Toxicity interaction of polystyrene nanoplastics with sulfamethoxazole on the microalgae Chlamydomonas reinhardtii: A closer look at effect of light availability.

The coexistence of nanoplastics and antibiotics in the aquatic environment has raised a complicated risk for ecosystems and human health. How the environmental factors e.g., light, regulate the interaction between nanoplastics and antibiotics and the resulting combined toxicity is poorly understood. Here, we investigated the individual and combined toxicity of polystyrene nanoplastics (nPS, 100 mg L1) and sulfamethoxazole (SMX, 2.5 and 10 mg L-1) toward the microalgae Chlamydomonas reinhardtii under low (LL, 16 µmol m-2·s-1), normal (NL, 40 µmol m-2·s-1), and high light (HL, 150 µmol m-2·s-1) in terms of cellular responses. Results indicated that the joint toxicity of nPS and SMX commonly exhibited a strong antagonistic/mitigative effect under LL/NL at 24 h, and under NL at 72 h. nPS could adsorb more SMX under LL/NL at 24 h (1.90/1.33 mg g-1) and under NL at 72 h (1.01 mg g-1), thereby alleviating SMX toxicity to C. reinhardtii. However, the self-toxicity of nPS had a negative influence on the degree of antagonism between nPS and SMX. The experimental results coupled with computational chemistry further revealed that the adsorption capacity of SMX on nPS was stimulated by low pH under LL/NL at 24 h (∼7.5), while by less co-existing saline ions (0.83 ppt) and algae-derived dissolved organic matter (9.04 mg L-1) under NL at 72 h. nPS toxicity that was responsible for the toxic action modes was mainly attributed to the shading effect induced by hetero-aggregation and hindrance of light transmittance (>60%), as well as being regulated by additives leaching (0.49-1.07 mg L-1) and oxidative stress. Overall, these findings provided a critical basis for the risk assessment and management of multiple pollutants in the complex natural environment.

Plastic structures for diverse substrates: A revisit of human ABC transporters.

ATP-binding cassette (ABC) superfamily is one of the largest groups of primary active transporters that could be found in all kingdoms of life from bacteria to humans. In humans, ABC transporters can selectively transport a wide spectrum of substrates across membranes, thus playing a pivotal role in multiple physiological processes. In addition, due to the ability of exporting clinic therapeutics, some ABC transporters were originally termed multidrug resistance proteins. Increasing investigations of human ABC transporters in recent years have provided abundant information for elucidating their structural features, based on the structures at distinct states in a transport cycle. This review focuses on the recent progress in human ABC structural analyses, substrate binding specificities, and translocation mechanisms. We dedicate to summarize the common features of human ABC transporters in different subfamilies, and to discuss the possibility to apply the fast-developing techniques, such as cryogenic electron microscopy, and artificial intelligence-assisted structure prediction, for future studies.

Preparation of a Self-Assembled Rhein-Doxorubicin Nanogel Targeting Mitochondria and Investigation on Its Antihepatoma Activity.

Mitochondria are involved in the regulation of apoptosis, making them a promising target for the development of new anticancer drugs. Doxorubicin (DOX), a chemotherapeutic drug, can induce reactive oxygen species (ROS)-mediated apoptosis, improving its anticancer effects. Herein, Rhein, an active ingredient in rhubarb, with the capability of self-assembly and mitochondrial targeting, was used in conjunction with DOX to form efficient nanomaterials (Rhein-DOX nanogel) capable of sustained drug release. It was self-assembled with a hydrogen bond, π-π stacking interactions, and hydrophobic interactions as the main driving force, and its loading efficiency was up to 100%. Based on its self-assembly characteristics, we evaluated the mechanism of this material to target mitochondria, induce ROS production, and promote apoptosis. The IC50 of the Rhein-DOX nanogel (3.74 µM) was only 46.3% of that of DOX (11.89 µM), and the tumor inhibition rate of the Rhein-DOX nanogel was 79.4% in vivo, 2.3 times that of DOX. This study not only addresses the disadvantages of high toxicity of DOX and low bioavailability of Rhein, when DOX and Rhein are combined for the treatment of hepatoma, but it also significantly improved the synergistic antihepatoma efficacy of Rhein and DOX, which provides a new idea for the development of long-term antihepatoma agents with low toxicity.

[Pharmacokinetic study of Polydopamine Guttate Pills loaded with active components of Sarcandrae Herba in rats].

An ultra-high performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS) method was established for the determination of active components of Sarcandrae Herba, and applied to the pharmacokinetics study of multiple dosage forms. After SD rats were administered by gavage with three dosage forms [Sarcandrae Herba extract, commercial Sarcandrae Herba Guttate Pills, and polydopamine guttate pills loaded with active components of Sarcandrae Herba(PDA-Sg Guttate Pills)], blood samples were collected from the inner canthus at different time points. After protein precipitation, plasma samples were separated on ACQUITY UPLC C_(18) column(2.1 mm×100 mm, 1.7 µm). The mobile phase consisted of water containing 0.2% formic acid and acetonitrile in gradient elution. The negative ions were measured simultaneously in the multi-reaction monitoring(MRM) mode. The pharmacokinetic parameters were calculated and fitted by DAS 2.0. All four components could be detected in the plasma of rats in each group at each time point except the neochlorogenic acid and cryptochlorogenic acid in the Sarcandrae Herba extract group. The guttate pills group showed a significant increase in drug content at each time point. The exposure of the main components of Sarcandrae Herba in blood was effectively increased by PDA-drug loading effect in PDA-Sg Guttate Pills(The AUC_(0-24 h) of neochlorogenic acid, cryptochlorogenic acid, isaziridin and rosmarinic acid reached 2.45, 32.90, 1.54, 4.81 times that of the commercial guttate pills). This study proves the measurability of the above-mentioned multi-component in vitro-in vivo delivery process. The pharmacokinetic study has shown that PDA-Sg Guttate Pills can effectively delay the elimination time and improve the bioavailability of the four components, which can provide theoretical data for the production of the drug.

Acupoint nanocomposite hydrogel for simulation of acupuncture and targeted delivery of triptolide against rheumatoid arthritis.

BACKGROUND: Attenuating inflammatory response and relieving pain are two therapeutic therapeutical goals for rheumatoid arthritis (RA). Anti-inflammatory and analgesic drugs are often associated with many adverse effects due to nonspecific distribution. New drug delivery systems with practical targeting ability and other complementary strategies urgently need to be explored. To achieve this goal, an acupoint drug delivery system that can target deliver anti-inflammatory drugs and simulate acupuncture in relieving pain was constructed, which can co-deliver triptolide (TP) and 2-chloro-N (6)-cyclopentyl adenosine (CCPA). RESULTS: We have successfully demonstrated that acupoint nanocomposite hydrogel composed of TP-Human serum album nanoparticles (TP@HSA NPs) and CCPA could effectively treat RA. The result shows that CCPA-Gel can enhance analgesic effects specifically at the acupoint, while the mechanical and thermal pain threshold was 4.9 and 1.6 times compared with non-acupoint, respectively, and the nanocomposite gel further enhanced. Otherwise, the combination of acupoint and nanocomposite hydrogel exerted synergetic improvement of inflammation, bone erosion, and reduction of systemic toxicity. Furthermore, it could regulate inflammatory factors and restore the balance of Th17/Treg cells, which provided a novel and effective treatment strategy for RA. Interestingly, acupoint administration could improve the accumulation of the designed nanomedicine in arthritic paws (13.5% higher than those in non-acupoint at 48 h), which may explain the better therapeutic efficiency and low toxicity. CONCLUSION: This novel therapeutic approach-acupoint nanocomposite hydrogel, builds a bridge between acupuncture and drugs which sheds light on the combination of traditional and modern medicine.

Enhanced oral bioavailability of 10-hydroxycamptothecin through the use of poly (n-butyl cyanoacrylate) nanospheres.

The article describes the preparation, physicochemical characterization, drug release, and in vivo behavior of 10-hydroxycamptothecin-loaded poly (n-butyl cyanoacrylate) (PBCA) nanospheres (HCPT-PBCA-NSs). HCPT-PBCA-NSs were successfully prepared via emulsion polymerization of n-butyl cyanoacrylate (BCA) monomer in acidic medium with the aid of two colloidal stabilizers (Poloxamer 188 and Dextran 70). The influence of pH, the time of polymerization, and the dosage of the drug on particle size and encapsulation efficiency (EE) were studied. HCPT-PBCA-NSs were of spherical shape and uniformly dispersed with a particle size of 135.7 nm, and zeta potential of -18.18 mV. EE, drug loading (DL), and yield of HCPT-PBCA-NSs were 51.52, 0.63, and 88.25%, respectively. FTIR, 1H NMR, and DSC showed complete polymerization of BCA monomer and HCPT existed in the form of molecular or amorphous in NSs. In vitro release of the drug from HCPT-PBCA-NSs exhibited sustained-release behavior with an initial burst release and about 60% of HCPT was released from the formulation within 24 h of dialysis. The pharmacokinetic study in healthy rats after oral administration showed that encapsulation of HCPT into PBCA-NSs increased the Cmax about 3.84 times and increased AUC0-t about 5.40 times compared with that of HCPT suspension. It was concluded that PBCA-NSs could be a promising drug carrier to load HCPT for oral drug delivery if efforts are made in the future to improve its poor DL capacity.

Fabrication of a Micro-Needle Array Electrode by Thermal Drawing for Bio-Signals Monitoring.

A novel micro-needle array electrode (MAE) fabricated by thermal drawing and coated with Ti/Au film was proposed for bio-signals monitoring. A simple and effective setup was employed to form glassy-state poly (lactic-co-glycolic acid) (PLGA) into a micro-needle array (MA) by the thermal drawing method. The MA was composed of 6 × 6 micro-needles with an average height of about 500 µm. Electrode-skin interface impedance (EII) was recorded as the insertion force was applied on the MAE. The insertion process of the MAE was also simulated by the finite element method. Results showed that MAE could insert into skin with a relatively low compression force and maintain stable contact impedance between the MAE and skin. Bio-signals, including electromyography (EMG), electrocardiography (ECG), and electroencephalograph (EEG) were also collected. Test results showed that the MAE could record EMG, ECG, and EEG signals with good fidelity in shape and amplitude in comparison with the commercial Ag/AgCl electrodes, which proves that MAE is an alternative electrode for bio-signals monitoring.

[Anti-tumor effect of brucine-loaded chitosan nanoparticles in vitro].

We designed two novel polymer materials N-glycyrrhetinic acid-polyethylene glycol-chitosan derivatives (NGPC) and N-quaternary ammonium-chitosan derivatives (NQC). We prepared three kinds of drug loaded chitosan nanoparticles (brucine/NGPC-NPs, brucine/NQC-NPs, brucine/MNPs) by ionic crosslinking method with brucine as a model drug and chitosan nanoparticles（brucine/NGPC-NPs, brucine/NQC-NPs） as the reference formulation. Using high content analysis, flow cytometry, immunofluorescence, transmission electron microscopy and other advanced technology, we tested the effect of 20 µg·mL(-1) concentration of brucine solution and brucine/ chitosan nanoparticles（brucine/CTS-NPs） in hepatocarcinoma (HEpG2) cells and evaluated the apoptosis induced by the treatment. The results suggested that brucine-CTS/NPs had a strongest activity in killing tumor cells, and increased the total cell apoptosis rate with a significant formation of "crescent-shaped" body, swelling mitochondria, mitochondria cristae missing, decreased mitochondrial membrane potential and release of cytochrome C. The activity was enhanced by multifunctional nanocomposite particles that increased the cumulative amount of drug in the mitochondria for the anti-tumor effect.

Brucine-loaded liposomes composed of HSPC and DPPC at different ratios: in vitro and in vivo evaluation.

OBJECTIVE: The objective of this study is to test the hypothesis that the phase transition temperature (T(m)), the main property of liposomes, can be easily controlled by changing the molar ratio of hydrogenated soy phosphatidylcholine (HSPC) and 1,2-dipalmitoyl-sn-glycero-3-phosphacholine (DPPC) after drug encapsulation. MATERIALS AND METHODS: Brucine, an antitumor alkaloid, was encapsulated into the liposomes with different HSPC/DPPC compositions. The T(m)s of the brucine-loaded liposomes (BLs) were determined by differential scanning calorimetry (DSC). Then the physicochemical properties and pharmacokinetics of the BLs with different HSPC/DPPC compositions were investigated and compared. RESULTS: The results of DSC revealed that HSPC and DPPC can combine into one phase. The findings of molecular modeling study suggested that HSPC interacts with DPPC via electrostatic interaction. The molar ratio of HSPC/DPPC influenced the sizes of BLs but had little effect on the entrapment efficiency (EE). The stability of BLs was improved with the increase of the HSPC ratios, especially with the presence of plasma. Following i.v. administration, it was found that AUC values of BLs in vivo were directly related to the HSPC/DPPC ratios of BLs, namely the T(m)s of BLs. DISCUSSION: The behavior of liposomes, especially in vivo pharmacokinetic behavior, can be controlled by the modification of T(m). CONCLUSION: The characterization of BLs in vitro and in vivo had demonstrated that the Tm could be flexibly modified for liposomes composed of both HSPC and DPPC. Using HSPC/DPPC composition may be an efficient strategy to control the T(m), thus control the in vivo pharmacokinetic behavior, of BLs.

Physiological responses and molecular mechanism of Chlorella sorokiniana to surgical mask exudates in wastewater.

Microalgae-based bioremediation is likely to be challenged by the microplastics (MPs) in wastewater induced by the widely use of surgical masks (SMs) during COVID-19. However, such toxic impact was generally evaluated under high exposure concentrations of MPs, which was not in agreement with the actual wastewater environments. Therefore, this study investigated the microalgal cellular responses to the surgical mask exudates (SMEs) in wastewater and explored the underlying inhibitory mechanism from the molecular perspective. Specifically, 390 items/L SMEs (including 200 items/L MPs which was the actual MP level in wastewater) significantly inhibited nutrient uptake and photosynthetic activities interrupted peroxisome biogenesis and induced oxidative stress which destroyed the structure of cell membrane. Moreover, the SMEs exposure also affected carbon fixation pathways, suppressed ABC transporters while promoted oxidative phosphorylation processes for the ATP accumulation These comprehensive processes led to an 8.5% reduced microalgae growth and variations of cellular biocomponents including lipid, carbohydrate, and protein. The increased carotenoids and consumed unsaturated fatty acid were considered to alleviate the SMEs-induced stress, and the enhanced EPS secretion facilitated the homogeneous aggregation. These findings will enhance current understandings of the SMEs effects in wastewater on microalgae and further improve the practical relevance of microalgae wastewater bioremediation technology.

Natural Binary Herbal Small Molecules Self-Assembled Nanogel for Synergistic Inhibition of Respiratory Syncytial Virus.

Respiratory syncytial virus (RSV) is one of the most significant pathogenic infections in childhood, associated with high morbidity and mortality rates. Currently, there is no effective and safe drug or vaccine available for RSV. Glycyrrhizic acid (GA), an active compound derived from the natural herb licorice, has been reported to provide protection against influenza and coronaviruses, exhibiting notable antiviral and anti-inflammatory properties. Ephedrine (EPH) is a commonly prescribed medication for the treatment of cough and asthma, and it also demonstrates certain antiviral effects. In this study, EPH and GA were combined to form an efficient nanomaterial (EPH-GA nanogel). The self-assembly of this nanogel is driven by hydrogen bonding and hydrophobic interactions, allowing it to serve as an antiviral nanomedicine without the need for a dual-component carrier, achieving a 100% drug loading efficiency. Oral administration of the EPH-GA nanogel significantly reduced viral load in the lungs of mice and improved lung lesions and tissue infiltration caused by RSV. Notably, we discovered that the assembled drug may create a "physical barrier" that prevents RSV from adsorbing to host cells, while free GA and EPH may compete with RSV for protein binding sites, thereby enhancing cellular uptake of EPH. Consequently, this prevents RSV infection and proliferation within host cells. Furthermore, the EC50 values changed from 310.83 µM for EPH and 262.88 µM for GA to 68.25 µM for the EPH-GA combination, with a combination index of 0.458. In addition, the in vivo biopharmaceutic process of GA and EPH was investigated, revealing that the oral administration of EPH-GA significantly increased the bioavailability of EPH while maintaining its plasma concentration at a relatively stable level. This enhancement may contribute to a synergistic antiviral effect when combined with GA. Furthermore, the in vivo process of EPH-GA demonstrates the advantage of delivering the drug to the lesion at elevated levels, thereby facilitating its antiviral mechanism at the cellular level. In this study, we identified an effective nanomedicine, EPH-GA nanogel, which can inhibit the proliferation of RSV and mitigate lung lesions resulting from viral infection by influencing the biopharmaceutical process in vivo. This research not only offers a novel strategy for the nanomedicine treatment of RSV but also elucidates, to some extent, the compatibility mechanisms of the multicomponents of traditional Chinese medicine.

Combined ROS Responsive Polydopamine-Coated Berberine Nanoparticles Effective Against Ulcerative Colitis in Mouse Model.

Introduction: Enhancing the efficacy of berberine (BBR) in the treatment of ulcerative colitis (UC) through the development of dopamine-coated berberine nanoparticles (PDA@BBR NPs) with ROS-responsive and adhesive properties. Methods: Berberine nanoparticles (BBR NPs) were synthesized using the nonsolvent precipitation method, and their surfaces were coated with polydopamine (PDA) through oxidative polymerization. The PDA@BBR NPs were characterized by transmission electron microscopy (TEM), size analysis, and zeta potential analysis. Drug loading and encapsulation efficiency were analyzed using fluorescence spectroscopy. The responsiveness of these nanoparticles to reactive oxygen species (ROS) was assessed in vitro, while their adhesive properties and therapeutic efficacy on UC were evaluated in vivo. Results: Physicochemical property studies showed that PDA coated BBR NPs nanoparticles have good dispersion and stability. In vitro results showed that PDA@BBR NPs could prolong the retention time of the drug at the colonic site and could realize the gradual drug release under ROS environment. In addition, animal studies showed that PDA@BBR NPs exhibited significant anti-inflammatory effects on DSS-induced colitis and effectively reduced intestinal mucosal damage. Conclusion: PDA@BBR NPs are ROS-responsive nanoparticles that adhere well and have a high drug loading capacity. They have shown therapeutic effects in mice with UC, indicating that this formulation may be a promising treatment option.

Influence of lipid composition on the phase transition temperature of liposomes composed of both DPPC and HSPC.

OBJECTIVE: Phase transition of the lipid membrane is one of the most important properties of liposomes. The objective of this study was to investigate the influence of molar ratio of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and hydrogenated soy phosphatidylcholine (HSPC) on the phase transition temperature (T(m)) of the liposomes. MATERIALS AND METHODS: The T(m)s of the liposomes with different phosphatidylcholine (PC) composition were determined by calcein release test and differential scanning calorimetry (DSC). RESULTS: Only one phase transition was observed for liposomes composed of both DPPC and HSPC, indicating that DPPC and HSPC might combine into one phase with single phase transition. The T(m) of the liposomes composed of both DPPC and HSPC was directly dependent on the molar ratio of the two PCs. Moreover, DPPC percentage and T(m) relationship could be fitted with a linear equation (r(2) > 0.98). In addition, the serum stability of the liposomes at 37°C was directly increased with the increase of DPPC percentage. When 10% DSPE-PEG2000 was added, the significant increase of calcein release at T(m) and decrease at 37°C were observed. DISCUSSION: It is easy to obtain liposomes with a T(m) in between that of DPPC and HSPC by modifying the molar ratio of DPPC and HSPC. CONCLUSION: With the modification of T(m), the liposomes containing various ratios of DPPC and HSPC may have promising application potential in the field of thermosensitive liposomes (TSLs). After 10% DSPE-PEG2000 is added, a formulation of sterically stabilized liposomes with the proper thermal sensitivity can be obtained.

[Preparation and pharmacokinetics of brucine hydrogel patch].

OBJECTIVE: To investigate the effect of dose on pharmacokinetic properties of brucine hydrogel patch. METHODS: The plasma concentration of brucine was determined by HPLC. Brucine hydrogel patch was prepared and its pharmaceutical characterization was investigated. After transdermal administration of different dose brucine hydrogel patch; Plasma concentration versus time profiles were determined and pharmacokinetic parameters were calculated by DAS program. RESULTS: The pharmaceutical properties of brucine hydrogel patch were satisfactory. The AUC0-1 values were 7.24 +/- 0.61, 16.02 +/- 2.34 and 54.84 +/- 26.59 microg x h/mL after administration of 30, 60 and 180 mg/kg brucine hydrogel patch, respectively. The corresponding C(max) values were 0.73 +/- 0.23, 1.45 +/- 0.28 and 4.59 +/- 1.85 microg/mL, respectively. And the corresponding T(max) values were 8.67 +/- 2.07, 11.67 +/- 2.66 and 8.33 +/- 2.65 h, respectively. CONCLUSION: The pharmacokinetic properties of brucine do not vary with the dose of brucine hydrogel patch.

Dual-targeted enzyme-sensitive hyaluronic acid nanogels loading paclitaxel for the therapy of breast cancer.

In this study, a CD44 and biotin receptors dual-targeted enzyme-sensitive hyaluronic acid nanogel loading paclitaxel (PTX/Bio-NG) for targeting breast cancer was constructed. Spherical nanogels with a mean particle size of 149.1 ± 1.6 nm, higher entrapment efficiency (90.17 ± 0.52 %) and drug loading (15.28 ± 0.10 %) were obtained. PTX/Bio-NG quickly released drugs under the catalysis of hyaluronidase and/or lipase. Cell studies revealed that the uptake of Bio-NG by 4T1 cells was mediated by CD44 receptor and Bio-specific receptor. Compared with PTX-loaded biotin-free NG (PTX/NG), PTX/Bio-NG had higher cytotoxicity against breast cancer cells (4T1 cells). The rats pharmacokinetic profile indicated higher AUC0-t but lower clearance rates of PTX/NG (6.24 times and 15.96 %, respectively) and PTX/Bio-NG (6.66 times and 14.89 %, respectively) than control group (Taxol). In vivo studies showed that PTX/Bio-NG possessed excellent therapeutic efficacy in 4T1 tumor-bearing Balb/c mice, which suggest that PTX/Bio-NG could be an excellent candidate for the treatment of breast cancer.

[Water in oil microemulsions containing NaCl for transdermal delivery of fluorouracil].

This study is to prepare the W/O microemulsion containing NaCl and fluorouracil (5-Fu) as a model drug to investigate the transdermal characteristics and skin irritation of the microemulsion in vitro. Isopropylmyristate (IPM) acting as oil phase, Aerosol-OT (AOT) as surfactant, Tween 85 as cosurfactant, NaCl solution was added dropwise to the oil phase to prepare W/O microemulsion at room temperature using magnetic stirring, and then 5-Fu powder was added. According to the area of microemulsion based on the pseudo-tertiary phase diagrams, the optimum formulation was screened initially. And the permeation flux of fluorouracil across excised mice skin was determined in vitro using Franz diffusion cells to study the influence of the amount of water and the drug loading capacity and optimize the formulation further. Refer to 5-Fu cream, the irritation of microemulsion on the rat skin was studied. The optimum formulation was composed of 0.7% (w/v) 5-Fu, 50% NaCl solution (0.05 mol x L(-1)), 20% mix-surfactant (AOT/Tween 85, K(m) = 2) and 29.3% oil (IPM). The cumulative amount of fluorouracil permeated in 12 h was (2 013.4 +/- 41.6) microg x cm(-2), 20.23 folds and 10.38 folds more than 0.7% fluorouracil aqueous solution and 2.5% (w/w) fluorouracil cream, respectively. Microemulsion exhibited some irritation, but could be reversed after drug withdrawal. The addition of NaCl significantly increased the content of water and the drug loading in microemulsion systems. The NaCl/AOT-Tween 85/IPM microemulsion system promoted the permeation of fluorouracil greatly, which may be a promising vehicle for the transdermal delivery of fluorouracil and other hydrophilic drug.

[Compound erythromycin sustained release preparation and its in vitro release].

Using the weight-average molecular weight 50 000 polylactic acid (PLA) as a carrier, and a certain proportion of erythromycin (EM) and prednisone acetate (PNA) to mixed prepare the compound erythromycin sustained release preparation (sustained-release tablets). Using ultraviolet spectrophotometry and high performance liquid chromatography (HPLC) to detect separately the release amount of EM and PNA in vitro medium. The sustained-release tablets release for about 21 days, the average content of EM is 99.7 mg/table, RSD = 0.82%; and the average content of PNA is 10.03 mg/table, RSD = 0.93%. Within 21 days, the cumulative releases of EM and PNA are 86.1% and 78.3%, respectively. The drug release is steady and slow after 5 days, the burst release phenomenon in early stage is more significant. The results showed that the sustained-release tablet preparation method is feasible, the release performance is good and the clinical efficacy is significant.

The efficacy and safety of antimuscarinics for the prevention or treatment of catheter-related bladder discomfort: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: This meta-analysis aimed to evaluate the efficacy and safety of antimuscarinics for the prevention or treatment of catheter related bladder discomfort (CRBD). METHODS: The MEDLINE, EMBASE, and Cochrane Controlled Trials Register (from 1987 to July 2021) were used to search randomized controlled trials. The PRISMA checklists were followed. RevMan5.4.0 was used for statistical analysis. RESULTS: Eleven studies involving 1165 patients were involved in the analysis. The study reported that the incidence of CRBD observed in the antimuscarinics group was significantly lower than that of the control group at 0-, 1-, 2-, and 6-h after drug therapy (P = 0.001, P < 0.0001, P = 0.0005, and P = 0.001, respectively). For side effects, there were not statistical differences between the antimuscarinics group and the control group, mainly including dry mouth (risk ratio (RR) = 1.31, 95% confidence interval (CI) = 0.95 to 1.80, P = 0.09), postoperative nausea and vomiting (RR = 1.02, 95% CI = 0.55 to 1.90, P = 0.87), facial flushing (RR = 1.06, 95% CI = 0.43 to 2.61, P = 0.90), and blurred vision (RR = 0.95, 95% CI = 0.35 to 2.58, P = 0.91). Besides, rescue analgesics were required less in the antimuscarinics group than in the control group (RR = 0.51, 95% CI = 0.32 to 0.80, P = 0.003). CONCLUSIONS: Compared with the control group, the antimuscarinics group had a significant improvement on CRBD, the patients were well tolerated and the use rate of rescue analgesics was low.

Enhanced Embolization Efficacy with the Embolic Microspheres Guided by the Aggregate Gradation Theory Through In Vitro and Simulation Evaluation.

PURPOSE: Size of the embolic microspheres is of critical importance in the transcatheter arterial chemoembolization (TACE) of hepatocellular carcinoma (HCC) to achieve the optimal embolization therapy. In this regard, to optimize the size distribution of the embolic microspheres and enhance the embolization efficacy, the aggregate gradation theory is used to formulate the microspheres. METHODS: Finite element analysis (FEA) and in vitro experiments confirmed a better embolic efficacy for the poly(vinyl alcohol) (PVA) microspheres formulated according to the aggregate gradation theory. RESULTS: The average volume flow of the graded group was 1.31 × 10-4 mL/s in vitro experiment, which was lowest among all the groups suggesting the graded group had the optimal embolic effect. The graded group has the largest pressure gradient of 314.22 Pa/µm in FEA among all the groups, which can be attributed to the highest packing density of the graded group compared with other groups. CONCLUSIONS: The graded embolic microspheres have a larger drag coefficient compared with the narrow size distribution groups both in vitro experiment and FEA. These findings can be used to formulate the embolic agents with optimal size distributions and are significant for the improvement of clinical embolization therapy.

Systematic review and meta-analysis of the efficacy and safety of vibegron vs antimuscarinic monotherapy for overactive bladder.

BACKGROUND: Vibegron is a new ß3-adrenergic receptor agonist which has been demonstrated for the treatment of overactive bladder (OAB). We carried out meta-analysis to evaluate the efficiency of vibegron vs antimuscarinic monotherapy for treating OAB. METHODS: Randomized controlled trials (RCTs) of Vibegron vs antimuscarinic monotherapy for OAB were searched systematically by using EMBASE, MEDLINE, and the Cochrane Controlled Trials Register. The RevMan version 5.3.0. was used to analysis the data. RESULTS: Three RCTs involving a total of 1751 patients were studied in the Systematic review and Meta-analysis. Efficacy end points: the mean number of micturitions episodes/d (P = .16); the mean number of urgency episodes/d (P = .05); mean number of urgency incontinence episodes/d (P = .11) and mean number of incontinence episodes/d (P = .14) indicated that vibegron and antimuscarinic had no significant differences in terms of OAB treatment. Mean volume voided/micturition showed a distinct difference in the two groups (P = .009). With regard to dry mouth and drug related treatment-emergent adverse event (TEAE), vibegron showed better tolerance than antimuscarinic. Serious adverse event (SAE) and discontinuations due to adverse event (AE) did not show a significant difference between the two groups. CONCLUSIONS: The therapeutic effect of vibegron is similar to that of antimuscarinic, but vibegron does not increase the risk of AE.