Dezocine as preemptive analgesia alleviates ultrapulse CO2 fractional laser treatment induced pain in patients with acne scars.

BACKGROUND: Ultrapluse CO2 fractional laser technology has emerged as an effective treatment for scar management. However, one drawback of this modality is the pain caused during the procedure. This study aims to explore the efficacy and safety of dezocine (DZC) as preemptive analgesia for reduction of pain induced by ultrapulse CO2 fractional laser treatment for acne scars. METHODS: The study cohort included 78 outpatients with acne scars between February and April 2023. Patients were randomly assigned into three groups with intravenous injection (iv) of DZC prior to laser treatment: (1) control, iv of saline; (2) DZC group 1 (DZC_1), iv of DZC at 0.15 mg/kg; and (3) DZC_2, iv of DZC at 0.20 mg/kg. After 30 min, one session of ultrapulse CO2 fractional laser treatment on acne scars was performed. Hemodynamics, visual analogue scale (VAS), and anxiety visual analog test (AVAT) were monitored prior to, during, and after the procedure. RESULTS: Operative success rates for patients in the control, DZC_1, and DZC_2 groups were 34.6%, 84.6%, and 100%, respectively. DZC administered with either dosage significantly reduced the VAS and AVAT scores of patients in treatment groups as compared with the subjects in the control group during the course of ultrapulse CO2 fractional laser treatment. Patients in DZC_1 and DZC_2 groups did not show any significant difference in hemodynamic parameters, VAS, and AVAT scores. Temporary adverse effects such as nausea and dizziness were observed in some subjects after treatment; the symptoms were quickly dissolved after a rest in supine position. CONCLUSIONS: DZC as preemptive analgesia could effectively reduce pain and anxiety induced by ultrapulse CO2 fractional laser treatment in patients. This study provided an option of preemptive anesthesia to minimize the pain and discomforts associated with laser treatments in clinical practices.

Intraneuronal ß-amyloid impaired mitochondrial proteostasis through the impact on LONP1.

Mitochondrial dysfunction plays a critical role in the pathogenesis of Alzheimer's disease (AD). Mitochondrial proteostasis regulated by chaperones and proteases in each compartment of mitochondria is critical for mitochondrial function, and it is suspected that mitochondrial proteostasis deficits may be involved in mitochondrial dysfunction in AD. In this study, we identified LONP1, an ATP-dependent protease in the matrix, as a top Aß42 interacting mitochondrial protein through an unbiased screening and found significantly decreased LONP1 expression and extensive mitochondrial proteostasis deficits in AD experimental models both in vitro and in vivo, as well as in the brain of AD patients. Impaired METTL3-m6A signaling contributed at least in part to Aß42-induced LONP1 reduction. Moreover, Aß42 interaction with LONP1 impaired the assembly and protease activity of LONP1 both in vitro and in vivo. Importantly, LONP1 knockdown caused mitochondrial proteostasis deficits and dysfunction in neurons, while restored expression of LONP1 in neurons expressing intracellular Aß and in the brain of CRND8 APP transgenic mice rescued Aß-induced mitochondrial deficits and cognitive deficits. These results demonstrated a critical role of LONP1 in disturbed mitochondrial proteostasis and mitochondrial dysfunction in AD and revealed a mechanism underlying intracellular Aß42-induced mitochondrial toxicity through its impact on LONP1 and mitochondrial proteostasis.

Association of serum 25-hydroxy vitamin D with gait speed and handgrip strength in patients on hemodialysis.

BACKGROUND: Muscle dysfunction is prevalent in dialysis patients. Gait speed and handgrip strength are simple and reliable methods of assessing muscle function. Numerous observational studies have linked 25-hydroxy vitamin D[25(OH)D] status with gait speed and handgrip strength in populations without kidney diseases. This study aimed to evaluate the potential associations of 25(OH)D status with gait speed and handgrip strength in patients on hemodialysis. METHODS: In this observational cross-sectional study, demographic data, biological data, and dialysis parameters were collected. Gait speed and handgrip strength were measured. Multiple linear regression and logistic regression analysis were used to investigate the relationship of 25(OH)D status with gait speed and handgrip strength after adjusting for potential confounders. RESULTS: Overall, a total of 118 participants undergoing hemodialysis were included. Seventy-one (60.2%) participants were male. The median 25(OH)D status in participants was 11.58 (interquartile range: 8.51 to 15.41) ng/ml. When controlling for age, gender, dialysis vintage, and other confounders with a p-value < 0.15 in univariate analyses, 25(OH)D was significantly positively associated with gait speed (ß = 0.16, 95% CI 0.05 to 0.28, p = 0.006) and handgrip strength (ß = 3.83, 95% CI 1.09 to 6.56, p = 0.007). CONCLUSION: Our study showed that 25(OH)D status seemed to be associated with gait speed and handgrip strength in patients on hemodialysis. However, these results were not robust. The relationships between 25(OH)D status and gait speed and handgrip should be further explored.

CircAGFG1 promotes cervical cancer progression via miR-370-3p/RAF1 signaling.

BACKGROUND: In past decades, circular RNAs (circRNAs) have achieved increasing attention because of its regulatory role in different kinds of cancers. However, how circAGFG1 regulates cervical cancer (CC) is still largely undiscovered. This study aims to evaluate the role of a novel circRNAs and related molecular mechanism in CC cells. METHODS: High or low level of circAGFG1 was detected in CC cells or normal cell line with qRT-PCR. The proliferative and migratory abilities of CC cells were assessed with loss-of function assays. The downstream miRNA and mRNA of circAGFG1 were searched out and proved by using bioinformatics analysis and mechanism experiments. Recue assays were designed to confirm the role of circAGFG1/miR-370-3p/RAF1 axis in CC cell activities. RESULTS: The levels of circAGFG1 was abundant in CC cells in comparison with normal cervical cell End1/E6E7. The inhibitory effect of decreased circAGFG1 level on the proliferative and migratory abilities of CC cells was assessed. CircAGFG1 and miR-370-3p were localized in the cytoplasm and they can interact with each other. Moreover, miR-370-3p was downregulated in CC cells. We also determined the negative effect of miR-370-3p on RAF1. CircAGFG1 could promote RAF1 expression by absorbing miR-370-3p, thereby activating RAF/MEK/ERK pathway. circAGFG1 promoted proliferation and migration of CC cells via enhancing the activity of RAF/MEK/ERK pathway by sponging miR-370-3p and further regulating RAF1. CONCLUSION: The results of this study provided new evidence that circAGFG1 acted as a vital regulator in cervical cancer proliferation and migration, giving great promise to apply it as a potential biomarker for diagnosis and therapy in CC treatment.

Z-Scheme Photocatalyst Constructed by Natural Attapulgite and Upconversion Rare Earth Materials for Desulfurization.

The Er3+:CeO2/ATP (attapulgite) nanocomposites were prepared by a facile precipitation method. The samples were characterized by various measurements. XRD and TEM showed that Er3+:CeO2 nanoparticles were well-crystallized and loaded on the surface of ATP. The visible light was converted into ultraviolet light by Er3+:CeO2 as evidenced by upconversion photoluminance (PL) analysis. The mass ratio of Er3+:CeO2 to ATP on the desulfurization efficiency was investigated. Results showed that the desulfurization rate reached 87% under 4 h visible light irradiation when the mass ratio was 4:10. The mechanism was put forward as follows. Er3+:CeO2 and ATP formed Z-scheme heterostructure intermediated by oxygen vacancy, leading to the enhanced separation of photogenerated charges and preservation of high oxidation-reduction potential, both of which favored for the generation of radicals to oxidize sulfur species.

miR-199a-3p enhances cisplatin sensitivity of ovarian cancer cells by targeting ITGB8.

Drug resistance remains a large obstacle for the treatment of ovarian cancer. miRNAs have been reported to be involved in cisplatin (CDDP) resistance in ovarian cancer. The aim of the present study was to investigate the function and mechanism of miR-199a-3p in the CDDP resistance in ovarian cancer. We found that miR-199a-3p was significantly downregulated in chemoresistant ovarian cancer tissues, as well as CDDP-resistant SKOV3/CDDP cells, compared to chemosensitive carcinomas and SKOV3 cells. Restoration of miR-199a-3p in SKOV3/CDDP cells reduced cell proliferation, G1 phase cell cycle arrest, cell invasion, and increased cell apoptosis, resulting in enhanced CDDP sensitivity, while miR-199a-3p inhibition resulted in the opposite effects. Luciferase reporter assay showed that integrin ß8 (ITGB8), one of the integrins that is involved in the regulation of cell cycle and motility, was a direct target of miR-199a-3p. Overexpression of miR-199a-3p downregulated ITGB8 expression via binding to its 3'-UTR. In addition, overexpression of ITGB8 restored CDDP resistance inhibited by miR-199a-3p. Moreover, orthotopic ovarian cancer mouse model showed that miR­199a-3p enhanced CDDP sensitivity of ovarian cancer in vivo. Therefore, our results indicate that miR-199a-3p enhances CDDP sensitivity of ovarian cancer cells through downregulating ITGB8 expression, and miR-199a-3p may serve as a therapeutic target for the treatment of ovarian cancer patients with CDDP-resistance.

NOD2 promotes cell proliferation and inflammatory response by mediating expression of TSLP in human airway smooth muscle cells.

The newly discovered intracytosolic pattern recognition receptor nucleotide-binding oligomerization domain 2 (NOD2) has been studied as an important indicator of T helper 2 (Th2) inflammation, and its effect on regulatory T (Treg) cells is likely to modulate the immune response. In this study, we attempted to study the expression of NOD2 and its impact in human airway smooth muscle cells (HASMC). Quantitative real-time PCR (qRT-PCR) was used to measure the expression level of NOD2 in HASMC and comparisons were made between those from asthmatic and non-asthmatic donors; we found that NOD2 was significantly upregulated in asthma patient tissues and cell lines. In addition, overexpression of NOD2 apparently promotes cell proliferation and migration in HASMC. Gain-of-function in vitro experiments further showed that NOD2 overexpression significantly promotes pro-inflammatory cytokine release in HASMC. Subsequent experimental analysis indicated that thymic stromal lymphopoietin (TSLP) is involved in NOD2-mediated cellular effects in HASMC. Therefore, our results indicate that NOD2 is an asthma-related factor that can promote cell proliferation and inflammatory response by mediated expression of TSLP in HASMC. Taken together, our results indicate that NOD2 could serve as a potential diagnostic biomarker and therapeutic option for human asthma in the near future.

[Effect of Moxibustion Stimulation of "Feishu" (BL 13) and "Xinshu" (BL 15) on Expression of Myocardial MyD 88 Protein and Caspase 3 mRNA in Chronic Heart Failure Rats].

OBJECTIVE: To observe the effect of moxibustion stimulation of "Feishu" (BL 13) and "Xinshu" (BL 15) on pathological changes of myocardium and the expression of myocardial myeloid differentiation factor 88 (MyD 88) protein and Caspase 3 mRNA in chronic heart failure (CHF) rats, so as to explore its mechanism underlying improvement of CHF. METHODS: SD male rats were randomly divided into normal (n=9), model (n=8), moxibustion (n=8), medication (n=8) and moxibustion + medication (n=8) groups. In addition, the other 6 rats (3/normal and 3/model groups) were used for measuring cardiac ventricle weight and H.E. stain. The CHF model was made by intraperitoneal injection of Adriamycin (ADR, from 1 to 4 mg/kg, once every other day for 15 days). Mild moxibustion was applied to bilateral BL13 and BL15 for 15 min, once daily for 3 weeks. Rats of the medication group were treated by Captopril (gavage) for 3 weeks. The expression of myocardial Caspase 3 mRNA and MyD 88 protein of the left ventricle was determined by quantitative real time-PCR and Western blot, respectively. RESULTS: In comparison with the normal group, the myocardial damage (cell swelling, cytoplasma vaculation, and disordered arrangement, rupture and lysis of some cardiac muscle fibers), and the expression levels of myocardial MyD 88 protein and Caspase 3 mRNA were obviously increased in the model group(P<0.01). After the interventions, the myocardial damage was relatively milder, and the expression of myocardial MyD 88 protein and Caspase 3 mRNA were significantly down-regulated in the moxibustion, me-dication and moxibustion+medication groups in comparison with the model group(P<0.05). No significant differences were found among the 3 treatment groups in the expression levels of MyD 88 protein and Caspase 3 mRNA(P>0.05). CONCLUSIONS: Moxibustion intervention can suppress CHF induced up-regulation of expression of myocardial MyD 88 protein and Caspase 3 mRNA in rats, which may contribute to its effect in relieving myocardial injury.

Pharmacodynamic and pharmacokinetic study of pegylated liposomal doxorubicin combination (CCOP) chemotherapy in patients with peripheral T-cell lymphomas.

AIM: To investigate the pharmacodynamic and pharmacokinetic parameters of pegylated liposomal doxorubicin (PLD) combined with cyclophosphamide, vincristine, and prednisolone in patients with peripheral T-cell lymphomas (PTCL). METHODS: Seven chemonaive patients and four patients with relapsed peripheral T-cell lymphomas were treated with a CCOP regimen consisting of an intravenous administration of cyclophosphamide (750 mg/m(2)), vincristine (1.4 mg/m(2)), and PLD (30 mg/m(2)) on d 1, as well as an oral administration of prednisolone (60 mg/m(2)) on d 1-5. This regimen was repeated every 3 weeks for six cycles, and the clinical response and toxicity of the regimen were monitored. In addition, the plasma concentration of PLD at different time points was determined before and after treatment. The pharmacokinetics (PKs) software was used to estimate the pharmacokinetic parameters of PLD. RESULTS: The 11 PTCL patients received 35 treatment cycles. Three of them achieved complete response (CR), two partial response (PR), four stable disease (SD), and two progressive disease (PD). The overall response rate (ORR) was 45.5%, and the CR rate was 27.3%. In the 7 chemonaive patients, three achieved CR, two PR, one SD, and one PD. The ORR was 71.4%, and CR rate was 42.9%. The median follow-up time was 15 months, but 6 out of 11 patients were dead at the time of data analysis. The 1-year overall survival rate was 45.5%, and the median progression-free survival (PFS) rate was 6.5 [95% confidence interval (95% CI) 3.17-19.02] with a survival rate of 11.5 months (95% CI 6.65-16.36). The main toxicity was myelosuppression. Oral mucositis and hand-foot syndrome seldom occurred. The PLD plasma concentration from nine patients ranged from 1.7036 to 9.2207 mg·L(-1) after administration of the CCOP regimen (0-168 h). The pharmacokinetic parameters AUC(0-∞), CL, t(1/2), and V(d) were 910.76 mg/L·h, 0.043 L·h(-1)·m(-2), 68.40 h, and 3.56 L/m(2), respectively. CONCLUSION: The CCOP regimen was effective and well tolerated in patients with peripheral T-cell lymphomas. The results of the pharmacokinetic parameters showed that PLD had long retention time in blood circulation.

Phase II trial of gemcitabine plus cisplatin in patients with advanced non-small cell lung cancer.

AIM: To investigate the pharmacodynamics and pharmacokinetics of gemcitabine (dFdC) administered on d 1 and 5 plus cisplatin administered on d 1 in chemonaive patients with stage IIIB or IV non-small cell lung cancer (NSCLC). METHODS: In each combination cycle, gemcitabine was administered at a dose of 1250 mg/m(2) as a 30 min intravenous (iv) infusion on d 1 and 5 followed by cisplatin at a dose of 75 mg/m(2) as a 3 h iv infusion on d 1 every 3 weeks. There was an interval of 1 h between the two infusions. Clinical response and toxicity of the regimen were observed. Furthermore, the plasma concentrations of gemcitabine (dFdC) and its metabolite (dFdU) at different time points were detected during the first cycle of infusion. Pharmacokinetic software (PKS) was used to estimate the pharmacokinetic parameters of gemcitabine and its metabolite dFdU. RESULTS: A total of 28 patients was enrolled in the study. The median age was 54 years (range 27-75 years), and most patients were in good clinical condition. Twenty-seven patients received two or more treatment cycles. The overall clinical response rate was 33.3%. The median overall survival time was 13 months. The estimated median time to tumor progression (TTP) was 6.2 months, and the 1-year survival rate was 55.6%. Toxicities were tolerated. The main toxicity was myelosuppression; 35.7% of patients had grade 3/4 hematologic toxicities and 28.6% had grade 3/4 non-hematologic toxicities, which were commonly gastrointestinal responses. The pharmacokinetic parameters of dFdC and dFdU were not different between pre- and post-administration of gemcitabine on d 1 and 5. dFdU was minimal (0.729+/-0.637 microg/mL) before gemcitabine was infused on d 5, and gemcitabine was not present. CONCLUSION: The regimen is active and well tolerated in chemonaive patients with advanced NSCLC. After gemcitabine was administered on d 1 and 5, the pharmacokinetic parameters of dFdC and dFdU showed no difference from those before the infusion, and dFdU was minimal before gemcitabine was administered on d 5.

[Effects of fasudil on the expression of Rho kinase-1 and airway inflammation in a mouse model of asthma.].

OBJECTIVE: To explore the role of Rho kinase-1 (ROCK-1) in airway inflammation of asthma by observing the effects of fasudil, a specific inhibitor of ROCK-1, on the expression of Rho kinase-1 and airway inflammation in a mouse model of asthma. METHODS: Twenty-four female BALB/c mice were randomly divided into 3 groups (n = 8 each): a control group, an asthmatic group and a treatment group. Mice in the asthmatic and the treatment groups were sensitized by intraperitoneal injection of OVA (25 microg) precipitated with 1 mg of alum in 200 microl of saline on days 1 and 15, and subsequently challenged by nebulization of 2% OVA on days 22-26. Mice in the control group were sensitized with Al(OH)3 saline and challenged with saline instead of OVA. Mice of the treatment group were injected intraperitoneally with fasudil (10 mg/kg) 1 h before each OVA challenge. All the mice were killed 24 h after the final challenge, and bronchoalveolar lavage fluid (BALF) was collected for counting total inflammatory cells and eosinophils (EOS). Cytokines and chemokines in BALF were measured by ELISA. The lung tissue slides were examined histologically. The protein and mRNA expression of ROCK-1 were measured by immunohistochemistry and RT-PCR respectively. RESULTS: (1) OVA challenge in mice of the asthmatic group caused a marked increase in the number of the total cells and eosinophils in BALF (q = 25.909, 35.002, respectively, all P < 0.01). When fasudil was applied, both the total cell counts and the eosinophil numbers were significantly decreased. The total cell number was decreased from (1.45 +/- 0.12) x 10(9)/L to (0.89 +/- 0.09) x 10(9)/L (q = 16.676, P < 0.01), and the number of eosinophils was decreased from (0.52 +/- 0.06) x 10(9)/L to (0.20 +/- 0.04) x 10(9)/L (q = 21.537, P < 0.01). (2) Compared with the control group, OVA challenge in mice of the asthmatic group induced eotaxin, IL-5 and IL-13 release into BALF (q = 18.246, 23.009, 25.826, respectively, all P < 0.01). The eotaxin, IL-5 and IL-13 levels in BALF after OVA challenge were (45 +/- 8) ng/L, (157 +/- 23) ng/L and (429 +/- 46) ng/L, respectively. Application of fasudil resulted in inhibition of the augmented levels of eotaxin, IL-5 and IL-13 in BALF, decreased to (20 +/- 5) ng/L, (57 +/- 14) ng/L and (254 +/- 28) ng/L, respectively (q = 13.119, 17.503, 8.449, respectively, all P < 0.01). (3) Mice in the control group showed no detectable inflammatory response in the lung, whereas OVA-challenged mice induced infiltration of inflammatory cells around airways and blood vessels. The majority of the infiltrated inflammatory cells were eosinophils. Application of fasudil significantly reduced the infiltration of inflammatory cells in the peribronchial areas compared with the asthmatic mice. (4) The expression levels of ROCK-1 mRNA and protein in mice of the asthmatic group (0.67 +/- 0.05 and 1.09 +/- 0.06) were much higher than those of the control group (0.26 +/- 0.05 and 0.87 +/- 0.09) (q = 25.614, 8.156, all P < 0.01). When fasudil was administered, the expression levels of ROCK-1 mRNA and protein were significantly attenuated to 0.35 +/- 0.04 and 0.98 +/- 0.08, compared with those of the asthmatic group (q = 20.379, 4.135, all P < 0.01). (5) The expression level of ROCK-1 mRNA was positively correlated with the number of eosinophils and the levels of eotaxin, IL-5 and IL-13 in BALF (r = 0.709, 0.600, 0.613, 0.650, all P < 0.01). CONCLUSION: Airway inflammation of bronchial asthma was improved by inhibiting expression and activity of ROCK-1 by fasudil, suggesting that ROCK-1 may be involved in asthmatic airway inflammation induced by OVA challenge.

Complete surface plasmon-polariton band gap and gap-governed waveguiding, bending and splitting.

We show theoretically that a complete band gap for surface plasmon-polaritons (SPPs) can exist in a flat metal surface coated with a two-dimensional periodic array of dielectric cylinders. Based on the SPP band gap, gap-governed SPP waveguides, bends and splitters at telecom wavelengths can be achieved by introducing line defects. Numerical simulations show that the proposed SPP waveguides have a very low loss, while SPP bends and splitters can bend and split guided SPPs efficiently. The proposed SPP waveguides, bends and splitters could thus be exploited to construct compact integrated optical circuits in the emerging field of plasmonics.

Enhanced transmission mediated by guided resonances in metallic gratings coated with dielectric layers.

Transmission properties of metallic gratings coated symmetrically with a dielectric layer on both sides are studied theoretically. For subwavelength narrow slits, besides cavity resonances in slits and surface plasmon-polaritons, a new kind of mechanisms for enhanced transmission in coated metallic gratings, namely, guided resonances in the dielectric coating layers, is found. Transmission peaks mediated by guided resonances are found to be much sharper than those mediated by cavity or surface plasmon-polariton resonances.