Few cases of tenofovir resistance have been reported, and the appropriate treatment for such cases remains unclear. We aimed to share a case of a chronic hepatitis B mono-infected patient with potential tenofovir resistance who required combined lamivudine and tenofovir therapy to achieve adequate viral suppression. The patient’s viral load (plasma) was monitored using the cobas® hepatitis B virus Test on the cobas® 6800 system. Hepatitis B antiviral drug resistance (AVDR) mutations were assessed by amplicon-based sequencing. Plasma was extracted using the MagNa Pure 24 system, and polymerase chain reaction targeting the polymerase gene (860bp) was performed. Sequencing was conducted on GridION R10.4.1 flow cells, and the resulting FASTQ files were analyzed using DeepChek®-HBV Software. We describe a female patient in her 60s with chronic hepatitis B who was e-antigen positive. She met treatment criteria in May 2020, when her alanine transaminase levels were 1.5 times above the upper limit of normal. She was initially started on entecavir but had to switch to tenofovir alafenamide in June 2020 due to a rash. Despite three years of tenofovir therapy, her viral load remained unsuppressed. AVDR testing identified two suspected tenofovir resistance mutations (V191I and A317S). Since no mutations associated with lamivudine resistance were detected, the patient was treated with a combination of lamivudine and tenofovir, achieving viral suppression after four months. Although rare, tenofovir resistance should be considered in patients with persistent viremia despite long-term therapy. AVDR sequencing facilitated the detection of potential tenofovir resistance and guided treatment decisions, leading to successful viral suppression in this case.

Precision medicine involves tailoring an individual’s genes or proteins to prevent, diagnose, or treat diseases such as cancer. Given the recent advances in cancer immunotherapy, there is now a focus on developing vaccines as a new treatment modality. Therapeutic vaccines for cancer are a precision medicine approach that has made enormous progress in recent years due to advances in vaccine engineering. This technology uses antigens derived from the patient’s tumor to create vaccines that are unique and specific to that patient. Although challenges remain, significant progress has been made in recent years, largely due to the advent of mRNA vaccines. This mini-review primarily focuses on developments in vaccine engineering, outstanding therapeutic obstacles, and recent human clinical trials.

Hepatocellular carcinoma (HCC) is one of the most fatal malignancies. Epigenetic mechanisms have revealed that noncoding RNAs, such as microRNAs (miRNAs) and circular RNAs (circRNAs), are involved in HCC progression. This study aimed to construct a circRNA-miRNA-mRNA network in HCC and validate one axis within the network.

HCC-related transcriptome data were obtained from the Gene Expression Omnibus, and HCC-related genes were sourced from GeneCards to identify differentially expressed circRNAs and miRNAs. The targeting relationships between circRNA-miRNA and miRNA-mRNA interactions were predicted. The involvement of the hsa_circ_0001726/miR-140-3p/KRAS axis in HCC was evaluated through cellular experiments and survival analyses.

We identified six differentially expressed circRNAs in HCC, which were linked to 13 miRNAs and 88 mRNAs. A network containing 34 circRNA-miRNA pairs and 194 miRNA-mRNA pairs was constructed. Cell proliferation and migration assays confirmed the role of hsa_circ_0001726 in promoting HCC progression, possibly through the miR-140-3p/KRAS axis. Survival analysis verified that hsa_circ_0001726 was a prognostic factor for overall survival in patients with HCC. The hsa_circ_0001726/miR-140-3p/KRAS axis also mediates lenvatinib resistance in HCC cells.

The HCC circRNA/miRNA/mRNA network provides new insights into the post-transcriptional regulatory mechanism of HCC. The hsa_circ_0001726/miR-140-3p/KRAS axis is involved in HCC progression and lenvatinib resistance.

Infection with HPV16, a high-risk human papillomavirus (HPV), can cause cervical cancer in humans. These infections carry a high risk of morbidity and mortality globally in females. This study aimed to conduct an in vivo comparison of Poly (D,L-lactic-co-glycolide) (PLGA)-encapsulated peptide mixture nanoparticles and PLGA microspheres as delivery systems for vaccines.

PLGA polymers were used to form microspheres for a therapeutic vaccine against cervical cancer. The target antigens were the L1 and L2 capsid proteins and the E6 and E7 oncoproteins from HPV16. These antigens were selected based on their immunogenicity, allergenicity, and toxicity. We predicted epitopes for cytotoxic T lymphocytes (CTLs) and helper T lymphocytes. In our investigation of CTL epitopes, we employed synthetic chimeric PLGA microsphere peptides, consisting of multiple H-2Db-restricted HPV16 peptides, coupled with other immune-potentiating adjuvants as predicted by our work.

H-2Db-restricted HPV16 peptides, when administered subcutaneously, enabled CTLs to eliminate in vitro TC-1 tumor cells expressing E6 and E7 of HPV16. Additionally, TC-1 cells protected C57BL/6 mice against in vivo challenges. To address this problem, peptide-based vaccines, which are among the most effective vaccine systems, have been extensively studied. Combining peptide-based vaccinations with microsphere peptide mixture particles and delivery technologies enhances their efficacy in stimulating cellular immune responses and eliminating tumor cells.

This approach may provide a potential therapeutic candidate vaccine based on microsphere-encapsulated peptides for the prevention of cervical cancer caused by HPV.

Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder associated with liver disease, ranging from fibrosis to hepatocellular carcinoma. The disease remains asymptomatic until its final stages when liver transplantation is the only available therapy. Biomarkers offer an advantage for disease evaluation. The presence of microRNAs (miRNAs) in plasma extracellular vesicles (EVs) presents a noninvasive approach to assess the molecular signatures of the disease. In this study, we aimed to identify miRNA biomarkers to distinguish molecular signatures of the liver disease associated with AATD in AATD individuals.

Using small RNA sequencing and qPCR, we examined plasma EV miRNAs in healthy controls (n = 20) and AATD patients (n = 17). We compared the EV miRNAs of AATD individuals with and without liver disease, developing an approach for detecting liver disease. A set of miRNAs identified in the AATD testing cohort was validated in a separate cohort of AATD patients (n = 45).

We identified differential expression of 178 EV miRNAs in the plasma of the AATD testing cohort compared to controls. We categorized AATD individuals into those with and without liver disease, identifying 39 differentially expressed miRNAs. Six miRNAs were selected to test their ability to discriminate liver disease in AATD. These were validated for their specificity and sensitivity in an independent cohort of 45 AATD individuals. Our logistic model established composite scores with three- and four-miRNA combinations, achieving areas under the curve of 0.737 and 0.751, respectively, for predicting AATD liver disease.

We introduce plasma EV-derived miRNAs as potential biomarkers for evaluating AATD liver disease. Plasma EV-associated miRNAs may represent a molecular signature of AATD liver disease and could serve as valuable tools for its detection and monitoring.

Shufeng Jiedu Capsules (SFJD), a traditional Chinese medicine preparation, are widely used in the clinical treatment of influenza, yet their mechanism of action remains unclear. This study aimed to systematically explore the molecular mechanism of SFJD in the treatment of influenza using network pharmacology and bioinformatics techniques.

The active ingredients of SFJD were retrieved from traditional Chinese medicine databases, and their targets were identified using the Swiss Target Prediction and TCMSP databases. Influenza disease genes were obtained from the GEO, GeneCards, and DisGeNET databases, and a Venn diagram was used to identify potential targets by mapping SFJD targets to influenza disease genes. Network construction and analysis of potential therapeutic targets were performed using the STRING12.0 database and Cytoscape3.9.1 software, leading to the identification of key targets. The expression of potential therapeutic targets in tissues and cells was retrieved using the BioGPS database. Functional enrichment analysis of these targets was conducted using the DAVID database. Molecular docking was then used to assess the interactions between key targets and core active ingredients.

SFJD contains 193 active ingredients and 985 targets. There are 510 influenza disease genes, 97 of which are potential therapeutic targets for SFJD in treating influenza, with 27 key targets identified through network construction and analysis. Tissue/cell-specific analysis revealed that 39 potential therapeutic targets are highly expressed in 37 specific tissues/cells. Functional enrichment analysis highlighted pathways such as the C-type lectin receptor signaling pathway, tumor necrosis factor signaling pathway, and hypoxia-inducible factor-1 signaling pathway. Molecular docking results indicated strong interactions between the core active ingredients and the key targets.

This study systematically reveals that the mechanism of action of SFJD in treating influenza is complex, involving multiple targets and pathways related to antiviral, anti-inflammatory, and immune regulation effects. The findings provide valuable reference information for future clinical treatment and basic research on influenza.

Patients with corona virus disease 2019 (COVID-19) face not only physical strains but also significant psychological stress, highlighting the importance of addressing their mental health concerns. This study aimed to evaluate the impact of Lianhua Qingwen on the psychological well-being of asymptomatic and mildly symptomatic COVID-19 patients, providing empirical evidence to guide clinical practices.

Conducted in eight shelter hospitals in Shanghai, the study employed a cluster randomization method to allocate patients equally into either the Lianhua Qingwen group or the control group. The Lianhua Qingwen group received oral doses of four capsules or one packet of granules three times daily for 14 days. In contrast, the control group received standardized treatment according to the diagnostic and treatment plan, excluding Lianhua Qingwen. Mental health was assessed using the Self-rating Depression Scale and Self-rating Anxiety Scale, with symptom reporting on the 7th and 14th days, accompanied by nucleic acid test result screenshots. A follow-up investigation on new disease occurrence was conducted six months post-discharge.

Among the 2,652 valid questionnaire respondents, the Lianhua Qingwen group accounted for 1,665 cases, characterized by a higher proportion of females (32.7% vs. 26.9%), younger age (44.8 vs. 46.2 years), lower percentages of asymptomatic infections (27.6% vs. 38.5%), higher baseline Patient Health Questionnaire-9 scores (2.7 vs. 1.9), and higher Generalized Anxiety Disorder 7 scores (1.9 vs. 1.4). Further multivariate logistic regression analysis explored factors influencing the alleviation of depressive and anxiety symptoms during follow-up, revealing that Lianhua Qingwen use was an independent factor in reducing anxiety (odds ratio = 1.37, 95% confidence interval 1.14–1.65, p = 0.001) and depression (odds ratio = 1.42, 95% confidence interval 1.19–1.69, p < 0.0001). Lianhua Qingwen increased the likelihood of reducing anxiety by 37% and depression by 42%.

Lianhua Qingwen significantly alleviated anxiety and depression symptoms in COVID-19 patients, suggesting its potential therapeutic efficacy in mitigating these conditions.

Data regarding risk factors and long-term outcomes of U.S. patients with biopsy-proven metabolic dysfunction-associated steatotic liver disease (MASLD) are limited. This study aimed to investigate the role of clinical and histologic risk factors on long-term outcomes in patients with MASLD.

A retrospective cohort study of 451 adults with biopsy-proven MASLD was conducted at a U.S. academic hospital from 2012 to 2020. An experienced pathologist evaluated the index liver biopsy. Patients with a prior liver transplant or alternative etiologies of chronic liver disease were excluded. The duration of the risk exposure was determined from the date of the index liver biopsy to an outcome event or the last follow-up examination. Outcome events of interest included incident liver-related events, liver decompensation, and all-cause mortality.

In the final cohort of 406 patients followed for a median of 3.7 years (interquartile range: 4.8 years), 35 patients died, 41 developed hepatic decompensation, and 70 experienced a liver-related event. Among histologic risk factors, stage 3 (adjusted Hazard ratio (aHR) 2.68, 95% confidence interval (CI) 1.18–6.11) and stage 4 (aHR 6.96, 95% CI 3.55–13.64) fibrosis were associated with incident liver-related events compared to stage 0–1 fibrosis. Stage 4 (aHR 8.46, 95% CI 3.26–21.99) fibrosis alone was associated with incident liver decompensation events compared to stage 0–1 fibrosis. Among clinical risk factors, hypertension (aHR 2.58, 95% CI 1.05–6.34) was associated with incident liver decompensation.

In a U.S. single-center cohort of patients with biopsy-proven MASLD, advanced fibrosis was the primary risk factor for incident liver decompensation and liver-related events.

The effect of tenofovir amibufenamide (TMF) on blood lipid profiles in patients with chronic hepatitis B (CHB) remains unclear. This study aimed to explore whether TMF affects blood lipids during 48 weeks in patients with CHB.

A total of 91 patients with CHB undergoing TMF treatment for 48 weeks were divided into two groups: Lipid Normal (n = 42) and Lipid Abnormal (n = 49), based on baseline blood lipid levels. Lipid indices, virological responses, and biochemical indicators were compared between the two groups. Clinical observations were further verified through in vitro experiments.

After an average follow-up of 373 ± 121 days, lipid indices in all 91 patients had not significantly changed compared with baseline (total cholesterol: 4.67 vs. 4.69 mmol/L, P = 0.2499; triglycerides: 1.08 vs. 1.04 mmol/L, P = 0.4457; high-density lipoprotein cholesterol: 1.25 vs. 1.25 mmol/L, P = 0.3063; low-density lipoprotein cholesterol: 3.03 vs. 3.02 mmol/L, P = 0.5765). Subgroup comparisons showed lipid indices remained stable. Among treatment-naïve patients (n = 82), complete viral suppression rates were 23.2%, 59.8%, 70.7%, and 86.6% at four, 12, 24, and 48 weeks, respectively. Cellular experiments revealed that TMF did not promote lipid metabolism in primary hepatocytes and AML12 cells.

Regardless of baseline blood lipid characteristics, 48 weeks of antiviral treatment with TMF in patients with CHB had no significant lipid-raising effect.