SGLT2 inhibitor empagliflozin alleviates cardiac remodeling and contractile anomalies in a FUNDC1-dependent manner in experimental Parkinson's disease.

Recent evidence shows a close link between Parkinson's disease (PD) and cardiac dysfunction with limited treatment options. Mitophagy plays a crucial role in the control of mitochondrial quantity, metabolic reprogramming and cell differentiation. Mutation of the mitophagy protein Parkin is directly associated with the onset of PD. Parkin-independent receptor-mediated mitophagy is also documented such as BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3) and FUN14 domain containing 1 (FUNDC1) for receptor-mediated mitophagy. In this study we investigated cardiac function and mitophagy including FUNDC1 in PD patients and mouse models, and evaluated the therapeutic potential of a SGLT2 inhibitor empagliflozin. MPTP-induced PD model was established. PD patients and MPTP mice not only displayed pronounced motor defects, but also low plasma FUNDC1 levels, as well as cardiac ultrastructural and geometric anomalies (cardiac atrophy, interstitial fibrosis), functional anomalies (reduced E/A ratio, fractional shortening, ejection fraction, cardiomyocyte contraction) and mitochondrial injury (ultrastructural damage, UCP2, PGC1α, elevated mitochondrial Ca2+ uptake proteins MCU and VDAC1, and mitochondrial apoptotic protein calpain), dampened autophagy, FUNDC1 mitophagy and apoptosis. By Gene set enrichment analysis (GSEA), we found overtly altered glucose transmembrane transport in the midbrains of MPTP-treated mice. Intriguingly, administration of SGLT2 inhibitor empagliflozin (10 mg/kg, i.p., twice per week for 2 weeks) in MPTP-treated mice significantly ameliorated myocardial anomalies (with exception of VDAC1), but did not reconcile the motor defects or plasma FUNDC1. FUNDC1 global knockout (FUNDC1-/- mice) did not elicit any phenotype on cardiac geometry or function in the absence or presence of MPTP insult, but it nullified empagliflozin-caused cardioprotection against MPTP-induced cardiac anomalies including remodeling (atrophy and fibrosis), contractile dysfunction, Ca2+ homeostasis, mitochondrial (including MCU, mitochondrial Ca2+ overload, calpain, PARP1) and apoptotic anomalies. In neonatal and adult cardiomyocytes, treatment with PD neurotoxin preformed fibrils of α-synuclein (PFF) caused cytochrome c release and cardiomyocyte mechanical defects. These effects were mitigated by empagliflozin (10 µM) or MCU inhibitor Ru360 (10 µM). MCU activator kaempferol (10 µM) or calpain activator dibucaine (500 µM) nullified the empagliflozin-induced beneficial effects. These results suggest that empagliflozin protects against PD-induced cardiac anomalies, likely through FUNDC1-mediated regulation of mitochondrial integrity.

Hysteresis effects of different levels of storm flooding on susceptible enteric infectious diseases in a central city of China.

BACKGROUND: Recently, attention has focused on the impact of global climate change on infectious diseases. Storm flooding is an extreme weather phenomenon that not only impacts the health of the environment but also worsens the spread of pathogens. This poses a significant challenge to public health security. However, there is still a lack of research on how different levels of storm flooding affect susceptible enteric infectious diseases over time. METHODS: Data on enteric infectious diseases, storm flooding events, and meteorology were collected for Changsha, Hunan Province, between 2016 and 2020. The Wilcoxon Rank Sum Test was used to identify the enteric infectious diseases that are susceptible to storm flooding. Then, the lagged effects of different levels of storm flooding on susceptible enteric infectious diseases were analyzed using a distributed lag nonlinear model. RESULTS: There were eleven storm flooding events in Changsha from 2016 to 2020, concentrated in June and July. 37,882 cases of enteric infectious diseases were reported. During non-flooding days, the daily incidence rates of typhoid/paratyphoid and bacillary dysentery were 0.3/100,000 and 0.1/100,000, respectively. During flooding days, the corresponding rates increased to 2.0/100,000 and 0.8/100,000, respectively. The incidence rates of both diseases showed statistically significant differences between non-flooding and flooding days. Correlation analysis shows that the best lags for typhoid/paratyphoid and bacillary dysentery relative to storm flooding events may be 1 and 3 days. The results of the distributed lag nonlinear model showed that typhoid/paratyphoid had the highest cumulative RR values of 2.86 (95% CI: 1.71-4.76) and 8.16 (95% CI: 2.93-22.67) after 4 days of general flooding and heavy flooding, respectively; and bacillary dysentery had the highest cumulative RR values of 1.82 (95% CI: 1.40-2.35) and 3.31 (95% CI: 1.97-5.55) after 5 days of general flooding and heavy flooding, respectively. CONCLUSIONS: Typhoid/paratyphoid and bacillary dysentery are sensitive enteric infectious diseases related to storm flooding in Changsha. There is a lagging effect of storm flooding on the onset of typhoid/paratyphoid and bacillary dysentery, with the best lagging periods being days 1 and 3, respectively. The cumulative risk of typhoid/paratyphoid and bacillary dysentery was highest at 4/5 days lag, respectively. The higher of storm flooding, the higher the risk of disease, which suggests that the authorities should take appropriate preventive and control measures before and after storm flooding.

Landscape Changes and Optimization in an Ecological Red Line Area: A Case Study in the Upper Reaches of the Ganjiang River.

The key to optimizing ecological management is to study the spatial configuration of the landscape and the dynamic changes and their driving mechanisms at the landscape scale. The ecological red line area in the hilly area of the upper reaches of the Ganjiang River was chosen as the research area in this study. Based on the theory of landscape ecology and the evolution of biological communities, a multiscale coupling model was adopted and combined with remote sensing (RS) and geographical information system (GIS) technologies to systematically study the evolution of key landscape ecosystems such as forests, patch characteristics, and changes in diversity. The study revealed that: (1) forests represented the largest proportion in the study area, followed by croplands and grasslands; (2) the biological community tended to progress toward climax between 1986 and 1995, but then it moved toward regressive successions between 1995 and 2005 before recovering; (3) the study area was characterized by a high proportion of dominant ecosystems, most of which were at their climax with stable ecological species groups, and which were connected by ecological corridors; and (4) during the period from 1995 to 2010, most landscapes showed a trend of fragmentation. However, during the period from 2010 to 2018, the forest patches were gradually connected. The proportion of dominant landscapes increased, and the landscape uniformity was reduced. Based on the findings, we proposed an ecosystem management strategy that includes strengthening crop management, focusing on the natural restoration of the ecosystems and the cultivation of large patches, exploring disturbances due to mining activities, and applying methods to mitigate damage to and optimize the ecosystem.

A lysosome-targetable fluorescent probe based on HClO-mediated cyclization reaction for imaging of hypochlorous acid.

Misplaced or excessive hypochlorous acid in lysosomes has a close association with lots of diseases, so monitoring hypochlorous acid in lysosomes is particularly necessary. In the present work, a novel lysosome-targetable fluorescent probe (Lyso-R-HClO) for hypochlorous acid based on a HClO-mediated cyclization reaction was developed. In the fluorescent probe, the morpholine unit and the site of a HClO-mediated cyclization reaction were, respectively, used as the lysosome-targetable group and the response group. The probe has high selectivity and high sensitivity to hypochlorous acid, with a linear range from 5.0 × 10-8 to 3.0 × 10-6 M and a detection limit of 15 nM; it was successfully used to image endogenous and exogenous lysosomal HClO. Finally, Lyso-R-HClO was further applied to image lysosomal HClO produced in bacteria-infected macrophage with satisfactory results, which indicate that it is an useful tool for studies of lysosomal HClO and the role of lysosome.

Mitochondrial aldehyde dehydrogenase (ALDH2) rescues cardiac contractile dysfunction in an APP/PS1 murine model of Alzheimer's disease via inhibition of ACSL4-dependent ferroptosis.

Alzheimer's disease (AD) is associated with high incidence of cardiovascular events but the mechanism remains elusive. Our previous study reveals a tight correlation between cardiac dysfunction and low mitochondrial aldehyde dehydrogenase (ALDH2) activity in elderly AD patients. In the present study we investigated the effect of ALDH2 overexpression on cardiac function in APP/PS1 mouse model of AD. Global ALDH2 transgenic mice were crossed with APP/PS1 mutant mice to generate the ALDH2-APP/PS1 mutant mice. Cognitive function, cardiac contractile, and morphological properties were assessed. We showed that APP/PS1 mice displayed significant cognitive deficit in Morris water maze test, myocardial ultrastructural, geometric (cardiac atrophy, interstitial fibrosis) and functional (reduced fractional shortening and cardiomyocyte contraction) anomalies along with oxidative stress, apoptosis, and inflammation in myocardium. ALDH2 transgene significantly attenuated or mitigated these anomalies. We also noted the markedly elevated levels of lipid peroxidation, the essential lipid peroxidation enzyme acyl-CoA synthetase long-chain family member 4 (ACSL4), the transcriptional regulator for ACLS4 special protein 1 (SP1) and ferroptosis, evidenced by elevated NCOA4, decreased GPx4, and SLC7A11 in myocardium of APP/PS1 mutant mice; these effects were nullified by ALDH2 transgene. In cardiomyocytes isolated from WT mice and in H9C2 myoblasts in vitro, application of Aß (20 µM) decreased cell survival, compromised cardiomyocyte contractile function, and induced lipid peroxidation; ALDH2 transgene or activator Alda-1 rescued Aß-induced deteriorating effects. ALDH2-induced protection against Aß-induced lipid peroxidation was mimicked by the SP1 inhibitor tolfenamic acid (TA) or the ACSL4 inhibitor triacsin C (TC), and mitigated by the lipid peroxidation inducer 5-hydroxyeicosatetraenoic acid (5-HETE) or the ferroptosis inducer erastin. These results demonstrate an essential role for ALDH2 in AD-induced cardiac anomalies through regulation of lipid peroxidation and ferroptosis.

A review: biosynthesis of plant-derived labdane-related diterpenoids.

Plant-derived labdane-related diterpenoids (LRDs) represent a large group of terpenoids. LRDs possess either a labdane-type bicyclic core structure or more complex ring systems derived from labdane-type skeletons, such as abietane, pimarane, kaurane, etc. Due to their various pharmaceutical activities and unique properties, many of LRDs have been widely used in pharmaceutical, food and perfume industries. Biosynthesis of various LRDs has been extensively studied, leading to characterization of a large number of new biosynthetic enzymes. The biosynthetic pathways of important LRDs and the relevant enzymes (especially diterpene synthases and cytochrome P450 enzymes) were summarized in this review.

Advances in biotechnological production of santalenes and santalols.

Sandalwood essential oil has been widely used not only as natural medicines but also in perfumery and food industries, with sesquiterpenoids as its major components including (Z)- α-santalol and (Z)-ß-santalol and so on. The mature heartwoods of Santalum album, Santalum austrocaledonicum and Santalum spicatum are the major plant resources for extracting sandalwood essential oil, which have been overexploited. Synthetic biology approaches have been successfully applied to produce natural products on large scale. In this review, we summarize biosynthetic enzymes of santalenes and santalols, including various santalene synthases (STSs) and cytochrome P450 monooxygenases (CYPs), and then highlight the advances of biotechnological production of santalenes and santalols in heterologous hosts, especially metabolic engineering strategies for constructing santalene- and santalol-producing Saccharomyces cerevisiae.

Effects of meteorological factors on the incidence of mumps and models for prediction, China.

BACKGROUND: Mumps is an acute respiratory infectious disease with obvious regional and seasonal differences. Exploring the impact of climate factors on the incidence of mumps and predicting its incidence trend on this basis could effectively control the outbreak and epidemic of mumps. METHODS: Considering the great differences of climate in the vast territory of China, this study divided the Chinese mainland into seven regions according to the administrative planning criteria, data of Mumps were collected from the China Disease Prevention and Control Information System, ARIMA model and ARIMAX model with meteorological factors were established to predict the incidence of mumps. RESULTS: In this study, we found that precipitation, air pressure, temperature, and wind speed had an impact on the incidence of mumps in most regions of China and the incidence of mumps in the north and southwest China was more susceptible to climate factors. Considering meteorological factors, the average relative error of ARIMAX model was 10.87%, which was lower than ARIMA model (15.57%). CONCLUSIONS: Meteorology factors were the important factors which can affect the incidence of mumps, ARIMAX model with meteorological factors could better simulate and predict the incidence of mumps in China, which has certain reference value for the prevention and control of mumps.

Spatial-temporal analysis and visualization of scarlet fever in mainland China from 2004 to 2017.

This study retrospectively analyzed the spatio-temporal distribution and spatial clustering of scarlet fever in mainland China from 2004 to 2017. In recent years, the incidence of scarlet fever is increasing. Previous studies on the spatial distribution of scarlet fever in China are mainly focused at the provincial and municipal levels, and there is few systematic report on the spatial and temporal distribution characteristics of scarlet fever on the national level. Based on the incidence information of scarlet fever in mainland China between 2004 and 2017 collected from the China Center for Disease Control, this paper systematically explored the Spatio-temporal distribution of scarlet fever by three methods, contains spatial autocorrelation analysis, Spatio-temporal scanning analysis, and trend surface analysis. The results demonstrate that the incidence of scarlet fever varies by seasons, which is in line with double-peak distribution.The first peak generally occurs from May to June and the second one from November to December, while February and August is the lowest period of incidence. Trend surface analysis indicates that the incidence of scarlet fever in northern China is higher than the south, slightly higher in western compared to the east, and lower in the central part. Additionally, the results show that the clustering regions of scarlet fever centrally distributed in the northeast, northwest, north china and some provinces in the east, such as Zhejiang, Shanghai, Shandong, and Jiangsu.

Research about the optimal strategies for prevention and control of varicella outbreak in a school in a central city of China: based on an SEIR dynamic model.

Varicella is an acute respiratory infectious diseases, with high transmissibility and quick dissemination. In this study, an SEIR (susceptible-exposed-infected-recovered) dynamic model was established to explore the optimal prevention and control measures according to the epidemiological characteristics about varicella outbreak in a school in a central city of China. Berkeley Madonna 8.3.18 and Microsoft Office Excel 2010 software were employed for the model simulation and data management, respectively. The result showed that the simulated result of SEIR model agreed well with the reported data when ß (infected rate) equal to 0.067. Models showed that the cumulative number of cases was only 13 when isolation adopted when the infected individuals were identified (assuming isolation rate was up to 100%); the cumulative number of cases was only two and the TAR (total attack rate) was 0.56% when the vaccination coefficient reached 50%. The cumulative number of cases did not change significantly with the change of efficiency of ventilation and disinfection, but the peak time was delayed; when δ (vaccination coefficient) = 0.1, m (ventilation efficiency) = 0.7 or δ = 0.2, m = 0.5 or δ = 0.3, m = 0.1 or δ = 0.4 and above, the cumulative number of cases would reduce to one case and TAR would reduce to 0.28% with combined interventions. Varicella outbreak in school could be controlled through strict isolation or vaccination singly; combined interventions have been adopted when the vaccination coefficient was low.

Circular RNA circ-Foxo3 inhibits esophageal squamous cell cancer progression via the miR-23a/PTEN axis.

Circ-Foxo3 is a circRNA encoded by the human FOXO3 gene and works as a sponge for potential microRNAs (miRNAs) to regulate cancer progression. However, the role of circ-Foxo3 in esophageal squamous cell cancer (ESCC) is not clear. In this study, circ-Foxo3 was lowly expressed in cell lines and ESCC tissues. Meanwhile, overexpression of circ-Foxo3 inhibited cell growth, migration, and invasion, whether in vivo or in vitro. Mechanically, we found a potential miRNA target, miR-23a, which negatively correlated with circ-Foxo3 in ESCC. Then, a luciferase assay confirmed the relationship between the circ-Foxo3 and miRNA. Moreover, circ-Foxo3 upregulation of PTEN occurred through "sponging" miR-23a. Taken together, these results indicated that the circ-Foxo3/miR-23a/PTEN pathway was critical for inhibiting the ESCC progression. This may provide a promising target for treat ESCC.

The study on the early warning period of varicella outbreaks based on logistic differential equation model.

Chickenpox is a common acute and highly contagious disease in childhood; moreover, there is currently no targeted treatment. Carrying out an early warning on chickenpox plays an important role in taking targeted measures in advance as well as preventing the outbreak of the disease. In recent years, the infectious disease dynamic model has been widely used in the research of various infectious diseases. The logistic differential equation model can well demonstrate the epidemic characteristics of epidemic outbreaks, gives the point at which the early epidemic rate changes from slow to fast. Therefore, our study aims to use the logistic differential equation model to explore the epidemic characteristics and early-warning time of varicella. Meanwhile, the data of varicella cases were collected from first week of 2008 to 52nd week of 2017 in Changsha. Finally, our study found that the logistic model can be well fitted with varicella data, besides the model illustrated that there are two peaks of varicella at each year in Changsha City. One is the peak in summer-autumn corresponding to the 8th-38th week; the other is in winter-spring corresponding to the time from the 38th to the seventh week next year. The 'epidemic acceleration week' average value of summer-autumn and winter-spring are about the 16th week (ranging from the 15th to 17th week) and 45th week (ranging from the 44th to 47th week), respectively. What is more, taking warning measures during the acceleration week, the preventive effect will be delayed; thus, we recommend intervene during recommended warning weeks which are the 15th and 44th weeks instead.

Two-stage versus single-stage procedure for the management of cholecystocholedocholithiasis in elderly patients: a retrospectively cohort study

Background: there is an increasing incidence rate of cholecysto-choledocholithiasis associated with the increasing proportion of senile individuals. Methods: a total of 100 elderly patients (over 80 years of age) suffering both from cholelithiasis and choledocholithiasis were retrospectively studied from January 2010 to December 2016. Patients were scheduled for either a single-stage or two-stage procedure. The LCBDE group (n = 54) included cases that underwent a single stage procedure of laparoscopic exploration of the common bile duct combined with cholecystectomy. The ERCP/EST group (n = 46) included cases that underwent a two stage procedure of preoperative endoscopic retrograde cholangiopancreaticography with endoscopic sphincterotomy followed by cholecystectomy. Comorbidity conditions, presenting symptoms, bile duct clearance, length of hospital stay and the frequency of procedural, postoperative and long-term complications were recorded. Results: the LCBDE group had a higher stones clearance rate than the ERCP/EST group (100.0% vs 89.1%, p < 0.05). Postoperative complications and hospitalization length were comparable in the two groups (p > 0.05). There were more procedural complications in the ERCP/EST group than in the LCBDE group (10.8% vs 0%, p < 0.05). Furthermore, a patient in the ERCP/EST group died due to duodenal perforation. More patients in the ERCP/EST group experienced long-term complications than those in the LCBDE group (23.9% vs 3.7%, p < 0.05) during a mean follow-up period of 28.4 months. Conclusions: the single-stage procedure is a safe and effective technique for elderly patients with cholecysto-choledocholithiasis. LCBDE provides a good stone clearance rate with few long term complications

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Health care and risk of adverse pregnancy outcomes among diabetic women: an updated meta-analysis.

PURPOSE: Diabetic women appear to have adverse pregnancy outcomes. Although there were two meta-analyzes that examined the association between health care and adverse pregnancy outcomes, their results were limited because they only included congenital anomaly and perinatal mortality, and they did not clarify the detailed situations of diabetes and health care. This meta-analysis aims to completely evaluate the effects of health care in improving adverse pregnancy outcomes among diabetic mothers. METHODS: CNKI, EMBASE, Web of Science, and PubMed databases were searched for eligible studies up to December 2017, without any restrictions. Relevant cohort studies characterizing the relationship between health care and adverse pregnancy outcomes were selected for inclusion in the meta-analysis. We also screened the reference list of relevant studies. The fixed-effect models or random-effect models were used to calculate the risk estimates. The potential sources of heterogeneity were explored by stratified and sensitivity analyzes. RESULTS: Twenty-one studies with 6685 cases were included in our analysis. Health care was associated with significantly decreased risk of congenital anomaly (RR 0.237; 95% CI 0.166-0.338), perinatal death (RR 0.457; 95% CI 0.294-0.712), large for gestational age (LGA) (RR 0.794; 95% CI 0.640-0.986), and neonatal hypoglycemia (RR 0.672; 95% CI 0.486-0.929). Publication bias was not found in most results, with the exception of congenital anomaly and small for gestational age (SGA). CONCLUSION: Health care is associated with decreased risk of congenital anomaly, perinatal death, LGA, neonatal hypoglycemia.

Upregulation of DAPK2 ameliorates oxidative damage and apoptosis of placental cells in hypertensive disorder complicating pregnancy by suppressing human placental microvascular endothelial cell autophagy through the mTOR signaling pathway.

Death-associated protein kinase 2 (DAPK2) has indicated functional roles in cellular processes, including survival, apoptosis, and autophagy. This study is aimed to identify the effect of DAPK2 on oxidative damage and apoptosis of placental cells in hypertensive disorder complicating pregnancy (HDCP) through mTOR pathway. Microarray-based gene expression analysis was performed to predict the differentially expressed genes related to HDCP. To investigate the specific mechanism of DAPK2 in HDCP cells, placental microvascular endothelial cells were treated with mimic or siRNA of DAPK2 and mTOR to detect the expression of related genes, cell autophagy and apoptosis and oxidative damage. Finally, rats were modeled with HDCP to verify the cell experiment results. DAPK2 was downregulated in HDCP, and could activate mTOR. Besides, DAPK2 overexpression led to decreases in autophagy in HPVECs as well as apoptosis and oxidative damage in placental cells indicated by a substantial decrease in Beclin-1, LC3 II/LC3 I and Bax along with an increase in Bcl-2, 4EBP1 and p70S6K. It also ameliorates blood pressure elevation in HDCP rats. The study defined remission effect of DAPK2 on placental cell oxidative damage and apoptosis in HDCP via mTOR activation. Together, DAPK2 regulating mTOR pathway presents a promising therapy for HDCP treatment.

LncRNA-H19 activates CDC42/PAK1 pathway to promote cell proliferation, migration and invasion by targeting miR-15b in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the main causes of cancer-related death. This study aims to explore the role and underlying mechanism of H19 in HCC. METHODS: qRT-PCR detected miR-15b-5p and H19 expression, as well as the mRNA level of EMT-associated genes. Western blotting detected protein level of EMT-associated genes. Immunohistochemistry (IHC) examined CDC42 in HCC tissues. Dual luciferase reporter assay verified the regulatory mechanism among H19, miR-15b and CDC42. Colony formation, wound healing assay, transwell, flow cytometry measured proliferation, migration, invasion and apoptosis, respectively. RESULTS: H19 and CDC42 were up-regulated while miR-15b was down-regulated in HCC cells and tissues. miR-15b interacted with H19 and CDC42 3'-UTR. H19 knockdown inhibited proliferation, migration and invasion, and increased apoptosis, which was rescued by miR-15b inhibitor. H19 knockdown suppressed CDC42/PAK1 pathway and EMT progress. CONCLUSION: H19 knockdown inhibited proliferation, migration and invasion, and promoted apoptosis of HCC cells via targeting miR-15b/CDC42/PAK1 axis.

Two-stage versus single-stage procedure for the management of cholecystocholedocholithiasis in elderly patients: a retrospectively cohort study.

BACKGROUND: there is an increasing incidence rate of cholecysto-choledocholithiasis associated with the increasing proportion of senile individuals. METHODS: a total of 100 elderly patients (over 80 years of age) suffering both from cholelithiasis and choledocholithiasis were retrospectively studied from January 2010 to December 2016. Patients were scheduled for either a single-stage or two-stage procedure. The LCBDE group (n = 54) included cases that underwent a single stage procedure of laparoscopic exploration of the common bile duct combined with cholecystectomy. The ERCP/EST group (n = 46) included cases that underwent a two stage procedure of preoperative endoscopic retrograde cholangiopancreaticography with endoscopic sphincterotomy followed by cholecystectomy. Comorbidity conditions, presenting symptoms, bile duct clearance, length of hospital stay and the frequency of procedural, postoperative and long-term complications were recorded. RESULTS: the LCBDE group had a higher stones clearance rate than the ERCP/EST group (100.0% vs 89.1%, p < 0.05). Postoperative complications and hospitalization length were comparable in the two groups (p > 0.05). There were more procedural complications in the ERCP/EST group than in the LCBDE group (10.8% vs 0%, p < 0.05). Furthermore, a patient in the ERCP/EST group died due to duodenal perforation. More patients in the ERCP/EST group experienced long-term complications than those in the LCBDE group (23.9% vs 3.7%, p < 0.05) during a mean follow-up period of 28.4 months. CONCLUSIONS: the single-stage procedure is a safe and effective technique for elderly patients with cholecysto-choledocholithiasis. LCBDE provides a good stone clearance rate with few long term complications.

TPX2 gene silencing inhibits cell proliferation and promotes apoptosis through negative regulation of AKT signaling pathway in ovarian cancer.

Ovarian cancer (OC) is the leading cause of death from gynecological malignancy. Accumulated studies have revealed that targeting protein for Xklp2 (TPX2) was tightly associated with the development and progression of OC. The present study further determined a novel mechanism of TPX2 in OC via the AKT signaling pathway. The differentially expressed genes were screened in GEO database for gene expression microarray of OC. Bioinformatics was used to analyze the key differentially expressed genes in OC. We prepared CD133/1+ OC stem cells. Then cells were treated with TPX2-1 siRNA and perifcsine to explore the correlation of TPX2 and the AKT signaling pathway. We determined the expression of TPX2, AKT, Pl3 K, PTEN, caspase-3, Bax and Bcl-2 in OC cells. Cell proliferation, migration, invasion, and apoptosis rate were respectively measured using MTT and EdU assays, Transwell assay, Scratch test, and flow cytometry. Xenograft tumor in nude mice was used to determine the effect of TPX2 in OC cells in vitro. Initially, TPX2 overexpression was observed in OC, and TPX2 mediated the effect of the AKT signaling pathway in OC. TPX2 knockdown decreased expression of AKT, Pl3 K, and Bcl-2, and the extent of AKT phosphorylation, but increased expression of PTEN, Caspase-3, and Bax. Furthermore, TPX2 knockdown suppressed OC cell proliferation, migration and invasion, but promoted OC cell apoptosis. Taken together, TPX2 silencing negatively regulates the AKT signaling pathway by which OC cell proliferation was inhibited yet cell apoptosis was accelerated, suggesting a potential therapeutic approach to OC.

Biliary exploration via the left hepatic duct orifice versus the common bile duct in left-sided hepatolithiasis patients with a history of biliary tract surgery: A randomized controlled trial.

BACKGROUND: Hepatectomy and additional common bile duct exploration are required for the treatment of left-sided hepatolithiasis (LSH). METHODS: Eligible LSH patients (n = 62) scheduled for open left lateral segmentectomy or left hemihepatectomy with intraoperative biliary exploration via the left hepatic duct orifice (LHD group, n = 35) or the common bile duct (CBD group, n = 27) were retrospectively studied. T-tube insertion was performed on selected patients. Primary outcome measures included overall operative time, length of hospital stay, intraoperative complications, residual stones, and postoperative bile leaks. RESULTS: There were no residual stones observed in the 2 groups. Ten patients in the CBD group received T-tube placement, whereas no patients in the LHD group received T-tube placement. There were more patients in the CBD group suffered intraoperative complications and postoperative bile leakage than LHD group (P < .05). The LHD group had a significantly shorter operative time and hospitalization than the CBD group (P < .05). CONCLUSION: For left-sided hepatolithiasis patients with a history of biliary tract surgery, LHD cholangioscopy is an accessible technique that simplifies the operation procedure by avoiding choledochotomy and subsequent T-tube insertion, which results in lower complication rates as well as shorter operative duration and length of hospitalization.