Liposomal Bupivacaine Single-Injection Compared With Continuous Local Anesthetic Nerve Blocks for Painful Surgeries: A Meta-Analysis of Randomized Controlled Trials and Trial Sequential Analysis.

OBJECTIVE: This meta-analysis aimed to determine whether liposomal bupivacaine (LB) single-injection could achieve an analgesic effect similar to that of continuous local anesthetic nerve blocks (CNBs) after painful surgeries. METHODS: Embase, PubMed, and the Cochrane Library databases were comprehensively searched. Randomized controlled trials (RCTs) with a modified Jadad score ≥ 4 compared LB single-injection with CNBs in patients after painful surgeries were included. The primary outcomes were VAS pain score and opioid consumption. The secondary outcomes were complications and length of hospital stay. Review Manager 5.3 and trial sequential analysis (TSA) 0.9.5.10 were used to analyze the extracted data. RESULTS: Six RCTs of 625 patients were included for meta-analysis. Both groups in 5 RCTs described standard concomitant treatment with multimodal analgesia. There were no significant differences in mean VAS scores for postoperative day 0 (P = 0.12), day 1 (P = 0.18), and day 2 (P = 0.41); highest VAS scores for day 0 (P = 0.18), day 1 (P = 0.46), and day 2 (P = 0.18); total opioid consumption for day 0 (P = 0.05), day 1 (P = 0.28), and day 2 (P = 0.57); complications (P = 0.30); and length of hospital stay (P = 0.64) between the 2 groups. TSA of primary outcomes showed that all cumulative Z curves failed to cross the TSA boundary and did not reach the required information size. CONCLUSIONS: This meta-analysis showed that LB single-injection and CNBs have similar efficacy of pain relief and safety in patients after painful surgeries when concomitant with multimodal analgesia. However, the results of TSA indicate that further trials are still needed to confirm these findings.

Polyethylene glycol loxenatide (PEX168) in subjects with renal impairment: A pharmacokinetic study.

AIMS: Type 2 diabetes mellitus (T2DM) is commonly complicated by renal impairment. Polyethylene glycol loxenatide (PEX168) is a novel long-acting glucagon-like peptide-1 receptor agonist for T2DM. PEX168 pharmacokinetics was studied to identify requirements for dose-modification in T2DM complicated by renal impairment. METHODS: This was a single-centre, open-labelled, parallel-group, single-dose, phase I clinical trial of patients with mild and moderate renal impairment, and with or without T2DM. Age-, sex- and body mass index-matched subjects with normal renal function, and with or without T2DM were recruited as controls. Subjects received a single abdominal subcutaneous injection of PEX168 200 µg. Pharmacokinetic samples were taken at 0, 24, 48, 72, 96, 120, 144, 216, 312, 480, 648 and 720 hours. RESULTS: Twenty-three patients were included in the pharmacokinetics analysis. Vz/F and CL/F were lower in the moderate impairment group than in the other groups. The mean t1/2 (163 hours) in the moderate impairment group was prolonged compared to the mild impairment (117 hours) and normal (121 hours) groups. AUC0-inf increased by 13 and 100.7% in patients with mild and moderate renal impairment, respectively. Most adverse events were mild gastrointestinal disorders, with only 1 serious adverse event observed. CONCLUSION: A single dose of 200 µg of PEX168 was in general well tolerated in patients with renal impairment. The in vivo clearance rate of PEX168 in patients with moderate renal impairment is slower than in patients with mild renal impairment and normal renal function and dose adjustment might be required (ClinicalTrials.org #NCT02467790).

Salinomycin-loaded lipid-polymer nanoparticles with anti-CD20 aptamers selectively suppress human CD20+ melanoma stem cells.

Melanoma is the deadliest type of skin cancer. CD20+ melanoma stem cells (CSCs) are pivotal for metastasis and initiation of melanoma. Therefore, selective elimination of CD20+ melanoma CSCs represents an effective treatment to eradicate melanoma. Salinomycin has emerged as an effective drug toward various CSCs. Due to its poor solubility, its therapeutic efficacy against melanoma CSCs has never been evaluated. In order to target CD20+ melanoma CSCs, we designed salinomycin-loaded lipid-polymer nanoparticles with anti-CD20 aptamers (CD20-SA-NPs). Using a single-step nanoprecipitation method, salinomycin-loaded lipid-polymer nanoparticles (SA-NPs) were prepared, then CD20-SA-NPs were obtained through conjugation of thiolated anti-CD20 aptamers to SA-NPs via a maleimide-thiol reaction. CD20-SA-NPs displayed a small size of 96.3 nm, encapsulation efficiency higher than 60% and sustained drug release ability. The uptake of CD20-SA-NPs by CD20+ melanoma CSCs was significantly higher than that of SA-NPs and salinomycin, leading to greatly enhanced cytotoxic effects in vitro, thus the IC50 values of CD20-SA-NPs were reduced to 5.7 and 2.6 µg/mL in A375 CD+20 cells and WM266-4 CD+ cells, respectively. CD20-SA-NPs showed a selective cytotoxicity toward CD20+ melanoma CSCs, as evidenced by the best therapeutic efficacy in suppressing the formation of tumor spheres and the proportion of CD20+ cells in melanoma cell lines. In mice bearing melanoma xenografts, administration of CD20-SA-NPs (salinomycin 5 mg·kg-1·d-1, iv, for 60 d) showed a superior efficacy in inhibition of melanoma growth compared with SA-NPs and salinomycin. In conclusion, CD20 is a superior target for delivering drugs to melanoma CSCs. CD20-SA-NPs display effective delivery of salinomycin to CD20+ melanoma CSCs and represent a promising treatment for melanoma.

Heterodimer Formation of BnPKSA or BnPKSB with BnACOS5 Constitutes a Multienzyme Complex in Tapetal Cells and is Involved in Male Reproductive Development in Brassica napus.

Multienzyme associations localized to specific subcellular sites are involved in several critical functions in cellular metabolism, such as plant survival and reproduction. To date, few multienzyme complexes involved in male fertility have been examined in Brassica napus Here, we reported that in B. napus, the members of a multienzyme complex work in an interaction pattern different from that in Arabidopsis thaliana for sporopollenin biosynthesis. 7365A, a male-sterile mutant with a relatively smooth anther cuticle, was found to have a dramatic reduction in both cutin monomers and wax composition. Proteomic comparison between the mutant 7365A and wild-type 7365B showed down-regulation of three sporopollenin biosynthetic enzymes, namely BnPKSA, BnPKSB and BnTKPR; these enzymes were tightly co-expressed with BnACOS5. BnPKSA and BnPKSB showed similar expression patterns but distinct accumulation levels, suggesting that they had partially distinct functions during sporopollenin biosynthesis. In vitro and in vivo analyses demonstrated that BnPKSB directly interacted with BnPKSA and BnACOS5, but no such interactions were found in the present investigation for BnTKPR1. Interestingly, the interaction between PKSA and PKSB has not been discovered in Arabidopsis, which may indicate a new interaction representing an additional efficient regulation method in B. napus Taken together, we propose that BnPKSA and BnPKSB may comprise a heterodimer combined with BnACOS5, constituting a sporopollenin metabolon in tapetal cells that is related to male reproductive development in B. napus.

Bone morphogenic protein-2 regulates the myogenic differentiation of PMVECs in CBDL rat serum-induced pulmonary microvascular remodeling.

Hepatopulmonary syndrome (HPS) is characterized by an arterial oxygenation defect induced by intrapulmonary vasodilation (IPVD) that increases morbidity and mortality. In our previous study, it was determined that both the proliferation and the myogenic differentiation of pulmonary microvascular endothelial cells (PMVECs) play a key role in the development of IPVD. However, the molecular mechanism underlying the relationship between IPVD and the myogenic differentiation of PMVECs remains unknown. Additionally, it has been shown that bone morphogenic protein-2 (BMP2), via the control of protein expression, may regulate cell differentiation including cardiomyocyte differentiation, neuronal differentiation and odontoblastic differentiation. In this study, we observed that common bile duct ligation (CBDL)-rat serum induced the upregulation of the expression of several myogenic proteins (SM-α-actin, calponin, SM-MHC) and enhanced the expression levels of BMP2 mRNA and protein in PMVECs. We also observed that both the expression levels of Smad1/5 and the activation of phosphorylated Smad1/5 were significantly elevated in PMVECs following exposure to CBDL-rat serum, which was accompanied by the down-regulation of Smurf1. The blockage of the BMP2/Smad signaling pathway with Noggin inhibited the myogenic differentiation of PMVECs, a process that was associated with relatively low expression levels of both SM-α-actin and calponin in the setting of CBDL-rat serum exposure, although SM-MHC expression was not affected. These findings suggested that the BMP2/Smad signaling pathway is involved in the myogenic differentiation of the PMVECs. In conclusion, our data highlight the pivotal role of BMP2 in the CBDL-rat serum-induced myogenic differentiation of PMVECs via the activation of both Smad1 and Smad5 and the down-regulation of Smurf1, which may represent a potential therapy for HPS-induced pulmonary vascular remodeling.

Sequential combination therapy with pegylated interferon leads to loss of hepatitis B surface antigen and hepatitis B e antigen (HBeAg) seroconversion in HBeAg-positive chronic hepatitis B patients receiving long-term entecavir treatment.

Nucleos(t)ide analogues rarely result in a durable off-treatment response in chronic hepatitis B infection, whereas pegylated interferon (Peg-IFN) induces a long-lasting response only in a subset of patients. We assessed the effect of sequential combination therapy with Peg-IFN-α2a and entecavir in hepatitis B e antigen (HBeAg)-positive patients with prior long-term entecavir therapy and investigated the predictors of response to treatment. HBeAg-positive individuals who did not achieve HBeAg seroconversion during previous long-term entecavir therapy, receiving Peg-IFN-α2a added to ongoing entecavir therapy (sequential combination [S-C] therapy; n = 81) for 48 weeks or remaining on entecavir monotherapy (n = 116), were retrospectively included. A matched pair was created at a 1:1 ratio from each treatment group. The primary endpoint was HBeAg seroconversion at week 48. Subgroup analysis of response prediction was conducted for 81 patients with S-C therapy. More patients in the S-C therapy group achieved HBeAg seroconversion than those in the entecavir group (44% versus 6%; P < 0.0001). An HBeAg level of <200 signal-to-cutoff ratio (S/CO) at baseline was a strong predictor for higher HBeAg seroconversion than that achieved when HBeAg was ≥200 S/CO (64.2% versus 17.9%; P < 0.0001). Hepatitis B surface antigen (HBsAg) levels at baseline and the decrease in HBsAg levels predicted HBsAg loss in the S-C therapy group. The combination of baseline HBeAg of <200 S/CO and HBsAg of <1,000 IU/ml and an HBsAg decline at week 12 of ≥0.5 log10 IU/ml provided the highest rate of HBeAg seroconversion (92.31%) and HBsAg loss (83.3%) at week 48. Patients receiving sequential combination therapy have a higher rate of HBeAg seroconversion and are more likely to experience HBsAg clearance than do those continuing entecavir monotherapy. Sequential combination therapy can be guided by baseline HBsAg/HBeAg levels and on-treatment HBsAg dynamics.

Effects of vitamin E-coated dialysis membranes on anemia, nutrition and dyslipidemia status in hemodialysis patients: a meta-analysis.

BACKGROUND: This was controversial whether vitamin E-coated dialyzer therapy was beneficial for the complications associated with hemodialysis. Therefore, we performed this systematic review to evaluate the effects of vitamin E-coated dialyzer. METHODS: Related trials were searched from multiple electronic databases. We conducted meta-analysis to assess changes in the predefined outcomes using RevMan 5.3 software. RESULTS: Meta-analysis showed vitamin E-coated dialyzer therapy could decrease erythropoietin (EPO) resistance index (SMD, -0.24; 95% CI, -0.47 to -0.01; p = 0.04). However, pooled-analysis showed vitamin E-coated dialyzer therapy could not decrease weekly EPO dose (SMD, -0.11; 95% CI, -0.32 to 0.09; p = 0.28) and intima-media thickness (IMT) of the carotid artery (MD, -0.09; 95% CI, -0.2 to 0.01; p = 0.09), and vitamin E-coated dialyzer therapy did not improve the serum hemoglobin (MD, -0.03; 95% CI, -0.18 to 0.13; p = 0.74), albumin levels (SMD, -0.64; 95% CI, -1.62 to 0.34; p = 0.2), in addition, there was no significant difference in serum cholesterol (SMD, -0.07; 95% CI, -0.45 to 0.31; p = 0.71), triglycerides (MD, -2.77; 95% CI, -32.42 to 26.87; p = 0.85), high density lipoprotein (HDL) (SMD, 0.24; 95% CI, -0.14 to 0.62; p = 0.22) and low density lipoprotein (LDL) (SMD, 0.00; 95% CI, -0.38 to 0.37; p = 0.98) levels. CONCLUSIONS: Vitamin E-coated dialyzer may reduce the EPO resistance, but there is no conclusive evidence that vitamin E-coated dialyzer can improve the renal anemia, malnutrition, dyslipidemia and atherosclerosis status in hemodialysis (HD) patients. However, high-quality trials with hard clinical endpoints are required to fully elucidate the clinical value of vitamin E-coated dialyzer therapy.

Ligustilide-loaded liposome ameliorates mitochondrial impairments and improves cognitive function via the PKA/AKAP1 signaling pathway in a mouse model of Alzheimer's disease.

BACKGROUND: Oxidative stress is an early event in the development of Alzheimer's disease (AD) and maybe a pivotal point of interaction governing AD pathogenesis; oxidative stress contributes to metabolism imbalance, protein misfolding, neuroinflammation and apoptosis. Excess reactive oxygen species (ROS) are a major contributor to oxidative stress. As vital sources of ROS, mitochondria are also the primary targets of ROS attack. Seeking effective avenues to reduce oxidative stress has attracted increasing attention for AD intervention. METHODS: We developed liposome-packaged Ligustilide (LIG) and investigated its effects on mitochondrial function and AD-like pathology in the APPswe/PS1dE9 (APP/PS1) mouse model of AD, and analyzed possible mechanisms. RESULTS: We observed that LIG-loaded liposome (LIG-LPs) treatment reduced oxidative stress and ß-amyloid (Aß) deposition and mitigated cognitive impairment in APP/PS1 mice. LIG management alleviated the destruction of the inner structure in the hippocampal mitochondria and ameliorated the imbalance between mitochondrial fission and fusion in the APP/PS1 mouse brain. We showed that the decline in cAMP-dependent protein kinase A (PKA) and A-kinase anchor protein 1 for PKA (AKAP1) was associated with oxidative stress and AD-like pathology. We confirmed that LIG-mediated antioxidant properties and neuroprotection were involved in upregulating the PKA/AKAP1 signaling in APPswe cells in vitro. CONCLUSION: Liposome packaging for LIG is relatively biosafe and can overcome the instability of LIG. LIG alleviates mitochondrial dysfunctions and cognitive impairment via the PKA/AKAP1 signaling pathway. Our results provide experimental evidence that LIG-LPs may be a promising agent for AD therapy.

MOFs-alginate/polyacrylic acid/poly (ethylene imine) heparin-mimicking beads as a novel hemoadsorbent for bilirubin removal in vitro and vivo models.

Metal-organic frameworks (MOFs) have a potential application in blood purification, but their microcrystalline nature has hampered their industrial application. Here, novel MOFs-polymer beads based on UiO, sodium alginate, polyacrylic acid, and poly (ethylene imine) were prepared and applied as a whole blood hemoadsorbent for the first time. The amidation among polymers immobilized UiO66-NH2 into the network of the optimal product (SAP-3), and the NH2 of UiO66-NH2 significantly increased the removal rate (70 % within 5 min) of SAP-3 on bilirubin. The adsorption of SAP-3 on bilirubin mainly obeyed the pseudo-second-order kinetic, Langmuir isotherm and Thomas models with a maximum adsorption capacity (qm) of 63.97 mg·g-1. Experimental and density functional theory simulation results show that bilirubin was mainly adsorbed by UiO66-NH2via electrostatic force, hydrogen bonding, and π-π interactions. Notably, the adsorption in vivo show that the total bilirubin removal rate in the whole blood of the rabbit model was up to 42 % after 1 h of adsorption. Given its excellent stability, cytotoxicity, and hemocompatibility, SAP-3 has a great potential in hemoperfusion therapy. This study proposes an effective strategy for settling the powder property of MOFs and could provide experimental and theoretical references for application of MOFs in blood purification.

Artificial saliva precipitation index (ASPI): An efficient evaluation method of wine astringency.

Astringency is one of the most important organoleptic characteristics of red wines, and its intensity evaluation method has been the focus of research in recent years. An artificial saliva system was developed to establish an accurate and reliable evaluation method for the astringency intensity of dry red wines based on saliva precipitation index (SPI). To achieve this, five key protein families, which presented high reactivities and sensitivities in protein-tannin binding reactions, were selected from human whole saliva. The concentrations of the five proteins (proline-rich protein, α-amylase, lactoferrin, lysozyme, and albumin) and pH were optimized using response surface methodology based on the human salivary conditions to simulate the real salivary environment. The artificial saliva precipitation index method was applied to 60 commercial dry red wines and it exhibited a high correlation (CoefASPI = 0.94) with the sensory scores, indicating better performance than the traditional SPI method and other analytical approaches.

BnMs3 is required for tapetal differentiation and degradation, microspore separation, and pollen-wall biosynthesis in Brassica napus.

7365AB, a recessive genetic male sterility system, is controlled by BnMs3 in Brassica napus, which encodes a Tic40 protein required for tapetum development. However, the role of BnMs3 in rapeseed anther development is still largely unclear. In this research, cytological analysis revealed that anther development of a Bnms3 mutant has defects in the transition of the tapetum to the secretory type, callose degradation, and pollen-wall formation. A total of 76 down-regulated unigenes in the Bnms3 mutant, several of which are associated with tapetum development, callose degeneration, and pollen development, were isolated by suppression subtractive hybridization combined with a macroarray analysis. Reverse genetics was applied by means of Arabidopsis insertional mutant lines to characterize the function of these unigenes and revealed that MSR02 is only required for transport of sporopollenin precursors through the plasma membrane of the tapetum. The real-time PCR data have further verified that BnMs3 plays a primary role in tapetal differentiation by affecting the expression of a few key transcription factors, participates in tapetal degradation by modulating the expression of cysteine protease genes, and influences microspore separation by manipulating the expression of BnA6 and BnMSR66 related to callose degradation and of BnQRT1 and BnQRT3 required for the primary cell-wall degradation of the pollen mother cell. Moreover, BnMs3 takes part in pollen-wall formation by affecting the expression of a series of genes involved in biosynthesis and transport of sporopollenin precursors. All of the above results suggest that BnMs3 participates in tapetum development, microspore release, and pollen-wall formation in B. napus.

Supramolecular aggregation/disaggregation-based molecular sensing: a review focused on investigations from China.

Supramolecular aggregation and disaggregation induced by external stimuli can impact the optical or electrical signals of the aggregates/constituting units (receptors). Therefore, manipulating supramolecular aggregation/disaggregation has recently been employed to construct novel and promising photoluminescence (PL)-based sensing and recognition systems. The sensing systems were capable of substantially enhancing the sensitivity, relying on cooperative interactions occurring in the assembly/disassembly processes (mostly operating in emission turned-on or emission-enhanced mode). This review focuses mainly on recent advances in the new emerging PL-based sensing platforms, based on manipulating the behaviours of supramolecular aggregation/disaggregation, including aggregation-induced emission (AIE), metallophilic interactions-related sensing (metallophilic interactions-induced aggregation/disaggregation), metal coordination polymers-related sensing, and other sensing systems involving supramolecular aggregation/disaggregation. In particular, those sensing systems developed by scientists in China are summarized and highlighted.

Repair of exposure and fracture of the porous high-density polyethylene framework after ear reconstruction.

OBJECTIVE: To assess the repair method of exposure or fracture of the porous high-density polyethylene ear framework after total auricle reconstruction. STUDY DESIGN: A prospective case study. METHODS: From April 2018 to October 2021, 11 patients with framework exposure or fracture after total auricle reconstruction were admitted to the hospital for repair. In these 11 patients, the repair was performed using (1) a temporal muscle flap combined with free skin graft in 5 patients, (2) a mastoid fascia flap combined with free skin graft in 2 patients, (3) a simple local skin flap in 1 patient, (4) combination of a temporalis muscle flap and a mastoid fascia flap together with free skin graft in 2 patients, and (5) a Su-Por helix material combined with a temporal muscle flap and free skin graft in 1 patient. RESULTS: After follow-up for 3-36 months, except for one patient in whom local exposure again occurred at the same site, the framework was in a good shape in the other patients, and all the skin graft survived. CONCLUSION: The defect of the upper part of the auricle can be repaired using a temporal muscle flap combined with temporal muscle fascia and skin graft. The defect of the middle and lower part of the auricle can be repaired using a mastoid fascia flap combined with skin graft. For framework fracture, the damaged site can be first strengthened with another ear material and then combined with the adjacent fascia flap and free skin graft.

Microplastics: A review of analytical methods, occurrence and characteristics in food, and potential toxicities to biota.

Microplastics (MPs) are ubiquitous in various environment compartments, including food. Here, we collected research reports of MPs in food published during 2010-2020, and summarized the analytical methods developed and utilized by researchers (e.g., digestion, separation and identification, as well as related QA/QC measures implemented), the occurrence, and the characteristics of MPs in six kinds of food. The potential effects on biota from exposure to MPs were also reviewed. The results showed that most researchers digested food samples using chemical solutions such as HNO3, H2O2, KOH, or NaOH. FT-IR and Raman spectroscopy were the main technique for identifying MPs, and microscopes were used to count MP particles. The abundances MPs were in the ranges of 0-5860, 2.00-1100, 0-698, 4.00-18.7, 0-5.68 × 104 and 900-3000 particles/kg in beverages, condiments, honey, meat, seafood and vegetables, respectively. The "maximum" annual human intake of MPs from these foods is approximately 1.42 × 105-1.54 × 105 particles/capita, equivalent to the consumption of 50 plastic bags (size: 0.04 mm × 250 mm × 400 mm, density: 0.98 g/cm3) each year. Blue-colored and fiber-shaped MP particles were the most commonly observed in food, predominated by PA, PE, PES, PET and PP types. Toxicity studies indicated that MPs, additives of MPs and adsorbents or microorganisms on the surfaces of MPs were all somewhat toxic to cells or biota. Exposure to MPs may induce oxidative stress, inflammation, neurotoxicity, and reproductive toxicity, and change the structure of intestinal microflora in cells or biota. Therefore, we call for more investigation into the residual, excretion and bioavailability of MPs or related absorbents/additives in biota and humans.

Auricular reconstruction using Medpor combined with different hearing rehabilitation approaches for microtia.

BACKGROUND: Congenital microtia-atresia affects patients in two specific ways: severe conductive hearing loss and difficulty in integrating into social environments due to auricle malformation. AIMS/OBJECTIVES: To investigate the safety and efficacy of single-stage auricular reconstruction and hearing rehabilitation in children with microtia and external auditory canal atresia. MATERIAL AND METHODS: From January 2016 to December 2019, we included 32 patients with microtia and external canal atresia who received auricle reconstruction with high-density polyethylene (Medpor) framework and three different hearing rehabilitation approaches at the Ninth People's Hospital affiliated to Shanghai Jiao Tong University School of Medicine. Twenty patients underwent the traditional external auditory canal and middle ear repair (EACR), eight patients were implanted with Bonebridge (BB) devices, and four patients were implanted with bone-anchored hearing aid (BAHA) in one stage. Postoperative changes in auricle morphology and hearing and speech recognition and occurrence of complications were evaluated. RESULTS: After 6-24 months of follow-up, the auricle shape recovered well in all three groups, and the average score of 14 fine structures in the auricle was 9.43 (EACR), 10.67 (BB), and 9.75 (BAHA) points. The average score of auricle symmetry was 6.83 (EACR), 6.00 (BB), and 6.44 (BAHA) points. No significant differences in auricle shape were observed among the three groups (p > .05). After surgery, the average hearing improvement in the BB group was 43.33 dB, and the average speech recognition threshold declined to 42.28 dB. In the BAHA group, the average hearing improvement was 35 dB, and the average speech recognition threshold declined to 33.5 dB, similar to that of the BB group. However, in the EACR group, the average hearing improvement was only 4.13 dB, and the average speech recognition threshold declined to 11.36 dB. No vertigo, tinnitus, cerebrospinal fluid leakage, facial nerve paralysis, osseointegration failure, and other complications occurred in all the patients. In the EACR group, auricle stent fracture, ear canal restenosis, and canal atresia occurred in one patient each. In the BAHA group, two patients developed local ear infections. CONCLUSIONS AND SIGNIFICANCE: The procedure of single-stage auricular reconstruction and hearing rehabilitation for microtia is feasible and effective. The appropriate method of hearing reconstruction should be determined by evaluating the development of the inner and middle ear of the patients. For those patients with poor development of the mastoid and ossicular chain, hearing aid devices are recommended to achieve a stable and significant hearing effect.

You are what you eat: Microplastics in the feces of young men living in Beijing.

PURPOSE: Microplastics have been widely detected in the environment and marine organisms. However, few studies have investigated the presence of microplastics in humans. This preliminary study identified and quantified the microplastic content in human feces. METHODS: A total of 26 young male students aged 18-25 years were recruited from Beijing, China. A self-administered 7-day 24-h fluid intake record was used to document fluid intake, and food intake was recorded for 3 days. Feces were collected by participants using a sterile fecal collector. Microplastics in the remaining fecal residues were measured and identified using fourier transform infrared micro-spectroscopy. RESULTS: Eventually, twenty-four participants completed the study. The fecal samples of 23 (95.8%) participants tested positive for microplastics. In these 23 samples, the abundance of microplastics varied from 1 particle/g to 36 particles/g (size 20 to 800 µm). The summed mass of all microplastic particles per participant ranged from 0.01 to 14.6 mg. Qualitative analysis of the microplastics indicated the presence of one to eight types of microplastics in each sample, with polypropylene (PP) being the most abundant; it was found in 95.8% of fecal samples. We examined associations between water intake habits and the abundance of microplastics in their feces. A moderate correlation was observed between packaged water and beverage intake and microplastic abundance in feces (r = 0.445, P = 0.029). CONCLUSION: Various types of microplastics were detected in human feces, with PP being found in the highest proportion. There may be an association between water intake habits and microplastic abundance in feces.

Efficacy and safety of a novel submucosal injection solution for endoscopic resection in porcine models.

OBJECTIVE: A submucosal injection is usually required to improve the efficacy and safety of endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR). This study aimed to evaluate the performance of 3.3% sodium carboxymethyl starch (Na-CMS) solution, a novel submucosal injection solution, for ESD and EMR. METHODS: Na-CMS, normal saline (NS) and two commercially available agents (sigMAVisc and Eleview) were injected into the esophageal submucosa of randomly grouped pigs. The level of submucosal elevation was examined. Subsequently, ESD or EMR procedures using 3.3% Na-CMS or NS as submucosal injections were performed in the gastrointestinal tract of the pigs. RESULTS: Submucosal elevation was significantly higher and more sustained in the 3.3% Na-CMS group than in the controls (P < 0.05). The volume required for ESD or EMR was significantly lower in the 3.3% Na-CMS group than in the NS group (ESD: 12.21 ± 4.09 mL vs 28.25 ± 8.02 mL, P < 0.001; EMR: 3.99 ± 1.98 mL vs 7.15 ± 3.67 mL, P = 0.001). The ESD resection time was significantly shorter in the 3.3% Na-CMS group than in the NS group (16.58 ± 7.30 min vs 25.29 ± 11.89 min, P = 0.004). Hemorrhage after ESD in the 3.3% Na-CMS group was less severe than that in the NS group (P = 0.006). CONCLUSION: 3.3% Na-CMS is an effective, safe and low-cost submucosal injection solution and holds promise as preferable agent for submucosal injection in ESD and EMR procedures.

[Inhibition of hepatitis B virus (HBV) replication using antisense LNA targeting to both S and C genes in HBV].

OBJECTIVE: To investigate the inhibitory effect on HBV replication of antisense locked nucleic acid (LNA) targeting to both S and C genes in HBV transgenic mice. METHODS: Thirty HBV transgenic mice were randomly divided into five groups (n = 6): glucose control group were treated with 5% glucose solution, liposome control group were treated with liposome alone, S group were treated with LNA targeting to S gene, C group were treated with LNA targeting to C gene, and dual-target group were treated with LNA targeting to both S and C genes. Antisense LNA was injected into mice via the tail vein. Serum HBsAg was quantified by TRFIA. Serum HBV DNA was quantified by real-time PCR. The expression of HBV C-mRNA in the liver was detected by RT-PCR. The expression of HBsAg and HBcAg in the liver was detected by immunohistochemistry. Serum ALB, ALT, BUN and CR were measured using an automatic biochemical analyzer. The effects of antisense LNA on mouse organs were investigated by HE staining. RESULTS: 5 days after LNA injection, serum HBsAg levels in the dual-target group were reduced by 72.8%, and serum HBV DNA levels were decreased by 52.9%. These values were significantly higher than those in the control groups (all P < 0.05). No significant differences were noted in serum ALB, ALT, BUN and CR between the experiment groups and the control groups (all P > 0.05). The expression levels of HBsAg and HBcAg in the liver of dual-target group were significantly lower than those in the control groups. No significant histopathological abnormality was found in liver and kidney tissues in all groups. CONCLUSION: Antisense LNA targeting to both S and C genes can significantly inhibit HBV replication in transgenic mice.

[Effects of copper content on the antibacterial performance and corrosion resistance of CoCrMoCu alloy].

OBJECTIVE: This study aimed to determine the effects of copper content on the corrosion resistance of CoCrMoCu alloy and its in vitro antibacterial performance. METHODS: CoCrMoCu specimens with different Cu contents (2%, 3%, 5%, and 7%) were prepared by vacuum melting method. CoCrMo without Cu served as control. The corrosion resistance of the specimens was measured by electrochemistry. The antibacterial effects of the specimens on Staphylococcus aureus and Escherichia coli were analyzed by coating-film method. RESULTS: Compared with CoCrMo without Cu, the addition of 2%-5% Cu to CoCrMo improved the pitting and uniform corrosion of CoCrMo alloy and decreased the corrosion current density. The antibacterial performance of CoCrMoCu alloy increased with increased Cu content. The antibacterial rate of alloy was 99% when Cu content exceeded 5%. CONCLUSIONS: Cu addition had a statistically significant influence on the corrosion resistance and antibacterial performance of CoCrMoCu. CoCrMoCu has better corrosion resistance and antibacterial performance when Cu content is 5%.

Oral microbial community assembly under the influence of periodontitis.

Several ecological hypotheses (e.g., specific plaque, non-specific plaque and keystone pathogen) regarding the etiology of periodontitis have been proposed since the 1990s, most of which have been centered on the concept of dysbiosis associated with periodontitis. Nevertheless, none of the existing hypotheses have presented mechanistic interpretations on how and why dysbiosis actually occurs. Hubbell's neutral theory of biodiversity offers a powerful null model to test hypothesis regarding the mechanism of community assembly and diversity maintenance from the metagenomic sequencing data, which can help to understand the forces that shape the community dynamics such as dysbiosis. Here we reanalyze the dataset from Abusleme et al.'s comparative study of the oral microbial communities from periodontitis patients and healthy individuals. Our study demonstrates that 14 out of 61 communities (23%) passed the neutrality test, a percentage significantly higher than the previous reported neutrality rate of 1% in human microbiome (Li & Ma 2016, Scientific Reports). This suggests that, while the niche selection may play a predominant role in the assembly and diversity maintenance in oral microbiome, the effect of neutral dynamics may not be ignored. However, no statistically significant differences in the neutrality passing rates were detected between the periodontitis and healthy treatments with Fisher's exact probability test and multiple testing corrections, suggesting that the mechanism of community assembly is robust against disturbances such as periodontitis. In addition, our study confirmed previous finding that periodontitis patients exhibited higher biodiversity. These findings suggest that while periodontitis may significantly change the community composition measured by diversity (i.e., the exhibition or 'phenotype' of community assembly), it does not seem to cause the 'mutation' of the 'genotype" (mechanism) of community assembly. We argue that the 'phenotypic' changes explain the observed link (not necessarily causal) between periodontitis and community dysbiosis, which is certainly worthy of further investigation.