Pregabalin-induced delayed cutaneous hypersensitivity reaction occurring after 40 days of use: a case report.

Pregabalin is the first-line treatment for neuropathic pain. Cases of cutaneous hypersensitivity reactions caused by pregabalin generally occur within 2 weeks of initiating medication. We report a rare case of a delayed cutaneous hypersensitivity reaction caused by pregabalin, which was confirmed by a drug provocation test. A 72-year-old man with severe herpes zoster neuralgia developed maculopapular drug eruption covering 80% to 90% of his total body surface area after 40 days of combined multidrug analgesia. A drug provocation test for pregabalin was positive. The time interval between initiating medication and the onset of the patient's rash was the longest and he also had the largest area of skin affected compared with patients with a similar condition in previous related reports. Remaining vigilant for possible adverse cutaneous hypersensitivity reactions during treatment is important because of the long-term course of pregabalin treatment for neuropathic pain.

Current scenario and challenges of clinical pharmacists to implement pharmaceutical care in DRG/DIP payment hospitals in China: a qualitative interview study.

Purpose: The Diagnosis-Related Group (DRG) or Diagnosis-Intervention Packet (DIP) payment system, now introduced in China, intends to streamline healthcare billing practices. However, its implications for clinical pharmacists, pivotal stakeholders in the healthcare system, remain inadequately explored. This study sought to assess the perceptions, challenges, and roles of clinical pharmacists in China following the introduction of the DRG or DIP payment system. Methods: Qualitative interviews were conducted among a sample of clinical pharmacists. Ten semi-structured interviews were conducted, either online or face to face. Thematic analysis was employed to identify key insights and concerns related to their professional landscape under the DRG or DIP system. Results: Clinical pharmacists exhibited variable awareness levels about the DRG or DIP system. Their roles have undergone shifts, creating a balance between traditional responsibilities and new obligations dictated by the DRG or DIP system. Professional development, particularly concerning health economics and DRG-based or DIP-based patient care, was highlighted as a key need. There were calls for policy support at both healthcare and national levels and a revised, holistic performance assessment system. The demand for more resources, be it in training platforms or personnel, was a recurrent theme. Conclusion: The DRG or DIP system's introduction in China poses both opportunities and challenges for clinical pharmacists. Addressing awareness gaps, offering robust policy support, ensuring adequate resource allocation, and recognizing the evolving role of pharmacists are crucial for harmoniously integrating the DRG or DIP system into the Chinese healthcare paradigm.

Profile of Pancreatic and Ileal Microbiota in Experimental Acute Pancreatitis.

Acute pancreatitis (AP) is accompanied by gut microbiota dysbiosis. However, the composition of the pancreatic and ileal microbiota associated with AP is still unknown. This study aims to examine the alterations in the microbial composition of the pancreas and ileum in the context of experimental acute pancreatitis, as well as explore the potential interplay between these two regions. Methods: Caerulein (CAE), caerulein+lipopolysaccharide (CAE+LPS), and L-arginine (ARG) were used to induce AP in mice. The pancreas and ileum were collected for histological study and bacterial 16S rRNA gene sequencing. The results showed microbial structural segregation between the AP and control groups and between ARG and the two CAE groups (CAE, CAE+LPS) in the pancreas and ileum. Taxonomic analysis at the genus level and linear discriminant analysis effect size (LEfSe) at the operational taxonomic units (OTUs) level illustrated that AP mice exhibited a marked increase in the relative abundance of Muribaculaceae and a decrease in that of Dietzia both in the pancreas and ileum, and a reduction in Bifidobacterium only in the ileum; in addition, Roseburia was enriched in the two CAE groups in the pancreas and/or ileum, while Escherichia-Shigella expanded in the pancreas of the ARG group. Spearman correlation analysis between pancreatic and ileal microbiota revealed that the abundance of Muribaculaceae and Dietzia in the pancreas was related to that in the ileum. These findings demonstrated that caerulein and L-arginine differentially disturbed the pancreatic and ileal microbiota when inducing AP. Furthermore, these findings provide preliminary support for an association between the microbiota of the pancreas and ileum, which could be caused by AP-induced microbial translocation.

Can vitamin B6 alleviate the adverse reactions of quadruple anti-Helicobacter pylori regimen? : randomized controlled trial.

BACKGROUND: Vitamin B6 is an essential water-soluble vitamin for humans. It is often used to prevent a variety of neuropathies, relieve vomiting, and relieve symptoms such as hand and foot neuritis. AIM: To evaluate whether vitamin B6 can alleviate the adverse reactions caused by the quadruple anti-Helicobacter pylori treatment regimen containing minocycline and metronidazole. METHODS: In this randomized controlled trial, 280 patients with H. pylori infection were randomly placed into one of two treatment groups-the conventional treatment group and the vitamin B6 supplement treatment group-for 2 weeks. The primary endpoint was the total incidence of adverse reactions up to 2 weeks after treatment initiation. The study was designed according to CONSORT Medicinal Interventions. And it was registered with Chinese Clinical Trial Registry under the number ChiCTR2100053833. RESULTS: In terms of efficacy, vitamin B6 does not affect the efficacy of conventional regimen. In the vitamin B6 supplement treatment group, the incidence of adverse reactions was 56.92%, which was significantly lower than the 74.62% observed in the conventional treatment group. In addition, the severity of adverse reactions was also significantly reduced. The proportion of moderate to severe central nervous system symptoms decreased from 58.7 to 14.63%. And, the proportion of moderate to severe gastrointestinal reactions decreased from 33.33 to 0%. We speculate that the mechanism of vitamin B6 of reducing adverse reaction may be related to the production of GABA in the brain. CONCLUSIONS: Vitamin B6 can alleviate adverse reactions of the quadruple anti-H. pylori regimen containing minocycline and metronidazole.

Characterization of Duodenal Microbiota in Patients with Acute Pancreatitis and Healthy Controls.

OBJECTIVE: The small intestinal bacterial overgrowth (SIBO) in acute pancreatitis correlates with the severity of the disease. However, corresponding studies on the microbial composition of the duodenal mucosa of patients are uncommon. METHODS: Duodenal mucosal biopsies were collected by gastroscopy from 16 patients with mild acute pancreatitis (the Ap group) and 16 healthy individuals (the control group) and subjected to histological studies as well as bacterial 16S rRNA gene sequencing. Caerulein and L-arginine were used to induce mild acute pancreatitis (MAP) and severe acute pancreatitis (SAP) in mice, respectively, and their pancreas and duodenum were collected for histological studies. RESULTS: H&E analysis displayed no significant pathological damage in the descending duodenum of patients with acute pancreatitis compared with that of the controls. Immunofluorescence and Real-time PCR revealed that the expressions of tight junction proteins (TJPs) in duodenal mucosa were decreased in acute pancreatitis. The results of the alpha diversity analysis revealed no significant difference between the two groups, while LEfSe and the random forest revealed a few differences, indicating that the descending duodenum mucosal microbiota changed slightly in patients with mild acute pancreatitis. We observed the pathological changes and the expression of TJPs in the duodenum in the three groups of mice and found that SAP mice had more severe pathological damage in the duodenum. Furthermore, the expression of TJPs in the duodenum was lower in the MAP and SAP groups of mice compared to control mice, but it was similar in both groups. CONCLUSION: Patients with mild acute pancreatitis had mild duodenal barrier dysfunction and slight changes in duodenal mucosal microbiota.

Effectiveness and Safety of Lianhua Qingwen Capsules for COVID-19: A Propensity-Score Matched Cohort Study.

As a traditional Chinese medicine, Lianhua Qingwen capsules have been widely used to treat Coronavirus Disease 2019 (COVID-19). This study was aimed to demonstrate the association between treatment with Lianhua Qingwen capsules and the clinical outcomes of hospitalized patients with COVID-19. This retrospective study was conducted at four hospitals in Central China. Data of hospitalized COVID-19 patients were collected between December 19, 2019 and April 26, 2020. Based on whether Lianhua Qingwen capsules were used, patients were classified into Lianhua Qingwen and non-Lianhua Qingwen (control) groups. To control for confounding factors, we used conditional logistic regression in a propensity-score matched (PSM) cohort (1 : 1 balanced), as well as logistic regression without matching as sensitivity analysis. A total of 4918 patients were included, 2760 of whom received Lianhua Qingwen capsules and 2158 of whom did not. In the PSM model, after adjusting for confounders, the in-hospital mortality was similar between the Lianhua Qingwen group and the control group (6.8% vs. 3.3%, adjusted OR, 0.66 [95% CI, 0.38-1.15], p = 0.138). The negative conversion rate of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection was higher in the Lianhua Qingwen group (88.3% vs. 96.1%, adjusted OR, 4.02 [95% CI, 2.58-6.25], p < 0.001). The incidence of acute liver injury was comparable between the two groups (14.0% vs. 11.5%, adjusted OR: 0.85 [95% CI, 0.71-1.02], p = 0.083), and the incidence of acute kidney injury was lower in the Lianhua Qingwen group (5.3% vs. 3.0%, adjusted OR: 0.71 [95% CI, 0.50-1.00], p = 0.048). Treatment with Lianhua Qingwen capsules was not significantly associated with in-hospital mortality in COVID-19 patients. In the Lianhua Qingwen group, the negative conversion rate of SARS-CoV-2 infection was higher and the incidence of acute kidney injury was lower than in the control group.

The impact of Helicobacter pylori infection and eradication therapy containing minocycline and metronidazole on intestinal microbiota.

BACKGROUND: Helicobacter pylori (H. pylori) infection is associated with remodeling of gut microbiota. Many studies have found H. pylori infection and eradication therapy can alter the gut microbiota. However, few studies explored the impact of eradication therapy containing minocycline and metronidazole on gut microbiota. AIM: The objective of the present study was to explore the changes of gut microbiota after H. pylori infection. Besides, learn more about the dynamic changes of gut microbiota during different stages of eradication treatment containing minocycline, metronidazole, bismuth agents and proton pump inhibitors. METHODS: Sixty stool samples from the patients with H. pylori infection before eradication, 14 and 42 days after eradication, and ten stool samples from non-infected individuals were collected. Subsequently, we performed 16S rRNA gene amplicon sequencing to analyze these samples, and the results were evaluated by using alpha diversity, beta diversity and microbial composition analyses. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States was also used to predict the metabolic pathways according to the Kyoto Encyclopedia of Genes and Genomes database. RESULTS: The alpha and beta diversity of the microbiota changed significantly in H. pylori infected individuals, but returned to baseline 42 days after eradication therapy. At the genus level, the abundances of Bacteroidetes, [Ruminococcus]_gnavus_group, Ruminococcaceae_Incertae_Sedis, Tuzzrealla, Butyricicoccus were significantly lower in the H. pylori infected group. Bacterial abundance was also dynamically changing during eradication treatment. In addition, PICRUST analysis found the levels of uronic acid metabolism, uncharacterized transport system, and biosynthesis of unsaturated fatty acids were higher in H. pylori infected individuals than in the non-infected group. CONCLUSIONS: Intestinal microbiota diversity, composition, functional predictions altered significantly after H. pylori infection, and gradually returned to healthy control levels after the application of eradication therapy containing minocycline and metronidazole in one month and a half.

Ambroxol for the treatment of COVID-19 among hospitalized patients: A multicenter retrospective cohort study.

Ambroxol is a commonly used mucolytic agent principally used to treat respiratory diseases, which may have a role as adjunctive therapy for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, but there is lack of evidence about its effectiveness on coronavirus disease-2019 (COVID-19) patients. To study the association between ambroxol use and clinical outcomes among hospitalized patients of COVID-19 infection. We conducted a multicenter retrospective cohort study involving 3,111 patients with confirmed SARS-CoV-2 infection from three hospitals in Wuhan from 19 December 2019 to 15 April 2020, and the primary outcome was in-hospital mortality. COVID-19 patients were classified into ambroxol and non-ambroxol groups based on the administration of ambroxol during hospitalization. Two analyses including propensity score matching (PSM) to obtain a 1:1 balanced cohort and logistic regression were used to control for confounding factors. The average age of 3,111 patients was 57.55 ± 14.93 years old, 127 of them died during hospitalization, and 924 of them used ambroxol. Treatment with ambroxol did not have a significant effect on in-hospital mortality of COVID-19 patients when compared with non-ambroxol in PSM model after adjusting for confounders (8.0% vs. 3.5%, adjusted OR, 1.03 [95% CI, 0.54-1.97], p = 0.936). Adverse events such as nausea/vomiting, headache, and rash were comparable between the two groups. Our results suggest that the use of ambroxol is not significantly associated with in-hospital mortality in COVID-19 patients, which provides evidence for evaluating the effects of ambroxol on COVID-19 patient outcomes and may be helpful for physicians considering medication alternatives for COVID-19 patients.

Voriconazole-induced severe skin allergy and neurological adverse event in a liver failure patient: A case report.

WHAT IS KNOWN AND OBJECTIVE: Triazole antifungal-associated severe skin allergy has received little attention. Here we report a case of an acute-on-chronic liver failure (ACLF) patient with diffused skin allergy pervading from the chest, abdomen, back, knees to perineum, with red colour and partially desquamation as well as a neurological adverse (insomnia) event after voriconazole treatment. CASE SUMMARY: A 40-year-old man with liver failure in our hospital had received voriconazole for invasive fungal infection therapy, and while waiting for liver transplantation exhibited a severe diffuse rash and a neurological adverse event. WHAT IS NEW AND CONCLUSION: To the best of our knowledge, this is the first report of a liver failure patient who suffered a severe allergy accompanied with a neurological adverse event after voriconazole administration.

Association Between Drug Treatments and the Incidence of Liver Injury in Hospitalized Patients With COVID-19.

The outbreak of coronavirus disease 2019 (COVID-19) has led to the emergence of global health care. In this study, we aimed to explore the association between drug treatments and the incidence of drug-induced liver injury (DILI) in hospitalized patients with COVID-19. A retrospective study was conducted on 5113 COVID-19 patients in Hubei province, among which 395 incurred liver injury. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by Cox proportional hazards models. The results showed that COVID-19 patients who received antibiotics (HR 1.97, 95% CI: 1.55-2.51, p < 0.001), antifungal agents (HR 3.10, 95% CI: 1.93-4.99, p < 0.001) and corticosteroids (HR 2.31, 95% CI: 1.80-2.96, p < 0.001) had a higher risk of DILI compared to non-users. Special attention was given to the use of parenteral nutrition (HR 1.82, 95% CI: 1.31-2.52, p < 0.001) and enteral nutrition (HR 2.71, 95% CI: 1.98-3.71, p < 0.001), which were the risk factors for liver injury. In conclusion, this study suggests that the development of DILI in hospitalized patients with COVID-19 needs to be closely monitored, and the above-mentioned drug treatments may contribute to the risk of DILI.

Knowledge, Attitude and Practice of Hospital Pharmacists in Central China Towards Adverse Drug Reaction Reporting: A Multicenter Cross-Sectional Study.

Background: Healthcare professionals' knowledge and attitudes towards adverse drug reactions (ADRs) and ADR reporting play a significant role in pharmacovigilance. This study aims to investigate the gap between knowledge and practice in ADR reporting among hospital pharmacists. Methods: This study is a multi-center, cross-sectional study based on a questionnaire survey. A semi-structured questionnaire was developed including knowledge, attitudes, and practices (KAP) towards ADR reporting. From October to November 2021, questionnaires were filled out on the internet by hospital pharmacists from a central province of China. The data analysis used a one-way ANOVA to analyze the differences between the pharmacist's characteristics and knowledge and attitude, respectively. The ordinal logistic regression method was used to analyze the predictors of practice. Results: A total of 1,026 valid questionnaires from 512 medical institutions were collected. It was found that 88.8% of participants have a clear understanding of the ADR definition, while 59.6% of them have misunderstandings about the reporting time of new and serious adverse reactions. Most pharmacists showed positive attitudes towards ADR reporting. Higher education background, higher professional title, attending training, and clinical pharmacist resulted in higher knowledge scores. Higher education background, shorter working years, attending training, and from non-tertiary hospital related to higher attitude scores. In terms of practice, age, hospital type, working years, training, and pharmacist type all have significant associations with practice scores. Pharmacists' knowledge score and attitude score were significant predictors of practice score with OR being 1.19 (95% CI: 1.06, 1.33) and 1.04 (95% CI: 1.005, 1.07). Conclusion: Although most hospital pharmacists showed positive attitudes towards ADR reporting, their knowledge and practice were still insufficient. Hospital pharmacists' knowledge and attitude are associated with their practice towards ADR reporting. The training had a significant impact on the pharmacist's knowledge, attitude, and practice.

Mucosal bacterial dysbiosis in patients with nodular lymphoid hyperplasia in the terminal ileum.

BACKGROUND: Nodular lymphoid hyperplasia (NLH) in the small intestine is a rare benign lesion characterized by multiple small nodules on the intestinal surface. Patients with terminal ileal NLH may experience long-term abdominal pain, diarrhea, and abdominal distension, among other symptoms. Supplementation with probiotics could mitigate these symptoms. NLH is linked to the immune system, and it may result from accumulation of plasma-cell precursors due to a maturational defect during the development of B lymphocytes. The intestinal microbiome plays an essential role in the immune system. Thus, we speculate that the gut flora plays a key role in terminal ileal NLH. AIM: To explore the correlation between intestinal flora and terminal ileal NLH. METHODS: We collected mucosal biopsy samples that were obtained via colonoscopy from 15 patients with terminal ileal NLH (the test group) and 15 normal subjects (the control group). We subsequently performed 16S-rRNA gene amplicon sequencing of these samples, and the results were evaluated using alpha diversity, beta diversity and microbial composition analyses. The Phylogenetic Investigation of Communities by Reconstruction of Unobserved States was used to predict the metabolic pathways and orthologous groups according to the Kyoto Encyclopedia of Genes and Genomes database. RESULTS: Compared with the control group, the terminal ileal NLH group showed an increased alpha diversity (P < 0.05). The overall intestinal microbiota in the NLH group was significantly different from that of the control group (P < 0.05), implying that there was the dysbiosis in the terminal ileal NLH patients. The relative abundance of phylum Bacteroidetes was significantly lower in the NLH group, while that of Patescibacteria and Campilobacterota was significantly higher. The genus Bacteroides was the dominant gut microbiota in both groups, but its abundance was significantly lower in the test group than it was in the control group. Conversely, the relative abundances of Haemophilus, Streptococcus, Pseudomonas, Actinomyces, TM7X, Fusobacterium nucleatum, Parvimonas, Granulicatella, Helicobacter, and the [Eubacterium] nodatum group were significantly higher in the test group than they were in the control group. In addition, several altered metabolic pathways, orthologous groups, and modules were found. For example, the Peptidoglycan biosynthesis and Aminoacyl tRNA biosynthesis were both increased in the test group. CONCLUSION: Maintaining the microbial balance and supplementing targeted protective bacteria could improve symptoms and potentially reduce the risk of lymphoma transformation in patients with terminal ileal NLH.

Niches and interspecific association of major shrimp and crab species in Pishan waters of Zhejiang Province, China.

Based on the fishery resource investigation data in Pishan waters of Zhejiang coastal area in November of 2015 (autumn), February (winter), May (spring) and August (summer) of 2016, we analyzed the spatio-temporal niche characteristics and interspecific association of the domi-nant shrimp and crab species using the methods of niche test, variance ratio, chi-square test, Spearman test and redundancy analysis. A total of 34 shrimp and crab species belonging to 14 families and 20 genera were identified. Among them, 10 species were collected in all the four seasons. Dominant species were Parapenaeopsis hardwickii, Exopalaemon carinicauda and Portunus trituberculatus. The temporal, spatial and spatio-temporal niche breadths of the major shrimp and crab species ranged from 0.03-1.34, 2.07-3.63 and 0.08-4.64, respectively. The cluster analysis of niche breadths suggested that all the species could be divided into narrow, medium and wide niche breadth groups under the 90% similarity level. In addition, the spatio-temporal niche overlap values of the major species in Pishan Sea were mainly at low level (68.9% of the species's Qik<0.3), implying little interspecific competition for resource utilization. The analysis of variance ratio showed that the major shrimp and crab species were mainly positively correlated, with 11.1% of the species showing significantly positive association. The JI index, OI index and Spearman test all showed the relationship between major shrimp and crab species tended to be positive correlation as a whole. Redundancy analysis showed that surface temperature, bottom temperature, and surface salinity were the main environmental factors affecting the distribution of shrimp and crab species in Pishan waters.

Spatio-temporal niche of major fish species in Pishan waters off Zhejiang Province, China.

Based on seasonal bottom trawl surveys in November 2015 (autumn), February (winter), May (spring) and August (summer) in 2016, the index of relative importance (IRI), Shannon index and Pianka index were used to analyze the breadth and overlap of spatio-temporal niche of major fish species in the Pishan waters off Zhejiang Province. Redundancy analysis and interspecific competition coefficient were used to examine the competition relationship and niche differentiation of those major fish species. The results showed that a total of 61 fish species were recorded throughout the year, which belonged to 13 orders, 29 families and 48 genera. A total of 19 species with IRI>100 were identified as major fish species. The temporal niche overlap value between Chelidonichthys kumu and Atule kalla was largest, indicating high temporal synchronization. Both the spatial niche overlap value and the spatio-temporal niche overlap value between Trpauchen vagina and Cynoglossus interruptus were largest, indicating that their spatial homology was high and that the use of spatial and temporal two-dimensional resource of both species were consistent. The percentage of species pairs with spatio-temporal niche overlap at the significant level (Qik>0.6) was only 5.8% in Pishan waters, indicating that the spatial and temporal distribution of those species were quite different. The overlap of spatio-temporal niche significantly varied across different seasons. The results of the interspecific competition coefficient were basically consistent with the niche overlap. Results of the redundancy analysis revealed the relationships between major fish species and environmental factors (temperature, salinity, dissolved oxygen), and further explained the niche diffe-rentiation among species.

An analytical study of drug utilization, disease progression, and adverse events among 165 COVID-19 patients.

BACKGROUND: The coronavirus disease 2019 (COVID-19) epidemic has lasted for nearly 4 months by this study was conducted. We aimed to describe drug utilization, disease progression, and adverse drug events of COVID-19. METHODS: A retrospective, single-center case series study enrolled 165 consecutive hospitalized COVID-19 patients who were followed up until March 25, 2020, from a designated hospital in Wuhan. Patients were grouped by a baseline degree of severity: non-severe and severe. An analytical study of drug utilization, disease progression, and adverse events (AEs) of COVID-19 was conducted. RESULTS: Of the 165 COVID-19 cases, antivirals, antibacterials, glucocorticoids, and traditional Chinese medicine (TCM) were administered to 92.7%, 98.8%, 68.5%, and 55.2% of patients, respectively. The total kinds of drugs administered to the severe subgroup [26, interquartile range (IQR) 18-39] were 11 more than the non-severe subgroup (15, IQR 10-24), regardless of comorbidities. The 2 most common combinations of medications in the 165 cases were 'antiviral therapy + glucocorticoids + TCM' (81, 49.1%) and 'antiviral therapy + glucocorticoids' (23, 13.9%). Compared with non-severe cases, severe cases received more glucocorticoids (88.5% vs. 66.2%, P=0.02), but less TCM (50.0% vs. 63.3%, P=0.20), and suffered a higher percentage of death (34.6% vs. 7.2%, P=0.001). At the end of the follow-up, 130 (78.8%) patients had been discharged, and 24 (14.5%) died. There were 13 patients (7.9%) who had elevated liver enzymes, and 49 patients (29.7%) presented with worsening kidney function during the follow-up. CONCLUSIONS: Of the 165 COVID-19 patients, the fatality rate remained high (14.5%). Drug utilization for COVID-19 was diverse and generally complied with the existing guidelines. Combination regimens containing antiviral drugs might be beneficial to assist COVID-19 recovery. Additionally, liver and kidney AEs should not be ignored.

CircHECTD1 up-regulates mucin 1 expression to accelerate hepatocellular carcinoma development by targeting microRNA-485-5p via a competing endogenous RNA mechanism.

BACKGROUND: Non-coding RNAs have attracted considerable attention for their vital role in cancer. The purpose of this study was to determine the effects of non-coding RNAs on hepatocellular carcinoma (HCC) and reveal their regulatory mechanism in the pathophysiological process. METHODS: We measured the expression of mucin 1 (MUC1) and miR-485-5p in tissues from 15 HCC patients and in liver cancer cell lines by quantitative real-time polymerase chain reaction and Western blot, screened for aberrantly expressed microRNAs (miRNAs) by miRNA microarrays. Bioinformatics tools were used to find the miRNA and circular RNA that regulated MUC1, which were validated by RNA immunoprecipitation assay and luciferase reporter assay. Cell counting kit-8, Transwell assays, and flow cytometry were used to conduct functional experiments. Proteins were examined by western blot and immunohistochemical staining assays. Significant differences between groups were estimated using the one-way analysis of variance. A P < 0.05 was considered statistically significant. RESULTS: MUC1 was overexpressed in HCC tissues compared with that in paratumor tissues (normal vs. tumor, 1.007 ±â€Š0.215 vs. 75.213 ±â€Š18.403, t = 18.401, P < 0.001) while miR-485-5p was down-regulated (normal vs. tumor, 4.894 ±â€Š0.684 vs. 1.586 ±â€Š0.398, t = 16.191, P < 0.001). Inhibition of miR-485-5p promoted cell proliferation (73.33% ±â€Š5.13% vs. 41.33% ±â€Š3.51%, t = 8.913, P < 0.001), migration (102 ±â€Š8 cells vs. 46 ±â€Š8 cells, t = 8.681, P < 0.001), invasion (59 ±â€Š7 cells vs. 28 ±â€Š2 cells, t = 8.034, P < 0.01), and suppressed apoptosis (22.64% ±â€Š6.97% vs. 36.33% ±â€Š3.96%, t = 2.958, P < 0.05) of HepG2 cells with which MUC1 is knocked down. Mechanically, miR-485-5p binds to MUC1, while circHECTD1 binds to miR-485-5p, resulting in the indirect up-regulation of the MUC1 level. CONCLUSIONS: Our findings reveal that circHECTD1 facilitates HCC progression by sponging miR-485-5p to up-regulate MUC1.

[Preparation and characterization of salvianolic acids-tanshinones composite powder for inhalation via co-micronized method].

Salvianolic acids and tanshinones are main hydrophilic and lipophilic extracts from Salvia Miltiorrhiza with significant anti-pulmonary fibrosis effects. The aim of this study was to prepare a co-micronized salvianolic acids-tanshinones composite powder for inhalation using a planetary ball mill. The micronization process parameters were optimized by central composite design (CCD) and response surface methodology (RSM). Treatment time, rotation speed and the ball/sample weight ratio were selected as the independent variables, and the volume fraction of particle size in 1-5 µm was taken as the dependent variable. The powder properties were evaluated by scanning electron microscopy (SEM), laser diffraction and X-ray powder diffraction (XRPD). The powder flow and hygroscopicity were determined with repose angle, compressibility index and critical relative humidity(CRH). According to the results, the salvianolic acids-tanshinones composite powder produced in optimal conditions had a narrow and unimodal particle size distribution and a smaller D50 of 2.33 µm. The volume fraction of particle size in 1-5 µm was 80.82%. The repose angle was (50.60±1.13) °, and the critical relative humidity is about 77%. After being micronized, the particle size significantly reduced, and the number of amorphous substances slightly increased, with no significant changes in powder flow and hygroscopicity. These findings indicate that the grinding method with a planetary ball mill can be used to co-micronize various components with different properties and prepare composite drug powders for dry powder inhalation.

Curcumin-piperine mixtures in self-microemulsifying drug delivery system for ulcerative colitis therapy.

Curcumin (CUR) is a poorly water-soluble drug and its absorption is very low. In this study, CUR and piperine (PIP) were co-encapsulated into the nanoformulation called self-microemulsifying drug delivery system (SMEDDS) to improve the stability and water-solubility of CUR and enhance its anti-colitis activity. The formulation of CUR-PIP-SMEDDS was prepared to encapsulate two hydrophobic components CUR and PIP, and then was characterized by assessing appearance, morphology, particle size, zeta potential and drug encapsulation efficiency. The appearance of CUR-PIP-SMEDDS remained clarified and transparent, and the microemulsion droplets appeared spherical without aggregation. The mean size of microemulsion droplet formed from CUR-PIP-SMEDDS was 15.87 ± 0.76 nm, and the drug encapsulation efficiency of SMEDDS for CUR and PIP were (94.34 ± 2.18)% and (90.78 ± 2.56)%, respectively. The vitro stability investigation of CUR-PIP-SMEDDS in colon tissue suggested that using SMEDDS as a delivery vehicle and co-encapsulated with PIP, CUR was more stable than drug solution in colons site. Meanwhile, the anti-inflammatory activity of CUR-PIP-SMEDDS was evaluated on DSS-induced colitis model. The results showed that CUR-PIP-SMEDDS exhibited definite anti-colitis activity by directing CUR-PIP-SMEDDS to inflammatory colon tissue through retention enema administration. Our study illustrated that the developed CUR-PIP-SMEDDS formulation was a potential carrier for developing colon-specific drug delivery system of CUR for ulcerative colitis treatment.

[Optimization and characterization of curcumin-piperine dual drug loaded self-microemulsifying drug delivery system by simplex lattice design].

The objective of the study was to prepare and evaluate the quality of curcumin-piperinedual drug loaded self-microemulsifying drug delivery system(Cur-PIP-SMEDDS). Simplex lattice design was constructed using optimal oil phase, surfactant and co-surfactant concentration as independent variables, and the curcumin and piperine were used as model drugs to optimize Cur-PIP-SMEDDS formulation. In the present study, the drug loadings of curcumin and piperine, mean particle size of Cur-PIP-SMEDDS were made as indicators, and the experiment design, model building and response surface analysis were established using Design Expert 8. 06 software to optimize and verify the composition of SMEDDS formulation. The quality of Cur-PIP-SMEDDS was evaluated by observing the appearance status, transmission electron microscope micrographs and determining particle diameter, electric potential, drug entrapment efficiency and drug loading of it. As a result, the optimal formulation of SMEDDS was CapryoL 90-Cremophor RH40-TranscutoL HP (10:60:30). The appearance of Cur-PIP-SMEDDS remained clarified and transparent, and the microemulsion droplets appeared spherical without aggregation with uniform particle size distribution. The mean size of microemulsion droplet formed from Cur-PIP-SMEDDS was 15.33 nm, the drug loading of SMEDDS for Cur and PIP were 40.90 mg · g(-1) and 0.97 mg · g(-1), respectively, the drug entrapment efficiency were 94.98% and 90.96%, respectively. The results show that Cur-PIP-SMEDDS can increase the solubility and stability of curcumin significantly, in the expectation of enhancing the bioavailability of it. Taken together, these findings can provide the reference to a preferable choice of the Cur formulation and contribute to therapeutic application in clinical research.

Up-regulation of microRNA-1290 impairs cytokinesis and affects the reprogramming of colon cancer cells.

Abnormal cytokinesis increases the possibility of nuclear fusion in tumor cells. However, the role of microRNAs (miRNAs) in abnormal cytokinesis is unclear. Here, we found that miR-1290 was significantly up-regulated in clinical colon cancer tissues. Up-regulation of miR-1290 postponed cytokinesis and led to the formation of multinucleated cells. KIF13B was a target of miR-1290 that was involved in aberrant cytokinesis. Furthermore, enforced expression of miR-1290 activated the Wnt pathway and increased the reprogramming-related transcript factors c-Myc and Nanog. Our results suggest that up-regulation of miR-1290 in colon cancer cells impaired cytokinesis and affected reprogramming.