Poor Efficacy Research Articles

Mechanical Thrombectomy for Aseptic, Atraumatic, Medically Refractory Cerebral Venous Sinus Thrombosis: aSystematic Review.

Cerebral venous sinus thrombosis (CVST) follows asevere clinical course in 13.5% of cases. Practice guidelines recommend endovascular therapy (EVT); no randomised control trials (RCTs) exist comparing EVTs. To determine whether specific EVTs are superior to alternatives. CENTRAL, Medline, Embase, five other databases and four clinical trials registers. Grey literature searches, reference checking, citation searching, and author contact. All CVST cases treated with mechanical thrombectomy (MT) were includible. Paediatric, and trauma-related or infection-related thromboses were excluded. Standard Cochrane review procedures. Primary outcome measures; clinical efficacy (modified Rankin Score, mRS), technical efficacy (recanalisation), and clinical safety (procedure-related complications and death). Subgroup analyses were performed, comparing outcome measures between demographic groups, clinico-radiological severity, interventional strategies, and degrees of recanalisation. In this study 124 papers were included (n = 486). All patients underwent MT, with 69.5% of patients receiving concomitant chemolysis. New/expanding intracerebral haemorrhage (ICH) occurred in 5.1%; non-haemorrhagic complications in 1.4%; 10.7% died. Predictors of poor efficacy included age ≥ 55years, altered mental status (AMS), Glasgow Coma Scale (GCS) < 8. Predictive of poor safety outcomes included pre-existing ICH, deep system thrombosis, and AMS. Complete recanalisation was associated with improved clinical efficacy and safety outcomes. The review is based on case reports/series, increasing bias-risk. Myriad of potentially includible studies were necessarily excluded due to lack of requisite details. Predictors of poor outcomes with medical therapy predict poor outcomes with MT; these measures should not dictate candidacy. Complete recanalisation predicts favorable clinical and safety outcomes. Local chemolysis is safe, improves recanalisation, and should be recommended, provided there is no contraindication. Clot maceration strategies and stent-retriever thrombectomy are associated with superior clinical efficacy and safety endpoints, as compared with balloon angioplasty and rheolysis.

543 - Early repigmentation of stable vitiligo through point-of-care melanocyte transfer using non-cultured autologous skin cell suspension

Abstract Introduction Vitiligo is an acquired depigmenting skin condition characterized by the loss of skin pigmentation, impacting 0.5% to 2% of the global population.1–3 Vitiligo presents as distinct depigmented patches resulting from autoimmune melanocyte destruction. Individuals with visual vitiligo lesions often experience negative body image, diminished self-confidence, discomfort, and overall lower quality of life (QoL).4 While there are medical treatment options available, these can be associated with poor efficacy and low medication compliance.4 Residual lesions after treatment may require surgical intervention which allows for melanocyte transplantation from an area that is pigmented to one that is lacking functional melanocytes. Through a point-of-care device, a non-cultured autologous skin cell suspension (ACSC) can be prepared using a small skin sample; the ASCS contains healthy melanocytes and is immediately applied onto skin treated with ablative laser to aid in the repigmentation of affected areas. Objective The objective of this study was to evaluate the one-time application of ASCS, with a 1:20 donor to treatment site expansion ratio, for the safe and effective repigmentation of stable vitiligo lesions. Methods A randomized, within-subject controlled, central observer-blinded study was conducted to compare the clinical performance of laser ablation, ASCS, and NB-UVB to NB-UVB alone for repigmentation of stable vitiligo lesions in adults. Subjects received NB-UVB phototherapy on both ASCS-treated and controlled lesions as per recommended by the Vitiligo Working Group. Repigmentation of ASCS-treated and control lesions were categorized by a Central Review Committee (CRC) of blinded dermatologists as one of the following: 0%-25%, 26%-50%, 51%-79%, or 80-100%. The primary effectiveness endpoint was defined as the proportion of lesions achieving ≥80% repigmentation for ASCS-treated versus control areas at Week 24. Early regimentation was assessed at Weeks 4 and 12 as a post hoc analysis. Results A significantly higher proportion of the ASCS-treated areas (36.0%, n = 9) compared to control-treated areas (0.0%) attained ≥80% repigmentation at Week 24 (P = 0.012). At Week 4, 30.4% (n = 7/23) of ASCS-treated areas had ≥26% repigmentation compared to 4.3% (n = 1/23) in the control areas. At Week 12, 56.5% (n = 13/23) of ASCS-treated areas had ≥26% repigmentation compared to 21.7% (n = 5/23) in the control areas. At Week 24, 64% (n = 16/25) of ASCS-treated areas had ≥26% repigmentation compared to 28% (n = 7/25) in the control areas. Conclusion A one-time treatment of ASCS, with the addition of NB-UVB, can result in excellent repigmentation results by 24 weeks, with most subjects seeing ≥26% repigmentation as early as 4 to 12 weeks.

Comparative Evaluation of Antimicrobial and Smear Layer Removal Efficacy of Mangifera indica Kernel Extract as Root Canal Irrigant in Primary Molar: An In Vitro Study.

Endodontic therapy aims to disinfect the entire root canal system. Extracts from the kernel of Mangifera indica has the potential to be a novel root canal irrigant that has yet to be studied. Hence, the present study evaluated the antimicrobial, and smear layer removal efficacy of the M. indica kernel extract as a root canal irrigant in primary molars. Methanolic extract of M. indica was prepared using the standard method. The antimicrobial efficacy of M. indica kernel extract was determined by agar diffusion method with 3% sodium hypochlorite and distilled water as controls, and the smear layer removal efficacy was assessed under the SEM after processing the root samples with different concentrations of M. indica kernel extract with 17% EDTA and distilled water as positive and negative controls, respectively. A statistically significant antimicrobial efficacy was observed with the largest mean zone of inhibition recorded with 50 μl of M. indica kernel extract at 24 hr of incubation period, when compared to sodium hypochlorite as a root canal irrigant against Enterococcus faecalis using agar diffusion method at MIC value of 0.625 mg/ml. The smear layer removal efficacy of the M. indica kernel extract was not satisfactory, when compared with EDTA as a root canal irrigant in primary molars and observed under SEM. In contrast, a complete smear layer removal was observed with 17% EDTA solution. M. indica kernel extract has an enhanced antimicrobial efficacy but poor smear layer removal efficacy when used as a root canal irrigant.

Overnight switch from carbamazepine to eslicarbazepine in a real-life clinical scenario: a retrospective study.

Carbamazepine (CBZ) is a first-choice anti-seizure medication (ASM) whose efficacy is often invalidated by adverse effects (AEs). Eslicarbazepine (ESL) is a structural derivative of CBZ with better pharmacokinetic/tolerability profiles. We describe our experience of the overnight CBZ to ESL switch in people with epilepsy (PwE) to improve seizure control, AEs, and ASMs adherence. We retrospectively included 19 PwE (12 females, 53 ± 21years old) who underwent CBZ to ESL overnight switch due to single/multiple issues: poor efficacy (pEff, N = 8, 42%), tolerability (pToll, N = 11, 58%), adherence (pAdh, N = 2, 10%). 9/19 (47%) had psychiatric comorbidities. Clinical variables, seizure frequency, and AEs were recorded at switch time (T0) after 3.5 ± 3 (T1) and 6.5 ± 1.5months (T2). At T1, in pEff group, 1/8 (13%) was seizure free, 2/8 (25%) were responders (> 50% seizure reduction), 2/8 (25%) had no seizure changes, 3/8 (37%) had seizure worsening; the latter were those with the most severe epilepsy and encephalopathy. In pToll group, all PwE experienced AEs disappearance/amelioration. In pAdh group, all PwE reported adherence amelioration. Four dropouts. At T2, no changes were recorded within groups, while in the whole sample, 6/15 (40%) were responders, and 4/15 (27%) were seizure-free. No one complained of Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation psychiatric worsening, while 6/19 (32%) experienced mood/behavior benefits. CBZ to ESL overnight switch offers an opportunity to improve efficacy, tolerability, adherence, and psychiatric symptoms.

Cuproptosis: Mechanism, role, and advances in urological malignancies.

Prostate, bladder, and kidney cancers are the most common malignancies of the urinary system. Chemotherapeutic drugs are generally used as adjuvant treatment in the middle, late, or recurrence stages after surgery for urologic cancers. However, traditional chemotherapy is plagued by problems such as poor efficacy, severe side effects, and complications. Copper-containing nanomedicines are promising novel cancer treatment modalities that can potentially overcome these disadvantages. Copper homeostasis and cuproptosis play crucial roles in the development, adaptability, and therapeutic sensitivity of urological malignancies. Cuproptosis refers to the direct binding of copper ions to lipoylated components of the tricarboxylic acid cycle, leading to protein oligomerization, loss of iron-sulfur proteins, proteotoxic stress, and cell death. This review focuses on copper homeostasis and cuproptosis as well as recent findings on copper and cuproptosis in urological malignancies. Furthermore, we highlight the potential therapeutic applications of copper- and cuproptosis-targeted therapies to better understand cuproptosis-based drugs for the treatment of urological tumors in the future.

A Randomized Controlled Trial Comparing the Management of Incomplete Abortion with Oral 600 mg Misoprostol with Manual Vacuum Aspiration (MVA).

In the first trimester, almost one in five identified pregnancies end in spontaneous miscarriage, and another 22% result in induced abortion. After a spontaneous and/or induced abortion, there may be retained products of conception (POC). Because of its relatively poor efficacy and the unpredictability of the time interval until spontaneous evacuation, expectant treatment is not often chosen by healthcare professionals. In view of these facts, the current study's objective was to weigh the effectiveness of MVA and oral misoprostol 600 mg in managing incomplete abortion. The investigation was conducted at the tertiary care center in India. The survey was conducted for one year. Subjects were selected from those attending the department for either spontaneous or induced abortions. A total of 230 women were randomly assigned to receive the interventions of a single dose of oral misoprostol 600 mcg or MVA. They were equally distributed to two groups and observed for the various parameters of success, signs and symptoms, satisfaction, and complications. The obtained values were compared statistically for the significance at <0.05 of P values. Of the 200 subjects (30 lost to follow-up), there was no significant variance in the demographics, clinical outcomes, and complications between the groups. However, the pain, fever, shivering, and satisfaction parameters were statistically variant between the groups. Fever, shivering, and pain were lower for the MISO subjects while satisfaction was reported higher from subjects in MISO group. MISO and MVA are acceptable, safe, and efficient therapies for first-trimester un-complicated incomplete abortion. Nonetheless, misoprostol appears to be a marginally superior option to MVA in terms of accessibility, low therapy costs, reduced pain, and reduced demand for specialized personnel or equipment.

Self-compassion and parenting efficacy among mothers who are breast cancer survivors: Implications for psychological distress.

Mothers who are breast cancer survivors may experience psychological distress in relation to diminished parenting efficacy. Self-compassion may protect mothers from psychological distress, yet little is known about self-compassion in this population. The extent to which self-warmth (self-kindness, mindfulness and sense of common humanity) and self-coldness (self-judgement, isolation and over-identification) dimensions of self-compassion moderate parenting efficacy in predicting depression, anxiety and stress was examined in a sample of 95 mothers who were breast cancer survivors. Independently, poorer parenting efficacy was associated with more depression and stress symptoms. Within regression models, self-coldness was a direct predictor of depression, anxiety and stress, while self-warmth moderated the relationship between parenting efficacy and stress. Self-warmth presents as a potential protective factor for stress associated with poor parenting efficacy, while self-coldness is a potential direct risk factor for psychological distress. Mothers who are breast cancer survivors may benefit from self-compassion focused psychosocial interventions.

Correlation Between Risk Factors, Degree of Vascular Restenosis, and Inflammatory Factors After Interventional Treatment for Stroke: A Two-Center Retrospective Study.

To study the correlation between risk factors, degree of vascular restenosis, and inflammatory factors after interventional treatment for stroke. The clinical data of 96 stroke patients who received interventional therapy in our hospital from April 2020 to June 2021 were selected for retrospective study, and the postoperative follow-up was 1 year. Univariate and multivariate regression were used to analyze identified factors associated with interventional stroke efficacy. At the same time, the value of inflammatory factor levels in predicting vascular restenosis after interventional stroke was analyzed. According to our findings, several risk factors, including body mass index ≥ 25.51kg/m 2 , smoking, drinking, hypertension, and diabetes, were identified as contributors to poor postoperative efficacy following stroke intervention ( P <0.05). Furthermore, a notable association was observed between the severity of vascular stenosis ( P <0.001) and the levels of interleukin 6, interleukin 2, TNF-α, and C-reactive protein. The combined assessment of these serum inflammatory factors exhibited excellent predictive capability for postoperative vascular restenosis and stenosis severity, yielding a sensitivity of 84.30%, a specificity of 81.20%, and an area under the curve of 0.882. Obesity, smoking, alcohol consumption, hypertension, and diabetes have been found to be associated with suboptimal outcomes following interventional treatment for stroke. The assessment of preoperative levels of inflammatory factors holds promise in predicting the likelihood of postoperative restenosis to a certain degree.

Outcomes of 3-year follow up with induction vs first line chemotherapy in oral cancer patients: An observational hospital-based study.

Our study aims to analyse and compare the efficacy, adverse effect profile and survival among the Paclitaxel/Cisplatin/5-Flurouracil (TPF) induction chemotherapy and Paclitaxel/carboplatin (PC) first line or cisplatin chemotherapy in a high-volume tertiary care cancer centre. 215 patients with oral cavity cancer were recruited in this study. Patients with stages I-IIc underwent surgical resection or radiation therapy 66-74 GY/fraction. Patients of Stages III-IV were administered with either induction chemotherapy TPF or PC or cisplatin regimen. Treatment responses were assessed by CT and MRI. Response rates, survival and adverse effects data were tabulated and analysed. The mean age was 49.2 ± 11.68 years. Symptoms were ulceration (33.5%), growth (20.5%), pain (13%), ulcer-proliferative growth (8.4%) and swelling (13, 6%). The tumour site was found at the base of the tongue, C01 (42.2%) followed by C06 (35.8%), C08 (6.5%), C07 (5.2%) and C05 (4.6%). There were no significant differences ( P > 0.05) in efficacy and survival outcomes between the different groups of treatment. Median survival was achieved within 36 months. The major side effect observed were anaemia (15.81%), diarrhoea (36.2%), dyspepsia (28.8%), fever (33.95%), mucositis (28.85%), myalgia (33.95%) and nausea (7.9%). Survival among the responder categories (CR, PR and NR) was significantly different as per Log-rank analysis ( P = 0.015). TPF induction therapy and PC first line chemotherapy showed similar efficacy, safety profile and survival whereas cisplatin shows poor efficacy and safety and survival in Indian oral cancer patients.

TRIP13 Enhances Radioresistance of Lung Adenocarcinoma Cells through the Homologous Recombination Pathway

Radiation therapy is one of the most common treatments for non-small cell lung cancer (NSCLC). However, the insensitivity of some tumor cells to radiation is one of the major reasons for the poor efficacy of radiotherapy and the poor prognosis of patients, and exploring the underlying mechanisms behind radioresistance is the key to solving this clinical challenge. This study aimed to identify the molecules associated with radioresistance in lung adenocarcinoma (LUAD), identified thyroid hormone receptor interactor 13 (TRIP13) as the main target initially, and explored whether TRIP13 is related to radioresistance in LUAD and the specific mechanism, with the aim of providing theoretical basis and potential targets for the combination therapy of LUAD patients receiving radiotherapy in the clinic. Three datasets, GSE18842, GSE19188 and GSE33532, were selected from the Gene Expression Omnibus (GEO) database and screened for differentially expressed genes (|log FC|>1.5, P<0.05) in each of the three datasets using the R 4.1.3 software, and then Venn diagram was used to find out the differentially expressed genes common to the three datasets. The screened differential genes were then subjected to protein-protein interaction (PPI) analysis and module analysis with the help of STRING online tool and Cytoscape software, and survival prognosis analysis was performed for each gene with the help of Kaplan-Meier Plotter database, and the TRIP13 gene was identified as the main molecule for subsequent studies. Subsequently, the human LUAD cell line H292 was irradiated with multiple X-rays using a sub-lethal dose irradiation method to construct a radioresistant cell line, H292DR. The radioresistance of H292DR cells was verified using cell counting kit-8 (CCK-8) assay and clone formation assay. The expression levels of TRIP13 in H292 and H292DR cells were measured by Western blot. Small interfering RNA (siRNA) was used to silence the expression of TRIP13 in H292DR cells and Western blot assay was performed. The clone formation ability and migration ability of H292DR cells were observed after TRIP13 silencing, followed by the detection of changes in the expression levels of proteins closely related to homologous recombination, such as ataxia telangiectasia mutated (ATM) protein. Screening of multiple GEO datasets, validation of external datasets and survival analysis revealed that TRIP13 was highly expressed in LUAD and was associated with poor prognosis in LUAD patients who had received radiation therapy. And the results of gene set enrichment analysis (GSEA) of TRIP13 suggested that TRIP13 might be closely associated with LUAD radioresistance by promoting homologous recombination repair after radiation therapy. Experimentally, TRIP13 expression was found to be upregulated in H292DR, and silencing of TRIP13 was able to increase the sensitivity of H292DR cells to radiation. TRIP13 is associated with poor prognosis in LUAD patients treated with radiation, possibly by promoting a homologous recombination repair pathway to mediate resistance of LUAD cells to radiation.

The efficacy of chemotherapy for colorectal cancer with early recurrence after adjuvant chemotherapy.

43 Background: Adjuvant chemotherapy is the standard treatment for patients with stage III colorectal cancer (CRC) underwent surgery.However, the efficacy of chemotherapy for early recurrence after adjuvant chemotherapy remains unclear. This study aimed to assess the efficacy of chemotherapy for CRC with early recurrence during or after adjuvant chemotherapy. Methods: We retrospectively reviewed CRC patients who underwent surgery at 3 institutions between 2016 and 2021. The inclusion criteria were as follows: ECOG performance status was 0 or 1, histology was adenocarcinoma, patients who received adjuvant chemotherapy following surgical resection, early recurrence during or within 12 months after adjuvant chemotherapy and no prior treatment for CRC after early recurrence. The interval from the last administration of adjuvant chemotherapy to recurrence was defined as the recurrence-free interval (RFI). Overall survival (OS), progression-free survival (PFS), objective response rates (ORR), and disease control rate (DCR) were assessed according to the RFI. Results: Of 448 patients, 32 patients were eligible. Median age was 57 years (range 26–79), 14 patients (44%) were male and ECOG performance status 0 / 1 was 29 (91%) / 3 (9%). RAS wild-type / mutant was 12 (38%) / 20 (62%) and right / left as sidedness was 21 (66%) / 11 (34%). Regarding adjuvant chemotherapy, 4 patients (12%) received single-agent therapy, while 28 patients (88%) received combination therapy with two agents. Palliative chemotherapy after early recurrence included Oxaliplatin-based regimens in 13 patients (41%), irinotecan-based regimens in another 13 patients (41%), and other regimens in 6 patients (18%). For all patients, the median PFS and OS were 10.4 months and 43.0 months, respectively. The ORR and DCR were 34.4% and 75.0%, respectively. When patients were divided into RFI &lt; 6 months and RFI ≥ 6 months, the ORR was superior in the RFI ≥ 6 months group to RFI &lt; 6 months group (56 % vs. 26%). The PFS (median 10.4 months vs. 17.8 months, HR 0.92; 95% Cl 0.36-2.38, p = 0.87) and OS (median 31.3 months vs. 43.0 months, HR 0.97; 95% Cl 0.31-3.08, p = 0.97) did not differ between the RFI &lt; 6 months group and the RFI ≥ 6 months group. Multivariate analysis for OS indicated a trend toward a poor prognosis in the RFI &lt; 6 months group compared to the RFI ≥ 6 months group (HR 1.78; 95% CI 0.35-8.98, p = 0.48). Conclusions: In patients with CRC experienced early recurrence, the RFI &lt; 6 months group had a trend of poor efficacy compared to the RFI of ≥ 6 months group.

DNA barcoding for the identification and authentication of medicinal deer (Cervus sp.) products in China.

Deer products from sika deer (Cervus nippon) and red deer (C. elaphus) are considered genuine and used for Traditional Chinese Medicine (TCM) materials in China. Deer has a very high economic and ornamental value, resulting in the formation of a characteristic deer industry in the prescription preparation of traditional Chinese medicine, health food, cosmetics, and other areas of development and utilization. Due to the high demand for deer products, the products are expensive and have limited production, but the legal use of deer is limited to only two species of sika deer and red deer; other wild deer are prohibited from hunting, so there are numerous cases of mixing and adulteration of counterfeit products and so on. There have been many reports that other animal (pig, cow, sheep, etc.) tissues or organs are often used for adulteration and confusion, resulting in poor efficacy of deer traditional medicine and trade fraud in deer products. To authenticate the deer products in a rapid and effective manner, the analysis used 22 deer products (antler, meat, bone, fetus, penis, tail, skin, and wool) that were in the form of blind samples. Total DNA extraction using a modified protocol successfully yielded DNA from the blind samples that was useful for PCR. Three candidate DNA barcoding loci, cox1, Cyt b, and rrn12, were evaluated for their discrimination strength through BLAST and phylogenetic clustering analyses. For the BLAST analysis, the 22 blind samples obtained 100% match identity across the three gene loci tested. It was revealed that 12 blind samples were correctly labeled for their species of origin, while three blind samples that were thought to originate from red deer were identified as C. nippon, and seven blind samples that were thought to originate from sika deer were identified as C. elaphus, Dama dama, and Rangifer tarandus. DNA barcoding analysis showed that all three gene loci were able to distinguish the two Cervus species and to identify the presence of adulterant species. The DNA barcoding technique was able to provide a useful and sensitive approach in identifying the species of origin in deer products.

Annonaceous Acetogenins Synergistically Inhibit Hepatocellular Carcinoma with Sorafenib.

Sorafenib was first approved as the standard treatment for advanced hepatocellular carcinoma (HCC). Despite providing an advantage in terms of patient survival, sorafenib has shown poor clinical efficacy and severe side effects after long-term treatment. Thus, combination treatment is a potential way to increase the effectiveness and reduce the dose-limiting toxicity of sorafenib. Extracts of the seeds of Annona montana have shown synergistic antitumor activity with sorafenib, and seven annonaceous acetogenins, including three new acetogenins, muricin P (2), muricin Q (3), and muricin R (4), were isolated from the extracts by bioguided fractionation and showed synergy with sorafenib. The structures of these compounds were determined using spectroscopic and chemical methods. Annonacin (1) and muricin P (2), which reduced intracellular ATP levels and promoted apoptosis, exhibited synergistic cytotoxicity with sorafenib in vitro. In vivo, annonacin (1) displayed synergistic antitumor activity by promoting tumor cell apoptosis. Moreover, the potential mechanism of annonacin (1) was predicted by transcriptomic analysis, which suggested that SLC33A1 is a potential target in HCC. Annonacin (1) might be a novel candidate for combination therapy with sorafenib against advanced HCC.

Early Repigmentation of Stable Vitiligo through Point-of-Care Melanocyte Transfer Using Non-Cultured Autologous Skin Cell Suspension

Introduction: Vitiligo is an acquired depigmenting skin condition characterized by the loss of skin pigmentation, impacting 0.5% to 2% of the global population.1,2 Vitiligo presents as distinct depigmented patches resulting from autoimmune melanocyte destruction. Individuals with visual vitiligo lesions often experience negative body image, diminished self-confidence, discomfort, and overall lower quality of life (QoL).3 While there are medical treatment options available, these can be associated with poor efficacy and low medication compliance.4 Residual lesions after treatment may require surgical intervention which allows for melanocyte transplantation from an area that is pigmented to one that is lacking functional melanocytes. Through a point-of-care device, a non-cultured autologous skin cell suspension (ACSC) can be prepared using a small skin sample; the ASCS contains healthy melanocytes and is immediately applied onto skin treated with ablative laser to aid in the repigmentation of affected areas. The objective of this study was to evaluate the one-time application of ASCS, with a 1:20 donor to treatment site expansion ratio, for the safe and effective repigmentation of stable vitiligo lesions. Methods: A randomized, within-subject controlled, central observer-blinded study was conducted to compare the clinical performance of laser ablation, ASCS, and NB-UVB to NB-UVB alone for repigmentation of stable vitiligo lesions in adults. Subjects received NB-UVB phototherapy on both ASCS-treated and controlled lesions as per recommended by the Vitiligo Working Group. Repigmentation of ASCS-treated and control lesions were categorized by a Central Review Committee (CRC) of blinded dermatologists as one of the following: 0%-25%, 26%-50%, 51%-79%, or 80-100%. The primary effectiveness endpoint was defined as the proportion of lesions achieving ≥80% repigmentation for ASCS-treated versus control areas at Week 24. Early regimentation was assessed at Weeks 4 and 12 as a post hoc analysis. Results: A significantly higher proportion of the ASCS-treated areas (36.0%, n = 9) compared to control-treated areas (0.0%) attained ≥80% repigmentation at Week 24 (P = 0.012). At Week 4, 30.4% (n = 7/23) of ASCS-treated areas had ≥26% repigmentation compared to 4.3% (n = 1/23) in the control areas. At Week 12, 56.5% (n = 13/23) of ASCS-treated areas had ≥26% repigmentation compared to 21.7% (n = 5/23) in the control areas. At Week 24, 64% (n = 16/25) of ASCS-treated areas had ≥26% repigmentation compared to 28% (n = 7/25) in the control areas. Conclusion: A one-time treatment of ASCS, with the addition of NB-UVB, can result in excellent repigmentation results by 24 weeks, with most subjects seeing ≥26% repigmentation as early as 4 to 12 weeks.

Five invasive alien plant powders, Norway spruce (Picea abies [L.] H. Karst.) wood ash and diatomaceous earth against Sitophilus oryzae (L.) adults: are they closer to guns or roses?

We tested the insecticidal efficacy of different powders as surface treatment against the rice weevil (Sitophilus oryzae) adults. We have applied dusts from five invasive alien plant species (Solidago canadensis, Solidago gigantea, Amorpha fruticosa, Rhus typhina, Ailanthus altissima) and two inert dusts, i.e. wood ash from Norway Spruce (Picea abies) and commercial product SilicoSec® (as diatomaceous earth). Mortality was evaluated from 1st till 7th day after exposure, at 20 and 25 °C, two values of relative humidity and two doses (20 and 40 g/m2). After Day 7, alive beetles were placed into clean Petri dishes, and mortality counts were measured from 8th till 14th day. In general, we have detected poor efficacy of plant powders against S. oryzae. SilicoSec® at 20 g/m2 caused 100 % mortality at 25 °C and 55% RH, after seven days. Wood ash (13.46% SiO2) was less effective in comparison to SilicoSec® (79.48% SiO2), as approx. 60% mortality was recorded at the same conditions. We have detected that leaves of A. altissima and flowers od S. gigantea are rich with polyphenols (like catechin hydrate), on average almost 17 mg/g in S. gigantea flowers. Flowers and leaves of Solidago species are also rich with essential oil, like beta-copaene. The results of our research indicate that the powders of invasive plants are closer to fragrant roses in controlling S. oryzae adults, while the gun for this pest is only diatomaceous earth. To improve the effectiveness of invasive plant products, we suggest testing their independent effectiveness in liquid form as well as combinations of their essential oils with inert dusts.

Dual-targeting nanomedicine achieves synergistic multimodal therapy for tumor

BackgroundThe poor targeting delivery efficiency and limited efficacy of single therapeutic approach have consistently posed significant challenges in tumor management.ResultsIn this research, we have conceived and synthesized a dual-targeting nanodrug delivery system denoted as PDA-DEM-Fe3O4@M, which incorporates a polydopamine nanoparticle (PDA) with photothermal properties, diethyl maleate (DEM) as a chemotherapy agent accelerating tumor apoptosis, iron oxide nanoparticles (Fe3O4) eliciting magnetic targeting effects, and tumor cell membranes (M) contributing to homologous targeting capabilities. The synergistic effect of PDA-induced photothermal therapy and DEM-mediated chemotherapy has been demonstrated in this study to exert a robust inhibitory and cytotoxic influence on tumor cells. Additionally, the biocompatibility of this system has also been demonstrated.ConclusionsThrough the synergistic effects of PDA’s photothermal therapy and DEM’s chemotherapy, this system demonstrated excellent inhibition and killing effects on tumor cells. Furthermore, we established its excellent biological safety profile. This study demonstrated the potential of this nanomaterial for clinical application in tumor therapy.

In vivo assembly enhanced binding effect augments tumor specific ferroptosis therapy

Emerging evidence indicates that the activation of ferroptosis by glutathione peroxidase 4 (GPX4) inhibitors may be a prominent therapeutic strategy for tumor suppression. However, the wide application of GPX4 inhibitors in tumor therapy is hampered due to poor tumor delivery efficacy and the nonspecific activation of ferroptosis. Taking advantage of in vivo self-assembly, we develop a peptide-ferriporphyrin conjugate with tumor microenvironment specific activation to improve tumor penetration, endocytosis and GPX4 inhibition, ultimately enhancing its anticancer activity via ferroptosis. Briefly, a GPX4 inhibitory peptide is conjugated with an assembled peptide linker decorated with a pH-sensitive moiety and ferriporphyrin to produce the peptide-ferriporphyrin conjugate (Gi-F-CAA). Under the acidic microenvironment of the tumor, the Gi-F-CAA self-assembles into large nanoparticles (Gi-F) due to enhanced hydrophobic interaction after hydrolysis of CAA, improving tumor endocytosis efficiency. Importantly, Gi-F exhibits substantial inhibition of GPX4 activity by assembly enhanced binding (AEB) effect, augmenting the oxidative stress of ferriporphyrin-based Fenton reaction, ultimately enabling antitumor properties in multiple tumor models. Our findings suggest that this peptide-ferriporphyrin conjugate design with AEB effect can improve the therapeutic effect via induction of ferroptosis, providing an alternative strategy for overcoming chemoresistance.

Efficacy and safety analysis of stereotactic body radiotherapy for brain multi-metastases in non-small cell lung cancer patients.

Lung cancer is prone to metastasize to the brain, which is difficult for surgery and leads to poor prognosis due to poor chemotherapy efficacy. Our aim is to evaluate the efficacy and safety of stereotactic body radiotherapy (SBRT) for brain multi-metastases. In the retrospective study, a total of 51 non-small cell lung cancer (NSCLC) patients with brain multi-metastases (3-5 metastases) receiving SBRT in the local hospital between 2016 and 2019 were enrolled for analyzing the efficacy and safety of SBRT. The primary endpoints included 1-year local control rate, radiotherapy toxicity, overall survival and progression-free survival. The median follow-up for the enrolled patients was 21 months, and the 1-year and 2-year OS rates were 82.4% and 45.1%, respectively. Demographic analysis showed no significant differences between SBRT alone and combination with whole brain radiotherapy in clinical characteristics including age, gender and Eastern Cooperative Oncology Group performance status. The 1-year local control rate was 77.3% (17/22) for SBRT alone, which was comparable to 79.3% (23/29) of combined radiotherapy. Cox proportional hazard regression demonstrated that the prognostic benefit of combining WBRT was not significantly superior to SBRT alone (HR = 0.851, P= 0.263). Their radiotherapy toxicity rate was lower in SBRT alone group (13.6%, vs. 44.8% for combination; P= 0.017). The current research suggested that SBRT alone could effectively relieve tumor burden and improve the prognosis and quality of life for NSCLC patients with brain multi-metastases, which should be validated in further prospective clinical trials.

Stimulating thyroglobulin to TSH ratio predict long-term efficacy of 131I therapy in patients with differentiated thyroid cancer after total thyroidectomy: a retrospective study.

This study utilized the stimulated thyroglobulin (sTg) to thyroid stimulating hormone (TSH) ratio to predict the long-term efficacy of 131I therapy in patients with moderate-to-high-risk differentiated thyroid cancer (DTC). This study retrospectively analyzed 960 DTC patients with a median follow-up time of 30 months (6-92 months). The median age was 44 years. All patients underwent total thyroidectomy, lymph node dissection, and at least one 131I therapy. Patients were subjected to a final efficacy evaluation according to American Thyroid Association's 2015 guidelines. Patients were grouped according to their TSH levels before the initial 131I therapy and the final efficacy evaluation, and factors influencing TSH levels and final efficacy were analyzed. Construction of nomograms using independent risk factors affecting long-term outcomes. The cut-offs of sTg and sTg/TSH ratios were calculated for different long-term outcomes. Progression-free survival (PFS) of patients was analyzed by making Kaplan-Meier survival according to the cut-offs of sTg and sTg/TSH ratio. TSH (mU/L) levels were more concentrated at 60-90 in females (71.5%) and 30-60 in males (39.0%), while patients with younger age, more lymph node metastases, shorter time interval between surgery and the first 131I therapy, and lower dose of levothyroxine sodium taken prior to the first 131I therapy would have higher TSH levels (All P < 0.05).Patients who are male, have primary tumor involvement of the strap muscles, lymph node metastasis, distant metastasis, and higher sTg and sTg/TSH are more likely to have poor long-term outcomes (All P < 0.05).The cut-offs of sTg and sTg/TSH for long-term efficacy were 7.515 and 0.095. STg, sTg/TSH, tumor size, lymph node metastasis, and distant metastasis were shown to be independent risk factors for long-term efficacy. The mean PFSs were longer for patients who had sTg/TSH ≤ 0.095 and/or sTg≤7.515 ug/L. For patients with moderate-to-high-risk DTC, when sTg>7.515 ug/L and/or sTg/TSH > 0.095 before the first 131I therapy, patients are more likely to have a poor long-term efficacy after full 131I therapy. This means that this group of patients may require further surgical treatment or targeted drug therapy after 131I therapy.

Improved Pharmacokinetic and Pharmacodynamic Profile of Deuterium-Reinforced Tricyclic Antidepressants Doxepin, Dosulepin, and Clomipraminein Animal Models.

Doxepin, dosulepin, and clomipramine are tricyclic antidepressants (TCAs) that act as serotonin and noradrenaline reuptake inhibitors. The metabolites formed by N-dealkylation of these tricyclic antidepressants contribute to overall poor pharmacokinetics and efficacy. Deuteration of the methyl groups at metabolically active sites has been reported to be a useful strategy for developing more selective and potent antidepressants. This isotopic deuteration can lead to better bioavailability and overall effectiveness. The objective is to study the effect of site-selective deuteration of TCAs on their pharmacokinetic and pharmacodynamic profile by comparison with their nondeuterated counterparts. In the current study, the pharmacokinetic profile and antidepressant behavior of deuterated TCAs were evaluated using the forced swim test (FST) and tail suspension test (TST), using male Wistar rats and male Swiss albino mice, respectively; additionally, a synaptosomal reuptake study was carried out. Compared with the nondeuterated parent drugs, deuterated forms showed improved efficacy in the behavior paradigm, indicating improved pharmacological activity. The pharmacokinetic parameters indicated increased maximum concentration in the plasma(Cmax), elimination half-life (t1/2), and area under the concentration-time curve (AUC) in deuterated compounds. This can have a positive clinical impact on antidepressant treatment. Synaptosomal reuptake studies indicated marked inhibition of the reuptake mechanism of serotonin (5-HT) and norepinephrine. Deuterated TCAs can prove to be potentially better molecules in the treatment of neuropsychiatric disorders as compared with nondeuterated compounds. In addition, we have demonstrated a concept that metabolically active, site-selective deuteration can be beneficial for improving the pharmacokinetic and pharmacodynamic profiles of TCAs. A further toxicological study of these compounds is needed to validate their future clinical use.