Combined Treatment Group Research Articles

Efficacy and safety of tripterygium glycosides combined with ACEI/ARB on diabetic nephropathy: a meta-analysis

AimsThis study aims to evaluate the efficacy and safety of tripterygium glycosides combined with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARBs) in treating Diabetic nephropathy and provide high-level evidence to support its standardized application.MethodsLiteratures were retrieved from PubMed, Web of Science, EMBASE, Cochrane Library, CNKI, Wanfang and VIP databases, the search time frame was defined as from the time of establishment to April 2023. This study only included randomized controlled trials of tripterygium glycosides combined with ACEI/ARB in the treatment of diabetic nephropathy, and the final included studies were identified according to the inclusion and exclusion criteria, and meta-analysis of data was performed using RevMan 5.3 software.ResultsA total of 44 RCTs with 3537 DN patients were included in the study. Compared with the control group, tripterygium glycosides combined with ACEI/ARB significantly reducing 24 h-UTP (24 h urine total protein) [SMD = −1.46, 95% CI (−1.70, −1.23), P < 0.00001], increasing effective rate [RR = 1.23, 95% CI (1.17,1.29), P < 0.00001], elevating serum albumin [SMD = 0.85, 95% CI (0.69, 1.02), P < 0.00001], improving serum creatinine [SMD = −0.35, 95% CI (−0.59, −0.11), P = 0.004], with no difference in BUN (blood urea nitrogen) [SMD = −0.17, 95% CI (−0.48,0.13), P = 0.27], the adverse reactions rate was higher than those of the control group [RR = 1.96, 95%CI (1.43, 2.68), P < 0.0001].ConclusionThis study showed that the combination of tripterygium glycosides and ACEI/ARB was more effective than ACEI/ARB alone. However, the side effects of the combined treatment group were higher than those of the control group, especially liver function damage, which also suggested that its safety in the treatment of diabetic nephropathy was worth considering. Therefore, although tripterygium glycosides provided a choice for the clinical treatment of diabetic nephropathy, its side effects limited its clinical application. In future studies, we need to further optimize tripterygium glycosides and reduce its side effects to ensure the safety of clinical application.

Short-term efficacy and safety of upadacitinib combined with 308 excimer light versus upadacitinib alone and 308 excimer light alone in patients with progressing facial vitiligo.

Patients with progressing facial vitiligo who had been treated with upadacitinib, 308nm excimer light and upadacitinib combined with 308nm excimer light were selected for retrospective analysis and comparison of their efficacy and safety. Efficacy was evaluated using the Vitiligo Area Severity Index (VASI) and Dermatology Life Quality Index (DLQI) at baseline, after 8weeks, and after 20weeks. The progression of skin lesions was monitored through reflectance confocal microscopy (RCM), while adverse reactions were documented. In the combination treatment group, the average VASI at baseline was 0.875 ± 0.4111, which decreased to 0.56 ± 0.32 at week 8 and 0.23 ± 0.218 at week 20 of follow-up (F = 9.918, p = 0.001). RCM analysis indicated that cases achieving VASI100 showed restoration to normalcy regarding loss of integrity within the pigment ring in lesion areas. Although one patient experienced exacerbation of acne, this condition was manageable with topical medication. In contrast, the average VASI score in the 308nm excimer light group prior to treatment was recorded at 0.908 ± 0.334; by week twenty, it further declined to an average of 0.495 ± 0.4196. The differences observed were statistically significant (F = 28.644, p < 0.001). For patients in the upadacitinib group, the initial average VASI score was noted as being 0.825 ± 0.34; by twenty weeks it averaged approximately 0.53 ± 0.33; however, these differences did not reach statistical significance (F = 2.87, p = 0.14). The efficacy of the combined treatment group was significantly superior compared to both other groups (F = 3.927, p = 0.026). In conclusion, upadacitinib combined with308nm excimer light represents an effective therapeutic option for progressive facial vitiligo and is associated with fewer adverse reactions as well as improved quality of life for patients.

Total Glycosides of Paeony Activates PI3K/Akt Pathway to Alleviate Cardiomyocyte Hypertrophy Induced by AngII.

Total glucosides of paeony (TGP) have been investigated for their effects on cardiomyocyte hypertrophy induced by angiotensin II (Ang II). In this study, rat cardiomyocyte H9c2 cells were treated with various doses of TGP (0, 12.5, 25, 50, 100, 200, and 400 μmol/L), and cell viability was assessed using the MTT method to determine an optimal dose. To establish the cardiomyocyte hypertrophy model, Ang II (1 μmol/L) was used. The experimental groups included the control (Ctrl) group, the hypertrophy group (Ang II), the TGP treatment group (TGP+Ang II), and a combined treatment group (TGP+Ang II+LY), where LY294002, a PI3K/Akt inhibitor, was used. The surface area of H9c2 cells was analyzed using image analysis software, and apoptosis was assessed via flow cytometry. Western blotting was employed to evaluate markers related to cell proliferation, cardiac hypertrophy, apoptosis, and autophagy, as well as the phosphorylation of the PI3K/Akt pathway. The results revealed that Ang II inhibited cell viability and increased cell surface area, apoptosis, and autophagy, all of which were significantly reversed by TGP treatment. Moreover, the addition of LY294002 partially attenuated the effects of TGP, reducing cell viability and promoting hypertrophy, apoptosis, and autophagy. Additionally, Ang II reduced PI3K/Akt signaling activity, while TGP restored it. LY treatment reversed the effects of TGP and suppressed the PI3K/Akt pathway. In conclusion, TGP improves cardiomyocyte hypertrophy induced by Ang II by activating the PI3K/Akt signaling pathway.

KW2478 and Cisplatin Synergistically Anti-colorectal Cancer by Targeting PI3K/AKT/mTOR Pathway.

The objective of this study is to examine the impact of KW-2478 combined with DDP on colorectal cancer cells both in vitro and in vivo and to elucidate the molecular mechanism of KW-2478 in colorectal cancer. qRT-PCR and Western blot were employed to assess HSP90 mRNA and protein expression in normal intestinal epithelial and colorectal cancer cells. DLD-1 and HCT116 were selected for the experiment. CCK-8 was used to detect cytotoxicity; apoptosis rate was measured using flow cytometry; Western blot was employed to measure the expression levels of apoptotic and PI3K/AKT/mTOR pathway proteins. HCT116 was used to construct a subcutaneous tumor model in nude mice. After treatment with KW-2478 and DDP, the growth rate, volume, and weight of the tumor were observed. The expression of Ki67 was detected by immunohistochemistry. Apoptosis of tumor cells was detected using TUNEL. Western blot was employed to measure the expression levels of apoptotic and PI3K/AKT/mTOR pathway proteins. HSP90 mRNA and protein levels were elevated in colorectal cancer cells compared to normal colorectal epithelial cells. HSP90 mRNA and protein expression levels were also significantly elevated in HCT116 and DLD-1 cells compared to other colorectal cancer cells. In DLD-1 and HCT116 cells, KW2478 and DDP inhibited cell viability. The combination of KW2478 and DDP exhibited a significantly higher inhibitory effect compared to either KW2478 or DDP alone. DDP markedly triggered apoptosis in HCT116 and DLD-1. KW2478 at 3 μg/ml and 6 μg/ml induced apoptosis in HCT116 cells but not in DLD-1 cells. The combination of KW2478 and DDP induced a significantly higher apoptosis rate as compared to either KW2478 or DDP alone. Treatment of HCT116 and DLD-1 with KW2478 or DDP alone increased Bax, Caspase9, and Caspase3 protein expression, while decreasing BCL-2. The KW2478+DDP combined treatment group exhibited more significant changes. Phosphorylation of PI3k, AKT, and mTOR decreased in the KW2478 or DDP treatment groups, with more significant changes observed in the KW2478 + DDP combination group. The growth rate, volume, and weight of subcutaneous tumors in the KW2478 or DDP treatment groups were significantly lower than control, and the KW2478+DDP combination group was more affected. Ki67 expression in subcutaneous tumors was reduced in the KW2478 or DDP treatment groups compared to the vehicle control group, with the lowest expression observed in the KW2478 + DDP combination group. The fluorescence intensity of subcutaneous tumors was higher in both the KW2478 and DDP treatment groups compared to the vehicle control group, and the KW2478 + DDP combination group exhibited the strongest fluorescence intensity among them. The combination of KW2478 and cisplatin inhibits colorectal cancer cell proliferation and induces apoptosis by regulating the PI3K/AKT/mTOR pathway.

Treatment outcomes in young adults with gastric cancer

Introduction. According to global data, gastric cancer (GC) is the 5-th most common malignancy with a high cancer-related mortality rate. However, in recent decades, there has been a tendency towards an increase in the incidence of GC among young patients (18 to 40 years old), which currently amounts to 4.4–9.8%. Aim: to evaluate the effectiveness of surgical, combined and palliative treatment options in early-onset GC. Material and Methods. the study included 129 patients aged 18–45 years, who underwent radical, cytoreductive and palliative surgery with or without combination with drug therapy for localized, locally-advanced and primary disseminated GC. the patients were divided into three clinical groups: 1) the surgical group (n=27) included patients with only surgical treatment; 2) the group of combined treatment (n= 58) included patients with PCI &lt;7 who underwent surgery with the volume of CC0 in combination with CT (neoadjuvant, adjuvant, perioperative, simultaneously with or without hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) and patients who underwent only HIPEC; 3) the additional (palliative) group (n=44) included patients with PCI&gt;7 who underwent systemic CT in combination with pressurized intraperitoneal aerosol chemotherapy (PIPAC). Results. the median overall survival (OS) in three groups was 58, 30 and 13 months, respectively. In patients with IV stage of disease who underwent HIPEC with CC0 surgery, OS in the 2nd group was 17 in comparison with 13 months in the third group (PIPEC). Conclusion. Aggressive multimodal treatment in the absence of comorbid status in young patients will allow for intensification of both the perioperative drug therapy component and the implementation of extended multivisceral resections that facilitate radical surgical treatment to improve both DFS and OS.

Evaluation of the efficacy, safety, and satisfaction rate of topical latanoprost in patients with hypopigmented burn scars treated with fractional CO2 laser: a double-blind randomized controlled clinical trial.

Burn scars present psychological and social challenges for patients, classified into atrophic and hypertrophic types. Treatments like corticosteroid injections, laser therapy, and platelet-rich plasma (PRP) injections are commonly recommended for hypertrophic scars, while regenerative medicine and fractional CO2 lasers are linked to some degree of improvement for atrophic scars. Hypopigmented and depigmented burn scars pose ongoing challenges for healthcare providers and patients, with therapies such as intense pulsed light and fractional CO2 laser showing variable effects in treating these conditions. This study evaluates the effectiveness of latanoprost, a prostaglandin analog, in combination with fractional CO2 laser for repigmentation of hypopigmented burn scar lesions. During the study, patients were treated with 0.005% latanoprost eye drop or normal saline twice a day for 6months and underwent six monthly fractional CO2 laser sessions. Treatment instructions were provided by the physician, and patients were instructed to report any complications and avoid using other medications in the treatment area. Assessments included photography at the start of the study and in three follow-up sessions at three-month intervals. Improvement was assessed using the Subject Global Aesthetic Improvement Scale (SGAIS) by both the physician and patients. Patient satisfaction was evaluated using a Grade scale, and side effects were monitored in all follow-up sessions. In the third follow-up session, physicians assessing the Subject Global Aesthetic Improvement Scale (SGAIS) observed that a higher proportion (85.7%) of cases in the fractional CO2 laser with latanoprost group achieved a grade of 4 (50-74% improvement). In the placebo group, 0% of patients achieved grade 4, and 71.4% were classified as grade 2 (0-24% improvement), indicating a significant difference (P-value: 0.0001). Patient satisfaction, measured by the "Grade scale to evaluate patient satisfaction" index, revealed a notable contrast between the two groups, with average satisfaction scores of 8.50 ± 0.65 and 4.64 ± 1.00 for the fractional CO2 laser with latanoprost and placebo groups, respectively, indicating a statistically significant difference (P = 0.0001). Furthermore, throughout the study, no severe side effects were reported by any of the patients. Prostaglandin analogs, particularly latanoprost, have proven to be effective in promoting repigmentation of hypopigmented and depigmented burn scar lesions. When this topical medication is combined with fractional CO2 laser treatment, it enhances the laser's efficacy and overall effectiveness in treating the lesions. This combination is crucial for improving hypopigmented scar treatment by enhancing both the laser's effectiveness in scar improvement and the delivery of latanoprost through the laser. WHAT IS ALREADY KNOWN ABOUT THIS TOPIC? : Hypopigmented burn scars are one of the manifestations of burns that are resistant to treatment. These scars not only cause discomfort for patients but also present a treatment challenge for physicians. In previous studies, latanoprost and bimatoprost, analogs of prostaglandin PGF2a, showed effectiveness in repigmenting vitiligo lesions. However, no study has examined the role of these topical drugs in treating hypopigmented and depigmented burn scars. WHAT DOES THIS STUDY ADD? : The fractional CO2 laser caused significant repigmentation in hypopigmented lesions of burn scars. 64.3% of the patients who received this intervention showed grade 2 improvement (0-24% improvement), 7.1% showed grade 3 improvement (25-49% improvement), and 28.6% showed no improvement (grade 1) in the third follow-up session based on the SGAIS criteria as evaluated by the patients. The combination of CO2 fractional laser and latanoprost caused significant repigmentation in hypopigmented burn scar lesions. 85.7% of patients showed grade 4 improvement (50-74% improvement), and 14.3% showed grade 3 improvement (25-49% improvement) and 0% showed no improvement (grade 1) in the third follow-up session based on the SGAIS criteria as evaluated by the patients. The combination of CO2 fractional laser and latanoprost was significantly more effective than CO2 fractional laser alone based on the SGAIS criteria, as evaluated by physicians and patients in all three follow-up sessions. Additionally, the satisfaction of the patients in the combined treatment group was significantly higher than that of the CO2 fractional laser treatment group.

Synergistic Effects of Hydrogen Peroxide Preconditioning and Valproic Acid on Hepatic Differentiation of Mesenchymal Stem Cells.

Ex vivo preconditioning increases the therapeutic potential of mesenchymal stem cells (MSCs) in terms of antioxidant activity, growth factor production, homing, differentiation, and immunomodulation. Therefore, it is considered an effective strategy to be used before transplantation and therapeutic application of MSCs. Histone deacetylase inhibitor (HDACi), valproic acid (VPA), has been reported to induce hepatic differentiation in MSCs. Although individual studies have shown that preconditioning and epigenetic modification enhance the survival and differentiation of MSCs, the combined effects of these therapies have not been fully explored. This study aims to investigate the combined effect of hydrogen peroxide (H2O2) preconditioning and HDACi (valproic acid) on the differentiation of bone marrow-derived mesenchymal stem cells (BM-MSCs) into hepatic-like cells. MSCs were first preconditioned with H2O2 and then cultured with VPA. The migration and proliferation potential of the treated cells were evaluated using wound healing and colony-- forming unit assays. Furthermore, the expression of hepatic genes (FOXA2, CK8, CK18, TAT) and proteins (AFP, ALB, TAT) was evaluated in all treated groups. The combined therapy group exhibited enhanced cell migration and proliferation, as evidenced by wound healing and colony-forming unit assays. Additionally, the combined treatment group showed higher expression of FOXA2, CK8, and CK18 hepatic genes and TAT protein, suggesting an improved differentiation of stem cells into hepatocytes. In conclusion, the combination of H2O2 and VPA emerges as an important factor in promoting hepatocyte differentiation. However, further studies are required to optimize this protocol for future therapeutics.

Safety and efficacy of argatroban combined with antiplatelet therapy for acute mild-to-moderate ischemic stroke with large artery atherosclerosis

Background and PurposePatients with stroke due to large artery atherosclerosis are at risk of early progression and recurrence. The efficacy and safety of argatroban in stroke patients who did not receive reperfusion therapy, and which patients may benefit from it, are uncertain. MethodsWe conducted a cohort study to assess whether argatroban given within 72 hours of symptom onset, combined with antiplatelet therapy, improved neurological outcomes of patients with acute mild to moderate ischemic stroke in China. Patients were divided into the combined treatment group and the control group. Inverse probability of treatment weighting was used to balance baseline covariates. The primary efficacy outcome is the proportion of mRS score 0-2 at 90 days. The secondary efficacy outcomes included END proportion, change in NIHSS score from the baseline to day 7, recurrent cardiovascular events, and cardiovascular death. The safety outcomes were hemorrhagic transformation (HT) of infarction and organ hemorrhage at 7 days. ResultsCompared with the control group, a higher proportion of mRS (0-2) at 90 days was found in patients in the combined treatment group (85.3% vs 74.5%, p=0.042). There was no significant difference in the safety outcomes between the two groups. Exploratory subgroup analysis showed positive associations with argatroban combined therapy and good prognosis in NIHSS score ≥5 and age ≥70 subgroups. ConclusionsOur study suggested that argatroban can improve neurological outcomes for mild to moderate LAA patients but not increase the risk of bleeding.

The combination of polystyrene microplastics and di (2-ethylhexyl) phthalate promotes the conjugative transfer of antibiotic resistance genes between bacteria.

Plastic pollution has become a common phenomenon. The process of plastic degradation is accompanied by the release of microplastics and plasticizers. However, the coexistence of microplastics and plasticizers on the transfer of antibiotic resistance genes (ARGs) has not been reported until now. Here, polystyrene (PS) microplastics and plasticizer di (2-ethylhexyl) phthalate (DEHP) were used for combined treatment experiment and their effects and mechanisms on the transfer of ARGs between bacteria were explored. By increasing cell membrane permeability and the expression of correlated genes, the combined treatment group showed promoting effects on the transfer of ARGs than that of control, with the highest promoting effects observed at 1 mg/L PS and 0.1 mg/L DEHP, which was 3.0 times higher in ARGs transfer rate than that of control. It was found that PS and DEHP treatment alone also led to a higher conjugative transfer frequency, and the frequency of the combined treatment was lower than that of the corresponding single treatment group. This indicated that the effects of DEHP and microplastics on ARGs transfer might be antagonistic. Transcriptome analysis indicated that the transfer of ARGs affects bacterial ion binding, oxidative stress, and energy metabolism processes, while the expression of genes related to cell membrane permeability, DNA repair, bacterial drug resistance, and quorum sensing also increase. This study may provide new insights for explaining the combined effects of various pollutants in the environment on the spread of ARGs.

Study on the damage and variation of Agropyron mongolicum induced by the combined action of discharge plasma and plasma-activated water.

To investigate the effect of combined action of discharge plasma (DP) and plasma-activated water (PAW) in mutagenesis breeding, this study focuses on Agropyron mongolicum. We utilized high-voltage DC pulsed dielectric barrier discharge for seed treatment, alone and in combination with PAW. The research focused on germination rates, evolution of physicochemical properties of imbibition residual solution, reactive oxygen species (ROS), malondialdehyde (MDA), and volatile organic compounds (VOCs) to assess DP-induced damage and variability in Agropyron mongolicum. Results indicated that after 18h of combined treatment, the germination rate of Agropyron mongolicum dropped to 29.67%, below the LD50 threshold. Treated seedlings exhibited elevated ROS and MDA levels compared to controls. The concentration of reactive nitrogen and oxygen species (RONS) in the imbibition residual solution of the combined treatment group was lower than in freshly prepared PAW, indicating RONS penetration into the seed embryo via water, leading to oxidative damage. Enhanced lateral root differentiation, early tillering, increased biomass, and albino variant plants were observed in the surviving seedlings post-treatment. Transmission electron microscope (TEM) and Gas Chromatography-Ion Mobility Spectrometry (GC-IMS) analysis confirmed that plasma treatment induced oxidative damage in Agropyron mongolicum. In conclusion, high-power, long-duration direct DP treatment caused oxidative damage and reduced germination rates in Agropyron mongolicum, with PAW intensifying these effects. PAW was identified as the main driver of variation and lethality, while DP played a supportive role. Combined DP and PAW treatment induced variations in Agropyron mongolicum, providing experimental evidence and theoretical insights for applying DP treatment in plant mutagenesis breeding.

Utilizing a Combination of Supplements Comprising Boric Acid, Magnesium, Vitamin D3, and Extra Virgin Olive Oil to Improve Metabolism in Menopausal Ovariectomized Rats.

Metabolic syndrome during menopause can lead to diabetes, cardiovascular problems, and increased mortality rates. Hormone replacement therapy is recommended to manage climacteric complications, but it has serious adverse effects. This study, therefore, investigated the potential of supplementing some minerals, vitamins, and natural products like boric acid, magnesium, vitamin D3, and extra virgin olive oil on metabolic status of menopausal ovariectomized rats. Fourty-two female adult rats were randomly assigned to seven groups: a) Sham Control, b) Ovariectomized Control, c) Ovariectomized + Boric acid, d) Ovariectomized + Magnesium, e) Ovariectomized + Vitamin D3, f) Ovariectomized + Extra virgin olive oil, and g) Ovariectomized + Combined treatment groups. Serum inflammatory and oxidative stress markers, serum lipogram pattern, hepatic triglycerides, body weight, fasting blood glucose, serum insulin, leptin, and adiponectin, as well as hepatic insulin signaling cascade, IRS1/pAKT/GLUT4 were measured in each group to assess metabolic function. Results revealed a significant improvement in inflammation, oxidative stress, and metabolic parameters by individual and concomitant treating ovariectomized rats with boric acid, magnesium, vitamin D3, and extra virgin olive oil. Interestingly, the concurrent use of these supplements displayed a better impact than individual use, suggesting their valuable therapeutic potential for managing metabolic syndrome in menopausal women. However, the necessity of all four supplements for optimal therapeutic effects remains unsubstantiated.

Information and Access for Safe Narcotic Disposal: A Cluster-Randomized Trial Among Pediatric Orthopaedic Surgical Patients in Los Angeles County

Introduction: Greater than two-thirds of individuals report unused opioids following surgical procedures. The need for improved prescribing practices notwithstanding, efforts to improve safe narcotic disposal are requisite to decreasing aberrant narcotic availability and opioid-related hospitalizations. This study aimed to evaluate the additive efficacy of education and access to DEA-compliant narcotic return receptacles on narcotic disposal rates among pediatric orthopaedic surgical patients. Methods: From July 2021 to July 2023, patients aged 5 to 17 years at two disparate sites were recruited for enrollment. Cluster randomization was done weekly to determine whether education was given on safe narcotic disposal versus standard discharge instructions. Halfway through the study, narcotic disposal receptacles were introduced as an additive intervention. Postoperatively, participants were asked to self-report opioid disposal rates and complete the Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference Short Form to gauge pain control. Two sample z test of proportions and Fisher exact tests were used to compare disposal rates from both the isolated and combined interventions. Results: Analysis was restricted to 131 of 576 total patients: 44 (33.6%) disposed of unused narcotic medications and 87 (66.4%) did not. No notable difference was observed in disposal rates between those who received education or not (28/70 [40.0%] vs. 16/61 [26.2%], P &gt; 0.05) and those who had bin access or not (18/59 [30.5%] vs. 26/72 [36.1%], P &gt; 0.05). Furthermore, no notable difference was found between the control group and combination intervention group receptacles (6/25 [24.0%] vs. 8/23 [34.8%], P &gt; 0.05) or the education only and combination intervention group (20/47 [42.5%] vs. 8/23 [34.8%], P &gt; 0.05). Discussion: Neither preoperative education alone nor the addition of convenient disposal bins improved narcotic disposal rates following surgery. Conclusion: Retention rates remained high despite either intervention. Therefore, efforts to decrease narcotic availability must be nuanced and multimodal. Further studies may investigate the role of longitudinal patient education to better influence risk perception and subsequent behavioral changes.

The Simultaneous Treatment of PC-3 Cells with the DNA-Demethylating Agent Decitabine and S-Adenosylmethionine Leads to Synergistic Anticancer Effects.

Background: Epigenetic dysregulation is a common feature of cancer. Promoter demethylation of tumor-promoting genes and global DNA hypomethylation may trigger tumor progression. Epigenetic changes are unstable; thus, research has focused on detecting remedies that target epigenetic regulators. Previous studies have suggested that concordantly targeting hypomethylation and hypermethylation is beneficial for suppressing both the oncogenic and pro-metastatic functions of cancer cells. Therefore, we aimed to investigate the effect of a combination of S-adenosylmethionine (SAM) and the demethylating agent decitabine on prostate cancer cells. Materials and Methods: Prostate cancer cells (PC-3) were treated with SAM, decitabine, or a combination of both. Proliferation, migration, invasion, and methylation assays were also performed. A transcriptome study was conducted to detect different gene clusters between the treatment groups, followed by analyses using the Kyoto Encyclopedia of Genes and Genomes pathway and ingenuity pathway analysis. Finally, to gain information on differential gene expression, promoter methylation studies were performed. Results: Groups treated with decitabine, SAM, or their combination showed reduced proliferative capacity. The decitabine-treated group showed a marginal increase in cell migration and invasion, whereas the SAM-treated and combination treatment groups showed reduced invasion and migration potential. Methylation assays demonstrated the restoration of decitabine-induced demethylation in prostate cancer samples, whereas the transcriptome study revealed the upregulation of different gene clusters between the treatment groups. Methylation studies confirmed that SAM could restore the decitabine-induced demethylation of proto-oncogenes, but it did not induce the re-methylation of tumor-suppressor genes. Conclusions: Combination treatment with SAM and decitabine had an additive effect and did not nullify each other.

Effects of Vitamin C and E Supplementation with High-Intensity Swimming on Bone Adaption in Mice

The importance of physical activity has grown in recent years, as seen by a rise in physical activity. High-intensity exercise can be harmful to bone health if not done correctly. This study investigates the effect of high-intensity exercise mixed with vitamin C and supplementation on bone cellular plasticity, with the goal of discovering new techniques to improve skeletal integrity. A study was performed on 28 female mice (Mus musculus) that were healthy, not pregnant, and were between 3 and 4 months. The mice weighed between 18 and 35 grams. The mice were allocated into four groups through a random process: a control group (CON), which did not receive any specific treatment; a group that received supplementation of vitamins C and E (VIT); a group that underwent high-intensity swimming exercise (EXC); and a combined treatment group that received both vitamin supplementation and high-intensity exercise (CBD). After a period of 28 days, femur bones were gathered for histological examination in order to quantify the amount of osteoblasts, osteocytes, osteoclasts, and cortex thickness. The EXC group had the fewest osteoblasts (25.86 ± 4.667) and osteocytes (26.86 ± 4.667), which suggests that the intense exercise caused a lot of bone breakdown. In contrast, the group that received both exercise and vitamin supplementation, known as the CBD group, had markedly larger numbers of osteoblasts (37.86 ± 3.635) and osteocytes (54.7 ± 7.154), while having the lowest count of osteoclasts (0.714 ± 0.184). The statistical analysis showed significant disparities in the number of osteocytes and osteoblasts between the EXC group and both the VIT and CBD groups (p&lt;0.05). Intense activity in mice leads to an increase in bone resorption, which may negatively affect bone health. Supplementation with vitamins C and E has been shown to have a preventive effect by promoting bone formation. Additional investigation is necessary to examine the fundamental processes and lasting consequences.

Outcome of Solifenacin Monotherapy and Combined Solifenacin and Mirabegron Therapy in Patient with Overactive Bladder

Background: Overactive bladder has a profound detrimental effect on quality of life. In the vast majority of the patients, the management plan entails behavioral modification and the anti-muscarinic drug solifenacin, which has considerable side effects and lower patients satisfaction rate. Mirabegron, a β3-adrenoceptor agonist, significantly improves OAB symptoms and plays an important role in the management algorithm. Objectives: This study examined the effectiveness and safety of solifenacin monotherapy versus mirabegron and solifenacin combination therapy in the treatment of OAB. Methods: This study was conducted as a quasi-experimental model. A total of 90 patients were included in the study through purposive sampling and divided into two comparison groups: Group A (control group) receiving Solifenacin (5 mg) once daily at night for 12 weeks, and Group B (experimental group) receiving a combination of Solifenacin (5 mg) and Mirabegron (25 mg) nightly for the same period. Follow-up visits were conducted at 4, 8, and 12 weeks to track the number of micturitions, urgency, urge incontinence, nocturia, and voided volume over 24 hours. Data analysis was conducted using SPSS version 22, and the chi-square test was used to compare percentages of different outcome variables. A p-value of less than 0.05 was considered statistically significant. Results: Solifenacin (5 mg) monotherapy and combined miragraben (25 mg) and solifenacin (5 mg) showed comparable efficacy in alleviating symptoms of OAB, but greater improvement with regard to frequency of micturition, urgency, and urge incontinence were showed in the combined therapy group. Conclusion: The combination of Solifenacin and Mirabegron provides a more effective treatment for overactive bladder compared to Solifenacin alone. Although the combined treatment group experienced more adverse effects, these differences were not statistically significant between the two groups. Since the adverse effects were generally mild and temporary, the combined therapy remains a viable option for managing overactive bladder. J Com Med Col Teachers Asso July 2024; 28(2): 75-81

Osimertinib exacerbates immune checkpoint inhibitor-related severe adverse events by activating the IL-6/JAK/STAT3 pathway in macrophages.

The combination of epithelial growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and immune checkpoint inhibitors (ICIs) leads to an increased incidence of severe immune-related adverse events (irAEs). However, the mechanisms underlying macrophages in irAEs have not been elucidated. An osimertinib and ICI-induced irAE mouse model was constructed. Lung micro-CT scans were used to assess the degree of inflammatory infiltration. Hematoxylin-eosin staining was used to analyze the histopathologic inflammatory infiltration in mouse liver and lung tissues. Flow cytometry was used to detect the percentages of T cells, NK cells, and macrophages and the expression of EGFR. Enzyme-linked immunosorbent assay (ELISA) was used to detect the serum interleukin (IL)-6, alanine transaminase (ALT), ferritin, and tumor necrosis factor (TNF)-α levels. Total RNA extracted from mouse liver macrophages was analyzed by RNA-seq. Simple Western blot analysis was used to detect the IL-6/JAK/STAT3 pathway activation state. Osimertinib combined with ICIs upregulated EGFR expression on macrophages with increased serum IL-6, ALT, and ferritin levels. RNA-seq and simple Western blot analysis of mouse liver macrophages confirmed that that the IL-6/JAK/STAT3 pathway was activated in the combination treatment group. Ruxolitinib blocked the IL-6/JAK/STAT3 pathway and significantly decreased the serum IL-6, ALT, and ferritin levels in the combination treatment group. An osimertinib and ICI-induced irAE mouse model was constructed that showed osimertinib combined with ICIs inhibited EGFR phosphorylation and activated the IL-6/JAK/STAT3 signaling pathway in mouse liver macrophages, which led to the release of relevant cytokines.

Hepatic arterial infusion chemotherapy plus regorafenib compared with regorafenib alone as second-line therapy for advanced hepatocellular carcinoma: a randomised controlled trial protocol

IntroductionThe exact role of hepatic arterial infusion chemotherapy (HAIC) in advanced hepatocellular carcinoma (aHCC) is still unknown. The combination of HAIC and sorafenib has been proven to be more effective...

Synergistic inhibition of proliferation and induction of apoptosis in oral tongue squamous cell carcinoma by mebendazole and paclitaxel via PI3K/AKT pathway mitigation.

Serve as one of common cancer in the mouth, oral tongue squamous cell carcinoma (OTSCC) is a serious problem affecting human oral health. The aim of this study was to evaluate the effects of mebendazole (MBZ) alone and combined with paclitaxel on the proliferation and occurrence of OTSCC and its molecular mechanism. Cell viability, apoptosis, cell cycle distribution, and the expression of PI3K, p-PI3K, AKT, and p-AKT were evaluated by Cell Counting Kit-8 (CCK-8), flow cytometry, and Western blot, respectively. Immunofluorescence was used to assess changes in microtubule morphology of CAL-27 and UM-SCC-1 cells with α-tubulin antibody labeling. The CCK-8 assay revealed a dose-dependent inhibitory effect of both MBZ and paclitaxel on CAL-27 and UM-SCC-1 cells. The apoptosis assay showed significantly elevated levels of apoptosis-specific markers, cleaved caspase-3, and cleaved PARP, in the combined treatment group compared to the control and single-agent groups. The combination of MBZ and paclitaxel showed enhanced inhibition of key PI3K/AKT pathway proteins' phosphorylation and reduced expression of Cyclin B and PCNA compared to the control. The α-tubulin staining area was notably reduced in the combined treatment group relative to the other groups. Both MBZ and paclitaxel treatments inhibited of cell proliferation and microtubule formation by reducing the PI3K/AKT pathway in CAL-27 and UM-SCC-1 cells, with the combination demonstrating synergistic effects. Our study suggests MBZ and paclitaxel as potential agents for the treatment of OTSCC.

Clinical Study of Psycho-cardiology Combined with FNS in the Treatment of SCAD with Depression

To investigate the effects of psycho-cardiology combined with fastigial nucleus stimulation (FNS) on patients with stable coronary artery disease (SCAD) complicated with depression, we observed the changes of concentrations of N-terminal pro-B type natriuretic peptide (NT-proBNP), tumor necrosis factor-α(TNF-α), 5-hydroxytryptamine (5-HT), dopamine (DA) and depressive symptoms in these patients. One hundred and fifty patients, who were hospitalized the Department of Cardiology at the Third People&amp;apos;s Hospital of Mianyang from February 2020 to October 2021 with a confirmed diagnosis of SCAD combined with depression, were selected as study subjects. Patients were randomly divided into a control group, a psycho-cardiology treatment group and a combined treatment group. The control group was given conventional treatment of SCAD and pseudo-stimulation of the fastigial nucleus, the psycho-cardiology treatment group was given conventional treatment of SCAD, psychological interventions and pseudo-stimulation of the fastigial nucleus, and the combined treatment group was given conventional treatment of SCAD, psychological intervention and FNS. The changes of concentrations of TNF-α, NT-proBNP, 5-HT and DA were observed in the three groups of patients, and the changes of the state of depression were assessed by Hamilton Depression Scale (HAMD). Serum NT-proBNP and TNF-α concentrations decreased significantly after treatment in the three groups. Especially, the decrease in the combined treatment group was the most significant(&amp;lt;i&amp;gt;p&amp;lt;0.05&amp;lt;/i&amp;gt;). Serum 5-HT and DA concentrations were not statistically different in the three groups before and after treatment (&amp;lt;i&amp;gt;p&amp;gt;0.05&amp;lt;/i&amp;gt;). However, they were significantly higher in the psycho-cardiology treatment group and the combined treatment group(&amp;lt;i&amp;gt;p&amp;lt;0.05&amp;lt;/i&amp;gt;) and the increase in the combined treatment group was more significant than in the psycho-cardiology treatment group. In the control group, the difference of HAMD scores was not statistically significant before and after treatment (&amp;lt;i&amp;gt;p&amp;gt;0.05&amp;lt;/i&amp;gt;), in the psycho-cardiology treatment group and the combined treatment group, the scores decreased significantly after treatment compared to before treatment (&amp;lt;i&amp;gt;p&amp;lt;0.05&amp;lt;/i&amp;gt;). Furthermore, compared to the psycho-cardiology treatment group, the decrease was more significant in the combined treatment group (&amp;lt;i&amp;gt;p&amp;lt;0.05&amp;lt;/i&amp;gt;). Our data suggested that Psycho-cardiology medicine combined with FNS can effectively reduce the level of serum NT-proBNP and TNF-α, increase the serum concentrations of 5-HT and DA and improve the symptoms of depression in patients with SCAD complicated with depression.

Outcome of combined surgery with compression therapy for management of venous leg ulcer

Background: Venous leg ulcers (VLUs) are late indicators of chronic venous insufficiency (CVI) and venous hypertension. Compression therapy (CT) with multilayer bandage is the first line of treatment modality of ulcer management. But CT has a slow ulcer healing rate and high chance of recurrence. The present study was conducted to identify the outcome of combined surgery with compression therapy to manage VLU. Methods: In this prospective study, 60 patients were included who presented to the department of cardiovascular surgery of Dhaka Medical College and Hospital between January 2021 to December 2023. The patients were divided into two groups. Group A included the patients who underwent surgery combined with compression therapy while Group B patients received only compression therapy (CT). Ulcer healing time, recurrence rate and Venous Clinical Scoring System (VCSS) were analysed to determine the outcome. Results: There was no significant difference in the demographic variables between two groups. 30 limb ulcers healed in the combined treatment group with a median healing time of 1.6 months (95% CI, 1.42–1.82), while 24 limb ulcers healed in the CT alone group with a median healing time of 2.15 months (95% CI, 1.92–2.45). The ulcer healing time was shorter in the combined treatment group than in the CT alone group (HR for ulcer healing 1.98, 95% CI, 1.474–2.309, p&lt;0.05). Recurrence rate was higher in CT group (16.66% vs 53.33%). Besides VCSS was lower in Combined group that CT group after 1month, 6 month and 12 month of follow-up which was statistically significant. (p&lt;0.05) Conclusions: The present study has demonstrated combined treatments can shorten the ulcer healing time and reduce the ulcer recurrence rate compared with CT alone for treating VLU. Further randomized large scale multicenter study is recommended to provide a better management to the patients.