Combined Treatment Group Research Articles

Melatonin and mesenchymal stem cells co-administration alleviates chronic obstructive pulmonary disease via modulation of angiogenesis at the vascular-alveolar unit.

Chronic obstructive pulmonary disease (COPD) is considered a severe disease mitigating lung physiological functions with high mortality outcomes, insufficient therapy, and pathophysiology pathways which is still not fully understood. Mesenchymal stem cells (MSCs) derived from bone marrow play an important role in improving the function of organs suffering inflammation, oxidative stress, and immune reaction. It might also play a role in regenerative medicine, but that is still questionable. Additionally, Melatonin with its known antioxidative and anti-inflammatory impact is attracting attention nowadays as a useful treatment. We hypothesized that Melatonin may augment the effect of MSCs at the level of angiogenesis in COPD. In our study, the COPD model was established using cigarette smoking and lipopolysaccharide. The COPD rats were divided into four groups: COPD group, Melatonin-treated group, MSC-treated group, and combined treated group (Melatonin-MSCs). We found that COPD was accompanied by deterioration of pulmonary function tests in response to expiratory parameter affection more than inspiratory ones. This was associated with increased Hypoxia induciblefactor-1α expression and vascular endothelial growth factor level. Consequently, there was increased CD31 expression indicating increased angiogenesis with massive enlargement of airspaces and thinning of alveolar septa with decreased mean radial alveolar count, in addition to, inflammatory cell infiltration and disruption of the bronchiolar epithelial wall with loss of cilia and blood vessel wall thickening. These findings were improved significantly when Melatonin and bone marrow-derived MSCs were used as a combined treatment proving the hypothesized target that Melatonin might augment MSCs aiming at vascular changes.

Efficacy of ganglion impar block combined with pudendal nerve pulsed radiofrequency for pudendal neuralgia management—a randomized clinical trial

BackgroundPudendal neuralgia is a chronic and debilitating condition. Its prevalence ranges from 5 to 26%. Currently, therapeutic approaches to treat pudendal neuralgia include patient education, medication management, psychological and physical therapy, and procedural interventions, such as nerve block, trigger point injections, and surgery. Drug therapy has a limited effect on pain relief. A pudendal nerve block may cause a significant decrease in pain scores for a short time; however, its efficacy significantly decreases over time. In contrast, pudendal nerve pulsed radiofrequency can provide pain relief for 3 months, and ganglion impar block has been widely used for treating chronic perineal pain and chronic coccygodynia. This study aimed to determine the efficacy and safety of monotherapy (pudendal nerve pulsed radiofrequency) and combination therapy (pudendal nerve pulsed radiofrequency plus ganglion impar block) in patients with pudendal neuralgia.MethodsThis randomized, controlled clinical trial will include 84 patients with pudendal neuralgia who failed to respond to drug or physical therapy. Patients will be randomly assigned into one of the two groups: mono or combined treatment groups. The primary outcome will be a change in pain intensity measured using the visual analog scale. The secondary outcomes will include a Self-Rating Anxiety Scale score, Self-Rating Depression Scale score, the use of oral analgesics, the Medical Outcomes Study Health Survey Short Form-36 Item score, and the occurrence of adverse effects. The study results will be analyzed using intention-to-treat and per-protocol analyses. Primary and secondary outcomes will be evaluated between the mono and combined treatment groups. Subgroup analyses will be conducted based on the initial ailment, age, and baseline pain intensity. The safety of the treatment will be assessed by monitoring adverse events, which will be compared between the two groups.DiscussionThis study protocol describes a randomized, controlled clinical trial to determine the efficacy and safety of mono and combination therapies in patients with pudendal neuralgia. The study results will provide valuable information on the potential benefits of this combination therapy and contribute to the development of more effective and safer treatments for patients with pudendal neuralgia.Trial registrationChinese Clinical Trial Registry (ChiCTR2200061800).

The STING agonist IMSA101 enhances chimeric antigen receptor T cell function by inducing IL-18 secretion

As a strategy to improve the therapeutic success of chimeric antigen receptor T cells (CART) directed against solid tumors, we here test the combinatorial use of CART and IMSA101, a newly developed stimulator of interferon genes (STING) agonist. In two syngeneic tumor models, improved overall survival is observed when mice are treated with intratumorally administered IMSA101 in addition to intravenous CART infusion. Transcriptomic analyses of CART isolated from tumors show elevated T cell activation, as well as upregulated cytokine pathway signatures, in particular IL-18, in the combination treatment group. Also, higher levels of IL-18 in serum and tumor are detected with IMSA101 treatment. Consistent with this, the use of IL-18 receptor negative CART impair anti-tumor responses in mice receiving combination treatment. In summary, we find that IMSA101 enhances CART function which is facilitated through STING agonist-induced IL-18 secretion.

Intervention of computer-assisted cognitive training combined with occupational therapy in people with mild cognitive impairment: a randomized controlled trial

ObjectiveInvestigate the impact of combined computerized cognitive training and occupational therapy on individuals with mild cognitive impairment (MCI).MethodsWe randomly assigned 118 MCI patients into two groups: a combined intervention group (n = 37) and a control group (n = 81), the latter receiving standard nursing care. The intervention group additionally underwent 12 weeks of computerized cognitive training and occupational therapy. Blind assessors evaluated cognitive performance, anxiety, depression, and daily living activities before the intervention, post-intervention, and at a 3-month follow-up.ResultsRepeated-measures analysis of variance showed that the sMoCA scores, HAMA scores, and ADL scores of the experimental group at T2 (post-intervention) and T3 (3-month follow-up) were higher than those of the control group, and the difference was statistically significant (p < 0.001, p < 0.001, p = 0.026).ConclusionComputerized cognitive training combined with occupational therapy can improve patients’ cognitive status, enhance their compliance with continuing care, and maintain their anxiety and self-care ability at a stable level.Clinical trial registrationhttps://www.chictr.org.cn/index.html, identifier ChiCTR2200065014.

Effects of C-reactive protein rapid testing and communication skills training on antibiotic prescribing for acute cough. A cluster factorial randomised controlled trial

This cluster randomised clinical trial carried out in 20 primary care centres in Barcelona was aimed at assessing the effect of a continuous intervention focused on C-reactive protein (CRP) rapid testing and training in enhanced communication skills (ECS) on antibiotic consumption for adults with acute cough due to lower respiratory tract infection (LRTI). The interventions consisted of general practitioners and nurses’ use of CRP point-of-care and training in ECS separately and combined, and usual care. The primary outcomes were antibiotic consumption and variation of the quality-adjusted life years during a 6-week follow-up. The difference in the overall antibiotic prescribing between the winter seasons before and after the intervention was calculated. The sample size calculated could not be reached due to the COVID-19 outbreak. A total of 233 patients were recruited. Compared to the usual care group (56.7%) antibiotic consumption among patients assigned to professionals in the ECS group was significantly lower (33.9%, adjusted odds ratio [aOR] 0.38, 95% CI 0.15–0.94, p = 0.037), whereas patients assigned to CRP consumed 43.8% of antibiotics (aOR 0.70, 95% CI 0.29–1.68, p = 0.429) and 38.4% in the combined intervention group (aOR 0.45, 95% CI, 0.17–1.21; p = 0.112). The overall antibiotic prescribing rates in the centres receiving training were lower after the intervention compared to those assigned to usual care, with significant reductions in β-lactam rates. Patient recovery was similar in all groups. Despite the limited power due to the low number of patients included, we observed that continuous training achieved reductions in antibiotic consumption.

Effects of combined resistance training and Tai Chi on oxidative stress, blood glucose and lipid metabolism and quality of life in elderly patients with type 2 diabetes mellitus

ABSTRACT This study examined the effects of resistance training (RT), Tai Chi (TC) and combination intervention (RT & TC) on the oxidative stress, blood glucose and lipid metabolism and quality of life of elderly patients with type 2 diabetes mellitus (T2DM). Ninety-four elderly patients with T2DM were randomly divided into an RT group (RTG, n = 23), TC group (TCG, n = 24), combination intervention group (CIG, n = 24) and control group (CG, n = 23). All participants were given nutrition and medication. On this basis, RTG, TCG and CIG were administered for 24 weeks (3 times/week, 40 minutes/time). Observation indicators were malondialdehyde (MDA), superoxide dismutase (SOD), 8-hydroxy-2 deoxyguanosine (8-OHdG), fasting plasma glucose (FPG), postprandial plasma glucose (PPG), haemoglobin A1c (HbA1c) and diabetes specific quality of life (DSQL). RT, TC and joint intervention can reduce the oxidative stress damage on elderly patients with T2DM to different degrees, control the levels of blood sugar and blood lipid and improve the quality of life. Compared with single intervention, combination intervention can further reduce the level of oxidative stress but has no additional benefits on blood glucose and lipid control and quality of life.

Efficacy and safety of herbal medicine combined with acupuncture in pediatric epilepsy treatment: A meta-analysis of randomized controlled trials.

To evaluate the efficacy and safety of herbal medicine and acupuncture combination for pediatric epilepsy treatment. Databases were searched from their interception until October 2023 to identify randomized controlled trials focusing on the therapeutic efficacy of herbal medicine-acupuncture combination (intervention group) for pediatric epilepsy. The primary outcome was the risk of treatment failure, whereas the secondary outcomes included the risk of post-treatment electroencephalogram (EEG) abnormalities and adverse events. Subgroup analyses were conducted based on the type of herbal compound formulas. Meta-regression analysis was conducted to examine the influence of patient demographics and clinical history on the therapeutic efficacy of herbal medicine-acupuncture combination for pediatric epilepsy. To assess the cumulative evidence, trial sequential analysis (TSA) was performed. The analysis included 10 trials involving a total of 882 pediatric patients. Meta-analysis revealed that the intervention group had a lower risk of treatment failure than the control group (risk ratio [RR] = 0.3, 95% confidence interval [CI]: 0.19-0.47, P<0.00001, I2 = 0%, 10 trials). Subgroup analyses showed that therapeutic efficacy was consistent among the different herbal compound formulas. Meta-regression analysis revealed that the efficacy of the treatments did not significantly vary with patient age, male sex, and duration of seizure history. TSA suggested that herbal medicine-acupuncture combination exerted a robust and conclusive effect on seizure treatment. Although the combined used of herbal medicine and acupuncture was not associated with a lower risk of post-treatment EEG abnormalities (RR = 0.82, 95%CI:0.6-1.11, P = 0.2, 3 trials), the risk of adverse events was reduced (RR = 0.27, 95%CI:0.18-0.41, P<0.00001, 4 trials). The meta-analysis suggested that combined use of herbal medicine and acupuncture is a promising and safe clinical approach for pediatric epilepsy treatment. Further large-scale studies are necessary to conclusively determine the efficacy and safety of herbal medicine and acupuncture in pediatric epilepsy treatment.

Molecular interactions between metformin and D-limonene inhibit proliferation and promote apoptosis in breast and liver cancer cells

BackgroundCancer is a fatal disease that severely affects humans. Designing new anticancer strategies and understanding the mechanism of action of anticancer agents is imperative.Hypothesis/PurposeIn this study, we evaluated the utility of metformin and D-limonene, alone or in combination, as potential anticancer therapeutics using the human liver and breast cancer cell lines HepG2 and MCF-7.Study designAn integrated systems pharmacology approach is presented for illustrating the molecular interactions between metformin and D-limonene.MethodsWe applied a systems-based analysis to introduce a drug–target–pathway network that clarifies different mechanisms of treatment. The combination treatment of metformin and D-limonene induced apoptosis in both cell lines compared with single drug treatments, as indicated by flow cytometric and gene expression analysis.ResultsThe mRNA expression of Bax and P53 genes were significantly upregulated while Bcl-2, iNOS, and Cox-2 were significantly downregulated in all treatment groups compared with normal cells. The percentages of late apoptotic HepG2 and MCF-7 cells were higher in all treatment groups, particularly in the combination treatment group. Calculations for the combination index (CI) revealed a synergistic effect between both drugs for HepG2 cells (CI = 0.14) and MCF-7 cells (CI = 0.22).ConclusionOur data show that metformin, D-limonene, and their combinations exerted significant antitumor effects on the cancer cell lines by inducing apoptosis and modulating the expression of apoptotic genes.

Abstract PO3-04-05: Efficacy and safety of the recombinant humanized anti-HER2 monoclonal antibody-MMAE conjugate RC48-ADC in patients with HER2-positive or HER2-low expressing, metastatic breast cancer: a single-arm phase II study

Abstract Background: Current treatment options for HER2-positive (IHC 3+, or IHC 2+/FISH+) advanced or metastatic breast cancer at third-line and above have shown limited clinical benefit. There is no recommended HER2-targeting treatment for HER2-low expressing (IHC 2+/FISH-, or IHC 1+) population. RC48 (Disitamab vedotin), a newly developed antibody-drug conjugate (ADC), is comprised of three well-defined components: hertuzumab against the prominent tumor target-HER2, monomethyl auristatin E (MMAE) and a cleavable linker, with a bystanding effect in tumor cell killing. There is a lack of data on the administration of RC48 in the Chinese population. Here, we report the efficacy and safety of RC48-ADC in the advanced or metastatic breast cancer. Methods: Patients with HER2-positive or HER2-low expressing, locally advanced or metastatic breast cancer were eligible and received RC48 2.5 mg/kg every two weeks alone or combined with drugs with different anti-tumor mechanisms, such as immune checkpoint inhibitors (ICIs), tyrosine kinase inhibitors (TKIs) and antiangiogenic compounds. The primary endpoint was the objective response rate (ORR) assessed by the primary researcher. Secondary endpoints included progression-free survival (PFS), overall survival (OS), disease control rate (DCR), time to progression, and safety. Results: At the time of data cutoff (June 30, 2023), 120 chinese female breast cancer patients were enrolled and treated with RC48-ADC. 82 patients (68.3%) were HER2-positive and 38 patients (31.7%) were HER2-low expressing. At baseline, 52 patients (43.3%) had liver metastases, 40 patients (33.3%) had brain metastases, 70 patients (58.3%) had ≥3 metastases lesions, and 84 patients (70.0%) had received ≥3 prior chemotherapy regimens. In the overall population, the ORR was 38.3% (95% confidence interval [CI]: 30.0%-47.3%). The median PFS was 5.7 months (95% CI: 4.6-6.9 months). The DCR was 64.2% (95% CI: 54.9%-72.6%). In the HER2-positive subgroup, the ORR and mPFS were 42.7% (95% CI: 32.0%-54.1%) and 6.3 months (95% CI: 4.9-7.6 months). In the HER2-low expressing subgroup, the ORR and mPFS were 29.0% (95% CI: 16.0%-46.1%) and 3.6 months (95% CI: 2.0-5.3 months). In addition, the mPFS in the dual drug combination-treated group were longer than those in the single drug treatment group, with mPFS of 7.1 months (95% CI: 5.0-9.2 months) and 4.6 months (95% CI: 3.5-5.8 months), respectively. The most frequently reported treatment-related adverse events (TRAEs) were increased AST (45.8%), increased ALT (41.7%), decreased white blood cell count (25.0%), and fatigue (25%), most were grade 1-2 in severity. Conclusions: RC48-ADC showed consistent efficacy in HER2-positive and HER2-low expressing subgroups. No new safety signals were observed. Coadministration with ICIs, TKIs and antiangiogenic compounds demonstrated substantially enhanced efficacy compared to the monotherapies and could be a future direction in development of ADC. Citation Format: Fei Qu, Wei Li, Yongmei Yin, Qian Liu. Efficacy and safety of the recombinant humanized anti-HER2 monoclonal antibody-MMAE conjugate RC48-ADC in patients with HER2-positive or HER2-low expressing, metastatic breast cancer: a single-arm phase II study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-04-05.

Mechanistic Insights into Yifei Sanjie Pill's Regulation of EMT to Enhance Gefitinib Treatment effect in NSCLC by in silico analysis and experimental validation

Ethnopharmacological relevanceThe Yi-Fei San-Jie pill (YFSJ) is a well-known Chinese medicine that has been used to treat non-small cell lung cancer in China for decades. Aim of the studyPrevious studies have shown that YFSJ combined with gefitinib can effectively inhibit the proliferation of gefitinib-resistant non-small cell lung cancer (NSCLC) cell lines by promoting apoptosis and autophagy, but the molecular biological mechanisms involved and whether YFSJ combined with gefitinib can have synergistic effects still need to be further explored. Thus, the present study aimed to establish an in silico and experimental framework to decipher the underlying mechanism by which YFSJ augments the efficacy of gefitinib in treating NSCLC. Materials and methodsIntegrated approaches, including microarray analysis, network pharmacology, RNA sequencing, bioinformatics algorithm analysis and in vivo and in vitro experiments, were applied to elucidate the underlying mechanism. ResultsAnalysis of microarray datasets indicated that gefitinib may play a role in the regulation of the epithelial–mesenchymal transition (EMT) of PC9 cells. EMT-related Gene Ontology (GO) terms and the MAPK pathway were found to be enriched in the differentially expressed genes (DEGs), and a decreasing trend was observed in the EMT score. Network pharmacology analysis revealed that the potential NSCLC-related targets of YFSJ also showed enrichment in EMT-related GO terms and the MAPK pathway. Experimental findings demonstrated that combined YFSJ-treated serum and gefitinib treatment significantly inhibited PC9 cell migration and invasion. In addition, the combined treatment dramatically reduced the tumour volume in an animal model. The effectiveness of the combination treatment surpassed that of gefitinib alone in both cell and animal experiments. RNA sequencing analysis revealed significant enrichment of DEGs in EMT-related GO terms for the gefitinib treatment group, YFSJ treatment group, and combination treatment group compared to the control group. Notably, the negative regulation of EMT showed significant enrichment in the DEGs of the combination treatment group. The MAPK pathway was significantly enriched among the different groups. Moreover, combined treatment with YFSJ and gefitinib may exert synergistic anti-NSCLC effects by inhibiting the p-p38 MAPK/GSK3β signalling axis, subsequently suppressing downstream EMT processes. ConclusionCombined treatment with YFSJ and gefitinib could enhance the sensitivity of NSCLC cells to gefitinib by suppressing EMT through the EGFR/p-p38 MAPK/GSK3β signalling axis. YFSJ may serve as an important adjunctive medication for NSCLC patients receiving gefitinib treatment in clinical practice

Effects of metformin, saxagliptin and repaglinide on gut microbiota in high-fat diet/streptozocin-induced type 2 diabetic mice

IntroductionThere has been increasing evidence that the gut microbiota is closely related to type 2 diabetes (T2D). Metformin (Met) is often used in combination with saxagliptin (Sax) and repaglinide (Rep)...

Comparative evaluation of bone marrow and dental pulp mesenchymal stem cells for motor functional recovery in rat sciatic nerve injury.

This study delves into the impact of mesenchymal stem cells derived from bone marrow (BM-MSCs) and those sourced from dental pulp (DP-MSCs) on the recovery of motor function and morphological aspects of the rat's sciatic nerve after crush injuries. The findings highlight that the groups treated with BM-MSCs, DP-MSCs or a combination of both (BM + DP-MSCs) displayed enhanced sciatic functional index values when juxtaposed with the sham group. This points to bettered motor functionalities. A deeper morphological analysis showed that all the groups had retained perineurium structure and fascicular arrangement. Notably, the sham and BM-MSCs groups had very few inconsistencies. All groups showed standard vascular density. Remarkably, the combined treatment group (BM + DP-MSCs) presented diminished oedema and a lower count of inflammatory cells. Through immunohistochemical methods, the presence of S100 expression was noted in the groups that underwent treatment. In summation, the study suggests that both BM-MSCs and DP-MSCs, whether used singly or in combination, can significantly aid in motor function restoration and morphological enhancements. An interesting observation from our research and earlier studies is that stem cells from dental pulp, which are sourced with less discomfort from milk and wisdom teeth, show a heightened propensity to evolve into nerve cells. This is in contrast to the more uncomfortably acquired BM-MSCs.

A potential strategy for bladder cancer treatment: inhibiting autophagy to enhance antitumor effects of Nectin-4-MMAE

Research and development on Nectin-4 antibody-drug conjugates (ADC) have been greatly accelerated since the approval of enfortumab vedotin to treat uroepithelial cancer. During the course of this study, we identified that autophagy serves as a cytoprotective mechanism during Nectin-4-MMAE treatment and proposed a strategy to enhance the antitumor effects of Nectin-4-MMAE in bladder cancer. Nectin-4-MMAE rapidly internalized into bladder cancer cells in 30 minutes and released MMAE, inducing the onset of caspase-mediated apoptosis and leading to the inhibition of tumor cell growth. Transcriptomics showed significant alterations in autophagy-associated genes in bladder cancer cells treated with Nectin-4-MMAE, which suggested autophagy was activated by Nectin-4-MMAE. Furthermore, autophagy activation was characterized by ultrastructural analysis of autophagosome accumulation, immunofluorescence of autophagic flux, and immunoblotting autophagy marker proteins SQSTM1 and LC3 I/II. Importantly, inhibiting autophagy by LY294002 and chloroquine significantly enhances the cytotoxicity effects of Nectin-4-MMAE in bladder cancer cells. Additionally, we detected the participation of the AKT/mTOR signaling cascade in the induction of autophagy by Nectin-4-MMAE. The combination of Nectin-4-MMAE and an autophagy inhibitor demonstrated enhanced antitumor effects in the HT1376 xenograft tumor model. After receiving a single dose of Nectin-4-MMAE, the group that received the combination treatment showed a significant decrease in tumor size compared to the group that received only one type of treatment. Notably, one mouse in the combination treatment group achieved complete remission of the tumor. The combination group exhibited a notable rise in apoptosis and necrosis, as indicated by H&E staining and immunohistochemistry (cleaved caspase-3, ki67). These findings demonstrated the cytoprotective role of autophagy during Nectin-4-MMAE treatment and highlighted the potential of combining Nectin-4-MMAE with autophagy inhibitors for bladder cancer treatment.

Effects of robot-assisted upper limb training combined with intermittent theta burst stimulation (iTBS) on cortical activation in stroke patients: A functional near-infrared spectroscopy study.

The therapeutic effect and mechanism of robot-assisted upper limb training (RT) combined with intermittent theta burst stimulation (iTBS) for stroke patients are unclear. The purpose of this study was to evaluate changes in brain activation after combination therapy and RT alone using functional near-infrared spectroscopy (fNIRS). Patients were randomly assigned to two groups (iTBS + RT Group, n = 18, and RT Group, n = 18). Training was conducted five times a week for four weeks. fNIRS was used to measure changes in oxyhemoglobin in both the primary motor cortex (M1) and pre-motor and supplementary motor area (pSMA) during affected limb movement. Fugl-Meyer Assessment-Upper Extremity (FMA-UE) was employed for evaluating the function of upper limbs. Thirty-two patients with subacute stroke completed the study. The cortex of both hemispheres was extensively activated prior to treatment in the RT group. After training, overactivation decreased. The brain activation of the combined treatment group transferred to the affected side after the treatment. There was a notable enhancement in the FMA-UE scores for both groups, with the combined group's progress significantly surpassing that of the RT group. RT combined with iTBS can improve the motor function of stroke patients and promote the balance between cerebral hemispheres.

A randomized controlled trial on the effect of early eschar dermabrasion combined with antimicrobial soft silicone foam dressing in the treatment of deep partial-thickness burn wounds in children

Objective: To explore the effect of early eschar dermabrasion combined with antimicrobial soft silicone foam dressing (hereinafter referred to as foam dressing) in treating the deep partial-thickness burn wounds in children. Methods: This study was a randomized controlled trial. From June 2021 to December 2022, 78 pediatric patients with deep partial-thickness burns who met the inclusion criteria were admitted to the Department of Burns in Guiyang Steel Plant Employees Hospital. According to the random number table, the pediatric patients were divided into two groups, with 38 cases left in combined treatment group (with 20 males and 18 females, aged 26.00 (16.75, 39.75) months) and 39 cases in foam dressing group (with 21 males and 18 females, aged 19.00 (14.00, 31.00) months) after the exclusion of one dropped-out child in follow-up. The pediatric patients in combined treatment group underwent eschar dermabrasion of the wound within 48 hours after injury, the wound was covered with foam dressing after operation, and the dressing was replaced once every 7 days; for the pediatric patients in foam dressing group, the wound was sterilized within 48 hours after injury and covered with foam dressing, and the dressing was replaced once every 2 to 3 days. After the wound healing, the children in both groups were routinely applied with silicone gel twice a day for 3 weeks before started wearing elastic sleeves for more than 18 hours a day, and continuously for over than 6 months. The degree of pain during dressing change was evaluated using the children's pain behavior inventory FLACC. The adverse reactions during the treatment period, number of dressing changes, and wound healing time were observed and recorded. Six months after wound healing, the Vancouver scar scale (VSS) was used to evaluate the condition of the wound scar. Results: When changing dressing, the FLACC score for pain of pediatric patients in combined treatment group was 3.5 (2.0, 5.0), which was significantly lower than 6.0 (5.0, 8.0) in foam dressing group (Z=-5.40, P<0.05). During the treatment period, no adverse reactions such as wound edema, fluid accumulation, or peripheral skin rash allergies occurred in any pediatric patient in both groups. The number of dressing changes of pediatric patients in combined treatment group was 3 (3, 4) times, which was significantly less than 8 (7, 10) times in foam dressing group (Z=-7.58, P<0.05). The wound healing time of pediatric patients in combined treatment group was (19±5) days, which was significantly shorter than (25±6) days in foam dressing group (t=-4.48, P<0.05). Six months after wound healing, the VSS score for scar of pediatric patients in combined treatment group was 5 (2, 8), which was significantly lower than 7 (5, 10) in foam dressing group (Z=-3.05, P<0.05). Conclusions: Compared with using foam dressings alone, early eschar dermabrasion combined with foam dressings can reduce the number of dressing changes, alleviate the pain during dressing changes, and shorten the wound healing time in treating children with deep partial-thickness burns, and effectively alleviate scar hyperplasia by combining with anti-scar treatment post burns.

The synergistic bactericidal effect of simultaneous 222 nm krypton-chlorine excilamp and 307 nm UVB light treatment on sliced cheese and its mechanisms

In this study, we investigated the combined effect of 222 nm krypton-chlorine excilamp (EX) and 307 nm ultraviolet-B (UVB) light on the inactivation of Salmonella Typhimurium and Listeria monocytogenes on sliced cheese. The data confirmed that simultaneous exposure to EX and UVB irradiation for 80 s reduced S. Typhimurium and L. monocytogenes population by 3.50 and 3.20 log CFU/g, respectively, on sliced cheese. The synergistic cell count reductions in S. Typhimurium and L. monocytogenes in the combined treatment group were 0.88 and 0.59 log units, respectively. The inactivation mechanism underlying the EX and UVB combination treatment was evaluated using fluorescent staining. The combination of EX and UVB light induced the inactivation of reactive oxygen species (ROS) defense enzymes (superoxide dismutase) and synergistic ROS generation, resulting in synergistic lipid peroxidation and destruction of the cell membrane. There were no significant (P > 0.05) differences in the color, texture, or sensory attributes of sliced cheese between the combination treatment and control groups. These results demonstrate that combined treatment with EX and UVB light is a potential alternative strategy for inactivating foodborne pathogens in dairy products without affecting their quality.

Effect of acupuncture for anisometropic amblyopia: A randomized clinical trial and potential mechanism: 针刺治疗屈光参差性弱视:一项随机对照试验及其潜在起效机制

ObjectiveTo evaluate the effect of acupuncture on anisometropic amblyopia (AA) and explore its potential mechanism for children with AA. MethodsSeventy-six children with monocular AA were randomized into a conventional treatment group and a combined treatment group of acupuncture and conventional treatment, with 38 patients in each group. In the conventional treatment group, on the base of patching regimen, the red flashing, grating and visual stimulation were delivered. Each approach lasted for 5 min per session and was given once every two days, three times a week, for 4 consecutive weeks. In the acupuncture-combined treatment group, on the base of the regimen of conventional treatment group, acupuncture was applied to Jingming (BL1), Cuanzhu (BL2), Fengchi (GB20) and Guangming (GB37), with needles retained for 20 min per session, once every two days, three times of intervention a week and for 4 consecutive weeks. Before and after treatment, the best corrected vision acuity (BCVA) was observed to evaluate the clinical effect in the two groups. Before treatment started, 15 patients with AA on left side were randomized selected from each group and the resting-state functional magnetic resonance imaging (rs-fMRI) was operated before and after treatment. Simultaneously, eight healthy children with normal visual acuity were recruited to be the normal control group and received one-time rs-fMRI scanning. Based on the activation likelihood estimation (ALE), the visual “what” pathway network was constructed. By analyzing the amplitude of low frequency fluctuation (ALFF) and the regional homogeneity (ReHo), the differences in the regional autonomous function activities in the key brain areas of the “what” pathway were compared among the three groups. Results(1) Clinical effect: After treatment, BCVA was (0.6 [0.5, 0.6]), higher than that (0.4 [0.3, 0.5]) before treatment, presenting the statistical difference (P < 0.05) in the conventional treatment group. BCVA was (0.6 [0.6, 0.8]), higher than that (0.4 [0.4, 0.5]) before treatment, presenting the statistical difference (P < 0.05) in the acupuncture-combined treatment group. BCVA in the acupuncture-combined treatment group was higher than that of the conventional treatment group (P < 0.05) after treatment. The total effective rate was 86.1% in the acupuncture-combined treatment group, higher than that (65.8%) of the conventional treatment group (P < 0.05). (2) Mechanism: ① ALFF: In comparison with the healthy control group, the ALFF in the primary visual cortex of the “what” pathway for AA children was reduced significantly (P < 0.05), and ALFF in the right fusiform gyrus and the right inferior temporal gyrus increased significantly when compared with the healthy children (P < 0.05). Compared with that before treatment, there was no significant difference in the brain areas of the “what” pathway after treatment in the conventional treatment group (P > 0.05). In the acupuncture-combined treatment group, ALFF in the right inferior occipital gyrus and the right fusiform gyrus of the “what” pathway increased after treatment when compared with that before treatment (P < 0.05). After treatment, in comparison with the conventional treatment group, there was no significant difference in the brain areas of “what” pathway in the acupuncture-combined treatment group (P > 0.05). ② ReHo: ReHo in the right inferior occipital gyrus, the right fusiform gyrus and the right inferior temporal gyrus in the “what” pathway was elevated significantly in AA children when compared with that in the healthy control group (P < 0.05). ReHo of the left inferior occipital gyrus and the left fusiform gyrus increased significantly after treatment when compared with that before treatment in the conventional treatment group (P<0.05). ReHo of the right inferior occipital gyrus, the left and the right fusiform gyrus increased significantly after treatment when compared with that before treatment in the acupuncture-combined treatment group (P < 0.05). After treatment, ReHo of the right inferior temporal gyrus in the “what” pathway in the acupuncture-combined treatment group was significantly higher than that of the conventional treatment group (P < 0.05). ConclusionThe acupuncture combined with conventional treatment improves BCVA and the total effective rate of AA children. The changes in the regional function activity of the brain areas within the “what” pathway were dominated by the compensatory increase of the autonomous activity in the occipital lobe (inferior occipital gyrus) and the temporal lobe (inferior temporal gyrus) in AA children. Both conventional treatment and acupuncture can enhance the intensity of autonomous function activities in the occipital lobe (inferior occipital gyrus) and the temporal lobe (fusiform gyrus / inferior temporal gyrus) in the “what” pathway so as to relieve visual impairment. ReHo in the inferior temporal gyrus in the acupuncture-combined treatment group was higher than that of the conventional treatment group and it suggests that the inferior temporal gyrus may be the key brain area to the improvement of visual function in the “what” pathway.

Investigating the synergistic effects of amitriptyline and H. pylori eradication on depressive-like behaviors and inflammatory cytokines in mice

BackgroundRecent research has highlighted the potential role of Helicobacter pylori in the pathogenesis of psychiatric disorders. This study aimed to evaluate the potential synergistic effects of an antidepressant drug and H. pylori eradication therapy in a mouse model. MethodsMale C57BL/6 mice were divided into four groups: control, H. pylori infection, antidepressant treatment, and combined treatment. H. pylori infection was induced by oral gavage with a clinically relevant strain, and the antidepressant drug was administered via intraperitoneal injections. Behavioral tests including the forced swim test, sucrose preference test, and open field test were conducted to assess depressive-like behaviors and locomotor activity. ResultsThe study demonstrated that H. pylori infection induced depressive-like behaviors in mice, as evidenced by increased immobility time in the forced swim test and reduced sucrose preference. Antidepressant treatment alone partially ameliorated these behavioral changes. Strikingly, the combined treatment of the antidepressant drug and H. pylori eradication therapy led to a significantly greater reduction in depressive-like behaviors compared to either treatment alone. Furthermore, the combined treatment group exhibited increased locomotor activity in the open field test, suggesting a potential improvement in overall psychomotor functioning. ELISA assays revealed alterations in inflammatory cytokines in the H. pylori-infected mice, which were partially attenuated by the combined treatment. ConclusionThe study provides novel evidence for the potential synergistic effects of an antidepressant drug and H. pylori eradication therapy in alleviating depressive-like behaviors in a mouse model.

Comparative efficacy of different interventions on executive function in adolescents with internet use disorder

BackgroundThe formation and relapse of Internet use disorder (IUD) are related to the decline in executive function. Previous studies have indicated that exercise intervention and high-definition transcranial direct current stimulation (HD-tDCS) can improve the cognitive abilities of adolescents with IUD. However, the combined intervention's impact on executive function in these adolescents remains unclear. Therefore, this study aims to explore the effects and differences of multimodal exercise, HD-tDCS intervention, and combined intervention on the executive function of adolescents with IUD. MethodsForty-eight adolescents with IUD were randomly assigned to the multimodal exercise group, HD-tDCS intervention group, combined intervention group, and control group. The intervention groups received 4 weeks of moderate-intensity multimodal exercise, HD-tDCS intervention (2 mA, 20min/session, 3 times/week), or combined multimodal exercise with HD-tDCS intervention. The control group received conventional educational learning. Executive function measurements were taken before intervention, after intervention, and 2 weeks post-intervention. ResultsCompared to pre-intervention, different interventions effectively improved the behavioral performance of adolescents with IUD in executive function tasks. In comparison to single interventions, the combined intervention significantly outperformed multimodal exercise and HD-tDCS intervention in influencing the executive function (especially inhibitory control and working memory) in adolescents with IUD. ConclusionCombined multimodal exercise with HD-tDCS intervention proves to be an effective means of enhancing executive function in adolescents with IUD, particularly contributing to the improvement of explicit behavioral performance related to executive function.

Left atrial appendage closure in conjunction with radiofrequency ablation: Effects on left atrial functioning in patients with paroxysmal atrial fibrillation.

In the present study, we investigated the impact of left atrial appendage closure (LAAC) following catheter ablation (CA) on the left atrial structure and functioning of patients with paroxysmal atrial fibrillation (AF). Patients with paroxysmal AF were enrolled in this single-center prospective cohort study between April 2015 and July 2021; 353 patients received CA alone, while 93 patients received CA in combination with Watchman LAAC. We used age, gender, CHA2DS2-VASc, and HAS-BLED scores as well as other demographic variables to perform propensity score matching. Patients with paroxysmal AF were randomly assigned to the CA combined with Watchman LAAC group (combined treatment group) and the simple CA group, with 89 patients in each group. The left atrial structure, reserve, ventricular diastole, and pump functions and their changes in patients were assessed using routine Doppler echocardiography and 2D speckle tracking echocardiography over the course of a 1-year follow-up. At 1-week follow-up, the reserve, ventricular diastole, and pump functions of the left atrium (LA) increased in both groups; these functions were gradually restored at the 1- to 3-month follow-up; they were close to or returned to their pre-operative levels at the 3-month follow-up; and no significant differences were found compared with the pre-operative levels at the 12-month follow-up. In the first 3 months, the reserve (Ƹ, SRs) and pump functions (SRa) in the combined treatment group decreased significantly when compared with the simple CA group, and the differences were statistically significant. Patients with paroxysmal AF may experience a short term, partial effect of LAAC on LA reserve and pump functions, which are gradually restored and the effect disappears by 12 months.