Efficacy and safety of topical minocycline foam (FMX101 4%) in treatment of Chinese subjects with moderate-to-severe facial acne vulgaris: A phase 3, multi-centre, randomized, double-blind, vehicle-controlled study.

BACKGROUND: FMX101 4%, as a topical foam formulation of minocycline, has been approved by US Food and Drug Administration for the treatment of moderate-to-severe acne vulgaris (AV). OBJECTIVE: To evaluate the efficacy and safety of FMX101 4% in treating Chinese subjects with moderate-to-severe facial AV. METHODS: This was a multi-centre, randomized, double-blind, vehicle-controlled phase 3 study in Chinese subjects with moderate-to-severe AV. Eligible subjects were randomized 2:1 to receive either FMX101 4% or vehicle foam treatment for 12 weeks. The primary efficacy endpoint was the change in inflammation lesion count (ILC) from baseline at week 12. The key secondary endpoint was the treatment success rate according to Investigator's Global Assessment (IGA) at week 12. RESULTS: In total, 372 subjects were randomized into two groups (FMX101 4% group, n = 248; vehicle group, n = 124). After 12 weeks treatment, the reduction in ILC from baseline was statistically significant in favour of FMX101 4%, compared with vehicle foam (-21.0 [0.08] vs. -12.3 [1.14]; LSM [SE] difference, -8.7 [1.34]; 95% CI [-11.3, -6.0]; p < 0.001). FMX101 4% treatment yielded significantly higher IGA treatment success rate at week 12 as compared to the control treatment (8.06% vs. 0%). Applying FMX101 4% also resulted in significant reduction in noninflammatory lesion count (nILC) versus vehicle foam at week 12 (-19.4 [1.03] vs. -14.9 [1.47]; LSM [SE] difference, -4.5 [1.74]; 95% CI [-8.0, -1.1]; p = 0.009). Most treatment-emergent adverse events (TEAEs) were mild-to-moderate in severity, and no treatment-related treatment-emergent serious adverse event (TESAE) occurred. Thus, FMX101 4% was considered to be a safe and well-tolerated product during the 12-week treatment period. CONCLUSION: FMX101 4% treatment for 12 weeks could lead to significantly reduced ILC and nILC, and improved IGA treatment success rate in Chinese subjects with moderate-to-severe facial AV. It also showed a well acceptable safe and tolerability profile.

Synthesis and Preclinical Evaluation of a Novel FAPI-04 Dimer for Cancer Theranostics.

Overexpression of fibroblast activation protein (FAP) in cancer-associated fibroblasts in a wide variety of tumors enables a highly selective targeting strategy using FAP inhibitors (FAPIs). Quinoline-based FAPIs labeled with radionuclides have been widely developed for tumor-targeted nuclear medicine imaging. However, the short retention time of FAPIs at the tumor site limits their application in radionuclide therapy. In this study, a novel FAPI-04 dimer was synthesized and labeled with radionuclides to prolong the retention time in tumors for imaging and therapy. To prepare the FAPI-04 dimer complex, DOTA-Suc-Lys-(FAPI-04)2, we used Fmoc-Lys(Boc)-OH as the linker to conjugate two FAPI-04 structures by an amide reaction. The resulting product was further modified by DOTA groups to allow for conjugation with radioactive metals. Both [68Ga]Ga-(FAPI-04)2 and [177Lu]Lu-(FAPI-04)2 showed a radiochemical purity of >99% and remained stable in vitro. In vivo, micro-PET images of SKOV3, A431, and H1299 xenografts revealed that the tumor uptake of [68Ga]Ga-(FAPI-04)2 was about twice that of [68Ga]Ga-FAPI-04 and that the accumulation of [68Ga]Ga-(FAPI-04)2 at the tumor site did not significantly decrease even 3h after injection. The tumor-abdomen ratio of [68Ga]Ga-(FAPI-04)2 images was significantly higher than that of [18F]F-FDG images. For radionuclide therapy, [177Lu]Lu-(FAPI-04)2 effectively retarded tumor growth and displayed good tolerance. In conclusion, the DOTA-Suc-Lys-(FAPI-04)2 design enhanced its uptake in FAP-expressing tumors, improved its retention time at the tumor site, and produced high-contrast imaging in xenografts after radionuclide labeling. Furthermore, it showed a noticeable antitumor effect. DOTA-Suc-Lys-(FAPI-04)2 provides a new approach for applying FAPI derivatives in tumor theranostics.

Evaluation of the Effectiveness of Telehealth Chronic Disease Management System: Systematic Review and Meta-analysis.

BACKGROUND: Long-term daily health monitoring and management play a more significant role in telehealth management systems nowadays, which require evaluation indicators to present patients' general health conditions and become applicable to multiple chronic diseases. OBJECTIVE: This study aims to evaluate the effectiveness of subjective indicators of telehealth chronic disease management system (TCDMS). METHODS: We selected Web of Science, ScienceDirect, Scopus, Cochrane library, IEEE, and Chinese National Knowledge Infrastructure and Wanfang, a Chinese medical database, and searched papers published from January 1, 2015, to July 1, 2022, regarding randomized controlled trials on the effectiveness of the telehealth system on patients with chronic diseases. The narrative review summarized the questionnaire indicators presented in the selected studies. In the meta-analysis, Mean Difference (MD) and Standardized Mean Difference (SMD) with a 95% CI were pooled depending on whether the measurements were the same. Subgroup analysis was conducted if the heterogeneity was significant, and the number of studies was sufficient. RESULTS: Twenty RCTs with 4153 patients were included in the qualitative review. Seventeen different questionnaire-based outcomes were found, within which quality of life, psychological well-being (including depression, anxiety, and fatigue), self-management, self-efficacy, and medical adherence were most frequently used. Ten RCTs with 2095 patients remained in meta-analysis. Compared to usual care, telehealth system can significantly improve the quality of life (SMD 0.44; 95% CI 0.16-0.73; P=.002), whereas no significant effects were found on depression (SMD -0.25; 95% CI -0.72 to 0.23; P=.30), anxiety (SMD -0.10; 95% CI -0.27 to 0.07; P=.71), fatigue (SMD -0.36; 95% CI -1.06 to 0.34; P<.001), and self-care (SMD 0.77; 95% CI -0.28-1.81; P<.001). In the subdomains of quality of life, telehealth statistically significantly improved physical functioning (SMD 0.15; 95% CI 0.02 to 0.29; P=.03), mental functioning (SMD 0.37; 95% CI 0.13-0.60; P=.002), and social functioning (SMD 0.64; 95% CI 0.00-1.29; P=.05), while there was no difference on cognitive functioning (MD 8.31; 95% CI -7.33 to 23.95; P=.30) and role functioning (MD 5.30; 95% CI -7.80 to 18.39; P=.43). CONCLUSIONS: TCDMS positively affected patients' physical, mental, and social quality of life across multiple chronic diseases. However, no significant difference was found in depression, anxiety, fatigue, and self-care. Subjective questionnaires had the potential ability to evaluate the effectiveness of long-term telehealth monitoring and management. However, further well-designed experiments are warranted to validate TCDMS's effects on subjective outcomes, especially when tested among different chronically ill groups.

A multi center real world observation to evaluate the efficacy of cryotherapy versus local hyperthermia for the treatment of plane warts.

Most plane warts are recalcitrant to treatment. Both cryotherapy and local hyperthermia have been applied to treat plane warts. However, no direct comparative study on their respective efficacy and safety has ever been performed. To assess the efficacy and safety of local hyperthermia at 43 ± 1°C versus liquid nitrogen cryotherapy for plane warts. Sequential patients with plane warts entered the study, either receiving cryotherapy or local hyperthermia therapy at the discretion of the patients and the recommendations of consultants. Cryotherapy with liquid nitrogen was delivered in two sessions 2 weeks apart, while local hyperthermia was delivered on three consecutive days, plus two similar treatments 10 ± 3 days later. The temperature over the treated skin surface was set at 43 ± 1°C for 30 min in each session. The primary outcome was the clearance rates of the lesions 6 months after treatment. Among the 194 participants enrolled, 183 were included in the analysis at 6 months. Local hyperthermia and cryotherapy achieved clearance rates of 35.56% (48/135) and 31.25% (15/48), respectively (p = 0.724); recurrence rates of 16.67% (8/48) and 53.33% (8/15) (p = 0.01); and adverse events rates of 20.74% (28/135) and 83.33% (40/48), respectively (p < 0.001). Cryotherapy had a higher pain score (p < 0.001) and a longer healing time (p < 0.001). Local hyperthermia at 43°C and cryotherapy had similar efficacy for plane warts. Local hyperthermia had a safer profile than cryotherapy but it required more treatment visits during a treatment course. More patients preferred local hyperthermia due to its treatment friendly nature.

Efficacy and Safety of Janus Kinase Inhibitors for the Treatment of Atopic Dermatitis: A Systematic Review and Meta-Analysis.

BACKGROUND: Current therapeutic options for atopic dermatitis (AD) are limited. Janus kinase (JAK) inhibitors may be viable alternatives. OBJECTIVES: To assess the efficacy and safety of JAK inhibitors for AD treatment. METHODS: We searched PubMed, Embase, the Cochrane Controlled Register of Trials, Web of Science, Global Resource of Eczema Trials database, and ClinicalTrials.gov from inception to September 1, 2020. Randomized clinical trials (RCTs) comparing JAK inhibitors with placebo/vehicle treatment for AD patients were included. The primary study outcomes included (1) the change (%) from the Eczema Area and Severity Index (EASI) baseline expressed as weighted mean difference (WMD) and 95% confidence interval (95% CI), and (2) the Investigator's Global Assessment (IGA) response and safety outcomes expressed as relative risk (RR) and 95% CI. RESULTS: We included 14 RCTs published in 13 studies (3,822 patients). Treatment with JAK inhibitors significantly improved IGA response (RR 2.83, 95% CI 2.25-3.56, p < 0.001) and EASI score (WMD -28.82, 95% CI -34.48 to -23.16, p < 0.001). JAK inhibitor treatment achieved the largest improvement in both IGA response (RR 3.59, 95% CI 2.66-4.84, p < 0.001) and EASI score (WMD -42.00, 95% CI -48.64 to -35.36, p < 0.001) by week 4 of treatment. Topical JAK inhibitors were significantly more efficacious than oral inhibitors. Upadacitinib treatment for 4 weeks was most effective in reducing EASI score (WMD -53.92, 95% CI -69.26 to -38.58, p < 0.001), while abrocitinib for 4 weeks led to the most effective IGA response (RR 5.47, 95% CI 2.74-10.93, p < 0.001). There was no difference in the frequency of adverse events (AEs) leading to discontinuation; however, JAK inhibitors use, especially abrocitinib, led to a higher incidence of treatment-emergent AEs (RR 1.25, 95% CI 1.10-1.42, p = 0.001). CONCLUSION: Our results imply that JAK inhibitors are an effective and safe AD treatment. Nevertheless, further trials with longer duration and head-to-head comparisons of different JAK inhibitors are needed.

Local Hyperthermia Versus Cryotherapy for Treatment of Plantar Warts: A Prospective Multi-centre Non-randomized Concurrent Controlled Clinical Trial.

Cryotherapy is one of the most common treatments for warts; however, pain during treatment and relatively high recurrence rates limit its use. Local hyperthermia has also been used successfully in the treatment of plantar warts. The aim of this study was to compare the clinical effectiveness of local hyperthermia vs cryotherapy for the treatment of plantar warts. This multi- centre, open, 2-arm, non-randomized concurrent controlled trial included 1,027 patients, who received either cryotherapy or local hyperthermia treatment. Three months after treatment, local hyperthermia and cryotherapy achieved complete clearance rates of 50.9% and 54.3%, respectively. Recurrence rates were 0.8% and 12%, respectively. Pain scores during local hyperthermia were significantly lower than for cryotherapy. Both local hyperthermia and cryotherapy demonstrated similar efficacy for clearance of plantar warts; while local hyperthermia had a lower recurrence rate and lower pain sensation during treatment.

The application research of AI image recognition and processing technology in the early diagnosis of the COVID-19.

BACKGROUND: This study intends to establish a combined prediction model that integrates the clinical symptoms,the lung lesion volume, and the radiomics features of patients with COVID-19, resulting in a new model to predict the severity of COVID-19. METHODS: The clinical data of 386 patients with COVID-19 at several hospitals, as well as images of certain patients during their hospitalization, were collected retrospectively to create a database of patients with COVID-19 pneumonia. The contour of lungs and lesion locations may be retrieved from CT scans using a CT-image-based quantitative discrimination and trend analysis method for COVID-19 and the Mask R-CNN deep neural network model to create 3D data of lung lesions. The quantitative COVID-19 factors were then determined, on which the diagnosis of the development of the patients' symptoms could be established. Then, using an artificial neural network, a prediction model of the severity of COVID-19 was constructed by combining characteristic imaging features on CT slices with clinical factors. ANN neural network was used for training, and tenfold cross-validation was used to verify the prediction model. The diagnostic performance of this model is verified by the receiver operating characteristic (ROC) curve. RESULTS: CT radiomics features extraction and analysis based on a deep neural network can detect COVID-19 patients with an 86% sensitivity and an 85% specificity. According to the ROC curve, the constructed severity prediction model indicates that the AUC of patients with severe COVID-19 is 0.761, with sensitivity and specificity of 79.1% and 73.1%, respectively. CONCLUSIONS: The combined prediction model for severe COVID-19 pneumonia, which is based on deep learning and integrates clinical aspects, pulmonary lesion volume, and radiomics features of patients, has a remarkable differential ability for predicting the course of disease in COVID-19 patients. This may assist in the early prevention of severe COVID-19 symptoms.

Mdivi-1 alleviates atopic dermatitis through the inhibition of NLRP3 inflammasome.

Atopic dermatitis (AD) is a chronic inflammatory cutaneous disorder with few treatment options. Dynamin-related protein 1 (Drp1)-dependent mitochondrial fission contributes to the activation of NLRP3 inflammasome, and inhibiting Drp1 has been become an attractive therapeutic strategy for inflammatory diseases. This study aimed to investigate the effects of Drp1 inhibitor mdivi-1 on experimental AD. We firstly detected the effects of mdivi-1 on primary human keratinocytes in an inflammatory cocktail-induced AD-related inflammation in vitro. Results showed that mdivi-1 inhibited NLRP3 inflammasome activation and pyroptosis which were evidenced by decreased expression of NLRP3, ASC, cleavage of caspase-1, GSDMD-NT, mature interleukin (IL)-1ß and IL-18 in keratinocytes under AD-like inflammation. Next, mouse model of AD-like skin lesions was induced by epicutaneous application of 2,4-dinitrochlorobenzene (DNCB) and mdivi-1 (25 mg/kg/day, days 5-33 during construction of AD model) was intraperitoneally injected into DNCB-induced mice. AD mice with mdivi-1 treatment exhibited ameliorated AD symptoms, lower serum IgE level, and reduced epidermal thickening, mast cells infiltration, and production of IL-4, IL-5 and IL-13 in the lesional tissues. Indeed, mdivi-1 significantly inhibited NLRP3 inflammasome activation and pyroptotic injury occurred in DNCB-treated skin tissues. Mechanically, mdivi-1 regulated the expression of mitochondrial dynamic proteins and suppressed the activation of NF-κB signal pathway which is an upstream of NLRP3 inflammasome both in vitro and in vivo. This study demonstrated that mdivi-1 could protect against experimental AD through inhibiting the activation of NLRP3 inflammasome and subsequent inflammatory cytokine release, and mdivi-1 might exert this function by inhibiting mitochondrial fission and subsequently blocking NF-κB pathway.

Retracted: Anthecotulide Sesquiterpene Lactone Exhibits Selective Anticancer Effects in Human Malignant Melanoma Cells by Activating Apoptotic and Autophagic Pathways, S-Phase Cell Cycle Arrest, Caspase Activation, and Inhibition of NF-κB Signalling Pathway.

Retracted, due to breach of publishing guidelines, following the identification of non-original and manipulated figure images. Reference: Chenyang Li, Xiuping Han: Anthecotulide Sesquiterpene Lactone Exhibits Selective Anticancer Effects in Human Malignant Melanoma Cells by Activating Apoptotic and Autophagic Pathways, S-Phase Cell Cycle Arrest, Caspase Activation, and Inhibition of NF-kappaB Signalling Pathway. Med Sci Monit 2019; 25:2852-2858. 10.12659/MSM.913771.

Smart 131 I-Labeled Self-Illuminating Photosensitizers for Deep Tumor Therapy.

Stimulating photosensitizers (PS) by Cerenkov radiation (CR) can overcome the light penetration limitation in traditional photodynamic therapy. However, separate injection of radiopharmaceuticals and PS cannot guarantee their efficient interaction in tumor areas, while co-delivery of radionuclides and PS face the problem of nonnegligible phototoxicity in normal tissues. Here, we describe a 131 I-labeled smart photosensitizer, composed of pyropheophorbide-a (photosensitizer), a diisopropylamino group (pH-sensitive group), an 131 I-labeled tyrosine group (CR donor), and polyethylene glycol, which can self-assemble into nanoparticles (131 I-sPS NPs). The 131 I-sPS NPs showed low phototoxicity in normal tissues due to aggregation-caused quenching effect, but could self-produce reactive oxygen species in tumor sites upon disassembly. Upon intravenous injection, 131 I-sPS NPs showed great tumor inhibition capability in subcutaneous 4T1-tumor-bearing Balb/c mice and orthotopic VX2 liver tumor bearing rabbits. We believed 131 I-sPS NPs could expand the application of CR and provide an effective strategy for deep tumor theranostics.

Melanoma Cancer Immunotherapy Using PD-L1 siRNA and Imatinib Promotes Cancer-Immunity Cycle.

PURPOSE: Cancer-Immunity Cycle is a cascade of anticancer immune responses in the body that continues and fights against the cancer expansion. The Cancer-Immunity Cycle is halted by tumor cell immunosuppression of host T cell through programmed cell death receptor 1 (PD-1) and programmed cell death ligand 1 (PD-L1) interactions that induce the functional suppression of tumor-reactive cytotoxic T cells and actively promotes the tumorigenesis via the mTOR signaling pathway. METHODS: Here, we demonstrated that this Cycle could be enhanced by the synergistic knock down of PD-L1 through co-delivery of siRNA-PD-L1 (siPD-L1) and imatinib (IMT) in a liposomal nanoparticle. RESULTS: The siPDIN effectively downregulated the protein expressions of PD-L1 and significantly knocked down the expression of p-S6k protein at in vitro and in vivo conditions which inhibited tumorigenic mTOR pathway. The combination-based siPDIN exhibited a significantly higher cytotoxic effect compared to that of individual anticancer agents. B16F10 cells treated with siPDIN exhibited a significantly higher cancer cell apoptosis (~60%) compared to cocktail combination of siRNA+IMT (~35%) analyzed by flow cytometer. Importantly, siPDIN significantly delayed the tumor growth with significantly lower tumor-specific growth rate than the animals treated with individual free IMT or siRNA. siPDIN produced a 3-fold higher IFN-γ compared to control in DLNs and 4-fold higher IFN-γ in spleens. CONCLUSION: Overall, results revealed that the tumors treated with siPDIN restored the immunity of CTLs by potentially inhibiting the immune checkpoint interactions, suppressed the mTOR signaling pathway and exhibited an enhanced anticancer efficacy in melanoma.

Anthecotulide Sesquiterpene Lactone Exhibits Selective Anticancer Effects in Human Malignant Melanoma Cells by Activating Apoptotic and Autophagic Pathways, S-Phase Cell Cycle Arrest, Caspase Activation, and Inhibition of NF-κB Signalling Pathway.

BACKGROUND We examined the anticancer potential of anthecotulide against SK-MEL-24 malignant melanoma cells. The apoptotic and autophagic effects of anthecotulide were also investigated. MATERIAL AND METHODS The cell viability of SK-MEL-24 human malignant melanoma cells was evaluated by WST-1 assay. Fluorescence microscopy using acridine orange and ethidium bromide staining, as well as Western blot analysis, were used to study apoptotic effects induced by anthecotulide. Autophagy was assessed by Western blot analysis and fluorescence microscopy. Effects of anthecotulide on cell cycle progression were analyzed by flow cytometry. RESULTS The results revealed that anthecotulide exerts significant growth-inhibitory effects on SK-MEL-24 cells. The IC50 of anthecotulide against the SK-MEL-24 cells was found to be 10 µM. However, the anticancer effects against the normal cells were minimal (IC50; 100 µM). Investigation of the underlying mechanism revealed that anthecotulide prompts apoptotic cell death of the SK-MEL-24 cells, which was linked with increased expression of Bax and decreased expression of Bcl-2. It also triggered concentration-dependent activation of caspase 3 and 9. Anthecotulide induced autophagy in the SK-MEL-24 cells, which was associated with upregulation of LC3 II and Beclin-1 expression. Anthecotulide also halted the SK-MEL-24 cells at S-phase of the cell cycle and downregulated the expression of Cyclin B1. However, the expression of p27 was upregulated. CONCLUSIONS These results indicate anthecotulide is a potent lead molecule for the treatment of melanoma. In vivo and other related experiments are warranted to further assess this promising drug candidate.

Silencing of astrocyte elevated gene-1 inhibits proliferation and migration of melanoma cells and induces apoptosis.

Melanoma is an aggressive skin malignancy with a high mortality. Astrocyte elevated gene-1 (AEG-1), a downstream target of Ras and c-Myc, has been implicated in the development of multiple tumours, but its role in melanoma remains unclear. In the present study, the role of AEG-1 in melanoma was explored through AEG-1 silencing. Our results showed that silencing AEG-1 inhibited the proliferation of melanoma cells, induced cell cycle arrest, and reduced levels of cyclin A, cyclin B, cyclin D1, cyclin E, and cyclin-dependent kinase 2. AEG-1silencing also induced apoptosis in melanoma cells and altered the levels of cleaved caspase-3, B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein. Moreover, silencing AEG-1 suppressed the migration and invasion of melanoma cells, reduced the expressions and activities of matrix metallopeptidase (MMP)-2 and MMP-9, and inhibited the activation of the Wnt/ß-catenin signalling pathway in melanoma cells. Furthermore, in vivo experiments revealed that AEG-1 silencing inhibited the growth of melanoma xenografts in nude mice. In summary, our study demonstrates an oncogenic role of AEG-1 in melanoma and suggests that AEG-1 may serve as a potential therapeutic target in the treatment of melanoma.

Tracking control of wheeled mobile robots via intermittent control.

This paper was concerned with the trajectory tracking control of wheeled mobile robots using aperiodic intermittent control. By establishing the corresponding motion model of the wheeled mobile robot, a tracking control strategy was proposed based on the intermittent control approach and backstepping method. Compared to the controllers using continuous state feedback, the proposed control strategy was activated only on separate time intervals, which combined the features of closed- and open-loop control. An example was given to illustrate the effectiveness of the obtained result.

Prevalence of cutaneous manifestations in COVID-19: A meta-analysis.

The global epidemic of coronavirus disease 2019 (COVID-19) endangers more and more people. Many studies on cutaneous manifestations related to COVID-19 have emerged, but their prevalence has varied widely. The objective of this study was to conduct a meta-analysis estimating the prevalence of skin manifestations in COVID-19. Four databases PubMed, Web of Science, CBM, and CNKI were searched, and the results were screened by two reviewers. A random-effects model was used to evaluate the overall prevalence. Heterogeneity was assessed by I2 . Further subgroup analyses were conducted by region, sample size, sex, age, and severity of COVID-19. A funnel plot and Egger's test were performed to assess publication bias. The pooled prevalence of cutaneous manifestation of 61 089 patients in 33 studies was 5.6% (95% confidence intervals [CI] = 0.040-0.076, I2  = 98.3%). Severity of COVID-19 was probably the source of heterogeneity. Studies with sample size <200 report higher prevalence estimates (10.2%). The prevalence of detailed types was as follows: maculopapular rash 2%, livedoid lesions 1.4%, petechial lesions 1.1%, urticaria 0.8%, pernio-like lesions 0.5%, vesicular lesions 0.3%. Petechial lesions and livedoid lesions contain a higher proportion of severe patients than other skin manifestations. The prevalence rates of pernio-like lesions, urticaria and petechial lesions vary greatly in different regions.

The differential impact of air pollutants on acute urticaria and chronic urticaria: a time series analysis.

Several studies have revealed a relationship between short-term exposure to air pollution and the exacerbation of certain skin conditions. This study was developed to expand on these findings by exploring the potential association between exposure to air pollutants including particulate matter, sulfur dioxide, and ozone and the incidence of acute and chronic urticaria in Shenyang, China, from 2016 to 2018. Exposure-response relationships between daily mean concentrations of these airborne pollutants and visits to outpatient dermatological clinics for acute urticaria and chronic urticaria were evaluated via a time series analysis approach using a generalized additive model. This analysis revealed that a 10 µg/m3 increase in daily mean O3_8h concentrations was associated with a 0.36% (95% CI, 0.31-0.41%), 0.35% (95% CI, 0.30-0.40%), and 0.34% (95% CI, 0.29-0.39%) increase in the number of outpatient visits for acute urticaria on that day (lag0), lagging day 1 (lag1), and lagging day 2 (lag2), respectively. O3 levels also had a similar but weaker effect on the frequency of patients seeking outpatient care for chronic urticaria. These analyses also revealed that estimated 0.47% (95% CI, 0.41-0.52%) and 0.46% (95% CI, 0.40-0.51%) increases in dermatological outpatient acute urticaria visits were observed for every 10µg/m3 rise in O3_8h concentrations on cumulative lagging days (lag01 and lag02). Increases in particulate matter (PM2.5, PM10) levels had a similar cumulative effect on patients with chronic urticaria. In summary, these results suggest that short-term O3, PM2.5, and PM10 exposure can increase the risk of acute urticaria and chronic urticaria.

Idarubicin-loaded biodegradable microspheres enhance sensitivity to anti-PD1 immunotherapy in transcatheter arterial chemoembolization of hepatocellular carcinoma.

Transarterial chemoembolization (TACE) is an image-guided locoregional therapy used for the treatment of patients with primary hepatocellular carcinoma (HCC). However, conventional TACE formulations such as epirubicin-lipiodol emulsion are rapidly dissociated due to the instability of the emulsion, resulting in insufficient local drug concentrations in the target tumor. To overcome these limitations, we used biodegradable Idarubicin loaded microspheres (BILMs), which were prepared from gelatin and carrageenan and could be loaded with Idarubicin (IDA-MS). The morphology and the ability to load and release IDA of BILMs were characterized in vitro. We evaluated tumor changes and side effects after TACE treatment with IDA-MS in VX2 rabbit and C57BL/6 mice HCC models. In addition, the effect of IDA-MS on the tumor immune microenvironment of HCC tumors was elucidated via mass spectrometry and immunohistochemistry. Result showed that IDA-MS was developed as a new TACE formulation to overcome the poor delivery of drugs due to rapid elimination of the anticancer drug into the systemic circulation. We demonstrated in rabbits and mice HCC models that TACE with IDA-MS resulted in significant tumor shrinkage and no more severe adverse events than those observed in the IDA group. TACE with IDA-MS could also significantly enhance the sensitivity of anti-PD1 immunotherapy, improve the expression of CD8+ T cells, and activate the tumor immune microenvironment in HCC. This study provides a new approach for TACE therapy and immunotherapy and illuminates the future of HCC treatment. STATEMENT OF SIGNIFICANCE: Conventional transarterial chemoembolization (TACE) formulations are rapidly dissociated due to the instability of the emulsion, resulting in insufficient local drug concentrations in hepatocellular carcinoma (HCC). To overcome these limitations, we used biodegradable microspheres called BILMs, which could be loaded with Idarubicin (IDA-MS). We demonstrated in rabbits and mice HCC models that TACE with IDA-MS resulted in significant tumor shrinkage and no more severe adverse events than those observed in the IDA group. TACE with IDA-MS could also significantly enhance the sensitivity of anti-PD1 immunotherapy, improve the expression of CD8+ T cells, and activate the tumor immune microenvironment in HCC. This study provides a new approach for TACE therapy and immunotherapy and illuminates the future of HCC treatment.

Randomized, Placebo-Controlled, Multicenter Clinical Study on the Efficacy and Safety of Lidocaine Patches in Chinese Patients with Postherpetic Neuralgia.

INTRODUCTION: To evaluate the efficacy and safety of lidocaine patches in Chinese patients with postherpetic neuralgia (PHN). METHODS: Patients were randomized to receive lidocaine patches or placebo every day for 4 weeks. Efficacy endpoints included the decrease of analogue scale score (VAS) value at week 4, 2 and 1 and the percentage of patients that achieved a 30% decrease of VAS value. Safety analyses were conducted as well. RESULTS: Two hundred forty Chinese patients were randomized. At week 1, lidocaine patch-treated patients had a higher clinical response versus placebo, and at week 4, the mean (SD) decreases of VAS value compared to the baseline were 14.01 (14.35) in the treatment group and 9.36 (12.03) in the placebo group (p = 0.0088). Overall, the safety profile in the treatment group was consistent with that observed in the placebo group [adverse event (AE) incidence rate: 33.33% versus 37.29%, p = 0.5857]. CONCLUSIONS: Lidocaine patches resulted in improved clinical response versus placebo in the treatment of PHN patients and were well tolerated.

High-Resolution Computer Tomography Image Features of Lungs for Patients with Type 2 Diabetes under the Faster-Region Recurrent Convolutional Neural Network Algorithm.

The objective of this study was to adopt the high-resolution computed tomography (HRCT) technology based on the faster-region recurrent convolutional neural network (Faster-RCNN) algorithm to evaluate the lung infection in patients with type 2 diabetes, so as to analyze the application value of imaging features in the assessment of pulmonary disease in type 2 diabetes. In this study, 176 patients with type 2 diabetes were selected as the research objects, and they were divided into different groups based on gender, course of disease, age, glycosylated hemoglobin level (HbA1c), 2 h C peptide (2 h C-P) after meal, fasting C peptide (FC-P), and complications. The research objects were performed with HRCT scan, and the Faster-RCNN algorithm model was built to obtain the imaging features. The relationships between HRCT imaging features and 2 h C-P, FC-P, HbA1c, gender, course of disease, age, and complications were analyzed comprehensively. The results showed that there were no significant differences in HRCT scores between male and female patients, patients of various ages, and patients with different HbA1c contents (P > 0.05). As the course of disease and complications increased, HRCT scores of patients increased obviously (P < 0.05). The HRCT score decreased dramatically with the increase in the contents of 2 h C-P and FC-P after the meal (P < 0.05). In addition, the results of the Spearman rank correlation analysis showed that the course of disease and complications were positively correlated with the HRCT scores, while the 2 h C-P and FC-P levels after meal were negatively correlated with the HRCT scores. The receiver operating curve (ROC) showed that the accuracy, specificity, and sensitivity of HRCT imaging based on Faster-RCNN algorithm were 90.12%, 90.43%, and 83.64%, respectively, in diagnosing lung infection of patients with type 2 diabetes. In summary, the HRCT imaging features based on the Faster-RCNN algorithm can provide effective reference information for the diagnosis and condition assessment of lung infection in patients with type 2 diabetes.

Deep Learning Algorithm-Based MRI Image in the Diagnosis of Diabetic Macular Edema.

This study investigates the value of magnetic resonance imaging (MRI) based on a deep learning algorithm in the diagnosis of diabetic macular edema (DME) patients. A total of 96 patients with DME were randomly divided into the experimental group (N = 48) and the control group (N = 48). A deep learning 3D convolutional neural network (3D-CNN) algorithm for MRI images of patients with DME was designed. The application value of this algorithm was comprehensively evaluated by MRI image segmentation Dice value, sensitivity, specificity, and other indicators and diagnostic accuracy. The results showed that the quality of MRI images processed by the 3D-CNN algorithm based on deep learning was significantly improved, and the Dice value, sensitivity, and specificity index data were significantly better than those of the traditional CNN algorithm (P < 0.05). In addition, the diagnostic accuracy of MRI images processed by this algorithm was 93.78 ± 5.32%, which was significantly better than the diagnostic accuracy of 64.25 ± 10.24% of traditional MRI images in the control group (P < 0.05). In summary, the 3D-CNN algorithm based on deep learning can significantly improve the accuracy and sensitivity of MRI image recognition and segmentation in patients with DME, can significantly improve the diagnostic accuracy of MRI in patients with DME, and has a good clinical application value.