Endocrine disrupting effects of binary mixtures of 17ß-estradiol and testosterone in adult female western mosquitofish (Gambusia affinis).

Androgens and estrogens often co-exist in aquatic environments and pose potential risks to fish populations. However, little is known about the endocrine disrupting effects of the mixture of androgens and estrogens in fish. In this study, transcriptional level of target genes related to the hypothalamic-pituitary-gonadal-liver (HPGL) axis, sex hormone level, VTG protein concentration, histology and secondary sex characteristic were assessed in the ovaries and livers of adult female western mosquitofish (Gambusia affinis) exposed to 17ß-estradiol (E2), testosterone (T), and mixtures of E2 and T for 91 days. The results showed that the transcriptional expression of cytochrome P450, family 19, subfamily A, polypeptide 1a (Cyp19a1a) was suppressed in the 200 ng/L T treatment and the 50 ng/L E2 + 200 ng/L T treatment in the ovaries. Steroidogenic acute regulatory protein (Star) and Cyp11a1 showed a similar expression pattern in the T treatment to its corresponding T + E2 mixtures. In the ovaries, the concentrations of 17ß-estradiol and testosterone were decreased in most treatments compared with the solvent control. VTG protein was induced in all steroid treatment. However, exposure to T or E2 + T mixture did not cause the abnormal cells of the ovaries and livers and an extension of the anal fins in female G. affinis. This study demonstrates that chronic exposure to E2, T and their mixtures affects the transcripts of genes in the HPGL axis, steroid hormone level and VTG protein concentration in the ovaries and livers, but fails to cause the histopathological effect of the ovaries and livers and alter the morphology of the anal fins in G. affinis.

Recent advances in copper-catalysed radical-involved asymmetric 1,2-difunctionalization of alkenes.

The radical-involved 1,2-difunctionalization of alkenes has developed into a robust tool for preparation of complex organic molecules. Despite significant advances in this area, the catalytic asymmetric version still remains a challenging task mainly due to the difficulty in the stereocontrol of the highly reactive radical intermediates. Recently, owing to the good single-electron transfer ability and coordination with chiral ligands of copper catalysts, remarkable achievements in radical-involved asymmetric alkene difunctionalization have been made via synergistic combination of copper and chiral ligands. This tutorial review highlights the recent progress in copper-catalysed radical-involved asymmetric 1,2-difunctionalization of alkenes and the mechanistic scenarios governing the stereocontrol, with an emphasis on utilization of chiral ligands.

Phase-shifted pentafluorobutane nanoparticles for ultrasound imaging and ultrasound-mediated hypoxia modulation.

The integration of ultrasound (US) contrast enhancement with oxygen-loading nanoagents provide the synergistic strategy for simultaneously US imaging and hypoxic microenvironment modulation. Herein, we synthesize pentafluorobutane (PFB)-loading methoxy poly(ethylene glycol)-b-poly(l-lactide) (PLLA) nanoparticle as the novel US-contrast-enhanced agent and demonstrate that PFB@PLLA effectively loads oxygen. We characterize the nanosize, phase-transformation property and oxygen-loading amount of PFB@PLLA and investigate the effectiveness of these nanoagents in US-contrast-enhanced imaging. The PFB@PLLA displays a perfect temperature-responsive phase-transition property and its liquid-to-gas phase transition temperature is 45°C, which produces microbubbles in the targeted regions. Moreover, PFB@PLLA loads high amount of oxygen and US-triggering PFB@PLLA reoxygenation effectively inhibits the expression of hypoxia-related proteins (HIF-1α and CAIX), reduces lactate secretion and glycolysis, which modulates hypoxic microenvironment and inhibits cancer cell migration and invasion in vitro. This study demonstrates that the US contrast-enhanced activity of PFB@PLLAs and the promising utility of oxygen-loading nanoagents to improve hypoxic microenvironment.

Vertebral Artery Dissection Probably Caused by Massage: A Case Report.

MASSAGE has been recommended to more people as an adjunct to health care. We illustrate a case of vertebral artery dissection (VAD) probably caused by massage that almost resulted in the patient's death. The patient experienced sudden cardiac arrest and paralysis. After treatment with anticoagulation and antiplatelet, he finally discharged without any sequelae.

Masculinization and reproductive effects in western mosquitofish (Gambusia affinis) after long-term exposure to androstenedione.

Androstenedione (AED) is a naturally occurring steroid hormone. It is metabolized to potent androgens, which may induce androgenic effects in fish. However, little is known whether and how the androgens interfere with the fish gonadal development and reproduction. This study aimed at demonstrating the effects of long-term AED exposure on reproduction and development in mosquitofish (Gambusia affinis). The growth, development and several morphological endpoints, including the segment number and length of anal fin, histological changes of gonads and liver, were evaluated in mosquitofish during development from fertilized embryo to adulthood (180 days) after exposure of AED at environmentally relevant concentrations. We found that the growth (length, body weight and condition factor) of fish was negatively correlated with AED concentration in females, but not in males. The significant elongation of the ray and increment of segment numbers in the anal fin, were detected in all mosquitofish after exposure. Moreover, AED exposure (0.4gµ/L) caused damages in gonads and reduced the number of pregnant females. These findings indicate that AED has adverse effects on the growth and development of the western mosquitofish after long-term exposure (180d). Long-term exposure (180d) to AED, including environmentally relevant concentration (0.4µg/L and 4µg/L), induced masculinization in female mosquitofish under the experimental conditions.

Changes in Histopathology, Enzyme Activities, and the Expression of Relevant Genes in Zebrafish (Danio rerio) Following Long-Term Exposure to Environmental Levels of Thallium.

Thallium is a rare-earth element, but widely distributed in water environments, posing a potential risk to our health. This study was designed to investigate the chronic effects of thallium based on physiological responses, gene expression, and changes in the activity of relevant enzymes in adult zebra fish exposed to thallium at low doses. The endpoints assessed include mRNA expression of metallothionein (MT)2 and heat shock protein HSP70; enzymatic activities of superoxide dismutase (SOD) and Na+/K+-ATPase; and the histopathology of gill, gonad, and liver tissues. The results showed significant increases in HSP70 mRNA expression following exposure to 100 ng/L thallium and in MT2 expression following exposure to 500 ng/L thallium. Significantly higher activities were observed for SOD in liver and Na+/K+-ATPase activity in gill in zebra fish exposed to thallium (20 and 100 ng/L, respectively) in comparison to control fish. Gill, liver, and gonad tissues displayed different degrees of damage. The overall results imply that thallium may cause toxicity to zebra fish at environmentally relevant aqueous concentrations.

Transvaginal genital fistula repair with insertion of Foley catheter via fistula tract.

AIM: Genital fistula is one of the most devastating injuries in women. Despite advances in medical care, it continues to be a distressing problem, and the success rate of repair surgery is still limited. We herein describe our experience with the surgical approach using Foley catheter to repair genital fistula after gynecological surgery. METHODS: We retrospectively reviewed 29 patients who had received genital fistula repair surgery with Foley catheter between October 2011 and December 2013. Based on traditional transvaginal genital fistula repair surgery, we inserted a Foley catheter into the bladder or intestine through the fistula opening. As a result, the fistula opening could be tracked, which allows for a clear view to improve fistula repair. All 29 patients were followed up at 1, 4, and 12 weeks postoperatively. RESULTS: Of the 29 patients, 28 had successful surgical outcome (96.55% success rate). The mean operative time was 85 ± 8.1 min. The mean blood loss was 109 ± 23.4 mL. No intraoperative complications were observed. The mean postoperative hospitalization time was 10 ± 2.8 days. The follow-up rate was 100%. CONCLUSIONS: Repair of transvaginal genital fistula using Foley catheter had a high success rate, short operative time, minimal blood loss, low morbidity and short hospital stay. Therefore, this approach is minimally invasive and effective.

Clinical efficacy of add-back therapy in treatment of endometriosis: a meta-analysis.

OBJECTIVE: A meta-analysis was conducted to determine the effectiveness of using gonadotropin-releasing hormone analogues (GnRH-a), both with and without hormonal add-back therapy, for the management of endometriosis. METHODS: Cochrane library, Ovid (Embase) and Pubmed databases were searched between the years 1998 and 2013 for published, prospective, randomised controlled trials (RCT) that assessed the effectiveness of "add-back" therapy for EMs treatment. The meta-analysis was performed using RevMan V5.0. The main outcome measures were as follows: lumbar spine bone mineral density (BMD) immediately after treatment and after 6 months of follow-up; femoral neck BMD; serum estradiol levels; changes in the Kupperman index score; the pelvic pain score, including dysmenorrhoea and dyspareunia; and pelvic tenderness. RESULTS: A total of 13 RCT, including 945 participants, were identified. The evidence suggested that "add-back" therapy was more effective for symptom relief than GnRH-a alone. BMD was significantly different when comparing "add-back" therapy to GnRH-a alone, both immediately after treatment and at 6 months. The "add-back" therapy increased serum oestrogen and did not reduce the efficacy of GnRH-a for treating dysmenorrhoea and dyspareunia. A variety of add-back regimens had a same effect for the treatment of endometriosis. CONCLUSIONS: "Add-back" therapy, based on the GnRH-a dose, does not reduce the efficacy of using GNRH-a for the management of endometriosis. "Add-back" therapy reduced the occurrence of side effects that can occur with GnRH-a therapy alone, such as osteoporosis and menopausal syndrome. There were no statistically significant differences when comparing the effectiveness of a variety of "add-back" regimens to each other.

Dual targeting biomimetic liposomes for paclitaxel/DNA combination cancer treatment.

Combinations of chemotherapeutic drugs with nucleic acid has shown great promise in cancer therapy. In the present study, paclitaxel (PTX) and DNA were co-loaded in the hyaluronic acid (HA) and folate (FA)-modified liposomes (HA/FA/PPD), to obtain the dual targeting biomimetic nanovector. The prepared HA/FA/PPD exhibited nanosized structure and narrow size distributions (247.4 ± 4.2 nm) with appropriate negative charge of -25.40 ± 2.7 mV. HA/FA/PD (PTX free HA/FA/PPD) showed almost no toxicity on murine malignant melanoma cell line (B16) and human hepatocellular carcinoma cell line (HepG2) (higher than 80% cell viability), demonstrating the safety of the blank nanovector. In comparison with the FA-modified PTX/DNA co-loaded liposomes (FA/PPD), HA/FA/PPD showed significant superiority in protecting the nanoparticles from aggregation in the presence of plasma and degradation by DNase I. Moreover, HA/FA/PPD could also significantly improve the transfection efficiency and cellular internalization rates on B16 cells comparing to that of FA/PPD (p < 0.05) and PPD (p < 0.01), demonstrating the great advantages of dual targeting properties. Furthermore, fluorescence microscope and flow cytometry results showed that PTX and DNA could be effectively co-delivered into the same tumor cell via HA/FA/PPD, contributing to PTX/DNA combination cancer treatment. In conclusion, the obtained HA/FA/PPD in the study could effectively target tumor cells, enhance transfection efficiency and subsequently achieve the co-delivery of PTX and DNA, displaying great potential for optimal combination therapy.

[Effect of mechanical stress on human parametrial ligament fibroblasts apoptosis].

OBJECTIVE: To explore the possible mechanism of mechanical factors in the pathogenesis of pelvic organ prolapse (POP). METHODS: The experiment material were uterosacral ligament and cardinal ligament- derived fibroblast from 10 patients who received total hysterectomy due to benign disease except POP. Fibroblast were cultured after collagenase digestion and identified by morphology and immocytochemical methods. Fibroblasts of 4-8 generations were stretched by four-point bending system for 0µ (0 mm), 1 333 µ (1 mm), 2 666 µ (2 mm), 5 333 µ (4 mm) strain, using 0 mm strain as the control group. Parameters was set to a frequency of 0.1 Hz, 4 hours. Cell apoptosis was tested by flow cytometry. RESULTS: Mechanical strain increased cell apoptosis [0 µ: (7.4 ± 1.5)%, 1 333 µ: (8.7 ± 2.2)%, 2 666 µ: (19.4 ± 3.4)%, 5333 µ: (50.9 ± 6.6)%, respectively]. Cell apoptosis rate was significantly higher under strong mechanical strain (2 666 µ and 5 333 µ versus 0 µ, all P < 0.05). CONCLUSION: Increased mechanical stress loading on human parametrial ligament fibroblasts could raise the rate of apoptosis.

Combined effects of binary mixtures of 17ß-estradiol and testosterone in western mosquitofish (Gambusia affinis) after full life-cycle exposure.

Estrogens and androgens are typical steroid hormones and often occur together in contaminated aquatic environments, but their mixed effects in aquatic organisms have been less well reported. In this study, the endocrine disrupting effects of binary mixtures of 17ß-estradiol (E2) and testosterone (T) in western mosquitofish (Gambusia affinis) were assessed by analyzing the sex ratio, secondary sex characteristics, gonadal histology, and transcriptional expression of target genes related to the hypothalamic-pituitary-gonadal (HPG) axis in G. affinis (from embryos) continuously exposed to E2 (50 ng/L), T (T1: 50 ng/L; T2: 200 ng/L), and mixtures of both (E2 + T1: 50 + 50 ng/L; E2 + T2: 50 + 200 ng/L) for 119 d. The results showed that exposure to E2 + T1 and E2 + T2 reduced the length ratio of ray 4/6 ratio in male G. affinis, suggesting feminized phenomenon in male G. affinis. Furthermore, 16.7-38.5 % of female G. affinis showed masculinized anal fins and hemal spines when exposed to T alone and in combination with E2. Importantly, the transcriptional levels of certain target genes related to the HPG axis were significantly altered in G. affinis following exposure to E2 and T alone and in combinations. Moreover, exposure to E2 and T in combinations can lead to combined effects (such as synergistic and antagonistic effects) on the transcriptional levels of some genes. These results collectively suggest that exposure to environmentally relevant concentrations of E2 and T alone and in mixtures can impact the endocrine system of G. affinis, and may pose potential risks in aquatic systems.

Interaction of 17α-ethinylestradiol and methyltestosterone in western mosquitofish (Gambusia affinis) across two generations.

The interactions between estrogen and androgen in aquatic animals remain largely unknown. In this study, two generations (F0 and F1) of western mosquitofish (Gambusia affinis) were continuously exposed to 17α-ethinylestradiol (EE2, 10 ng/L), methyltestosterone (MT, 10 ng/L (MTL); 50 ng/L (MTH)), and mixtures (EE2+MTL and EE2+MTH). Various endpoints, including sex ratio (phenotypic and genetic), secondary sex characteristics, gonadal histology, and transcriptional profile of genes, were examined. The results showed that G. affinis exposed to MTH and EE2+MTH had a > 89.7 % of phenotypic males in F1 generation, with 34.5 and 50.0 % of these males originated from genetic females, respectively. Moreover, females from F0 and F1 generations exposed to MTH and EE2+MTH exhibited masculinized anal fins and skeletons. The combined effect of MT and EE2 on most endpoints was dependent on MT. Furthermore, significant transcriptional alterations in certain target genes were observed in both the F0 and F1 generations by EE2 and MT alone and by mixtures, showing some degree of interactions. These findings that the effects of EE2+MTH were primarily on the phenotypic sex of G. affinis in offspring generation suggest that G. affinis under chronic exposure to the binary mixture contaminated water could have sex-biased populations.

Exposure to estrone disrupts the endocrine system of western mosquitofish (Gambusia affinis).

Estrone (E1) is one of the predominant natural estrogens detected in aquatic environments, yet little is known about its effects on the endocrine system in fish. In this study, the sex ratio, secondary sexual characteristics, gonadal histology, and transcriptional levels of genes closely related to sex differentiation and hypothalamic-pituitary-gonadal-liver (HPGL) axis were assessed in western mosquitofish (Gambusia affinis) after a full life-cycle exposure to E1 (0, 25.4, 143, 740, and 4300 ng/L) for 119 days. The results showed that exposure to 4300 ng/L of E1 resulted in 100% female and inhibited the growth of females. Exposure to environmentally relevant concentrations of E1 (143 and 740 ng/L) led to obvious feminization of skeletons and anal fins in males. Exposure to 740 and 4300 ng/L of E1 increased the proportion of mature spermatocytes in females, and exposure to 143 and 740 ng/L decreased the proportion of mature spermatocytes in males. Moreover, the transcripts of genes related to sex differentiation and HPGL axis were changed in the E1-exposed adult fish and embryos inside females. This study has provided valuable data on the endocrine disruption effects of E1 at environmentally relevant concentrations in G. affinis.

Controllable acoustic deterrent based on the warning signals generated by nonel detonators.

Acoustic deterrents are a practical strategy to mitigate the impact of underwater noise on marine mammals. However, their safety and effectiveness are still debatable. This study proposes a controllable acoustic deterrence method to protect marine mammals threatened by underwater blasting noise. The method creates strong-randomness warning signals using nonel detonators and establishes an escape time for animals protected. Combining the BELLHOP ray-based acoustic model with the marine environmental parameters and animals' auditory characteristics, we built a prediction model to establish a link between the acoustic fields and the adjustable source parameters, and provide a Risk zone and Deterrent zone for animals. The simulation and experimental results demonstrated that the root mean squared error between the simulated and measured sound pressure spectral density levels did not exceed 4.5 dB and the coefficient of determination remained at approximately 0.8, indicating that the new deterrent is an effective method with good controllable performances.

Transgenerational effects of androstadienedione and androstenedione at environmentally relevant concentrations in zebrafish (Danio rerio).

Androgens androstadienedione (ADD) and androstenedione (AED) are predominant steroid hormones in surface water, and can disrupt the endocrine system in fish. However, little is known about the transgenerational effects of ADD and AED in fish. In the present study, F0 generation was exposed to ADD and AED from 21 to 144 days post-fertilization (dpf) at nominal concentrations of 5 (L), 50 (M) and 500 (H) ng L-1, and F1 generation was domesticated in clear water for 144 dpf. The sex ratio, histology and transcription in F0 and F1 generations were examined. In the F0 generation, ADD and AED tended to be estrogenic in zebrafish, resulting in female biased zebrafish populations. In the F1 generation, ADD at the H level caused 63.5% females, while AED at the H level resulted in 78.7% males. In brain, ADD and AED had similar effects on circadian rhythm in the F0 and F1 generations. In the F1 eleutheroembryos, transcriptomic analysis indicated that neuromast hair cell related biological processes (BPs) were overlapped in the ADD and AED groups. Taken together, ADD and AED at environmentally relevant concentrations had transgenerational effects on sex differentiation and transcription in zebrafish.

[Treatment of acute unstable proximal clavicular fracture with hook plate of sternoclavicular joint].

OBJECTIVE: To investigate clinical effect of sternoclavicular hook plate in treating acute proximal clavicle fracture. METHODS: The clinical of 12 patients with acute unstable proximal clavicle fracture from June 2016 to June 2019 were retrospectively analyzed. There were 8 males and 4 females, aged from 46 to 63 years old. Ten patients caused by car accident and 2 patients caused by high falling. All patients had multiple injuries;the time from injury to surgery ranged from 2 to 14 d. All patients were treated with domestic sternoclavicular joint hook plate. The operative time ranged from 40 to 115 min. The intraoperative bleeding volume ranged from 30 to 110 ml, follow-up time ranged from 10 to 36 months, the fracture healing time ranged from 8 to 18 weeks. At the latest follow-up, the efficacy was evaluated by using shoulder joint function score (Rockwood score). RESULTS: All 12 patients were followed up, with no obvious pain at the latest follow-up. The rockwood scores of the affected shoulder ranged from 13 to 14, and the healthy shoulder ranged from 14 to 15. CONCLUSION: The sternocleidoclavicular joint plate is fixed with preformed plate. The cantilever is designed to retain the motion of the sternoclavicular joint. It's safe and simple, avoid, the injury of important organs during operation, and has a good prognosis. It is an ideal fixation method for the treatment of proximal clavicle fracture.

The addition of a pH-sensitive gel improves microemulsion stability for the targeted removal of colonic ammonia.

BACKGROUND: We prepared an oral W/O microemulsion for the removal of colonic ammonia (ME-RCA). The effect of this microemulsion was influenced by the digestion process in the gastrointestinal tract. In this paper, we aim to show that stability was improved by using a microemulsion-based gel for the removal of colonic ammonia (MBG-RCA). METHODS: MBG-RCA was prepared by adding sodium alginate to the ME-RCA. MBG-RCA and ME-RCA were passed through a simulated gastrointestinal environment, and the amount of colonic ammonia present was then determined by titration with a standard solution of hydrochloric acid. The pH of the gastrointestinal fluid was measured using a pH test paper and the size and form of the microemulsions were examined under the microscope. 18 healthy rats were randomly divided into three groups, fasted for 24 hours and allowed to drink normally. Three-way pipes were placed at the gastroduodenal junction in Group I, and at the terminal ileum in Group II. After the intragastric administration of ME-RCA, the stomach contents in Group I, the effluent from the terminal ileum in Group II and discharge from the anus in Group III were collected. The pH values of the gastrointestinal juice were measured by the pH test paper and those of the colon were determined by a universal indicator. These animal experiments were also used to test the effect of MBG-RCA. RESULTS: MBG-RCA showed a better removal rate of artificial colonic ammonia than ME-RCA (P < 0.05). The decrease in pH value of the artificial small intestinal fluid due to ME-RCA did not occur when MBG-RCA was used. In the simulated gastrointestinal process, MBG-RCA maintained greater stability and released the emulsion (ME-RCA) in the colonic fluid. In the gastrointestinal tract of normal SD rats, ME-RCA decreased in size and lost its stable form after entering the small intestine, while MBG-RCA remained stable and intact emulsion-drops were observed from the anus. Neither substance had any effect on the pH of the stomach or colon of normal rats (partly because normal rats were fasted for 24 hours and allowed to drink normally, which resulted in a low level of ammonia production in the colon). Unlike ME-RCA, MBG-RCA did not reduce the pH of the small intestine. CONCLUSIONS: MBG-RCA was more stable in the gastrointestinal tract and more effective at removing colonic ammonia when a higher concentration of ammonia was present. This made it possible to achieve the targeted removal of colonic ammonia and is a promising method to prevent hepatic encephalopathy (HE) in future studies.

Molecular characterization and expression pattern of three zona pellucida 3 genes in the Chinese sturgeon, Acipenser sinensis.

Chinese sturgeon (Acipenser sinensis) is a rare and endangered species and also an important resource for the sturgeon aquaculture industry. SMART cDNAs were synthesized from the ovary of A. sinensis, and the full-length cDNAs of three zona pellucida glycoprotein 3 genes (the new gene named AsZP3) were cloned and sequenced. AsZP3.1, AsZP3.2, and AsZP3.3 were 1,388 base pairs (bp), 1,288, and 1,290 bp in length, respectively, and they could be translated into proteins with 440, 394, and 398 amino acids, respectively. High level of amino acids sequence identity was seen between AsZP3.2 and AsZP3.3 (about 82%), but they share low identity with AsZP3.1 (26 and 23%, respectively). The AsZP3.1 has 42-50% amino acids sequence identity values with other fish and lower values with higher vertebrates (38%); AsZP3.2 and AsZP3.3 shared about 30-44% sequence identity with higher vertebrates and other fish. RT-PCR analysis indicated that AsZP3.1 displayed a wide tissue distribution at the mRNA levels including liver, kidney, spleen, heart, and ovary, but AsZP3.2 and AsZP3.3 mRNAs were expressed exclusively in the gonad. All three AsZP3 mRNAs were not detected during embryogenesis and early larval development; furthermore, they were not detected in the gonads of 1- and 2-year-old Chinese sturgeons. All three AsZP3 mRNAs were detected in the testes of 3-year-old males and in the ovaries of 4- and 5-year-old female Chinese sturgeons.

[Meta-analysis of efficacy and safety of liver transplantation in treating cholangiocarcinoma].

OBJECTIVE: To evaluate the therapeutic efficacy and safety of liver transplantation for patients with cholangiocarcinoma. METHODS: According to the requirements of Cochrane systematic review, a thorough literature search was performed in Pubmed/Medline, Embase and Cochrane Central Register electronic databases ranged between 1995 and 2009 in terms of the key words "liver transplantation", and "cholangiocarcinoma" or "cholangiocellular carcinoma" or "bile duct cancer". And restricted the articles published in the English language. Two reviewers independently screened the studies for eligibility, evaluated the quality and extracted the data from the eligible studies with confirmation by cross-checking. Data were processed for a meta-analysis by Stata 10 software with 1-, 3-, 5-year survival rates and incidence of complications. RESULTS: A total of 14 clinical trials containing 605 patients were finally enrolled in this study. The overall 1-, 3-, 5-year pooled survival rates were 73% (95%CI: 0.65 - 0.80), 42% (95%CI: 0.33 - 0.51) and 39% (95%CI: 0.28 - 0.51), respectively. Of note, preoperative adjuvant therapies (OLT-PAT group) rendered the transplanted individuals comparably favorable outcomes with 1-, 3-, 5-year pooled survival rates of 83% (95%CI: 0.57 - 0.98), 57% (95%CI: 0.18 - 0.92) and 65% (95%CI: 0.40 - 0.87), respectively. In addition, the overall pooled incidence of complications was 62% (95%CI: 0.44 - 0.78), among which that of OLT-PAT group (58%, 95%CI: 0.20 - 0.92) was relatively acceptable compared to those of liver transplantation alone (61%, 95%CI: 0.33 - 0.85) and liver transplantation with extended bile duct resection (78%, 95%CI: 0.55 - 0.94). CONCLUSIONS: In comparison to curative resection of cholangiocarcinoma with the 5-year survival rate reported from 20% to 40%, the role of liver transplantation alone is so limited, but neoadjuvant radiochemotherapy combined with liver transplantation can bring better short- and long-term prognosis.

Yishen Huoxue decoction attenuates unilateral ureteric obstruction-induced renal fibrosis and hypoxia-induced reactive oxygen species generation via adenosine monophosphate-activated protein kinase / peroxisome proliferator-activated receptor coactivator-1α / silent mating-type information regulation 2 homolog 3 pathway.

OBJECTIVE: To investigate the effeicacy of Yishen Huoxue decoction (YSHX) on renal fibrosis induced by unilateral ureteric obstruction (UUO), and on reactive oxygen species (ROS) homeostasis in human umbilical vein endothelial cells (HUVECs). METHODS: Forty male mice were randomly divided into six groups, sham group, UUO group, UUO+ resveratrol (RSV) (15 mg/kg) group, UUO + YSHX 20 mg/kg group (UUO + YSHX-L), UUO + YSHX 40 mg/kg group (UUO + YSHX-M), UUO + YSHX 80 mg/kg group (UUO + YSHX-H). Western blotting was used to measure protein expression levels. Reverse transcription-quantitative polymerase chain reaction was used to measure the mRNA expression. Immunohistochemistry was used to examine the histopathological changes of kidney tissue sample. Cell apoptosis was measured by Annexin V/PI staining. Cell viability was measured using CCK-8/WST-8 assay. RESULTS: YSHX treatment reduced α-SMA and Col-4 expressions, and increased CD31 and VE-cadherin expressions in UUO model mice. In vitro, YSHX increased cell viability and decreased apoptosis of HUVECs under hypoxic conditions. YSHX inhibited ROS generation by activating adenosine monophosphate-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor coactivator-1α (PGC-1α)/silent mating-type information regulation 2 homolog 3 (Sirt3) signaling. CONCLUSION: YSHX treatment reduced 109KJ UUO-induced renal injury and fibrosis. Furthermore, YSHX treatment attenuated hypoxia-induced oxidative stress by regulating AMPK/PGC-1α/Sirt3 signaling.