Tumor Microenvironment-Responsive Biodegradable Nanomedicine for Self-Enhanced Synergistic Chemo-, Photothermal, and Chemodynamic Therapy.

The nanoscale multidrug codelivery system for synergistic therapy is an effective strategy for tumor treatment. However, the low drug delivery efficiency and poor therapeutic effects limit its application. Here, based on the coordination effect of Artemisinin (Art), quercetin (Qc), and Fe3+, we had constructed a safe and efficient carrier-free hyaluronic acid (HA)-modified Art-Fe-Qc nanoparticles (AFQ@HA NPs) for enhanced chemotherapy/photothermal therapy (PTT)-chemodynamic therapy (CDT) synergistic therapy, which achieved an ultrahigh drug loading efficiency and a multifunction anticancer strategy. The results showed that high drug loading was achieved based on drug coordination self-assembly, with Art and Qc contents of 38.6 and 42.7%, respectively. At the same time, based on the Qc-Fe coordination molecular network, the system had excellent photothermal conversion performance with an efficiency of 57.3% and could effectively inhibit the expression of HSP70, achieving enhanced PTT. Further, under the stimulation of excessive H2O2 and glutathione (GSH) in the tumor microenvironment, the AFQ@HA NPs were continuously degraded, while releasing Art and Fe3+/Fe2+ to achieve iron ion-enhanced CDT. The results of in vitro and in vivo experiments showed that AFQ@HA NPs could achieve chemotherapy-PTT-CDT synergistic therapy in response to tumor microenvironment by passively targeting and actively targeting tumor cells with CD44, demonstrating its excellent targeted antitumor effects.

Uncovering the mechanisms of diosmin in treating obesity-related kidney injury based on network pharmacology, molecular docking, and in vitro validation.

Obesity increases the risk of kidney injury, involving various pathological events such as inflammation, insulin resistance, lipid metabolism disorders, and hemodynamic changes, making it a significant risk factor for the development and progression of chronic kidney disease. Diosmin, a natural flavonoid glycoside, exhibits anti-inflammatory, antioxidant, anti-lipid, and vasodilatory effects. However, whether diosmin has a protective effect on obesity-related kidney injury remains unclear. The molecular formula of diosmin was obtained, and diosmin and target genes related to obesity-related kidney injury were screened. The interaction between overlapping target genes was analyzed. GO functional enrichment and KEGG pathway enrichment analyses were performed on overlapping target genes. Molecular docking was employed to assess the binding strength between overlapping target genes. Palmitic acid-induced damage to HK-2 cells, which were then treated with diosmin. Subsequently, the expression levels of relevant mRNAs and proteins were measured. Network analysis identified 219 potential diosmin target genes, 6800 potential target genes related to obesity-related kidney injury, and 93 potential overlapping target genes. Protein-protein interaction networks and molecular docking results revealed that AKT1, TNF-α, SRC, EGFR, ESR1, CASP3, MMP9, PPAR-γ, GSK-3ß, and MMP2 were identified as key therapeutic targets, and they exhibited stable binding with diosmin. GO analysis indicated that these key targets may participate in inflammation, chemical stress, and protein phosphorylation. KEGG revealed that pathways in cancer, AGE-RAGE signaling pathway, PI3K-AKT signaling pathway, PPAR signaling pathway, and insulin resistance as crucial in treating obesity-related kidney injury. CCK-8 assay showed that diosmin significantly restored the viability of HK-2 cells affected by palmitic acid. Oil Red O staining demonstrated that diosmin significantly improved lipid deposition in HK-2 cells induced by palmitic acid. PCR results showed that diosmin inhibited the mRNA levels of AKT1, TNF-α, EGFR, ESR1, CASP3, MMP9, GSK-3ß, and MMP2 while promoting the mRNA level of PPAR-γ. Western blot analysis revealed that diosmin restored PPAR-γ protein expression, inhibited NF-kB p-p65 protein expression, and reduced TNF-α protein expression. Diosmin demonstrated multi-target and multi-pathway effects in the treatment of obesity-associated renal injury, with key targets including AKT1, TNF-α, EGFR, ESR1, CASP3, MMP9, PPAR-γ, GSK-3ß, and MMP2. The mechanism may be through the modulation of the PPAR-γ/NF-κB signaling pathway, which can attenuate inflammatory responses and protect the kidney.

A pooled mycoviral resource in a strain of Rhizoctonia solani are regulators of fungal virulence.

Rhizoctonia solani is a widespread and devastating soil-borne plant fungal pathogen that causes diseases, including rice sheath blight, which are difficult to control. Some mycoviruses are potential biocontrol agents for the control of fungal diseases. In order to investigate the factors that influence the virulence of R. solani and search for mycoviruses with the potential for biocontrol of R. solani, a rice-infecting R. solani strain, ZJXD1-1, was isolated and confirmed to contain eight mycoviruses via dsRNA extraction and high-throughput sequencing. The identified mycoviruses belong to families of Endornaviridae (RsEV11 and RsEV12) and Mitoviridae (RsMV125 to RsMV129), and an unclassified Toti-like clade (RsTLV1). The C39 domain in RsEV12, which shares a close evolutionary relationship with bacteria, is observed for the first time in a mycovirus. Strains with different virus combinations were obtained through viral horizontal transfer, and pathogenicity test deduced that the Endornaviruses RsEV11 and RsEV12, and Mitovirus RsMV129 might potentially enhance the pathogenicity of R. solani, while RsMV125 might reduce the virulence or interfere with the function of other Mitoviruses. Furthermore, virus curing via protoplast regeneration and viral horizontal transfer demonstrated that RsMV129 is the causal agent of R. solani hypervirulence. Overall, our study provided the resource pool of viruses that may contribute to the discovery of new biocontrol agents against R. solani and enhance our understanding of the pathogenesis of R. solani regulated by mycoviruses.

The therapeutic potential of gelsolin in attenuating cytokine storm, ARDS, and ALI in severe COVID-19.

Severe COVID-19 cases often progress to life-threatening conditions such as acute respiratory distress syndrome (ARDS), sepsis, and multiple organ dysfunction syndrome (MODS). Gelsolin (GSN), an actin-binding protein with anti-inflammatory and immunomodulatory properties, is a promising therapeutic target for severe COVID-19. Plasma GSN levels are significantly decreased in critical illnesses, including COVID-19, correlating with dysregulated immune responses and poor outcomes. GSN supplementation may mitigate acute lung injury, ARDS, and sepsis, which share pathophysiological features with severe COVID-19, by scavenging actin, modulating cytokine production, enhancing macrophage phagocytosis, and stabilizing the alveolar-capillary barrier. Preliminary data indicate that recombinant human plasma GSN improves oxygenation and lung function in severe COVID-19 patients with ARDS. Although further research is needed to optimize GSN therapy, current evidence supports its potential to mitigate severe consequences of COVID-19 and improve patient outcomes. This review provides a comprehensive analysis of the biological characteristics, mechanisms, and therapeutic value of GSN in severe COVID-19.

[Simultaneous determination of 10 quaternary ammonium salt bactericides in oral care products by high performance liquid chromatography-evaporative light-scattering detection].

Quaternary ammonium salt bactericides are broad-spectrum bactericides often used in oral care products because of their high antibacterial efficacy, strong penetration, and low toxicity. However, the excessive use of quaternary ammonium salt bactericides may cause contact dermatitis, scalding poisoning, and even death. Existing methods to determine quaternary ammonium salt bactericides are unable to meet current requirements owing to the lack of determination components. Therefore, establishing a simple and accurate method for the simultaneous detection of more quaternary ammonium salt bactericides is necessary. In this study, a method that couples sample pretreatment with high performance liquid chromatography-evaporative light-scattering detection (HPLC-ELSD) was developed for the simultaneous determination of quaternary ammonium salt bactericides in oral care products, including dodecyltrimethylammonium chloride, dodecyldimethylbenzylammonium chloride, benzethonium chloride, tetradecyl trimethyl ammonium chloride, tetradecyldimethylbenzylammonium chloride, N-hexadecyltrimethylammonium chloride, benzyldimethylhexadecylammonium chloride, trimethylstearylammonium chloride, stearyldimethylbenzylammonium chloride, and docosyltrimethylammonium chloride. Some of these bactericides do not absorb ultraviolet light, so a universal evaporative light-scattering detector was used owing to testing cost and stability concerns. The paste samples contained thickening agents, which are highly soluble in water but insoluble in organic solvents; these agents can seriously affect the results of sample pretreatment and damage the chromatographic column. Hence, sample dehydration was necessary. In this study, four dehydration methods were compared. Anhydrous sodium sulfate (Na2SO4) was selected, and the amount of Na2SO4 was optimized. Based on the solubility of the 10 target compounds and extraction efficiency, three extraction solvents were compared, and ethanol was selected. Ultrasonic extraction was the primary extraction process used in this study. The effects of different ultrasonication times, temperatures, and powers on the extraction recoveries were also investigated. Ultimately, the optimized conditions were as follows: extraction of the dehydrated paste and powder samples using ethanol at room temperature (25 ℃) for 20 min under 100 W ultrasound power, and dilution of the liquid sample with ethanol. After extraction, the samples were separated on an Acclaim Surfactant column (150 mm×4.6 mm, 5 µm) with 50 mmol/L ammonium acetate aqueous solution (pH=5.5) (A) and acetonitrile (B) as mobile phases. The gradient elution program were as follows: 0-5.0 min, 75%A-35%A, 5.0-15.0 min, 35%A-20%A, 15.0-20.0 min, 20%A, 20.0-21.0 min, 20%A-75%A, 21.0-25.0 min, 75%A. An external standard method was used for quantitative determination. The 10 compounds were analyzed within 25 min. Linear equations, correlation coefficients, and linear ranges were obtained by analyzing a series of mixed standard working solutions. The limits of detection (LODs, S/N=3) and quantification (LOQs, S/N=10) of the 10 components were determined. Stearyldimethylbenzylammonium chloride and docosyltrimethylammonium chloride showed good linear relationships in the range of 10-200 mg/L, while the other compounds demonstrated good linear relationships in the range of 5-100 mg/L. In all cases, correlation coefficients (R2) of no less than 0.9992 were obtained. The LODs and LOQs were in the range of 1.42-3.31 mg/L and 4.25-9.94 mg/L, respectively. Ten analytes were spiked in blank matrices, such as toothpaste (paste), mouthwash (liquid), and dentifrice powder (powder) at three levels, and the recoveries and precisions were calculated. The average recoveries were 87.9%-103.1%, and the corresponding relative standard deviations (RSDs) did not exceed 5.5% (n=6). The developed method was used to detect 109 oral care products. Benzyldimethylhexadecylammonium chloride and stearyldimethylbenzylammonium chloride revealed high detection rates. Moreover, the amount of stearyldimethylbenzylammonium chloride in one toothpaste sample exceeded regulatory requirements. Given its advantages of good precision and accuracy, the developed method is suitable for the quantitative analysis of the 10 aforementioned compounds in typical oral care products. The study findings can serve as a reference for the quality and safety monitoring of oral care products.

Subanesthetic Dose of Esketamine Improves the Sedative and Analgesic Effects of Dexmedetomidine and Remifentanil in Liposuction Anesthesia: A Prospective, Double-Blinded, Randomized Controlled Trial.

Purpose: Esketamine have anesthetic and analgesic properties. This study aimed to observe the enhancing effect of subanesthetic doses of esketamine (0.15-0.3 mg/kg/h) with dexmedetomidine and remifentanil during anesthesia for liposuction surgery. Patients and Methods: A total of 155 subjects were randomized with a 1:1 ratio to Group E (esketamine-dexmedetomidine/remifentanil, n=78) or Group C (saline-dexmedetomidine/remifentanil group, n=77). The primary outcome was satisfaction of patient and surgical team with the procedure. The secondary outcomes were the postoperative Athens Insomnia Scale (AIS) and Hospital Anxiety and Depression Scale (HADS) scores, hemodynamic and respiratory changes, drug consumption, adverse event rates, and predictors associated with patient satisfaction. Results: Patient and surgical team satisfaction with the procedure was significantly higher in Group E than in Group C (4.7 ± 0.6 vs 4.2 ± 0.7, P < 0.001; 4.7 ± 0.5 vs 4.4 ± 0.7, P = 0.005). The postoperative AIS (4 [1, 6] vs 5 [2, 9], P = 0.012) and HADS-A (1 [0, 3] vs 2 [0, 6], P = 0.012) scores were significantly lower in Group E than in Group C. Hemodynamic and respiratory parameters were more stable in Group E than in Group C, with the lower opioids consumption of sufentanil (0 [0, 4] vs 5 [2.5, 7.7], P < 0.001) and remifentanil (700 [480, 900] vs 800 [500, 1200], P = 0.023) in Group E compared to Group C. On ordinal logistics regression, postoperative sleep quality (OR, 0.70; 95% CI, 0.62-0.79), anxiety level (OR, 0.77; 95% CI, 0.62-0.95) and recovery time in post-anesthesia care unit (PACU) (OR, 0.69; 95% CI, 0.56-0.98) were identified as significant predictors associated with patient satisfaction. Conclusion: A subanesthetic dose of esketamine (0.15-0.3 mg/kg/h) as an adjuvant can improves the sedative and analgesic effects of dexmedetomidine and remifentanil during anesthesia for liposuction surgery. Clinical Trial Registration: ChiCTR2400080363.

Predictive value of intracranial high-density areas in neurological function.

BACKGROUND: Intracranial high-density areas (HDAs) have attracted considerable attention for predicting clinical outcomes; however, whether HDAs predict worse neurological function and mental health remains controversial and unclear, which requires further investigation. AIM: To investigate the predictive value of intracranial HDAs for neurological function and mental health after endovascular treatment. METHODS: In this prospective study, 96 patients with acute ischemic stroke (AIS) who accepted endovascular mechanical thrombectomy (EMT) were included. The enrolled patients underwent cranial computed tomography (CT) examination within 24 hours after EMT. Clinical data in terms of National Institutes of Health Stroke Scale (NIHSS), the 3-month modified Rankin Scale (mRS), self-rating depression scale (SDS), and self-rating anxiety scale (SAS) scores were collected and compared between patients with HDAs and non-HDAs and between patients with good and poor clinical prognosis. RESULTS: Compared to patients without HDAs, patients with HDAs presented severe neurological deficits (admission NIHSS score: 18 ± 3 vs 19 ± 4), were more likely to have post-stroke disabilities (mRS < 3: 35% vs 62%), and suffered more severe depression (SDS score: 58 ± 16 vs 64 ± 13) and anxiety disorder (SAS score: 52 ± 8 vs 59 ± 10). Compared to patients with a good prognosis, patients with a poor prognosis presented severe neurological deficits (admission NIHSS score: 17 ± 4 vs 20 ± 3), were more likely to have HDAs on CT images (64% vs 33%), and suffered more severe depression (SDS score: 55 ± 19 vs 65 ± 11) and anxiety (SAS score: 50 ± 8 vs 58 ± 12). Multivariate analysis revealed that HDAs were independent negative prognostic factors. CONCLUSION: In conclusion, HDAs on CT images predicted poor prognosis and severe depressive and anxiety symptoms in patients with AIS who underwent EMT.

Sex difference in alcohol consumption associated with colorectal cancer risk in Quzhou, China: A nested case-control study.

Objective: Colorectal cancer (CRC) incidence has been increasing worldwide over time. This study investigated whether drinking was associated with CRC risk. Methods: We designed a case-control study nested in a mass CRC screening program in Quzhou, China. Cases were newly diagnosed CRC in 2020-2022. Controls were randomly sampled using frequency match. Drinking variables included drinking status, frequency, duration, and others. Logistic regressions were used to estimate odds ratio (OR) and 95 % confidence interval (CI). Results: The crude OR (cOR) (95 % CI) of drinking between 153 cases and 650 controls was 1.46 (0.99, 2.16) in current drinkers, 3.31 (1.44, 7.60) in former drinkers, 1.82 (1.21, 2.74) in drinking 6-7 days/week, and 3.48 (1.29, 9.37) in drinking 1-19 years. Stratifying by sex, all drinking variables in women but not all in men were consistently associated with CRC risk. The adjusted OR (aOR) (95 % CI) was 1.01 (0.59, 1.74) in current drinking men, 2.27 (0.78, 6.64) in former drinking men, and 4.24 (1.61, 11.13) in current drinking women. The aOR (95 % CI) of drinking whisky was 0.19 (0.04, 0.83), 1.89 (0.86, 4.17), 2.25 (1.05, 4.83), and 1.82 (0.85, 3.92) in men drinking ≤0.5, >0.5-≤1.0, >1.0-≤1.5, and >1.5 Liter/week (P trend = 0.011), and 3.80 (1.03, 14.00) and 9.92 (2.01, 49.00) in women drinking ≤0.5 and >0.5 Liter/week (P trend = 0.001), respectively. Conclusions: There was sex difference in drinking associated with increased risk of CRC which association was stronger in women than that in men. Men's association between drinking whisky and CRC risk was J-shaped.

[The Effecacy and Safety of Daratumumab Based Regimens in Relapsed/Refractory Multiple Myeloma: A Single-Center Real-World Data Analysis].

OBJECTIVE: To investigate the efficacy and safety of daratumumab based regimens in relapse and/or refractory multiple myeloma (RRMM) in the real world, as well as the impact of daratumumab on stem cell collection and engraftment. METHODS: The clinical data of patients with RRMM who received daratumumab in hematology department of the First Affiliated Hospital of Xiamen University from February 2019 to March 2023 and had evaluable efficacy were retrospective analysis. RESULTS: All 43 RRMM patients were treated with daratumumab-based combination regimens, including Dd, DVd, DRd, Dkd, DId, and Dara-DECP. With median follow-up time 10.1 (2.1-36.6) months, the best overall response rate (ORR) was 74.4% and a best complete response rate (CR) was 25.6%. 1-year overall survival rate (OS) was 84.5%. The most common severe hematologic adverse events (Grade>3) are 3/4 grade leukopenia（18.6%）, and the most common severe non-hematologic adverse events were infusion-related reactions (IRRs， 20.9%) and infections（7.0%）. Multivariate prognostic analysis showed that extramedullary infiltration was an independent adverse prognostic factor affecting OS （P =0.004）. The use of daratumumab has no effect on stem cell collection, or engraftment. CONCLUSION: Daratumumab is safe and effective in RRMM.

Analysis of the efficacy of hyperbaric oxygen therapy for disorders of consciousness: A retrospective cohort study.

OBJECTIVE: To analyze the efficacy and associated factors affecting the prognosis in patients with disturbance of consciousness after hyperbaric oxygen (HBO) treatment. METHODS: A retrospective study was carried out on patients with disorders of consciousness (DOC) receiving HBO treatment from January to January 2022 in the Second Department of Rehabilitation Medicine of the Second Hospital of Hebei Medical University, China. RESULTS: HBO therapy improved the Glasgow Coma Scale (GCS) and Chinese Nanjing Persistent Vegetative State Scale (CNPVSS), as well as the clinical efficacy in patients with DOC. The comparison of GCS and CNPVSS scores in patients with DOC before and after HBO treatment was all statistically significant, with 325 patients (67.1%) showing effective results and 159 patients (32.9%) having unchanged outcomes. Univariate analysis indicated that there were statistically significant differences in age, HBO intervention time, HBO treatment times, pre-treatment GCS score, and etiology and underlying diseases between the good and poor prognoses groups. Multivariate regression analysis showed that HBO intervention time ≤7 days, HBO treatment ＞ times, high GCS score before HBO treatment, and brain trauma were independent influencing factors in achieving a good prognosis for patients with DOC. Low pre-treatment GCS scores were an independent risk factor for a poor prognosis in patients with brain trauma while being male, late HBO intervention time, fewer HBO treatment times, and low pre-treatment GCS scores were independent risk factors for a poor prognosis in patients with DOC after a stroke. Being ≥50 years of age, late HBO intervention time, and low pre-treatment GCS scores were independent risk factors for a poor prognosis in patients with DOC after hypoxic-ischaemic encephalopathy. CONCLUSION: HBO therapy can improve the GCS, CNPVSS scores and clinical efficacy in patients with DOC, and the timing of HBO intervention ≤7 days, times of HBO treatment, high pre-treatment GCS score, and brain trauma were the independent influencing factors of good prognosis in patients with DOC.

Establishment of stellate ganglion block in mice.

BACKGROUND: There have been no reports on the successful implementation of stellate ganglion block (SGB) in mice. OBJECTIVES: This study aims to investigate a new method for implementing SGB in mice by placing them in a supine position with abducted upper limbs and touching the trachea and sternoclavicular joint with the hand. METHODS: Fifty BABL/C mice, 8-10 weeks, were selected and randomly divided into four groups: control group (n = 5); SGB-R group (n = 15); SGB-L group (n = 15); and SGB-L + R (group n = 15). SGB was administered with 0.15% ropivacaine solution in a volume of 0.1 mL. The control group received equal volumes of saline. Horner's syndrome, heart rate, and complications such as brachial plexus block, vascular injury, pneumothorax, local anesthetic toxicity, and death were observed. RESULTS: Horner's syndrome developed in 100% of SGB surviving mice; no difference was seen in the time to onset (100.4 ± 13.4 vs 96.7 ± 12.4, mean ± SD, seconds) and duration (264.1 ± 40.5 vs 296.3 ± 48.0, mean ± SD, min) of Horner's syndrome in the left and right SGB (P > 0.05). Compared with the control group (722 [708-726], median [IQR], bpm), the heart rate was significantly slowed down in the right SGB (475 [451.5-491], median [IQR], bpm) (P < 0.05). While the heart rate was slowed down after performing the left SGB, the difference was not statistically significant (P > 0.05). The overall complication rate was 18.4%, with a brachial plexus block rate of 12.3%, a vascular injury rate of 4.6%, and a mortality rate of 1.5%, as well as no local anesthetic toxicity (includes bilateral implementation of SGB) or pneumothorax manifestations were found. CONCLUSIONS: This method allows for the successful implementation of SGB in a mouse model.

Gender associations between phthalate exposure and biomarkers of oxidative stress: A prospective cohort study.

Previous epidemiologic research has shown that phthalate exposure in pregnant women is related to adverse birth outcomes in a sex-specific manner. However, the biological mechanism of phthalate exposure that causes these birth outcomes remains poorly defined. In this research, we investigated the association between phthalate exposure and placental oxidative stress in a large population-based cohort study, aiming to initially explore the relationship between phthalate exposure and gene expression in placental oxidative stress in a sex-specific manner. Quantitative PCR was performed to measure the expression of placental inflammatory mRNAs (HO-1, HIF1α, and GRP78) in 2469 placentae. The multiple linear regression models were used to investigate the associations between mRNA and urinary phthalate monoesters. Phthalate metabolites monomethyl phthalate (MMP) and mono-n-butyl phthalate (MBP) were positively correlated with higher HIF1α expression in placentae of male fetuses (p < .05). Mono-benzyl phthalate (MBzP) increased the expression of HO-1, HIF1α, and GRP78 in placentae of male fetuses, and mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) up-regulated the expression of HIF1α and GRP78. Additionally, mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) was negatively correlated with HO-1, HIF1α, and GRP78 in placentae of female fetuses. Maternal phthalate exposure was associated with oxidative stress variations in placental tissues. The associations were closer in the placentas of male fetuses than in that of female ones. The placenta oxidative stress is worth further investigation as a potential mediator of maternal exposure-induced disease risk in children.

Impact of simulation-based training on bougie-assisted cricothyrotomy technique: a quasi-experimental study.

BACKGROUND: Cricothyrotomy is a lifesaving surgical technique in critical airway events. However, a large proportion of anesthesiologists have little experience with cricothyrotomy due to its low incidence. This study aimed to develop a multisensory, readily available training curriculum for learning cricothyrotomy and evaluate its training effectiveness. METHODS: Seventy board-certificated anesthesiologists were recruited into the study. Participants first viewed an instructional video and observed an expert performing the bougie-assisted cricothyrotomy on a self-made simulator. They were tested before and after a one-hour practice on their cricothyrotomy skills and evaluated by a checklist and a global rating scale (GRS). Additionally, a questionnaire survey regarding participants' confidence in performing cricothyrotomy was conducted during the training session. RESULTS: The duration to complete cricothyrotomy was decreased from the pretest (median = 85.0 s, IQR = 72.5-103.0 s) to the posttest (median = 59.0 s, IQR = 49.0-69.0 s). Furthermore, the median checklist score was increased significantly from the pretest (median = 30.0, IQR = 27.0-33.5) to the posttest (median = 37.0, IQR = 35.5-39.0), as well as the GRS score (pretest median = 22.5, IQR = 18.0-25.0, posttest median = 32.0, IQR = 31.0-33.5). Participants' confidence levels in performing cricothyrotomy also improved after the curriculum. CONCLUSION: The simulation-based training with a self-made simulator is effective for teaching anesthesiologists to perform cricothyrotomy.

Effect and Safety of Herbal Medicine Foot Baths in Patients with Diabetic Peripheral Neuropathy: A Multicenter Double-Blind Randomized Controlled Trial.

OBJECTIVE: To evaluate the effect and safety of foot baths with Tangbi Waixi Decoction (TW) in treating patients with diabetic peripheral neuropathy (DPN). METHODS: It is a multicenter double-blinded randomized controlled trial. Participants with DPN were recruited between November 18, 2016 and May 30, 2018 from 8 hospitals in China. All patients received basic treatments for glycemic management. Patients received foot baths with TW herbal granules either 66.9 g (intervention group) or 6.69 g (control group) for 30 min once a day for 2 weeks and followed by a 2-week rest, as a therapeutic course. If the Toronto Clinical Scoring System total score (TCSS-TS) ⩾6 points, the patients received a total of 3 therapeutic courses (for 12 weeks) and were followed up for 12 weeks. The primary outcome was change in TCSS-TS score at 12 and 24 weeks. Secondary outcomes included changes in bilateral motor nerve conduction velocity (MNCV) and sensory nerve conduction velocity (SNCV) of the median and common peroneal nerve. Safety was also assessed. RESULTS: Totally 632 patients were enrolled, and 317 and 315 were randomized to the intervention and control groups, respectively. After the 12-week intervention, patients in both groups showed significant declines in TCSSTS scores, and significant increases in MNCV and SNCV of the median and common peroneal nerves compared with pre-treatment (P<0.05). The reduction of TCSS-TS score at 12 weeks and the increase of SNCV of median nerve at 24 weeks in the control group were greater than those in the intervention group (P<0.05). The number of adverse events did not differ significantly between groups (P>0.05), and no serious adverse event was related with treatment. CONCLUSION: Treatment of TW foot baths was safe and significantly benefitted patients with DPN. A low dose of TW appeared to be more effective than a high dose. (Registry No. ChiCTR-IOR-16009331).

Reconfigurable Microlens Array Enables Tunable Imaging Based on Shape Memory Polymers.

Microlens arrays (MLAs) with a tunable imaging ability are core components of advanced micro-optical systems. Nevertheless, tunable MLAs generally suffer from high power consumption, an undeformable rigid body, large and complex systems, or limited focal length tunability. The combination of reconfigurable smart materials with MLAs may lead to distinct advantages including programmable deformation, remote manipulation, and multimodal tunability. However, unlike photopolymers that permit flexible structuring, the fabrication of tunable MLAs and compound eyes (CEs) based on transparent smart materials is still rare. In this work, we report reconfigurable MLAs that enable tunable imaging based on shape memory polymers (SMPs). The smart MLAs with closely packed 200 × 200 microlenses (40.0 µm in size) are fabricated via a combined technology that involves wet etching-assisted femtosecond laser direct writing of MLA templates on quartz, soft lithography for MLA duplication using SMPs, and the mechanical heat setting for programmable reconfiguration. By stretching or squeezing the shape memory MLAs at the transition temperature (80 °C), the size, profiles, and spatial distributions of the microlenses can be programmed. When the MLA is stretched from 0 to 120% (area ratio), the focal length is increased from 116 to 283 µm. As a proof of concept, reconfigurable MLAs and a 3D CE with a tunable field of view (FOV, 160-0°) have been demonstrated in which the thermally triggered shape memory deformation has been employed for tunable imaging. The reconfigurable MLAs and CEs with a tunable focal length and adjustable FOV may hold great promise for developing smart micro-optical systems.

Diosmin ameliorates renal fibrosis through inhibition of inflammation by regulating SIRT3-mediated NF-κB p65 nuclear translocation.

BACKGROUND: Renal fibrosis is considered an irreversible pathological process and the ultimate common pathway for the development of all types of chronic kidney diseases and renal failure. Diosmin is a natural flavonoid glycoside that has antioxidant, anti-inflammatory, and antifibrotic activities. However, whether Diosmin protects kidneys by inhibiting renal fibrosis is unknown. We aimed to investigate the role of Diosmin in renal interstitial fibrosis and to explore the underlying mechanisms. METHODS: The UUO mouse model was established and gavaged with Diosmin (50 mg/kg·d and 100 mg/kg·d) for 14 days. HE staining, Masson staining, immunohistochemistry, western blotting and PCR were used to assess renal tissue injury and fibrosis. Elisa kits were used to detect the expression levels of IL-1ß, IL-6, and TNF-α and the activity of SIRT3 in renal tissues. In addition, enrichment maps of RNA sequencing analyzed changes in signaling pathways. In vitro, human renal tubular epithelial cells (HK-2) were stimulated with TGF-ß1 and then treated with diosmin (75 µM). The protein and mRNA expression levels of SIRT3 were detected in the cells. In addition, 3-TYP (selective inhibitor of SIRT3) and SIRT3 small interfering RNA (siRNA) were used to reduce SIRT3 levels in HK-2. RESULTS: Diosmin attenuated UUO-induced renal fibrosis and TGF-ß1-induced HK-2 fibrosis. In addition, Diosmin reduced IL-1ß, IL-6, and TNF-α levels in kidney tissues and supernatants of HK-2 medium. Interestingly, Diosmin administration increased the enzymatic activity of SIRT3 in UUO kidneys. In addition, Diosmin significantly increased mRNA and protein expression of SIRT3 in vitro and in vivo. Inhibition of SIRT3 expression using 3-TYP or SIRT3 siRNA abolished the anti-inflammatory effects of diosmin in HK-2 cells. Enrichment map analysis by RNA sequencing indicates that the nuclear factor-kappa B (NF-κB) signaling pathway was inhibited in the Diosmin intervention group. Furthermore, we found that TGF-ß1 increased the nuclear expression of nuclear NF-κB p65 but had little significant effect on the total intracellular expression of NF-κB p65. Additionally, Diosmin reduced TGF-ß1-caused NF-κB p65 nuclear translocation. Knockdown of SIRT3 expression by SIRT3 siRNA increased the nuclear expression of NF-κB p65 and abolished the inhibition effect of Diosmin in NF-κB p65 expression. CONCLUSIONS: Diosmin reduces renal inflammation and fibrosis, which is contributed by inhibiting nuclear translocation of NF-κB P65 through activating SIRT3.

ERRα regulates synaptic transmission through reactive oxygen species in hippocampal neurons.

Reactive oxygen species (ROS) play multiple roles in synaptic transmission, and estrogen-related receptor α (ERRα) is involved in regulating ROS production. The purpose of our study was to explore the underlying effect of ERRα on ROS production, neurite formation and synaptic transmission. Our results revealed that knocking down ERRα expression affected the formation of neuronal neurites and dendritic spines, which are the basic structures of synaptic transmission and play important roles in learning, memory and neuronal plasticity; moreover, the amplitude and frequency of miniature excitatory postsynaptic currents (mEPSCs) and miniature inhibitory postsynaptic currents (mIPSCs) were decreased. These abnormalities were reversed by overexpression of human ERRα. Additionally, we also found that knocking down ERRα expression increased intracellular ROS levels in neurons. ROS inhibitor PBN rescued the changes in neurite formation and synaptic transmission induced by ERRα knockdown. These results indicate a new possible cellular mechanism by which ERRα affects intracellular ROS levels, which in turn regulate neurite and dendritic spine formation and synaptic transmission.

Third ventricular width by transcranial sonography is associated with cognitive impairment in Parkinson's disease.

BACKGROUND: One-fourth of Parkinson's disease (PD) patients suffer from cognitive impairment. However, few neuroimaging markers have been identified regarding cognitive impairment in PD. OBJECTIVE: This study aimed to explore the association between third ventricular width by transcranial sonography (TCS) and cognitive decline in PD. METHOD: Participants with PD were recruited from one medical center in China. Third ventricular width was assessed by TCS, and cognitive function was analyzed by the Mini-Mental State Examination (MMSE). Receiver operating characteristic (ROC) analysis and Cox model analysis were utilized to determine the diagnostic and predictive accuracy of third ventricular width by TCS for cognitive decline in PD patients. RESULT: A total of 174 PD patients were recruited. Third ventricular width was negatively correlated with MMSE scores. ROC analysis suggested that the optimal cutoff point for third ventricular width in screening for cognitive impairment in PD was 4.75 mm (sensitivity 62.7%; specificity 75.6%). After 21.5 (18.0, 26.0) months of follow-up in PD patients without cognitive impairment, it was found that those with a third ventricular width greater than 4.75 mm exhibited a 7.975 times higher risk of developing cognitive impairment [hazard ratio = 7.975, 95% CI 1.609, 39.532, p = 0.011] compared with patients with a third ventricular width less than 4.75 mm. CONCLUSION: Third ventricular width based on TCS emerged as an independent predictor of developing cognitive impairment in PD patients.

Structure-activity relationships of bensulfuron methyl and its derivatives as novel agents against drug-resistant Candida auris.

With the emergence of the human pathogen Candida auris as a threat to human health, there is a strong demand to identify effective medicines to prevent the harm caused by such drug-tolerant human fungi. Herein, a series of 33 new derivatives of bensulfuron methyl (BSM) were synthesized and characterized by 1 H NMR, 13 C NMR, and HRMS. Among the target compounds, 8a possessed the best Ki value of 1.015 µM against C. auris acetohydroxyacid synthase (CauAHAS) and an MIC value of 6.25 µM against CBS10913, a clinically isolated strain of C. auris. Taken together the structures of BSM and the synthesized compounds, it was found that methoxy groups at both meta-position of pyrimidine ring are likely to provide desirable antifungal activities. Quantum calculations and molecular dockings were performed to understand the structure-activity relationships. The present study has hence provided some interesting clues for the discovery of novel antibiotics with this distinct mode of action.