Mid-infrared reconfigurable all-dielectric metasurface based on Ge2Sb2Se4Te1 phase-change material.

In this paper, a reconfigurable all-dielectric metasurface based on Ge2Sb2Se4Te1 (GSST) phase-change material is proposed. By changing GSST from amorphous state to crystalline state, the metasurface can achieve high circular dichroism (CD) and wideband polarization conversion for circularly polarized waves in the mid-infrared (MIR) band. The maximum CD value reaches 0.95 at 74 THz, and circular polarization conversion efficiency is more than 90% in the wideband range of 41 THz - 48 THz. In addition, based on Pancharatnam-Berry phase, three kinds of wavefront manipulation of light have been realized: abnormal refraction, orbital angular momentum vortex beam and orbital angular momentum vortex beam splitting. This work has potential applications in the future MIR optical integrated system.

Prior nasal delivery of antagomiR-122 prevents radiation-induced brain injury.

Radiation-induced brain injury is a major adverse event in head and neck tumor treatment, influencing the quality of life for the more than 50% of patients who undergo radiation therapy and experience long-term survival. However, no effective treatments are available for these patients, and preventative drugs and effective drug-delivery methods must be developed. Based on our results, miR-122-5p was upregulated in the mouse radiation-induced brain injury (RBI) model and patients with nasopharyngeal carcinoma (NPC) who received radiation therapy. Intranasal administration of a single antagomiR-122-5p dose before irradiation effectively alleviated radiation-induced cognitive impairment, neuronal injury, and neuroinflammation in the mouse RBI model. Results further indicated that miR-122-5p inhibition in microglia reduced the levels of proinflammatory cytokines and enhanced the phagocytic function to protect against radiation-induced neuronal injury in cell models. Further, we profiled transcriptome data and verified that Tensin 1 (TNS1) may be the target of miR-122-5p in RBI. In summary, our results reveal a distinct role for miR-122-5p in regulating neuroinflammation in RBI, indicating that a non-invasive strategy for intranasal miR-122-5p administration may be an attractive therapeutic target in RBI, providing new insights for clinical trials. Further systematic safety assessment, optimization of drug administration, and clarity of mechanism will accelerate the process into clinical practice.

Circular dichroism metamirror with diversified chiral molecules combinations.

In this paper, we propose a giant circular dichroism (CD) chiral metamirror that differentially absorbs circularly polarized (CP) waves with dual/multi bands. The structure is composed of two variable τ resonators with counter split opening directions and different eigenfrequencies. Even more important, these two resonators are aligned vertically, and then integrated into one periodical unit cell, which results in the high-efficiency absorptive CD. The chiral metamirror has a narrow-band absorption of the left-handed circularly polarized (LCP) wave for lower resonance, and a broadband absorption of the right-handed circularly polarized (RCP) wave in the higher-frequency range. Optical resonator designs with diversified chiral molecules combinations are further studied in detail. Through the study of different periodic arrangements, parameters scanning optimization, and power loss distributions, it is proved that the overall permutation symmetry breakdown of total combined chiral molecules is the determining factor for the absorptive CD. Based on the principle in the microwave model, two mid-infrared chiral metamirrors are further realized, which can still show good spin-dependent absorption. This multi-polarization and multifunction response advance novel photonic devices for a variety of applications including CP laser, biomolecules detection, and energy harvester.

Development and validation of a simple-to-use nomogram to predict the deterioration and survival of patients with COVID-19.

BACKGROUND: COVID-19 pandemic has forced physicians to quickly determine the patient's condition and choose treatment strategies. This study aimed to build and validate a simple tool that can quickly predict the deterioration and survival of COVID-19 patients. METHODS: A total of 351 COVID-19 patients admitted to the Third People's Hospital of Yichang between 9 January to 25 March 2020 were retrospectively analyzed. Patients were randomly grouped into training (n = 246) or a validation (n = 105) dataset. Risk factors associated with deterioration were identified using univariate logistic regression and least absolute shrinkage and selection operator (LASSO) regression. The factors were then incorporated into the nomogram. Kaplan-Meier analysis was used to compare the survival of patients between the low- and high-risk groups divided by the cut-off point. RESULTS: The least absolute shrinkage and selection operator (LASSO) regression was used to construct the nomogram via four parameters (white blood cells, C-reactive protein, lymphocyte≥0.8 × 109/L, and lactate dehydrogenase ≥400 U/L). The nomogram showed good discriminative performance with the area under the receiver operating characteristic (AUROC) of 0.945 (95% confidence interval: 0.91-0.98), and good calibration (P = 0.539). Besides, the nomogram showed good discrimination performance and good calibration in the validation and total cohorts (AUROC = 0.979 and AUROC = 0.954, respectively). Decision curve analysis demonstrated that the model had clinical application value. Kaplan-Meier analysis illustrated that low-risk patients had a significantly higher 8-week survival rate than those in the high-risk group (100% vs 71.41% and P < 0.0001). CONCLUSION: A simple-to-use nomogram with excellent performance in predicting deterioration risk and survival of COVID-19 patients was developed and validated. However, it is necessary to verify this nomogram using a large-scale multicenter study.

LncRNA H19 rs4929984 Variant is Associated with Coronary Artery Disease Susceptibility in Han Chinese Female Population.

Long non-coding RNAs (lncRNAs) have been reported to play an important role in cardiovascular diseases. The present study aimed to investigate the levels of lncRNA H19 in patients with coronary artery disease (CAD) and the genetic association of lncRNA H19 rs217727 and rs4929984 polymorphisms with CAD susceptibility. We detected an upregulated expression of lncRNA H19 in the peripheral blood of CAD patients compared with healthy controls, and the area under the receiver operating characteristic curve of lncRNA H19 for CAD diagnosis was 0.918. In addition, rs4929984 was associated with the susceptibility of Han Chinese females to CAD, as shown in the additive and dominant models, and the significant association remained after adjusting for age and Bonferroni correction. The A allele carriers of rs4929984 were correlated with females' susceptibility to CAD compared with the C allele, and the A-G haplotype of rs4929984-rs217727 was associated with females' susceptibility to CAD. Furthermore, rs217727 and rs4929984 were associated with the levels of clinicopathological parameters of CAD cases. We suggest that lncRNA H19 has a potential to be a diagnostic biomarker for CAD; rs4929984 polymorphism is associated with females' susceptibility to CAD in the Han Chinese population, and lncRNA H19 variants may influence lipid metabolism, inflammation, and coagulation function of CAD patients.

Chirality selective metamaterial absorber with dual bands.

In this paper, a sensitive chirality selective metamaterial absorber (CSMA) is constructed by using 'I-shaped' resonator with asymmetric twisted metallic wires. Absorption of 95.18% and 91.77% at two resonant frequencies can be achieved for left-handed circularly polarized (LCP) incident wave, with little loss of right-handed circularly polarized (RCP) incident wave, which results in significant absorptive circular dichroism. Not only can the CSMA intensely absorb LCP illumination with dual bands, but also circularly polarized (CP) conversion for RCP wave is achieved over a broad bandwidth. The spin-dependent absorption, closely linked to chiral symmetry breaking, is investigated through oblique incidence, power loss distribution and scanning parameters optimization. The proposed strategy is further demonstrated in mid-infrared band which could advance the applications in polarization manipulation to circularly polarized detectors/lasers, chiral sensing/bolometers, and molecular spectroscopy.

Characterization of newly emerged NADC30-like strains of porcine reproductive and respiratory syndrome virus in China.

Different strains of porcine reproductive and respiratory syndrome virus (PRRSV) have emerged and circulated in different regions of mainland China since 1996, particularly after 2006. In 2012, NADC30-like PRRSV was first isolated in Henan Province. By 2016, it had spread to most provinces in China. In the present study, the whole genomes (excluding the poly(A) tails) of 13 newly emerged NADC30-like PRRSV strains were sequenced and analyzed. Furthermore, the pathogenicity of SD53-1603, one of the 13 PRRSV strains, was assessed. Phylogenetic analysis showed that these 13 newly emerged NADC30-like PRRSV strains, together with some reference strains, formed a new subgroup (subgroup 5), characterized by a predicted 131-amino-acid deletion in the nonstructural protein (NSP) 2. However, low levels of whole-genome similarity and a wide variety of recombination patterns complicated the classification of the NADC30-like PRRSV isolates. Interestingly, almost all of the recombination breakpoints found in these 13 PRRSV isolates and other NADC30-like PRRSV isolates occurred in genes encoding NSPs and/or minor structural proteins. In addition, piglets infected with the newly emerged NADC30-like strain SD53-1603 displayed clear clinical respiratory symptoms and underwent typical pathological changes. The findings may be useful for elucidating the characteristics and epidemic status of NADC30-like PRRSV in China.

Enhanced asymmetric transmission due to Fabry-Perot-like cavity.

In this paper, a three layered metamaterial composed of a ring-chain structure sandwiched between two layers of twisted sub-wavelength cut-wire arrays is proposed and investigated. The designed structure is optimized such that asymmetric transmission with an extremely broad bandwidth, sharp rejection stop-band and high transmittance is achieved. The physical mechanism is accounted for that the metallic layers form the Fabry-Perot-like resonance cavity, enhancing the polarization conversion efficiency between two orthogonal linearly polarized waves. To some extent, this approach offers a way to strengthen asymmetric transmission effect.

Association of physical activity with MAFLD/MASLD and LF among adults in NHANES, 2017-2020.

OBJECTIVES: To investigate the correlations between physical activity (PA) and metabolic associated fatty liver disease (MAFLD) or metabolic dysfunction-associated steatotic liver disease (MASLD) within a substantial population-based survey, and to examine the association between PA and liver fibrosis (LF). METHODS: Data from the 2017-2020 NHANES cycle were utilized in this study. PA was divided into four types: leisure-time PA (LTPA), transportation-related PA (TPA), occupational PA (OPA) and total time PA (total PA, which is composed of OPA, TPA and LTPA). Weighted logistic regression models were performed to analyze the associations between PA and MAFLD/MASLD and LF. Mediation analysis was used to explore whether LTPA completely mediated the statistically significant relationship between total PA and MAFLD/MASLD or LF. RESULTS: The study encompassed a sample size of 5897 participants aged 20 years and above, among the total participants, 2568 individuals with MAFLD and 2588 individuals with MASLD. There was no statistically significant correlation observed between OPA/TPA and MAFLD/MASLD and LF; however, active LTPA demonstrated an inverse association with MAFLD/MASLD (OR: 0.548; 95% CI: 0.458, 0.656/OR: 0.543; 95% CI: 0.453, 0.650), as well as a negative correlation with significant/advanced LF (OR: 0.457; 95% CI: 0.334,0.625/OR: 0.427; 95% CI: 0.295,0.619). There was also a significant inverse association between total PA and MAFLD/MASLD or LF, but this association was carried by the difference in LTPA. CONCLUSION: Participation in active LTPA is associated with a reduced likelihood of MAFLD/MASLD and LF, while neither OPA nor TPA can replace these effects of LTPA.

Mature solid teratoma of the uterine cervix: A rare case report and review of the literature.

RATIONALE: Most of the mature teratomas are found in the ovaries. Extragonadal teratomas are extremely rare. To date, there are only a handful of reports of uterine cervical teratomas documented in the English literature. PATIENT CONCERNS: Herein we describe a rare case of a 40-year-old patient who was presented to our hospital for a cervical polypoid mass, which was finally confirmed to be mature solid teratoma in uterine cervix. DIAGNOSES: Histological examination of the polypoid mass was found to consist of ciliated pseudostratified columnar respiratory epithelium, intestinal epithelium and smooth muscle tissue, adipose tissue and mature glial component, epidermis, and skin adnexa. Meanwhile, no history of abortion, dilatation, and curettage was present in this patient, so implantation of fetal tissue was excluded. Therefore, we make a diagnosis of uterine cervical mature teratoma. INTERVENTIONS: Tumorectomy was performed after discovering the cervical polypoid mass. OUTCOMES: The patient had been followed-up for next 3 months after surgery and no recurrence was documented until now. LESSONS: Though teratomas of the uterine cervix are extremely rare, more attention should be paid on this rare but possible tumor for appropriate treatment in these patients.

Sigmoid colonic metastasis from a squamous cell carcinoma of the cervix: A rare case report with literature review.

RATIONALE: As the third most common cancer in women, cervical cancer usually spreads to adjacent organs. Distant metastasis from the cervix to the gastrointestinal tract is an extremely rare occurrence. PATIENT CONCERNS: Herein, we present a rare case of a 57-year-old woman who was treated by hysterectomy and bilateral salpingo-oophorectomy with pelvic lymphadenectomy for squamous cell carcinoma (SCC) of the uterine cervix. A metastatic location in the sigmoid colon was revealed after 8 years causing an acute intestinal obstruction in this patient. DIAGNOSES: Final surgical pathology showed an invasive lesion with squamous differentiation in full thickness of the colon wall from mucosa to serosa. Meanwhile, the results of immunohistochemistry (IHC) showed the cancer cells were positive for CK5/6, P63, P40, and P16 confirming the diagnosis of metastatic sigmoid colonic carcinoma originating from SCC of the uterine cervix. INTERVENTIONS: Sigmoid colon resection with lymph node dissection followed by adjuvant chemotherapy (paclitaxel, carboplatin, and paprillizumab) was performed on the patient. OUTCOMES: The patient was disease-free 16 months after surgery. LESSONS SUBSECTIONS: SCC is one of the rare malignant tumors of the gastrointestinal tract occurring as either a primary or secondary lesion. However, the secondary SCC of the colon has a poorer prognosis compared with the primary SCC. Therefore, colonic metastasis must be considered in the differential diagnosis of acute intestinal obstruction, especially in patients with the medical history of SCC in other organs.

Supersaturated Drug Delivery System of Oxyberberine Based on Cyclodextrin Nanoaggregates: Preparation, Characterization, and in vivo Application.

Propose: Oxyberberine (OBB), one of the main metabolites of berberine derived from intestinal and erythrocyte metabolism, exhibits appreciable anti-hyperuricemic activity. However, the low water solubility and poor plasma concentration-effect relationship of OBB hamper its development and utilization. Therefore, an OBB-hydroxypropyl-ß-cyclodextrin (HP-ß-CD) supersaturated drug delivery system (SDDS) was prepared and characterized in this work. Methods: OBB-HP-ß-CD SDDS was prepared using the ultrasonic-solvent evaporation method and characterized. Additionally, the in vitro and in vivo release experiments were conducted to assess the release kinetics of OBB-HP-ß-CD SDDS. Subsequently, the therapeutic efficacy of OBB-HP-ß-CD SDDS on hyperuricemia (HUA) was investigated by means of histopathological examination and evaluation of relevant biomarkers. Results: The results of FT-IR, DSC, PXRD, NMR and molecular modeling showed that the crystallized form of OBB was transformed into an amorphous OBB-HP-ß-CD complex. Dynamic light scattering indicated that this system was relatively stable and maintained by formation of nanoaggregates with an average diameter of 23 nm. The dissolution rate of OBB-HP-ß-CD SDDS was about 5 times higher than that of OBB raw material. Furthermore, the AUC0-t of OBB-HP-ß-CD SDDS (10.882 µg/mL*h) was significantly higher than that of the raw OBB counterpart (0.701 µg/mL*h). The oral relative bioavailability of OBB-HP-ß-CD SDDS was also enhanced by 16 times compared to that of the raw material. Finally, in vivo pharmacodynamic assay showed the anti-hyperuricemic potency of OBB-HP-ß-CD SDDS was approximately 5-10 times higher than that of OBB raw material. Conclusion: Based on our findings above, OBB-HP-ß-CD SDDS proved to be an excellent drug delivery system for increasing the solubility, dissolution, bioavailability, and anti-hyperuricemic potency of OBB.

Development and application of a blocking ELISA based on a N protein monoclonal antibody for the antibody detection against porcine reproductive and respiratory syndrome virus 2.

Porcine reproductive and respiratory syndrome (PRRS) is one of the most widespread illnesses in the world's swine business. To detect the antibodies against PRRSV-2, a blocking enzyme-linked immunosorbent assay (B-ELISA) was developed, utilizing a PRRSV-2 N protein monoclonal antibody as the detection antibody. A checkerboard titration test was used to determine the optimal detection antibody dilution, tested pig serum dilution and purified PRRSV coated antigen concentration. After analyzing 174 negative pig sera and 451 positive pig sera, a cutoff value of 40 % was selected to distinguish between positive and negative sera using receiver operating characteristic curve analysis. The specificity and sensitivity of the assay were evaluated to equal 99.8 % and 96 %, respectively. The method had no cross-reaction with PCV2, PRV, PPV, CSFV, PEDV, TGEV, and PRRSV-1 serum antibodies, and the coefficients of variation of intra-batch and inter-batch repeatability experiments were both <10 %. A total of 215 clinical serum samples were tested, and the relative coincidence rate with commercial ELISA kit was 99.06 %, and the kappa value was 0.989, indicating that these two detection results exhibited high consistency. Overall, the B-ELISA should serve as an ideal method for large-scale serological investigation of PRRSV-2 antibodies in domestic pigs.

[Enhancing the attendance rate of psychiatric day care patients].

BACKGROUND & PROBLEMS: Attending rehabilitation programs at psychiatric daycare wards has been shown to stabilize psychiatric patients' daily routines, reduce patient symptoms, and help them regain social functions. Non-attendance increases risks of patient decompensation and return to the inpatient unit, which reduces quality of care and increases medical costs. The attendance rate for psychiatric daycare patients at our hospital was 73%. To maximize rehabilitation and treatment success, we developed a special project to raise patient program-attendance motivation. PURPOSE: This study aimed to enhance the attendance rate of our psychiatric day care patients to improve patient independence and their capacity to return to the community. RESOLUTION: Methods used included rehabilitation game cards, holding medication educational workshops, utilizing reward systems, making attendance passports, and designing activity booklets. RESULTS: The attendance rate of psychiatric day care patients rose from 73% to 89%, a 16% increase. CONCLUSION: This program not only increased the attendance rate of psychiatric day care patients but also improved communications between professional care staff and patient family members. In addition, this program strengthened daycare ward staff teamwork, which further enhanced treatment quality. We suggest considering rehabilitation program attendance as an important ward quality control criterion to assess and improve treatment and nursing care quality.

Association between serum vitamin C and chronic kidney disease among adults in NHANES, 2017-2018.

OBJECTIVE: The current study evaluated the relationship between serum vitamin C and chronic kidney disease. METHODS: The database from the National Health and Nutrition Examination Survey (NHANES, 2017-2018) was used to perform a cross-sectional study. Multivariate logistic regression was performed to analyze the relationship between serum vitamin C and chronic kidney disease (CKD), and stratified analysis by sex was performed to assess whether there were sex differences in the association between serum vitamin C and CKD. RESULTS: Before stratified analysis, multivariate logistic regression showed that serum vitamin C was negatively associated with CKD in all models (All OR > 1, P< 0.05), the risk of CKD decreased by one quantile increase in serum vitamin C (P for trend< 0.001) and low vitamin C status was associated with a higher risk of CKD (All OR > 1, P< 0.05). Stratified analyses by sex showed that the association between serum vitamin C and CKD remained negative in men, but not in women. CONCLUSION: There were a negative correlation between serum vitamin C and CKD, low levels of vitamin C were associated with a higher risk of CKD, and these associations were only found in men, but not in women.

Goblet cell adenocarcinoma of the anal canal with perianal Paget disease: A rare case report with literature review.

INTRODUCTION: AS an uncommon neoplasm, goblet cell adenocarcinoma (GCA) is characterized by mixed endocrine-exocrine features. It is almost exclusively found in the appendix. Primary GCA of the anal canal is extremely rare. CASE PRESENTATION: Herein we describe a novel rare case of 74-year-old Chinese female who is diagnosed with GCA in the anal canal with perianal Paget disease, including a brief review of the literature. In the lesion of anal canal, the tumor was composed of signet-ring-like cells on confluent growth model and copious mucin was produced as well. Simultaneously, the results of immunohistochemistry showed signet-ring-like cells were positive for CK20, CDX2, synaptophysin (Syn), CD56, carcinoembryonic antigen (CEA) and Villin. Meanwhile, the Ki67-labeling index reached 40%. In the lesion of perianal Paget disease, the small groups of atypical neoplastic cells were present in the epidermis. Immunohistochemically, the neoplastic cells were positive for CK20, CDX2 and epithelial membrane antigen, but negative for CK7, GCDFP15, S100, HMB45, and P63. The Ki67-labeling index reached 60% in the most concentrated spot. CONCLUSIONS: Extra-appendiceal GCA was rare and easily under-recognizable. The diagnosis of GCA was seldom made preoperatively. Occasionally, GCA could occur in the anal canal accompanied by perianal Paget disease. So careful rectal examination was important in the patient with perianal Paget disease for avoid missing diagnosis of GCA on anal canal. GCA may show aggressive clinical behavior compared with typical well-differentiated neuroendocrine tumors. Therefore, we should pay more attention on the recognization of this rare disease.

Metastasis of endometrial adenocarcinoma masquerading as a primary rectal cancer: A rare case report with literature review.

RATIONALE: The majority of rectal malignancies are primary tumors, secondary tumors are unusual. The rectal metastasis of endometrial carcinoma is reported to be extremely rare, especially in the absence of endometriosis. PATIENT CONCERNS: Herein we present a rare case of a 68-year-old postmenopausal woman with a history of endometrial adenocarcinoma, metastasizing to the rectum 5 years after a hysterectomy and bilateral salpingo-oophorectomy treatments with pelvic lymphadenectomy were performed. DIAGNOSES: Histological examination of the rectal neoplasm revealed an invasive lesion in submucosal and muscular layers without definitely invaded evidence in the serous membrane and there was also no obvious endometriosis. The results of immunohistochemistry showed the cancer cells were positive for CK7, estrogen receptor, progesterone receptor, and negative for CK20, villin, confirming the diagnosis of metastatic rectal adenocarcinoma originating from uterine endometrial adenocarcinoma. Meanwhile, the results of immunohistochemical staining showed positive expression of MSH2, MSH6, and negative expression of MLH1 and PMS2, hinting at microsatellite instability which may be related to Lynch syndrome. INTERVENTIONS: The Dixon operation with lymph node dissection was performed. Chemotherapy was also performed on this patient for the next 6 months. OUTCOMES: The patient was followed up for the next 6 months after surgery and no recurrence was documented until now. LESSONS SUBSECTIONS: Though rectal and endometrial adenocarcinoma could share some similar morphologic features, different immunohistochemical profiles could be revealed between them. Most endometrial carcinoma in the colon or rectum develop from endometriosis. Secondary rectal cancer with endometrial origination in the absence of endometriosis and serosal implants was extremely rare. Therefore, we should pay more attention to this rare but possible presentation for appropriate diagnosis and treatment of these patients.

Risk factors for anastomotic fistula development after radical colon cancer surgery and their impact on prognosis.

BACKGROUND: Colon cancer is a common malignant tumor in the gastrointestinal tract that is typically treated surgically. However, postradical surgery is prone to complications such as anastomotic fistulas. AIM: To investigate the risk factors for postoperative anastomotic fistulas and their impact on the prognosis of patients with colon cancer. METHODS: We conducted a retrospective analysis of 488 patients with colon cancer who underwent radical surgery. This study was performed between April 2016 and April 2019 at a tertiary hospital in Wuxi, Jiangsu Province, China. A t-test was used to compare laboratory indicators between patients with and those without postoperative anastomotic fistulas. Multiple logistic regression analysis was performed to identify independent risk factors for postoperative anastomotic fistulas. The Functional Assessment of Cancer Therapy-Colorectal Cancer was also used to assess postoperative recovery. RESULTS: Binary logistic regression analysis revealed that age [odds ratio (OR) = 1.043, P = 0.015], tumor, node, metastasis stage (OR = 2.337, P = 0.041), and surgical procedure were independent risk factors for postoperative anastomotic fistulas. Multiple linear regression analysis showed that the development of postoperative anastomotic fistula (P = 0.000), advanced age (P = 0.003), and the presence of diabetes mellitus (P = 0.015), among other factors, independently affected prognosis. CONCLUSION: Postoperative anastomotic fistulas significantly affect prognosis and survival rates. Therefore, focusing on the clinical characteristics and risk factors and immediately implementing individualized preventive measures are important to minimize their occurrence.

Self-Assembled nanoparticles Combining Berberine and Sodium Taurocholate for Enhanced Anti-Hyperuricemia Effect.

Propose: Berberine (BBR) is extensively studied as an outstanding anti-hyperuricemia drug. However, the clinical application of BBR was limited due to its poor absorption and low bioavailability. Therefore, there is an urgent necessity to find a novel drug formulation to address the issues of BBR in clinical application. Methods: Herein, we conducted the solubility, characterization experiments to verify whether BBR and sodium taurocholate (STC) self-assembled nanoparticles (STC@BBR-SANPs) could form. Furthermore, we proceeded the release experiment in vitro and in vivo to investigate the drug release effect. Finally, we explored the therapeutic effect of STC@BBR-SANPs on hyperuricemia (HUA) through morphological observation of organs and measurement of related indicators. Results: The solubility, particle size, scanning electron microscopy (SEM), and stability studies showed that the stable STC@BBR-SANPs could be formed in the BBR-STC system at ratio of 1:4. Meanwhile, the tissue distribution experiments revealed that the STC@BBR-SANPs could accelerate the absorption and distribution of BBR. In addition, the pharmacology study demonstrated that both BBR and STC@BBR-SANPs exhibited favorable anti-HUA effects and nephroprotective effects, while STC@BBR-SANPs showed better therapeutic action than that of BBR. Conclusion: This work indicated that STC@BBR-SANPs can be self-assembly formed, and exerts excellent uric acid-lowering effect. STC@BBR-SANPs can help to solve the problems of poor solubility and low absorption rate of BBR in clinical use, and provide a new perspective for the future development of BBR.

Intestines-erythrocytes-mediated bio-disposition deciphers the hypolipidemic effect of berberine from Rhizoma Coptidis: A neglected insight.

ETHNOPHARMACOLOGICAL RELEVANCE: Rhizoma Coptidis (RC), the dried rhizome of Coptis Chinensis Franch., can dispel dampness and heat within the body and has been traditionally used for the treatment of cardiovascular disease (CVD)-associated problems including hyperlipidemia in China. Berberine (BBR) is the main active component of RC, which has been shown to possess significant therapeutic potential. However, only 0.14% of BBR is metabolized in the liver, and the extremely low bioavailability (<1%) and blood concentration of BBR in experimental and clinical settings is insufficient to achieve the effects as observed under in vitro conditions, which imposes challenges to explain its excellent pharmacological actions. Intense efforts are currently being devoted to defining its specific pharmacological molecular targets, while the exploration from the perspective of its pharmacokinetic disposition has rarely been reported to date, which could hardly make a comprehensive understanding of its hypolipidemic enigma. AIM OF THE STUDY: This study made a pioneering endeavor to unveil the hypolipidemic mechanism of BBR from RC focusing on its unique intestines-erythrocytes-mediated bio-disposition. MATERIALS AND METHODS: The fate of BBR in intestines and erythrocytes was probed by a rapid and sensitive LC/MS-IT-TOF method. To analyze the disposition of BBR, a reliable HPLC method was subsequently developed and validated for simultaneous determination of BBR and its key active metabolite oxyberberine (OBB) in whole blood, tissues, and excreta. Meanwhile, the enterohepatic circulation (BDC) of BBR and OBB was verified by bile duct catheterization rats. Finally, lipid overloading models of L02 and HepG2 cells were employed to probe the lipid-lowering activity of BBR and OBB at in vivo concentration. RESULTS: The results showed that BBR underwent biotransformation in both intestines and erythrocytes, and converted into the major metabolite oxyberberine (OBB). The AUC0-t ratio of total BBR to OBB was approximately 2:1 after oral administration. Besides, the AUC0-t ratio of bound BBR to its unbound counterpart was 4.6:1, and this ratio of OBB was 2.5:1, indicative of abundant binding-type form in the blood. Liver dominated over other organs in tissue distribution. BBR was excreted in bile, while the excretion of OBB in feces was significantly higher than that in bile. Furthermore, the bimodal phenomenon of both BBR and OBB disappeared in BDC rats and the AUC0-t was significantly lower than that in the sham-operated control rats. Interestingly, OBB significantly decreased triglycerides and cholesterol levels in lipid overloading models of L02 and HepG2 cells at in vivo-like concentration, which was superior to the prodrug BBR. CONCLUSIONS: Cumulatively, BBR underwent unique extrahepatic metabolism and disposition into OBB by virtue of intestines and erythrocytes. BBR and OBB were mainly presented and transported in the protein-bound form within the circulating erythrocytes, potentially resulting in hepatocyte targeting accompanied by obvious enterohepatic circulation. The unique extrahepatic disposition of BBR via intestines and erythrocytes conceivably contributed enormously to its hypolipidemic effect. OBB was the important material basis for the hypolipidemic effect of BBR and RC.