Universal screening and treatment towards the elimination of chronic hepatitis C in China: an economic evaluation.

OBJECTIVES: China has the largest number of hepatitis C virus (HCV) infection in the world, but current levels of diagnosis and treatment are low. The objective of this study was to assess the cost-effectiveness of various universal HCV screening and treatment strategies in China and inform decisions on health policy. STUDY DESIGN: A cost-effectiveness analytical study. METHODS: We developed a Markov model to investigate cost-effectiveness of different HCV screening and treatment strategies in China. We simulated several screening scenarios for Chinese people aged 18-70 years. We estimated incremental cost-effectiveness ratios (ICERs) of different intervention scenarios compared with status quo. RESULTS: Expanded HCV screening and treatment strategy with prioritisation for high-risk groups (Scenario S5) was the most cost-effective strategy (ICER: USD $11,667.71/quality-adjusted life-year [QALY] gained), which resulted in great reduction in HCV-related diseases and deaths, with a 67.11% reduction in cases of chronic HCV. Universal HCV screening and treatment implementation remains a cost-effective strategy when delayed until 2025 (ICER: USD $17,093.69/QALY), yet the delayed strategy is less effective in reducing HCV-related deaths. CONCLUSIONS: Expanded HCV screening and treatment strategy with prioritisation for high-risk groups is the most cost-effective strategy and has lead to a significant reduction in both HCV morbidity and mortality in China, which would essentially eliminate HCV as a public threat.

A Drimane Meroterpenoid Borate as a Synchronous Ca+ Oscillation Inhibitor from the Coral-Associated Fungus Alternaria sp. ZH-15.

Territrem F (1), a drimane meroterpenoid bearing a unique borate ring system, was isolated together with its diol precursor territrem B (2) from the fungus Alternaria sp. ZH-15 associated with the soft coral Lobophytum crassum collected in the South China Sea. The structure of the new compound was elucidated by spectroscopic analysis and an X-ray single-crystal diffraction study, representing a new type of boron-containing natural product. Both compounds significantly inhibited spontaneous synchronous Ca2+ oscillations (SCOs) and epileptic discharges induced by 4-aminopyridine, showing the potential for antiepileptic drug research. The 5,9-boronic ester derivative of 2 did not change its SCO inhibitory activity.

[Effects of Rehmanniae Radix and Rehmanniae Radix Praeparata on proteomics and autophagy in mice with type 2 diabetes mellitus induced by high-fat diet coupled with streptozotocin].

To compare the pancreatic proteomics and autophagy between Rehmanniae Radix-and Rehmanniae Radix Praeparata-treated mice with type 2 diabetes mellitus(T2DM). The T2DM mouse model was established by high-fat diet coupled with streptozotocin(STZ, intraperitoneal injection, 100 mg·kg~(-1), once a day for three consecutive days). The mice were then randomly assigned into a control group, low-(5 g·kg~(-1)) and high-dose(15 g·kg~(-1)) Rehmanniae Radix groups, low-(150 mg·kg~(-1)) and high-dose(300 mg·kg~(-1)) catalpol groups, low-(5 g·kg~(-1)) and high-dose(15 g·kg~(-1)) Rehmanniae Radix Praeparata groups, low-(150 mg·kg~(-1)) and high-dose(300 mg·kg~(-1)) 5-hydroxymethyl furfuraldehyde(5-HMF) groups, and a metformin(250 mg·kg~(-1)) group. In addition, a normal group was also set and each group included 8 mice. The pancreas was collected after four weeks of administration and proteomics tools were employed to study the effects of Rehmanniae Radix and Rehmanniae Radix Praeparata on protein expression in the pancreas of T2DM mice. The expression levels of proteins involved in autophagy, inflammation, and oxidative stress response in the pancreatic tissues of T2DM mice were determined by western blotting, immunohistochemical assay, and transmission electron microscopy. The results showed that the differential proteins between the model group and Rehmanniae Radix/Rehmanniae Radix Prae-parata group were enriched in 7 KEGG pathways, such as autophagy-animal, which indicated that the 7 pathways may be associated with T2DM. Compared with the control group, drug administration significantly up-regulated the expression levels of beclin1 and phosphorylated mammalian target of rapamycin(p-mTOR)/mTOR and down-regulated those of the inflammation indicators, Toll-like receptor-4(TLR4) and Nod-like receptor protein 3(NLRP3), in the pancreas of T2DM mice, and Rehmanniae Radix showed better performance. In addition, the expression levels of inducible nitric oxide synthase(iNOS), nuclear factor erythroid 2-related factor 2(Nrf2), and heine oxygenase-1(HO-1) in the pancreas of T2DM mice were down-regulated after drug administration, and Rehmanniae Radix Praeparata demonstrated better performance. The results indicate that both Rehmanniae Radix and Rehmanniae Radix Praeparata can alleviate the inflammatory symptoms, reduce oxidative stress response, and increase the autophagy level in the pancreas of T2DM mice, while they exert the effect on different autophagy pathways.

Global Patterns and Trends in Gastric Cancer Incidence Rates (1988-2012) and Predictions to 2030.

BACKGROUND & AIMS: The long-term trend in gastric cancer rates has rarely been reported from a global perspective. We aimed to explore the past temporal trends (1988-2012) in gastric cancer incidence rates in 43 countries and to predict future trends (2012-2030). METHODS: Data on yearly gastric cancer incidence by age group and sex were drawn from 108 cancer registries in 43 countries in the Cancer Incidence in Five Continents Time Trends (CI5plus) database. Age-standardized incidence rates per 100,000 persons were computed from 1988-2012. The number of new cases and incidence rates were predicted to 2030 using the Bayesian age-period-cohort model. RESULTS: Persistent decreasing trends in gastric cancer incidence rates were observed from 1988-2012 worldwide, with an overall average annual percentage change of -2.1% (95% confidence interval, -2.5--1.7). The trends will continue or remain stable until 2030 in most of the selected countries except for Ecuador and Lithuania, whose gastric cancer incidence rates will experience substantially increasing trends in the next several decades. CONCLUSION: The incidence rates of gastric cancer are expected to decrease through 2030 in most countries except Ecuador and Lithuania. Reductions in smoking and Helicobacter pylori prevalence and improvement in diet probably contributed to the decrease. Gastric cancer still represents a major cancer burden worldwide, and the large number of gastric cancer cases worldwide may still call for lifestyle interventions in terms of smoking and diet and massive efforts for H pylori screening and treatment, especially in countries with predicted increasing incidence rates of gastric cancer.

Global cirrhosis prevalence trends and attributable risk factors-an ecological study using data from 1990-2019.

BACKGROUND AND AIMS: Cirrhosis is a major public health issue worldwide with significant morbidity and mortality. We aimed to explore the time series associations between varying levels of risk factors and cirrhosis prevalence and predict the cirrhosis prevalence under alternative scenarios to consolidate evidence for further intervention plans. METHODS: We collected data of cirrhosis and its risk factors from 1990 to 2019 across 178 countries and used a generalized linear mixed model to explore the time series associations between cirrhosis and risk factors. We simulated scenarios with varying levels of risk factors and investigated benefits gained from the control of risk factors compared with the status quo. RESULTS: The global cirrhosis prevalence varied geographically, with the highest observed in East and Southeast Asia, mainly due to high hepatitis prevalence. Our study revealed that each 1% increase in prevalence of hepatitis B and C, cirrhosis prevalence would correspondingly increase 0.028% and 0.288%. There would be approximately 392.15 million fewer cirrhosis patients if the goals of a 65% reduction in prevalence of hepatitis and a 10% reduction in alcohol consumption were achieved. CONCLUSIONS: Given that cirrhosis prevalence has different risk factors depending on geography, it is important to identify an appropriate set of interventions for cirrhosis that are adapted to the epidemiological situation in a specific country. Interventions targeting hepatitis may have a significant impact on global cirrhosis prevalence, therefore, the adoption of specific interventions for hepatitis in high-burden regions and high-risk groups is warranted to lower the global burden of cirrhosis.

A Standardized Step-by-Step Approach for the Diagnosis and Treatment of Sepsis.

Sepsis is the major culprit of death among critically ill patients who are hospitalized in intensive care units (ICUs). Although sepsis-related mortality is steadily declining year-by-year due to the continuous understanding of the pathophysiological mechanism on sepsis and improvement of the bundle treatment, sepsis-associated hospitalization is rising worldwide. Surviving Sepsis Campaign (SSC) guidelines are continuously updating, while their content is extremely complex and comprehensive for a precisely implementation in clinical practice. As a consequence, a standardized step-by-step approach for the diagnosis and treatment of sepsis is particularly important. In the present study, we proposed a standardized step-by-step approach for the diagnosis and treatment of sepsis using our daily clinical experience and the latest researches, which is close to clinical practice and is easy to implement. The proposed approach may assist clinicians to more effectively diagnose and treat septic patients and avoid the emergence of adverse clinical outcomes.

CYP4CJ6-mediated resistance to two neonicotinoid insecticides in Sitobion miscanthi (Takahashi).

The wheat aphid Sitobion miscanthi (CWA) is an important harmful pest in wheat fields. Insecticide application is the main method to effectively control wheat aphids. However, CWA has developed resistance to some insecticides due to its extensive application, and understanding resistance mechanisms is crucial for the management of CWA. In our study, a new P450 gene, CYP4CJ6, was identified from CWA and showed a positive response to imidacloprid and thiamethoxam. Transcription of CYP4CJ6 was significantly induced by both imidacloprid and thiamethoxam, and overexpression of CYP4CJ6 in the imidacloprid-resistant strain was also observed. The sensitivity of CWA to these two insecticides was increased after the knockdown of CYP4CJ6. These results indicated that CYP4CJ6 could be associated with CWA resistance to imidacloprid and thiamethoxam. Subsequently, the posttranscriptional regulatory mechanism was assessed, and miR-316 was confirmed to participate in the posttranscriptional regulation of CYP4CJ6. These results are crucial for clarifying the roles of P450 in the resistance of CWA to insecticides.

MicroRNA-190-5p confers chlorantraniliprole resistance by regulating CYP6K2 in Spodoptera frugiperda (Smith).

The fall armyworm Spodoptera frugiperda (Smith) (FAA) is responsible for considerable losses in grain production, and chemical control is the most effective strategy. However, frequent insecticide application can lead to the development of resistance. In insects, cytochrome P450 plays a crucial role in insecticide metabolism. CYP6K2 is related to FAA resistance to chlorantraniliprole. However, the regulatory mechanism of CYP6K2 expression is poorly understood. In this study, a conserved target of isolated miRNA-190-5p was located in the 3' UTR of CYP6K2 in FAA. A luciferase reporter analysis showed that in FAA, miRNA-190-5p can combine with the 3'UTR of CYP6K2 to suppress its expression. Injected miRNA-190-5p agomir significantly reduced CYP6K2 abundance by 54.6% and reduced tolerance to chlorantraniliprole in FAA larvae, whereas injected miRNA-190-5p antagomir significantly increased CYP6K2 abundance by 1.77-fold and thus improved chlorantraniliprole tolerance in FAA larvae. These results provide a basis for further research on the posttranscriptional regulatory mechanism of CYP6K2 and will facilitate further study on the function of miRNAs in regulating tolerance to chlorantraniliprole in FAA.

International trends in esophageal cancer incidence rates by histological subtype (1990-2012) and prediction of the rates to 2030.

BACKGROUND: We provide an up-to-date overview of recent international trends (1990-2012) and predicted trends (2013-2030) in the incidence rates of esophageal cancer. METHODS: We used data from the Cancer Incidence in Five Continents (CI5plus) database that contains annual incidence data by cancer site, age, and sex as well as corresponding populations. The age-standardized esophageal cancer incidence rates of each country were calculated and plotted from 1990 through 2012 and were predicted to 2030 using a Bayesian age-period-cohort model. RESULTS: Globally, esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) showed opposing trends between 1990 and 2012; ESCC showed a decreasing trend, with an AAPC of - 1.5 (95% CI - 2.4, - 0.7), yet EAC showed an increasing trend, with an AAPC of 5.2 (95% CI 4.2, 6.2). The increasing trend in EAC was commonly observed in high-income countries. The predicted trend to 2030 indicated that most countries will continue to experience a decreasing trend or a stable trend in esophageal cancer incidence, except Denmark, the Netherlands, and the UK, where the overall esophageal cancer incidence rates, mainly driven by EAC, are predicted to increase. CONCLUSIONS: Decreasing trends in ESCC have been observed worldwide in both low- and middle-income countries and high-income countries, which may have been offset by increasing trends in EAC in high-income countries. The changing patterns of these two main subtypes of esophageal cancer may call for interventions, especially innovative interventions, to address obesity, GERD, and Barrett's esophagus.

Worldwide trend in human papillomavirus-attributable cancer incidence rates between 1990 and 2012 and Bayesian projection to 2030.

BACKGROUND: There is a paucity of global comparative trend analyses of all human papillomavirus (HPV)-attributable cancers. In addition, most analyses by international sources only describe past trends; few studies have projected the future trend of HPV-attributable cancers. METHODS: Data were used from the Cancer Incidence in Five Continents (CI5plus) database that contains annual incidence by cancer site, age, and sex, as well as corresponding populations. Age-standardized HPV-attributable cancer incidence rates were calculated and plotted from 1990 through 2012. A Bayesian age-period-cohort model was used to project the HPV-attributable cancer incidence rates of each country up to 2030. RESULTS: A significant but small decreasing trend worldwide in the HPV-attributable cancer incidence rate was observed with an average annual percent change (AAPC) of -0.3 (95% CI, -0.6 to -0.1). Notably, Uganda had a consistently increasing trend of HPV-attributable cancer incidence rate, with an AAPC of 1.7 (95% CI, 0.6-2.9). U-shaped trends were observed in some high-income countries because of a recent increase in oral cavity and oropharyngeal cancers. Most countries experience a decreasing or stable trend in HPV-attributable cancers incidence rates between 1990 and 2030. However, Japan, the United Kingdom, the Netherlands, Italy, Costa Rica, and Uganda will have an increasing trend during the projection period. CONCLUSIONS: Analyses revealed favorable downward trends in HPV-attributable cancer incidence rates in most of the included countries. However, the persistently increasing trend in HPV-attributable cancer incidence rates in Uganda and the recent increase in oral cavity and oropharyngeal cancer incidence rates in some high-income countries may present a new challenge for global HPV-attributable cancer prevention. LAY SUMMARY: Analyses revealed favorable downward trends in human papillomavirus (HPV)-attributable cancer incidence rates in most of the included countries. However, the persistently increasing trend in HPV-attributable cancer incidence rates in Uganda and the recent increase in oral cavity and oropharyngeal cancer incidence rates in some high-income countries may present a new challenge for global HPV-attributable cancer prevention.

Chuanxiongdiolides R4 and R5, phthalide dimers with a complex polycyclic skeleton from the aerial parts of Ligusticum chuanxiong and their vasodilator activity.

Chuanxiongdiolides R4-R6 (1-3), three novel phthalide dimers featuring two classes of unreported monomeric units (ligustilide/senkyunolide A and ligustilide/neocnidilide) with an unprecedented linkage style (3a,7'/7a,7'a), were isolated from the aerial parts of Ligusticum chuanxiong, together with three pairs of enantiomeric phthalide dimers [(-)/(+)-4a/4b, 5a/5b, and 6a/6b]. The bioassays revealed that compounds 1, 3, 4, 5, and 6 showed significant vasodilation effects, and the mechanism may be attributed to Cav1.2 activation blockade. Based on the established compounds library, the structure activity relationship of the phthalides was proposed. Our findings afford possible leads for developing new vasodilator against cardiovascular and cerebrovascular diseases such as hypertension and ischemic stroke.

An innovative adjustable prone positioning frame for treatment of severe kyphosis secondary to ankylosing spondylitis with two-level osteotomy.

PURPOSE: This study aims to introduce an innovative adjustable prone positioning frame (APPF) and explore its feasibility and safety for treatment of severe kyphosis secondary to ankylosing spondylitis (AS) with two-level osteotomy. METHODS: A retrospective, non-controlled study was conducted to illustrate the process where 13 patients diagnosed with severe kyphosis secondary to AS received operations on the APPF. Parameters of chin brow vertical angle (CBVA), global kyphosis (GK), thoracolumbar kyphosis (TLK), lumbar lordosis (LL) and sagittal vertical axis (SVA) were measured. Positioning time, operation time, intraoperative blood loss ahd complications were also determined. The Scoliosis Research Society outcomes instrument (SRS-22) was applied for clinical assessment. RESULTS: All patients were placed on the APPF successfully with the positioning time of 2.92 ± 0.76 min, received operation with 457.00 ± 88.04 min and had blood loss of 2330.77 ± 1423.25 ml. Four cases experienced pain due to tensional skin of the abdomen and one case suffered cerebrospinal fluid leakage postoperatively, but these patients were all cured conservatively. No neurological complications were observed, although sagittal translation occurred in four patients. Significant improvements were detected in CBVA, GK, TLK, LL and SVA postoperatively (P < 0.05), but no significant difference was observed between postoperation and the final follow-up (P > 0.05). The SRS-22 scores at 2 years after operation were significantly higher than those before operation (P < 0.05). CONCLUSION: The innovative APPF provided great convenience to place patients with severe kyphosis secondary to AS in a prone position. Performing two-level osteotomy with the aid of APPF is safe, feasible and effective.

Acute right ventricular dysfunction in severe COVID-19 pneumonia.

To investigate the right heart function in coronavirus disease 2019 (COVID-19) patients with acute respiratory distress syndrome (ARDS), a retrospective analysis of 49 COVID-19 patients with ARDS was performed. Patients were divided into severe group and critically-severe group according to the severity of illness. Age-matched healthy volunteers were recruited as a control group. The cardiac cavity diameters, tricuspid annular plane systolic excursion (TAPSE), tricuspid valve regurgitation pressure gradient biggest (TRPG), pulmonary arterial systolic pressure (PASP), maximum inferior vena cava diameter (IVCmax) and minimum diameter (IVCmin), and inferior vena cava collapse index (ICV-CI) were measured using echocardiography. We found that the TAPSE was significantly decreased in pneumonia patients compared to healthy subjects (P < 0.0001), and it was significantly lower in critically-severe patients (P = 0.0068). The TAPSE was less than 17 mm in three (8.6%) severe and five (35.7%) critically-severe patients. In addition, the TAPSE was significantly decreased in severe ARDS patients than in mild ARDS patients. The IVCmax and IVCmin were significantly increased in critically-severe patients compared to healthy subjects and severe patients (P < 0.01), whereas the ICV-CI was significantly decreased (P < 0.05). COVID-19 patients had significantly larger right atrium and ventricle than healthy controls (P < 0.01). The left ventricular ejection fraction (LVEF) in critically-severe patients was significantly lower than that in severe patients and healthy controls (P < 0.05). Right ventricular function was impaired in critically-severe COVID-19 patients. The assessment and protection of the right heart function in COVID-19 patients should be strengthened.

Changing trends in viral hepatitis mortality in East and Southeast Asia between 1987 and 2015 and its prediction until 2030.

BACKGROUND & AIMS: Trends in long-term mortality rates for viral hepatitis in East and Southeast Asia have been rarely reported. The aim of our study was to explore the long-term trends in viral hepatitis mortality rates in East and Southeast Asian countries between 1987 and 2015 and provide predictions of mortality to 2030. METHODS: We obtained viral hepatitis mortality data from the WHO Mortality Database for six East and Southeast Asian countries between 1987 and 2015. We produced choropleth maps of viral hepatitis mortality rates in 1987 and 2015 in East and Southeast Asia to illustrate geographic variations. We made predictions of mortality rates for each included country until the year 2030 using a series of joinpoint models. RESULTS: Viral hepatitis mortality rates declined in China (the average annual percent change (AAPC) = -5.1%, 95% CI: -7.5, -2.6), Singapore (AAPC = -5.4%, 95% CI: -7.5, -3.2), and the Philippines (AAPC = -3.4%, 95% CI: -4.9, -1.8). In contrast, Japan, the Republic of Korea, and Malaysia have experienced increasing trends in mortality rates, followed by decreasing trends. Our predictions indicate that all countries will experience slight to moderate downward trends until 2030. CONCLUSION: Favourable decreasing trends have been noted in East and Southeast Asian countries, which may not only inform the control and management of viral hepatitis in this region but also guide the prevention of viral hepatitis deaths in another region with a similar viral hepatitis epidemic.

[Priligy combined with behavioral therapy and psychological counseling for primary premature ejaculation].

OBJECTIVE: To observe the clinical effect of priligy (dapoxetine hydrochloride) combined with behavioral therapy and psychological counseling in the treatment of primary premature ejaculation (PPE). METHODS: A total of 202 PPE patients diagnosed from 2017 to 2018 were randomized into a control (n = 100) and an experimental group (n = 102), the former treated with oral priligy at 30 mg 1－3 hours before anticipated sexual activity, and the latter by the same medication combined with 30-minute behavioral therapy and psychological counseling once a month for two times. The therapeutic effects were evaluated according to the Premature Ejaculation Profile (PEP) scores of the patients at 1 and 2 months of treatment. RESULTS: After 1 month of treatment, both groups of the patients showed significant improvement, as compared with the baseline, in the PEP scores on personal distress related to ejaculation (P < 0 05), interpersonal difficulty related to ejaculation (P < 0.05) and satisfaction with sexual intercourse (P < 0.05) but not on perceived control over ejaculation (P > 0.05). At 2 months, however, the patients' scores on all the four PEP items were dramatically improved, even more significantly in the experimental than in the control group, as on perceived control over ejaculation (2.73 ± 0.95 vs 2.22 ± 0.68, P < 0.05), personal distress related to ejaculation (2.97 ± 1.07 vs 2.57 ± 0.69, P < 0.05), interpersonal difficulty related to ejaculation (3.19 ± 1.03 vs 2.77 ± 0.69, P < 0 05) and satisfaction with sexual intercourse (2.85 ± 0.99 vs 2.35 ± 0.63, P < 0.05). There was no statistically significant difference in the incidence rate of adverse events between the experimental and control groups (21.6% vs 20.0%, P > 0.05), and all the symptoms were relieved within 24 hours. CONCLUSIONS: Priligy combined with behavioral therapy and psychological counseling is more effective than priligy alone in improving the sexual function of PPE patients, raise their interest in sexual life and increase the intimacy between the partners, and can even achieve clinical cure in some patients.

Immunomodulatory Biscembranoids and Assignment of Their Relative and Absolute Configurations: Data Set Modulation in the Density Functional Theory/Nuclear Magnetic Resonance Approach.

Five new biscembranoids, bistrochelides A-E (3-7), were isolated together with glaucumolides A (1) and B (2) from the soft coral Sarcophyton trocheliophorum. Their structures and absolute configurations were determined by spectroscopic methods, X-ray crystal diffraction, and DFT/NMR (density functional theory/nuclear magnetic resonance) and TDDFT/ECD (time-dependent density functional theory/electronic circular dichroism) calculations. A new approach is introduced to determine the relative configuration of a stereocenter through the dynamic evaluation of the mean absolute errors (MAEs) between the investigated diastereoisomers, moving from an "extended" to a more diagnostic "restricted" set of atoms. This research leads to the structure revision of glaucumolides A and B. In in vitro immunomodulatory screening, compounds 1 and 4 significantly induced the proliferation of CD3+ T cells, while compounds 1 and 5 significantly increased the CD4+/CD8+ ratio at 3 µM.

Methyl chanofruticosinate type alkaloids from the aerial parts of Kopsia lancibracteolata Merr.

A chemical investigation on the 70% ethanol extract from the leaves and stems of Kopsia lancibracteolata Merr. resulted in the isolation of three new methyl chanofruticosinate type alkaloids, 12-hydroxyl prunifoline A (1), 12-hydroxyl prunifoline C (2), and N(4)-oxide prunifoline D (3). Structural elucidation of all the compounds was performed by spectral methods such as 1D- and 2D-NMR, IR, UV, and HR-ESI-MS. The isolated alkaloids were tested in vitro for cytotoxic potential against five tumor cell lines (BGC-823, HepG2, MCF-7, SGC-7901, and SK-MEL-2). As a result, alkaloid 3 exhibited significant cytotoxic activity against all tested tumor cell lines with IC50 values from 7.2 to 8.9 µM.

Efficacy and safety profile of drug-eluting beads transarterial chemoembolization by CalliSpheres® beads in Chinese hepatocellular carcinoma patients.

BACKGROUND: This study aimed to investigate the efficacy and safety of drug eluting beads transarterial chemoembolization (DEB-TACE) treatment by CalliSpheres® in Chinese patients with hepatocellular carcinoma (HCC) as well as the predicting factors for response. METHODS: 99 patients with HCC were consecutively enrolled in this study. All participants were treated by CalliSpheres® DEB-TACE. Clinical response was evaluated according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria. Common Terminology Criteria for Adverse Events (CTCAE) was used to assess the adverse events and liver dysfunction during and after the operation. RESULTS: Post treatment, 16 patients (16.2%) achieved CR and 59 (59.6%) achieved PR, the ORR was 75.8%. Subgroup analysis showed that patients with higher BCLC stage were of worse CR and ORR rates, and the CR as well as ORR between patients with cTACE history and patients without cTACE history were similar. Univariate logistic regression analysis displayed that number of nodules > 3, higher BCLC stage and previous cTACE might be correlated with worse ORR but with no statistical significance. As to liver function, CTCAE grades of laboratory indexes for liver function were increased at 1 week compared to baseline and recovered to the baseline grades at 1-3 months post operation. Besides, most of the common adverse events were light and moderate in our study. CONCLUSIONS: In conclusion, DEB-TACE by CalliSpheres® was efficient and well tolerated in Chinese HCC patients, and BCLC stage, number of nodules and cTACE history were possibly correlated with treatment response.

The Hippo signaling pathway: a potential therapeutic target is reversed by a Chinese patent drug in rats with diabetic retinopathy.

BACKGROUND: The Hippo signaling pathway is reported to be involved in angiogenesis, but the roles of the Hippo pathway in diabetic retinopathy have not been addressed. Fufang Xueshuantong Capsule has been used to treat diabetic retinopathy in China; however, the effect of Fufang Xueshuantong Capsule on the Hippo pathway has not been investigated. METHODS: In this study, diabetes was induced in Sprague-Dawley rats with intraperitoneal injection of streptozotocin. Twenty weeks later, Fufang Xueshuantong Capsule was administered for 12 weeks. When the administration ended, the eyes were isolated for western blot and immunohistochemistry analyses. The levels of P- mammalian sterile 20-like (MST), large tumor suppressor homolog (Lats), P- yes-associated protein (YAP), transcriptional co-activator with PDZ binding motif (TAZ) and TEA domain family members (TEAD) were measured. RESULTS: Diabetic rats had a decreased P-MST level in the inner plexiform layer and reduced expression of P-YAP in the photoreceptor layers of their eyes. In addition, diabetic rats displayed remarkable increases in Lats, TAZ and TEAD in their retinas. Furthermore, Fufang Xueshuantong Capsule restored the changes in the Hippo pathway. CONCLUSIONS: The Hippo signaling pathway is important for the progression of diabetic retinopathy and will hopefully be a targeted therapeutic approach for the prevention of diabetic retinopathy.

An La-related protein controls cell cycle arrest by nuclear retrograde transport of tRNAs during diapause formation in Artemia.

BACKGROUND: In eukaryotes, tRNA trafficking between the nucleus and cytoplasm is a complex process connected with cell cycle regulation. Such trafficking is therefore of fundamental importance in cell biology, and disruption of this process has grave consequences for cell viability and survival. To cope with harsh habitats, Artemia has evolved a special reproductive mode to release encysted embryos in which cell division can be maintained in a dormancy state for a long period. RESULTS: Using Artemia as a peculiar model of the cell cycle, an La-related protein from Artemia, named Ar-Larp, was found to bind to tRNA and accumulate in the nucleus, leading to cell cycle arrest and controlling the onset of diapause formation in Artemia. Furthermore, exogenous gene expression of Ar-Larp could induce cell cycle arrest in cancer cells and suppress tumor growth in a xenograft mouse model, similar to the results obtained in diapause embryos of Artemia. Our study of tRNA trafficking indicated that Ar-Larp controls cell cycle arrest by binding to tRNAs and influencing their retrograde movement from the cytoplasm to the nucleus, which is connected to pathways involved in cell cycle checkpoints. CONCLUSIONS: These findings in Artemia offer new insights into the mechanism underlying cell cycle arrest regulation, as well as providing a potentially novel approach to study tRNA retrograde movement from the cytoplasm to the nucleus.