HiCervix: An Extensive Hierarchical Dataset and Benchmark for Cervical Cytology Classification.

Cervical cytology is a critical screening strategy for early detection of pre-cancerous and cancerous cervical lesions. The challenge lies in accurately classifying various cervical cytology cell types. Existing automated cervical cytology methods are primarily trained on databases covering a narrow range of coarse-grained cell types, which fail to provide a comprehensive and detailed performance analysis that accurately represents real-world cytopathology conditions. To overcome these limitations, we introduce HiCervix, the most extensive, multi-center cervical cytology dataset currently available to the public. HiCervix includes 40,229 cervical cells from 4,496 whole slide images, categorized into 29 annotated classes. These classes are organized within a three-level hierarchical tree to capture fine-grained subtype information. To exploit the semantic correlation inherent in this hierarchical tree, we propose HierSwin, a hierarchical vision transformer-based classification network. HierSwin serves as a benchmark for detailed feature learning in both coarse-level and fine-level cervical cancer classification tasks. In our comprehensive experiments, HierSwin demonstrated remarkable performance, achieving 92.08% accuracy for coarse-level classification and 82.93% accuracy averaged across all three levels. When compared to board-certified cytopathologists, HierSwin achieved high classification performance (0.8293 versus 0.7359 averaged accuracy), highlighting its potential for clinical applications. This newly released HiCervix dataset, along with our benchmark HierSwin method, is poised to make a substantial impact on the advancement of deep learning algorithms for rapid cervical cancer screening and greatly improve cancer prevention and patient outcomes in real-world clinical settings.

Machine learning and weighted gene co-expression network analysis identify a three-gene signature to diagnose rheumatoid arthritis.

Background: Rheumatoid arthritis (RA) is a systemic immune-related disease characterized by synovial inflammation and destruction of joint cartilage. The pathogenesis of RA remains unclear, and diagnostic markers with high sensitivity and specificity are needed urgently. This study aims to identify potential biomarkers in the synovium for diagnosing RA and to investigate their association with immune infiltration. Methods: We downloaded four datasets containing 51 RA and 36 healthy synovium samples from the Gene Expression Omnibus database. Differentially expressed genes were identified using R. Then, various enrichment analyses were conducted. Subsequently, weighted gene co-expression network analysis (WGCNA), random forest (RF), support vector machine-recursive feature elimination (SVM-RFE), and least absolute shrinkage and selection operator (LASSO) were used to identify the hub genes for RA diagnosis. Receiver operating characteristic curves and nomogram models were used to validate the specificity and sensitivity of hub genes. Additionally, we analyzed the infiltration levels of 28 immune cells in the expression profile and their relationship with the hub genes using single-sample gene set enrichment analysis. Results: Three hub genes, namely, ribonucleotide reductase regulatory subunit M2 (RRM2), DLG-associated protein 5 (DLGAP5), and kinesin family member 11 (KIF11), were identified through WGCNA, LASSO, SVM-RFE, and RF algorithms. These hub genes correlated strongly with T cells, natural killer cells, and macrophage cells as indicated by immune cell infiltration analysis. Conclusion: RRM2, DLGAP5, and KIF11 could serve as potential diagnostic indicators and treatment targets for RA. The infiltration of immune cells offers additional insights into the underlying mechanisms involved in the progression of RA.

Effect of Temperature Variation on the Incidence of Acute Myocardial Infarction.

BACKGROUND: Harsh temperature exposure has been associated with a high risk of cardiovascular events. We sought to investigate the influence of temperature change on long-term incidence of acute myocardial infarction (AMI) in Korean patients. METHODS: From the National Health Insurance Service (NHIS) customized health information database (from 2005 to 2014), data from a total of 192,567 AMI patients was assessed according to the International Classification of Disease 10th edition code and matched with temperature reports obtained from the Korea Meteorological Administration database. We analyzed data for a 10-year period on a monthly and seasonal basis. RESULTS: The incidence rate per 100,000 year of AMI exhibited a downward trend from 69.1 to 56.1 over the period 2005 to 2014 (P < 0.005), and the seasonal AMI incidence rate per 100,000 year was highest in spring (63.1), and winter (61.3) followed by autumn (59.5) and summer (57.1). On a monthly basis, the AMI incidence rate per 100,000 year was highest during March (64.4) and December (63.9). The highest incidence of AMI occurred during temperature differences of 8-10° in each season. Moreover, AMI incidence tended to increase as the mean temperature decreased (r = -0.233, P = 0.001), and when the mean daily temperature difference increased (r = 0.353, P < 0.001). CONCLUSION: The AMI incidence rate per 100,000 year has a decreasing trend over the 10-year period, derived from the Korean NHIS database. Modest daily temperature differences (8-10°) and the spring season are related to higher AMI incidence, indicating that daily temperature variation is more important than the mean daily temperature.

Intestinal Barrier Function and Neurodegenerative Disease.

Neurodegenerative diseases are caused by the loss of neurons and/or their myelin sheaths, which deteriorate over time and become dysfunctional. Alzheimer's disease, Parkinson's disease, and multiple sclerosis are among the most prominent neurodegenerative diseases that affect millions of older adults worldwide. Despite extensive research over several decades, controversies still surround the etiology of neurodegenerative diseases, and many of them remain incurable. Meanwhile, an increasing number of new mechanistic studies related to the microbiota-gut-brain axis have emerged, among which the relationship between the function of the intestinal barrier and neurodegenerative diseases has received widespread attention. As one of the first lines of defense between the body and the external environment, the impaired function of the intestinal barrier is closely related to the development of neurodegenerative pathologies. Among them, the microbiota-gut-brain axis disorder characterized by intestinal barrier disruption mainly includes impaired function of the intestinal microbial barrier, chemical barrier, mechanical barrier, and immune barrier. This review focuses on the structure and molecular mechanisms of the various layers of the intestinal barrier as well as their relationship with neurodegenerative lesions. In recent years, intestinal barrier repair therapies have provided new ideas for the studied disease treatment modalities. We believe that a better understanding of the role of the intestinal barrier in neurodegenerative diseases would provide new insights for the development of viable therapeutic strategies for patients.

Longitudinal surveillance of three biomarkers to predict recurrence of hepatocellular carcinoma after radical resection.

BACKGROUND: Radical resection is a curative treatment for patients with hepatocellular carcinoma (HCC), but the incidence of recurrence remains high. We aimed to explore the performance of predicting HCC recurrence by longitudinal surveillance of the protein induced by vitamin K absence (PIVKA-II), alpha- fetoprotein (AFP), and lectin-reactive AFP (AFP-L3) during postoperative follow-up. METHODS: Patients who underwent radical resection for HCC at the Ningbo Medical Centre Lihuili Hospital between January 2015 and December 2020 were included. All enrolled patients regularly monitor PIVKA-II, AFP, AFP-L3 every 3 months during postoperative follow-up. The surveillance performance of PIVKA-II, AFP, AFP-L3 during follow-up for the prediction of HCC recurrence was compared in patients. The generalized estimation equation (GEE) was used to analyze the trends of the tumor biomarkers and interactions with time. Area under the receiver operator characteristic (AUROC) curves, the optimal cut-off value, the sensitivity and specificity were calculated to evaluate the performance of the three biomarkers. The recurrence-free survival (RFS) and overall survival (OS) of patients with any of the elevated biomarkers was analyzed by Kaplan-Meier curves and the log-rank test. Multivariate logistic regression models were used to analyze potential risk factors for recurrence. RESULTS: The GEE analysis indicated that PIVKA-II, AFP, AFP-L3 in the recurrence patients were higher than the no recurrence patients during follow-up, PIVKA-II and AFP showed increasing trends from 6 months before recurrence. In predicting recurrence, the AUROCs for PIVKA-II, AFP, AFP-L3 and their combination were 0.885, 0.754, 0.781 and 0.885 respectively, the optimal cut-off value for PIVKA-II, AFP, AFP-L3 was 29.5 mAU/ml, 10.7 ng/L, 1.5% respectively. The sensitivity in predicting recurrence for PIVKA-II, AFP, AFP-L3 and combination were 75.0, 54.7, 57.8 and 79.7% respectively. The RFS and the OS of patients with any of the biomarkers elevated during the follow-up was significantly shorter than that without elevated biomarkers ( P  < 0.001). Multivariate analysis showed that any of the biomarkers elevated was the independent risk factor of recurrence. CONCLUSION: Longitudinal surveillance of PIVKA-II, AFP and AFP-L3 can effectively predict recurrence of HCC after operation.

Role of Dual-Acquisition Noninvasive Cardiac CT Imaging for the Detection of Vasospastic Angina.

BACKGROUND: Vasospastic angina (VSA) is characterized by chest pain at rest with transient ischemic electrocardiographic changes in the ST segment, and a prompt response to nitrates. Vasospastic angina is among the most frequent of the coronary artery diseases in Asia, and coronary computed tomography angiography (CCTA) may become available as a non-invasive diagnosis method. METHODS: We prospectively enrolled 100 patients with suspected vasospastic angina at two centers from 2018 to 2020. All patients underwent baseline CCTA without a vasodilator in the early morning followed by catheterized coronary angiography and spasm testing. CCTA with intravenous infusion of nitrate (IV) was repeated within 2 weeks of baseline CCTA. Vasospastic angina as detected by CCTA was defined as significant stenosis (≥50%) with negative remodeling without definite plaques or diffuse small diameter (<2 mm) of a major coronary artery with a beaded appearance on baseline CT that completely dilated on IV nitrate CT. We analyzed diagnostic performance of dual-acquisition CCTA for the detection of vasospastic angina. RESULTS: The patients were categorized into three groups according to their provocation test result (negative, n = 36; probable positive, n = 18; positive, n = 31). The diagnostic accuracy in terms of CCTA per patient had a sensitivity of 55% (95% CI, 40-69), specificity of 89% (95% CI, 74-97), positive predictive value (PPV) of 87% (95% CI, 72-95), and negative predictive value (NPV) of 59% (95% CI, 51-67). CONCLUSIONS: Dual-acquisition CCTA can support the non-invasive detection of vasospastic angina with relatively good specificity and PPV. CCTA was helpful for non-invasive screening of variant angina.

MTM-HCC at Previous Liver Resection as a Predictor of Overall Survival in Salvage Liver Transplantation.

OBJECTIVES: Salvage liver transplantation (sLT) is considered an effective method to treat hepatocellular carcinoma (HCC) recurrence. This multicenter research aimed to identify the prognostic factors associated with recurrence-free survival (RFS) and overall survival (OS) after sLT. MATERIAL AND METHODS: A retrospective analysis of 114 patients who had undergone sLT for recurrent HCC between February 2012 and September 2020 was performed. The baseline and clinicopathological data of the patients were collected. RESULTS: The 1-, 3-, and 5-year RFS rates after sLT were 88.9%, 75.2%, and 69.2%, respectively, and the OS rates were 96.4%, 78.3%, and 70.8%. A time from liver resection (LR) to recurrence < 1 year, disease beyond the Milan criteria at sLT and macrotrabecular massive (MTM)-HCC were identified as risk factors for RFS and were further identified as independent risk factors. A time from LR to recurrence < 1 year, disease beyond the Milan criteria at sLT and MTM-HCC were also risk factors for OS and were further identified as independent risk factors. CONCLUSIONS: Compared with primary liver transplantation (pLT), more prognostic factors are available from patients who had undergone LR. We suggest that in cases of HCC recurrence within 1 year after LR, disease beyond the Milan criteria at sLT and MTM-HCC patients, sLT should be used with caution.

Design and synthesis of novel anti-multidrug-resistant staphylococcus aureus derivatives of glycyrrhetinic acid by blocking arginine biosynthesis, metabolic and H2S biogenesis.

With the soaring number of multidrug-resistant bacteria, it is imperative to develop novel efficient antibacterial agents and discovery new antibacterial pathways. Herein, we designed and synthesized a series of structurally novel glycyrrhetinic acid (GA) derivatives against multidrug-resistant Staphylococcus aureus (MRSA). The in vitro antibacterial activity of these compounds was evaluated using the microbroth dilution method, agar plate coating experiments and real-time growth curves, respectively. Most of the target derivatives showed moderate antibacterial activity against Staphylococcus aureus (S. aureus) and MRSA (MIC = 3.125-25 µM), but inactivity against Escherichia coli (E. Coli) and Pseudomonas aeruginosa (P. aeruginosa) (MIC > 200 µM). Among them, compound 11 had the strongest antibacterial activity against MRSA, with an MIC value of 3.125 µM, which was 32 times and 64 times than the first-line antibiotics penicillin and norfloxacin, respectively. Additionally, transcriptomic (RNA-seq) and quantitative polymerase chain reaction (qPCR) analysis revealed that the antibacterial mechanism of compound 11 was through blocking the arginine biosynthesis and metabolic and the H2S biogenesis. Importantly, compound 11 was confirmed to have good biocompatibility through the in vitro hemolysis tests, cytotoxicity assays and the in vivo quail chicken chorioallantoic membrane (qCAM) experiments. Current study provided new potential antibacterial candidates from glycyrrhetinic acid derivatives for clinical treatment of MRSA infections.

Pyopneumothorax Caused by Trichomonas tenax and Porphyromonas endodontalis Coinfection in a Patient with Previous Cerebral Infarction: A Case Report and Literature Review.

Background: Even with the advent of NGS and PCR diagnostic tools, cases of chest infections caused by Trichomonas are still very rare. Such pathogens are less likely to be considered by clinicians. These cases frequently involve the pleura and lead to pneumothorax, hydropneumothorax, or pyopneumothorax, making the disease severe. Case Presentation: A 69-year-old man diagnosed with cerebral infarction a year ago sought medical attention for right-sided pyopneumothorax and respiratory failure. The pathogen found in the pleural fluid was highly suspected to be Trichomonas tenax (T. tenax). Pleural fluid mNGS confirmed T. tenax and Porphyromonas endodontalis coinfection. Metronidazole combined with piperacillin tazobactam was administered to counteract infection. Simultaneously, closed chest drainage and thoracoscopic release of pleural adhesions were performed. The patient was cured, discharged from the hospital, and was in good condition after six months of follow-up. Conclusion: When chest infections occur in patients with poor oral hygiene and underlying diseases that may lead to aspiration, the identification of Trichomonas infection should be noted. Early confirmation of the diagnosis often requires mNGS and PCR. Metronidazole is essentially effective against Trichomonas, and medical thoracoscopy can be used to manage pleural conditions if necessary.

Predictive Value of the TP53 p.G245S Mutation Frequency for the Short-Term Recurrence of Hepatocellular Carcinoma as Detected by Pyrophosphate Sequencing.

Aims: We explored the relationship between the mutation at the p.G245S site in TP53 and the short-term recurrence of hepatocellular carcinoma (HCC). Materials and Methods: 101 HCC patients were included in this study. The TP53 p.G245S mutation frequency spectrum was examined by direct sequencing of genomic DNA from tissue specimens of HCC patients. Univariate and multivariate Cox regression analyses were performed to evaluate the independent prognostic factors of tumor recurrence. ROC curve analysis was applied to determine the cut-off value for the p.G245S mutation frequency and to verify the predictive ability of the Cox model compared with single risk factor indices. Results: A multivariate Cox regression analysis showed that TP53 p.G245S mutation frequency (HR = 1.231, 95% CI: 1.006-1.505, p = 0.043), AFP (HR = 2.432, 95% CI: 1.297-4.561, p = 0.006), MTM (HR = 2.656, 95% CI: 0.930-7.583, p = 0.068), and PVTT (HR = 14.297, 95% CI: 3.085-66.243, p = 0.001) were independent prognostic factors for short-term recurrence. The cut-off value for the TP53 p.G245S mutation frequency (18.5%) was determined by ROC analysis. A predictive model integrating the TP53 p.G245S mutation frequency with PVTT, MTM, and AFP values appears to an excellent predictive indicator of short-term recurrence in HCC patients (AUC = 0.849, 95% CI = 0.748-0.950, p = 0.000001). Survival analysis indicated that the probability of short-term recurrence-free survival was significantly different among different TP53 p.G245S mutation frequency, MTM, PVTT, and AFP risk groups (p < 0.05). Conclusion: The mutation frequency of the p.G245S site is a novel prognostic risk factor for the short-term recurrence of HCC.

Successful treatment of Talaromyces marneffei pneumonia in a HIV-negative renal transplantation recipient: A case report.

RATIONALE: Talaromyces marneffei causes life-threatening opportunistic fungal infections in immunocompromised patients. It often has a poorer prognosis in non-human immunodeficiency virus (HIV)-infected than in HIV-infected individuals because of delayed diagnosis and improper treatment. PATIENT CONCERNS: A 51-year-old man presented with complaints of pyrexia, cough, and expectoration that had lasted for 15 day. This patient has been taking anti-rejection medication since kidney transplant in 2011. DIAGNOSIS: T marneffei pneumonia; post renal transplantation; renal insufficiency; hypertension. INTERVENTIONS: Intravenous moxifloxacin was administered on admission. After the etiology was established, moxifloxacin was discontinued and replaced with voriconazole. The tacrolimus dose was adjusted based on the blood concentration of tacrolimus and voriconazole. OUTCOMES: The patient was successfully treated and followed-up without recurrence for 1 year. LESSONS: A high degree of caution should be maintained for the possibility of T marneffei infection in immunodeficient non-HIV patients who live in or have traveled to T marneffei endemic areas. Early diagnosis and appropriate treatment can prevent progression of T marneffei infection and achieve a cure. Metagenomic next-generation sequencing (mNGS) can aid the physician in reaching an early pathogenic diagnosis. Close monitoring of tacrolimus and voriconazole blood levels during treatment remains a practical approach at this time.

Strongyloides stercoralis hyperinfection syndrome mimicking pseudomembranous enteritis, complicated by Escherichia coli bacteremia and Pneumocystis jirovecii pneumonia in a patient after immunosuppressive therapy: a case report.

BACKGROUND: Strongyloidiasis, caused by Strongyloides stercoralis (S. stercoralis), is endemic worldwide, especially in countries with warm and humid climates. Strongyloides stercoralis hyperinfection syndrome (SHS) is an extremely serious manifestation of strongyloidiasis, which results from an acute exacerbation of auto-infection and is often fatal. CASE PRESENTATION: We present a case of SHS mimicking pseudomembranous enteritis with a final definitive diagnosis of a triple infection including S. stercoralis, Escherchia coli (E. coli) and Pneumocytis jirovecii (P. jirovecii) that occurred in a microscopic polyangiitis (MPA) patient after immunosuppressive therapy. SHS, together with E. coli bacteremia and Pneumocytis jirovecii pneumonia (PJP) in the same patient, is rare in clinical practice, which is first reported worldwide, to our knowledge. After the diagnosis was confirmed, the treatment protocol was quickly adjusted; however, the patient's life could not be saved. CONCLUSION: This case reminds us of the necessity to consider strongyloidiasis as a differential diagnosis in immunocompromised populations who live in or have visited to S. stercoralis endemic areas, especially patients with suspected pseudomembranous enteritis, even if stool examination, serological tests, and eosinophilia are negative. For this group, it is advisable to complete the relevant endoscopy and/or PCR as soon as possible. The fundamental solution to prevent this catastrophic outcome is to implement effective preventive measures at multiple levels, including physicians, patients, and relevant authorities.

Relationship between Acute Respiratory Tract Infection and the Serum 25(OH) D3 Level in Chronic Kidney Disease Patients and Its Prevention and Treatment.

Observational studies and randomized controlled studies propose that vitamin D plays a significant role in preventing acute respiratory tract infection (RTI); however, results are inconsistent and the optimal serum 25-hydroxyvitamin D (25-OH-D3) concentration remains unknown. This study explores the risk factors associated with acute RTI in patients with chronic kidney disease (CKD) and analyzes its correlation with serum 25-OH-D3 levels, to provide appropriate preventive treatment measures for CKD patients complicated with acute RTI. Seventy cases of CKD patients treated in the department of nephrology of Jiangxi Provincial People's Hospital are recruited as the research objects and divided into a control group (CKD without RTI) and an observation group (CKD with RTI), with 35 cases in each group. The laboratory indexes and serum 25-OH-D3 levels are compared between the two groups. The area under the receiver operating characteristic curve (ROC) of 25-OH-D3 in the diagnosis of CKD patients complicated with RTI is 0.892, and the standard error is 0.038. The glomerular filtration rates (GFR) are 48.32 ± 9.87 mL/min and 50.18 ± 20.71 mL/min in the control group and the experimental group, respectively, with no statistical significance between the two groups (P > 0.05). The serum 25-OH-D3 content in the control group (35.08 ± 6.2 nmol/L) is dramatically higher than that in the observation group (20.71 ± 5.87 nmol/L) (P < 0.05). The proportion of patients with diabetes mellitus (DM) in the control group and observation group is 25.71% and 68.57%, respectively, with a considerable difference (P < 0.05). In the control group and the experimental group, the proportion of patients with oral vitamin D receptor agonists is 54.29% and 11.43%, respectively, and the difference is significant (P < 0.05). Results show that the serum 25-OH-D3 level is highly correlated with the occurrence of RTI in CKD patients. In addition, it is related to patients' age, DM, and vitamin D receptor agonists.

Synthesis and biological activity evaluation of podophyllotoxin-linked bile acid derivatives as potential anti-liver cancer agents.

Podophyllotoxin's undifferentiated cytotoxicity and poor selectivity limit its clinical application. To improve above disadvantages, conjugation of bile acids with podophyllotoxin could improve cell line selectivity of liver cancer to achieve clinical translation further. Enlightened by the bile acids' moiety magic characters, thirty podophyllotoxin-linked bile acid derivatives had been designed and synthesized. The cytotoxicity of these compounds in vitro was evaluated on HepG2, HCT-116, A549 and MDCK cell lines. After conjunction with bile acids, most of the derivatives (IC50 = 0.066-0.831 µM) were more potent against above three types of tumor cells than Etoposide (VP-16, IC50 = 4.319-41.080 µM) and exhibited similar antitumor activity compared with doxorubicin (DOX, IC50 = 0.230-0.745 µM). Moreover, structure-activity relationship displayed the length of the linker chain between podophyllotoxin and bile acids affected the cytotoxicity. Especially, compound 23 exhibited strong activity against HepG2 cell lines (IC50 = 0.188 ± 0.01 µM) than MDCK cell lines (IC50 = 4.780 ± 0.50 µM) and its SI (IC50MDCK/IC50HepG2) value of compound 23 was 25.4. Further antitumor mechanism studies showed that compound 23 acted as Topo Ⅱ inhibition and induced cell apoptosis with S cell cycle arrest. In particular, compound 23 showed valid antitumor efficacy at 10 mg/kg by intraperitoneal administration with a tumor inhibition rate of 60.9% in the Hepa1-6 xenograft mice model. The current research displayed that introduction of bile acids contributed to improve selectivity and activity to cell, and compound 23 could be a promising anti-tumor candidate.

RhoA improves cryopreservation of rooster sperm through the Rho/RhoA-associated kinase/cofilin pathway.

Cryopreservation of rooster sperm leads to relatively low semen quality due to cytoskeletal damage during the freeze-thawing process. This study aimed to explore how the addition of RhoA recombinant protein affected the viability and subcellular structure of rooster sperm after freeze-thawing and elucidated the molecular mechanisms of sperm cryopreservation. Semen quality and acrosome integrity testing revealed that the addition of 0.5 µg/mL RhoA recombinant protein to the cryoprotectant fluid significantly increased sperm motility, survival rate, linearity, straight-line velocity, and acrosome integrity after freeze-thawing (P < 0.05). Ultrastructure analysis of cryopreserved sperm showed structural damage to the sperm plasma membrane, nuclear membrane, and tail. However, compared to the control, these structural changes were reduced upon the addition of RhoA recombinant protein to the cryoprotective fluid (P < 0.05). Western blotting revealed that the expression of Rho/RhoA-associated kinase and p-cofilin was increased, and cofilin expression was decreased after sperm cryopreservation with recombinant RhoA protein. Treatment with Y-27632, a ROCK antagonist, suppressed ROCK and p-cofilin expression and decreased semen quality, acrosome integrity, and ultrastructure integrity. In summary, we have demonstrated a cryoprotective effect in spermatozoa involving the Rho/ROCK pathway during freeze-thawing. Furthermore, the addition of 0.5 µg/mL RhoA recombinant protein to the cryoprotective fluid improved rooster semen quality and subcellular structural homeostasis after freeze-thawing via the Rho/ROCK pathway. This pathway may regulate the dynamic reorganization of the actin cytoskeleton by regulating the cofilin phosphorylation.

Differences in Optimal Platelet Reactivity after Potent P2Y12 Inhibitor Treatment in Acute Coronary Syndrome Patients Undergoing Percutaneous Coronary Intervention.

Background: East Asian patients receiving treatment with the potent P2Y12 inhibitors prasugrel or ticagrelor experience more potent platelet inhibition than with clopidogrel. Methods: This study investigated differences in OPR rates with reduced doses of prasugrel (n = 38) or ticagrelor (n = 40) for maintenance therapy in 118 Korean ACS patients who had undergone PCI, in comparison to conventional-dose clopidogrel (n = 40). We assessed drug responses at one- and three-months post-PCI with VerifyNow and multiple electrode aggregometry assays. Results: At the one-month period, patients receiving standard-dose prasugrel or ticagrelor had lower platelet reactivity as determined by the three assays than those receiving the conventional dose of clopidogrel (VN: p = 0.000; MEA: p = 0.000; LTA: p = 0.000). At the 3-month point, platelet reactivity was lower in those receiving reduced-dose prasugrel or ticagrelor than the clopidogrel-treated patients (VN: p = 0.000; MEA: p = 0.012; LTA: p = 0.002). Prasugrel resulted in significantly lower platelet inhibition than ticagrelor as determined by VN and LTA (VN: p = 0.000; LTA: p = 0.003). At three months, there was a significant overall difference in OPR among the three groups when measured by VN (p < 0.001), but not when measured by MEA (p = 0.596). OPR in the reduced-dose prasugrel group was not significantly different to the clopidogrel group at three months (VN: p = 0.180; MEA: p = 0.711). OPR in the reduced-dose ticagrelor group was similar to clopidogrel as determined by MEA at three months, but was different when assessed by VN (VN: p = 0.000; MEA: p = 0.540). Compared to standard-dose, the reduced-dose prasugrel OPR rate was significantly increased (VN: p = 0.008; MEA: p = 0.020). Conclusions: OPR values for reduced-dose prasugrel and conventional-dose clopidogrel at three months were similar but higher than for reduced-dose ticagrelor as determined by VN, but no differences were noted by MEA. The MEA assay might have less sensitivity and consistency than the VN assay. Further studies are needed to explore this discrepancy.

Portulaca Oleracea-associated oxalate nephropathy complicated with an ANCA-positive acute renal injury: A case report.

Oxalate nephropathy is a rare disease that can lead to acute kidney injury (AKI). In clinical practice, as renal biopsy is required for diagnosis, physicians often do not have sufficient understanding of this disease. When AKI is associated with positive blood anti-neutrophil cytoplasmic antibodies (ANCA), a diagnosis of renal injury due to ANCA-associated vasculitis is likely to be made, leading to treatment with immunosuppressive therapy. A case of AKI after eating a large quantity of Portulaca oleracea is reported. While blood P-ANCA was positive, both urine proteinuria and urine occult blood were negative. Renal biopsy was performed and identified an acute tubulointerstitial injury: disc-shaped crystals were seen in the lumen of renal tubules that demonstrated birefringence under polarized light, and an oxalate nephropathy was therefore diagnosed. Typical histological changes of an ANCA-associated vasculitis with renal injury such as cellulose-like necrosis and crescent formation were not present. After the patient stopped eating P. oleracea, and following rehydration and hemodialysis, renal function returned to normal. In patients with AKI, the secondary causes of hyperoxalemia should be sought and attention paid to excluding an oxalate nephropathy. In patients with AKI who are ANCA-positive, it is prudent to complete the renal pathological diagnostic process before assuming that the renal injury is caused by an ANCA-associated vasculitis, and before starting hormone and immunosuppressive therapy.

Effectiveness of clinical pharmacist-led smartphone application on medication adherence, insulin injection technique and glycemic control for women with gestational diabetes receiving multiple daily insulin injection: A randomized clinical trial.

AIM: To investigate the efficacy of a clinical pharmacist-led smartphone application (app) on medication adherence, insulin injection technique (IIT) and diabetes-related outcomes among women with gestational diabetes mellitus (GDM) receiving insulin therapy. METHOD: In all, 124 women were randomly (1:1 ratio) assigned to receive app intervention plus usual care (intervention) or usual care (control), and were followed up till 12 weeks postpartum. Interventions centralized on medication adherence and IIT. Primary outcome was medication adherence assessed by the 5-item Medication Adherence Report Scale. Secondary outcomes included IIT, insulin requirement, prepartal and puerperal glycemic control, hypoglycemia, and pregnancy and neonatal outcomes. RESULTS: A total of 119 patients completed the follow-up evaluation (58 intervention, 61 control). Significant more women with high medication adherence in the intervention group was observed (69.0% vs. 34.4%, p = 0.000). The other notable benefits (all p < 0.05) included patient percentage with appropriate IIT, lesser preprandial insulin dose, patient proportion with both qualified prepartal FPG and 2 hPG, and puerperal FPG or HbA1c, fewer hypoglycemia, and lower neonatal intensive care unit (NICU) admission rate. Cesarean delivery rate was higher among intervention cases (p < 0.05). Qualified prepartal glycemic control was related to high medication adherence and proper IIT. NICU admission was associated with complicated with gestational hypertension, deficient medication adherence and premature rupture of fetal membrane. CONCLUSION: Combined with usual care, clinical pharmacist-led smartphone app might be a valid tool for GDM management.

Bolbostemma paniculatum (Maxim.) Franquet extract suppresses the development of colorectal cancer through downregulation of PI3K/Akt pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Bolbostemma paniculatum (Maxim.) Franquet (BPF), a kind of Chinese medicine, has been traditionally used in treating mastitis, dysentery, phlegm nuclear, and sore swelling poison. AIM OF THE STUDY: In current study, we tried to investigate the possible anti-colorectal cancer (CRC) effects of BPF. MATERIALS AND METHODS: The effects of BPF extract on human colon cancer cells HCT-116 and SW-620, and a colitis associated colorectal cancer (CACC) mouse model were evaluated using the method of experimental pharmacology combined with network pharmacology. RESULTS: The ethyl acetate extract 3 (EA3) of BPF showed the most potent growth inhibitory effect in CRC cells. It could inhibit the clone formation, induce the apoptosis and cell cycle arrest in G1 phase as well as suppress the invasion and migration of CRC cells. And EA3 prevented ICR mice against CACC effectively. Both KEGG and GO analysis indicated that EA3 may inhibit CRC through influencing PI3K/Akt pathway. Results of Western blot analysis and ELISA confirmed that the molecules in the pathway were affected by EA3. CONCLUSIONS: These results demonstrate that EA3 from BPF could suppress the development of CRC through inhibiting the activity of PI3K/Akt pathway.