Safety assessment of dapagliflozin: Real-world adverse event analysis based on the FAERS database from 2012 to 2023.

Background: Dapagliflozin possesses the capacity to cure a wide range of diseases, however, there are many adverse events (AEs) that have not yet been acknowledged or recorded. Aim: Safety assessment of dapagliflozin based on the Food and Drug Administration Adverse Event Reporting System (FAERS) database, to explore differences between the reported AEs to provide a overview of the safety profile of dapagliflozin. Methods: We extracted data from the United States FAERS database, including from the fourth quarter of 2012 to the third quarter of 2023. Reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and empirical Bayesian geometric average (EBGM) were used to evaluate the relationship between dapagliflozin and its associated AEs. Results: A total of 13,593,946 case reports were gathered from the Food and Drug Administration Adverse Event Reporting System database for this investigation. Among these, there were 44,506 episodes of adverse events that were associated with dapagliflozin. Included in the analysis were 341 preferred words and 2 system organ classes that showed statistical significance according to all four methods simultaneously. The system organ classes encompassed illnesses related to metabolism and nutrition, as well as problems affecting the renal and urinary systems. PT levels were screened for adverse drug reaction signals including scrotal gangrene, scrotal cellulitis, perineal cellulitis, diabetic ketoacidosis, and pancreatitis. Conclusion: The majority of our findings aligned with the specification, however, certain novel indicators of AEs such as acute pancreatitis were not accounted for. The analysis of the AE signals may provide support for clinical monitoring and risk identification of dapagliflozin. Due to the inherent limitations of FAERS data, well-designed studies are required to demonstrate the safety of dapagliflozin.

Colon cancer with colovesical fistula: A report of four cases and a literature review.

Colon cancer with colovesical fistula (CVF) is a rare complication of colon cancer that possesses an extremely poor prognosis. Surgical treatment can improve the prognosis. The current study presents four cases of CVF, in which the first two cases were treated conservatively and the other two were treated surgically. The first case presented with intestinal obstruction for 3 days, and computed tomography (CT) was performed. The patient refused surgery and still exhibited lower abdominal pain 11 months later. The second case presented with urinary frequency and urgency that lasted for 2 days, and CT was performed. The patient refused surgery and died 2 months later. The third case presented with fecaluria that lasted for 1 month, and CT, endoscopy and one-stage palliative surgery were performed. The patient was lost to follow-up 5 months later. The fourth case presented with acute urinary tract symptoms for 4 months, and CT, endoscopy and one-stage radical surgery were performed. The patient remained disease-free 10 months later. The four cases reported in the present study not only represent excellent examples of the disease spectrum, but also act as a reminder of the possibility of detecting CVF at an early stage of the disease. The present study discusses the epidemiology of CVF, and presents the pattern of CVF in terms of signs, symptoms and imaging examinations, including CT, cystoscopy and colonoscopy, as well as treatment in the early stage of the disease.

Marked shifts of harmful algal blooms in the Bohai Sea linked with combined impacts of environmental changes.

The Bohai Sea, a semi-enclosed inland sea in China and an important mariculture region, has experienced extensive harmful algal blooms (HABs) and their negative impacts for several decades. To investigate the changes of HABs and their potential drivers over time and space, a dataset of 230 HAB events (1952-2017), along with corresponding environmental data (1990-2017) was compiled. The frequency of HAB events in the Bohai Sea has increased over time but plateaued in the last decade, and our analysis showed that history of HABs in the Bohai Sea could be categorized into three periods based on their frequency, scale, and HAB-forming species. The seasonal window of HAB events has started earlier and lasted longer, and the main hotspot has moved from Bohai Bay to coastal waters of Qinhuangdao over time. There were marked shifts in the representative HAB-forming microalgae, from dinoflagellates in the first period (before 2000) to haptophytes in the second period (2000-2009), and pelagophytes in the third period (2009 onwards). These community changes are accompanied by a trend toward diversification of HAB-forming microalgae, decrease in cell-size, and increase in negative impacts. Statistical analyses indicate that long-term changes in HABs in the Bohai Sea are linked with the combined effects of climate change, eutrophication and mariculture development. The results of the present study require to refine future monitoring programs, develop adaptive management strategies and predictive models for HABs in the Bohai Sea.

Brown tides linked to the unique nutrient profile in coastal waters of Qinhuangdao, China.

Brown tides caused by the pelagophyte Aureococcus anophagefferens have frequently occurred in the Bohai Sea since 2009 and have led to a dramatic collapse of the local scallop culture. To determine why brown tides occurred in the Bohai Sea rather than in other eutrophic coastal waters of China, phytoplankton communities and nutrients were evaluated and nutrient addition experiments were conducted in the Qinhuangdao coastal area. The concentration of dissolved organic nitrogen (DON) was nearly five times higher than that of dissolved inorganic nitrogen (DIN) during brown tides. High levels of phytoplankton biomass and nutrients were observed in the inshore waters, and the patterns of different nutrients were heterogeneous, which could be due to the uneven distribution of pelagophytes and non-brown tide phytoplankton populations (NBTP). The nutrient enrichment results indicated that the growth of the phytoplankton community was nitrogen-limited. Enrichment of DON, especially urea, could promote the growth of pelagophytes during the development stages of the brown tide. In brief, the results of this study imply that the unique nutrient profile (rich in DON but deficient in DIN) could support the outbreak of brown tides in the inshore waters of Qinhuangdao.

Spontaneous renal rupture due to renal calculi: A case report and literature review.

Spontaneous renal parenchymal rupture is a rare clinical emergency. The formation of benign and malignant tumors is the most common underlying cause of spontaneous rupture of renal parenchyma. To the best of our knowledge, 15 cases of renal parenchymal rupture have been reported to date. This report describes a rare case of renal parenchyma rupture in the lower left kidney caused by kidney calculi. Furthermore, previously published cases and articles were reviewed. The patient underwent four extracorporeal shockwave lithotripsy procedures within 2 years. The renal parenchyma rupture caused by the stones was successfully treated by removing the stones and repairing the kidney. However, a large hematoma was discovered around the lower pole of the left kidney, suggesting the possibility of a renal tumor. Therefore, radical nephrectomy was performed. Postoperative pathology revealed the lesion to be consistent with an intrarenal stone, where no malignancy, infection or vascular disease was observed. The present case highlights the requirement to also take into account the patient's clinical history in cases where imaging cannot completely identify the underlying cause of renal parenchymal rupture. Accurate identification of the underlying etiology of spontaneous renal rupture may determine the best treatment for the patient. The purpose of the present report is to facilitate the identification of the disease and reduce the rate of clinical misdiagnosis.

Evolution of harmful algal blooms in the East China Sea under eutrophication and warming scenarios.

Harmful algal blooms (HABs) worldwide are experiencing obvious changes under the combined impacts of global warming, eutrophication, and other driving forces. In the East China Sea (ECS), large-scale blooms caused by dinoflagellates occurred since 2000 and there has been an apparent shift of bloom-causative microalgae from diatoms to dinoflagellates. To predict the future evolution of HABs in this region, a model was developed based on the competition between diatoms and dinoflagellates, which would serve to reproduce the seasonal succession of microalgal blooms driven by multiple environmental factors. The evolution features of HABs were then projected under different scenarios of eutrophication and global warming. Under the 'business as usual' scenario, dinoflagellate blooms are expected to become more frequent with higher peak biomass concentrations over the next 30 years. Changes in nutrient composition of the Changjiang riverine discharge may largely give rise to this phenomenon, and accelerated warming associated with climate change may result in earlier occurrence of dinoflagellate blooms. To prevent further intensification of dinoflagellate blooms, efforts could be made to reduce nitrogen inputs and maintain or even increase silicate inputs from the Changjiang river.

Monitoring, modeling and projection of harmful algal blooms in China.

This review assesses monitoring, modeling and projection of harmful algal blooms (HABs) in China, with a focus on near-term warning and long-term trend projection. We reviewed phytoplankton monitoring as early warning, remote sensing for offshore environments, building models to describe ecological processes, modeling and forecasting near-term or seasonal HAB events, and projection of long-term HAB trend in China. Over the past 40 years, great progresses were made in traditional observation capability of HABs, and some reliable remote sensing algorithms were developed for HABs in optically complex coastal waters in Chinese seas. Numerical models have been applied to simulating real-world algal bloom events successfully; and these models, to some degree, are capable of predicting the time and place of HAB occurrence. In terms of long-term trend, HABs appeared to have shown diversified forms, being more miniaturized and more harmful. The development of an integrated monitoring and early-warning system of algal blooms and HABs should be a necessary first step to provide an effective management tool for mitigating damages associated with the occurrence of HABs in China.

Pigment Characterization of the Giant-Colony-Forming Haptophyte Phaeocystis globosa in the Beibu Gulf Reveals Blooms of Different Origins.

The giant-colony-forming haptophyte Phaeocystis globosa has caused several large-scale blooms in the Beibu Gulf since 2011, but the distribution and dynamics of the blooms remained largely unknown. In this study, colonies of P. globosa, as well as membrane-concentrated phytoplankton samples, were collected during eight cruises in the Beibu Gulf from September 2016 to August 2017. Pigments were analyzed by high-performance liquid chromatography coupled with a diode array detector (HPLC-DAD). The pigment 19'-hexanoyloxyfucoxanthin (hex-fuco), generally considered a diagnostic pigment for Phaeocystis, was not detected in P. globosa colonies in the Beibu Gulf, whereas 19'-butanoyloxyfucoxanthin (but-fuco) was found in all colony samples. Moreover, but-fuco in membrane-concentrated phytoplankton samples exhibited a similar distribution pattern to that of P. globosa colonies, suggesting that but-fuco provided the diagnostic pigment for bloom-forming P. globosa in the Beibu Gulf. Based on the distribution of but-fuco in different water masses in the region prior to the formation of intensive blooms, it is suggested that P. globosa blooms in the Beibu Gulf could originate from two different sources. IMPORTANCE Phaeocystis globosa has formed intensive blooms in the South China Sea and even around the world, causing huge social economic losses and environmental damage. However, little is known about the formation mechanism and dynamics of P. globosa blooms. 19'-Hexanoyloxyfucoxanthin (hex-fuco) is often used as the pigment proxy to estimate Phaeocystis biomass, while this is challenged by the giant-colony-forming P. globosa in the Beibu Gulf, which contains only 19'-butanoyloxyfucoxanthin (but-fuco) but not hex-fuco. Using but-fuco as a diagnostic pigment, we traced two different origins of P. globosa blooms in the Beibu Gulf. This study clarifies the development process of P. globosa blooms in the Beibu Gulf, which provides a basis for the early monitoring and prevention of the blooms.

Spatiotemporal variation of paralytic shellfish toxins in the sea area adjacent to the Changjiang River estuary.

The Changjiang (Yangtze River) River estuary (CRE) and its adjacent coastal waters is a notable region for nutrient pollution, which results in severe problems of coastal eutrophication and harmful algal blooms (HABs). The occurrence of HABs, particularly those of dinoflagellate Alexandrium spp. capable of producing paralytic shellfish toxins (PSTs), has an increasing risk of contaminating seafood and poisoning human-beings. The investigation of PSTs, however, is often hampered by the relatively low abundance of Alexandrium spp. present in seawater. In this study, a monitoring strategy of PSTs using net-concentrated phytoplankton from a large volume of seawater was employed to examine spatiotemporal variations of PSTs in the CRE and its adjacent waters every month from February to September in 2015. Toxins in concentrated phytoplankton samples were analyzed using high-performance liquid chromatography coupled with a fluorescence detector (HPLC-FLD). The results showed that PSTs could be detected in phytoplankton samples during the sampling stage in the CRE and its adjacent waters. Toxin content increased gradually from February to May, reached the peak in June, and then decreased rapidly from July to September. The maximum value of PST content was 215 nmol m-3 in June. Low-potency toxins N-sulfocarbamoyl toxins 1/2 (C1/2) were the most dominant components of PST in phytoplankton samples from February to June in 2015, while high-potency gonyautoxin 4 (GTX4) became the dominant component from July to September. Toxins were mainly detected from three regions, the sea area north to the CRE, the sea area east to the CRE, and sea area near Zhoushan Island south to the CRE. Based on the results of this study, it can be inferred that the three regions around the CRE in May and June is of high risk for PST contamination and seafood poisoning.

Resolving phytoplankton taxa based on high-throughput sequencing during brown tides in the Bohai Sea, China.

Large-scale blooms formed by pico-sized phytoplankton, which strongly inhibited feeding activity and growth of cultured scallops, have been recorded along the coast of Qinhuangdao in the Bohai Sea since 2009. Based on pigment profiles and clone library analysis of phytoplankton samples during the blooms, the major bloom-forming species was primarily identified as pelagophyte Aureococcus anophagefferens Hargraves et Sieburth, the causative species of intensive brown tides in the United States and South Africa. Due to the indistinct morphological features of the bloom-forming microalgae and limited knowledge on the composition of phytoplankton communities, there were still disputes concerning the causative species of the blooms. In this study, the method of high-throughput sequencing targeted 18S rDNA V4 region was used to study the composition of pico- and nano-sized phytoplankton communities in 2013 and 2014. A total of 18 groups of eukaryotic microalgae at the class level and more than 2000 operational taxonomic units (OTUs) were identified in phytoplankton samples collected from the brown-tide zone in the Qinhuangdao coastal waters. For both years, A. anophagefferens was the most dominant species during the bloom period and its maximum relative abundance exceeded 60 percent. Along with other evidence, the results further confirm that A. anophagefferens is the major causative species of the pico-sized phytoplankton blooms in the Bohai Sea. The outbreak of brown tide exhibited a strong inter-annual variation between 2013 and 2014, and an increasing dominance of dinoflagellates could be observed in the Qinhuangdao coastal waters.

Resolving the complex relationship between harmful algal blooms and environmental factors in the coastal waters adjacent to the Changjiang River estuary.

The sea area adjacent to the Changjiang River estuary is the most notable region for harmful algal blooms (HABs1) in China as both diatom and dinoflagellate blooms have been recorded in this region. Affected by the Changjiang diluted water (CDW2) and currents from the open ocean (i.e., Taiwan warm current, TWC3), the environmental conditions in the coastal waters adjacent to the Changjiang River estuary are quite complex. To obtain a better understanding of the mechanisms of HABs in this region, analyses based on field investigation data collected by the National Basic Research Priority Program (CEOHAB I4) were performed using principle component analysis (PCA5), multiple regression analysis (MRA6) and path analysis (PA7). The results suggested that phosphate and silicate are the major factors that directly affect the diatom bloom, while dissolved inorganic nitrogen (DIN8), temperature and turbidity are the factors that influence the dinoflagellate bloom. CDW and the TWC have different roles in affecting the two types of algal blooms. CDW, which has a high concentration of nitrate and silicate, is essential for the diatom bloom, while the intrusion of the TWC (mainly Kuroshio subsurface water that is rich in phosphate at the bottom) is critical for the maintenance of the dinoflagellate bloom. The results of this study offer a better understanding of the mechanisms of HABs in the East China Sea.

Enhanced biodegradation of alkane hydrocarbons and crude oil by mixed strains and bacterial community analysis.

In this study, two strains, Acinetobacter sp. XM-02 and Pseudomonas sp. XM-01, were isolated from soil samples polluted by crude oil at Bohai offshore. The former one could degrade alkane hydrocarbons (crude oil and diesel, 1:4 (v/v)) and crude oil efficiently; the latter one failed to grow on alkane hydrocarbons but could produce rhamnolipid (a biosurfactant) with glycerol as sole carbon source. Compared with pure culture, mixed culture of the two strains showed higher capability in degrading alkane hydrocarbons and crude oil of which degradation rate were increased from 89.35 and 74.32 ± 4.09 to 97.41 and 87.29 ± 2.41 %, respectively. In the mixed culture, Acinetobacter sp. XM-02 grew fast with sufficient carbon source and produced intermediates which were subsequently utilized for the growth of Pseudomonas sp. XM-01 and then, rhamnolipid was produced by Pseudomonas sp. XM-01. Till the end of the process, Acinetobacter sp. XM-02 was inhibited by the rapid growth of Pseudomonas sp. XM-01. In addition, alkane hydrocarbon degradation rate of the mixed culture increased by 8.06 to 97.41 % compared with 87.29 % of the pure culture. The surface tension of medium dropping from 73.2 × 10(-3) to 28.6 × 10(-3) N/m. Based on newly found cooperation between the degrader and the coworking strain, rational investigations and optimal strategies to alkane hydrocarbons biodegradation were utilized for enhancing crude oil biodegradation.

Biodegradation of crude oil by a newly isolated strain Rhodococcus sp. JZX-01.

A highly efficient oil-degrading bacteria JZX-01 was isolated from the oil-contaminated soil of the seacoast near the Boxi Offshore Oil Field of China. Morphological, physiological, and 16S rDNA gene sequence analyses indicated that JZX-01 was assigned to the genus Rhodococcus sp. This strain decomposed 65.27 ± 5.63 % of the crude oil in 9 days. Gas chromatography-mass spectrometry analysis showed that even the long-chain hydrocarbons (C31-C38) and branched alkanes (pristine and phytane), which were regarded as the stubborn ones, could be degraded. Further study showed that the bacteria still has good oil degradation ability at low temperatures as well as under high salt conditions. Moreover, JZX-01 was found to have a biosurfactant-producing capacity, which significantly favors the surface tension reduction and crude oil degradation. The promising isolated strain Rhodococcus sp. JZX-01 could be further used for the bioremediation of oil-polluted soil or seawater in a wide range of temperatures and high salt conditions.