Clinical outcomes of active specific immunotherapy in advanced colorectal cancer and suspected minimal residual colorectal cancer: a meta-analysis and system review

<p>Abstract</p> <p>Background</p> <p>To evaluate the objective clinical outcomes of active specific immunotherapy (ASI) in advanced colorectal cancer (advanced CRC) and suspected minimal residual colorectal cancer (suspected minimal residual CRC).</p> <p>Methods</p> <p>A search was conducted on Medline and Pub Med from January 1998 to January 2010 for original studies on ASI in colorectal cancer (CRC). All articles included in this study were assessed with the application of predetermined selection criteria and were divided into two groups: ASI in advanced CRC and ASI in suspected minimal residual CRC. For ASI in suspected minimal residual CRC, a meta-analysis was executed with results regarding the overall survival (OS) and disease-free survival (DFS). Regarding ASI in advanced colorectal cancer, a system review was performed with clinical outcomes.</p> <p>Results</p> <p>1375 colorectal carcinoma patients with minimal residual disease have been enrolled in Meta-analysis. A significantly improved OS and DFS was noted for suspected minimal residual CRC patients utilizing ASI (For OS: HR = 0.76, P = 0.007; For DFS: HR = 0.76, P = 0.03). For ASI in stage II suspected minimal residual CRC, OS approached significance when compared with control (HR = 0.71, P = 0.09); however, the difference in DFS of ASI for the stage II suspected minimal residual CRC reached statistical significance (HR = 0.66, P = 0.02). For ASI in stage III suspected minimal residual CRC compared with control, The difference in both OS and DFS achieved statistical significance (For OS: HR = 0.76, P = 0.02; For DFS: HR = 0.81, P = 0.03). 656 advanced colorectal patients have been evaluated on ASI in advanced CRC. Eleven for CRs and PRs was reported, corresponding to an overall response rate of 1.68%. No serious adverse events have been observed in 2031 patients.</p> <p>Conclusions</p> <p>It is unlikely that ASI will provide a standard complementary therapeutic approach for advanced CRC in the near future. However, the clinical responses to ASI in patients with suspected minimal residual CRC have been encouraging, and it has become clear that immunotherapy works best in situations of patients with suspected minimal residual CRC.</p

Interactions Between Emodin and Efflux Transporters on Rat Enterocyte by a Validated Ussing Chamber Technique

Emodin, a major active anthraquinone, frequently interacts with other drugs. As changes of efflux transporters on intestine are one of the essential reasons why the drugs interact with each other, a validated Ussing chamber technique was established to detect the interactions between emodin and efflux transporters, including P-glycoprotein (P-gp), multidrug-resistant associated protein 2 (MRP2), and multidrug-resistant associated protein 3 (MRP3). Digoxin, pravastatin, and teniposide were selected as the test substrates of P-gp, MRP2, and MRP3. Verapamil, MK571, and benzbromarone were their special inhibitors. The results showed that verapamil, MK571, and benzbromarone could increase digoxin, pravastatin, and teniposide absorption, and decrease their Er values, respectively. Verapamil (220 μM) could significantly increase emodin absorption at 9.25 μM. In the presence of MK571 (186 μM), the Papp values of emodin from M-S were significantly increased and the efflux ratio decreased. With the treatment of emodin (185, 370, and 740 μM), digoxin absorption was significantly decreased while teniposide increased. These results indicated that emodin might be the substrate of P-gp and MRP2. Besides, it might be a P-gp inducer and MRP3 inhibitor on enterocyte, which are reported for the first time. These results will be helpful to explain the drug–drug interaction mechanisms between emodin and other drugs and provide basic data for clinical combination therapy

Compressed CO₂ mediated synthesis of bifunctional periodic mesoporous organosilicas with tunable porosity

A facile and green method is proposed for the fabrication of bifunctional periodic mesoporous organosilicas using compressed CO2.</p

Upregulation of miR-214 Induced Radioresistance of Osteosarcoma by Targeting PHLDA2 via PI3K/Akt Signaling

Osteosarcoma is an aggressive bone tumor with high resistance to radiotherapy. Pleckstrin homology-like domain family A member 2 (PHLDA2) displays low expression in human osteosarcoma as a proapoptosis factor. miRNAs have been shown to be important in modulating translation and therapeutic responsiveness in solid tumors. Herein, we used luciferase assay to show that miR-214 downregulates the PHLDA2 expression by targeting its 3′-untranslated region (UTR). A high level of miR-214 was identified in tumor tissues from 30 osteosarcoma patients via qPCR analysis, associated positively with lung metastasis. Ectopic expression miR-214 enhanced radioresistance in osteosarcoma cells, with decreased IR-induced apoptosis. Moreover, the depletion of miR-214 enhanced radiosensitivity in both osteosarcoma cells and mouse xenograft models. Importantly, we showed that miR-214 regulated the activation of phosphatidylinositol-3-kinase/Akt signaling pathway by inhibiting PHLDA2. Finally, the introduction of PHLDA2 cDNA lacking the 3′-UTR or treatment with Akt inhibitor LY294002 partially abrogated miR-214-induced radioresistance. In summary, our results reveal that the upregulation of miR-214 as a frequent event in osteosarcoma contributes to radioresistance by regulating the PHLDA2/Akt pathway. The miR-214/PHLDA2/Akt axis provides a new avenue toward understanding the mechanism of radiosensitivity and may be a potential target for osteosarcoma intervention

CagA-positive Helicobacter pylori may promote and aggravate scrub typhus

Helicobacter pylori (H. pylori) infection may alter the host’s resistance to tsutsugamushi disease pathogens through the Th1 immune response, leading to potential synergistic pathogenic effects. A total of 117 scrub typhus cases at Beihai People’s Hospital and affiliated hospitals of Youjiang University for Nationalities and Medical Sciences were studied from January to December 2022, alongside 130 healthy individuals forming the control group. All participants underwent serum H. pylori antibody testing. The prevalence of H. pylori infection was significantly higher among scrub typhus patients (89.7%) compared to healthy individuals (54.6%) (p &lt; 0.05). Moreover, type I H. pylori infection was notably more prevalent in scrub typhus cases (67.5%) compared to healthy individuals (30%) (p &lt; 0.05). Multifactorial analysis demonstrated type I H. pylori infection as an independent risk factor for scrub typhus (adjusted odds ratio: 2.407, 95% confidence interval: 1.249–4.64, p = 0.009). Among scrub typhus patients with multiple organ damage, the prevalence of type I H. pylori infection was significantly higher (50.6%) than type II H. pylori infection (15.4%) (χ2 = 4.735, p = 0.030). These results highlight a higher incidence of H. pylori infection in scrub typhus patients compared to the healthy population. Additionally, type I H. pylori strain emerged as an independent risk factor for scrub typhus development. Moreover, individuals infected with type I H. pylori are more susceptible to multiple organ damage. These findings suggest a potential role of H. pylori carrying the CagA gene in promoting and exacerbating scrub typhus

Radiomic signature of the FOWARC trial predicts pathological response to neoadjuvant treatment in rectal cancer

Background We aimed to develop a radiomic model based on pre-treatment computed tomography (CT) to predict the pathological complete response (pCR) in patients with rectal cancer after neoadjuvant treatment and tried to integrate our model with magnetic resonance imaging (MRI)-based radiomic signature. Methods This was a secondary analysis of the FOWARC randomized controlled trial. Radiomic features were extracted from pre-treatment portal venous-phase contrast-enhanced CT images of 177 patients with rectal cancer. Patients were randomly allocated to the primary and validation cohort. The least absolute shrinkage and selection operator regression was applied to select predictive features to build a radiomic signature for pCR prediction (rad-score). This CT-based rad-score was integrated with clinicopathological variables using gradient boosting machine (GBM) or MRI-based rad-score to construct comprehensive models for pCR prediction. The performance of CT-based model was evaluated and compared by receiver operator characteristic (ROC) curve analysis. The LR (likelihood ratio) test and AIC (Akaike information criterion) were applied to compare CT-based rad-score, MRI-based rad-score and the combined rad-score. Results We developed a CT-based rad-score for pCR prediction and a gradient boosting machine (GBM) model was built after clinicopathological variables were incorporated, with improved AUCs of 0.997 [95% CI 0.990–1.000] and 0.822 [95% CI 0.649–0.995] in the primary and validation cohort, respectively. Moreover, we constructed a combined model of CT- and MRI-based radiomic signatures that achieve better AIC (75.49 vs. 81.34 vs.82.39) than CT-based rad-score (P = 0.005) and MRI-based rad-score (P = 0.003) alone did. Conclusions The CT-based radiomic models we constructed may provide a useful and reliable tool to predict pCR after neoadjuvant treatment, identify patients that are appropriate for a 'watch and wait' approach, and thus avoid overtreatment. Moreover, the CT-based radiomic signature may add predictive value to the MRI-based models for clinical decision making

Patient-physician mistrust and violence against physicians in Guangdong Province, China: a qualitative study.

OBJECTIVE: To better understand the origins, manifestations and current policy responses to patient-physician mistrust in China. DESIGN: Qualitative study using in-depth interviews focused on personal experiences of patient-physician mistrust and trust. SETTING: Guangdong Province, China. PARTICIPANTS: One hundred and sixty patients, patient family members, physicians, nurses and hospital administrators at seven hospitals varying in type, geography and stages of achieving goals of health reform. These interviews included purposive selection of individuals who had experienced both trustful and mistrustful patient-physician relationships. RESULTS: One of the most prominent forces driving patient-physician mistrust was a patient perception of injustice within the medical sphere, related to profit mongering, knowledge imbalances and physician conflicts of interest. Individual physicians, departments and hospitals were explicitly incentivised to generate revenue without evaluation of caregiving. Physicians did not receive training in negotiating medical disputes or humanistic principles that underpin caregiving. Patient-physician mistrust precipitated medical disputes leading to the following outcomes: non-resolution with patient resentment towards physicians; violent resolution such as physical and verbal attacks against physicians; and non-violent resolution such as hospital-mediated dispute resolution. Policy responses to violence included increased hospital security forces, which inadvertently fuelled mistrust. Instead of encouraging communication that facilitated resolution, medical disputes sometimes ignited a vicious cycle leading to mob violence. However, patient-physician interactions at one hospital that has implemented a primary care model embodying health reform goals showed improved patient-physician trust. CONCLUSIONS: The blind pursuit of financial profits at a systems level has eroded patient-physician trust in China. Restructuring incentives, reforming medical education and promoting caregiving are pathways towards restoring trust. Assessing and valuing the quality of caregiving is essential for transitioning away from entrenched profit-focused models. Moral, in addition to regulatory and legal, responses are urgently needed to restore trust

Forty-eight-week efficacy of adefovir dipivoxil alone versus combined with lamivudine in treatment of lamivudine-resistant HBeAg-positive chronic hepatitis B

ObjectiveTo observe the therapeutic efficacy and safety of adefovir dipivoxil (ADV) alone versus combined with lamivudine (LAM) in the treatment of LAM-resistant HBeAg-positive chronic hepatitis B (CHB). MethodsForty patients with LAM-resistant HBeAg-positive CHB were randomly assigned to monotherapy group (n=20) and combination therapy group (n=20). The monotherapy group received ADV alone, while the combination therapy group received ADV combined with LAM. After 24 and 48 weeks of treatment, serum HBV DNA level, undetectable HBV DNA rate, HBeAg loss rate, alanine aminotransferase (ALT) normalization rate, adverse reactions, and drug resistance were assessed. The two groups were compared by t-test for continuous data and chi-square test for categorical data. ResultsThere were no significant differences in sex, age, and pretreatment levels of serum HBV DNA and ALT between the two groups (P＞0.05). After 48 weeks of treatment, serum undetectable HBV DNA rate and ALT normalization rate for the combination therapy group were 90% and 95%, respectively, significantly higher than those for the monotherapy group (60% and 65%) (P＜0.05); there was no significant difference in HBeAg loss rate between the combination therapy group and monotherapy group (45% vs 35%, χ2=0.417, P=0.519). ConclusionADV alone or combined with LAM has good clinical efficacy in the treatment of LAM-resistant HBeAg-positive CHB. However, the combination therapy can increase undetectable HBV DNA rate and ALT normalization rate and has good safety, and it holds promise for clinical application