is currently used for treatment of chronic hepatitis B as first line recommendation. The Vietnamese market is currently circulating a tenofovir alafenamide generic. This formulation has not been assessed for in vivo bioequivalence. This study has been performed with the aim of development, validation, and application of LC-MS/MS procedure for quantitation of TAF and TFV in human plasma.

Methods: Internal standard (IS), and analytical parameters were investigated to find out the suitable IS and conditions. Chromatographic conditions were optimized by considering the column type, mobile phase component, concentration of the buffer solutions and strength, oven temperature, flow rate, and injection volume. Human plasma samples were treated by protein precipitation with acetonitrile. The assay was validated in compliance with US-FDA and EMA guidelines. This assay was applied to evaluate the bioequivalence of the generic and reference products of 25 mg TAF in the healthy Vietnamese subjects under fed conditions.

Results: TAF, TFV, IS were ionized using ESI and detected by MRM mode to obtain molecular and fragment ions for quantification. The recovery of all analytes from human plasma was above 70%. The chromatographic conditions contained a C6-Phenyl column and mobile phase including acetonitrile and 0.5% formic acid. The specificity, precision, accuracy, matrix effect of all the analytes were in the acceptable range. Thirty six subjects finished the fed trial. The two products’ geometric mean ratios for AUC0-t, AUC0-∞, and Cmax (80.00% to 125.00%) met the bioequivalence acceptance criteria.

Conclusions: A LC-MS/MS procedure for simultaneous quantitation of TAF and TFV in human plasma was developed, validated, applied.

Graphical abstract

A case report of COVID-19-associated severe psychotic symptoms and suicidal behavior: a late psychiatric intervention

Case Study

Abstract

A 25-year-old previously healthy female patient experienced new-onset psychosis and showed suicidal behavior after contracting COVID-19. Based on the International Statistical Classification of Diseases and Related Health Problems (ICD-10), the diagnosis of an acute and transient psychotic disorder (ATPD) was appropriate. Due to poor insight into illness, the patient received an oral solution containing 2 mg/mL haloperidol and fully recovered after the first month of treatment. This is the first case of a COVID-19-associated psychotic episode showing full recovery with late intervention, which occurred nearly 45 days after exhibiting the first psychotic symptoms. Additionally, the patient would require long-term follow-up owing to an ultra-high risk of relapse.

Graphical abstract

Electroacupuncture at Trigger point gains better pain relief effectiveness than Electroacupuncture at Meridian point: A non-blind randomized trial of chronic neck pain treatment among patients at Traditional Medicine Hospital

Original Research

Abstract

Introduction: Neck pain is one of the leading causes of disabilities and increasing economic and social burden. Methods affecting the trigger point (TrP) have initially shown good pain relief effectiveness and decreased degree of invasion in patients. The research is conducted to evaluate the effectiveness of Electroacupuncture (EA) at TrP in chronic neck pain (CNP) treatment.

Methods: A non-blind randomized study on 125 patients with CNP at Traditional Medicine Hospital in Ho Chi Minh City from September 2020 to June 2021. Patients will be randomly classified into EA at the TrP group or EA at the meridian points group.

Results: There were 62 patients in the TrP group and 63 patients in the other group. After 4 weeks, in the TrP group, the Questionnaire Douleur Saint-Antoine (QDSA) score of 38.2 ± 2.6 decreased to 9.3 ± 5.7, compared with the meridian points group’s QDSA score of 37.8 ± 2.3 decreased to 12.3 ± 7.1. The percentage of patients to reach good pain relief effectiveness of EA at TrP measured by QDSA is 71.0%, statistically significantly higher than 47.6% of the other group. The decrease in the number of TrPs of EA at TrP is higher and has statistical value compared with EA at meridian points.

Conclusions: EA at TrP showed better pain relief effectiveness, has a higher percentage of patients reaching good pain relief effectiveness measured by QDSA, and decreases the number of TrPs more than EA at meridian points does on patients with CNP.

Graphical abstract

The effectiveness of thread embedding acupuncture in reducing wrinkles at nose and mouth

Original Research

Abstract

Introduction: Beauty need is a growing demand these days; thus, the search for non-invasive beautifying methods that effectively and safely reduce the wrinkles on the face is of great need. Thread embedding acupuncture (TEA) has been proven to be effective in rejuvenating the facial skin and consists of advantages such as little invasion, few side-effects.

Methods: The study was a single-arm pre-post study, 20 female volunteers, aged 35-60. TEA is conducted on Daying (ST5), Jiache (ST6), Dicang (ST4), Yingxiang (LI20), and Hegu (LI4) with mono-filament Polydioxanone (PDO). The participants were monitored and evaluated after 1, 2 and 3 months. The variables are Nasolabial fold (NF), Marionette line (ML), Alexiades-Armenakas laxity scale (AALS), Global aesthetic improvement scale (GAIS).

Results: Both sides NF, ML and AALS after 1 month TEA, 2 months TEA, 3 months TEA compared to pre-intervention showed decrease of statistical significance. NF, ML of both sides after 1 month TEA, 2 months TEA compared to the previous 1 month showed decrease of statistical significance. However, after 3 months, compared with 2-month threshold, difference has no statistical significance. AALS after 2 months and 3 months TEA, differences have no statistical significance. There were 17 persons “improved” (85%), 3 persons “unchanged” (15%) according to GAIS. No side effect of any kind was recorded.

Conclusions: This research proved TEA method is effective on the acupuncture points that the research used in facial wrinkle reduction treatment. However, a RCTs (Randomized Controlled Trial study) is needed to confirm effectiveness.

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Analysis of single-cell RNA sequencing data revealed the upregulation of Wnt signaling pathway and potential biomarkers in Oral Squamous Cell Carcinoma cancer-associated fibroblasts

Original Research

Abstract

Background: CAFs (cancer-associated fibroblasts) and tumor-associated p-EMT (partial epithelial mesenchymal transition) cells coexist and contribute to the formation of epithelial tumors like OSCC (oral squamous cell carcinoma). In oral cancer, Wnt signaling pathway contributes to the tumor progression, invasion and metastasis. Here we deeply analyzed Wnt signaling pathway using our previous single-cell RNA-seq data of CAFs and p-EMT tumor cells in OSCC by computational methods.

Material and methods: Integrated single-cell RNA sequencing data of OSCC CAF and p-EMT clusters were obtained from our previous study. These cells were from samples being primary tumor, oral cavity location, metastasis information and then analyzed by R, Python to investigate the gene expression, cell-cell communication, gen set enrichment analysis (GSEA) and overall survival analysis across metastasis conditions regarding Wnt signaling pathway.

Results: Genes related to Wnt signaling pathway upregulated in CAFs and p-EMT cancer cells, especially under metastasis condition including WNT2, WNT5A, FZD1-4, ROR2 in CAFs, and WNT7B, FZD2/5/6 in p-EMT cells. Cell-cell interaction analysis and GSEA in CAFs and p-EMT tumor cells highlighted non-canonical Wnt signaling pathway in CAFs and canonical Wnt signaling pathway in p-EMT tumor cells. CTHRC1 and SFRP2 were suggested as biomarkers in Wnt signaling pathway of CAFs from the gene expression, GSEA and overall survival analysis.

Conclusion: Our study found CTHRC1 and SFRP2 as biomarkers for HSCC and OSCC prognosis belong to CAFs of TME. It might pave the way for targetable treatment based on WNT ligand-receptor interaction and Wnt signaling modulation in OSCC CAFs based on metastatic status.

Graphical abstract

Effectiveness and safety of thread embedding acupuncture for drug-resistant epilepsy outpatient in Viet Nam: a two-arm parallel design, randomized, controlled clinical trial

Original Research

Abstract

Introduction: People with drug-resistant epilepsy (DRE) are at high risk of sudden unexpected deaths and lower quality of life. Experiments showed thread embedding acupuncture (TEA) has a seizure-reducing effect; however, data on DRE has been limited. This trial aimed to establish the efficacy and safety of TEA in people with DRE.

Method: This was a two-arm, randomized controlled trial conducted on 30 DRE outpatients, which was fulfilled drug-resistant International League Against Epilepsy. The study was conducted at the Epilepsy clinic, Nguyen Tri Phuong Hospital, Ho Chi Minh City, from December 2020 to March 2022. All procedures for TEA and sham TEA (STEA) groups were identical. Seizure frequency diaries at the baseline and monthly follow-up visits by the participants. The Quality of Life in Epilepsy Inventory (QOLIE-31) scores at the baseline and 16 weeks; the National Hospital Seizure Severity Scale (NHS3) scores at the baseline, 8 weeks, and 16 weeks and the adverse events at monthly follow-up visits by a researcher.

Results: A reduction in relative seizure frequency and the score change in QOLIE-31 and NHS3 in the TEA group were significantly different from the STEA group when analyzing each group separately (p<0.05). However, when comparing two groups, no significant difference was found in the change in seizure freedom and QOLIE-31 (p>0.05). Mild pain appeared in all participants after the intervention, but no serious adverse effects of TEA were observed.

Conclusion: TEA is a safe technique to use in people with DRE. However, the effectiveness of TEA needs further study. 

Graphical abstract

The laparoscopic surgery results of isolated enteric duplication in the transverse mesocolon: A case report

Case Study

Abstract

Introduction: Enteric duplication cysts found throughout the alimentary tract are rare congenital mass lesions, which usually share a common wall with the gastrointestinal tract. However, many cases of isolated enteric duplication (IED) cysts, reported in the literature, are without any attachment to the gastrointestinal tract. We report a case of an IED cyst located in the transverse mesocolon, which was successful treatment with laparoscopy, in Children’s Hospital #1, Ho Chi Minh City, Vietnam.

Case presentation: A girl turned 3 years old presented with dull abdominal pain and vomiting. Abdominopelvic computed tomography revealed a lesion located around duodenojejunal flexure with a thick wall. Laparoscopy detected a mobile cystic mass found on the mesentery of the transverse colon, which was not connection or attachment to any part of the adjacent intestine. Histopathology of the cyst wall was compatible with an EDC.

Conclusion: The IED cyst is an unusual phenomenon that confuse with other diagnosis in clinical. The definitive diagnosis of IED is based on histopathology. Laparoscopic resection of the cyst is the preferred treatment. 

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Gastric adenocarcinoma mimicking a submucosal tumor- a diagnostic pitfall in the pediatric population: report of two cases

Case Study

Abstract

Introduction: Pediatric gastric adenocarcinoma (GAC) is sporadic with limited relevant data, and gastric adenocarcinoma, which presents as submucosal, has seldom been reported. The clinical presentation and outcome have not yet been thoroughly understood.

Case presentation: Two boys (10 and 14-year-old) were admitted to the hospital with severe malnutrition. Abdominal CT demonstrated the tumor protruding into the stomach, irregular border, and peritoneal metastasis. Gastric biopsies showed pleomorphic cells, variable size, and increased N/C ratio. These cells were arranged into sheet growth patterns, clusters of cells or incomplete tubules with neutrophils infiltrating. The malignant cells showed strong expression of CK, negativity for CD99, NSE, myogenin, CD3, CD20, ALK, and CD30. Both cases were consistent with poorly differentiated gastric adenocarcinomas, diffuse type with lymphovascular invasion.

Discussion and Conclusion: Pediatric GAC presented with a more advanced stage and poor differentiation. However, the clinical presentation is similar to adult GAC. Because of data limitations, the diagnosis and treatment of pediatric GAC remain a significant challenge. GAC should be kept in mind, especially when a submucosal tumor-like lesion appears in the stomach. Additional molecular investigations, including E-cadherin or HER2 testing of the tumor samples, may offer more treatment choices for these patients. 

Graphical abstract

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